Secondary sclerosing cholangitis following major burn.

BACKGROUND AND AIMS: Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a relatively new previously unrecognized entity which may lead to severe biliary disease with rapid progression to cirrhosis. We present for the first time a case series of patients with rapidly progressive SSC-CIP requiring aggressive intensive care treatment following major burn injury. RESULTS: SSC-CIP was diagnosed in 4 consecutive patients hospitalized due to major burn injuries at our Intensive Care Unit (ICU). SSC-CIP was diagnosed when ERCP (n = 1) or MRCP (n = 3) demonstrated irregular intrahepatic bile ducts with multiple strictures and dilatations and, when a liver biopsy (n = 3) demonstrated severe cholestasis and bile duct damage. All patients were males; none of whom had pre-existing liver disease. Ages: 18-56 y. All patients suffered from severe (grade 2-3) burn injuries with total burn surface area ranging from 35 to 95%. Mean length of ICU hospitalization was 129.2 ± 53.0 days. All patients required mechanical ventilation (with a mean PEEP of 8.4 ± 2.1 cm H2O) and the administration of catecholamines for hemodynamic stabilization. All patients demonstrated severe cholestasis. Blood cultures and cultures from drained liver abscesses grew hospital acquired multiple resistant bacteria. Liver cirrhosis developed within 12 months. One patient underwent orthotopic liver transplantation. Two patients (50%) died. In conclusion, SSC-CIP following major burn injury is a rapidly progressive disease with a poor outcome. Liver cirrhosis developed rapidly. Awareness of this grave complication is needed for prompt diagnosis and considerations of a liver transplantation.

Novel targeted therapies in head and neck cancer.

INTRODUCTION: Molecularly targeted therapy, with the potential for increased selectivity and fewer adverse effects, hold promise in the treatment of HNSCC. AREAS COVERED: Targeted agents for HNSCC expected to improve the effectiveness of current therapy including HER family, Src-family kinase, cell cycle, MET, AKT, HDAC, PARP, COX inhibitors and antiangiogenesis. EXPERT OPINION: Epidermal growth factor receptor inhibitors are established in HNSCC and the need now is to find biomarkers for sensitivity to better select patients. Moreover, other pathway inhibitors hold significant promise and are being tested in clinical trials. Angiogenesis inhibition is likely to yield only modest efficacy alone but may augment existing standards. Lastly, one clinical arena where targeted therapies may find secure purchase is in the adjuvant or prevention setting where minimal or preneoplastic disease can be affected by inhibition of a single or few targets.

Role of molecular markers in the management of head and neck cancers.

PURPOSE OF REVIEW: Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide. Despite advances in treatment, the prognosis remains poor. HNSCC comprise a wide spectrum of neoplasms with different tumor biologies, prognosis and response to therapies. Current tumor classification is based on morphology and anatomic distribution, which leads to a homogeneous treatment for different diseases. Moreover, traditional diagnostic methods such as clinical assessment, histopathological examination, and imaging techniques are limited in their capacity to provide information on prognosis and decision making. RECENT FINDINGS: Molecular markers have increased the understanding of the pathogenesis of head and neck cancer because they give increasing insight into tumor biology, prognosis, and response to therapy. The practical application of these discoveries is beginning to assist greatly in the evaluation and treatment of HNSCC to achieve a more personalized and effective approach. SUMMARY: This article focuses on the molecular markers that have already been extensively studied such as epidermal growth factor receptor and human papillomavirus as well as those that offer potential for personalized therapy such as HIF-1 and ERCC-1. The ideal biomarker should be assayed accurately and easily, highly specific, and cost effective. Thus, a validation is required before their implementation into clinical guidelines.