Transanal Total Mesorectal Excision of the Rectum

IP 1184 [IPGXXX]

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE INTERVENTIONAL PROCEDURES PROGRAMME Transanal total mesorectal excision of the rectum

This procedure is used for patients who need to have their whole rectum removed (for example, patients with rectal cancer or chronic inflammatory bowel disease that has not responded well enough to treatment). The rectum is removed using instruments introduced through the anus, combined with laparoscopic (keyhole) surgery through the abdomen, rather than through a long incision in the lower abdomen. Introduction

The National Institute for Health and Care Excellence (NICE) has prepared this interventional procedure (IP) overview to help members of the Interventional Procedures Advisory Committee (IPAC) make recommendations about the safety and efficacy of an interventional procedure. It is based on a rapid review of the medical literature and specialist opinion. It should not be regarded as a definitive assessment of the procedure. Date prepared

This IP overview was prepared in April 2014. Procedure name

 Transanal total mesorectal excision of the rectum

Specialist societies

 Association of Coloproctology of Great Britain and Ireland  British Association of Surgical Oncology (BASO).

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Description

Indications and current treatment

Transanal total mesorectal excision (TaTME) can be used to treat malignant or benign disease of the rectum.

Malignant disease: The incidence of rectal cancer rises sharply with age. Symptoms include rectal bleeding and change in bowel habit, although the early stages may be asymptomatic. Treatment of rectal cancer depends upon its stage which is conventionally assessed using Dukes’ classification system:

 stage A – confined to the lining of the rectum  stage B – grown into the muscle wall  stage C – spread to at least one lymph node in the area  stage D – spread to another organ in the body.

Surgery is the main treatment modality for patients with locally confined disease. It involves resection of the affected part of the rectum, with or without preservation of the anus (and formation of a colostomy when preservation of the anus is not technically possible). Adjunctive radiotherapy and chemotherapy may also be used to reduce the risk of local recurrence and prevent metastatic disease.

Benign disease: Benign conditions that may lead to the need for resection of the rectum include ulcerative colitis and Crohn’s disease. Both are chronic conditions, characterised by periods of clinical relapse and remission.

Treatment depends on the severity and extent of the disease and is aimed at reducing the frequency and severity of recurrences. Drug therapy, which may include corticosteroids and immunosuppressive agents (such as azathioprine), usually controls the disease adequately. For more severe cases, treatment with a monoclonal antibody (such as infliximab) may be considered. Surgical removal of the affected areas may be necessary for severe cases that don’t respond to medical treatment.

What the procedure involves

TaTME aims to improve the clinical outcome of rectal excision, and to reduce the length of stay in hospital and morbidity after surgery. It may facilitate proctectomy that would otherwise be difficult in people with a narrow pelvis or high body mass index or where the position of the tumour is low in the rectum.

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Before surgery, the patient has bowel preparation and prophylactic antibiotics. With the patient under general anaesthesia and in the lithotomy position, an operating platform is inserted into the anus using endoscopic guidance. Laparoscopic instruments are usually inserted at this stage in order to assist with identification of the plane of excision for mesorectal dissection, mobilisation of the left colon and subsequent creation of an ileostomy. Dissection of the rectum is done through the anal platform. A purse-string suture is used to close the rectal lumen and then full-thickness proctectomy is done. The specimen can be removed through the transanal platform or, if the tumour is large, through the abdomen using a laparoscope. Anastomosis to connect the colon and the anus can be done using sutures (hand-sewn technique) or staples. When anastomosis is not possible, the patient is given a temporary or permanent colostomy. When an anastomosis is done, a temporary ileostomy is usually created.

Outcome measures

Quality of the mesorectal excision. Quirke's grading assesses the quality of the mesorectal envelope from 3 indicating a completely intact specimen to 1 indicating an incomplete mesorectal envelope. It is assigned by pathologists. Literature review

Rapid review of literature

The medical literature was searched to identify studies and reviews relevant to transanal total mesorectal excision of the rectum. Searches were conducted of the following databases, covering the period from their commencement to 16 April 2014: MEDLINE, PREMEDLINE, EMBASE, Cochrane Library and other databases. Trial registries and the Internet were also searched. No language restriction was applied to the searches (see appendix C for details of search strategy). Relevant published studies identified during consultation or resolution that are published after this date may also be considered for inclusion.

The following selection criteria (table 1) were applied to the abstracts identified by the literature search. Where selection criteria could not be determined from the abstracts the full paper was retrieved.

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Table 1 Inclusion criteria for identification of relevant studies Characteristic Criteria Publication type Clinical studies were included. Emphasis was placed on identifying good quality studies. Abstracts were excluded where no clinical outcomes were reported, or where the paper was a review, editorial, or a laboratory or animal study. Conference abstracts were also excluded because of the difficulty of appraising study methodology, unless they reported specific adverse events that were not available in the published literature. Patient Patients with benign or malignant rectal disease. Intervention/test Transanal total mesorectal excision of the rectum Outcome Articles were retrieved if the abstract contained information relevant to the safety and/or efficacy. Language Non-English-language articles were excluded unless they were thought to add substantively to the English-language evidence base.

List of studies included in the IP overview

This IP overview is based on approximately 170 patients from 1 non-randomised comparative study1 and 9 case series2-10.

Other studies that were considered to be relevant to the procedure but were not included in the main extraction table (table 2) have been listed in appendix A.

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Table 2 Summary of key efficacy and safety findings on transanal total mesorectal excision of the rectum

Study 1 Velthuis S (2014)

Details Study type Non-randomised comparative study Country Netherlands Recruitment period 2012-13 (for transanal TME) and 2011-2012 (for laparoscopic TME) Study population and n=50 patients with distal or mid rectum carcinomas (25 transanal TME versus 25 laparoscopic TME) number Age and sex Transanal TME mean 64 years [range 49 to 86 years]; 72% (18/25) male. Laparoscopic TME mean 65 years [range 38 to 81 years]; 72% (18/25) male. Mean BMI: 25 kg/ m2 [range 20 to 36kg/ m2] (transanal TME) versus mean BMI: 27 kg/ m2 [range 21 to 34 kg/ m2] (laparoscopic TME) Patient selection criteria Transanal TME group: consecutive patients with histologically proven distal or mid rectum carcinomas, without evidence of distant metastases. Exclusion criteria: T4 tumours or previous abdominal surgery. Cohort matched for gender and type of procedure with a cohort of patients who underwent traditional laparoscopic low anterior resection (LAR) or abdominoperineal resection (APR) by TME principles. Technique Patients received mechanical bowel preparation before surgery, epidural analgesia for pain control after surgery, and prophylactic antibiotics. Patients were treated according to enhanced recovery after surgery (ERAS) guidelines. Transanal TME: a Scott retractor (Lone Star Medical Products) facilitated the full-thickness circumferential transection. Either a SILS port (Covidien) or a GelPOINT Path Transanal Access Platform (Applied Medical) were introduced into the anus and used for the TME. The laparoscopic part of the procedure was performed using a second SILS Port introduced at the future ileostomy site in the abdomen. A coloanal anastomosis was made either by hand or by using an EEA Haemorrhoid Stapler (Covidien). An ileostomy was created in all patients. Traditional laparoscopic TME: 4 trocars were used. An anastomosis was created by using an EEA Haemorrhoid Stapler (Covidien) after which an ileostomy was created. In case of distal tumours which needed an APR, an intersphincteric dissection was performed before closure of the rectal stump. Follow-up Not reported. Conflict of interest/source None. of funding

Analysis Follow-up issues: none. Study design issues:  Matched case control study.  The pathologist was not informed about the type of surgery performed.  Retrospective study.  Both procedures were performed by 2 experienced laparoscopic surgeons. Study population issues:  Possible patients overlap with Velthuis 2013 (study 9).  2 groups were similar in the following characteristics: neoadjuvant therapy received, tumour distance to the anal verge, tumour stage, tumour size, lymph nodes status and number of lymph nodes.  Mean distance of the tumour to the anal verge comparable in both groups.  Neoadjuvant therapy: 76% (19/25) versus 80% (20/25) of patients received radiotherapy, completed 1 week before surgery and 24% (6/25) versus 20% (5/25) of patients received chemoradiotherapy completed 6 weeks before surgery. Other issues: In the first 5 patients, the surgeons started the dissection with the transanal phase. The sequence of phases was then reversed because of nuisance due to pneumatosis of the retroperitoneum while performing the abdominal phase after the transanal phase.

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 50 (25 transanal TME versus 25 laparoscopic TME) Not reported

Resection and staging characteristics Characteristic Transanal TME Laparoscopic TME P value (n=25) (n=25) Number of lymph nodes Mean (range) 14 (7-24) 13 (1-36) 0.42* Length of resected specimen (cm) Median (range) 18 (12-28) 20 (10-80) Circumferential resection margin involvement Positive (<2mm) 4% (1/25) 8% (2/25) Circumferential resection margin (mm) Mean (range) 13 (1.5-30) 12 (0-25) Distal resection margin (mm) Median (range) 23 (5-80) 25 (0-55) * Independent T test

Macroscopic quality of mesorectum Transanal TME (n=25) Laparoscopic TME (n=25) P value Mesorectum total Complete 96% (24/25) 72% (18/25) <0.05** Nearly complete 4% (1/25) 8% (2/25) Incomplete 0 20% (5/25) Mesorectum LAR Complete 100% (19/19) 84% (16/19) Nearly complete 0 5% (1/19) Incomplete 0 11% (2/19) Mesorectum APR Complete 83% (5/6) Nearly complete 17% (1/6) Incomplete 0 ** Pearson’s chi-squared test

Abbreviations used: APR, abdominoperineal resection; ASA, American society of anesthesiology; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CI, confidence interval; CRM, circumferential resection margin; CRT, chemoradiotherapy; ECOG, eastern cooperative oncology group; EEA, end-to-end anastomotic; FOLFOX, 5-FU + oxaliplatin; IMA, inferior mesenteric artery; ISR, intersphincteric resection; LAR, low anterior resection; LN, Lymph nodes; LOS, hospital length of stay; LRR, locoregional recurrence; MRI, magnetic resonance imaging; N, no; POSSUM , physiological and operative severity score for the enumeration of mortality and morbidity; SD, standard deviation; SE, standard error; SILS, single-incision laparoscopic surgery; TAEP, transanal endoscopic proctectomy; TAMIS, transanal minimally invasive surgery; TEMS, transanal endoscopic microsurgery; TEO, transanal endoscopic operation; TES, transanal endoscopic surgery; TME, total mesorectal excision; Y, yes.

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Study 2 Rouanet P (2013)

Details Study type Case series Country France Recruitment period 2009-11 Study population and n=30 patients with rectal cancer number Age and sex Median 65 years [range 43 to 82 years]; 100% (30/30) male Median BMI: 26 kg/ m2 [range 21 to 32.4 kg/ m2] Patient selection criteria All patients underwent laparoscopic resection by using a transanal endoscopic proctectomy (TAEP) procedure for rectal tumours. Indications for TAEP: combination of difficult anatomical conditions such as narrow pelvis (defined as a distance between the ischial tuberosities <10 cm and between the ischial spines< 12cm), fatty mesorectum, high BMI, large prostate, presence of fibrosis, with unfavourable tumour characteristics including a large anterior tumour and a weak predictive anterior radial margin (≤1mm) on MRI. The decision to perform the TAEP was made either preoperatively according to tumour and patient MRI characteristics, or during examination under general anaesthesia, or after unexpected intraoperative findings in relation to the pelvic anatomy or tumour bulk. Technique Transanal endoscopic proctectomy procedure combined with standard laparoscopy. Patients received mechanical bowel preparation the day before surgery and prophylactic antibiotics during the procedure. A TEO proctoscope with a laparoscopic insufflator and a Harmonic scalpel (Ethicon endo-surgery) were used for the transanal dissection. In most cases, the surgeons began the TME dissection posteriorly. After the removal of the TEO device, the TME resection was finished with a classic abdominal laparoscopic approach. The surgeons removed the specimen either by a small suprapubic incision or through the anus and they performed a coloanal anastomosis. In all cases, the surgeons constructed a covering loop ileostomy. Follow-up Median 21 months Conflict of interest/source None reported. of funding

Analysis Follow-up issues: overall, 93% (27/29) patients completed the neoadjuvant treatment; 2 patients discontinued chemotherapy because of infectious complications or cardiotoxicity. Study design issues: selection bias related to the study cohort exclusively composed of high-risk patients with locally advanced tumours, sometimes with synchronous metastases. Study population issues: 2  27% (8/30) patients had a BMI ≥ 30 kg/m .  97% (29/30) patients received neoadjuvant treatment: 70% (21/30) long-courses chemoradiotherapy, 17% (5/30) induction chemotherapy followed by chemoradiotherapy and 10% (3/30) intensive chemotherapy alone (including 2 for locoregional recurrence and 1 because of previous pelvic radiotherapy).  10% (3/30) of patients had a diagnosis of synchronous liver or lung metastases.  Main indications for TAEP: narrow pelvis (77% [23/30]), fatty mesorectum (47% [14/30]), large and anterior tumour (73% [22/30]), previous radiotherapy (7% [2/30]). Other issues: there might be an overlap between 1 death and 1 locoregional recurrence for the clinical outcomes at 21 months.

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 30  Reoperation (< 30 days): 7% (2/30) Surgical outcome  No 30-day postoperative mortality. Surgical outcome Patients  Overall 30-day postoperative morbidity rate: 30% TME grading Quirke 3 (=complete) 100% (30/30) (9/30). Conversion to open surgery 7% (2/30)  Postoperative blood transfusion: 20% (6/30) Cause: posterior fixity of the tumour Intraoperative complications Median lymph node yield (range) 13 (8-32) Complication Patients Other Urethral injury 6.7% 1 due to a difficult dissection of (2/30) an anterior bulky tumour and 1 Clinical outcome at median 21-month follow-up due to the presence of a Outcome Patients Other concurrent prostatic Disease-free 43.3% carcinoma. These 2 localised survival (13/30) wounds were diagnosed and sutured under TEO. The Cancer-related 13.3% One death due to an isolated postoperative period was free deaths (4/30) locoregional recurrence (LRR) and 1 of any complications for both death caused by cirrhosis. patients. Locoregional 40% Four patients had a LRR alone (1 Air embolism 1 patient Patient showed an oxygen or distant (12/30) developed potentially resectable desaturation with suspicion of recurrence LRR 2 years after an R1 resection air embolism after the for a ypT3N1 residual tumour; 1 had posterior prostate resection. LRR 6 months after curative resection for an initial pT4 prostate anterior tumour staged ypT2N0 with Postoperative complications a CRM of 11mm on specimen; 1 was Early Patients Other classified LRR for a persistent morbidity disease of a T4 prostatic tumour that (< 30 days) remained ypT4R2 on specimen; 1 had perineal skin recurrence cured Sepsis 1 peritonitis was by abdominoperineal resection). Peritonitis 6.7% (2/30) secondary to a minor ileal wound without a direct

Septic shock 1 patient link with the TAEP Survival estimation procedure. One patient Survival Time Value 95% CI required critical care because of a sepsis Overall survival 12 months 96.6% 78.0 to 99.5 (partly explained by his Overall survival 24 months 80.5% 53.0 to 92.9 general condition and Relapse-free survival 12 months 93.3% 75.9 to 98.3 comorbidities including a lymphoma associated Relapse-free survival 24 months 88.9% 69.0 to 96.3 with chronic renal failure and diabetes). Pathological findings Bowel 6.7% (2/30) Both patients recovered Characteristic Patients obstruction after medical treatment. Median CRM, mm (range) 7 (0-17) Anastomotic 1 patient ≤1 13% (4/30) leakage >1 87% (26/30) Transient 6.7% (2/30) postoperative Median distal margins, mm (range) 9 (3-40) urinary disorder Curative resection R0 87% (26/30)  Incontinence 12 months after stoma closure: - 15% of patients reported incontinence to liquids, 35% Median operative time: 304 min (range 120 to 432 min) to gas, and 25% had stool fragmentation (only Median hospitalisation time: 14 days (range 9 to 25 days) percentages reported). - Median Wexner score (from 0 to 20 with 0 indicating perfect faecal continence and 20 complete faecal incontinence): 11.

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Abbreviations used: APR, abdominoperineal resection; ASA, American Society of Anesthesiology; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CI, confidence interval; CRM, circumferential resection margin; CRT, chemoradiotherapy; ECOG, eastern cooperative oncology group; EEA, end-to-end anastomotic; FOLFOX, 5-FU + oxaliplatin; IMA, inferior mesenteric artery; ISR, intersphincteric resection; LAR, low anterior resection; LN, Lymph nodes; LOS, hospital length of stay; LRR, locoregional recurrence; MRI, magnetic resonance imaging; N, no; POSSUM , physiological and operative severity score for the enumeration of mortality and morbidity; SD, standard deviation; SE, standard error; SILS, single-incision laparoscopic surgery; TAEP, transanal endoscopic proctectomy; TAMIS, transanal minimally invasive surgery; TEMS, transanal endoscopic microsurgery; TEO, transanal endoscopic operation; TES, transanal endoscopic surgery; TME, total mesorectal excision; Y, yes.

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Study 3 Atallah S (2013)

Details Study type Case series Country Not reported Recruitment period 2010-13 Study population and n=20 patients with rectal cancer number Age and sex Median 57 years [range 36 to 73 years]; 70% (14/20) male Patient selection criteria Locally advanced rectal cancer of the middle and distal rectum. Distal rectal cancer in combination with obesity and anatomic constraints such as a narrow male pelvis. Technique Transanal total mesorectal excision (TME) using the transanal minimally invasive surgery (TAMIS) platform. TAMIS-TME uses a combined abdominal approach for proximal colonic mobilization and for initiation of the medial to lateral approach, as well as construction of a diverting or permanent stoma. The approach used was laparoscopic + TAMIS-TME in 55% (11/20) of the patients, robotic-assisted + TAMIS-TME in 30% (6/20) of the patients and open + TAMIS-TME in 15% (3/20) of the patients. The abdominal portion of the operation was completed first. For transanal TME using TAMIS, the patient was placed in the dorsal lithotomy position. For TAMIS access, a GelPOINT® Path Transanal Access Platform (Applied Medical) was used in 90% (18/20) of the patients and a SILSTM Port (Covidien) was used in 10% (2/20) of the patients. For low-lying tumours, an intersphincteric dissection was started prior to admission of a TAMIS port, under direct vision using an anorectal retractor and electrocautery. For higher lesions, the TAMIS port was introduced first and the purse-string suture was performed at a safe distance from the tumour distally. Follow-up Median 6 months [range 1 to 24 months] Conflict of None interest/source of funding

Analysis Follow-up issues: anoscopy, rigid proctosigmoidoscopy, and digital rectal examination were performed every 3 months during the follow-up period. Study design issues:  Operations were undertaken by 4 experienced surgeons.  Initially, 23 patients were selected to undergo TAMIS-TME but 3 were excluded from further study because their procedures were completed for benign disease (ulcerative colitis).  3 different methods were used for the abdominal portion of the operation as well as variations in the approach to transanal TME.  When robotic-assisted + TAMIS-TME approach was used, in one case robotic-assisted transanal surgery was performed.  When laparoscopic + TAMIS-TME approach was used, in one case TAMIS-assisted APR was performed. Study population issues: 2  30% (6/20) patients had a BMI ≥ 30 kg/m .  85% (17/20) patients received neoadjuvant chemoradiotherapy. Other issues:  The TME resection quality was not formally graded for 1 patient.  Ileostomy closure was performed within the first 3 months after TAMIS-TME in 64% (9/14) of patients who underwent diversion of the faecal stream. The remaining 36% (5/14) were closed within 1 year.

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 20  No intraoperative complications.  No 30-day postoperative mortality. Surgical outcomes  Death at 8 weeks: 1 patient died Characteristic Value suddenly, without prodrome, 8 weeks after TAMIS-TME. The cause of death TME grading was acute pulmonary embolism. Quirke 3 55% (11/20)  Mean estimated blood loss: 153ml Quirke 2 30% (6/20) (range 30 to 500 ml) Quirke 3 + 2 (complete or nearly complete 85% (17/20) mesorectal envelope) Surgical complications after surgery Quirke 1 10% (2/20) Early morbidity Patients Unknown 5% (1/20) Pelvic abscess 20% (4/20) Lymph node harvest* 22.5 (9-51) Prolonged ileus 20% (4/20) Negative surgical margins (distal and 90% (18/20) circumferential) Wound infection 10% (2/20) Recurrence rate 1 patient developed distant Pneumonia 1 patient metastasis 9 months after Acute renal failure 1 patient surgery (case 4). However he Anastomotic leak 1 patient was not eligible to receive adjuvant chemotherapy due to Late morbidity Patients grade III toxicity encountered Anastomotic 20% (4/20) during neoadjuvant therapy. strictures* *Median (range) Peri-anastomotic 10% (2/20) fluid collections Mean operative time: 243 min (range 140 to 495 min) *Subclinical structuring noted on physical exam, patients asymptomatic. Mean postoperative hospital length of stay: 4.5 days (range 3 to 24 days) All surgical complications were managed

conservatively and resolved without sequelae except the anastomotic leak which necessitated permanent end colostomy. The anastomotic disruption was secondary to ischemia. Faecal incontinence after ileostomy closure  Most patients stated they had mild faecal incontinence (< 1 accident/ day).  5% (1/20) of patients reported lifestyle- limiting incontinence which had not improved 12 months post-resection. Abbreviations used: APR, abdominoperineal resection; ASA, American Society of Anesthesiology; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CI, confidence interval; CRM, circumferential resection margin; CRT, chemoradiotherapy; ECOG, eastern cooperative oncology group; EEA, end-to-end anastomotic; FOLFOX, 5-FU + oxaliplatin; IMA, inferior mesenteric artery; ISR, intersphincteric resection; LAR, low anterior resection; LN, Lymph nodes; LOS, hospital length of stay; LRR, locoregional recurrence; MRI, magnetic resonance imaging; N, no; POSSUM , physiological and operative severity score for the enumeration of mortality and morbidity; SD, standard deviation; SE, standard error; SILS, single-incision laparoscopic surgery; TAEP, transanal endoscopic proctectomy; TAMIS, transanal minimally invasive surgery; TEMS, transanal endoscopic microsurgery; TEO, transanal endoscopic operation; TES, transanal endoscopic surgery; TME, total mesorectal excision; Y, yes.

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Study 4 De Lacy AM (2013)

Details Study type Case series Country Spain Recruitment period 2011-2012 Study population and n=20 patients with rectal adenocarcinoma or high-grade dysplasia arising from rectal polyps number Age and sex Mean 65 years [range 44 to 77 years]; 55% (11/20) male Mean BMI: 25.3 kg/ m2 [range 19 to 33 kg/ m2] Patient selection criteria Biopsy-proven rectal adenocarcinoma or high-grade dysplasia arising from rectal polyps. Exclusion criteria: BMI>35 kg/m2, presence of cT4 disease, tumour recurrence, contraindications to pneumoperitoneum. Technique The day before surgery, patients underwent anterograde lavage with Bohn solution. Prophylactic antibiotics were administered intravenously. Patients placed in lithotomy position. Combined transrectal and laparoscopy dissection (using 3 ports) for all cases using a multiport rectal device (GelPOINT Path Transanal; Applied Medical, USA). A 3D flexible-tip endoscope (3D EndoEye 5 mm flexible-tip videolaparoscope; Olympus KeyMed, Europe) was introduced through the single port device. Full-thickness rectal transection was initiated circumferentially and the posterior dissection was done in accordance with TME principles. The mesorectal plane was dissected entirely transanally up to the level of peritoneal reflection in the superior pelvis. In all cases, the specimen was removed transanally. Proximal colonic resection was performed extracorporeally. Pain control via epidural catheter perioperatively. Follow-up 30 days Conflict of Dr A Lacy is a consultant for Covidien and Olympus Medical. Dr P Sylla has received an honorarium from interest/source of Genzyme for consulting and an honorarium from Applied Medical for teaching. Dr Rattner is a consultant for funding Olympus.

Analysis

Follow-up issues: none Study design issues: none Study population issues:  70% (14/20) patients received neoadjuvant chemoradiotherapy completed 6-8 weeks before surgery.  Authors stated ‘study has bias in the selection of patients’.  25% patients (5/20) had a previous abdominal surgery.  75% patients had mild systemic disease and 25% patients had severe, non incapacitating systemic disease (American Society of Anesthesiologists classification).  15% (3/20) patients had high-grade dysplasia polyps. Other issues: none

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 20 Complications after surgery Postoperative Value Complication Pathological case characteristics morbidity, Clavien- Dindo grade Characteristic Value I 10% 2 patients had urinary Distal margin* 2.6 ± 1.6 cm (0.7-5) (2/20) retention Circumferential margin* 1.8 ± 0.7 cm (0.5-3) II 10% 1 patient had Number of retrieved lymph nodes* 15.9 ± 4.3 (2/20) postoperative ileus Number of patients with lymph nodes 80% (16/20) and 1 patient had retrieved > 12 severe dehydration Pathological stage due to increased ileostomy output High-grade dysplasia polyps, ypTNM 10% (2/20) III 0% stage IV 0% I 20% (4/20) II 35% (7/20) V (death) 0% III 30% (6/20) IV 5% (1/20) No additional complications or readmissions at 15 and 30 days. *mean ± SE (range)

 Distal and circumferential margins free of tumour (confirmed Mean estimated blood loss: 45 ± 15 mL (range 10 to 110 by pathologic analysis). mL)  Quality of the mesorectal plane reported as satisfactory in all

the specimens.  No laparoscopic/ open conversion.

Recovery outcomes after surgery Characteristic Value Days until oral intake* 1.8 ± 0.9 Days until regular diet* 3.8 ± 2.1 Days until discharge* 5.8 ± 2.6 Pain control with oral analgesia* 5.4 ± 2.2 *mean ± SE

Mean operative time: 234.7 ± 56 min (range 150 to 325 min) Mean postoperative hospital length of stay: 6.5 ± 3.1 days

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Study 5 Wolthuis AM (2014)

Details Study type Case series Country Belgium Recruitment period 2012 to 2013 Study population n=14 patients with benign disease (64.3% [9/14]) and American society of and number Anaesthesiology (ASA) grade 3 patients with a rectal carcinoma (35.7% [5/14]) who required either intersphincteric proctectomy or coloanal anastomosis. Age and sex Median 65 years [range 28 to 87 years]; 36% (5/14) male Median BMI: 25 kg/ m2 [range 17 to 32 kg/ m2] Patient selection Consecutive patients who were candidates for either proctectomy or manual coloanal criteria anastomosis for benign disease. Exclusion criteria: locally advanced rectal cancer or neoadjuvant chemoradiotherapy. Technique Patients had standard preoperative bowel preparation the day before surgery. All procedures were performed with the patient under general anaesthesia and prophylactic antibiotics were given. First, a Lone Star Retractor (CooperSurgical) was inserted. After a sleeve mucosectomy or intersphincteric dissection, a Gelpoint path (Applied Medical) was placed into the anal muscular cuff. Standard laparoscopic insufflator and ‘Chip-on-the-tip’ laparoscope A50002A (EndoEye, Olympus Medical Europe Holding GmbH) were used. In case of a reconstruction, a handsewn straight coloanal anastomosis was made. Follow-up Median 6 months [range 2 to 14 months] Conflict of Not reported. interest/source of funding

Analysis Follow-up issues: none Study design issues: none Study population issues:  Benign indications were intractable supralevatoric fistula (7.1% [1/14]), refractory faecal incontinence (7.1% [1/14]),rectovaginal fistula and incontinence after a failed stapled transanal resection of the rectum procedure (7.1% [1/14]), iatrogenic rectal stenosis after stapled hemorrhoidopexy (14.3% [2/14]), Crohn’s proctitis (7.1% [1/14]), ulcerative colitis (7.1% [1/14]), and circular tubulovillous adenoma (14.3% [2/14]). Other issues: none

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 14 Intraoperative difficulties hindering Conversion rate to open proctectomy dissection: Type of Patie Conversion Reason Type of intraoperative Patients procedure nts rate to open difficulty proctectomy Maintaining insufflation 14.3% Laparoscopically 79% 18% (2/11) Extensive (2/14) assisted (11/1 intra- Bleeding 1 patient procedure (hybrid 4) abdominal Fibrosis after 1 patient TAMIS-rectal adhesions radiotherapy for excision) after prostate cancer previous laparotomy Rectal perforation in a 1 patient and BMI= patient who had rectal 32 kg/m2 cancer with metastasis for 1 of the to the liver and the patients lungs Pure TAMIS- 21% None N/A rectal excision (3/14) Postoperative complications Postoperative Patients Complication morbidity, Operative characteristics Clavien-Dindo Type of procedure Patients grade Hand-sewn coloanal anastomosis 50% (7/14) I 43% 2 transient  with temporary defunctioning (6/14) fever 3 urinary tract ileostomy* 43% (3/7) infections TAMIS-rectal excision with end 43% (6/14) 1 small pelvic colostomy hematoma Proctocolectomy with end ileostomy 7% (1/14) requiring no surgical *All ileostomies had been closed when the paper went to treatment press. II 0%

Median operative time TAMIS: 55 min (range 35 to 95min) III 0% [calculated by IP analyst] IV 0% Mean total operating time: 148 min (range 85 to 250min) V (death) 0% [calculated by IP analyst] Mean postoperative hospital length of stay: 8.7 days No readmissions within 30 days. Mean (range 3 to 14 days) [calculated by IP analyst] estimated blood loss: 48.6 ml (range 0 to 150ml) [calculated by IP analyst] Abbreviations used: APR, abdominoperineal resection; ASA, American society of anesthesiology; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CI, confidence interval; CRM, circumferential resection margin; CRT, chemoradiotherapy; ECOG, eastern cooperative oncology group; EEA, end-to-end anastomotic; FOLFOX, 5-FU + oxaliplatin; IMA, inferior mesenteric artery; ISR, intersphincteric resection; LAR, low anterior resection; LN, Lymph nodes; LOS, hospital length of stay; LRR, locoregional recurrence; MRI, magnetic resonance imaging; N, no; POSSUM , physiological and operative severity score for the enumeration of mortality and morbidity; SD, standard deviation; SE, standard error; SILS, single-incision laparoscopic surgery; TAEP, transanal endoscopic proctectomy; TAMIS, transanal minimally invasive surgery; TEMS, transanal endoscopic microsurgery; TEO, transanal endoscopic operation; TES, transanal endoscopic surgery; TME, total mesorectal excision; Y, yes.

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Study 6 Liyanage C (2013)

Details Study type Case series Country Not reported Recruitment period 2007 to 2011 Study population n=12 patients with ulcerative colitis (50% [6/12]), Crohn’s disease ( 25% [3/12]), rectal and number adenomas (17% [2/12]), or radiation proctitis (8% [1/12]). Age and sex Mean 66 years [range 41 to 88 years]; 58% (7/12) male Patient selection Consecutive patients needing proctectomy. criteria Exclusion criteria: unfitness for general anaesthesia Technique Transanal endoscopic microsurgery proctectomy. A single surgeon performed all the procedures under general anaesthesia with patients in the lithotomy position and standard thrombo-prophylaxis and antibiotics. Excision began with an intersphincteric dissection following which the transanal endoscopic microsurgery (TEMS) (WOLF) proctoscope was inserted and close rectal dissection was performed using the Ultracision Harmonic scalpel (Ethicon Endosurgery), entering the peritoneal cavity. Following perineal extraction of the specimen, the external sphincter and skin were closed with an absorbable suture. Follow-up 30 days Conflict of Not reported interest/source of funding

Analysis Follow-up issues: none Study design issues:  The perineal approach was supplemented by an abdominal approach in 17% (2/12) of patients.  Planned laparoscopy was performed in1 patient to free potentially adherent small bowel.  Mobilisation of small-bowel adhesions was performed successfully through the TEMS scope in 92% (11/12) of patients. 1 patient required a small laparotomy. Study population issues:  92% (11/12) of patients had an American Society of Anesthesiology (ASA) grade of II, 8% (1/12) of patients had an ASA grade of III on a scale from I to VI with I indicating a normal healthy patient and VI a declared brain-dead patient.  Mean Physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) score: 18.2 (range 13.7 to 30.3).

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 12 Complications after surgery Complicatio Value Other Mean operative time: 215.4min (range 123 to n 345min) [calculated by IP analyst] Delayed 33.3% 16.7% (2/12) Median postoperative hospital length of stay: healing of the (4/12) patients required 5.5 days (range 1 to 28 days). perineal drainage of a wound perineal wound Mean (SD) rectal stump length: 17.8 (±6.1) cm infection

Incarcerated 1 Authors say this ‘was parastomal patien presumably hernia t precipitated by the pneumoperitoneum. After routine use of an abdominal binder, this complication did not occur again’. Colocutaneou 1 The proximal end of s fistula patien the TEMS t proctectomy was stapled across leaving the loop stoma in situ with a distal blind efferent limb. A leak from the staple line led to the formation of a fistula to the perineal wound which was successfully treated by resecting the blind efferent limb and converting the stoma to an end colostomy.

No perioperative (30-day) mortality.

Estimated blood loss< 100ml in all patients.

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Study 7 McLemore EC (2013)

Details Study type Retrospective case series Country USA Recruitment period 2011 to 2013 Study population n=6 patients with proctitis: diversion (17%[1/6]), radiation (17%[1/6]), ulcerative colitis and number (33%[2/6]), Crohn’s disease (33%[2/6]). Age and sex Mean 49 years [range 22 to 74 years]; 33% (2/6) male Mean BMI: 30.5 kg/m2 [range 22 to 51 kg/m2] Patient selection Proctitis in a retained rectum. criteria Technique Patients were in the lithotomy position in 83% (5/6) of cases and in the prone position in 1 case because of severe osteoarthritis and contractures limiting hip flexion. The Gelpoint Path (Applied Medical) transanal access platform was used. Follow-up Range 3 to 19 months. Conflict of Not reported interest/source of funding

Analysis

Follow-up issues: none Study design issues:  4 applications of transanal endoscopic surgical (TES) proctectomy were performed. Study population issues: patient 4 had CRT completed 11 months before surgery. Other issues: none.

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 6 Complications after surgery Complicatio Other Operative data n (1 each) TES operation Patients Urinary tract Patient is doing well at infection 19-month follow-up TES completion proctectomy 50% (3/6) (UTI) TES assisted single incision 1 Chronic Re-operative excision of abdominal perineal resection draining the sinus tract. Patient is TES assisted laparoscopic 1 sinus from doing well at 12-month proctosigmoidectomy with the perineal follow-up. coloanal anastomosis and wound diverting loop ileostomy Perineal Complications managed TES assisted laparoscopic 1 wound with soft tissue restorative proctocolectomy infection and reconstructive surgery. with ileal pouch anal dehiscence Patient remained in anastomososis and diverting hospital for 2 months for loop ileostomy management of his perineal wound dehiscence with Mean operative time: 293.8 min (range 140 to 557 min) prolonged inpatient [calculated by IP analyst] hospitalisation secondary Mean postoperative hospital length of stay: 14.2 days to lack of eligibility for (range 2 to 66 days) [calculated by IP analyst] skilled nursing facility or home based wound care. Patient is doing well at 15-month follow-up.

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Study 8 Sylla P (2013)

Details Study type Case series Country USA Recruitment period 2011 to 2012 Study population n=5 patients with rectal cancer and number Age and sex Mean 48.6 years [range 36 to 63years]; 60% (3/5) male Mean BMI: 25.7 kg/m2 [range 21.7 to 27.6 kg/m2] Patient selection Adult patients with clinically staged T1 (with 1 or more high-risk histologic features criteria identified on pathology) , T2 or T3 node-negative rectal adenocarcinoma, a predictive mesorectal margin≥ 5mm on pelvic MRI and no evidence of metastasis, who were deemed good candidates for laparoscopic low anterior resection with TME and creation of a temporary diverting loop ileostomy. Tumours located 4 to 12 cm from the anal verge and over 1 cm from the anorectal ring. Exclusion criteria: severely symptomatic rectal tumours, inflammatory bowel disease, prior colorectal malignancy, extensive prior abdominal or pelvic surgery or pelvic radiation, large uterine fibroids, or fecal incontinence. Pregnant patients or patients with an ASA class 3 or 4, an Eastern Cooperative Oncology Group (ECOG) score> 2, and a BMI> 40kg/m2. Technique Transanal endoscopic TME with laparoscopic assistance. Standard preoperative intravenous antibiotherapy. Number and location of laparoscopic trocars and use of a pelvic drain used at the discretion of the primary surgeon. Tumours located 1 to 1.5 cm from the anorectal ring: partial intersphincteric resection was performed. Tumours> 1.5 cm from the anorectal ring: the PPH anoscope (Covidien) was inserted for exposure. Following rectal occlusion, the TEO proctoscope (Karl Storz) was inserted transanally. Full-thickness rectal dissection was done using a flexible-tip L-hook with monopolar cautery (Cambridge Endo) and the Harmonic scalpel (Ethicon). Patients were discharged when a soft solid diet was tolerated with a functioning stoma. Epidural catheter provided postoperative pain control, Adjuvant therapy for patients with stage IIA or IIIA rectal cancer was initiated 6 to 8 weeks after surgery. Follow-up Mean 5.4 ± 2.3 months (SD) Conflict of 5 of the authors have received honoraria from manufacturers. interest/source of The study was funded by a Grant from the Center for Integration of Medicine and funding Innovative Technology (CIMIT).

Analysis Follow-up issues: none Study design issues: none Study population issues:  Tumours stage: T1N0M0 (2/5), T2N0M0 (1/5) and T3N0M0 (2/5).  Patients with T3 tumours underwent standard preoperative CRT for 6 weeks followed by surgical resection and completion of 4 months of postoperative chemotherapy with FOLFOX prior to ileostomy closure.  Tumours were located in the lower rectum (≤5 cm from the anal verge) in 80% (4/5) of patients and in the upper rectum (10 cm from the anal verge) in 1 patient.  Among patients with clinical T1N0M0 rectal tumours, 1 was found to have 3 polypoid masses in the rectum with the 1 polyp containing at least intramucosal carcinoma. The other one had undergone transanal excision of a 1.8 cm invasive adenocarcinoma arising in a tubulovillous adenoma 2 months earlier. On pathology review, invasive cancer was noted to extend to within 1 mm of the tumour margin.

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 5 No intraoperative complications Mean number of lymph nodes harvested: 33 ± 15 (range 16 to 53) No conversions to open TME. Complications after surgery All patients are disease-free at mean 5.4-month follow-up. Complicatio Other Intraoperative outcomes n (1 each) Patient ISR Pelvi Approach for TME Approach for Urinary Occurred 15 dysfunction days after Gende c IMA division and acute removal of Foley r drain renal failure catheter in male 1 F N N Complete transanal Transanal patient who 2 M Y Y Partial transanal* Laparoscopic underwent pISR and was 3 M Y Y Complete transanal Transanal complicated by 4 M Y Y Partial transanal* Transanal readmission for 5 F N N Complete transanal Transanal acute renal failure. *Anterior mesorectal dissection was performed in part transanally and Urodynamic in part laparoscopically. testing 1 month after surgery Pathologic characteristics demonstrated minimal detrusor Pt Final TNM LN TME quality Distal CRM activity stage harves margin (cm) consistent with a t (cm) neurogenic 1 ypT2N0M0 41 Complete 10 0.6 bladder. Patient 2 ypT2N0M0 16 Complete 1.5 1 required self- catheterization 3 pT1N0M0 53 Complete 2 1.1 for 5 months but 4 pT2N1M0 34 Complete 0.8 0.2 completely 5 pT0N0M0 21 Complete N/A* N/A* recovered normal urinary *No residual tumour function Mean operative time: 274.6 ± 85.4 min (range 214- 423 min) thereafter. Mean postoperative hospital length of stay: 5.2 ± 2.6 days (range Urinary Occurred 4-10 days) dysfunction following Foley removal at day 2 in a male patient who underwent pISR, requiring Foley reinsertion. Catheter was removed at 1 month with full recovery of normal urinary function. Ileus Managed conservatively without nasogastric tube decompression. Timing not reported.

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± 101 ml (range 80 to 300 ml) Abbreviations used: APR, abdominoperineal resection; ASA, American society of anesthesiology; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CI, confidence interval; CRM, circumferential resection margin; CRT, chemoradiotherapy; ECOG, eastern cooperative oncology group; EEA, end-to-end anastomotic; FOLFOX, 5-FU + oxaliplatin; IMA, inferior mesenteric artery; ISR, intersphincteric resection; LAR, low anterior resection; LN, Lymph nodes; LOS, hospital length of stay; LRR, locoregional recurrence; MRI, magnetic resonance imaging; N, no; POSSUM , physiological and operative severity score for the enumeration of mortality and morbidity; SD, standard deviation; SE, standard error; SILS, single-incision laparoscopic surgery; TAEP, transanal endoscopic proctectomy; TAMIS, transanal minimally invasive surgery; TEMS, transanal endoscopic microsurgery; TEO, transanal endoscopic operation; TES, transanal endoscopic surgery; TME, total mesorectal excision; Y, yes.

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Study 9 Velthuis S (2013)

Details Study type Case series Country Netherlands Recruitment period June to August 2012 Study population n=5 consecutive unselected patients with rectal adenocarcinomas and number Age and sex Mean 69.4 years [range 63 to 79 years] (calculated by IP analyst) ; 60% (3/5) male Patient selection Histologically proven mid-rectal T2 or T3 adenocarcinomas. criteria Exclusion criteria: previous history of abdominal surgery. Technique Combination of transanal TME technique and SILS. Prophylactic antibiotics were given. Transanal phase of the procedure used a Scott retractor (Lone Star Medical Products) to facilitate the full-thickness circumferential resection. One single-incision laparoscopic surgery (SILS) port (Covidien) was introduced into the anus. Another SILS port was introduced at the previously marked future ileostomy site. A hand-sutured coloanal anastomosis was created for the first 2 patients and a stapled anastomosis was formed in the last 3 patients. A loop ileostomy was created after removing the SILS port. Postoperative pain was controlled with an epidural. Follow-up Not reported Conflict of None interest/source of funding

Analysis Follow-up issues: none Study design issues: none Study population issues:  Patients with T2-3N0-1 tumours underwent preoperative radiotherapy. Surgery was performed in the week following cessation of radiotherapy. Patients with T2-3N2 tumours underwent CRT and surgery was performed 6 weeks after the end of the neoadjuvant treatment.  Possible patients overlap with Velthuis 2014 (study 1). Other issues: none

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Key efficacy and safety findings Efficacy Safety Number of patients analysed: 5 Perioperative complications  1 patient developed extreme Transanal endoscopic dissection of the complete rectum perioperative pneumatosis of possible in all patients. the retroperitoneum and mesentery of the small bowel, Complete mobilisation of the sigmoid possible using the SILS port at making laparoscopic the ileostomy site in 80% (4/5) of patients. In 1 patient, 2 extra trocars mobilisation of the sigmoid were used for complete mobilisation because the mesentery of the difficult. sigmoid was too bulky.

Clear surgical margins (circumferential and distal): 100% (5/5)

Median number of lymph nodes harvested: 12 (range 11 to 17) Postoperative complications (1 Intact mesorectal fascia: 100% (5/5) each)

Complicatio Other n Day 5: small Patient with Tumour pathology and perioperative outcomes bowel ileus pneumatosis. Patient Distance Tumou Histology Number Pneumonia Ileus resolved with Gender to anal r stage after of lymph verge (MRI) neoadjuvan nodes conservative (cm) t therapy harveste measures. d Patient had severe COPD 1 F 5 T3N0 ypT3N0 12 and developed 2 M 5 T3N2 ypT0N0 17 pneumonia 3 M 8 T3N0 ypT2N0 11 necessitating antibiotic 4 F 5 T3N0 ypT3N1 12 treatment. 5 M 7 T2N0 ypT2N0 15 Presacral Treated by abscess repeat Median operative time: 175min (range 160 to 194 min) laparoscopic drainage. CT did not reveal anastomotic leakage.

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Study 10 Nassif G (2013) [conference abstract only]

Details Study type Case series Country Not reported Recruitment period Not reported Study population n=8 patients with rectal cancer and number Age and sex 57.2 years [range 36 to 65 years]; 75% (6/8) male BMI: 26.2 kg/m2 [range 18 to 35 kg/m2] Patient selection Not reported. criteria Technique Surgeons used standard laparoscopic instruments, cameras and single port transanal platforms. Follow-up 2.4 months [range 0 to 6 months] Conflict of Not reported. interest/source of funding

Analysis Follow-up issues: none Study design issues: retrospective study. Study population issues:  75% (6/8) of patients received neoadjuvant radiation.  75% (6/8) of patients had a loop ileostomy and 25% (2/8) had an end colostomy.  The tumours were at different stages. Other issues: none

Key efficacy and safety findings Efficacy Safety Efficacy findings from conference abstracts are not Postoperative morbidity normally considered adequate to support decisions on  Myocardial infarction: 1 patient efficacy and are not generally selected for presentation in the overview.

Abbreviations used: APR, abdominoperineal resection; ASA, American society of anaesthesiology; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CI, confidence interval; CRM, circumferential resection margin; CRT, chemoradiotherapy; ECOG, eastern cooperative oncology group; EEA, end-to-end anastomotic; FOLFOX, 5-FU + oxaliplatin; IMA, inferior mesenteric artery; ISR, intersphincteric resection; LAR, low anterior resection; LN, Lymph nodes; LOS, hospital length of stay; LRR, locoregional recurrence; MRI, magnetic resonance imaging; N, no; POSSUM , physiological and operative severity score for the enumeration of mortality and morbidity; SD, standard deviation; SE, standard error; SILS, single-incision laparoscopic surgery; TAEP, transanal endoscopic proctectomy; TAMIS, transanal minimally invasive surgery; TEMS, transanal endoscopic microsurgery; TEO, transanal endoscopic operation; TES, transanal endoscopic surgery; TME, total mesorectal excision; Y, yes.

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Efficacy

Overall survival

A case series of 30 patients with rectal cancer treated by transanal endoscopic proctectomy reported an overall survival rate of 97% at 12 months (95% confidence intervals [CI] 78.0 to 99.5) and 81% at 24 months (95% CI: 53.0 to 92.9) (rates calculated by using the Kaplan–Meier estimator)2.

Relapse-free survival

The case series of 30 patients reported a relapse-free survival rate of 93% at 12 months (95% CI 75.9 to 98.3) and 89% at 24 months (95% CI 69.0 to 96.3) (rates calculated by using the Kaplan–Meier estimator)2.

Disease-free survival

The case series of 30 patients reported disease-free survival in 43% (13/30) of patients at 21 months2. A case series of 5 patients with rectal cancer reported that all patients were disease-free after mean 5.4 months8.

Cancer-related deaths

The case series of 30 patients reported cancer-related deaths in 13% (4/30) of patients at 21 months (including 1 death caused by an isolated locoregional recurrence (LRR) and 1 death caused by cirrhosis)2.

Locoregional or distant recurrence

The case series of 30 patients reported locoregional or distant recurrence in 40% (12/30) of patients at 21 months (13% [4/30] of patients had a LRR alone)2. In a first case series of 20 patients, 1 patient developed distant metastasis 9 months after surgery3.

Quality of mesorectal excision

A non-randomised comparative study of 50 patients treated by transanal total mesorectal excision (TaTME) or laparoscopic total mesorectal excision (TME) reported that macroscopic evaluation of the completeness of mesorectal excision was significantly better for the TaTME group; 96% (24/25) of the specimens had a complete mesorectum compared with 72% (18/25) of the specimens in the laparoscopic TME group (p<0.05)1. The case series of 30 patients and 2 case series of 5 patients with rectal cancer treated by TaTME reported that the mesorectum had been completely excised in 100% of specimens2,8,9. The first case series of 20 patients with rectal cancer reported that the TME grade was complete in 55% (11/20) of patients, nearly complete in 30% (6/20) of patients, incomplete in 10% (2/20) and unknown in 1 patient3. A second case series of

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20 patients with rectal adenocarcinoma or high-grade dysplasia arising from rectal polyps and the second case series of 5 patients with rectal adenocarcinomas reported the quality of the mesorectal plane as satisfactory in 100% of the specimens4,9.

Resection margins

The non-randomised comparative study of 50 patients reported circumferential resection margins (CRM) of less than 2 mm in 1 patient of the TaTME group (n=25) and in 8% (2/25) of patients in the laparoscopic TME group1. The case series of 30 patients reported CRM of less than or equal to 1 mm in 13% (4/30) of patients2. The first case series of 20 patients reported positive surgical margins (circumferential and distal) in 10% (2/20) of patients3. In the second case series of 20 patients, the distal and circumferential margins were free of tumour for all patients (confirmed by pathologic analysis)4. The second case series of 5 patients reported clear circumferential and distal margins in all patients9.

Conversion rate

The case series of 30 patients reported a conversion to open surgery in 7% (2/30) of patients because of the posterior fixation of the tumour2. In the second case series of 20 patients, no laparoscopic or open conversions were reported4. A case series of 14 patients with benign or malignant disease reported a conversion rate to open proctectomy of 18% (2/11) for the 79% (11/14) of patients treated by laparoscopically assisted TAMIS-rectal excision. One of the patients who had the conversion was obese (BMI=32 kg/m2) and had extensive intra-abdominal adhesions after previous laparotomy. There was no conversion to open proctectomy in the 21% (3/14) of patients treated by pure TAMIS-rectal excision5. The first case series of 5 patients reported no conversions to open TME8.

Lymph node yield

The non-randomised comparative study of 50 patients reported a mean (range) numbers of lymph nodes of 14 (7–24) and 13 (1–36) in the TaTME group and in the laparoscopic TME group respectively (p=not significant)1. The case series of 30 patients reported a median lymph node yield of 13 (range 8–32)2. The first case series of 20 patients reported a median lymph node harvest of 22.5 (range 9–51)3. The second case series of 20 patients reported a mean number of retrieved lymph nodes of 15.9±4.3 (standard error [SE]) with 80% (16/20) of patients having had more than 12 lymph nodes retrieved4. The first case series of 5 patients reported a mean number of lymph nodes harvested of 33±15 (SE) [range 16–53]8. The second case series of 5 patients reported a median number of lymph nodes harvested of 12 (range 11–17)9.

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Safety

Perioperative mortality

No 30-day postoperative mortality was reported in a case series of 30 patients with rectal cancer treated by a combined transanal and laparoscopic approach and in a case series of 12 patients with benign or malignant disease treated by transanal endoscopic microsurgery proctectomy 2,6. Death 8 weeks after the procedure was reported in 1 patient in a first case series of 20 patients with rectal cancer treated by a combined transanal and laparoscopic approach (the cause was acute pulmonary embolism)3.

Anastomotic leakage

Anastomotic leakage was reported in 1 patient in the case series of 30 patients with rectal cancer (no further details provided)2. Anastomotic leakage was reported in 1 patient in the first case series of 20 patients; the patient needed a further procedure to remove the coloanal anastomosis and construct a permanent end colostomy. This anastomotic leakage was secondary to ischaemia, most likely secondary to disruption of the blood supply to the proximal (descending) colon3.

Peri-anastomotic fluid collections were reported in 10% (2/20) of patients in the first case series of 20 patients3.

Fistula

Colocutaneous fistula was reported in 1 patient in the case series of 12 patients; the fistula was successfully treated by resection and creation of an ileostomy6.

Anastomotic strictures

Asymptomatic anastomotic strictures noted on physical examination were reported in 20% (4/20) of patients in the first case series of 20 patients; they were treated by manual dilatation3.

Urethral injury

Urethral injury was reported in 7% (2/30) of patients in the case series of 30 patients (1 urethral injury was caused by a difficult dissection of a large anterior tumour and the other by the presence of a concurrent prostatic carcinoma). Both were treated endoscopically with no subsequent complications (no further details provided)2.

Renal failure

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Acute renal failure was reported in 1 patient in the first case series of 20 patients (no further details provided)3.

Urinary dysfunction

Urinary retention was reported in 10% (2/20) of patients in a second case series of 20 patients treated by a combined transanal and laparoscopic approach (no further details provided)4. Urinary dysfunction was reported in 40% (2/5) of patients in a first case series of 5 patients treated by TaTME with laparoscopic assistance; both cases occurred after removal of a Foley catheter in male patients who underwent intersphincteric resection. The first patient was readmitted for acute renal failure and tests showed a neurogenic bladder which required self-catherisation for 5 months, but the patient recovered completely thereafter; the second patient had Foley reinsertion and recovered fully after the catheter was removed at 1 month8.

Incontinence

Incontinence for liquid stools was reported in 15% of patients and for gas in 35% of patients; and 25% of patients had stool fragmentation in the case series of 30 patients at 12 months after stoma closure (number of patients not reported).The median Wexner score reported was 11 (on a scale from 0 to 20, with 0 indicating perfect faecal continence and 20 complete faecal incontinence)2. Mild faecal incontinence after ileostomy closure (<1 accident per day) was reported in most patients and lifestyle-limiting incontinence which had not improved 12 months after resection was reported in 1 patient, in the first case series of 20 patients3.

Post-operative infection

Pelvic abscess was reported in 20% (4/20) of patients in the first case series of 20 patients3. Presacral abscess, which was treated by repeat laparoscopic drainage, was reported in 1 patient in a second case series of 5 patients treated by a combined TaTME and laparoscopic approach9.

Sepsis was reported in 10% (3/30) of patients (2 had peritonitis and 1 had septic shock) in the case series of 30 patients; 1 peritonitis was secondary to a minor ileal wound that could not be directly linked to the transanal endoscopic procedure and 1 patient with sepsis needed critical care (co-morbidities included lymphoma, chronic renal failure and diabetes)2. Wound infection was reported in 10% (2/20) of patients in the first case series of 20 patients3. Transient fever was reported in 14% (2/14) of patients in a case series of 14 patients treated by transanal minimally invasive surgery with or without laparoscopic assistance5. Perineal wound infection and dehiscence was reported in 1 patient in a case series of 6 patients with proctitis treated by transanal endoscopic surgery; this was managed with soft tissue reconstructive surgery and the patient was doing well at 15 months7. IP overview: Transanal total mesorectal excision of the rectum

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Urinary tract infection was reported in 21% (3/14) of patients in the case series of 14 patients and in 1 patient in the case series of 6 patients5,7.

Delayed wound healing

Delayed healing of the perineal wound was reported in 33% (4/12) of patients in the case series of 12 patients and 50% (2/4) of these patients needed drainage of a perineal wound infection6. Chronic draining sinus from the perineal wound was reported in 1 patient in the case series of 6 patients. The sinus tract was removed and the patient was doing well at 12 months7.

Ileus and bowel obstruction

Prolonged ileus was reported in 20% (4/20) of patients in the first case series of 20 patients3.

Bowel obstruction was reported in 7% (2/30) of patients in the case series of 30 patients; both patients recovered after medical treatment2.

Pneumatosis

Extreme perioperative pneumatosis of the retroperitoneum and mesentery of the small bowel were reported in 1 patient in the second case series of 5 patients. This complicated the laparoscopic mobilisation of the sigmoid colon during surgery. The patient also developed a small bowel ileus that resolved with conservative measures at day 5 and pneumonia necessitating treatment by antibiotics (reported in a previous section).9

Blood loss

Blood transfusion after surgery was required in 20% (6/30) of patients in the case series of 30 patients2.

Hernia

Incarcerated parastomal hernia was reported in 1 patient in the case series of 12 patients.6

Reoperation

Reoperation within 30 days of the procedure was reported in 7% (2/30) of patients in the case series of 30 patients (no further details provided)2.

Pneumonia

Pneumonia was reported in 1 patient in the first case series of 20 patients and in 1 patient who had severe chronic obstructive pulmonary disease in the second case series of 5 patients3,9. IP overview: Transanal total mesorectal excision of the rectum

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Myocardial infarction

Myocardial infarction was reported in 1 patient in a case series of 8 patients with rectal cancer treated by transanal minimally invasive surgery total mesorectal excision (no further details provided)10.

Dehydration

Severe dehydration because of an increased ileostomy output was reported in 1 patient in the second case series of 20 patients4.

Validity and generalisability of the studies

 Limitation of the evidence base: lack of long-term data, lack of comparative studies (only 11), small number of patients included in the studies, quality of the mesorectum excision not graded in all studies.  Surgery techniques, names of the techniques and transanal port used vary between studies (procedures with or without laparoscopic-assistance, transanal TME, transanal proctectomy, robotic-assisted procedures were included).  Existence and length of neoadjuvant chemoradiotherapy not always reported.  Patient populations mainly included patients with rectal cancer but 3 studies included patients with benign disease5,6,7.  Two trials may have patient overlaps1,9.  One study included only very high-risk patients2.

Existing assessments of this procedure

There were no published assessments from other organisations identified at the time of the literature search.

Related NICE guidance

Below is a list of NICE guidance related to this procedure. Appendix B gives details of the recommendations made in each piece of guidance listed.

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Interventional procedures  Stapled transanal rectal resection for obstructed defaecation syndrome (review). NICE interventional procedure guidance 351 (2010). Available from http://guidance.nice.org.uk/IPG351  Preoperative high dose rate brachytherapy for rectal cancer. NICE interventional procedure guidance 210 (2006). Available from http://guidance.nice.org.uk/IPG201

Technology appraisals  Laparoscopic surgery for colorectal cancer (review). NICE technology appraisal 105 (2006). Available from http://guidance.nice.org.uk/TA105

Clinical guidelines  Ulcerative colitis. NICE clinical guideline 166 (2013). Available from http://guidance.nice.org.uk/CG166  Crohn's disease. NICE clinical guideline 152 (2012). Available from http://guidance.nice.org.uk/CG152  Colorectal cancer. NICE clinical guideline 131 (2011). Available from http://guidance.nice.org.uk/CG131. This guidance is currently under review and is expected to be updated in December 2014. For more information, see http://www.nice.org.uk/Guidance/InDevelopment/gid-cgwave0716

Specialist advisers’ opinions

Specialist advice was sought from consultants who have been nominated or ratified by their specialist society or royal college. The advice received is their individual opinion and does not represent the view of the society.

Mr Steven Arnold, Mr Roel Hompes, Mr Alex Mirnezami (Association of Coloproctology of Great Britain and Ireland).

 Two specialist advisers performed the procedure regularly and 1 adviser had never performed the procedure.

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 One adviser considered the procedure to be definitely novel and of uncertain safety and efficacy. Two advisers considered it to be between a minor variation of an existing procedure and a definitely novel procedure.  All 3 specialist advisers listed the relevant key comparators to the procedure as total mesorectal excision by laparoscopic, robotic or open surgery.  All 3 specialist advisers stated that fewer than 10% of specialists are engaged in this area of work.  Key efficacy outcomes include technical ease of dissecting the rectum low down in a narrow pelvis, quality of low rectal sealing and anastomotic healing, rate of conversion to open surgery, operative time, pain after surgery, quality of the TME specimen, length of stay in hospital, cosmetic outcome, patient- reported outcome measures, and urinary and sexual function after surgery.  One specialist adviser stated that ‘it is felt unlikely that this procedure would have an impact on cancer-related outcomes’.  Theoretical adverse events include damage to specimens, major postoperative complications including bleeding or injury to vital pelvic structures such as ureter, bladder, urethra, prostate, pelvic nerves, due to unfamiliar anatomy, post-operative infections in the pelvis requiring additional surgery, poor cancer outcomes from increased local or distant recurrence, anastomotic leaks, ileus, increased faecal incontinence from the prolonged instrumentation of the anal canal, bowel dysfunction, post-operative sphincter weakness or dysfunction in patients having restorative procedures, and functional problems (urinary and sexual dysfunction).  Anecdotal adverse events listed included bleeding from the pelvic sidewall, pelvic haematoma (from 1 specialist adviser’s experience), dissection in the incorrect plane into the pelvic sidewall, injury to vital pelvic anatomical structures, ascites, and longer operating time whilst on the surgical learning curve.  Adverse events reported in the literature included iatrogenic damage to adjacent organs (such as ureter, urethra), post-operative deep pelvic abscess

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that eventually required additional surgery, retroperitoneal pneumatosis which subsequently resulted in a post-operative ileus, delayed recovery and – which may have been instrumental in a patient developing a post-operative pneumonia – longer operation time.  There were concerns or uncertainties about the efficacy of the procedure because of the lack of comparative and large studies with long-term follow up. There was particular uncertainty about the quality of the specimens, the conversion rates, the risk profile of the procedure, the long-term oncologic data, the reduction in length of stay, the increase in the number of cases that can be fully dealt with by a minimally invasive approach, the decrease in postoperative pain and the significance of the cosmetic effect versus established minimally invasive measures. A specialist adviser also stated that ‘so far, all cases are being performed in well selected patients and in centres with experience in laparoscopic and transanal surgery. We need to await the impact of this technique when this will be done in centres which are less experienced in these approaches’.  The advisers reported that the surgeons undertaking this procedure should be experienced in (laparoscopic) colorectal cancer surgery and transanal surgery (TEM, TEO or TAMIS). One adviser highlighted the importance of training for this procedure.  One specialist adviser stated that the facilities required were ‘ideally an integrated laparoscopic theatre that allows 2 teams to work independently from each other.’ Another specialist adviser stated that ‘routine surgical facilities for minimally invasive abdominal surgery are present in almost all major hospitals and additional facilities required are a suitable platform for transanal surgery’.  Two advisers mentioned that the first register in the UK and worldwide had just gone live in May 2014 (TaTME Lorec register, in association with the Pelican Foundation). One adviser noted that a group in the Netherlands is working on a randomised controlled trial: TaTME versus standard laparoscopic approach

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(COLOR III), and that in the US they will soon start a multi-centric feasibility study, set-up by their national governing body (ASCRS).  Recently presented/ published abstracts included:  Malik et al. Transanal rectal resection (TARR): A novel and evolving technique in the operative management of low rectal pathology. Presented to Royal Society of Medicine overseas meeting May 2014.  A manuscript on robotic TaTME (n=3) from the group based in Florida (Atallah S.). This has just recently been accepted for publication, so will not yet be on PubMed.  A. Lacy (Barcelona) is about to publish his results on the first 100 cases, the results have been presented in a recent symposium on TaTME (his talk is available online: http://aischannel.com/conference/4th-international- congress-results/4th-international-congress-hospital-clinic-results).  C Sietses reported in the same symposium on their initial 50 patients (to be published soon) and the comparative study they did (n=25 patients).  One of the specialist advisers will present an abstract/manuscript soon (n=15 patients).  One adviser stated that the key controversies are centred on whether the adoption of the procedure will lead to a poorer cancer outcome in cases performed for malignant disease and whether the theoretical efficacies will be demonstrable in a comparative setting against current standards of care.  Outcome measures of benefit by which this procedure could be audited include conversion rate, quality of resection of the specimen, functional outcomes (urinary, sexual and colorectal function; incontinence and pelvic floor functional score; and general and disease-specific quality of life), local recurrence, distant recurrence, length of operation, length of hospital stay, healthcare costs.  Adverse outcomes by which this procedure could be audited include intraoperative complications, post-operative morbidity and mortality, anastomotic leaks, increased sphincter dysfunction, problems with perineal wound healing,

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damage to adjacent structures, functional outcomes (short and long term) (urinary, sexual and colorectal function; general and disease-specific quality of life).  One specialist adviser anticipated a slow diffusion of the procedure. One adviser stated that ‘it is already generating interest in the colorectal community from specialists who possess the basic skills’. One adviser anticipated a ‘relatively quick’ diffusion because this is seen as a minor and easier variation from existing techniques. He noted that there ‘might be a potential risk if surgeons are not well trained’ because of the learning curve (estimated by the adviser between 10 and 12 cases).  Two advisers predicted that the procedure was likely to be carried out in most or all district general hospitals and 1 adviser in a minority of hospitals, but at least 10 in the UK.  Two advisers estimated that the potential impact of the procedure on the NHS in terms of numbers of patients eligible for treatment and use of resources was moderate and 1 adviser estimated it as major.  One adviser added that he thinks ‘that for all surgeons that perform these procedures in the UK, registration into the TaTME registry should be mandatory. This will allow us to collect high quality and relevant data about this technique in order to provide an early warning of issues relating to patient safety and primary efficacy markers. It will drive continuous improvement of the quality of the procedure and enable research.’

Patient commentators’ opinions

NICE’s Public Involvement Programme sent 25 questionnaires to 2 NHS trusts for distribution to patients who had the procedure (or their carers). NICE received 1 completed questionnaire.

The patient commentators’ views on the procedure were consistent with the published evidence and the opinions of the specialist advisers.

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Issues for consideration by IPAC

 IPAC to agree on a final title.  One case series of 100 patients is about to be published.

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References

1. Velthuis S, Nieuwenhuis DH, Ruijter TE et al. (2014) Transanal versus traditional laparoscopic total mesorectal excision for rectal carcinoma. Surg Endosc. doi:10.1007/s00464-014-3636-1. 2. Rouanet P, Mourregot A, Azar CC et al. (2013) Transanal endoscopic proctectomy: an innovative procedure for difficult resection of rectal tumors in men with narrow pelvis. Dis Colon Rectum 56(4):408-15. 3. Atallah S, Martin-Perez B, Albert M et al. (2013) Transanal minimally invasive surgery for total mesorectal excision (TAMIS-TME): results and experience with the first 20 patients undergoing curative-intent rectal cancer surgery at a single institution. Tech.Coloproctol 18:473-480. 4. De Lacy AM, Rattner DW, Adelsdorfer C et al. (2013) Transanal natural orifice transluminal endoscopic surgery (NOTES) rectal resection: "down-to- up" total mesorectal excision (TME)--short-term outcomes in the first 20 cases. Surgical Endoscopy 27:3165-3172. 5. Wolthuis AM, de Buck van OA, and D'Hoore A. (2014) Dynamic article: transanal rectal excision: a pilot study. Diseases of the Colon & Rectum 57:105-109. 6. Liyanage C, Ramwell A, Harris GJ et al. (2013) Transanal endoscopic microsurgery: a new technique for completion proctectomy. Colorectal Disease 15:e542-e547. 7. McLemore EC, Leland H, Devaraj B et al. (2013) Transanal Endoscopic Surgical Proctectomy for Proctitis Case Series Report: Diversion, Radiation, Ulcerative Colitis, and Crohn's Disease. Global Journal of Gastroenterology and Hepatology 1:51-57. 8. Sylla P, Bordeianou LG, Berger D et al. (2013) A pilot study of natural orifice transanal endoscopic total mesorectal excision with laparoscopic assistance for rectal cancer. Surgical Endoscopy 27:3396-3405. 9. Velthuis S, van den Boezem PB, van der Peet DL et al. (2013) Feasibility study of transanal total mesorectal excision. British Journal of Surgery 100:828-831. 10. Nassif G, Polavarapu H, DeBeche-Adams T et al. (2013) Tamis total mesorectal excision for distal rectal cancer: Early experience with short- term outcomes. Diseases of the Colon and Rectum.Conference: Annual Meeting of the American Society of Colon and Rectal Surgeons, ACSRS 2013 Phoenix, AZ United States.Conference Start: 20130427 Conference End: 20130501.Conference Publication: (var.pagings).56 (4) (pp e223- e224).

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Appendix A: Additional papers on transanal total mesorectal excision of the rectum

The following table outlines the studies that are considered potentially relevant to the IP overview but were not included in the main data extraction table (table 2). It is by no means an exhaustive list of potentially relevant studies.

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Article Number of Direction of conclusions Reasons for non- patients/follow- inclusion in table 2 up Atallah S, Albert M, Case reports Patient 3: the completely resected Individual case DeBeche-Adams T et al. n=5 but only specimen revealed grossly reports. Larger (2013) Transanal cases 3 and 5 negative margins with an intact studies are included. minimally invasive surgery relevant. mesorectal envelop. The patient (TAMIS): applications recovered without any morbidity or beyond local excision. Follow-up=18 further sequelae. No evidence of Techniques in weeks for case cancer recurrence 3 months after Coloproctology 17:239- 3 and 18 months ileostomy closure. for case 5. 243. Patient 5 continues to do well at 18-month follow-up. Atallah S. (2014) Review Transanal TME is an excellent Description of Transanal minimally approach to distal rectal transanal TME with a invasive surgery for total mobilization and provides an historical perspective. mesorectal excision. important new method to No new data Minimally Invasive approach distal rectal tumours. reported. Therapy 23:10-16 Chen YG, Hu M, Lei J et Case report 25 lymph nodes were retrieved Article in Chinese. al. (2010) NOTES n=1 from the specimen of mesorectum transanal endoscopic total which was complete. 5 nodes of mesorectal excision for Follow-up= not the lower mesorectum were rectal cancer. China J reported pathologically positive. Endosc 16:1261–1265 Dumont F, Goere D, Case series No conversion was necessary. Studies with more Honore C et al. (2012) n=4 The pathologic variables were patients are included. Transanal endoscopic total satisfactory and the Wexner mesorectal excision Median follow- scores indicated no severe combined with single-port up=4.3 months incontinence after ileostomy laparoscopy. Diseases of (range 3-9 closure. An anastomotic fistula the Colon & Rectum months). . reported in 1 patient was treated 55:996-1001. without reoperation. Rectal resection via the transanal approach combined with single- port laparoscopic assistance may be easier and safer than the traditional approach, especially in male patients with a narrow pelvis. Emhoff IA, Lee GC and Review Early clinical series of transanal No meta-analysis. Sylla P. (2014) Transanal TME with laparoscopic assistance Velthuis 2013, De colorectal resection using (n=-72) are promising, with overall Lacy 2013, Rouanet natural orifice intraoperative and postoperative 2013 and Sylla 2013 translumenal endoscopic complication rates of 8.3% and included in table 2. surgery (NOTES). Dig 27.8% respectively, similar to The other case series Endosc. 26 Suppl 1:29-42. laparoscopic TME. The only include between mesorectal specimen was intact in 1 and 4 patients (with all patients, and 94.4% had 3 single case negative margins. There was no reports). oncological recurrence in average-risk patients at short-term follow-up, and 2-year survival rates in high-risk patients were comparable to that after laparoscopic TME. Han Y, He YG, Zhang HB Case series No conversion to open surgery. All Sigmoid and rectal et al. (2013) Total n=34 patients resection margins were negative. surgery and partial or laparoscopic sigmoid and with colon and Six patients developed TME performed. rectal surgery in postoperative anastomotic Results not specific IP overview: Transanal total mesorectal excision of the rectum

Page 40 of 50 IP 1184 [IPGXXX] combination with transanal rectal tumours leakage. Total laparoscopic to the kind of endoscopic microsurgery: Follow-up not sigmoid and rectal surgery in procedure. a preliminary evaluation in reported. combination with TEM is a safe, China. Surg Endosc feasible and minimally invasive 27(2):518-24. technique. Heald RJ. (2013) A new Editorial Descriptive paper. No solution to some old new data reported. problems: transanal TME. Techniques in Coloproctology Volume 17, Issue 3, pp 257-258. Hompes R, Arnold S and Review The transanal TME (TaTME) is an Descriptive paper. Warusavitarne J.(2014) exciting innovation in colorectal Towards the safe surgery which has the potential to introduction of transanal increase the number of patients total mesorectal excision: who may benefit from the role of a clinical laparoscopic/ endoscopic rectal registry. Colorectal Dis. surgery. The TaTME national 16(7):498-501. registry will be able to report such outcomes as operation time, blood loss, conversion rates, local recurrence, pelvic nerve injury and function. Until long-term oncological outcome data are available, these procedures should be performed under institutional protocol, with multidisciplinary team discussion by surgeons experienced in all aspects of minimal access surgery and comfortable with all types of ultra-low anastomoses. Lacy AM and Adelsdorfer Case report Transanal rectosigmoidectomy Larger studies are C. (2011) Totally n=1 with TME using TEM is a feasible included. transrectal endoscopic and oncologically safe option. total mesorectal excision Follow-up=4 (TME). Colorectal Disease days 13 Suppl 7:43-6. Lacy AM, Adelsdorfer C, Case series Distal and circumferential margins Larger studies are Delgado S et al. (2013) n=3 were free of tumour invasion, and included. Minilaparoscopy-assisted quality of mesorectum resection transrectal low anterior Follow-up=30 was reported satisfactory. One resection (LAR): a days patient had to be readmitted preliminary study. Surgical because of severe dehydration Endoscopy 27:339-346. due to increased ileostomy output. The patient was discharged 3 days after readmission without renal failure. In this preliminart report, transrectal minilaparoscopy-assisted low anterior resection was feasible and safe. Leroy J, Barry BD, Melani Case report First pure transanal NOTES Larger studies are A et al. (2013) No-scar n=1 (Natural orifice transluminal included. transanal total mesorectal endoscopic surgery) total excision: the last step to Follow-up=3 mesorectal excision with pure NOTES for colorectal days retroperitoneal sigmoid surgery. JAMA Surgery mobilisation and coloanal, side-to- 148:226-230. end anastomosis successfully

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completed. One simple small pelvic hematoma was reported at 3 days. Meng W and Lau K. Case series Transanal TME by synchronous Larger studies are (2014) Synchronous n=3 laparoscopic low anterior included. laparoscopic low anterior resection and transanal and transanal endoscopic Follow- endoscopic surgery is feasible. microsurgery total up=range 5 to 8 mesorectal resection. days. Minimally Invasive Therapy & Allied Technologies: Mitat 23:70- 73. Sylla P, Rattner DW, Case report Mesorectal excision was Larger studies are Delgado S et al. (2010) n=1 complete. The final pathology included. NOTES transanal rectal demonstrated pT1N0 with 23 cancer resection using Follow-up=4 negative lymph nodes and transanal endoscopic days. negative proximal, distal, and microsurgery and radial margins. NOTES transanal laparoscopic assistance. endoscopic rectosigmoid Surgical Endoscopy resection using TEM and 24:1205-1210. laparoscopic assistance is feasible and safe. Tuech JJ, Bridoux V, Case report NOTES rectal resection is Larger studies are Kianifard B et al. (2011) n=1 feasible. The mesorectal excision included. Natural orifice total was complete and intact final mesorectal excision using Follow-up: not pathology demonstrated transanal port and reported pT1sm3N0 (of 15 sampled lymph laparoscopic assistance. nodes). European Journal of Surgical Oncology 37:334- 335. Zhang H, Zhang YS, Jin Case report The mesorectum was completely Larger studies are XW et al. (2013) Transanal n=1 removed with negative distal and included. single-port laparoscopic circumferential margin. The final total mesorectal excision Follow-up=7 pathological stage was pT3N1M0 in the treatment of rectal days. with 1 positive lymph node (1/12). cancer. Techniques in Pure-NOTES performed as Coloproctology 17:117- transanal single-port laparoscopic 123. TME for rectal cancer appears to be feasible and safe. Zorron R, Phillips HN, Case reports Distal and circumferential margins Larger studies are Coelho D et al. (2012) n=2 were free of disease. One of the included. Perirectal NOTES access: patients had a transitory "down-to-up" total Follow-up=60 paresthesia of both feet due to mesorectal excision for days. intraoperative positioning, which rectal cancer. Surgical disappeared after 10 days. Innovation 19:11-19. Successful human reports on transcolonic NOTES suggest potential applications.

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Appendix B: Related NICE guidance for transanal total mesorectal excision of the rectum

Guidance Recommendations Interventional Stapled transanal rectal resection for obstructed procedures defaecation syndrome. NICE interventional procedure guidance 351 (2010) 1.1 Current evidence on the safety and efficacy of stapled transanal rectal resection (STARR) for obstructed defaecation syndrome (ODS) is adequate in the context of this condition, which can significantly affect quality of life. The procedure may therefore be used with normal arrangements for clinical governance, consent and audit. 1.2 Stapled transanal rectal resection for ODS should be carried out only in units specialising in the investigation and management of pelvic floor disorders. Patient selection and management should involve a multidisciplinary team including a urogynaecologist or urologist and a colorectal surgeon experienced in this procedure. Interventional Preoperative high dose rate brachytherapy for rectal procedures cancer. NICE interventional procedure guidance 210 (2006) 1.1 Current evidence on the short-term safety of preoperative high dose rate brachytherapy for rectal cancer and its efficacy in reducing tumour bulk appears adequate. However, evidence about the advantages of the procedure as an adjunct to surgery and its effect on long-term survival is not adequate to support the use of this procedure without special arrangements for consent, audit and clinical governance. 1.2 Clinicians wishing to undertake preoperative high dose rate brachytherapy for rectal cancer should take the following actions.  Inform the clinical governance leads in their Trusts.  Inform patients, as part of the consent process, about the uncertainty of the procedure influencing their long- term survival, and provide them with clear written information. Use of the Institute's information for patients ('Understanding NICE guidance') is recommended.  Audit and review clinical outcomes of all patients having preoperative high dose rate brachytherapy for rectal cancer (see section 3.1). 1.3 Further research will be useful, and clinicians are encouraged to enter patients into well-designed trials and to collect longer-term follow-up data. The Institute may review the IP overview: Transanal total mesorectal excision of the rectum

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procedure upon publication of further evidence. Technology appraisals Laparoscopic surgery for colorectal cancer (review). NICE technology appraisal 105 (2006) 1.1 Laparoscopic (including laparoscopically assisted) resection is recommended as an alternative to open resection for individuals with colorectal cancer in whom both laparoscopic and open surgery are considered suitable. 1.2 Laparoscopic colorectal surgery should be performed only by surgeons who have completed appropriate training in the technique and who perform this procedure often enough to maintain competence. The exact criteria to be used should be determined by the relevant national professional bodies. Cancer networks and constituent Trusts should ensure that any local laparoscopic colorectal surgical practice meets these criteria as part of their clinical governance arrangements. 1.3 The decision about which of the procedures (open or laparoscopic) is undertaken should be made after informed discussion between the patient and the surgeon. In particular, they should consider:  the suitability of the lesion for laparoscopic resection  the risks and benefits of the two procedures  the experience of the surgeon in both procedures. Clinical guidelines Ulcerative colitis. NICE clinical guideline 166 (2013) 1.3 Information about treatment options for people who are considering surgery These recommendations apply to anyone with ulcerative colitis considering elective surgery. The principles can also be applied to people requiring emergency surgery. Information when considering surgery 1.3.1 For people with ulcerative colitis who are considering surgery, ensure that a specialist (such as a gastroenterologist or a nurse specialist) gives the person (and their family members or carers as appropriate) information about all available treatment options, and discusses this with them. Information should include the benefits and risks of the different treatments and the potential consequences of no treatment. 1.3.2 Ensure that the person (and their family members or carers as appropriate) has sufficient time and opportunities to think about the options and the implications of the different treatments. 1.3.3 Ensure that a colorectal surgeon gives any person who is considering surgery (and their family members or carers as appropriate) specific information about what they can expect in the short and long term after surgery, and discusses this with them.

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1.3.4 Ensure that a specialist (such as a colorectal surgeon, a gastroenterologist, an inflammatory bowel disease nurse specialist or a stoma nurse) gives any person who is considering surgery (and their family members or carers as appropriate) information about:  diet  sensitive topics such as sexual function  effects on lifestyle  psychological wellbeing  the type of surgery, the possibility of needing a stoma and stoma care. 1.3.5 Ensure that a specialist who is knowledgeable about stomas (such as a stoma nurse or a colorectal surgeon) gives any person who is having surgery (and their family members or carers as appropriate) specific information about the siting, care and management of stomas. Information after surgery 1.3.6 After surgery, ensure that a specialist who is knowledgeable about stomas (such as a stoma nurse or a colorectal surgeon) gives the person (and their family members or carers as appropriate) information about managing the effects on bowel function. This should be specific to the type of surgery performed (ileostomy or ileoanal pouch) and could include the following:  strategies to deal with the impact on their physical, psychological and social wellbeing  where to go for help if symptoms occur  sources of support and advice. Clinical guidelines Crohn's disease. NICE clinical guideline 152 (2012) 1.5 Surgery Crohn's disease limited to the distal ileum 1.5.1 Consider surgery as an alternative to medical treatment early in the course of the disease for people whose disease is limited to the distal ileum, taking into account the following:  benefits and risks of medical treatment and surgery  risk of recurrence after surgery[13]  individual preferences and any personal or cultural considerations.

Record the person's views in their notes. 1.5.2 Consider surgery early in the course of the disease or before or early in puberty for children and young people whose disease is limited to the distal ileum and who have:  growth impairment despite optimal medical treatment and/or IP overview: Transanal total mesorectal excision of the rectum

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 refractory disease.

Discuss treatment options within the multidisciplinary team and with the person's parent or carer and, if appropriate, the child or young person. Managing strictures 1.5.3 Consider balloon dilation particularly in people with a single stricture that is short, straight and accessible by colonoscopy. 1.5.4 Discuss the benefits and risks of balloon dilation and surgical interventions for managing strictures[14] with:  the person with Crohn's disease and/or their parent or carer if appropriate and  a surgeon and  a gastroenterologist. 1.5.5 Take into account the following factors when assessing options for managing a stricture:  whether medical treatment has been optimised  the number and extent of previous resections  the rapidity of past recurrence (if appropriate)  the potential for further resections  the consequence of short bowel syndrome  the person's preference, and how their lifestyle and cultural background might affect management. 1.5.6 Ensure that abdominal surgery is available for managing complications or failure of balloon dilation. Clinical guidelines Colorectal cancer. NICE clinical guideline 131 (2011) 1.2.4 Laparoscopic surgery The recommendations in this section are from Laparoscopic surgery for colorectal cancer (NICE technology appraisal guidance 105). Colorectal cancer. NICE clinical guideline update in development. Review question 2: treatments for early rectal cancer 2.2.6 Recommendations For patients with stage I rectal cancer: 5. Explain to patients and their family members or carers (as appropriate) that there is very little good quality evidence comparing treatment options for stage I rectal cancer. [new 2014] 6. After discussion in the MDT responsible for the management of early rectal cancer, discuss uncertainties about the potential risks and benefits of all treatment options with patients and their family members and carers (as

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appropriate), taking into account each patient’s circumstances. [new 2014] 7. Offer patients the chance to take part in a randomised controlled trial (if available) that compares treatment options for stage I rectal cancer. [new 2014]

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Appendix C: Literature search for transanal total mesorectal excision of the rectum

Databases Date Version/files searched Cochrane Database of Systematic 23/04/2014 Issue 4 of 12, April 2014 Reviews – CDSR (Cochrane) Database of Abstracts of Reviews of 23/04/2014 Issue 1 of 4, January 2014 Effects – DARE (Cochrane) HTA database (Cochrane) 23/04/2014 Issue 1 of 4, January 2014 Cochrane Central Database of 23/04/2014 Issue 3 of 12, March 2014 Controlled Trials – CENTRAL (Cochrane) MEDLINE (Ovid) 16/04/2014 1946 to April Week 1 2014 MEDLINE In-Process (Ovid) 16/04/2014 April 14, 2014 EMBASE (Ovid) 16/04/2014 1974 to 2014 Week 15 BLIC (Dialog DataStar) 23/04/2014 n/a PubMed 23/04/2014

Trial sources searched on 15 April 2014  National Institute for Health Research Clinical Research Network Coordinating Centre (NIHR CRN CC) Portfolio Database  Current Controlled Trials metaRegister of Controlled Trials – mRCT  Clinicaltrials.gov

Websites searched on 15 April 2014  National Institute for Health and Care Excellence (NICE)  NHS England  Food and Drug Administration (FDA) - MAUDE database  French Health Authority (FHA)  Australian Safety and Efficacy Register of New Interventional Procedures – Surgical (ASERNIP – S)  Australia and New Zealand Horizon Scanning Network (ANZHSN)  Conference websites <>  General internet search IP overview: Transanal total mesorectal excision of the rectum

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The following search strategy was used to identify papers in MEDLINE. A similar strategy was used to identify papers in other databases.

((Transanal* or transrectal*) adj4 (proctect* or dissect* or operat* or 1 platform* or surg* or treat* or tech* or therap*)).tw. 2 (TES or TAMIS).tw. 3 Natural Orifice Endoscopic Surgery/ (Natural* adj4 orifice* adj4 transluminal* adj4 endoscopic* adj4 4 (surg* or treat* or tech* or therap*)).tw. 5 NOTES.tw. 6 (Total* adj4 mesorectal* adj4 excisi*).tw. 7 TME.tw. 8 (Reverse* adj4 proctect*).tw. 9 Digestive System Surgical Procedures/ 10 or/1-9 ((anal or anus or rectal* or rectum* or colorectal* or colon* or bowel* 11 or coloanal* or colo-anal*) adj4 (dissect* or excis* or remov* or close*)).tw. 12 ((coloanal* or colo-anal*) adj4 anastomos*).tw. 13 11 or 12 14 10 and 13 15 animals/ not humans/ 16 14 not 15 17 limit 16 to english language

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