Sampliner Re

A Randomized, Controlled Trial of Interferon Alfa-2b Alone and after Prednisone Withdrawal for the Treatment of Chronic Hepatitis B

Abstract Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P<0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest indep...

Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett’s oesophagus

Background: The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett’s oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett’s mucosa would be helpful. Aim: To study the utility of high magnification chromoendoscopy (MCE) in the detection of IM, LGD, and HGD in patients with Barrett’s oesophagus. Methods: Consecutive patients detected with columnar mucosa in the distal oesophagus were studied using an Olympus magnification endoscope (GIF-Q16OZ, 115×). The distal oesophagus was sprayed with indigo carmine solution and the oesophageal columnar mucosa patterns were noted under high magnification and targeted for biopsy. All biopsies were read by pathologists blinded to the endoscopic findings. Results: Eighty patients with suspected Barrett’s oesophagus (that is, columnar lined distal oesophagus) were studied: mean age 62.7 years (range 35–81). Mean length of columnar mucosa was 3.7 cm (range 0.5–17). Three types of mucosal patterns were noted within the columnar mucosa after spraying indigo carmine and using MCE: ridged/villous pattern, circular pattern, and irregular/distorted pattern. The yield of IM on target biopsies according to the patterns was: ridged/villous 57/62 (97%) and circular 2/12 (17%). Six patients had an irregular/distorted pattern and all had HGD on biopsy (6/6 (100%)). Eighteen patients had LGD on target biopsies; all had the ridged/villous pattern. All patients with long segment Barrett’s were identified using MCE whereas 23/28 patients (82%) with short segment Barrett’s had the ridged/villous pattern. Conclusions: MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.

Pathological diagnosis of chronic hepatitis C: A multicenter comparative study with chronic hepatitis B

BACKGROUNDnHepatic histological responses described in hepatitis C virus (HCV) infection include bile duct damage, lymphoid follicles and/or aggregates in portal tracts, large- and small-droplet fat, Mallory body-like material in hepatocytes, liver cell dysplasia and multinucleation, and activation of sinusoidal inflammatory cells. The specificity of these lesions for HCV infection is uncertain.nnnMETHODSnIn two multicenter trials of recombinant interferon alfa therapy for chronic hepatitis C and B, the frequency of these eight lesions in pretherapy and posttherapy liver biopsy specimens was examined to determine the set of features, if any, that distinguishes HCV from hepatitis B virus (HBV) infection. The lesions were scored in 317 HCV biopsy specimens and 299 HBV specimens.nnnRESULTSnStepwise logistic regression determined a set of three features more likely to be seen in HCV than in HBV infection: bile duct damage [odds ratio (OR), 4.7; 95% confidence interval (Cl), 1.8-12.3], lymphoid follicles and/or aggregates (OR, 2.4; 95% Cl, 1.2-4.7), and large-droplet fat (OR, 2.4; 95% Cl, 1.4-4.1). A fourth lesion, Mallory body-like material, was seen only in HCV biopsy specimens (OR, 71.6; 95% Cl, 4.4-996.1).nnnCONCLUSIONSnThese four histological lesions are useful pathological parameters in the diagnosis of liver disease caused by HCV.

Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia

BACKGROUND Biopsy specimens obtained from the gastro-oesophageal junction can reveal intestinal metaplasia in patients presenting for routine upper endoscopy. The site of biopsy may play a critical role in determining the dysplasia risk of a patient. AIMS To evaluate prospectively the dysplasia risk in patients with intestinal metaplasia of the distal oesophagus or within the gastric cardia. METHODS Patients with short segment Barretts oesophagus (SSBO) and cardia intestinal metaplasia (CIM) were followed prospectively. RESULTS 177 patients with SSBO were identified (mean age 62 years, range 38–82; 91% whites). Twenty prevalence cases of dysplasia in SSBO were detected: 17 low grade dysplasia (LGD), three high grade dysplasia (HGD). Seventy six patients with CIM were identified (mean age 67 years, range 37–81; 81% whites). A single prevalence case of LGD in CIM was detected. During follow up of 78 SSBO and 34 CIM patients, dysplasia developed in nine (seven LGD, two HGD) with SSBO and in one (LGD) with CIM. There were significant differences between the two groups with respect to age, ethnicity, dysplasia prevalence, and incidence. Time to dysplasia progression was significantly longer in CIM compared with SSBO patients. Of the five patients with SSBO and HGD, one developed adenocarcinoma of the oesophagus on follow up. No HGD or cancers have been detected over this time period in CIM patients. CONCLUSIONS The dysplasia risk is significantly greater in SSBO than in CIM patients, indicating two potentially different clinical processes. Future studies should separate SSBO from CIM in order to enhance the understanding of the pathophysiology and malignant potential of each entity.

Diagnostic inconsistencies in Barrett's esophagus

Abstract Background/Aims: Few studies have compared the precision of various diagnostic tests used to determine the presence of Barretts esophagus. The aim of this study was to compare the results of histological, endoscopic, and manometric tests for patients with Barretts esophagus in two closely spaced examinations. Methods: In a Veterans Administration Cooperative Study, 192 patients with complicated gastroesophageal reflux disease had esophageal manometry and endoscopy performed at baseline and after 6 weeks. At each examination, the endoscopist localized the most proximal level of Barretts epithelium and the lower esophageal sphincter and obtained esophageal biopsy specimens. Results: One hundred sixteen patients met the criteria for Barretts esophagus on at least one of the two endoscopic examinations. Among patients with specialized columnar epithelium, 20% had specialized columnar epithelium found on only one of the two examinations. Although the mean lower esophageal sphincter level did not change, approximately 10% of patients had a change ≥4 cm on endoscopy and manometry between examinations. This led to an apparent change in the diagnosis in 18% of patients with Barretts esophagus. Conclusions: From one endoscopic examination to another, inconsistencies in the ability to detect specialized columnar epithelium are common. This may lead to substantial problems in establishing an accurate diagnosis of Barretts esophagus.

Correlation of oesophageal acid exposure with Barrett's oesophagus length

BACKGROUND Gastro-oesophageal reflux disease (GORD) plays a major role in the development of Barretts oesophagus. However, it has yet to be elucidated what factors determine the length of Barretts mucosa in each individual patient. AIMS To determine if there is a correlation between oesophageal acid exposure and the length of Barretts mucosa. We also compared the extent of oesophageal acid exposure between patients with short segment (SSBE) and long segment (LSBE) Barretts oesophagus. METHODS Twenty seven patients with Barretts oesophagus were recruited prospectively into the study from the outpatient gastroenterology clinic at the Southern Arizona VA Health Care System. Diagnosis of Barretts oesophagus and its anatomical characteristics were determined during upper endoscopy. Ambulatory 24 hour oesophageal pH monitoring assessed the extent of oesophageal acid exposure. RESULTS There was a significant correlation between per cent total time pH less than 4 and length of Barretts mucosa (r=0.6234, p=0.0005). In addition, there was a significant correlation between per cent upright and supine time pH less than 4 and length of Barretts mucosa (r=0.5847, p=0.0014 andr=0.6265 p=0.0006, respectively). Patients with SSBE had significantly less oesophageal acid exposure than patients with LSBE, in terms of both per cent total time and per cent supine time pH less than 4 (p<0.05). CONCLUSIONS The length of Barretts mucosa correlated with the duration of oesophageal acid exposure. Patients with LSBE experienced significantly more oesophageal acid exposure than patients with SSBE. Duration of oesophageal acid exposure appears to be an important contributing factor in determining the length of Barretts mucosa.

A randomised controlled trial of ablation of Barrett’s oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results

Background: Many modalities have been used to ablate Barrett’s oesophagus (BO). However, long term results and comparative effectiveness are unknown. Aims: Our aim was to compare the long term efficacy of achieving complete reversal (endoscopic and histological) between multipolar electrocoagulation (MPEC) and argon plasma coagulation (APC) in BO patients and assess factors influencing successful ablation. Methods: Patients with BO, 2–6 cm long, underwent 24 hour pH testing on proton pump inhibitor (PPI) therapy. Patients were then randomised by BO length to undergo ablation with MPEC or APC every 4–8 weeks until endoscopic reversal or maximal of six treatment sessions. Results: Thirty five BO patients have been followed for at least two years following endoscopic ablation, 16 treated with MPEC and 19 with APC. There was complete reversal of BO in 24 patients (69%); 75% with MPEC and 63% with APC (pu200a=u200a0.49). There was no difference in the number of sessions required in the two groups. There was no difference in age, pH results, BO length, PPI dose, or hiatal hernia size between patients with and without complete reversal. One patient developed an oesophageal stricture but there were no major complications such as bleeding or perforation. Conclusions: In BO patients treated with MPEC or APC in combination with acid suppression, at long term follow up, complete reversal of BO can be maintained in approximately 70% of patients, irrespective of the technique. There are no predictors associated with achieving complete reversal of BO. Continued surveillance is still indicated in the post ablative setting. As yet, these techniques are not ready for clinical application (other than for high grade dysplasia or early oesophageal adenocarcinoma) and cannot be offered outside the research arena.

The omeprazole test is as sensitive as 24‐h oesophageal pH monitoring in diagnosing gastro‐oesophageal reflux disease in symptomatic patients with erosive oesophagitis

Ambulatory 24‐h oesophageal pH monitoring and a short course of high dose omeprazole can be used as diagnostic modalities for GERD. However, comparative studies of the diagnostic accuracy and reliability of both strategies have not been performed.

Failure of oesophageal acid control in candidates for Barrett's oesophagus reversal on a very high dose of proton pump inhibitor

Normalization of oesophageal acid exposure using high dose proton pump inhibitors in patients who are candidates for ablation therapy has been suggested to be essential for successful Barretts reversal. However, the success rate for achieving pH normalization has not been determined.

Biomarker studies in reversed Barrett's esophagus.

Objective:The purpose of this study was to use biomarkers to assess for cancer risk in Barretts esophagus patients with either squamous islands or complete reversal of their intestinal metaplasia to squamous epithelium.Methods:The biomarkers included proliferation characteristic using Ki-67, p53 abnormalities using immunohistochemical methods with two antibodies, DO-1 and DO-7, and ornithine decarboxylase (ODC) activity.Results:Eleven patients had complete reversal produced by a combination of acid suppression and thermal injury (multipolar electrocoagulation). Ki-67 staining was indistinguishable from that of normal squamous esophageal epithelium, i.e., basal layer staining only. All 11 cases were negative for p53. ODC activity was low and in the range for normal squamous epithelium. Fourteen patients had squamous islands (partial reversal) after prolonged proton pump inhibitor therapy. Multilayer Ki-67 staining occurred in nine cases (64%), and six (43%) had areas of positive p53 staining.Conclusion:Initial biomarker studies suggest that completely reversed squamous epithelium is biologically similar to normal squamous epithelium and of low cancer risk. In contrast, partial reversal, manifest as squamous islands, is accompanied by biomarker abnormalities.