Microvessel Landscape Assessment in Pancreatic Ductal Adenocarcinoma: Unclear Value of Targeting Endoglin (CD105) as Prognostic Factor of Clinical Outcome.

OBJECTIVES: Tumor angiogenesis based on microvessel density assessment has been associated with poor prognosis in several studies of patients with pancreatic ductal adenocarcinoma (PDAC). Expression of endoglin (CD105), a tumor-induced vascularization marker, has been found to represent a negative prognostic factor in many malignant tumors. The aim of our study was to assess the value of tumoral microvascularity both with pan-endothelial markers and endoglin as well, in correlation with the clinical outcome of patients with PDAC. METHODS: Fifty-eight patients with PDAC, 36 males and 22 females, with a mean (SD) age of 65.4 (10.0) years were included in the study. Deparaffinized sections from formalin-fixed areas both from the center and periphery (invasion front) of the tumors were immunostained for CD105 as well as for the endothelial markers CD31 and CD34. Tumoral angiogenesis was assessed on the basis of microvessel density (number of vessels per square millimeter) and on microvascular area (square micrometers) as well. RESULTS: High intratumoral microvascular area, in endoglin-stained sections, was found to be of marginal prognostic significance for recurrence (log rank, P 0.05). Survival was also marginally associated with CD31 intratumoral microvascular area (log rank, P 0.05). CONCLUSIONS: Further studies are needed before endoglin replaces the conventional angiogenesis markers in PDCA.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Perioperative risk assessment for hepatocellular carcinoma by using the MELD score.

BACKGROUND/AIMS: The aim of this study was to evaluate the ability of Model for End-Stage Liver Disease (MELD) in predicting post hepatectomy outcome for hepatocellular carcinoma (HCC). METHODS: Between 2001 and 2005, 94 cirrhotic patients with HCC underwent hepatectomy and were analyzed retrospectively. MELD score associated with postoperative mortality and morbidity, hospital stay, and 3-year survival. RESULTS: Twenty-eight major and 66 minor resections were performed. Thirty-day mortality rate was 6.4%. MELD 9 (p = 0.01). Overall morbidity rate was 32%; 21% when MELD 9 (p = 0.01). Median hospital stay was 11 days (7 days, when MELD 9; p = 0.03). Three-year survival reached 48% (63% when MELD 9; p < 0.01). In multivariate analysis, MELD > 9 (p = 0.01), clinical tumor symptoms (p = 0.04), and American Society of Anesthesiologists score (p = 0.04) were independent predictors of perioperative mortality; MELD > 9 (p = 0.01), tumor size >5 cm (p = 0.01), presence of tumor symptoms (p = 0.02), high tumor grade (p = 0.01), and absence of tumor capsule (p = 0.01) were independent predictors of decreased long-term survival. CONCLUSION: MELD score seems to predict outcome of cirrhotic patients with HCC after hepatectomy.

Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines.

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.

Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines.

The aim of this article is to propose new criteria for the diagnosis and severity assessment of acute cholecystitis, based on a systematic review of the literature and a consensus of experts. A working group reviewed articles with regard to the diagnosis and treatment of acute cholecystitis and extracted the best current available evidence. In addition to the evidence and face-to-face discussions, domestic consensus meetings were held by the experts in order to assess the results. A provisional outcome statement regarding the diagnostic criteria and criteria for severity assessment was discussed and finalized during an International Consensus Meeting held in Tokyo 2006. Patients exhibiting one of the local signs of inflammation, such as Murphy's sign, or a mass, pain or tenderness in the right upper quadrant, as well as one of the systemic signs of inflammation, such as fever, elevated white blood cell count, and elevated C-reactive protein level, are diagnosed as having acute cholecystitis. Patients in whom suspected clinical findings are confirmed by diagnostic imaging are also diagnosed with acute cholecystitis. The severity of acute cholecystitis is classified into three grades, mild (grade I), moderate (grade II), and severe (grade III). Grade I (mild acute cholecystitis) is defined as acute cholecystitis in a patient with no organ dysfunction and limited disease in the gallbladder, making cholecystectomy a low-risk procedure. Grade II (moderate acute cholecystitis) is associated with no organ dysfunction but there is extensive disease in the gallbladder, resulting in difficulty in safely performing a cholecystectomy. Grade II disease is usually characterized by an elevated white blood cell count; a palpable, tender mass in the right upper abdominal quadrant; disease duration of more than 72 h; and imaging studies indicating significant inflammatory changes in the gallbladder. Grade III (severe acute cholecystitis) is defined as acute cholecystitis with organ dysfunction.