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KRAS testing is relevant for the choice of the most appropriate first-line therapy of metastatic colorectal cancer (CRC). Strategies for preventing unequal access to the test should be implemented, but their relevance in the practice is related to economic sustainability. The study adopted the Delphi technique to reach a consensus on several topics. Issues related to execution of KRAS testing were identified by an expert's board and proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The emerging proposal was evaluated by decision analyses models employed by technology assessment agencies in order to assess cost-effectiveness. Alternative therapeutic strategies included most commonly used chemotherapy regimens alone or in combination with cetuximab or bevacizumab. The survey indicated that time interval for obtaining KRAS test should not exceed 15 days, 10 days being an optimal interval. To assure the access to proper treatment, a useful strategy should be to anticipate the test after radical resection in patients at high risk of relapse. Early KRAS testing in high risk CRC patients generates incremental cost-effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY) gained. In extensive sensitivity analyses ICER's were always below 15,000 Euro per QALY gained, far within the threshold of 60,000 Euro/QALY gained accepted by regulatory institutions in Italy. In metastatic CRC a time interval higher than 15 days for result of KRAS testing limits access to therapeutic choices. Anticipating KRAS testing before the onset of metastatic disease in patients at high risk does not affect the sustainability and cost-effectiveness profile of cetuximab in first-line mCRC. Early KRAS testing may prevent this inequality in high-risk patients, whether they develop metastases, and is a cost-effective strategy. Based on these results, present joined recommendations of Italian societies of Oncology and Pathology should be updated including early KRAS testing. © 2014 Barone et al.

Objective: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma. Design: Retrospective multicenter study including 17 Italian hepatobiliary surgery units. Patients: A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007. Main Outcome Measures: Postoperative mortality, morbidity, overall survival, and disease-free survival. Results: Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (rightor right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P =. 03 and P =. 006, respectively); in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P =. 05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival. Conclusions: Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis. Arch Surg. 2012; 147(1): 26-34

OBJECTIVE: To evaluate the role of an absorbable fibrin sealant patch (TachoSil) in reducing postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). BACKGROUND: POPF remains the main complication after DP. METHODS: This was a prospective, open, randomized, study in which patients undergoing elective DP were randomized to standard surgical suturing or stapling with or without TachoSil. The primary end point was the incidence of POPF according to International Study Group on Pancreatic Fistula criteria. Amylase level in drainage fluid, number of days until removal of drain, and duration of hospital stay were secondary end points. RESULTS: A total of 275 patients were enrolled at 19 centers over a 2-year period (TachoSil, n = 145; standard, n = 130). Twenty percent of procedures were laparoscopic and 21% were spleen-preserving resections. The incidence of POPF was not significantly different between groups (TachoSil, 62%; standard 68%; P = 0.267). Grade A fistula rate was similar in both groups (TachoSil 54%; standard 55%), whereas the grade B + C fistula rate was 8% with TachoSil versus 14% without (P = 0.139). Amylase drainage level on postoperative day 1 was significantly reduced with TachoSil (P = 0.025). Median number of days until drainage removal and length of hospital stay were similar in both groups (7 and 10 days, respectively). CONCLUSIONS: The POPF rate was higher than expected when International Study Group on Pancreatic Fistula criteria were strictly applied, although the majority were biochemical fistulas. TachoSil had no significant effect on the rate of POPF, although there was a significant reduction of amylase level in drainage fluid on postoperative day 1.

Background Patients with large numbers of colorectal liver metastases (CRLMs) are potential candidates for resection, but the benefit from surgery is unclear. Methods Patients undergoing resection for CRLMs between 1998 and 2012 in two high-volume liver surgery centres were categorized according to the number of CRLMs: between one and seven (group 1) and eight or more (group 2). Overall (OS) and recurrence-free (RFS) survival were compared between the groups. Multivariable analysis was performed to identify adverse prognostic factors. Results A total of 849 patients were analysed: 743 in group 1 and 106 in group 2. The perioperative mortality rate (90 days) was 0·4 per cent (all group 1). Median follow-up was 37·4 months. Group 1 had higher 5-year OS (44·2 versus 20·1 per cent; P < 0·001) and RFS (28·7 versus 13·6 per cent; P < 0·001) rates. OS and RFS in group 2 were similar for patients with eight to ten, 11–15 or more than 15 metastases (48, 40 and 18 patients respectively). In group 2, multivariable analysis identified three preoperative adverse prognostic factors: extrahepatic disease (P = 0·010), no response to chemotherapy (P = 0·023) and primary rectal cancer (P = 0·039). Patients with two or more risk factors had very poor outcomes (median OS and RFS 16·9 and 2·5 months; 5-year OS zero); patients in group 2 with no risk factors had similar survival to those in group 1 (5-year OS rate 44 versus 44·2 per cent). Conclusion Liver resection is safe in selected patients with eight or more metastases, and offers reasonable 5-year survival independent of the number of metastases. However, eight or more metastases combined with at least two adverse prognostic factors is associated with very poor survival, and surgery may not be beneficial.

BACKGROUND: Traditionally, survival estimates have been reported solely as survival from the time of surgery, but future survival probability likely changes based on the survival time already accumulated after therapy-otherwise known as conditional survival (CS). We sought to assess the comparative performance of various colorectal liver metastasis prognostic scoring systems, as well as to investigate the CS of patients who underwent resection of colorectal liver metastasis. STUDY DESIGN: Between 1982 and 2008, 949 patients who underwent colorectal liver metastasis resection were identified from an international multi-institutional database. Various prognostic scoring systems were evaluated using Cox proportional hazards models and calculated concordance index (c). CS estimates were calculated as CS = S((x+5))/S((x)). RESULTS: Overall survival after liver resection was 65% at 3 years and 45% at 5 years, with a median survival of 52 months. All of the prognostic scoring systems had poor-to-moderate prognostic discriminatory ability (Fong c = 0.57, Nordlinger c = 0.56, Memorial Sloan-Kettering Cancer Center nomogram c = 0.58). Using CS, the probability of surviving an additional 5 years, given that the patient had already survived 1, 3, or 5 years, was 41%, 40%, or 50%, respectively. The inadequate performance of the prognostic scoring systems was explained by the fact that as survival from liver resection increased from 0 to 5 years, the 5-year observed CS improved substantially for patients who were initially predicted to have poor survival at the time of surgery. CONCLUSIONS: Colorectal liver metastasis prognostic scoring systems have fair-to-moderate performance. CS can provide more accurate prognostic information for patients and physicians after colorectal liver metastasis resection and should be incorporated into the quantification of survival.

Background A randomized clinical trial was performed to compare D1 and D2 gastrectomy in specialized Western centres. This paper reports short-term results. Method A total of 267 patients with gastric cancer were randomly assigned to either a D1 or a D2 procedure in five specialized centres. Based on the findings of the phase II trial and published phase III trials, a prespecified non-inferiority boundary at 12 per cent difference between groups was set regarding total morbidity. Results In the intention-to-treat analysis, the overall morbidity rate after D2 and D1 dissections was 17·9 and 12·0 per cent respectively (P = 0·178), with a 95 per cent confidence interval of the difference of 0 to 13·0 per cent, slightly exceeding the prespecified non-inferiority limit. There was a single duodenal stump leak in the D2 arm (0·7 per cent). The postoperative 30-day mortality rate was 3·0 per cent after D1 and 2·2 per cent after D2 gastrectomy (P = 0·722). Conclusion In specialized centres the rate of complications following D2 dissection is much lower than in published randomized Western trials. D2 dissection, in an appropriate setting, can therefore be considered a safe option for the radical management of gastric cancer in Western patients. Registration number: ISRCTN11154654 (http://www.controlled-trials.com).

Liver surgery for colorectal metastasis has moved toward a parenchymal sparing strategy in order to reduce postoperative liver failure, to resect an higher number of metastases and to allow a future re-resection. Patients undergone hepatectomy in our Department before and after 1999 were retrospectively compared. In the recent years surgery became more aggressive: a higher number of patients with multiple and bilateral lesions were treated. Short-term results improved in the recent series. After 1999, the rate of wedge resections was significantly increased with the same oncological radicality and with improved long-term results. Moreover, parenchymal sparing strategy allowed a higher re-resection rate in patients with liver recurrence.