Biliary stent therapy for dominant strictures in patients affected by primary sclerosing cholangitis.

The diagnosis and the treatment of dominant strictures (DS) in patients with primary sclerosing cholangitis (PSC) is challenging and the scientific literature on the subject is quite limited. Only level II and level III evidence is available to guide physicians managing patients with DS and PSC. For the diagnosis, intraductal endoscopic ultrasound is the most sensitive (64%) and specific (95%) test. However, the majority of cases require a combination of several different diagnostic tests, as there is no single investigation that can rule out malignancy in this group of patients. For the treatment, serial endoscopic or percutaneous dilatations provide 1- and 3-year biliary duct patency in 80 and 60% of patients, respectively. Dilatation and stenting are the most common interventions, although the optimal duration of treatment has still not been clearly defined. Bile duct resection and/or bilioenteric bypass are currently indicated only for patients with preserved liver function. For all other patients, benign DS can be treated with endoscopic dilatation with short-term stenting. This approach is effective and safe and does not increase the risk of malignant transformation or complications for liver transplant candidates. During the last decade, the use of self-expandable metallic stents for benign diseases has become an innovative option. The aim of this article is to review the diagnostic and therapeutic strategies for patients affected by PSC and DS with specific emphasis on the outcomes of patients treated with temporary stents.

Meta-analysis of phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer.

OBJECTIVES: For patients with unresectable pancreatic cancer (PC), the efficacy and safety of molecular targeted agents (MTAs) in combination with gemcitabine are still unclear. Published randomized controlled trials (RCTs) have reported conflicting results. This study aimed to conduct a systematic review of the literature and to perform a meta-analysis if appropriate. METHODS: Seven electronic databases were searched using a standard technique to November 2011 without restriction on publication status or language. The primary aim was to assess overall survival (OS). Secondary aims were to assess progression-free survival (PFS), overall response rates (ORRs) and grade 3, 4 and 5 toxicities. A random-effects model was used for the meta-analysis. RESULTS: Seven Phase III RCTs were identified; 1981 patients were treated with MTAs and gemcitabine, and 1992 patients received gemcitabine with or without placebo. No statistically significant difference in OS was found between the two groups [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.85-1.02; P = 0.13]. The addition of MTAs improved PFS (HR = 0.86, 95% CI 0.79-0.93; P = 0.000) and ORR (odds ratio 1.35, 95% CI 1.05-1.74; P = 0.01). However, these benefits were accompanied by significantly higher toxicity (P = 0.001). CONCLUSIONS: The findings of this study suggest that the palliation of PC with gemcitabine and MTAs does not provide a significant survival benefit and is associated with increased grade 3 and 4 toxicities.

Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010.

Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.

Analytical review of diagnosis and treatment strategies for dominant bile duct strictures in patients with primary sclerosing cholangitis.

BACKGROUND: The diagnosis and treatment of indeterminate dominant strictures (DS) in patients with primary sclerosing cholangitis (PSC) is challenging and the literature on the subject is scarce. OBJECTIVES: This review aims to appraise and synthesize the evidence published in the English-language medical literature on this topic. METHODS: Scientific papers published from 1950 until week 4 of July 2010 were extracted from MEDLINE, Ovid Medline In-Process, the Cochrane Database of Systematic Reviews, the Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, EMBASE, PubMed and the National Library of Medicine Gateway. RESULTS: Strategies for the optimal management of DS in PSC patients are supported only by level II and III evidence. Intraductal endoscopic ultrasound appears to be the most sensitive (64%) and specific (95%) diagnostic test for the evaluation of DS in PSC. Endoscopic and percutaneous dilatations achieve 1- and 3-year palliation in 80% and 60% of patients, respectively. Although dilatation and stenting are the most common palliative interventions in DS, no randomized trials on the optimal duration of treatment have been conducted. CONCLUSIONS: In benign DS, endoscopic dilatation with short-term stenting seems to be effective and safe and does not increase the risks for malignant transformation or complications after liver transplantation. Surgical bile duct resection and/or bilioenteric bypass are indicated only in patients with preserved liver function.

Clinical epidemiological analysis of the mortality rate of liver transplant candidates living in rural areas.

MELD score has been used to predict 90-day mortality of subjects listed for liver transplantation (OLT). Validation of MELD score for patients on the waiting list in transplant programmes serving rural areas in North America is lacking. A retrospective cohort of patients affected by end-stage liver disease was studied to assess the mortality rate within 90 days after being listed at our transplant centre. Secondary aims were to identify differences between predicted and observed 90-days mortality using MELD and MELDNa scores at the time of listing. Among 126 patients included in this study, waiting list mortality was 35.0%. Ninety-day mortality was 21.1%, which was significantly greater than the mortality estimated by the MELD (9.1%, 95% CI: 6.6-11.5) and MELDNa (9.3%, 95%CI: 6.0-12.5). Despite this underestimation, AUC for MELD and MELDNa was 0.80 and 0.78 respectively. In our study, independent predictors of waiting list mortality were age, diagnosis of cholestatic disease and residence over 500 km from our transplant centre. MELD and MELDNa underestimated the 90-day mortality in patients with liver failure living in rural areas. Validation of these models should be performed in other transplant centres serving patients with limited access to specialized services.