Prognostic significance of postoperative complications for patients with hepatocellular carcinoma relative to alpha-feto protein and tumor burden score.

BACKGROUND: We sought to elucidate the impact of postoperative complications on patient outcomes relative to differences in alpha-fetoprotein-tumor burden score (ATS) among patients with hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. Moderate/severe complications were defined using the optimal cut-off value of the comprehensive complication index (CCI) based on the log-rank test. RESULTS: A total of 1124 patients was included. CCI cut-off value of 16.6 was identified as the optimal prognostic threshold. Patients who experienced moderate/severe complications were more likely to have worse recurrence free survival [RFS] versus individuals who had no/mild complications (2-year RFS; no/mild complication: 55.9% vs. moderate/severe complication: 38.1% p < 0.001). Of note, low and medium ATS patients who experienced moderate/severe complications had a higher risk of recurrence (2-year RFS; no/mild complication: postoperative complications 70.0% vs. moderate/severe complication: 51.1%, p = 0.006; medium: no/mild complication: 50.8% vs moderate/severe complication: 56.7%, p = 0.01); however, postoperative complications were not associated with worse outcomes among patients with high ATS (no/mild complication: 39.1% vs. moderate/severe complication: 29.2%, p = 0.20). CONCLUSION: These data serve to emphasize how reduction in postoperative complications may be crucial to improve prognosis, particularly among patients with favorable HCC characteristics.

Evidence and Future Perspectives for Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Scoping Review.

Pancreatic cancer (PC) is a lethal disease that requires innovative therapeutic approaches to enhance the survival outcomes. Neoadjuvant treatment (NAT) has gained attention for resectable and borderline resectable PC, offering improved resection rates and enabling early intervention and patient selection. Several retrospective studies have validated its efficacy. However, previous studies have lacked intention-to-treat analyses and appropriate resectability classifications. Randomized comparative trials may help to enhance the clinical applicability of evidence. Therefore, after searching the MEDLINE database, this scoping review presents a comprehensive summary of the evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials. Diverse regimens and their outcomes were explored for both resectable and borderline resectable PC. While some trials have supported the efficacy of NAT, others have demonstrated no clear survival benefits for patients with resectable PC. The utility of NAT has been confirmed in patients with borderline resectable PC, but the optimal regimens remain debatable. Ongoing trials are investigating novel regimens, including immunotherapy, thereby highlighting the dynamic landscape of PC treatment. Studies should focus on biomarker identification, which may enable precision in oncology. Future endeavors aim to refine treatment strategies, guided by precision oncology.

Multiple asynchronous recurrence as a predictive factor for refractoriness against locoregional and surgical therapy in patients with intermediate-stage hepatocellular carcinoma.

Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child-Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child-Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44-2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3-5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.

Textbook outcome in liver surgery: open vs minimally invasive hepatectomy among patients with hepatocellular carcinoma.

BACKGROUND: We sought to investigate whether minimally invasive hepatectomy (MIH) was superior to open hepatectomy (OH) in terms of achieving textbook outcome in liver surgery (TOLS) after resection of hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. TOLS was defined by the absence of intraoperative grade ≥2 events, R1 resection margin, posthepatectomy liver failure, bile leakage, major complications, in-hospital mortality, and readmission. RESULTS: A total of 1039 patients who underwent HCC resection were included in the analysis. Although most patients underwent OH (n = 724 [69.7%]), 30.3% (n = 315) underwent MIH. Patients who underwent MIH had a lower tumor burden score (3.6 [IQR, 2.6-5.2] for MIH vs 6.1 [IQR, 3.9-10.1] for OH) and were more likely to undergo minor hepatectomy (84.1% [MIH] vs 53.6% [OH]) than patients who had an OH (both P < .001). After propensity score matching to control for baseline differences between the 2 cohorts, the incidence of TOLS was comparable among patients who had undergone MIH (56.6%) versus OH (64.8%) (P = .06). However, MIH was associated with a shorter length of hospital stay (6.0 days [IQR, 4.0-8.0] for MIH vs 9.0 days [IQR, 6.0-12.0] for OH). Among patients who had MIH, the odds ratio of achieving TOLS remained stable up to a tumor burden score of 4; after which the chance of TOLS with MIH markedly decreased. CONCLUSION: Patients with HCC who underwent resection with MIH versus OH had a comparable likelihood of TOLS, although MIH was associated with a short length of stay.

Preoperative predictive factors for positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas: a retrospective study.

BACKGROUND: The clinical importance of positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas remains controversial. We evaluated the prognosis of these patients and the predictive preoperative risk factors for positive peritoneal cytology results. METHODS: We retrospectively reviewed patients who underwent curative-intent surgery at our institution between May 2010 and June 2020. Preoperative risk factors for positive peritoneal cytology results were identified using logistic regression analysis. A scoring model was constructed using the total number of significant independent predictors for positive peritoneal cytology results. RESULTS: Of 233 patients, 18 (7.7%) had positive peritoneal cytology results. The recurrence-free survival and cancer-specific survival were markedly worse in patients with positive peritoneal cytology results than in those with negative peritoneal cytology results (recurrence-free survival: 6.0 months vs. 16.6 months, p = 0.050; cancer-specific survival: 19.4 months vs. 47.5 months, p = 0.034). Tumor location (odds ratio: 3.760, 95% confidence interval: 1.099-11.818, p = 0.023), tumor size > 25 mm (odds ratio: 3.410, 95% confidence interval: 1.031-11.277, p = 0.046), preoperative serosal invasion (odds ratio: 5.193, 95% confidence interval: 1.099-24.531, p = 0.038), and preoperative carcinoembryonic antigen level > 5.6 ng/mL (odds ratio: 3.816, 95% confidence interval: 1.248-10.667, p = 0.019) were identified as significant independent predictive factors. Our predictive model's optimal cutoff and positive predictive values for positive peritoneal cytology results were 3 and 27.9%, respectively. CONCLUSIONS: The indications for curative-intent surgery should be considered carefully in patients with high-risk factors for positive peritoneal cytology results.

The complication-overall survival (CompOS) risk tool predicts risk of a severe postoperative complications relative to long-term survival among patients with primary liver cancer.

BACKGROUND: This study aimed to develop a tool based on preoperative factors to predict the risk of perioperative complications based on the Comprehensive Complication Index (CCI) and long-term survival outcomes after liver resection for primary liver cancer. METHODS: Patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent hepatectomy between 1990 and 2020 were identified using a multi-institutional international database. RESULTS: Among 1411 patients who underwent curative-intent hepatic resection (HCC: 997, 70.7%; ICC: 414, 29.3%), median patient age was 66.0 years (IQR, 57.0-73.0), and most patients were male (n = 1001, 70.9%). In the postoperative setting, 699 patients (49.5%) experienced a complication; moreover, 112 patients (7.9%) had major complications. Although most patients had a favorable risk complication-overall survival (CompOS) profile (CCI score > 40 risk of <30% and median survival of >5 years: n = 778, 55.1%), 553 patients (39.2%) had an intermediate-risk profile, and 80 patients (5.7%) had a very unfavorable risk profile (CCI score > 40 risk of ≥30% and/or median survival of ≤1.5 years). The areas under the curve of the test and validation cohorts were 0.73 and 0.76, respectively. CONCLUSION: The CompOS risk model accurately stratified patients relative to short- and long-term risks, identifying a subset of patients at a high risk of major complications and poor overall survival.

Next­generation sequencing to identify genetic mutations in pancreatic cancer using intraoperative peritoneal washing fluid.

The efficacy of next-generation sequencing (NGS) of tumor-derived DNA from intraoperative peritoneal washing fluid (IPWF) of patients with pancreatic ductal adenocarcinoma (PDAC) who intend to undergo curative resection remains unclear. The aim of the present study was to evaluate whether genomic mutations in tumor-derived DNA from IPWF samples of patients with PDAC who intend to undergo curative resection could be detected using NGS. A total of 12 such patients were included in this study. Cytology of IPWF (CY) was assessed and NGS of genomic tumor-derived DNA from the IPWF was performed to determine whether genomic mutations could be detected in these patient samples. A total of 2 patients (16.7%) had a CY(+) status and 1 patient (8.3%) showed intraoperative macro-peritoneal dissemination; 11 patients underwent radical surgery. Actionable gene alterations were detected in 8 (80.0%) out of the 10 patients with CY(-) status based on NGS of IPWF samples, and 3 (37.5%) patients among those with actionable gene mutations identified from IPWF samples underwent peritoneal dissemination after surgery within ~12 months. The most common genomic mutation was in KRAS (9 patients, 75.0%), followed by TP53 (3 patients, 25.0%), SMAD4 (1 patient, 8.3%) and CDKN2A (1 patient, 8.3%). These findings indicated that the genomic mutations identified in tumor-derived DNA from IPWF samples of patients with PDAC with a CY(-) status who intend to undergo curative resection are potential biomarkers for predicting the recurrence of early peritoneal dissemination.

The aMAP score predicts long-term outcomes after resection of hepatocellular carcinoma: a multi-institutional analysis.

BACKGROUND: The aMAP score is a proposed model to predict the development of hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis. The role of the aMAP score to predict long-term survival among patients following resection of HCC has not been determined. METHODS: Patients undergoing resection for HCC between 2000 and 2020 were identified using a multi-institutional database. The impact of the aMAP score on long-term outcomes following HCC resection was assessed. RESULTS: Among 1377 patients undergoing resection for HCC, a total of 972 (70.6 %) patients had a low aMAP score (≤63), whereas 405 (29.4 %) individuals had a high aMAP score (≥64). aMAP score was associated with 5-year OS in the entire cohort (low vs high aMAP score:66.5 % vs. 54.3 %, p < 0.001). aMAP score predicted 5-year OS following resection among patients with HBV-HCC (low vs. high aMAP:68.8 % vs. 55.6 %, p = 0.01) and NASH/other-HCC (64.7 % vs. 53.7, p = 0.04). aMAP score could sub-stratify 5-year OS among patients undergoing HCC resection within (low vs. high aMAP:81.5 % vs. 67.4 %, p < 0.001) and beyond (55.9 % vs. 38.8 %, p < 0.001) Milan criteria. DISCUSSION: The aMAP score predicted postoperative outcomes following resection of HCC within and beyond Milan criteria. Apart from a surveillance tool, the aMAP score can also be used as a prognostic tool among patients undergoing resection of HCC.

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma.

INTRODUCTION: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. METHODS: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class <3, body mass index <35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. RESULTS: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0-67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. CONCLUSIONS: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.

Perioperative Lymphopenia is Associated with Increased Risk of Recurrence and Worse Survival Following Hepatectomy for Hepatocellular Carcinoma.

INTRODUCTION: Immune dysregulation may be associated with cancer progression. We sought to investigate the prognostic value of perioperative lymphopenia on short- and long-term outcomes among patients undergoing resection of hepatocellular carcinoma (HCC). METHODS: Patients undergoing resection of HCC between 2000 and 2020 were identified using an international database. The incidence and impact of perioperative lymphopenia [preoperative, postoperative day (POD) 1/3/5], defined as absolute lymphocyte count (ALC) <1000/µL, on short- and long-term outcomes was assessed. RESULTS: Among 1448 patients, median preoperative ALC was 1593/µL [interquartile range (IQR) 1208-2006]. The incidence of preoperative lymphopenia was 14.0%, and 50.2%, 45.1% and 35.6% on POD1, POD3 and POD5, respectively. Preoperative lymphopenia predicted 5-year overall survival (OS) [lymphopenia vs. no lymphopenia: 49.1% vs. 66.1%] and 5-year disease-free survival (DFS) [25.0% vs. 41.5%] (both p < 0.05). Lymphopenia on POD1 (5-year OS: 57.1% vs. 71.2%; 5-year DFS: 30.0% vs. 41.1%), POD3 (5-year OS: 57.3% vs. 68.9%; 5-year DFS: 35.4% vs. 42.7%), and POD5 (5-year OS: 53.1% vs. 66.1%; 5-year DFS: 32.8% vs. 42.3%) was associated with worse long-term outcomes (all p < 0.05). Patients with severe lymphopenia (ALC <500/µL) on POD5 had worse 5-year OS and DFS (5-year OS: 44.7% vs. 54.3% vs. 66.1%; 5-year DFS: 27.8% vs. 33.3% vs. 42.3%) [both p < 0.05], as well as higher incidence of overall (45.5% vs. 25.3% vs. 30.9%; p = 0.013) and major complications (18.2% vs. 3.4% vs. 4.5%; p < 0.001) versus individuals with moderate (ALC 500-1000/µL) or no lymphopenia following hepatectomy for HCC. After adjusting for competing risk factors, prolonged lymphopenia was independently associated with higher hazards of death [hazard ratio (HR) 1.38, 95% CI 1.11-1.72] and recurrence (HR 1.22, 95% CI 1.02-1.45). CONCLUSION: Perioperative lymphopenia had short- and long-term prognostic implications among individuals undergoing hepatectomy for HCC.

Postoperative morbidity after simultaneous versus staged resection of synchronous colorectal liver metastases: Impact of hepatic tumor burden.

BACKGROUND: We sought to characterize the risk of postoperative complications relative to the surgical approach and overall synchronous colorectal liver metastases tumor burden score. METHODS: Patients with synchronous colorectal liver metastases who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Propensity score matching was employed to control for heterogeneity between the 2 groups. A virtual twins analysis was performed to identify potential subgroups of patients who might benefit more from staged versus simultaneous resection. RESULTS: Among 976 patients who underwent liver resection for synchronous colorectal liver metastases, 589 patients (60.3%) had a staged approach, whereas 387 (39.7%) patients underwent simultaneous resection of the primary tumor and synchronous colorectal liver metastases. After propensity score matching, 295 patients who underwent each surgical approach were analyzed. Overall, the incidence of postoperative complications was 34.1% (n = 201). Among patients with high tumor burden scores, the surgical approach was associated with a higher incidence of postoperative complications; in contrast, among patients with low or medium tumor burden scores, the likelihood of complications did not differ based on the surgical approach. Virtual twins analysis demonstrated that preoperative tumor burden score was important to identify which subgroup of patients benefited most from staged versus simultaneous resection. Simultaneous resection was associated with better outcomes among patients with a tumor burden score <9 and a node-negative right-sided primary tumor; in contrast, staged resection was associated with better outcomes among patients with node-positive left-sided primary tumors and higher tumor burden score. CONCLUSION: Among patients with high tumor burden scores, simultaneous resection of the primary tumor and liver metastases was associated with an increased incidence of postoperative complications.

Comparison Between Plastic and Metallic Biliary Stent Placement for Preoperative Patients with Pancreatic Head Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimal preoperative biliary drainage for patients with pancreatic cancer before pancreatoduodenectomy remains unclear. This study aimed to investigate the comparison of efficacy and safety between a metallic stent (MS) and a plastic stent (PS). METHODS: Comparative studies on the use of MS and PS for pancreatic cancer before pancreatoduodenectomy were systematically searched using the MEDLINE and Web of Science databases. Pre- and postoperative data also were extracted. Random-effects meta-analyses were performed to compare post-endoscopic retrograde cholangiopancreatography (ERCP) complications as well as intra- and postoperative outcomes between the two arms of the study, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 percent confidence intervals (CIs). RESULTS: The study analyzed 12 studies involving 683 patients. Insertion of MS was associated with a lower incidence of re-intervention (OR, 0.06; 95% CI 0.03-0.15; P < 0.001), increased post-ERCP adverse events (OR, 2.22; 95% CI 1.13-4.36; P = 0.02), and similar operation time (MD, 18.0 min; 95% CI -29.1 to 65.6 min; P = 0.46), amount of blood loss (MD, 43.0 ml; 95% CI -207.1 to 288.2 ml; P = 0.73), and surgical complication rate (OR, 0.78; 95% CI 0.53-1.15; P = 0.21). The cumulative stent patency rate after 3 months was higher in the MS group than in the PS group (70-100 % vs 30.0-45.0 %). CONCLUSION: For biliary drainage in patients with pancreatic cancer during this era of multidisciplinary treatment, MS use might be the first choice because MS provides a more durable biliary drainage and a similar risk of postoperative outcomes compared with PS.

The shortage of surgeons in Japan: Results of an online survey of qualified teaching hospitals that take part in the surgical training programs for board certification by the Japan Surgical Society.

PURPOSE: A collapse in regional healthcare through the maldistribution of physicians has been a long-debated issue in Japan and amidst this situation, a new system of board certification was initiated. The Japan Surgical Society (JSS) conducted a nation-wide survey to grasp the current distribution of surgeons in Japan, and their roles. METHODS: All 1976 JSS-certified teaching hospitals were invited to respond to a web-based questionnaire. The responses were analyzed to seek a solution to the current issues. RESULTS: Responses to the questionnaire were received from 1335 hospitals. The surgical departments of medical universities serve as an internal labor market and were the source of surgeons for most hospitals. More than 50% of teaching hospitals throughout the country claimed a shortage of surgeons even in well-populated prefectures such as Tokyo and Osaka. Hospitals rely on surgeons to cover the deficits in medical oncology, anesthesiology, and emergency medicine. These additional responsibilities were identified as significant predictors of a shortage of surgeons. CONCLUSIONS: Surgeon shortage is a serious issue throughout Japan. Given the limited number of surgeons and surgical trainees, hospitals should make every effort to recruit specialists in the additional fields where surgeons are filling the gaps and allow surgeons to engage more in surgery.

Liver transplantation access and outcomes: Impact of variations in liver-specific specialty care.

BACKGROUND: We sought to characterize the impact access to gastroenterologists/hepatologists has on liver transplantation listing, as well as time on the liver transplantation waitlist and post-transplant outcomes. METHODS: Liver transplantation registrants aged >18 years between January 1, 2004 and December 31, 2019 were identified from the Scientific Registry of Transplant Recipients Standard Analytic Files. The liver transplantation registration ratio was defined as the ratio of liver transplant waitlist registrations in a given county per 1,000 liver-related deaths. RESULTS: A total of 150,679 liver transplantation registrants were included. Access to liver transplantation centers and liver-specific specialty physicians varied markedly throughout the United States. Of note, the liver transplantation registration ratio was lower in counties with poor access to liver-specific care versus counties with adequate access (poor access 137.2, interquartile range 117.8-163.2 vs adequate access 157.6, interquartile range 127.3-192.2, P < .001). Among patients referred for liver transplantation, the cumulative incidence of waitlist mortality and post-transplant graft survival was comparable among patients with poor versus adequate access to liver-specific care (both P > .05). Among liver transplantation recipients living in areas with poor access, after controlling for recipient and donor characteristics, cold ischemic time, and model for end-stage liver disease score, the area deprivation index predicted graft survival (referent, low area deprivation index; medium area deprivation index, hazard ratio 1.52, 95% confidence interval 1.03-12.23; high area deprivation index, 1.45, 95% confidence interval 1.01-12.09, both P < .05). CONCLUSION: Poor access to liver-specific care was associated with a reduction in liver transplantation registration, and individuals residing in counties with high social deprivation had worse graft survival among patients living in counties with poor access to liver-specific care.

Optimal policy tree to assist in adjuvant therapy decision-making after resection of colorectal liver metastases.

BACKGROUND: Although systemic postoperative therapy after surgery for colorectal liver metastases is generally recommended, the benefit of adjuvant chemotherapy has been debated. We used machine learning to develop a decision tree and define which patients may benefit from adjuvant chemotherapy after hepatectomy for colorectal liver metastases. METHODS: Patients who underwent curative-intent resection for colorectal liver metastases between 2000 and 2020 were identified from an international multi-institutional database. An optimal policy tree analysis was used to determine the optimal assignment of the adjuvant chemotherapy to subgroups of patients for overall survival and recurrence-free survival. RESULTS: Among 1,358 patients who underwent curative-intent resection of colorectal liver metastases, 1,032 (76.0%) received adjuvant chemotherapy. After a median follow-up of 28.7 months (interquartile range 13.7-52.0), 5-year overall survival was 67.5%, and 3-year recurrence-free survival was 52.6%, respectively. Adjuvant chemotherapy was associated with better recurrence-free survival (3-year recurrence-free survival: adjuvant chemotherapy, 54.4% vs no adjuvant chemotherapy, 46.8%; P < .001) but no overall survival significant improvement (5-year overall survival: adjuvant chemotherapy, 68.1% vs no adjuvant chemotherapy, 65.7%; P = .15). Patients were randomly allocated into 2 cohorts (training data set, n = 679, testing data set, n = 679). The random forest model demonstrated good performance in predicting counterfactual probabilities of death and recurrence relative to receipt of adjuvant chemotherapy. According to the optimal policy tree, patient demographics, secondary tumor characteristics, and primary tumor characteristics defined the subpopulation that would benefit from adjuvant chemotherapy. CONCLUSION: A novel artificial intelligence methodology based on patient, primary tumor, and treatment characteristics may help clinicians tailor adjuvant chemotherapy recommendations after colorectal liver metastases resection.

Early-onset hepatic veno-occlusive disease after liver transplantation: an institutional experience and analysis of a literature-based cohort.

PURPOSE: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. METHODS: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature. RESULTS: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. CONCLUSION: Early-onset HVOD developing within 14 days after LT has a poor prognosis.

Long-term survival after surgical resection for bone metastasis from pancreatic cancer: A case report.

INTRODUCTION: Pancreatic cancer (PC) is highly malignant and metastatic; however, bone metastases are rare. Although the effectiveness of conversion surgery for distant metastases of PC has been reported in a few cases, there are no reports on surgical resection for bone metastases. Here, we report a case of long-term survival after resection of bone metastasis from PC. PATIENT CONCERNS: A 60-year-old woman underwent pancreaticoduodenectomy after neoadjuvant chemoradiotherapy for pancreatic head cancer. At 28 months after surgery, multiple lung metastases from PC were diagnosed, and chemotherapy was administered. After 59 months, chemotherapy was terminated because all target lesions had disappeared on imaging. DIAGNOSIS: At 77 months after the initial surgery, bone metastasis in the left 9th rib was detected by positron emission tomography/computed tomography, which was performed due to elevated carbohydrate antigen 19-9 levels. INTERVENTIONS: Chemotherapy was readministered as the initial treatment. Subsequently, due to the long-term well-controlled status of the recurrence site and the absence of other metastases, thoracoscopic-assisted partial resection of the left 9th rib was performed 128 months following pancreaticoduodenectomy. Pathological examination revealed adenocarcinoma metastasis from PC. OUTCOMES: The patient is currently alive without recurrence 44 months after resection for bone metastasis and 172 months after the initial surgery. CONCLUSION: Surgical resection may be favorable in patients with bone metastasis of PC that is well-controlled with chemotherapy.

Phase I study of neoadjuvant S-1 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02).

Aim: Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study. Methods: Patients diagnosed with resectable stage II-IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg/m2), 80 mg/m2 of S-1, and 50.4 Gy of external beam radiation. The recommended dose was defined as a dose one-step lower than the maximum-tolerated dose, which was defined when dose-limiting toxicity was observed in three or more of the six patients. Results: Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose-limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum-tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery. Conclusion: We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality.

An attempt to establish and apply global benchmarks for liver resection of malignant hepatic tumors.

BACKGROUND: Benchmarking is a process of continuous self-evaluation and comparison with best-in-class hospitals to guide quality improvement initiatives. We sought to define global benchmarks relative to liver resection for malignancy and to assess their achievement in hospitals in the United States. METHODS: Patients who underwent curative-intent liver resection for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or colorectal or neuroendocrine liver metastases between 2000 and 2019 were identified from an international multi-institutional database. Propensity score matching was conducted to balance baseline characteristics between open and minimally invasive approaches. Best-in-class hospitals were defined relative to the achievement rate of textbook oncologic outcomes and case volume. Benchmark values were established relative to best-in-class institutions. The achievement of benchmark values among hospitals in the National Cancer Database was then assessed. RESULTS: Among 2,624 patients treated at 20 centers, a majority underwent liver resection for hepatocellular carcinoma (n = 1,609, 61.3%), followed by colorectal liver metastases (n = 650, 24.8%), intrahepatic cholangiocarcinoma (n = 299, 11.4%), and neuroendocrine liver metastases (n = 66, 2.5%). Notably, 1,947 (74.2%) patients achieved a textbook oncologic outcome. After propensity score matching, 6 best-in-class hospitals with the highest textbook oncologic outcome rates (≥75.0%) were identified. Benchmark values were calculated for margin positivity (≤11.7%), 30-day readmission (≤4.1%), 30-day mortality (≤1.6%), minor postoperative complications (≤24.7%), severe complications (≤12.4%), and failure to achieve the textbook oncologic outcome (≤22.8%). Among the National Cancer Database hospitals, global benchmarks for margin positivity, 30-day readmission, 30-day mortality, severe complications, and textbook oncologic outcome failure were achieved in 62.9%, 27.1%, 12.1%, 7.1%, and 29.3% of centers, respectively. CONCLUSION: These global benchmarks may help identify hospitals that may benefit from quality improvement initiatives, aiming to improve patient safety and surgical oncologic outcomes.

Survival Benefit Relative to Treatment Modalities Among Patients with Very Early Intrahepatic Cholangiocarcinoma: an Analysis of the National Cancer Database.

BACKGROUND: Liver transplantation (LT) has been considered a potential curative treatment for patients with very early intrahepatic cholangiocarcinoma (ICC) and cirrhosis, yet the survival benefit of LT has not been well defined. This study aimed to compare the long-term survival outcomes of patients who underwent LT with that of individuals who received resection and non-curative intent treatment (non-CIT). METHODS: Patients who underwent LT, hepatectomy, and non-CIT between 2004 and 2018 were included in the National Cancer Database. Survival benefits of LT over resection and non-CIT were analyzed relative to overall survival (OS). RESULTS: Among 863 patients, 54 (6.3%) underwent LT, while 342 (39.6%) underwent surgical resection, and 467 (54.1%) received non-CIT, respectively. While the rates of non-CIT increased over time, the percentages of LT remained consistent during the study period. LT patients had similar 5-year OS to individuals who underwent resection (referent, resection: LT, HR 0.95, 95%CI 0.84-1.58, p=0.84). In contrast, 5-year OS was better among patients who underwent LT versus individuals who had non-CIT after controlling other variables using propensity score overlapping weighting (5-year OS, LT 57.1% vs. LR 25.8%, p<0.001). CONCLUSIONS: The outcomes of very early ICC patients who underwent LT were similar to individuals who underwent hepatectomy, but better than patients treated with non-CIT. LT should be may be a consideration as a treatment option for patients with early stage ICC who are unsuitable candidates for resection.