Surgeons' assessment versus risk models for predicting complications of hepato-pancreato-biliary surgery (HPB-RISC): a multicenter prospective cohort study.

BACKGROUND: Several studies advise the use of risk models when counseling patients for hepato-pancreato-biliary (HPB) surgery, but studies comparing these models to the surgeons' assessment are lacking. The aim of this study was to assess whether risk prediction models outperform surgeons' assessment for the risk of complications in HPB surgery. METHODS: This prospective study included adult patients scheduled for HPB surgery in three centers in the UK and the Netherlands. Primary outcome was the rate of postoperative major complications. Surgeons assessed the risk prior to surgery while blinded for the formal risk scores. Risk prediction models were retrieved via a systematic review and risk scores were calculated. For each model, discrimination and calibration were evaluated. RESULTS: Overall, 349 patients were included. The rate of major complications was 27% and in-hospital mortality 3%. Surgeons' assessment resulted in an AUC of 0.64; 0.71 for liver and 0.56 for pancreas surgery (P = 0.020). The AUCs for nine existing risk prediction models ranged between 0.57 and 0.73 for liver surgery and between 0.51 and 0.57 for pancreas surgery. CONCLUSION: In HPB surgery, existing risk prediction models do not outperform surgeons' assessment. Surgeons' assessment outperforms most risk prediction models for liver surgery although both have a poor predictive performance for pancreas surgery. REGISTRATION INFORMATION: REC reference number (13/SC/0135); IRAS ID (119370). TRIALREGISTER.NL: NTR4649.

The desmoplastic reaction surrounding hepatic colorectal adenocarcinoma metastases aids tumor growth and survival via alphav integrin ligation.

PURPOSE: The treatment of metastatic colorectal carcinoma represents a major clinical challenge. We investigated the hypothesis that the desmoplastic reaction within the liver elicited by metastatic adenocarcinoma, characterized by collagen I deposition and altered collagen IV distribution, promotes the growth and survival of hepatic colorectal carcinoma metastases. EXPERIMENTAL DESIGN: Partial hepatectomy specimens for metastatic colorectal adenocarcinoma were examined immunohistochemically for differential integrin expression. Human colorectal adenocarcinoma cell lines HT-29, KM12SM, and KM12c were grown on wild-type collagen I or IV, or cleavage-resistant r/r collagen I, and assessed for their growth, survival, and resistance to 5-fluorouracil. The effect of alpha(v)beta(3) and alpha(v)beta(5) integrin blockade by neutralizing antibodies was examined. RESULTS: Collagen I, in contrast to collagen IV, significantly enhanced the growth, survival, and chemoresistance of colorectal carcinoma cells. Blockade of the alpha(v)beta(3) and alpha(v)beta(5) integrins significantly reduced colorectal carcinoma cell proliferation on collagen, especially in the cell line with the most metastatic potential. These in vitro findings correlated with the pattern of integrin expression identified within resected hepatic colorectal carcinoma metastases. Using matrix metalloproteinase-resistant r/r collagen I as a dominant negative ligand for alpha(v) integrins, we showed a key role for this integrin-ligand interaction in mediating the survival and proliferation of colorectal carcinoma cells. CONCLUSIONS: Desmoplasia has an important role in the development of hepatic colorectal carcinoma metastasis. The interaction between integrin and collagen I is identified as a potential therapeutic target.