Objective:The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT).Background:Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression.Methods:A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome—RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention.Results:Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%–100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%–72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6–26.6); P < 0.0001]. No differences in complications (Clavien–Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4–2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3–6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9–7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS.Conclusion:ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

Objective: To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation. Background: Patients with nonresectable colorectal cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 μg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation. Methods: In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year. Results: At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study. Conclusion: Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.

In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued implementation of laparoscopic liver resection.

BackgroundLaparoscopic liver resection is used in specialized centers all over the world. However, laparoscopic liver resection has never been compared with open liver resection in a prospective, randomized trial.Methods/DesignThe Oslo-CoMet Study is a randomized trial into laparoscopic versus open liver resection for the surgical management of hepatic colorectal metastases. The primary outcome is 30-day perioperative morbidity. Secondary outcomes include 5-year survival (overall, disease-free and recurrence-free), resection margins, recurrence pattern, postoperative pain, health-related quality of life, and evaluation of the inflammatory response. A cost-utility analysis of replacing open surgery with laparoscopic surgery will also be performed. The study includes all resections for colorectal liver metastases, except formal hemihepatectomies, resections where reconstruction of vessels/bile ducts is necessary and resections that need to be combined with ablation. All patients will participate in an enhanced recovery after surgery program. A biobank of liver and tumor tissue will be established and molecular analysis will be performed.DiscussionAfter 35 months of recruitment, 200 patients have been included in the trial. Molecular and immunology data are being analyzed. Results for primary and secondary outcome measures will be presented following the conclusion of the study (late 2015). The Oslo-CoMet Study will provide the first level 1 evidence on the benefits of laparoscopic liver resection for colorectal liver metastases.Trial registrationThe trial was registered in ClinicalTrals.gov (NCT01516710) on 19 January 2012.

Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Continuous antigen stimulation of CD4 + CD25 -T cells leads to generation of adaptive CD4 + CD25 + FOXP3 + regulatory T (T R ) cells. Here, we show that highly suppressive adaptive CD8 + CD25 + FOXP3 + T cells can be generated in the same manner by continuous antigen stimulation in the presence of CD14 + monocytes. During the course of stimulation, acquisition of immunosuppressive properties develops in parallel with up-regulation and expression of cytotoxic molecules. The CD8 + T R cells inhibit CD4 + and CD8 + T cell proliferation and cytokine production, but do not alter the expression of granzyme A and granzyme B or perforin in CD8 + effector T cells. Although, the CD8 + T R cells express prostaglandin E 2 , IL-10 and TGF-b, the mechanism of suppression was independent of these soluble factors. In contrast to adaptive CD4 + T R cells, the CD8 + T R cells suppress mainly by a contact-dependent mechanism as evident from transwell experiments. However, neither blocking antibodies to CTLA-4, CD80 nor CD86 could reverse CD8 + T R -mediated suppression, indicating that other mechanism(s) must be employed by these cells. IntroductionCD4 + regulatory T (T R ) cells maintain self-tolerance to autoantigens and are involved in the pathogenesis of various clinical conditions such as autoimmune diseases, chronic viral infections and cancer. Several subsets of CD4 + T R cells have been characterized [1,2]. Whereas naturally occurring CD4 + CD25 + FOXP3 + T R cells are generated in the thymus and suppress effector T cells in a cell contact-dependent manner [3][4][5], adaptive CD4 + CD25 + FOXP3 + T R cells are induced from naive T cells in the periphery and the suppressive activity is independent of cell contact [2,[6][7][8].Suppressive T cells are not strictly confined to the CD4 + T cell compartment and CD8 + T R cells have been characterized in both clinical and experimental conditions [9][10][11][12]. The CD8 + T R cells share phenotypic features with CD4 + T R cells, and as their counterpart, CD8 + T R cells can be generated both in the thymus and in the periphery [13][14][15][16][17][18].In humans, two subsets of adaptive CD8 + CD28 -T R cells exist. Type 1 CD8 + T R cells are generated by stimulation of naive T cells with allogeneic antigenpresenting cells (APC) [19][20][21] properties appears in parallel with up-regulation and expression of cytotoxic molecules. Although the adaptive CD8 + T R cells express prostaglandin E 2 (PGE 2 ), IL-10 and TGF-b, the suppressive mechanism appears to be cell contact-dependent. This is in contrast to adaptive CD4 + T R cells that inhibit T cell immune responses by secretion of humoral factors. Figure 1. Generation of adaptive CD8 + T R cells by continuous antigen stimulation. (A) CD25 + cell-depleted PBMC were stimulated with SEB (4 days). CD8 + CD25 + T cells were added in increasing concentrations to CD25 -cells stimulated with SEB from the autologous blood donor. Proliferation of responding T cells was assessed by CFSE proliferation assay. Representative data are shown (n = 2...

We suggest that adaptive T(R) cells contribute to an immunosuppressive microenvironment in CRC and inhibit effector T cells by a COX-2-PGE(2)-dependent mechanism and thereby facilitate tumor growth. Therapeutic strategies targeting T(R) cells and the PGE(2)-cAMP pathway may be interesting to pursue to enhance anti-tumor immune activity in CRC patients.

Gladhaug (2016) Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma -A population-based cohort study, Acta Oncologica, 55:3,[265][266][267][268][269][270][271][272][273][274][275][276][277] DOI: 10.3109 conclusions. MMT completion is strongly associated with reduced mortality risk in patients with resectable PDAC undergoing the SF approach. Early disease progression and PMC/poor performance status preclude MMT completion in more than one third of the patients. These reasons for failure to complete MMT underscore the need for strategies to improve patient selection and reduce surgical morbidity in patients with resectable PDAC.