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Discussion on Perforated Peptic Ulcer Disease
                                 Muhamad Na’im B. Ab Razak
                                  University Sains Malaysia


74 years old Malay lady with history of indigestion for the past one year , and fall one week
prior to admission and on tablet pain killer presented with signs of peritonism and symptomatic
anemia on the day of admission. Erect chest x- ray shows a gas under diaphragm. After
stabilizing the patient, she was prepared for emergency laparatomy which then reveals
perforated duodenal ulcer. It is then repaired with Simple Graham's patches and the abdominal
cavity is irrigated with 10L of normal saline.

                                             *****

Peptic ulcers are defects or breach in the gastric or duodenal mucosa that extends through the
muscularis mucosa.

Abnormal acid secretion with an elevated duodenal acid load was considered the primary
disorder leading to mucosal ulceration and while acid secretion remains important, successful
treatment of H. pylori infection virtually eliminates ulcer recurrences showing that H. pylori
infection is the primary abnormality. An infectious etiology is found in at least 95% of duodenal
ulcers and 70-100% of gastric ulcers. [Stephan Miehlke]

However, the most common causes are H. pylori infection and use of non-steroidal anti-
inflammatory drugs.

H. pylori is a Gram-negative microaerophilic non-invasive spiral bacillus which has the ability to
colonize the gastric mucosa. It has a powerful urease enzyme which catalyses hydrolysis of urea
to ammonia, enabling the bacteria to survive in the acid milieu. Although it induces a strong host
local and systemic immune response (which is important in pathogenesis) it has also developed
mechanism to evade host immunity. [Debabrata Majumdar]

Approximately half of all strains of H. pylori contain a 40-kb DNA virulence cassette known as
the pathogenicity island (PAI) encodes a type IV secretion system that injects the CagA protein
into the host epithelial cell. H. pylori possessing this cassette produce greater gastric
inflammation and a higher risk of intestinal-type malignancies than strains that do not contain
this gene. [Jonathan Volk]

H. pylori can undergo point mutations and chromosomal rearrangements, making it more subject
to resistance to certain types of antibiotic.
The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is, overall, of
only about 60%, which contrasts with the 90–100% figure usually reported in non- complicated
ulcer disease. However, the most important factor associated with H. pylori-negative perforated
peptic ulcer is non-steroidal anti-inflammatory drugs use, and if this factor is excluded,
prevalence of infection is almost 90%, similar to that found in patients with non-perforating ulcer
disease. [J.P. Gisbert et al]

Other, less common causes of Peptic Ulcer Disease, PUD includes hypersecretory states, such as
Zollinger-Ellison syndrome, G-cell hyperplasia, mastocytosis, and basophilic leukemias.

PUD was the major indication for gastro duodenal surgery during the 1950s though the 1970s.
However, by the 1980s, the number of operations performed for PUD began to decrease
substantially. Multiple investigators have shown 50% to 80% decreases in operations for PUD in
the United States and Europe during this time period. This decrease in surgical procedures has
occurred primarily as a result of the near-complete disappearance of elective surgery for PUD .In
fact, during the last 10 to 15 years; there has been evidence that the number of perforated and
bleeding ulcers may be increasing [George A. Sarosi]

The usage of protein pump inhibitors and histamine blocker has showed remarkable decrease in
surgery for PUD.

Perforated PUD is not a common complication. However, the risk increases as the age of the
patient increases. According to study made by Steven F. Fowler, the majority of the patient
operated due to this type of complication (99 of 109 patients (86%) required an emergent
operation) is elderly with the age of more than 60 which comprise of 71% of all patients.

Even so if the complication has occurred, current treatment for perforated gastric ulcers has
revolving from time to time with the development of antibiotic and also new advance technology
in laparoscopy, hence providing a better outcome for the patient, post-operatively.

In diagnosing perforated PUD, few parameters are very useful in establishing the diagnosis.
According to Elfatih Elnagib et al, 74.1% of the patient has history of dyspepsia for three
months, 77.6% of patients presented with board-like rigidity of the abdomen, Ninety percent of
those who underwent CXR showed gas under the diaphragm.

If patient is too ill for erect chest X-ray, a left lateral recumbent X-ray is also useful. Abdominal
ultrasound may also helpful in detecting gas under diaphragm. Once the diagnosis is confirmed,
then definitive treatment will be done.
From the historical aspect, an attempt to close perforated gastric ulcer was firstly done by
Mikulicz in 1880 but fail. Nearly 30 years later, then only the first successful suture of perforated
gastric ulcer was done by Heusner.

Keetley advocated emergency gastrectomy in 1902, and definitive surgery was widely used until
Graham described 2% mortality among his patients with duodenal perforation who underwent
simple suture with an omental plug (Graham, 1937). Since then simple suture has been widely
used for the treatment of both gastric and duodenal perforation. [J. Wilson-Macdonald et al]

An alternative way for management of perforated peptic ulcers is by treating the patient
conservatively by using Taylor's approach, i.e; gastric aspiration following peptic perforation. If
it's failed, then radical surgery involving vagotomy and even gastrectomy has been performed.
Suture closure-is still the treatment of choice for perforated peptic ulcers, despite the proven
efficacy of Taylor's conservative approach. Such conservative management, however, has been
proven less effective in high-risk patients and those with perforations more than 12 h old
[D. Urbano et al]

The development of new and wide-spread use of acid suppressing medication and H. Pylori
eradication has reduced significantly the need of radical surgery.

A new approach towards managing the case of perforated peptic ulcer that gaining popularity
now a day is via laparoscopic method.

This method is pioneered by Mouret who reported the first laparoscopic sutureless repair with
fibrin glue omental patch for a perforated duodenal ulcer. Meanwhile, in the same year,
Nanthanson has successfully performed laparoscopic suture repair for perforated peptic ulcer.

As compared to open surgery, laparoscopic approach increased operative time, reduced
requirement for postoperative analgesia, reduced time to return to a normal diet, shorter hospital
stay and earlier return to work. There is no difference was found in blood loss, stress response
(as determined by endotoxemia, bacteremia, and inflammatory markers), postoperative gastric
emptying, or morbidity or mortality. [Faisal Aziz]

Post-operatively, rate of recoveries determined by various factors including the initial
presentation of the patient to the hospitals. Patient might be complicated with wound infection,
burst abdomen, hematemesis, gastro-duodenal fistula, enterocutaneous fistula, intraperitoneal
abscess, respiratory complications and death

According to Smita S Sharma et al, they are 17 factors that could potentially influence the
postoperative morbidity and mortality – 14 measured on admission and 3 measured operatively.
The predictors measured on admission were age, sex, duration of pain, vomiting, abdominal
distension, history suggestive of oliguria, history suggestive of acid peptic disease, history
suggestive of shock, history suggestive of dehydration, history of smoking, presence of
associated medical condition(s), tenderness, presence of bowel sounds and blood group

 At the end through her study, she concluded that abdominal distension, presence of a
concomitant medical illness and a history suggestive of shock at the time of admission warrant a
closer and alacritous postoperative management in patients of perforated peptic ulcer.

Emergency operations for peptic ulcer perforation carry a mortality risk of 6-30%. [Faisal Aziz]


Reference:

   1) Debabrata Majumdar, James Bebb & John Atherton, "Helicobacter pylori Infetion and
      Peptic Ulcer", Medicine, Volume 35, Issue 4, April 2007, Pages 204-209 , Elsevier Ltd

   2) D. Urbano, M. Rossi, P. De Simone, et al, "Alternative laparoscopic management of
      perforated peptic ulcers", Surgical Endoscopy, Vol. 8, No 10, October 1994, Springer
      New York

   3) Elfatih Elnagib, Seif Eldin I Mahadi & Mohamed E Ahmed, "Perforated peptic ulcer in
      Khartoum", Kharoum Medical Journal, Vol. 01, No. 02 pp. 62-64, 2008

   4) Faisal Aziz, "Perforated Peptic Ulcer", http://emedicine.medscape.com/article/197643-
      overview, accessed 26 March 2010, 1.50 a.m

   5) George A. Sarosi, Jr.,Kshama R. Jaiswal, Fiemu E. Nwariaku, et al, "Surgical therapy of
      peptic ulcers in the 21st century: more common than you think", The American Journal
      of Surgery 190, 775–779, Excerpta Medica Inc, 2005

   6) Jonathan Volk& Julie Parsonnet, "Epidemiology of Gastric Cancer and Helicobacter
      pylori; The Biology of Gastric Cancers", Springer New York, 2009.

   7) J.P. Gisbert, J. Legido, I. Garcia-Sanz & J.M. Pajares, "Helicobacter pylori and
      perforated peptic ulcer Prevalence of the infection and role of non-steroidal anti-
      inflammatory drugs", Digestive and Liver Disease 36, 116–120,Elsevier Ltd, 2004.

   8) J. Wilson-Macdonald, N. J. Mortensen and R. C. Williamson, "Perforated gastric ulcer",
      Postgrad Med J 1985 61: 217-220, The Fellowship of Postgraduate Medicine.
9) Smita S Sharma, Manju R Mamtani, Mamta R Sharma & Hemant Kulkarni, "A
   prospective cohort study of postoperative complications in the management of perforated
   peptic ulcer", BMC Surgery 2006, 6:8, Sharma et al; licensee BioMed Central Ltd

10) Steven F. Fowler, Jake F. Khoubian, Ron A. Mathiasen & Daniel R. Margulies, "Peptic
    ulcers in the elderly is a surgical disease", The American Journal of Surgery 182, 733–
    737, Excerpta Medica, 2002.

11) Tri H Le, MD, "Peptic Ulcer Disease", http://emedicine.medscape.com/article/181753-
    overview, accessed on 26 March 2010, 12.20 a.m

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Perforated Peptic Ulcer Discussion

  • 1. Discussion on Perforated Peptic Ulcer Disease Muhamad Na’im B. Ab Razak University Sains Malaysia 74 years old Malay lady with history of indigestion for the past one year , and fall one week prior to admission and on tablet pain killer presented with signs of peritonism and symptomatic anemia on the day of admission. Erect chest x- ray shows a gas under diaphragm. After stabilizing the patient, she was prepared for emergency laparatomy which then reveals perforated duodenal ulcer. It is then repaired with Simple Graham's patches and the abdominal cavity is irrigated with 10L of normal saline. ***** Peptic ulcers are defects or breach in the gastric or duodenal mucosa that extends through the muscularis mucosa. Abnormal acid secretion with an elevated duodenal acid load was considered the primary disorder leading to mucosal ulceration and while acid secretion remains important, successful treatment of H. pylori infection virtually eliminates ulcer recurrences showing that H. pylori infection is the primary abnormality. An infectious etiology is found in at least 95% of duodenal ulcers and 70-100% of gastric ulcers. [Stephan Miehlke] However, the most common causes are H. pylori infection and use of non-steroidal anti- inflammatory drugs. H. pylori is a Gram-negative microaerophilic non-invasive spiral bacillus which has the ability to colonize the gastric mucosa. It has a powerful urease enzyme which catalyses hydrolysis of urea to ammonia, enabling the bacteria to survive in the acid milieu. Although it induces a strong host local and systemic immune response (which is important in pathogenesis) it has also developed mechanism to evade host immunity. [Debabrata Majumdar] Approximately half of all strains of H. pylori contain a 40-kb DNA virulence cassette known as the pathogenicity island (PAI) encodes a type IV secretion system that injects the CagA protein into the host epithelial cell. H. pylori possessing this cassette produce greater gastric inflammation and a higher risk of intestinal-type malignancies than strains that do not contain this gene. [Jonathan Volk] H. pylori can undergo point mutations and chromosomal rearrangements, making it more subject to resistance to certain types of antibiotic.
  • 2. The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is, overall, of only about 60%, which contrasts with the 90–100% figure usually reported in non- complicated ulcer disease. However, the most important factor associated with H. pylori-negative perforated peptic ulcer is non-steroidal anti-inflammatory drugs use, and if this factor is excluded, prevalence of infection is almost 90%, similar to that found in patients with non-perforating ulcer disease. [J.P. Gisbert et al] Other, less common causes of Peptic Ulcer Disease, PUD includes hypersecretory states, such as Zollinger-Ellison syndrome, G-cell hyperplasia, mastocytosis, and basophilic leukemias. PUD was the major indication for gastro duodenal surgery during the 1950s though the 1970s. However, by the 1980s, the number of operations performed for PUD began to decrease substantially. Multiple investigators have shown 50% to 80% decreases in operations for PUD in the United States and Europe during this time period. This decrease in surgical procedures has occurred primarily as a result of the near-complete disappearance of elective surgery for PUD .In fact, during the last 10 to 15 years; there has been evidence that the number of perforated and bleeding ulcers may be increasing [George A. Sarosi] The usage of protein pump inhibitors and histamine blocker has showed remarkable decrease in surgery for PUD. Perforated PUD is not a common complication. However, the risk increases as the age of the patient increases. According to study made by Steven F. Fowler, the majority of the patient operated due to this type of complication (99 of 109 patients (86%) required an emergent operation) is elderly with the age of more than 60 which comprise of 71% of all patients. Even so if the complication has occurred, current treatment for perforated gastric ulcers has revolving from time to time with the development of antibiotic and also new advance technology in laparoscopy, hence providing a better outcome for the patient, post-operatively. In diagnosing perforated PUD, few parameters are very useful in establishing the diagnosis. According to Elfatih Elnagib et al, 74.1% of the patient has history of dyspepsia for three months, 77.6% of patients presented with board-like rigidity of the abdomen, Ninety percent of those who underwent CXR showed gas under the diaphragm. If patient is too ill for erect chest X-ray, a left lateral recumbent X-ray is also useful. Abdominal ultrasound may also helpful in detecting gas under diaphragm. Once the diagnosis is confirmed, then definitive treatment will be done.
  • 3. From the historical aspect, an attempt to close perforated gastric ulcer was firstly done by Mikulicz in 1880 but fail. Nearly 30 years later, then only the first successful suture of perforated gastric ulcer was done by Heusner. Keetley advocated emergency gastrectomy in 1902, and definitive surgery was widely used until Graham described 2% mortality among his patients with duodenal perforation who underwent simple suture with an omental plug (Graham, 1937). Since then simple suture has been widely used for the treatment of both gastric and duodenal perforation. [J. Wilson-Macdonald et al] An alternative way for management of perforated peptic ulcers is by treating the patient conservatively by using Taylor's approach, i.e; gastric aspiration following peptic perforation. If it's failed, then radical surgery involving vagotomy and even gastrectomy has been performed. Suture closure-is still the treatment of choice for perforated peptic ulcers, despite the proven efficacy of Taylor's conservative approach. Such conservative management, however, has been proven less effective in high-risk patients and those with perforations more than 12 h old [D. Urbano et al] The development of new and wide-spread use of acid suppressing medication and H. Pylori eradication has reduced significantly the need of radical surgery. A new approach towards managing the case of perforated peptic ulcer that gaining popularity now a day is via laparoscopic method. This method is pioneered by Mouret who reported the first laparoscopic sutureless repair with fibrin glue omental patch for a perforated duodenal ulcer. Meanwhile, in the same year, Nanthanson has successfully performed laparoscopic suture repair for perforated peptic ulcer. As compared to open surgery, laparoscopic approach increased operative time, reduced requirement for postoperative analgesia, reduced time to return to a normal diet, shorter hospital stay and earlier return to work. There is no difference was found in blood loss, stress response (as determined by endotoxemia, bacteremia, and inflammatory markers), postoperative gastric emptying, or morbidity or mortality. [Faisal Aziz] Post-operatively, rate of recoveries determined by various factors including the initial presentation of the patient to the hospitals. Patient might be complicated with wound infection, burst abdomen, hematemesis, gastro-duodenal fistula, enterocutaneous fistula, intraperitoneal abscess, respiratory complications and death According to Smita S Sharma et al, they are 17 factors that could potentially influence the postoperative morbidity and mortality – 14 measured on admission and 3 measured operatively.
  • 4. The predictors measured on admission were age, sex, duration of pain, vomiting, abdominal distension, history suggestive of oliguria, history suggestive of acid peptic disease, history suggestive of shock, history suggestive of dehydration, history of smoking, presence of associated medical condition(s), tenderness, presence of bowel sounds and blood group At the end through her study, she concluded that abdominal distension, presence of a concomitant medical illness and a history suggestive of shock at the time of admission warrant a closer and alacritous postoperative management in patients of perforated peptic ulcer. Emergency operations for peptic ulcer perforation carry a mortality risk of 6-30%. [Faisal Aziz] Reference: 1) Debabrata Majumdar, James Bebb & John Atherton, "Helicobacter pylori Infetion and Peptic Ulcer", Medicine, Volume 35, Issue 4, April 2007, Pages 204-209 , Elsevier Ltd 2) D. Urbano, M. Rossi, P. De Simone, et al, "Alternative laparoscopic management of perforated peptic ulcers", Surgical Endoscopy, Vol. 8, No 10, October 1994, Springer New York 3) Elfatih Elnagib, Seif Eldin I Mahadi & Mohamed E Ahmed, "Perforated peptic ulcer in Khartoum", Kharoum Medical Journal, Vol. 01, No. 02 pp. 62-64, 2008 4) Faisal Aziz, "Perforated Peptic Ulcer", http://emedicine.medscape.com/article/197643- overview, accessed 26 March 2010, 1.50 a.m 5) George A. Sarosi, Jr.,Kshama R. Jaiswal, Fiemu E. Nwariaku, et al, "Surgical therapy of peptic ulcers in the 21st century: more common than you think", The American Journal of Surgery 190, 775–779, Excerpta Medica Inc, 2005 6) Jonathan Volk& Julie Parsonnet, "Epidemiology of Gastric Cancer and Helicobacter pylori; The Biology of Gastric Cancers", Springer New York, 2009. 7) J.P. Gisbert, J. Legido, I. Garcia-Sanz & J.M. Pajares, "Helicobacter pylori and perforated peptic ulcer Prevalence of the infection and role of non-steroidal anti- inflammatory drugs", Digestive and Liver Disease 36, 116–120,Elsevier Ltd, 2004. 8) J. Wilson-Macdonald, N. J. Mortensen and R. C. Williamson, "Perforated gastric ulcer", Postgrad Med J 1985 61: 217-220, The Fellowship of Postgraduate Medicine.
  • 5. 9) Smita S Sharma, Manju R Mamtani, Mamta R Sharma & Hemant Kulkarni, "A prospective cohort study of postoperative complications in the management of perforated peptic ulcer", BMC Surgery 2006, 6:8, Sharma et al; licensee BioMed Central Ltd 10) Steven F. Fowler, Jake F. Khoubian, Ron A. Mathiasen & Daniel R. Margulies, "Peptic ulcers in the elderly is a surgical disease", The American Journal of Surgery 182, 733– 737, Excerpta Medica, 2002. 11) Tri H Le, MD, "Peptic Ulcer Disease", http://emedicine.medscape.com/article/181753- overview, accessed on 26 March 2010, 12.20 a.m