A patient who underwent conversion surgery after atezolizumab plus bevacizumab for hepatocellular carcinoma with portal vein thrombosis and perihepatic lymph node metastases achieved a pathological complete response.

Here, we present a patient with hepatocellular carcinoma complicated by tumor thrombosis into the main portal trunk and perihepatic lymph node metastases who was treated with atezolizumab plus bevacizumab. Shrinkage of the main tumor, portal vein thrombosis, and lymph node metastases were achieved; therefore, hepatectomy with lymphadenectomy could be performed. Final pathology indicated a complete pathological response in the main tumor, portal vein thrombosis, and perihepatic lymph nodes. The patient is currently alive with no evidence of recurrence on radiological assessment at 3 months after surgery.

Surgical Intervention After Lenvatinib Treatment in Patients With Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood. PATIENTS AND METHODS: Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed. RESULTS: Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks. Progression-free survival (PFS) was significantly longer in patients who underwent surgical intervention than in patients with non-surgical treatment (median, 8.6 vs. 5.1 months, p=0.019). Non-significantly longer overall survival (OS) was also observed in patients with surgical intervention compared to patients with non-surgical treatment (median, unreached vs. 21.0 months, p=0.206). In patients who underwent surgical intervention, two patients had a partial response, and 12 had stable disease according to RECIST ver. 1.1 criteria. The serum alpha-fetoprotein (AFP) level was significantly lower after lenvatinib treatment than before lenvatinib treatment (median, 19.2 vs. 196.5 ng/ml, p=0.0081). Eleven patients underwent curative surgery with a 14% major postoperative complication (Clavien-Dindo ≥IIIa) rate. Patients who exhibited decreases in AFP levels or maintained AFP levels within the normal range during lenvatinib treatment had significantly longer PFS (median, 8.6 vs. 3.0 months, p=0.0009) and OS (median, unreached vs. 12.4 months, p=0.012) compared to those with persistently elevated AFP levels beyond the normal range. CONCLUSION: Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC.

Intra-Articular Injection of Chitin Nanofiber Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis.

Background: This study aimed to evaluate the effect of chitin nanofibers (CNF) produced from crab shells as a medical material for the knee in an osteoarthritic rat model. Methods: The effect of intra-articular CNF injection was evaluated histologically among three groups: saline, hyaluronic acid (HA), and CNF injection groups. The Osteoarthritis Research Society International (OARSI) cartilage, subchondral bone, synovial, and meniscus scores were used for scoring. Results: At 4 weeks, the CNF group had significantly lower scores than the saline group. The Synovial score was lower in HA and CNF groups at 4 weeks than in the saline group. At 4 weeks post-treatment, the thickening of the subchondral bone plate and angiogenesis were significantly reduced in the CNF treatment group compared to those in the saline treatment group (P = 0.02). Conclusion: The anti-inflammatory effects of CNF on knee osteoarthritis were comparable to that of HA in the early stages.

Protocol of the RACB study: a multicenter, single-arm, prospective study to evaluate the efficacy of resection of initially unresectable hepatocellular carcinoma with atezolizumab combined with bevacizumab.

BACKGROUND: Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. METHODS: The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a Child‒Pugh score of 5-6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. DISCUSSION: This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. TRIAL REGISTRATION: This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Clinically relevant model of oxaliplatin-induced sinusoidal obstruction syndrome.

AIM: Sinusoidal obstruction syndrome (SOS) induced by oxaliplatin-including chemotherapies (OXCx) is associated with impaired hepatic reserve and higher morbidity after hepatic resection. However, in the absence of an appropriate animal experimental model, little is known about its pathophysiology. This study aimed to establish a clinically relevant reproducible model of FOLFOX-induced SOS and to compare the clinical/histopathological features between the clinical and animal SOS settings. METHODS: We performed clinical/pathological analyses of colorectal liver metastasis (CRLM) patients who underwent hepatectomy with/without preoperative treatment of FOLFOX (n = 22/18). Male micro-minipigs were treated with 50% of the standard human dosage of the FOLFOX regimen. RESULTS: In contrast to the monocrotaline-induced SOS model in rats, hepatomegaly, ascites, congestion, and coagulative necrosis of hepatocytes were absent in patients with CRLM with OXCx pretreatment and OXCx-treated micro-minipigs. In parallel to CRLM cases with OXCx pretreatment, OXCx-challenged micro-minipigs exhibited deteriorated indocyanine green clearance, morphological alteration of liver sinusoidal endothelial cells, and upregulated matrix metalloproteinase-9. Using our novel porcine SOS model, we identified the hepatoprotective influence of recombinant human soluble thrombomodulin in OXCx-SOS. CONCLUSIONS: With distinct differences between monocrotaline-induced rat SOS and human/pig OXCx-SOS, our pig OXCx-SOS model serves as a preclinical platform for future investigations to dissect the pathophysiology of OXCx-SOS and seek preventive strategies.

Liver stiffness measured by virtual touch quantification predicts the occurrence of posthepatectomy refractory ascites in patients with hepatocellular carcinoma.

PURPOSE: This study assessed the significance of measuring liver stiffness using virtual touch quantification before hepatectomy to predict posthepatectomy refractory ascites. METHODS: A total of 267 patients with hepatocellular carcinoma who underwent hepatectomy were prospectively analyzed. Liver stiffness was defined as the median value of the virtual touch quantification (Vs; m/s) by acoustic radio-force-impulse-based virtual touch. RESULTS: A multivariate analysis showed that Vs and the aspartate aminotransferase-to-platelet ratio index were independent risk factors for postoperative refractory ascites (odds ratio = 3.27 and 3.08, respectively). The cutoff value for Vs was 1.52 m/s (sensitivity: 59.5%, specificity: 88.6%) as determined by the analysis of the receiver-operating characteristic curve, and the area under the receiver-operating characteristic curve was 0.79. The cutoff value for the aspartate aminotransferase-to-platelet ratio was 0.952 (sensitivity: 65.5%, specificity: 82.9%), and the area under the receiver-operating characteristic curve was 0.75. CONCLUSIONS: Vs is an independent risk factor for refractory ascites after hepatectomy. The measurement of liver stiffness by virtual touch quantification before hepatectomy can help estimate the risk of postoperative refractory ascites. Nonsurgical treatments should be considered for the management of patients who are at high risk for refractory ascites.

Sinusoidal Obstruction Syndrome Promotes Liver Metastatic Seeding of Colorectal Cancer Cells in a Rat Model.

BACKGROUND/AIM: Sinusoidal obstruction syndrome (SOS) after neoadjuvant chemotherapy with oxaliplatin for colorectal liver metastases (CRLM) has been reported to lead to early recurrence. This study investigated the effects of SOS on the development of CRLM in a rat model. MATERIALS AND METHODS: RCN-H4 cells were injected into the spleen or liver of ten monocrotaline-treated (SOS group) and ten untreated (control group) rats. The number and size of liver tumors were compared between the groups. RESULTS: The number of liver tumors in the splenic RCN-H4 injection model was significantly higher in the SOS group than in the control group (332±213 vs. 16±5, p=0.029); however, the largest tumor diameter in the hepatic model was similar between groups (6.2±1.8 vs. 6.4±2.4 mm, p=0.87). CONCLUSION: SOS promotes CRLM development by splenic RCN-H4 cell injection. This might be due to the higher incidence of cancer cell implantation into the liver.

Conditional Recurrence-Free Survival after Oncologic Extended Resection for Gallbladder Cancer: An International Multicenter Analysis.

BACKGROUND: Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. PATIENTS AND METHODS: Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000-2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. RESULTS: Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3-T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49-3.13, P < 0.001], 12-month recurrence-free (HR 3.42, 95% CI 1.88-6.23, P < 0.001), and 24-month recurrence-free (HR 2.71, 95% CI 1.11-6.62, P = 0.029). Of the 125 patients without these risk factors, only 2 had recurrence after 36 months. CONCLUSION: C-RFS improves over time, and only T3-T4 disease remains a risk factor for recurrence at 24 months after OER for GBC. For all recurrence-free survivors after 36 months, the probability of recurrence is similar regardless of T category or disease stage.

Low level of postoperative plasma antithrombin III is associated with portal vein thrombosis after liver surgery.

PURPOSE: Although decreased antithrombin-III (AT-III) is a risk factor for portal vein thrombosis (PVT) in patients with liver cirrhosis, the association between postoperative PVT and postoperative AT-III levels is unknown in patients undergoing hepatectomy. METHODS: Patients who underwent hepatectomy between 2015 and 2018 were retrospectively analyzed. Postoperative PVT was assessed on CT at days 6-9 after hepatectomy. One-to-one propensity score (PS) matching was used to match the baseline characteristics. RESULTS: Of the 295 patients included in this analysis, 19 patients (6.4%) were diagnosed with postoperative PVT. The AT-III level on postoperative day (POD) 3 predicted postoperative PVT with a sensitivity/specificity of 74%/59% (AUC, 0.644; cut-off value, 60%; p = 0.032). Multivariate analysis revealed that AT-III levels ≤ 60% on POD3 (OR, 3.01; 95% CI 1.02-8.89; p = 0.046), cirrhosis (OR, 5.88; 95% CI 1.92-18.0; p = 0.002) and right-sided hepatectomy (OR, 4.16; 95% CI 1.45-11.9; p = 0.0079) were significant risk factors for postoperative PVT. After PS matching, 56 patients with and without AT-III supplementation were analyzed. The two groups had a similar incidence of PVT (p = 0.489). CONCLUSIONS: Patients with AT-III levels ≤ 60% on POD3 should be carefully followed up regarding postoperative PVT. Our results did not support the efficacy of routine AT-III supplementation for the prophylaxis of postoperative PVT.

A new sequential treatment strategy for multiple colorectal liver metastases: Planned incomplete resection and postoperative completion ablation for intentionally-untreated tumors under guidance of cross-sectional imaging.

PURPOSE: We retrospectively evaluated outcomes of a new sequential treatment strategy for patients with multiple colorectal liver metastases (CLM): planned incomplete resection and postoperative percutaneous completion ablation for intentionally-untreated lesions under cross-sectional imaging guidance. METHODS: Patients with CLM who underwent curative-intent hepatectomy and ablation during 2007-2018 were analyzed. Complications, local tumor progression (LTP) rates at ablation site(s), and overall survival (OS) estimated using the Kaplan-Meier method were compared between patients who underwent CLM resection and postoperative percutaneous ablation for intentionally-untreated lesions (completion ablation) and patients who underwent CLM resection and concomitant intraoperative CLM ablation under ultrasound guidance. RESULTS: Number and largest diameter of CLM and liver resection complexity did not differ significantly between the completion ablation (n = 23) and intraoperative ablation (n = 92) groups. Microwave (versus radiofrequency) ablation was used more frequently in the completion ablation group than in the intraoperative ablation group (61% [14/23] vs. 6% [6/92], P = 0.001). The complication rate after hepatectomy and ablation was significantly lower in the completion ablation group (21% [5/23] versus 48% [44/92], P = 0.033). No death was observed in either group. The 5-year LTP cumulative incidence was significantly lower in the completion ablation group (31.7% versus 62.4%, P = 0.030). The 5-year OS rate did not differ significantly between groups (53%, completion ablation; 42%, intraoperative ablation; P = 0.407). CONCLUSIONS: Resection and postoperative percutaneous completion ablation under cross-sectional imaging guidance may be a safe and effective treatment pathway in patients with CLM in whom liver resection alone cannot achieve R0 resection.

Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-RAS status for unresectable colorectal liver metastasis (BECK study): Long-term results of survival.

BACKGROUND/PURPOSE: To investigate the long-term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. METHODS: Recurrence and survival data with long-term follow-up were analyzed in the cohort of a multi-institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). RESULTS: A total of 22/12 patients with K-RAS wild-type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left-sided primary tumors than in right-sided tumors (75.0% vs 30.0%, P = .022). The median follow-up was 72.6 months. The 5-year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5-year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow-up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5-year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1-4). CONCLUSIONS: Conversion hepatectomy achieved a similar long-term survival to the results of previous studies in initially resectable patients, although many of them experienced several post-hepatectomy recurrences. Left-sided primary was found to be the predictor for conversion hepatectomy.

Anatomic Resection Is Not Required for Colorectal Liver Metastases with RAS Mutation.

BACKGROUND: Non-anatomic resection (NAR) has emerged as a safe and effective technique for resection of colorectal liver metastases (CRLM). More recently, RAS mutation has been identified as an important indicator of aggressive disease, which may require anatomic resection (AR). In this retrospective study, we compared the long-term outcomes of AR versus NAR in CRLM patients with and without RAS mutations. METHODS: Patients with known RAS mutation status who underwent AR or NAR for CRLM between 2006 and 2016 were included. Differences in baseline characteristics were adjusted using 1:1 propensity score matching, including the most important factors that contributed to the decision to use the resection technique. Overall survival (OS), recurrence-free survival (RFS), and liver-specific recurrence-free survival (L-RFS) were compared between cohorts. RESULTS: Among 622 total patients, 338 (54%) underwent AR and 284 (46%) NAR. There was no difference in OS or L-RFS between the AR and NAR groups, regardless of mutation status. There was increased RFS in the RAS WT patients with NAR (P = 0.034), but no difference in RFS in the whole cohort or RAS mutant group. After propensity score matching, 360 patients were analyzed, and no differences in OS, RFS, or L-RFS rates were seen between any groups. There was also no difference in margin recurrence. CONCLUSIONS: Similar outcomes can be achieved with both AR and NAR, regardless of RAS mutation status. These data do not support a universal requirement for AR in RAS mutant CRLM when not necessary to achieve an R0 resection.

Characteristics of atypical large well-differentiated hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood. METHODS: Patients who underwent hepatectomy for HCC between 1998-2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm). RESULTS: Of 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p < 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis. CONCLUSION: Patients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.

Incidental versus non-incidental gallbladder cancer: index cholecystectomy before oncologic re-resection negatively impacts survival in T2b tumors.

BACKGROUND: Conflicting data exists whether non-oncologic index cholecystectomy (IC) leading to discovery of incidental gallbladder cancer (IGBC) negatively impacts survival. This study aimed to determine whether a subgroup of patients derives a disadvantage from IC. METHODS: Patients with IGBC and non-IGBC treated at an academic USA and Chilean center during 1999-2016 were compared. Patients with T1, T4 tumor or preoperative jaundice were excluded. T2 disease was classified into T2a (peritoneal-side tumor) and T2b (hepatic-side tumor). Disease-specific survival (DSS) and its predictors were analyzed. RESULTS: Of the 196 patients included, 151 (77%) had IGBC. One hundred thirty-six (90%) patients of whom 118 (87%) had IGBC had T2 disease. Three-year DSS rates were similar between IGBC and non-IGBC for all patients. However, for T2b patients, 3-year survival rate was worse for IGBC (31% vs 85%; p = 0.019). In multivariate analysis of T2 patients, predictors of poor DSS were hepatic-side tumor hazard ratio [HR], 2.9; 95% CI, 1.6-5.4; p = 0.001) and N1 status (HR, 2.4; 95% CI, 1.6-3.6; p < 0.001). CONCLUSIONS: Patients with T2b gallbladder cancer specifically benefit from a single operation. These patients should be identified preoperatively and referred to hepatobiliary center.

Positive cystic duct margin at index cholecystectomy in incidental gallbladder cancer is an important negative prognosticator.

BACKGROUND: Prognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER). METHODS: This retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed. RESULTS: The study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; p = 0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04-2.78; p = 0.034). CONCLUSIONS: A positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes.

Long-term survival after post-hepatectomy liver failure for colorectal liver metastases.

BACKGROUND: While post-hepatectomy liver failure (PHLF) accurately predicts short-term mortality, its role in prognosticating long-term overall survival (OS) remains unclear. METHODS: Patients who underwent hepatectomy for colorectal liver metastases (CRLM) after portal vein embolization during 1999-2015 were evaluated retrospectively. PHLF was defined per International Study Group of Liver Surgery (ISGLS) criteria and as PeakBil >7 mg/dl. Survival was analyzed using log-rank statistic and Cox regression; patient mortality within 90 days was excluded. RESULTS: Of 175 patients, 68 (39%) had PHLF according to ISGLS criteria, including 40 (23%) with ISGLS grade B/C, and 14 (8%) had PeakBil >7 mg/dl. Patients with PeakBil >7 mg/dl had significantly worse OS than patients without PHLF (median OS, 16 vs 58 months, p = 0.001). Patients with ISGLS defined PHLF (p = 0.251) and patients with ISGLS grade B/C PHLF (p = 0.220) did not have worse OS than patients without PHLF. CONCLUSION: Peak bilirubin >7 mg/dl impacts on long-term survival after hepatectomy for CRLM and is a better predictor of long-term survival than ISGLS-defined PHLF.

Conceptual framework of middle hepatic vein anatomy as a roadmap for safe right hepatectomy.

BACKGROUND: While the middle hepatic vein (MHV) guides parenchymal transection during right hepatectomy, its most proximal tributaries can be difficult to identify, and injury to its tributaries can be a source of major bleeding. METHOD: Following simulation modeling of right hepatectomy, reconstructed MHV data was pooled from 40 patients. MHV-tributaries and MHV-relationship to the portal pedicle were mapped out to facilitate their identification from the beginning of parenchymal transection. RESULTS: Hotspots for injury were identified: A median of 1 (1-3) tributaries draining segment 5 (V5) were within 45-90mm from the MHV termination, and 16mm above and 22mm caudal to the portal trunk. Simulation demonstrated a constant anatomic relationship between portal pedicle and the proximal MHV. A median of 2 (0-4) tributaries draining segment 8 (V8) were located 9-35mm from the MHV termination. This information was compiled into an "MHV-road-map" demonstrating 86% of the MHV tributaries at risk for significant bleeding are within 15mm of the MHV, while only thin tributaries are located in the outer area. CONCLUSIONS: The MHV-road-map led to a peripheral-to-central parenchymal transection approach to minimize the risk of MHV-injury thereby reducing bleeding during open and minimally invasive right hepatectomy.

Loss of muscle mass during preoperative chemotherapy as a prognosticator for poor survival in patients with colorectal liver metastases.

BACKGROUND: The survival impact of specific body composition changes during preoperative chemotherapy in patients with colorectal liver metastases undergoing curative-intent surgery remains unclear. This study aimed to determine the impact of changes in body weight and muscle mass during preoperative chemotherapy on survival after hepatectomy in patients with colorectal liver metastases. METHODS: Consecutive patients with colorectal liver metastases undergoing preoperative chemotherapy and curative hepatectomy during 2009-2013 were retrospectively analyzed. Recurrence-free and overall survival were examined according to body compositions, including muscle mass, as measured by skeletal muscle index (area of muscle [cm2]/square of height [m2]), and body weight before and after preoperative chemotherapy. RESULTS: The median follow-up duration in overall 169 patients was 47 months. Skeletal muscle index and body weight changed significantly during chemotherapy (skeletal muscle index: -0.52 cm2/m2, P = .03; body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (≥7%) had significantly shorter median RFS than patients with no or minor muscle mass loss (<7%) (9.6 months vs 15.9 months; P = .02). Although major muscle mass loss was associated with poor outcome, skeletal muscle index before or after preoperative chemotherapy was not associated with recurrence-free or overall survival. On multivariate analysis, major muscle mass loss was independently associated with poorer recurrence-free survival (hazard ratio, 1.76; P = .045). CONCLUSION: Major loss of muscle mass but not body weight loss during preoperative chemotherapy is significantly associated with poor recurrence-free survival after hepatectomy in patients with colorectal liver metastases. The mechanisms mediating this association may inform future trials on maintaining muscle mass with dedicated nutrition and exercise programs to improve outcomes.