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TITLE

THE DEVELOPMENT, VALIDATION AND ANALYSIS OF NEW

ENDOSURGICAL PROCEDURES IN UPPER GASTROINTESTINAL

SURGERY.

Thesis submitted for the degree of Doctor of Medicine in the University of Adelaide

by

Justin Raymond Bessell, M.B.,B.S. (Adelaide)

July 1995

The work described was performed within the Department of Surgery of the University

of Adelaide TABLE OF CONTENTS

TITLE I

TABLE OF CONTENTS .... ii TABLE OF FIGURES v ACKNOWLEDGEMENTS vlll PREFACE. x

SUMMARY x11 DECLARATION...... XV

1. AIMS I 2.INTRODUCTION J

2.1 Evolution of the capability to perform advanced laparoscopic abdominal surgery3 2.I.1lmpact on surgical research in South Australia 2.l.2Historical perspective of operative and technical advances 4 2.2 Complications of laparoscopic surgery .. 9 2.2.1 Complications related to needle and trocar insertion ...... 10 2.2.2 Complications related to the presence of a tension pneumoperitoneum ...... l5 2.2.3 Complications related to insertion and manipulation of instrumentation .....17 3. GENERAL PROBLEMS OF LAPAROSCOPY 18

3. I Temperature regulation...... 18 3.1 .I Introduction ...... 18 Effect of warmed gas...... 2r Aims ...... 2r 3.1.2 Methods ...... 22 3.1.3 Results...... 25 3. 1.4 Discussion...... 28 3.2 Thromboembolism ...... 33 3.2. 1 Introduction ...... 33 3 .2.2 Thromboembolic risk induced by hypercoagulability...... 3s Introduction...... 36 Aim...... 38 Methods ...... 38 Results ...... 39 Discussion. 42 3.2.3 Thromboembolic risk induced by impaired blood flow in splanchnic visceral vessels 44 Introduction. 45 Locoregional effect of pneumoperitoneum on splanchnic visceral vasculature45 Effect of systemic haemodynamics on splanchnic visceral vasculature ...... 48 Measurement of splanchnic visceral microcirculatory blood flow...... ' 50 Aims .53 Methods .54

1l Anaesthesia...... 54 Cannulation...... 54

Preparation of microspheres ...... 55 Standard sample...... 56 Dose of microspheres ...... 56

Baseline measurement of organ blood flows...... 56 Insufflation ..57 Post-insufflation measurement of organ blood flows ..57 Sacrifice and organ harvest...... 58 Ethical implications ...... 58 Statistical analysis 59 Results. 60 Discussion... 63 3.2.4 Thromboembolic risk induced by impaired blood flow in lower limb vessels6T 3.2.5 Thromboembolic risk induced by vessel wall abnormalities ...... 72 3.2.6 Summary of net thromboembolic risk during laparoscopy...... 72 3.2.7 Tfuomoembolism prophylaxis for laparoscopy...... 73 4. DEVELOPMENT AND EVALUATION OF NEV/ APPLICATIONS IN

LAPAROSCOPIC GASTROINTESTINAL SURGERY 76

4.1 Oesophagectomy 76 4.1.1 Introduction 76 Perivisceral oesophagectomy 76 Thoracoscopic oesophagectomy .. 80 Aim...... 9l 4.1.2 Methods ...... 9t Anaesthesia...... 92 Operative details 92 Thoracoscopic oesophageal dissection...... 93 Laparoscopic gastric mobilisation...... 94 Thoracoscopic oesophagogastric anastomosis 95 4. 1.3 Results ...... 101 4. 1.4 Discussion...... 102 4.2 Highly selective vagotomy 107 4.2.1 Introduction 107 History of open vagotomy 107 Development of minimal-access vagotomy ...... 110 Aims tt4 4.1.2 Methods ...... rt4 Cervical tube oesophagostomy ll5 Gastric acid output studies...... 118 Gastric emptying studies 119 Assessment of gastro-oesophageal reflux... 122 Operative procedures 122 Statistical analysis 124 4.1.3 Results ...... 125 Clinical outcome.... 125 Gastric acid output ...125 Gastric emptying ... 126 Assessment of oesophageal reflux ...r29 4.1.4 Discussion.. ... 130 4.3 Gastrostomy ...134 4.3.1 Introduction t34 Aim...... t36 4.3.2 Methods ...... t36 4.3.3 Results ...... 140 4.3.4 Discussion...... 140 5. ASSESSMENT OF ROUTINE LAPAROSCOPIC PROCEDURES ....143

5.1 Historical development of hernionhaphy r43 5.1.1 Traditional methods of inguinal hernia repair t43 Bassini t43 Halsted..... r43 McVay (Coopers ligament repair)... r44 Shouldice r4s Lichtenstein ...... 146 Preperitoneal repairs with and without mesh t47 5.I.2Laparoscopic methods of inguinal hernia repair 148 Laparoscopic ligation of the neck of the sac ...... t49 Laparoscopic plug (+ small mesh) repair 151 Laparoscopic transabdominal intraperitoneal (onlay) patch.. 152 Laparoscopic transabdominal preperitoneal patch 155 Laparoscopic extraperitoneal patch 159 Specific complications of laparoscopic hernia repair...... 161 5.2 Transabdominal preperitoneal herniorrhaphy...... t63 5.2. I Introduction ...... r63 5.2.2 Methods ...... r63 5.2.3 Results ...... t64 5.2.4 Discussion...... 170 5.3 Extraperitoneal herniorrhaphy ...... t74 5.3. 1 Introduction .... 174 5.3.2 Methods ...... 174 5.3.3 Results 174 5.3.4 Discussion...... r82 6. SUMMARY AND CONCLUSIONS.. 188

6.1 General problems of laparoscopy. 189 6. 1. 1 Temperature regulation. 189 6.1.2 Thromboembolism 190 6.2 Development and evaluation of new applications in laparoscopic gastrointestinal surgery ...... I92 6.2.1 Oesophagectomy 192 6.2.2 Highly selective vagotomy 193 6.2.3 Gastrostomy... 194 6.3 Assessment of routine laparoscopic procedures 195

1V 7. BIBLIOGRAPHY r97

V TABLE OF FIGURES

TABLE I: INSUFFLATING GAS TEMPERATURE AT A FLOW RATE OF IO L/\4IN (MANUFACTURERS TNFORMATTON) 23 FIGURE I: INTRAPERITONEAL TEMPERATURE 27 FIGURE 2: OESOPHAGEAL TEMPERATURE 28 TABLE 2: LEVELS OF COAGULATION INDICES IN VENOUS BLOOD IN PATIENTS UNDERGOING OPEN ORLAPAROSCOPIC ABDOMINAL SURGERY. 40 FIGURE 3: LEVELS OF FIBRINOGEN IN G/L FOR OPEN AND LAPAROSCOPIC PROCEDURES.42 TABLE 3: MEAN MICROVASCULAR BLOOD FLOV/ RATES (MLS/MIN/100G TISSUE) FOR VITAL INTRA-ABDOMINAL ORGANS BEFORE AND AFTER LAPAROSCOPIC

INSUFFLATION 63 FIGURE 4: (FROM LEFT TO RIGHT) 33MM CANNULA AND TROCAR, SPECIMEN

EXTRACTTON ADAPTOR, AND PORT EXCHANGE ROD (ENDOPATH-ETHTCON) 97

FIGURE 5: ENDOSURGICAL CIRCULAR STAPLER (STEALTH-ETHICON) WITH SPECIALLY

ADAPTED CONICAL ANVIL. 98 FIGURE 6: TEFLON STAPLERANVIL MODIFIED TO FACILITATE ENTRY INTO OPEN PROXIMAL OESOPHAGEAL REMNANT. 99 FIGURE 7: STAPLERANVIL FIXED IN PROXIMAL OESOPHAGUS BY AN ENDOLOOP. GASTRIC ANASTOMOTIC MARGIN IS INDICATED BY THE BROAD ARROW. THIN

ARROIù/ POINTS TO THE ENDOLOOP INTRODUCED THROUGH A CANNULA. lOO FIGURE 8: PLASTIC T-TUBE OESOPHAGOSTOMY 117 TABLE 4: DIFFERENCE BETWEEN THE PRE AND POSTOPERATIVE GASTRIC ACID OUTPUT VALUES 126 FIGURE 9: BASAL ACID OUPUT 126 FIGURE IO: PREOPERATIVE LIQUID GASTzuC EMPTYING 128 FIGURE I I: POSTOPERATIVE LIQUID GASTzuC EMPTYING 128 TABLE 5:DIFFERENCE BETWEEN PRE AND POSTOPERATIVE GASTRIC EMPTYING VALUES127

FIGURE 12: PRE AND POSTOPERATIVE REFLUX SCORES 129 TABLE6: DIFFERENCEBETWEENPREANDPOSTOPERATIVEREFLUX SCORES 129

FIGURE 13: THE ANTERIOR WALL OF THE BODY OF THE STOMACH GRASPED BY

BABCOCK FORCEPS, WITH TRANSABDOMINAL SUTURES PLACED BY AN ENDOSCOPIC NEEDLE HOLDER. I38

FIGURE 14: FOLEY CATHETER MOUNTED ON AN ÍNTRODUCER PASSED INTO THE PERITONEAL CAVITY, AND DIRECTED INTO THE STOMACH UNDER LAPAROSCOPIC VISUALISATION. 139 TABLE 7:COMPARISON OF THE TWO PATIENT GROUPS 166

FIGURE 15: MEDIAN ACTIVITY LEVELS MEASURED ON AN ANALOGUE SCALE OF 0 - 10.167

vl FIGURE 16: MEDIAN PAIN LEVELS MEASURED ON AN ANALOGUE SCALE OF 0 - 10. 167

FIGURE 17: MEAN NUMBER OF TOTAL ANALGESIC TABLETS TAKEN POST-OPERATIVELY PERPATIENT. 168 TABLES:MORBIDITY 169 TABLE 9: PATIENTS' OPINION OF DAY CASE SURGERY 170 FIGURE 18: BREAKDOWN OF PATIENT GROUPS AFTER RANDOMISATION 176 TABLE l0: COMPARISON OF THE TWO PATIENT GROUPS 178

FIGURE 19: MEDIAN ACTIVITY LEVELS MEASURED ON AN ANALOGUE SCALE OF 0 - 10.180 FIGURE 20: MEDIAN PAIN LEVELS MEASURED ON AN ANALOGUE SCALE OF 0 - 10. 180 FIGURE 21: MEAN NUMBER OF TOTAL ANALGESIC TABLETS TAKEN POST-OPERATIVELY PERPATIENT. I8I TABLE 1l: POST-OPERATIVE MORBIDITY 182

vl1 ACKNOWLEDGEMENTS

The work which is reported in this thesis was made possible by a Medical Postgraduate

Research Scholarship awarded by the National Health and Medical Research Council of

Australia. Instruments and some specific project grant support were supplied by the

AutoSuture and Ethicon surgical instrument companies.

The studies described involved the Departments of Surgery within The Queen Elizabeth

Hospital, The Royal Adelaide Hospital and the University of Adelaide, and The Royal

Adelaide Centre for Endoscopic Surgery. Several studies involving animals were

conducted on the premises of the Institute of Medical and Veterinary Science.

The foremost acknowledgements must be for the important contributions of the two

supervisors, Professor G. J. Maddern and Professor G. G. Jamieson. Their innovative

concepts and suggestions were tempered by a clarity of insight that can only be aspired

to. Despite heavy workloads, their preparedness to become involved beyond the

scientific scope of the work was greatly appreciated. They provided continued personal

encouragement, and offered assistance with burdensome administrative and financial

matters. The fertile research environment they have provided to their Departments is

testimony to their dedication, and contributed to the completion of this work in no small

measure. Tribute must also be made to many others, by whose contributions this work

is honoured:

. Within The Queen Elizabeth Hospital Department of Surgery; Mr. A Slavotinek, Mr.

P. Byrne, Ms. S. Millard, Ms. S. Ireland, Ms L. Martin, Ms.O. Kapaniris, Mr. K.

Porter, Mr. A. Hines and Mr. P. Leppard.

vilt o V/ithin The Royal Adelaide Hospital Department of Surgery and The Royal Adelaide

'Watson, Centre for Endoscopic Surgeryl Dr. G. Pike, Mr. D. Mr. P. Devitt, Mr. P. G

Gill, Mr. N. DeYoung, Ms. N. Ascott, Ms. P. Baxter and Ms. E. Cunningham. o Within the Institute of Medical and Veterinary Science; Dr. T. Kuchel, Dr. D

Noonan, Ms. K. Kaiser, Ms. T. Little and Ms. G. Summersides o V/ithin the AutoSuture company; Mr. R. FazzalaÅ and Mr. A. Nicolo. o V/ithin the Ethicon company; Ms. J. Prior, Mr. J. Meek, Dr. S. Straface. o Within the Cook company; Mr. G. Taddeo, Mr. A. Ward. o V/ithin the Kendall company; Ms. J. Richards

lx PREFACE

Part of the work described in this thesis has been published or accepted for publication.

These publications are listed below in the order they were submitted.

1. Maddern GJ, Rudkin G, Bessell JR, Devitt P, Ponte L. A Comparison of

Laparoscopic and Open Inguinal Hernia Repairs as a Day Surgical Procedure.

Surgical Endoscopy 1994; 8: 1404-08.

2. Bessell JR, Maddern GJ, Manncke K, Ludbrook G, Jamieson GG. Combined

Thoracoscopic and Laparoscopic Oesophagectomy and Oesophagogastric

Reconstruction. Endoscopic Surgery and Allied Technologies 1994;2: 32-36

3. Bessell JR, Stanley B, Maddern GJ. The Emerging Role for Laparoscopic

Gastrostomy: A Case Report. Australian and New Zealand Journal of Surgery 1994;

64: 515-517.

4. Facchin M, Bessell JR, Maddern GJ. A Simplified Technique for Laparoscopic

Instrument Ties. Australian and New Zealand Journal of Surgery 1994; 64: 569-571

5. Bessell JR, Karatassas A, Patterson JR, Jamieson GG, Maddern GJ. Hypotherrnla

Induced by Laparoscopic Insufflation: A Randomised Study in a Pig Model. Surgical

Endos copy. 1995 : 9 : 7 9l -7 96

6. Bessell JR, Patkin M,Isabel L. Durability and Function of Disposable Vs Reusable

Laparoscopic Instrumentation. Endoscopic Surgery and Allied Technologies 1995;3

r43-146.

7. Maddern GJ, Bessell JR. [Editorial] Disposable vs. Reusable Laparoscopic

Instrumentation. Endoscopic Surgery and Allied Technologies 1995;3: 125-126.

X 8. Maddern GJ, Bessell JR. Disposable Vs Reusable Laparoscopic Instrumentation

[Glossary]. Endoscopic Surgery and Allied Technologies. 1995;3: 151-152.

9. Bessell JR, Devitt PG, Goyal S, Jamieson GG. Prolonged survival follows resection

of oesophageal SCC downstaged by prior chemoradiotherapy. Australian and New

Zealand Journal of Surgery. In press. lO.Bessell JR, Pike G, Jamieson GG, Maddern GJ. Physiological outcome following

laparoscopic highly selective vagotomy: A controlled study in a pig model. Surgical

Endoscopy. In press

11.Pike GK, Mathew G, Bessell JR, Watson DI, Mitchell PC, Jamieson GG. The

assessment of hypercoagulability in patients undergoing open and laparoscopic

Nissen fundoplication. Australian and New Zealand Journql of Surgery.In press

xl SUMMARY

This thesis develops, analyses, and validates the role of therapeutic laparoscopy in situations where it is likely to be encountered in the practice of upper alimentary tract surgery. This is achieved by an analysis of some general problems of laparoscopy, particularly in relation to induced physiological disturbances; by development and evaluation of new applications in laparoscopic gastrointestinal surgeryl and by assessing the efficacy of laparoscopic procedures which have already entered routine practice.

The thesis commences with investigation into the hitherto relatively unexplored area of the physiological sequelae of laparoscopic surgery. The impact of laparoscopy on perioperative heat balance is documented in an animal study that quantifies changes in core temperature over a three-hour period of high-flow carbon dioxide insufflatron.

Insufflation is shown to result in a significant fall in core temperature, and it is revealed that currently available devices that provide warmed rather than cold insufflated gas confer no protection against perioperative heat loss. The thromboembolic risk posed by laparoscopic surgery is investigated by studying two of the three elements of Virchow's triad; hypercoagulability and impaired blood flow. In a controlled human study, changes in the level of blood coagulation markers before and after open and laparoscopic Nissen fundoplication indicated that minimally-invasive procedures may not protect against the risk of postoperative hypercoagulability. The potential for laparoscopic insufflation to impair blood flow to vital intraabdominal organs was considered in the light of reports detailing cases of fatal mesenteric thrombosis.

Radiolabelled microspheres were used to determine blood flow distributions in pigs, but using this model decreased blood flow at the tissue level in the setting of laparoscopic abdominal surgery could not be established.

xlt The place of laparoscopy in upper gastrointestinal surgery is expanded and clarified by the development and evaluation of three procedures hitherto unfamiliar in the laparoscopic environment. In an animal model, a new 3-step totally endoscopic operation for the surgical treatment of oesophageal carcinoma was devised. Another controlled animal study demonstrated the physiological validity of laparoscopic highly selective vagotomy. The outcome of laparoscopic highly selective vagotomy in terms of gastric acid output, liquid gastric emptying and ambulatory pH monitoring suggested that the use of laparoscopic highly selective vagotomy in clinical practice is appropriate

This section of the thesis concludes with a clinical study, in which a technique for laparoscopic gastrostomy is reported which offers an alternative form of enteral access after failed percutaneous endoscopic gastrostomy

Although inguinal hernias are not anatomically located in the upper gastrointestinal tract, their treatment comprises a routine component of upper gastrointestinal surgical practice. To resolve the current indications for laparoscopic herniorrhaphy, two randomised-controlled clinical trials were conducted in a day surgery setting. These determined that laparoscopic transabdominal preperitoneal herniorrhaphy should be confined to the repair of recurrent, bilateral or undiagnosed hernias only, rather than emerge as the standard operation. Similarly, laparoscopic extraperitoneal hernionhaphy should not enter clinical practice until subjected to further study under trial conditions with the aid of larger study populations and greater technical expertise, whilst the results of long-term recurrence rates are awaited.

xltl To my wife, Sara, whose love and support contributes immeasurably to the success of

my work.

To my parents Ray and Raylee, and my brother Kim, whose company throughout the

years has been the foundation of my fulfilling life

xlv DECLARATION

I declare that this thesis contains no material which has been accepted for the award of

any other degree or diploma in any other University and that to the best of my knowledge and belief, the thesis contains no material previously published or written by

another person, except where due reference is made in the text of the thesis. I further

consent to the thesis being made available for photocopying and loan if applicable if

accepted for the award of the degree.

sofr lrs

Justin Bessell

XV 1. AIMS

There were three specific objectives that guided the course of this thesis. These were

(i) To determine if particular physiological changes induced by the laparoscopic environment predispose to increased patient risk.

(ii) To develop and evaluate new applications of laparoscopic upper gastrointestinal surgery.

(iii) To assess the efficacy of routine laparoscopic procedures which had entered clinical practice without prior validation.

Therefore, answers to the following questions were sought:

(i) Is there an increased risk of deleterious core temperature changes during laparoscopic insuffl ation?

(ii) Is there an increased risk of thrombo-embolism induced by hypercoagulability during laparoscopic surgery?

(iii) Is there an increased risk of thrombo-embolism induced by impaired visceral blood fl ow during laparoscopic insuffl ation?

(iv) Is it possible to devise an endosurgical operative technique with the potential to improve the outcome of patients undergoing oesophagectomy for oesophageal carcinoma?

(v) Can the physiological validity of laparoscopic highly selective vagotomy be demonstrated?

I (vi) Can laparoscopic gastrostomy be developed to provide a feasible and desirable altemative for enteral access?

(vii) Is laparoscopic transabdominal preperitoneal hernionhaphy more efficacious than the conventional open approach?

(viii) Is laparoscopic extraperitoneal herniorrhaphy more effrcacious than the conven- tional open approach?

-L-a 2. INTRODUCTION

2.1 Evolution of the capability to perform advanced laparoscopic abdominal surgery

2.1.1 lmpact on surgical research in South Australia Laparoscopic cholecystectomy was introduced into major South Australian teaching hospitals in 1990. The enduring success of this operation for routine removal of the diseased gallbladder demonstrated first-hand to local surgeons the feasibility of operative abdominal laparoscopy. The South Australian perception of laparoscopic surgery soon followed the course of other international surgical communities; what was previously obstinate resistance became an almost blind enthusiasm to adopt untested and unproven laparoscopic procedures. Cuschieri has called this global phenomenon

"the biggest unaudited free-for-all in the history of surgery"(Cuschieri, 1995). At the time of conceptualization of this thesis in late 1992, academic surgeons within the

Royal Adelaide Hospital and The Queen Elizabelh Hospital came to realizeihat leadership in the field of laparoscopic surgery would not be sustained indefinitely by involvement in the race to become the hrst to undertake a new laparoscopic operation.

A more enduring contribution could be made by subjecting the advantages of these new techniques to the same rigorous analysis that had established the place of all prevrous innovations. This became the principle underlying the structure of this thesis, and there was no shortage of new procedures waiting to be validated! However, technical and operative development was not abandoned, as oesophageal surgery in particular had suffered from a relative paucity of the application of laparoscopic technology

Furthermore, because of the rapidly changing nature of this field of surgery, this research had to be sufficiently flexible to cope with continual extensive refinements in technology and procedure, and also be able to provide insight into new problems that

-J- only became obvious as more complex surgery was attempted. Therefore the underlying aims were more suitably addressed by proposing multiple hypotheses, rather than one all-encompassing proj ect.

-4- 2.1.2 Historical perspective of operative and technical advances The evolution of laparoscopic surgery is inextricably linked to technological advances which allow surgery to be conducted in anatomical locations that cannot be reached except by the use of large incisions. The hrst published attempt to examine an internal body cavity was published by Bozzini in 1806, who constructed a crude apparatus to visualize the urethra for stones and tumours(Bozzini, 1806). However, it was 60 years later before the first serviceable endoscope was developed by Desormeaux in 1865 to inspect the bladder, cervix and uterus. This apparatus included a kerosene lamp, a chimney vent, and a mirror(Desonneaux, 1865). Further developments in optical technology and the invention of the Edison incandescent light bulb in 1880 allowed a more contemporary-style cystoscope to be produced in Germany by Nitze in 1897. This operating endoscope also included a working channel for the passage of customised instruments. The Nitze cystoscope was used by Kelling in 1902 to examine the abdominal cavity of a live dog following the creation of a pneumoperitoneum with filtered air(Kelling,1902). Kelling later reported on his experience in humans, but it was Jacobaeus who was the first surgeon to report a series of laparoscopies and thoracoscopies in man in 1910, performed without pneumoperitoneum(Jacobaeus,

1e10).

These early techniques used filtered air as the insufflated gas, usually pumped in by a syringe, until the development of a pneumoperitoneal needle by Goetze in 1918(Goetze,

1918). ln 1926 Zollikofer proposed the use of carbon dioxide as the insufflating gas as a more rapidly absorbed substitute for air, and this was followed by the introduction of a new insufflation needle by Veress in 1938(Veress, 1938). This needle, which still bears his name, comprised a spring-loaded obturator contained within the outer stylet of the

-5- needle. The obturator retracted during fascial penetration, and then emerged to cover the sharp needle point after entering the body cavity. It was originally designed as a safe means to create a pneumothorax, which was at the time a treatment for pulmonary tuberculosis.

Operative laparoscopy had its beginnings in the 1930's when Kalk advocated the dual- puncture technique to accommodate his specially-designed instruments, and he also introduced the oblique 135o lens system laparoscope to allow a change in the viewing direction by merely rotating the scope along its longitudinal axis. During this decade,

Fervers performed the first laparoscopic adhesiolysis(Fervers, 1933), Ruddock described the biopsy of abdominal organs using monopolar electrocautery(Ruddock,

1934), and Boesch performed the first laparoscopic tubal sterilization(Boesch, 1936)

Laparoscope technology was further revolutionizedin 1952 when Fourestier eliminated the risks of intemal electrical or thermal injury due to incandescent lighting by developing a cold light system whereby an intense light was transmitted along a quartz rod from the proximal to distal ends of the scope(Fourestier et al., 1952). Twelve months later, Hopkins invented the rod-lens system(Hopkins, 1953), in which small air lenses were combined with long glass rods (previously small glass lenses were combined with long air spaces). This optical system doubled the light transmitting capacity of endoscopes, and provided a significantly larger clear aperture

Kurt Semm of Kiel University in Germany is the patriarch of operative laparoscopy in the modem era. His most often cited achievement is the development of an automatic insufflation device. However, from the 1960's onward he contributed enormously by many other innovative advances such as the suction-irrigator, hook scissors, the

-6- laparoscopic morcellator, the endoloop applicator, needle-holders and laparoscopic suturing, clip appliers, atraumatic forceps, and the endotrainer. Semm's technological advances led to more complicated therapeutic laparoscopic procedures, predominantly in the field of gynaecology. Operative innovations attributed to his team include laparoscopic management of ectopic pregnancy, salpingostomy, oophorectomy, salpingolysis, fimbriolysis, adhesiolysis, tumour biopsy, staging and debulking, and the first laparoscopic appendicectomy in 1983(Semm, 1983)

Pioneering developments in the field of endoscopic surgery were also being advanced during the early 1980's by another German Surgeon, Gerhard Buess, working from the

Johannes-Gutenberg University in Mainz. He used a technologically-advanced stereoscopic magnifying optical system, insufflation, and endoscopic instruments for the endoluminal resection of rectal and sigmoid colon tumours in an operation called

Transanal Endoscopic Microsurgery (TEM) that closely mimiced the subsequent performance of laparoscopic intraabdominal surgery(Buess et al., 1988; Buess et al.,

1989). Although an important innovation in its own right, the importance of this technique in terms of laparoscopic surgery was the pre-emptive development of a wide range of endoscopic technology that later provided surgeons with immediate operative capabilities once video technology arrived.

Despite other early protagonists such as George Berci(Berci et al., 1973), Alfred

Cuschieri(Cuschieri et al., I978), Paul Sugarbaker(Sugarbaker and Wilson, 1976), and

Andrew V/arshaw(V/arshaw et al., 1986) who advocated a role for laparoscopy in the

1970's and early 1980's, it failed to gain a foothold in General Surgical practice at that time

-7 - Acceptance of laparoscopy awaited the development of the computer chip video camera in 1986. Although laparoscopy could never have developed without the substantial aforementioned contributions, this breakthrough was surely the single most important factor which sealed the influential place of laparoscopic surgery in modem surgical practice. V/ithin one year, Mouret of Lyon had performed the first laparoscopic cholecystectomy in a human, finally exciting momentous worldwide interest in operative laparoscopy by General Surgeons. However several groups claim prior independent development of laparoscopic cholecystectomy in an animal model, namely

Cuschieri and Nathanson in Dundee(Cuschieri and Buess, 1992), and Filipi(Filipi et al.,

1991). The first published report using a multipuncture technique in humans was by

Dubois in 1989(Dubois et al., 1989), and during that year the procedure was established in Bordeaux by Perissat(Perissat et al., 1989), in Nashville by Reddick and

Olsen(Reddick and Olsen, 1990), in Dundee by Cuschieri and Nathanson(Cuschieri et a1.,1990), and in Los Angeles by Berci(Berci, 1991). Since then, the practice of laparoscopic cholecystectomy has snowballed internationally, and spawned the development of the plethora of laparoscopic intraabdominal operations which are currently performed

It is the reduced trauma of access offered by operative laparoscopy that has captured the imagination of the General Surgical community. Several tiny incisions can replace a long laparotomy or thoracotomy incision. The subsequent patient benefits that flow from this include reduced total operative trauma, reduced incidence of major wound complications, reduced adhesive complications, shorter hospital stay, and a quicker return to work or normal activities(Cuschieri, 1995). However, laparoscopy is not necessarily benehcial for every abdominal operation, and in some cases it may actually

-8- be detrimental. The total operative trauma sustained by a patient undergoing a surgical operation has 2 components;

. access trauma related to the exposure of the operative region (e.g. by laparoscopy or

laparotomy), and o procedural trauma, which is the injury inflicted in executing the operative procedure.

The benefit of laparoscopic surgery over conventional open surgery is greatest when access trauma constitutes a large component of the total operative insult(Cuschieri, lees).

-9- 2.2 Complications of laparoscopic surgery As the capability to perform laparoscopic intraabdominal surgery evolved to to the extent that it triggered a revolutionary change in the practice of gastro-intestinal surgery, so did the capability for surgeons utilising this technology to create unfamiliar complications. A generation of fully trained surgeons was required to re-enter the learning-curve for operative surgery, resulting in a heightened awareness of potential and observed complications unique to laparoscopy(Altman,1992). The complications of laparoscopy can be broadly divided into two major groups; those inherent to laparoscopy and those related to the specific operative procedure.

Complications related to specific operative procedures analysed in this work are considered in the appropriate sections. Reference to complications related to other specific operative procedures capable of being performed laparoscopically is beyond the scope of this thesis. In contrast, investigation of complications universally inherent to laparoscopy comprises a large part of this thesis, and an introductory overview is conceptually useful as many can be avoided with knowledge of the pertinent technical details. The complications inherent to laparoscopy include those related to needle and trocar insertion; those related to the presence of a tension pneumoperitoneum; and those related to the manipulation of laparoscopic instrumentation(Crist and Gadacz, 1993).

9

-10- 2.2.1 Complications related to needle and trocar insertion The occurrence of injury to intraabdominal structures complicating insertion of laparoscopic needles and trocars is well documented. The most serious injuries are those inflicted on major vascular structures in the retroperitoneum and on splanchnic viscera. The incidence of injury to major retroperitoneal vessels has been reported as

0.03% in two major studies; one analysing 100,000 laparoscopic gynaecologic procedures(Mintz, 1977), and the other carefully followingup 3229laparoscopic herniorrhaphies(Phillips et al., 1995). Between 9Yo and 13 o/o of patients sustaining such an injury will die(Deziel etal.,1993 ; Baadsgaard et al., 1989). Vascular injury during

Veress needle insertion is usually obvious during aspiration manouevres as blood appears in the syringe. Injury during trocar insertion may be concealed, and only evidenced by intra-operative hypotension. Haemodynamic instability may be delayed until the postoperative period if haemorrhage is contained in the retroperitoneum, or if tamponaded by pneumoperitoneal pressure - especially in the case of venous injury

Immediate laparotomy and repair is mandatory as soon as major vascular injury is suspected. Minor vascular injuries may also occrÍ during needle or trocar insertion, and typically involve the epigastric vessels. These can usually be controlled by electrocautery or suture ligation, and may be avoided by transillumination of the anterior abdominal wall prior to trocar entry, and by visually controlled trocar egress at the completion of the procedure.

Splanchnic viscera most commonly injured during initial laparoscopic abdominal access are bowel and bladder, with a reported incidence of 0.1%o (Phillips et al., 1995 ; Deziel et al., 1993). These may go unrecognised with potentially fatal consequences(McKernan and Champion, 1995). Identification of such an injury can be made because of the odour

- 11- produced, or visually by directly witnessing intestinal laceration, or indirectly by bilious

or faecal staining. Bladder injuries can be recognised by the appearance of blood or gas

in the urinary catheter bag. Most such injuries will require primary suture repair and

decompression of the viscus concemed until healing has been achieved. To avoid

splanchnic visceral injury, it is customary to position the patient in reverse

Trendelenburg tilt to displace viscera from the umbilicus, and nasogastric compression

of the stomach and urinary catheter drainage are also strongly recommended(Crist and

Gadacz,1993).

Techniques designed to minimize the complications of needle and initial blind trocar

access continue to evolve. The most popular is to perform "open laparoscopy" followed

by placement of a blunt{ipped Hasson trocar under direct vision(Hasson, 1971). Two

comparative studies have reported a lower complication than with the alternative Veress

needle technique(Ballem and Rudomanski, 1993 ; Sigman et al., 1993). Although the

Hasson approach is simple and requires no extra equipment, it does not provide the

definitive solution. It is technically more demanding if access to the umbilical

"window" is precluded by obesity or the consequences of previous surgery, and

conclusive data from large studies is still not evident(l.lathanson,1995). A newer

development designed to achieve safer access is the use of an "optical Veress needle"

that allows visual control of abdominal wall penetration prior to pneumoperitoneal

insufflation and trocar entry(Schaller et a1.,1995). Endoscopically-controlled trocar

insertion can also be achieved using a variety of other techniques, a selection of which

have been reviewed by Melzer(Melzer et al., 1995), including the "windo'wed trocar", the "optical trocar", the "Visiport", arrd the "optical scalpel". An additional measure of

safety may be introduced to visually-guided endoscopic access by the use of suction to

-12- anchor the peritoneum to the trocar, thereby preventing tenting and minimizing the depth of penetration of the needle(Klemm and Salm, 1995).

Disposable trocars have a reputed safety advantage whereby a shield mechanism protects the trocar point from damaging intra-abdominal organs. However the use of shielded trocars does not completely eliminate the risk of visceral injury, and the importance of the safety shield may be over-rated. First, the safety advantage of trocar shields is proportional to the brevity of the interval between entry into the abdomen and engagement of the shield(Oshinsky and Smith, 1992).If this interval is prolonged, for example by excess penetration force or inadequate pneumoperitoneum, the trocar tip will no longer be protected. Second, it may lull the unwary into a false sense of security(Nathanson, 1995), which is perhaps the reason some surgeons report a paradoxically lower rate of injury using trocars without a safety shield(Voyles et al.,

1992). Less tangible safety benefits have been attributed to the use of disposable trocars, deriving from the guarantee that previously unused instruments are always sharp, and can be utilised with greater precision in the knowledge that less force is required to divide tissue. For example, one study has reported that disposable trocars can be introduced with approximately half as much force (7.14 lb. or approximately 32

N) than is required for a similar reusable device (14.55 lb. or approximately 66 N). It was suggested that the greater control imparted from a reduction in force could translate to fewer trocar-related injuries(Corson et al., 1989).

Other potential problems associated with abdominal entry include complications at the port site. Postoperative herniation at port sites has been well documented, and occurs in about 1 in 1000 cases (Crist and Gadacz,1993; Phillips et al., 1995), with or without

-13- strangulation or obstruction of the herniated viscus. Fascial closure of the umbilical wound and all port sites lOmm or larger is now widely practiced in an attempt to reduce the incidence of hernia formation. Use of cutting trocars may predispose to hernia formation because of the capacious gap they create in transit through the abdominal muscle layers by comparison with conical trocars.

Port sites may also become contaminated with micro-organisms or malignant cells.

'Wound infection at port sites is reported with an incidence of 0.l2Yo following laparoscopic herniorrhaphy(Phillips et al., 1995),1% following laparoscopic cholecystectomy and up to 3Yo following laparoscopic appendicectomy(Crist and

Gadacz,1993). As one would expect, these figures suggest that extraction of contaminated specimens is more likely to precipitate wound infection than procedures in which port sites are used only for instrument access

A more vexing problem is that of putative contamination of port sites with exfoliated malignant cells following resection of intraabdominal tumours, resulting in port site metastases. It is disturbing to read reports of subcutaneous metastases following apparent curative laparoscopic resection of early stage tumours(Lauroy et a1., 1994;

Gleeson et al., 1993). This problem is of sufficient topical concern to have warranted a leading review in the British Journal of Surgery(Vy'exner and Cohen, 1995). Wexner and Cohen observe that at least 30 port site recurrences after laparoscopic operations have been reported. By summarizing existing reports, they derive a 6.30/o incidence of this complication after laparoscopic colorectal surgery for cure of malignancy. They contrast the frequency with which this problem is reported against the paucity of evidence for wound recuffence after colorectal surgery via a standard laparotomy. Only

-14- one such series is available(Hughes et al., 1983), citing al%oincidence of wound recurrence, considerably lower than the derived incidence for port site recurrence.

Although the aetiology of port site metastasis is unknown, it is associated with some unusual features. Recurrence may occur at a port site distant from where the specimen was retrieved(Wexner and Cohen,1995), recurrence is not limited to colorectal malignancy(Gleeson et al., 1993), and preferential seeding of port sites compared with the laparotomy wound has been observed when the operation has been converted to an open approach(Jacobi et al., 1994).

Problems of port site contamination with micro-organisms may be minimized by retrieving specimens in a sterile bag prior to extraction, and several commercial devices designed to facilitate this process are now available. Unfortunately, for the reasons outlined above, the same may not be true for port site contamination with malignant cells, and there is presently no known way to avoid this complication besides restricting the use of laparoscopy to the treatment of benign disease or palliative operations(Ramos et al., 1994).

-15- 2.2.2 Complications related to the presence of a tension pneumoperitoneum Complications related to the physical presence of a tension pneumoperitoneum have been amply reported in the anaesthetic and gynaecologic literature, but are less familiar to alimentary tract surgeons, perhaps because their manifestations are isolated from the site of the operative procedure. Systemic cardio-respiratory complications pursuant to carbon-dioxide pneumoperitoneum are the best known (see Section3.2.3, Effect of systemic haemodynamics on splanchnic visceral vasculature) and include alterations in venous return and cardiac output, cardiac arrythmias, reduced lung compliance and functional residual capacity, pneumothorax, and pneumomediastinum

Haemodynamic variations may also be induced by pneumoperitoneum at a loco- regional rather than systemic level, adversely affecting the viability of splanchnic viscera (see Section3.2.3, Locoregional effect of pneumoperitoneum on splanchnic visceral vasculature) and haemodynamic changes at all levels combined with haematologic alterations may accentuate the risk of thromboembolic sequelae (see

Section 3.2.6, Summary of net thromboembolic risk during laparoscopy).

Creation of a pneumoperitoneum with cold, and particularly non-humidified carbon- dioxide can result in hypothermia with its attendant problems (see Section 3.1,

Temperature regulation). Misplacement or escape of gas into real or potential spaces other than the peritoneal cavity results in surgical emphysema. This usually involves subcutaneous or preperitoneal planes, and provided it is detected and corrected tends to cause few clinical problems and resolves spontaneously. A rare but very dangerous complication of gas under pressure is the opportunity for gas embolism. This may occur directly if the insufflating needle or trocar enters a vessel, or indirectly if a large venous channel is opened. Although small amounts of CO2 are rapidly absorbed from the

-16- bloodstream and generally cause little problem(Gaff et al., 1959), entry of large amounts of gas into the circulation can cause sudden cardiovascular collapse when trapped in the right ventricle or pulmonary circulation. In addition to hypotension, the clinical scenario includes tachycardia, a "mill-wheel" murmur, widened QRS interval and increased P6CO2. Immediate treatment must consist of cessation of insufflation, complete evacuation of the pneumoperitoneum, and positioning the patient in

Trendelenburg with left lateral tilt to prevent gas migrating to the outflow tract of the right ventricle(McKernan and Champion, 1995). Artificial hyperventilation to blow-off

CO2 and aspiration of central venous gas should also be undertaken(Crist and Gadacz, tee3).

2.2.3 Complications related to insertion and manipulation of instrumentation Complications directly attributable to deficiencies in instrument durability and function include potential transmission of infection, visceral injury or leakage from malfunction, electrical inj.try from insulation failure, and thermal injury from contact with light sources. Furthermore, a legion of complications similar to those described for initial trocar entry can also arise as a result of the surgeon's insertion of the instruments rather than arising from the instrument per se

-17 - 3. GENERAL PROBLEMS OF LAPAROSCOPY

3.1 Temperature regulation 3.1.1 lntroduction Clinical hypothermia has been defined as core temperature below 36o Centigrade (C)

(Morris and Kumar,1972). Perioperative hypothermia results from the effects of anaesthesia, augmented by certain characteristics of the individual patient. General anaesthesia influences the development of intraoperative hypothermia by disturbing thermal regulatory mechanisms. This occurs in three phases(Sessler, 1993). In the first instance anesthesia reduces the thermoregulatory threshold for vasoconstriction by 2.5"

C, resulting in a core-to-peripheral redistribution of body heat(Sessler,1993). A second decrease in body temperature is a result of heat loss exceeding metabolic heat production.

Heat production decreases only minimally during anaesthesia(Stevens et al., l97I), and respiratory heat loss is relatively small(Bickler and Sessler, 1990), therefore the predominant site of heat loss is cutaneous. For example, exposure of the unclad, immobile patient to the cool theatre environment(Morris and Wilkey,1970; Morris and

Kumar, 1972 ; Clark et a1.,1954 ; Morris, l97I), evaporative water losses from surgical incisions(Morris and Kumar, 1972), evaporation of surgical skin preparation solution, and use of cold intravenous infusions or irrigating fluids(Imrie and Hall, 1991 ; Shanks et al., 1988) can all cause heat loss through the skin. Certain types of surgery, such as laparotomy, contribute to loss of heat from surgical incisions by increasing the surface area of the patient available for heat exchange(Tollofsrud et al., 1984 ; Roe, 1971)

After 3-4 hours, core temperature finally reaches a plateau. Patients that are kept relatively warrn require no active thermoregulation at this stage. If not kept warm,

-18- thermoregulatory vasoconstriction decreases cutaneous heat loss(Sessler et al., 1992), and sequesters metabolic heat to the core(Belani et al., 1993).

Patient characteristics such as age, size and associated medical conditions augment both the degree of hypothermia and also the resultant effects. For example, in elderly patients with limited cardiopulmonary reserves marked postoperative thermogenic shivering can dramatically increase oxygen consumption, risking cardiac arrythmias, failure, or myocardial infarction(Tollofsrud et al, 1984 ; Heymann, 1977).

The importance of perioperative hypothermia becomes apparent when the numerous deleterious effects it may cause are considered. Conditions such increased susceptibility to dermal infection(Sheffield et a1.,1994), induction of a hypokalaemic state(Boelhou\À/er et al., 1987 ; Laszlo et al., 1990), impaired myocardial function(Mattheussen et al., 1990), respiratory depression, negative nitrogen balance(Carli et al., 1989), thrombocytopaenia, and depletion of clotting factors(Ellis et aI.,1957) have been reported.

The net effect of these complications is reflected in the mortality rate of patients thus affected. One study reported a24%o mortality in postoperative patients who remained hypothermic after 2 hours compared with4yo of their normothermic counterparts(Slotman et al., 1985). There is a financial penalty as well, because hypothermic patients are reported to spend up to t hr longer in the Recovery

Ward(Conahan,1982).

In the past it had been assumed that the impact of laparoscopy would be to decrease the risk of heat loss by comparison with the corresponding "open" procedure. This assumption was based on the knowledge that the predominant thermal loss during

-19- surgery is from exposed surfaces. During laparotomy the open abdomen exposes a greater surface area, whereas during laparoscopy with the abdomen sealed there is less potential heat loss from convection as well as conduction and radiation. Despite the peritoneal cavity not being in contact with the ambient theatre environment, thermal loss is at least comparable during open and laparoscopic cholecystectomy(V/allasvaara,

1992), and some factors unique to laparoscopy may actually increase the risk of heat loss during this type of surgery(Ott,I99la; Monagle et al., 1993).

Laparoscopic procedures may take longer to perform than their open counterparts, predisposing the patient to greater heat losses from prolonged exposure in the anaesthetised state. In addition, during laparoscopy heat loss also occurs due to the use of CO2 gas which is insufflated into the peritoneal cavity to provide surgical access

Some laparoscopic procedures require only modest CO2 flow rates, however other advanced laparoscopic procedures such as colorectal and oesophageal operations frequently result in large gas leaks due to the use of multiple large ports of up to 33mm in diameter, insertion and removal of laparoscopic instruments, extraction of electrocautery smoke which may obscure vision, aspiration of gas by the sucker as intraperitoneal fluid is removed, and inadvertent removal of ports not fixed securely to the abdominal wall. Insufflation may therefore be required at high-flow rates to maintain adequate pneumoperitoneum over a sustained period. These factors of prolonged laparoscopic surgery, flow rate greater than 3llmin, and frequent gas extraction have previously been confirmed to result in thermal losses(Ott, l99la;

Seitzinger and Dudgeon, 1993)

The capability to perform advanced laparoscopic intra-abdominal surgery has resulted in this mode of access currently accounting for a large proportion of operative

-20 - procedures, yet controlled studies detailing the influence of laparoscopic surgery on perioperative hypothermia are scarce. The existence of this problem in a clinical practice setting, although widely recognised, is represented in the literature by a solitary retrospective analysis published in 1993(Seitzinger and Dudgeon, 1993). Seitzinger measured patients' temperatures during laparoscopic cases ranging between three and six hours, and observed an average beginning temperature of 36.1o C fell to an average of 33.3" C. Four to six hours rewarming was required in the recovery room to return the patient to a normal temperature.

Effect of warmed gas To counteract the cooling effect of CO2 some companies have provided insufflators with built-in heating elements, despite the absence of controlled evidence that laparoscopy contributes to perioperative hypothermia, or that gas warming devices are protective against it. The only study to address this issue reported that postoperative temperatures in 20 patients receiving warmed CO2 (35" -35.5" C) were within 0.lo C of pre- and intra-operative findings(Ott, 1991b). This contrasted to a control group receiving unwarmed CO2 (21" C) where a thermal loss of 0.3" C per 50L of consumed

CO2 was reported. Unfortunately, this valuable study was not randomised and different operations were performed both between and within groups. Non-commercial warming devices were used, and similar but not identical flow rates and volumes of CO2 were used. These methodological factors could have introduced errors and the conclusion that the use of physiologic temperature CO2 helps diminish thermal loss remains to be proven.

-21 - Aims The aim of this study was to determine if there is an increased risk of deleterious core temperature changes during laparoscopic insufflation. It was hypothesized:

1. That insufflation of CO2 gas contributes to hypothermia during laparoscopic surgery

if high-flow rates are required over a prolonged period of time

2. That insufflation of warmed rather than cold CO2 gas minimizes the extent of

hypothermia during laparoscopic surgery if high-flow rates are required over a

prolonged period of time.

3.1.2 Methods Ethical approval for this project was granted by the Animal Ethics Committees of The

Queen Elizabeth Hospital and the University of Adelaide. Six pigs of approximately 30 kg were studied. Each pig was anaesthetised and studied on 3 occasions, acting as its own control. The order of these studies were randomised. Each of the studies were performed one week apart to allow complete recovery of the animal from the anaesthetic.

On one occasion the animal was anaesthetised for three-hours and temperature measured without pneumoperitoneum being established. On another occasion, the animal had cold CO2 insufflated at approximately 25" C (Table l) for three-hours. The abdominal pressure was maintained at 10 mm Hg. The COr was delivered through a modified LINS-1000 insufflator (Cook Medical Technology, QLD Australia) via a l0 mm port (Ethicon Australia) inserted into the peritoneal cavity through the umbilicus.

A second, supra-umbilical 10 mm port allowed a standardised "leak" of CO2 at l0

Llmin from the peritoneal cavity by fully opening the 3 way stopcock. This was

-22- performed to simulate the repeated gas losses that are experienced clinically during some advanced laparoscopic procedures.

On the remaining occasion, the animal had warmed CO2 insufflated at approximately

30' C (Table l) for three-hours, otherwise experimental parameters remained as for the second occasion.

-23 - Table 1: Insufflating gas temperature at a flow rate of 10 L/min (manufacturers information)

Time (min) Temperature (C) with heater turned Temperature (C) with heater tumed

off on

0 24.0 25.9

I 25.0 28

2 2s.2 29

J 25.4 29.6

4 2s.4 30

5 25.5 30. r

6 2s.6 30.2

7 25.5 30

8 25.5 29.8

9 25.5 29.9 l0 25.3 29.8

Pigs were sedated using subcutaneous azaperone (Stresnil, Janssen Pharmaceutica) or ketamine, and anaesthetised with intravenous pentobarbitone sodium (Nembutal,

Boehringer Ingelheim) prior to endotracheal intubation. Anaesthesia was maintained by self-ventilation of a 1.0 - 1.5% halothanelO2mixture at 1000 ml/min through an open circuit. Core temperature was measured at 15 minute intervals by atr esophageal thermoresistor (Series 700, Yellow Springs Instrument Co., Ohio USA) displayed on a

Tele-Thermometer (Model46, Yellow Springs Instrument Co., Ohio USA) and by a

-24- second similar thermoresistor placed into the peritoneal cavity through the umbilical

1Omm port to monitor intra-peritoneal temperature

Ambient temperature was also recorded at 15 minute intervals, and the temperature of the theatre environment was maintained close to 24" C. A metallic reflective blanket was wrapped around the animal to reduce thermal loss from cutaneous exposure.

All procedures were performed under aseptic conditions, and animals received a single perioperative dose of intramuscular penicillirVstreptomycin. The animals were anaesthetised before the placement of and during removal of laparoscopic ports. As only two 1Omm diameter ports were required, postoperative analgesia was not required. As no intra-abdominal procedure was carried out, post-operative ileus did not occur, and no alteration to the animals eating pattem was observed. The one week interval between studies allowed complete recovery from the effects of anaesthesia. Before reversal of anaesthesia all ports were removed, and fascial and skin defects were closed with sutures. At the completion of the final anaesthetic, the animals were killed by an intravenous overdose of pentobarbitone.

The statistical method utilised was repeated measures analysis of variance, with grouping factors of treatment (no gas, cold gas, warmed gas) and a within factor of time. This method of analysis was the most appropriate for the described experimental situation(Ludbrook, 1994). Analysis was performed using 5V, BMDP statistical software UCLA (1991), with significance analyses performed at a probability level of

0.05.

-25 - 3.1.3 Resu/fs Using repeated measures analysis of variance, regression lines representing the predicted temperature effect over time were fitted to each of the three treatment groups.

The mean room temperature over all experiments was 23.7" C. Both intraperitoneal and oesophageal temperature were significantly affected by the duration of the experiment and the whether or not the animal received gas insufflation. It was found that the regression lines summarizing changes over time for the cold gas and warm gas treatment groups were statistically indistinguishable. Consequently, there was no signihcant temperature difference between animals that received cold or warmed gas over a 3 hour period, and these two groups can be considered to behave as one.

The intraperitoneal temperature at the commencement of anesthesia for control animals that received no gas insufflation was 37.7" C, at 3 hours a significant rise in temperature to 38o C was observed. The intraperitoneal temperature at the commencement of anesthesia for animals that had cold or warmed gas insufflated was again3T.7" C,btú fell to 36" C at 3 hours, a statistically significant difference of 1.7" C (p < 0.001). The regression line that summarized temperatures recorded by control animals (no gas) was significantly different from the pooled estimate of animals undergoing gas insufflation

O < 0.001), reaching almost 2o C after 3 hours (Figure 1).

-26 - Figure L : Intraperitoneal temperature

3B

37.5

37 o c, 36. 5

a! o CL 36 ts o 35.5 -. - No gas 35 a- cold gas --A--.uarmedgas 34.5 o Time (hours) 3

The oesophageal temperature at the commencement of anesthesia for control animals that received no gas insufflation was 36.9" C, however after 3 hours a significant rise to

37.2" C was recorded. The oesophageal temperature at the commencement of anesthesia for animals that had cold or warmed gas insufflated was again36.9o C, but fell to 36.1o

C at 3 hours, a statistically significant difference of 0.8o C (p < 0.001). There was also a significant difference between the temperatures recorded by control animals and those undergoing gas insufflation (p < 0.001), a variation of 1.17" C after 3 hours (Figure 2).

-27 - Figure 2: Oesophageal temperature

37.4

37.2

37

36.8 o o 36.6 J (! 36.4 o CL 36.2 (1, F 36

35.8 -o- Nogas #cold gas 35.6 - - Â- - .uarmed gas 35.4 o Time (hours) 3

3.1.4 Discussion Laparoscopic insufflators use high-pressure bottles as the source of CO2. In delivering gas from a bottle source to the patient, the gas pressure must be brought from a pressure in the range 1350 mm Hg (180 kPa) to 37,600 mm Hg (5000 kPa) down to a pressure of

15 mm Hg Q kPa). Associated with the change of pressure at the regulator is gas expansion. As the gas expands, it cools, and being in contact with the regulator, this cools as well. The degree of cooling is dependent on the flow rate; at high gas-flow rates the cooling will be more pronounced. In this study the temperature of the CO, as it exited the insufflator at a flow rate of l0 L/min was approximately 25" C(Table 1).

The commercial insufflator used in this study was provided with a 100V/ heating element in contact with the gas flow regulator. Application of heat at the regulator prevents cooling of the CO2 delivered to the patient. V/ith the heater element activated,

-28 - the regulator could be held at 45" C, and the temperature of the CO2 as it exited the insufÍlator at a flow rate of 10 L/min was approximately 30o C (Table 1).

The methodology of this experiment controlled for the predominant confounding factors which are known to cause intraoperative hypothermia; cutaneous heat losses from exposure to an ambient theatre environment of less than24" C, evaporative water losses from surgical incisions, and use of cold intravenous infusions or irrigating fluids.

Although inhaled gases were not warmed, the control arm of this experiment (no gas insufflation) indicates that respiratory heat losses were not a contributing factor, and this correlates with previous reports that respiratory heat losses are minimal(Bickler and

Sessler, 1990). Therefore the only factor acting to alter body temperature between the 3 arms of the experiment was the insufflation of cold or warmed gas.

Insufflation of CO2 gas at a flow rate of 10 L/min over a three-hour period resulted in a statistically significant decrease in body temperature. The magnitude of this hypothermic effect (up to 2" C) due solely to laparoscopy would exert a clinically signif,rcant impact, especially when added to the numerous other factors tending to reduce body temperature during general anaesthesia. The changes we observed concur with two previous uncontrolled studies addressing the matter of laparoscopic hypothermia in which it was reported that changes in core temperature as a result of laparoscopy can be expected to fall by only 0.3o C for each 50L of CO2 delivered(Ott, l99la; Ott, l99lb). Although it is true that an average leak of l0l/min is unlikely to be tolerated for prolonged periods in most laparoscopic operations, this exaggerated

"worse-case" scenario was chosen as the model to unmask any effect which may be potentially disguised by a more clinically modest situation. It is also perhaps trivial that

-29 - the difference between the cold and warmed gas was only 5o C, but this represents the limit of the capabilities of commercially-available insufflators. The design of the study was intended to reflect the reality faced by surgeons in current clinical operating conditions, therefore precluding the study of a potentially more useful warmed gas temperature of 40o C, for example. Yet if laparoscopic gas warmers were to heat gas to higher temperatures, this may introduce a deleterious drying effect on intra-abdominal membranes and therefore the gas would also have to be humidified. Unfortunately, this would cause condensation inside the insufflator and present an electrical safety hazard.

For the time being, the provision of humidified, physiological temperature gas is a technological problem.

It is of interest that control pigs anaesthetised for three-hours at a mean temperature of

23.7" C recorded a rise in body temperature. A positive correlation between the rate of body temperature rise and ambient room temperature has been reported in adult surgical patients under general anaethesia(Clark et al., 1954), and this phenomenon has also been shown to occur in dogs(Allen, 1986).

Our results have left one question unanswered - why was warrned gas no better, although it exited the insufflator 5o warmer than the cold gas? A simple thermodynamic calculation indicates that the heat required to raise the temperature of the CO2 gas flowing at l0 L/min from 25 to 37" C is 0.9 W, and the heat required to raise the temperature of the CO2 gas from 30 to 37" C is 0.48 W. Both of these are minuscule in comparison to the basal metabolic rate of 80 W, and would reduce body temperature by less than 0.lo over 3 hours. This confirms that the observed core temperature differences cannot be explained by the difference in gas temperature used in this study.

-30- So where did the heat go? A further thermodynamic calculation shows that the latent heat required to evaporate body water in the pig to saturate the initially dry CO2 stream of 10 L/minat37o C is l8 W. This indicates that the evaporation of body water to saturate the CO2 is a much greater source of heat requirement and the corresponding predicted temperature drop after 3 hours is 1.6o C for a 30 kg animal. V/ithin the errors of measurement, this would account for the most of the observed intraperitoneal temperature drop of 1.7o C.

In addition, a subsequent experiment prompted by these findings has shown that the temperature of the gas, which was measured at the patient outlet of the insufflator, rather than as it entered the abdomen, actually falls exponentially along the insufflator tubing until it reaches room temperature. It was observed that the gas temperature will fall roughly 63%o for every 1.5m length of insufflator tubing. Because standard insufflator tubing is 3m long, the temperature of gas entering the abdomen in the

"\¡y'arm" and "cold" cases actually differed by only 0.7" C.

In summary, the results indicate that laparoscopic gas insufflation causes a significant fall in core temperature, and the provision of warmed rather than cold gas using currently available insufflators will confer no protection against a fall in perioperative core temperature heat loss. However, it is suggested that humidification of the insufflated CO2 would largely resolve the problem of laparoscopy-induced hypothermia, but in addition, insufflator tubing should be equipped with an insulated heating wire to prevent warmed gas equilibrating with room temperature as it flows to the patient. However the provision of humidified, heated gas to minimize perioperative hypothermia is a problem which remains to be overcome. Controlled studies will be required to validate the clinical utility of future generations of insufflator apparatus,

- 31 - with monitoring of gas saturation and temperature as it exits the device and as it enters the patient's abdomen

-32- 3.2 Thromboembolism 3.2.1 lntroduction Venous thromboembolism following surgery is associated with significant morbidity and mortality(Caprini and Natonson, 1989). The magnitude of the problem in the

United States alone has been cited at 630 000 cases annually, with 200 000 deaths(Dalen and Alpert, 1975). Most pulmonary emboli arise from thromboses in the iliac and femoral veins. Such deep vein thrombosis (DVT) can be a source of considerable morbidity, even if it does not precipitate pulmonary embolism. The complications of chronic venous insufficiency, secondary varicose veins, and venous gangrene consume large amounts of health care resources for their treatment.

Epidemiological studies have reported postphlebitic syndromes in up to 2o/o of the population, and have projected that 800 000 Americans suffer from venous ulceration as a result(Caprini et al., 1988).

Vascular thromboembolism occurs following both open and laparoscopic procedures(Jamieson et al.,1994). The risk of fatal pulmonary embolism in patients over 40 years of age undergoing open general surgical procedures is 0.65%(Caprini and

Arcelus, 1994). Although the incidence of postoperative thromboembolic disease following minimally invasive procedures has not been objectively established, the risk of pulmonary embolism must not be underestimated(Mitchell and Jamieson,1994;

Caprini and Arcelus, 1994). In a review of 77,604 patients undergoing laparoscopic cholecystectomy at 4,292 American hospitals, 3 deaths were recorded as a result of pulmonary embolism and2 from ischaemic bowel, giving a 0.006 0/o incidence of fatal thromboembolic events(Deziel et al., 1993). A review of 12 000 patients undergoing this procedure has reported l0 postoperative deaths (0.08%) (Scott et al., 1992). A

-JJ- higher incidence of fatal postoperative pulmonary embolism of 0.14Yowas reported by

Dubois amongst 690 patients undergoing laparoscopic cholecystectomy(Dubois et al.,

1991). One particular series reported two clinically evident deep venous thromboses and one fatal pulmonary embolism in 78 patients undergoing laparoscopic colorectal surgery for malignant disease(Guillou et aL.,1993).

Death due to mesenteric thrombosis has been reported following uncomplicated laparoscopic Nissen fundoplication(Mitchell and Jamieson, 1994) and laparoscopic cholecystectomy(Paul et al., 1994) in otherwise healthy patients. Fatal portal vein thrombosis following straightforward laparoscopic appendicectomy in a fit young patient has also occurred (personal communication). These deaths secondary to thromboembolism occurring after routine laparoscopic surgery have raised widespread concern that some factor exacerbated by laparoscopy is acting to modify the danger to patients that would previously have been considered low risk.

It has been estimated that clinically detectable non-fatal deep venous thrombosis develops in 5Yo of patients undergoing open cholecystectomy who have not received prophylaxis(Bergqvist et a1.,1990). There have not been any prospective series objectively documenting the incidence of DVT after laparoscopic cholecystectomy, but for comparison Caprini has recorded one DVT from amongst 74 patients prospectively screened by duplex ultrasound (I.3%), after receiving graduated prophylaxis according to risk(Caprini and Arcelus, 1994).It must be acknowledged that because most thrombi remain silent, and discharge home occurs at an early stage following laparoscopic procedures, it is likely that a considerable proportion of patients manifesting thromboembolic complications are being missed.

-34- Factors contributing to thromboembolism were originally described by Virchow, and include hypercoagulability, impaired blood flow, and vessel wall abnormalities. During laparoscopic surgery, changes in one or more of these factors may contribute to an altered risk of postoperative thrombosis. These triad of factors are still considered the most important influencing the pathogenesis of thromboembolism, but the hazard is increased further in the presence ofadditional risk factors. Inherited risk factors consist of antithrombin III deficiency, protein C or protein S deficiency, and dysfibrinogenaemia. Acquired risk factors include advanced age, obesity, malignancy, past history of thromboembolism. For the risk of thromboembolism to be accurately assessed, the occurrence of any of the above predisposing factors must be recognised in each patient.

This section investigates the thromboembolic risk during laparoscopic surgery by experimental study of 2 of the 3 factors in Virchow's triad; hypercoagulability and impaired blood flow in splanchnic visceral vessels. In order to formulate an comprehensive analysis of the net risk of thromboembolic during laparoscopic surgery, this section subsequently considers the available literature dealing with the remaining elements of Virchow's triad; impaired blood flow in lower limb vessels, and vessel wall abnormalities during laparoscopy. The section is completed by suggestions for appropriate prophylaxis directed against this physiological complication of laparoscopy based on sound theoretical principles and scientific evidence.

-35- 3.2.2 Thromboembolic risk induced by hypercoagulability Introduction The risk of venous thromboembolism following surgery has been demonstrated to correlate with hypercoagulability which can be measured by a variety of tests. This is the basis for using anticoagulants for the prevention of postoperative thromboembolism.

However, a direct relationship between any single test, hypercoagulability and the incidence of thrombosis is not well established(Donaldson et al., 1990 ; V/alenga et al.,

1992).In addition, the specific process which initiates an increase in blood coagulation following surgery has not been clearly identified.

Previously published work has documented hypercoagulability following open surgery as in the past most operations were performed in this manner. A wide variety of coagulation indices have been used to investigate this effect of open surgery, such as protein C, protein S, antithrombin III, lupus-like anticoagulant(Donaldson et al., 1990), heparin-induced platelet activation(Donaldson et al., 1990), factor VIII coagulant, Von willebrand factor antigen, partial thromboplastin time(claes et al., 1992), and plasminogen activator inhibitor-l (PAI-1) (Rosenfeld et al., 1993). Hypercoagulability during the postoperative period has been documented thromboelastographically in patients who do not receive prophylactic heparinization in a controlled study of 60 patients(Martinez et al., 1988). In a study of patients undergoing cholecystectomy compared with healtþ controls, postoperative hypercoagulability could be traced in the former group by a recalcification time system to determine first fibrin formation(Lundquist and Sewdenborg, I 98 1).

Several of the above indicators remain unvalidated for routine use and are available only as specific research tools. In contrast, D-dimer assays are generally available and

-36- have been successfully used as markers for venous thrombosis following abdominal surgery. Plasma D-dimer is a measurement of crosslinked fibrin degradation products released as a result of fibrinolysis, and differs from earlier serum fibrin(ogen) degradation product assays because of improved sensitivity and specificity for the lysis of intravascular crosslinked f,rbrin(Rowbotham et al., 1992).In a study of 135 patients undergoing major abdominal surgery, D-dimer levels preoperatively and on the first postoperative day were significantly higher in the 3l patients who developed venous thrombosis (by positive venography) than in the 104 patients who did not (by negative

Ir25 fibrinogen leg scanxRowbotham et al., Igg2).Another study assessing the correlation between thrombotic tendency (as confirmed by venography) and D-dimer levels in 185 postoperative patients determined an89Yo sensitivity for the assay(Bounameaux et al., 1992).

Fibrinogen assays are also universally available and within the realm of the standard battery of haematological investigations. Fibrinogen is a soluble plasma protein involved in the fundamental reaction in blood clotting. The conversion of fibrinogen to insoluble fibrin involves the release of polypeptides from the hbrinogen molecule allowing the remaining fibrin monomer to polymerizeto form hbrin. The trend towards hypercoagulability in the postoperative period can be demonstrated by elevation of fibrinogen levels. Collins et al observed significant and predictable rises in fibrinogen levels on the third and seventh day postoperatively in two groups of patients undergoing major abdominal and major vascular surgery(Collins, Jr. et al., 1977). Other investigators studying patients undergoing major abdominal surgery(Knight et al.,

1977), and extremity vascular surgery(Rosenfeld et al., 1993) have corroborated

-Jt- elevated fibrinogen levels in the first72 hours postoperatively indicative of hypercoagulability

V/ith the increasing use of laparoscopic methods for a variety of operations, further investigation into the development of hypercoagulability and the accompanying incidence of thrombosis has become necessary. To date, only one study, published in abstract form, has addressed this matter(Caprini et al., 1991). Thirty-five consecutive patients undergoing laparoscopic cholecystectomy taking a mean operative duration of

139 minutes were studied by this group in Illinois. Blood thromboelastography (TEG), partial thromboplastin time (PTT), and prothrombin time (PT) were performed preoperatively and on the first postoperative day. A significant increase in the TEG index, and a significant reduction in the PTT were observed, suggesting that laparoscopic cholecystectomy induces significant hypercoagulability on the first postoperative day. Unfortunately this study was not controlled, and the results may therefore not be unique to laparoscopic surgery but rather reflect other factors which contribute to the well-established hypercoagulability that occurs after open surgery.

Aim The aim of this clinical study was to assess fibrinogen, cross-linked fibrin degradation products (D-dimer), prothrombin international normalised ratio (INR), activated partial thromboplastin time (APTT) and platelets, during and following both open and laparoscopic Nissen fundoplication to determine whether risk of thrombo-embolism induced by hypercoagulability is increased by laparoscopic fundoplication.

-38- Methods

Ten male and ten female patients were entered in the study. The patients' mean age \À/as

50 years (range 27 - 74 years). Seven patients underwent open Nissen fundoplication and thirteen were performed by the laparoscopic technique.

Blood samples were drawn immediately prior to induction of anaesthesia þre- induction), 15 minutes after skin incision (intraoperative), and on the first postoperative day (day 1). All samples were analysed for levels of fibrinogen, cross-linked fibrinogen degradation products (D-dimer), prothrombin international normalised ratio(INR), activated partial thromboplastin time (APTT) and platelets. D-dimer values were grouped within the following ranges: 0 - 0.25; 0.25-0.5; 0.25-0.5; 0.5-1.0; I - 2 mglL.

Data is expressed as mean + SEM and statistical differences were examined using repeated measures analysis of variance (RM ANOVA) with contrasts using SAS PC

6.04 statistical software (SAS Institute lnc, Cary, North Carolina, USA). The protocol for this study was approved by the Royal Adelaide Hospital Research Ethics

Committee.

-39- Results The results of blood coagulation indices are summarised in Table 2. Some sets of results are incomplete due to sample clotting and this has been accounted for by the statistical method used. The only coagulation marker to change significantly between the 3 time periods was fibrinogen. Fibrinogen concentration changed to a similar degree in both open and laparoscopic groups, decreasing after skin incision then increasing on day 1 to a level above pre-induction values (Figure 3). For the open group, on day 1 pre- induction and intraoperative levels were significantly different (p<0.05 and p<0.01 respectively). Likewise for the laparoscopic group, pre-induction and intraoperative results were also significantly different on day I (p<0.005 in both cases).

No differences were evident between the open and laparoscopic groups, nor between pre-induction, intraoperative and day I samples for any of the other coagulation indices.

No patient in this study developed a clinical deep vein thrombosis or pulmonary embolism.

-40- Table 2: Levels of coagulation indices in venous blood in patients undergoing open or laparoscopic abdominal surgery. OPEN LAP

Preop. Intraop. Dayl Preop. Intraop. Dayl

Fibrinogen 2.8+l-0.3(6) 2.0+l- 4.1+l- 2.7+l- 2.5+l- 3.8+/-

@fi) 0.3(7) 0.4(4) 0.2(t2) 0.2(e) 0.4(11)

D-dimer <0.2s(6) <0.2s(7) <0.2s(s) <0.2s(11) <0.2s(9) <0.2s(11)

(mg/l)

Prothrombin l.I+l- 1.2+l- I.t+l- t.t+l- t.t+l- t.t+l-

INR 0.03(6) 0.06(6) 0.04(s) 0.08(11) 0.02(10) 0.02(11)

APTT 28+l-1.2(6) 27+l- 29+l- 29+L 28+t- 28+l-

2.0(6) 1.e(s) 0.e(11) 1.1(10) 1.0(l l)

Platelets 276+l-71(3) 208(l) 293+l- 249+l- 235+l- 227+/-

47.1(4) 1e(8) 2t(6) 18.7(e)

Values are mean + SEM, except for D-dimer where the value is expressed as a median of a series of ranges. The bracketed values are the number of samples.

-4t- Figure 3: Levels of fïbrinogen in g/l for open and laparoscopic procedures.

5

4

c3 o o) o^ Open 'ËL\ € o, tL¿ Laparoscop c

1

0 pre intra dayl

Values are expressed as mean + SEM. Pre-induction (pre) and intraoperative (intra) values are significantly different from values for the first postoperative day (day 1) in both open and laparoscopic groups. No significant difference was observed between open and laparoscopic groups.

Discussion The changes in the fibrinogen levels from the pre-operative values to the higher post- operative values on Day I is the definitive hnding in this study. Of lesser importance was changes representing lower fibrinogen levels intraoperatively. The coagulation status of the patients in this study as measured by the INR, APTT and platelet count would not be expected to change unless there was some other systemic disease process present to cause this or a surgical complication. The D-dimer levels would only rise if substantial venous thrombosis had occurred and Xlinked fibrin degradation products subsequently released as a result of fibrinolysis.

-42- Although significant changes in coagulability over time were demonstrated by fibrinogen, it is important to emphasize that this measured factor is only one of many other factors potentially involved in the balance between coagulation and anticoagulation. Post-operative thrombosis may be associated with procoagulants or defects such as resistance to activated Protein C or deficiencies ofProtein S, antithrombin III and lupus-like anticoagulant. The possible importance of these other indices is relevant, as has been mentioned in the introduction. However they are frequently difficult to measure and many analyses of such indices remain unvalidated for routine use and are limited to use only as specific research tools. Furthermore, to gauge the relative importance of the plethora of interacting factors would require a study in which each factor was measured and the results subjected to a multivaúate analysis - a task of such magnitude and expense as to be unrealistic in practical terms.

For these reasons and with these provisos it is appropriate to consider the fibrinogen results in isolation as markers of variability in coagulability.

Hypercoagulability demonstrated by elevated f,rbrinogen levels after open abdominal surgery is the rule rather than the exception, and in this respect our results corroborate available literature(Collins, Jr. et al., 1977 ; Knight et al., 1977 ; Caporale et al., l9S9).

The changes in fibrinogen levels we observed also suggest intraoperative hypocoagulability during open fundoplication. Early reduction in fibrinogen concentration has been similarly reported in cardiopulmonary bypass patients within minutes of introduction of the bypass(Kern et al., 1992).

Fibrinogen alterations have not however, been used as markers for hypercoagulability or to predict risk of postoperative thrombotic complications amongst patients

-43- undergoing laparoscopic surgery. This study is the hrst to demonstrate that minimally- invasive procedures do indeed precipitate elevated postoperative fibrinogen levels, and corroborates likewise results that had been previously reported using different coagulation indices following laparoscopic cholecystectomy(Caprini et al., I99l).

Surgical stress, as measured by attenuated metabolic and acute-phase reactants, has recently been shown to be reduced in laparoscopic compared with open abdominal surgery(Jakeways et aL,1994). The rise in fibrinogen on day I in both open and laparoscopic patients in this study suggests that increase in coagulability occurs regardless of the degree of access trauma. Laparoscopic surgery may therefore not offer superior protection from the development of thrombosis. Until the incidence and relative risk of thrombotic complications after laparoscopy is definitively established, it is suggested that surgeons consider patients undergoing laparoscopic operations as of equal or possibly higher risk than their open counterparts, and institute prophylaxis appropriately.

-44- 3.2.3 Thromboembolic risk induced by impaired blood flow in splanchnic visceralvesse/s lntroduction Reports of fatal small bowel necrosis following uncomplicated laparoscopic operations on low-risk patients have suggested that insufflation of gas into a patient's abdomen to provide access for laparoscopic surgery decreases the blood flow to the small bowel and other vital intra-abdominal organs(Mitchell and Jamieson, 1994; Paul et al., 1994). The mechanism whereby pneumoperitoneum may change splanchnic visceral blood flow is not fully understood. Possible theories include some locoregional effect on visceral vascular beds, alteration in systemic haemodynamic indices, or modification of the other two factors in Virchow's triad such that thrombosis in visceral vessels is precipitated

Locoregional effect of pneumoperitoneum on splanchnic visceral vasculature An indication of the potential effect of laparoscopic insufflation on locoregional splanchnic vasculature can be gained from analyses of visceral blood flows as a result of elevated intraabdominal pressure (IAP) during the pre-laparoscopic era(Caldwell and

Ricotta, 1987 ; Diebel et al, 1992). Such studies were undertaken to determine the sequelae of intraabdominal bleeding, tense ascites, or the application of military anti- shock trousers to trauma patients. Caldwell and Ricotta studied the effect of elevated

IAP in nine anaesthetised dogs by means of an inflatable plastic bag inserted via a laparotomy(Caldwell and Ricotta,1987). End-organ flows were determined by the radioactive microsphere method. At an IAP of 20 mm Hg, there was a significant decrease in absolute blood flow to the following organs: Oesophagus, stomach, gastric mucosa, duodenum, jejunum, ileum, colon, pancreas, liver, spleen and renal cortex. In addition, at an IAP of 40 mm Hg, a significant decrease in absolute blood flow to the

-45- omentum, gallbladder, and adrenal was also seen. When absolute blood flows were adjusted for changes in cardiac output, significant falls in blood flow to omentum, oesophagus, stomach, gastric mucosa, duodenum, and jejunum were still observed at 20 mm Hg pressure. Similarly, pancreas, liver and spleen in addition showed a significant diminutions of flow at 40 mm Hg pressure. The results of this study clearly demonstrated that elevated IAP causes a marked decrease in visceral blood flow to most organs, although at the time the mechanism responsible or clinical importance remained in question. The advent of routine laparoscopic abdominal surgery has certainly provided the hitherto quested clinical importance of these discoveries. Findings of reduced renal tissue perfusion as a consequence of elevated IAP have recently been independently confirmed in a study where laser Doppler flowmetry was measured during laparoscopic insuffl ation(Chiu et al., 1994).

In1992, intraperitoneal Ringer's lactate solution was described as an alternative technique to generated graded increases in IAP. Diebel et al used this method in anaesthetised pigs to study the effect on hepatic blood flow measured by laser Doppler flowmetry(Diebel et al., 1992). They showed that with constant normal mean arterial pressure, hepatic microvascular blood flow fell significantly at 10 mm Hg, and at20 mm Hg wasTlYo of the control value. At 30 and 40 mm Hg pressure, hepatic blood flow was reduced even more. The authors fail to explain why an apparently cumbersome methodology was used despite the availability laparoscopic insufflators in this era, although presumably crystalloid solution more closely mimicked the fluid likely to be found in traumatised abdomens. The elegance of this methodology in relation to laparoscopic physiology is that reduced hepatic blood flow with elevated IAP was demonstrated on a purely mechanical basis as a consequence of increased

-46- mesenteric vascular resistance, in the absence of the confounding metabolic effects of

CO2. Although not discussed in the manuscript, this is a valuable inference.

There is concern that any locoregional effect of pneumoperitoneum on the splanchnic circulation may pose a particular risk because of the presence of two susceptible capillary beds in sequence. Berggren et al have presented evidence to suggest that a pneumoperitoneal pressure of 25 mm Hg causes the combined effect of increasing gastrointestinal vascular resistanceby 2l8o/o and hepatic portal vascular resistance by

588%(Berggren et a1.,1993), calculated with the use of invasive mesenteric pressure monitoring and ultrasound flow probes. The net effect of these changes was to reduce portal blood flow resultant from vasoconstriction of the gastrointestinal vascular bed and increased resistance to blood flow across the liver. Ishizaki et al likewise found reductions in portal venous blood flow and superior mesenteric artery blood flow measured by Doppler flow probes in dogs undergoing CO2 insufflation at a pressure of

16 mm Hg(Ishizaki et al., 1993b). Two points of interest emerge from this paper. First, these parameters did not decrease at pneumoperitoneal pressures lower than l6 mm Hg.

Secondly, hepatic artery blood flow was not decreased at any level of IAP, in contrast to the study by Diebel (Diebel et al., 1992) where increases in intraabdominal pressure tended to have a more negative impact on hepatic arterial blood flow than on portal venous flow. In a follow-up paper, the author proposed several locoregional mechanisms to account for the decrease in splanchnic blood flow due to laparoscopic insufflation(Ishizaki et al., 1993a). First, a pneumoperitoneal pressure of 16 mm Hg mechanically compresses splanchnic veins, and according to Poiseuille's Law

-47 - Pr)ra _n(Pu - O gV/ where Q: flow and r: radius, any reduction in the radius of the vessel will decrease blood flow and also increase resistance in each vascular bed. Second, humorally-mediated vasoconstriction may occur as a result of peritoneal distention and vasopressin release. Third, compression of venous outflow and subsequent elevated intravascular pressures could trigger intrinsic myogenic vasoconstriction of splanchnic vessels.

-48- Effect of systemic haemodynamics on splanchnic visceral vasculature Systemic haemodynamic changes have also been investigated in several of these studies that assessed locoregional splanchnic blood flow. Reduced organ blood flow with elevated IAP has been observed despite adjustment for changes in cardiac output(Caldwell and Ricotta, 1987), and has also been documented in the presence of constant cardiac output(Diebel et al., 1992), decreased cardiac output(Ishizaki et al.,

1993b; Ishizaki et al., 1993a), and increased cardiac output(Devitt et al., 1994 ;

Kashtan et al., 1981). Similar variability in central venous pressures have been recorded in the face of consistently reduced visceral blood flow. Reduced splanchnic flow with elevated IAP has been demonstrated in models devoid of the confounding effect of CO2 insufflation on primary cardiac mechanics(Diebel et al., 1992). These studies provide a weight of evidence to suggest that diminished local splanchnic perfusion is a predictable and reproducible event when intraabdominal pressure is raised, regardless of the mechanism used, and irrespective of the variable concurrent systemic physiological alterations encountered. On the basis of current data it would appear that impaired visceral blood flow is predominantly affected by the locoregional environment, and systemic haemodynamics play a minor role in moderated clinical situations. However, it is acknowledged that the greater diversity of conditions that may be encountered in the operating theatre as compared with controlled experimental situations may infrequently yield extreme systemic haemodynamic fluctuations with the potential to influence splanchnic blood flow more profoundly.

Because of the limited relevance of systemic haemodynamics to visceral microvasculature in the presence of pneumoperitoneum, an extensive consideration of the topic is beyond the scope of this work. The subject has been thoroughly investigated, and sçveral good reviews have been published(Schauer and Schwesinger,

-49- 1995 ; Safran and Orlando,1994). These articles indicate that in contrast to the local situation in splanchnic vasculature, elevated IAP and CO2 can be identified to contribute independent effects to systemic haemodynamics. When they act in combination, as with CO2 pneumoperitoneum, it can become very difficult to separate the individual contribution of each to the net response. Reduced cardiac output has been reported to result from the effects of hypercarbia following transperitoneal absorption of

Co2(Safran and orlando, 1994; v/illiams and Murr, 1993 ; Ho et ar., 1992). Although moderate to severe hypercarbia causes arteriolar dilatation and reduced myocardial contractility, the overall change in cardiac function is thought to be mediated by the predominantly ß-adrenergic effect of catecholamine release(Safran and Orlando, 1994).

However mild hypercarbia appears to have little impact on haemodynamic function, and moderate to severe increases in Pç62 are likely to be mitigated by the actions of the anaesthetist and artificial ventilation. Cardiac output is also usually independently reduced by elevated IAP. This results from decreased preload (decreased venous return), and increased afterload (increased systemic vascular resistance)(Mclaughlin et a1.,1995). These responses may be modified by the effect of heart rate and contractility on cardiac output, as well as other secondary factors such as the patient's positioning and volume status, and cardiac and pulmonary reserves. Obesity and the administration of different types and doses of anaesthetic agents can also modulate the haemodynamic

response(Schauer and Schwesinger, 1 995).

-50- Measurement of splanchnic visceral microcirculatory blood flow Measurement of visceral microcirculatory blood flow has been performed by a number of different methods. Current evidence suggests the radionuclide-labelled microsphere technique is particularly suited for measurement of tissue blood flow and appears to be superior to the "contact" measurements using laser Doppler or tissue implanted electrical conductance probes(Heymann et al., 1977 ; Kvietys et al., 1998). The latter method appears to indicate relative flows only. In addition, the indicator dilution techniques, which are usually reliable, are limited because only one flow measurement is possible. Using the radioisotope-labelled microsphere technique with appropriate scintillation counting, it is possible to distinguish gamma emission energies of the different nuclides such that up to l1 multiple flow measurements are possible under different conditions during the same experiment.

Microspheres were developed in the late 1960's and consist of spherical particles made from a biologically inert plastic or resin with a specific gravity slightly greater than whole blood. The microsphere technique itself is based on the assumption that if the microspheres are large enough (15 microns) they will mix with, flow with, and distribute in the same manner as blood. All except those passing through any patent arteriovenous shunts will be trapped in the tissue of interest during their first passage through the microvasculature. Assuming that following intra-cardiac administration such labelled microspheres are completely cleared from the circulation by being trapped in the capillary bed, and that they are distributed in proportion to the cardiac output, then the blood flow to any organ (ml min -l; can be calculated using the following equation:

-51 - Number of microspheres in target organ -)x f:oCtxdt

'Where Ct represents the number of microspheres in a millilitre of arterial blood at time t.

Experimentally, this type of integration can be performed by mechanically withdrawing blood at a predetermined rate from a distal point in the arterial system, thus creating an artificial organ with known blood flow, which then can be compared with that of other organ of interest.

The tissue flow (Q ) can then be calculated by determining the number of injected microspheres in the withdrawal arterial sample (ia) the number of microspheres in the tissue of interest (it) and relating these two values to the rate of withdrawal of arterial blood (Fa).

itxFa o: ia

This methodology was first described by Rudolph and Heymann(Rudolph and

Heymann, 1967) has been widely used in previous microvasculature investigations and found reliable for the measurement of blood flow in all tissues except for portal flow(Hales,1974). several excellent reviews of this methodology have been published(Hales, 1994 ; Heymann et al., 1977 ; wagner et al., 1969 ; Hales, 1974), and prominent in the field is Professor J.R.S. Hales of the University of N.S.W., formerly of the C.S.I.R.O. in Adelaide.

-52- In addition to tissue blood flow, the microsphere technique can be applied to the regional distribution of blood flow in the same organ, total cardiac output, and for measurement of total circulating blood passing through actual or potential arteriovenous anastomoses(Hales, 1973 , 1994). The technique is relatively simple, has high degree of reproducibility, and sources of error are well documented as are the appropriate

mechanisms for avoiding it(Hales,1973; Rudolph and Heymann,lg7l; Hales, 1994 ;

Buckberg et al., l97l).It is important to note that the effect of laparoscopic insufflation on splanchnic blood flow has not been assessed by this method, despite being successfully employed to assess the effect of elevated IAP on splanchnic blood flow in the pre-laparoscopic era(Caldwell and Ricotta, 19S7). Most recent laparoscopic studies have addressed the broader perspective of liver and mesenteric blood flow in preference to determining the end-organ flow within the viscera (with the exception of liver(Hashikura et al,1994) and kidney(Chiu et al., 1994)), and have used methodologically inferior "contact" measurements.

Aims An animal study was designed to address the specific question of whether there an increased risk of thrombo-embolism induced by impaired visceral blood flow during laparoscopic insufflation. The aim was to determine if there are any discernible alterations in blood flow to vital intra-abdominal organs (stomach, small and large bowel, kidneys, and liver) before and after a period of 2 hours of sustained pneumoperitoneum.

Because this study was designed to be of a pilot nature, a second aim was to elucidate whether the results supported a definitive investigation including greater numbers in the study samples, and whether methodological improvements could be incorporated.

-53- The long-term goal was to provide information to surgeons on any potential deleterious effects of prolonged pneumoperitoneum, such that conditions which may precipitate visceral ischaemia and organ dysfunction could be avoided.

The hypothesis (H1) was that a decrease in blood flows to vital visceral organs occurs during laparoscopic insufflation, and the null hypothesis (H¡) was that there is no change in organ blood flows during laparoscopic insufflation.

Methods Domestic white pigs weighing approximately 25 kgwere used as the model for this pilot study. Eleven animals were studied, the first of which was used for the purpose of familiarisation with the methodology to be used, and whose results were not included in the data analysis. The study sample proper comprised 5 experimental animals and 5 control animals, differentiated only by the presence or absence of a two hour period of laparoscopic gas insufflation. The order of conducting control and experimental studies was alternated for each pair.

Anaesthesia Animals were initially sedated using subcutaneous ketamine hydrochloride (10 mg/ml) given to effect. Anaesthesia was induced using approximately 8 mg of intravenous pentobarbitone sodium (60 mg/ml) and maintained with an inhalational oxygen/nitrous oxide mixture, administered by intermittent positive pressure ventilation with a tidal volume of 15-20 ml/kg. Small top-up doses of approximately I - 2 mg of intravenous pentobarbitone were additionally administered when necessary.

-54- Cannulation Through a left neck incision a polyetþlene catheter was placed into the internal carotid

artery and advanced into the left ventricle for injection of microspheres, and an identical catheter was placed in the internal jugular vein and advanced into the right atrium for withdrawal of blood that escaped first-pass capture in the circulation.

Peripheral arterial access was achieved through the right femoral artery for withdrawal of blood as an artificial organ, and through the left femoral artery for monitoring of intra-arterial blood pressure (IABP) and heart rate (HR). A Grass Instruments polygraph, calibrated against a sphygmomanometer, was used primarily to confirm the siting ofall cannulae by the characteristic changes in pressure transducer recordings.

The traces were subsequently used to continuously monitor IABP and HR to serve as a visual guide to the haemodynamic stability of the animal throughout the duration of the experiment.

Core temperature (CT) was measured before and after the period of insufflation by an oesophageal thermoresistor (Series 700, Yellow Springs Instrument Co., Ohio USA) displayed on a Tele-Thermometer (Model46, Yellow Springs Instrument Co., ohio

USA). Ambient room temperature (RT) was also recorded at each interval, and the temperature of the theatre environment was maintained close to 24" C.

After cannulation was complete, the animal was allowed to stabilise for 30 minutes, during which period the microspheres were prepared for injection.

-55- Preparation of microspheres

Standard sample A standard sample representing the number of radioactive counts per microsphere was generated for each experiment as follows: A dilute suspension of microspheres was prepared and placed on a hlter paper premarked with a grid pattem. The microspheres were accurately counted using a microscope and placed in a sealed tube to be counted with specimens from each experiment.

Dose of microspheres The volume of the microspheres to be injected was calculated knowing the total activity of the stock supplied, the activity per gram of the microspheres and the number of microspheres per gram. The drawn up dose in the injection chamber was counted both before and after the experiment and the resulting counts were compared with that of the accurately counted spheres in the standard sample to obtain the exact number of spheres in the injection dose. These measurements were done using an activated iodide crystal coupled to a gamma spectrometer (biogamma TH Beckman Instruments). lniection Before drawing up the injection dose, the stock supply was thoroughly mixed using a vortex mixer and the required volume of the mixture was drawn up into the container using a I ml syringe. This syringe was then replaced with one containing saline. The spheres were then kept mixed by continual agitation of the injection chamber and the infusion into the left ventricle began 15 seconds after the start of the withdrawal of the reference sample. The dose of microspheres was given over 30 seconds and the reference sample withdrawal continued for another 30 seconds after this.

-56- Baseline measurement of organ blood flows Approximately 0.5 x 106 15 micron sized microspheres kg-l of body weight (suspended in l}Yo Dextran and 0.01% Tween) were then injected in the left ventricle using an injection chamber. Strontiumss and Ceriumtot lab.ll"d microspheres with specific activities in an approximate rutio of 2:1 or 3:l were used to measure baseline and post- insufflation organ blood flows respectively, with the order of administration of the differently-labelled nuclides alternated for each control/experimental pair.

It was only possible to determine cardiac output in the first two pairs of animals.

Because of the subsequent unavailability of a gamma counter that covered high KV's and high doses due to equipment failure in another Department, it was necessary for the counting of all subsequent samples to be undertaken using a particularly sensitive gamma counter. As the methodology dictated cardiac output be calculated by relating the total number of microspheres injected with the total number of microspheres in the arterial withdrawal sample, energy yields in such samples simply overwhelmed the g¿ìmma counter available.

lnsufflation Insufflation of CO2 into the abdominal cavity was established in experimental animals by means of a 5mm umbilical port using a LINS-1000 insufflator (Cook Medical

Technology, Qld) to maintain a sustained pneumoperitoneal pressure of 12 mm Hg over a period of two hours. This step was omitted for control animals, which were maintained under anaesthesia with no other intervention for this two hour period.

-57 - Post-insufflation measurement of organ blood flows After the two hour period had elapsed, blood flow estimations using the radiolabelled microsphere method were repeated. Insufflation was then stopped, and intra-peritoneal pressure was released completely.

Sacrifice and organ haruest The experiment was then immediately concluded and the animal was killed by an intravenous overdose of pentobarbitone. organ samples comprising 1.5 - 2.5 g of abdominal viscera (small bowel, large bowel, liver, and kidneys) were placed in 3 preweighed vials which conformed with the counting equipment geometry. These were sealed and reweighed, and their radioactivity determined using a Canberra multichannel analyser adjusted to cover the main energy peaks of the various tracers, with the assistance of a Maestro computer program. The blood from the femoral reference sample was also placed into preweighed tubes and reweighed (to work out the withdrawal rate) and then taken for counting of radioactivity with the other samples and standards. The right atrial (pulmonary) blood withdrawn was also measured to provide an approximation of microspheres that escaped first-pass capture in the circulation, with the assumption that bronchial blood flow did not change significantly.

The intestinal mucosal blood flow as well as the renal cortical and medullary blood flow were studied by separately counting of previously separated gut mucosa as well as medullary and cortical elements of the kidney. Multiple specimens of each organ were obtained in an attempt to reduce sampling elror, and the counts pooled for each organ before statistical analysis.

-58- Ethical implications As the animals were anaesthetised before the placement of catheters and induction of pneumoperitoneum, and killed before the completion of anaesthesia, the experiment resulted in no pain to the animals. No special housing of the animals was required preoperatively.

Approval was granted from the Radiation Safety Officer of The Queen Elizabeth

Hospital, from the Animal Ethics Committee of The Queen Elizabeth Hospital (N-15-

94), and from the Animal Ethics Committee of The University of Adelaide (M73194).

Sfafrsfica/ analysis Statistical analysis was performed using repeated measures analysis of variance, applying a between-subject factor according to group (control, or experimental animal) and a within-subject factor of time (before, or after insufflation). Analysis was performed using SPSS for Windows 6.1 statistical software (Chicago), with significance defined as a probability level of 0.05.

As the null hypothesis was applied to each variable a priori, it was considered that each variable represented an independent entity, and professional statistical advice indicated that adjustments for multiple comparisons with a control were therefore unnecessary.

Repeated measures analysis of variance analyses were repeated applying a second within-subject factor being the order in which Cerium or Strontium microspheres were injected (i.e. Cerium for before insufflation measurements and Strontium for after insufflation measurements, and vice-versa).

This study was designed to be of a pilot nature because of the time and expense incurred by using radiolabelled microsphere methodology to measure microcirculature, and

-59- ethical responsibilities to limit the number of animals to the minimum required to answer the hypothesis. However it was possible to determine the number of pigs required in each group for a subsequent definitive study of visceral blood flow using the microsphere method by a statistical calculation using the following equation (for given power against a specified difference(Armitage and Berry, 1994)):

2 n>2

Where n represents the number of experimental subjects required, and z2orepresents the standardised normal deviate with probability 2a (for 2a: 0.05, z2o:1.96). p represents

Type II error, therefore at80Yo power I - Ê : 0.2 andz2p:0.842. o represents the known standard deviation from observed results in the pilot study, and õ1 represents the specified mean difference in blood flow between control and experimental animals.

-60- Results Table 3 shows the microvascular blood flow rates in control and experimental animals

before and after insufflation. Thep values are the results of the repeated measures

analysis of variance, and indicate that for all but one organ there were no significant

differences between the before and after flows in control compared with experimental animals. The right lobe of the liver was the only organ in which a significant fall in blood flow could be detected after laparoscopic insufflation.

There were no significant inequalities in variance between control and experimental sample populations in all of the measured variables shown in Table 3.

Statistical results indicated there was a significantly lower ambient room temperature in experimental pigs at the time post-insufflation blood flows were measured (p < 0.001).

However, the magnitude of the 0.6' C difference (24.20" C compared with 23.60" C) was not considered clinically signif,rcant, and fuithermore did not influence the animals' core temperatures, which were not significantly different at the time of before and after flow measurements in control compared with experimental animals.

In the two pairs of pigs where cardiac output results were able to be incorporated in the repeated measures analysis of variance, there was no significant difference between the outputs before and after insufflation in control compared with experimental animals, with an observed power of 50%o at the 0.05 level. IABP and HR remained stable under experimental conditions in all animals. Mean blood pressure was 120196 for control animals, and 118/86 for experimental animals, and this difference was not significant.

Creation and deflation of a 12 mm Hg tension pneumoperitoneum both caused transitory elevations in systolic and diastolic blood pressure which reverted back to normal levels very quickly. No sustained blood pressure alterations were induced by

-61 - changes insufflation or desufflation, making analysis of these haemodynamic effects meaningless.

There was also no significant difference between the total number of microspheres

injected before and after insufflation in control compared with experimental animals,

and good mixing with systemic cardiac outflow was confirmed by consistent clustering of raw counts in kidney samples. The alternating order in which the two radionuclides

(Cerium or Strontium) were administered appeared to have no significant bearing on the results of before and after organ flows in control compared with experimental animals for the measured variables. Microspheres retrieved from venous withdrawal from the right atrium represent those that have escaped first-pass capture in the circulation. The number of microspheres withdrawn after f,rrst injections were on average 2.7 x l}-a of the dose, and after second injections were only 3.5 x 10-s of the dose, eliminating this potential source of error.

On the basis of observed results in this pilot study, and using the equation shown in the

Statistical analysis section of the Methods, it was determined that a minimum of 12 pigs would be required in each of the control and experimental groups for a dehnitive study of small bowel blood flow using the microsphere method. Mid-small-bowel (whole) was chosen as the key variable to provide a standard deviation (o) of l3 mls/min. A two-sided significance level (24) of 0.05 was used and a power of 80% was required against a specified mean difference (õ1) of 15 mls/min. This specified mean difference between mid-small-bowel blood flow in control and experimental pigs was chosen as it represents roughly a 50Yo reduction in total flow (see Table 3).

-62- Table 3: Mean microvascular blood flow rates (mls/min/100g tissue) for vital intra- abdominal organs before and after laparoscopic insufflation CONTROL EXPERIMENTAL VARIABLE BEFORE AFTER BEFORE AFTER p

Caecum 30.00 36.33 34.46 48.96 0.66

Ileum mucosa 36.80 63.20 30.97 30.39 0.25

Ileum whole 2t.13 41.13 24.4r 24.39 0.17

Jejunum mucosa 35.00 41.60 37.77 34.50 0.38 Jejunum whole 26.40 32.20 3r.52 35.34 0.84

Left kidney 166.00 229.80 208.1 8 247.00 0.s4

Left kidney cortex 236.80 3s3.60 217.74 272.90 0.36

Left kidney medulla 24.80 16.40 44.25 33.26 0.69

Left lobe liver 49.80 82.00 56.0s 45.7s 0.075

Mid-small-bowel 32.20 37.00 43.50 34.25 0.16 mucosa

Mid-small-bowel 23.s3 29.93 34.01 35.81 0.64 whole

Right kidney 154.60 217.60 168.00 202.64 0.s3

Right kidney cortex 220.00 324.80 207.79 269.77 0.5

Right kidney medulla 33.20 28.40 50.28 44.96 0.96 Right lobe liver 59.60 93.80 5t.54 32.42 0.046

Rectum 9.75 12.75 2r.85 20.28 0.62

Transverse colon 24.00 11.00 37.90 40.45 0.56

-63- Discussion Anecdotal reports of fatal small bowel necrosis following uncomplicated laparoscopic

operations on otherwise healthy patients have recently emerged(Mitchell and Jamieson,

1994 ; Paul et a1.,1994). There is concem that such complications may comprise part of

a spectrum of an increased thromboembolic risk posed by laparoscopic surgery, in

particular by affecting blood flow in splanchnic visceral vessels. However at present the

scientihc evidence to support such conjecture is limited to four published studies. Three

of these studies measured blood flow changes at the mesenteric level, rather than microvascular flow in the specific organs at risk(Berggren et al., 1993 ; Ishizaki et al.,

I993b; Ishizaki et al., 1993a). Diminished splanchnic perfusion at high insufflation presswes (> 16 mm Hg) appears to be a reproducible finding. The only study to assess the effect of laparoscopic insufflation at an end-organ level focused only on perfusion changes in renal tissue(Chiu et al., 1994). At moderate intraabdominal insufflation pressures (I5 - 20 mm Hg) renal cortical blood flow was approximately doubled, and renal medullary blood flow approximately halved.

The study herein contrasts with these existing works by concentrating investigation predominantly on the end-organs responsible for the published episodes of fatal intestinal ischaemia, namely the small and large bowel, and assessing respective blood flow distribution at the tissue level. Furthermore, the microsphere methodology used is well-established as a highly accurate and reproducible technique, and is superior to the

"contact" flow measurement methods (such as Doppler) employed in the few available laparoscopic studies (see Introduction - Measurement of visceral microcirculatory blood flow). The results of this study corroborate the reliability of the microsphere methodology. At the two measurement intervals, no significant differences were

-64- detected between control and experimental animals in terms of the statistical variance of

flows for each organ, the total number of microspheres injected, the order of

radionuclide injection, or the mixing ability of microspheres with the systemic

circulation. Unrelated to the microsphere technique, but also pertinent to the soundness

of the methodology used was absence of any observable difference in haemodynamic

parameters (cardiac output, IABP or HR) between study groups.

Scrutiny must also be directed towards circumstances that conspired to generate

methodological flaws, for two reasons. The scientific evidence subsequently produced

must therefore be considered conditional, and the identification of methodological problems answered the second aim of this pilot study which was to allow for improvements in a future definitive investigation.

Attempts to calculate the power of the study a priori werc rendered impossible by the absence of biological standards for porcine organ flows, with the result that when the observed po\¡/er at the 0.05 level for each measured variable was calculat ed, post hoc, it

\À/as generally below 50%. This indicated that there was only a low chance of registering signif,rcant differences between measured variables from the control and experimental populations due to inadequate sample sizes.

Furthermore, due to logistical problems it was not possible to control for changes in cardiac output in the last 3 pairs of pigs, and endeavors to perform cardiac output determinations using 7F thermodilution catheters were unfortunately also unsuccessful due to the small size of the pigs and anatomic variation from humans.

Hales has shown using microsphere techniques that if an animal's ambient environment is changed from being thermoneutral, cardiac output is redistributed while its absolute

-65- level remained unchanged(Hales, 1994).It is for this reason that the observed mismatch

in room temperature over time between control and experimental groups is of concem,

and occurred despite airconditioned operating room facilities with ambient temperatures

thermostatically controlled close to 24 C. Fortunately the magnitude of the difference

was clinically insignificant, and did not effect the animals core temperature.

The only other recognised methodological shortcoming was the potential for

intermittent intravenous pentobarbitone anaesthesia to become inadequate, and the requirement for repeated top-up doses could have made between-subject standardisation difficult. This problem was fortunately not experienced, however it is acknowledged that pentobarbitone administration by intravenous infusion would be superior.

Additionally, digital rather than analogue monitoring equipment would also have facilitated more accurate data recording.

The evidence emanating from this pilot study implies that atwo hour period of laparoscopic insufflation results in a significant decrease in blood flow to tissue in the right lobe of the liver, even at the relatively modest pneumoperitoneal pressure of 12 mm Hg. However, fuither evidence suggests that a definitive study of this nature would require at least l2 pigs in each group, assuming a clinically significant change would be represented by a 50%o reduction in pre-insufflation blood flow rates to mid-small-bowel.

Because of statistical indications that there was a high likelihood our results were confounded by Type II error, to accept the results of this pilot study that laparoscopic insufflation does not diminish blood flow to the tissues of other vital intraabdominal organs would be at the risk of falsely rejecting the hypothesis (H1). The results in Table

3 show a trend indicating that blood flow in many organs fell after the insufflation

-66- period, and with a larger study population it is possible that these changes may become

signif,rcant.

In light of all the information assimilated from this study, it is impossible to make a judgement on the validity of the hypothesis that laparoscopic insufflation may impair

visceral blood flow and contribute to thromboembolic events in the vessels of

intraabdominal organs. The weight of existing evidence (see Introduction, Impaired

blood flow in splanchnic visceral vessels) supports the theory that diminished

splanchnic perfusion is a reproducible event when IAP is raised from any cause -

laparoscopic or otherwise.

It is concluded that proof of decreased blood flow at the tissue level in the setting of laparoscopic abdominal surgery remains to be established. A definitive investigation to assimilate such evidence would be feasible using the microsphere technique, if at least

12 pigs were studied in each group. The methodology of such a project should incorporate cardiac output determinations in all animals, an experimental environment of controlled ambient temperature, maintenance anaesthesia by intravenous pentobarbitone infusion, and continuous digital data recording.

-67 - 3.2.4 Thromboembolic risk induced by impaired blood flow in lower /imb yesse/s Femoral venous stasis during laparoscopic surgery occurs as a result of several separate but cumulative mechanisms; diminished blood clearance rate from the legs by reduced

femoral venous velocity resultant from the loss of the normal calf muscle pump from immobility and neuromuscular blockade, calf dilatation during induction of general anaesthesia(Coleridge Smith et al., 1990), reverse Trendelenburg positioning(Arcelus et

a1.,1993), and the creation of a tension pneumoperitoneum(Jorgensen et al., 1994).

Operative venodilation yielding diminished capacitance has been confirmed to occur in at least two separate studies during open surgery. Coleridge-Smith studied changes in calf vein diameter using high resolution ultrasound in 62 patients undergoing a range of

General Surgical procedures(Coleridge Smith et al., 1990). Significant venous distention of between 22% - 28Yo was observed by the end of the procedure, accentuated by dependent positioning (37%) and intravenous fluid administration

(48%), as would be the case during laparoscopic operations. Their data was interpreted to show that as venous diameter increases during the operation, the ability to further increase in response to a rise in venous pressure is reduced. Venous distention during anaesthesia has been shown to occur in the upper limbs during the course of surgical procedures(Comerota et a1.,1989). Dilatation in excess of 20%o was shown to correlate with the risk of postoperative radiofibrinogen-detectable DVT. Venodilation has also

been demonstrated during laparoscopic cholecystectomy(Jorgenson et al., 1 994). Six patients were studied by Jorgenson et al using Doppler ultrasound after creation of a l2mmHg pneumoperitoneum. A significant increase in mean common femoral vein diameter of 30%o was observed.

-68- Reverse Trendeleburg positioning of 30" - 45" head up not only accentuates

intraoperative increases in venous diameter and cross-sectional area(Coleridge Smith et

a1.,1990; Arcelus et al., 1993) but also diminishes blood clearance rate from the legs

by reducing femoral venous velocity. In a study on 5 pigs undergoing laparoscopic

Nissen Fundoplication, an ultrasound flow probe applied to the femoral vein

demonstrated a reduction in femoral venous outflow during reverse Trendelenburg position for any given intraabdominal pressure(Jorgensen et al., 1994).

Reduced linear blood flow velocity from lower limb veins during open surgery has been confirmed using thermodilution probes, radioisotopic NaCl2a measurement, phlebography, and Doppler ultrasonography(Millard et al.,1993). This occurs as a result of the abolition of the soleal calf muscle pump during the immobility and muscle relaxation inherent in general anaesthesia. In the anaesthetised patient, venous return from the legs therefore depends predominantly on the pressrre gradient between the venules (12-18 mm Hg) and the right atrium (4-5 mm Hg). The introduction of an additional pressure barrier between these sites such as a15-20 mm Hg pneumoperitoneum could be expected to further reduce venous retum. This has been conf,rrmed by a number of studies assessing femoral venous pressure, peak blood velocity, venous pulsatility, and venous flow measurements.

Beebe et al examined the common femoral veins of 8 patients undergoing laparoscopic cholecystectomy using duplex ultrasound and invasive venous pressure monitoring(Beebe et al., 1993). Compared with preoperative measurements, a 14 mm

Hg pneumoperitoneum resulted in a significant increase in femoral venous pressure and a significant reduction in peak blood flow velocity, as well as reducing or eliminating

-69- pulsatility in75Yo of patients indicating partial proximal venous obstruction. These

changes were maintained during the entire period of insufflation, but were restored to

preoperative levels upon deflation. It was concluded that abdominal insufflation causes

venous stasis during laparoscopic cholecystectomy.

Millard et al studied the combination of pneumoperitoneal insufflation at 13- l5 mm Hg

and 30o reverse Trendelenburg tilt during laparoscopic cholecystectomy in 20

patients(Millard et al., 1993). They measured peak femoral blood flow velocity using

ultrasound, and also investigated the effect of intermittent pneumatic compression. A

significant 42Yo decrease in peak blood flow velocity was observed, and intermittent pneumatic compression reversed that effect, returning blood flow velocity to normal.

Jorgensen et al also studied the effects of insufflation during laparoscopic

cholecystectomy(Jorgenson et a1.,1994). They measured femoral blood flow velocity using ultrasound, however at a pneumoperitoneal pressure of 12 mm Hg. The effects of intermittent pneumatic compression and intermittent electric calf stimulators were also investigated. Their study againconfirmed that intraoperative venous stasis was significantly increased by the presence of a pneumoperitoneum, additional to any decrease resulting from general anaesthesia. Although both intermittent pneumatic compression and intermittent electric calf stimulation increased peak venous blood flow velocity during general anaesthesia, with a pneumoperitoneum in place neither device was able to retum the depressed blood flow velocity to the values recorded without a pneumoperitoneum, in contrast to the f,rndings by Millard et al(Millard et al., 1993).

The influence of a third intraoperative prophylactic modality against venous stasis; graduated compression stockings (TED, Kendall), was investigated by V/ilson et al in a

-70- randomised study of 40 patients undergoing laparoscopic cholecystectomy at

pneumoperitoneal pressures of 15 mm Hg with 20" of reverse Trendelenburg

tilt(Wilson et al., 1994). Venous occlusion plethysmography was used to monitor

venous outflow. In the 20 patients not wearing stockings, venous outflow fell in 65Yo of

patients, returning to normal once pneumoperitoneum was released. In the group

wearing stockings, these changes were abolished in90o/o of patients. The only

significant result was the observation that at mid-operation median venous outflow was

significant less in the group not wearing stockings.

These studies provide strong evidence to suggest that independent of all other risk

factors, creation of a laparoscopic pneumoperitoneum leads to an increased chance of

thromboembolism by impairing lower limb venous flow beyond that resultant from the

loss of the normal calf muscle pump during general anaesthesia. This has prompted

investigation into the most appropriate thromboprophylactic measures to meet this new challenge.

It must be stated that in all of these studies the pneumoperitoneal stimulus was not controlled for by an equivalent non-insufflated group. In the studies by Millard(Millard et al., 1993) and V/ilson(Wilson et al., 1994) it is impossible to isolate the individual contribution of the coincident pneumoperitoneum and reverse Trendelenburg tilt.

In the study by V/ilson(Wilson et al., 1994) median venous outflow during surgery was significantly better in patients wearing TED stockings that those who were not, but whether this flow benefit in the stockinged group is significantly better than pre- insufflation levels remains unresolved. Jorgensen(Jorgenson et al., 1994) has shown that intermittent electric calf stimulators do not appear to be an effective deterrent against

-71 - venous stasis during laparoscopy, and the evidence determining the benefit of

intermittent pneumatic compression is conflicting.

Furthermore blood velocity, not flow was the parameter measured in the studies

utilising ultrasound, and many vascular surgeons believe that the objectivity of venous

Doppler is compromised by the inherent interobserver variation and error, and propose

that thermodilution flow measurements should remain as the gold standard

investigation.

3.2.5 Thromboembolic risk induced by yesse/ wall abnormalities Endothelial damage during laparoscopic surgery is an unresolved issue, but it has been

suggested that venous dilatation may cause endothelial cracking that is followed by

exposure of subendothelial collagen, platelet adhesion, and activation of the coagulation

cascade(Schaub et a1.,1978; Comerota et a1.,1989). The site of endothelial damage then acts as a nidus for thrombosis formation in the veins.

3.2.6 Summary of net thromboembolic risk during laparoscopy In light of the introductory and experimental evidence presented, it is appropriate to now review the net thromboembolic risk posed by laparoscopic surgery. There is currently no definitive clinical evidence of the absolute degree of risk, but anecdotal reports of disastrous thromboembolic complications have caused great concem and awareness of the problem. Experimentally, postoperative hypercoagulability has been proven, impaired blood flow in lower limb vessels has also been proven, and impaired blood flow in visceral vessels appears likely on previous evidence in spite of the failure of the study herein to ascribe a significant to the effect of CO2 insufflation. The final element in Virchow's triad, vessel wall abnormalities, ¿ìre unproven during laparoscopic surgery, but theories of endothelial damage are plausible.

-72- In summary, laparoscopy is certainly not minimally-invasive in terms of the

development of postoperative thrombosis. In fact, laparoscopy may well negatively

influence all 3 elements of Virchow's triad, sometimes beyond that of open surgery, and

possibly result in a cumulatively greater risk for the development of venous

thromboembolism.

3.2.7 Thromoembolism prophylaxis for laparoscopy This risk can be minimized by addressing each component of Virchow's triad in turn.

Hypercoagulability can be safely prevented by unfractionated low-dose subcutaneous

heparin or low-molecular weight heparin(Collins et al., 1988 ; Lassen et a1.,1991),

whereas dextran and oral anti-coagulants are now rarely used as prophylactic measures

in General Surgical patients. Venous stasis in lower limbs can be overcome using physical methods such as graduated compression stockings (TED@, Kendall), or the sequential pneumatic compression device (Kendall). Both have been shown to be effective in significantly improving femoral venous blood flow (see Section 3.2.4

Thromboembolic risk induced by impaired blood flow in lower limb vessels). It is important to note that electrical calf stimulators have not been proven to be an effective deterrent against venous stasis during laparoscopy. Impaired blood flow in visceral vessels and venodilation are both caused by elevated IAP, and can be prevented by keeping insufflation pressures to < 16 mm Hg. The problem of elevated IAP can be completely abolished by the use of gasless laparoscopy, and this may become ultimately the safest option.

On present evidence, the recommendation is to tailor these prophylactic options according to the patient's disease and degree of risk. This is facilitated by including a risk factor assessment sheet in the preoperative workup of all laparoscopy patients. A

-73 - prototype form has been designed by Caprini, whereby patients are stratified into low,

moderate, or high risk on a number of designated criteria(Caprini and Arcelus, 1994).

For low risk patients, early ambulation is encouraged and graduated compression

stockings are reconìmended. For moderate risk patients, either conventional low-dose

heparin, or a combination of graduated compression stockings with a sequential

pneumatic compression device should be used. For high risk patients, a combination of

heparin, a sequential pneumatic compression device as well as graduated compression

stockings are recommended.

Caprini also makes the point that because laparoscopic patients get discharged early, it

is advisable that patients wear their graduated compression stockings at home for at

least four weeks(Caprini and Arcelus, 1994). Regardless of risk, all patients should have insufflation pressures kept below 16 mm Hg, and for very-high risk patients the use of gasless laparoscopy should be considered.

Gasless laparoscopy is simply the use of retractor systems that permit laparoscopic exposure without the creation of a pneumoperitoneum. Many technological devices have been invented, most of which are attached to a winch and 'Goligher'-type framework above the patient's chest.

The simplest systems use T-bar or U-shaped retractors inserted into the peritoneal cavity, usually around the falciform ligament, to provide an isolated area of lift which enhances the exposure provided by pneumoperitoneum(Gazayetli, I99l ; Kitano et al.,

1992).Insufflation pressures can therefore be kept very low in these cases. Other authors have described a technique that uses long surgical wires placed into the subcutaneous tissue of the anterior abdominal wall(Nagai et al., 1991). An Australian-

-74- developed system now offers what look like intraperitoneal coathangers to elevate the

anterior abdominal wall. However the most advanced system is the planar lift

device(Smith et al., 1993). V/ith this system an expandable fan-shaped retractor is

positioned in the peritoneal cavity via a 2 - 3 cm periumbilical incision, and attached to

an electrically-powered 'lift' fixed to the side rail of the table. In obese patients further

exposure can be provided by the use of a second retractor.

The major advantage of gasless laparoscopy is that it abolishes the requirement for

elevated IAP and by so doing diminishes the risk of thromboembolism. Other

advantages are also apparent. Because there is no need to maintain an airtight seal,

incisions or valveless ports can be used instead of conventional sealed trocars. This type

of access permits considerably more degrees of freedom for instrument

maneuverability, which is ergonomically desirable, and allows a wider range of

instruments to be used, even conventional needle-holders and the like.

The disadvantages of gasless laparoscopy are that some of these devices require additional small incisions and may potentiate more pain. Device assembly can sometimes be complicated, and the operative exposure is somewhat different to that provided by CO2 insufflation. Whereas the distention provided by pneumoperitoneum is dome-shaped, the exposure provided by a retractor is like a truncated pyramid, and is generally limited to a specific quadrant of the abdomen.

-75 - 4. DEVELOPMENT AND EVALUATION OF NEW APPLICATIONS IN

LAPAROSCOPIC GASTROINTESTINAL SURGERY

4.1 Oesophagectomy 4.1.1 lntroduction The invasiveness of conventional techniques of oesophagectomy entail a significant

morbidity and mortality rate in oesophageal cancer patients who have an increased

operative risk because of their age, depressed pulmonary function, portal hypertension,

and nutritional deficiencies(Earlam and Cunha-Melo, 19S0). Open oesophagectomy

without thoracotomy (blunt transhiatal oesophagectomy) has been advocated to reduce

the morbidity associated with an abdomino-thoracic approach to

oesophagectomy(orringer and Sloan, 1978). However, the proposed theoretical

advantages have not been demonstrated(Goldminc et al., 1993 ; Siewert et al., 1986).

Disadvantages to blunt transhiatal oesophagectomy have been reported however, and include significant intraoperative blood loss, trauma to the azygos vein, trauma to the bronchial tree, lesions of the recurrent laryngeal nerves, and cardiac arrythmias. In addition, curative resection (if feasible) is impaired because nodal dissection is impossible, and there is a significarfi (4%to 9%) conversion rate to thoracotomy because of adherence to mediastinal structures(Goldminc et al., 1993 ; Orringer, 1984).

A minimally-invasive approach to the intrathoracic oesophagus is considered to be an evolving solution by overcoming the disadvantages of blunt transhiatal oesophagectomy whilst retaining the advantages conferred by avoidance of a thoracotomy. The ability to perform radical node dissections and curative en-bloc resections under direct vision without thoracotomy is a major advantage of this technique, and could lead to improved survival(Goldminc et al., 1993 ; Akiyama et al., 19S4).

-76- Perivisceral oesoohaoectomv A spectrum of endosurgical techniques for oesophagectomy have been reported over the

last six years, however no one method has become standard(Buess, l99l ; Leahy et al.,

1990 ; Gossot et al., 1992; Buess, 1992; Dallemagne et al., 1923 ; Cuschieri, 1993).

The first published technique for minimally-invasive oesophagectomy was described in

1989 by Kipfmuller et al(Kipfmuller et al., 1989), and described as "Endoscopic

Microsurgical Dissection of the Oesophagus (EMDE)". Subsequently this procedure has

become known as "Perivisceral (Endoscopic) oesophagectomy". The oesophagus is

approached with a bulbous-tipped operating mediastinoscope inserted via a cervical

incision anterior to the left sternomastoid muscle, taking care not to damage the vagus

or recurrent laryngeal nerves. The perioesophageal tissues are exposed for dissection by

mechanical dilatation of the space in front of the instrument, and this avoids the

requirement for pneumatic dilatation of the posterior mediastinum (as would be

required for a thoracoscopic dissection).

An operating mediastinoscope was specifically-designed to enable this novel surgical technique to be performed. A rigid cold-light fiberoptic endoscope fits inside an outer

sheath which has an integrated aspiration and inigation system. The distal end of the outer sheath is bell-shaped and enlarged, and has been more recently modified to incorporate an indentation to centre the instrument over the oesophagus(Becker et al.,

1993). The top of the distal end of the outer sheath with aspiration openings is flattened to reduce the risk of damage to the membranous trachea. The outer sheath has an 8mm working channel down which can be passed instruments enabling dissection, coagulation, irrigation and aspiration. To reduce the rate of instrument changes, an 8mm continuous suction probe has been developed. The tip of the probe allows monopolar

-77 - electrocautery, and another central channel permits the passage of 5mm endoscopic

scissors. If the scissors are withdrawn slightly back into the central channel, the suction

that has been applied is allowed to take effect and aspirate any fluid in front of the probe

without a change of instruments. The internal rigid endoscope has a 10" obliquely offset

eyepiece which can be connected to a laparoscopic video camera, thereby allowing

circumferential dissection of the thoracic oesophagus under two to four times magnified

vision. This allows a close up view of the wall of the oesophagus and blood vessels

entering the oesophagus which can then be safely coagulated or clipped, and then

divided under direct vision. This is in contrast to the blunt transhiatal oesophagectomy

technique which frequently results in uncontrolled rupture of these vessels and is

associated with bleeding into the mediastinum which in many cases leads to respiratory

morbidity and mortality.

The oesopheageal dissection is carried downwards to the hiatus in a circumferential

fashion using the longitudinal muscle fibres of the oesophagus as a guide. When the

abdominal cavity is reached, a laparotomy is performed and the stomach is prepared as the neo-oesophagus (a second abdominal team can perform this concurrently if desired).

A nasogastric tube is passed up through the hiatus, grasped by forceps passed down through the operating mediastinoscope, and retracted out of the cervical incision. The cervical oesophagus is then divided by a linear stapler, after which the cranial end of the nasogastric tube is attached to distal margin of division. Traction then extracts the oesophagus downwards into the abdomen, followed by operating mediastinoscope to divide any remaining attachments. The gastric tube to be used for the oesophageal replacement is brought upward to the neck under endoscopic control, and a two layer hand-sewn cervical anastomosis completes the reconstruction. The operative technique

-78- has undergone minor revisions since initially described, and has been reported in some

detail in a recent publication(Manncke et al., I994b).

This work was initially described in an animal model. Cardiopulmonary parameters

(heart rate, arterial blood pressure and PaO2) were reported to be significantly less

depressed during and after EMDE in comparison with abdominothoracic and blunt

transhiatal oesophagectomy(Kipfmuller et al., 1990). The first report of use of this

technique in humans appeared in 1990, published by Buess and Becker from Tübingen

in Germany(Buess and Becker, 1990). The first patient was operated on in September

1989, and by May 1990 six men and one woman with Tl to T3 tumours had been

operated on. Blood loss was under 100 mls for all patients, and the operation time was

between three and four hours. No intra- or post-operative problems were reported. By

october of the same year their experience had increased to 17 unselected patients(Buess, 1991). The mean operation time in this series was 205 minutes and the mortality was 5.9o/o. Average intra-operative blood loss was less than 200 mls and the respiratory morbidity rate was low. The most recent results from the Tübingen group were documented in 1993(Becker et aI,1993). The authors had performed the procedure in 31 patients by that time. The majority of the patients had middle third tumours, and T3 lesions predominated. Mediastinal blood loss was still less than 200 mls, but mean total duration of the operation had decreased to 186 minutes, with a mean time for the mediastinoscopic procedure of 61 minutes. The conversion rate to thoracotomy was 6%io, and the post-operative mortality rate was 6.4%. The only complication attributable to the to the mediastinoscopic technique was recurrent laryngeal nerve palsy in one patient. Thirteen of the 29 surviving patients experienced

-79- minor pulmonary complications. Postoperative radiographic contrast studies showed

minor anastomotic insufficiency in 6 patients, 4 of which were subclinical.

Two subsequent studies have been published by Siewert's group in Munich describing

uncontrolled prospective series(Bumm et a1.,1993; Bumm and Siewert,l994).In their

experience with 57 patients where the perivisceral endoscopic oesophagectomy

technique was applied, a 30-day mortality rate of 5.3o/owas observed, with no fatalities

related to the perivisceral dissection. A steep learning curye for the procedure was of

some note, operation time decreasing sharply during the study period, and 3

oesophageal injuries occurring during perivisceral dissection in the initial phase(Bumm

and Siewert,1994).In a separately published study including a subset of 30 of the same

patients, perivisceral oesophagectomy was compared with transhiatal oesophagectomy

in a matched case-control study(Bumm et aI.,1993). Mortality was similar in both

groups (6.6%vs.I3.3Yo respectively), but importantly pulmonary complications were

significantly less severe in the perivisceral group. The risk of injury to the recurrent laryngeal nerve with the open technique was reportedly reduced by the perivisceral oesophagectomy technique, and in the opinion of the authors, this played an important role in postoperative pulmonary rehabilitation by preventing "silent" aspiration.

Although further evaluation of this method is required, these initial reports suggest that the perivisceral technique is associated with reduced blood loss and a more controlled dissection of the oesophagus, with especially good results achieved with small distal tumours, particularly adenocarcinomas. It is possible that a significant reduction in the pulmonary morbidity and corresponding mortality of oesophagectomy will be forthcoming.

-80- Thoracoscopic oesophagectomy Although unproven, it can reasonably be anticipated that thoracoscopic oesophageal

resection will offer similar benefits of improved postoperative respiratory function,

early discharge from the Intensive Care Unit, reduced postoperative pain, and

diminished risk to intrathoracic structures. In addition, thoracoscopic dissection has the

advantage of improved access to the lower oesophagus by comparison with perivisceral

oesophagectomy. In the event of a potential curative resection radical lymphadenectomy

may also be performed and enlarged nodes removed separately or en-bloc with the

oesophagus.

The first report of thoracoscopic oesophagectomy appeared in 1990(Leahy et al., 1990),

but all techniques have three common elements:

o A thoracoscopic oesophageal dissection,

o formation of a gastric tube as the oesophageal substitute, and

o arr o€sophagogastric anastomosis.

Thoracoscopic oesophageal dissection is a relatively straightforward procedure, and became quickly established in many groups. However, it is usually combined with an open abdominal procedure for mobilisation of the stomach. It is conceivable that some of the gains achieved by thoracoscopy may be nullified by the presence of a laparotomy incision. However laparoscopic gastric mobilisation is much more technically demanding, and reports of combined minimally-invasive oesophagogastric procedures are less frequent. Perhaps the greatest technological hurdle to the completion of a totally endosurgical oesophagectomy is the construction of a safe oesophagogastric anastomosis. When total oesophagectomy has been performed with the proximal resection margin situated in the upper third, this is not so much of a problem, as a low-

-81 - morbidity cervical incision can be employed to fashion a traditional hand-sewn

anastomosis. However, if a subtotal oesophagectomy has been undertaken, the

anastomosis is more problematic, and some form of stapled anastomosis is necessary if

open access is to be avoided. Suitable endoscopic stapling instruments making the

anastomosis practically feasible only became available in 1993 (e.g. Stealth stapler -

Ethicon Australia, North Ryde, NSW), and even then were not specifically designed for

this application and were often modified. Customised endoscopic staplers for

intrathoracic anastomosis are still not commercially available in Australia because of

the small market and lack of standardisation for this operation. Until now, no studies

have successfully demonstrated all three components (a thoracoscopic oesophageal

dissection, laparoscopic formation of a gastric tube, and a circular intrathoracic stapled

oesophagogastric anastomosis) in the same procedure.

In 1990 Leahy et al first described oesophagectomy in the pig(Leahy et al., 1990). A left thoracoscopic approach was used without insufÍlation, ambient pressure being adequate.

Four puncture access was required, and due to deficiencies in laparoscopic instruments available at the time, conventional sponge holders and retractors were required.

Although Leahy reported that the stomach could be easily mobilised from above, and a stapled side-to-side oesophagogastric anastomosis constructed after division of the diaphragm(Leahy et al., 1990), this technique has not been duplicated because of theoretical concems with staple closure of the large diaphragmatic defect created.

Experimental thoracoscopic dissection of the oesophagus in swine was next described by Gossot in 1992(Gossot et al., 1992), but no attempt was made to mobilise the stomach or construct an anastomosis. Later that year, Dallemagne et al published a case

-82- report of the first successful human oesophagectomy in an 80 year old man with a

squamous cell carcinoma of the middle third(Dallemagne et al., 1923). A thoracoscopic

dissection was combined with a laparoscopic gastroplasty and an open cervical

anastomosis. The procedure lasted nine and a half hours, and tubalisation of the

stomach required eleven cartridges of an EndoGIA stapler, and the technique appeared

awkward. Although the cost in operative time and consumables appeared dramatic, the

elderly patient made an equally dramatic postoperative recovery and was discharged on

day 9.In 1992 Peracchia et al also reported using thoracoscopic mobilisation in 10

patients with oesophageal cancer, recording no intraoperative or postoperative

complications(Peracchia et al.,l992a). No further detail was given, and it is

unfortunately impossible to judge the importance of this contribution. Lointier et al,

1993, performed a study of thoracoscopic dissection in two human cadavers to

determine the optimum operating room setup and sites for trocar placement(Lointier et

al.,l993a). The feasibility of thoracoscopic dissection that had been described in

existing reports was confirmed. They advocated the advantages of supine patient positioning for the dissection, thereby obviating the need to turn the patient for

subsequent stages of the operation, and allowing two surgical teams to operate simultaneously. Perhaps the most important contribution of this paper was to highlight the anatomical differences that limit the practical value of animal models in the development of minimally-invasive oesophagectomy. The oesophagus of the pig lies much more exposed, and the vessels are clearly visible, facilitating dissection. In contrast, the human mediastinum contains much more compactfat and connective tissue, and dissection is somewhat more difficult.

-83- Thoracoscopic oesophagectomy through a right-sided posterolateral approach was also

clinically applied by Cuschieri in five patients with the only complication being one

vocal cord palsy(Cuschieri et al., 1992). However these patients required open

synchronous abdominal and cervical procedures for mobilisation of the stomach and for

the oesophagogastric anastomosis respectively. Insertion of a flexible gastroscope was

used to facilitate the procedure, as the lighted tip aids identification of the oesophagus,

but more importantly by flexing the instrument the organ can be lifted out of the

vertebral gutter. The time taken for the thoracoscopic procedure ranged from 3 - 4

hours, and the total duration of operation from 4.5 - 7.5 hours. Remarkably,

postoperative opiate analgesia was not required after the second day, and patients were

discharged after a median of 11 days. Cuschieri makes the point in this paper that

mediastinal node dissection is much easier with thoracoscopy than with the limited view provided by the mediastinoscopic approach developed by Buess. This series was expanded to 27 consecutive patients in a subsequent paper by the same author in

1993(Cuschieri, 1993). Seven patients had to be excluded because of inoperabrlity (74% resectability rate). Thoracotomy was required in one of the remaining 20 patients because of massive aortic bleeding encountered during the separation of a large tumour from the aorta. Of the 19 successful thoracoscopic dissections there was no measurable blood loss with a median duration of 5.5 hours. There \ /as no mortality in this series,

and apart from the previously mentioned vocal cord palsy, one further patient developed a significant anastomotic leak, and three additional patients developed respiratory complications. This author made the important observation that the incidence of postoperative pulmonary complications does not appear to be reduced solely by the avoidance of thoracotomy. He concluded that thoracoscopic oesophagectomy required a

-84- considerably longer operating time, was technically demanding beyond the already

arduous open operation, and the investment in the required technology rendered it a

more expensive surgical option. At the time he was a pre-eminent world leader in this

operation, and his results and calls for the justification of this procedure in terms of

patient outcome had a significant moderating influence on global enthusiasm. This

opinion would seem to be mirrored by a Surgical Workshop published by Azagra in the

British Journal of Surgery(AzagraJ. 1993). They reported eight patients who underwent

oesophagectomy for cancer in which thoracotomy was replaced by thoracoscopy during

their standard three-stage resection. Although they reported the oesophageal dissection

to be technically easy, pulmonary complications were notable by their prominence.

Intraoperatively, intermittent pulmonary re-expansion was requested by the anaesthetic team in one patient, another developed a pulmonary infection postoperatively, and six

others showed radiological evidence of oedematous lesions on the right side resulting

from poor pulmonary re-expansion.

By this time it was becoming clearly apparent that CO2 capnothorax had significant implications for the anaesthetist, and the corresponding lung collapse was likely to be the major factor precipitating the failure to demonstrate reduced pulmonary complications following thoracoscopy. Peden and Prys-Roberts explored these physiological changes in more detail during ten thoracoscopic oesophageal dissections where the right lung was collapsed by the use of a double-lumen endotracheal tube and insuffflation of CO2 into the thoracic cavity(Peden and Prysroberts,1993). The mean period of one-lung anaesthesia lasted up to 3 hours (mean 2 hours) but the majority of the changes in physiological variables occurred within the first few minutes, coinciding with rapid insufflation of CO2 and deflation of the lung. The commonest problems were

-85- an increase in P¡CO2 requiring increased fresh gas flow and minute ventilation. A more

alarming problem was the sudden decrease in blood pressure during insufflation of CO2

whereby the systolic pressure decreased in five of the ten patients by between 15 and 35

mm Hg from a previously stable level of 90 to 120 mm Hg. cessation of co2

insufflation, and escape of the CO2 from the thorax rapidly retumed the respiratory and

haemodynamic variables to their previous level. In one patient thoracoscopy had to be

abandoned because of dangerous fluctuations in these physiological parameters.

Extensive patient monitoring was considered mandatory. The authors stated that the haemodynamic instability and hypoxia resulting from rapid or excessive insufflation of

CO2, or failure to of the lung to adequately deflate in response to compression by CO2 was likened to a tension pneumothorax. If this occurs the capnothorax should be immediately released and the patient stabilised before cautious reintroduction of slow insufflation. Postoperatively, residual pneumothorax can create problems if undetected, and can result from residual pockets of CO2 especially if the lung is not fully re-inflated, or from pneumothorax of the opposite lung caused by excessive intrathoracic pressures.

Recurrent laryngeal nerve damage was also thought to be a factor contributing to postoperative pulmonary morbidity by provoking aspiration.

Subsequent series of thoracoscopic mobilisation of the oesophagus as part of a multi- stage procedure (Collard et al., 1993), (Gossot et al., 1993) have similarly reported unfavourably high pulmonary complication rates. McAnena et al(McAnena et al., 1994) reported some degree of right lung consolidation in all nine patients in their series.

Three required bronchoscopy to assist removal of bronchial secretions, and all but one required assisted ventilation for at leastT2 hours. The authors recommended that thoracoscopic oesophagectomy not be routinely adopted until measures to overcome the

-86- postoperative respiratory problems are resolved. Intraoperative difficulties were

responsible for conversion rates to thoracotomy in the order of 15%(Collard et al.,

1993)to2ÙYo(Gossot et a1.,1993). Difficulties in exposure of the posterior mediastinum

by a right lateral thoracoscopy were reported to be contributory, and were considered to

impair the surgeon's ability to manage any untoward intraoperative injuries to

mediastinal structures.

Fortunately, an elegantly simple solution to the problems of acute capnothorax and poor

exposure of the mediastinum has been developed by Cuschieri(Cuschieri, 1994), who

had previously voiced reservations about thoracoscopic oesophagectomy. The patient is

positioned in the prone jack-knife position. This results in lateral displacement of the

scapula and excellent access to the mediastinum and the entire intrathoracic

oesophagus. As the right lung falls away form the operative field by gravity, good visualisation is achieved without the need for one-lung anaesthesia or CO2 insufflation.

The renewed enthusiasm of this prominent surgeon in the procedure was shared by many, and a consensus developed that one of the major impediments to the further development of this promising new operation had been overcome.

The laparoscopic mobilisation and tubalisation of the stomach is not a major technical obstacle to complete endosurgical oesophagectomy. Apart from the few instances in which it has been reported as part of a three-stage oesophagectomy, partial gastrectomy has been reported as an individual procedure for treatment of ulcer disease and benign or malignant neoplasms. Laparoscopic local excisions of benign or submucosal tumours have been reported on several occasions(Abercrombie et al., 1993 ;Fowler and White,

I99l ;Lttkaszcyzyk and Preletz,1992). A totally-intraabdominal laparoscopic Billroth-

-87 - II gastrectomy was performed by Goh in 1992(Goh et al., 1992). Although the

procedure required 4 hours and 17 applications of the EndoGIA stapler, the patient's

intraoperative course was uneventful, and postoperative recovery was remarkable.

Another similar case was reported by Lointier in 1993(Lointier et al., 1993b). Anvari

has recently reported a series of three laparoscopic-assisted vagotomies and distal

gastrectomies, with continuity re-established by Billroth I or II anastomoses(Anvari and

Park,1994). Operation time ranged from2 hours 35 minutes to 4 hour 40 minutes,

blood loss was minimal, and patients recovered well. A 5cm muscle-splitting incision

was used to construct the anastomosis, despite which a considerable number of

laparoscopic staplers were still required. Most authors comment that laparoscopic

gastric resections can be performed safely and within a reasonable length of time by

surgeons with experience in this area. The majority of the technical descriptions to date

probably reflect reports ofthe respective surgeons' learning curves, and considerable reductions in operating duration and consumables can be reasonably expected with

further experience.

The problematic oesophagogastric anastomosis has been addressed by two other studies concurrent to my own, and subsequently published after completion of my study(Manncke et al.,I994a; Lloyd et al., 1994). An important point of differentiation is that the stapled intrathoracic anastomotic techniques described in these animal and human studies required at least a minilaparotomy for insertion of the circular staple gun.

Manncke et al described a non-survival porcine study in which a stapled intrathoracic anastomosis was performed transgastrically in eleven animals, and transorally in a further eight(Manncke et al,l994a). Extensive modifications \¡/ere required to the available stapling devices for these techniques to be performed. In the transgastric

-88- approach the detached stapler anvil is inserted into the proximal oesophageal stump

under thoracoscopic guidance, and fixed with two PDS endoloops. The staple gun is

inserted into the abdomen via a laparotomy and then into the stomach via an

antrostomy. The hand-piece of the stapler is used to push the tubalised stomach

transhiatally into the thorax. Thereafter the stomach wall is perforated by the spike, the

two parts of the stapler are reconnected, and the anastomosis is completed. In the

transoral approach the stapler is wound open after being inserted into the oesophagus

from a cranial direction. The oesophagus is ligated in continuity with two ligatures

positioned at the side of the gun and at the anvil. The oesophagus is transected between

these ligatures, and the stapler disconnected. This allows a separate stapler spike with

an attached trailing wire to be inserted into the anvil/oesophageal specimen complex.

As the oesophageal specimen is extracted into the abdomen via alaparotomy, the anvil

and trailing wire follow. After the stomach has been prepared, the anvil is re-inserted

into the stomach via an antrostomy and fixed with a purse-string suture. By traction on the wire, the stomach can be pulled into the thorax, after which the wire is removed.

The anastomosis is then performed by reconnecting and approximating both parts of the stapler. This procedure was found to be complicated by the insufficient length and rigidity of the staplers, makingperorum insertion difficult, and this technically descriptive manuscript reported no outcome parameters. The transoral approach, although ingenious, has many steps liable to increase the chance of technical error or malfunction, and is unlikely to be practically feasible until long, flexible circular staplers become commercially available(Rossi, 1994). The transgastric approach has the fundamental limitation of requiring a laparotomy, and as a totally endosurgical procedure was not entertained, the necessity or superiority of an intrathoracic

-89- anastomosis beyond the easier and perhaps safer hand-sewn cervical anastomosis is

questionable.

Transgastric circular stapled oesophagogastric anastomosis under thoracoscopic control

has been attempted in eight patients by Lloyd et al, and was successful in five(Lloyd et

a1.,1994). A slightly simpler technique for manouevring the anvil into the.oesophageal

remnant is described, by means of a clear plastic suction tube passed perorum. This tube

is passed out of a thoracic oesophagotomy above the tumour and delivered through the

hiatus into the abdomen. Again the minimally-invasive value of the operation is

diminished by the need for a laparotomy to guide the tube outside the abdomen. This is

required to allow the stapler anvil with spike to be pushed firmly onto the tubing. By

cranial traction on the tube, the anvil is drawn back into the oesophagus. After

thoracoscopic transection of the oesophagus by a linear stapler and orthodox formation

of a gastric tube has been completed, the staple gun/stomach assembly is delivered

transhiatally to approximate the oesophageal remnant. It is stated that by pushing on the plastic tube from above, the anvil spike may be driven through the proximal

oesophageal staple line, but no details are given on how this works in practice. It would be natural to assume that the exit point of the spike would be imprecise, and that it would be difficult to deliver enough force to achieve penetration given the flexible nature of the suction tubing. Once the anvil and staple gun are re-engaged and fired, the entire assembly, with the suction tubing still attached to the anvil, is withdrawn out of the abdominal incision. Importantly, the integrity of all double-stapled anastomoses in this series v/as proven by barium swallow at day ten postoperatively. These investigators are not only the sole group to have demonstrated the practicability of a thoracoscopic circular stapled anastomosis, but have demonstrated its safety as well.

-90- Unfortunately the novelty of the suction tube technique to place the anvil may well become a liability if and when this approach is used during laparoscopic gastric mobilisation, as it unlikely this large bore tube could be successfully manouevred out of currently available laparoscopic ports. Theoretical concerns also exist about dissemination of malignant cells by the passage of intraluminal instruments prior to construction of anastomoses, which could potentially be accentuated by laparoscopy(Gertsch et al., 1992; Berends et al., 1994 ;Norgrenj and Svensson, 19g5).

To date all described stapled anastomotic techniques require a laparotomy, àtê technically complex, and would translate poorly to a laparoscopic approach. In the final analysis, as will be shown by -y results, they are unnecessary.

Aim The aim of this study was to investigate whether existing techniques of minimally- invasive oesophageal and gastric mobilization could be advanced sufficiently in combination with a thoracoscopic oesophagogastric anastomosis to allow complete endosurgical oesophagectomy to be safely performed.

-91 - 4.1.2 Methods Anaesthesia Ten 70 kg domestic pigs were used as the animal model. General anaesthesia was

induced with ketamine 10 mg/kg administered subcutaneously followed by 2%

halothane in oxygen via a face-mask. A Robert-Shaw type 42F left-sided double-lumen

endotracheal tube was introduced into the trachea via a tracheostomy and then the

endobronchial lumen, and correctly positioned by ausculatation of the chest. The

animals were paralysed using pancuronium administered intravenously 0.1 mg/kg and

ventilated using a Bird Mark 8 ventilator. Anaesthesia was maintained using 1 - 2 %

halothane in oxygen and muscle paralysis maintained with intravenous pancuronium

0.05 mg/kg/hr. Single lung ventilation with collapse of the right lung was used during

thoracoscopy. A large bore orogastric tube was used to empty the stomach before

surgery commenced.

The first two animals died during thoracoscopy. In the next eight animals arterial

saturation was continuously monitored using a pulse oximeter with a probe on the left

ear, and arterial pressure measured using a20G cannula inserted into an artery in the

left hindlimb and connected to a Deseret transducer with systolic and diastolic pressure

continuously displayed on a liquid crystal display. In these animals, four to six litres of normal saline was administered via a cannula into an ear vein during the course of surgery to minimise the cardiovascular effects of reverse Trendelenburg positioning, positive intraperitoneal pressure during laparoscopy and mediastinal pressure during thoracoscopy. In the last eight animals, there were no episodes of significant hypotension.

-92 - Operative details The surgical team consisted of the surgeon, an assistant to hold the camera & retractors,

and a second assistant to assist with retraction and to manipulate a gastroscope. A 3

stage operation was performed, commencing with a thoracoscopic dissection of the

oesophagus with the animal in the left lateral position.

Thoracoscopic oesophageal dissection Carbon dioxide was insufflated into the right thoracic cavity to a maximum pressure of

6 mmHg. A 30 degree telescopelcamerc assembly was inserted to provide a view of the

operative field through the trocar in the 9th intercostal space in the mid-axillary line. The

remaining four trocars were inserted under videoendoscopic control in the following

locations; one 1Omm trocar for the fan-shaped lung retractor was placed in the 7th

intercostal space in the mid-clavicular line, one 1Omm trocar was placed in the 7th

intercostal space in a paravertebral position , one 1Omm trocar was placed in the 5th

intercostal space in the mid-axillary line for dissection or Babcock forceps, and one

5mm trocar was inserted in the 5th intercostal space in a paravertebral position for

insertion of Endoloops. A good view of the upper and lower limits of dissection was

obtained by moving the telescopelcamera assembly between the upper and lower ports

in the mid-axillary line. A flexible oesophagoscope insertedper orLtm, as described by

Cuschieri(Cuschieri et al., 1992), assisted dissection by manipulating the position of the oesophagus with the endoscope's flexible tip. The oesophagus was initially approached in its lower third, commencing with division of the mediastinal pleura to expose the oesophagus, and dissection was then undertaken caudally to fully mobilise the oesophagus within the hiatus and divide the inferior pulmonary ligament. The oesophagus was elevated by Babcock forceps and dissected free from its posterior attachments to the aorta, which were cauterised or clipped, and divided. It was

-93 - necessary to divide both vagal trunks to achieve full mobilizationof the thoracic

oesophagus. The middle third of the oesophagus was then separated from its

attachments. Depending on the level of resection the upper third of the oesophagus was

then mobilised.

After oesophageal dissection was complete an extra-corporeally tied ligature was

snugged at the upper limit of resection in order to minimize the potential spillage of

"tumour" cells, and the oesophagus was divided just above this point, leaving an open

proximal oesophageal remnant. Subsequent laparoscopic mobilisation of the intra-

abdominal oesophagus was considerably facilitated by guiding the lighted tip of the

endoscope through the hiatus from above before concluding the thoracoscopy.

Laparoscopic gastric mobilisation The second stage was performed with the animal in the supine position and standard

abdominal laparoscopy was commenced with insufflation of carbon dioxide through the umbilicus to a maximum pressure of 12 mmHg. Five trocars were inserted into the abdominal cavity (four lOmm and one 12mm). The oesophageal hiatus was rapidly identified by the light of the endoscope. It was dissected free which then allowed the operative specimen to be pulled into the abdomen. The subsequent ability to retract the gastroesophageal junction in any direction made exposure and dissection of the stomach much easier. The gastrophrenic ligament was transected and dissection continued with ligation and division of the short gastric vessels. Following this the lesser curvature of the stomach was mobilised by dividing the vessels in the cephalad portion of the lesser omentum between clips. When suffrcient gastric mobility to enable the stomach to reach into the left hemithorax had been achieved, the left upper quadrant 10mm port was exchanged for an 18mm port through which a linear endostapler was passed to divide

-94- the oesophagus at the gastroesophageal junction. The l8 mm port was then exchanged

for a 33mm port. The specimen extraction adaptor for the 33mm Endopath port (Figure

4) was a safe and simple way to deliver the resected oesophagus intact. A longitudinal

gastrotomy was performed by elevating the pylorus between 2 Babcock forceps. The

laparoscopic circular endoluminal stapler (Stealth - Ethicon) (Figure 5) was inserted

through the 33mm port and manoeuvred into the stomach so the spike could be made to

perforate the fundus. The stapler anvil was connected to the spike using the anvil

docking instrument (Ethicon) and was wound down to hold the stomach in position. A

Babcock forcep was used to hold the gastrotomy edges apposed to avoid spillage of

gastric contents. The stapler assembly was then passed through the hiatus. The hiatus

was usually able to admit the stomach without constricting it, but was the hiatus

enlarged by anterior division if necessary.

Th oracoscop i c oe so p h ag og astric anasfomosls The final step of the operation involved construction of a circular 25 mmdiameter

stapled intrathoracic oesophagogastric anastomosis. Under direct thoracoscopic visualisation the anvil of the stapler was extended and inserted into the open proximal oesophageal remnant. This manouevre was facilitated by a modification to the anvil such that it was longer and more conical in shape (Figure 6). The anvil was then fixed in position with an Endoloop ligature (Figure 7). Excess tissue was trimmed, the device was adjusted to provide the correct degree of tension, and the staples were fired. The instrument was removed and the anastomosis and doughnuts were inspected for any break in continuity. The anastomosis was further checked to be watertight by installation of saline through the orogastric tube after gently occluding the fundus with an endoscopic bowel clamp. The gastrotomy was closed as a pyloroplasty by firing a

-95- linear endostapler transversely across the defect. The trocars were removed and the animals were then killed with pentobarbitone without reversal of anaesthesia.

All procedures on the animals were recorded on videotape to allow review of the operative performance. This allowed enors to be identified and refinements to surgical technique to be planned before the next procedure, maximising the experience gained from each animal, and ensuring progress in experimentation. Paired data was analysed by a V/illcoxon matched-pairs signed-ranks test and unpaired data by a Willcoxon analysis.

-96- Figure 4: (From left to right) 33mm cannula and trocar- specimen extraction adaptcr, ænd parÉ exchange rod (Endopath-Ethican)

-97 - Figure 5: EndosurgicaË cireular sÉaptrer (SÉealÉh-Ethican) rvith speciatlv adepied conieal anvil.

-98- Figure 6: Teflon stapler anvil modified to facilitate entry into open proximal oesophageal remnant.

-99- Figure 7: Stapler anvil lixed in proximal oesophagus by an Endoloop. Gastric anastomotíc margin is indicated by the broad arrow. Thin arrow points to the Endoloop introduced through a cannula.

-100- 4.1.3 Resu/fs Successful thoracoscopic dissection of the oesophagus was achieved in all 10 plgs.

proximal resection margin was situated in the middle third in three cases, and in the

lower third in seven cases. The median length of oesophagus resected was 8.5 cm

(range 6.5 - 13.5 cm). Bleeding was minimal in each oesophageal dissection, and no

other major complications were recorded for this stage. Extensive pleural adhesions

were divided in three animals. For each oesophageal dissection 5 trocars , I endoloop,

and one fan-shaped retractor were used. A clip applier was used twice to control arterial

branches passing directly from the aorta to the oesophagus. The median operative

duration for this stage was 49 minutes (range 30 - 110 minutes).

Laparoscopic mobilisation of the stomach was performed successfully in all but one

animal. This pig had not been adequately fasted, and the large volume of feed present in the stomach was unable to be removed laparoscopically and prevented adequate mobilization. This was the longest part of the procedure with a median duration of 60 minutes (range 60 - 135 minutes). For each gastric dissection, the following consumables were used: Three 1Omm trocars, one 12mm trocar, one 18mm trocar and one 33 mm trocar. In addition, one clip applier/divider, one Stealth device, and one linear stapler with a reloaded cartridge were required.

On one occasion after the dissection was complete, a disposable fan-retractor breached the capsule of the liver and entered an hepatic vein resulting in afatalhaemorrhage.

Bleeding complications during this stage were otherwise minimal.

In the first animal there was some spillage of gastric contents from the gastrotomy as the Stealth device was inserted.

-101 - Thoracoscopic oesophagogastric anastomosis was the quickest stage of the procedure

with a median duration of 40 minutes (range l5 - 60 minutes ). A mean of 1.4

endoloops was required. Anastomoses were situated in the middle third of the

oesophagus in three pigs, and in the lower third of the oesophagus in six pigs. An

anastomosis was not performed in the animal who died from hepatic bleeding. Seven of

the ten anastomoses \À/ere watertight. However leakage was detected on three occasions

and was repaired with intemrpted Vicryl sutures. The donuts of tissue within the stapler

were intact in eight cases. The median duration for the procedures was 171 minutes

(range 134 - 2I0 minutes ).

4.1 .4 Drscussion In the past, most methods of endosurgical oesophagectomy have relied on conventional open oesophagogastric anastomosis via a cervical incision(Buess, 1991 ; Dallemagne et

al., 1923 ; cuschieri , 1993). The only two previous studies to have attempted a minimally-invasive stapled anastomosis have required at least a minilaparotomy(Manncke et al,I994a; Lloyd et al., Lgg4),notwithstanding such additional requirements as extensively modified instrumentation and technically complicated operative manouevres. This study has developed a potential solution to the problematic stapled intrathoracic anastomosis, which is the limiting step in the completion of total endosurgical oesophagectomy. Fully laparoscopic oesophagectomy was successfully performed in six animals without the necessity for division of the diaphragm. Even in the animals where extensive pleural and peritoneal adhesions were encountered, it was possible to successfully complete the operation without conversion to open surgery.

-102- The duration of surgery was relatively short, with the median duration being a little

under three hours. The fact that the operations were performed on normal pigs without

bulky oesophageal tumours may be thought to mitigate this achievement. However if

preoperative synchronous chemoradiotherapy is administered to human subjects, the

tumour is not macroscopically apparent at the time of surgery 1n 46Vo of patients(Gill

and Jamieson,1992). With the greater precision demanded and their larger size, it is

likely that the operating time would be considerably longer in human subjects.

However, the duration of surgery for minimally-invasive oesophagectomy is likely to

compare favourably with open oesophagectomy because of the considerable time

savings achieved from the rapid ingress and egress from the operative sites. Other

factors which are likely to make the application of this technique to humans more

difficult compared to the pig include the greater f,rxity and adiposity of the human

oesophagus, the larger and more constant human azygos vein, the more substantial

greater omentum and short gastric vessels and the difficulty of directing the stapler in an

orientation which will allow insertion of the head into the proximal oesophagus.

The technical advantages of a laparoscopic gastric mobilisation over laparotomy include the excellent view of the hiatus and the ease of its dissection. Once the intra-abdominal portion of the oesophagus is mobilised it can be extracted from the thorax into the peritoneal cavity without difficulty. This provides the surgeon with the unique ability to retract on the gastroesophageal junction in any direction which considerably facilities gastric mobilisation. However this manouevre also allows the escape of insufÍlated intra-abdominal gas into the thorax under pressure, and leakage of gas may occur from the mouth if the open proximal oesophageal remnant is not sealed. As with conventional open gastric surgery, the surgeon must be a\¡/are of the position of the

-103- common bile duct during mobilisation of the distal stomach, as it is at risk should the

mobilisation be carried too far distally. It was always possible to obtain sufhcient

gastric mobility in the pig without performing a Kocher manouevre.

The circular endoluminal stapler used was an Ethicon ILS redesigned for laparoscopic

bowel anastomoses. However it was well adapted to oesophagogastric anastomosis by

virtue of the additional length provided and particularly by the degree of distal

curvature. These features are so particularly suited to intra-thoracic anastomosis that we

advocate the use of this instrument with open gastric mobilisation when orientation of

the instrument is less of a problem. The length of oesophagus resected and site of

anastomosis are constrained only by the length of the shaft, and this factor could be

corrected in future generations of the instrument. The flat anvil provided, however, was

unsuitable because it was difficult to insert into the lumen of the proximal oesophageal

remnant, and had to be inserted almost sideways. The modified Teflon conical anvil was demonstrably easier to insert, but required greater vigilance during passage through the hiatus as surrounding structures were at risk of trauma from its pointed tip.

Insertion of the circular stapler through a longitudinal gastrotomy sited at the pylorus was necessary to prevent the gastrotomy being pulled up into the chest with the proximal stomach, and had the advantage of being easily closed transversely by alinear stapler thereby conveniently accomplishing a pyloroplasty as a drainage procedure(Snyders, 1993).

It is of vital importance for the stomach to be emptied before the operation is commenced otherwise gastric mobilisation is very diffrcult, and insertion of the circular stapler may lead to a flood of gastric juice into the peritoneal cavity. A Babcock forcep

-to4- applied to the two sides of the gastrotomy beneath the stapler helps to seal any potential

leak, and allows retrograde traction to be exerted on the fundus as the stapler spike is

extended. Perforation ofthe spike through the gastroesophagealjunction had been seen

to cause the linear staple line to open in a previous trial animal. Therefore puncture of

the anterior fundus is considered safer and it also provides greater gastric length.

Oesophagogastric anastomosis performed with the circular stapler has been documented

to have a very low leakage rate (0%oto 3.5%) (Wong et al., 1987 ; Ajani et al., 1993).

The endoscopic method described is very similar to the open technique, and an

equivalent degree of safety can be expected. As with the open procedure, the surgeon

must be aware of the inherent problems with stapled oesophageal anastomoses.

Anastomotic insufficiency from insecure fixation of the proximal margin to the anvil by

the endloop, excess tension on the gastric fundus, or too much intervening tissue

between the ends to be joined will contribute to anastomotic leakage. Seven of ten of

our anastomoses were watertight, and those that leaked were able to be repaired by

laparoscopically-placed sutures. Although the doughnuts were not intact in two animals,

their respective anatomoses \À/ere watertight and they appeared intact to visual

inspection. No difhculty was encountered in constructing anastomoses of 25mm diameter in pigs, however 25mm circular stapled anastomoses in humans have been associated with postoperative stricture rates of up to 29Yo(Wong et al., 1987 ; Chassin,

ree3).

The major complications \ /ere the intraoperative deaths of three animals. As a response to the deaths of the first two pigs in our series, invasive intra-arterial pressure monitoring and pulse oximetry was undertaken and no further diffrculties were

-105- encountered. It appears great caution must be taken to prevent the hypotensive effects of

gas insufflated into the abdomen and thorax. The third animal death was a result of

traumatic laceration of a hepatic vein by a disposable fan-shaped liver retractor, caused

by unexpected movement of the animal. Videotape review revealed that if the blade of

this style of retractor is turned side-on, it can act as a knife on the structure it is

supporting. Subsequent use of an alternate retractor removed any risk of this occurring.

Total endosurgical oesophagectomy is feasible, and it is likely that a stapled

intrathoracic anastomosis can be constructed without exposing patients to risks beyond

those of the equivalent open technique. The method developed appears to be a viable

option for palliation or cure of oesophageal tumors. In the context of existing literature,

it seems likely that thoracoscopic oesophagectomy can be performed safely in the

majority of selected patients, although it should not be seen as a panacea to all the

problems that have dogged orthodox oesophagectomy for so long. Rather, the likely

benefits of reduced postoperative pain, quicker recovery time, and reduced

intraoperative blood loss should be considered in light of other requirements of the

individual patient. Thoracoscopic oesophagectomy is now a useful surgical option that

can be added to the armamentarium of treatments for oesophageal cancer. Pulmonary complications may or may not be reduced using this approach, and the merits of thoracoscopic resection must await confirmation by controlled trials.

-106- 4.2 Highly selective vagotomy 4.2.1 lntroduction

Historv of ooen vaootomv The vagus nerves were first described by Galen in about 200 AD, but it was not until

1814 that Brodie first demonstrated that vagotomy in dogs reduced gastric

secretion(Brodie, 1814). However the first human vagotomy (apparently performed by

Jaboulay in 1901) was not for peptic ulcer disease but rather to relieve abdominal pain

in a patient with tabes dorsalis(Woodward, l9S7).

It was Latarjet in 1920 who first used truncal vagotomy therapeutically on patients with

duodenal ulcers(Skandalakis et al., 1986). He recognised delayed gastric emptying and

later added a gastroenterostomy to the procedure. In spite of his success, it took another

20 years before Dragstedt's work convinced Americans that vagotomy was a viable

alternative to partial gastrectomy, which up until then had been the preferred treatment for duodenal ulcer disease(Dragstedt, 1945).

Truncal vagotomy combined with antrectomy was introduced by Farmer & Smithwick in 1952(Farmer and Smithwick,7952). The combined operation became very popular when it became apparent that peptic ulcer recurrence rate was less than 1%. The physiological success of this operation stems from the fact that the removal of the gastric antrum renders the parietal cell mass less sensitive, and since a small amount of parietal cell innervation probably persists in most patients after vagotomy, this innervation is nullified because of the diminished presence of gastrin.

Selective vagotomy was the next development, in an attempt to decrease postvagotomy diarrhoea. The hepatic and coeliacvagal divisions to the gallbladder and small intestine were spared, intemrpting only the anterior and posterior descending gastric divisions

-t07- (the nerves of Laterjet). However this operation still caused gastric stasis, and it did not

achieve widespread acceptance until Griffith & Harkins combined it with a drainage

procedure in l957(Griffith and Harkins, 1957).

In 1969 Johnston & V/ilkinson from Leeds demonstrated that it was possible to divide

only the vagal branches to the parietal cells, preserving the nerves of Latarjet and motor

innervation to the pylorus and antrum(Johnston and Wilkinson, 1969). This highly

selective vagotomy reduces acid secretion as effectively as truncal vagotomy, and is

very safe with an operative mortality rate well under IYo. The innervated antrum

provides undisturbed solid emptying, and preservation of the pylorus reduces the tendency for duodeno-gastric reflux. There is a low incidence of unwanted side-effects

such as dumping and post-vagotomy diarrhoea(Taylor, I982a). Many surgeons believe that HSV is the optimal surgical treatment for chronic duodenal ulcer refractory to medical therapy.

However, there are inherent disadvantages to HSV that have prevented it from gaining widespread acceptance. The ulcer recurrence rate tends to be higher than for truncal vagotomy and pyloroplasty(Taylor et al., 1990). There is a risk of damaging the the nerve of Latarjet which may delay gastric emptying, and a risk of ischaemic necrosis of the lesser curve which although rare, can be fatal. The operation can also be protracted and technically diffrcult. In 1978 Hill and Barker developed a technically simpler modification(Hill and Barker,1978). They combined an anterior HSV with a posterior truncal vagotomy. This operation achieved a reduction in acid output reportedly similar in magnitude to highly selective vagotomy without any increase in gastric emptying difficulties.

-108- In the early 1980's Thomas Taylor published the details of another operation as an

alternative to HSV(Taylor, 1982b). The technique denervates the parietal cell mass in a

more expedient manner without the risk of ischaemic necrosis of the lesser curve nor

damage to the the nerve of Latarjet(Taylor, 1982a). Followup studies have shown this

procedure to relatively simple, quick, and easy to perform(Taylor, 19S5). Delayed

gastric emptying has been reported in L7o/o of patients. Post-vagotomy diarrhoea has

been troublesome in only O.33%(Taylor et al., 1990). Ulcer recuffence rates have been

reported in the range of 6Yo - 8%(Taylor et al., 1990 ; Oostvogel and van Vroonhoven,

1988). By comparison with truncal vagotomy and pyloroplasty the Taylor operation has

a lower incidence of dumping and diarrhoea and achieves better overall Visick grading,

with no reported difference in ulcer recurrence rates at this stage(Taylor et al., 1990).

Comparison with HSV has shown similarly good clinical outcomes and low ulcer

recurrence rates, but HSV takes considerably longer to perform than the Taylor procedure(Oostvogel and van Vroonhoven, 1988). Sharp dissection of the seromyotomy may cause occasional mucosal perforation, and Taylor has modified the operation to include an "overlap repair" with lateral displacement to reinforce the stomach(Taylor,

1982b; Taylor, 1982a).

Gomez-Ferrer subsequently further modified the Taylor procedure, whereby the seromyotomy is performed by a linear stapler rather than sharp dissection. The stapler accomplishes simultaneous division and reanastomosis along the lesser curye of the stomach, and then a posterior truncal vagotomy is performed. Results in an open environment showed recurrent ulceration in I2Yo of patients, good reductions in postoperative basal and peak acid outputs, but residually innervated strips of mucosa on

-109- the lesser curve were observed following Endoscopic Congo Red Testing(Monis et al.,

lee3).

Development of minimal-access vagotomy In open abdominal procedures, the duration of hospitalisation and time required to

retum to normal activities are often related to the trauma of laparotomy(Neugebauer et

al., 1991). Following the introduction of laparoscopic access for abdominal surgery, it

was quickly realised that laparoscopic vagotomy might offer the same physiological

eflrcacy as established anti-ulcer procedures(Cuschieri,1992), but with the additional

benefits conferred by minimally-invasive access. The entire spectrum of open vagotomy

procedures have since been duplicated in the laparoscopic environment.

A thoracoscopic approach to the vagal trunks was popularizedby Wittmoser in the

1950's using a single-puncture technique(Schurr and Buess, 1993), but never gained

wide acceptance for the treatment of peptic ulcer disease. Since 1989, elective truncal

vagotomy for chronic duodenal ulcer has been described by Dubois using the

thoracoscopic route(Dubois, 1992), with selective simultaneous or subsequent

endoscopic balloon dilatation of the pylorus if pylorospasm is a problem. He contends that if patients with a history of diarrhoea are excluded, serious post-vagotomy diarrhoea is uncommon, and routine pyloroplasty is unnecessary. The advantages of this procedure are portrayed to be a lower rate of recurrent ulceration than HSV, and the technical simplicity and speed of the thoracoscopic operation. In a series of 21 patients all ulcers were healed after short follow-up, and minimal morbidity was encountered(Dubois, 1994).In particular no long-term gastric stasis was observed, despite two patients requiring pyloric dilatation. Larger series of this procedure have not been forthcoming, and it is now considered to be reserved for use in patients with

- 110- evidence of incomplete vagotomy, where a redo laparoscopic procedure may be

diffrcult due to scarring and adhesion formation(Branicki and Nathanson, 1994 ;

Corbelle, Jr and Corbelle, 1993). Truncal vagotomy and pyloromyotomy can also be

performed via the laparoscopic route(Pietrafitta et al., l99l ; Dubois, 1992), but this

would appear to have little advantage over the more straightforward thoracoscopic

approach.

Laparoscopic posterior truncal vagotomy and anterior seromyotomy has become a

popular procedure, as evidenced by the numerous literature reports(Voeller et al.,l99l ;

Shapiro et al., l99I ; Mouiel and Katkhouda,1992; Katkhouda and Mouiel, l99l :

Croce et al., 1994). This operation was introduced by Katkhouda and Mouiel in

1990(Katkhouda and Mouiel, l99l), and to date Katkhouda has reported the largest

experience in a series of 90 patients(Katkhouda et a1.,1994). There was no mortality or

conversions to an open procedure. Postoperatively, mild diamhoea was observed in

three patients, and mild symptomatic gastric stasis in a further three, but all settled with

conservative treatment. An ulcer recuffence rate of 4.2Yo after follow-up of 2 - 4I

months was reported, and basal and maximal acid outputs were reduced by 79Yo and

83olo respectively. These early results suggest laparoscopic posterior truncal vagotomy

and anterior seromyotomy is safe, and may produce a clinical outcome similar to that

obtained in open surgery. However this procedure is unlikely to be adopted by the many

surgeons who retain misgivings about the corresponding open operation because of the theoretical risk of leaving a strip residually innervated mucosa on the lesser curve, and who prefer HSV because of its anatomic and pathophysiological elegance.

- 111 - Laparoscopic HSV was first reported by Bailey in 1991, combined with a laparoscopic

cholecystectomy in a patient with intractable duodenal ulcer disease and symptomatic

biliary colic(Bailey et al., 1991). The tedious dissection associated with the open

procedure was reportedly made easier by videoscopic magnification. The largest

published series was conducted by Dallemagne, who reported the results of 35 patients,

25 of whom also underwent an anti-reflux procedure(Dallemagne et al., 1994). Gastric

acid studies were performed in only 12 patients, and the mean follow-up after operation

was 7.3 (range 3 - 22) months. The mean operating time was 110 (range 85 - 205)

minutes for HSV alone. There was no 30 day mortality or morbidity, and the mean

length of hospital stay was 3.6 (range 2 - 6) days. All ulcers were seen to be healed on

postoperative endoscopy, and only two patients remained symptomatic on follow-up;

one with epigastric discomfort and the other with diarrhoea. Apparent reductions in

basal and maximal acid outputs were reported but not subjected to statistical analysis.

Despite a lack of controlled data, these basic clinical results suggest that laparoscopic

HSV may be as safe and possibly as effective as the open operation, but with the

advantages of a70o/o reduction in hospital stay, and 50%o reduction in the overall recovery period. Furthermore, a cost-benefit analysis of medical therapy compared to conventional as well as laparoscopic vagotomy has reported that surgery is more cost- effective than medicine at 2 years, and safer than medicine at 4 years as a result of complications from failed medical therapy. It was suggested that the impact of laparoscopic surgery will be to widen the margin of benefit for surgery(Fletcher, 1993).

The first reported case of anterior HSV and posterior truncal vagotomy was performed by Nottle, an Australian surgeon, in July 1991(Nottle, 1991). Kum and Goh described their technique in a another case report in 1992 (Kum and Goh, 1992), and have

-rt2- subsequently reported their fuither experience in 6 patients in 1993(Kum and Goh,

1993). There is little data on which a judgement can be made on the clinical outcome,

utility, or efftcacy of this procedure however. It is currently recommended that this

procedure remain an altemative in the armamentarium of laparoscopic vagotomy

procedures, to be used dependant on the suitable configuration ofthe anterior vagus

nerve and its branches(Branicki and Nathanson, 1994).

In 1992 Hannon reported his adaptation of the Gomez-Ferrer vagotomy, describing a

technique of laparoscopic linear stapled anterior seromyotomy and posterior truncal

vagotomy used in two patients(Hannon et al., 1993). Although no clinical outcome data

is available for this operation, the authors promote the ease and speed of use it provides.

Truncal vagotomy and distal gastrectomy has been the last established anti-ulcer

procedure to make the transition to the laparoscopic environment. In 1994 Anvari and

Park(Anvari and Park, 1994) reported the cases of three patients whose vagal trunks

were divided in the abdomen by laparoscopy, followed by stapled distal gastric

resections and single-layer hand-sewn extracorporeal anastomoses via a 5-6 cm

subcostal muscle-splitting incision. Although the procedures lasted up to 4 h 40 min in duration, and required a wide array of expensive instruments, the patients were discharged on days 4,5, and 6. No follow-up or comparative outcome data were presented, mortality and morbidity were absent, and hospital stay was clearly shorter than is the general experience for the corresponding open operation.

Unfortunately this multiplicity of minimally-invasive vagotomy techniques, combined with low refer¡al rates for surgery has meant that the experience of each group has been limited to relatively small series. No long-term clinical results are available by which the efficacy of laparoscopic vagotomy can be definitively judged.

-113- Aims The aim of this study was to demonstrate the physiological validity of laparoscopic

highly selective vagotomy. Specific hypotheses tested can be summarized as follows.

l. To assess whether laparoscopic HSV is as effective in reducing the acid output of the

stomach as its open counterpart.

2. Thatthe laparoscopic HSV causes no greater disturbance of non-nutrient liquid

gastric emptying than its open counte{part.

3. That the laparoscopic HSV procedure causes no disturbance of gastro-oesophageal

competence and does not facilitate the development of acid gastro-oesophageal

reflux.

4.1.2 Methods Twenty-five kg domestic white pigs were chosen as a suitable model due to their gastro- oesophageal anatomic similarity to humans, and to allow a controlled series which would eliminate confounding variables from the analysis. Animals were treated in accordance with the Australian Code of Practice for the Care and Use of Animals for

Scientific Purposes, and ethical approval was granted by the Animal Ethics Committees of the University of Adelaide and the Institute for Medical and Veterinary Science.

Twenty-two animals were studied in 4 groups. The first group did not have any operative procedure. Because the pigs doubled in size over the 8 week study period, these pigs controlled for the effect of growth on the physiological tests that were performed at the beginning and end of the study. The second group of pigs underwent laparoscopy and mobilisation of the stomach, but did not have a vagotomy performed.

This group controlled for any effect that may be attributable to the laparoscopic environment alone. The third group of pigs underwent a traditional open HSV to act as

-rt4- controls for the operative technique under investigation, and the fourth group underwent

the experimental procedure, the laparoscopic HSV.

The study period was broken up into 3 discrete stages, a 2 week preoperative period, a

one week perioperative period, and a 5 week postoperative period. To enable gastric

access, the animals underwent insertion of a cervical oesophagostomy on week one.

Preoperative gastric physiological studies were performed on week two, and the

operative procedure was performed on week three. Animals were then housed for 5

weeks postoperatively with regular review of their clinical progress. Four weeks after

their operative procedure, the gastric physiological studies were repeated. on

completion of the tests the animals were killed, and if any complication had supervened

a post-mortem was performed.

Cervical tube oesophagostomy Operations were performed after a 12hour fast. General anaesthesia was induced with ketamine 10 mg/kg (10Omg/ml) administered subcutaneously followed by 2%halothane in oxygen via a face-mask. An endotracheal tube was introduced into the trachea per orum, and correctly positioned by auscultation of the chest. The animals were ventilated using a Bird Mark 8 ventilator. Anaesthesia was maintained using I - 2 % halothane in oxygen. A large bore orogastric tube was used to localise the oesophagus.

Animals received 2.5-3.0 mls (250mglml) of penstrep preoperatively and on days I to 3 postoperatively in a single intramuscular dose. The neck was shaved immediately preoperatively, cleaned with chlorhexidine and prepared with aqueous Betadine.

Using full aseptic technique a transverse incision was made in the left hand side of the neck just below the cricoid cartilage. Using a combination of sharp and blunt dissection

- 115 - the oesophagus was exposed, aided by palpation of the orogastric tube. using coagulation diathermy a2 mm hole was made into the lumen of the oesophagus, and gently stretched open. 2/0 Surgipro (USSC) running pursestring suture maintained approximation of the mucosa to the muscular wall of the oesophagus.

A t-tube plastic oesphagostomy was placed into the lumen (Figure 8), and the pursestring suture tightened and tied. The oesophagostomy was brought out onto the skin through a separate caudal stab incision. The skin was closed with 3/0 nylon.

Postoperatively animals received water only on the first day, milk only on the second day, after which a soft diet was gradually re-introduced. Analgesia was achieved by use of finadyne (flunixin meglumine - Herriet Agvet) 2mlsl45kg. Pigs were thereafter able to maintain normal nutrition and body weight.

-116- Figure 8: Plastic t-tube oesophagostomy

-rr7 - Gastric acid output studies The pigs were allowed one week to recover from oesophagostomy insertion before the

preoperative baseline physiological tests were commenced. Gastric acid output

measurements were made after a 12 hour fast. Pigs were trained to stand quietly in a

metabolic crate while the position of the lower oesophageal sphincter was determined

by pull-through manometry. A 14 F Ryle's tube was then able to be accurately placed in

the stomach through the oesophagostomy. The length of the orogastric tube was

measured and a mark was made at the level of the lower oesophageal sphincter. Correct

positioning of the tip of the tube in the stomach was confirmed by a water-recovery test

(Hassan and Hobsley,1970) i.e. aspiration was attempted, and if unsuccessful the

position of the tube was readjusted until some aspirate was obtained. Twenty ml of

water was then instilled through the tube and aspiration attempted. If 16-20 ml of water

was recovered the tube was said to have passed the water-recovery test and the tip was

assumed to be in the stomach). The tube was then withdrav¡n2.5 cm at a time, the

water-recovery test being repeated. The tube was fixed in the shortest possible position

at which it passed the water-recovery test. Low intermittent suction was applied to the

tube to empty any resting juice and air. If any residual debris was detected the stomach

was lavaged with isotonic saline until the return was clear.

Gastric juice was collected under resting conditions by four 15 minute aspirates. Basal

secretion is used conventionally to describe the fasting gastric secretion. It represents the secretion of the parietal cell mass being excited under the resting conditions of the test. Transpyloric loss of secreted acid was assumed to be minimal because of continuous suction. Polyethylene glycol was not used as an indicator of gastric emptying, to maintain parity with the majority of described methods in the literature,

- 118 - and because of previously documented minimal transpyloric loss of this marker during

acid secretery studies(Hunter et al., 1989). Secretion during the first half hour of a basal

hour's collection is greater than in the second half hour, presumably due to the

stimulatory effect of swallowing the nasogastric tube, so only the second half hour

results were used, and these have been reported to show good

reproducibility(Hallenbeck et al., 197 6).

To elicit the peak acid output of the stomach, parietal cells were artifrcially stimulated

by intramuscular pentagastrin (Peptavlon ICI, 6 ¡tglkg). The drug was allowed to take

effect for 15 minutes, then four fifteen minutely specimens of gastric juices were again

collected by aspiration for one hour under maximally-stimulated conditions. The

samples were immediately filtered through gaulze into specimen containers. Peak acid

output (mmol/hr) was dehned as the sum of the 2 highest consecutive 15 minute

samples multiplied by 2.Inthis study, maximal acid output (defined as highest

observed acid output), or maximum acid output (MAO, defined as the output in the

whole hour after a stimulant) are not reported. For each 15 minute specimen the volume

(ml), pH and titratable acidity (mlWL) were measured:

. pH was measured using a pH meter.

o Titratable acidity was the number of mmol of 0.lN NaOH(Lavigne et a1.,1979)

added per litre of stomach content needed to raise the pH to 7.O(Baron, 1978).

. Acid output (mmol) was calculated as volume (mL) x titratable acidity (mmol/L).

- 119- Gastric emotvinq studies Gastric emptying studies were performed on a separate occasion. The pigs were fasted,

and a l4 F tube was placed in the stomach through the oesophagostomy with the

animals awake and upright. Correct positioning of the tip of the tube in the stomach was

confirmed by a recovery test(Hassan and Hobsley, 1970). Low intermittent suction was

applied to the tube to empty any residual debris and the stomach lavaged with isotonic

saline until the return was clear. Mixing was performed by aspirating and re-injecting

the stomach contents with a 50 mL syringe for one minute, with a pumping action

performed at least 12 times.

The analytic method used was based on the double sampling technique of

George(George, 1968), extended with Beckers calculation procedure to correct for

gastric secretion and net test meal outflow(Beckers et al., 1988). This method shows a

high degree of correlation with Hunt's chloride technique(Hunt, 1974), which is used

for estimating gastric secretion. Non-nutrient isotonic test meals were used because hyperosmolar and nutrient liquids can slow gastric emptying by feedback from

duodenal osmoreceptors(V/ilbur and Kelly,1973). Solid emptying was not addressed because proximal gastric vagotomy is associated with near noÍnal levels of solid emptying(Lavigne et al., 1979).

Samples of the dilute test meal and concentrated dye solutions were taken for quantitative analysis. Liquid test meals consisting of 600m1 of isotonic saline containing

15 mglL of phenol red (20 mls of concentrated solution + 670 mls distilled water) was administered through the tube, mixed with gastric contents, and an initial sample immediately taken. High volume liquid test meals were used because larger volumes provide more reproducible results by avoiding the small individual differences in

-t20- emptying associated with recovery of small volumes(Gleysteen et al., 1976). 5 ml

samples were taken at2,5,10, 15, 20,30, and 40 minutes. on each occasion a sample

was taken, l0 ml of dye (500 mgll-) was added and mixed, and then a second 5 ml

sample was taken. To obtain the phenol red concentration an aliquot of every sample

was diluted 20-fold with a 0.25-0.5mol/L concentration NaOH/lr{aHCO3 buffer, and

measured on a spectrophotometer at 560 nm(Schedl,1966).

where:

Vsnb : volume of gastric contents before adding dye (ml)

Vtrru : volume of gastric contents after adding dye (ml)

Vir, : volume of dye added (ml)

Vtn : volume of test meal (ml)

CSnb : dye concentration in gastric contents before adding dye (mglml)

Ctrru : dye concentration in gastric contents after adding dye (mglml)

Cir, : dye concentration in volume of added dye (mg/ml)

Anb : amount of dye in gastric contents before adding dye (mg)

: Vsnb x Csnb

Ana : amount of dye in gastric contents before adding dye (mg)

: VSna x CSna

-t2t- calculation of gastric volume: calculation of test meal volume:

, Ct" - Ct* Anu Ain-r¡r Aro VSnb: Vln x Vt, X x vtl Çsm - Çs"r A1n_r¡u A1n-z¡u Ato

By measuring the phenol red concentration of every sample the test meal volumes at

each time point could be calculated, and gastric emptying could then be derived by the

change in test meal volume.

Assessment of gastro-oesophageal reflux Oesophageal reflux was measured using static 8 hour ambulatory pH monitoring; longer recording periods were not practically feasible. The lower oesophageal high pressure zone was first localised by pull-through manometry. The pH probe (Monocrystant) was then positioned 5cm proximal to this level, and pH recorded for 8 hours using a datalogger (Digitrapper Mk II, Synectics Medical, Sweden). The pigs were partially restrained in a metabolic crate throughout the study but were allowed to feed normally.

The pH data was analysed using Esophagram software (Synectics Medical, Sweden), and a reflux score was derived representing the percentage of time that pH was below

4.O(Heij et al., l99l).

-122- Operative procedures On week 3 the operative procedures were performed, excepting the control group which

had no surgery. General anaesthesia was induced by animal house staff using

subcutaneous ketamine and inhalational halothane. Open HSV was performed by the

well-established technique(Goligher J.C. 1974) under supervision by a specialist upper

gastrointestinal surgeon.

The laparoscopic HSV was performed with a zero degree telescope inserted via a lQmm

umbilical cannula. Two additional 10mm working ports were inserted just above the

umbilicus in paramedian positions. A 5mm trocar was placed in the right subcostal

region to retract the liver, and a left flank trocar was used to apply tension to the

stomach. The avascular portion of the lesser omentum was divided to gain access to the

oesophageal hiatus. The peritoneum overlying the right crus and oesophagus was

dissected, allowing both vagal trunks to be identified. The anterior and posterior leaves

of the lesser omentum were then serially separated from the lesser curve of the stomach

to the left of the crow's foot in a manner similar to the open procedure. The

neurovascular structures were diathermied, or clipped and divided if sufficiently large.

The lowermost 5-7cm of oesophagus was then bared of any remaining nerve fibers

running onto the stomach. During laparoscopic HSV, an Endoscopic Congo Red Test was used to show total denervation of the parietal cell mass(Donahue et al., 1987). An

endoscope was prepared by securing a I4F or l6F nasogastric tube by means of 3 rubber bands placed 5 cm apart connected to a 50cc Tooumi syringe. Three 500m1 basins were prepared containing:

l. Normal saline

2. 0.5% NaHCO3 (30cc of 8.4%o NaHCO3 diluted to 5O0cc(Schneider and Andrus,

-123- 1992)) + 0.3o/o Congo Red (3g in 500m1).

3. 2.0% NaHCO3 + 0.3% Congo Red

Because general anaesthesia depresses acid secretion, pentagastrin ("peptavlon" ICI)

íVglkgwas injected subcutaneously 15-20 minutes before the test(Donahue et al.,

1986). A preliminary gastric lavage was performed with saline if the first view of the

stomach shows food debris or particulate matter. The gastroesophageal junction was

tethered with a catheter to minimize the risk of acid reflux into the oesophagus, and the

duodenum was obturated by a laparoscopic bowel clamp. Two hundred ml of the 0.5%

NaHCO3 solution was injected into the stomach via the attached nasogastric tube. The

stomach was manipulated to ensure coating of the entire surface. The stomach was

aspirated via the tube and the tube bunged. If the entire gastric mucosa was coated the

time was noted and the test proceeded. If any of the surface remained uncoated, the

inigation/aspiration sequence was repeated.

Positive findings were defined as blackened areas seen within 2 minutes (indicating a

pH of < 3.0). In contrast successfully denervated areas secrete acid slowly enough to

delay the colour change for 8 to 10 minutes. If the entire stomach was black within 2 minutes, lavage was repeated with a 2Yo solution, to show a differenti al rate of secretion between innervated and denervated mucosa.

In the sham laparoscopic group the stomach was mobilised by division of the lesser omentum in an identical manner to the laparoscopic HSV, except no neurovascular structures were divided.

-r24- Statistical analvsis The statistical method utilised was repeated measures analysis of variance, with

grouping factors of treatment (control, open HSV, laparoscopic gastric mobilisation and

laparoscopic HSV) and a within factor of time. Significant results were defined as p

values of 0.05 or less. Analysis was performed using SAS PC 6.04 statistical software

(SAS Institute Inc., Cary, N.C.).

4.1.3 Resu/fs Clinical outcome During the postoperative period 5 pigs died of gas bloat; 4had undergone open HSV

and one a laparoscopic gastric mobilisation. This is a well known veterinary condition

whereby the stomach became massively distended with air, and was refractory to

repeated attempts at decompression. One animal died from an adhesional small bowel

obstruction following an open HSV, and another died when a laparoscopically

mobilised stomach became strangulated in the thorax. No postoperative complications

were observed in animals that underwent laparoscopic HSV. Clinically, animals in the

laparoscopic HSV group recovered more quickly than those in the open HSV group, and most of the former were back to a near normal diet by day 3.

Gastric acid output Table 4 shows the statistical differences between the pre and postoperative gastric acid output values for each of the 4 groups. Because the pigs grew vigorously over the 8 week study period, postoperative values were corrected by a factor corresponding to the mean weight gain observed in the control group. Basal acid output results were analysed on a logarithmic scale to achieve a normal distribution of the values, thereby increasing the power of the statistical test. Basal acid output was significantly reduced after both open and laparoscopic HSV (p : 0.005 and p :0.02 respectively), but was statistically

-t2s- unchanged in the control and sham laparoscopic gastric mobilisation groups, as illustrated by Figure 9. None of the groups showed a significant reduction in postoperative peak acid output

Table 4: Difference between the pre and postoperative gastric acid output values GROUP BASAL ACID OUTPUT (log) PEAK ACID OUTPUT

CTRL p:0.67 p: 1.0

SHAM p:0.19 p:0.71

OPEN p:0.005 p:0.62

LAP p:0.02 p:0.94

Figure 9: Basal acid ouput

3.5

3.0

2.5

I 2.O E E D Preop ê ¡ Postop. 1.5 !

1.0

0.5

0.0 CTRL SHAM OPEN LAP

-126- Gastric emotvino

Pre and postoperative gastric volume changes over time are represented in Figures 10

and 11 respectively, and Table 5 indicates the statistical difference between these pre

and postoperative values, however only significant results are reported. Following open

HSV, postoperative liquid gastric emptying was significantly impaired at 1 and 30

minutes (p: 0.04). The open HSV also caused significant interference with gastric

emptying at 10 minutes when compared with controls. Laparoscopic HSV was not

observed to significantly interfere with liquid gastric emptying. Control animals showed

a significantly delayed "postoperative" gastric emptying at 2 minutes, limiting the

inferences that can be drawn from the remaining 2 minute results listed in Table 5.

Table 5: Difference between pre and postoperative gastric emptying values GROUP TIME p

OPEN t: 1 min p:0.04

OPEN t:30 min p:0.04

OPEN vs CTRL t: l0 min p:0.04

CRTL t:2min p:0.03

SHAM vs CTRL t:2min p:0.03

OPENvs CTRL t:2min p:0.02

-127- Figure 10: Preoperative liquid gastric emptying

800

7(X)

600

J 500 E +SHAM E .. + -.OPEN ã 400 - :---LAP ,9 +CTRL ü ñ o 300

200

100

0

2 't0 15 20 30 40 llME (min!)

Figure 11: Postoperative liquid gastric emptying

800

700

600

1 500 +SHAM E t ..G- OPEN 400 - o. LAP .E +CTRL

o 300

a 200

100

0

2 l0 t5 30 40 TIME (n¡ns)

-128- Assessment of oesophageal reflux Pre and postoperative reflux scores for each group are plotted in Figure 12.

Considerable variability is evident, and no useful central tendency can be reported for the groups because many animals recorded scores of zero. No apparent difference is evident and statistical analysis reveals that there were no significant differences between pre and postoperative reflux scores for any of the 4 groups (Table 6)

Figure l2z Pre and postoperative reflux scores

30

25

oE20

&15

10

PREOP POSTOP PREOP POSTOP PREOP POSTOP PREOP POSTOP SHAM OPEN LAP. CTRL

Reflux scores of zero are not separately represented, resulting in the apparent inequality of numbers in each group

-129- Table 6: Difference between pre and postoperative reflux scores GROUP p

CTRL p:0.91

SHAM p :0.8

OPEN p: 0.22

LAP p:0.34

4.1 .4 Drscussion Gastric physiological studies endure as the only objective criteria by which the new laparoscopic vagotomy techniques can be validated to be as good as the existing procedures. Because laparoscopic vagotomy has only been technologically feasible for

5 years, the follow-up of operated patients is necessarily too short to allow comparison of the clinical efficacy of the procedure with the documented long-term outcome of open HSV. In addition, the impact of medical therapy on peptic ulcer disease, notably the development of successful regimens for the eradication of Helicobacter pylori and proton pump inhibitor drugs, have resulted in a considerable diminution in the numbers of patients referred for surgery. Furthermore, the collective experience of laparoscopic vagotomy within specialist centres has been diluted by the plethora of alternative techniques competing to become the procedure of choice. For example, selected reports from current literature reveal Dubois promoting thoracoscopic truncal vagotomy in a series of 2l patients(Dubois,1994), Katkhouda supporting laparoscopic posterior truncal vagotomy and anterior seromyotomy in a series of 90 patients(Katkhouda et al.,

1994), Dallemagne advocating laparoscopic HSV in a series of 35 patients(Dallemagne

-130- et al., 1994), Kum and Goh reporting the use of anterior HSV and posterior truncal

vagotomy in 6 patients(Kum and Goh, 1992), and Hannon describing his technique of

linear stapled laparoscopic anterior seromyotomy and posterior truncal

vagotomy(Hannon et al., 1993).

The use of gastric secretory studies for the physiological assessment of vagotomy is a

well-established technique, despite ongoing criticism. When performed routinely after

vagotomy they serve as a functional measure of the degree of parietal cell denervation

which represents the technical efficacy of the surgery. After open highly selective

vagotomy, the reduction in acid output is about 80 - 90% for basal, and 50 - 60%o for

pentagastrin-stimulated acid secretion, influenced however by a leaming curve effect

attributable to the technical difficulty of the operation whereby substantially lower acid

outputs have been reported following vagotomies by specialist compared with novice or

general surgeons(Baron, 1978). Basal acid output may be a more relevant determinant

of the quality of vagotomy than stimulated acid output, as it reflects the period of

gastric secretion when acid may act on the stomach unbuffered by food. Historically, an

80o/o reduction in basal acid output has been considered proof of adequate

vagotomy(Nylamo, 1987). More recently, a reduction in basal acid output of < 80% has

been reported to accurately predict recurrent ulceration after open highly selective

vagotomy(Cohen et al., 1993).

The two largest published reports(Cadiere et al., 1994; Dallemagne et al., 1994) of

laparoscopic HSV have observed the procedure to be very safe with no postoperative morbidity or mortality amongst a total of 68 patients, and complete ulcer healing was observed on endoscopy for all but 3 patients. However gastric secretory studies were

-131 - performed in only 16 of the 68 patients, and no attempt was made to statistically

analyse whether a significant decrease in acid secretory response had been achieved. No

human controlled trials have compared the efficacy of laparoscopic HSV against the

open operation. One controlled animal study assessed the completeness of vagotomy at

2 weeks by killing the animals and mapping innervated gastric mucosa with Congo

Red, a non-standard technique which is unlikely to be applicable to future human

comparisons(Schneider et al., 1992).In this study, both open and laparoscopic HSV

resulted in a signif,rcant reduction in basal acid output, but such changes were not

evident in the 2 control groups. Although signihcant reductions in peak acid outputs

were not observed in any of the groups, other investigators have reported that pigs

commonly have a paradoxical response to agents that cause hypersecretion in humans,

such as pentagastrin(Fitzgibbons, 1994).

Gastric emptying of liquids is controlled by the fundus of the stomach. After vagotomy,

receptive relaxation of the fundus is abolished resulting in higher intragastric pressures

and faster liquid emptying(V/ilbur and Kelly, 1973). The situation with solids is

different. Solid gastric emptying is regulated by the antrum and pylorus rather than the

fundus. Parietal cell vagotomy is associated with near normal levels of solid emptying because the vagal innervation to the pylorus and antrum is preserved(Lavigne et al,

1979). To date, no other studies have quantitated the effect of laparoscopic HSV on gastric emptying. In this study open HSV caused significant interference with gastric emptying at 1 and 30 minutes, and also at 10 minutes when compared with controls, but no impairment of gastric emptying was evident following laparoscopic HSV.

-t32- It remains controversial whether or not HSV precipitates gastro-oesophageal reflux. A number of theories have been proposed to explain why this might occur. It now seems clear that HSV causes no signihcant changes in resting sphincter pressure, but that there may be a loss of the adaptive response of the sphincter when intra-abdominal pressure rises(Martinoli, 1982). Mobilisation of the stomach during HSV also results in a degree of gravitational dependence which may alter the angle of His(Temple and McFarland,

I975). No significant differences between pre and postoperative acid reflux scores for any of the 4 groups were observed in this study. Given the limitation of the pH recording duration, these results suggest that laparoscopic HSV is unlikely to precipitate gastro-oesophageal reflux.

In conclusion, this study observed that domestic white pigs were prone to gas bloat after laparotomy, but in contrast laparoscopic procedures were well tolerated. Laparoscopic

HSV was as effective as its open counterpart in reducing basal acid output, and laparoscopic HSV was superior to open HSV because it did not interfere with liquid gastric emptying. Neither open nor laparoscopic HSV were observed to precipitate gastro-oesophageal reflux. This data suggests that the continued use of laparoscopic

HSV in clinical practice is appropriate. In the future, the methodological protocol described for gastric secretory studies should be routinely applied to assess the physiological outcome of laparoscopic vagotomy in human patients.

-133- 4.3 Gastrostomy 4.3.1 lntroduction Following the advent of percutaneous endoscopic gastrostomy (PEG) for patients

requiring long-term enteral access or gastric decompression, it has replaced surgical

open gastrostomy (OG) as the preferred technique. Retrospective comparisons have

reported a significantly lower mortality and morbidity with PEG compared with open

gastrostomy(Sali et al., 1993 ; Ponsky and Gauderer, 1989). However a randomised

prospective trial of the two methods reported equivalent morbidity and mortality

providing both are performed under local anaesthesia(Stiegmann et al., 1990), but this is

less often possible with OG than PEG and the results may not reflect the clinical

experience of other centres. Percutaneous gastrostomy can also be performed using a

Seldinger technique under radiological guidance, and although less popular it has

achieved similar results to endoscopic gastrostomy(Halkier et al., 19S9).

Under certain circumstances percutaneous gastrostomy is contraindicated or may fail.

These situations occur with a reported incidence of 3o/o and 5Yo respectively(Stiegmann

et al., 1990), and until recently OG has been the only alternative. The documented

complications of OG, and the knowledge that most patients excluded from percutaneous

gastrostomy are poor surgical candidates combine to make OG an unattractive proposition. Two recent developments have changed this situation.

In 1990 Mansberger described a technique of combined endoscopic and surgical placement of a gastrostomy under local anaesthesia when PEG is contraindicated(Mansberger and Kavouklis, 1990). General anaesthesia nor a laparotomy is required. The gastrostomy is placed under direct vision through a2cm abdominal incision using endoscopic guidance, and secured by a gastric purse-string

-r34- and suture fixation to the abdominal wall. This technique reportedly eliminates unsatisfactory adhesion between the gastric serosa and anterior abdominal wall, a complication which is frequently fatal(Ditesheim et al., 19S9).

With the rapid acceptance of laparoscopic upper gastrointestinal surgery a second minimally invasive alternative to percutaneous gastrostomy has emerged. Laparoscopic gastrostomy was first described in 1991(Edelman and Unger, I99l ; Shallman, l99l), and several recent variations to the technique have been reported(Cossa et al., 1992;

Haggie, 1992; Mr.phy et al., 1992; Duh and V/ay, 1993b). These methods use an adaptation of the Russell PEG technique(Russell et al., 1984) by direct puncture of the stomach either immediately by a laparoscopic port or by a peel away sheath following progressive dilatation of a needle tract. All describe suture fixation of the stomach to the anterior abdominal wall under direct vision with the sutures tied over skin bolsters.

Accurate fixation of the stomach to the anterior abdominal wall under direct vision is a major advantage of laparoscopic gastrostomy. This makes it safer than radiologically- placed percutaneous tubes in patients with upper aero-digestive obstruction preventing

PEG. Although combined endoscopic and surgical placement of a gastrostomy can also overcome conditions which hinder satisfactory adhesion of an endoscopically placed tube, the use of laparoscopy is within the realm of the majority of General Surgeons and does not rely on the availability of an endoscope or a trained endoscopist. Evidence is accumulating to indicate that gastroesophageal reflux is precipitated or worsened by gastrostomy tube feeding(Jarnagin et a1^, 1992; Grunow et al., 1989). In the recent

Australian study, two patients died following continued aspiration after placement of

PEG tubes(Sali et a1.,1993). This has lead to the suggestion that jejunostomy feeding may be preferable for patients at risk of aspiration pneumonia(Gottfried and Plumser,

-r35- 1984), or that prophylactic fundoplication be combined with gastrostomy tube

placement(Bui et al., 1989). If a laparoscopic approach is used, the surgeon can choose

between either of these measures which can be employed quickly and easily during the

procedure. Laparoscopic jejunostomy may well evolve as the preferred measure in

patients at high risk for aspiration of gastrostomy feeds, and a recent report detailed

excellent results using this technique(Duh and W'ay, I993a).

Aim It was hypothesized that laparoscopic gastrostomy could offer a viable alternative to

enteral access after failed percutaneous endoscopic gastrostomy (PEG). When enteral

access by PEG is contra-indicated, it was proposed that laparoscopic gastrostomy could

present a less invasive alternative than open gastrostomy (OG), and could be easily

performed by General Surgeons with basic laparoscopic skills without the assistance of

an endoscopist.

4.3.2 Methods The procedure was performed on a previously healthy l5 year old female cyclist who

sustained severe head injuries after being struck by a car. Over the succeeding

hospitalisation pharyngeal inco-ordination required prolonged nasoenteric feeding. pEG was attempted but was unsuccessful as the stomach was situated entirely above costal margin and was unable to be apposed to the anterior abdominal wall.

The operation was performed under general anaesthesia four days after the failed pEG.

The procedure commenced with the insertion of a 10-12mm umbilical port into the peritoneal cavity using an open technique, followed by CO2 insufflation to a pressure of

5mm Hg. The telescope-camera assembly was inserted through the umbilical port and under direct vision a second 10-l2mm and a third 5mm port were placed in left and

-136- right paramedian positions respectively. A fourth 5mm port was placed in the right upper quadrant. The anterior wall of the body of the stomach was grasped with

Babcock forceps and approximated to a convenient position beneath the left anterior abdominal wall, above which a2mm incision was made in the skin of the left upper quadrant and a subcutaneous pouch fashioned. Four 2/0 Vicryl sutures on 36mm curved atraumatic needles were passed through the anterior abdominal wall into the peritoneal cavity where they were grasped with endoscopic needle holding forceps

(Figure 13). These sutures were were then placed at four appropriate anchor points through the gastric wall and passed back out through the anterior abdominal wall. A lcm gastrotomy was made between the sutures using the coagulating diathermy hook.

A24F silastic Foley catheter was passed through the anterior abdominal wall into the peritoneal cavity mounted on a catheter introducer and directed into gastric lumen under laparoscopic visualisation (Figure 14). The balloon was inflated with 3Omls of normal saline and traction on the catheter brought the stomach into close apposition with anterior abdominal wall. The Vicryl sutwes were then hand tied extra-corporeally with the knots situated in the subcutaneous pouch. At completion of the operation the pneumoperitoneum was released while the gastrostomy was under direct vision. The camera and all ports were removed, and the left upper quadrant skin incision closed with subcuticular 3/0 Prolene. The catheter was fixed to the skin with a temporary 210 silk suture. The fascial port sites were closed with 3/0 Vicryl and the overlying skin with steri-strips

-137 - Figure 13: The anterior wall of the body of the stomach grasped by Babcock forceps, with transabdominal sutures placed by an endoscopic needle holder.

-138- Figure 14: Foley catheter mounted on an introducer passed into the peritoneal cavity, and directed into the stomach under laparoscopic visualisation.

-139- 4.3.3 Resu/ús Post-operatively the gastrostomy remained patent when flushed with 20mls of normal saline four times a day. By day four the patient's bowel sounds were present and gastrostomy feeding was commenced. The patient's post-operative progress was uncomplicated, and the gastrostomy continued to function well following discharge from hospital to a rehabilitation institution.

4.3.4 Drscussion Gastrostomy for enteral feeding or gastric decompression has traditionally been performed by open surgery. Recent reports indicating a lower morbidity and mortality rate for PEG compared with OG(Sali et al., 1993 ; Ponsky and Gauderer, 1989) have justif,red the more minimally-invasive approach that percutaneous techniques provide.

PEG is not immune from complications, in particular as a result of insecure fixation of the stomach to the anterior abdominal wall(Ditesheim et al., 1989), and post-procedural reflux and aspiration pneumonia(Jamagin et al., 1992 ; Grunow et al., 1989). In situations where PEG is contraindicated or has failed, laparoscopic gastrostomy can offer a minimally-invasive alternative.

Curved needles were used to place fixation sutures in the case reported. These were not ideal as some difficulty was encoutered passing them accurately out through the anterior abdominal wall. However the normal straight needles as would be used for subcuticular sutures are also not useful as they are too long to easily manipulate laparoscopically, and dedicated laparoscopic needles are too short to pass through the anterior abdominal wall in all but slim individuals. The use of T-Fasteners (Ross Laboratories, Columbus,

Ohio) to retract and anchor the stomach is an innovative solution to this unique diffrculty(Duh and V/ay, 1993a ; Duh and Way, 1993b). These devices consist of a

-r40- metal T-bar lcm long, lmm in diameter with a nylon suture attatched to its centre. They are introduced percutaneously into the enteric lumen by a slotted needle and dislodged by a stylet, after which both needle and stylet are removed. Until such equipment becomes locally available, the choice of the appropriate suture needle will have to be made on a case-by-case basis.

In this patient it was technically easier to to approximate the stomach to the anterior abdominal wall under laparoscopic control than at PEG, perhaps related to the more comprehensive view of intra-abdominal landmarks offered by the laparoscope making it easier to choose an appropriate location beneath the costal margin. Four-point suture fixation and balloon traction ensured firm apposition of the gastric mucosa and anterior abdominal wall, but the addition of a gastric purse-string could add a further measure of safety. The use of a skin incision and subcutaneous pouch into which the extra- corporeal knots were snugged is a minor technical improvement over previous descriptions where skin bolsters \ilere used, risking pressure necrosis should the sutures be tied under excess tension. A further technical modification employed in the reported case was to minimize the potential for damage to adjacent structures by not puncturing the stomach by a direct percutaneous route, but rather via a small gastrotomy made with the coagulating hook.

It is concluded that laparoscopic gastrostomy is a viable option when PEG is contraindicated or has failed. In some respects it provides benefits surpassing PEG, because poor apposition between the stomach and anterior abdominal wall can be prevented, and prophylaxis against reflux and aspiration pneumonia can be easily incorporated into the procedure. However, whether it is better than OG remains to be proven in randomised controlled trials, because laparoscopic gastrostomy has to be

-t4t- carried out under general anaesthesia while OG can be performed under local anaesthesia.

-t42- 5. ASSESSMENT OF ROUTINE LAPAROSCOPIC PROCEDURES

5.1 Historical development of herniorrhaphy

5.1.1 Traditional methods of inguinal hernia repair An extensive review of traditional methods of inguinal hernia repair is beyond the scope of this work, however an introduction to some differentiating concepts in the management of the posterior inguinal wall is relevant to place the development of laparoscopic hernia repair in perspective.

Bassini From the time of his original description in 1887, Bassini's operation has become a standard for inguinal hernia repairs. Perhaps his greatest contribution was to be the first to suggest opening the neck of the inguinal canal to deal with the neck of the sac at the deep inguinal ring. Relatively recently, new English translations of the original operation of Bassini were published from his original Italian manuscript and subsequent treatise in German 3 years later in 1890(Brown et al., 1966). These indicate that Bassini stitched the triple layer of internal oblique, the transversus abdominis muscle, and the transversalis fascia to the isolated posterior border of the inguinal (Poupart's) ligament between the pubic tubercle medially and the spermatic cord laterally. It is this stage of the operation that is most commonly associated with the name of Bassini.

Since then, there have been many modifications to this repair, predominant being the descriptions by Halsted(Halsted, 1893 ; Halsted, 1903), McVay(McVay and Anson,

1942; McVay, 1989), and from the Shouldice Hospital(Shearbum and Myers, 1969).

These techniques share the same time-honoured principles of isolation and excision of the hernial sac with reconstruction and reinforcement of the posterior wall of the inguinal canal.

-143- Halsted In 1893, Halsted himself admitted that his operation and that of Bassini were nearly identical, but elucidated some minor differences(Halsted, 1S93). Bassini always brought the cord out through the deep inguinal ring, but the position that Halsted selected was determined by the condition of the muscles. In contrast to Bassini, Halsted advocated reducing the bulk of the cord by excising superfluous veins. Furthermore, he initially described allowing the cord to remain in the subcutaneous plane, preferring not to reapproximate the external oblique aponeurosis by sutures as Bassini described, however by 1903 he had incorporated this step in his repair(Halsted, 1903).

McVav lCoooers lioament reoeir) An excellent description of the technique and results of the McVay operation (Cooper's ligament repair) was published by Rutledge in 1988(Rutledge, 1988). Over a 25 year period he performed this operation on942 patients and had personally followed up 906 repairs in 7 47 patients for an aveÍage of 9 years. For primary repairs he observe d a I .9Yo recurrence rate. He concluded that a Cooper's ligament repair provides a strong posterior inguinal wall and repairs all of the defects that can occur in the groin.

McVay's basic anatomical concept is that for all practical pu{poses, groin hernias are concemed only with the transversus abdominus layer (muscle, aponeurosis, and fascia)(McVay, 1989). The normal insertion of these elements of the posterior inguinal wall is Cooper's ligament, and hence the rationale for using this as the anchoring structure in the repair of groin hernias in which the posterior wall has been damaged

(direct, large indirect, or femoral). Proponents of techniques that reconstruct this specific area argue that Bassini's repair and variants thereof are unanatomical because all layers of the posterior wall are brought down (often under tension) to the inguinal

-t44- ligament, which many believe to be solely the site of insertion of the extemal oblique aponeurosis(Glassow, 1986). These points are considered critical to minimising the recuffence rate, and are ignored by Bassini-type repairs.

The essential differentiating features of the operation are that the posterior wall of the inguinal canal is incised and Cooper's ligament is dissected free. Obturator and external spermatic tributeries of the inferior epigastric artery are divided, and any attenuated conjoint tendon is resected. All preperitoneal tissues are imbricated, and the femoral canal is closed with sutures. The repair is constructed with intemrpted sutures being placed between the transversus abdominis arch and Cooper's ligament as far laterally as the femoral vein. The repair is continued laterally between the transversus abdominis arch and the inguinal (Poupart's) ligament until the cord exits laterally and obliquely out the internal ring.

Shouldice The Shouldice hernioplasty originated from the Surgeon and Hospital of the same name in Toronto, Canada, and had evolved to its present form by 1950. Although it has been called the modern equivalent of the original Bassini operation(Wantz,1989), it owes perhaps greater similarity to the McVay technique because it shares the same recognition of the basic importance of reconstructing the defective transversalis fascia.

Vital to the understanding of this operation is that when the posterior inguinal wall is divided, two flaps of transversalis fascia result, an upper and lower(Glassow, l936). A total of four lines of continuous nonabsorbable sutures are then used in the repair of the posterior inguinal wall. The f,trst suture line begins at the pubic tubercle and ends medial to the internal ring, approximating the free upper edge of the lower transversalis flap underneath the upper flap, which then overlaps it. The second suture line is a

-145- continuation of the first, reversed at the internal ring, attaching the free edge of the upper transversalis flap to the shelving surface of the inguinal (Poupart's) ligament. The third suture line commences with a new thread at the internal ring and brings the internal oblique and transversus abdominis muscles down to the inguinal ligament. The fourth suture line is a continuation of the third, reversed at the pubic bone, to reinforce these same structures to one another at a slightly more superficial level.

Glassow reported on 12 548 repairs conducted at the Shouldice Hospital between 1954 and 1974, and cited a recurrence rate of only l.l % for primary repairs(Glassow, l9S6)

The same publication included a summary of seven other series all using the same technique with at least 10 year follow-up, and reported a mean recuffence rate of 1.5 % from 1l 809 patients

Lichtenstein Lichtenstein and colleagues from Cedars-Sinai Medical Centre in Los Angeles contend that all of the abovementioned repairs share the common disadvantage of tension on the suture line(Lichenstein et al., 1989). They believe that this is the eventual cause of postoperative disruption, and is the prime aetiology of hernia recrrrrence. In 1989, they described a technique of tension-free hernionhaphy(Lichenstein et aL.,1989). In this repair, the posterior inguinal wall is dealt with by overlaying a suitable size of polypropelene mesh. The lower edge is sutured to the lacunar ligament proceeding laterally along the inguinal ligament beyond the intemal ring. A slit in the mesh at this site allows the emergence of the cord. The superior edge of the mesh is sutured to the rectus sheath and conjoint tendon. The lateral tails of the mesh are fixed to the inguinal ligament by a single suture.

-146- Using this approach, the usual approximation of aponeurotic tissue under tension is avoided. Furthermore, the technique is simple, quick, and requires less dissection making it less painful and suitable for local anaesthesia. In a subsequent paper,

Lichtenstein's group reported a recuffence rate of only 0.13 % in a series of 1552 consecutive, unselected, primary hernia repairs(Schulman et a1.,1992). These excellent results were coffoborated by four other series cited in the same paper, where an overall

o/o recuffence rate of 0.22 and infection rate of 0.03 %o was observed from amongst 3019 operations

Preoeritoneal repairs with and without mesh The definitive technique for preperitoneal herniorrhaphy was first described by Cheatle in 192O(Cheatle,1920), and despite significant contributions by Henry and McEvedy, it was not popularised until the work of Nyhus and Condon in the 1960's(Read, 1989)

This approach can be utilised for a variety of repairs, including suture, fascial graft, iliopubic tract, or Cooper's ligament techniques. It has gained wide acceptance for its particular suitability to the management of recurrent or strangulated hernias.

In the classic description by Nyhus(1.{yhus et al., 1960), after entering the preperitoneal space through a transverse incision, a complete view is obtained of the posterior inguinal wall from behind. The peritoneal sac can be dissected, or simply divided and left in-situ. Sutures are then placed between the transversus arch superiorly and the iliopubic tract inferiorly depending on the location of the defect. Using an identical technique for the repair of 248 consecutive first-time recurrent hernias, Greenberg reported a I.7 Yo recurrence rate within 5 years(Greenberg, 1987)

More recently, the use of polypropelene prostheses to buttress the posterior wall of the inguinal canal has been reported using a preperitoneal approach. Nyhus placed a tai-

-147 - lored piece of mesh as part of a preperitoneal repair of recurrent defects, reporting a 1 .7 o/o re-recurrence rate in 115 hernias over a 10 year period(Nyhus et al., 1988). Stoppa and'Warlaumont also described a technique of preperitoneally placed polyester mesh prostheses which are tacked to the posterior wall of the inguinal canal(Stoppa and

Warlaumont, 1993). This approach has the advantage of covering the hernial defect as well as adjacent normal tissue beyond the limits of the defect, with intra-abdominal pressure creating an effrcient means of fixing of the mesh over the site of the hernia, rather than by the apposition of tissues.

5.1.2 Laparoscopic methods of inguinal hernia repair The first human laparoscopic herniorrhaphy was performed by Ger (Ger, 1982) by intra- abdominal stapling of the neck of the hernial sac. Laparoscopic herniorrhaphy tech- niques subsequently evolved into two main groups; plug or patch repairs. Many surgeons have since abandoned the plugging techniques because ofthe high recurrence rate. Patch repairs remain popular, and three different types have been described; trans- abdominal intraperitoneal, transabdominal prepreperitoneal, and extraperitoneal.

A plethora of publications considering the merits of laparoscopic hernionhaphy are now available, however at the time of conception of this work reports of laparoscopic herniorrhaphies in humans had been few with the number of patients undergoing surgery and the follow up period usually being quite limited. Enough evidence had accumulated to substantiate the alleged advantages of reduced post-operative pain(Salerna et al., l99l ; Corbitt, l99I), shorter hospital stay and a more rapid return to work(Dion and Morin, 1992; Salerna et al., I99I ; McKeman and Laws, 1993 ; Dion and Morin, 1992), however there had not been any published randomised controlled trials comparing the laparoscopic technique with a conventional open repair. There still

-148- remains no published randomised controlled trial investigating the increasingly popular laparoscopic extraperitoneal hernia repair. Furthermore, while open hernia repair as a day surgical procedure was well established in many centres, the place of day surgery in laparoscopic hernia repair had not been critically assessed.

Laparoscopic liqation of the neck of the sac In 1982, Ger developed a technique whereby incidental groin hemiae found at the time of laparotomy for other intraabdominal conditions could be dealt with by closing the peritoneal opening with clips(Ger, 1982). He treated 14 patients in this manner, and followed them up for periods ranging between 26 to 44 months. Only one recunence was noted. The success of this method led to an experimental study designed to test the feasibility of this technique in the laparoscopic environment. Fifteen beagle dogs with congenital indirect inguinal hernias were operated on, 12 laparoscopically(Ger et al.,

1990). In addition to the usual video-laparoscopy setup, a customised combination l2mm stapler with extendable forceps was developed by the author to facilitate the procedure (Herniastat, Innovative Surgical Devices,Westbury, NY). This is used to pick up the edges of the hernial opening, approximate them, and apply 14mm titanium staples of 0.5mm in diameter. Peritoneum, subperitoneal tissue, and transversalis fascia are approximated; the number of staples placed depends on the size of the hernial orifrce. In all 12 dogs operated on the hernia was cured. Examination of en-bloc inguinal specimens showed that if the staples were properly applied, they sank below the peritoneum and disappeared from view, whereas superficial application resulted in staple migration and loss of effective closure.

Ger and colleagues believe this technique is effective for small indirect hernias, particularly in young adult and paediatric patients. For larger indirect hernias, and other

-r49- types, they advocate supplementing the repair by mesh insertion into the sac. They caution that if too much mesh is placed in the sac, problems of discomfort and an externally palpable mass are manifested. If the mesh protrudes into the abdominal cavity, it may cause intestinal perforation or adhesional obstruction. In their most recent paper, Ger had closed 31 hernias with satisfactory results in27 instances(Ger et al.,

1993). On the basis of these results, the authors believe laparoscopic hemia repair offers a rapid recovery and earlier retum to work with far less discomfort, and the highest possible ligation of the sac, although no objective comparative data is provided to support these assertions. By not dissecting the inguinal canal, they also suggest the risk of ischaemic orchitis and entrapment neuropathy is diminished. However, they qualify their assertions by highlighting the potential disadvantages incurred by the inherent dangers of laparoscopy, and the unknown long-term recurrence rate.

A novel technique for cure of indirect hernias by laparoscopic closure of the internal ring has been described by Geraghty (Geraghty et al., 1994). They use a hollow J-needle inserted percutaneously, which is directed through the superior and inferior margins of the deep ring under laparoscopic guidance. An 0 nylon suture is passed through the needle, which is subsequently withdrawn, and the thread is tied extemally. Three sutures are usually sufficient to close the deep ring completely. This technique was used successfully in25 consecutive patients, with no recurrences over 8.5 months follow-up and one instance of urinary retention. The authors laud the technique because it is simple, inexpensive, and does not require clips or prosthetic material.

Techniques of ring closure have been critcised for the requirement that patients restrict activities for 6 weeks to allow the scar to strengthen, obviously nulliÛring return to work advantages conferred by laparoscopy(Anegui et al., 1993). Furthermore, other

-150- defects in the posterior wall may be missed because the inguinal floor has not been completely inspected. It seems the wheel may turn full circle, and this technique will find a place to close incidentally found small indirect hernias during other laparoscopic procedures.

Laparoscopic plug (t small mesh) repair The laparoscopic mesh plug repair was developed by Schultz, who was also the first to report a series of laparoscopic hernionhaphies in 1990(Schultz et al., 1990). The peritoneum adjacent to the indirect hernial sac was incised, and the sac dissected by a laser fibre. The indirect defect was plugged with rolls of polypropylene mesh covered by two or three fuither small flat pieces of mesh until the defect was filled. The peritoneum was re-approximated with clips. In the initial series, 20 hernia repairs were followed for 3 - 11 months, with one recuffence attributed to an unrecognised direct component. In a subsequent presentation of their results, six direct recurïences were detected in the first 50 patients(Cheslyn-Curtis and Russell, 1993), leading the authors to revise their technique by including additional placement of a large flat mesh fashioned to cover the entire inguinal area.

Corbitt was another early adopter of laparoscopic mesh plugging techniques, publishing a series in 1991 of 20 inguinal hernia repairs performed as day cases(Corbitt, 1991). He used a modified mushroom-shaped mesh plug with an attached square patch laid across the intemal ring to act as a stopper to prevent plug migration. Although initially enthusiastic because patients were pain-free and returned to normal activity the first post-operative day, after following these patients for up to two years there was a greater than l5 o/o recurrence rate(Cheslyn-Curtis and Russell,1993).

-151 - Schultz and Corbitt have since abandoned this technique in favour of transabdominal preperitoneal mesh placement. The unacceptably high incidence of recurrence was explained by limited dissection of the inguinal floor so missing concomitant hernias. A recent review of the place for plug repairs suggested that it should be confined to use in recurrent direct or indirect hernias up to 3.5 cm in diameter, primary femoral hernias, and recurrent femoral hemias(Schulman et al., 1994).

Laparoscopic transabdominal intraperitoneal (onlay) patch The next development in laparoscopic hemiorrhaphy was in retrospect a retrograde step

Once it had become apparent that preperitoneal plug repairs must be supplemented or superseded by preperitoneal mesh patches, some groups questioned the need for extensive preperitoneal dissection and suggested it could be eliminated and the same result achieved by simply affixing an onlayed prosthesis directly on the peritoneum.

This was expected to result in a simpler and quicker operation, less morbidity and consequently improved functional outcome for the patient. However some significant disadvantages have become evident. Because the mesh is anchored mainly to the peritoneum, the entire complex can slip into the hemia defect. Another well-recognised problem caused by intraperitoneal polypropylene or Marlex mesh is erosions of, and adhesions to the bowel, or infection of the prosthesis, with complications related to these occurrences.

To test this hypothesis, Fitzgibbons, Salerno, Filipi and others conducted an animal study in which polypropylene mesh, with and without an oxidised regenerated cellulose adhesion barrier, was used to repair indirect hernias by the intraperitoneal onlay technique(Fitzgibbons et al., 1994). Groups of male pigs were followed for both short- term (6 weeks) and long-term (7.1 month) time frames. All herniorrhaphies were

-152- successful with no recurrences. After short-term follow-up, 8l%o of 26laparoscopically- placed prostheses adhered to the bladder or small bowel. After long-term follow-up,

48% of 42 laparoscopically-placed prostheses adhered to the bladder, small bowel, or

seminal vesicles. No complications related to mesh placement were obseryed, nor did mesh stapled over cord structures appear to affect fertility by constricting the vas deferens or spermatic vessels. The oxidised regenerated cellulose adhesion barrier appeared to have no value decreasing the rate ofadhesions for laparoscopically-placed prostheses. This study has quantified the degree of visceral adhesion formation to intraperitoneal mesh, which would appear to occur in at least half of all laparoscopic cases. No complications were observed as a consequence of this in pigs, but clinically significant complications are well-recognised in humans. The success of the repairs in this study is of minor consequence, as the dynamic forces in quadripeds would not be expected to reflect the situation in the human groin. Therefore this study did not resolve the problems of mesh slippage or uffecognised preperitoneal hernias. The most reassuring result was the absence of fertility complications. Although this study was only published in 1994, encouraging results emanating from this study (as early as

1990) have been cited on several different occasions in varying stages of completeness to support the use of this technique. Literature reviews on the subject of laparoscopic herniorrhaphy therefore tend to over-represent the importance of this approach, giving a misleading impression that this technique is more widely advocated that it is. One of these reviews \ /as written by the authors of the study, citing the manuscript in I992had been submitted to an anonymous journal(Filipi et al., 1992), another review cites the former review written by the authors of the study(Anegui et ar.,1993) and other reviews cite two different book chapters also written by the authors of the

-153- study(cheslyn-curtis and Russell,1993; Hanaff, 1993). This seems to be a good

example of how easily untested laparoscopic procedures can be disseminated into

surgical practice by enthusiastic advocates.

The benefits of polytetrafluoroethylene (PFTE) or Gore-Tex mesh in comparison to

other synthetic materials are based on the possibility of its use as an onlay mesh without

re-peritonealisation, and its characteristic of providing frbroblast proliferation without a

severe foreign body reaction. Toy and Smoot have described a laparoscopic

herniorrhaphy technique using an expanded PFTE Gore-Tex patch peritoneal onlay with

staple fixation(Toy and Smoot, 1992). Eighty-three hemioplasties were done under

general anaesthesia on 7 5 patients in an outpatient surgical facility, and followed for a

maximum of 20 months. There were2 recurrences (2.4%). The first occurred due to

staple disruption along the border of the Gore-Tex patch, and the authors now advocate

longer-leg staples. The second recurrence was attributed to inadequate fixation to

Cooper's ligament, and their technique was subsequently modified to incorporate

peritoneal dissection to enable direct visualisation of this structure. Toy and Smoot

considered laparoscopic hernioplasty to be at an investigational stage, and concluded

that its use should be confined to prospective studies. The authors noted that it was

gratifuing that awell-organised, multicentre trial, with defined outcome measures had

been commenced, and more recently publicised(Go, 1995).

The preliminary results of a prospective randomised trial of laparoscopic onlay

herniorrhaphy using expanded PFTE versus conventional inguinal hernia repair have

recently been published(Vogt et al., 1995). Thirty patients were randomised to the

laparoscopic group, 3l to the open group, and followed for a mean of g months.

Unfortunately, although the laparoscopic arm was standardised, in the open arm neither

-r54- the operative technique nor the anaesthetic was controlled, instead relying on the surgeons' or patients' preference. Apparently the Bassini and McVay repairs were the most popular methods, and one could argue that these do not represent the state-of-the- art in tension-free or anatomical open inguinal hernia repair. The authors' laparoscopic onlay technique also incorporated the peritoneal dissection to enable direct visualisation of Cooper's ligament, as described by Toy and Smoot. Full peritoneal dissection was carried out if the hernia was unable to be visualised endoscopically. This would appear to make this technique only minimally different to preperitoneal patch repairs, but with the disadvantages entailed by exposed intraperitoneal mesh. Nevertheless, the authors observed that in the laparoscopic group, mean operative time was shorter, post- operative pain was significantly less, and return to normal activity was significantly shorter. Two recurrences were witnessed in the open group and one in the laparoscopic group, and overall complications and morbidity was low. If the methodological flaws in this study are ignored, the results indicate that in all parameters besides the unassessable recurrence rate, laparoscopic hemiorrhaphy is an efficacious procedure.

-15s- Laparoscopic transabdominal preperitoneal patch The basis of this method is the open preperitoneal technique of Stoppa (Stoppa and warlaumont, 1993). The laparoscopic adaptation was devised by Arregui, who description was published in l992(Anegui et a1., 1992). Since that time, articles detailing the results of transabdominal preperitoneal patch repairs (TAPP) have

increasingly proliferated(Dion and Morin,1992; Voeller et al., 1993 ; Corbitt, 1993 ; 'Wheler, Himpens, 1993 ; Katkhouda and Mouiel,1993; 1993 : Geis et a1.,1993 ;

Newman et al., 1993 ; wheeler, 1993 ; Seid et al., 1992; Morrison, 1993 ; polglase and

McMunick, 1994; Catts et al., 1994 : Paget, 1994 ; Winchester et al., 1993 ; panton and Panton,1994; Kavic, 1995 ; Dion, 1993 ; Stoker et al., 1994 ; Millikan et a1.,1994

; Milkins et al., 1993 ; Cornell and Kerlakian,lgg4) and are indicative of the wide popularity of this approach. Therefore only some of the most important papers will be considered in this review(Arregui et a1.,1992; Brooks, 1994 ; Payne et al., 1994).

Arregui describes that the peritoneal cavity is entered laparoscopically in the usual manner, after which the hemia sac is excised at its neck facilitating entry into the preperitoneal space. This whole area is bluntly dissected to expose predominantly the transversalis fascia and surrounding structures. In indirect hernias, the internal ring is tightened with an interrupted suture, and in direct hernias the transversalis fascia is loosely closed with a running suture. Polypropylene mesh (approximately 2.5 x 4.5 inches) is then fashioned to fit as a complete sheet over the internal ring, the testicular vessels, the spermatic cord laterally, Hesselbach's triangle medially, and Cooper's ligament inferiorly. The authors observe that the inferior epigastric vessels do not need to be divided nor passed over the mesh. The mesh is anchored with 3-0 Vicryl sutures to the transversalis fascia and the transversus abdominis arch superomedially, to the

-156- iliopubic tract or Cooper's ligament inferiorly, and to the transversalis fascia and transversus abdominis lateral to the internal ring. Lastly, the peritoneum is closed over the mesh with a continuous absorbable suture. Sixty-one repairs were performed on 52 patients followed for a mean of 2.3 months. Patients were discharged on the same or next day, and were allowed free activity. Only three minor complications ensued, and no recurrences were evident in this very brief follow-up. The technique is admittedly time-consuming, but this has been redressed in subsequent studies where staples rather than sutures were used.

Comparative trials between laparoscopic TAPP herniorrhaphy and traditional open inguinal hernia repair began appearing in print in April 1994. Six studies have been published, of which are prospective three case control studies(Millikan et a1.,1994 ;

Brooks, 1994 ; Cornell and Kerlakian,lgg4) and three are randomised controlled trials; one from the UK(Stoker et al, L994), one from the USA(payne et a1.,1994), and one from Australia(Maddern et al., 1994).

Stoker et al published the first randomised controlled trial of laparoscopic herniorrhaphy(Stoker et a1.,1994). The laparoscopic repair was performed as described by Arregui, but using staples to fìx the Prolene mesh. The tension-free open repair was performed in an identical manner to that at our institution (see Section 5.2.2 Methods,

Transabdominal preperitoneal herniorrhaphy), except that all repairs were conducted under general anaesthesia. Following a learning-curve of 35 laparoscopic patients, excluded from the analysis, 150 patients were randomised in equal numbers to each group, and followed for a mean of 7 months during which no recuffences were observed in either group. Their results showed the laparoscopic operation took on average l5

-t57- minutes longer for unilateral repairs, but was only 30 minutes total for the last 20 cases in the trial. Mean analogues pain scores were recorded on eight separate occasions until

day 7 post-operatively, and were significantly lower on each occasion in the laparoscopic group. The median time taken to return to normal activity was significantly shorter in the laparoscopic group (3 days cf 7 days), as was median time taken to return to work (14 days cf 28 days). The complication rate was also lower in the laparoscopic group (8 % cf 2r %). The extra expense of materials for the laparoscopic procedure was f 168 per case, but such costs were expected to be recouped by the community with fewer days lost from work. This trial represented a significant advance in the management of hemiae, convincingly proving that in all parameters besides recurrence (not assessed), the laparoscopic operation was better.

The work conducted at our institution was the second randomised controlled trial, published in August 1994(Maddern et a1.,1994), and is discussed in Section 5.2,

Transabdominal preperitoneal herniorrhaphy. The only other randomised controlled trial was published in September 1994 by Payne and others from the University of

Honolulu(Payne et a1.,1994). Fifty-two patients were randomised to the Lichenstein tension-free open hemioplasty performed under local anaesthesia, and 48 to a laparoscopic TAPP hernioplasty as described by Arregui, except mesh was stapled in place. Unilateral laparoscopic repairs lasted an average of 68 minutes, which was not significantly different to the open operation. Patients were discharged after a mean of

4.8 hours following laparoscopic repairs, againthis was not signihcantly different to patients who underwent the open operation. Patients having primary open repair of unilateral hernias returned to work after amean of l7 days. Following laparoscopy, the mean time to return to work on objective measures was 8.9 days, and multiple

-158- regression analysis controlling for the intensity of the job found this difference to be

significant. Eighteen percent of patients in the open group , and 12 Yo inthe laparoscopic

group sustained minor, transient complications. No recuffences were detected after a median follow-up period of 10 months. The mean total hospital cost was almost

US$600 more for the laparoscopic operation. From these results it can be concluded that in terms of operative and hospitalisation times, and short-term outcome, these two modern operations are equally good. The balance between cost savings generated by an earlier retum to work or a less expensive procedure cannot be appropriately generalised, and is really a matter for resolution between the surgeon and the individual patient.

The studies by Stoker(stoker et al., 1994) and Payne(Payne et al., 1994) were methodologically sound, and compared a standardised laparoscopic operation against well-established, currently favoured open hemiorrhaphies. Until long-term data is available, these studies justifu the continued use of laparoscopic TAPP repairs in a trial setting.

Laparoscopic extraperitoneal patch A totally extraperitoneal approach to inguinal hemiorrhaphy had been advocated by

McKeman as early as 1993(McKernan and Laws, 1993), and has as its main advantage the potential to eliminate all early and late complications related to violation of the peritoneal cavity associated with other transabdominal laparoscopic hernia repairs.

Although prosthetic mesh is introduced by a different access route, the final preperitoneal destination of the mesh makes it principally another laparoscopic variant of the Stoppa and Warlaumont open hernioplasty.

-159- In his most recent article McKernan describes his technique(McKernan,1993). A20

mm umbilical skin incision is deepened to the rectus sheath, which is opened in the

midline and the rectus muscle bluntly separated. A tunnel is then created by blunt

dissection in the plane between rectus and the peritoneum, and dissection towards the pubis is continued with the aid of low-pressure insufflation. Care must be taken at all times not to perforate the peritoneum. Dissection of the groin commences initially at

Cooper's ligament cephalad to the iliac vein and in the region of a direct hernia.

Peritoneal dissection is extended cephalad to expose the internal ring and indirect sac, which can be dissected from the cord if small, or severed and ligated proximally if large. A 3 x 5 inch piece of polypropylene mesh is then introduced into the preperitoneal space and positioned to cover the hernia defect. The mesh is split to allow passage of the cord and secured in position with a hernia stapler.

McKernan has successfully performed 100 herniorrhapies in 68 patients using this technique. Minor complications included an Il Yo incidence of seroma formation at sites of large direct hernias. Operative time averaged just over one hour, and all patients were discharged by the first post-operative day. All had returned to normal activities within one week. No recurrences were detected after mean follow-up of 10 months.

A larger series of 200 repairs in 155 patients was detailed by the French surgeon Begin in 1993(Begin, 1993). The technique was as previously described, but expanded PFTE

(GoreTex) mesh was used in 5 cases. The average duration of the procedure for unilateral hernias was 45 minutes, however in I I patients there was significant breaching of the peritoneum. The mean duration of stay was 44 hours; essentially patients were discharged the day after surgery, at which time their mean analogue pain

-160- score was 2.5 on a scale of 0 to 10. Only 25 Yo of patients needed analgesia following

discharge. Begin also makes mention of early postoperative groin effusions requiring

aspiration on 3 instances, and noted one scrotal haematoma. Persistent postoperative

pain was a feature in 6 patients, requiring operative intervention to free a trapped lateral

cutaneous nerve in one patient. Ninety-six percent of patients regarded the results as

good or excellent. The mean duration for return to normal activity was 17 days,

although the reader gains the impression that results were not normally distributed, and

perhaps if non-parametric descriptive statistics were more appropriately used, the

median return to work would have been closer to 7 days. In the maximum follow-up period of 22 months, one recuffence was seen, and re-operation revealed prosthetic

slippage due to inadequate f,rxation. No comment was made on efforts to redress the potential for this to occur in the future.

These studies indicate the extraperitoneal approach is safe and not prohibitively difficult, the early results show some promise, and the procedure seems destined for increasing popularity. Unfortunately even short-term outcome parameters have not yet been subjected to the rigourous evaluation of a randomised controlled trial, and it is therefore difficult to identifu a place for the procedure in current surgical practice besides that of an experimental technique.

Specific complications of laparoscopic hernia repair MacFayden was the first to assimilate the data from multiple series such that some general impression of the incidence of complications following laparoscopic herniorrhaphy could be gauged(MacFayden et al., 1993). Subsequently a comprehensive collective series of outcome data from multiple institutions has been published, and includes some of the same patients(Phillips et al., 1995). There is little

-161 - one could add to this excellent treatise which represents the current state of knowledge

on this topic, and although all of its results are worthy of mention, only some will be

considered.

The study reports on the complications of 322g laparoscopic hernia repairs in2559 patients. Sixty percent of patients underwent the TAPP repair, 18 % the intraperitoneal onlay mesh technique, 9 %othe plug and patch repair, and2 o/o simple closure of the neck of the sac. Major complications, defined as requiring intervention or readmission

o/o occurred in 0.5 of patients, and minor complications in 8 %. With a mean follow-up of 22 months there were 1 .6 Yo recunences. No technique seemed to be associated with any specific complications though simple closure of the neck of the sac had a3 %o recurrence rate and a moderate incidence of haematomas and testicular pain, surprising given the simple nature of the procedure. The authors placed laparoscopic complications in perspective with those observed after open herniorrhaphy, and reported that the incidence of ischaemic orchitis/testicular pain, seromas, hydrocoeles, and neuralgia was similar to that seen following traditional anterior approaches.

The authors identified two complications unique to the laparoscopic approach. Small bowel obstruction occurred in 0.2 o/o of patients. Four of the five obstructions occurred in the TAPP group due to hemiation through inadequately closed peritoneum, highlighting the concems about contact of prosthetic mesh with intraperitoneal viscera.

One obstruction resulted from a port-site hernia. Lateral cutaneous nerve injury or entrapment was the other complication unique to laparoscopy. The authors concluded that ifpatients are properly selected and surgeons are adequately trained, laparoscopic herniorrhaphy can be performed with an acceptably low incidence of complications.

-162- 5.2 Transabdominal preperitoneal herniorrhaphy 5.2.1 lntroduction The aim of this study was to compare the efficacy of laparoscopic transabdominal preperitoneal inguinal hernia repair to a conventional open approach in a day surgical unit. with assessment of post operative pain, activity levels, clinical outcome and cost.

5.2.2 Methods Eighty six patients scheduled for elective inguinal hernia repair at the Royal Adelaide

Hospital were investigated in a randomised controlled study. The patients were randomised to receive either the laparoscopic or standard open hernia repair, and a preoperative assessment was made regarding the presumed nature of the hernia (direct or indirect).

The laparoscopic repair was performed under general anaesthesia via a transabdominal preperitoneal approach. Access was via two 1Omm and one 5mm cannulae, the umbilical port for the camera assembly, and bilateral iliac fossa ports for grasping, dissection and stapling instruments. The peritoneum was incised above the hemial defect from within the abdomen and the hemial sac was invaginated. A polypropylene mesh (Prolene, Ethicon, North Ryde, NSW) was individually sized for each patient, introduced into the preperitoneal space, and stapled to the posterior wall of the inguinal canal using an Ethicon Endoscopic Multifeed Stapler (EMS). The peritoneum was then reapproximated with staples. The port holes were closed with 1 Ethibond and infiltrated with0.25%o Marcaine with l:400 000 adrenaline.

The open repair was performed under local anaesthesia. A total of 50 ml of l%o

Lignocaine with l:100 000 adrenaline was infiltrated using a22 gauge short bevel needle to find the correct tissue plane for the ilioinguinal, iliohypogastric, and

-163- genitofemoral nerves and the peritoneal sac. The proposed incision was infiltrated with

a22 gauge spinal needle. Additional analgesia was provided by further injection into

the spermatic cord and pubic tubercle during the procedure with sedation when

necessa"ry. Excess hernial sac was dealt with by high ligation and excision in the case of

indirect hernias and by invagination in direct hernias. The posterior inguinal wall was

repaired by a variant of the Shouldice technique whereby a continuous 0 Prolene suture

approximated the transversalis fascia to the iliopubic tract. This was overlayed by a tension-free double darn of 0 Prolene between the conjoint tendon and inguinal

(Poupart's) ligament. The wound was closed in layers and20 ml of 0.25Yo Marcaine with 1:400 000 adrenaline was infiltrated.

For both operations records were kept of operation time (skin incision to skin closure), consumables used, complications, and type of hernia found.

Patients were also contacted 30 days after surgery by a third party to gain their impression of the Day Surgery experience. They were asked to classiff their experience as "very satisfied", "satisfied", "not satisfied" or "would not agree again".

Comparative results for 2 independent samples were analysed on SPSS for Windows

6.1 statistical software (Chicago) using the Mann-Whitney U test with a2-tailed,a level of 0.05.

5.2.3 Resu/fs There were 86 patients in the study, of which 44 underwent conventional open hernia repair and 42 underwent laparoscopic hernia repair. Seventeen patients had bilateral hernias. Fifteen of these patients were randomised to have the laparoscopic repair with both hernias repaired simultaneously. Two patients with bilateral hernias were randomised to have the open repair and included as separate attendances because each

-164- hernia was repaired on a different occasion. One hundred and one hernia repairs were performed in total. The median follow up period to date is 179 days with a range of 97 to 289 days. All of the patients in the study were male with the exception of 5 females

in the open group and2 in the laparoscopic group.

The measured parameters for the two groups of patients are given in Table 7. From the

42 patients who had an open repair only 3 required conversion to a general anaesthetic.

All patients undergoing the laparoscopic repair had general anaesthesia. Table 7 also indicates the type of hernias found at operation. The preoperative examination predicted the operative hernia type in 79%o of cases excluding the pantaloon hernias, as none of the pantaloon hernias were confidently diagnosed prior to surgery.

The median operation time for the bilateral operations performed laparoscopically was

60 minutes (range 30 - 100). When bilateral hernia repairs were excluded, the median operation time was not significantly different between the open and laparoscopic repairs. In contrast, in patients who were day cases and did not require admission the median post-operative discharge time was signihcantly shorter for the open group þ <

0.05) (Table 7). The median number of days required to return back to work or normal activity was not significantly different between the open and laparoscopic groups, even when only unilateral hernias were considered, however a trend towards an earlier return to work in the laparoscopic group was present.

-l6s- Table 7: Comparison of the two patient groups

Open Laparoscopic

Patients 44 42

Hernias 44 57

Weight (kg) 69.5 (range 36 - 94) 74.5 (range 44 - 92)

Age (yrs) 67 .5 (range23 - 97) 59.5 (range 20 - 80¡*

Operationtime (mins) 30.5 (range 15 - 70) 35 (range 20 - 55)

Discharge time (mins) 134.5 (range 95 - 385) 225 (range 120 - 960)I

Retum to work (days) 30 (range 7 - l8) 17.5 (range 5 - 73)

Hernias found at operation

Indirect 22 (s0%) 2e (st%)

Direct 14 (32%) 23 (40%)

Recurrent 3 (7%) 4 (7%)

Pantaloon s (tr%) t (2%)

Valuesaremedians *p<0.01 f p<0.05

The median activity levels achieved by the two study groups is shown in Figure 15. The median post operative pain levels for the two groups were not significantly different between the open and the laparoscopic groups (Figure l6), although the open group did use significantly more analgesic drugs on day I (p: 0.01) (Figure 17).

-t66- Figure 15: Median activity levels measured on an analogue scale of 0 - 10.

10 10 10 10 9.25 9

I 7.75 7.75

7

b 55 ! open 5 lap 4

3

2

1

o

Preop Day 1 Day 3 Day 10 Day 30 Day'180

Figure 16: Median pain levels measured on an analogue scale of 0 - 10. 44 4

35 3 3

25 -9(! o 2 lj open at 2 .= o I lap o- 5 11 1

o5 oo oo o

Day 1 Day 3 Day 10 Day 30 Day 180

Values for Day 30 and Day 180 were zero.

-t67 - Figure 17: Mean number of total analgesic tablets taken post-operatively per patient.

9 I

7

6 U, -g lt 5 OPEN (! -T o 4 _^_ LAP zct 3

2

o

DAY 1 DAY3 DAY 10 DAY3O DAYI8O

Morbidity of the open and the laparoscopic groups is documented in Table 8. Four patients in the laparoscopic group developed symptoms of neuropraxia, of which one was attributable to the medial cutaneous nerve of the thigh and three to the lateral cutaneous nerve of the thigh. All resolved within 6 weeks. To date there have been2 recunences within 30 days in the laparoscopic group and no recuffences in the open group. The total number of admissions to the hospital ward was 10, with 4 from the open group and 6 from the laparoscopic group. Only 3 admissions (1 open and2laparo- scopic) were as a direct consequence of the surgery. The remainder were admitted because ofsocial reasons or geographic isolation.

-168- Table 8 : Morbidity Complication Open Laparoscopic

Bruising/swelling t4 5

Seroma./traematoma 2 2

Neuropraxia 2 4

Scrotal(bruising/swelling) 3 4

Porthole complication 0 I

Intra-abdominal bleed 0 1

Small bowel obstruction 0 I

Vasovagal collapse 1 0

Total 2r (47%) 17 (40%)

All but 3 patients were contacted to obtain their opinion of day case surgery. Eighty five percent of these patients were satisfied with day surgery and l5Yo were not satisfied

(Table 9).

-169- Table 9: Patients'Opinion of Day Case Surgery Opinion Open Laparoscopic Total

Very satisfied t9 16 3s (48%)

Satisfied 15 t2 27 (37%)

Not satisfied 24 6 (8%)

Would not agree again 3 2 s (7%)

Total 39 34 73 (r00%)

With respect to the added costs associated with laparoscopic hernia repair, there was a mean of 1.1 staplers used for every hernia repaired, and each patient required 3 trocars.

In2 patients a disposable surgical clip applier was required to control bleeding from the inferior epigastric vessels, additionally all laparoscopic patients required general anaesthesia rather than local anaesthetic infiltration.

5.2.4 Discussion At the time of conception of this work in early 1992, no other randomised controlled study had been conducted to compare laparoscopic hernia repair with a conventional open technique. The number of laparoscopic hemia repairs performed in this study and

the follow up period, although short, are similar to other published series(Popp,1993 ;

McKernan and Laws, 1993 ; Corbitt, l99I ; Halverson and McVay,1970).

In order to compare the optimal operative techniques for the repair of hernias, local anaesthetic with sedation as necessary was used for the open inguinal hernia repairs and general anaesthetic for the laparoscopic hernia repairs. Only 3 patients under local

-170- anaesthesia needed conversion to general anaesthesia during the operation, usually due

to inadequate block in obese patients. Although many surgeons continue to repair

hemias under general anaesthesia, local anaesthesia has the advantages of being more

cost-effective and eliminating the risks associated with general anaesthesia.

The relationship between the surgeon's classification of inguinal hemias on

examination and the type of hernia found at operation has been previously

documented(Ralphs et al., 1980). This study suggests that correct identification of the

type of hernia before operation is possible in79Yo of cases when pantaloon hernias are

not present.

The results indicate that laparoscopic transabdominal preperitoneal inguinal hernia

repair is comparable to the conventional open repair with respect to operation time,

post-operative pain and activity levels, as well as the number of days required for return to work. This is in contrast to previous uncontrolled studies (Dion and Morin, 1992 ;

Salerna et al., l99l ; McKernan and Laws, 1993 ; Corbitt, 1991) reporting reduced post- operative pain and a more rapid return to work for patients with hernias repaired laparo- scopically. Although the number of patients studied was small, a trend to earlier return to work for the laparoscopic group did exist. Post-operative pain was low after laparo- scopic inguinal hernia repair, but the results of this study show that post operative pain was equally low following the open repair. This could be attributed to gentler handling of the tissues and greater precision during open hernia repair because the patient had only local anaesthetic infiltration. While recorded pain levels were not significantly different, there were greater analgesic requirements in the open group to achieve this result (Figure 17). The shorter discharge time for the open group was not surprising

-t7I- considering the majority were performed under local anaesthesia and were able to

recover sooner and avoided the side effects ofgeneral anaesthesia.

Because of the remote location of several of our patients or the inability to locate a

responsible family member for the first postoperative night, 7 patients required "hotel"

admissions. If one considers the true medical admissions, 3 patients (l open and2

laparoscopic) required admission. An 8l year old female in the open group required

admission for observation due to a vasovagal attack just prior to discharge. In the

laparoscopic group, one admission was due to a signihcant intra-abdominal bleed and

the other because of a porthole haemorrhage which required re-operation. The patient

who developed an intra-abdominal bleed suffered from a known bleeding disorder, and

recovered spontaneously with fluid and blood transfusion.

The small bowel obstruction diagnosed on day 10 in a patient of the laparoscopic group

resulted from adherence of bowel to the prosthetic mesh because of a disrupted lateral

peritoneal closure post-operatively. The bowel obstruction and peritoneal defect were

subsequently dealt with by a laparotomy.

Although the follow up period was suitable for the assessment of post-operative pain

and activity levels, it was not sufficient to draw any definite conclusions regarding

recurrence rates. The two recurrences reported in this study were in asthmatic patients,

both with a history of severe coughing during the post-operative period. One of these

patients was also on high dose steroids, and the other was later found to have an occult

sigmoid colon carcinoma. These factors may have contributed to early recuffence.

The implications of this study for day case inguinal hernia surgery are promising.

Hernia repair as a day case surgical procedure has not adversely affected the patients in

-172- terms of post-operative pain and activity levels. In addition, there was a high degree of

satisfaction with the procedure from patients in both the laparoscopic and open groups.

The results indicate that both types of surgery can be successfully performed as day

case procedures, with the corresponding hnancial benefits(Flanagan and Bascom,

r e8 1).

In summary, laparoscopic transabdominal preperitoneal hemiorrhaphy has not been

shown to be superior to a conventional open inguinal hemia repair with respect to

reducing post-operative pain and increasing post-operative activity levels. Similarly, it

has not been demonstrated by this study that laparoscopic transabdominal preperitoneal

herniorrhaphy leads to a quicker return to work. In terms of major complications

requiring re-operation or admission, the laparoscopic operation appears inferior. These

results, in combination with the added cost, suggest that this laparoscopic approach

currently does not warrant widespread use in unilateral hernia repairs. Laparoscopic transabdominal preperitoneal herniorrhaphy does have a clear place for a patients with bilateral hemias, recurrent hernias or clinically doubtful hernias. The bilateral hernias can be repaired simultaneously, and yet the patient can still be discharged on the same day, avoiding the need for two separate admissions or hospitalisations. In the case of recurrent hernias, the laparoscopic approach permits access through previously undisturbed tissue. In the obese patient or small symptomatic hernias a laparoscopic examination can also accurately clarifu the nature of any hernial defect.

-173- 5.3 Extraperitoneal herniorrhaphy

5.3.1 Introduction The aim of this study was to compare the efficacy of laparoscopic extraperitoneal ingui-

nal hernia repair to a conventional open approach in a day surgical unit, with

assessment of post operative pain and activity levels, and clinical outcome.

5.3.2 Methods

One hundred and four patients scheduled for elective inguinal hernia repair at the Royal

Adelaide Hospital and the Queen Elizabeth Hospital were investigated in a randomised

controlled study. After being judged suitable for Day Surgery, patients were randomised

to receive either an extraperitoneal laparoscopic or standard open hernia repair, and all

operations were performed by or under the immediate guidance of four Consultant

Surgeons experienced in the appropriate techniques.

The laparoscopic repair was performed under general anaesthesia via an extraperitoneal

approach. Access was via two 1Omm and one 5mm cannulae, the umbilical port for the

camera assembly, and bilateral iliac fossa ports for grasping, dissection and stapling

instruments. The peritoneum was dissected from the abdominal wall and the hernial sac was reduced. A polypropylene mesh (Prolene) was individually sized for each patient, introduced into the preperitoneal space, and stapled to the posterior wall of the inguinal canal using an Ethicon Endoscopic Multifeed Stapler (EMS). The port holes were closed with I Ethibond and infiltrated with 0.25% Marcaine with l:400 000 adrenaline.

The open repair was performed as described in Section 5.2.2, Methods, Transabdominal preperitoneal herni orrhaphy.

For both operations records were kept of operation time (skin incision to skin closure), complications, and type of hernia found.

Comparative results for 2 independent samples were analysed on SPSS for'Windows

6.1 statistical software (Chicago) using the Mann-Whitney U test with a2-tailedc¿ level of 0.05.

-174- 5.3.3 Resu/ús There were 104 patients in the study, of whom 72 underwent conventional open hernia

repair and32 underwent laparoscopic extraperitoneal hernia repair.

After being judged suitable for day surgery, 50 patients were randomised to have the

laparoscopic repair, and 54 the open repair. The final disparity in group sizes occurred

because 18 laparoscopic patients crossed-over to the open group for the following

reasons, which are represented graphically in Figure 18: One patient was subsequently

deemed unsuitable for day surgery general anaesthesia and therefore required an open

procedure under local anaesthesia. Three patients were unsuitable for laparoscopic

repairs because of large inguinoscrotal hernias. Four patients had previous abdominal

scars precluding laparoscopic access or extraperitoneal dissection. Two patients refused

laparoscopic operations, and two patients with bilateral hernias were randomised to

have the laparoscopic repair under general anaesthesia but elected to have open surgery

on both sides performed during the same operation. Six patients were converted from

laparoscopic to open herniorrhaphy because of intraoperative difficulties. These have been included in analysis of the open group. However retained in the analysis of the laparoscopic group were three patients who had a failed extraperitoneal herniorrhaphy and were converted to the transperitoneal technique.

-175- Figure 18: Breakdown of petient groups after randomisation

Suitable for Day Surgery 104

Open Laparoscopic 54 50

Anaesthetic r¡sk

1

Unsuitable 3

Scars 4

Refused 2

Bilateral 2

Failed 6

Open Laparoscopic 72 32

Transperitoneal Extraperitoneal 3 29

-t76- Eleven patients had bilateral hernias. Seven of these patients were randomised to have the laparoscopic repair with both hernias repaired simultaneously. Two of these patients were randomised to have the open repair and were recorded as separate attendances because each hernia was repaired on a different occasion. As stated above, the remaining two patients with bilateral hernias were randomised to have the laparoscopic repair but elected to have open surgery on both sides performed during the same operation. One hundred and thirteen hernia repairs were performed in total.

From the 72 patients who had an open repair, 14 underwent general anaesthesia and 56 underwent local anaesthesia, of whom I required conversion to a general anaesthetic.

All patients undergoing the laparoscopic repair had general anaesthesia.

Table 10 indicates the type of hernias found at operation. The median follow up period to date is 220 days with a range of 9 to 568 days. All of the patients in the study were male with the exception of 2 females in the open group and 4 in the laparoscopic group.

The measured parameters for the two groups of patients are also listed in Table 10.

-177 - Table 10: Comparison of the two patient groups

Open Laparoscopic

Patients 72 32

Hernias 74 39

Weight (kg) 76 (range 49 - 110) 77 (range 55 - 100)

Age (yrs) 50 (range 17 - 86) 55.5 (range 19 - 78)

Operation time (mins) 50 (range 26 - 155) 87.5 (range 40 - 165)*

Discharge time (mins) 162.5 (range 60 - 2880) 240 (range 95 - 1630)T

Return to work (days) 32 (range 4 - 374) 30.5 (range 4 - 181)

Hernias found at operation

Unilateral indirect 47 l3

Unilateral direct 18 1l

Bilateral indirect 0 6

Bilateral direct 4 2

Bilateral indirect/direct 2 2

Bilateral type not recorded 2 4

Unknown I 1

Values are medians. * p < 0.0001 t p : 0.003

-178- The median operation time for the bilateral operations performed laparoscopically was

115 minutes (range 90 - 160). When bilateral hernia repairs were excluded in both groups, the median operation time was still signifrcantly greater for laparoscopic repairs

(37 mins for open, 69 mins for laparoscopic, p < 0.0001). For patients who were successfully performed as day cases and did not require admission, the median time until post-operative discharge remained significantly shorter for the open group (39 mins for open, 62 mins for laparoscopic, p : 0.0001). The median number of days required to return back to work or normal activity was not significantly different between the open and laparoscopic groups, even when only unilateral hernias were considered, however a trend towards an earlier retum to work in the laparoscopic group was present.

The median activity levels achieved by the two study groups is shown in Figure 19. The median post-operative pain levels between the open and the laparoscopic groups were not significantly different (Figure 20), except on day 3 when patients in the open group recorded significantly greater discomfort (p:0.02). Figure 21 indicates the open group did use significantly more analgesic drugs on days I and 3 (p: 0.0045 and p: 0.001 respectively).

-179- Figure 19: Median activity levels measured on an analogue scale of 0 - 10.

l0 10 10 10 10 10 10 10 10

9 I I

7 7

I b o6 o Lap ø 55 5 ¡ Open :t o 4

3 25

2

0

Preop Day 1 Day 3 Day 10 Day 30 Day 180 Day 360

Figure 20: Median pain levels measured on an analogue scale of 0 - 10.

5 5

45

4

35 35

3

I6 o Lap o 25 ¡ ¡ Open a o- 2

1.5 15 1'l

05 05

00 00 00 0 0

Day 1 Day 3 Day 10 Day 30 Day 180 Day 360 Day 540

Values for Day 30, Day 180, Day 360, and Day 540 (for the open group) were zero

- 180 - Figure 21: Mean number of total analgesic tablets taken post-operatively per patient.

ø s ¡G E LAp o g Open zd

2

Day I Day 3 Day 10 Day 30

Surgical morbidity is detailed in Table I 1. Major complications, defined as requiring re- intervention or admission, were evident in 5 of the 72 patients in the open group (7 %), and 4 of the 32 patients in the laparoscopic group (I2.5 %). Two patients in the open group developed significant postoperative haematomas. One patient in the laparoscopic group suffered bleeding as a result of a port-site complication, and one other patient was re-admitted 2 days postoperatively with wound pain which resolved spontaneously within 24 hours. There have been 2 recurrences in the laparoscopic group, one at 30 days and the other at2I0 days, and no recurrences in the open group. The total number of admissions to the hospital ward was I 1, with 9 admissions (5 open and 4laparo- scopic) as a direct consequence of the surgery, and a fuither 2 admissions in the open group because ofsocial reasons.

-181 - Table 11: Post-operative morbidity

Open Laparoscopic

Admissions (maj or complications) Admissions (maj or complications)

- 2 haematomas - 1 assisted ventilation after

GA

- 1 prophylaxis against resp. - I portsite bleed

complications

- I for observation after GA - I for observation after GA

(unspecified) (unspecified)

- 1 for wound pain (no - 1 for wound pain (no

abnormality detected) abnormality detected)

Minor complications

- t haematomaday 7

- I haematoma day 10

Total 7 (9.7 %) Total 4 (12.5 %)

-182- 5.3.4 Drscussion In considering data detailing the outcome of hernia repair, the statistics collated by

Lichtenstein(Lichenstein et al., 1989) are particularly salient to deficiencies in the current knowledge regarding the status of laparoscopic hernionhaphy. He noted that a

1983 study by the Rand Corporation indicated that at least 10 %o of all primary repairs will fail(Rand Corporation, 1983). Of these, 50 % first appear five or more years after the initial operation, and75 0/o of those hernias that recur become apparent within ten years of the original operation(Lichtenstein and Shore, I976). Furthermore,20 Yo of recurrences will not become apparent until 15 to 25 years postoperatively(Ravitch,

1969).In addition, he stated that many reports are flawed because of inappropriate comparison of different surgical methods, or differences in individual techniques with the same method, and also because significant numbers of patients are lost to follow-up, amongst which are likely to be the highest number of recurrences. In light of such information, it will be some time yet before any reliable data about recurrence following laparoscopic hemiorrhaphy is available. It is clearly too early to make a f,rnal decision on the place of laparoscopy in the spectrum of hernia surgery, and all currently available information, including that herein must be regarded as somewhat shrouded by the preliminary nature of the findings. It is easy to lose cognisance of this basic tenet if one becomes absorbed in the atmosphere of didactic argument put forward by both proponents and opponents of laparoscopic herniorrhaphy operations.

However, as laparoscopic hernia surgery has progressed from elementary to anatomical techniques, a need has emerged to assess specific operative approaches and determine which provides optimal results. In this respect, the information from this study fills the

- 183 - curent void of randomised controlled trials investigating the effrcacy of laparoscopic

extraperitoneal hernionhaphy.

The potential advantages of laparoscopic extraperitoneal hernionhaphy have been

welcomed by surgeons. A totally extraperitoneal approach avoids the inherent technical

dangers of intraperitoneal laparoscopy (see Section 2.2, Complications of laparoscopy).

These general complications may be more imagined than real insofar as herniorrhaphy

is concerned, as a large multi-institutional series of 3229 laparoscopic hernia repairs

failed to document any such general complications not specifically related to technical

aspects of the repair(Phillips et a1.,1995).

The extraperitoneal approach should also avoid any risk of intraperitoneal migration of

prosthetic mesh and the complications associated with adherence of mesh to visceral

structures. Extraperitoneally-placed mesh is not immune from slippage however, and

laparoscopic hemia reculrence has been attributed to this process(Begin, 1993).

Not so welcome for laparoscopic surgeons is the technically demanding nature of

extraperitoneal hernionhaphy beyond that of TAPP or intraperitoneal repairs. A high

degree ofskill and concentration is required for the dissection to stay in the correct

plane during progress from umbilicus to groin. The extraperitoneal operations in this

study took a median of 52 minutes longer than the TAPP repairs cited previously (see

Section 5.2, Transabdominal preperitoneal herniorrhaphy), and a median of almost 40

minutes longer than patients randomised to the open repair. Peritoneal breaches

mandated conversion from extraperitoneal to TAPP repairs in 2 of the 32 laparoscopic patients in this study (6.25 %), and peritoneal breaching was observed in 1l of 155 patients (7 %) in the series reported by Begin(Begin, 1993). This is not an insignificant

- 184 - problem, and the 16 o/o overall conversion rate from extraperitoneal to other operative approaches in this study reached almost unacceptable levels. More recently this dissection has been facilitated by the use of a balloon trocar dissector which obviates the need for CO2 insufflation(Ferzli and Dysarz,1994; Kieturakis et al., 1994). This innovation, first described by Ferzli and Dysart in mid-1994 makes progress in the extraperitoneal plane much easier, and had it been used in this series may have considerably minimised the conversion rate.

Despite the added technical challenge presented by the extraperitoneal repair, surgical morbidity was low (I2.5 %), and comparable to patients randomised to the open repair

(9.7 %).It is of note that the overall complication rate in both open and laparoscopic groups was considerably lower than detected in the previous TAPP study, and can only be attributed to greater familiarity with both laparoscopic hemiorrhaphy and the use of local anaesthesia during open repairs, given that diligence of follow-up was equivalent in both studies. The high rate of post-operative seroma formation after laparoscopic extraperitoneal repairs witnessed in previous series(McKernan, 1993 ; Begin, 1993) was not in evidence amongst the patients in this study. However, the two early recurrences amongst only 32 patients is a cause for concern, as it likely more will become evident with the progression of time, but as explained earlier this parameter will be withheld from consideration of the outcome of laparoscopic hernionhaphy until longer follow-up periods have elapsed.

The results indicate that laparoscopic extraperitoneal inguinal hernia repair is comparable to the conventional open repair with respect to post-operative activity levels and the number of days required for return to work. A median of 30.5 days was required

- 185 - for patients to return to work after the laparoscopic operation, considerably longer than reported in previous uncontrolled studies(McKernan, 1993 ; Begin, 1993 ; Cable et al.,

1994), although correlating well with the patients' median activity levels, which did not uniformly return to normal until day 30 (Figure l9). Patients' pain levels were near to pre-operative levels by day 10, so it appears unlikely that activity and return to work were delayed by the pain of the procedure. It is postulated that demographic differences account for the disparity between the time taken to retum to work in this and other studies. For viable inter-study comparisons to be made about post-operative activity and functional recovery, subjective tools such as the analogue scales commonly used can be dehcient. An objective measurement tool for these variables has been applied to laparoscopic transabdominal preperitoneal herniorrhaphy by Payne(Payne et al., 1994), and would facilitate assimilation of this body of literature if adopted in future studies.

Laparoscopic extraperitoneal inguinal hernia repair is inferior to the conventional open repair in terms of operation time and time to hospital discharge. The technical challenges posed by the extraperitoneal approach have been discussed above, and the shorter discharge time for the open group can be attributed to the more rapid recovery after local anaesthesia.

The laparoscopic herniorrhaphy is superior to the open repair with respect to post- operative pain levels and analgesic requirements. Although during conventional repairs under local anaesthesia patient's tissues were handled gently, patients in this group still suffered more pain on day 3, despite the intake of a significantly greater analgesic load at this time (Figure2l).

- 186 - A methodological shortcoming of this study must be acknowledged. There were considerably fewer patients in the laparoscopic group, introducing the risk of errors in statistical inference. The groups were otherwise well matched for age, sex and weight. It could be argued that the statistical differences that did occur amongst measured variables in laparoscopic patients were highly significant to a degree of magnitude that suggests errors of Type I or Type II would have not influenced the result to a large extent. Although approximately equal numbers of patients were randomised initially, a greater proportion of laparoscopic patients at the Royal Adelaide Hospital crossed-over to the open group. This may indicate inconstancies in surgeons' technical abilities.

In conclusion, laparoscopic extraperitoneal herniorrhaphy has features comparable to, inferior to and superior to conventional open repair. At present, the individual surgeon must balance the disadvantages and potential costs of the prolonged operation and the longer period spent in hospital against the benefits to the patient of less pain and analgesia requirements. Other factors in the assessment of this operation include the technical difflrculty and higher conversion rate, the low incidence of post-operative complications, and the unknown long-term recurrence rate. There will also be certain patients for whom this operation may be unsuitable, such as those with abdominal scars from previous surgery. Laparoscopic extraperitoneal herniorrhaphy is a promising operation, and can no longer be regarded as a Phase I experimental procedure. However on current evidence it is unlikely to become the dominant form of groin hernia repairs.

It should be subjected to further study under trial conditions such that its position can be clarified with the aid of larger study populations and greater technical expertise, whilst awaiting the results of long-term follow-up on recuffence rates.

-t87 - 6. SUMMARY AND CONCLUSIONS

The capability for laparoscopic abdominal surgery has had unprecedented impact on the technical implementation of clinical surgery. The success of laparoscopic cholecystectomy in demonstrating that minimally-invasive procedures can result in significantly shorter hospitalisation, disability, and pain for the patient ensured enduring enthusiasm for this type of access. However the subsequent ardour to adopt other untested laparoscopic procedures challenged, and perhaps even threatened academic swgery to keep pace with contemporary practice yet establish the place of these new innovations by rigorous analysis. It was this atmosphere that was the genesis for the research contained herein.

A historical perspective of operative and technical advances that allowed laparoscopic surgery to reach this state of development is outlined in the introductory chapter. The evolution of surgery in previously inaccessible locations is followed from 1806, when

Bozzini constructed a crude apparatus to visualize the urethra, to the contributions of

Kurt Semm who is the father of operative laparoscopy in the modern era. Widespread adoption of laparoscopy ensued once computer-chip video-cameras became available in

1986. It was this breakthrough which sealed the influential place of laparoscopic surgery in modern surgical practice.

The new information provided by this thesis contributes to a better understanding and a clearer definition for the role of therapeutic laparoscopy in the practice of upper alimentary tract surgery. This was achieved by determining the risks to patients from the physiological effects of laparoscopy, by the development and evaluation of new applications for minimally-invasive surgery, and by assessing the efhcacy of routine laparoscopic procedures which had entered the clinical arena without prior validation.

- 188 - In order to marshall the evidence required to address these issues, several separate studies were required to answer relevant questions, and the contribution of each can now be summarized.

6.1 General problems of laparoscopy

6.1 .1 Temperature regulation Hypothermia is a common postsurgical problem more marked in patients at the extremes of age. Maintenance of perianaesthetic normothermia is of great importance to counteract the numerous deleterious consequences of hypothermia, yet information documenting the impact of laparoscopy on perioperative heat balance is scarce.

The impact of laparoscopy on perioperative heat balance was documented in a study that quantified changes in core temperature over a three-hour period of high-flow carbon-dioxide insufflation in a randomised, controlled trial of six pigs. Each animal was anaesthetised and studied on three occasions under standardised conditions, acting as its own control by insufflation with no gas compared with insufflation by cold gas and warmed gas. Insufflation of carbon-dioxide at high flow rates over a prolonged period of time was shown to result in a significant fall in core temperature. Yet the provision of warmed rather than cold insufflated gas conferred no protection against changes in core temperature, due to the small amount of heat required to warm the gas to body temperature. A much greater effect can be attributed to the latent heat required to saturate the insufflated gas, and most of the hypothermic effect is due to this cause.

It is concluded that humidification of the insufflated carbon-dioxide would largely resolve the problem of laparoscopy-induced hypothermia, but in addition, insufflator tubing should be equipped with an insulated heating wire to prevent warmed gas equilibrating with room temperature as it flows to the patient. However technical

-189- problems remain to be overcome before insufflators can provide humidified, heated gas to minimize perioperative hypothermia, and it is recommended that controlled studies validate the clinical utility of future generations of insufflator apparatus before they enter the marketplace.

6.1.2 Thromboembolism Minimally-invasive access for abdominal operations has been proven to reduce the risk of some postoperative complications. However thromboembolism is not amongst them, by virtue of the absence of any definitive clinical data detailing the incidence of thromboembolism after laparoscopic surgery. Uncontrolled clinical audits suggest the incidence of fatal thromboembolic events may be low, but because most thrombi remain silent, and discharge home often occurs early following laparoscopic procedures, it is likely thal a considerable number of patients are being missed. Further evidence of the problem can be found in case reports which have been published documenting death due to mesenteric thrombosis and infarction.

The factors comprising Virchow's triad are still considered the most important in the pathogenesis of thromboembolism, and include hypercoagulability, impaired blood flow, and vessel wall abnormalities. In the absence of definitive clinical data, experimental evidence documenting changes in one or more of these factors during laparoscopic surgery may be usefully employed to extrapolate the risk of postoperative thrombosis to patients in current clinical practice.

The experimental evidence associating hypercoagulability and laparoscopic surgery was collected in a controlled human study which measured fibrinogen, D-dimer, prothrombin, APTT and platelet levels before, during and after open and laparoscopic

-190- Nissen fundoplication. Hypercoagulability was demonstrated to be present on the first postoperative day compared to preoperative values, irrespective of whether the operation was performed open or laparoscopically. It was concluded that minimally- invasive procedures do not protect against the risk of postoperative hypercoagulability

Impaired femoral venous blood flow during general abdominal sugery occurs as a result of several separate but cumulative mechanisms; loss of the normal calf muscle pump, calf venodilatation during general anaesthesia, and reverse Trendelenburg positioning. Recent evidence suggest that in addition, creation of a tension pneumoperitoneum independently impairs lower limb venous flow. When a pneumoperitoneum is combined with existing factors tending to cause venous stasis during open surgery, their net effect may be greatly magnified.

The potential for laparoscopic insufflation to impair blood flow is not limited to femoral vessels, but may also affect vessels supplying vital intraabdominal organs. This hypothesis was investigated by the use of radiolabelled microspheres to determine blood flow distributions in a pig model. Proof of decreased blood flow at the tissue level in the setting of laparoscopic abdominal surgery was not established. It was concluded that a definitive investigation to assimilate such evidence would be feasible using the microsphere technique, if the study incorporated larger sample populations and methodolo gical refi nements

There is currently no experimental evidence to suggest that laparoscopic surgery causes endothelial damage. However, a widely held theory postulates that operative venodilatation resultant from insufflation and general anaesthesia may cause endothelial cracking, followed by exposure of subendothelial collagen, platelet adhesion, and

-l9t- activation of the coagulation cascade. The site of endothelial damage may then act as a nidus for thrombosis formation during laparoscopy

In summary, laparoscopy can not be said to be minimally-invasive in terms of the development of postoperative thrombosis. Laparoscopy appears to negatively influence all three elements of Virchow's triad, sometimes beyond that of open surgery, and may result in a cumulatively greater risk for the development of venous thromboembolism

Until definitive clinical studies become available, it is recommended that patients undergoing laparoscopic operations be considered to be of equal or possibly higher risk than their open counterparts, and that appropriate prophylaxis be instituted.

6.2 Development and evaluation of new applications ¡n laparoscopic gastro¡ ntest¡nal su rgery 6.2.1 Oesophagectomy Subtotal oesophagectomy and immediate oesophagogastric reconstruction is a favoured option for cure or palliation of oesophageal carcinoma. The conventional approach involves a thoracotomy and laparotomy exposing the patient to the attendant pulmonary and intrathoracic complications. Alternative approaches to oesophagectomy without thoracotomy have failed to diminish the complication rate and may compromise the chance of cure. An endoscopic approach to the surgical management of oesophageal carcinoma is considered to be an evolving solution because it rernoves the need for thoracotomy and laparotomy but adheres to established oncologic principles.

A 3-step minimally-invasive operation was devised consisting of thoracoscopic oesophageal dissection, laparoscopic gastric mobilisation and thoracoscopic end-to-end oesophago-gastric anastomosis using a circular endoluminal stapler. This total endosurgical oesophagectomy was shown to be technically feasible in an animal model,

-192- and the stapled oesophagogastric anastomosis was capable of being safely performed in a manner comparable to the conventional procedure.

It is concluded that endosurgical treatment of oesophageal carcinoma has potential to reduce the number of postoperative complications or deaths. However, it will need to demonstrate clear superiority over existing specific treatment modalities before it could be advocated to enter clinical practice.

6.2.2 Highly selective vagotomy Since Latarjetin 1920 and Dragstedt in 1943 demonstrated the therapeutic utility of vagotomy for the treatment of patients with peptic ulcer disease, the operation has undergone continuous development and refinement in an effort to eradicate troublesome side-effects such as disturbed gastric emptying, dumping and diarrhoea. In 1969

Johnston & Wilkinson demonstrated that it was possible to divide only the vagal branches to the parietal cells, preserving the nerves of Latarjet and motor innervation to the pylorus and antrum. This highly selective vagotomy reduces acid secretion as effectively as truncal vagotomy, and is very safe with an operative mortality rate well under lYo.The innervated antrum provides undisturbed solid emptying, and preservation of the pylorus reduces the tendency for duodeno-gastric reflux.

Open highly selective vagotomy has withstood the rigours of objective evaluation to become the optimal surgical treatment for chronic duodenal ulcer refractory to medical therapy in many centres. Laparoscopic highly selective vagotomy has not been subjected to the same scrutiny before entering clinical practice. A variety of laparoscopic vagotomy procedures have been developed but unfortunately the multiplicity of techniques combined with low referral rates for surgery has meant that

-193- the experience of each group has been limited to relatively small series. No long-term clinical results are available by which the effrcacy of laparoscopic vagotomy can be definitively judged. To address this deficiency in the present state of knowledge, a controlled animal study was conducted to demonstrate the physiological validity of laparoscopic vagotomy.

Gastric acid output was measured by an aspiration technique, liquid gastric emptying was calculated by the double sampling technique of George, and gastro-oesophageal reflux was assessed by 8 hour ambulatory pH monitoring. Laparoscopic highly selective vagotomy was shown to be as effective as its open counterpart in reducing basal acid output, and did not interfere with liquid gastric emptying in contrast to the open operation. Neither open nor laparoscopic highly selective vagotomy were observed to precipitate gastro-oesophageal reflux. It is concluded that the continued use of laparoscopic highly selective vagotomy in clinical practice is appropriate.

6.2.3 Gastrostomy Gastrostomy for enteral feeding or gastric decompression has traditionally been performed by open surgery. Recent reports indicating a lower morbidity and mortality rate for percutaneous endoscopic gastrostomy compared with open gastrostomy have justified the more minimally invasive approach that percutaneous techniques provide.

Percutaneous endoscopic gastrostomy is not immune from complications, in particular as a result of insecure fixation of the stomach to the anterior abdominal wall, and post- procedural reflux and aspiration pneumonia.

Following a review of the available literature on the feasibility of laparoscopic gastrostomy, a viable technique was developed to offer an alternative form of enteral access, and successfully performed in the case reported. The procedure incorporates a

-194- modification to existing laparoscopic techniques whereby the anchoring sutures are hand-tied and buried in a subcutaneous pouch. Laparoscopic gastrostomy is less invasive than open gastrostomy, and can be easily performed by General Surgeons with basic laparoscopic skills without the assistance of an endoscopist. In some respects it provides benefits surpassing percutaneous endoscopic gastrostomy, because the poor apposition between the stomach and anterior abdominal wall can be prevented, and prophylaxis against reflux and aspiration pneumonia can be easily incorporated into the procedure. It is concluded that laparoscopic enteral access has emerged as the preferred approach when percutaneous endoscopic gastrostomy is contraindicated or has failed.

6.3 Assessment of routine laparoscopic procedures Although inguinal hernias are not anatomically located in the upper gastrointestinal tract, their treatment comprises a significant and controversial component of the practice of upper gastrointestinal surgery. A wide variety of eponymous traditional methods of inguinal hernia repair have been developed from the time of Bassini's original description in 1887, differentiated primarily in their management of the posterior inguinal wall

Laparoscopic herniorrhaphy was first performedin 1979, and operative techniques have evolved into two main groups; plug or patch repairs. Many surgeons have abandoned the plugging techniques because of the high recurrence rate, but patch repairs remain popular, and three different types have been described; transabdominal intraperitoneal, transabdominal preperitoneal, and extraperitoneal. However, as laparoscopic hernia surgery has progressed from elementary to anatomical techniques, a need has emerged to resolve the indications for laparoscopic herniorrhaphy, and to assess which operative approach provides optimal results.

-195- Two randomised-controlled trials were conducted in a day surgery setting. A standard conventional open hemioplasty was compared with transabdominal preperitoneal laparoscopic hemiorrhaphy, and extraperitoneal laparoscopic herniorrhaphy respectively. The laparoscopic transabdominal preperitoneal approach provided no advantages in duration of operation, postoperative pain or time taken to return to work.

It was concluded that this operation should be confined to recurrent, bilateral or undiagnosed hernias only, rather than emerge as the routine operation. In contrast, some features of laparoscopic extraperitoneal hemiorrhaphy were superior to the open repair, indicating it should no longer be regarded only as a Phase I experimental procedure

However it was concluded that laparoscopic extraperitoneal hernionhaphy should not enter clinical practice until subjected to fuither study under trial conditions with the aid of larger study populations and greater technical expertise, whilst the results of long- term recurrence rates are awaited.

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