Impact of Metformin Use on Survival in Patients Undergoing Liver Resection for Colorectal Cancer Metastases

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.

A case of laparoscopic partial hepatic S7 resection for postoperative liver metastasis of rectal malignant melanoma

Background Anorectal malignant melanoma (ARMM) has an extremely poor prognosis, and there is no report of resection of liver metastases so far. We report herein a rare case of postoperative laparoscopic partial hepatic S7 resection for rectal malignant melanoma. Case presentation A 51-year-old female patient with a diagnosis of an ARMM underwent a laparoscopic rectal amputation. Eleven months later, computed tomography (CT) revealed a 14-mm nodule in liver segment 7 (S7), which was diagnosed as a hepatic recurrence of the ARMM. Because no other recurrences were found, a laparoscopic partial resection of S7 was performed. Pathological analysis found intracellular melanin deposition, and immunostaining was S-100 (+), HMB-45 (+), and SOX-10 (+). Based on these findings, a liver metastasis of malignant melanoma was diagnosed. The patient is alive 7 months after the second surgery and has so far experienced no recurrences. Conclusion We reported an extremely rare case of a laparoscopic resection of a liver metastasis following surgery for ARMM.

Ex Vivo Liver Resection and Autotransplantation as Surgical Option for Zone II–III Leiomyosarcoma of IVC: A Case Report and Literature Review

We report the first documented case of leiomyosarcoma at zone II-III of inferior vena cava with thrombi in three hepatic veins undergoing ex vivo liver resection and autotransplantation (ELRA) and hepatic veins thrombectomy. A 33-year-old female patient presented with abdominal distention and lower extremities edema. Abdominal wall varicosis and shifting dullness were positive on physical examination. Her liver function was classified as Child-Pugh B and a solid tumor at retro-hepatic vena cava extending to right atrium with thrombi in three hepatic veins were confirmed. The diagnosis of leiomyosarcoma with Budd-Chiari syndrome was highly suspected with preoperative ultrasound, echocardiogram, CT scan, and three-dimensional reconstruction. A zone II-III leiomyosarcoma of IVC origin was confirmed at surgery and ex vivo liver resection and autotransplantation, and hepatic vein thrombectomy with atrial reconstruction were performed under cardiopulmonary bypass (CPB). Operative time, anhepatic time, and CPB time were 12 h, 128 min, and 84 min, respectively. The patients experienced post-operative liver dysfunction and was cured with conservative therapy. Hepatic recurrence two years after surgery was managed with radiofrequency. The patient was alive with liver metastasis three years after surgery. Despite being regarded as an extremely aggressive procedure, ELRA could be considered in the treatment of advanced leiomyosarcoma with Budd-Chiari syndrome and hepatic vein thrombi.

Differential effects of KRAS mutational status on long-term survival according to the timing of colorectal liver metastases

Background The relationship between KRAS mutational status and timing of colorectal liver metastasis (CRLM) remains unclear. This study evaluated the relationship between KRAS mutational status and long-term survival in patients with synchronous CRLM. Methods Of the 255 patients who underwent initial hepatic resection for CRLM between January 2001 and December 2018, the KRAS mutational status was examined in 101 patients. Medical records of these patients were reviewed to evaluate recurrence and survival outcomes. Results KRAS mutant status was identified in 38 patients (37.6%). The overall survival (OS) was significantly better in patients with wild-type KRAS than in those with mutant KRAS status. In patients with synchronous metastases, the OS of patients with wild-type KRAS was significantly better than those with mutant KRAS. Multivariate analyses indicated shorter OS to be independently associated with positive primary lymph node, and large tumor size and R1 resection in patients with metachronous metastasis, whereas to be independently associated with mutant KRAS status in patients with synchronous metastasis. Furthermore, in the subgroup of patients with synchronous metastases, the repeat resection rate for hepatic recurrence was significantly high in those with wild type KRAS than in those with mutant KRAS. Conclusion KRAS mutation is an independent prognostic factor in patients with synchronous CRLM, but not in patients with metachronous CRLM.

Thoracoscopic Ablation of Critically Located Liver Tumors: A Safety and Efficacy Cohort Study

Background: Liver resection represents the first curative treatment to treat primary and secondary hepatic tumors. Thoracoscopic liver ablation is a viable and minimally invasive alternative treatment, especially for patients with previous multiple abdominal surgeries. The aim of the study was to evaluate the safety and efficacy of thoracoscopic ablation for liver tumors.Methods: Retrospective analysis of a prospective database of patients with liver tumors, treated with thoracoscopic trans-diagrammatic ablation (MWA or RFA) at our institution from 2012 to 2018. The primary endpoint was post-operative mortality at 30 days, while secondary endpoints were morbidity and efficacy of ablation (i.e., response rate evaluated according to mRECIST criteria, and overall patient survival). Patient demographics, operational characteristics, and complications were recorded.Results: A total of 13 nodules were treated in 10 patients with a median age of 65.5 years. Post-operative mortality was 0%, and overall morbidity was 40% (Clavien-Dindo I complications 30%, II 0%, III 10%, IV 0%). Complete radiological response was obtained in 83.3% of nodules at 3 months. After a median follow-up of 20.95 months, the local tumor progression rate was 30%, with an intra-segmental-recurrence of 30%, and an intra-hepatic-recurrence of 30%. The overall 1-, 2-, and 3-years survival rates were 80%, 58%, and 58%.Conclusion: Thoracoscopic trans-diaphragmatic ablation proved to be a safe and effective way to treat liver tumors when abdominal approach is not feasible. Considering the low morbidity, it is a viable option to treat patients with recurrent disease and/or previous multiple abdominal surgeries.

Hepatic Steatosis Predicts Higher Incidence of Recurrence in Colorectal Cancer Liver Metastasis Patients

Purpose: Colorectal liver metastasis (CRLM) is the major cause of death due to colorectal cancer. Although great efforts have been made in treatment of CRLM, about 60–70% of patients will develop hepatic recurrence. Hepatic steatosis was reported to provide fertile soil for metastasis. However, whether hepatic steatosis predicts higher incidence of CRLM recurrence is not clear. Therefore, we aimed to determine the role of hepatic steatosis in CRLM recurrence in the present study.Methods: Consecutive CRLM patients undergoing curative treatment were retrospectively enrolled and CT liver-spleen attenuation ratio was used to detect the presence of hepatic steatosis. In patients with hepatic steatosis, we also detected the presence of fibrosis. Besides, a systematic literature search was performed to do meta-analysis to further analyze the association between hepatic steatosis and CRLM recurrence.Results: A total of 195 eligible patients were included in our center. Patients with hepatic steatosis had a significantly worse overall (P = 0.0049) and hepatic recurrence-free survival (RFS) (P = 0.0012). Univariate and multivariate analysis confirmed its essential role in prediction of RFS. Besides, hepatic fibrosis is associated with worse overall RFS (P = 0.039) and hepatic RFS (P = 0.048). In meta-analysis, we included other four studies, with a total of 1,370 patients in the case group, and 3,735 patients in the control group. The odds ratio was 1.98 (95% CI: 1.25–3.14, P = 0.004), indicating that patients with steatosis had a significantly higher incidence of CRLM recurrence.Conclusion: In summary, patients with hepatic steatosis had a significantly worse overall and hepatic RFS and it's associated with higher incidence of CRLM recurrence.

Feasibility of Right Upper Transversal Hepatectomy in the Absence of an Inferior Right Hepatic Vein: New Insights regarding This Complex Procedure

Background. Right upper transversal hepatectomy (RUTH) is defined as the removal of liver segments 7, 8, and 4A with ligature of the right and middle hepatic veins and is considered one of the most complex techniques of parenchymal-sparing hepatectomies. This procedure can be performed, without venous reconstruction, if collateral veins are present communicating within remnant liver segments to a large inferior right hepatic vein and/or to the left hepatic vein. This venous network could maintain outflow from the inferior right segments (S5, S6) to the left liver when a RUTH is performed, even in the absence of an inferior right hepatic vein. The aim of this study is to present our experience with RUTH without venous reconstruction in patients with and without the presence of an inferior right hepatic vein (IRHV). Methods. Patients submitted to RUTH for treatment of liver metastases were selected from our database. The presence of an IRHV, clinical and surgical characteristics of the patients, immediate outcomes, viability of liver segments 5 and 6, and long-term survival were analyzed. Results. RUTH was successfully performed in four patients. In two patients, IRHV was not present, but intrahepatic communicating veins between proximal right and middle hepatic veins and left hepatic vein were present. No venous reconstructions were performed. Mild congestion of the inferior right segments occurred in the patients where there was no IRHV but no immediate, early, or late complications were observed. Conclusions. RUTH is feasible and can be performed even in the absence of an IRHV, without venous reconstruction. Some degree of congestion of the right inferior liver segments might occur when an IRHV is absent, yet this is not clinically significant when communicating veins are present. Maximum parenchyma preservation might prevent postoperative liver failure and allow repeated resections in case of hepatic recurrence.