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Background Since homologous recombination deficiency (HRD) is relatively uncommon in pancreatic cancer (PC), its impact on time-to-treatment failure (TTF) among patients undergoing systemic chemotherapy for unresectable and recurrent PC remains uncertain. Methods Among patients with unresectable and recurrent PC enrolled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database by July 2023, a total of 1394 patients who underwent first-line chemotherapy with either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FFX) and received tissue-based CGP tests after disease progression were included in this study. HRD was defined as the presence of germline or somatic genetic mutations in homologous recombination repair (HRR)-related genes such as ATM, BARD1, BRIP1, BRCA1/2, CHEK2, CDK12, PALB, and RAD51C/D . We investigated the correlation between HRD and TTF among patients treated with GnP and FFX. Results First-line chemotherapy consisted of GnP in 69% of the cases and FFX in 31%. The CGP tests used were NCC OncoPanel and FoundationOne CDx in 26% and 74%, respectively. HRR-related genetic abnormalities were identified in 107 patients (7.6%): BRCA2 ( n  = 51), ATM ( n  = 34), BRCA1 ( n  = 9), PALB2 ( n  = 9), among others. In the GnP cohort, the median TTF was comparable between the HRD and non-HRD groups (5.3 vs 4.6 months, P  = 0.44). Conversely, in the FFX cohort, it was significantly longer in the HRD group compared to the non-HRD group (7.3 vs. 4.7 months, p  < 0.01). Conclusions Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.

Background Excess body weight may modulate the progression of various cancer types. The prognostic relevance of body mass index (BMI) has not been fully examined in patients with biliary tract cancer. Methods Using a single-institutional cohort of 360 patients receiving gemcitabine-based chemotherapy for advanced biliary tract cancer, we examined the association of BMI with overall survival (OS). Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for OS according to BMI. The findings were validated using a Japanese nationwide inpatient database including 8324 patients treated at 201 hospitals. Results In the clinical cohort, BMI was not associated with OS ( P trend  = 0.34). Compared to patients with BMI = 18.5–24.9 kg/m 2 , patients with BMI < 18.5 kg/m 2 and ≥ 25.0 kg/m 2 had adjusted HRs for OS of 1.06 (95% CI, 0.78–1.45) and 1.01 (95% CI, 0.74–1.39), respectively. There was no evidence on a non-linear relationship between BMI and OS ( P nonlinearity  = 0.63). In the nationwide cohort, the null findings were validated ( P trend  = 0.18) with adjusted HRs of 1.07 (95% CI, 0.98–1.18) for BMI < 18.5 kg/m 2 and 1.05 (95% CI, 0.96–1.14) for BMI ≥ 25.0 kg/m 2 (vs. BMI = 18.5–24.9 kg/m 2 ). In the clinical cohort, BMI was not associated with progression-free survival ( P trend  = 0.81). Conclusions BMI was not associated with survival outcomes of patients with advanced biliary tract cancer. Further research is warranted incorporating more detailed body composition metrics to explore the prognostic role of adiposity in biliary tract cancer.

Abstract Aims Plasma volume status (PVS) is recognized as a marker of systemic congestion, but its clinical utility in patients with mitral regurgitation (MR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) has not been well established. This study aimed to evaluate the prognostic significance of PVS in these patients. Methods and results Data from 3763 patients who underwent M-TEER were analysed from a Japanese multicentre registry. Patients were classified into functional MR (FMR) and degenerative MR (DMR) according to MR aetiology, and the median PVS values for each were calculated (FMR 12.7, DMR 14.4). The median value was used as the cut-off, stratifying the cohort into a high PVS group (n = 1882) and a low PVS group (n = 1881). All-cause mortality, cardiovascular death, and heart failure (HF) hospitalization between these two groups were compared up to 3 years in the overall, FMR, and DMR populations. The cumulative incidence rates of all-cause mortality, cardiovascular death, and HF hospitalization were higher in the high PVS group than in the low PVS group (47.0% vs. 22.2%, P < 0.001, 31.6% vs. 13.6%, P < 0.001, and 35.9% vs. 24.7%, P < 0.001, respectively). Similar trends in terms of all-cause mortality, cardiovascular death, and HF hospitalization were observed in the FMR and DMR cohorts (all P < 0.05). In the multivariate Cox regression analysis, the high PVS compared with the low PVS group was independently associated with the increased risk of all-cause death (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01–1.03; P < 0.001), cardiovascular death (HR, 1.02; 95% CI, 1.01–1.03, P < 0.001) and HF hospitalization (HR, 1.02; 95% CI, 1.01–1.02, P < 0.001). An independent association between a high PVS and all-cause death, cardiovascular death, and HF hospitalization was also found in FMR and DMR sub-groups (all P < 0.05) while reducing MR severity to moderate or less after M-TEER was associated with improved outcomes in both the high and low PVS groups. Conclusions Preoperative PVS is a strong independent prognostic marker in patients undergoing M-TEER, correlating with increased risk of mortality and HF hospitalization. PVS may provide valuable clinical insights for patient stratification and management strategies in M-TEER patients.

Background Appropriate distribution of health care resources is required to adjust regional disparities in the quality of health care. Besides, the number of community pharmacists in Japan has increased recently, but the impact of this increase on the distribution of community pharmacists is unknown. Thus, we aimed at investigating the effect of the increase in the number of community pharmacists on the distribution per population and per area of inhabitable land. Methods Data from 2008 to 2018 were used. Equity among municipalities in the number of community pharmacists per population and per area of inhabitable land was assessed using the Gini coefficient. A mosaic plot was used to demonstrate the relationship between the population density and increase in the number of community pharmacists per municipality. Results The number of community pharmacists increased by approximately 1.3-fold from 2008 to 2018 in Japan. The Gini coefficient per population decreased gradually, whereas that per area increased slightly, with no change in distribution per area of inhabitable land. The number of community pharmacists per population increased regardless of the population density, but this increase per area was smaller for lower population density groups and larger for higher population density groups. Conclusion The increase in the number of community pharmacists has improved the distribution of community pharmacists per population, but not that per area of inhabitable land. The maldistribution of community pharmacists per area implies an imbalance in the distance between pharmacies and residents. Thus, there is need for measures to improve the distribution of community pharmacists.

Background and aimsEndoscopic biliary drainage for malignant biliary obstruction (MBO) in patients with surgically altered anatomy is challenging, and technical difficulty could differ by the anatomy. Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) and endoscopic ultrasonography-guided biliary drainage (EUS-BD) are both emerging procedures, and we conducted the single-center, retrospective study to compare clinical outcomes of BE-ERCP and EUS-BD for MBO.MethodsConsecutive patients with surgically altered anatomy who underwent BE-ERCP or EUS-BD for MBO were retrospectively studies. Technical and clinical success rates, adverse events (AEs), and time to recurrent biliary obstruction (TRBO) were compared.ResultsPatient characteristics were comparable between BE-ERCP (n = 118) and EUS-BD (n = 32), other than more patients with hepaticojejunostomy in the BE-ERCP group (66% vs. 44%, P = 0.03). Technical success rate was significantly higher in the EUS-BD group (70% vs. 94%, P = 0.005), but clinical success rates (84% vs. 90%, P = 0.55), early AE (14% vs. 22%, P = 0.29) and late AE rates (42% vs. 38%, P = 0.84), and RBO rates (31% vs. 34%, P = 0.67) were comparable between the groups. TRBO was 170 and 206 days in the BE-ERCP and EUS-BD group (P = 0.37). In the subgroup analysis of patients with the intact papilla, the technical success rate of BE-ERCP was as low as 55%, compared to 94% in EUS-BD (P = 0.003).ConclusionEUS-BD was associated with higher technical success rate than BE-ERCP for MBO in patients with surgically altered anatomy.

Background and aimBalloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is an emerging procedure for pancreatobiliary diseases in patients with surgically altered anatomy. However, data on BE-ERCP for hepatolithiasis after hepaticojejunostomy (HJS) are still limited.MethodsStone removal success, adverse events and recurrence were retrospectively studied in consecutive patients who underwent BE-ERCP for hepatolithiasis after HJS between January 2011 and October 2022. Subgroup analysis was performed to compare clinical outcomes between patients who had undergone HJS over 10 years before (past HJS group) and within 10 years (recent HJS group).ResultsA total of 131 patients were included; 39% had undergone HJS for malignancy and 32% for congenital biliary dilation. Scope insertion and complete stone removal were successful in 89% and 73%, respectively. Early adverse events were observed in 9.9%. Four patients (3.1%) developed gastrointestinal perforation but could be managed conservatively. Hepatolithiasis recurrence rate was 17%, 20% and 31% in 1-year, 3-year, and 5-year after complete stone removal. The past HJS group was the only risk factor for failed stone removal (odds ratio 10.4, 95% confidence interval 2.99–36.5) in the multivariable analysis. Failed scope insertion (20%) and failed guidewire or device insertion to the bile duct (22%) were two major reasons for failed stone removal in the past HJS group.ConclusionsBE-ERCP for hepatolithiasis was effective and safe in cases with HJS but the complete stone removal rate was low in the past HJS group. Recurrent hepatolithiasis was common and careful follow up study is needed even after complete stone removal.

BackgroundCoaptation gap (CG) is one of the challenging anatomies of mitral transcatheter edge-to-edge repair (TEER), but its impact on patient outcomes is unclear. This study aimed to evaluate the impact of CG on procedural and clinical outcomes in patients with functional mitral regurgitation (MR).MethodsData from 2140 patients undergoing TEER for functional MR were analysed, focusing on the presence of CG, which is a missing leaflet coaptation between the anterior and posterior leaflets during systole. The primary outcome was a composite of death, heart failure hospitalisation and mitral valve reintervention.ResultsOf the 2140 patients, 219 (10%) had CG and 1921 (90%) did not, as assessed by baseline transoesophageal echocardiography. In patients with CG, baseline MR grade and New York Heart Association (NYHA) functional class were more severe, and long/wide clip types were used more frequently. Post-TEER, patients with CG had significantly lower achievement of MR grade ≤2+ (93%) and ≤1+ (65%) compared with patients without CG (97%, p<0.01; 82%, p<0.01, respectively). NYHA functional class at 1 year was similar in both groups. The cumulative incidence of the primary outcome was comparable between CG and non-CG groups (51% vs 53% at 3 years, p=0.71). While residual MR grade 2+ was associated with the higher primary outcome incidence compared with ≤1+ in patients without CG (p<0.01), no significant difference was found in patients with CG (p=0.51).ConclusionCG was associated with less MR reduction but with no clear difference in adverse clinical outcomes after TEER. Similar outcomes between residual MR grade 2+ and ≤1+ in CG patients highlight the importance of procedural endpoint in anatomically challenging cases.Trial registration numberUMIN000023653.

The synthesis, structural, and photophysical investigations of CuI complexes with a disilanylene-bridged bispyridine ligand 1 are herein presented. Dinuclear (2) and ladder-like (3) octanuclear copper(I) complexes were straightforwardly prepared by exactly controlling the ratio of CuI/ligand 1. Single-crystal X-ray analysis confirmed that dinuclear complex 2 had no apparent π…π stacking whereas octanuclear complex 3 had π…π stacking in the crystal packing. In the solid state, the complexes display yellow-green (λem = 519 nm, Φ = 0.60, τ = 11 µs, 2) and blue (λem = 478 nm, Φ = 0.04, τ = 2.6 µs, 3) phosphorescence, respectively. The density functional theory calculations validate the differences in their optical properties. The difference in the luminescence efficiency between 2 and 3 is attributed to the presence of π…π stacking and the different luminescence processes.

Background: Multidisciplinary treatment of hepatocellular carcinoma (HCC) has made notable advancements with the emergence of novel agents for systemic therapies, including receptor tyrosine kinase inhibitors (TKIs) and cancer immuno-oncology therapy (IO) utilizing immune checkpoint inhibitors. Although each of these regimens is effective as monotherapy for advanced HCCs, combining them with local treatments (LRT), such as transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and radiotherapy (RT), provides an additional antitumor effect. The emergence of novel systemic therapies has given rise to anticipation for the development of multidisciplinary treatments with a combination of systemic therapy and LRT, which aim to achieve curative-intent resection and improve long-term prognosis after resection. Summary: Perioperative combination therapy, a combination of multiple treatment modalities including systemic therapy (TKI and/or IO) and LRT (TACE, HAIC, or RT), is attracting attention as a potentially useful approach for multidisciplinary curative-intent surgical resection or ablation. Currently, there is no evidence-based guidance regarding selection criteria and optimal regimens for perioperative combination therapy. The definition of oncological resectability for HCC is being pursued to establish the indication and protocol for perioperative combination therapy, which broadly encompasses conversion as well as neoadjuvant and adjuvant therapy for intermediate-to-advanced HCC. Key Messages: Perioperative combination therapy, which positions curative-intent surgical resection or ablation within the combination of multiple modalities including systemic therapy and LRT, provides perspectives for improving the long-term prognosis of patients with initially unresectable HCC and borderline resectable HCC with a high risk of recurrence.

Serrated polyps have recently been reported in patients with ulcerative colitis (UC); however, their prevalence and detailed characteristics remain unclear. The prevalence and clinicopathological and biological characteristics of serrated polyps in patients with UC were retrospectively examined in a single tertiary inflammatory bowel disease center in Japan from 2000 to 2020. Among 2035 patients with UC who underwent total colonoscopy, 252 neoplasms, including 36 serrated polyps (26 in colitis-affected segments, 10 in colitis-unaffected segments), were identified in 187 patients with UC. The proportion of serrated polyps was 1.8% (36/2035). Serrated polyps in colitis-affected segments were common with extensive colitis (88%), history of persistent active colitis (58%), and long UC duration (12.1 years). Serrated polyps in colitis-affected segments were more common in men (88%). Of the 26 serrated polyps in colitis-affected segments, 15, 6, and 5 were categorized as sessile serrated lesion-like dysplasia, traditional serrated adenoma-like dysplasia, and serrated dysplasia not otherwise specified, respectively. Sessile serrated lesion-like dysplasia was common in the proximal colon (67%) and with BRAF mutation (62%), whereas traditional serrated adenoma-like dysplasia and serrated dysplasia not otherwise specified were common in the distal colon (100% and 80%, respectively) and with KRAS mutations (100% and 75%, respectively). Serrated polyps comprised 14% of the neoplasias in patients with UC. Serrated polyps in colitis-affected segments were common in men with extensive and longstanding colitis, suggesting chronic inflammation in the development of serrated polyps in patients with UC.