Search

Background: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings., Methods: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort., Results: Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88)., Conclusion: BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis., Methods: Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n = 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell's C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n = 1,307) and 3 European (n = 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated., Results: Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11-1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57-0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79-75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942 × mean corpuscular volume + 0.399 × alkaline phosphatase-0.339 × albumin-12) × 10 (median, 16; range, 1-30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index = 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively)., Conclusion: Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Data regarding clinical outcomes of patients undergoing hepatic resection for BRAF-mutated colorectal liver metastases (CRLM) are scarce. Most of the studies report an impaired median overall survival (OS) in BRAF-mutated patients, but controversial Results regarding both recurrence-free survival (RFS) and recurrence patterns. The purpose of this updated meta-analysis was to better precise the impact of BRAF mutations on clinical outcomes following liver surgery for CRLM study, especially on recurrence., Methods: A systematic literature review was performed to identify articles reporting clinical outcomes including both OS and RFS, recurrence patterns, and clinicopathological details of patients who underwent complete liver resection for CRLM, stratified according to BRAF mutational status., Results: Thirteen retrospective studies, including 5192 patients, met the inclusion criteria. The analysis revealed that both OS (OR = 1.981; 95% CI = [1.613-2.432]) and RFS (OR = 1.49; 95% CI [1.01-2.21]) were impaired following liver surgery for CRLM in BRAF-mutated patients. Risks of both hepatic (OR = 0.42; 95% CI [0.18-0.98]) and extrahepatic recurrences (OR = 0.53; 95% CI [0.33-0.83] were significantly higher in BRAF-mutated patients. These patients tended to have higher rates of right-sided colon primary tumors, primary positive lymph nodes, and multiple CRLM., Conclusions: This meta-analysis confirms that BRAF mutations impair both OS and RFS following liver surgery. Therefore, BRAF mutational status should probably be included in further prognostic scores for the assessment of the expected clinical outcomes following surgery for CRLM., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status were developed: modified CRS (mCRS) and GAME score. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS., Methods: Patients undergoing hepatectomy for CRLM (2000-2018) in 10 centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrell's C-index and Akaike's Information Criterion., Results: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14 405, 14 447, and 14 319, respectively., Conclusion: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The utility of adjuvant chemotherapy after resection of colorectal liver metastasis (CLM) in patients with rapid recurrence after adjuvant chemotherapy for their primary tumor is unclear. The aim of this study was to evaluate the oncologic benefit of adjuvant hepatic arterial plus systemic chemotherapy (HAIC + Sys) in patients with early CLM., Methods: A retrospective analysis of patients with early CLM (≤12 months of adjuvant chemotherapy for primary tumor) who received either HAIC + Sys, adjuvant systemic chemotherapy alone (Sys), or active surveillance (Surgery alone) following resection of CLM was performed. Recurrence and survival were compared between treatment groups using Kaplan-Meier methods and Cox proportional hazards models., Results: Of 239 patients undergoing resection of early CLM, 79 (33.1%) received HAIC + Sys, 77 (32.2%) received Sys, and 83 (34.7%) had Surgery alone. HAIC + Sys was independently associated with reduced risk of RFS events (adjusted hazard ratio [HRadj]: 0.64, 95%CI:0.44-0.94, p = 0.022) and all-cause mortality (HRadj: 0.54, 95%CI:0.36-0.81, p = 0.003) compared to Surgery alone patients. Largest tumor >5 cm (HRadj: 2.03, 95%CI: 1.41-2.93, p < 0.001) and right-sided colon tumors (HRadj: 1.93, 95%CI: 1.29-2.89, p = 0.002) were independently associated with worse OS., Conclusion: Adjuvant HAIC + Sys after resection of early CLM that occur after chemotherapy for node-positive primary is associated with improved outcomes., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Combined preoperative portal and hepatic vein embolization (biembolization, BE) has been recently described and may further enhance preoperative FLR growth. The objective of this study was to compare the efficacy of combined preoperative biembolization and portal vein embolization (PVE)., Methods: This study was performed between 2010 and 2017. From 2010 to 2014, patients only underwent preoperative PVE. After 2014, BE was proposed as an alternative to PVE. Liver volumetry was assessed by a CT-scan before BE or PVE and then three weeks later., Results: During the study period, 72 patients underwent radiological procedures that included 41 PVE (PVE group) and 31 BE (BE group). The time elapsing between the procedure and surgery was similar (p = 0.760). The mean percentage of FLR ratio hypertrophy in the PVE group was 31.9% (±34), but reached 51.2% (±42) in the BE group (p = 0.018) and this difference remained significant under multivariate analysis that included age, gender, body mass index, diabetes mellitus, cirrhosis and NASH. The kinetic growth rates were 19% (±17%) and 8% (±13%) in the BE and PVE groups, respectively (p = 0.026)., Conclusion: This study shows that BE induces higher hypertrophy than portal vein embolization before major liver resection with no more morbidity., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To analyze clinical outcomes and prognostic variables of patients undergoing hepatic resection for BRAF mutant (BRAF-mut) colorectal liver metastases (CRLM)., Background: Outcomes following hepatectomy for BRAF-mut CRLM have not been well studied., Methods: All patients who underwent hepatectomy for CRLM with complete resection and known BRAF status during 2001 to 2016 at 3 high-volume centers were analyzed., Results: Of 4124 patients who underwent hepatectomy for CRLM, 1497 had complete resection and known BRAF status. Thirty-five (2%) patients were BRAF-mut, with 71% of V600E mutation. Compared with BRAF wild-type (BRAF-wt), BRAF-mut patients were older, more commonly presented with higher ASA scores, synchronous, multiple and smaller CRLM, underwent more major hepatectomies, but had less extrahepatic disease. Median overall survival (OS) was 81 months for BRAF-wt and 40 months for BRAF-mut patients (P < 0.001). Median recurrence-free survival (RFS) was 22 and 10 months for BRAF-wt and BRAF-mut patients (P < 0.001). For BRAF-mut, factors associated with worse OS were node-positive primary tumor, carcinoembryonic antigen (CEA) >200 μg/L, and clinical risk score (CRS) ≥4. Factors associated with worse RFS were node-positive primary tumor, ≥4 CRLM, and positive hepatic margin. V600E mutations were not associated with worse OS or RFS. A case-control matching analysis on prognostic clinicopathologic factors confirmed shorter OS (P < 0.001) and RFS (P < 0.001) in BRAF-mut., Conclusions: Patients with resectable BRAF-mut CRLM are rare among patients selected for surgery and more commonly present with multiple synchronous tumors. BRAF mutation is associated with worse prognosis; however, long-term survival is possible and associated with node-negative primary tumors, CEA ≤ 200 μg/L and CRS < 4.

Background: Colorectal liver metastases that demonstrate a complete radiographic response during chemotherapy are increasingly common with advances in chemotherapy regimens and are described as disappearing liver metastases (DLMs). However, these DLMs often continue to harbor residual viable tumor. If these tumors are found in the operating room with ultrasound (US), they should be treated. The intraoperative sonographic visualization of these lesions, however, can be hindered by chemotherapy-associated liver parenchyma changes. The objective of this study was to evaluate the use of an intraoperative image guidance system, Explorer (Analogic Corporation, Peabody, MA), to aid surgeons in the identification of DLMs initially undetected by US alone., Study Design: In a single-arm prospective trial, patients with colorectal liver metastases undergoing liver resection and/or ablation with one or more DLMs during neoadjuvant chemotherapy were enrolled. Intraoperatively, DLMs were localized with conventional US. Any DLM not found by conventional US was re-evaluated with the image guidance system. The primary outcome was the proportion of sonographically occult DLMs subsequently located by image-guided US., Results: Between April 2016 and November 2017, 25 patients with 61 DLMs were enrolled. Thirty-eight DLMs (62%) in 14 patients (56%) were not identified with US alone. Six (16%) DLMs in five patients (36%) were subsequently located with assistance of the image guidance system. The image guidance changed the intraoperative surgical plan in four of these patients., Conclusions: Image guidance can aid surgeons in the identification of initially sonographically occult DLMs and facilitate the complete surgical clearance of all sites of liver disease.

Background: Insufficient volume of the future liver remnant (FLR) is a major cause of non-resectable disease in patients presenting with primary or metastatic liver tumours. The objective of this study was to evaluate the safety and efficacy of the combined preoperative portal and hepatic vein embolization (biembolization) before extended right liver resections., Methods: This retrospective study was performed in a tertiary centre between 2014 and 2015. Combined right portal and hepatic vein embolization (biembolization) was proposed, as an alternative to ALPPS procedure, for all patients with primary or metastatic liver tumour, before right extended hepatectomy. CT scan liver volumetry was assessed before biembolization, three weeks after biembolization and one week after surgery., Results: Seven patients underwent biembolization. All patients had right portal vein embolization (PVE) combined with right hepatic vein embolization (HVE, n = 4), median HVE (n = 2) and right + median HVE (n = 1). Three patients had preoperative liver disease and two received preoperative chemotherapy. No biembolization procedure-related complications occurred. The mean FLR regeneration rate was 52.6% (range: 18.2-187.9) after the biembolization. One patient with gallbladder carcinoma was not operated because of peritoneal carcinomatosis diagnosed after the biembolization. The remnant six patients did not develop postoperative liver failure., Conclusions: Biembolization seems to induce safe, reproducible and effective FLR growth before extended right hepatectomy, in patients with primary or metastatic liver tumour.

Background: The purpose of this study is to report prolonged survival in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) managed by chemotherapy and surgery., Methods: Between January 2009 and August 2013, 284 patients with metastatic PDAC were managed in our oncologic department. Among them, three (1%) with a single metastasis (liver in two cases and interaorticaval in one case) underwent one- or two-stage surgical resection of the metastasis and the main tumor. Perioperative data were recorded retrospectively, including disease-free and overall survival., Results: The three patients had chemotherapy (FOLFOX or FOLFIRINOX regimen) with objective response or stable disease prior to surgery. Median time between chemotherapy and surgery was 9 (8 to 15) months. Resection consisted in pancreaticoduodenectomy in the three cases. None of the patients had grade III/IV postoperative complications, and median hospital stay was 12 (12 to 22) days. All the patients had postoperative chemotherapy. Only one patient experienced recurrence 11 months after surgery and died after 32.5 months. The two other patients were alive with no recurrence 26.3 and 24.7 months after initial treatment., Conclusion: Radical resection of PDAC with single distant metastases can offer prolonged survival with low morbidity after accurate selection by neoadjuvant chemotherapy.

The management of hepatic metastases from colorectal cancer (HMCRC) is multimodal including chemotherapy, surgical resection, radiation therapy, and focused destruction technologies. Radiofrequency ablation (RFA) is the most commonly used focused destruction technology. It represents a therapeutic option that may be potentially curative in cases where surgical excision is contra-indicated. It also increases the number of candidates for surgical resection among patients whose liver metastases were initially deemed unresectable. This article explains the techniques, indications, and results of radiofrequency ablation in the treatment of hepatic colorectal metastases., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by both right PVL and ligation of the glissonian branches of segment 4 for colorectal liver metastases surrounding the right and median hepatic veins. After surgery, the patient developed massive hepatic necrosis with secondary pulmonary and renal insufficiency requiring transfer to the intensive care unit. This so-called toxic liver syndrome finally regressed after hemofiltration and positive oxygen therapy. Diagnosis of acute congestion of the ligated lobe was suspected. The mechanism suspected was an increase in arterial inflow secondary to portal vein ligation concomitant with a decrease in venous outflow due to liver metastases encircling the right and median hepatic vein. This is the first documented case of toxic liver syndrome in a non-cirrhotic patient with favorable issue, and a rare complication of PVL.

At time of diagnosis, 10 to 25% of patients with colorectal cancer present synchronous liver metastases. The treatment of such patients remains controversial without any evidence based organization. Therapeutic sequences are discussed including chemotherapy, colorectal surgery, liver resection and even radio-chemotherapy for some rectal cancers. In case of resectable liver metastases, preoperative chemotherapy offers the advantage of earlier treatment of micro-metastases as well as evaluation of tumor responsiveness, which can help shape future therapy. In this setting, different surgical strategies can be chosen (classical staged procedures with colorectal surgery followed by liver surgery, simultaneous resections or liver first approach) depending on the importance of the primary and metastatic tumors. The literature remains limited, but the results of these strategies seem identical in term of postoperative morbidity and long-term survival. Staged procedures are preferred in case of major liver resection. Location of the primary tumor on the low or mid rectum will necessitate preoperative long course chemoradiotherapy and a more complex multidisciplinary organization. For patients with extensive liver metastases, non-resectability must be assessed by experienced surgeon and radiologist before treatment and during chemotherapy. In this group of patients, improved chemotherapy regimen associated with targeted therapies and new surgical strategies (portal vein embolization, ablation, staged hepatectomies…) have improved resection rate (15 to 30-40%) and long-term survival. Treatment organization for the primary tumor remains controversial. Resection of the primary to manage symptoms such as obstruction, perforation or bleeding is advocated. For patients with asymptomatic primary a non-surgical approach permits to begin rapidly chemotherapy and obtain a better control of the disease. On the other hand, initial resection of the primary may avoid complications and the need for urgent surgical procedures. Both of these strategies are practiced without definitive evidence supporting one treatment option over the other.