Paul Kerlin

Only patients with dysplasia progress to adenocarcinoma in Barrett's oesophagus.

Columnar lined oesophagus (Barretts oesophagus) carries a risk for the development of adenocarcinoma. Epithelial dysplasia appears to be a precursor but the utility of this marker for predicting subsequent adenocarcinoma is unsettled. We therefore prospectively studied 81 patients with histologically proven columnar epithelium of at least the distal 3 cm of the tubular oesophagus with regular endoscopic biopsies for a total of 289.2 patient years (mean 3.6 years, range 0.5-8). Twenty three patients (28%) had epithelial dysplasia detected during follow up. Both patients with persistent high grade dysplasia present on initial biopsies developed adenocarcinoma after 2.6-4.5 years, despite the absence of gross macroscopic change. The initial single layer pleomorphic high grade dysplasia in one patient regressed to low grade dysplasia which has persisted for 1.5 years. Of 10 patients with initial low grade dysplasia, one progressed to adenocarcinoma in 4.3 years. The low grade dysplasia persisted unchanged in seven patients for 1.5-7 years and appears to have regressed in two patients after three to five years. Ten patients developed low grade dysplasia during the surveillance period. This has persisted unchanged in six patients from 0.5-5 years, regressed in three for 0.5-5 years and has appeared after the first yearly biopsy in one patient. No patient without dysplasia has developed adenocarcinoma. The incidence of adenocarcinoma in Barretts oesophagus in this study is one case per 96 patient years. This is 61 times (95% confidence limits 12-176) the age adjusted incidence of oesophageal cancer in Australia. Persistent high grade dysplasia appears to be a sensitive indicator for the development of subsequent adenocarcinoma.

Breath Hydrogen Testing in Bacterial Overgrowth of the Small Intestine

The indirect, noninvasive technique of breath hydrogen (H2) analysis was evaluated in 45 patients suspected of having bacterial overgrowth of the small intestine. Bacterial overgrowth, defined as a jejunal culture yielding at least 10(5) organisms/ml, was present in 27 patients. After dietary preparation and a 12-h fast, subjects received in random order and on separate days 50 g of glucose or 50 g of rice flour in the form of two pancakes. Normal values were established in 20 healthy controls. Twelve of 27 patients with proven bacterial overgrowth had an elevated (greater than 15 ppm) fasting breath H2 level on at least 1 test day. Fifteen of 18 patients with negative cultures had low fasting breath H2 levels. Based on values in controls, a positive breath test was defined as an increase in breath H2 of greater than or equal to 12 ppm after glucose or greater than or equal to 14 ppm after rice flour. A 2-h glucose breath H2 test had a sensitivity of 93% and a specificity of 78% in the diagnosis of overgrowth. The predictive value of a positive test was 86% and that of a negative test was 88%. The combination of both a high fasting breath H2 level and a diagnostic rise of breath H2 after glucose was present in 41% of patients with overgrowth and in none of the patients without overgrowth. Extending the test to 4 h did not increase sensitivity, but decreased specificity. Rice flour was a less satisfactory substrate in predicting the presence of bacterial overgrowth. In conclusion, a high fasting breath H2 level after dietary preparation suggests bacterial overgrowth but lacks sensitivity. The finding of a rise in breath H2 of at least 12 ppm within 2 h of a 50-g glucose challenge is a simple screen for bacterial overgrowth. The combined criteria of a high fasting breath H2 level and a significant rise after glucose are specific for bacterial overgrowth.

Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus.

Background and Goals Acute food bolus impaction is a common emergency in gastrointestinal practice. Management previously used the endoscope with an overtube to allow retrieval of the bolus per os. The push technique using air insufflation and gentle pressure on the bolus provides an alternative approach. Esophageal mucosal biopsy at the time of the initial endoscopy has not been a part of traditional practice. In view of the increasing recognition of eosinophilic esophagitis (EE) as a cause of dysphagia and food bolus obstruction in adults the etiology needs to be reassessed. Study Forty-three consecutive adults presenting with acute dysphagia secondary to food bolus obstruction of the esophagus were studied. The bolus was advanced into the stomach with the push technique or removed per os with a retrieval net. Protocol biopsies from the proximal and distal esophagus were obtained in 29 patients. Biopsies were contraindicated or not obtained in the remainder. Results Forty-one patients were successfully treated at endoscopy. Two subjects with a food bolus impacted at the crico-pharyngeal region required general anesthesia with endotracheal intubation for safe removal. Of 29 patients biopsied, 15 had peptic esophageal stricture as the cause. Fourteen patients (all males, mean age 32 y, range 19 to 62 y) had EE identified histologically. This represents 50% of those biopsied. Patients with EE had typical endoscopic features of linear furrows, mucosal rings, or narrow bore esophagus. Most had prior episodes of food bolus obstruction. Conclusions Food bolus obstruction can be safely managed by the push technique. EE is an important cause of food bolus obstruction that can be suspected on history and endoscopic appearance and confirmed on histology.

Predicting Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis Before Transplantation

Patients with primary sclerosing cholangitis are at an increased risk of developing cholangiocarcinoma, which is difficult to diagnose because the biliary tree is already distorted. Eleven patients with primary sclerosing cholangitis who underwent orthotopic liver transplantation at this hospital were evaluated. Four patients had coincidental histologically proved cholangiocarcinoma. Patients with cholangiocarcinoma in contrast to patients without tumour presented with rapid onset of persistent jaundice, pruritus, and weight loss associated with an appreciable rise in bilirubin (8x v 2x) and alkaline phosphatase (3.5x v 1.2x) over one year. Cholangiography and computed tomography showed appreciably dilated intrahepatic bile ducts (3/4 v 0/7). The diagnosis of cholangiocarcinoma could only be established before operation in one patient by fine needle aspiration cytology. Tumour was recognised at operation in one other. Histological examination of hepatectomy specimens showed that patients with cholangiocarcinoma had less advanced histological features of primary sclerosing cholangitis. Multiple areas of carcinoembryonic antigen positive epithelial atypia and carcinoma in situ were found in all patients with cholangiocarcinoma. Cholangiocarcinoma recurred in two patients at 14 and 39 months after transplantation. Superimposed cholangiocarcinoma can be predicted in most patients with cholangitis before transplantation, although a definitive diagnosis is difficult to make. Their prognosis after successful transplantation is guarded.

Sclerosing Peritonitis: Identification of Diagnostic, Clinical, and Radiological Features

Sclerosing peritonitis is a rare, but serious complication of peritoneal dialysis. To attempt the early identification of patients at risk of developing this life-threatening problem, we performed a cross-sectional study of 15 patients: five had died of sclerosing peritonitis, four had stopped peritoneal dialysis because sclerosing peritonitis was suspected, and six were considered to be at increased risk because of more than 4 years on peritoneal dialysis. We examined the duration of dialysis, number of episodes of peritonitis, strength of peritoneal dialysis bags, the type of dialysate, and the use of beta blockers. We also used a number of radiologic investigations, including abdominal x-ray, a measure of colonic transit using radiopaque markers, abdominal ultrasound, and computed tomography scanning. Of the clinical features, only duration of dialysis could be shown to be an important risk factor. We identified a number of radiologic features that we believe to be early signs of peritoneal sclerosis. The two computed tomography scans that were available from the deceased patients demonstrated peritoneal thickening, as did those from three of the four living patients who stopped peritoneal dialysis with suspected disease and from two of the six patients who had been on peritoneal dialysis for over 4 years. Ultrasound demonstrated a characteristic trilaminar appearance in four patients, but was unable to be demonstrated without peritoneal fluid in situ. Delayed colon transit was demonstrated in three of the four living patients with clinically suspected disease. Radiologic screening to detect sclerosing peritonitis early in high-risk patients requires further study.

Detection of male DNA in the liver of female patients with primary biliary cirrhosis

BACKGROUND/AIMS Primary biliary cirrhosis is a chronic cholestatic liver disease characterized by progressive inflammatory destruction of bile ducts, with eventual hepatic fibrosis and cirrhosis. Since primary biliary cirrhosis affects predominantly middle-aged women and has pathological similarities to hepatic graft-versus-host-disease, we investigated whether fetal cell microchimerism might be involved in the development of this disease. METHODS The presence of Y-chromosome-specific sequences was analyzed by polymerase chain reaction using peripheral blood mononuclear cells from women with primary biliary cirrhosis (n=18) and healthy (control) women (n=18), and by in situ hybridization of liver biopsy sections from women with primary biliary cirrhosis (n=19) and women with chronic hepatitis C or alcoholic liver disease (n=20). RESULTS Male cells were detected in liver biopsy specimens of 8 of 19 patients (42%) with primary biliary cirrhosis. Y-chromosome-containing cells were not seen in any of the liver biopsy specimens from women with chronic hepatitis C or alcoholic liver disease. Male cells were detected in peripheral blood mononuclear cells from one healthy control at a level of 1 male cell per 10(6) female cells, but were not detected in peripheral blood mononuclear cells of women with primary biliary cirrhosis. CONCLUSIONS The presence of male cells in the liver of women with primary biliary cirrhosis raises the possibility that fetal cell microchimerism may be involved in the pathogenesis of this chronic liver disease.

Improvement in chronic hepatocerebral degeneration following liver transplantation

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation.

Universal occurrence of glomerular abnormalities in patients receiving liver transplants

We conducted a prospective study of renal histology and function in 18 consecutive nonalcoholic patients who underwent orthotopic liver transplantation (OLT). Despite well-preserved renal function, all patients had abnormal renal biopsies. Four patterns of glomerular injury were identified: minor glomerular abnormalities (eight patients), hepatic glomerulosclerosis (seven), membranoproliferative glomerulonephritis (one), and IgA nephropathy (one). In one patient there was insufficient tissue to allow classification. There was a trend toward lower plasma bilirubin and higher plasma albumin in patients with minor glomerular abnormalities than in the group of patients with more severe forms of glomerular injury (29 v 82 mumol/L, 35.5 v 30 g/L; P = 0.1, 0.1 greater than P greater than 0.05, respectively). Glomerular changes persisted in the three patients who died within 7 weeks post-OLT. IgM immunofluorescence was present in all biopsies and IgA in 11. IgM-containing circulating immune complexes occurred in five patients, suggesting a pathogenic role for IgM immune complex deposition. The significance of cirrhosis-associated glomerular abnormalities is not yet known. They may contribute to the hepatorenal syndrome and the renal dysfunction that occurs in up to 94% of patients post-OLT.

Spontaneous intramural rupture of the oesophagus.

The clinical, endoscopic, and radiological features of seven patients with an uncommon oesophageal injury characterised by long lacerations of the oesophageal mucosa with haematoma formation but without perforation are reported. The injuries were not related to forceful vomiting or any other definable cause but were similar to those previously described as intramural oesophageal rupture. Upper gastrointestinal endoscopy undertaken to identify the cause of haematemesis in six patients proved safe and useful. When dysphagia and odynophagia occurred early in the clinical course to alert the clinician to possible oesophageal injury, radiological contrast studies were used to exclude perforation. One patient in this study had oesophageal cavernocapillary haemangiomatosis which may have caused intramural oesophageal bleeding and submucosal dissection but in the remainder the aetiology of intramural oesophageal rupture remains uncertain. Conservative management was successful in all patients.

Patient and graft survival after liver transplantation for hereditary hemochromatosis: Implications for pathogenesis

The clinical outcome of patients who have undergone liver transplantation for hereditary hemochromatosis (HH) or who have received iron‐loaded donor grafts is unclear. We reviewed 3,600 adult primary orthotopic liver transplants and assessed the outcomes in 22 patients with HH. We also evaluated graft function and iron mobilization in 12 recipients of iron‐loaded donor grafts. All 22 subjects who received liver transplants for HH were male; 13 had other risk factors for liver disease. HH patients had comparatively poor outcomes following transplantation: survival at 1, 3, and 5 years posttransplantation were 72%, 62%, and 55%, respectively. Recurrent hepatocellular cancer was the most common cause of death. There was no convincing evidence of reaccumulation of iron in the grafted liver in HH; however, 1 subject demonstrated increased serum ferritin concentration and grade 2 hepatic siderosis. Liver iron stores were slow to mobilize in 7 of the 12 recipients of iron‐loaded grafts. These recipients had appropriate early graft function, but 2 patients with heavy iron loading and increased hepatic iron developed hepatic fibrosis. In conclusion, (1) HH is an uncommon indication for liver transplantation, and the majority of patients requiring transplantation had other risk factors for chronic liver disease; (2) reaccumulation of liver iron in HH patients is very unusual, but increased iron stores may be slow to mobilize in normal recipients of iron‐loaded grafts, potentially compromising late graft function; (3) post‐liver transplant survival is reduced in HH, and affected patients require careful clinical evaluation of perioperative and postoperative risk factors. Our data suggest that iron excess in HH does not wholly depend on intestinal iron absorption but is also influenced by liver factors that moderate iron metabolism. (HEPATOLOGY 2004;39:1655–1662.)