ﺑﺴﻢ ﺍﷲ ﺍﻟﺮﲪﻦ ﺍﻟﺮﺣﻴﻢ UNIVERSITY OF KHARTOUM Faculty of Medicine Postgraduate Medical Studies Board
Perforated peptic ulcer in Khartoum state
By Dr. Al Fatih Mohamed Ahmed Alnajib M.B.B.S (University of Gezira)
A thesis Submitted in partial fulfillment for the requirements of the Degree of Clinical MD in Surgery, October, 2002
Supervisor Prof. Mohamed El Makki Ahmed MS, FRCSI, Professor of Surgery
ﺑﺴﻢ ﺍﷲ ﺍﻟﺮﲪﻦ ﺍﻟﺮﺣﻴﻢ
ﻗﺎﻝ ﺍﷲ ﺗﻌﺎﻟﻰ : {ﻗﺎﻟﻮﺍ ﺳﺒﺤﺎﻧﻚ ﻻ ﻋﻠﻢ ﻟﻨﺎ ﺇﻻ ﻣﺎ ﻋﻠﻤﺘﻨﺎ ﺇﻧﻚ ﺃﻧﺖ ﺍﻟﻌﻠﻴﻢ ﺍﻟﺤﻜﻴﻢ}.
ﺻﺪﻕ ﺍﷲ ﺍﻟﻌﻈﻴﻢ
CONTENTS Page Dedication I Acknowledgements II List of abbreviations III English abstract IV
V Arabic abstract
VI List of tables
VIII List of figures
CHAPTER ONE
1 Introduction and Literature review
Objectives 25
CHAPTER TWO Patients & Methods 26
CHAPTER THREE Results 28
CHAPTER FOUR Discussion 58 Conclusion 65 Recommendations 67 References 68
APPENDIX Questionnaire 69 APACHE II Score 73
Dedications
To my parents, teachers, Sisters & brothers
ACKNOWLEDGEMENT
I will always feel indebted to my supervisor Prof. Mohamed El Makki Ahmed, Professor of surgery, Faculty of Medicine, University of Khartoum, for his kind and meticulous supervision, encouragement, and guidance in this work with great patience from it’s beginning to the final touches. I would also like to express my sincere thanks and gratitude to my colleagues the registrars of surgery and the house officers who help a lot in data collection, their indefatigable efforts and cheerful co-operation are without parallel. Special thanks for all those helped or participated in this work to come to the light, not forgetting to thank Miss. Widad for help in typing and Mr. Hassan for the data analysis.
ABBREVIATIONS
APACHE Acute physiology and chronic health evaluation
CXR Chest X-ray
COX Cyctooxygenase
DU Duodenal ulcer
GU Gastric ulcer
H2 receptors Histamine 2 receptors
H. pylori Helicobacter pylori
PPI Proton pump inhibitor
PPU Perforated peptic ulcer
ZES Zollingar Ellesions Syndrome
ABSTRACT
Background: Although perforated peptic ulcer (PPU) is evaluated in different parts of the World, no study was held to evaluate the disease in Sudan. This study aimed to evaluate the incidence, clinical presentation, management and outcome of perforated peptic ulcer. Methods: Data from 58 consecutive patients with PPU was collected and analysed in the period between November 1999 and April 2002. Fifty-two (89.6%) were male patients and six (10.4%) females. Results: Twenty-five (43.1%) of the studied group were below 30 years of age, only 10(17.2%) were known cases of peptic ulcer disease. Twenty-two (40%) of perforations occurred during the month of Ramadan and most of the patients were fasting 20(34.4%). Forty-two (72.4%), of the total number of patients, presented during the winter season. Fifty- three (91.3%) were perforated duodenal ulcers and three (5.2%) were perforated gastric ulcers. Fifty-five (94.8%) had surgical treatment, 53(91.3%) patients had simple closure with omental patch. Postoperative complications occurred in 18 (31%) patients and there were seven (12%) deaths. The most significant factors for both morbidity and mortality were old age group, late presentation, concomitant medical illness, size of perforation more than two cm and shock on presentation. Conclusion: PUP predominantly occurred in young age group as compared to International data and most of the patients were not known to suffer from peptic ulcer disease. The incidence increased in winter season and during fasting.
ﻤﻠﺨﺹ ﺍﻷﻁﺭﻭﺤﺔ
ﺗﻘﺪﱘ: ﱂ ﻳﺘﻢ ﺗﻘﻴﻴﻢ ﺍﻧﻔﺠﺎﺭ ﺍﻟﻘﺮﺣﺔ ﺍﳍﻀﻤﻴﺔ ﻣﻦ ﻗﺒﻞ ﰱ ﺍﻟﺴﻮﺩﺍﻥ، ﺃﺟﺮﻳﺖ ﻫﺬﻩ ﺍﻟﺪﺭﺍﺳﺔ ﻟﺘﺴﻠﻴﻂ ﺍﻟﻀﺆ ﻋﻠﻰ ﺍﳊﺪﻭﺙ ﻭﺍﺠﻤﻟﻰﺀ ﺍﻟﺴﺮﻳﺮﻱ، ﺍﳌﻌﺎﳉﺔ ﻭﺍﻟﻨﺎﺗﺞ.
ﺍﻟﻔﻜﺭﺓ: ﺘﻡ ﺘﺠﻤﻴﻊ ﺍﻟﻤﻌﻠﻭﻤﺎﺕ ﻋﻥ ﺜﻤ ﺎﻨﻴﺔ ﻭﺨﻤﺴﻴﻥ ﻤ ﺭ ﻴ ﻀ ﺎﹰ ﻋﻠﻰ ﺍﻟﺘﺘﺎﻟﻲ ﻤﺼـﺎﺒﻴﻥ ﺒﺎﻟﻘﺭﺤـﺔ
ﺍﻟﻬﻀﻤﻴﺔ ﺍﻟﻤﻨﻔﺠﺭﺓ ﻭﻤﻥ ﺜﻡ ﺘﻡ ﺘﺤﻠﻴﻠﻬﺎ.
ﺍﻟﻨﺘﺎﺌﺞ: ﻤﻥ ﺸﻬﺭ ﻨﻭﻓﻤﺒﺭ ﻋﺎﻡ 1999ﻡ ﻭﺤﺘﻰ ﻤﺎﺭﺱ 2002ﻡ، ﺤﻀﺭ 52 ﺫﻜﺭ ﻭﺴﺕ ﺇﻨﺎﺙ
ﻤﺼﺎﺒﻭﻥ ﺒﺈﻨﻔﺠﺎﺭ ﺍﻟﻘﺭﺤﺔ ﺍﻟﻬﻀﻤﻴﺔ.
ﺃﻜﺜﺭ ﺍﻷﻋﻤﺎﺭ ﺘ ﺄ ﺜ ﺭ ﺍﹰ ﻫﻡ ﻤﺎ ﺩﻭﻥ ﺍﻟﺜﻼﺜﻴﻥ ﺴﻨﺔ . ﻋﺸﺭﺓ ﻤﺭﻀﻰ ﻓﻘﻁ ﻜﺎﻨﻭﺍ ﻤﻌﺭﻭﻓﻴﻥ ﺍﻹﺼﺎﺒﺔ
ﺒﻤﺭﺽ ﺍﻟﻘﺭﺤﺔ ﺍﻟﻬﻀﻤﻴﺔ ﻗﺒل ﺤﺩﻭﺙ ﺍﻹﻨﺜﻘﺎﺏ، 40% ﺘﻘﺭﻴﺒﺎﹰ ﻤﻥ ﺠﻤﻠﺔ ﺤﺎﻻﺕ ﺍﻹﻨﺜﻘﺎﺏ ﺤـﺩﺜﺕ ﺨـﻼل
ﺸﻬﺭ ﺭﻤﻀﺎﻥ "ﻋﺩﺩ 22 ﻤﺭﻴﺽ ". ﻜﺎﻥ ﻤﻌﻅﻡ ﺍﻟﻤﺭﻀﻰ ﺼﺎﺌﻤﻴﻥ "ﻋﺩﺩ 20 ﻤﺭﻴﺽ "، 42(24.7%) ﻤﻥ
ﺤﺎﻻﺕ ﺇﻨﻔﺠﺎﺭ ﺍﻟﻘﺭﺤﺔ ﺤﺩﺜﺕ ﺨﻼل ﺍﻟﺸﺘﺎﺀ . 53(96.4%) ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﻜﺎﻨﺕ ﻗﺭﺤـﺔ ﺍﻷﺜﻨـﻲ ﻋﺸـﺭ،
ﻭﺜﻼﺙ ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﻜﺎﻨﺕ ﻗﺭﺤﺔ ﺍﻟﻤﻌﺩﺓ . ﻜل ﺍﻟﻤﺭﻀﻰ ﺘﻘﺭﻴﺒﺎﹰ "ﻋﺩﺩ 55" ﺘﻤﺕ ﻤﻌﺎﻟﺠﺘﻬﻡ ﺠ ﺭ ﺍ ﺤ ﻴ ﺎﹰ ﺒﻭﺍﺴﻁﺔ
ﺍﻟﻘﻔل ﺍﻟﺒﺴﻴﻁ ﻤﻊ ﺭﻗﻌﺔ ﺍﻟﺜﺭﺏ . ﻤﻀﺎﻋﻔﺎﺕ ﺒﻌﺩ ﺍﻟﻌﻤﻠﻴﺔ ﺤﺩﺜﺕ ﻓﻰ 17 (31.8%) ﻜﻤﺎ ﺃﻥ ﻫﻨﺎﻟﻙ ﺴـﺒﻌﺔ
ﺤﺎﻻﺕ ﻭﻓﺎﺓ.
ﺍﻟﻌﻭﺍﻤل ﺍﻷﻜﺜﺭ ﺇﻋﺘﺒﺎﺭﻴﺔ ﻤﻥ ﺤﻴﺙ ﺍﻟﻤﺭﺍﻀﺔ ﻭﺍﻟﻭﻓﺎﺓ ﻜﺎﻨﺕ، ﻜﺒﺭ ﺍﻟﺴﻥ، ﻋﻨﺼـﺭ ﺍﻟﻨﺴـﺎﺀ ،
ﺍﻟﺤﻀﻭﺭ ﺍﻟﻤﺘﺄﺨﺭ، ﻭﺠﻭﺩ ﻤﺭﺽ ﻤﻌﺎﺼﺭ، ﺤﺠﻡ ﺍﻟﺜﻘﺏ ﺍﻜﺜﺭ ﻤﻥ 2 ﺴﻡ، ﺍﻟﺼﺩﻤﺔ ﺍﻟﺩﻭﺭﺍﻨﻴﺔ ﻋﻨﺩ ﺍﻟﺤﻀﻭﺭ
ﺒﺎﻹﻀﺎﻓﺔ ﺇﻟﻰ ﻨﻘﺹ ﺍﻟﺼﻭﺩﻴﻭﻡ ﻭﺍﻟﺒﻭﺘﺎﺴﻴﻭﻡ.
ﺍﻟﺨﻼﺼﺔ: ﻴﺒﺩﻭ ﺃﻥ ﺍﻨﻔﺠﺎﺭ ﺍﻟﻘﺭﺤﺔ ﺍﻟﻬﻀﻤﻴﺔ ﻤﺭﺽ ﻴﺼﻴﺏ ﺍﻟﺸﺒﺎﺏ ﻏ ﺎ ﻟ ﺒ ﺎﹰ ﻟﻴﺴـﻭﺍ ﻤﺭﻀـﻰ
ﻤﻌﺭﻭﻓﻴﻥ ﺒﺎﻟﻘﺭﺤﺔ ﺍﻟﻬﻀﻤﻴﺔ ﻭﺘﺯﻴﺩ ﺤﺎﻻﺕ ﺍﻟﺤﺩﻭﺙ ﻓﻰ ﻓﺼل ﺍﻟﺸﺘﺎﺀ ﻜﻤﺎ ﻭﺃﻥ ﺍﻟﺼـﻴﺎﻡ ﻴﺒـﺩﻭ ﻜﻤﺤﻔـﺯ
ﻟﺤﺩﻭﺙ ﺍﻻﻨﻔﺠﺎﺭ.
INTRODUCTION
Peptic ulcer perforation (PUP) occurs in about 10% of patients with peptic ulcer disease. (1) It is the commonest perforation of the upper gastrointestinal tract. Being a life threatening complication of Peptic ulcer disease (PUD) it needs prompt resuscitation and appropriate surgical management, if mortality and morbidity are to be avoided. It is the deep penetrating ulcers in the anterior surface of the duodenum and stomach that usually perforate in the peritoneal cavity. (2) Posterior surface lesions usually penetrate into the pancreas and present as bleeding rather than free perforation. A revolution in both diagnosis and management of PU disease occurred in the last few decades namely the H. pylori relations to the disease together with H2 receptor antagonists and PPI remedies and improvement in endoscopic facilities. In spite of all these, the incidence of
PUP seems to be unaffected,(3) the thing which could be attributed to
NSAIDs ingestion.
¾ Anatomy:
The stomach lies in the left upper quadrant crossing the midline at the pylorus. The most proximal part is the cardia, small area, just distal to the GOJ. Populated by mucus gland cells.
The corpus is the largest portion, lies between the cardia and antrum. It contains mucus, parietal and chief cells, the last two secrete acid and pepsin respectively.
The antrum separated from the corpus by the incisura in the lesser curvature and the point where the left gastroepiploic artery enter the stomach along the greater curvature. Its populated by G- cells which secret gastrin which important in regulation of gastric acid secretion.
The pylorus has strong muscles; it pumps the gastric contents into the duodenum.
Blood supply:
The left gastric artery is the largest artery supplying the stomach.
It arises from the celiac trunk and runs a long the lesser curvature.
The right gastric artery, from the common hepatic. The right gastroepiploic artery from the gastroduodenal artery, courses a long the greater curvature from right to left.
The left gastroepiploic artery, a branch from the splenic artery, supplies the greater curvature of the fundus.
The duodenum is supplied in it is superior part by the superior pancreaticoduodenal artery, a branch of gastroduodenal artery. The inferior part is supplied by the inferior pancreato-duodenal artery, a branch of the superior mesenteric artery.
The stomach and duodenum have extensive submucosal channels that ensure a rich blood supply to the mucosa. This ensures adequate blood supply to the stomach even if only one of the four major vessels is intact. Venous drainage is through coronary, gastroepiploic and splenic vein to the portal vein.(4)
Nerve supply:
The stomach is supplied by the two major vagal trunks. The largest is the posterior, which is closely adherent to intra-abdominal oesophagus and slightly to the left of the midline. It’s large and easily identified during surgery.
The anterior vagus resides slightly to the right of the intraabdominal oesophagus, it’s much smaller than the anterior and more difficult to localize.
The nerve of Grassi is a branch of the posterior vagus that innervates the fundus. Failure to ligate this branch may result in ulcer recurrence following vagotomy.
The nerves of Laterjet (Crow’s foot) are a tangle of nerves,
Branches from the main trunks at the incisura. They innervate the antrum and must be spared in highly selected vagotomy.(5)
¾ Physiology:
Acid secretion:
Acid secretion occurs in the gastric corpus and fundus by the parietal cells. These cells secrete acid against very high concentration gradients. The maximum luminal acid concentration is 0.15N so acid concentration is more than ten million times the concentration of hydrogen in the blood. Acid in this concentration is highly corrosive and would disintegrate any tissue coming into contact. The stomach has several protective mechanisms against acid digestions;
The tight intercellular junctions prevent luminal acid from penetrating the gastric epithelium;
The luminal bicarbonate secretion, for each acid molecule generated a molecule of bicarbonate ion is secreted. Although most of it is carried away by gastric blood flow, some is secreted into the thick mucus gel. It also has a thick alkaline mucus gel lies immediately adjacent to the gastric epithelium, protecting it from injury. There is also a net outward fluid flux into the lumen which must exist with both acid and bicarbonate, this flux of water has a greater ability to maintain the gradient than any amount of mucus or bicarbonate. Because of the constant exposure to very high concentration of acid, gastric ulceration is unrelated to acid
production. The primary responsible mechanism is the loss of gastric epithelial protective mechanism.(2,5)
Signals of gastric acid secretion:
Vagal activation: Stimulates secretion by several mechanisms; the release acetylcholine in the immediate vicinity of parietal cell. This cholinergic stimulation results in increase intracellular calcium of the parietal cells which leads to acid secretion.
Stimulation of antral interneurons to release gastrin releasing peptide "GRP", which stimulates antral G. cells release of gastrin into the blood stream, this hormone stimulates parietal cells to secrete acid.
Both vagal stimulation and gastrin cause gastric mucosal mast cells to release histamine immediately adjacent to the parietal cells.
Histamine is a very potent stimulus for acid secretion. It causes receptor- mediated increase in the parietal cell intracellular ATP which in turn results in acid secretion.
Division of the vagus is highly effective in reducing acid secretion because it simultaneously reduces all three acid secretary stimulatory systems. However, gastrin can still be secreted in the absence of vagus activity; this is why both vagotomy and antrectomy is needed to ensure elimination of acid secretion in peptic ulcer disease.
Gastric parietal cells have receptors to acetylcholine, gastrin, prostaglandins and histamine. Histamine is probably the most potent stimulus, because its inhibition by H2 blockers results in marked reduction in acid secretion. However, the other receptors play a role as acid secretion can not be totally suppressed by histamine inhibition.
Proton pump inhibitors completely block acid secretion, making them very potent medications for the treatment of peptic disorder.
Prostaglandins inhibit acid secretion by reducing adenylate cyclase activity.(5)
Motility:
Contractile activity of the gastrointestinal tract (GIT) initiates in the stomach. The gastric pace-maker is located a long the greater curvature in the upper third of the stomach. This pacemaker cycles at three times per minute. Not all pacemaker activity translated to muscular contractions.
The migrating motor complexes are complexes of muscular contractions that are highly coordinated and sweep down the GI tract during fasting cleaning the luminal contents between feedings.
The vagus nerve plays a crucial role in regulating gut contractile activity. As food enters the stomach receptive relaxation will occur,
mediated by vagus. Vagotomy abolishes this mechanism, contributing to
the postoperative fullness.
The antrum is a powerful pump that drives the gastric contents
against the pylorus, serving to pump out small amount of gastric material
into the duodenum. This activity is also mediated by the vagus. Vagotomy
profoundly decreases antral contractile activity, necessitating pyloroplasty
to facilitate gastric emptying. Without which functional gastric
obstruction occur because the reduced force of antral contractions can not
overcome the resistance of the pylorus.(2,5)
¾ Causes of peptic ulcer:
There are many causes for peptic ulceration, the most important are:
i. Helicobacter pylori infection.
ii. Nonsteroidal anti-inflammatory drugs.
iii. Pathological hypersecretory states "Zollinger-Ellison
Syndrome".
All forms of ulceration result from imbalance between gastric
acid-pepsin secretion and the ability of the gastrointestinal mucosa to
withstand auto digestion.(6)
¾ Special forms of peptic ulcer:
1- Stress ulcers:
These are multiple, small superficial erosions in the stomach or
duodenum, which occur after major surgery, trauma or severe illness. The
key factor is altered mucosal resistance by bile reflux or fall in mucosal
blood flow during shock.(7)
2- Curling's ulcer:
This is special form of stress ulcer of the duodenum seen in
patients with severe burn.(7)
3- Cushing's ulcer:
This type of ulcer develops in the duodenum or stomach in
patients with neurological illness. Usually associated with increased
gastric secretion possibly due to increase vagal activity as a consequence
of increase intracranial pressure". They are usually single and can erode
deeply and perforate.(7)
Sites of peptic ulceration:
1- Duodenum:
Ulceration of the first part is the commonest form of PU. While
ulceration of the more distal duodenum is exceptional without the rare
(Zollinger- Ellison Syndrome).(7,8)
2- The stomach:
It’s the second commonest form of peptic ulcer, classified into four types:
Type I:
This develops a long the lesser curve probably due to damage to mucosal defenses by bile reflux. It is usually associated with gastritis. It’s found in the junction between acid secreting and non-acid secreting gastric mucosa.
Type II:
These are seen in the middle of the corpus; they are secondary to duodenal ulceration and usually arise because of stasis due to duodenal deformity.
Type III:
Occurs in the pyloric channel or prepyloric area, they may be associated with normal or increase gastric acid secretion.
Type IV:
Occur high in the lesser curve below the gastrooesophageal junction.
In contrast to type I and IV, type II and III GU are the result of acid induced epithelial injury and are treated similarly to DU.
3- Oesophagus:
Oesophageal ulcers are due to reflux of acid and pepsin from the stomach. They are small and superficial but may be large and penetrating when they occur in columnar mucosa (as in Barrett’s oesophagus in which columnar metaplasia occurs. It’s considered premalignant).
Jejunal ulcers are uncommon but can develop in Zollinger-Ellison
Syndrome and in gastrojejunal anastomosis, whilst ileal ulcers occur adjacent to Mechel's diverticulum with ectopic acid secreting mucosa.(7,8)
Helicobacter pylori:
This is a microaerophilic, gram negative rod, well adapted for growth in the gastric acidic environment. Infection occurs by the fecal- oral route "contaminated water is a major source for the organism". The infection rate is very high in developing countries and in lower socioeconomic groups in developed nations. Sixty percent of the population become infected by the time they reach 20 years of age.(1) In developed countries 50% of population are infected by the time they are
60 years old.
The organism swims freely in the gastric mucosa, secreting urease that catalizes ammonia synthesis. The ammonia protect the bacteria from acid induced injury, but it damages the gastric epithelium resulting
in gastritis (type B).(2,5,9) Acytotoxic secreting strain characterized by the marker CagA is especially virulent.
H. pylori has the ability to induce gastric epithelial interleukine-
8 (IL-8) and other cytokine that may result in gastritis.
A part from peptic ulcer disease H. pylori has been implicated in the pathogenesis of gastric lymphoma and carcinoma.
Acute H. pylori infection is manifested by nausea, vomiting, abdominal pain and fever lasting 3-14 days. Several weeks following the initial infection, gastritis result in achlorhydria that may persist for several months. A chronic infection is often asymptomatic.
Gastric and duodenal ulcer diseases have been attributed to
H. pylori because 95% of patients with DU and 50 -80% with GU harbour this organism. The organism is not found in the saliva or dental plaques.(10,11)
• Diagnosis:
1- Visualization of the organism in biopsy specimen by Gemsa staining or
the Ethin-stray sliver stain.(2,5)
2- Culture, which is generally not needed.(5)
3- Breathe tests for ammonia after giving the patient C13-C14 labeled urea
and the CLO test "a commercially available kit".
4- Serologically by ELISA for antibody detection but these antibodies
remain present in 50% of patient after eradication of the organism.
Proton pump inhibitors obscure test results and should be discontinued
two weeks before testing for H. pylori.
• Treatments:
1- Bismuth compounds and antibiotics "Bismuth subsalicylate or
bismuth subcitrate combined with metronidazole or tetracycline or
amoxicillin for two weeks".
2- Omeprazole and amoxicillin for two weeks.
3- In resistant cases culture and sensitivity is indicated.
Eradication is confirmed by a negative breath test, which must be
performed at least two weeks following the discontinuation of
omeprazole.(5)
There are some Limitations to the H- pylori hypothesis as a cause of
PU:
- In contrast to NSAID ingestion of H. pylori by Warren and Marchal
in 1980 resulted in gastritis but not in ulcer development.(2)
- Only 10% to 20% of those with H. pylori gastritis develop ulcers (5) of
these most of the ulcers are duodenal whereas the organism resides
primarily the stomach.
- Indeed strongest epidemiological evidence associates H. pylori
infection with duodenal and not gastric ulcer disease.(6,7)
NSAIDs – induced ulceration:
The wide spread use of NSAIDs, has resulted in an increase in
the incidence of ulcer disease. Bleeding and perforation are more common
now than a decade ago.(10)
The gastric epithelium contains cyctooxygenase 1“Cox-1”, an
enzyme essential for prostaglandin synthesis.(5) Prostaglandin preserves
gastric mucosal blood flow, increases mucus production and bicarbonate
secretion.
Each of these is essential for maintaining gastric epithelial
protective systems. NSAIDs act by inhibiting Cox-1. Aspirin is an acidic
molecule that easily enters the gastric epithelium under the acidic
conditions of the stomach and clearly result in topical injury.
NSAIDs induce injury when administered intravenously or
transdermally. The ulceration does improve with antacid therapy such that
patients requiring long term NSAID use should receive concurrent H2-
blockers or PPIs.
Recently, Cox-2 has been identified as the Cox isoform in inflammatory tissue. Specific blocking agents are available that have anti- inflammatory effects with minimal effect on gastric Cox-1. They appear to relieve pain without resulting in significant ulcer disease. (5,10,11)
Z.E- syndrome:
This is an uncommon disease occurring in 0.1 to 1.0 percent of all patients with peptic ulcer. But it is the best understood form of gastroduodenal mucosal injury.(6) The ulceration result from massive hyper secretion of acid, which is stimulated by entopic gastrin production from a non beta islet cell tumor “the gastrinoma”. These tumours produce several forms of gastrin; the predominant form is gastrin- 17, whereas gastrin 34, with its longer half-life, is the major circulating form.
Gastrinoma may arise from the pancreas or the duodenum “ectopic lesion”.
In 20 percent of patients it’s associated with MEN-I which include hyperparathyroidism and pituitary tumors. Parietal cell mass expand to three to six times as large as that of normal individual because of the trophic effect of gastrin.(6) ZE syndrome can now be treated effectively by oral or intravenous PPI.(12)
¾ Diagnosis of peptic ulcer:
Duodenal ulcer:
History:
Episodic pain, felt in the center of the epigastrium and slightly to the right, may radiate through to the back. Relieved by food or antacid, come on when patient is hungry. The pain will often awake the patient at two O'clock in the morning, is seldom very severe unless complications arise.(13) Sometimes the history is atypical with the pain in the umbilical region or lower chest or with nature and severity suggesting biliary origin.
Physical examination:
Abdominal examination is usually normal. Sometimes valuable signs may be present in addition to signs of concomitant illness.
Tenderness in the epigastrium and in rare occasion DU may form a palpable tumour. If obstruction occurs the stomach may be visible, palpable and a succussion splash may be present.(14)
Assessment of patient:
Diagnosis of DU should be confirmed by fibre optic gastroduodunoscopy. Barium examination is no longer being
recommended as first line of investigation. Antral biopsy to confirm the presence or absence of H. pylori.
Treatment:
If the presence of DU is confirmed, the first line of treatment is medical, more than 97% of ulcers are associated with H. pylori infection, so the regimen is designed to both heal the ulcer and eradicate H. pylori.
If H. Pylori is negative and there is no history of NSAIDs ingestion rarer causes of PU should be sought. e.g. ZE-syndrome.
Surgical treatment is preserved for those with failed medical treatment and those presenting with complications" Haemorrhage, perforation, or pyloric stenosis".(13)
Gastric ulcer:
Gastric ulcer pathogenesis is still not fully understood. The possibility that GU may be malignant must never be forgotten. This is more common in the elderly. It occurs in those with normal or low acid output. The plan would be to do endoscope with four quadrant biopsies and if proved to be benign, it’s treated medically with H2 receptors antagonists, PPI or other cytoprotective agents, e.g. Sucralfate or mesoprosol. Then an endoscope and biopsy to be carried out 6-8 weeks later. If the ulcer is not healed gastrectomy should be considered.
In both types of ulcers patients are advised to:
Have regular meals, Give up cigarettes and alcohol and Avoid drugs such as aspirin and endomethazine if possible.
Complications of peptic ulcer:
Obstruction occur (five percent) Perforation in (ten percent)
Penetration "sealed perforation" in (five percent) and Haemorrhage in
(15%) (Melaena more than hematemesis).(15)
¾ Peptic ulcer perforation (PUP):
Perforated DU is more common than perforated GU.(2)
The usual presentation is sudden onset of severe abdominal pain, enough to urge the patient to come to hospital within few hours, pain may be referred to the shoulders; The patient may or may not give a history of previously diagnosed ulcer disease. Frequently the patient might not recall the previous dyspeptic symptoms due to the distress of perforation.
Abdominal rigidity due to peritoneal soilage and chemical peritonitis felt as "board like rigidity" is the most striking findings. The disease course depends upon the size of perforation and amount of peritoneal soiling and the time from onset to presentation.(16)
If the perforation is small and walled off by surrounding
structures with only minimal contamination, the perforated ulcer may be
overlooked and the patient may recover without complications.(16,17)
The distribution of gastric contents within the abdomen will
affect the presentation hence it may be confused with pancreatitis,
appendicitis, cholecystitis, diverticulitis and ovarian pathology in females.
The diagnosis of PUP is usually easily made on clinical grounds.
Investigations:
1- Erect chest x-ray or in left lateral decubitus position to demonstrate
free air under the diaphragm.
2- White blood cell count may show mild leukocytosis, which
increases as bacterial contamination intervenes.
3- Serum amylase may show mild elevation due to it's absorption from
the peritoneum.
4- Occasionally gastrographin meal may be used in which case
diagnosis is established by demonstration of leak from the perforation
in the peritoneal cavity.(16)
5- Investigations to assess the general condition of the patient.
Management:
Resuscitative treatment should begin immediately in the form of
nasogastric suction, correction of fluid and electrolytes disturbance by
intravenous administration, establishment of good urinary output as a guide to adequate resuscitation and administration of broad spectrum antibiotics.
Surgical management of PPU:
The surgical treatment of perforation is affected by the size of the perforation, the time of presentation to hospital after perforation (>24 hours), the general condition of the patient and the presence of concomitant medical illness.
Options of treatment:
Simple closure which is limited by the size of perforation and the sutures cutting through the inflamed duodenal wall has the first method introduced in treatment of PUP.
Closure with an omental patch is the most widely used method, it was described by Cellan-Jones in 1929, however, thought unreliable in closing large ulcers.(2) Carrying out definitive procedure is a time consuming procedure and it is unwise to be performed in patients with the risk factors mentioned earlier. However, it is indicated when perforation occurs, while the patient taking antiulcer therapy or the patient had a previous ulcer complication.
In cases of large perforation in which simple closure or closure with omental patch is impossible and performing a definitive procedure is
risky because of the presence of one or more of the risk factors, a new technique of a nasogastric tube advanced by the anaesthetist and guided by the surgeon to protrude through the perforation with a peace of omentum attached to the tube using one or two catgut sutures. Then the tube is withdrawn and the plug pulled into the perforation. Blocking the perforation securely the edges of the omental plug are tacked to the margins using one or two catgut sutures this followed by the routine meticulous peritoneal toilet with the subhepatic space drained using a fine suction drain. The nasogastric tube is placed on a low-pressure suction
(50 mmHg) for 72 hours with the patient given H2 antagonists intravenously. Nasogatric tube is removed after one week when the catgut suture attach it to the omentum is dissolved.(18)
Laparoscopic repair of perforated peptic ulcer:
Laparoscopic techniques for perforated peptic ulcers have developed over the past few years with development of both sutured and sutureless repairs.
Laparoscopic sutureless repair is performed using fibrin glue and a gelatin plug. The safety of the technique has already been evaluated.
Study aimed to define patients who may not benefit from laparoscopic techniques, compared 219 patients of PPU treated by simple repair, 109
patients treated by laparoscopic sutureless (fibrin glue) repair and 46 by laparoscopic suture repair.
The overall leakage rate of laparoscopic suture and suture less repair was six percent and 16% respectively.
Leakage was noted to be associated with a significantly high rate of wound infection, intra-abdominal abscess formation, prolonged ileus and long hospital stay.
Multivariate analysis demonstrated that acute physiology and chronic health evaluation (APACHE) II score on admission predicted the likely hood of leak after laparoscopic fibrin glue repair (P=0.006). So
APACHC II score may be a useful index for selecting patients for laparoscopic fibrin glue repair.(17,19,20)
Non-operative management of PPU:
Immediate operative repair is the widely practiced therapy for
DU perforation seems to be the only conceivable course to be recommended for most patients. Some times patients may refuse operation or at operation the perforation has some times already sealed of by omentum.
The successfulness of non-operative treatment of PPU has been recognized since 1870. In 1964 Herman Taylor reported the conservative
treatment of 256 patients with perforations with only 21 patients require surgery and the over all mortality rate was 11%.
Seely and Campbell reported seven deaths in 139 patients treated conservatively, a mortality rate of 5%.
A more recent series from Dublin confirmed that conservative treatment can have acceptable results.
The only randomized controlled comparison between non- operative treatment and surgery was performed in Hong Kong indicating that an initial period of expectant treatment does not increase the mortality or morbidity in patients with PPU. More than 70% of patients in the expectant treatment group recovered without an operation.
Non-operative management should only be employed, if an experienced surgeon interested in this form of treatment is willing to personally supervise patient's progress.
Nasogatric tube should be inserted to empty the stomach and reduce leakage. The success depends on keeping the stomach empty by nasogastric suction. Intravenous fluid administered at a rate depending upon the degree of dehydration to maintain a urine output of at least
30-60ml/h. Broad-spectrum antibiotics are also administered, the patient is carefully monitored and should be examined at least twelve hourly by the surgeon who made the initial assessment.
Improvement is indicated by decrease in the pulse rate, temperature, abdominal tenderness, and by an improvement in the general well being of the patient. The surgeon must be prepared to abandon conservative management and to undertake operative intervention without delay if the patient fails to improve.
The majority of patients will dramatically improve within twelve to 24 hours with oral fluid to be started when signs of peritonitis disappear and intestinal activity returns. Normal diet is resumed within few days.
H2 receptor antagonists or PPI should be given, followed by upper GI endoscopy six weeks later. Depending on the individual circumstances a decision is made whether to stop treatment or to continue long term maintenance with PPI or H2 blockers.
It was noted that conservative treatment may improve the outcome for frail elderly patients who may be too ill to withstand general anaesthesia. Unfortunately perforations are less likely to seal spontaneously in elderly patients because of atrophic omentum, also the elderly patients withstand continued intra-abdominal sepsis poorly.(20,21)
Effect of Helicobacter pylori eradication:
Helicobacter pylori eradication after simple closure of a perforation is studied in 202 patients with perforated ulcer in whom simple closure was done and then randomized in two groups, to receive
ranitidine alone or quadruple therapy (ranitidine, colloidal bismuth. subcitrate, metronidazole and tetracycline) the study showed a reduction in the incidence of residual and recurrent ulcers in those received eradication therapy. (22)
H. pylori infection was found in 80% of those with perforated
DU. Predominantly in younger patients, who had less NSAIDs consumption and more prolonged dyspepsia. Non-NSAIDs induced duodenal ulcer perforation are probably due to H. pylori infection.(9)
DISCUSSION
Perforated peptic ulcer is a serious complication of peptic ulcer disease. This study is the first of its kind to address this problem in Sudan.
In this country the disease affects young age group. In this study 50% of the patients were under the age of 30 years. This is exactly the opposite to the western data which shows a tendency of the disease to occur in an elderly group as a result of increased use of NSAIDs in the treatment of arthritis.(1,10)However, case reports of PUP in the young age group is also known in the literature.(8,23)
In this study it is clear that younger age group were less likely to develop postoperative complications, as more than three quarters of those who developed postoperative complications were above the age of 41 years. This is in line with what is mentioned in many studies that old age is one of the risk factors of morbidity and mortality.(22,24) Six out of the seven deaths were above 51 years. It is also shown that out of the 13 patients who did not show evidence of generalized peritonitis “board like rigidity” were above the age of 51 years. It had been reported in the literature that silent perforation commonly occur in elderly patients.(5)
The disease is well known to affect male patients with male to female ratio of 2 : 1, in this study the ratio is exaggerated to almost 10: 1.
Two thirds of the female patients developed postoperative complications
“four out of the six” two of them died “out of the total seven deaths”. The severe course of the disease noticed in female patients could be attributed in one patient who died to the misdiagnosis due to the presence of gallstones that lead to diagnosis of acute cholecystitis. A similar one in male patient also ended in fatality. It is reported in the literature that PPU may mimic gall bladder disease. (25) Study from Singapore in the adverse operative risk factors for PPU concluded that female gender is among the risks.(26)
In this study 40(68.4%) patients were referred from outside
Khartoum State and 18(31.6%) were citizens of the capital. Nearly 50% of the patients were originally from northern Sudan and 30% from central
Sudan. There is well known diversity in the dietary culture in different parts of the Sudan. Northern Sudan is nearer to the capital, which ease movement to reach the medical service. It is obvious that in such an acute disease patients are unlikely to be referred to Khartoum from remote regions of the Sudan for treatment. However, it’s our impression from personal contact with other regions that the incidence is rather low.
The most striking finding in this study was the increased incidence of perforation during fasting [22 out of 58(38.6%)] which occurred in the holly month “Ramadan”, the 9th month in moon calendar when people abstain from food, drinks and refreshments from dawn to
sunset “about 14 hours”. Another important finding is that perforation in fasting patients occurred, in most cases, towards the end of the day, and even higher percentage towards the end of the month. This indicated that fasting is a triggering factor for perforations.
Most of our patients were not known to be diagnosed as PU patients and hence were not on regular anti-ulcer medications. It could be hypothesized that the neglected PUD, plus the hunger and stress of fasting together lead to the development of perforation. This fact has been mentioned in a study from Turkey concluding that fasting increases peptic ulcer complications, (27).
An interesting observation seen in the study is the seasonal variation in the incidence of perforation. Forty-two (72.4%), of perforations occurred during the winter season. In Sudan this starts some times around November and continues to March “about 4 months”.
To the best of our knowledge this relation has not been mentioned in the literature.
The possibility of physiological changes during winter, tendency for eating hot and species foods and stress of the cold weather could be a possible explanation.
Concurrent illness occur in only 9(15.5%) patients, this is because most of the studied population were young, so correlation of the
presence of concurrent illness to postoperative complications gave statistically insignificant result (P = 0.103).
In this study erect CXR and upper abdomen showed gas under the diaphragm in 90% of those investigated. International data showed lower sensitivity “gas under the diaphragm occurs in 60–70%).(6,28,29,30)
This indicate the value of this investigation as a sensitive tool for diagnosis.
In the same context correlation of size of perforation to presence or absence of gas under the diaphragm was not statistically significant
(P= 0.897), indicating that the presence of gas under the diaphragm has nothing to do with the size of perforation.
Electrolyte disturbances, namely hypokalaemia and hyponatraemia are both significant in the development of postoperative complication. These findings had been recently reported.(17) It is the delay in the presentation that leads to ileus and vomiting resulting in electrolyte disturbances.
Eleven of the 18 patients who developed postoperative complications did present primarily with circulatory collapse
(hypotension & tachycardia), (P<0.004), this is similar to what was mentioned e.g. the study of F.Y.J. Lee & Colleagues who related
incidence of postoperative leak to the (APCHE II score)(Appendix) on admission.(17)
Hypotension and tachycardia actually occurred on those presented late with bacterial peritonitis, vomiting and/or septicaemia.
During laparotomy 10(17.9%) patients were having pus in the peritoneal cavity, seven (12.5%) of them later developed postoperative complications, which gave a high statistically significant result (P =
0.0084).
The presence of pus could also be attributed to late presentation when bacterial peritonitis follows the chemical peritonitis. In the same context the study showed that those who were fasting during perforation are less likely to develop postoperative complications as only four out of the 22 who were fasting developed postoperative complications
(pneumonia in three cases and adhesive intestinal obstruction in one).
It seems that empty stomach during perforation may contribute to a lesser incidence of sepsis, abscess, wound infection and death.
There were seven deaths (12.1%) in this study. Six of them reached the hospital more than 24 hours after perforation. This could be attributed to many factors. Misdiagnosis happened in two cases, other two were referred from a remote area with the journey taking 10-14 hours, and two were diabetics. The last one was a case of re-perforation treated in the
first time by simple patch repair and was put on omeprazole, and then he was lost to flow up and presented after three years with features of PPU.
Chest x-ray demonstrated free gas under the diaphragm. The patient was shocked on presentation, and died before doing laparotomy. Postmortem was not done.
It is obvious that delayed presentation and presence of concurrent medical disease are two risk factors for mortality, which is also mentioned in most of the studies.(21,31)
Out of the nine patients with giant perforation (>10mm), only one of them died. The correlation of size of perforation to the postoperative complications showed no statistically significant results (P
= 0.148). This indicates that the size of the perforation on its own is not a risk factor for mortality.
However Chandhary from India studied a group of patients with giant perforation (> 10cm) with death occurred in three out of nine patients,(32) which is higher than the number in this study.
In the same context correlating the sum of complications to the size of perforation showed statistically significant result (P= 0.0369).
Perhaps because large size perforation increases the septic load and requires a longer operative time to deal with it.
In this study most of patients were treated by simple closure with an omental patch 53(91%) with only two were treated by other methods and the last three, one was treated conservatively, one found already sealed perforation and one died before surgery. Hence when correlating the different methods of treatment to postoperative complications, it showed statistically insignificant result (P=0.698). This is because only small number of patients were treated by methods other that simple closure with omental patch.
Overall mortality in this study is seven (12%) and other complications eleven (18.9%). This is compatible with the figures in the literature. However, with exclusion of patients who were not treated by simple patch closure; mortality reduces to (8.5%) relatively lower than international figures.
RECOMMENDATIONS
1- Erect chest x-ray should be used, as it is a simple quick
examination in all patients presented with upper abdominal pain.
2- Younger age group who complain of dyspeptic symptoms early in
the beginning of the fasting month should not be taken lightly as due to
disturbance of pattern of life and should be endoscoped to exclude
PUD.
3- Strong antiulcer therapy e.g. omeprazole should be prescribed to be
taken by those whom are PU patients at night during Ramadan.
4- Those who are known cases of PUD and on maintenance therapy or
no therapy should either be encouraged to continue anti-ulcer
treatment or closely observe during winter season.
REFERENCES
1) Stephen WE, Lee LS, Nathomiel JS, Michael L. Mastery of
endoscopic and laparoscopic surgery. Philadelphia: PA 2000;
19106-3780; USA P. 194-203.
2) Russel RC, Williams NS, Bulstrode CJ. Baley & Love's short
practice of surgery. 23rd ed. London NW1: Arnold, 338 Euston
Road. BBH; 2000; P. 901-914.
3) Towfigh S, Chandler C, Hines DJ, Mcfaddey DW. Outcomes
from peptic ulcer surgery have not benefited from advances in
medical therapy. Am Surg 2002; 68(4): 385-389.
4) Harlod E. Anatomy of stomach and duodenum. In: Clinical
anatomy, a revision and applied anatomy for clinical students,
7th ed. Chicago: Year Book Medical Publishers; 1986. P. 83-88.
5) Jeffrey AN, Randal R, Alfred EC, Stephen FH, Robert WT.
Surgery basic science and clinical evidence. USA: Donnelley
and Sons, Willard OH; 2001. P. 489 - 500.
6) Seymour IS, Tom G, Frank CS, John MD, Josef EF, Aubrey
CG. Principles of surgery, 7th ed. Singapore: McGraw-Hill
Book Co; 1999. P. 1181-1201.
7) Tale JJ, Dawson JW, Lau AK. Sutureless laparoscopic treatment
of perforated duodenal ulcer. Br J S 1993; 80: 235.
8) Anthony JV, Migvel C. Perforated peptic ulcer in an eleven year
old (case report). Jack Sonville Med 1999 (www.tgila.com).
9) EKWNG, Chung SC, Sung JY, Lam YH, Lee WH, Law JY,
Ling TK, Lau WY. High prevalence of H. Pylori infection in
duodenal ulcer perforations not caused by Nonsteroidal anti-
inflammatory drugs. Br J Surg 1996; 83: 1779-81.
10) Courtney M, Townsend MD, John WH. Peptic ulcer. In:
Sabliston Textbook of surgery the biological bases of modern
surgical practice, 16th ed. USA: W.B Saunders Company; 2001.
P. 837-55.
11) Ng EK, Lam YH, Sung JJ. Eradication of H. pylori
prevents recurrence of ulcer after simple closure of duodenal
ulcer perforation. Ann Surg 2000; 231: 153 -58.
12) Mez DC, Forsmork C, Lew EA. Replacement of proton
pump inhibitors with I.V pentoprazole to effectively control
gastric acid hyper secretion on patients with ZE syndrome. Am J
Gastroentrol 2001; 96(12): 827-80.
13) Michael JZ, Seymour IS, Horold E, Stanley W, David
WM. Peptic ulcer disease. In: Maingot's abdominal operations,
10th ed. USA: Kathleen McCullough Production Service: York
Production Service Libby Schmitz; 2000; 941 -994.
14) James DH, John SK, Harvey I. Peptic ulcer. In: Hady's
textbook of surgery, 2nd ed. Philadelphia: Pennsylvania: JB
Lippmcott Company Cast Washington Square; 1905.
15) YongH, HahnMD. Duodenal
ulcer.1995.http://chorus.rad.mcw.edu/doc/00940.
16) Kevin GB, Anthony EY. Peptic ulcer. In: The new Aird's
Companion in surgical studies, 2nded. London: Copyright
Licensing Agency Ltd, 90 Nottingham Court Road; 1988: P.
771-72.
17) Lee FY, Leung KL, Lai PB, Lan WY. Selection of
patients for laparoscopic repair of perforated peptic ulcer. BJS
2001; 88: 133-36.
18) Karanjia ND, Shanahan DJ, Knight MJ. Omental patching
of a large perforated duodenal ulcer: a new method. Br J S.
1993; 80: 65.
19) Tate JJ, Dawson JW, Lau WY. Suture-less laparoscopic
treatment of perforated duodenal ulcer. Br J Surg 1993; 80: 235.
20) Sunderland GT, Chisholm EM, Lau WY. Laparoscopic
repair of perforated peptic ulcer. Br J Surg 1992; 79: 785.
21) Arther KC, Sydney SC. Non-operative management of
perforated peptic ulcer. http://www.club-03.narod.ru/oxifor/non-oper-man-
htm.
22) John AG. Management of peptic ulcer. Br J Surg 1994;
81: 161-163.
23) Feng CY, Hsu WM, Chen Y. Perforated peptic ulcer in
an infant. J Formos Med Assoc 2001; 100(2): 131.
24) Sillakivi T, Long A, Tem AP. Evaluation of risk factors
for mortality in surgically treated perforated peptic ulcer. Hepato
Gastroentrol 2000; 47(36): 1765-8.
25) Gabriela G. Perforated peptic ulcer masquerading as gall
bladder disease: CT-finding. Isr Med Assoc J 2002; 4(4): 304-5.
26) Chan WH, Wong WK, Khin LW, Soo KC. Adverse
operative risk factors for perforated peptic ulcer. An Acad Med
Singapore 2000; 29(2): 164-67.
27) Donderici O, Temizham A,Kucukbas T, Eskioglu E
.Effect of Ramadan on peptic ulcer complications. Scand J
Gastroenterol 1994Jul ; 29 (7) :603-6.
28) Alden HH, Ernest EM. Peptic ulceration. In: Abernathy's
surgical secrets, 4thed. Philadelphia: Hanley & Bdfus; 2000. P.
143-148.
29) Hitan CP, Bernard G, Harlen HS. Peptic ulcer. In: Basic
surgery. Missouri: Karen Bergert; 1993. P. 86-95, 203-10.
30) Al Fallouji MA. Perforated peptic ulcer. In: The
postgraduate Surgery: The candidate's guide, 2nd ed. Oxford:
Linacre House Jordan Hill; 1998. P. 325-28.
31) John M, Graeme D, Kevin O. Perforated peptic ulcer. In:
Surgical emergencies, 1st ed. Italy: Canale & C. SPA, Turin;
1999. P. 113-121.
32) Chaudhary A, Bose SM, Gupta NM. Giant perforation of
duodenal ulcer. Indian J Gastroenterol 1991; 10(1): 14-15.