Treatment of hepatitis C: critical appraisal of the evidence

Chronic hepatitis C virus infection is currently the most common cause of end stage liver disease worldwide. Although the conclusions of the last National Institutes of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues remain unanswered. This paper reviews the available data using an evidence-based approach. Current evidence is sufficient to recommend IFN treatment for all patients with acute hepatitis. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during month 1 is the best treatment option. The current gold standard of efficacy for treatment-naive patients with chronic hepatitis C is the combination of pegylated IFN and ribavirin. The overall sustained viral response rate to these regimens is 54 - 56% following a 48-week course of therapy. Patients with genotype 1 infection will have a 42 - 51% likelihood of response to 48weeks of therapy. Those with genotypes 2 or 3 infection will respond to 24weeks in 78 - 82% of cases. Debate continues regarding the optimal dose and duration of peginterferon (PEG-IFN), not only in patients infected with genotype 2 or 3 but also in those infected with genotype 1. The optimal dose of ribavirin has yet to be determined. Available data show the need to give the highest tolerable doses (1000-1200mg/day) to the difficult-to-treat patients (genotype 1, cirrhotics, obese), although there is a greater likelihood of intolerance. Genotypes 2 and 3 may receive 800mg/day, which is also the most appropriate lower dose for those patients who require dosage modification for anaemia or other side effects. Tolerability and compliance to therapy are still a problem, as approximately 15- 20% of patients within trials and > 25% in clinical practice withdraw from therapy. New PEG-IFNs are more effective than conventional IFN in improving liver histology. Monotherapy with PEG-IFN induces a marked reduction in staging in virological sustained responders, and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48weeks of treatment. The use of maintenance therapy in virological nonresponders aiming to improve histology should be considered experimental and of unproven benefit. Pooling data from the literature suggests a slight preventive effect of IFN on hepatocellular carcinoma development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit may be due to spurious associations. The preventive effect is more evident among sustained responders to IFN

Combined hepatectomy and radiofrequency ablation for multifocal hepatocellular carcinoma: a case report

Introduction: At the present time, the best possible choice for the local management of a multifocal hepatocellular carcinoma (HCC) developing on liver cirrhosis is multimodal treatment of the disease. Combined approach based on simultaneous radiofrequency ablation (RFA) together with limited surgical resection represents a valid choice of treatment. Case presentation: A 75-year-old white female patient affected of HCV-associated cirrhosis in BChild-Pugh\u2019s functional class A5, developed a bifocal HCC. The patient had undergone a limited surgical resection together with simultaneous RFA, without intraoperative and postoperative surgical complications. At 36 months after surgery, still shows no sign of disease relapse. Conclusion: This strategy directed at the management of multifocal HCC, may prove more useful for the reduction of surgical risk and post-operative progression of the liver cirrhosis than large-scale hepatectomy, since it presents no peri-operative mortality and a complication rate of less than 10%

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Le "droghe cardiache" nel succedersi dei secoli.

Plants were the first medicines used by men. From the 16th to the 18th century, the unavailability of medicines having a sure therapeutic effect was the cause of a high death rate, even in the cardiological field. As a consequence of this, the researchers of the 19th century focused their studies and research on same plants, that were considered having therapeutic effects on some cardiac pathologies. The results of the studies of the 19th century are still the starting point for new research about cardiac therapeutic medicines. In this paper the authors explain the main historical events concerning the medicines used in cardiology, from ancient times to the dawn of our times

An evaluation score of the difficulty of thyroidectomy considering operating time and preservation of recurrent laryngeal nerve

The purpose of this study was to edit a renovated thyroidectomy difficulty scale (rTDS) in order to identify underlying thyroid diseases with a longer operative time and higher technical difficulty, also considering preservation of recurrent laryngeal nerve. We developed a renovated scale with a maximum score of 20 points by creating a form in which five variables were considered: vascularity, friability, mobility/fibrosis, gland size and difficulty in preservation of the recurrent laryngeal nerve. Two surgeons separately evaluated each of these. Through a simple linear regression analysis, we have analyzed the relationship between rTDS score and operative times, and between rTDS score and preservation of recurrent nerve. Eventually, Spearman’s rank correlation coefficient has been used in order to evaluate our double-blind study. Our cohort included 131 patients undergoing total thyroidectomy. The mean of the rTDS was 9.00 ± 3.67 for Surgeon A and 8.31 ± 3.42 for Surgeon B, with Spearman’s rank correlation coefficient between surgeons of 0.85 (p < 0.0001). We have shown that the rTDS score significantly influences the operating times (R2 = 0.44 for surgeon A, R2 = 0.46 for B, p < 0.0001 for both). Moreover, we can say that the rTDS score significantly influences preservation of the recurrent nerve (R2 = 0.37, Beta 0.61, 8.84 t test, p < 0.0001). Our rTDS is a useful tool and, thanks to it, we identified hyperthyroidism and goiter as the hardest underlying disease for surgery. Thus our scale could change operative approach, resulting in better surgeries’ scheduling and identification of pathologies that require higher attention

I MOMENTI STORICI DI UNA FREQUENTE PATOLOGIA ANALE: LE EMORROIDI

In this report the authors outline the main historical aspects of haemorrhoids after a thorough review of the literature. The first texts concerning haemorrhoids are the ancient Egyptian papyruses. The twenty centuries of the history of haemorrhoids are marked by multiple pathogenetic theories, and of these the vascular and the sliding of the anal mucosa are still valid. From an analysis of the historical texts and the most recent publications, we deduce that the principles of therapy are substantially unchanged since the days of Hippocrates. In conclusion, we can say that, as in ancient times, the therapy of haemorrhoids is based on three fundamental approaches: surgical treatment, ambulatorial non-surgical treatment and medical treatment