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Background: Immune infiltrate impacts prognosis of several tumors. To assess the prognostic impact of tumor-infiltrating lymphocytes and macrophages in patients undergoing resection for intrahepatic cholangiocellular carcinoma (ICC)., Methods: All consecutive patients undergoing surgery for ICC between 2008 and 2016 were considered. Inclusion criteria were complete resection and follow-up > 12 months. Tissue sections were immunostained for CD3+, CD4+, CD8+, Foxp3+, and CD68+. The number of positive cells was quantified using a computer-aided image analysis system. Different cut-off values were tested as predictors of overall survival (OS)., Results: Fifty-three patients were analyzed. ICC were T1 in 28 patients, multifocal in 11, and N+ in 13. After a median follow-up of 42 months, 5-year OS was 52.1%. The following immune infiltrate values were associated with better OS: CD3+ > 0.10% (5-year OS 63.3% vs. 13.6% if ≤ 0.10%, p = 0.001); CD8+ > 0.10% (56.2% vs. 28.6% if ≤ 0.10%, p = 0.051); Foxp3+ absent (59.4% vs. 16.0% if present, p = 0.049). CD4+ and CD68+ infiltrates were not associated with OS. Three-year OS rates in patients with 0, 1, and ≥ 2 negative prognostic factors were 73.6%, 47.3%, and 14.3%, respectively (p < 0.001). CD3+ infiltrate stratified prognosis in T1 tumors (3-year OS 71.7% if CD3+ > 0.10% vs. 14.3% if ≤ 0.10%, p < 0.001)., Conclusions: Tumor-infiltrating lymphocytes are associated with prognosis of ICC patients after complete surgery. CD3+ and CD8+ infiltrate is associated with higher survival and lower recurrence risk, while Foxp3+ infiltrate is associated with worse prognosis. CD3+ infiltrate allows refining prediction of prognosis in early tumors.

Background: Preliminary series have shown the feasibility of combined laparoscopic resection of colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). The aim of this study was to compare the short- and long-term outcomes for matched patients undergoing combined resections., Methods: An international multicenter database of 142 patients that underwent combined laparoscopic resection of CRC and SCRLM between 1997 and 2013 was compared to a database of 241 patients treated by open during the same period. Comparison of short- and long-term outcomes was performed after propensity score adjustment., Results: After matching, 89 patients were compared in each group including mostly ASA I-II patients, presenting with mean number of 1.5 CRLM, with a mean diameter of 30 mm, and resectable by a wedge resection or a left lateral sectionectomy. A rectal resection was required in 46 and 43 % of laparoscopic and open procedures, respectively (p = 0.65). There was no difference in global operative time, blood loss and transfusion rates between the two groups. A conversion was required in 7 % of the laparoscopic procedures. Morbidity rates were similar in the two groups (p = 1.0). The 3-year overall survival in the laparoscopy and open groups were 78 and 65 %, respectively (p = 0.17)., Conclusions: In patients without severe comorbidities presenting with one, small (≤3 cm), CRLM resectable by a wedge resection or a left lateral sectionectomy, combined laparoscopic resection of CRC and SCRLM allowed similar short- and long-term outcomes compared with the open approach.

When suitable, surgery still remains the therapeutic option to be preferred for patients carrier of colorectal liver and lung metastases. Since thoracophrenolaparotomy should be helpful during liver resection for some of these patients, simultaneous removal of right lung metastases can be proposed through this approach. Eleven consecutive patients (median age of 53 years) carrier of colorectal liver and lung metastases, underwent single session surgical resection of both liver and right lung lesions by means of J-shaped thoracophrenolaparotomy. The median number of liver metastases removed was 5 (range 2-30) and of lung metastases removed was 2 (range 1-3). Lung metastases were located in the upper lobe in 1 patient, in the middle lobe in 2, in the lower lobe in 6, and in the upper and lower lobe in 2. Mortality and major morbidity were nil. Two patients had a minor morbidity: one had wound infection and bile leakage treated conservatively and the other had transient fever. Mean overall survival was 24.4 months. An aggressive surgical approach should be undertaken for colorectal metastases: in case of multifocal liver disease with complex presentations, J-shaped thoracophrenolaparotomy could be considered as safe approach for combined liver and right lung metastasectomies.

Background: With the advance of modern laparoscopic technology, laparoscopic colorectal surgery and laparoscopic liver surgery are both worldwide accepted. Preliminary brief series have shown the feasibility of combined laparoscopic resection of colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). We aim to report a large International multicenter series of laparoscopic simultaneous resection of CRC and SCRLM., Methods: Between 1997 and 2013, 142 laparoscopic liver resections were performed with simultaneous colorectal surgery for SCRLM. The surgical and postoperative variables evaluated were the duration of the intervention, blood loss, transfusion rate, conversion rate, resection margin, specific and overall morbidity, perioperative mortality, length of hospital stay, and survival. Univariate and multivariate analyses were performed examining postoperative morbidity in the all cohort of patients., Results: The median number of liver lesions was 1 (1-9) and the median larger diameter at diagnosis was 28 (2-100) mm. The median operative time was 360 (120-690) min. Seven patients (4.9%) required conversion. The global morbidity was 31.0% and the mortality was 2.1%. After a median follow-up of 29 (1-108) months, 40 patients (28.2%) developed tumor recurrence. Curative treatment of recurrence was possible in 17 patients (12.0%), including a second liver resection in 13 patients (9.1%), which was performed by laparoscopy in 7 patients (4.9%). Overall 1-, 3-, and 5-year survivals were 98.8, 82.1, and 71.9%, respectively. By multivariate analysis, ASA score≥3 [OR 13.6 (1.8-99.6); P=0.01] and operative time [OR 1.008 (1.001-1.016); P=0.03] were independent predictors of postoperative morbidity., Conclusions: Our combined data show that in experienced centers, simultaneous laparoscopic approach is technically feasible, safe, and associated with good oncological outcomes.

Background: The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined., Methods: Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients)., Results: The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01)., Conclusions: An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.

Laparoscopic major hepatectomy remains a relatively rare operation because it is a difficult and technically demanding procedure, and a standard, safe, reproducible technique has not been widely adopted. This is compounded by "major hepatectomy" encompassing multiple different operations each with their own anatomic and procedural considerations. In 2010, we investigated our learning curve for laparoscopic liver resection. We found a significant increase in the number of major hepatectomies performed over a 12-year period, with concurrent reductions in the use of hand-assistance, pedicle clamping, median clamping time, median operative time, blood loss and morbidity. This learning curve was confirmed by a subsequent multinational study. Both hospital and surgeon volume have been shown to affect outcomes, and defining a sufficient number of repetitions before the learning curve plateaus is not easy for laparoscopic major hepatectomy. We recommend that laparoscopic competencies be developed upon a foundation of open liver surgery and that laparoscopic major hepatectomy should only be attempted after competency with less technically complex laparoscopic resections. A center advanced along its institutional learning curve provides the collective expertise necessary for safe patient selection and management. An environment with colleagues willing to share their acquired proficiency allows the surgeon to observe and critique his or her performance against colleagues. Also, the guidance of like-minded surgeons supports technical development and improved outcomes. In conclusion, steady progress can be made along the learning curve through committed practice of increasingly complex tasks and with proper coaching in a high-volume environment.

Background: Management of patients with synchronous liver metastasis (SLM) is complex and the surgical decision process should be based on a comprehensive oncological strategy. The aim of the study was to compare outcome of single-center management of patients with colorectal cancer (CRC) and resectable SLM to those of referred patients for liver resection only after removal of their primary tumor (PT)., Methods: Between 2000 and 2007, 47 patients with CRC and SLM underwent resection of both the PT and metastases under our care (unicentric) and 32 were referred after resection of their PT., Results: The two groups were comparable for demographics, PT and metastatic disease data. In unicentric group, 23% received upfront chemotherapy with the PT in place, 53% had a combined CRC and SLM resection, 11% had a two-stage hepatectomy with resection of the primary during the first stage and 36% underwent delayed hepatectomy. The number of surgical interventions, the delay between diagnosis and liver resection (9 vs. 5 months, P < 0.001), the median number of cycles of chemotherapy before hepatectomy (12 vs. 6 months, P < 0.001) were significantly higher in the referred group. Postoperative morbidity was significantly higher in the referred group (75 vs. 47%, P = 0.023). The median follow-up was 43 months. OS and DFS were not significantly different between the two groups., Conclusion: Although the survival benefit is not proven, single-center management of patients with CRC and resectable SLM reduces the number of interventions, the number of cycles of chemotherapy and postoperative morbidity., (Copyright © 2012. Published by Elsevier Masson SAS.)

Background: This study assessed the feasibility and outcomes of combined colorectal and hepatic resection as the first step of two-stage hepatectomy in patients with bilobar synchronous colorectal liver metastases., Methods: All patients with bilobar synchronous colorectal liver metastases who were considered for two-stage hepatectomy, combining resection of the primary tumour with the first stage of hepatectomy, between 2000 and 2008 were selected from a prospectively collected database at two institutions. Data were analysed retrospectively on an intention-to-treat basis., Results: Thirty-three patients were studied. Twenty patients received neoadjuvant chemotherapy. Combined colorectal resection and clearance of left-sided liver metastases was the first-stage procedure in all but one patient, in whom right clearance was performed. In 17 patients right portal vein ligation was undertaken at the same time. No patient died. Two patients had anastomotic leakage. Interval chemotherapy was given to 25 patients, five of whom also had percutaneous portal vein embolization. Twenty-five patients had the second-stage hepatectomy, but not eight patients with disease progression. There was one postoperative death after the second stage, and eight patients experienced morbidity. Median follow-up from the first stage was 28.7 months. Overall and disease-free survival rates for patients who completed the procedure were 80 and 44 per cent respectively at 3 years, and 48 and 22 per cent at 5 years., Conclusion: In patients with bilobar synchronous colorectal liver metastases who are candidates for two-stage hepatectomy, combined resection of the primary tumour and first-stage hepatectomy reduces the number of procedures, optimizes chemotherapy administration and may improve outcome., (Copyright 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate the "learning curve" effect on feasibility and reproducibility of laparoscopic liver resection (LLR)., Summary Background Data: LLR is currently limited to few centers and to few procedures. Its reproducibility is still debated., Methods: : Patients undergoing LLR between 1996 and 2008 were included. Indications and type of hepatectomies were compared with those of open resections performed in the same period, considering 3 periods (1996-1999, 2000-2003, and 2004-2008). LLRs were divided into 3 equal groups of 58 cases and technical data and outcomes were compared. Risk-adjusted Cumulative Sum model was used for determining the learning curve based on the need for conversion., Results: Of 782, 174 (22.3%) patients underwent LLR. Proportion of LLR progressively increased (17.5%, 22.4%, and 24.2%), such as hepatocellular carcinoma (17.6%, 25.6%, and 39.4%, P < 0.05), colorectal metastases (0%, 6.5%, and 13.1%, P < 0.05), major hepatectomies (1.1%, 9.1%, 8.5%, P < 0.05), and right hepatectomies (0%, 13.2%, and 13.1%, P < 0.05). Comparing groups, results of LLR significantly improved in terms of conversion rate (15.5%, 10.3%, and 3.4%, P < 0.05), operative time (210, 180, and 150 minutes, P < 0.05), blood loss (300, 200, and 200 mL, P < 0.05), and morbidity (17.2%, 22.4%, and 3.4%, P < 0.05). Pedicle clamping was less used over time (77.6%, 62.1%, and 17.2%, P < 0.05) and for shorter durations (45, 30, and 20 minutes, P < 0.05). Having adjusted for case-mix, the Cumulative Sum analysis demonstrated a learning curve for laparoscopic hepatectomies of 60 cases., Conclusion: A slow but constant evolution of LLR occurred: indications and magnitude of procedures increased and technical outcomes improved. The learning curve demonstrated in this study suggests that LLR is reproducible in liver units but specific training to advanced laparoscopy is required.

Background: Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy., Methods: The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B)., Results: Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064), Conclusions: Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.

Aim: To evaluate the impact of postoperative injection into the hepatic artery of 131-iodine-labeled lipiodol on disease-free and overall survival rates in patients who underwent liver surgical resection for hepatocellular carcinoma., Methods: Ten consecutive patients with HCV (hepatitis C virus)-related cirrhosis who underwent liver surgical resection for hepatocellular carcinoma were treated with adjuvant injection of 131-iodine-labeled lipiodol. They were matched with 20 HCV-positive cirrhotic controls who underwent liver resection alone; patients were paired in terms of age, Child-Pugh class, tumor size, microscopic vascular invasion, tumor histological pattern, presence of satellite nodules and type of surgical resection. Recurrence was defined as the development of a new hypervascularizated nodule in the liver., Results: No significant differences were found between the two groups in clinical, biologic and histologic characteristics, except a lower platelet count in the control group. None of the treated patients developed an intrahepatic recurrence until the 15th month from liver resection, whereas recurrences occurred in nine of the 20 patients in the control group (p=0.01). From 18 months onwards, recurrences appeared also in the treated patients, and after 36 months of follow-up both recurrence rate and overall survival were not significantly different between the two groups., Conclusions: Intrahepatic injection of 131-iodine-labeled lipiodol improves the disease-free survival rate following liver resection of hepatocellular carcinoma in the short term up to 15 months; this advantage fades, however, away after 36 months.

In recent decades, surgical treatment of hilar cholangiocarcinoma has moved toward liver surgery in association with biliary resection in order to increase radicality and to achieve better survival. Results of local resection compared with hepatectomy associated with bile duct resection and its actual indications have to be clarified. A systematic review of relevant studies published before December 2007 was performed. Original published studies comparing the results of isolated local excision with those of hepatectomy associated with bile duct resection were identified and the reported results were synthesized. The pathologic data suggest that isolated bile duct resection cannot be adequate: required wide surgical margins; neoplastic extension along perineural sheaths; Segment 1 neoplastic invasion. Considering postoperative outcomes, in the 1990s, local resection had significantly lower mortality rates than liver resection. In recent years, the short-term results of liver surgery have improved significantly, while mortality rates have decreased. The R0 resection rate is significantly higher after associated liver resection. Comparison of survival results between local resection and associated liver surgery is difficult because, in the majority of series, the treatment was planned according to tumor extension. Better long-term outcomes have been reported after liver resection than after isolated bile duct resection, even for Bismuth-Corlette type I-II cholangiocarcinoma. Long-term survivors after local resection have been reported in a few selected patients with Bismuth-Corlette type I Tis-T1 or papillary neoplasm. [ABSTRACT FROM AUTHOR]