Because acute cholangitis sometimes rapidly progresses to a severe form accompanied by organ dysfunction, caused by the systemic inflammatory response syndrome (SIRS) and/or sepsis, prompt diagnosis and severity assessment are necessary for appropriate management, including intensive care with organ support and urgent biliary drainage in addition to medical treatment. However, because there have been no standard criteria for the diagnosis and severity assessment of acute cholangitis, practical clinical guidelines have never been established. The aim of this part of the Tokyo Guidelines is to propose new criteria for the diagnosis and severity assessment of acute cholangitis based on a systematic review of the literature and the consensus of experts reached at the International Consensus Meeting held in Tokyo 2006. Acute cholangitis can be diagnosed if the clinical manifestations of Charcot’s triad, i.e., fever and/or chills, abdominal pain (right upper quadrant or epigastric), and jaundice are present. When not all of the components of the triad are present, then a definite diagnosis can be made if laboratory data and imaging findings supporting the evidence of inflammation and biliary obstruction are obtained. The severity of acute cholangitis can be classified into three grades, mild (grade I), moderate (grade II), and severe (grade III), on the basis of two clinical factors, the onset of organ dysfunction and the response to the initial medical treatment. “Severe (grade III)” acute cholangitis is defined as acute cholangitis accompanied by at least one new-onset organ dysfunction. “Moderate (grade II)” acute cholangitis is defined as acute cholangitis that is unaccompanied by organ dysfunction, but that does not respond to the initial medical treatment, with the clinical manifestations and/or laboratory data not improved. “Mild (grade I)” acute cholangitis is defined as acute cholangitis that responds to the initial medical treatment, with the clinical findings improved.

BackgroundPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Methodology/Principal FindingsFormalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.Conclusions SignificanceLow miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.

This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with standard resection in pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, when compared with extended pancreaticoduodenal resection. (NCT00679913)?

Combined interpretation of CT and direct cholangiographic images by using our revised criteria resulted in overall accuracy of 74.5% for prediction of resectability for hilar cholangiocarcinoma.

The clinicopathologic features of the intraductal growth (IG) type of peripheral cholangiocarcinoma (PCC) were examined retrospectively. Out of 112 patients who underwent surgery for PCC at Seoul National University Hospital, Seoul, Korea, between January 1980 and December 1997, 16 were classified as having the IG type. Thirteen were men and 3 were women. Their ages ranged from 38 to 73 years with a mean age of 55.9 years. Abdominal pain was the most common symptom and jaundice was found in 18.8%. Five patients had associated clonorchiasis and 6 patients experienced hepatolithiasis. Tumor sizes ranged from 0.5 cm to 14.0 cm with a mean of 4.3 cm. The tumor was located in the right lobe in 7 cases and the left lobe in 9 cases. Thirteen patients underwent major hepatic resection, and 3 underwent minor resection, involving a subsegmentectomy. Mucin was found in the bile in 4 cases. Pathology showed papillary adenocarcinoma with a background of adenomatous hyperplasia, and the absence of lymph node metastasis in all cases. The tumors were confined to the mucosa in 5 cases. Out of the 16 hepatic resections, 1 was palliative due to a positive margin. In 2 of the patients who underwent minor resections, recurrences developed, and 1 of these died 56 months after resection. Out of the 16 patients, 15 remain alive, ranging from 1 to 13 years, postoperatively. In conclusion, the IG type of PCC should be distinguished from other types of PCC because a favorable prognosis can be expected after complete surgical resection. (HEPATOLOGY 2000;31:12-17.)Intrahepatic or peripheral cholangiocarcinoma (PCC), a primary adenocarcinoma of the liver originating from the intrahepatic bile ducts (IHD), is the second most common primary hepatic malignancy, next to hepatocellular carcinoma. 1 Because the lesion is advanced by the time of diagnosis, 2 the possibility of surgical resection is limited and the prognosis is generally poor. [3][4][5][6][7][8][9] In 1992, Yamamoto et al. 10 classified PCC into 2 types, mass-forming (MF) and periductal-infiltrating (PI), and showed their different clinical behaviors. The MF type creates an apparent lesion in the liver, with frequent remnant hepatic recurrence after resection. The PI type causes a stricture or an obstruction of the IHD without forming a definite mass in the liver. It spreads along the Glisson' s capsule and metastasizes to the hilar lymph nodes. Later, another type, intraductal growth (IG), was added. 11 This type of tumor shows a papillary growth into the lumen of the bile duct. 12 There have been a few scattered reports about the clinical and pathological features of the IG type of PCC. 13,14 Here, we describe the clinical and pathological features of the IG type of PCC in 16 patients who underwent surgical resection at

Cholangiocarcinomas that involve areas from the peripheral intrahepatic duct to the distal common duct have similar morphologic features, and traditional classification schemes based on the location of the involved ducts sometimes overlap. Nevertheless, cholangiocarcinoma is usually classified as either intrahepatic or extrahepatic, and intrahepatic cholangiocarcinoma is further classified as either peripheral or hilar. However, the distinction between peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma is largely based on the site of origin. Therefore, in some tumors that arise peripheral to the secondary bifurcation of one of the hepatic ducts, clear differentiation between the two types of cholangiocarcinoma is not always possible. In addition, the distinction between hilar cholangiocarcinoma and extrahepatic cholangiocarcinoma is not clearly defined. The different biologic behaviors of the tumors seem to be caused by their varying locations and their size at the time of diagnosis. Further molecular or biochemical investigation is needed to support the "field theory," which states that all cholangiocarcinomas are biologically the same tumor originating from the same biliary epithelium.

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Active surgical resection should be attempted even in patients with poor prognostic factors. As there were various types of pathology among the long-term survivors, typical ductal adenocarcinoma of the pancreas might have a poorer survival rate.