Interventional endoscopic therapy in chronic pancreatitis including temporary stenting: a definitive treatment?

OBJECTIVE: In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. MATERIAL AND METHODS: In 98 patients suffering from symptomatic CP (84 M, 14 F, 49+/-12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35+/-28 (8 days-111) months. All data were assessed retrospectively. RESULTS: As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3+/-1 (1 day-11) months. Total stent treatment time was 10+/-10 (6 days-49) months. At 46+/-27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. CONCLUSIONS:Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.     

Patent foramen ovale: conservative or surgical therapy?

Notwithstanding the difficulties in definitely confirming paradoxical embolism, the association between patent foramen ovale (PFO) and cryptogenic stroke has repeatedly been demonstrated in clinical studies. Moreover, the recurrence rate of cerebral ischemia in patients with PFO and an unexplained stroke was found to be 3-4% per year in two recently published series. With the exception of right atrial pressure elevation in the setting of major pulmonary embolism, a reliable risk stratification of patients with PFO based on clinical or echocardiographic findings is not yet possible. The presence of atrial septal aneurysm, a wide opening of the defect during the cardiac cycle and a large atrial shunt have been implicated as risk factors by some investigators. Long-term prevention of paradoxical embolism with oral anticoagulants seems to be of questionable benefit. Besides, these agents are poorly tolerated and carry the risk of significant or fatal bleeding at a rate of 2-5% per year. Surgery of the atrial septum has been performed for many decades in patients with atrial septal defect and evidence accumulates that it is a safe and highly effective procedure in patients with PFO. At present, surgical closure of the PFO appears to be the treatment of choice for secondary prevention of paradoxical embolism. However, further studies are needed to define the appropriate candidates for surgical treatment. Devices for catheter-based sealing of PFO are also available and are currently being evaluated in clinical trials. However, experience with their use remains confined to specialized centers. Furthermore, further technical improvements of these systems are needed in order to optimize successful delivery and positioning, increase their long-term stability, and reduce periprocedural complications.     

Optimal treatment of dyslipidemia in high-risk patients: intensive statin treatment or combination therapy?

A recent update to the National Cholesterol Education Program's Adult Treatment Panel III guidelines suggests low-density lipoprotein cholesterol (LDL-C) goals of <70 mg/dL in very-high-risk patients and <100 mg/dL in high-risk patients. Currently available 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are not equal in their ability to lower LDL-C, and it is unlikely that the substantial LDL-C reductions that are often needed in high-risk persons can be achieved with starting doses of some of the older statins. Possible alternatives in such cases include the use of high-dose statin therapy, a more efficacious statin, or combination therapy. Recent clinical data have demonstrated a greater likelihood of coronary heart disease event reduction with aggressive statin therapy that lowers LDL-C in a robust fashion (>30%-40%) than with moderate therapy. Until data from ongoing trials of combination therapy are available, however, monotherapy with a potent statin should be initiated to lower LDL-C. Nonetheless, for residual elevation in triglycerides and/or reduced high-density lipoprotein cholesterol, adding a second agent (eg, fenofibrate, niacin) is a reasonable option.     

Myocardial revascularization: surgery or stenting?

There is current debate regarding the relative merits and roles of surgical revascularization and percutaneous revascularization for patients with obstructive coronary artery disease. This article reviews the current literature relating to this subject.     

Directly administered antiretroviral therapy in the treatment of HIV infection: benefit or burden?

While combination antiretroviral treatment has had a profound impact on the morbidity and mortality of human immunodeficiency virus (HIV) infection, the adherence demands of this therapy are high and failure to maintain viral suppression is common. Directly administered antiretroviral therapy (DAART) has garnered attention recently as a strategy to improve medication adherence and clinical outcomes in HIV-infected individuals. This review is intended to provide an update on the use of DAART and the challenges posed by this strategy, explore settings in which DAART may be used, discuss the role of antiretroviral regimens with improved pharmacokinetic features, and propose future directions for DAART strategies. DAART is modeled on directly observed therapy (DOT) for the treatment of tuberculosis. However, differences in curability, medication dosing frequency, duration of treatment, and the biologic dynamics of infection, pose unique challenges to DAART strategies. Numerous settings have been proposed for DAART, including community based outreach programs, prisons, long-term care facilities, substance abuse treatment sites, and resource-poor countries. Experience with DAART to date has been limited to pilot studies or retrospective comparisons. The prospect of simplified, once-daily antiretroviral therapy holds promise for DAART. However, improvements in antiretroviral therapy may also improve outcomes in patients taking therapy on a self-administered basis. Randomized controlled trials of DAART are needed before this strategy can be embraced in any setting. In future studies it will be important to compare DAART with self-administered therapy in terms of initial virologic and immunologic responses, durability of responses, the development of antiretroviral resistance, and cost effectiveness.     

Helicobacter pylori treatment: is sequential or quadruple therapy the answer?

Clarithromycin resistance is a growing problem in many countries. Eradication rates for Helicobacter pylori have declined to unacceptable levels in recent years, in large measure because of clarithromycin resistance. Two treatment strategies (quadruple therapy and sequential therapy) are emerging as alternatives to triple therapy for the initial treatment of patients infected with H. pylori. Evidence shows that both quadruple therapy and sequential therapy are superior to triple therapy in patients with resistant strains of H. pylori. Studies that compare sequential and quadruple therapy are necessary and are awaited.     

Using white light during photodynamic therapy: visualization only or treatment?

BACKGROUND: Photodynamic therapy (PDT) involves selective uptake and retention of a photosensitizer in a tumor, followed by irradiation with light (usually a 630 nm diode laser), initiating tumor necrosis through formation of oxidized products or singlet oxygen. Successful PDT of early cancers of the esophagus and of Barrett's esophagus with severe dysplasia has been reported. However, side effects (edema, stricture, etc.) and treatment failure have been observed. This study aims to evaluate the possible photodynamic effect induced by illumination from the endoscope on the PDT effect, since a photon emitted to see the lesion can potentially be a photon to treat it! MATERIALS AND METHODS: Two fiber endoscopes (Olympus GIFPQ20 and Pentax FG34X) and one videoendoscope (Olympus GIFQ140) were evaluated. Output power, irradiance and emission spectrum were measured. Using the molar extinction coefficient of Photofrin and optical coefficients of the esophagus, the relative photodynamic reaction yield, determined as a function of depth, was compared with that obtained with a 630 nm diode laser. RESULTS: The irradiance at 1 and 2 cm was, respectively, 18.4 and 4.6 mW/cm (Pentax FG34X), 10.6 and 2.65 mW/cm (Olympus GIFPQ20), and 2.7 and 3.2 mW/cm (Olympus GIFQ140). The highest irradiance could lead to a relative photodynamic reaction yield at the surface of the esophagus similar to (Olympus GIFPQ20) or greater than (Pentax FG34X) that obtained using a diode laser alone. CONCLUSIONS: Our results could explain side effects sometimes observed when performing PDT. 'Endoscopic' illumination, however, could also represent an interesting alternative to the 630 nm diode laser. When using white light, superficial efficacy of PDT could be reinforced and transmural necrosis leading to perforation or stenoses reduced, since there is less red light in depth compared with a diode laser.     

CD40 in hepatocellular carcinoma: relevant or not?

The expression of the CD40 receptor in different tumours suggests that it might be involved in tumour development and proliferation. In this article, we discuss recent findings on CD40 expression in hepatocellular carcinoma, its possible biological role for tumour development, and different experimental therapeutic strategies such as gene therapy and immunotherapy protocols.     

Statin therapy in renal disease: Harmful or protective?

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit, if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.     

Osteoarthritis: can anti-cytokine therapy play a role in treatment?

Osteoarthritis (OA) is the most common joint disorder worldwide, and it has an enormous socioeconomic impact both in the United States and throughout the world. The degree of articular inflammation is usually associated with the disease’s progression, indicating that this process could contribute to articular damage. IL-1 beta and anti-TNF alpha are the two major cytokines players in the physiopathology of OA. Hence, we aimed to review the current literature on the effects of IL-1 and TNF-alpha neutralization as a new OA therapy. In vitro and experimental models showed a reduction in cartilage destruction with IL-1 inhibition therapy by IL-1 receptor antagonists (IL-1Ra). Despite this favorable evidence in animal models, studies on the inhibition of IL-1R in humans are still scarce. Although there is clear evidence that TNF-alpha plays a role in the pathophysiology of OA, only a few experimental trials have investigated the efficacy of blocking this pro-inflammatory cytokine in the treatment of OA. So far, the few studies available in humans using anti-TNF-alpha and IL-1 receptor antagonist are not remarkable, suggesting that further investigation and new therapeutic approaches are needed.