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Background and objective The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary. Methods A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained. Results The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images. Conclusions This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.

Cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14th most common cause of death worldwide but fourth in central Europe. Increasingly, cirrhosis has been seen to be not a single disease entity, but one that can be subclassified into distinct clinical prognostic stages, with 1-year mortality ranging from 1% to 57% depending on the stage. We review the current understanding of cirrhosis as a dynamic process and outline current therapeutic options for prevention and treatment of complications of cirrhosis, on the basis of the subclassification in clinical stages. The new concept in management of patients with cirrhosis should be prevention and early intervention to stabilise disease progression and to avoid or delay clinical decompensation and the need for liver transplantation. The challenge in the 21st century is to prevent the need for liver transplantation in as many patients with cirrhosis as possible.

Acute liver failure is a rare but life-threatening critical illness requiring intensive care. This article reviews common causes, diagnostic approaches, and therapeutic interventions. Acute liver failure is a rare but life-threatening critical illness that occurs most often in patients who do not have preexisting liver disease. With an incidence of fewer than 10 cases per million persons per year in the developed world, acute liver failure is seen most commonly in previously healthy adults in their 30s and presents unique challenges in clinical management. The clinical presentation usually includes hepatic dysfunction, abnormal liver biochemical values, and coagulopathy; encephalopathy may develop, with multiorgan failure and death occurring in up to half the cases (Figure 1). 1 – 3 The rarity of acute liver failure, along with . . .

Cancer of the pancreas is predominantly adenocarcinoma and involves activating KRAS mutations in the large majority of cases. Surgical resection can be effective in localized disease; combination chemotherapy offers some palliation in advanced disease. Pancreatic ductal adenocarcinoma is the most lethal common cancer because it is usually diagnosed at an advanced stage and is resistant to therapy. In this article, we review current understanding of the biology and treatment of pancreatic adenocarcinoma. Epidemiology and Risk Factors Pancreatic adenocarcinoma is rarely diagnosed in persons younger than 40 years of age, and the median age at diagnosis is 71 years. Worldwide, the incidence of all types of pancreatic cancer (85% of which are adenocarcinomas) ranges from 1 to 10 cases per 100,000 people, is generally higher in developed countries and among men, and has remained stable . . .

In this randomized trial involving patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy. In patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy. Acute pancreatitis is the third most common gastrointestinal disorder requiring hospitalization in the United States, with annual costs exceeding $2 billion. 1 , 2 Necrotizing pancreatitis, which is associated with an 8 to 39% rate of death, develops in approximately 20% of patients. 3 The major cause of death, next to early organ failure, is secondary infection of pancreatic or peripancreatic necrotic tissue, leading to sepsis and multiple organ failure. 4 Secondary infection of necrotic tissue in patients with necrotizing pancreatitis is virtually always an indication for intervention. 3 , 5 – 7 The traditional approach to the treatment of necrotizing pancreatitis with secondary infection of necrotic . . .

A timeline for pancreatic cancer Christine Iacobuzio-Donahue and colleagues use whole-genome exome sequencing to analyse primary pancreatic cancers and one or more metastases from the same patients, and find that tumours are composed of distinct subclones. The authors also determine the evolutionary maps by which metastatic cancer clones have evolved within the primary tumour, and estimate the timescales of tumour progression. On the basis of these data, they estimate a mean period of 11.8 years between the initiation of pancreatic tumorigenesis and the formation of the parental, non-metastatic tumour, and a further 6.8 years for the index metastasis clone to arise. These data point to a potentially large window of opportunity during which it might be possible to detect the cancer in a relatively early form. Peter Campbell and colleagues use next-generation sequencing to detect chromosomal rearrangements in 13 patients with pancreatic cancer. The results reveal considerable inter-patient heterogeneity and indicate ongoing genomic instability and evolution during the development of metastases. But for most of the patients studied, more than half of the genetic rearrangements found were present in all metastases and the primary tumour, making them potential targets for therapeutic intervention at early and late stages of the disease. Here, whole-genome sequencing has been used to analyse primary pancreatic tumours and one or more metastases from the same patients. The findings show that tumours are composed of several geographically distinct subclones, and allow maps to be produced showing how metastatic cancer clones evolve within the primary tumour. Moreover, a quantitative analysis of the timing of the genetic evolution of pancreatic cancer has been performed. Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated 1 , 2 , is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy 3 . Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.

Each year, more than half a million people worldwide receive a diagnosis of hepatocellular carcinoma, and hepatocellular carcinoma related to HCV is the fastest rising cause of U.S. cancer-related deaths. This review summarizes recent advances in prevention, surveillance, diagnosis, and treatment. Each year, hepatocellular carcinoma is diagnosed in more than half a million people worldwide, including approximately 20,000 new cases in the United States. 1 , 2 Liver cancer is the fifth most common cancer in men and the seventh in women. Most of the burden of disease (85%) is borne in developing countries, with the highest incidence rates reported in regions where infection with hepatitis B virus (HBV) is endemic: Southeast Asia and sub-Saharan Africa (Figure 1). 3 Hepatocellular carcinoma rarely occurs before the age of 40 years and reaches a peak at approximately 70 years of age. Rates of liver cancer among . . .

Cholangiocarcinoma represents a diverse group of epithelial cancers united by late diagnosis and poor outcomes. Specific diagnostic and therapeutic approaches are undertaken for cholangiocarcinomas of different anatomical locations (intrahepatic, perihilar, and distal). Mixed hepatocellular cholangiocarcinomas have emerged as a distinct subtype of primary liver cancer. Clinicians need to be aware of intrahepatic cholangiocarcinomas arising in cirrhosis and properly assess liver masses in this setting for cholangiocarcinoma. Management of biliary obstruction is obligatory in perihilar cholangiocarcinoma, and advanced cytological tests such as fluorescence in-situ hybridisation for aneusomy are helpful in the diagnosis. Liver transplantation is a curative option for selected patients with perihilar but not with intrahepatic or distal cholangiocarcinoma. International efforts of clinicians and scientists are helping to identify the genetic drivers of cholangiocarcinoma progression, which will unveil early diagnostic markers and direct development of individualised therapies.

Summary Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Patients with cirrhosis are at highest risk of developing this malignant disease, and ultrasonography every 6 months is recommended. Surveillance with ultrasonography allows diagnosis at early stages when the tumour might be curable by resection, liver transplantation, or ablation, and 5-year survival higher than 50% can be achieved. Patients with small solitary tumours and very well preserved liver function are the best candidates for surgical resection. Liver transplantation is most beneficial for individuals who are not good candidates for resection, especially those within Milano criteria (solitary tumour ≤5 cm and up to three nodules ≤3 cm). Donor shortage greatly limits its applicability. Percutaneous ablation is the most frequently used treatment but its effectiveness is limited by tumour size and localisation. In asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread not amenable to curative treatments, chemoembolisation can provide survival benefit. Findings of randomised trials of sorafenib have shown survival benefits for individuals with advanced hepatocellular carcinoma, suggesting that molecular-targeted therapies could be effective in this chemoresistant cancer. Research is active in the area of pathogenesis and treatment of hepatocellular carcinoma.