Is there a role for cholangioscopy in patients with primary sclerosing cholangitis?

OBJECTIVES: Assess the role of cholangioscopy in primary sclerosing cholangitis for 1) detection of cholangiocarcinoma using cholangioscopy-assisted biopsy 2) detection of stones not seen on cholangiography 3) stone removal with cholangioscopy-directed lithotripsy. METHODS: Prospective cohort of consecutive patients referred for cholangioscopy to evaluate dominant strictures or stones. A data collection sheet was employed. Follow-up was by chart review/phone contact. Clinical improvement was defined as resolution of jaundice or > or =50% reduction in pain or cholangitis episodes requiring hospitalization. RESULTS: 41 patients (30M, 11F) had 60 cholangioscopy procedures (55 per oral, 5 percutaneous). 33/41 (80%) patients underwent 44 tissue sampling events. Histology: positive for extrahepatic cholangiocarcinoma (N = 1), negative/atypical (N = 31), and inadequate (N = 1). Stones were found in 23/41 (56%) patients, of which 7/23 (30%) were missed on cholangiography and detected only by cholangioscopy. 9/23 (39%) underwent cholangioscopy-directed lithotripsy. Stone clearance: complete (N = 10, 7 by cholangioscopy-directed lithotripsy after failed conventional stone extraction); partial (N = 7); and not attempted (N = 6). Median follow-up was 17.0 months (range 1-56). Clinical improvement was achieved in 25/40 (63%). Eight patients have undergone transplant and cholangiocarcinoma was present in the explant of two at 1 and 12 months post-cholangioscopy, respectively. CONCLUSIONS: This is the first series of patients with primary sclerosing cholangitis undergoing cholangioscopy for the evaluation of dominant strictures and cholangioscopy-directed stone therapy with demonstrable clinical benefits. Stones detected by cholangioscopy were missed by cholangiography in nearly one of three patients. Cholangioscopy-directed lithotripsy may be superior to conventional ERCP for achieving complete stone clearance. Despite the use of cholangioscopy, diagnosis of cholangiocarcinoma remains technically challenging.     

Is there a role for antiarrhythmic drugs in patients with implantable defibrillators?

With remarkable advancement in technology and clinical research, implantable cardioverter defibrillators (ICDs) have replaced antiarrhythmic drugs as the preferred modality for both primary and secondary prevention of arrhythmic deaths. However, concomitant use of antiarrhythmics in patients with ICDs remains common, often for prevention or reduction of appropriate and inappropriate shocks caused by ventricular and supraventricular arrhythmias, respectively. The role of empiric antiarrhythmic therapy in this patient population remains less clearly defined, with conflicting information from various small randomized trials. Use of antiarrhythmic drugs in the ICD patient population not only can cause potentially serious side effects but can also interact or interfere with the ICD device function. In addition, the effect on survival in patients with ICDs is not well characterized. Given the many potential side effects, drug-device interactions, unclear survival effect, and lack of convincing clinical data supporting its use, empiric antiarrhythmic therapy in the ICD patient population cannot be recommended at this time.     

Is there still a role for radiotherapy in acromegaly?

External radiotherapy (ideally 3-field radiotherapy with a daily fractional dose no higher than 1.8 Gy or conformal irradiation) has been used extensively in the treatment of acromegaly, and virtually all studies have documented a predictable but slow reduction in growth hormone (GH) excess, which is at its maximum in the first year after treatment (30-50%) and continues at an average rate of 10-15% thereafter in the long term. Therefore, achievement of 'safe' GH concentrations in an acceptable time interval after radiotherapy will be realized only in those patients who have lower GH concentrations prior to irradiation either as a result of mild disease or previous surgery. Recent studies have demonstrated the value of stereotactic radiotherapy (either as multiple arc X-irradiation or as 'gamma knife' therapy) in the post-surgical treatment of acromegaly or as salvage therapy for disease persisting after conventional external irradiation. The development of potent medical therapies for acromegaly (somatostatin analogues and the GH receptor antagonist) has called into question the role of radiotherapy in the treatment of this disease. However, even if the concept of primary, open-ended medical therapy for selected patients is accepted, reference to the success rates of surgery and response rates to somatostatin analogues indicates that approximately 10-20% of all patients with acromegaly will require consideration of radiotherapy for hormonal or tumour mass control. For these reasons, radiotherapy (both conventional external and stereotactic irradiation) continues to have a major role in controlling acromegaly in selected patients.     

Is there a role for maintaining sinus rhythm in patients with atrial fibrillation?

Recent studies have indicated that outcomes in patients with atrial fibrillation who are managed with rate control and anticoagulation are similar to those in patients who have maintenance of sinus rhythm. These studies did not include important groups of patients with atrial fibrillation in whom antiarrhythmic therapy may be appropriate. This perspective argues for the maintenance of sinus rhythm and for the use of antiarrhythmic therapy that includes medications, invasive procedures, and a combination of both in appropriate patients.     

Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome?

Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity and mortality, because of the underlying tumor and the sequelae of severe hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory. Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have somatostatin receptors. While this suggests that somatostatin analogs may reduce ACTH production and treat patients with EAS, the therapeutic role of these agents is still evolving. Here we demonstrate the spectrum of responses to octreotide therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide scan did not predict the therapeutic response to octreotide. Two patients with positive somatostatin receptor scintigraphy failed to respond to octreotide, while one with a negative scan reached eucortisolemia on a maintenance dose of 75 microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that octreotide is not a first line agent to control hypercortisolemia but may be a useful agent when other inhibitors of steroidogenesis fail or parenteral administration is required. Before therapy an octreotide challenge test may predict therapeutic response. Cortisol levels should be monitored regularly on somatostatin analog therapy, because of its unpredictable long-term pharmacodynamic profile.     

Is there still a role for cardiac autopsy in 2007?

Concerns have emerged in recent years with regard to the role to be played by the pathologist in reaching a final diagnosis. When considering the field of the congenitally malformed heart, it is true that the richness of detail now provided by imaging techniques is truly amazing. Alongside these developments, there has also been a significant decline in the number of autopsies performed in tertiary medial centres around the World. In this review, we consider some of the factors that have contributed to this decrease in autopsies, and review the reasons why strong steps should be taken to reverse this trend. When considering the reasons for the decline in autopsies, there can be little doubt that the scandal devolving on inappropriate retention of organs, which came to light in the United Kingdom, but which had reverberations throughout the World, contributed in no small way to the reticence of families to grant appropriate permission to conduct a post-mortem examination. It is sincerely hoped that the changes in practise that followed these revelations will stop, and indeed reverse, this unfortunate decline. The inappropriate retention of organs came into the public domain in an attempt to emphasise the value of the autopsy in clinical practise, research, and education. All of these good reasons for performing the autopsy remain. From the stance of education, we emphasise the importance of retaining existing archives, which have long since proved their value. From the stance of improving clinical practise, we reiterate that the attitude of the morphologist, working side-by-side with the clinician or surgeon, has always been fundamental in expanding this aspect of knowledge. We recognise, nonetheless, that performance of the autopsy still carries financial considerations. In this respect, when considering the congenitally malformed heart, we stress the option of having the pathologist working in harness with an experienced cardiac morphologist, or alternatively with a properly trained pathologist's assistant. In terms of training, we show how, with the advantage of a few simple rules, it becomes an easy matter to describe and analyse the congenitally malformed heart. Thereafter, having reviewed means of increasing the number of autopsies, and discussing new techniques, we complete our review with a detailed account of the fetal, perinatal, and paediatric autopsy in the patients with a congenitally malformed heart, taking particular account of the role to be played by the properly trained pathologist's assistant.     

Is there a role for adaptive immunity in nonalcoholic steatohepatitis?

The growing diffusion of nonalcoholic fatty liver disease (NAFLD) is a consequence of the worldwide increase in the prevalence of obesity. Oxidative stress is widely recognized to play a pivotal role in NAFLD evolution to nonalcoholic steatohepatitis (NASH). Here we review recent evidence suggesting that oxidative stress-derived antigens originating within fatty livers stimulate both humoral and cellular adaptive immune responses and the possible mechanisms involved in sustaining hepatic inflammation in NASH.     

Is there a role for polyenes in treating invasive mycoses?

PURPOSE OF REVIEW: This is a clinical review on the current role of polyene antifungals in the treatment of invasive fungal infections. It is timely and relevant because the number of new antifungals being developed has never been greater than today. In addition to re-examining the landmark clinical trials of the past, the more recent findings are put into perspective. The past year has been particularly rich in clinical trials. RECENT FINDINGS: The main topics of this review are invasive candidiasis, invasive aspergillosis, and the so-called rare fungal infections: zygomycosis, fusariosis, cryptococcosis and histoplasmosis. SUMMARY: Practical implications of the recent developments are the almost complete replacement of amphotericin B deoxycholate by lipid-based formulations; antifungal efficacy without compromising safety; and treatment choices for infections previously considered untreatable.     

Is there a role for decision aids in cancer-related decisions?

Cancer-related decisions are challenging, requiring patients to evaluate associated medical and psychological outcomes within the context of their personal values. In response, a number of decisional support tools have been developed. Clinical decision aids are decisional support tools designed to facilitate patient-driven decision-making by providing relevant information on the options while eliciting and incorporating patient preferences; they have been designed to support decision-making in the prevention, screening, and treatment of cancer. The development begins with identification of an appropriate clinical problem, followed by needs assessment to determine content and optimal methods of data presentation. Because implementation of a decision aid requires time and financial commitment, its efficacy in improving the quality of patients' decisions must be evaluated. In randomized controlled trials, cancer-related decision aids have been shown to increase patients' knowledge regarding their disease, and may facilitate patients playing a more active role in decision-making. Some studies suggest less decisional conflict and improved satisfaction with decision-making as a result. Whether use of a decision aid impacts the actual decisions made by patients, however, is less evident.     

Is there a role for anti-CD20 antibodies in CLL?

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Is there a role for glycosuria testing in sub-Saharan Africa?

BACKGROUND: With increasing urbanization and westernization, rates of diabetes in sub-Saharan Africa (sSA) are likely to rise. Early detection and intervention plays an important role in delaying development of complications. In sSA in particular there is need for an affordable, reliable, safe, feasible test to avert human suffering and exhausting already stressed health facilities. METHODS: Data from two large community-based studies were used to assess the value of glycosuria testing in the detection of diabetes in adults in a sub-Saharan country. A first study (A) tested participants for glycosuria by dipstick; if positive, fasting capillary glucose was measured. A later study (B) measured glucose concentration in venous blood 2 h after a 75-g glucose load; if glycaemia was > or = 10 mmol/l, urine was tested for glycosuria. RESULTS: The positive predictive value of glycosuria for a diagnosis of diabetes (fasting glucose > or = 6.7 mmol/l) was 48%. Sensitivity was 64% (57% if a 2-h-value > or = 10 mmol/l was used as gold standard). Sensitivity was higher among overweight and/or hypertensive subjects, among elderly people in the urban area, and among subjects with higher blood glucose levels. Extrapolated specificity was 99.7%, and the likelihood ratio 190. CONCLUSIONS: Glycosuria testing can identify a considerable number of undiagnosed diabetic patients when specially targeted at high-risk groups (obese, hypertensive, or elderly people). Dipstick glycosuria testing is an appropriate, safe, feasible test for sSA, where the prevalence of diabetes is expected to increase considerably in the near future.     

Is there a place for bone turnover markers in the assessment of osteoporosis and its treatment?

As populations age, the number of osteoporotic fractures will increase. Bone mineral density (BMD) measurement remains the major way to diagnose osteoporosis and to indicate therapy. The FRAX tool, based on clinical risk factors, estimates the 10-year risk of hip and major osteoporotic fractures. The association of BMD and FRAX measurements has improved the identification of patients who are most at risk. However, some patients can still be overlooked and denied therapy. It is sound that adding the measure of bone turnover markers to the former risk factors and their follow-up during therapy could best address the efficacy of treatment of osteoporosis. Whether this behavior is cost-effective remains to be settled.     

Atherosclerosis and restenosis: Is there a role for rage?

Diabetic vascular complications are a major cause of morbidity and mortality. Furthermore, such vascular disease is only incompletely explained by "traditional" risk factors in the nondiabetic complications. This situation has prompted the search for factors contributing to the pathogenesis of accelerated and more severe vascular disease in patients with diabetes. We review evidence that receptor for advanced glycation end products (RAGE), via its interaction with ligands, serves as a cofactor exacerbating diabetic vascular disease. RAGE is a member of the immunoglobulin superfamily of cell surface molecules with a diverse repertoire of ligands reminiscent of pattern recognition receptors. In the diabetic milieu, two classes of RAGE ligands, products of nonenzymatic glycoxidation and S100 proteins, appear to drive receptor-mediated cellular activation and, potentially, acceleration of vascular disease.