Liver biopsies in adult hemophiliacs with hepatitis C: a United States center's experience.

We report a case series of 13 adult hemophiliacs with serological evidence of hepatitis C who underwent percutaneous liver biopsies without major complications. We also briefly review the recent literature on safety of liver biopsies in this population, and conclude that these patients may be safely biopsied using appropriate precautions regardless of the severity of hemophilia.

Laparoscopy-assisted endoscopic removal of a stromal-cell tumor of the stomach.

Endoscopic resection of gastrointestinal tumors is being performed with increased frequency. Submucosal mass lesions pose a particular problem, because of the risk of malignancy and the risk of complications associated with endoscopic removal. Increased incidences of both perforation and bleeding have been reported. We report here on a case in which we used a combined approach that included gastrointestinal endoscopy, laparoscopy, and laparoscopic ultrasound to resect a gastric leiomyoma. We consider that this approach enhanced our diagnostic capabilities, provided intraoperative options for resection, and enhanced the safety of the procedure.

A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C.

BACKGROUND & AIMS: Oxidative stress mediates activation and stimulates collagen production of cultured hepatic stellate (Ito) cells. The aim of this study was to assess whether oxidative stress contributes to hepatic fibrogenesis in chronic hepatitis C. METHODS: In liver biopsy specimens of patients with chronic hepatitis C, the following fibrogenesis cascade was analyzed: (1) oxidative stress, determined by the presence of malondialdehyde protein adducts; (2) activation of stellate cells as indicated by their expression of alpha-smooth muscle actin; (3) stimulation of c-myb expression in stellate cells, a critical step in the activation of these cells; and (4) induction of collagen gene expression as detected by in situ hybridization. RESULTS: Treatment with d-alpha-tocopherol (1200 IU/day for 8 weeks) in 6 of these patients, who were refractory to interferon therapy, prevented the fibrogenesis cascade observed before antioxidant treatment. In addition, d-alpha-tocopherol treatment significantly decreased the carbonyl modifications of plasma proteins, a sensitive index of oxidative stress. However, 8 weeks of d-alpha-tocopherol treatment did not significantly affect serum alanine aminotransferase levels, hepatitis C virus titers, or histological degree of hepatocellular inflammation or fibrosis. CONCLUSIONS: These data suggest that enhanced oxidative stress initiates a fibrogenesis cascade in the liver of patients with chronic hepatitis C.

Pleuropulmonary amebiasis.

Amebiasis is the third leading parasitic cause of death in the world. Approximately 500 million people worldwide are infected with Entamoeba histolytica. Invasive disease is more common in the immunosuppressed, pregnant women, children, and alcoholics. Amebic colitis and liver abscess are the most common intestinal and extraintestinal manifestations of E. histolytica infection. Pleuropulmonary complications occur almost exclusively in individuals with a liver abscess. Common pleuropulmonary complications include right-sided sympathetic effusions, empyema, basilar atelectasis, lung infiltration, and lung abscess. Bronchohepatic fistula is an unusual and distinctive problem characterized by expectoration of sputum that may resemble anchovy paste. Left hepatic lobe abscesses occasionally produce left-sided pleuropulmonary complications and may result in lethal rupture into the pericardium. Diagnosis is based on demonstration of the organism in clinical specimens; however, false-negative microbiological study results commonly occur even with active infection. Serological studies can confirm the diagnosis in the appropriate clinical setting, and newer immunological tests on blood, fluid, and tissue specimens show promise. Metronidazole remains the treatment of choice, and although surgical drainage is contraindicated, percutaneous drainage of abscesses and empyema may occasionally be indicated.

Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

Sclerosing mesenteritis: an unusual cause of abdominal pain in an HIV-positive patient.

Sclerosing mesenteritis is a rare, idiopathic, and benign mesenteric lesion that is characterized by fat necrosis, fibrosis, and chronic inflammation. We report a case of sclerosing mesenteritis presenting as recurrent abdominal pain in an HIV-positive patient. Because of the wider differential diagnosis in such cases, the patient underwent an extensive workup culminating in a laparoscopy with biopsy. Tamoxifen has been shown to be useful in the treatment of desmoid tumors and idiopathic retroperitoneal fibrosis. We present the first case of sclerosing mesenteritis to respond to tamoxifen therapy. Because this drug is relatively safe and simple to dose, its utility as therapy for patients with this benign but debilitating disease should be considered.

Diagnostic yield of duodenal biopsy and aspirate in AIDS-associated diarrhea.

OBJECTIVES: To evaluate the diagnostic yield of performing duodenal biopsies and aspirates in AIDS patients with chronic diarrhea. METHODS: Retrospective review of esophagogastroduodenoscopy (EGD) records from January 1993 to March 1995 to identify those patients who underwent EGD for evaluation of AIDS associated diarrhea and had a duodenal biopsy and/or aspirate. Biopsies were examined for pathogens using routine histology and special stains, viral culture, and electron microscopy. Duodenal aspirates were evaluated for ova and parasites. All patients had previous negative stool studies. Pathology laboratory charges (hospital and professional fees) for each test and charges per positive test were determined. RESULTS: Of the 57 patients included in this study, 56 had a duodenal biopsy and 42 had a duodenal aspirate. An established pathogen was identified in only 15 (26%) patients. One patient had both Mycobacterium avium complex and microsporidia. Pathogens were identified in seven patients by hematoxylin and eosin stain, in three patients by acid-fast bacillus stain, and in six patients by electron microscopy. No pathogens were identified with Gomori's methenamine silver stain (44 patients), duodenal aspirate for ova and parasites (46 patients), immunoperoxidase stains (4 patients), or viral culture (4 patients). Cryptosporidia were identified in six, microsporidia in five, Mycobacterium avium complex in three, and Giardia lamblia and adenovirus each in one patient. CONCLUSIONS: In this series, the diagnostic yield of EGD with duodenal biopsy and aspirate in AIDS associated diarrhea was low. Pathogens were identified in 26% of patients; predominantly Cryptosporidium organisms and microsporidia. The routine performance of aspiration of duodenal contents for parasite examination and staining of duodenal tissue with Gomori's methenamine silver stain for fungal identification are not recommended. One should consider obtaining tissue for electron microscopy whenever duodenal biopsies are performed. The utility of EGD in AIDS associated diarrhea may improve as more effective therapies become available.

Ascites and the acquired immunodeficiency syndrome. Report of 54 cases.

We identified 54 patients with AIDS and ascites seen over a 4.5-year period at a university hospital. This retrospective study is the largest reported series of patients with AIDS and ascites. Patients with AIDS who are evaluated for ascites should be stratified by the CD4 + cell count and the presence or absence of portal hypertension based upon the serum-ascites albumin gradient and clinical presentation. Awareness of possible surgery-related causes of ascites is crucial, as these patients may not manifest the usual signs and symptoms of peritonitis or abdominal catastrophes seen in immunocompetent hosts. Patients with evidence of portal hypertension due to hepatic cirrhosis and an elevated ascitic neutrophil count should be suspected to be infected with common bacterial pathogens associated with peritonitis unless the CD4 + cell count is below 50 cells/mm3. When the CD4 + cell count declines below this threshold, infections due to Mycobacterium avium complex, cytomegalovirus, and other opportunistic infections should be considered.

Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea.

BACKGROUND/AIMS: Diarrhea is a significant problem in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine octreotide effectiveness in refractory AIDS-associated diarrhea. METHODS: In a 3-week protocol, 129 patients with a stool weight of > 500 g/day despite standard antidiarrheal therapy were randomized to receive octreotide or placebo (3:2 ratio). Octreotide dose was increased 100 micrograms weekly to a maximum of 300 micrograms three times a day based on weekly 72-hour stool collections. Subsequently, patients received open-label octreotide at doses of up to 500 micrograms three times a day. RESULTS: A 30% decrease in stool weight defined response. After 3 weeks, 48% of octreotide- and 39% of placebo-treated patients had responded (P = 0.43). At 300 micrograms three times a day, 50% of octreotide- and 30.1% of placebo-treated patients responded (P = 0.12). At a baseline stool weight of 1000-2000 g/day, 57% of octreotide- and 25% of placebo-treated patients responded (P = 0.06). Response rates based on CD4 counts, diarrhea duration, body weight, human immunodeficiency virus risk factor, and presence or absence of pathogens showed no benefit of octreotide. Adverse events were more frequent in the octreotide-treated group. CONCLUSION: In the doses studied, octreotide was not more effective than placebo in patients with refractory AIDS-associated diarrhea. This lack of effectiveness may be attributable to inadequate sample size, doses, and duration of study treatment.

Colorectal cancer.

I'd like to summarize by letting you know that the field is very aggressively expanding in the areas of molecular biology. There isn't much new in terms of chemotherapy or surgery other than the advances I've just spoken to you about, but I think screening tests will allow us to decrease the mortality from colon cancer. We have been able to document that sigmoidoscopy can decrease the risk of colon cancer by about 45 percent in the United States; the mortality rates are continuing to decrease. I'd be happy to answer some questions that I might have stimulated. Thank you.

Treatment of pancreatic pseudocysts with percutaneous drainage and octreotide. Work in progress.

In an attempt to decrease catheter drainage of pancreatic pseudocysts, a combined regimen of percutaneous drainage and administration of octreotide acetate was used in eight symptomatic patients. Indications for the combined therapy were pseudocyst recurrence (four patients), pancreatic fistula from percutaneous drainage (two patients), or elective treatment to restrict pancreatic drainage. Octreotide acetate was administered subcutaneously in doses of 50-1,000 micrograms three times a day. The drug was well tolerated and produced only limited adverse effects in four patients: pain at the injection site, hypoglycemia, diarrhea, headaches, and lower-extremity edema (more than one adverse effect was experienced by each patient). The combined use of percutaneous drainage and administration of octreotide was effective in seven patients and failed in one patient who had distal pancreatic duct occlusion. In five patients, catheter drainage decreased to no measurable amount by a mean of 13.8 days. These results suggest octreotide is effective in decreasing the output from pancreatic pseudocysts drained percutaneously.

Examiner dependence on physical diagnostic tests for the detection of splenomegaly: a prospective study with multiple observers.

OBJECTIVE: To determine the reliability and validity of various physical diagnostic techniques (including three methods of palpation and three methods of percussion) in detecting ultrasonographically identified splenomegaly. DESIGN: Prospective, double-blind study. SETTING: University hospital. PATIENTS: Twenty-seven hospitalized male patients with suspected human immunodeficiency virus (HIV) infection. INTERVENTIONS: Three methods of palpation (bimanual, ballottement, and palpation from above) and three methods of percussion (as described by Nixon, Castell, and Barkun et al.) were performed on each patient by eight examiners. Splenic ultrasonography was performed within 96 hours of admission. MEASUREMENTS AND MAIN RESULTS: The prevalence of splenomegaly by ultrasonography (defined as a spleen > or = 13 cm on the longitudinal scan) in this population was 33.3%. The sensitivity and specificity of each method of palpation and percussion varied by examiner. The ranges of sensitivity across examiners for the three methods of palpation and the three methods of percussion were 0%-64.3% and 7.7%-75%, respectively. The ranges of specificity across examiners for the three methods of palpation and the three methods of percussion were 50%-100% and 60%-100%, respectively. Likelihood ratios pooled across observers revealed that for palpation, palpation from above, and percussion, Castell's method had the highest likelihood ratios [LR = 2.66 and 1.97, respectively; 95% CI = 1.52-4.64 and 1.22-3.19, respectively]. A combination of tests (either palpation or percussion) increased the diagnostic accuracy. CONCLUSION: Physical diagnostic techniques for the detection of splenomegaly are relatively insensitive but specific. In this study there was high interobserver variability, which did not appear to be associated to the level of experience. Combining tests increases diagnostic accuracy.

Pleuropulmonary manifestations of hepatic amebiasis.

Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess.

Increased production of collagen in vivo by hepatocytes and nonparenchymal cells in rats with carbon tetrachloride-induced hepatic fibrosis.

We have shown, using the proline:ornithine dual label method, that in normal rats, hepatocytes contribute in vivo about 80 to 90% of the newly synthesized hepatic collagen. In order to quantify the contribution of hepatocytes and nonparenchymal cells to collagen synthesis in vivo in hepatic fibrogenesis, rats with CCl4-induced liver fibrosis were given [5(3H)]proline and [14C]ornithine intraperitoneally. About 80% of the 14C in albumin and transferrin was present as arginine, following conversion of [14C]ornithine via the urea cycle. In contrast to hepatocyte proteins, in nonparenchymal cells and serum a negligible percentage of the radioactivity was present as [14C]arginine. These combined findings indicate that, in spite of the hepatocellular damage, the labeling of hepatocyte proteins was efficient and specific, validating the use of the proline:ornithine method in this experimental model of hepatic fibrosis. We calculated the [3H]proline/[14C]arginine ratio in hepatic collagen (after correcting for the relative frequencies of amino acids) as a percentage of the same ratio in either albumin or transferrin, the index hepatocyte proteins. In this experimental model, during active fibrogenesis, both hepatocytes and nonparenchymal cells increase their production of collagen 2-fold when compared to normal animals, and hepatocytes produce the majority of the newly synthesized hepatic collagen.