Ferroptosis-related gene glutathione peroxidase 4 promotes reprogramming of glucose metabolism via Akt-mTOR axis in intrahepatic cholangiocarcinoma.

The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.

High expression of autotaxin is associated with poor recurrence-free survival in cholangiocarcinoma.

BACKGROUND AND AIM: Autotaxin (ATX) is an extracellular lysophospholipase D that catalyzes the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA). Recent accumulating evidence indicates the biological roles of ATX in malignant tumors. However, the expression and clinical implications of ATX in human cholangiocarcinoma (CCA) remain elusive. METHODS: In this study, the expression of ATX in 97 human CCA tissues was evaluated by immunohistochemistry. Serum ATX levels were determined in CCA patients (n = 26) and healthy subjects (n = 8). Autotaxin expression in cell types within the tumor microenvironment was characterized by immunofluorescence staining. RESULTS: High ATX expression in CCA tissue was significantly associated with a higher frequency of lymph node metastasis (p = 0.050). High ATX expression was correlated with shorter overall survival (p = 0.032) and recurrence-free survival (RFS) (p = 0.001) than low ATX expression. In multivariate Cox analysis, high ATX expression (p = 0.019) was an independent factor for shorter RFS. Compared with low ATX expression, high ATX expression was significantly associated with higher Ki-67-positive cell counts (p < 0.001). Serum ATX levels were significantly higher in male CCA patients than in healthy male subjects (p = 0.030). In the tumor microenvironment of CCA, ATX protein was predominantly expressed in tumor cells, cancer-associated fibroblasts, plasma cells, and biliary epithelial cells. CONCLUSIONS: Our study highlights the clinical evidence and independent prognostic value of ATX in human CCA.

Is routine lymph node dissection recommended for liver resection of intrahepatic cholangiocarcinoma? A systematic review and meta-analysis.

BACKGROUND/PURPOSE: This meta-analysis aimed to elucidate the therapeutic effects of routine lymph node dissection (LND) with liver resection on intrahepatic cholangiocarcinoma (ICC). METHODS: Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing LND and non-LND for ICC liver resection. The primary outcome was overall survival (OS), and secondary outcomes were disease-free survival (DFS), in-hospital morbidity, blood loss, and R0 rate. RESULTS: Seventeen studies involving 4407 patients were included. The OS did not differ between the LND (n = 2158) and non-LND (n = 2249) groups (HR, 1.05; 95% CI, 0.83-1.32). The secondary outcomes did not differ significantly between the groups. Subgroup analyses stratified by the risk of bias showed a significant difference in OS between the high- and low-risk groups (P = 0.0008). In the low-risk group, LND (vs. non-LND) was associated with superior OS (HR, 0.76; 95% CI, 0.59-0.98). Most studies in low-risk groups involved patients who were clinically node-negative. CONCLUSIONS: The therapeutic effects of routine LND for ICC have not been demonstrated. However, LND had a positive impact on OS in studies with a low risk of bias, thus suggesting that there may be a subset of ICC patients who would benefit from LND.

Impact of the Intermittent Pringle Maneuver for Predicting Post-hepatectomy Liver Failure: A Cohort Study of 597 Consecutive Patients.

BACKGROUND: Intermittent Pringle maneuver (PM) is widely performed to reduce blood loss during hepatectomy; however, its impact on clinically relevant post-hepatectomy liver failure (PHLF) remains controversial. This study aimed to assess the impact of PM on PHLF and explore whether PM provides additional value for predicting PHLF. METHODS: Consecutive patients, who underwent hepatectomy without biliary and/or vascular reconstruction between 2011 and 2018 in a single institution, were retrospectively analyzed. The main outcome was PHLF grades B/C as defined by the International Study Group of Liver Surgery. A multivariable logistic regression model of variables significantly associated with PHLF was established. The model's predictive ability was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 597 patients, PHLF occurred in 42 (7.0%). PM was applied in 421 patients (70.5%) and was associated with the development of PHLF (PM vs. no-PM: 9.7 vs. 0.6%, P < 0.001). After the propensity score matching, patients with PM experienced significantly increased rates of PHLF (P = 0.010). Rem-ALPlat index (including future liver remnant, preoperative albumin level, and platelet count; P < 0.001), the number of PMs (P = 0.032), and blood loss (P = 0.007) were identified as significant predictors of PHLF. The model's AUROC combined with the intraoperative variables was higher than that of the preoperative model alone (0.877 vs. 0.789, P = 0.004). CONCLUSIONS: PM was involved in the occurrence of clinically relevant PHLF. Further, intraoperative factors including PM may provide additional value to predict PHLF and may facilitate early post-hepatectomy intervention.

A Conceptual Classification of Resectability for Hepatocellular Carcinoma.

BACKGROUNDS: In the era of multidisciplinary treatment strategy, resectability for hepatocellular carcinoma (HCC) should be defined. This study aimed to propose and validate a resectability classification of HCC. METHODS: We proposed following the three groups; resectable-(R), borderline resectable-(BR), and unresectable (UR)-HCCs. Resectable two groups were sub-divided according to the value of indocyanine green clearance of remnant liver (ICG-Krem) and presence of macrovascular invasion (MVI); BR-HCC was defined as resectable HCCs with MVI and/or ICG-Krem≥0.03-<0.05, and R-HCC was the remaining. Consecutive patients with HCC who underwent liver resection (LR) and non-surgical treatment(s) (i.e., UR-HCC) between 2011 and 2017 were retrospectively analyzed to validate the proposed classification. RESULTS: A total of 361 patients were enrolled in the study. Of these, R-, BR- and UR-HCC were found in 251, 46, and 64 patients, respectively. In patients with resected HCC, ICG-Krem≥0.05 was associated with decreased risk of clinically relevant posthepatectomy liver failure (p=0.013) and the presence of MVI was associated with worse overall survival (OS) (p<0.001). The 3-5-years OS rates according to the proposed classification were 80.3, and 68.3% versus 51.4, and 35.6%, in the R and BR groups, respectively (both p<0.001). Multivariate analysis showed BR-HCC was independently associated with poorer OS (p<0.001) after adjusting for known tumor prognostic factors. Meanwhile, BR-HCC was associated with benefit in terms of OS compared with UR-HCC (p<0.001). CONCLUSION: Our proposal of resectability for HCC allows for stratifying survival outcomes of HCC and may help to determine treatment strategy.

Impact of liver volumetric regeneration on survival outcomes in patients with hepatocellular carcinoma after major hepatectomy.

PURPOSE: Prognostic value of liver volumetric regeneration (LVR) in patients with hepatocellular carcinoma (HCC) who undergo major hepatectomy remains unknown. The aim of this study was to investigate the impact of LVR on long-term outcomes in these patients. METHODS: Data of 399 consecutive patients with HCC who underwent major hepatectomy between 2000 to 2018 were retrieved from a prospectively maintained institutional database. The LVR-index was defined as the relative increase in liver volume from 7 days to 3 months (RLV3m/RLV7d, where RLV3m and RLV7d is the remnant liver volume around 3 months and postoperative 7 days after surgery). The optimal cut-off value was determined using the median value of LVR-index. RESULTS: A total of 131 patients were eligible in this study. The optimal cut off value of LVR-index was 1.194. The 1-, 3-, 5- and 10-year overall survival (OS) rate of patients in the high LVR-index group were significantly better compared to those in the low LVR-index group (95.5%, 84.8%, 75.4% and 49.1% vs. 95.4%, 70.2%, 56.4%, and 19.9%, p = 0.002). Meanwhile, there was no significant difference with regards to time to recurrence between the two groups (p = 0.607). Significance of LVR-index for OS was retained after adjusting for known prognostic factors (p = 0.002). CONCLUSION: In patients with HCC undergoing major hepatectomy, LVR-index may serve as a prognostic indicator for OS.

Impact of patient-specific three-dimensional printed liver models on hepatic surgery safety: a pilot study.

BACKGROUND: Simulation and navigation technologies in hepatobiliary surgery have been developed recently. In this prospective clinical trial, we evaluated the accuracy and utility of our patient-specific three dimensional (3D)-printed liver models as an intraoperative navigation system to ensure surgical safety. METHOD: Patients requiring advanced hepatobiliary surgeries during the study period were enrolled. Three cases were selected for comparison of the computed tomography (CT) scan data of the models with the patients' original data. Questionnaires were completed after surgeries to evaluate the utility of the models. Psychological stress was used as subjective data and operation time and blood loss as objective data. RESULTS: Thirteen patients underwent surgery using the patient-specific 3D liver models. The difference between patient-specific 3D liver models and the original data was less than 0.6 mm in the 90% area. The 3D model assisted with intra-liver hepatic vein recognition and the definition of the cutting line. According to the post-operative subjective evaluation, surgeons found the models improved safety and reduced psychological stress during operations. However, the models did not reduce operative time or blood loss. CONCLUSION: The patient-specific 3D-printed liver models accurately reflected patients' original data and were an effective intraoperative navigation tool for meticulously difficult liver surgeries. CLINICAL TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trial Registry (UMIN000025732).

Oncological Resection for Liver Malignancies: Can the Laparoscopic Approach Provide Benefits?

Laparoscopic surgery has become an increasingly popular alternative approach to open surgery, resulting in a paradigm shift in liver surgery. Although laparoscopic liver resection (LLR) was initially indicated for small benign and peripheral tumors, at present more than half of LLRs are performed in malignant tumors. Several studies have reported the feasibility of LLR in malignant disease and suggested various short-term benefits compared to open liver resection, including decreased blood loss and postoperative complications and a shorter hospital stay. Although these benefits are important to surgeons, patients, and providers, the main goal of surgery for malignancies is to achieve a maximum oncologic benefit. The relevance of the laparoscopic approach must be assessed in relation to the possibility of respecting basic oncological rules and the expertise of the center. Easy LLRs can be safely performed by most surgeons with minimum expertise in liver surgery and laparoscopy, and can therefore probably provide an oncological benefit. On the other hand, intermediate or difficult LLRs require technical expertise and an oncological benefit can only be achieved in expert centers. Technical standardization is the only way to obtain an oncological benefit with this type of resection, and many problems must still be solved.

Increased Expressions of Programmed Death Ligand 1 and Galectin 9 in Transplant Recipients Who Achieved Tolerance After Immunosuppression Withdrawal.

Programmed death 1 (PD1)/its ligand PD-L1 concomitant with T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)/its ligand galectin 9 (Gal-9) and the forkhead box P3 (FOXP3) might be involved in tolerance after liver transplantation (LT). Liver biopsies from 38 tolerant, 19 nontolerant (including 16 samples that triggered reintroduction of immunosuppression [IS] and 19 samples after IS reintroduction), and 38 control LT patients were studied. The expressions of PD1, PD-L1, Gal-9, and FOXP3 were determined by immunohistochemical and immunofluorescence (IF) staining. The success period of IS withdrawal was calculated using Kaplan-Meier curve analysis. Tolerant and control patients exhibited higher PD-L1, Gal-9, and FOXP3 levels than nontolerant patients at the moment of triggering IS reintroduction. High expressions of PD-L1 and Gal-9 were associated with prolonged success of tolerance (83.3% versus 36.7% [P < 0.01] and 73.1% versus 42.9% [P = 0.03]). A strong correlation between PD-L1 and Gal-9 expression levels was detected (Spearman r = 0.73; P ≤ 0.001), and IF demonstrated colocalization of PD-L1 and Gal-9 in the cytoplasm of hepatocytes. In conclusion, the present study demonstrated that increased expressions of PD-L1 and Gal-9 were associated with sustained tolerance after IS withdrawal in pediatric liver transplantation.

Impact of Preoperative CEA Uptrend on Survival Outcomes in Patients with Colorectal Liver Metastasis After Hepatectomy.

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) has been reported as a prognostic factor in patients with colorectal liver metastasis (CRLM) after hepatectomy. However, the impact of a preoperative "CEA uptrend" on prognosis after hepatectomy in these patients remains unknown. This study assessed the impact of CEA uptrend on prognosis in patients undergoing hepatectomy for CRLM. METHODS: Consecutive patients with CRLM who underwent hepatectomy between 2009 and 2018 were retrospectively analyzed. Patients with CRLM for whom CEA was measured both around 1 month before (CEA-1m) and within 3 days (CEA-3d) before hepatectomy were enrolled. A CEA-3d higher than both the upper limit of normal (5 ng/ml) and CEA-1m was defined as a CEA uptrend. RESULTS: Study participants comprised 212 patients with CRLM. Of these, 88 patients (41.5%) showed a CEA uptrend. CEA uptrend indicated better discriminatory ability (corrected Akaike information criteria, 733.72) and homogeneity (likelihood ratio chi-square value, 18.80) than CEA-3d or CEA-1m. Patients with CEA uptrend showed poorer overall survival than those without CEA uptrend (p < 0.001). After adjusting for known prognostic factors, the prognostic significance of CEA uptrend retained (hazard ratio 2.63, 95% confidence interval 1.63-4.26, p < 0.001). In subgroup analyses, the prognostic significance of CEA uptrend was retained irrespective of the status of RAS mutation or response to preoperative chemotherapy. CONCLUSIONS: CEA uptrend offers better prediction of survival outcomes than conventional CEA measurements in patients undergoing hepatectomy for CRLM.

Learning process of laparoscopic liver resection and postoperative outcomes: chronological analysis of single-center 15-years' experience.

BACKGROUND: Limited studies have reported the actual learning process of laparoscopic liver resection (LLR). This study aimed to chronologically evaluate our 15 years' experience of LLR. METHODS: All consecutive LLRs between 2006 to 2020 were retrospectively analyzed. The time period was divided into three groups; first (2006-2010), second (2011-2015), and third (2016-2020) period. The primary endpoint of this study was a composite of overall (Clavien-Dindo grade ≥ II) or major (grade ≥ IIIa) postoperative complications within 30 days. Using the IWATE criteria (four difficulty levels based on six indices), LLR was categorized as basic (< 7 points) and advanced (≥ 7 points) one. All analyses were performed based on the intention-to-treat principles. RESULTS: During the study period, a total of 382 LLRs were gradually performed (first period, n = 54; second period, n = 114, and third period, n = 214). Low incidences of overall and major complications were maintained (9.3, 10.5, and 7.0%, p = 0.514, and 1.9, 2.6, and 2.3%, p = 1.000). Meanwhile, pure LLRs (i.e., LLRs without hand-assisted or hybrid approach) and advanced LLRs were increasingly performed in 25 (46.3%), 71 (62.3%), and 205 (95.8%) patients (p < 0.001) and 3 (5.6%), 18 (15.8%), and 58 (27.1%) patients (p < 0.001), respectively. CONCLUSIONS: This study suggests that stepwise approach from basic to advanced procedures and use of hand-assisted or hybrid approach during the early phases for starting LLR practice may allow for maintaining low morbidity in specialized center.

The long-term outcomes of laparoscopic versus open pancreatoduodenectomy for ampullary carcinoma showed similar survival: a case-matched comparative study.

BACKGROUND: Few studies have compared the oncological benefit of laparoscopic (LPD) and open pancreatoduodenectomy (OPD) for ampullary carcinoma. The aim of this study was to compare the oncological results of these two approaches. METHODS: Between 2011 and 2020, 103 patients who underwent PD for ampullary carcinoma, including 31 LPD and 72 OPD, were retrospectively analyzed. Patients were matched on a 1:2 basis for age, sex, body mass index, American Society of Anaesthesiologists score, and preoperative biliary drainage. Short- and long-term outcomes of LPD and OPD were compared. RESULTS: The 31 LPD were matched (1:2) to 62 OPD. LPD was associated with a shorter operative time (298 vs. 341 min, p = 0.02) than OPD and similar blood loss (361 vs. 341 mL, p = 0.747), but with more intra- and post-operative transfusions (29 vs. 8%, p = 0.008). There was no significant difference in postoperative mortality (6 vs. 2%), grades B/C postoperative pancreatic fistula (22 vs. 21%), delayed gastric emptying (23 vs. 35%), bleeding (22 vs. 11%), Clavien ≥ III morbidity (22 vs. 19%), or the length of hospital stay (26 vs. 21 days) between LPD and OPD, respectively, but there were more reinterventions (22 vs. 5%, p = 0.009). Pathological characteristics were similar for tumor size (21 vs. 22 mm), well differentiated tumors (41 vs. 38%), the number of harvested (23 vs. 26) or invaded lymph nodes (48 vs. 52%), R0 resection (84 vs. 90%), and other subtypes (T1/2, T3/4, phenotype). With a comparable mean follow-up (41 vs. 37 months, p = 0.59), there was no difference in 1-, 3-, and 5-year overall (p = 0.725) or recurrence-free survival (p = 0.155) which were (93, 74, 67% vs. 97, 79, 76%) and (85, 58, 58% vs. 90, 73, 73%), respectively. CONCLUSION: This study showed a similar long-term oncological results between LPD and OPD for ampullary carcinoma. However, the higher morbidity observed with LPD compared to OPD, restricting its use to experienced centers.

Surgery for Recurrent Hepatocellular Carcinoma: Achieving Long-term Survival.

OBJECTIVE: To evaluate the long-term outcomes of surgery for recurrent hepatocellular carcinoma (HCC). BACKGROUND: HCC recurs with high incidence after liver resection. Little is known about long-term outcomes of patients undergoing surgery for recurrent HCC. METHODS: Among 989 patients who underwent R0/R1 liver resection for HCC between 1995 and 2014, 676 patients who exhibited recurrence were included. Repeat surgery was performed in 128 patients (RS group), and not in the remaining 548 patients (NS group). Prognostic value after repeat surgery was evaluated by comparing survival after recurrence (SAR) between the RS and NS groups. Subgroup analyses according to the 3 recurrence patterns [intrahepatic recurrence (IHR), extrahepatic recurrence (EHR), and intra plus extrahepatic recurrence (IHR + EHR)] were performed. RESULTS: Seventy-three of 430 patients (17.0%) with IHR, 17 of 57 patients (29.8%) with EHR, and 38 of 189 patients (20.1%) with IH + EHR underwent repeat surgery. Compared with the NS group, the RS group had better liver function and their time to recurrence was significantly longer (16.5 vs 11.4 months; P < 0.001). In the overall and 3 recurrence patterns, the 5-year SAR rate was better in the RS group compared with the NS group (RS vs NS group; overall, 53.0% vs 25.7%; IHR, 73.8% vs 37.2%; EHR, 30.0% vs 0%; IHR + EHR, 34.1% vs 10.6%; all P < 0.001, respectively). On multivariate analysis, repeat surgery was identified as an independent factor for better SAR (P < 0.001). CONCLUSION: Surgery for recurrent HCC may yield long-term survival for not only IHR but also for EHR in selected patients.

Liver surface nodularity: a novel predictor of post-hepatectomy liver failure in patients with colorectal liver metastases following chemotherapy.

OBJECTIVES: The goal of this study was to assess the relationship between liver surface nodularity (LSN), chemotherapy-associated liver injury (CALI), and clinically relevant post-hepatectomy liver failure (CR-PHLF) (i.e., ≥ grade B) in patients undergoing hepatectomy for colorectal liver metastases (CLM). METHODS: Preoperative CT scans of patients who underwent chemotherapy followed by hepatectomy for CLM between 2010 and 2017 were retrospectively analyzed. LSN was measured using semi-automated CT software CT images in patients who had available preoperative CT scans within 6 weeks before hepatectomy, and was computed based on the means of one to 10 measurements by two abdominal radiologists consensually. The association of LSN, CALI, and CR-PHLF was analyzed. RESULTS: Two hundred fifty-six patients were analyzed (149 men and 107 women; overall median age, 61 [range, 29-88 years]). A total of 26 patients (10.2%) developed CR-PHLF. The optimal LSN cut-off value for detecting CR-PHLF was 2.5, as determined by receiver operative characteristic analysis (p < 0.001). LSN ≥ 2.5 was associated with prolonged chemotherapy (> 6 cycles, p = 0.018), but not with CALIs. After propensity score matching, LSN remained significantly associated with CR-PHLF (p = 0.031). Furthermore, multivariate analysis identified LSN ≥ 2.50 and future liver remnant (FLR) < 30% as significant preoperative predictors of CR-PHLF in 102 patients undergoing major hepatectomy. LSN ≥ 2.50 was more frequent in patients undergoing major hepatectomy despite FLR ≥ 30% (p = 0.008). CONCLUSION: LSN quantified on CT is an independent surrogate of CR-PHLF in patients who undergo chemotherapy followed by hepatectomy for CLM and may provide a valuable additional tool in the preoperative assessment of these patients. KEY POINTS: • LSN was not associated with chemotherapy- associated liver injury but high LSN (defined ≥ 2.5) was associated with prolonged chemotherapy (> 6 cycles). • High LSN was an independent predictor of clinically relevant postoperative liver failure in patients undergoing hepatectomy for CRLM. • LSN ≥ 2.50 was more frequent in patients with PHLF after major hepatectomy despite a future liver remnant ≥ 30%.

Identifying Patients Who May Benefit from Liver Resection Compared to Living Donor Liver Transplantation for Hepatocellular Carcinoma Using 18F-FDG PET.

BACKGROUND: This study aimed to assess an oncologic setting where patients with hepatocellular carcinoma (HCC) could benefit from liver resection (LR) compared to living donor liver transplantation (LDLT) using 18F-fluorodeoxyglucose (FDG) positron emission tomography. METHODS: The consecutive data of patients with HCC who underwent 18F-FDG PET before LR (LR group, n = 314) and LDLT (LDLT group, n = 65) between 2003 and 2015 were retrospectively analyzed. Tumor 18F-FDG avidity was quantified as the tumor to liver standardized uptake value ratio (TLR, cut-off value was defined at 2). Multivariate analysis was performed to assess significant preoperative tumor factors in the LR group. Survival outcomes between the two groups were stratified by these factors. RESULTS: The 5-year overall survival (OS: 56.9% vs. 73.8%, LR vs. LDLT, p < 0.001) and recurrence-free survival rate (RFS: 27.4% vs. 70.7%, p < 0.001) were significantly better in the LDLT group compared to the LR group. In the LR study, multivariate analysis identified TLR and tumor multiplicity as significant preoperative tumor factors for OS. In patients with solitary and TLR < 2 HCC, the 5-year OS rate was not significantly different between the LR and LDLT groups (70.3% vs. 71.8%, p = 0.352); meanwhile, RFS rate was better in the LDLT group (34.3% vs. 71.8%, p = 0.001). CONCLUSIONS: LDLT is associated with better long-term outcomes than LR in patients with HCC; however, selected patients with solitary and TLR < 2 HCC may benefit from LR.

Laparoscopic Versus Open Liver Resection for Hepatocellular Carcinoma: A Case Controlled Study with Propensity Score Matching.

BACKGROUND: Several studies have suggested that laparoscopic liver resection (LLR) is associated with fewer postoperative complications than open liver resection (OLR) for hepatocellular carcinoma (HCC). However, this issue remains controversial since the data may have been attributable to an imbalance in patients' background. METHODS: We retrospectively analyzed 290 hepatectomies for HCC undertaken between 2011 and 2019. Liver resection difficulty was based on the 3 levels of the Institut Mutualiste Montsouris classification. Resection ratio was calculated using computed tomography volumetry. Patient characteristics were compared between the LLR and OLR groups. Propensity score matching (PSM) was adopted to adjust the imbalance between the cohorts, and the incidence of postoperative complications was compared. RESULTS: The difficulty and resection ratio were significantly lower in LLR (n = 112) than in OLR (n = 178) (difficulty grade I/II/III: 84/10/18 vs. 43/39/96, p < 0.001; resection ratio: 11.4 ± 12.7 vs. 22.7 ± 17.2%, p < 0.001). The incidence of postoperative complications (Clavien-Dindo grade III or more) was lower in LLR (2.7% vs. 21.9%, p < 0.001), which was mainly attributable to fewer incidences of ascites and pleural effusion. PSM generated 68 well-matched patients in each group. The lower incidence of postoperative complications in LLR was also maintained in the PSM cohort (2.9% vs. 16.2%, p = 0.017). On multivariate analysis, LLR was the independent predictor of postoperative complications (OR 0.184, 95% CI 0.051-0.672, p = 0.010). CONCLUSION: The present study demonstrated that a laparoscopic approach reduces the incidence of postoperative complications in liver resection for HCC.

Liver resection for octogenarians in a French center: prolonged hepatic pedicle occlusion and male sex increase major complications.

PURPOSE: The prolonged life expectancy and increase in aging of the population have led surgeons to propose hepatectomy in the elderly population. In this study, we evaluate the surgical outcome of octogenarians in a single French center. METHODS: Between 2000 and 2020, 78 patients over 80 years old were retrospectively analyzed. The risk factors of major complications (Clavien-Dindo ≥ grade IIIa) and patient performance after surgery by using textbook outcome (TO) (no surgical complications, no prolonged hospital stay (≤ 15 days), no readmission ≤90 days after discharge, and no mortality ≤90 days after surgery) were studied. RESULTS: The main surgical indication was for malignancy (96%), including mainly colorectal liver metastases (n = 41; 53%) and hepatocellular carcinoma (n = 22; 28%), and major hepatectomy was performed in 28 patients (36%). There were 6 (8%) postoperative mortalities. The most frequent complications were pulmonary (n = 22; 32%), followed by renal insufficiency (n = 22; 28%) and delirium (n = 16; 21%). Major complications occurred in 19 (24%) patients. On multivariate analysis, the main risk factors for major complications were the median vascular clamping time (0 vs 35; P = 0.04) and male sex (P = 0.046). TO was ultimately achieved in 30 patients (38%), and there was no prognostic factor for achievement of TO. CONCLUSIONS: Hepatectomy in octogenarians is associated with acceptable morbidity and mortality. Meanwhile, prolonged hepatic pedicle clamping should be avoided especially if hepatectomy is planned in a male patient.

A systematic review of prediction models for post-hepatectomy liver failure in patients undergoing liver surgery.

BACKGROUND: The aim of this systematic review is to evaluate the current evidence in the context of clinical prediction model for post-hepatectomy liver failure (PHLF). METHODS: A systematic search of the English literature for a period from December 2005 to September 2020 was conducted. Primary outcome was defined using the three common PHLF criteria (50-50 criteria, peak bilirubin>7 mg/dl criteria, and ≥ grade B PHLF criteria by the International Study Group of Liver Surgery). Studies that reported the value of area under receiver operative characteristic curve (AUC) for the occurrence of PHLF were included. RESULTS: Twenty eight of 1327 screened articles were eligible for inclusion. Eighteen studies developed the prediction models. The median AUC was found to be 0.79 (0.65-0.933). The parameters related to the amount of future liver remnant volume were most commonly identified as significant predictors for PHLF in statistical analysis (24 studies) and were most frequently incorporated in the prediction models (18 studies). The parameters associated with portal hypertension were significant for predicting PHLF in 16 studies and were adopted in the prediction models in 14 studies. CONCLUSION: Parameters related to future liver remnant volume and portal hypertension seem to be facilitating in predicting PHLF.

Quantitative assessment of microvascular invasion in hepatocellular carcinoma using preoperative serological and imaging markers.

BACKGROUND: The aim of this study was to establish a quantitative equation to predict microvascular invasion (MVI) for patients with resectable hepatocellular carcinoma (HCC). METHODS: This retrospective study included 219 patients with resected HCC from 2004 to 2015. All had available three pre-operative serological markers (alfa-feto protein (AFP), fucosylated AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP)), and one imaging marker (tumor to liver ratio of SUVmax (TLR) by 18F-FDG-PET). A multiple linear regression model for predicting MVI was developed (2004-2009, n = 111) and then validated (2010-2015, n = 108). Further, impact on the obtained model on survival outcomes was assessed. RESULTS: Using the derivation cohort, following equation was developed; MVI probability (%) = 14.2 × log10DCP + 9.9 × TLR - 22.0. This model resulted in an area under receiver operating characteristic curve (ROC) of 0.806 and 0.751, in the derivation and validation cohort, respectively. Furthermore, MVI probability ≥40% determined by ROC analysis was associated with worse overall survival and recurrence-free survival in the derivation and the validation cohort (all p < 0.05). CONCLUSION: A quantitative model, using DCP and TLR, was able to preoperatively predict with good performance MVI and long-term outcomes in patients with HCC after liver resection.

Laparoscopic liver resection versus percutaneous radiofrequency ablation for small hepatocellular carcinoma.

BACKGROUND: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) play central roles to treat early-stage hepatocellular carcinoma (HCC, ≤3 cm, 1-3 nodules, and no macrovascular involvement), although data are lacking regarding whether LLR or RFA is preferable. This study aimed to compare outcomes of both treatments for small HCCs. METHODS: Treatment outcomes of small HCCs were compared between all the minor LLRs performed between 2005 and 2016 and RFAs performed between 2011 and 2016 at Kyoto University. RESULTS: A total of 85 and 136 patients underwent LLR and RFA, respectively. Patients that underwent LLR had higher incidence of blood transfusions, complications, and longer hospital stay. Overall and disease-specific survival rates were similar between LLR and RFA; however, recurrence-free (49.2% vs. 22.1% at 3-year) and local recurrence-free survival rates (94.9% vs. 63.6% at 3-year) were higher after LLR. Multivariate analyses identified that multiple nodules and 65-year-old and above are predictors of disease-specific survival, and that RFA is a predictor of recurrence and local recurrence. CONCLUSION: RFA is less invasive, although both LLR and RFA are safe and effective. LLR provides better local control with superior recurrence-free and local-recurrence free survival. These results help optimize treatment selection based on patient-specific factors.