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Purpose: The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long-term survival in CRLM patients., Methods: A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan-Meier plotter and compared using the log-rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data., Results: In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088-4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398-5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high-risk and low-risk groups. Notably, in the high-risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low-risk group., Conclusions: KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high-risk., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Chemotherapy is the mainstay treatment for liver metastasis from gastric cancer. However, some retrospective studies and meta-analyses have indicated the efficacy of hepatectomy, which is an aggressive treatment option. However, the optimal selection criteria for hepatectomy and the role of perioperative chemotherapy remain unclear. Therefore, a meta-analysis of studies on hepatectomy was performed to assess the impact of various factors on overall survival (OS). A systematic review was conducted in accordance with the PRISMA criteria using studies published until 2022. The primary outcome was the hazard ratio (HR) for OS. Comparisons were made between hepatectomy and nonhepatectomy, solitary and multiple metastases, synchronous and metachronous metastases, treatment with and without neoadjuvant chemotherapy, and treatment with and without adjuvant chemotherapy. A total of 50 studies involving 1966 patients who underwent hepatectomy were included in the analysis. The meta-analysis showed a 5-year OS rate of 25 %. A meta-analysis comparing hepatectomy with nonhepatectomy showed an HR of 0.2 for hepatectomy. A meta-analysis comparing solitary and multiple metastases showed a trend toward better OS in patients with solitary metastases (odds ratio [OR]: 0.35). A meta-analysis comparing synchronous and metachronous metastases showed favorable OS for patients with metachronous metastases (OR: 0.66). A meta-analysis comparing neoadjuvant chemotherapy with no neoadjuvant chemotherapy showed no difference in OS. In contrast, a meta-analysis comparing adjuvant chemotherapy with no adjuvant chemotherapy showed better OS for adjuvant chemotherapy (OR: 0.39). This retrospective study indicates that hepatectomy may benefit patients with liver metastases from gastric cancer, particularly those with solitary and metachronous metastases., Competing Interests: Declaration of competing interest M.T. has received research grants from Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squib Japan K.K., Yakult Honsha Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan, Pfizer Japan Inc., Daiichi Sankyo Ltd., Johnson and Johnson K.K., Medtronic Japan Co., Ltd., Intuitive Japan Inc., and Olympus Co., Ltd., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability., Methods: This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP., Results: A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03)., Conclusions: CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP., (© 2024. The Author(s).)

Background/aim: No clear treatment strategy for simultaneously detected liver and lung metastases (SLLM) of colorectal carcinoma has been established, to date. We aimed to identify the prognostic factors for SLLM and propose an appropriate treatment option., Patients and Methods: This retrospective study included 64 patients with SLLM: 32 underwent pulmonary resection after hepatectomy in 32, while the other 32 underwent hepatectomy alone in 32. Poor prognostic factors and a suitable strategy for SLLM were assessed., Results: Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) level ≥20 ng/ml (p=0.001) and unresected lung metastases (p=0.001) were independent prognostic factors for poor overall survival. Compared with the non-pulmonary resection group, the rate of R1 resection of liver tumors (46.8% vs. 15.6%; p=0.007), incidence of complications after hepatectomy (Clavien-Dindo grade ≥III: 21.8% vs. 0%; p=0.005) and having four or more metastatic lung nodules (40.6% vs. 3.2%; p=0.001) were significantly higher in the group that underwent hepatectomy only., Conclusion: Preoperative CEA ≥20 ng/ml and unresectable pulmonary nodules were prognostic factors for poor survival of patients with SLLM. Furthermore, the presence of more than four pulmonary nodules was a preoperative predictive factor for unresectable pulmonary nodules. R1 resection and the occurrence of complications after hepatectomy should be avoided; a smooth transition from hepatectomy to pulmonary resection is important., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection., Methods: A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1 cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables., Results: The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38 months (30-54) and 13 months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5 cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5 cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences., Conclusion: The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers., (© 2024. The Author(s).)

Background: Optimal management of colorectal liver metastasis (CRLM) is based on a combination of chemotherapy and surgical resection. The tumor regression grade (TRG) score is a histological scoring system to evaluate response to chemotherapy. The prognosis of a heterogeneous response in cases of multiple metastases has not been evaluated according to the TRG score., Patients and Methods: All patients who underwent liver resection for multiple CRLM after neoadjuvant chemotherapy in two tertiary centers from January 2015 to April 2019 were retrospectively included. Oncological characteristics and outcome between TRG 1-2-3 (good response group), TRG 4-5 (poor response group) and heterogeneous TRG (good and poor TRG among different lesions within the same patient) groups were compared., Results: Among the 327 patients included, 134 (41.0%) had good response (TRG 1-2-3), 120 (36.7%) had poor response (TRG 4-5), and 73 (22.3%) had heterogeneous response. The type and number of cycles of chemotherapy, k-Ras mutational status, and tumor number or size did not differ between the three groups. Use of irinotecan-based and anti-VEGF neoadjuvant therapy was associated with better TRG response [irinotecan-based: hazard ratio (OR) = 1.744; p = 0.045; anti-VEGF neoadjuvant therapy: 2.054; p = 0.005). Overall survival (OS) was higher in the 1-2-3 TRG group than in the heterogeneous TRG group (2-year OS = 81.3% vs. 60.3%, respectively; p = 0.003) and the 4-5 TRG group (2-year OS = 81.3% vs. 55.0%, respectively; p = 0.012) and similar between the heterogeneous and 4-5 TRG groups., Conclusions: The proportion of heterogeneous pathological response according to TRG is 22.3%, and the prognosis is comparable to that of poor pathological response., (© 2024. Society of Surgical Oncology.)

Background: Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression., Methods: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry., Results: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding., Conclusions: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luenstedt, Hoping, Feuerstein, Mauerer, Berlin, Rapp, Marx, Reichardt, von Elverfeldt, Ruess, Plundrich, Laessle, Jud, Neeff, Holzner, Fichtner-Feigl and Kesselring.)

Purpose: Distant metastasis develops in approximately one-third of patients with colorectal cancer (CRC) who undergo radical surgery, and colorectal liver metastasis (CRLM) is the most common form of distant metastasis in CRC. Hepatectomy is the only potentially curative treatment for CRLM, but few patients with metastatic CRC meet the criteria for this radical resection, and the 5-year survival rate is poor. Identifying risk factors for CRLM is critical. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for CRC. However, the effect of NAFLD on CRC liver metastasis after radical surgery remains unclear. Therefore, we examined the impact of NAFLD-associated hepatic fibrosis on liver metastasis after radical surgery for CRC., Methods: We retrospectively analyzed data from 388 patients who underwent curative surgery for CRC at our hospital between April 2008 and March 2015. The patients' clinical results, surgical procedures, postoperative course, and pathological and survival data were collected from the hospital records. The NAFLD fibrosis score was calculated and used to divide the patients into two groups (NAFLD and non-NAFLD)., Results: Recurrence was observed in 83/388 (21.4%) patients after a mean follow-up of 65.6 ± 15.1 months. Twenty-five patients had liver metastasis: 8 in the NAFLD group (8/45; 17.8%) and 17 in the non-NALFD group (17/343; 5.0%) (p = 0.004). Liver metastasis-free survival was significantly worse in the NAFLD than non-NAFLD group (p < 0.001). NAFLD and cancer stage were independent risk factors for liver metastasis recurrence., Conclusion: NAFLD may be a risk factor for liver metastasis in patients with CRC who undergo curative surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018., Aims: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy., Methods and Results: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy., Conclusion: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Introduction: Resection of colorectal liver metastasis has emerged as the standard treatment. Our study compares oncological outcomes of patients with resected synchronous bilobar versus unilobar colorectal liver metastasis., Methods: This retrospective study presents long-term follow-up data of 105 consecutive patients with primary colorectal cancer and synchronous liver metastasis. All patients underwent primary tumor and metastasis resections between 2007 and 2019., Results: Fifty-five patients with bilobar and 50 patients with unilobar colorectal liver metastases were included. No significant difference in overall, tumor-specific, or recurrence-free survival was observed between patients with bilobar and unilobar metastases. After case-control matching, the results were confirmed in patients with similar tumor burdens. In the multivariate analysis, chemotherapy following liver metastasis resection was a significant prognostic factor associated with improved overall survival (hazard ratio 0.518, 95% confidence interval: 0.302-0.888, p = 0.017)., Conclusion: Overall survival, as well as tumor-specific and recurrence-free survival, did not differ between patients with unilobar and bilobar liver metastasis. These findings contribute to the understanding that primary tumor and metastasis resection in eligible patients improve long-term outcomes., (© 2024 S. Karger AG, Basel.)

Background: The impact of hepatic resection for liver metastases (LM) on the survival of pediatric patients with Wilms' tumor (WT) is unclear. So far, there is a lack of studies investigating the best suited treatment for patients with WTLM, and the role of liver resection has rarely been investigated. Thus, the development of evidence-based guidelines concerning indications of liver resection for WTLM remains difficult., Aim: To investigate the role of surgery in the therapy of WTLM. All available data on liver resections and subgroup outcomes of patients with WTLM are analyzed. Main research question is whether liver resection improves survival rates of patients with WTLM compared to non-surgical treatment., Methods: A systematic literature search of MEDLINE, Web of Science, and Central provided the basis for this PRISMA-compliant systematic review. For the main analysis (I), all studies reporting on surgical treatment of pediatric WTLM were included. To provide a representative overview of the general outcome of WTLM patients, in analysis II all studies with cohorts of at least five WTLM patients, regardless of the kind of treatment, were reviewed and analyzed. A Multiple meta-regression model was applied to investigate the impact liver resection on overall survival., Results: 14 studies with reports of liver resection for WTLM were found (Analysis I). They included a total of 212 patients with WTLM, of which 93 underwent a liver resection. Most studies had a high risk of bias, and the quality was heterogenous. For the analysis II, eight studies with subgroups of at least five WTLM patients were found. The weighted mean overall survival (OS) of WTLM patients across the studies was 55% (SD 29). A higher rate of liver resection was a significant predictor of better OS in a multiple meta-regression model with 4 covariates (I2 29.43, coefficient 0.819, p = 0.038)., Conclusions: This is the first systematic review on WTLM. Given a lack of suited studies that specifically investigated WTLM, ecological bias was high in our analyses. Generating evidence is complicated in rare pediatric conditions and this study must be viewed in this context. Meta-regression analyses suggest that liver resection may improve survival of patients with WTLM compared to non-surgical treatment. Especially patients with persisting disease after neoadjuvant chemotherapy but also patients with metachronous LM seem to benefit from resection. Complete resection of LM is vital to achieve higher OS. Studies that prospectively investigate the impact of surgery on survival compared to non-surgical treatment for WTLM are highly needed to further close the current evidence gap., Study Registration: PROSPERO 2021 CRD42021249763  https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=249763 ., (© 2022. The Author(s).)

Purpose: Patients with liver metastasis of head-and-neck carcinoma and esophageal carcinoma are generally not treated with hepatic resection, but there are no established standard treatment methods. We report 11 cases of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma performed at 5 Japanese institutions., Methods: The subjects of this retrospective analysis were 11 patients who underwent hepatic resection for metastatic liver tumors, originating from head-and-neck carcinoma in 5 and from esophageal cancer in 6, between January, 2010 and March, 2020 RESULTS: There were nine men and two women (median age, 64 years; range 40-72 years). The primary disease was esophageal carcinoma in six patients and pharyngeal carcinoma in five patients. All cancers were squamous cell carcinoma. The time from the initial treatment to the diagnosis of liver metastasis was 15.3 months and the 1-year and 3-year overall survival rates after hepatic resection were 72% and 32%, respectively. The overall and disease-free survival rates after hepatic resection were significantly higher for patients who underwent hepatic resection more than 12 months after the initial treatment than for those who underwent hepatic resection within 12 months after the initial treatment (p = 0.0172 and p = 0.0120, respectively)., Conclusions: Liver resection may prolong the survival of patients with liver metastases controlled for more than 12 months after the initial treatment of head and neck or esophageal carcinoma., (© 2021. Springer Nature Singapore Pte Ltd.)

Introduction: Resection of colorectal liver metastases provides the best chance for survival in patients with Stage IV colorectal cancer; however, hepatic recurrence is frequent and the main cause of death. Multiple epidemiological studies have documented an association between metformin and anti-neoplastic effects in a variety of cancers. Given the vast literature, we evaluated the incidence on recurrence and survival of patients on metformin who undergo surgery for colorectal liver metastasis (CRLM)., Methods: We selected 270 consecutive patients with known CRLM who underwent hepatic metastases resection at our institution between January 1st 2012 and December 31st 2019. Patients were divided based on their use of metformin (n = 62) or no metformin (n = 208). Adjusted analysis of recurrence-free (RFS) and overall survival (OS) was performed., Results: Patients on metformin had significantly longer RFS (HR: .44, 95% CI: .26-.75, P < .002; Median RFS: 49 months vs 33 months) and OS (HR .60, 95% CI .31-.97, P < .048, Median OS: 72 months vs 60 months). Additional factors associated with shorter RFS on univariate analysis included the following: CEA > 200 ng/ml (HR: 2.23, 95% CI 1.21-4.03, P < .010), positive liver margin (HR: 3.70, 95% CI 2.27-6.03, P < .001), and >1 tumor (HR: 1.98, 95% CI 1.26-3.09, P < .003). Liver margin remained a significant factor for predicting shorter OS (HR: 4.99, 95% CI 2.49-10.0, P < .001)., Conclusion: In this study, we found that patients with CRLM on metformin have prolonged RFS and OS postliver resection. Further prospective randomized trials need to be carried out to evaluate the anti-neoplastic effect of metformin in diabetic and non-diabetic cancer patients.

Background/aim: We aimed to investigate the prognosis of patients who received radiofrequency ablation (RFA) for liver metastases of unresectable colorectal cancer (CRC)., Patients and Methods: We retrospectively compared 147 patients treated for CRC liver metastases, who underwent RFA (n=26), resection (n=92), and chemotherapy (n=29) between 2001 and 2021., Results: RFA and chemotherapy were performed for unresectable or non-operable cases, and resection was performed for suitable cases. The median overall survival (OS) was 44.9, 49.5, and 11.6 months for patients who underwent RFA, resection, and chemotherapy, respectively. RFA led to a significantly shorter OS compared to resection (p=0.027) but to a longer OS compared to chemotherapy (p=0.003). The 5-year survival rates were 34.6% and 42.4% for patients who underwent RFA and resection, respectively (p=0.508)., Conclusion: RFA has the potential to achieve long-term survival or radical cure, even for unresectable or non-operable cases of CRC with liver metastasis., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score., Methods: A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS., Results: Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p < .001). In the multivariate Cox model, a high OLGS was an independent predictor of 5-year OS (p < .001), and the hazard ratio (HR) of the OLGS-high group (HR = 7.171) was higher than that of the high clinical risk score group (HR = 4.337)., Conclusion: The OLGS, a simple and handy scoring system, better predicts the 5-year OS of patients with CRLMs after hepatectomy and warrants prospective validation., (© 2021 Wiley Periodicals LLC.)

Background/aim: The aim of this study was to investigate frailty as a prognostic factor in patients with colorectal liver metastasis undergoing hepatectomy., Patients and Methods: Eighty-seven patients who underwent hepatectomy at our institution were enrolled. Frailty was defined as a score of ≥4 on a clinical frailty scale. Patients were divided into frailty (n=29) and non-frailty (n=58) groups., Results: Overall and cancer-specific survival rates were significantly worse in the frailty group compared with the non-frailty group, and multivariate analysis revealed frailty as an independent prognostic factor. Disease-free survival tended to be worse in the frailty group. Fifty-eight patients relapsed after the first hepatectomy. Twenty-one of 58 recurrent patients were allocated to the frailty group. After recurrence, chemotherapy was significantly more frequently performed in the non-frailty group compared with the frailty group., Conclusion: Frailty can predict the prognosis of patients with colorectal liver metastasis undergoing hepatectomy., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Opinion Statement: Treatment for metastatic colorectal cancer (CRC) has changed significantly over the last few decades as cytotoxic and targeted chemotherapies have evolved and resection of (technically feasible) colorectal liver metastases (CRLM) has become standard of care for eligible patients. Overall, survival for metastatic CRC has considerably improved, but recurrences are common. Numerous clinical risk scores have been suggested to guide patient selection for CRLM resection, but none perfectly predict outcomes; therefore, a personalized approach to metastatic CRC treatment using genetic profiles for risk stratification and prognostication is a critically important advancement. All patients with suspected metastatic CRC should undergo genetic testing for common oncogene mutations (e.g., KRAS, BRAF, and NRAS) in addition to a triphasic CT scan of the chest, abdomen, and pelvis; if hepatectomy may be entertained and there is concern about the future liver remnant (FLR), liver volumetrics should also be performed. MRI and PET are useful adjuncts for cases in which diagnosis or extent of disease is unclear. The decision to operate should be individualized and based on each patient's condition, tumor biology, and technical resectability. Genetic profiles should be used to inform multidisciplinary meetings surrounding topics of chemotherapy and surgical resection, as well as patient discussions concerning the risks and benefits of surgery. In the end, most patients with technically resectable colorectal cancers and adequate cardiopulmonary fitness benefit from surgical resection, as it remains the only chance of long-term survival.

Surgical resection for primary and secondary hepatic neoplasms provides the best chance of cure. Advanced surgical techniques such as portal vein embolisation, two-staged hepatectomy and associated liver partition and portal vein ligation for staged-hepatectomy (ALPPS) have facilitated hepatic resection in patients with previously unresectable, bi-lobar disease. These techniques are frequently employed to ensure favourable clinical outcomes and avoid potentially fatal post-operative complications such as small for size syndrome and post-hepatectomy liver failure. However, they rely on the innate ability of the liver to regenerate. As our knowledge of liver organogenesis, liver regeneration and hepatocarcinogenesis has expanded in recent decades it has come to light that liver regeneration may also drive tumour recurrence. Clinical studies in patients undergoing portal vein embolisation indicate that tumours may progress following the procedure in concordance with liver regeneration and hypertrophy, however overall survival in these patients has not been shown to be worse. In this article, we delve into the mechanisms underlying liver regeneration to better understand the complex ways in which this may affect tumour behaviour and ultimately inform clinical decisions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Robotic approach to the liver may allow to perform difficult resections with a minimally invasive strategy in an easier way as compared to standard laparoscopy. The aim of this study is to review our experience with robotic major hepatectomies, reporting technical considerations, and describing the outcomes of patients that underwent either left (LRH) or right robotic hepatectomy (RRH). Our prospectively maintained database was screened to identify all patients that received a major liver resection for benign or malignant disease. Preoperative data and postoperative short-term and long-term outcomes were reported. 261 robotic procedures were performed in our Center between May 2014 and October 2020. 12 patients underwent robotic left hepatectomy (RLH) and 10 patients were treated by robotic right hepatectomy (RRH). In the RLH group, median operative time (OT) was 383 min, median estimated blood loss (EBL) was 300 ml, and median in-hospital stay was of 3 days. In the RRH group, median OT was 490 min, median EBL 725 ml, and median hospital stay was 5 days. Although one of the advantages of minimally invasive surgery is to obtain radical resections with parenchyma sparing strategies, patients that need a major hepatectomy may benefit of a robotic resection with good postoperative outcomes. Team learning curve and growth instead of personal progression is crucial to expand the limits of novel surgical techniques.

Background and Objectives: The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value., Methods: In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with 18 Fluorodeoxyglucose/positron emission tomography., Results: In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients., Conclusions: Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM., (© 2021 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: Simultaneous robot assisted colon and liver resections are being performed more frequently at present due to the expanded adoption of the robotic platform for surgical management of metastatic colon cancer. However, this approach has not been studied in detail with only case series available in the literature. The aim of this systematic review was to evaluate the current body of evidence on the feasibility of performing simultaneous robotic colon and liver resections., Methods: A systematic review was performed through PubMed to identify relevant articles describing simultaneous colon and liver resections for metastatic colon cancer., Results: A total of 28 patients underwent simultaneous resections robotically with an average operative time of 420.3 minutes and average blood loss of 275.6 ml. Postoperative stay was 8.6 days on average with all cases achieving negative surgical margins., Conclusions: Robotic simultaneous resection of colorectal cancer with liver metastases is technically feasible and seems oncologically equivalent to open or laparoscopic surgery. Further studies are urgently needed to assess benefits of robotic surgery in the patient population., Competing Interests: Conflicts of Interest: none., (© 2021 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Surgical resection remains the only curative therapy for colorectal adenocarcinoma and liver metastasis. Synchronous robotic resection for colorectal liver metastasis (CRLM) offers the advantage of avoiding double surgical stress, while providing the benefits of small incision, quicker recovery, shorter hospital stay and faster postoperative adjuvant therapy. Compared with the laparoscopic approach, robotic approach is mostly suitable for rectal cancer liver metastasis, which is associated with low conversion rate, good nerve protection, high success rate for major hepatectomy and resection of difficult segments. Appropriately selected patients, multidisciplinary cooperation and skillful robotic surgeons are the key to success. Current data have demonstrated the feasibility and safety of synchronous robotic resection for CRLM. With the coming randomized controlled trial data and evolution of robotic surgical system, the future of synchronous robotic resection for colorectal liver metastasis is promising.

Background: Synchronous colorectal cancer liver metastasis (CRLM) has been viewed as being more aggressive and having shorter survival than metachronous disease. Advances in CRLM management led us to examine differences in treatment characteristics of synchronous versus metachronous CRLM patients along with survival and recurrence., Materials and Methods: A retrospective review of hepatic resection for CRLM at a tertiary academic medical center was performed for two periods: a historic cohort from 1992 to 2010 (n = 121), and a modern cohort (n = 179) from 2012 to 2018. Clinical variables were compared between the patient groups, and survival outcomes were characterized., Results: Five-year disease-specific survival for the modern synchronous group compared to the historic synchronous group was 71.7% versus 44.3% (P = 0.02). Modern metachronous versus modern synchronous 5-y disease-specific survival rates were 49.8% versus 71.7% (P = 0.31). Compared to the historic cohort, the modern one had significantly different timing of hepatic resection (P < 0.01) with increased use of liver-first (30.1% versus 7.5%) and simultaneous liver-colon resections (24.1% versus 10.4%), along with greater use of neoadjuvant chemotherapy (96.4% versus 65.6%; P < 0.01). Significantly more patients in the modern synchronous cohort had disease-free or alive-with-disease status at last follow-up, compared to the historic group (P < 0.01), and experienced less disease recurrence (62.7% versus 77.6%; P < 0.05)., Conclusions: Modern synchronous CRLM patients who underwent hepatic resection experienced significantly improved survival compared to a historic cohort. We postulate that increased use of neoadjuvant chemotherapy and liver-first/simultaneous liver-colon resections in the modern synchronous cohort contributed to improved survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patient-related risk factors such as diabetes mellitus and obesity are increasing in western countries. At the same time the indications for liver resection in both benign and malignant diseases have been significantly extended in recent years. Major liver resection is performed more frequently in a patient population of old age, comorbidity and high rates of neoadjuvant chemotherapy. The aim of this study was to evaluate whether diabetes mellitus, obesity and overweight are risk factors for the short-term post-operative outcome after major liver resection., Methods: Four hundred seventeen major liver resections (≥ 3 segments) were selected from a prospective database. Exclusion criteria were prior liver resection in patient's history and synchronous major intra-abdominal procedures. Overweight was defined as BMI ≥ 25 kg/m 2 and < 30 kg/m 2 and obesity as BMI ≥ 30 kg/m 2 . Primary end point was 90-day mortality and logistic regression was used for multivariate analysis. Secondary end points included morbidity, complications according to Clavien-Dindo classification, unplanned readmission, bile leakage, and liver failure. Morbidity was defined as occurrence of a post-operative complication during hospital stay or within 90 days postoperatively., Results: Fifty-nine patients had diabetes mellitus (14.1%), 48 were obese (11.6%) and 147 were overweight (35.5%). There were no statistically significant differences in mortality rates between the groups. In the multivariate analysis, diabetes was an independent predictor of morbidity (OR = 2.44, p = 0.02), Clavien-Dindo grade IV complications (OR = 3.6, p = 0.004), unplanned readmission (OR = 2.44, p = 0.04) and bile leakage (OR = 2.06, p = 0.046). Obese and overweight patients did not have an impaired post-operative outcome compared patients with normal weight., Conclusions: Diabetes has direct influence on the short-term postoperative outcome with an increased risk of morbidity but not mortality. Preoperative identification of high-risk patients will potentially decrease complication rates and allow for individual patient counseling as part of a shared decision-making process. For obese and overweight patients, major liver resection is a safe procedure.

Background: Liver metastases are rare in children with Wilms tumor (WT), and their impact on the outcome is unclear., Patients and Methods: The French cohort of patients with WT presenting liver metastases at diagnosis and enrolled in the International Society of Pediatric Oncology (SIOP) 2001 study was reviewed., Results: From 2002 to 2012, 906 French patients were enrolled in the SIOP2001 trial. Among them, 131 (14%) presented with stage IV WT and 18 (1.9%) had liver metastases at diagnosis. Isolated liver metastases were displayed in four of them. After preoperative chemotherapy, persistent liver disease was reported in 14/18 patients, and 13 of them underwent metastasectomy after nephrectomy. In resected liver lesions, the same histology of the primary tumor was reported for three patients, blastemal cells without anaplasia were identified in one patient with DA-WT, and post-chemotherapy necrosis/fibrosis was identified for the other 10 patients. For the four patients who had liver and lung surgery, both sites had nonviable cells with post-chemotherapy necrosis/fibrosis. Six patients had hepatic radiotherapy. Sixteen patients achieved primary complete remission and were alive at the last follow-up (median follow-up: 6.4 years). The only two deceased patients presented diffuse anaplasia histology. The five-year EFS and OS were 83% (60%-94%) and 88% (66%-97%), respectively., Conclusion: Liver involvement does not appear to be an adverse prognostic factor in metastatic WT. The role of hepatic surgery and radiotherapy remains unclear, and should be carefully considered in case of persistent liver metastases, according to histology and radiological response to other metastatic sites., (© 2020 Wiley Periodicals, Inc.)

Background: Numerous reports regarding sarcopenia have focused on the quantity of skeletal muscle. In contrast, the impact of the quality of skeletal muscle has not been well investigated., Methods: A retrospective analysis of 115 patients who underwent initial hepatectomy for colorectal liver metastasis between January 2009 and December 2016 in our hospital was performed. Intramuscular adipose tissue content (IMAC) was used to evaluate the quality of skeletal muscle by analysing computed tomography (CT) images at the level of the umbilicus. The impact of poor skeletal muscle quality on short-term and long-term outcomes after hepatectomy for colorectal liver metastasis was analysed., Results: Patients were divided into two groups (high IMAC and normal IMAC) according to their IMAC values, and their backgrounds were compared. There were no significant differences in most factors between the two groups. However, both body mass index (P = 0.030) and the incidence of postoperative complications of Clavien-Dindo grade 3 or worse (P = 0.008) were significantly higher in the high-IMAC group. In multivariate analyses, an operative blood loss > 600 ml (P = 0.006) and high IMAC (P = 0.008) were associated with postoperative complications of Clavien-Dindo grade 3 or worse. Overall survival and recurrence-free survival were significantly lower (P < 0.001 and P = 0.045, respectively) in the high-IMAC group than in the normal IMAC group. In multivariate analyses for poor overall survival, high IMAC was associated with poor overall survival (P < 0.001)., Conclusions: IMAC is a prognostic factor for poor short- and long-term outcomes in patients with colorectal liver metastasis.

Background: Approximately one third of all patients with CRC present with, or subsequently develop, colorectal liver metastases (CRLM). The objective of this population-based analysis was to assess the impact of resection of liver only, lung only and liver and lung metastases on survival in patients with metastatic colorectal cancer (mCRC) and resected primary tumor., Methods: Ten thousand three hundred twenty-five patients diagnosed with mCRC between 2010 and 2015 with resected primary were identified in the Surveillance, Epidemiology and End Results (SEER) database. Overall, (OS) and cancer-specific survival (CSS) were analyzed by Cox regression with multivariable, inverse propensity weight, near far matching and propensity score adjustment., Results: The majority (79.4%) of patients had only liver metastases, 7.8% only lung metastases and 12.8% metastases of lung and liver. 3-year OS was 44.5 and 27.5% for patients with and without metastasectomy (HR = 0.62, 95% CI: 0.58-0.65, P < 0.001). Metastasectomy uniformly improved CSS in patients with liver metastases (HR = 0.72, 95% CI: 0.67-0.77, P < 0.001) but not in patients with lung metastases (HR = 0.84, 95% CI: 0.62-1.12, P = 0.232) and combined liver and lung metastases (HR = 0.89, 95% CI: 0.75-1.06, P = 0.196) in multivariable analysis. Adjustment by inverse propensity weight, near far matching and propensity score and analysis of OS yielded similar results., Conclusions: This is the first SEER analysis assessing the impact of metastasectomy in mCRC patients with removed primary tumor on survival. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in OS and CSS for liver resection but not for metastasectomy of lung or both sites.

Background: The management of distant metastatic cutaneous squamous cell carcinoma (cSCC) relies mainly on chemotherapies and radiotherapy. Management of patients with cSCC with surgically resectable distant metastatic lesions is not clear., Case Report: A 59-year-old male had 4×10 cm-sized cSCC on the perianal skin with inguinal lymph node metastasis. Surgical resection was performed followed by radiation and adjuvant carboplatin and farmorubicin combination therapy. Six months later, 25 mm-sized solitary metastatic nodule arose on the liver. Base on his favorable overall condition fulfilling the criteria of tumor resectability for the treatment of tumors in liver and having good performance status, laparoscopic partial hepatectomy and six courses of adjuvant irinotecan therapy were performed. The surgical margin was negative and the patient has maintained complete remission for over 3 years., Conclusion: The clinical course of the present case suggests that surgical approaches should also be considered as candidate additional therapy for resectable distant metastatic cSCC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: A laparoscopic approach is increasingly being utilized in simultaneous colorectal and liver resection (SCLR) for colorectal cancer with liver metastasis. However, this approach is technically challenging and hence has not been widely adopted. Robotic surgical systems could potentially overcome this problem. We aim to describe the feasibility and outcomes of robotic SCLR for colorectal carcinoma with liver metastasis., Methods: The medical records of 12 patients who underwent robotic SCLR for colorectal cancer with liver metastasis between January 2008 and September 2018 were reviewed retrospectively., Results: The mean age was 59 years (range, 37-77 years). The liver resections were comprised of two right hepatectomies, one left hepatectomy, one left lateral sectionectomy, one segmentectomy of S3 and wedge resection (segment 7), one caudate lobectomy, one associated liver partition and portal vein ligation for staged hepatectomy, and five wedge resections involving segments 4, 5, 6, 7, or 8. The colorectal procedures involved seven low-anterior resections, two anterior resections, two right hemicolectomies, and one left hemicolectomy. The mean operative time was 449 min (range, 135-682 min) with a mean estimated blood loss of 274.3 mL (range, 40-780 mL). The mean length of hospital stay was 12 days (range, 5-28 days). No patients required conversion to laparotomy. Liver resection-related complications were two liver abscesses (Clavien-Dindo classification, one grade II and one grade III) and one case of ascites (grade I), whereas colorectal resection-related complications included one anastomosis leak (grade III) and one superficial wound infection (grade II). There were no deaths reported within 30 days of the procedure. With a mean follow-up duration of 31.5 ± 26.1 months, the overall survival and disease-free survival values were 75.2 and 47.1 months, respectively., Conclusion: Robotic SCLR for colorectal neoplasm with liver metastasis can be performed safely even in cases requiring major liver resections, especially in a specialized center with a well-trained team.

Background: After treatment of primary ocular uveal melanoma (UM), up to 50% of patients will develop metastases, mostly in the liver. Systemic treatments do not provide any overall survival benefit for these patients and surgery remains the most effective therapy for selected patients. Radiofrequency ablation (RFA) alone or in combination with surgery is frequently used to spare hepatic parenchyma. When patients relapse after treatment of their first metastases, and when the liver recurrence is limited, new local liver treatment is questionable., Methods: A total of 14 patients with liver metastases from uveal melanoma (LMUM) were retrospectively evaluated. All patients had a complete first liver resection and a second treatment with RFA. Overall survival, recurrence-free interval after the first and the second treatment was evaluated., Results: Treatment of hepatic recurrence was percutaneous RFA for ten patients and per-operative RFA for four patients associated with new metastasectomy. The median time to onset of LMUMs after ocular UM treatment was 50 months, and the median time to recurrence of hepatic metastasis after the first liver treatment was 20 months. The overall survival was 70% at five years and 35% at ten years. The recurrence-free interval was 50% and 56% at two years after the first and the second treatment, respectively., Conclusion: Prolonged survival can be achieved by exclusive and iterative local treatment combining surgery and RFA in a small proportion of patients with a first recurrence of isolated LMUM., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Minimally invasive liver surgery has gained increasing popularity over the past decade. Nevertheless, laparoscopic treatment of lesions located in the posterior-superior locations remains challenging because of the difficulty to reach a safe exposition of those regions of the liver. We present a new retroperitoneoscopic approach for the minimally invasive treatment of posterior tumors. Materials and Methods: Between May and July 2018, 2 patients with solitary liver metastasis of colorectal origin underwent retroperitoneoscopic liver resection in the prone position. The operation was conducted with three to four trocars, the CO 2 insufflation pressure was set at 20 mmHg. Liver transection was carried out by alternating bipolar coagulation and clips, without clamping of the hepatic inflow. Results: There were no intra- or postoperative complications. The procedure was completed in both cases without conversion after 120 to 180 minutes, respectively. Complete resection was achieved in both cases. Hospital stay was 3 and 5 days. Conclusions: Retroperitoneoscopic liver resection is feasible and safe. This approach could be suggested as an additional therapeutic option, especially in cases of redo resection at the posterior segments.

Background: Indications and efficacy of surgical treatment for liver metastases from gastric cancer (LMGCs) remain controversial. This retrospective study was designed to clarify the benefits of surgical treatment and identify prognostic factors., Methods: Between December 1997 and December 2015, 34 consecutive patients underwent hepatic resection and surgical microwave ablation for synchronous or metachronous LMGCs at our institution. We analyzed their cumulative overall survival (OS) and recurrence-free survival (RFS) rates and clinical parameters to identify predictors of prognosis., Results: Of the 34 patients, 14 underwent hepatic resection, 13 underwent surgical microwave ablation, and 7 underwent hepatic resection combined with surgical microwave ablation. Their OS rates were 1-year: 84.4%, 3-year: 38.6%, and 5-year: 34.7%; and their RFS rates were 1-year: 38.5%, 3-year: 28.0%, and 5-year: 28.0%. OS did not significantly vary among the surgical procedures. In multivariable analysis, positive of both CEA and CA19-9 were independent predictors of poor survival (hazard ratio [HR] 4.51; P = 0.049) and early recurrence (HR 5.70; P = 0.047)., Conclusions: Both hepatic resection and surgical microwave ablation for LMGCs are effective and can improve survival in selected patients., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: This study aims to evaluate the feasibility and safety of resection of sarcoma liver metastases, and to identify possible prognostic factors for long-term survival., Methods: All patients who underwent resection of liver metastases of sarcoma in the Netherlands from 1998 to 2014 were included. Study data was retrospectively collected from patient files. Survival rates were calculated using Kaplan-Meier survival analysis., Results: Some 38 patients treated in 16 hospitals were included (15 male, 23 female). The median age was 57 years (37-80 years). The most common histological subtype was leiomyosarcoma (63%). The predominant site of primary tumour was the abdomen (59%). R0 resection was achieved in 16 patients. Mortality was 3 and 16% of included patients had 1 or more complications. The median follow-up period was 18 months (range 1-161). After liver resection, 1-, 3-, and 5-year survival were 88, 54, and 42% respectively. Median overall survival was 46 months (1-161 months). One- and three-year progression-free survival (PFS) after liver resection were 54 and 19% respectively. Median PFS was 16 months (1-61 months)., Conclusions: Liver surgery for sarcoma metastases is safe and leads to a relatively good survival. The choice for surgical treatment should always be discussed in a multidisciplinary sarcoma and liver team., (The Author(s). Published by S. Karger AG, Basel.)

While colorectal and hepatic resections are commonly performed through a laparoscopic approach, the safety and feasibility of total laparoscopic synchronous resections (LSR) of colorectal liver metastasis (CRLM) have not been established. In this systematic review, short- and long-term outcomes were comparable for patients undergoing LSR and open synchronous resection. LSR was safe and feasible for patients with synchronous CRLM and should be considered in well-selected patients., (© 2018 Wiley Periodicals, Inc.)

Background: Hepatocellular carcinoma is a highly prevalent and lethal primary neoplasia of the liver and metastases of other malignancies affect most frequently the liver. Minimally invasive surgical approach for liver resections is advancing. Dissection of liver parenchyma by laparoscopic technique remains challenging and new technologies are in need. Therefore, we asked whether it is feasible to dissect liver tissue comparably in terms of speed and hemostasis with a non-contact 1.9-µm cw-laser device and whether there are differences in the postoperative healing process compared to a gold standard device (ultrasound aspirator) in an experimental model., Methods: Laparoscopic laser and ultrasound aspirator standardized partial liver resections were performed in seven pigs. Resection time, hemostasis time, and blood loss were evaluated. After at least 10 days, representative specimen of the resection areas was collected via re-laparoscopy and biopsy and side effects like hematoma, abscess, or bilioma were noted. Histologically, coagulation necrosis margin, granulation tissue zone, tissue fibrosis, and giant cell count were analyzed., Results: Laparoscopic laser liver resection was three times faster compared to the laparoscopic ultrasound aspirator. Blood loss was equal in both groups. No side effects like hematoma or bilioma occurred. Histologically, specimen showed the same expansion of coagulation necrosis zone and granulation tissue. Fibrotic scar could be determined in three cases in both groups, respectively. However, giant cell count was significant higher in the laser resection group., Conclusions: The 1.9-µm cw-laser device enables a safe and fast liver resection in an experimental pig model compared to a gold standard (ultrasound aspirator) laparoscopic liver resection method. Wound healing is not interfered by laser liver resection.

Background: Most colorectal cancer liver metastases form nodules within the hepatic parenchyma, and hepatectomy is the only radical treatment for synchronous metastases. There is concern about intrabiliary tumor growth which may affect the surgical margin, resulting in local recurrence after hepatectomy for colorectal cancer liver metastasis; however, there has been no report of the dissemination in the bile duct after hepatectomy. Here, we report an unusual case of biliary dissemination of colorectal cancer that caused recurrent intrabiliary growth after hepatectomy, and discuss the management of intrabiliary metastasis of colorectal cancer., Case Presentation: A 69-year-old Japanese man underwent treatment for liver dysfunctions 3 years after aortic valve replacement. Computed tomography revealed an enhanced tumor within the hilar bile duct and dilatation of the left hepatic duct, typical of hilar cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography revealed tumor shadow in his bile duct, and the cytology confirmed malignant cells in the bile. We performed extended left hepatectomy with bile duct resection; his postoperative course remained good without acute complications. After 3 months postoperatively, he was readmitted for subacute cholangitis and obstructive jaundice. Immediately, percutaneous transhepatic cholangiography drainage was performed, followed by cholangiography that exhibited intrabiliary tumor growth in the remnant liver. On immunohistochemical examination, tumor cells were positive for cytokeratin 20 and CDX2 but negative for cytokeratin 7. Then, computed tomography revealed an enhanced tumor-like lesion at the descending colon. After 3 months, left hemicolectomy was performed. Meanwhile, the percutaneous transhepatic cholangiography drainage fluid turned bloody, which was considered to be bleeding from a residual bile duct tumor. Accordingly, radiotherapy was initiated to prevent tumor bleeding around the hilar bile duct, but, unfortunately, the effects were short-lived, and cholangitis rebooted after 1 month leading to our patient's death due to septic liver failure. Autopsy revealed a remnant tumor in the bile duct, but no noticeable nodular metastasis was observed, except for a single small metastasis in the lower lobe of the left lung., Conclusions: The intrabiliary growth of metastatic colorectal cancer mimics cholangiocarcinoma occasionally. To date, as the effect of chemotherapy or radiotherapy remains uncertain, the complete resection of a bile duct tumor is the only method which could result in a better prognosis.

Background: Liver resection is the first-line treatment for patients with resectable colorectal liver metastasis (CRLM), while radiofrequency ablation (RFA) can be used for small unresectable CRLM because of disease extent, poor anatomical location, or comorbidities. However, the long-term outcomes are unclear for RFA treatment in resectable CRLM. This study aimed to compare the recurrence rates and prognosis between resectable CRLM patients receiving either liver resection or RFA., Methods: Consecutive patients who underwent RFA or hepatic resection from November 2010 to December 2015 were assigned in this retrospective study. Propensity score analysis was used to eliminate baseline differences between groups. Survival and recurrence rates were compared between patients receiving liver resection and RFA., Results: With 1:2 ratio of propensity scoring, 46 patients in the RFA group and 92 in the resection group were successfully matched. Overall survival was similar between the two groups, but the resection group had a higher disease-free survival (median, 22 months vs. 14 months). Whereas among patients with a tumor size of ≤ 3 cm, disease-free survival was similar in the two groups (median, 24 months vs. 21 months). Compared to the resection group, the RFA group had a higher rate of intrahepatic recurrence (34.8% vs. 12.0%) and a shorter recurrence free period. The local and systemic recurrence rate and recurrence-free period for the same were insignificant in the two groups. Poor disease-free survival was associated with RFA, T4, tumor diameter > 3 cm, and lymph node positivity., Conclusion: Among patients with technically resectable CRLM, resection provided greater disease-free survival, although both treatment modalities provided similar overall survival.

Background: Colorectal cancer is common, and its incidence is increasing throughout the world. The liver is a major metastatic site, and colorectal liver metastasis (CRLM) has a poor prognosis. Although liver resection is the most effective therapy for CRLM, postoperative recurrence is common. Thus, prognostic markers for CRLM are greatly needed. D-dimer, a fibrin cleavage product, has been shown to be related to colorectal tumor progression, and is also associated with malignant progression and recurrence in various cancers. Therefore, we evaluated the value of D-dimer in predicting the prognosis in CRLM., Methods: We retrospectively evaluated 90 cases of resected CRLM to determine the correlation between D-dimer and patient survival. The cut-off value for D-dimer levels was determined using receiver operating characteristic curve analysis., Results: Significant differences occurred in the recurrence group with higher D-dimer levels (P = 0.00736*), while the optimal cut-off value was 0.6 µg/mL. High D-dimer levels (≥ 0.6 µg/mL) were associated with poor recurrence-free survival (RFS; P = 0.0000841*) and cancer-specific survival (CSS; P = 0.00615*). In the multivariate analysis, D-dimer correlated with CRLM prognosis and independently predicted RFS (P = 0.0179*)., Conclusion: High D-dimer levels were associated with poor RFS and CSS. D-dimer was an independent prognostic factor of RFS. Therefore, D-dimer may help predict recurrence and prognosis in patients with CRLM.

Aim: To compare and evaluate the hepatoprotective effect of remote ischemic preconditioning (RIPC) with local ischemic preconditioning (LIPC) of the liver during human liver resections., Methods: A prospective, single-centre, randomised control trial was conducted in the Clinical Hospital "***" from April 2017 to January 2018. A total of 60 patients, who underwent liver resection due to colorectal cancer liver metastasis, were randomised to one of three study arms: 1) a RIPC group, 2) an LIPC group and 3) a control group (CG) in which no ischemic preconditioning was done before liver resection. The hepatoprotective effect was evaluated by comparing serum transaminase levels, bilirubin levels, albumin, and protein levels, coagulograms and through pathohistological analysis. The trial was registered on ClinicalTrials.gov (NCT****)., Results: Significant differences were found in serum levels of liver transaminases and bilirubin levels between thegroups, the highest level in the CG and the lowest level in the LIPC group. Levels of cholinesterase were also significantly higher in the LIPC group. Pathohistological findings graded by the Rodriguez score showed favourable changes in the LIPC and RIPC groups versus the CG., Conclusion: Strong evidence supports the hepatoprotective effect of RIPC and LIPC preconditioning from an ischemia-reperfusion injury of the liver. Better synthetic liver function preservation in these two groups supports this conclusion., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Extensive, bilobular and multifocal colorectal liver metastases (CLM) or metastases that are critically situated require an experienced surgeon and advanced surgical techniques to enable curative resection., Objective: This article describes the toolbox of hepato-oncologic surgery including functional augmentation of liver segments by portal vein embolization/ligation, combinations of ablation and resection, two-stage resections and in situ split liver resection, also known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Furthermore, the curative resection of extrahepatic, oligometastatic disease are briefly discussed., Material and Methods: Review of current literature as well as discussion of the ALPPS procedure, which was developed at our institute., Results: In recent years, oncologic resections for CLM have been significantly refined, leading to a constant increase of curative resection rates., Conclusion: In a multimodality treatment setting, surgical resection of CLM remains the gold standard curative approach and even in the event of presumed hopeless cases with extensive metastasis, experienced hepatobiliary surgeons must evaluate the resectability of colorectal metastases.

Background: As minimally invasive techniques advances, minimally invasive surgery (MIS) has emerged as an alternative modality for advanced gastric cancer. In this study, we compared the short- and long-term surgical outcomes of MIS and conventional open surgery for gastric cancer liver metastasis (GCLM) in terms of safety, feasibility, and efficacy., Methods: This retrospective study used data from a prospective database at the Chinese People's Liberation Army General Hospital. From January 2006 to June 2016, 53 gastric cancer patients with synchronous liver metastasis accepted radical gastrectomy combined with either or both hepatectomy and radiofrequency ablation for liver metastases. The 53 patients enrolled in the study were divided into two groups: a conventional open surgery group (n = 42) and an MIS group (n = 11). Propensity score matching (PSM) analysis was performed to overcome possible bias., Results: With PSM performed at a 1:3 ratio, 11 patients who received MIS were compared with 33 open surgery cases. Mean operation time was significantly longer for the MIS group compared with the open surgery group (301 vs. 236 min, P = 0.032), while the open surgery group had a larger estimated blood loss than the MIS group (421 vs. 196 ml, P = 0.019). Time to first flatus and postoperative complications, including Clavien-Dindo classification, were similar in the two groups. However, patients undergoing MIS had a significantly shorter time to first sips of water (P = 0.020) and soft diet (P = 0.020) compared with open surgery counterparts. Long-term outcomes were comparable between groups (P = 0.090) after adjustment by PSM analysis., Conclusions: MIS achieved superior short-term outcomes and comparable long-term outcomes compared with open surgery in GCLM patients. For experienced surgeons, both laparoscopic and robotic methods of MIS are reasonable approaches for the management of highly selected GCLM patients.

Background: Repeat liver resection is an effective treatment, with long-term surgical outcomes for recurrent hepatocellular carcinoma and colorectal liver metastasis. However, the efficacy of a minimally invasive surgical approach for recurrent liver cancer is not yet confirmed. The purpose of this study is to examine the efficacy of minimally invasive repeat liver resection (MISRLR) compared with open repeat liver resection (ORLR) for primary and metastatic liver cancer. Here, we retrospectively analyzed the clinicopathological features and short-term surgical outcomes of patients undergoing MISRLR and ORLR., Methods: From 2005 to 2016, 97 patients with liver cancer underwent repeat hepatectomy. Of these patients, 68 patients receiving macroscopically curative resection and only hepatectomy, without other additional operations, were selected. Twenty patients underwent MISRLR and 48 patients underwent ORLR. We compared the clinicopathological and surgical parameters in the MISRLR group with those in the ORLR group., Results: There were no statistically significant differences in patients' gender, age, viral infection status, Child-Pugh classification, tumor size, tumor number, tumor location, or the presence of liver cirrhosis in the two groups. The operative times were similar, but blood loss was significantly lower in MISRLR group (159 vs. 502 ml, P = 0.0035). The length of the postoperative hospital stay was significantly shorter in the MISRLR group (14.2 vs. 19.2 days, P = 0.0275). Postoperative complications were observed only in the ORLR group, with a complication rate of 19%., Conclusions: We demonstrate that MISRLR for primary and metastatic liver cancer reduces blood loss and postoperative complications compared with ORLR. MISRLR might be a feasible and effective procedure for the selected patients.

Background: Surgical indication for hepatic resection is controversial in gastric cancer liver metastasis (GLM). The aim of this study is to clarify the effect of hepatic resection for GLM., Methodology: Ten patients who underwent hepatic resection for GLM between 2001 and 2013 were enrolled in this study. Six patients underwent synchronous hepatic resection and gastrectomy, and the remaining four patients underwent metachronous hepatic resection. Six patients had solitary liver metastasis, and 4 patients had multiple liver metastasis. The median follow-up period was 12.4 months (the range being 0.5 months to 50 months)., Result: The actual 1- year and 3-year overall survival rates for the patients who underwent hepatic resection are 88.9% and 17.8%, respectively. The median survival time was 21.5 months. And the 1-year recurrence free survival time was 20.0%. The median recurrence free survival rate was 4.7 months. Regarding post-operative recurrence, synchronous hepatic resection tended to be a recurrence factor (p=0.08)., Conclusion: Hepatic resection for GLM has an acceptable outcome. Metachronous hepatic resection tends to have a better outcome than synchronous hepatic resection for the treatment of GLM. J. Med. Invest. 65:27-31, February, 2018.

Metastatic colorectal cancer (mCRC) is a devastating disease causing 700.000 deaths annually worldwide. Metastases most frequently develop in the liver. Partial hepatectomy has dramatically improved clinical outcome and is the only curative treatment option for eligible patients with mCRC. Pre-clinical studies have shown that surgical procedures can have tumor-promoting local 'side-effects' such as hypoxia and inflammation, thereby altering the behaviour of residual tumor cells. In addition, systemically released factors following (colon or liver) surgery can act as a wakeup-call for dormant tumor cells in distant organs and/or help establish a pre-metastatic niche. Tumor handling during resection may also increase the number of circulating tumor cells. Despite the overwhelming amount of pre-clinical data demonstrating the pro-tumorigenic side effects of surgery, clinical evidence is scarce. Indications for hepatic surgery are rapidly increasing due to a rise in the incidence of mCRC and a trend towards more aggressive surgical treatment. Therefore, it is increasingly important to understand the principles of surgery-induced tumor growth, in order to devise perioperative or adjuvant strategies to further enhance long-term tumor control. In the current study we review the evidence for surgery-stimulated tumor growth and suggest strategies to assess the clinical relevance of such findings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Treatment of peritoneal metastases (PM) and liver metastases (LM) from colon cancer remains controversial. LM has been viewed as exclusion criterion for cytoreductive surgery (CRS) on the basis that such spread represents systemic disease. CRS and intraperitoneal chemotherapy (IPC) has gained increasing recognition as a treatment modality for selected patients with colon cancer and PM. This study analyses results of CRS and IPC for colon cancer and synchronous resection for treatment of LM and PM., Methods: Seventy-eight patients with PM/LM colon cancer were analysed. Forty-two patients with PM were treated for disease limited to the peritoneum (A), and 36 patients received treatment for both PM and LM (B). Overall survival (OS), disease-free survival (DFS), morbidity, mortality and recurrence were compared., Results: Median OS and DFS was 32.8 and 13.5 months. The median OS for A and B were 45.5 and 24.4 months respectively. Within B patients, 18 had a peritoneal carcinomatosis index (PCI) >7 and >3 LM and median survival of 21.8 months compared with 18 patients with PCI ≤7 and LM ≤3 with median survival of 38.4 months. Median DFS for A and B were 17.7 and 8.5 months respectively. Twenty-seven in total experienced major complications following surgery. Sixty-one patients recurred. Of A, 71.4% recurred compared with B at 86.1%., Conclusion: While our study is limited, it has demonstrated encouraging evidence that long-term survival outcomes can be achieved in this small but significant number of patients treated by CRS/IPC and additional synchronous liver resection with no significant increase in morbidity when compared with CRS/IPC alone., (© 2015 Royal Australasian College of Surgeons.)

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy to reduce the chance of post-hepatectomy liver failure in patients with borderline or insufficient future liver remnant. ALPPS is still in an early developmental stage and its techniques have not been standardized. This study aimed to review the technical modifications of the conventional ALPPS procedure., Data Sources: Studies were identified by searching MEDLINE and PubMed for articles published from January 2007 to December 2016 using the keywords "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS". Additional articles were identified by a manual search of references from key articles., Results: There have been a lot of modifications of the conventional ALPPS. These are classified as: (1) modifications aiming to improve surgical results; (2) modifications aiming to expand surgical indications; (3) salvage ALPPS; (4) ALPPS using the minimally invasive approach. Some of these modifications have made the conventional ALPPS procedure to become even more complex, although there have also been other attempts to make the procedure less complex. The results of most of these modifications have been reported in small case series or case reports. We need better well-designed studies to establish the true roles of these modifications. However, it is interesting to see how this conventional ALPPS procedure has evolved since its introduction., Conclusions: There is a trend for the use of minimally invasive procedure in the phase 1 or 2 of the conventional ALPPS procedure. Some of these modifications have expanded the use of ALPPS in patients who have been considered to have unresectable liver tumors. The long-term oncological outcomes of these modifications are still unknown., (Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.)

Liver metastases from breast cancer (LMBC) have long been considered as a systemic disease because of the hematological route of dissemination, requiring noncurative management. In fact, despite recent advances in drug therapies personalized to tumor phenotype, the chances of a cure are nil and there is little hope of long-term survivors after nonsurgical management alone. By contrast, there is a growing evidence in the literature for satisfactory long-term results after a combination of chemotherapy and liver resection, with 5-year survival reaching >40% in some series. The surgical management of LMBC is still restricted to carefully selected patients, managed in high-volume hepatobiliary surgery and cancer research centers. Under these conditions, resection can be performed at the price of very limited morbidity and near zero mortality. The best results after the resection of LMBC are obtained after applying selection criteria based on small metastases (<4-5 cm), minor hepatectomy, radical resection (ideally R0, or R1), stable disease (ideally in regression) after neoadjuvant therapy, and a delay between primary and secondary lesions longer than 1 or 2 years (reflecting a favorable oncologic context). The age of the patient, her hormone receptor status, and HER2 overexpression are not strong predictors of survival. The role of radiological alternatives still needs to be defined (radiofrequency, microwave ablation, radioembolization), and these raise questions regarding a reliable pretreatment assessment of tumor spread. Finally, surgical results are based on scarce evidence and need to be confirmed by large-scale studies so that they will be more widely accepted by the medical community., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Laparoscopic liver surgery has become an established procedure in the treatment of liver tumors. Due to its short-term and long-term advantages, the number of centers with experience in laparoscopic liver surgery has greatly increased in the last few years. The complexity of the interventions performed has nearly reached the level of open surgery. This article describes the importance of laparoscopic hepatic surgery and discusses the evidence for the procedure. In addition, the indications for the most frequently resected tumors, metastases of colorectal cancer and hepatocellular carcinoma are explained together with important aspects of certain tumor localizations. In addition, the authors explain the technical aspects of the surgical technique and give an overview on new developments. To illustrate the possibilities of laparoscopic liver surgery, a video of a complete laparoscopically performed associating liver partition and portal vein ligation (ALPPS) procedure is available as supplementary material.

Background: Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer., Methods: We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014., Results: The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors., Conclusions: Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)