[Liver failure in a 27 years old female patient]. / Leberversagen bei einer 27-jährigen Patientin.

We report about a 27-years old female patient with acute liver failure due to an acute Budd Chiari Syndrom (thrombosis of all three liver veins an vena cava inferior) with caval web, birth control pills and after long distance flight. After successfull aspiration of the caval thrombus and dilatation of caval web liver transplantation could be bypassed. Two weeks after intervention the patient was in a good healthy condition with normal laboratory values, normal liver size, normal perfusion of the V. cava inferior and signs of reperfusion of the middle liver vein.

[An uncommon cause of iron deficiency anemia]. / Eine nicht-alltägliche Ursache der Eisenmangel-Anämie.

A 55-year-old patient was diagnosed having a malignant melanoma metastatic to the small bowel as cause of an iron deficiency anemia. Although up to 60% of patients with metastatic melanoma are found to have intestinal metastases at autopsy, clinically apparent gastrointestinal involvement is rare during lifetime and often delayed after resection of the primary tumor. Diagnostic procedures include radiological imaging and endoscopic modalities. Early diagnosis is desirable for prognostic reason both in curative and palliative settings.

Is there an advantage to be gained from adding digital image cytometry of brush cytology to a standard biopsy protocol in patients with Barrett's esophagus?

BACKGROUND AND STUDY AIMS: The current gold standard in Barrett's esophagus monitoring consists of four-quadrant biopsies every 1-2 cm in accordance with the Seattle protocol. Adding brush cytology processed by digital image cytometry (DICM) may further increase the detection of patients with Barrett's esophagus who are at risk of neoplasia. The aim of the present study was to assess the additional diagnostic value and accuracy of DICM when added to the standard histological analysis in a cross-sectional multicenter study of patients with Barrett's esophagus in Switzerland. METHODS: One hundred sixty-four patients with Barrett's esophagus underwent 239 endoscopies with biopsy and brush cytology. DICM was carried out on 239 cytology specimens. Measures of the test accuracy of DICM (relative risk, sensitivity, specificity, likelihood ratios) were obtained by dichotomizing the histopathology results (high-grade dysplasia or adenocarcinoma vs. all others) and DICM results (aneuploidy/intermediate pattern vs. diploidy). RESULTS: DICM revealed diploidy in 83% of 239 endoscopies, an intermediate pattern in 8.8%, and aneuploidy in 8.4%. An intermediate DICM result carried a relative risk (RR) of 12 and aneuploidy a RR of 27 for high-grade dysplasia/adenocarcinoma. Adding DICM to the standard biopsy protocol, a pathological cytometry result (aneuploid or intermediate) was found in 25 of 239 endoscopies (11%; 18 patients) with low-risk histology (no high-grade dysplasia or adenocarcinoma). During follow-up of 14 of these 18 patients, histological deterioration was seen in 3 (21%). CONCLUSION: DICM from brush cytology may add important information to a standard biopsy protocol by identifying a subgroup of BE-patients with high-risk cellular abnormalities.

Lugol chromoendoscopy combined with brush cytology in patients at risk for esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Patients with achalasia or malignancies of the head and neck are at increased risk for esophageal squamous cell carcinoma. The discussion of a screening and surveillance program is controversial. The aim of the present study was to determine the diagnostic potential of Lugol chromoendoscopy combined with brush cytology to diagnose esophageal squamous cell carcinoma and high-grade dysplasia. Secondly, the benefit of additional biomarkers was investigated. PATIENTS AND METHODS: A total of 61 patients (21 patients with achalasia and 40 patients with malignancies of the head and neck) were included. Chromoendoscopy with 1.2% Lugol iodine solution with targeted biopsies and brush cytology processed by digital image cytometry (DICM) and fluorescence in situ hybridization (FISH) from unstained lesions (USLs) and stained mucosa were performed. RESULTS: Six of the 61 patients had USLs ≥2 cm. Four patients had high-grade dysplasia (HGD) or carcinoma in situ (CIS). One patient with HGD and one patient with CIS were detected only after Lugol chromoendoscopy. The sensitivity and specificity for detected HGD or CIS in USLs ≥2 cm were 100% and 96.5%. No dysplasia was found in USLs <2 cm. DNA ploidy by DNA cytometry and p53 loss of heterozygosity (LOH) by fluorescence in situ hybridization showed no additional impact on diagnostic accuracy. CONCLUSIONS: Lugol chromoendoscopy enhances the detection rate of high-risk lesions with dysplasia or carcinoma in situ in large unstained lesions. Biomarkers such as aneuploidy and p53 LOH from brush cytology were not of additional benefit in this setting.

Dual Transoral Endoscopic Resection of a Symptomatic Giant Brunneroma.

Brunneroma is a rare, benign, proliferative lesion arising from the Brunner's glands of the duodenum that exceptionally may evolve towards a malignant transformation, usually discovered incidentally at endoscopy. Occasionally, these lesions manifest as a rare cause of duodenal obstruction or upper gastrointestinal bleeding and require resection, usually for tumors larger than 4 cm. The special aspect of our case is the technically difficult but successful dual transoral endoscopic resection of a giant (6.5 × 4 × 2.4 cm) brunneroma with a very thick and long peduncle located extremely close to the pylorus, highlighting the possibilities of endosurgery. Distal stomach resection with Roux-en-Y reconstruction as an alternative would have caused higher morbidity and costs.

Prospective study examining the impact of multichannel intraluminal impedance on antireflux surgery.

BACKGROUND: Reflux monitoring using combined multichannel intraluminal impedance (MII) and pH-metry increases the sensitivity for identifying gastroesophageal reflux episodes. The likelihood of a positive symptom index (SI) for patients with reflux disease (gastroesophageal reflux disease [GERD] or nonerosive reflux disease [NERD]) receiving proton pump inhibitor (PPI) treatment has been used to select candidates for antireflux surgery. Little is known about the advantages of MII-pH monitoring compared with pH monitoring alone for evaluating GERD/NERD patients off PPI treatment considered as candidates for antireflux surgery or for assessing changes in MII-pH-detected reflux episodes after antireflux surgery. This study aimed to determine the additional value of MII over pH-metry alone for patients off PPI treatment before and after antireflux surgery. METHODS: For this study 12 patients (4 women and 8 men; mean age, 45 years; range, 27-74 years) were evaluated using ambulatory MII-pH monitoring before and 3 months after mesh-augmented hiatoplasty. Reflux events were identified by MII-pH (A) and pH-metry (B) as patients recorded symptoms on a data logger. For each symptom, a symptom index was calculated for reflux events identified by MII-pH and by pH-monitoring alone. RESULTS: Preoperatively, MII-pH monitoring identified 71.9 +/- 8.4 reflux episodes, whereas pH monitoring identified only 51.0 +/- 7.8 (p < 0.05). Postoperatively, MII-pH monitoring identified 35.5 +/- 6.6 reflux episodes, whereas pH monitoring identified only 19.6 +/- 4.7 (p < 0.05). The pre- and postoperative symptom index for MII-pH monitoring was higher than pH monitoring (preoperative 91.7% vs 25%, p = 0.006; postoperative 50% vs 16.7%, p = 0.012). CONCLUSION: Combined MII-pH-metry improves the pre- and postoperative assessment of GERD patients off PPI and results in a higher symptom-reflux association.

Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter randomized trial on diagnostic efficacy.

BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. PATIENTS AND METHODS: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.

Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.

Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated interferon (PEG-I) alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only 0.5 and 1.5 microg/kg body weight (BW), in spite of the previously shown flat dose-response curve at doses of > or =1.0 microg/kg. Our aim was to compare PEG-I alpha-2b 1.0 microg/kg with 1.5 microg/kg, both in combination with ribavirin. Open-label, randomized study in 227 patients with biopsy-proven chronic hepatitis C (Metavir < or =F2), receiving oral ribavirin (400 mg, twice daily) in combination with subcutaneous PEG-I alpha-2b (1.0 or 1.5 microg/kg, once weekly) for 24 weeks (genotype 2 or 3), or 48 weeks (other genotypes), followed by a 24-week drug-free period. Virologic response rates did not differ between the two doses of PEG-I alpha-2b: in patients infected with hepatitis C virus (HCV) genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW, 38% (22/58) had a sustained virologic response compared with 39% (27/70) in the PEG-I 1.5 microg/kg BW dose group (P = ns). The corresponding values in patients infected with HCV genotype 2 or 3 were 71% (39/55) and 81% (29/36) respectively (P = ns). Adverse events led to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg BW dose group (48/113 patients; 42%) than in the 1.5 microg/kg BW dose group (63/106 patients; 59%, P = 0.015). Furthermore, 89% of patients treated for 24 weeks but only 58% of patients treated for 48 weeks (P < 0.001) tolerated the treatment without relevant dose reduction or premature termination. In combination with ribavirin, PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5 microg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis.

Endoscopic transgastric debridement and drainage for splenic necrosis following an acute episode in chronic alcoholic pancreatitis.

Management of the complications and sequelae of acute and chronic pancreatitis is a clinical challenge. We report a case of successful transgastric drainage of splenic necrosis after occlusion of the splenic vessels during an acute episode in chronic pancreatitis.

[Acute fatty liver in pregnancy: clinical and histopathological course. Case report]. / Akute Schwangerschaftsfettleber: Klinischer und histopathologischer Verlauf. Kasuistik

Acute fatty liver of pregnancy is a rare disease which may be letal if diagnosis is missed. The pathogenesis is not completely clear, but there is some evidence that some cases have been associated with a genetic deficiency of fatty acid beta-oxidation. Other predisposing factors include primiparity, multiple pregnancy, male fetal sex and pre-eclampsia. Clinical presentation and laboratory findings are often unspecific. Increasing serum aminotransferases are characteristic in the early stage of the disease. Liver biopsy establishes the diagnosis and typically shows microvesicular, centrilobular fatty changes of hepatocytes. Differential diagnosis includes the HELLP-Syndrome, cholestasis of pregnancy, pre-eclampsia and viral or drug induced hepatitis. Without adequate treatment liver failure with coagulopathy and encephalopathy may develop. Two cases of acute fatty liver in pregnancy in an early stage are presented. Clinical and histopathological findings as well as diagnostic and therapeutic procedures are discussed.

[Pre- and postoperative transaminase changes within the scope of gastric banding in morbid obesity]. / Prä- und postoperative Transaminasenveränderungen im Rahmen der Magenbandeinlage bei morbider Adipositas.

UNLABELLED: 20-30% of obese patients without concomitant liver disease show elevated liver tests (ALAT, ASAT, GGT) which are known to normalize after weight reduction. Little is known about the impact of gastric banding on elevated liver enzymes. We investigated the role of gastric banding on weight reduction and liver enzymes in a cohort of patients with morbid obesity. 198 obese patients (166 female, 32 male: median age 37 [19-65] years) with BMI 46 kg/m2 were assessed prior to gastric banding and 6/12 months postoperative for BMI, ALAT, ASAT, GGT respectively. Specific liver diseases were excluded. 37 patients (18.7%) had elevated liver enzymes (ALAT 14.1%, ASAT 9.6%, GGT 6.6%) preoperatively. ALAT and ASAT returned to normal in all patients postoperatively (p < 0.01). In 14 patients with significant ALAT-elevation (i.e. > 10% above normal) we found a correlation between postoperative fall of ALAT and reduction of BMI within 12 month (r = 0.4998; p < 0.05). CONCLUSION: 18.7% of morbid obese patients (BMI 46 kg/m2) have elevated liver enzymes prior to laparoscopic gastric banding. The normalisation of elevated liver enzymes correlates to the extent of weight reduction after gastric banding. Our data show reversible liver enzyme abnormalities, correlating to the degree of obesity.

Diagnostic quality of biopsy specimens: comparison between a conventional biopsy forceps and multibite forceps.

BACKGROUND: The endoscopic biopsy is a prerequisite for histopathologic diagnosis. Various types of forceps are used to obtain tissue specimens. The aim of this study was to assess and compare the diagnostic quality of biopsy specimens obtained with a conventional forceps and a Multibite forceps. METHODS: In a prospective, partially blinded, and randomized trial that included 250 patients referred for diagnostic upper and/or lower endoscopy, 510 biopsy specimens obtained with the Multibite forceps were compared with 520 specimens obtained with a conventional forceps. An experienced, blinded pathologist evaluated the specimens for diameter, depth of specimen, artifacts, anatomic orientation, vitality, general histologic quality, and diagnostic quality. Statistical analysis was performed by using the Fisher exact test. A p value of < 0.05 was regarded as significant. RESULTS: There were no statistically significant differences between the specimens obtained with the 2 forceps. The p values for the evaluated parameters were as follows: diameter 0.45, depth of specimen 0.56, artifacts 1.0, pathoanatomic orientation 0.40, vitality 0.45, and histologic diagnostic quality 0.53. CONCLUSION: The quality of biopsy specimens obtained with the Multibite forceps is comparable with that of specimens taken with a conventional forceps. Use of the Multibite forceps saves time in that 4 specimens can be obtained in 1 pass in situations in which a large number of specimens are needed or when the potential for transmission of infection is of concern.

Relationship between APC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.

Diamond stents for palliation of malignant bile duct obstruction: a prospective multicenter evaluation.

BACKGROUND AND STUDY AIMS: Various types of self-expandable metal stents have been introduced for biliary drainage in patients with malignant jaundice, showing prolonged patency compared with plastic endoprostheses. However, there has only been prolonged experience with a meaningful number of patients using the Wallstent. We evaluated the Diamond stent, a self-expanding uncoated biliary metal stent, in a prospective uncontrolled multicenter setting. PATIENTS AND METHODS: The eligibility criterion was obstructive jaundice due to inoperable malignant disease. Between August 1995 and January 2000, 126 patients, who received a total of 134 Diamond stents in four European centers, were followed prospectively. RESULTS: Technical and clinical success rates were 96 % and 98 %, respectively. No major procedure-related complications occurred. The 30-day mortality rate was 13 %. Stent occlusion occurred in 28 patients (22 %). Overall median stent patency was 477 days; overall median survival was 173 days. Stent occlusion, confirmed by endoscopic retrograde cholangiopancreatography, was successfully treated with plastic stents in all patients. Cost analysis revealed estimated costs of 3440 euros per patient for palliative treatment with the Diamond stent. CONCLUSIONS: The Diamond stent compares favorably with other biliary metal stents for patients requiring biliary drainage of malignant jaundice.

[Generalized intestinal CMV infection with protein-losing syndrome in ulcerative colitis]. / Generalisierte intestinale CMV-Infektion mit Eiweissverlustsyndrom bei Colitis ulcerosa.

Infection by cytomegalovirus (CMV) in immunocompetent patients is rare, and if it occurs it is most often associated with ulcerative colitis. This case illustrates a CMV infection in a patient with an ulcerative colitis combined with CMV-induced protein losing enteropathy, a condition reported in immunocompetent individuals in only a very few cases worldwide. It demonstrates the importance of differentiating between a flare-up of ulcerative colitis and CMV colitis. The indication for antiviral therapy is discussed. A 76-years-old patient with a 23-year history of leftsided ulcerative colitis presented with acute pancolitis sparing the rectum. He showed no evidence of impaired host defence, nor has he ever had taken immunosuppressive drugs. Disseminated primary CMV infection involving of the colon, the oesophagus and the small intestine with protein losing enteropathy was diagnosed on the basis of histology, culture and serology. In view of the long duration of the illness and the highly active infection, antiviral therapy with ganciclovir was given and led to a dramatical improvement of all disease manifestations. The patient subsequently remained in remission from ulcerative colitis for three years.

Cytomegalovirus-induced transient protein-losing hypertrophic gastropathy in an immunocompetent adult.

Transient protein-losing hypertrophic gastropathy with similarity to Ménétrier's disease is described. Acute infection with cytomegalovirus (CMV) could be shown to play a causative role. Immunodeficiency was ruled out. The 34-year-old patient had complete resolution of the disease without antiviral treatment. To our knowledge the present report is the first case of CMV-associated protein-losing hypertrophic gastropathy in an immunocompetent adult. To date, a similar disorder has only been described in children. CMV infection should be considered in patients with acute and symptomatic protein loss of gastrointestinal origin.

Esophageal carcinoma: current staging strategies.

A patient with suspected esophageal carcinoma represents a challenge to the treating physicians. Most patients present with an advanced stage of disease, and in the majority of cases only palliative treatment can be offered. Various treatment modalities are available, which are applied according to the TNM stage of the disease and the performance status of the patient. A precise histological diagnosis and highly accurate tumor staging of a patient with esophageal carcinoma is a prerequisite for the selection of the most suitable treatment option. Endoscopic ultrasound (EUS) has emerged as the most accurate diagnostic modality for locoregional staging. Problems in identifying early tumor stages or tumor strictures can be generally overcome by using miniprobe sonography (MPS). EUS/fine-needle aspiration biopsy (FNA) technology provides a valuable means of identifying suspicious locoregional lymph nodes. Patients with a proximal tumor (trachea bifurcation) should undergo bronchoscopy to rule out infiltration of the tracheobronchial system. Ultrasound (US), computed tomography (CT), and possibly magnetic resonance imaging (MRI) are the diagnostic tools of choice for extended tumor staging. After excluding extended tumor stage and severe concomitant diseases, diagnostic laparoscopy with intra-abdominal ultrasound should be performed in patients with adenocarcinoma of the esophagus prior to esophagectomy. Intra-abdominal metastases which can be missed preoperatively in some cases have to be ruled out in order to avoid unnecessary surgery.

Endoscopic ultrasonography in the diagnosis, staging, and follow-up of anal carcinomas.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is a technique that is well established in gastroenterology for tumor staging, but so far very few data have been reported concerning the staging of anal carcinomas using EUS. The aim of this study is to underline the value of EUS in the staging and follow-up of anal carcinoma. PATIENTS AND METHODS: In this retrospective study, 30 consecutive patients with carcinoma of the anal canal (nine men, 21 women) were examined using EUS, and the tumors were classified according to the 1985 TNM classification. EUS was carried out either before the start of treatment (15 patients); after the initial treatment in order to plan further treatment; or during follow-up examinations (15 patients). The treatment given was based on the results of the EUS examination. RESULTS: The following tumor stages were diagnosed: four lesions in stage uT0, seven in stage uT1, seven in stage uT2, nine in stage uT3, and three in stage uT4. In seven patients, suspect lymph nodes were also detected by EUS. In all but three of the patients (lost to follow-up), EUS had a direct impact on the treatment selected. Depending on the tumor stage, patients either underwent surgery (four patients: one uT1, one uT2, two uT3); received radiotherapy alone (five patients: three uT2, two uT3); combined chemoradiotherapy (eight patients: three uT2, three uT3, two uT4); interstitial booster radiotherapy (four patients: three uT1, one uT3); or no therapy at all (six patients: four uT0, one uT3, one uT4), respectively. In two patients, the tumor was understaged at EUS: in one, a uT1 tumor proved to be a pT2 tumor, and in the other, a uT3 tumor proved to be a pT4 tumor. CONCLUSIONS: The advantage of EUS in the staging of anal cancer is that it allows precise assessment of the depth of infiltration and tumor spread into adjacent tissue, facilitating the choice of stage-dependent treatment decisions-particularly in determining the extent of interstitial booster radiotherapy needed. It also allows follow-up examinations after the initial treatment, with fine-needle aspiration biopsies of suspicious areas. Wider acceptance of this method might further decrease the performance of extensive surgery, with the impaired quality of life associated with rectal amputation. In addition, it might allow improved quality control of the various treatment modalities.

Enteric infections and diarrhea in human immunodeficiency virus-infected persons: prospective community-based cohort study. Swiss HIV Cohort Study.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at increased risk for diarrhea and enteric infections. We studied (1) the epidemiology of enteric pathogens associated with diarrhea, (2) the diagnostic yield of stool examination and endoscopic evaluation, (3) risks to develop diarrhea, and (4) the impact of diarrhea on patients' survival. METHODS: A total of 1933 participants in the Swiss HIV Cohort Study were prospectively followed up for a median of 25.5 months. A total of 560 diarrheal episodes were evaluated by standardized stool examination. Endoscopic evaluation was performed in 25% of patients with chronic diarrhea. RESULTS: The incidence of diarrhea was 14.2 per 100 person-years (95% confidence interval, 13.0-15.4). Among patients with CD4 cell counts below 0.05 x 10(9)/L, the probability to develop diarrhea within 1, 2, and 3 years was 48.5%, 74.3%, and 95.6%, respectively. The risk to develop diarrhea was increased among patients with severe immunodeficiency, homosexual men, and patients taking antiretroviral therapy. Pneumocystis carinii chemoprophylaxis did not reduce the risk of diarrhea. Diarrhea was an independent negative predictor of survival. Enteric pathogens were detected in 16.5% of 212 acute diarrheal episodes and in 46% of 348 chronic diarrheal episodes. The sensitivity of histological and stool examination was similar except for the diagnosis of intestinal cytomegalovirus infection and leishmaniasis, which required invasive evaluation. CONCLUSIONS: Intestinal infections were diagnosed in less than 50% of chronic diarrheal episodes. The prevalence of enteric pathogens tended to decrease during the observation period, possibly because of improved antiretroviral therapy. Endoscopic evaluation did not improve the diagnostic yield compared with stool examination except for the diagnosis of cytomegalovirus enteritis and leishmaniasis.