Allogeneic blood transfusion does not affect outcome after curative resection for advanced cholangiocarcinoma.

PURPOSE: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. METHODS: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. RESULTS: Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19-3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52-2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39-2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24-1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed. CONCLUSIONS: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves.

Neoadjuvant radiotherapy for rectal cancer: meta-analysis of randomized controlled trials.

BACKGROUND: Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer. METHODS: The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy. RESULTS: We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48-0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85-1.00). However, it was associated with increased perioperative mortality (1.48; 1.08-2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23-2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39-0.72), with no impact on perioperative outcome and long-term survival. CONCLUSIONS: Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation.

Bilirubin level in the drainage fluid is an early and independent predictor of clinically relevant bile leakage after hepatic resection.

BACKGROUND: Variations in the definition of bile leakage after hepatic resection have prevented the identification of risk factors for early diagnosis and efficient management. The International Study Group of Liver Surgery (ISGLS) definition standardizes reporting of this complication. It was our aim in the present study to prospectively validate the ISGLS definition of bile leakage after hepatic resection. Furthermore, we sought to identify early predictors of clinically relevant bile leakage. METHODS: A total of 265 patients who underwent elective hepatic resection were enrolled prospectively. Bilirubin concentrations were determined in the serum and drainage fluid until postoperative day 5. Risk factors of Grade B/C bile leakage were assessed by the use of univariate and multivariate analyses. RESULTS: Grade A, B, and C bile leakage was diagnosed in 23 (8.7%), 38 (14.3%), and 11 (4.1%) patients, respectively. The definition as well as severity grading of bile leakage correlated with the duration of drainage and intensive care unit and hospital stay. Perioperative mortality was 0% for Grade A, 5.2% for Grade B, and 45.4% for Grade C bile leakage (P < .0001). Multivariate analysis confirmed bilirubin concentration in the drainage fluid ≥2.4 mg/dL on postoperative day 2 (odds ratio 11.88; 95% confidence interval 5.33-26.49; P < .0001) and anatomic resection (odds ratio 3.59; 95% CI 1.08-11.97; P = .04) as independent predictors of clinically relevant bile leakage. CONCLUSION: The ISGLS definition and severity grading of bile leakage after hepatic resection is clinically meaningful. Bilirubin concentration in the drainage fluid on postoperative day 2 is a strong predictor of clinically relevant bile leakage.

Overexpression of RalBP1 in colorectal cancer is an independent predictor of poor survival and early tumor relapse.

The non-ABC transport protein RalBP1 has been shown to be overexpressed in various cancer cell lines and implicated in the process of metastasis formation, but its expression in tissue samples and prognostic significance has not been shown. In this study matched tumor-mucosa tissue samples from 78 CRC patients were investigated. The RalBP1 mRNA and protein levels were quantified by real-time quantitative PCR (qPCR) and ELISA. RalBP1 was found to be overexpressed in tumor at the mRNA level both overall (p = 0.027), and for stages I (p = 0.024), II (p = 0.038) and IV (p = 0.004). At the protein level, RalBP1 was only significantly overexpressed in stage IV patients (p = 0.018). Expression of RalBP1 mRNA and protein were inversely correlated (r = 0.4173; p = 0.0004). Multivariate Cox regression analysis including sex, age, stage, grade, and nodal status as covariates showed that overexpression of RalBP1 protein, but not mRNA, was an independent predictor of both decreased disease free survival (p = 0.016, RR = 6.892) and overall survival (p = 0.039, RR = 5.986). These results suggest that RalBP1 protein is an independent predictor of poor survival and early relapse for CRC patients. Owing to its multifunctional intermediary role in cell survival, chemotherapeutic resistance, and metastasis formation, RalBP1 represents a promising novel therapeutic target.

Clamp-crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH)--a randomized controlled trial (NCT01049607).

BACKGROUND: Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. METHODS/DESIGN: The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. DISCUSSION: The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01049607.

The predictive value of postoperative clinical risk scores for outcome after hepatic resection: a validation analysis in 807 patients.

BACKGROUND: Although early postoperative risk stratification might allow a more precise prediction of outcomes after hepatic resection, evaluation of different postoperative clinical risk indices has been lacking. METHODS: A total of 1,219 patients underwent hepatic resection between January 2002 and 2010, and 807 patients were eligible for final analyses. The model for end stage liver disease (MELD) score, the "50-50 criteria," and the International Study Group of Liver Surgery (ISGLS) definition of posthepatectomy liver failure (PHLF) were assessed as clinical risk scores on postoperative day 5. Risk factors for morbidity and mortality were analyzed using multivariate logistic regression analyses. RESULTS: The overall morbidity and mortality rates were 43 and 6%, respectively. Sensitivity of the MELD score, the 50-50 criteria and the PHLF for prediction of morbidity and mortality were 55, 6, 23 and 71, 26, 65%. On multivariate analyses MELD score [odds ratio (OR) 2.06; 95% confidence interval (95% CI) 1.41-3.02] and PHLF (5.61; 2.73-11.55) were associated with morbidity, whereas this association did not reach statistical significance for the 50-50 criteria (3.64; 0.78-17.02). The 50-50 criteria (16.45; 3.50-77.25) and PHLF (13.80; 4.27-44.61) were identified as powerful, independent predictors of mortality. This association was less strong for the MELD score (2.86; 0.98-8.31). CONCLUSION: Postoperative clinical risk scores are associated independently with outcome after hepatic resection. Owing to lack of sensitivity only the MELD score can be recommended for early prediction of overall morbidity, whereas the MELD score and the PHLF enabled adequate risk stratification regarding perioperative mortality.

Infrahepatic inferior vena cava clamping for reduction of central venous pressure and blood loss during hepatic resection: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of infrahepatic inferior vena cava (IVC) clamping for reduction of central venous pressure (CVP) and blood loss during hepatic resection. BACKGROUND: Low CVP during parenchymal transection has been widely accepted to reduce intraoperative hemorrhage via the hepatic veins and is commonly achieved by anesthesiological interventions such as fluid restriction. We hypothesized that infrahepatic clamping of the IVC may lower the intraoperative blood loss more effectively and, moreover, prevent potential adverse effects of fluid restriction such as hemodynamic instability. METHODS: Patients scheduled for elective hepatic resection were enrolled and allocated randomly to CVP reduction by infrahepatic IVC clamping or anesthesiological interventions including primarily fluid restriction with additional use of diuretics, nitro compounds, and opioids (control group). The primary efficacy endpoint was total intraoperative blood loss. Analyses were done following intention-to-treat principles. The protocol was submitted to the clinicaltrials.gov registry (NCT00732979). RESULTS: From April 2007 to December 2009, a total of 152 patients were randomized and 128 were eligible for final analyses. Baseline data were similar between both study groups. Despite higher CVP values during resection (4.0 ± 3.2 vs. 2.6 ± 1.8 mm Hg; P = 0.003), infrahepatic IVC clamping significantly reduced total intraoperative blood loss [550 (350.0-1150) mL vs. 900 (500-1500) mL; P = 0.02] and blood loss during parenchymal transection [150 (85-500) mL vs. 400 (200-700) mL; P = 0.006] compared with the control group. Postoperative mortality [4 (6.1%) vs. 2 (3.2%); P = 0.42] and total morbidity rates [38 (58.5%) vs. 37 (58.7%); P = 0.97] were comparable between both study groups. Although intraoperative hemodynamic instability occurred less frequently in patients with infrahepatic IVC clamping [0 vs. 4 (6.3%); P = 0.04], the incidence of pulmonary embolism was increased in this study arm [4 (6.1%) vs. 0; P = 0.04]. CONCLUSIONS: Infrahepatic IVC clamping is associated with significantly less intraoperative blood loss and may reduce the incidence of intraoperative hemodynamic instability. The potential association with postoperative pulmonary embolism represents a significant concern.

IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy--a randomised controlled trial in an interdisciplinary setting.

BACKGROUND: Intraoperative haemorrhage is a known predictor for perioperative outcome of patients undergoing hepatic resection. While anaesthesiological lowering of central venous pressure (CVP) by fluid restriction is known to reduce bleeding during transection of the hepatic parenchyma its potential side effects remain poorly investigated. In theory it may have negative effects on kidney function and tissue perfusion and bears the risk to result in severe haemodynamic instability in case of profound intraoperative blood loss. The present randomised controlled trial evaluates efficacy and safety of infrahepatic inferior vena cava (IVC) clamping as an alternative surgical technique to reduce CVP during hepatic resection. METHODS/DESIGN: The proposed IVC CLAMP trial is a single-centre randomised controlled trial with a two-group parallel design. Patients and outcome-assessors are blinded for the treatment intervention. Patients undergoing elective hepatic resection due to any reason are enrolled in IVC CLAMP. All patients admitted to the Department of General-, Visceral-, and Transplant Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility and written informed consent is obtained on the day before surgery. The primary objective of this trial is to assess and compare the amount of blood loss during hepatic resection in patients receiving surgical CVP reduction by clamping of the IVC as compared to anaesthesiological CVP without infrahepatic IVC clamping reduction. In addition to blood loss a set of general as well as surgical variables are analysed. DISCUSSION: This is a randomised controlled patient and observer blinded two-group parallel trial designed to assess efficacy and safety of infrahepatic IVC clamping during elective hepatectomy.