Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]}; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Boerhaave syndrome was first described by the physician Herman Boerhaave, Professor of Medicine at Leiden University, in a publication entitled “History of a Grievous Disease Not Previously Described”. Hundred years ago, polish clinical researcher professor W.Jaworski was the first to describe the spiral-shaped microorganism at Cracow Jagiellonian University In 1586, Marcellus Donatus of Mantua described gastric ulcers by performing autopsies. In 1688, Johannes von Murault gave detailed description of duodenal ulcers. The appropriate therapy for intestinal perforation in typhoid fever has been controversial since the late 1880s.

• Boerhaave syndrome was first described by the physician Herman Boerhaave, Professor of Medicine at Leiden University, in a publication entitled “History of a Grievous Disease Not Previously Described”.^[1]
• Dr. Herman Boerhaave (1668-1738) described esophageal rupture and the subsequent mediastinal sepsis based upon his careful clinical and autopsy findings. Hundreds of references have since been written about Boerhaave’s syndrome.^[2]
• Hundred years ago, polish clinical researcher professor W.Jaworski was the first to describe the spiral-shaped microorganism at Cracow Jagiellonian University
• In 1586, Marcellus Donatus of Mantua described gastric ulcers by performing autopsies
• In 1688, Johannes von Murault gave detailed description of duodenal ulcers.
• In 1821, Nepveu found a relationship between gastritis and gastric cancer.
• In 1875, G.Bottcher and M. Letulle hypothesize that ulcers are caused by bacteria.
• In 1889, Walery Jaworski found spiral organisms in sediment washings of humans and proposed that these organisms may be involved with gastric disease.^[3]
• In late 1970, J.R Warren, a pathologist in Perth, Australia found the appearance of spiral bacteria overlying gastric mucosa.
• In 1589, Dr. Hildanus was the first physician to discover diverticular lesion in the colon.^[4]
• In the 1700s, Alexis Littre was the first to describe diverticular diseases when he described a diverticular hernia.
• In 1812, Dr. Meckel described the diverticulum now known as Meckel’s diverticulum.
• In 1902, Dr. Deetz provided a full description of infection of the diverticulum.
• The appropriate therapy for intestinal perforation in typhoid fever has been controversial since the late 1880s.^[5]
• Around the turn of the century, surgery became the established mode of therapy, with a mortality of 69% based on 166 patients in the English-language medical literature, and continued to be the preferred treatment until the advent of chloramphenicol in 1948.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Gastrointestinal perforation may be classified based upon the etiology into instrumental perforation, perforation due to systemic diseases, perforation due to inflammatory causes, medications and neoplasms. Gastrointestinal perforation may also be divided based on age of the patient into adult type and neonatal type perforation.

There is no specific classification for gastrointestinal perforation but it can be classified by cause and by age of the patients.

• Instrumentation of the gastrointestinal tract includes upper endoscopy, sigmoidoscopy, colonoscopy, stent placement, endoscopic sclerotherapy, nasogastric intubation, esophageal dilation, and surgery. All of these procedures carry risk of gastrointestinal perforation.^[1][2]
• The area of the esophagus at most risk for instrumental perforation is Killian’s triangle, which is the part of the pharynx formed by the inferior pharyngeal constrictor and cricopharyngeus muscle.
• Gastrointestinal leakage can also occur postoperatively as a result of anastomotic breakdown.^[3]
• Immunosuppressed individuals may be at increased risk for perforation and deep organ space infection following surgery.^[4][5]

• Crohn’s disease^[6]
• Celiac disease^[7]
• Graft-vs-host disease^[8]
• Infections:
• Viral: Cytomegalovirus^[9]
• Bacteria: Salmonella paratyphi, mycobacterium tuberculosis^{[10][11][12][13]}
• Parasites: Ascaris lumbricoides^[14]
• Protozoa: Entameba histolytica^[15]
• Drugs: NSAIDs and indomethacin^[16][17]
• Enteric-coated potassium chloride^[18][19]
• Monoclonal antibodies: Bevacizumab^[20]
• Meckel’s diverticulum^[21][22]

• Crohn’s disease has a propensity to perforate slowly, leading to the formation of entero-enteric or enterocutaneous fistula^[6]
• Diseases such as typhoid, tuberculosis, or schistosomiasis can perforate the small intestine.^[23][24]
• The perforations usually occur in the ileum at necrotic Peyer’s patches.^[25]

• Aspirin, potassium, disease-modifying antirheumatic drugs, and non-steroidal anti-inflammatory drug use have been associated with perforation.^[26][27]

• Neoplasms can perforate by direct penetration and necrosis, or by producing obstruction.

• Adult-type gastrointestinal perforation
• Neonatal gastrointestinal perforation:^[28][29]
  • Necrotising enterocolitis
  • Spontaneous
  • Iatrogenic
  • Umbilical catheterization
  • Umbilical cord clamping
  • Nasogastric tube
  • Obstruction
  • Ileal atresia
  • Gastric volvulus
  • Gastroschisis
  • Perforated inguinal hernia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Perforation is full-thickness injury of the bowel wall. Perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction. Spontaneous perforation can be caused by inflammation, connective tissue disorders, and medications. Terminal ileum is the commonest site for spontaneous perforation and may be the jejunum and colon. In neonatal perforation, the terminal ileum and colon are the commonest sites for perforation. The pathogenesis of NEC remains unknown but there are many factors for infection such as: Ninety percent of NEC cases occur in preterm infants due to immaturity of the gastrointestinal tract. Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults. Regarding anatomy of GIT, the esophagus travels 3 regions of the body: the neck, thorax, and abdomen. Accordingly, it is divided into 3 parts: cervical, thoracic, and abdominal. The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. The GI tract can be divided into four concentric layers in the following order: Mucosa, Submucosa, muscular layer, and Adventitia or serosa. Perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction. Spontaneous perforation can be caused by inflammation, connective tissue disorders, and medications. With bowel obstruction, perforation occurs proximal to the obstruction as pressure builds up within the bowel, exceeding intestinal perfusion pressure, and leading to ischemia and subsequently necrosis. Acute colonic pseudo-obstruction is an acute dilatation of the colon without mechanical obstruction of the flow of intestinal contents. The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown. Spinal anesthesia and pharmacologic agents are suggested to be the causes due to impairment of autonomic system.

• The esophagus is a 25-cm-long vertical muscular tube that normally remains collapsed and that runs from the laryngopharynx in the neck through the thorax to the stomach in the abdomen.
• The esophagus travels 3 regions of the body: the neck, thorax, and abdomen. Accordingly, it is divided into 3 parts: cervical, thoracic, and abdominal.
• The cervical esophagus begins at the level of C6; it is only 5 cm long. In the neck, the esophagus is enclosed in a sheath of deep cervical fascia.

• The cardiac notch is the acute angle between the left border of the intra-abdominal esophagus and the gastric fundus.
• The body of the stomach leads to the pyloric antrum, which joins the duodenum at the pylorus, lying at the L1-L2 level to the right of the midline.
• The stomach has a shorter lesser curvature and a longer greater curvature. The lesser curvature is attached to the undersurface of the liver by lesser omentum and the greater curvature is attached to the transverse colon by greater omentum.

• The lower gastrointestinal tract includes most of the small intestine and all of the large intestine.
• The small bowel is anatomically divided into three portions: the duodenum, jejunum, and ileum.
• Duodenum: It is about 20–25 cm long which receives chymefrom the stomach, together with pancreatic juice containing digestive enzymes and bile from the gall bladder.
• The duodenum contains Brunner’s glands, which produce a mucus-rich alkaline secretion containing bicarbonate. These secretions, in combination with bicarbonate from the pancreas, neutralizes the stomach acids contained in the chyme.
• Jejunum: This is the midsection of the small intestine, connecting the duodenum to the ileum. It is about 2.5 m long, and contains the circular folds, and villi that increase its surface area. Products of digestion are absorbed into the bloodstream here.
• Ileum: The final section of the small intestine. It is about 3 m long, and contains villi similar to the jejunum. It absorbs mainly vitamin B12 and bile acids, as well as any other remaining nutrients.
• The large intestine is further divided into:
  1. Cecum and appendix
  2. Ascending colon
  3. Right colic flexure
  4. Transverse colon
  5. Left colic flexure
  6. Descending colon
  7. Sigmoid colon
  8. Rectum
  9. Anus

The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. 

The GI tract can be divided into four concentric layers in the following order:

• Mucosa
• Submucosa
• Muscular layer
• Adventitia or serosa

• The mucosa is the innermost layer of the gastrointestinal tract. that is surrounding the lumen.
• This layer comes in direct contact with chyme. The mucosa is made up of:

• Epithelium: innermost layer. Responsible for most digestive, absorptive and secretory processes.
• Lamina propria: a layer of connective tissue. Unusually cellular compared to most connective tissue
• Muscularis mucosae: a thin layer of smooth muscle that aids the passing of material and enhances the interaction between the epithelial layer and the contents of the lumen by agitation and peristalsis.

The mucosae are highly specialized in each organ of the gastrointestinal tract to deal with the different conditions. The most variation is seen in the epithelium.

The submucosa consists of a dense irregular layer of connective tissue with large blood vessels, lymphatics, and nerves branching into the mucosa and muscularis externa. It contains the submucosal plexus, an enteric nervous plexus, situated on the inner surface of the muscularis externa.

• The muscular layer consists of an inner circular layer and a longitudinal outer layer.
• The layers are not truly longitudinal or circular, rather the layers of muscle are helical with different pitches. The inner circular is helical with a steep pitch and the outer longitudinal is helical with a much shallower pitch.
• Between the two muscle layers is the myenteric plexus.
• The gut has intrinsic peristaltic activity due to its self-contained enteric nervous system. The rate can be modulated by the rest of the autonomic nervous system.

• The outermost layer of the gastrointestinal tract consists of several layers of connective tissue.
• Intraperitoneal parts of the GI tract are covered with serosa. These include most of the stomach, first part of the duodenum, all of the small intestine, caecum and appendix, transverse colon, sigmoid colon and rectum.
• In these sections of the gut there is clear boundary between the gut and the surrounding tissue. These parts of the tract have a mesentery.
• Retroperitoneal parts are covered with adventitia. They blend into the surrounding tissue and are fixed in position.
• These include the esophagus, pylorus of the stomach, distal duodenum, ascending colon, descending colon and anal canal.

• Perforation is full-thickness injury of the bowel wall.
• Perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction.^[1]
• Spontaneous perforation can be caused by inflammation, connective tissue disorders, and medications.
• With bowel obstruction, perforation occurs proximal to the obstruction as pressure builds up within the bowel, exceeding intestinal perfusion pressure, and leading to ischemia and subsequently necrosis.^[2]

• Acute colonic pseudo-obstruction is an acute dilatation of the colon without mechanical obstruction of the flow of intestinal contents.

• The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown.
• Spinal anesthesia and pharmacologic agents are suggested to be the causes due to impairment of autonomic system.^[3]
• Interruption of the parasympathetic fibers from S2 to S4 leaves an atonic distal colon and a functional proximal obstruction.
• The risk of colonic perforation are the absolute diameter of the colon (10 to 12 cm) and the duration of cecal dilation.^[4]

• Terminal ileum is the commonest site for spontaneous perforation and may be the jejunum and colon.^[5]
• Focal hemorrhagic necrosis with well-defined margins is observed in contrast to the ischemic and coagulative necrosis seen in necrotizing enterocolitis.^[6]
• The bowel appears normal proximal and distal to the perforation.
• The mechanism is not clear yet but may be due to absence of the muscularis propria at the perforation site.^[7]

• The terminal ileum and colon are the commonest sites for perforation.^[8]

• The pathogenesis of NEC remains unknown but there are many factors for infection such as:
• Ninety percent of NEC cases occur in preterm infants due to immaturity of the gastrointestinal tract.^[9]
• Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults.
• Preterm infants have high levels of cytokines such as tumor necrosis factor, IL-1, IL-6, IL-8, IL-10, IL-12, and IL-18 that increase vascular permeability and attract inflammatory cells.
• Human milk is more protective against NEC in preterm infants than formulas. The mucus coat of the intestine is less affected by human milk than formulas. Growth factors within human milk repair disturbed layers in intestine.

• Bacterial colonization is believed to play a pivotal role in the development of NEC. Rapid colonization of the intestinal tract by commensal bacteria from the maternal rectovaginal flora normally occurs.
• Ischemic insult to the GI tract has been proposed as a major contributor to NEC.
• Inflammatory mediators induced by ischemia, infectious agents, or mucosal irritants may cause mucosal injury.
• Circulatory events that have been attrubuted in the development of NEC include perinatal asphyxia, recurrent apnea, hypoxia from severe respiratory distress syndrome, hypotension, congenital heart disease, patent ductus arteriosus, heart failure, umbilical arterial catheterization, anemia, polycythemia, and red blood cell and exchange transfusions.
• Hyperosmolar medications may result in NEC. Oral medications such as theophylline, multivitamins, or phenobarbital contain hypertonic additives that might irritate the intestinal mucosa.^[10]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Instrumentation of the gastrointestinal tract includes upper endoscopy, sigmoidoscopy, colonoscopy, stent placement, endoscopic sclerotherapy, nasogastric intubation, esophageal dilation, and surgery is the commonest cause of gastrointestinal perforation. Other causes include medications, foreign bodies, violent retching, Peptic ulcer disease. Perforation of the small intestine can be related to bowel obstruction, acute mesenteric ischemia, inflammatory bowel disease. Colonic diverticulosis is common cause of perforation in large intestine. Causes of spontaneous intestinal perforation in adults include Crohn’s disease, Celiac disease, graft-vs-host disease, and infection. Causes of intestinal perforation in neonates include Necrotising enterocolitis, Iatrogenic, umbilical catheterization, umbilical cord clamping, nasogastric tube, Obstruction, and ileal atresia.

• Instrumentation of the gastrointestinal tract includes upper endoscopy, sigmoidoscopy, colonoscopy, stent placement, endoscopic sclerotherapy, nasogastric intubation, esophageal dilation, and surgery.^[1]
• The area of the esophagus at most risk for instrumental perforation is Killian’s triangle, which is the part of the pharynx formed by the inferior pharyngeal constrictor and cricopharyngeus muscle.
• Gastrointestinal leakage can also occur postoperatively as a result of anastomotic breakdown.^[2]
• Immunosuppressed individuals may be at increased risk for dehiscence and deep organ space infection following surgery.^[3]

• Medications: aspirin, potassium, disease-modifying antirheumatic drugs, and non-steroidal anti-inflammatory drug use has been associated with perforation.^[4]
• Foreign bodies such as sharp objects, food with sharp surfaces, or gastric bezoar.^[5]
• Violent retching can lead to spontaneous esophageal perforation, known as Boerhaave syndrome due to increased intraesophageal pressure in the lower esophagus.
• Peptic ulcer disease is the most common cause of stomach and duodenal perforation.^[6]
• Marginal ulcers may complicate procedures involving a gastrojejunostomy.
• Perforated gastric ulcer is associated with a higher mortality.^[7]

• Perforation of the small intestine can be related to bowel obstruction, acute mesenteric ischemia, inflammatory bowel disease.^[8]
• Abdominal wall, groin, diaphragmatic, internal hernia, paraesophageal hernia, and volvulus can all lead to perforation either related to bowel wall ischemia.
• Injuries to the small intestine during laparoscopic procedures are often not recognized during the procedure.
• Crohn’s disease has a propensity to perforate slowly, leading to formation of entero-enteric or enterocutaneous fistula formation.

• Diseases such as typhoid, tuberculosis, or schistosomiasis can perforate the small intestine.
• The perforations usually occur in the ileum at necrotic Peyer’s patches.^[9]

• Colonic diverticulosis is common in the developed world. They can become inflamed and perforate and may lead to abscess formation.^[10]
• Mesenteric ischemia increases the risk for perforation. Embolism, mesenteric occlusive disease, and heart failure lead to gastrointestinal ischemia.
• Neoplasms can perforate by direct penetration and necrosis, or by producing obstruction.^[11]

• Crohn’s disease^[13]
• Celiac disease^[14]
• Graft-vs-host disease^[15]
• Infections:
• Viral: Cytomegalovirus^[16]
• Bacteria: Salmonella paratyphi, mycobacterium tuberculosis^{[17][18][19][20]}
• Parasites: Ascaris lumbricoides^[21]
• Protozoa: Entameba histolytica^[22]
• Drugs: NSAIDs and indomethacin^[23][24][25]
• Enteric-coated potassium chloride^[26][27]
• Monoclonal antibodies: Bevacizumab^[28]
• Meckel’s diverticulum^[29][30]

• Radiation-induced vascular injury
• Atherosclerotic vascular occlusion
• Buerger’s disease
• Giant cell arteritis
• Wegener’s granulomatosis
• Henoch-schonlein purpura
• Allergic granulomatous arteritis

Intestinal perforation in neonates may be caused due to the following conditions:^[31][32]

• Necrotising enterocolitis
• Spontaneous
• Iatrogenic
• Umbilical catheterization
• Umbilical cord clamping
• Nasogastric tube
• Obstruction
• Ileal atresia
• Gastric volvulus
• Gastroschisis
• Perforated inguinal hernia
• Malrotation/midgut volvulus
• Congenital band

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

The incidence of iatrogenic esophageal perforation from instrumentation has decreased, but the number of esophageal perforations from external trauma and spontaneous rupture has increased to 1 per 8,000 admissions. Incidence rates of gastric perforation varied from 1.5 to 7.8/100000 per year and from 5.2 to 40.2 regarding peptic ulcer bleeding. A perforation rate of 110 per 100,000 for rigid endoscopy and 30 per 100,000 regarding flexible endoscopy. Sclerotherapy perforation rate is 1,000 to 5,000 per 100,000. The incidence of colonic perforation (CP) could be as low as 16 per 100,000 of all diagnostic colonoscopy procedures and may be seen in up to 5% of therapeutic colonoscopies. The incidence of CP following flexible sigmoidoscopy varies from 27 to 88 per 100,0000. Screening colonoscopy perforation rates are 1000 to 10,000 per 100,000. Anastomotic stricture dilation perforation rates are 0 to 6000 per 100,000.

• The incidence of iatrogenic esophageal perforation from instrumentation has decreased, but the number of esophageal perforations from external trauma and spontaneous rupture has increased.
• In the period from 1950 to 1954 there was 1 perforation per 20,000 admissions.
• The incidence has now risen to 1 per 8,000 admissions.

• There is lower incidence of peptic ulcer complications during the later years.
• Incidence rates varied from 1.5 to 7.8/100000 per year regarding perforated peptic ulcers and from 5.2 to 40.2 regarding peptic ulcer bleeding.

• A perforation rate of 110 per 100,000 for rigid endoscopy.
• Diagnostic endoscopy with a flexible endoscope perforation rate is 30 per 100,000.
• Stricture dilation perforation rate is 90 to 2200 per 100,000.
• Sclerotherapy perforation rate is 1,000 to 5,000 per 100,000.
• Pneumatic dilation for achalasia perforation rate is 2,000 to 6,000 per 100,000.
• The incidence of perforation related to endoscopy increases with procedural complexity.
• Mortality rates due to perforation are 20 percent.

• The incidence of colonic perforation (CP) could be as low as 16 per 100,000 of all diagnostic colonoscopy procedures and may be seen in up to 5% of therapeutic colonoscopies.
• The incidence of CP following flexible sigmoidoscopy varies from 27 to 88 per 100,0000.
• Rectal perforation during colonoscopy was reported to be around 10 per 100,0000.

• Screening colonoscopy perforation rates are 1000 to 10,000 per 100,000.
• Anastomotic stricture dilation perforation rates are 0 to 6000 per 100,000.
• Crohn’s disease stricture dilation perforation rates are 0 to 18,000 per 100,0000.
• Stent placement perforation rates are 4000 per 100,000.
• Colonic decompression tube placement perforation rates are 2000 per 100,000.
• Colonic endoscopic mucosal resection perforation rates are 0 to 5 per 100.000.
• Mortality rates from iatrogenic colonic perforation range from 0 to 650 per 100,000.
• The incidence of perforation during colonoscopy increases as the complexity of the procedure increases and is estimated at 1:1000 for therapeutic colonoscopy and 1:1400 for overall colonoscopies.
• The rectosigmoid area was most commonly perforated followed by the cecum, 53 percent and 24 percent, respectively.
• Most perforations were due to blunt injury, 27 percent of perforations occurred with polypectomy, and 18 percent of perforations were produced by thermal injury.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Risk factors for gastrointestinal perforation varies between instrumentation during upper endoscopy, sigmoidoscopy, colonoscopy, stent placement, endoscopic sclerotherapy, nasogastric intubation, esophageal dilatation, and surgery. Other risks include medications especially Aspirin, potassium supplements, disease-modifying antirheumatic drugs (DMARDs), and nonsteroidal anti-inflammatory drug. Peptic ulcer disease is the most common cause of stomach and duodenal perforation. Colonic diverticulosis is common risk for colonic perforation in the developed world. Mesenteric ischemia increases the risk for perforation. Embolism, mesenteric occlusive disease, and heart failure lead to gastrointestinal ischemia. In neonatal perforation, prematurity is the commonest risk factor. Antenatal administration of glucocorticoids, nonsteroidal antiinflammatory drugs, indomethacin, and magnesium sulfate had been initially reported to increase the risk of perforation.

• Instrumentation of the gastrointestinal tract includes upper endoscopy, sigmoidoscopy, colonoscopy, stent placement, endoscopic sclerotherapy, nasogastric intubation, esophageal dilatation, and surgery.^[1]
• The area of the esophagus at most risk for instrumental perforation is Killian’s triangle, the part of the pharynx formed by the inferior pharyngeal constrictor and cricopharyngeus muscle.
• Immunosuppressed individuals may be at increased risk for dehiscence and deep organ space infection following surgery.^[2]

• Medications: Aspirin, potassium supplements, disease-modifying antirheumatic drugs (DMARDs), and nonsteroidal anti-inflammatory drug (NSAID) use has been associated with perforation of colonic diverticula.^[3]
• Foreign bodies such as sharp objects, food with sharp surfaces, or gastric bezoar.

• Violent retching can lead to spontaneous esophageal perforation, known as Boerhaave syndrome due to increased intraesophageal pressure in the lower esophagus.^[4]

• Peptic ulcer disease is the most common cause of stomach and duodenal perforation.^[5]
• Marginal ulcers may complicate procedures involving a gastrojejunostomy.
• Perforated gastric ulcer is associated with a higher mortality, possibly related to delays in diagnosis.

• Perforation of the small intestine can be related to bowel obstruction, acute mesenteric ischemia, inflammatory bowel disease, or due to iatrogenic or noniatrogenic traumatic mechanisms.^[6]
• Abdominal wall, groin, diaphragmatic, internal hernia, paraesophageal hernia, and volvulus can all lead to perforation due to ischemia.
• Injuries to the small intestine during laparoscopic procedures are often not recognized during the procedure.
• Crohn’s disease has a propensity to perforate slowly, leading to formation of fistula.

• Diseases such as typhoid, tuberculosis, or schistosomiasis can perforate the small intestine.
• The perforations usually occur in the ileum at necrotic Peyer’s patches.
• A reperforation rate of 21.3 percent has been reported for typhoid perforation closure.

• Colonic diverticulosis is common in the developed world. These diverticula can become inflamed and perforate and may lead to abscess formation.^[7]

• Mesenteric ischemia increases the risk for perforation. Embolism, mesenteric occlusive disease, and heart failure lead to gastrointestinal ischemia.
• Neoplasms can perforate by direct penetration and necrosis, or by producing obstruction.

• Ninety percent of NEC cases occur in preterm infants due to immaturity of the gastrointestinal tract.
• Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults.
• Preterm infants have high levels of cytokines such as tumor necrosis factor, IL-1, IL-6, IL-8, IL-10, IL-12, and IL-18 that increase vascular permeability and attract inflammatory cells.^[8]
• Human milk is more protective against NEC in preterm infants than formulas. The mucus coat of the intestine is less affected by human milk than formulas.
• Growth factors within human milk repair disturbed layers in intestine.
• Bacterial colonization is believed to play a pivotal role in the development of NEC.
• Rapid colonization of the intestinal tract by commensal bacteria from the maternal rectovaginal flora normally occurs.^[9]
• Ischemic insult to the GI tract has been proposed as a major contributor to NEC. [30,49,50]. Inflammatory mediators induced by ischemia, infectious agents, or mucosal irritants may cause mucosal injury.^[10]
• Events that have been implicated in the development of NEC include:^[11]
• perinatal asphyxia
• Recurrent apnea
• Respiratory distress syndrome
• Hypotension
• Congenital heart disease
• Patent ductus arteriosus
• Umbilical arterial catheterization
• Anemia
• Polycythemia [54,55][59]
• Medications such as theophylline or phenobarbital might irritate the intestinal mucosa.^[12]

• Placental chorioamnionitis appears to be an antenatal risk factor for SIP.^[13]
• Antenatal administration of glucocorticoids, nonsteroidal antiinflammatory drugs, indomethacin, and magnesium sulfate had been initially reported to increase the risk of SIP.
• Delayed onset of feeding
• Intraventricular hemorrhage of Grade III or higher.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

There is insufficient evidence to recommend routine screening for gastrointestinal perforation.

There is insufficient evidence to recommend routine screening for gastrointestinal perforation.