Methods and timing of biliary drainage for acute cholangitis: Tokyo Guidelines

Biliary drainage is a radical method to relieve cholestasis, a cause of acute cholangitis, and takes a central part in the treatment of acute cholangitis. Emergent drainage is essential for severe cases, whereas patients with moderate and mild disease should also receive drainage as soon as possible if they do not respond to conservative treatment, and their condition has not improved. Biliary drainage can be achieved via three different routes/procedures: endoscopic, percutaneous transhepatic, and open methods. The clinical value of both endoscopic and percutaneous transhepatic drainage is well known. Endoscopic drainage is associated with a low morbidity rate and shorter duration of hospitalization; therefore, this approach is advocated whenever it is applicable. In endoscopic drainage, either endoscopic nasobiliary drainage (ENBD) or tube stent placement can be used. There is no significant difference in the success rate, effectiveness, and morbidity between the two procedures. The decision to perform endoscopic sphincterotomy (EST) is made based on the patient’s condition and the number and diameter of common bile duct stones. Open drainage, on the other hand, should be applied only in patients for whom endoscopic or percutaneous transhepatic drainage is contraindicated or has not been successfully performed. Cholecystectomy is recommended in patients with gallbladder stones, following the resolution of acute cholangitis with medical treatment, unless the patient has poor operative risk factors or declines surgery

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12

Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether, 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X-linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS.Peer reviewe

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

Setorectomia posterior direita laparoscópica no tratamento dos tumores hepáticos Laparoscopic right posterior sectioniectomy for treating hepatic tumors

INTRODUÇÃO: A ressecção de neoplasias no setor posterior direito costuma ser um desafio técnico pela dificuldade de sua abordagem. Adicionalmente, as hepatectomias laparoscópicas tem se tornado alternativa interessante em virtude de muitas vantagens (baixa morbidade, curto tempo de internação, retorno precoce as atividades laborais e bons resultados cosméticos). OBJETIVO: Relatar experiência em doentes submetidos à setorectomia posterior direita laparoscópica por uma única equipe. MÉTODOS: Cinco doentes foram operados entre novembro de 2008 a agosto de 2010. A idade variou de 21 a 63 anos com mediana de 43 anos. Foram quatro mulheres e um homem. A causa das neoplasias foi: adenoma (n=2), hepatocarcinoma (n=1) e metástases (n=2). A lesão foi solitária em três casos (60 %). A média do tamanho das lesões foi 3,3 cm (1,8-5). Foram analisados: tempo cirúrgico, sangramento operatório, morbimortalidade, tempo de internação e tempo de retorno à atividade habitual. RESULTADOS: A média de tempo cirúrgico foi de 160 minutos (90-260). A de sangramento intra-operatório foi de 200 ml (0-500). Nenhum doente foi transfundido. Não houve mortalidade e a morbidade foi nula. A mediana de internação foi de três dias (2-5). A mediana de retorno às atividades cotidianas foi de 12 dias (7-20). A mediana de seguimento foi de 13 meses (1-20). Não houve recidiva de lesão. CONCLUSÃO: A setorectomia posterior direita laparoscópica representa boa opção tática para o tratamento dos tumores hepáticos situados no setor posterior do lobo direito. É opção segura que evita grandes incisões com morbimortalidade. Também apresenta bom resultado cosmético e retorno precoce ao trabalho.<br>BACKGROUND: Resection of neoplasms arising in the posterior right sector is usually a technical challenge due to approach difficulties. Additionally, laparoscopic hepatectomy has become an interesting alternative with several advantages (low morbidity, short hospital stay, early return work activities and good cosmetic results). AIM: To report a series of patients who underwent laparoscopic right posterior sectioniectomy performed by a single surgical team. METHODS: Five patients were operated. Their ages ranged from 21 to 63 years (median 43 years). There were four women and one man. Etiology of the neoplasm was: adenoma (n=2), hepatocellular carcinoma (n=1) and metastasis (n=2). There was a single lesion in three cases (60 %). The mean lesion diameter was 3,3 cm (1,8-5). It was analyzed: operative time, intraoperative bleeding, morbidity, length of stay and time of return to usual activity. RESULTS: The mean surgical time was 160 minutes (90-260). The mean intraoperative blood loss was 200 ml (0-500). None of the patients received transfusions. There was no mortality and no morbidity. The median hospital stay was three days (2-5). The median length of time taken to return to day-to-day activities was 12 days (7-20). The median follow-up period was 13 months (1-20). There was no tumor recurrence. CONCLUSION: Laparoscopic right posterior sectioniectomy (bi-segmentectomy VI + VII) is a good option to treat hepatic tumors located in the posterior sector of the right lobe. It is a safe procedure that avoids large incisions with no mortality or morbidity is this series. This approach also bring good cosmetic result and early return to work