Intestinal Perforation

Back

Background

Upper-bowel perforation can be described as either free or contained. Free perforation occurs when bowel contents spill freely into the abdominal cavity, causing diffuse peritonitis (eg, duodenal or gastric perforation). Contained perforation occurs when a full-thickness hole is created by an ulcer, but free spillage is prevented because contiguous organs wall off the area (as occurs, for example, when a duodenal ulcer penetrates into the pancreas).

Lower-bowel perforation (eg, in patients with acute diverticulitis or acute appendicitis) results in free intraperitoneal contamination.

Lau and Leow have indicated that perforated peptic ulcer was clinically recognized by 1799, but the first successful surgical management of gastric ulcer was by Ludwig Heusner in Germany in 1892. In 1894, Henry Percy Dean from London was the first surgeon to report successful repair of a perforated duodenal ulcer.[1]

Partial gastrectomy, although performed for perforated gastric ulcer as early as 1892, did not become a popular treatment until the 1940s. This was carried out as a result of the perceived high recurrence rate of ulcer symptoms after simple repair. The physiologic effects of truncal vagotomy on acid secretion had been known since the early 19th century, and this approach was introduced to the treatment of chronic duodenal ulcer in the 1940s.

The next development in the management of peptic ulcer disease was the introduction of high selective vagotomy in the late 1960s. However, neither of these approaches proved to be useful, and several postoperative complications, including high rates of ulcer recurrence, have limited their use. Currently, in patients with gastric perforation, simple closure of perforated ulcers is more commonly performed than is gastric resection.[2]

During World War I, the mortality following isolated injuries of the small intestine and colon was approximately 66% and 59%, respectively. The possible reasons for the high mortality and morbidity rates at that time may have been related to the following factors:

During the early years of World War II, Ogilvie, a leading surgeon in the British Army, recommended colostomy for management of all colonic injuries. This notion was supported by a publication from the office of the Surgeon General of the United States. However, the data presented in Ogilvie's series were not convincing. He reported a mortality rate of 53% for colonic injuries treated with colostomy, a rate similar to that observed during World War I.

According to Ogilvie, colostomy apparently failed to improve the mortality rate in World War II because primary repairs were used to treat less-severe injuries during World War I. Many patients in World War I were treated expectantly and were not included in the mortality data. On the other hand, Ogilvie's data included all patients with bowel injuries. These apparent differences in the methodology used convinced surgeons to continue using colostomies in such injuries after World War II.

Several reports clearly indicated that surgeons used colostomy during the Korean and Vietnam wars, particularly in the management of left colonic injuries. However, in civilian injuries, it has been reported that primary repair can be successfully used. By the end of 1980s, primary repair was considered to the management strategy of choice, and it has replaced the use of colostomies in the treatment of civilian patients in most hospitals in the United States, the United Kingdom, Europe, and Australia. At present, primary repairs are widely used for such bowel injuries.

Anatomy

The peritoneal cavity is lined with a single layer of mesothelial cells, connective tissue (including collagen), elastic tissues, macrophages, and fat cells. The parietal peritoneum covers the abdominal cavity (ie, abdominal wall, diaphragm, pelvis); the visceral peritoneum covers all of the intra-abdominal viscera, forming a cavity that is completely enclosed except at the open ends of the fallopian tubes.

The peritoneal cavity is divided by the transverse mesocolon. The greater omentum extends from the transverse mesocolon and from the lower pole of the stomach to line the lower peritoneal cavity. Abdominal organs, such as the pancreas, duodenum, and ascending and descending colon, are located in the anterior retroperitoneal space; the kidneys, ureters, and adrenal glands are found in the posterior retroperitoneal space. Other abdominal organs, the liver, stomach, gallbladder, spleen, jejunum, ileum, transverse colon, sigmoid colon, cecum, and appendix are found within the peritoneal cavity.

A small amount of fluid sufficient to allow movement of organs is usually present in the peritoneal space. This fluid is normally serous (protein content of <30 g/L, <300 WBCs/µL). In the presence of infection, the amount of this fluid increases, its protein content climbs to more than 30 g/L, and the white blood cell (WBC) count increases to more than 500/µL; in other words, the fluid becomes an exudate.

Pathophysiology

Normally, the stomach is relatively free of bacteria and other microorganisms because of its high intraluminal acidity. Most persons who experience abdominal trauma have normal gastric functions and are not at risk of bacterial contamination following gastric perforation. However, those who have a preexisting gastric problem are at risk of peritoneal contamination with gastric perforation.

Leakage of acidic gastric juice into the peritoneal cavity often results in profound chemical peritonitis. If the leakage is not closed and food particles reach the peritoneal cavity, chemical peritonitis is succeeded by gradual development of bacterial peritonitis. Patients may be free of symptoms for several hours between the initial chemical peritonitis and the later occurrence of bacterial peritonitis.

The microbiology of the small bowel changes from its proximal to its distal part. Few bacteria populate the proximal part of the small bowel, whereas the distal part of the small bowel (the jejunum and ileum) contains aerobic organisms (eg, Escherichia coli) and a higher percentage of anaerobic organisms (eg, Bacteroides fragilis). Thus, the likelihood of intra-abdominal or wound infection is increased with perforation of the distal bowel.

The presence of bacteria in the peritoneal cavity stimulates an influx of acute inflammatory cells. The omentum and viscera tend to localize the site of inflammation, producing a phlegmon. (This usually occurs in perforation of the large bowel.) The resulting hypoxia in the area facilitates growth of anaerobes and produces impairment of bactericidal activity of granulocytes, which leads to increased phagocytic activity of granulocytes, degradation of cells, hypertonicity of fluid forming the abscess, osmotic effects, shift of more fluids into the abscess area, and enlargement of the abdominal abscess. If untreated, bacteremia, generalized sepsis, multiorgan failure, and shock may occur.

Etiology

Causes of intestinal perforation include the following:

Epidemiology

In children, small-bowel injuries following blunt abdominal trauma are infrequent, with an incidence of 1-7%. Evidence shows, however, that the incidence of these injuries is increasing.

In adults, perforations of peptic ulcer disease were a common cause of morbidity and mortality with acute abdomen until the latter half of the 20th century. The rate has fallen in parallel with the general decline in the prevalence of peptic ulcer disease. Duodenal ulcer perforations are 2-3 times more common than are gastric ulcer perforations. About a third of gastric perforations are due to gastric carcinoma.

Approximately 10-15% of patients with acute diverticulitis develop free perforation. Although most episodes of perforated diverticulum are confined to the peridiverticular region or pelvis, patients occasionally present with signs of generalized peritonitis. The overall mortality is relatively high (~20-40%), largely because of complications, such as septic shock and multiorgan failure.

In elderly patients, acute appendicitis has a mortality of 35% and a morbidity of 50%. A major contributing factor to morbidity and mortality in these patients is the presence of 1 or more severe medical conditions coexisting with, but predating, the appendicitis.

Endoscopy-associated bowel injuries are not a common cause of perforation. For example, perforations related to endoscopic retrograde cholangiopancreatography (ERCP) occur in about 1% of patients.[5]

Prognosis

Outcome is improved with early diagnosis and treatment. The following factors increase the risk of death:

History

A careful medical history often suggests the source of the problem, which is subsequently confirmed by clinical examination and radiologic study findings. Possible etiologies include the following:

With regard to abdominal pain, it is important to ask patients about the time of onset of pain, the duration and location of pain, the characteristics of pain, relieving and aggravating factors, and other symptoms associated with abdominal pain. A history of similar attacks may also suggest the etiology.

Sharp, severe, sudden-onset epigastric pain that awakens the patient from sleep often suggests perforated peptic ulcer. Differentiate this from conditions such as cholecystitis and pancreatitis. Painless perforation of a peptic ulcer can occur with steroid use. The presence of shoulder pain suggests involvement of the parietal peritoneum of the diaphragm.

In elderly patients, consider the possibility of perforated diverticulitis or ruptured acute appendicitis if the pain is located in the lower abdomen. Approximately 30-40% of elderly patients with acute appendicitis present more than 48 hours after the onset of abdominal pain. (Delayed presentation is usually associated with increased risk of perforation.) Elderly patients may have minimal pain.

In young adults with pain in the lower abdominal quadrant, consider perforated appendicitis as a possible diagnosis. Acute appendicitis with sudden perforation is usually associated with illness of several hours. The pain is typically localized in the right lower quadrant of the abdomen, unless the disease process has progressed to generalized peritonitis. In young women, also consider ruptured ovarian cyst and ruptured tubo-ovarian abscess in the differential diagnosis.

Physical Examination

Assess the patient's general appearance, take vital signs, and assess for any hemodynamic changes. (Take pulse and blood pressure measurements with the patient lying in bed and sitting, and note any postural changes.)

Examine the abdomen for any external signs of injury, abrasion, and/or ecchymosis. Observe patients' breathing patterns and abdominal movements with breathing, and note any abdominal distention or discoloration. (In perforated peptic ulcer disease, patients lie immobile, occasionally with knees flexed, and the abdomen is described as boardlike.)

Carefully palpate the entire abdomen, noting any masses or tenderness. Tachycardia, fever, and generalized abdominal tenderness may suggest peritonitis. Abdominal fullness and doughy consistency may indicate intra-abdominal hemorrhage. Tenderness on percussion may suggest peritoneal inflammation. Bowel sounds are usually absent in generalized peritonitis.

Rectal and bimanual vaginal and pelvic examinations may help in assessing conditions such as acute appendicitis, ruptured tubo-ovarian abscess, and perforated acute diverticulitis.

Laboratory Studies

A complete blood count (CBC) may reveal parameters suggestive of infection (eg, leukocytosis), though leukocytosis may be absent in elderly patients. Elevated packed blood cell volume suggests a shift of intravascular fluid. Blood culture for aerobic and anaerobic organisms is indicated. Findings from liver function and renal function tests may be within reference ranges (or nearly so) if no preexisting disorder is present.

Imaging Studies

Radiography

Erect radiographs of the chest are recognized as the most appropriate first-line investigation when a perforated peptic ulcer is considered likely.[15] However, in approximately 30% of patients, no free gas can be identified. Thus, an erect posteroanterior chest radiograph is not sufficiently sensitive to rule out pneumoperitoneum in patients presenting with upper abdominal pain.

Plain supine and erect radiographs of the abdomen are the most common first steps in the diagnostic imaging evaluation of patients presenting with medical history and/or clinical signs suggestive of bowel perforation. Findings suggestive of perforation include the following:

Water-soluble radiologic contrast media administered orally or through a nasogastric tube can be used as an adjunct diagnostic tool to detect any intraperitoneal leak.

The perforation has sealed at presentation in approximately 50% of patients. For those who favor a nonoperative approach, contrast radiology is routine in the management of these patients.

Ultrasonography

Localized gas collection related to bowel perforation may be detectable, particularly if it is associated with other ultrasonographic abnormalities (eg, thickened bowel loop). The site of bowel perforation can be detected by ultrasonography (eg, gastric vs duodenal perforation, perforated appendicitis vs perforated diverticulitis). Ultrasonograms of the abdomen can also provide rapid evaluation of the liver, spleen, pancreas, kidneys, ovaries, adrenals, and uterus.

Computed tomography

Computed tomography (CT) of the abdomen can be a valuable investigative tool, providing differential morphologic information not obtainable with plain radiography or ultrasonography.

CT scans may provide evidence of localized perforation (eg, perforated duodenal ulcer) with leakage in the area of the gallbladder and right flank with or without free air being apparent. They may show inflammatory changes in the pericolonic soft tissues and focal abscess due to diverticulitis (may mimic perforated colonic carcinoma). CT scans may not provide definitive radiographic evidence of perforated Meckel diverticulitis.

Diagnostic Procedures

Laparoscopy may significantly improve surgical decision making in patients with acute abdominal pain, particularly when the need for operation is uncertain.

Peritoneal diagnostic tap may be useful in determining the presence of intra-abdominal blood, fluid, and pus.

Peritoneal lavage is more valuable in the presence of a history of blunt abdominal trauma. The presence of blood or purulent material or the detection of bacteria on Gram stain suggests the need for early surgical exploration. Alkaline phosphatase concentration in the peritoneal lavage is a helpful and sensitive test that may be used to detect occult blunt intestinal injuries. A concentration greater than 10 IU/L has been shown to be a sensitive and reliable test in the detection of occult small bowel injuries.

Fine-catheter peritoneal cytology involves the insertion of a venous cannula into the peritoneal cavity, through which a fine umbilical catheter is inserted while the patient is under local anesthesia. Peritoneal fluid is aspirated, placed on a slide, and stained for examination under a light microscope for percentage of polymorphonuclear cells. A value greater than 50% suggests a significant underlying inflammatory process. This test, however, provides no clue as to the exact cause of inflammation.

Approach Considerations

The mainstay of treatment for intestinal perforation is surgery.[16] Surgery for intestinal perforation is contraindicated in the presence of general contraindications to anesthesia and major surgery, such as severe heart failure, respiratory failure, or multiorgan failure. It is also contraindicated if the patient refuses the operation and no evidence of generalized peritonitis exists. Finally, surgery is contraindicated if a contrast meal confirms spontaneous sealing of the perforation (eg, perforated duodenal ulcer) and the patient prefers a nonsurgical approach.[17]

Medical Therapy

Treatment is primarily surgical. Emergency medical care includes the following steps:

However, if symptoms and signs of generalized peritonitis are absent, a nonoperative policy may be used with antibiotic therapy directed against gram-negative and anaerobic bacteria.[18, 19]

Antibiotics

Antibiotics have proven effective in decreasing the rate of postoperative wound infection and in improving outcome in patients with intraperitoneal infection and septicemia.

Metronidazole is typically used in combination with an aminoglycoside to provide broad gram-negative and anaerobic coverage. It is reduced to a product that interacts with deoxyribonucleic acid (DNA) to cause a loss of helical DNA structure and strand breakage, resulting in inhibition of protein synthesis and cell death in susceptible organisms. Adult dosing is 7.5 mg/kg IV before surgery. Pediatric dosing is 15-30 mg/kg/day IV divided bid/tid for 7 days. It is a pregnancy category B drug.

Gentamicin is an aminoglycoside antibiotic with gram-negative coverage. It is used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Although it is not the drug of choice, it should be considered if penicillins or other less-toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. It may be given IV/IM. In adults, the loading dose before surgery is 2 mg/kg IV; thereafter, dosing is 3-5 mg/kg/day divided tid/qid. In infants, dosing is 7.5 mg/kg/day IV divided tid. In children, dosing is 6-7.5 mg/kg/day IV divided tid. It is a pregnancy category C drug.

Cefotetan is a second-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2 g IV once before surgery. In children younger than 3 months, dosing is not established. In those older than 3 months, dosing is 30-40 mg/kg IV once before surgery. It is a pregnancy category B drug.

Cefoxitin is also a second-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2 g IV once before surgery, followed by 4 doses of 2 g IV q4-6hr. In children younger than 3 months, dosing is not established. In those older than 3 months, dosing is 30-40 mg/kg IV before surgery, followed by 3 doses of 2 g IV q4-6hr for 24 hr. It is a pregnancy category B drug.

Cefoperazone sodium is a third-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2-4 g/day IV divided q12hr. Pediatric dosing is 100-150 mg/kg/day IV divided q8-12hr, not to exceed 12 g/day. It is a pregnancy category B drug.

Surgical Therapy

Goals of surgery

The goals of surgical therapy are as follows:

Procedural details

Preoperatively, correct any fluid or electrolyte imbalance. Replace extracellular fluid losses by administering Hartmann solution or a similar solution that has an electrolyte composition similar to plasma. Central venous pressure (CVP) monitoring is essential in critically ill and/or elderly patients, in whom cardiac impairment may be exacerbated by large fluid loss.

Administer systemic antibiotics (eg, ampicillin, gentamicin, metronidazole), making a best estimation regarding the likely organisms. Nasogastric suction is required to empty the stomach and reduce the risk of further vomiting. Urinary catheterization is used to assess urinary flow and fluid replacement. Administer analgesics, such as morphine, in small intravenous doses, preferably as a continuous infusion.

Operative management depends on the cause of perforation. Perform urgent surgery either on patients not responding to resuscitation or following stabilization and maintenance of adequate urine output. All necrotic material and contaminated fluid should be removed and accompanied by lavage with antibiotics (tetracycline 1 mg/mL). Decompress distended bowel via a nasogastric tube.

Laparoscopic or laparoscopic-assisted (minilaparotomy) surgery is also being increasingly used with outcomes comparable with conventional laparotomy.[20] Experience and the advancement in accessories have enabled endoscopic repair of a significant number of intestinal perforations, such as iatrogenic perforation. Management of such cases needs to be individualized to the patient.

In a study involving 934 patients with sigmoid diverticulitis, Ritz et al found that the risk of free perforation in acute sigmoid diverticulitis decreases with the increases in the number of previous episodes of sigmoid diverticulitis. They concluded that the first episode has the highest risk for a free perforation. Therefore, the indication for colectomy should not be made based on the potential risk of free perforation.[21]

Postoperative Care

Intravenous replacement therapy

The aim of intravenous replacement therapy is to maintain intravascular volume and hydrate the patient. Monitor by CVP measurement and urinary output.

Nasogastric drainage

Perform nasogastric drainage continuously until drainage becomes minimal. At that stage, the nasogastric tube may be removed.

Antibiotics

Continue administration of the antibiotics commenced preoperatively unless the results of cultures taken at the time of the operation reveal that the causative organisms are resistant to them.

The goal of antibiotic therapy is to achieve levels of antibiotics at the site of infection that exceed the minimum inhibitory concentrations for the pathogens present.

In the presence of intra-abdominal infections, gastrointestinal function is often impaired; therefore, oral antibiotics are not efficacious, and intravenous antibiotics are recommended.

If no obvious improvement in the patient's condition occurs within 2-3 days, consider the following possibilities:

Analgesics

Analgesics, such as intravenous morphine, should be given continuously or in small doses at frequent intervals.

Complications

Wound infection rates correlate with the bacterial load in the bowel, so this complication occurs more often with colonic perforation (eg, perforated diverticulitis). The judicious use of prophylactic antibiotics has been demonstrated to reduce the incidence of wound infection in contaminated and potentially contaminated wounds.

Wound failure (partial or total disruption of any or all layers of the operative wound) may occur early (ie, wound dehiscence) or late (ie, incisional hernia). The following factors are associated with wound failure:

Localized abdominal abscess may develop.

Multiorgan failure and septic shock may develop. Septicemia is defined as proliferation of bacteria in the bloodstream resulting in systemic manifestations such as rigors, fever, hypothermia (in gram-negative septicemia with endotoxemia), leukocytosis or leukopenia (in profound septicemia), tachycardia, and circulatory collapse. Septic shock is associated with a combination of the following:

Gram-negative infections are associated with a much worse prognosis than gram-positive infections, possibly because of associated endotoxemia.

Renal failure and fluid, electrolyte, and pH imbalance may occur.

Gastrointestinal mucosal hemorrhage is usually associated with failure of multiple organ systems and is probably related to a defect in the protective gastric mucosa.

Mechanical obstruction of the intestine is most often caused by postoperative adhesions.

The following factors may cause a predisposition to postoperative delirium:

Long-Term Monitoring

For patients treated with a nonsurgical approach, follow-up care consists of the following:

Author

Samy A Azer, MD, PhD, MPH, Professor of Medical Education, Chair of Medical Education Research and Development Unit, Faculty of Medicine, Universiti Teknologi MARA, Malaysia; Visiting Professor of Medical Education, Faculty of Medicine, University of Toyama, Japan; Former Senior Lecturer in Medical Education, Faculty Education Unit, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne and University of Sydney, Australia

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John Geibel, MD, DSc, MSc, MA, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

Disclosure: Received royalty from AMGEN for consulting; Received ownership interest from Ardelyx for consulting.

Acknowledgements

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

References

  1. Lau WY, Leow CK. History of perforated duodenal and gastric ulcers. World J Surg. 1997 Oct. 21(8):890-6. [View Abstract]
  2. Sarath Chandra S, Siva Kumar S. Definitive or conservative surgery for perforated gastric ulcer? - An unresolved problem. Int J Surg. 2008 Dec 25. [View Abstract]
  3. Goh H, Bourne R. Non-steroidal anti-inflammatory drugs and perforated diverticular disease: a case-control study. Ann R Coll Surg Engl. 2002 Mar. 84(2):93-6. [View Abstract]
  4. Lee JF, Leow CK, Lau WY. Appendicitis in the elderly. Aust N Z J Surg. 2000 Aug. 70(8):593-6. [View Abstract]
  5. Stapfer M, Selby RR, Stain SC, et al. Management of duodenal perforation after endoscopic retrograde cholangiopancreatography and sphincterotomy. Ann Surg. 2000 Aug. 232(2):191-8. [View Abstract]
  6. Anderson ML, Pasha TM, Leighton JA. Endoscopic perforation of the colon: lessons from a 10-year study. Am J Gastroenterol. 2000 Dec. 95(12):3418-22. [View Abstract]
  7. Iqbal CW, Cullinane DC, Schiller HJ, et al. Surgical management and outcomes of 165 colonoscopic perforations from a single institution. Arch Surg. 2008 Jul. 143(7):701-6; discussion 706-7. [View Abstract]
  8. Teoh AY, Poon CM, Lee JF, et al. Outcomes and predictors of mortality and stoma formation in surgical management of colonoscopic perforations: a multicenter review. Arch Surg. 2009 Jan. 144(1):9-13. [View Abstract]
  9. Namdar T, Raffel AM, Topp SA, et al. Complications and treatment of migrated biliary endoprostheses: a review of the literature. World J Gastroenterol. 2007 Oct 28. 13(40):5397-9. [View Abstract]
  10. Wei SC, Tan YY, Weng MT, Lai LC, Hsiao JH, Chuang EY, et al. SLCO3A1, a Novel Crohn's Disease-Associated Gene, Regulates NF-?B Activity and Associates with Intestinal Perforation. PLoS One. 2014. 9(6):e100515. [View Abstract]
  11. Kim JB, Kim SH, Cho YK, Ahn SB, Jo YJ, Park YS, et al. A case of colon perforation due to enteropathy-associated T-cell lymphoma. World J Gastroenterol. 2013 Mar 21. 19(11):1841-4. [View Abstract]
  12. Cheung CP, Chiu HS, Chung CH. Small bowel perforation after radiotherapy for cervical carcinoma. Hong Kong Med J. 2003 Dec. 9(6):461-3. [View Abstract]
  13. Deniz K, Ozseker HS, Balas S, et al. Intestinal involvement in Wegener's granulomatosis. J Gastrointestin Liver Dis. 2007 Sep. 16(3):329-31. [View Abstract]
  14. Catena F, Ansaloni L, Gazzotti F, et al. Gastrointestinal perforations following kidney transplantation. Transplant Proc. 2008 Jul-Aug. 40(6):1895-6. [View Abstract]
  15. Butler J, Martin B. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Detection of pneumoperitoneum on erect chest radiograph. Emerg Med J. 2002 Jan. 19(1):46-7. [View Abstract]
  16. Langell JT, Mulvihill SJ. Gastrointestinal perforation and the acute abdomen. Med Clin North Am. 2008 May. 92(3):599-625, viii-ix. [View Abstract]
  17. Kim JH, Ahn HD, Kwon KA, Kim YJ, Chung JW, Park DK, et al. Spontaneous healing of gastric perforation after endoscopic ligation for gastric varices. J Korean Med Sci. 2013 Apr. 28(4):624-7. [View Abstract]
  18. Crofts TJ, Park KG, Steele RJ. A randomized trial of nonoperative treatment for perforated peptic ulcer. N Engl J Med. 1989 Apr 13. 320(15):970-3. [View Abstract]
  19. Donovan AJ, Berne TV, Donovan JA. Perforated duodenal ulcer: an alternative therapeutic plan. Arch Surg. 1998 Nov. 133(11):1166-71. [View Abstract]
  20. Kim J, Lee GJ, Baek JH, Lee WS. Comparison of the surgical outcomes of laparoscopic versus open surgery for colon perforation during colonoscopy. Ann Surg Treat Res. 2014 Sep. 87(3):139-43. [View Abstract]
  21. Ritz JP, Lehmann KS, Frericks B, Stroux A, Buhr HJ, Holmer C. Outcome of patients with acute sigmoid diverticulitis: Multivariate analysis of risk factors for free perforation. Surgery. 2011 May. 149(5):606-13. [View Abstract]
  22. Cappendijk VC, Hazebroek FW. The impact of diagnostic delay on the course of acute appendicitis. Arch Dis Child. 2000 Jul. 83(1):64-6. [View Abstract]
  23. De Blaky M. Acute perforated gastroduodenal ulceration; statistical analysis and review of the literature. Surgery. 1940. 8:850.
  24. Herrington JL Jr. Historical aspects of gastric surgery. Scott HW Jr, Sawyers JL, eds. Surgery of the Stomach, Duodenum and Small Intestine. Boston, Mass: Blackwell Scientific; 1992.
  25. Holland AJ, Cass DT, Glasson MJ, et al. Small bowel injuries in children. J Paediatr Child Health. 2000 Jun. 36(3):265-9. [View Abstract]
  26. Isaacman DJ, Scarfone RJ, Kost SI, et al. Utility of routine laboratory testing for detecting intra-abdominal injury in the pediatric trauma patient. Pediatrics. 1993 Nov. 92(5):691-4. [View Abstract]
  27. Lim JH. Ultrasound examination of gastrointestinal tract diseases. J Korean Med Sci. 2000 Aug. 15(4):371-9. [View Abstract]
  28. Putcha RV, Burdick JS. Management of iatrogenic perforation. Gastroenterol Clin North Am. 2003 Dec. 32(4):1289-309. [View Abstract]
  29. Saxe JM, Cropsey R. Is operative management effective in treatment of perforated typhoid?. Am J Surg. 2005 Mar. 189(3):342-4. [View Abstract]
  30. Saxena V, Basu S, Sharma CL. Perforation of the gall bladder following typhoid fever-induced ileal perforation. Hong Kong Med J. 2007 Dec. 13(6):475-7. [View Abstract]
  31. Schnoll-Sussman F, Kurtz RC. Gastrointestinal emergencies in the critically ill cancer patient. Semin Oncol. 2000 Jun. 27(3):270-83. [View Abstract]
  32. Shah M, Azam B. Case report of an intra-abdominal desmoid tumour presenting with bowel perforation. Mcgill J Med. 2007 Jul. 10(2):90-2. [View Abstract]
  33. Velitchkov NG, Losanoff JE, Kjossev KT, et al. Delayed small bowel injury as a result of penetrating extraperitoneal high-velocity ballistic trauma to the abdomen. J Trauma. 2000 Jan. 48(1):169-70. [View Abstract]