Chapter 17: The Gastrointestinal Tract

A 19-year-old man is advised by other family members to see his physician because genetic screening has detected a disease in other family members. On physical examination, a stool sample is positive for occult blood. A colonoscopy is performed, followed by a colectomy. The figure shows the gross appearance of the mucosal surface of the colectomy specimen. Molecular analysis of this patient's normal fibroblasts is most likely to show a mutation in which of the following genes? □ (A) APC □ (B) p53 □ (C) K-RAS □ (D) HNPCC □ (E) NOD2

(A) APC (A) This young patient's colon shows hundreds of polyps. This is most likely a case of familial adenomatous polyposis (FAP) syndrome, which results from inheritance of one mutant copy of the APC tumor-suppressor gene (a few FAP cases are associated with DNA mismatch repair genes). Every somatic cell of this patient most likely has one defective copy of the APC gene. Polyps are formed when the second copy of the APC gene is lost in many colon epithelial cells. Without treatment, colon cancers arise in 100% of these patients because of accumulation of additional mutations in one or more polyps, typically before 30 years of age. Patients with the gene for hereditary nonpolyposis colorectal carcinoma also have an inherited susceptibility to develop colon cancer, but in contrast to patients with FAP, they do not develop numerous polyps. Sporadic colon cancers may have CpG island hypermethylation along with K-RAS mutations, while others have p53 mutations, but the somatic cells of patients with these cancers do not show abnormalities of these genes. NOD2 mutations are linked with Crohn disease.

A 38-year-old woman has had nausea for the past 6 months. She reports no vomiting or diarrhea. On physical examination, there are no remarkable findings. Upper gastrointestinal endoscopy shows diffuse gastric mucosal erythema with focal mucosal erosions, but no ulcerations. The esophageal and duodenal mucosal surfaces appear normal. Microscopic examination of gastric biopsy specimens shows increased numbers of neutrophils, lymphocytes, and plasma cells in the mucosa; edema; focal mucosal hemorrhage; and loss of the surface epithelium. No Helicobacter pylori organisms are seen. Laboratory studies show a normal serum gastrin level. Which of the following pharmacologic agents is most likely to produce these findings? □ (A) Acetylsalicylic acid (aspirin) □ (B) Acyclovir □ (C) Chlorpromazine □ (D) Cimetidine □ (E) Clindamycin □ (F) Omeprazole □ (G) Prednisone

(A) Acetylsalicylic acid (aspirin) (A) These findings are consistent with an acute gastritis. Heavy consumption of ethanol is probably the most common cause, but aspirin and nonsteroidal anti-inflammatory drugs, smoking, and chemotherapy agents can produce the same findings. Acyclovir (used to treat herpes simplex virus infections), chlorpromazine (used to treat nausea), and prednisone (a steroidal anti-inflammatory drug) do not have the same association. Cimetidine and omeprazole are used to treat peptic ulcer disease by reducing gastric acid production, increasing the serum gastrin. Cimetidine is an H2 receptor blocker, and omeprazole is a proton pump inhibitor. Clindamycin is a broad-spectrum antibiotic that may alter flora in the lower gastrointestinal tract.

A 68-year-old woman has had substernal pain after meals for many years. For the past year, she has had increased difficulty swallowing liquids and solids. On physical examination, there are no remarkable findings. Upper gastrointestinal endoscopy shows a lower esophageal mass that nearly occludes the lumen of the esophagus. A biopsy specimen of this mass is most likely to show which of the following neoplasms? □ (A) Adenocarcinoma □ (B) Leiomyosarcoma □ (C) Squamous cell carcinoma □ (D) Non-Hodgkin lymphoma □ (E) Carcinoid tumor

(A) Adenocarcinoma (A) Adenocarcinomas of the esophagus are typically located in the lower esophagus, where Barrett esophagus develops at the site of long-standing gastroesophageal reflux disease. Barrett esophagus is associated with a greatly increased risk of developing adenocarcinoma. Leiomyosarcoma of the esophagus is rare and is unrelated to a history of "heartburn." Squamous cell carcinomas of the esophagus are most often associated with a history of chronic alcoholism and smoking. Malignant lymphomas of the gastrointestinal tract do not commonly occur in the esophagus and are not related to reflux esophagitis. Carcinoid tumors occur in different parts of the gut, including the appendix, ileum, rectum, stomach, and colon.

A 70-year-old man saw his physician for a routine health maintenance examination. On physical examination, there were no remarkable findings, but a stool sample was positive for occult blood. A colonoscopy was performed and showed a 5- cm sessile mass in the upper portion of the descending colon at 50 cm from the anal verge. The histologic appearance at low power of a biopsy specimen of the lesion is shown in the figure. The patient refused further work-up and treatment. Five years later, he sees his physician because of constipation, microcytic anemia, and a 5-kg weight loss over the past 6 months. On surgical exploration, there is a 7-cm mass encircling the descending colon. Which of the following neoplasms is he now most likely to have? □ (A) Adenocarcinoma □ (B) Non-Hodgkin lymphoma □ (C) Carcinoid tumor □ (D) Leiomyosarcoma □ (E) Mucinous cystadenoma □ (F) Squamous cell carcinoma □ (G) Villous adenoma

(A) Adenocarcinoma (A) This patient had a large villous adenoma, as shown in the figure. There is a high probability that large villous adenomas will progress to invasive adenocarcinoma. When they occur in the descending colon, these lesions are annular and cause obstruction. In the colon, non-Hodgkin lymphomas are far less common than adenocarcinomas, and they do not manifest as mucosal sessile masses. Carcinoid tumors are typically small and yellowish, and most grow slowly. Leiomyosarcomas are rare; they produce large bulky masses, but they do not arise on the mucosa. Mucinous cystadenomas are cystic and are more likely to arise in an ovary or in the pancreas. Squamous cell carcinomas can arise in the esophagus or at the anorectal junction. The original lesion in this patient was a villous adenoma.

A 49-year-old woman sees her physician because she has had abdominal cramps and diarrhea with six stools per day for the past month. She has a history of similar episodes of self-limited pain and diarrhea, which have occurred several times during the past 20 years. Each episode lasts about 2 weeks and resolves without treatment. Findings on physical examination are unremarkable, but a stool sample is positive for occult blood. Laboratory studies show no ova or parasites in the stool. Colonoscopy shows diffuse and uninterrupted mucosal inflammation and superficial ulceration extending from the rectum to the ascending colon. Colonic biopsy specimens from the area show a diffuse, predominantly mononuclear infiltrate in the lamina propria. The patient is at high risk of developing which of the following complications? □ (A) Adenocarcinoma of the colon □ (B) Diverticulitis □ (C) Primary biliary cirrhosis □ (D) Fat malabsorption □ (E) Pseudomembranous colitis □ (F) Perirectal fistula formation

(A) Adenocarcinoma of the colon (A) This patient has clinical and histologic features of ulcerative colitis. Particularly important are relapsing and remitting episodes of diarrhea containing blood and mucus and diffuse inflammation and ulceration of the rectal and colonic mucosa. One of the most dreaded complications of ulcerative colitis is the development of colonic adenocarcinoma. There is a 20-fold to 30-fold higher risk in patients who have had ulcerative colitis for 10 or more years compared with control populations. Diverticulitis can produce abdominal pain and blood in the stool, but there is no association with ulcerative colitis. Ulcerative colitis is associated with several extraintestinal manifestations, including sclerosing cholangitis, but it has no relationship to primary biliary cirrhosis. Fat malabsorption usually does not occur in ulcerative colitis because the ileum often is not involved. Pseudomembranous colitis is caused by Clostridium difficile infections associated with antibiotic treatment. Perirectal fistula formation is more typical of Crohn's disease, in which there is transmural inflammation.

A 27-year-old man has had intermittent cramping abdominal pain and low-volume diarrhea for several weeks. On physical examination, he is afebrile; there is mild lower abdominal tenderness but no masses, and bowel sounds are present. A stool sample is positive for occult blood. The symptoms subside within 1 week. Six months later, the abdominal pain recurs with perianal pain. On physical examination, there is now a perirectal fistula. Colonoscopy shows many areas of mucosal edema and ulceration and some areas that appear normal. Microscopic examination of a biopsy specimen from an ulcerated area shows a patchy acute and chronic inflammatory infiltrate, crypt abscesses, and several noncaseating granulomas. Which of the following underlying disease processes best explains these findings? □ (A) Crohn disease □ (B) Amebiasis □ (C) Shigellosis □ (D) Sarcoidosis □ (E) Ulcerative colitis

(A) Crohn disease (A) The clinical and histologic features are consistent with Crohn disease, one of the idiopathic inflammatory bowel diseases. Crohn disease is marked by segmental bowel involvement and transmural inflammation that leads to strictures, adhesions, and fistula. Ulcerative colitis has mucosal involvement extending variable distances from the rectum. In contrast to Crohn disease, the mucosal involvement is diffuse and does not show "skip areas." Fissures and fistulas are not frequently seen in ulcerative colitis. The findings in Crohn disease and ulcerative colitis overlap, and in one sixth of cases, it may be impossible to differentiate between them on the basis of pathologic findings. Generally, crypt abscesses are more typical of ulcerative colitis, and granulomas are more typical of Crohn disease, but these features are not present in most biopsy specimens from patients with either condition. A story is told of an attending physician at an academic medical center who was known to berate students and residents on rounds for not definitively diagnosing ulcerative colitis and Crohn disease. When he retired, incomplete records for patients with idiopathic inflammatory bowel disease were found in his office; the records represented about one sixth of the total cases of inflammatory bowel disease that he had seen. Amebiasis and shigellosis are infectious processes that can cause mucosal ulceration, but they do not produce granulomas or fissures. Sarcoidosis can involve many organs and give rise to noncaseating granulomas; however, involvement of the intestines is uncommon, and sarcoidosis does not give rise to ulcerative disease.

A neonate born at 32 weeks' gestation was in stable condition and feeding well 3 days after birth. There was no respiratory distress. On day 4, the infant's abdomen was tender and appeared distended. A stool sample was positive for occult blood. Laboratory studies showed leukocytosis and a blood culture positive for growth of Escherichia coli. The infant died of septic shock. Which of the following is most likely to be found at autopsy? □ (A) Dark red necrotic ileum and cecum □ (B) Markedly dilated colon above the sigmoid □ (C) Purulent ascitic fluid □ (D) Markedly enlarged mesenteric lymph nodes □ (E) A 5-cm mass in the retroperitoneum

(A) Dark red necrotic ileum and cecum (A) This infant has neonatal necrotizing enterocolitis, a complication of prematurity. Necrotizing enterocolitis is believed to result from immaturity of the immune system of the gut and is often precipitated by oral feeding. The necrotic bowel can perforate. In Hirschsprung disease with colonic dilation above an aganglionic segment, stools are absent, but there is no necrosis. A bacterial peritonitis could be seen with ascites as a consequence of necrotizing enterocolitis; however, this is a complication, not the cause. Mesenteric lymphadenitis can accompany infection and occasionally cause bowel obstruction, but it is not the cause of necrotizing enterocolitis. A retroperitoneal mass, such as a neuroblastoma, can be present at birth and sometimes can cause bowel obstruction from a mass effect, but it does not cause necrotizing enterocolitis.

A 35-year-old woman has had increasing lower back pain for 5 years. At various times during the past year, she also has had arthritic pain involving the knees, hips, and wrists. A stool sample is positive for occult blood. A pelvic radiograph shows changes consistent with sacroiliitis. A colonoscopy is performed, and she undergoes a total colectomy. The figure shows the gross appearance of the colectomy specimen. What is the most likely diagnosis? □ (A) Dysregulated CD4+ T-cell responses □ (B) Cross-reaction of antibodies against gut bacteria □ (C) Auto-antibodies directed against tropomyosin □ (D) Mutations in the NOD2 gene □ (E) Germline inheritance of the APC gene mutation

(A) Dysregulated CD4+ T-cell responses (A) The segment of the colon shows the diffuse and severe ulceration characteristic of ulcerative colitis. The inflammation shown is so severe that areas of mucosal ulceration have produced pseudopolyps or islands of residual mucosa. Ulcerative colitis is a systemic disease; in some patients, it is associated with migratory polyarthritis, ankylosing spondylitis, and primary sclerosing cholangitis. The pathogenesis of ulcerative colitis is unclear, but is most likely mediated by a T-cell response to an unknown antigen (but not a gut infection), leading to an imbalance between T-cell activation and regulation. The CD4+ T cells present in the lesions secrete damaging substances. Autoantibodies against tropomyosin are present, but do not play a pathogenic role in ulcerative colitis. Mutations in the NOD2 gene are linked to Crohn disease, not ulcerative colitis. Inheritance of a germline APC mutation causes familial adenomatous polyposis coli with a very high risk for colon cancer. Ulcerative colitis also increases the risk for colon cancer, but not secondary to APC gene mutation.

A 51-year-old man has sudden onset of massive emesis of bright red blood. On physical examination, his temperature is 36.9°C, pulse is 103/min, respirations are 19/min, and blood pressure is 85/50 mm Hg. Laboratory studies show a hematocrit of 21%. The serologic test result for HBsAg is positive. He has had no prior episodes of hematemesis. The hematemesis is most likely to be a consequence of which of the following? □ (A) Esophageal varices □ (B) Barrett's esophagus □ (C) Candida albicans infection □ (D) Reflux esophagitis □ (E) Squamous cell carcinoma □ (F) Zenker diverticulum

(A) Esophageal varices (A) Variceal bleeding is a common complication of hepatic cirrhosis, which can be an outcome of chronic hepatitis B infection. The resultant portal hypertension leads to dilated submucosal esophageal veins that can erode and bleed profusely. Barrett esophagus is a columnar metaplasia that results from gastroesophageal reflux disease (GERD). Bleeding is not a key feature of this disease. Esophageal candidiasis may be seen in immunocompromised patients, but it most often produces raised mucosal plaques and is rarely invasive. GERD may produce acute and chronic inflammation and, rarely, massive hemorrhage. Esophageal carcinomas may bleed, but not enough to cause massive hematemesis. A Zenker diverticulum is located in the upper esophagus and results from cricopharyngeal motor dysfunction; it presents a risk for aspiration, but not for hematemesis.

A 50-year-old woman has a history of peptic ulcer disease for which she has been treated with omeprazole. She has had nausea with vomiting for the past 2 months. Upper GI endoscopy reveals 3 circumscribed, round, smooth lesions in the gastric body from 1 to 2 cm in diameter. Biopsies are taken and microscopically show the lesions to consist of irregular glands that are cystically dilated and lined by flattened parietal and chief cells. No inflammation, H. pylori, metaplasia, or dysplasia is present. What is the most likely diagnosis? □ (A) Fundic gland polyps □ (B) Gastric adenomas □ (C) Hyperplastic polyps □ (D) Hypertrophic gastropathy

(A) Fundic gland polyps (A) There is an association of fundic gland polyps with use of proton pump inhibitors and with familial adenomatous polyposis (FAP). Gastric adenomas are most common in the antrum, have intestinal metaplasia with dysplasia, and are precursors to adenocarcinoma; they may occur with FAP. Hyperplastic polyps are associated with chronic gastritis, often from H. pylori infection. One form of hypertrophic gastropathy is Menetrier disease from excessive secretion of transforming growth factor alpha (TGF-α) with diffuse enlargement of gastric rugae and protein-losing enteropathy.

A 35-year-old man has had epigastric pain for more than 1 year. The pain tends to occur 2 to 3 hours after a meal and is relieved if he takes antacids or eats more food. He has noticed a 4-kg weight gain in the past year. He does not smoke and drinks 1 glass of Johannisberg Riesling daily. The result of a urea breath test is positive, and a gastric biopsy specimen contains urease. He begins a 2-week course of antibiotics, but on day 4, he feels better and discontinues treatment. Several weeks later, the epigastric pain recurs. If the patient does not seek further treatment, which of the following complications is he most likely to develop? □ (A) Hematemesis □ (B) Fat malabsorption □ (C) Hepatic metastases □ (D) Carcinoid syndrome □ (E) Vitamin B12 deficiency

(A) Hematemesis (A) The clinical symptoms in this case suggest peptic ulcer disease. In most cases, peptic ulcers are associated with Helicobacter pylori infection. These bacteria secrete urease, which can be detected by oral administration of 14C-labeled urea. After drinking the labeled urea solution, the patient blows into a tube. If H. pylori urease is present in the stomach, the urea is hydrolyzed, and labeled carbon dioxide is detected in the breath sample. In the biopsy urease test, antral biopsy specimens are placed in a gel containing urea and an indicator, and if H. pylori is present, the color changes within minutes. If not properly treated, peptic ulcers can produce many complications, including massive bleeding that can be fatal. The patient does not have fat malabsorption because fat absorption does not occur in the stomach. Peptic ulcers rarely progress to gastric carcinoma; metastases are unlikely. Carcinoid tumors can occur in the stomach, but they are rare and are not related to peptic ulcer disease, which this patient has. Vitamin B12 deficiency can occur with autoimmune atrophic gastritis because intrinsic factor, which is required for vitamin B12 absorption, is produced in gastric parietal cells.

A 24-year-old woman gives birth to an infant at term after an uncomplicated pregnancy. Apgar scores are 9 and 10 at 1 and 5 minutes after birth. The infant's length and weight are at the 55th percentile. There is no significant passage of meconium. Three days after birth, the infant vomits all oral feedings. On physical examination, the infant is afebrile, but the abdomen is distended and tender, and bowel sounds are reduced. An abdominal ultrasound scan shows marked colonic dilation above a narrow segment in the sigmoid region. A biopsy specimen from the narrowed region shows an absence of ganglion cells in the muscle wall and submucosa. Which of the following is most likely to produce these findings? □ (A) Hirschsprung disease □ (B) Trisomy 21 □ (C) Volvulus □ (D) Colonic atresia □ (E) Necrotizing enterocolitis □ (F) Intussusception

(A) Hirschsprung disease (A) This patient has Hirschsprung disease. The aganglionic segment of the bowel wall produces a functional obstruction with proximal distention. Atresias are congenitally narrowed segments of bowel (usually the small intestine) that occur with other anomalies. Patients with trisomy 21 may have intestinal (usually duodenal) atresias. Complete absence of the colonic lumen at a point of atresia is a rare congenital anomaly and is not associated with loss of ganglion cells. Volvulus is a form of mechanical obstruction that occurs from twisting of the small bowel on the mesentery or twisting of a segment of the colon (sigmoid or cecal regions). Necrotizing enterocolitis is a complication of prematurity. Intussusception also is a cause of bowel obstruction in infants, but it is not caused by an aganglionic segment of bowel.

For the past year, a 20-year-old man has had increasingly voluminous, bulky, foul-smelling stools and a 10-kg weight loss. There is no history of hematemesis or melena. He has some bloating, but no abdominal pain. On physical examination, there are no palpable abdominal masses, and bowel sounds are present. Which of the following laboratory findings is most likely to be present on examination of his stool? □ (A) Increased stool fat □ (B) Giardia lamblia cysts □ (C) Occult blood □ (D) Vibrio cholerae □ (E) Entamoeba histolytica trophozoites

(A) Increased stool fat (A) This patient is most likely to have fat malabsorption. Smelly, bulky stools containing increased amounts of fat (steatorrhea) are characteristic. Pancreatic or biliary tract diseases are important causes of fat malabsorption. Giardiasis produces mainly a watery diarrhea. Malabsorption with steatorrhea is unlikely to be associated with bleeding. Cholera results in a massive watery diarrhea. Amebiasis can produce a range of findings from a watery diarrhea to dysentery with mucus and blood in the stool.

A 43-year-old woman has become increasingly tired and listless over the past 5 months. She has had menometrorrhagia for the past 3 months. On physical examination, there are no remarkable findings except for a positive result on stool guaiac testing. Laboratory studies show hemoglobin, 9.2 g/dL; hematocrit, 27.3%; and MCV, 75 μm3. Pelvic ultrasound reveals an enlarged uterus. A Pap smear shows abnormal cells of probable endometrial origin. Colonoscopy is performed, followed by partial colectomy; the gross appearance of the lesion is shown in the figure. Which of the following molecular abnormalities has most likely led to these findings? □ (A) Mutation in a DNA mismatch-repair gene □ (B) Germline inheritance of APC gene mutation □ (C) Tyrosine kinase activation owing to c-KIT mutation □ (D) Homozygous loss of PTEN gene □ (E) Inactivation of the Rb protein by HPV-16

(A) Mutation in a DNA mismatch-repair gene (A) The figure shows a large, fungating mass that is typical of adenocarcinoma of the right colon. Such cancers are unlikely to obstruct, but they can bleed a small amount over months to years, causing iron deficiency anemia. This relatively young woman has evidence for an additional cancer, an endometrial cancer, and this combination is most likely due to an inherited mutation in one of the DNA mismatch-repair genes, such as hMSH2 and hMLH1. Homozygous loss of these genes can give rise to right-sided colon cancer and endometrial cancer. Such a mutation is typically associated with microsatellite instability. In contrast the APC gene, a negative regulator of β-catenin in the WNT signaling pathway, is associated with familial adenomatous polyposis syndrome and most sporadic colon cancers. This latter pathway also is known as the "adenoma-carcinoma sequence" because the carcinomas develop through an identifiable series of molecular and morphologic steps. Mutation with activation of c-KIT tyrosine kinase activity occurs in gastrointestinal stromal tumors, which respond well to treatment with imatinib mesylate, a tyrosine kinase inhibitor also used to treat chronic myelogenous leukemia. Loss of the PTEN tumor-suppressor gene is seen in endometrial carcinomas not associated with colon carcinoma and with some hamartomatous polyps of the colon. Infection with some strains of human papillomavirus leads to Rb protein inactivation and development of cervical carcinoma.

After an uncomplicated pregnancy, a 23-year-old woman, G2, P1, gave birth at term to a boy of normal weight and length. The infant initially did well, but at 6 weeks, he began feeding poorly for 1 week, and his mother noticed that much of the milk he ingested was forcefully vomited within 1 hour. On physical examination, the infant is afebrile, and there are no external anomalies. The physician palpates a midabdominal mass. Bowel sounds are active. The medical history indicates that the mother and her first child had the same illness during infancy. Which of the following conditions is most likely to explain these findings? □ (A) Pyloric stenosis □ (B) Tracheoesophageal fistula □ (C) Diaphragmatic hernia □ (D) Duodenal atresia □ (E) Annular pancreas

(A) Pyloric stenosis (A) The infant's condition occurred several weeks after birth because of hypertrophy of pyloric smooth muscle. Pyloric stenosis manifests the genetic phenomenon of a "threshold of liability," above which the disease is manifested—more genetic risks are present. The incidence in males is 1/200 and in females is 1/1000, reflecting the fact that more risks must be present in females for the disease to occur; the threshold of liability would be exceeded more easily for males born into a family with the trait. Tracheoesophageal fistula, diaphragmatic hernia, and duodenal atresia are serious conditions that are manifested at birth and are often associated with multiple anomalies. Pyloric stenosis is an isolated condition that typically occurs without other anomalies. Annular pancreas is a rare anomaly.

A 57-year-old man goes to the emergency department because of increasing abdominal pain with distention that developed over the past 24 hours. On physical examination, there is diffuse abdominal tenderness. The abdomen is tympanitic, without a fluid wave, and bowel sounds are nearly absent. There is a well-healed, 5-cm transverse scar in the right lower quadrant of the abdomen. There is no caput medusae. A stool sample is negative for occult blood. An abdominal plain film shows dilated loops of small bowel with air-fluid levels, but there is no free air. At laparotomy, the surgeon notices a 20-cm portion of reddish black ileum that changes abruptly to pink-appearing bowel on distal and proximal margins. The patient's medical history is significant only for an appendectomy at age 25. Which of the following is most likely to have produced these findings? □ (A) Adenocarcinoma of the ileum □ (B) Adhesions □ (C) Angiodysplasia □ (D) Crohn disease □ (E) Indirect inguinal hernia □ (F) Intussusception □ (G) Volvulus

(B) Adhesions (B) The patient has acute bowel obstruction, and the findings at surgery show bowel infarction. The most common causes in developed nations are adhesions, hernias, and metastases. Adhesions are most often the result of prior surgery, as in this case, and produce "internal" hernias, where a loop of bowel becomes trapped (incarcerated), and the blood supply is compromised. Loops of bowel that become trapped in direct or indirect inguinal hernias also can infarct. When metastases are the cause, the primary site is generally known, and the cancer stage is high. Primary adenocarcinomas of the small bowel are uncommon. Angiodysplasia is often difficult to detect on gross examination, and it mainly leads to blood loss. Crohn disease can be focal and manifest with bowel obstruction, but it is uncommon in patients of this age. Intussusception can be focal, but it is uncommon. Volvulus may involve the cecal or sigmoid regions of the colon (because of their mobility). When volvulus involves the small intestine, torsion around the mesentery generally occurs, and there is extensive (not segmental) small bowel infarction.

A clinical study of adult patients with chronic bloody diarrhea is performed. One group of these patients is found to have a statistically increased likelihood for the following: antibodies to Saccharomyces cerevisiae but not anti-neutrophil cytoplasmic autoantibodies, NOD2 gene polymorphisms, 50% concordance rate in monozygous twins, higher rate of cigarette smoking, TH1 immune cell activation, vitamin K deficiency, pernicious anemia, and gallstones. Which of the following diseases is this group of patients most likely to have? □ (A) Angiodysplasia □ (B) Crohn disease □ (C) Diverticulitis □ (D) Ischemic enteritis □ (E) Ulcerative colitis

(B) Crohn disease (B) These are findings of idiopathic inflammatory bowel disease most likely to be Crohn disease. The ileal involvement accounts for the vitamin K and vitamin B12 deficiencies as well as disrupted enterohepatic circulation of bile salts predisposing to gallstone formation. The inflammatory response in Crohn disease may result from inappropriate innate immune responses to gut flora, as discussed in the text. Angiodysplasia leads to bleeding from abnormal submucosal vessels, most often in cecum of older adults. Diverticular disease is common in older persons but results from mechanical, not immune, mechanisms. Severe peripheral atherosclerosis may cause ischemic bowel disease, but this is usually an acute process.

A 16-year-old boy who is receiving chemotherapy for acute lymphoblastic leukemia sees the physician because he has had pain for 1 week when he swallows food. Physical examination shows no abnormal findings. Upper gastrointestinal endoscopy shows 0.5- to 0.8-cm mucosal ulcers in the region of the mid to lower esophagus. The shallow ulcers are round and sharply demarcated, and have an erythematous base. Which of the following is most likely to produce these findings? □ (A) Aphthous ulcerations □ (B) Herpes simplex esophagitis □ (C) Gastroesophageal reflux disease □ (D) Candida esophagitis □ (E) Mallory-Weiss syndrome

(B) Herpes simplex esophagitis (B) The "punched-out" ulcers described result from rupture of the herpetic vesicles. Herpesvirus and Candida infections typically occur in immunocompromised patients, and both can involve the esophagus. Candidiasis has the gross appearance of tan-to-yellow plaques. Aphthous ulcers (canker sores) also can be found in immunocompromised patients, but these shallow ulcers occur most frequently in the oral cavity. Gastroesophageal reflux disease (GERD) can produce acute and chronic inflammation with some erosion, although typically not in a sharply demarcated pattern; GERD has no relationship with immune status. Mallory-Weiss syndrome results from mucosal tears of the esophagus. Such laceration of the esophagus can occur with severe vomiting and retching.

A 65-year-old woman goes to her physician for a routine health maintenance examination. A stool sample is positive for occult blood. CT scan of the abdomen shows numerous air-filled, 1-cm outpouchings of the sigmoid and descending colon. Which of the following complications is most likely to develop in this patient? □ (A) Adenocarcinoma □ (B) Pericolic abscess □ (C) Bowel obstruction □ (D) Malabsorption □ (E) Toxic megacolon

(B) Pericolic abscess (B) This patient has colonic diverticulosis, which may be accompanied by intermittent minimal bleeding and, rarely, by severe bleeding. One or more diverticula may become inflamed (diverticulitis) or, less commonly, may perforate to produce an abscess, peritonitis, or both. Diverticular disease is not a premalignant condition. The diverticula project outward, and even with inflammation, luminal obstruction is unlikely. Malabsorption is not a feature of diverticular disease. Toxic megacolon is an uncommon complication of inflammatory bowel disease.

A 45-year-old woman is being treated in the hospital for pneumonia complicated by septicemia. She has required multiple antibiotics and was intubated and mechanically ventilated earlier in the course. On day 20 of hospitalization, she has abdominal distention. Bowel sounds are absent, and an abdominal radiograph shows dilated loops of small bowel suggestive of ileus. She has a low volume of bloody stool that is positive for Clostridium difficile toxin. At laparotomy, a portion of distal ileum and cecum is resected. The gross appearance of the mucosal surface is shown in the figure. What is the most likely diagnosis? □ (A) Mesenteric arterial thrombosis □ (B) Pseudomembranous enterocolitis □ (C) Intussusception □ (D) Cecal volvulus □ (E) Toxic megacolon

(B) Pseudomembranous enterocolitis (B) The opened colon shows fibrinopurulent debris attached to the mucosa. These patches are called pseudomembranes. Pseudomembranous enterocolitis is a complication of broad-spectrum antibiotic therapy, which alters gut flora to allow overgrowth of Clostridium difficile or other organisms that are capable of inflicting mucosal injury. This gross pattern also can appear from ischemic injury that is vascular or mechanical, but this patient's history and the time course support an iatrogenic cause. A dilated, thinned, toxic megacolon is an uncommon complication of ulcerative colitis. An ischemic colitis resulting from mesenteric artery thrombosis could appear similar, but it is not associated with C. difficile. Intussusception and volvulus are forms of mechanical bowel obstruction not related to infection.

A 70-year-old man with a lengthy history of chronic alcoholism has had increasing difficulty swallowing and has noticed a 6-kg weight loss over the past 2 months. On physical examination, there are no remarkable findings. Upper gastrointestinal endoscopy shows a 3-cm ulcerative mass in the midesophagus that partially occludes the esophageal lumen. Esophagectomy is performed; the gross appearance of the lesion is shown in the figure. Which of the following is most likely to be seen on microscopic section of this mass? □ (A) Multinucleated cells with intranuclear inclusions □ (B) Squamous cell carcinoma □ (C) Dense collagenous scar □ (D) Adenocarcinoma □ (E) Thrombosed vascular channels

(B) Squamous cell carcinoma (B) This large, ulcerated lesion with heaped-up margins is a malignant tumor of the esophageal mucosa. There are two main histologic types of esophageal carcinomas—squamous cell carcinoma and adenocarcinoma—with distinct risk factors. Smoking and alcoholism are the most frequent risk factors for esophageal squamous cell carcinoma in the Western world. Adenocarcinoma is most likely to arise in the lower third of the esophagus and to be associated with Barrett's esophagus. Intranuclear inclusions suggest infection with herpes simplex virus or cytomegalovirus, both of which are more likely to produce ulceration without a mass; both occur in immunocompromised patients. Chronic inflammation may lead to stricture and not to a localized mass. Thrombosed veins occur in sclerotherapy for esophageal varices; they do not produce an ulcerated mass. A dense, collagenous scar of the mid esophagus is uncommon, but it may occur after injury from ingestion of a caustic liquid.

A potluck lunch party is held at the office at noon on Thursday. Various meats, salads, breads, and desserts that were brought in earlier that morning are served. Everyone has a good time, and most of the food is consumed. By midafternoon, the single office restroom is being used by many employees who have an acute, explosive diarrhea accompanied by abdominal cramping. Which of the following infectious agents is most likely responsible for this turn of events? □ (A) Escherichia coli □ (B) Staphylococcus aureus □ (C) Vibrio parahaemolyticus □ (D) Clostridium difficile □ (E) Salmonella enteritidis □ (F) Bacillus cereus

(B) Staphylococcus aureus (B) The clinical features suggest food poisoning caused by the ingestion of a preformed enterotoxin. Staphylococcus aureus grows in food (milk products and fatty foods are favorites) and elaborates an enterotoxin that, when ingested, produces diarrhea within hours. Some strains of Escherichia coli can produce various diarrheal illnesses, but without a preformed toxin. Vibrio parahaemolyticus is found in shellfish. Clostridium difficile can produce a pseudomembranous colitis in patients treated with broad-spectrum antibiotics. Salmonella enteritidis is most often found in poultry products, but the diarrheal illnesses develop within 2 days. Bacillus cereus is better known for growing on reheated fried rice; it produces an exotoxin that causes acute nausea, vomiting, and abdominal cramping.

A 52-year-old, previously healthy man sustained an extensive thermal burn injury involving 70% of the total body surface area of his skin. He was hospitalized in stable condition. Three weeks after the initial burn injury, he had melanotic stools. His blood pressure was 80/40 mm Hg, and his hematocrit was 18%. Soon after, he experienced cardiac arrest and could not be resuscitated. At autopsy, where are gastrointestinal ulcerations most likely to be found in this man? □ (A) Esophagus □ (B) Stomach □ (C) Duodenum □ (D) Ileum □ (E) Colon

(B) Stomach (B) The patient has so-called stress ulcers, also known as Curling ulcers when they occur in patients with burn injuries. The ulcers are often small (<1 cm) and shallow, never penetrating the muscularis propria, but they can bleed profusely. Similar lesions can occur after traumatic or surgical injury to the central nervous system (Cushing ulcers). Esophageal varices can cause massive hematemesis, but they occur in patients with portal hypertension, caused most commonly by cirrhosis. Metaplastic columnar epithelium at the lower end of the esophagus is present in Barrett esophagus, resulting from chronic gastroesophageal reflux disease. Duodenal ulcers are typically peptic ulcers in individuals with Helicobacter pylori infection. Ileal ulcerations and colonic ulcerations are often due to inflammatory bowel disease that can be from infections such as shigellosis or idiopathic, as in Crohn's disease.

A 70-year-old man takes large quantities of nonsteroidal anti-inflammatory drugs because of chronic degenerative arthritis of the hips and knees. Recently, he has had epigastric pain with nausea and vomiting and an episode of hematemesis. On physical examination, there are no remarkable findings. A gastric biopsy specimen is most likely to show which of the following lesions? □ (A) Epithelial dysplasia □ (B) Hyperplastic polyp □ (C) Acute gastritis □ (D) Adenocarcinoma □ (E) Helicobacter pylori infection

(C) Acute gastritis (C) Prolonged use of nonsteroidal anti-inflammatory drugs is an important cause of acute gastritis. Excessive alcohol consumption and smoking also are possible causes. Acute gastritis tends to be diffuse and, when severe, can lead to significant hemorrhage that is difficult to control. Epithelial dysplasia may occur at the site of chronic gastritis. It is a forerunner of gastric cancer. Hyperplastic polyps of the stomach do not result from acute gastritis, but may arise in association with chronic gastritis. Acute gastritis does not increase the risk of gastric adenocarcinoma. Infection with Helicobacter pylori is not associated with acute gastritis.

A 59-year-old man has had increasing difficulty swallowing during the past 6 months. There are no significant findings on physical examination. Upper gastrointestinal endoscopy shows areas of erythematous mucosa above the Z-line. A biopsy specimen from the lower esophagus has the microscopic appearance shown in the figure. Which of the following complications is most likely to occur as a consequence of this patient's condition? □ (A) Hematemesis □ (B) Squamous cell carcinoma □ (C) Adenocarcinoma □ (D) Achalasia □ (E) Lacerations (Mallory-Weiss syndrome)

(C) Adenocarcinoma (C) The biopsy specimen shows columnar metaplasia, typical of Barrett esophagus. Patients with a focus of Barrett esophagus larger than 2 cm have a 30-fold to 40-fold higher risk of developing adenocarcinoma than the general population. Squamous cell carcinomas occur in the esophagus, but they do not arise in association with Barrett esophagus. Their occurrence is related to smoking and alcohol consumption. Hematemesis is a complication of esophageal varices and other conditions, such as peptic ulcers. Achalasia refers to failure of relaxation of the lower esophageal sphincter that gives rise to dilation of the proximal portion of the esophagus. Mallory-Weiss syndrome is associated with vertical lacerations in the esophagus that may occur with severe vomiting and retching.

A 60-year-old man has had increasing fatigue for the past 8 months. On physical examination, he appears pale. On digital rectal examination, no masses are palpable, but a stool sample is positive for occult blood. Physical examination of the abdomen shows active bowel sounds with no masses or areas of tenderness. Laboratory studies show hemoglobin, 8.3 g/dL; hematocrit, 24.6%; MCV, 73 μm3; platelet count, 226,000/mm3; and WBC count, 7640/mm3. Colonoscopy shows no identifiable source of the bleeding. Angiography shows a 1-cm focus of dilated and tortuous vascular channels in the mucosa and submucosa of the cecum. What is the most likely diagnosis? □ (A) Mesenteric vein thrombosis □ (B) Internal hemorrhoids □ (C) Angiodysplasia of the colon □ (D) Collagenous colitis □ (E) Colonic diverticulosis

(C) Angiodysplasia of the colon (C) Angiodysplasia refers to tortuous dilations of mucosal and submucosal vessels, seen most often in the cecum in patients older than 50 years. These lesions, although uncommon, account for 20% of significant lower intestinal bleeding. Bleeding usually is not massive, but can occur intermittently over months to years. This lesion is difficult to diagnose and is often found radiographically. The focus (or foci) of abnormal vessels can be excised. Mesenteric venous thrombosis is rare and may result in bowel infarction with severe abdominal pain. Hemorrhoids at the anorectal junction may account for bright red rectal bleeding, but they can be seen or palpated on rectal examination. Collagenous colitis is a rare cause of a watery diarrhea that is typically not bloody. Colonic diverticulosis can be associated with hemorrhage, but the outpouchings usually are seen on colonoscopy.

A 33-year-old man who lives in New York is bothered by a low-volume, mostly watery diarrhea associated with flatulence. The symptoms occur episodically, but they have been persistent for the past year. He has experienced a 5-kg weight loss. He has no fever, nausea, vomiting, or abdominal pain. On physical examination, there are no significant findings. A stool sample is negative for occult blood, ova, and parasites, and a stool culture yields no pathogens. An upper gastrointestinal endoscopy is performed. A biopsy specimen from the upper part of the small bowel shows severe diffuse blunting of villi and a chronic inflammatory infiltrate in the lamina propria. Which of the following serologic tests is most likely to be positive in this patient? □ (A) Anticentromeric antibody □ (B) Anti-DNA topoisomerase I antibody □ (C) Antigliadin antibody □ (D) Antimitochondrial antibody □ (E) Antinuclear antibody

(C) Antigliadin antibody (C) The clinical and histologic features suggest celiac disease. Characteristic serologic findings include positive tests for anti-transglutaminase, anti-gliadin, and anti-endomysial antibodies. This chronic disease may manifest in young adulthood but may escape diagnosis. Women are affected more than men. Celiac disease results from gluten sensitivity. Exposure to the gliadin protein in wheat, oats, barley, and rye (but not rice) results in intestinal inflammation. Gliadin sensitivity causes epithelial cells to produce IL-15, which in turn leads to accumulation of activated CD8+ T cells that bear the NK cell receptor NKG2D and damage the enterocytes expressing MIC-A. A trial of a gluten-free diet is the most logical therapeutic option. Patients usually become symptom-free, and normal histologic features of the mucosa are restored. Some patients develop dermatitis herpetiformis, and a few enteropathy-associated T-cell lymphomas. Anticentromeric antibody is most specific for limited scleroderma (CREST syndrome) with esophageal dysmotility. The anti-DNA topoisomerase I antibody is most specific for diffuse scleroderma, in which gastrointestinal tract involvement by submucosal fibrosis may be more extensive, and malabsorption may be present. Antimitochondrial antibody is more specific for primary biliary cirrhosis. Antinuclear antibody is present in a wide variety of autoimmune diseases, but it is not characteristic of celiac sprue.

One week after a trip to Central America, a 31-year-old woman had increasingly severe diarrhea. Gross examination of the stools showed mucus and streaks of blood. The diarrheal illness subsided within a couple of weeks, but now the patient has become febrile and has pain in the right upper quadrant of the abdomen. An abdominal ultrasound scan shows a 10-cm, irregular, partly cystic mass in the right hepatic lobe. Which of the following infectious organisms is most likely to produce these findings? □ (A) Giardia lamblia □ (B) Cryptosporidium parvum □ (C) Entamoeba histolytica □ (D) Clostridium difficile □ (E) Strongyloides stercoralis

(C) Entamoeba histolytica (C) Diarrhea with mucus and blood in the stools can be caused by several enteroinvasive microorganisms, including Shigella dysenteriae and Entamoeba histolytica. In most cases, the diarrhea is self-limited. The initial episode of diarrhea could have been caused by one of several organisms; however, the occurrence of a liver abscess after an episode of diarrhea most likely results from infection with E. histolytica. Colonic mucosal and submucosal invasion by E. histolytica allows the organisms to gain access to submucosal veins draining to the portal system and to the liver. Giardia produces a self-limited, watery diarrhea. Dissemination of Cryptosporidium and Strongyloides organisms may occur in immunocompromised patients. Clostridium difficile causes pseudomembranous colitis after antibiotic therapy.

A 23-year-old primigravida gives birth at term to a boy. Ultrasound examination before delivery showed polyhydramnios. A single umbilical artery is seen at the time of birth. It is noted that the infant vomits all feedings, then develops a fever and difficulty with respirations within 2 days. A radiograph shows both lungs and the heart are of normal size, but there are pulmonary infiltrates and no stomach bubble. What is the most likely diagnosis? □ (A) Achalasia □ (B) Diaphragmatic hernia □ (C) Esophageal atresia □ (D) Hiatal hernia □ (E) Pyloric stenosis □ (F) Squamous cell carcinoma □ (G) Zenker diverticulum

(C) Esophageal atresia (C) An esophageal atresia is often combined with a fistula between the esophagus and trachea. Gastrointestinal obstruction in utero can lead to polyhydramnios. The presence of a single umbilical artery suggests additional anomalies are present. Vomiting in an infant risks aspiration with development of pneumonia. Achalasia is incomplete relaxation of the lower esophageal sphincter and is usually not manifested at birth. Absence of a diaphragmatic leaf, usually on the left, results in herniation of abdominal contents into the chest and functional gastrointestinal obstruction, but in this case normal-sized lungs suggest no herniated contents were present. A hiatal hernia from widened diaphragmatic muscular crura predisposes to gastroesophageal reflux, and obstruction is not a typical complication. Pyloric stenosis is a cause for gastric outlet obstruction in an infant, but the onset is usually in the second or third week of life. Squamous cell carcinomas are seen in adults. A pharyngoesophageal (Zenker) diverticulum above the upper esophageal sphincter is usually a disease of adults.

One year after having an acute myocardial infarction, a 55-year-old man saw his physician because of severe abdominal pain and bloody diarrhea. On physical examination, the abdomen was diffusely tender, and bowel sounds were absent. Abdominal plain films showed no free air. Laboratory studies showed a normal CBC and normal levels of serum amylase, lipase, and bilirubin. His condition deteriorated, and he developed irreversible shock. At autopsy, which of the following lesions is most likely to be found? □ (A) Acute appendicitis □ (B) Acute pancreatitis □ (C) Intestinal infarction □ (D) Acute cholecystitis □ (E) Pseudomembranous colitis

(C) Intestinal infarction (C) The patient's history of myocardial infarction suggests that he had severe coronary atherosclerosis. Atheromatous disease most likely involved the mesenteric vessels as well, giving rise to thrombosis of the blood vessels that perfuse the bowel. The symptoms and signs suggest infarction of the gut. Acute appendicitis rarely leads to such a catastrophic illness, unless there is perforation. (The absence of free air in the radiograph argues against perforation of any viscus.) Acute pancreatitis can be a serious abdominal emergency, but the normal levels of amylase and lipase tend to exclude it. Acute cholecystitis can produce severe abdominal pain, but bloody diarrhea and absence of bowel sounds (paralytic ileus) are unlikely. Pseudomembranous colitis develops in patients receiving antibiotic therapy.

A 26-year-old man is brought to the emergency department after sustaining abdominal gunshot injuries. At laparotomy, while repairing the small intestine, the surgeon notices a 1-cm mass at the tip of the appendix. The yellow-tan submucosal mass is removed. The electron micrograph of a neoplastic cell from the mass is shown in the figure. Which of the following is the most likely cell of origin of this lesion? □ (A) Lipoblast □ (B) Ganglion cell □ (C) Neuroendocrine cell □ (D) Smooth muscle cell □ (E) Mucin-secreting epithelial cell

(C) Neuroendocrine cell (C) The figure shows a carcinoid tumor. The cytoplasm of the tumor cell contains small, dark, round granules with a dense core (neurosecretory granules), which are characteristic of neuroendocrine cells. The gross appearance of this tumor and its location also are characteristic of carcinoid tumors. Many small carcinoids and other small, benign bowel tumors are discovered incidentally; most are 2 cm or smaller. The other listed cell types do not have neurosecretory granules.

A 57-year-old woman has had burning epigastric pain after meals for more than 1 year. Physical examination shows no abnormal findings. Upper gastrointestinal endoscopy shows an erythematous patch in the lower esophageal mucosa. A biopsy specimen shows basal squamous epithelial hyperplasia, elongation of lamina propria papillae, and scattered intraepithelial neutrophils with some eosinophils. Which of the following is the most likely diagnosis? □ (A) Barrett esophagus □ (B) Esophageal varices □ (C) Reflux esophagitis □ (D) Scleroderma □ (E) Iron deficiency

(C) Reflux esophagitis (C) These findings indicate an ongoing inflammatory process resulting from reflux of acid gastric contents into the lower esophagus. Gastroesophageal reflux disease (GERD) is a common problem that stems from a variety of causes, including sliding hiatal hernia, decreased tone of the lower esophageal sphincter, and delayed gastric emptying. Patients may have a history of "heartburn" after eating. Barrett esophagus is a complication of long-standing GERD and is characterized by columnar metaplasia of the squamous epithelium that normally lines the esophagus. There may be inflammation and mucosal ulceration overlying varices, but this condition usually does not have heartburn as the major feature. Progressive fibrosis with stenosis is found in scleroderma. A rare complication of iron deficiency is the appearance of an upper esophageal web (Plummer-Vinson syndrome).

Over the past 3 months, a 45-year-old woman has noticed that her skin has become progressively more yellow. On physical examination, she is afebrile and has scleral icterus and generalized jaundice. Laboratory studies show total serum bilirubin of 8.9 mg/dL, direct bilirubin of 6.8 mg/dL, serum ALT of 125 U/L, and serum AST of 108 U/L. A liver biopsy specimen shows histologic features of sclerosing cholangitis. Which of the following diseases of the gastrointestinal tract is most likely to coexist with the liver disease? □ (A) Chronic pancreatitis □ (B) Diverticulosis □ (C) Ulcerative colitis □ (D) Celiac sprue □ (E) Peptic ulceration

(C) Ulcerative colitis (C) Sclerosing cholangitis is a serious extraintestinal manifestation of idiopathic inflammatory bowel disease, most often ulcerative colitis or, less often, Crohn disease. Pancreatitis and cholangitis may be complications of biliary tract lithiasis, but they have no association with sclerosing cholangitis. Diverticulosis may be complicated by diverticulitis, but the liver is not involved. Celiac disease may be associated with dermatitis herpetiformis, but not with liver disease. Peptic ulcer disease does not lead to hepatic complications.

A 30-year-old woman sees her physician because she has had diarrhea and fatigue and has noticed a 3-kg weight loss over the past 6 months. On physical examination, she is afebrile and has mild muscle wasting, but her motor strength is normal. Laboratory studies show no occult blood, ova, or parasites in the stool. A biopsy specimen from the upper jejunum is obtained, and microscopic findings are reviewed. The patient is placed on a special diet with no wheat or rye grain products. The change in diet produces dramatic improvement. Which of the following microscopic features is most likely to be seen in the biopsy specimen? □ (A) Lymphatic obstruction □ (B) Noncaseating granulomas □ (C) Villous blunting and flattening □ (D) Foamy macrophages within the lamina propria □ (E) Crypt abscesses

(C) Villous blunting and flattening (C) This patient has malabsorption that responded to dietary treatment. She probably has celiac disease (gluten sensitivity). The histologic features of celiac disease are flattening of the mucosa, diffuse and severe atrophy of the villi, and chronic inflammation of the lamina propria. There is an increase in intraepithelial lymphocytes. Lymphatic obstruction occurs in Whipple disease. In addition, foamy macrophages accumulate in the lamina propria. They contain PAS-positive granules, which, under electron microscope, show an actinomycete called Tropheryma whippelii. Noncaseating granulomas are found in the intestinal wall in Crohn's disease. Crypt abscesses are nonspecific and can be seen in inflammatory bowel disease.

A 30-year-old man has a routine health maintenance examination. A stool sample is positive for occult blood. On colonoscopy, an ulcerative lesion is seen projecting into the cecum. The microscopic appearance of a section of the excised lesion is shown in the figure. Which of the following molecular biologic events is thought to be most critical in the development of such lesions? □ (A) Overexpression of E-cadherin gene □ (B) Amplification of ERBB2 gene □ (C) Germline transmission of a defective RB gene □ (D) A defective DNA mismatch-repair gene □ (E) Translocation of retinoic acid receptor α gene

(D) A defective DNA mismatch-repair gene (D) The lesion is an adenocarcinoma, showing irregular glands infiltrating the muscle layer. Such a lesion in a 30-yearold man strongly indicates a hereditary predisposition. One hereditary form of cancer is called hereditary nonpolyposis colorectal carcinoma (HNPCC) and results from defective DNA mismatch-repair genes. As a result, mutations accumulate in microsatellite repeats (microsatellite instability) that lead to loss of transforming growth factor-β (TGF-β) receptormediated control of colonic epithelial cell proliferation and loss of pro-apoptotic BAX protein enhancing survival of these transformed cells. He could have taken NSAIDS that inhibit COX-2 expressed in most colonic adenomas and carcinomas. In contrast to familial adenomatous polyposis syndrome, HNPCC does not lead to the development of hundreds of polyps in the colon. E-cadherin is required for intercellular adhesion; its levels are reduced, not increased, in carcinoma cells. Detection of ERBB2 (HER2/NEU) expression is important in breast cancers. Germline inheritance of the tumor-suppressor gene RB predisposes to retinoblastoma and osteosarcoma, not colon carcinoma. Translocation of the retinoic acid receptor α gene is characteristic of acute promyelocytic leukemia.

A 53-year-old woman has had nausea, vomiting, and mid epigastric pain for 5 months. On physical examination, there are no significant findings. An upper gastrointestinal radiographic series shows gastric outlet obstruction. Upper gastrointestinal endoscopy shows an ulcerated mass that is 2 × 4 cm at the pylorus. Which of the following neoplasms is most likely to be seen in a biopsy specimen of this mass? □ (A) Non-Hodgkin lymphoma □ (B) Neuroendocrine carcinoma □ (C) Squamous cell carcinoma □ (D) Adenocarcinoma □ (E) Leiomyosarcoma

(D) Adenocarcinoma (D) The most likely cause of a large mass lesion in the stomach is a gastric carcinoma, and this lesion is an adenocarcinoma. Malignant lymphomas and leiomyosarcomas are less common and tend to form bulky masses in the fundus. Neuroendocrine carcinomas are rare. Squamous cell carcinomas appear in the esophagus.

A 44-year-old woman has had increasing difficulty swallowing liquids and solids for the past 6 months. On physical examination, her fingers have reduced mobility because of taut, nondeforming skin. A barium swallow shows marked dilation of the esophagus with "beaking" in the distal portion, where there is marked luminal narrowing. A biopsy specimen from the lower esophagus shows prominent submucosal fibrosis with little inflammation. Which of the following is most likely to produce these findings? □ (A) Portal hypertension □ (B) Iron deficiency □ (C) Barrett esophagus □ (D) CREST syndrome □ (E) Hiatal hernia

(D) CREST syndrome (D) Esophageal dysmotility is the "E" in CREST syndrome, the limited form of systemic sclerosis (scleroderma). Although the disease is autoimmune, little inflammation is seen by the time the patient seeks clinical attention. There is increased collagen deposition in submucosa and muscularis. Fibrosis may affect any part of the gastrointestinal tract, but the esophagus is the site most often involved. Portal hypertension gives rise to esophageal varices, not fibrosis. An upper esophageal web associated with iron deficiency anemia might produce difficulty in swallowing, but this condition is rare. For a diagnosis of Barrett esophagus, columnar metaplasia must be seen histologically, and there is often a history of gastroesophageal reflux disease. Hiatal hernia is frequently diagnosed in individuals with reflux esophagitis and can lead to inflammation, ulceration, and bleeding, but formation of a stricture is uncommon.

During summer "Black and White Days," a week-long local community celebration of the dairy industry (Holstein cows are black and white), a 40-year-old man has episodic abdominal bloating, flatulence, and explosive diarrhea. On physical examination, there are no remarkable findings. Laboratory studies show no increase in stool fat and no occult blood, ova, or parasites in the stool. A routine stool culture yields no pathogens. During the rest of the year, the patient does not consume milkshakes or ice cream sodas and is not symptomatic. Which of the following conditions best accounts for these findings? □ (A) Celiac disease □ (B) Autoimmune gastritis □ (C) Cholelithiasis □ (D) Disaccharidase deficiency □ (E) Cystic fibrosis

(D) Disaccharidase deficiency (D) Disaccharidase (lactase) deficiency is an uncommon congenital condition (or a rare acquired condition) in which the lactose in milk products is not broken down into glucose and galactose, resulting in an osmotic diarrhea and gas production from gut flora. Affected individuals do not always make the connection between diet and symptoms, or they do not consume enough milk products to become symptomatic. Celiac disease also is diet related and results from a sensitivity to gluten in some grains. An autoimmune gastritis is most likely to result in vitamin B12 malabsorption. Cholelithiasis can cause biliary tract obstruction with malabsorption of fats and right upper quadrant abdominal pain. Cystic fibrosis affects the pancreas and mainly produces fat malabsorption.

A 51-year-old woman has been feeling increasingly tired for the past 7 months. There are no remarkable findings on physical examination. Laboratory studies include hemoglobin, 9.5 g/dL; hematocrit, 29.1%; MCV, 124 μm3; platelet count, 268,000/mm3; and WBC count, 8350/mm3. The reticulocyte index is low. Hypersegmented polymorphonuclear leukocytes are found on a peripheral blood smear. Antibodies to which of the following are most likely to be found in this patient? □ (A) Gliadin □ (B) Tropheryma whippelii □ (C) Helicobacter pylori □ (D) Gastric H+,K+-ATPase □ (E) Intrinsic factor receptor

(D) Gastric H+,K+-ATPase (D) This patient has a megaloblastic anemia with a high MCV. Delayed maturation of the myeloid cells leads to hypersegmentation of polymorphonuclear leukocytes. She most likely has pernicious anemia, resulting from autoimmune atrophic gastritis. Loss of gastric parietal cells from autoimmune injury causes a deficiency of intrinsic factor. In the absence of this factor, vitamin B12 cannot be absorbed in the distal ileum. Among the various "antiparietal cell" antibodies are those directed against the acid-producing "proton pump" enzyme H+,K+-ATPase. Antigliadin antibodies are found with celiac disease that does not affect the gastric mucosa. Infection with Tropheryma whippelii causes Whipple disease, which may involve any organ, but most often affects intestines, central nervous system, and joints; malabsorption is common. H. pylori causes chronic gastritis and peptic ulcer disease, but does not injure parietal cells. In pernicious anemia, no antibodies are directed against intrinsic factor receptor on ileal mucosal cells.

A 20-year-old woman in her ninth month of pregnancy has increasing pain on defecation and notices bright red blood on the toilet paper. She has had no previous gastrointestinal problems. After she gives birth, the rectal pain subsides, and there is no more bleeding. Which of the following is the most likely cause of these findings? □ (A) Angiodysplasia □ (B) Ischemic colitis □ (C) Intussusception □ (D) Hemorrhoids □ (E) Volvulus

(D) Hemorrhoids (D) This patient has hemorrhoids. This is a common problem that can stem from any condition that increases venous pressure and causes dilation of internal or external hemorrhoidal veins above and below the anorectal junction. Angiodysplasia of the colon leads to intermittent hemorrhage, typically in older individuals. Ischemic colitis is rare in young individuals because the most common underlying cause (severe atherosclerotic disease involving mesenteric vessels) occurs in older patients. Intussusception and volvulus are rare causes of mechanical bowel obstruction; they occur suddenly in adults and are surgical emergencies.

A 45-year-old woman has had increasing abdominal distention for the past 6 weeks. On physical examination, there is an abdominal fluid wave, and bowel sounds are present. Paracentesis yields 1000 mL of slightly cloudy serous fluid. Cytologic examination of the fluid shows malignant cells consistent with adenocarcinoma. The patient's medical history indicates that she has had no major medical illnesses and no surgical procedures. Which of the following conditions is most likely to have preceded the development of the adenocarcinoma? □ (A) Angiodysplasia □ (B) Crohn disease □ (C) Diverticulosis □ (D) Hereditary nonpolyposis colon carcinoma □ (E) Hirschsprung disease □ (F) Peptic ulcer disease

(D) Hereditary nonpolyposis colon carcinoma (D) Of the conditions listed, the one most likely to lead to adenocarcinoma in a patient of this age is hereditary nonpolyposis colorectal carcinoma. Crohn disease is unlikely because the patient has not had prior serious illness, and Crohn disease of long duration is unlikely to remain asymptomatic. Although adenocarcinoma may complicate Crohn disease, it does not occur as frequently as in ulcerative colitis. This explains why colectomy is often performed for ulcerative colitis, but bowel resections are avoided, if possible, in Crohn disease. The other conditions listed are not premalignant.

A 41-year-old man has been HIV positive for the past 8 years and has been receiving highly active antiretroviral therapy for the past year. For the past 2 weeks, he has experienced pain when swallowing. He has had no episodes of hematemesis and no nausea or vomiting. There are no remarkable findings on physical examination. The CD4+ lymphocyte count is now 285/μL. Which of the following conditions is most likely to produce these findings? □ (A) Esophageal squamous cell carcinoma □ (B) Achalasia □ (C) Lower esophageal fibrosis with stenosis □ (D) Herpes simplex esophagitis □ (E) Gastroesophageal reflux disease

(D) Herpes simplex esophagitis (D) A patient who is HIV-positive and has low CD4+ cell counts is at great risk of developing infections. Herpes simplex and Candida are the most likely upper gastrointestinal infections involving the esophagus. Squamous cell carcinoma of the esophagus is not related to HIV infection. Achalasia, caused by a failure of relaxation of the lower esophageal sphincter, is not a feature of HIV infection or immunosuppression. Fibrosis with stenosis is a feature of gastroesophageal reflux disease and scleroderma.

A 52-year-old man has had a 6-kg weight loss and nausea for the past 6 months. He has no vomiting or diarrhea. On physical examination, there are no remarkable findings. Upper gastrointestinal endoscopy shows a 6-cm area of irregular, pale fundic mucosa and loss of the rugal folds. A biopsy specimen shows a monomorphous infiltrate of lymphoid cells. Helicobacter pylori organisms are identified in mucus overlying adjacent mucosa. The patient receives antibiotic therapy for H. pylori, and the repeat biopsy specimen shows a resolution of the infiltrate. What is the most likely diagnosis? □ (A) Chronic gastritis □ (B) Diffuse large B-cell lymphoma □ (C) Autoimmune gastritis □ (D) Mucosa-associated lymphoid tissue tumor □ (E) Crohn disease □ (F) Gastrointestinal stromal tumor

(D) Mucosa-associated lymphoid tissue tumor (D) Certain gastrointestinal lymphomas that arise from mucosa-associated lymphoid tissue (MALT) are called MALT lymphomas. Gastric lymphomas that occur in association with Helicobacter pylori infection are composed of monoclonal B cells, whose growth and proliferation depend on cytokines derived from T cells that are sensitized to H. pylori antigens. Treatment with antibiotics eliminates H. pylori and the stimulus for B-cell growth. MALT lesions can occur anywhere in the gastrointestinal tract, although they are rare in the esophagus and appendix. In H. pylori chronic gastritis, which may precede lymphoma development, there are lymphoplasmacytic mucosal infiltrates. Diffuse large B-cell lymphomas and other non-Hodgkin lymphomas that are not MALT lymphomas do not regress with antibiotic therapy. Autoimmune gastritis is a risk for development of gastric adenocarcinoma. Crohn disease is rare in the stomach and is not related to H. pylori infection. Gastrointestinal stromal tumors are uncommon; these tumors may be proliferations of interstitial cells of Cajal, myenteric plexus cells that are thought to be the pacemaker of the gut.

Two days after eating a chicken salad sandwich, a 35-year-old man experiences cramping abdominal pain with fever and watery diarrhea. Physical examination shows mild diffuse abdominal pain on palpation, but there are no masses. Bowel sounds are present. A stool sample is negative for occult blood. He recovers completely within a few days without treatment. Which of the following infectious organisms is most likely to produce these findings? □ (A) Yersinia enterocolitica □ (B) Escherichia coli □ (C) Entamoeba histolytica □ (D) Salmonella enteritidis □ (E) Rotavirus □ (F) Staphylococcus aureus □ (G) Bacillus cereus

(D) Salmonella enteritidis (D) Infection by one of several Salmonella species (not S. typhi) causes a self-limited diarrhea. This is a form of food poisoning, typically from contaminated poultry products. Yersinia enterocolitica is most often found in contaminated milk or pork products and may disseminate to produce lymphadenitis and further extraintestinal infection. Various diseases result from contamination with different strains of Escherichia coli, based on the characteristics of the organisms, and whether they invade or produce an enterotoxin. Poultry products are usually not contaminated with E. coli. Amebiasis from Entamoeba histolytica can be an invasive, exudative infection. The stools contain blood and mucus. Rotavirus is most often seen in children; in adults, a self-limited watery diarrhea occurs. There is no particular association between rotavirus infection and a specific food product. Staphylococcus aureus causes an acute onset of abdominal pain, bloating, and diarrhea not by directly infecting the gastrointestinal tract, but by producing an exotoxin while growing on food that is subsequently ingested. Bacillus cereus growing in foods such as reheated fried rice produces an exotoxin, which, on ingestion, can produce acute onset of nausea, vomiting, and abdominal pain.

A 59-year-old man has had nausea and vomiting for several months. He has experienced no hematemesis. On physical examination, there is no abdominal tenderness, and bowel sounds are present. Upper gastrointestinal endoscopy shows erythematous areas of mucosa with thickening of the rugal folds in the gastric antrum. The microscopic appearance of a gastric biopsy specimen with a Steiner silver stain is shown in the figure. Which of the following toxins from these organisms is most likely to be present on the luminal surface? □ (A) Cysteine proteinase □ (B) Heat-stable enterotoxin □ (C) Shiga toxin □ (D) Vacuolating toxin □ (E) Verocytotoxin

(D) Vacuolating toxin (D) Helicobacter pylori organisms reside in the gastric mucus and are associated with various gastric disorders, ranging from chronic gastritis with erythema and thickened rugal folds, as in this case, to peptic ulcers and to adenocarcinoma. H. pylori organisms elaborate several toxic substances that injure the epithelium. Vacuolating cytotoxin (VacA) causes cell injury characterized by vacuolization. Another H. pylori gene from a pathogenicity island encodes cytotoxin-associated antigen (CagA) and is present in many patients with chronic gastritis and peptic ulcers and increases their risk for gastric cancer. Cysteine proteinases produced by Entamoeba histolytica aid in tissue invasion. Heat-stable enterotoxin is produced by strains of Escherichia coli that cause traveler's diarrhea. Shiga toxin is elaborated by Shigella flexneri organisms, which cause a form of bacillary dysentery. Verocytotoxin produced by some E. coli strains is associated with hemolytic-uremic syndrome mediated by endothelial injury.

A 53-year-old woman comes to her physician for a routine health maintenance examination. The only abnormal finding is a stool specimen that contains occult blood. Colonoscopy shows a 1.5-cm, solitary, rounded, erythematous polyp on a 0.5-cm stalk at the splenic flexure. The polyp is removed; its histologic appearance is shown in the figure at low (A) and high (B) magnifications. When the physician discusses these findings with the patient, which of the following statements is most appropriate? □ (A) You have inherited one defective copy of the APC gene □ (B) Other family members probably have colonic polyps □ (C) Many more polyps will appear within the next few years □ (D) There is a high probability that you will develop endometrial cancer □ (E) A detailed work-up to detect metastases from this lesion is not warranted

(E) A detailed work-up to detect metastases from this lesion is not warranted (E) The figure shows a solitary pedunculated adenoma of the colon with no evidence of malignancy. High magnification shows a small focus of dysplastic, non-mucin-secreting epithelial cells lining a colonic crypt, giving rise to "tubular" architecture. Such a small (<2 cm), solitary, tubular adenoma is unlikely to harbor a focus of malignancy; a search for metastases is unwarranted. Individuals who inherit a mutant APC gene usually develop hundreds of polyps at a young age; this patient does not need genetic testing for a somatic mutation in the APC gene. Patients with hereditary nonpolyposis colorectal cancer have an increased risk of endometrial cancer and develop colon cancer at a young age.

A 22-year-old woman has had several episodes of aspiration of food associated with difficulty swallowing during the past year. On auscultation, crackles are heard at the base of the right lung. A barium swallow shows marked esophageal dilation above the level of the lower esophageal sphincter. A biopsy specimen from the lower esophagus shows an absence of the myenteric ganglia. What is the most likely diagnosis? □ (A) Hiatal hernia □ (B) Plummer-Vinson syndrome □ (C) Barrett esophagus □ (D) Systemic sclerosis □ (E) Achalasia

(E) Achalasia (E) In achalasia, there is incomplete relaxation of the lower esophageal sphincter. Most cases are "primary" or of unknown origin. They are believed to be caused by degenerative changes in neural innervation; the myenteric ganglia are usually absent from the body of the esophagus. There is a long-term risk of development of squamous cell carcinoma. Reflux esophagitis may be associated with hiatal hernia, but myenteric ganglia remain intact. Plummer-Vinson syndrome is a rare condition caused by iron deficiency anemia; it is accompanied by an upper esophageal web. In Barrett's esophagus, there is columnar epithelial metaplasia, but the myenteric plexuses remain intact. Systemic sclerosis (scleroderma) is marked by fibrosis with stricture.

A 27-year-old man has sudden onset of marked abdominal pain. On physical examination, his abdomen is diffusely tender and distended, and bowel sounds are absent. He undergoes surgery, and a 27-cm segment of terminal ileum with a firm, erythematous serosal surface is removed. The microscopic appearance of a section through the excised ileum is shown in the figure. Which of the following additional complications is the patient most likely to develop as a result of this disease process? □ (A) Metastatic adenocarcinoma □ (B) Mesenteric artery thrombosis □ (C) Intussusception □ (D) Hepatic abscess □ (E) Enterocutaneous fistula

(E) Enterocutaneous fistula (E) The ileum shows chronic inflammation with lymphoid aggregates. The inflammation is transmural, affecting the mucosa, submucosa, and muscularis. A deep fissure extending into the muscularis also is seen. These histologic features are highly suggestive of Crohn disease. Extension of fissures into the overlying skin can produce enterocutaneous fistulas, although enteroenteric fistulas between loops of bowel are more common. Although the risk of adenocarcinoma is increased in Crohn disease, this complication is less common than sequelae of inflammation. Mesenteric artery thrombosis, typically a complication of atherosclerosis, is unlikely in a 27-year-old man. Intussusception may occur when there is a congenital or acquired obstruction in the bowel. Hepatic abscess can follow amebic colitis.

A 46-year-old woman with a lengthy history of heartburn and dyspepsia experiences sudden onset of abdominal pain. On physical examination, she has severe mid epigastric pain with guarding. Bowel sounds are reduced. An abdominal plain film radiograph shows free air under the left leaf of the diaphragm. The patient is immediately taken to surgery, and a perforated duodenal ulcer is repaired. Which of the following organisms is most likely to have produced these findings? □ (A) Campylobacter jejuni □ (B) Cryptosporidium parvum □ (C) Entamoeba histolytica □ (D) Giardia lamblia □ (E) Helicobacter pylori □ (F) Salmonella typhi □ (G) Shigella flexneri □ (H) Yersinia enterocolitica

(E) Helicobacter pylori (E) Although they are not found in the duodenum, Helicobacter pylori organisms alter the microenvironment of the stomach, causing the stomach and duodenum to be susceptible to peptic ulcer disease. Virtually all duodenal peptic ulcers are associated with the presence of H. pylori. Ulceration can extend through the muscularis and result in perforation, as in this case. The other organisms listed are not related to peptic ulcer formation, but to infectious diarrheal illnesses. Salmonella typhi may produce typhoid fever with more systemic symptoms; the marked ulceration of Peyer's patches may lead to perforation.

An 11-month-old, previously healthy infant has not produced a stool for 1 day. The mother notices that the infant's abdomen is distended. On physical examination, the infant's abdomen is very tender, and bowel sounds are nearly absent. An abdominal plain film radiograph shows no free air, but there are distended loops of small bowel with air-fluid levels. Which of the following is most likely to produce these findings? □ (A) Meckel diverticulum □ (B) Duodenal atresia □ (C) Hirschsprung disease □ (D) Pyloric stenosis □ (E) Intussusception

(E) Intussusception (E) The infant has signs and symptoms of acute bowel obstruction. Intussusception occurs when one small segment of small bowel becomes telescoped into the immediately distal segment. This disorder can have sudden onset in infants and may occur in the absence of any anatomic abnormality. Almost all cases of Meckel diverticulum are asymptomatic, although in some cases functional gastric mucosa is present and can lead to ulceration with bleeding. Duodenal atresia (which typically occurs with other anomalies, particularly trisomy 21) and Hirschsprung disease (from an aganglionic colonic segment) usually manifest soon after birth. Pyloric stenosis is seen much earlier in life and is characterized by projectile vomiting.

A 68-year-old woman with a history of rheumatic heart disease is hospitalized with severe congestive heart failure. Several days after admission, she develops abdominal distention. On physical examination, she is afebrile. The abdomen is tympanitic, without a fluid wave, and bowel sounds are absent. A stool sample is positive for occult blood. An abdominal plain film shows no free air. Colonoscopy shows patchy areas of mucosal erythema with some overlying tan exudate in the ascending and descending colon. No polyps or masses are found. What is the most likely diagnosis? □ (A) Ulcerative colitis □ (B) Volvulus □ (C) Shigellosis □ (D) Mesenteric vasculitis □ (E) Ischemic colitis

(E) Ischemic colitis (E) Hypotension with hypoperfusion from heart failure is a common cause of ischemic bowel in hospitalized patients. The ischemic changes begin in scattered areas of the mucosa and become confluent and transmural over time. This can give rise to paralytic ileus and bleeding from the affected regions of the bowel mucosa. Ulcerative colitis usually produces marked mucosal inflammation with necrosis, usually in a continuous distribution from the rectum upward. Volvulus is a form of mechanical obstruction caused by twisting of the small intestine on its mesentery or twisting of the cecum or sigmoid colon, resulting in compromised blood supply that can lead to infarction of the twisted segment. Shigellosis is an infectious diarrhea that causes diffuse colonic mucosal erosion with hemorrhage. A mesenteric vasculitis is uncommon, but could lead to bowel infarction.

A 38-year-old man who has been HIV positive for 10 years has had severe nausea and vomiting for the past 2 weeks. On physical examination, he is afebrile. A stool sample is positive for occult blood. The abdomen is not distended, there are no palpable masses or organomegaly, and bowel sounds are present. The patient has oral thrush. There are several reddish purple, 0.5- to 1-cm nodules on the skin of the trunk. Laboratory studies show a CD4+ lymphocyte count of 118/μL. Upper gastrointestinal endoscopy shows 12 reddish purple, 0.6- to 1.8-cm, gastric mucosal nodules. A biopsy specimen of the nodules is most likely to show which of the following neoplasms? □ (A) Adenocarcinoma □ (B) Non-Hodgkin lymphoma □ (C) Carcinoid tumor □ (D) Gastrointestinal stromal tumor □ (E) Kaposi sarcoma □ (F) Peutz-Jeghers polyp □ (G) Squamous cell carcinoma □ (H) Tubular adenoma

(E) Kaposi sarcoma (E) Kaposi sarcoma, non-Hodgkin lymphoma, and anorectal squamous carcinoma are the only neoplasms listed that define AIDS in patients with HIV infection. Kaposi sarcoma most often involves the skin, but it can be found anywhere in the body, including the gastrointestinal tract. Kaposi sarcoma is a vascular lesion—hence the color. Non-Hodgkin lymphomas and squamous carcinomas have a white cut surface and rarely are large enough to cause obstruction. Adenocarcinoma of the stomach can produce a mass, or it can diffusely infiltrate the gastric wall. Carcinoid tumors can be multiple, but they are most common in the small and large bowel or appendix and have a yellowish appearance. Gastrointestinal stromal tumors are rare and are typically large masses that have a white cut surface. Peutz-Jeghers polyps are associated with mucocutaneous pigmentation. Tubular adenomas (adenomatous polyps) are most common in the colon in older adults.

A 20-year-old woman has had nausea and vague lower abdominal pain for the past 24 hours, but now the pain has become more severe. On physical examination, the pain is worse in the right lower quadrant, and there is rebound tenderness. A stool sample is negative for occult blood. Abdominal plain film radiographs show no free air. The result of a serum pregnancy test is negative. Which of the following laboratory findings is most useful to aid in the diagnosis of this patient? □ (A) Hyperamylasemia □ (B) Hypernatremia □ (C) Increased serum carcinoembryonic antigen □ (D) Increased serum alkaline phosphatase □ (E) Leukocytosis □ (F) Entamoeba histolytica cysts in the stool

(E) Leukocytosis (E) These findings indicate acute appendicitis. The elevated WBC count with neutrophilia is helpful but not decisive, and the decision to operate must be based on clinical judgment. Hyperamylasemia occurs in acute pancreatitis. Diarrhea with fluid loss and dehydration can lead to hypernatremia. The serum carcinoembryonic antigen level may be increased in patients with colonic cancers; however, this test is not specific for colon cancer. The alkaline phosphatase level may be increased in biliary tract obstruction. Amebiasis is most likely associated with a history of diarrhea.

In an epidemiologic study of infections of the gastrointestinal tract, cases of patients from whom definitive cultures were obtained are analyzed for clinical and pathologic findings that may be useful for diagnosis. A subset of patients is identified who initially had abdominal pain and diarrhea during week 1 of their illness. By week 2, these patients had splenomegaly and elevations in serum AST and ALT levels. By week 3, they were septic and had leukopenia. At autopsy, the patients who died were found to have ulceration of Peyer's patches. Which of the following infectious agents is most likely to produce these findings? □ (A) Campylobacter jejuni □ (B) Clostridium perfringens □ (C) Escherichia coli □ (D) Mycobacterium bovis □ (E) Salmonella typhi □ (F) Shigella sonnei □ (G) Yersinia enterocolitica

(E) Salmonella typhi (E) Typhoid fever begins as an intestinal infection, but it becomes a systemic illness. A chronic carrier state can occur in some infected individuals, with colonization of the gallbladder. Campylobacter jejuni may produce dysentery, but generally not systemic disease. Clostridium perfringens can cause gas gangrene. Some strains of Escherichia coli can produce enterohemorrhagic infection (from elaboration of a Shiga-like toxin) with features of hemolytic-uremic syndrome. Mycobacterium bovis is now rare because of pasteurization of milk products; it was best known as a cause of bowel obstruction from circumferential ulceration and scarring of the small bowel. Shigellosis can produce dysentery, but the infection is generally limited to the colon. Infection with Yersinia enterocolitica can produce extraintestinal infection with lymphadenitis, but generally not dysentery.

A 67-year-old woman has experienced severe nausea, vomiting, early satiety, and a 9-kg weight loss over the past 4 months. On physical examination, she has mild muscle wasting. Upper gastrointestinal endoscopy shows that the entire gastric mucosa is eroded and has an erythematous, cobblestone appearance. Upper gastrointestinal radiographs show that the stomach is small and shrunken. Which of the following is most likely to be found on histologic examination of a gastric biopsy specimen? □ (A) Early gastric carcinoma □ (B) Gastrointestinal stromal tumor □ (C) Granulomatous inflammation □ (D) Chronic atrophic gastritis □ (E) Signet-ring cell adenocarcinoma

(E) Signet-ring cell adenocarcinoma (E) The endoscopy findings describe the linitis plastica ("leather bottle") appearance of diffuse gastric carcinoma. Histologically, these carcinomas are composed of gastric-type mucus cells that infiltrate the stomach wall diffusely. The individual tumor cells have a signet-ring appearance because the cytoplasmic mucin pushes the nucleus to one side. Early gastric carcinoma is confined to the mucosa and submucosa. Gastrointestinal stromal tumors tend to be bulky masses. Granulomas are rare at this site. In chronic atrophic gastritis, the rugal folds are lost, but there is no significant scarring or shrinkage.

One day after a meal of raw oysters, a healthy 21-year-old woman develops a profuse, watery diarrhea. On physical examination, her temperature is 37.5°C. A stool sample is negative for occult blood. There is no abdominal distention or tenderness, and bowel sounds are present. The diarrhea subsides over the next 3 days. Which of the following organisms is most likely to produce these findings? □ (A) Yersinia enterocolitica □ (B) Staphylococcus aureus □ (C) Cryptosporidium parvum □ (D) Entamoeba histolytica □ (E) Vibrio parahaemolyticus

(E) Vibrio parahaemolyticus (E) Raw or poorly cooked shellfish can be the source of Vibrio parahaemolyticus, which tends to produce a milder diarrhea than Vibrio cholerae. Yersinia enterocolitica is invasive and can produce extraintestinal infection. Staphylococcus aureus can produce food poisoning through elaboration of an enterotoxin that causes an explosive diarrhea within 2 hours after ingestion. Cryptosporidium as a cause of watery diarrhea is most often found in immunocompromised individuals. Entamoeba histolytica produces colonic mucosal invasion along with exudation and ulceration; stools contain blood and mucus.

A 30-year-old man has sudden onset of hematemesis after a weekend in which he consumed large amounts of alcohol. The bleeding stops, but he has another episode under similar circumstances 1 month later. Upper gastroesophageal endoscopy shows longitudinal tears at the esophagogastric junction. What is the most likely mechanism to cause his hematemesis? □ (A) Absent myenteric ganglia □ (B) Autoimmune inflammation □ (C) Herpes simplex virus infection □ (D) Portal hypertension □ (E) Vomiting □ (F) Widened diaphragmatic crura

(E) Vomiting (E) This man has Mallory-Weiss syndrome with esophageal tears from severe vomiting. Most cases occur in the context of alcohol abuse. The bleeding is usually not as life-threatening as varices. Absent myenteric ganglia occur with achalasia. Autoimmunity underlies scleroderma with fibrosis and esophageal obstruction. Herpes simplex virus infection causes ulcerations that are usually superficial and cause pain, but do not bleed significantly. Portal hypertension leads to dilation of esophageal submucosal veins, which can bleed profusely; in this case, the patient's age argues against the presence of cirrhosis from alcohol abuse. Widened diaphragmatic crura are present with hiatal hernia that predisposes to gastroesophageal reflux, and this is not associated with alcohol abuse.

A 24-year-old man sees his physician because of abdominal pain and increasing fatigue that has developed over the past 6 months. On physical examination, he is afebrile and appears pale. On palpation, there is mild pain in the right lower quadrant of the abdomen. There are no masses, and bowel sounds are active. Laboratory studies show hemoglobin, 8.9 g/dL; hematocrit, 26.7%; MCV, 74 μm3; platelet count, 255,000/mm3; and WBC count, 7780/mm3. Upper gastrointestinal endoscopy and colonoscopy showed no lesions. One month later, the patient continues to experience the same abdominal pain. Which of the following is most likely to cause this patient's illness? □ (A) Acute appendicitis □ (B) Angiodysplasia □ (C) Celiac sprue □ (D) Diverticulosis □ (E) Giardiasis □ (F) Meckel diverticulum

(F) Meckel diverticulum (F) About 2% of individuals have Meckel diverticulum, an embryologic remnant of the omphalomesenteric duct, but only a subset of these individuals have ectopic gastric mucosa within it, which causes intestinal ulceration. The symptoms may mimic acute appendicitis, but appendicitis should not last for 1 month or cause significant blood loss. Angiodysplasia may be difficult to detect. It is almost always seen in patients older than 70 years and can cause significant blood loss. Celiac sprue can occur in young individuals, but it does not produce significant hemorrhage. Diverticulosis can be associated with hemorrhage, but the diverticula are almost always in the colon. Giardiasis produces a self-limited, watery diarrhea without hemorrhage.

An 8-month-old, previously healthy infant girl develops a watery diarrhea that lasts for 1 week. The infant has a mild fever during the illness, but has no abdominal pain or swelling. On physical examination, her temperature is 37.7°C. A stool sample is negative for occult blood, ova, or parasites. Her parents are told to give her plenty of fluids, and she recovers fully. Which of the following organisms is most likely to produce these findings? □ (A) Campylobacter jejuni □ (B) Cryptosporidium parvum □ (C) Escherichia coli □ (D) Listeria monocytogenes □ (E) Norwalk virus □ (F) Rotavirus □ (G) Shigella flexneri □ (H) Vibrio cholerae

(F) Rotavirus (F) Rotavirus is the most common cause of viral gastroenteritis in children. It is a self-limited disease that affects mostly infants and young children, who can lose a significant amount of fluid relative to their size and can quickly become dehydrated. The death rate is less than 1%. Campylobacter jejuni is more often seen in children and adults as a foodborne cause of fever, abdominal pain, and diarrhea. Cryptosporidiosis most often causes a watery diarrhea in immunocompromised adults. Enterohemorrhagic strains of Escherichia coli can produce hemolytic-uremic syndrome in young children. Listeriosis can be a congenital infection that is present along with meningitis and sepsis at birth; in infants, children, and adults, it is a food-borne or water-borne infection that tends to occur in epidemics. Norwalk virus is a common cause of dia

A 59-year-old man with a lengthy history of chronic alcoholism has noticed increasing abdominal girth for the past 6 months. He has had increasing abdominal pain for the past 2 days. On physical examination, his temperature is 38.2°C. Examination of the abdomen shows a fluid wave and prominent caput medusae over the skin of the abdomen. There is diffuse abdominal tenderness. An abdominal plain film radiograph shows no free air. Paracentesis yields 500 mL of cloudy yellow fluid. Gram stain of the fluid shows gram-negative rods. Which of the following is the most likely diagnosis? □ (A) Appendicitis □ (B) Collagenous colitis □ (C) Diverticulitis □ (D) Ischemic colitis □ (E) Pseudomembranous colitis □ (F) Spontaneous bacterial peritonitis

(F) Spontaneous bacterial peritonitis (F) Spontaneous bacterial peritonitis is an uncommon complication found in about 10% of adult patients with cirrhosis of the liver and ascites. The ascitic fluid provides an excellent culture medium for bacteria, which can invade the bowel wall or spread hematogenously to the serosa. Spontaneous bacterial peritonitis also can occur in children, particularly children with nephrotic syndrome and ascites. The most common organism cultured is Escherichia coli. Appendicitis has a peak incidence in younger patients, the pain is often (but not always) more localized in the right lower quadrant, and ascites is usually absent; appendicitis is not related to alcoholism. Collagenous colitis is uncommon; it most often leads to watery diarrhea in middle-aged women. Diverticulitis with rupture could produce peritonitis, but there is typically no ascites, and diverticulitis is not related to alcoholism. Ischemic colitis may produce infarction with rupture and peritonitis, but ascites is usually lacking, and individuals with chronic alcoholism are unlikely to have marked atherosclerosis. Pseudomembranous colitis is a complication of antibiotic therapy.