A Collection of Gastrointestinal Illnesses and Infections
Zenker Diverticulum
Love Dalal, MD
A 72-year-old man was evaluated for worsening dysphagia and weight loss. The dysphagia had been intermittent for 20 years, but in the past year it had begun to occur daily. He regurgitated food after every meal, often many hours after ingestion.
Laboratory testing. A barium swallow examination demonstrated a large (3x3x7 cm) Zenker diverticulum that originated from the posterior wall of the esophagus at the C5-C6 level (arrow). Esophagogastroduodenoscopy confirmed this finding and ruled out other lesions. The patient subsequently underwent a cricopharygomyotomy and plexy of the diverticulum. He is now able to swallow without difficulty and has regained weight.
Discussion. Zenker diverticula are usually found in older adults. Most patients present after the age of 60 (often after age 75) and have had symptoms for weeks to years. The disorder is more common in men than in women. The estimated incidence in 1 study was 2 per 100,000 a year.1 However, the true incidence may be difficult to evaluate, since many patients have minimal symptoms and may not seek medical attention.
A Zenker diverticulum consists of an outpouching of the mucosa through the Killian triangle, an area of muscular weakness between the oblique fibers of the lower inferior constrictor and the transverse fibers of the cricopharyngeus. Patients may have a persistent or intermittent sensation of sticking in the throat, transient dysphagia (particularly with solid foods), and intermittent cough. Severe symptoms develop as the diverticulum enlarges; these may include aggravation of dysphagia, regurgitation of food (ingested several hours earlier), halitosis, voice change, aspiration pneumonia, and weight loss. Small Zenker diverticula may be asymptomatic.
Diagnostic studies. Barium swallow—the diagnostic procedure of choice for Zenker diverticulum—characteristically demonstrates a herniated sac with a slender neck that typically originates just proximal to the cricopharyngeus. When the diverticulum enlarges, it can compress the esophagus and cause dysphagia. Endoscopy can exclude other pathology, such as malignancy; however, it should be performed with extreme care in these patients to avoid perforation of the diverticulum.
Treatment. Zenker diverticula can be treated with open surgery or an endoscopic approach. The surgical options are transcervical cricopharygomyotomy with resection of the diverticulum (diverticulotomy) and invagination of the diverticulum (diverticuloplexy).2 Endoscopic approaches may replace conventional surgery, because they are minimally invasive and have similar results. The endoscopic methods include a staple-assisted approach (esophagodiverticulostomy)3 and an approach using a flexible endoscope and a soft diverticuloscope.4 Symptoms may recur if a myotomy has been incomplete or if there is apposition of the cut muscle margins. This is more likely in patients with wide diverticula.
References:
1. Siddiq MA, Sood S, Strachan D. Pharyngeal pouch (Zenker's diverticulum). Postgrad Med J. 2001;77:506-511.
2. Townsend CM. Sabiston Textbook of Surgery. 17th ed. Philadelphia, PA: WB Saunders Co; 2004:1096-1150.
3. Scher RL, Richtsmeier WJ. Endoscopic staple-assisted esophagodiverticulostomy for Zenker's diverticulum. Laryngoscope. 1996;106:951-956.
4. Evrard S, Le Moine O, Hassid S, Deviere J. Zenker's diverticulum: a new endoscopic treatment with a soft diverticuloscope. Gastrointest Endosc. 2003;58:116-120.
Man with GI Symptoms and Weight Loss Attributable to Primary Duodenal Adenocarcinoma
John Godino, MD
A 71-year-old man presents with a 2-week history of early satiety, decreased appetite, postprandial nausea and vomiting, jaundice, dark urine, acholic stools, and generalized pruritus. In addition, he reports a 4.5 kg (10 lb) weight loss within the past 2 months.
He has a history of hypertension, diabetes mellitus, coronary artery disease, and alcohol abuse. His current medications include lisinopril, atenolol, and glyburide. He denies recent alcohol consumption and tobacco use. The patient underwent a screening colonoscopy 9 months earlier, which revealed a 5 mm tubulovillous adenoma and a 15 mm tubular adenoma in his transverse colon.
His sister died of pancreatic cancer at age 46. Breast cancer was diagnosed in his mother at age 60, and colorectal cancer was diagnosed in his maternal aunt at age 65.
Three months before the current symptoms developed, the patient had an episode of upper GI bleeding manifested by melena; there was no change in the hemoglobin level. An esophagoduodenoscopy revealed a “clean-based ulcer” in the descending portion of the duodenum (Figure 1). Biopsy of the ulcer was not performed at that time. Antral biopsies were negative for Helicobacter pylori. Pantoprazole (40 mg/d) was prescribed, and the patient was instructed to discontinue aspirin.
Laboratory testing. Vital signs are normal. Physical findings are essentially unremarkable except for jaundice. Abnormal serologic values include total bilirubin, 11.2 mg/dL (normal, 0 to 1 mg/dL); direct bilirubin, 7.5 mg/dL (normal, 0 to 0.3 mg/dL); alkaline phosphatase, 993 U/L (normal, 59 to 146 U/L); aspartate aminotransferase, 1262 U/L (normal, 0 to 37 U/L); alanine aminotransferase, 2096 U/L (normal, 0 to 40 U/L); amylase, 110 U/L (normal, 0 to 88 U/L); and lipase, 189 mIU/mL (normal, 16 to 63 mIU/mL). Results of a complete blood cell count, coagulation profile, and hepatitis profile are normal.
Diagnostic studies. A CT scan of the abdomen reveals a markedly dilated stomach with an obstructive mass in the descending portion of the duodenum; these findings are consistent with gastric outlet obstruction (Figure 2). In addition, biliary and pancreatic ductal dilatation and multiple liver masses are noted. Esophagoduodenoscopy shows near complete luminal obstruction by the mass (Figure 3). The scope is unable to pass beyond the markedly narrowed lumen. Results of biopsies of the duodenal mass reveal moderately differentiated invasive adenocarcinoma (Figure 4).
Discussion. Primary duodenal adenocarcinoma is rare. It represents less than 0.5% of all GI tract malignant neoplasms and up to 45% of small-bowel cancers.1 Adenocarcinomas account for 75% of all primary duodenal malignancies, including leiomyosarcoma, lymphoma, and carcinoid tumors. 2 The first case of duodenal adenocarcinoma was described in 1746; since then, more than 800 cases have been reported.3,4
The causative factors for primary adenocarcinoma of the duodenum are unknown. Patients with familial adenomatous polyposis, Gardner syndrome, Crohn disease, or celiac sprue are at increased risk for duodenal malignancies.3,5 This patient had none of these risk factors.
The diagnosis of primary duodenal adenocarcinoma is usually delayed—typically 7 months on average—from the onset of symptoms.6 This may be attributed to the nonspecific nature of the symptoms (eg, epigastric pain, dyspepsia, weight loss, and nausea). In addition, distal portions of the duodenum are generally not inspected during esophagoduodenoscopy. With progression of the disease, the symptoms may worsen and can produce gastric outlet obstruction and jaundice.
Treatment. Biopsy of benign-appearing ulcers in the duodenal bulb is not typically performed because these ulcers are commonly caused by infection with H pylori or are associated with the use of NSAIDs. However, ulcerations in a postbulbar location should raise suspicion of malignancy and lower the threshold for biopsy of the ulcer.
Outcome of the case. The patient subsequently undergoes palliative bypass surgery, which includes gastrojejunostomy and cholecystojejunostomy. Liver and peritoneal metastases are confirmed. The patient is referred to the oncology department for consideration of palliative chemotherapy.
In this patient, failure to perform a biopsy of the ulcer during his initial esophagoduodenoscopy, when he presented with melena, led to a delay in the diagnosis. This probably reduced his 5-year survival from 85% to 0%.
References:
1. Moss WM, McCart PM, Juler G, Miller DR. Primary adenocarcinoma of the duodenum. Arch Surg. 1974;108:805-807.
2. Lillemoe K, Imbembo AL. Malignant neoplasmsof the duodenum. Surg Gynecol Obstet. 1980;150:822-826.
3. Alwmark A, Andersson A, Lasson A. Primary carcinoma of the duodenum. Ann Surg. 1980;191:13-18.
4. Spira IA, Ghazi A, Wolff WI. Primary adenocarcinomaof the duodenum. Cancer. 1977;39:1721-1726.
5. Iida M, Yao T, Itoh H, et al. Natural history of duodenal lesions in Japanese patients with familial adenomatosis coli (Gardner's syndrome). Gastroenterology. 1989;96(5):1301-1306.
6. Cortese AF, Cornell GN. Carcinoma of the duodenum. Cancer. 1972;29:1010-1015.
Strongyloidiasis
Lucia C. Fry, MD and Klaus E. Monkermuller, MD
A 58-year-old man with type 2 diabetes mellitus and hypertension was hospitalized with acute diarrhea characterized by several brown, liquid depositions per day. He also complained of lower abdominal pain and bloating and a 10 lb weight loss in the past 2 months. He denied fever or chills, use of corticosteroids, and travel outside the United States.
Physical examination. Doctors noted orthostatic and bilateral lower abdominal tenderness on deep palpation and no rebound. His hemoglobin level was 11.5 g/dL (which indicated mild anemia); glucose, 229 mg/dL (normal, 70 to 105 mg/dL); and albumin, 3.5 g/dL (normal, 3.4 to 4.5 g/dL). The white blood cell count was 10,400/µL, with 22% eosinophils. Stool examination was negative for ova and parasites. Colonoscopy revealed multiple yellow-pigmented, xanthomalike lesions throughout the colon (Figure 1).
Discussion. Histopathologic examination of a specimen from these lesions showed focal, diffuse eosinophilic infiltration and Strongyloides larvae (Figure 2). Strongyloidiasis, caused by the nematode Strongyloides stercoralis, is endemic in tropical areas of Africa (where up to 21% of the population are infected), Asia, and Latin America, as well as in the southeastern United States (where 2.5% are infected). Once the parasite enters the skin from fecal-contaminated soil, it migrates through the venous circulation to the lungs and penetrates the alveoli. The parasite is then expectorated or expelled from the bronchi or trachea and swallowed. Adult forms of S stercoralis reside in the surface of the duodenum or jejunum and release ova in the lumen, where the ova become rhabditiform larvae. They develop into filariform larvae, which are able to penetrate intestinal mucosa or perianal skin (autoinfection). The cycle is then completed via the venous circulation. In contrast to other nematodes—which transform into infective filariform larvae outside the host—S stercoralis is the only helminth capable of completing the cycle within the host.
Therefore, autoinfection may persist for decades. The symptoms of strongyloidiasis are abdominal pain, diarrhea, vomiting and, in cases of extensive infection, malabsorption, steatorrhea, and weight loss. Strongyloidiasis can affect both immunocompetent as well as immunocompromised persons (such as those with a history of malignancy, organ transplantation, diabetes mellitus, or corticosteroid use).
However, in immunocompromised patients, Strongyloides infection can lead to hyperinfection syndrome with multisystemic disease, which can be life-threatening. Diagnostic accuracy by stool examination is no higher than 46%.
Diagnostic studies. The most accurate diagnostic method is duodenal aspiration or endoscopic biopsy. Laboratory data are usually not relevant; however, eosinophilia is frequently present in immunocompetent persons. For uncomplicated infections, ivermectin is recommended by the CDC. For disseminated infection or hyperinfection in immunocompromised patients, thiabendazole is recommended.
Outcome of the case. This patient was treated with thiabendazole for 2 days. His symptoms gradually resolved over a week.
References:
1. Mahmoud AA. Strongyloidiasis. Clin Infect Dis. 1996;23:949-953.
2. Pearson RD. Parasitic diseases: helminths. In: Yamada T, Alpers DH, Kaplowitz N, et al, eds. Textbook of Gastroenterology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:2608-2625.
Clostridium difficile-Associated Diarrhea
Lawrence R. Schiller, MD
A 47-year-old woman presented with abdominal cramps, low-grade fever, and bouts of watery diarrhea for several days. About 6 weeks earlier, she received fluoroquinolone therapy for acute sinusitis. The patient has no serious chronic conditions; her only long-term medication is a proton pump inhibitor (PPI) for reflux disease.
Discussion. For some time, diarrhea caused by Clostridium difficile has been a serious problem in hospitals. Recently, more virulent strains of this pathogen have started to show up in hospitals1,2 and in the community. In 2005, for example, a young pregnant woman died and a 10-year-old girl was hospitalized because of C difficile-associated illness.3 These patients were previously healthy and had no recent exposure to the traditional risk factors for infection—hospitals and antibiotics.
In addition, a new risk factor for C difficile infection has emerged. Evidence suggests that commonly prescribed acid-suppressive agents (most notably, PPIs) predispose patients to the disease, perhaps by eliminating the “acid barrier” to bacterial colonization of the gut.4
Laboratory testing. If C difficile is suspected, stool testing should be ordered to rule out toxins A and B. These toxins, which are released by the bacteria in the colon, damage the lining of the colon. In adults, a positive test result establishes the diagnosis. However, toxin tests are not infallible. Their reliability depends on which test the laboratory uses and whether it tests for both the A and B toxins. In some cases, repeated toxin tests—or culture of the organism—are needed to confirm the diagnosis. In addition, depending on the laboratory and method used, results may take up to 24 hours to be reported.
Diagnostic studies. Physicians are likely to be called on more often to diagnose and treat C difficile infection. Through informed and prudent prescribing habits, they can also play a key role in its containment.
A key clue is a high white blood cell count in a patient with diarrhea. Such a patient may well have C difficile infection, even if the history is somewhat atypical.
Despite reports that C difficile infections have been identified in community-dwelling patients previously thought to be at low risk, this is still an exceedingly rare occurrence. The standard risk factors remain the most important clues to the diagnosis. These include antibiotic use within the past 3 months, a hospital or nursing home stay during the past 3 months, and contact with someone who has been hospitalized or in a nursing home in the past 3 months.
Keep in mind that the majority of patients who present with diarrhea—even those in whom 1 or more of these risk factors are identified—will not have C difficile infection. Other diarrheal pathogens are still more common in the community setting.
If a patient has a severe diarrheal illness with symptoms that suggest colitis, colonoscopy or flexible sig-moidoscopy to examine the colonic mucosa can establish the diagnosis quickly. Typical findings of pseudomembranous colitis are characteristic of severe C difficile infection (Figure).
Treatment. Patients with mild to moderate illness who are able to maintain hydration with oral intake need not be hospitalized. However, patients with volume depletion and those with fever or peritoneal signs should be treated in the hospital.
Recent studies underscore the importance of “fastidious use” of barrier precautions and hand hygiene to help prevent spread of C difficile infection.5 Effective hand hygiene in this setting must include washing with soap and water, since alcohol-based hand sanitizers do not kill C difficile spores. While these recommendations were intended for hospitals and similar settings, it would be wise to advise the families of patients being treated at home to adopt them as well.
Once the diagnosis has been confirmed, either by a positive result on a fecal toxin test or by colonoscopy or sigmoidoscopy, treatment should be initiated. If possible, stop antibiotics that may have precipitated the illness. There is no evidence that stopping antisecretory drugs is helpful once C difficile-associated diarrhea is manifest; however, their continued use should be reassessed.
Nonspecific opiate antidiarrheal drugs are not known to cause problems in this setting, but they may not be effective against the intense secretory diarrhea produced by C difficile disease. Other nonspecific antidiarrheals, such as bismuth subsalicylate, can be used if desired.
In patients with proven or highly likely C difficile colitis, metronidazole remains the drug of choice, with oral vancomycin held in reserve (to limit the development of vancomycin-resistant enterococci). Preliminary studies suggest that rifaximin and nitazoxanide may be effective as alternative antibiotic choices, although neither has been approved by the FDA for this indication. Empiric antibiotic treatment is not recommended except for patients who are severely ill, such as those with toxic megacolon. To maximize chances of eradicating the organism, the initial course of antibiotic therapy should be at least 2 weeks long.
Recurrence is a common problem in patients with C difficile-associated diarrhea, usually because of inadequate immunity after the initial infection. Probiotics (such as Saccaromyces boulardii or Lactobacillus casei GG) may help reestablish more normal intestinal flora and have been proposed as a means of preventing recurrence. Although the evidence in the literature is mixed, I use probiotics fairly routinely in patients who have had or are at heightened risk for recurrent disease. Probiotics can be started as antibiotic therapy is being tapered off. While inexpensive, they sometimes seem to help. Bile acid-binding resins such as cholestyramine, which can bind the toxin, also may be used to prevent recurrence.
In many patients, antisecretory drugs are appropriate and necessary. In many others, however, once PPIs have been prescribed, the need for continued therapy is never reassessed. Whenever you see a patient who is receiving long-term PPI therapy, it is important to determine whether this drug is still needed, or whether symptoms can be adequately controlled with lifestyle measures or a lesser degree of acid suppression.
References:
1. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile–associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353:2442-2449.
2. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene–variant strain of Clostridium difficile. N Engl J Med. 2005;353:2433-2441.
3. Chernak E, Johnson CC, Weltman A, et al. Severe Clostridium difficile–associated disease in populations previously at low risk—four states, 2005. MMWR. 2005;54:1201-1205.
4. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid–suppressive agents and the risk of community-acquired Clostridium difficile–associated disease. JAMA. 2005;294:2989-2995.
5. Bartlett JG, Perl TM. The new Clostridium difficile—what does it mean? N Engl J Med. 2005;353:2503-2505.