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Experimental models with reversible biliary occlusion resulted in a high mortality of the animals, up to 20–60% according to the literature. Our aim was to assess a safe and valid technique for reversible biliary occlusion with a low mortality.

Abstract Background 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods/Design This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned. Discussion The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-20

Abstract Background Haemostasis in liver surgery remains a challenge despite improved resection techniques. Oozing from blood vessels too small to be ligated necessitate a treatment with haemostats in order to prevent complications attributed to bleeding. There is good evidence from randomised trials for the efficacy of fibrin sealants, on their own or in combination with a carrier material. A new haemostatic device is Sangustop®. It is a collagen based material without any coagulation factors. Pre-clinical data for Sangustop® showed superior haemostatic effect. This present study aims to show that in the clinical situation Sangustop® is not inferior to a carrier-bound fibrin sealant (Tachosil®) as a haemostatic treatment in hepatic resection. Methods/Design This is a multi-centre, patient-blinded, intra-operatively randomised controlled trial. A total of 126 patients planned for an elective liver resection will be enrolled in eight surgical centres. The primary objective of this study is to show the non-inferiority of Sangustop® versus a carrier-bound fibrin sealant (Tachosil®) in achieving haemostasis after hepatic resection. The surgical intervention is standardised with regard to devices and techniques used for resection and primary haemostasis. Patients will be followed-up for three months for complications and adverse events. Discussion This randomised controlled trial (ESSCALIVER) aims to compare the new collagen haemostat Sangustop® with a carrier-bound fibrin sealant which can be seen as a "gold standard" in hepatic and other visceral organ surgery. If non-inferiority is shown other criteria than the haemostatic efficacy (e.g. costs, adverse events rate) may be considered for the choice of the most appropriate treatment. Trial Registration NCT00918619

Abstract Background The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods/Design The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. Trial Register Trial registered at http://www.clinicaltrials.gov: NCT00355862 (EudraCT Number: 2005-005362-36)

Tissue transglutaminase 2 (TGM2) and matrix metalloproteinase 7 (MMP7) are suggested to be involved in cancer development and progression, however, their specific role in colon cancer remains elusive. The present study investigated whether TGM2 and MMP7 influence epithelial-mesenchymal-transition (EMT) processes of colon cancer cells. TGM2 was either overexpressed or knocked down in SW480 and HCT-116 cells, and MMP7 expression and activity analyzed. Conversely, MMP7 was silenced and its correlation with TGM2 expression and activity examined. Co-immunoprecipitation served to evaluate TGM2-MMP7-interaction. TGM2 and MMP7 expression were correlated with invasion, migration, EMT marker expression (E-cadherin, N-cadherin, Slug, Snail), and ERK/MEK signaling. TGM2 overexpression enhanced MMP7 expression and activity, promoted cell invasion, migration and EMT, characterized by increased N-cadherin and Snail/Slug expression. TGM2 knockdown resulted in the opposite effects. Knocking down MMP7 was associated with reduced TGM2 protein expression, cell invasion and migration. Down-regulation of MMP7 diminished ERK/MEK signaling, whereas its up-regulation activated this pathway. The ERK-inhibitor GDC-0994 blocked phosphorylation of MEK/ERK and suppressed TGM2 and MMP7. TGM2 communicates with MMP7 in colon cancer cells forces cell migration and invasion by the MEK/ERK signaling pathway and triggers EMT. Inhibiting TGM2 could thus offer new therapeutic options to treat patients with colon cancer, particularly to prevent metastatic progression., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024. Published by Elsevier B.V.)

Background: The impact of resection margin and lymph node status on survival in patients undergoing resection for perihilar cholangiocarcinoma (pCCA) is controversial. The aim of this study was to investigate the influence of nodal and resection margin status on long-term survival after resection for pCCA., Methods: Retrospective analysis of patients resected for pCCA at the University Hospital Frankfurt, Germany between 1999 and 2022. The patients were categorized in four groups according to resection margin (R) and nodal status (N). Survival was analyzed with univariable and multivariable Cox regression., Results: Out of 123 patients, 100 with long-term survival were included in the survival analysis. In the univariable analysis, negative resection margin (p = 0.02) and lower grade (p = 0.004) were the only significant positive prognostic factors, while the difference between N0 and N+ was not statistically significant (p = 0.062). Median survival in the groups R0N0, R0N+, R + N0 and R+N+ groups was 40.1, 29.9, 18.4 and 18.9 months, respectively (p = 0.03). In the multivariable analysis, after adjusting for grade, nodal and resection margin status, only grade and resection margin had prognostic significance., Conclusion: Patients with negative resection margin after resection for pCCA have a better prognosis, regardless of the presence of lymph node metastases., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to compare the combination therapy of transarterial chemoembolization (TACE) and microwave ablation (MWA) with MWA alone in treating liver metastases from colorectal cancer (LMCRC)., Materials and Methods: In this retrospective study, a total of 251 patients with unresectable and not to chemotherapy responding LMCRC were included. Group A consisted of 184 patients (104 male and 80 females; mean age: 64 ± 11.4 years) with 442 metastases who received a combination of TACE and MWA. A total of 67 patients (49 male and 18 females; mean age: 63.2 ± 11.8 years) with 173 metastases patients were included in group B, who received only MWA. Parameters assessed were local tumor progression (LTP), hepatic distant tumor progression (hDTP), hepatic progression-free survival (hPFS), and overall survival (OS)., Results: The rate of LTP was 4.9% in group A and 4.5% in group B (p-value: 0.062). The rate of hDTP was 71.7% and 83.6% for groups A and B (p-value: 0.81), respectively. The mean hPFS was 13.8 months (95% CI 10.9-16.8) for group A and 8.1 months (95% CI 6.1-10.1) for group B (p-value: 0.03). The median OS time for group A was 30 months (95% CI 26-34), with 1-, 2-, 3-, and 4-year OS rates of 84.2%, 61.1%, 40.8% and 31.3%, respectively. In group B however, the median OS time was 26 months (95% CI 18-34) with 1-, 2-, 3-, and 4-year OS rates of 82.3%, 53.2%, 34.6% and 28.2%, respectively (p-value: 0.67)., Conclusion: The combination therapy of TACE and MWA is superior to the monotherapy of MWA for LMCRC, especially regarding hDTP, hPFS and OS., (© 2024. The Author(s).)

Competing Interests: Die Übersicht über die Interessenkonflikte der Autorinnen und Autoren sind im Leitlinienreport veröffentlicht.

Purpose: This study aimed to evaluate the morbidity associated with excisional biopsy in patients with spontaneous gastric perforation., Methods: A retrospective, single-center, observational study was performed. All consecutive patients with spontaneous gastric perforation who underwent surgical therapy were included. Outcomes were assessed concerning the performance of excisional biopsy., Results: A total of 135 adult patients were enrolled. Of these, 110 (81.5%) patients underwent excisional biopsy, while 17 (12.6%) did not. The remaining eight (5.9%) patients who underwent gastric resection were excluded from the analysis. Patients undergoing excisional biopsy developed significantly higher rates of postoperative complications (p = 0.007) and experienced more severe complications according to the Clavien-Dindo classification, particularly type III and above (p = 0.017). However, no significant differences were observed regarding in-hospital mortality, reoperation, suture dehiscence, or length of hospital stay., Conclusion: Excisional biopsy for gastric perforation has been shown to be associated with increased morbidity. Surgical closure followed by early endoscopic biopsy may be a superior approach for gastric perforation management to rule out malignancy., (© 2024. The Author(s).)

Background: Prehabilitation is of becoming of growing interest in the medical specialist societies, especially before major surgical procedures in older and frail patients. The body of evidence in steadily growing., Objectives: Are there good digital solutions for a remote prehabilitation program at home?, Methods: Narrative review of the evidence and current study activities in analogous and digital prehabilitation., Results: Prehabilitation is becoming increasingly more important in the optimal preparation of patients before major surgical procedures. With the help of tailored programs patients can be improved and the risk of complications can be significantly lowered. With an optimal selection, this is not associated with a deterioration of the prognosis for patients with cancer during the intervention lasting for 3-6 weeks. There is still a lack of results and good evidence from well-designed trials for digital solutions., Conclusion: Prehabilitation can be safely implemented in the preparation of patients before major surgical procedures. Digital solutions are currently being developed and tested and could possibly increase the acceptance in the currently intensifying resource shortages., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer., Patients and Methods: This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS)., Results: Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms., Conclusions: Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical., (© 2024. The Author(s).)

BACKGROUND Transplant nephrectomy (TN) has historically been associated with high morbidity and mortality rates. Our objective is to share our own experience and compare indications and surgical outcomes between early and late TN and intracapsular (ICAN) and extracapsular allograft nephrectomy (ECAN) techniques. MATERIAL AND METHODS Our study included all 69 TN procedures performed between January 2010 and February 2021. Of these, 17 TN procedures were performed within the first 60 days after transplantation (referred to as 'early'), while the remaining 52 procedures were performed later ('late'). Within the late allograft nephrectomy (AN) group, we compared the outcomes of intracapsular (ICAN) and extracapsular (ECAN) techniques. We conducted a statistical analysis using the chi-square test and the 2-sample t test. RESULTS The primary indication for early TN was surgical transplant complications (94.1%), with 58.8% of these cases requiring emergency surgery. Morbidity (major complications) occurred in 47.1% of cases, and mortality was 5.9%. In contrast, graft intolerance syndrome was the leading indication for late TN (76.9%), with elective surgery performed in 88.5% of cases. Morbidity (major complications) occurred in 11.5% of cases, and mortality was 3.8%. Within the late TN group, 82.7% of cases were treated with ICAN and 17.3% with ECAN. Blood transfusion was required during surgery in 17.3% of cases, with no significant difference between the groups. Multivariate logistic regression analysis revealed that the timing of surgery was the only statistically significant predictor of complication occurrence. CONCLUSIONS Our data suggest that TN can be performed with relatively low morbidity. However, early TN remains the only independent risk factor for developing adverse outcomes.

The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA.

The aim of this study was to retrospectively evaluate the effects of conventional transarterial chemoembolization (cTACE) for the treatment of hepatocellular carcinoma over 20 years regarding overall survival (OS) and prognostic factors for OS. During the period from 1996 to 2016, 836 patients with HCC were treated with cTACE. Data evaluation was performed on the basis of pre- and postinterventional MRI and CT scans. Survival analysis was performed by Kaplan-Meier estimator; prognostic factors were determined by the use of Cox regression analysis. Overall, 4084 (mean 4.89 TACE sessions/patient) procedures were assessed. Median OS was 700 days (99% CI, 632.8-767.2). Depending on the indication, patients treated with a neoadjuvant intention showed the best OS (1229 days, 99% CI 983.8-1474.2) followed by curative intention (787 days, 99% CI 696.3-877.7), and then palliative intention (360 days, 99% CI 328.4-391.6). Portal vein thrombosis (HR 2.19, CI 1.63-2.96, and p < 0.01) and Child-Pugh class B or worse (HR 1.44, CI 1.11-1.86, and p < 0.001) were significantly associated with shorter OS. Patients with HCC benefit from TACE after careful patient selection. Portal vein thrombosis and Child-Pugh class B or worse are significantly unfavorable prognostic factors for patients' survival.