Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Edematous syndrome revealing an exudative lymphocytic gastritis: efficacy of omeprazole

Lymphocytic gastritis is characterized by intense lymphocytic infiltration of gastric epithelium. Excessive gastric protein loss is uncommon. We describe the case of a 49-year-old white woman suffering from generalized edema and abdominal pain. She had severe serum hypoproteinemia, hypoalbuminemia and hypogammaglobulinemia. There was no renal, cardiac or hepatic origin of protein loss, and no protein-losing enteropathy. Endoscopic examination showed diffuse varioliform gastritis and histology confirmed lymphocytic gastritis with > 30% intraepithelial lymphocytes without Helicobacter pylori. The protein loss stopped within two weeks of the beginning of omeprazole and extensive edema disappeared. Four years later, the patient was still free from edema. Inflammatory involvement of the gastric mucosa probably caused protein losing in this patient. Recognition of this exsudative gastropathy is important because long term remission is obtained with omeprazole.     

Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma

The purpose of this article was to study the efficacy and tolerance of liposomal daunorubicin (DaunoXome) in the treatment of AIDS-associated Kaposi sarcoma (KS) as prescribed in France between September 1996 and September 1997. All patients with a positive HIV serology, histologically proven KS, and having received at least one daunorubicin treatment cycle during the study period were eligible for entry. Ninety-four patient files from 13 university hospital departments were retrospectively studied. Of 94 patients, 80% received cytostatic treatment before the first daunorubicin treatment cycle. Initial mean CD4 lymphocyte count was 114/microl. Ninety percent of the patients received highly active antiretroviral treatment (HAART) during daunorubicin treatment. Daunorubicin was administered as single chemotherapy to 70% of the patients. The total number of treatment cycles was 1,422, with a mean number of 16.1 treatment cycles (1-68) per patient and a mean cumulative daunorubicin dose of 674 mg/m2 (40-2,749). According to the AIDS Clinical Trial Group criteria, partial and complete response rates were 26.5% and 11.5%, respectively. A hematopoietic growth factor was prescribed in 29% of the treatment cycles. At the final evaluation, 71% of the patients were alive. No severe cardiotoxic event was observed despite high cumulative drug doses and prolonged follow-up. Since the introduction of HAART, this study constitutes the only evaluation of daunorubicin in a wide population. Our study confirms that daunorubicin is effective in patients with advanced KS. Daunorubicin is well tolerated over the long term in association with HAART.     

Hepatitis C in France: A national survey in the departments of Internal Medicine and Infectious Diseases

Infection with Hepatitis C virus is a significant public health problem that has important clinical and financial consequences. Understanding of the epidemiology of HCV is needed to help define future therapeutic and preventive strategies. So far, the importance and characteristics of the epidemics have been best appreciated in specialist units dealing with liver disease. The purpose of our study was to survey the number and characteristics of hepatitis C antibody positive patients in Departments of Internal Medicine and Infectious Diseases. We conducted a multicentre national prospective analysis of all positive HCV-antibody patients, either inpatient or outpatient, reported over a period of one month across France. Two thousand and two cases were identified. Epidemiological clinical and therapeutic characteristics are described. Risk factors were identified in 86%. For 10% of the patients, hepatitis C seropositivity was discovered during the period of survey. At the time of first diagnosis, 47% of patients presented with no clinical or biological abnormality. Coinfection with HIV was frequent (59%). Only 20.3% of the patients had received or were receiving a treatment with interferon. Within the limits of the methodology used, this study shows that Hepatitis C infection is a substantial clinical problem in French Departments of Internal Medicine and Infectious Diseases. Our findings may help the public health authorities in better appreciating the impact of hepatitis C and making policy decisions.     

Peripheral neuropathy associated with essential mixed cryoglobulinaemia: a role for hepatitis C virus infection?

BACKGROUND--The prevalence of hepatitis C virus (HCV) infection has been estimated at 43 to 84% in patients with essential mixed cryoglobulinaemia in recent large series. Some of these cases have been successfully treated with interferon-alpha. The objective was to evaluate the prevalence and the possible role of HCV infection in essential mixed cryoglobulinaemia. METHODS--Fifteen patients (eight men and seven women; mean age: 61.2 (SD 16.5) years) with peripheral neuropathy (10 polyneuropathies and five multifocal mononeuropathies) and essential mixed cryoglobulinaemia were tested for serum anti-HCV antibodies. RESULTS--Antibodies were found in 10 of 15 patients involving either polyneuropathies (seven patients) or multifocal mononeuropathies (three patients). Electrophysiological studies and teased nerve fibre studies (in seven patients) allowed neuropathies to be classified as predominantly sensory axonopathies. Compared with HCV-negative (HCV -) patients, HCV-positive (HCV +) patients had a more pronounced and more widespread motor deficit; motor nerve conduction velocities in peroneal and median nerves were more impaired in HCV + patients, although significance was not reached except for the mean value of the amplitude of the compound muscle action potentials of the median nerves (P < 0.05); necrotising vasculitis was found in two of nine nerve biopsies from the HCV + patients studied and in none of the three HCV - patients. In addition, HCV + patients had more frequent cryoglobulin related cutaneous signs, higher aminotransferase and serum cryoglobulin concentrations, lower total haemolytic complement concentrations, and more frequent presence of rheumatoid factor. A liver biopsy performed in eight HCV + patients disclosed a range of lesions, from chronic active hepatitis (six patients) to persistent hepatitis (two patients). Lastly, treatment with interferon-alpha conducted over six months in two patients seemed to improve the peripheral neuropathy. CONCLUSIONS--Patients with peripheral neuropathy and essential mixed cryoglobulinaemia should be tested for anti-HCV antibodies to determine the appropriate treatment.     

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

Treatment of hepatitis C in HIV/hepatitis C co-infected patients: what is the evidence?

Before the advent of highly active antiretroviral therapy (HAART), the vast majority of HIV-infected patients died from AIDS-related diseases. But, amongst those with access to HAART, AIDS is no longer the leading cause of death. Instead, liver disease is fast becoming the commonest cause of death in HIV-infected patients, particularly in those who have a co-infection with hepatitis C (HCV). The four recent comparative trials of peginterferon and ribavirin in HIV/HCV coinfected patients have provided valuable new information about the most appropriate treatment of this difficult group of patients. As with HIV-negative patients, it is clear that peginterferon alpha has advantages over non-pegylated treatment, with superior efficacy, in the form of higher sustained virological responders and comparable safety. Discontinuation rates were higher than reported in HCV mono-infected patients but comparable for most treatment arms. Furthermore, in about half the patients, treatments were not stopped during the first months of treatment because of side effects, but due to non-early virological response.     

A pluridisciplinary point of view of hepatitis C virus infections

Various complementary actors are implied in the management of HCV infections: virologists, general practitioners, hepato-gastroenterologists and hospital residents, and they should all cooperate together. The role of biologist is crucial in assisting the practitioners in the choice of examinations to be prescribed for the diagnosis of HCV infections (search for RNA HCV), in establishing a prognosis and in deciding on the therapeutic strategy (genotyping, Fibrotest and Actitest). The role of the general practitioner is important at all stages of the management. The practitioner's involvement is also crucial in the recognition and follow-up of the concomitant diseases. THE ROLE OF THE SPECIALIST: The hepatologist, together with the general practitioner, are inseparable partners in the management of a patient suffering from hepatitis C. The specialist should only see patients exhibiting hepatitis C who are participating in a treatment program, since the indication for treatment is usually decided on by the specialist. The hepatologist should be informed of the various concomitant diseases and the treatments (replacement therapy or others) prescribed for them. CRUCIAL QUESTIONS: For the management of an HCV infection, in general 3 questions require an answer: who should be screened for such infections, what explorations should be performed in the case of positive serology and what follow-up is required during and after anti-HCV treatment?