Fluoroscopy-guided shaped endobiliary biopsy at endoscopic retrograde cholangiography can accurately diagnose biliary neoplasia: Results from a large cohort.

Background and study aims The sensitivity of using standard endobiliary forceps biopsy to diagnose neoplastic biliary lesions remains low. We have developed a unique biopsy approach, termed fluoroscopy-guided, shaped endobiliary biopsy (FSEB), in which the biopsy forceps are modified to improve diagnostic yield. In this study, we evaluate the diagnostic characteristics of FSEB for endobiliary lesions at endoscopic retrograde cholangiography (ERC). Patients and methods Consecutive patients undergoing FSEB between 1/2001 and 12/2014 were retrospectively enrolled. The identification of neoplastic lesions with FSEB, was the primary endpoint. The gold standard of neoplasia was histopathology, cytology or surgical histopathology. The benign cases were followed up for one year. Results A total of 204 patients undergoing 250 biopsy sessions by FSEB were analyzed. Per-patient analysis was performed and FSEB showed 81.1 % sensitivity and 88.2 % accuracy. FSEB detection of proximal biliary lesions was more sensitive (91.1 % vs 73.2 %, P  < 0.01) and accurate (94.9 % vs 82.2 %, P  < 0.01) compared to distal lesions. No complications from FSEB were reported. Conclusions FSEB shows high accuracy for diagnosis of neoplasia in biliary strictures, especially for proximal lesions. Future prospective randomized controlled studies are merited to further validate the role of FSEB as the first-line sampling tool for evaluation of biliary neoplasm.

Animal models and cell lines of pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs), also known as islet cell tumors, are mostly indolent neoplasms that probably arise from a network of endocrine cells that includes islet cells and pluripotent precursors in the pancreatic ductal epithelium. The incidence and prevalence of PNETs continue to rise in recent years because of more sensitive detection. The molecular pathogenesis, early detection, molecular predictors of tumor behavior, and targeted drug therapy of PNETs are not well understood and require additional basic and translational research. The rarity and indolent nature of these tumors, difficulty of access to appropriate patient tissue samples, and varying histopathology and secreted hormones pose particular challenges to PNET researchers. Animal models and cell lines are indispensable tools for investigating the pathogenesis, pathophysiology, mechanisms for tumor invasion and metastasis, and therapeutics of PNETs. This review summarizes currently available animal models and cell lines of PNETs, which have provided valuable insights into the pathogenesis and natural history of human PNETs. In the future, animal models and cell lines of PNETs should also be used to study early tumor detection and molecular predictors of tumor behavior and to test the responses to, and mechanisms for, novel targeted drug therapies.

Uses of probe-based confocal laser endomicroscopy: responses to a question to practitioners.

Confocal laser endomicroscopy is a novel imaging technology, which allows real-time visualization and interpretation of microscopic details in live tissues. Although several potential uses have been identified for this technology, no data are available regarding its real-world uses. We report the results of an email-based survey of experts in North America regarding their use of the technology.

Combination Therapy for Chronic Hepatitis B: Current Indications.

Hepatitis B infection remains a major public health problem globally and in the United States, with significant use of healthcare resources. Several therapeutic agents active against viral and host targets are currently available for its treatment. The success of combination therapy in HIV infection, which has similarities to hepatitis B in both therapeutic targets and treatment options, stimulated studies on the efficacy and safety of various combinations of available drugs in the treatment of hepatitis B infection. In this review, we analyze the current role of combination therapy in chronic hepatitis B infection.

Sudden deaths following the unexpected demise of a popular politician in India.

The recent death of a popular politician in India was followed by a spate of sudden deaths. In this letter, we analyze the deaths as reported in newspapers, and try to arrive at a reason for this strange phenomenon.

Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings.

BACKGROUND: Despite the advent and increasingly wide availability of antiretroviral therapy, cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with HIV infection in resource-limited settings. The ideal management of CM remains unclear. The aim of this review is to assess the evidence for deciding on which antifungal regimen to use as well as other modalities of management to utilise especially resource poor settings in order to achieve the best possible outcome and enable an individual with CM to survive their acute illness and benefit from antiretroviral therapy. OBJECTIVES: To determine the most effective initial and consolidation treatment strategy for CM in HIV infected adults. SEARCH STRATEGY: The Cochrane HIV/AIDS group search strategy was used. Key words in the search included, meningitis, cryptococcus neoformans, treatment, trial, human immunodeficiency virus, acquired immunodeficiency syndrome, antifungal agents, amphotericin, flucytosine, fluconazole, azole, lumbar puncture, cerebrospinal fluid (CSF) pressure and acetazolamide. SELECTION CRITERIA: Randomised of HIV-infected adults with a first episode of CM diagnosed on CSF examination, by India ink staining, CSF culture or cryptococcal antigen testing. DATA COLLECTION AND ANALYSIS: Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software. MAIN RESULTS: Six studies are included in the review. Five of the studies compared antifungal treatments and one study addressed lowering intracranial pressure. This study was stopped early due to excess adverse effects. The results of the other five studies as summarised as follows.Mayanja-Kizza 1998 compared fluconazole to fluconazole with 5 flucytosine. The dose of fluconazole used 200mg initially is lower than the recommended initial dose of 400mg. No survival advantage was found with the use of 5 flucytosine in addition to fluconazole.Two studies Brouwer 2004 and van der Horst 1997 compared Amphotericin (AmB) to AmB with 5 flucytosine. Both drugs were given at currently recommended doses for 2 weeks. No survival difference was found at 14 days or at 10 weeks (only recorded in Brouwer 2004). There were significantly more patients with sterile CSF cultures at 14 days in the group that received AmB with flucytosine.Brouwer 2004 compared AmB given alone to AmB given with flucytosine and fluconazole alone or in combination. This was a small study and no differences in mortality were noted between the groups.Bicanic 2008 compared high to standard dose AmB both with flucytosine. There was no difference in mortality between the two groups or adverse events.Leenders 1997 compared standard AmB to liposomal AmB. There was no difference in death rates between the two groups. But there were significantly fewer side effects in the group treated with liposomal AmB. AUTHORS' CONCLUSIONS: The main aim of this review was to determine the best treatment for cryptococcal meningitis in resource-limited settings. In these settings usually only AmB and fluconazole are available. No studies suitable for inclusion in the review were found that compared these two drugs. Therefore we are unable to recommend either treatment as superior to the other. The recommended treatment for CM is a combination of AmB and flucytosine. The optimal dosing of AmB remains unclear. Liposomal AmB is associated with less adverse events than AmB and may be useful in selected patients where resources allow.Future research into the management of cryptococcal meningitis in resource-limited settings should focus on the most effective use of medications that are available in these settings.Flucytosine in combination with AmB leads to faster and increased sterilisation of CSF compared to using AmB alone. As Flucytosine is often not available in developing countries, policy makers and national departments of heath should consider procuring this drug for HIV treatment programmes.

Factors associated with candiduria and related mortality.

BACKGROUND: Although candiduria and bacteriuria have many attributes in common, little data is available regarding factors associated specifically with candiduria. Despite the high mortality in subjects with candiduria, factors associated with such mortality have not been studied. METHODS: We undertook a single-center case-control study to evaluate factors associated with candiduria over a 10.5 month period. Cases and controls were prospectively recruited from hospitalized subjects with candiduria and bacteriuria, respectively. A subgroup analysis was performed to identify factors associated with mortality following candiduria. RESULTS: Among 145 subjects with candiduria, Candida tropicalis (30.5%) and other non-albicans species accounted for 71% of isolates. Among them, clinical characteristics and associations were studied among 80 hospitalized subjects. Prior antimicrobial use was documented in 92% with candiduria, with cephalosporins used most commonly. Independent associations with candiduria were demonstrated for use of antimicrobial agents in the preceding 30 days (odds ratio (OR) 8.1; 95% confidence interval (CI) 2.1-31.9) and plasma glucose > 180 mg/dL (OR 3.1; 95% CI 1.1-9.1). Death occurred among 21 (26.2%) subjects with candiduria. Factors associated with death included use of urinary diversion devices (OR 8.8; 95% CI 1.1-70.5), > or = 2 classes of antimicrobials (OR 4.1; 95% CI 1.2-13.9), intensive care (OR 3.3; 95% CI 1.1-9.3), and renal failure (OR 2.9; 95% CI 1.1-8.2). CONCLUSIONS: Many risk factors traditionally linked to candiduria may be associated with urinary tract infections in general. Factors which predicted occurrence of candiduria, as opposed to bacteriuria, included prior use of antimicrobial agents and elevated plasma glucose. Since factors found to have associations with death in candiduria were those expected in seriously ill patients, the high mortality may be a function of the severity of underlying diseases.

An outbreak of cadaver-acquired chickenpox in a health care setting.

The varicella-zoster virus (the chickenpox virus) is highly infectious and may affect nonimmune health care professionals. We report an outbreak of chickenpox in our hospital in which the source of infection was a cadaver. The spread of infection occurred in the course of an autopsy.