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Aim: Intrahepatic cholangiocarcinoma (ICC) is a rare disease; however, its incidence and mortality are increasing worldwide. The rapid aging of populations around the world is leading to an increased number of patients with cancer who develop disability in activities of daily living (ADL). This study was conducted to investigate the associations of perioperative ADL with patient survival after hepatic resection for ICC. Methods: We included 70 consecutive patients who underwent hepatectomy for ICC from 2010 to 2021 in the current study. Preoperative and postoperative ADL were evaluated based on the Barthel index, which yields a score of 0–100 points, with higher scores indicating greater independence. A preoperative or postoperative Barthel index score of <100 was defined as disability in perioperative ADL. Cox proportional hazards regression was used to calculate hazard ratios after adjusting for potential confounders. Results: Among the 70 patients, seven (10%) had a preoperative Barthel index score of <100, and 23 (33%) showed a postoperative Barthel index score of <100. Multivariate analyses revealed that disability in perioperative ADL was associated with shorter recurrence‐free survival (multivariable hazard ratios 2.38, 95% confidence interval 1.22–4.57; p = 0.011) and overall survival (multivariable hazard ratio 2.49, 95% confidence interval 1.09–5.70; p = 0.031). Conclusions: Disability in perioperative ADL is associated with shorter recurrence‐free and overall survival after hepatic resection for ICC. Upon validation, perioperative measurement of ADL may improve risk assessment, and improvement of perioperative ADL may lead to favorable clinical outcomes in patients with ICC. [ABSTRACT FROM AUTHOR]

Aim: Patients with malignant tumors are prone to develop nutritional disorders. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for assessing the nutritional status. This study was performed to evaluate whether the preoperative GNRI can serve as a prognostic factor in patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative surgery. Methods: This study included 123 consecutive patients with ICC who were treated with curative surgery. Kaplan–Meier analysis was performed to calculate the recurrence-free survival (RFS) and overall survival (OS), and Cox regression analysis was used to evaluate prognostic factors. Results: Of the 123 patients, 82 were male and 41 were female. The median age of the patients was 70 years, and the median follow-up period was 37.0 months (interquartile range, 16.2–71.7 months). The patients were classified by the median GNRI into a low GNRI group (GNRI < 105) and high GNRI group (GNRI ≥ 105). The patients in the low GNRI group had a significantly poorer prognosis in terms of RFS and OS than the patients in the high GNRI group (RFS, p = 0.0201; OS, p < 0.0001). Lymph node metastasis [hazard ratio (HR), 4.66; 95% confidence interval (CI), 2.46–8.85], postoperative complications (HR, 2.38; 95% CI, 1.32–4.31), and a low GNRI (HR, 2.53; 95% CI, 1.42–4.50) were independent poor prognostic factors for OS. Conclusion: The GNRI may be a useful prognostic indicator in patients with ICC undergoing curative hepatectomy. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to describe the surgical techniques for a thoracoscopic approach to treat hepatocellular carcinoma in the hepatic dome. Also, safety, feasibility, and long‐term outcomes were evaluated. Methods: Surgical procedures were selected based on liver function, the extent and location of the tumor, and each patient's general condition. Thoracoscopic hepatic resection was performed under direct vision through a diaphragmatic incision. Thoracoscopic radiofrequency ablation (TRFA) was performed either with a transdiaphragmatic puncture for deeply located tumors or under direct vision through a diaphragmatic incision for subcapsular tumors. Results: Thoracoscopic surgery was indicated for 107 patients with hepatocellular carcinoma in the hepatic dome. Among these patients, 5 underwent hepatectomy and 102 underwent radiofrequency ablation, which was more frequently employed in patients with impaired liver function. Of the patients who underwent radiofrequency ablation, 43 (42.2%) required a diaphragmatic incision. In the thoracoscopic hepatic resection group and TRFA group, the median operating time was 350 and 197 minutes, the median blood loss was 200 and 5 mL, and the complication rate was 12.7% and 20.0%, respectively. The 5‐year overall and disease‐free survival rates were 100% and 50.0% in the thoracoscopic hepatic resection group, respectively, and 60.7% and 18.1% in the TRFA group, respectively. Local recurrence after TRFA was observed in 10 patients (9.8%). Conclusion: The thoracoscopic approach is safe and feasible, with promising short‐ and long‐term outcomes. It could serve as a treatment option for hepatocellular carcinoma in the hepatic dome. [ABSTRACT FROM AUTHOR]

Purposes: Programmed death ligand 1 (PD-L1) is a key target for the treatment of several malignancies. The present study was conducted to clarify the role of serum PD-L1 in hepatocellular carcinoma (HCC). Methods: Serum PD-L1 (sPD-L1) was examined by an enzyme-linked immunosorbent assay in 153 patients with HCC who underwent curative hepatectomy at Kumamoto University in 2011–2016. The expression of PD-L1 in tissue (tPD-L1) was investigated by immunohistochemistry. The clinical roles of the PD-L1 expression in both serum and tissue were examined. Results: The sPD-L1 was significantly elevated in HCC patients compared to patients without any malignant or inflammatory disease (234 vs. 93 pg/mL, p < 0.0001). The percentage of the tPD-L1-positive area (%tPD-L1) in the background liver was significantly higher than in the tumor (1.52% vs. 0.48%, p < 0.0001). The %tPD-L1 in the background liver but not in the tumor was significantly correlated with the sPD-L1 level (p = 0.0079). The sPD-L1, %tPD-L1 in the tumor, and %tPD-L1 in the background liver were not correlated with the overall survival after surgery. Conclusion: PD-L1-expressing cells in the background liver, but not in the tumor tissue, appeared to contribute to the sPD-L1 level. The sPD-L1 level may thus not indicate the tumor burden in patients with HCC. [ABSTRACT FROM AUTHOR]

Purposes: Clinical predictive markers for the malignant potential of pancreatic neuroendocrine tumors (PNETs) are limited without histological investigation. We reported previously that a loss of the regular enhancement pattern in preoperative computed tomography (CT) was correlated with the malignant tumor phenotype. This study aimed to establish whether the metabolic aspect of the tumor evaluated by fludeoxyglucose (18F) positron emission tomography/computed tomography 18F-FDG PET/CT is associated with the tumor imaging characteristics and postoperative oncological outcome.Methods: Among 77 patients who underwent surgery with curative intent for a PNET at our institution between 2001 and 2017, 24 who received 18F-FDG PET/CT before surgery were enrolled in this study. The clinical importance of the standardized uptake value (SUVmax) was investigated with regard to tumor progression and prognosis after curative surgery.Results: There were four (16%) patients with insulinoma. The mean tumor size was 17 mm and when the median value of the SUVmax (= 2.0) was measured as the cut-off value, the SUVmax ≥ 2.0 group (n = 12) was associated with large tumor size (p = 0.021), high tumor grade (p = 0.015), and irregular pattern on CT (p = 0.0055). The SUVmax was not correlated with age, gender, whether the tumor was functioning or non-functioning, or lymph node metastasis. The SUVmax ≥ 2.0 group had significantly poorer disease-free survival (median, 3.5 vs 16.2 months; p = 0.023) and poorer overall survival (median, 8.8 vs 16.2 months; p = 0.042).Conclusion: An SUVmax ≥ 2.0 on 18F-FDG PET/CT might be associated with higher malignant potential of PNETs. [ABSTRACT FROM AUTHOR]

Immunotherapy using anti‐PD‐1/PD‐L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD‐L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD‐L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)‐α upregulated PD‐L1 expression in PDAC cells through NF‐κB signaling. The induction of PD‐L1 expression was also caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages. PD‐L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD‐L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. These findings indicate that tumor‐infiltrating macrophage‐derived TNF‐α could be a potential therapeutic target for PDAC. Survival analysis revealed that PD‐L1 expression was significantly associated with poor prognosis in PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. The induction of PD‐L1 expression was caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages. [ABSTRACT FROM AUTHOR]

Background: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC).Methods: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b+ neutrophils (TANs; tumour associated neutrophils), CD163+ M2 macrophages (TAMs; tumour associated macrophages), CD8+ T cells, and FOXP3+ regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated.Results: Tumour associated neutrophils were inversely correlated with CD8+ T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8+ T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence.Conclusions: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients. [ABSTRACT FROM AUTHOR]