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Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Objectives: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD. Methods: This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports. Results: During a median follow-up period of 70.5 months (3–120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer. Conclusion: Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD. [ABSTRACT FROM AUTHOR]

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75–81) years and 79 (range: 76–92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1–5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group. [ABSTRACT FROM AUTHOR]

Purpose: Since the introduction of the Exeter stem for clinical use in Japan in 1996, the number of stems used has continued to rise owing to its favorable results. We investigated the outcomes of patients who had previously undergone total hip arthroplasty with the Exeter stem in Japan with a 10-year + follow-up period. Methods: This retrospective cohort study used clinical and radiographic data of 682 cases of primary total hip arthroplasty performed using the Exeter stem. Results: The mean postoperative follow-up period was 13.3 years. Femoral-side revision was required in 14 hips, with no cases of aseptic stem loosening-associated revision observed. Kaplan–Meier survival analysis predicted 97.3% 15-year survival when revision for any reason was used as the endpoint. Conclusion: The obtained findings suggested the excellent long-term stability of the Exeter stem for primary total hip arthroplasty in Japan. [ABSTRACT FROM AUTHOR]

Aim: Japan faces a public health challenge of dementia, further complicated by the increasing complications from diabetes within its rapidly aging population. This study assesses the impact of diabetes on mortality and hospitalization among individuals aged ≥75 years with new dementia diagnoses. Methods: We analyzed administrative claims data in Japan from 73 324 individuals aged ≥75 years with dementia, of whom 17% had comorbid diabetes. Dementia and diabetes were identified from the International Classification of Diseases, Tenth Revision codes. We used Kaplan–Meier survival analysis, Cox proportional hazards analysis, and population attributable fractions (PAFs) to evaluate the impact on mortality and hospitalization after dementia diagnosis. Results: One‐year mortality and 1‐year hospitalization probabilities in individuals with dementia and diabetes (10.3% and 31.7%, respectively) were higher than those without diabetes (8.3% and 25.4%, respectively). The adjusted hazard ratios for individuals with diabetes, as compared to those without, were 1.126 (95% confidence interval [CI], 1.040–1.220) for mortality and 1.191 (95% CI, 1.140–1.245) for hospitalization. The PAFs from the comorbidity of dementia and diabetes were 2.2% for mortality and 3.1% for hospitalization. Subgroup analysis showed that the PAFs were highest in men aged 75–79 years and women aged 80–84 years for mortality and in individuals aged 75–79 for hospitalization. Conclusion: During the early postdiagnosis period, comorbid diabetes increases mortality and hospitalization risks in older adults with dementia. The variation in disease burden across age groups underscores the need for age‐specific health care strategies to manage comorbid diabetes in individuals with dementia. Geriatr Gerontol Int 2024; 24: 773–781. [ABSTRACT FROM AUTHOR]

Background: Whether the Western pT1acN0M0 gastric cancer (GC) patients who met the Japanese expanded criteria could be the candidates for endoscopic treatment (ET) remains unclear because of unknown long-term survival outcomes. Methods: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) program was performed. The survival differences between pT1acN0M0 gastric adenocarcinoma patients who received ET or gastrectomy treatment (GT) were evaluated using multivariate survival analysis. Results: A total of 314 pT1acN0M0 gastric adenocarcinoma patients who met the expanded criteria were included, 46 patients received ET and 268 patients received GT. pT1acN0M0 gastric adenocarcinoma patients met the expanded criteria underwent ET experienced a similar hazard of cancer-specific death compared with those underwent GT both in the multivariate Cox survival analysis (adjusted hazard ratio [HR]; 1.18, 95% confidence interval [CI] 0.40–3.49; P = 0.766) and the multivariate competing risk model (subdistribution HR [SHR], 1.12, 95% CI 0.38–3.29; P = 0.845). The result that pT1acN0M0 gastric adenocarcinoma patients met the expanded criteria underwent ET experienced comparable survival outcomes to those who underwent GT did not change even compared with those who underwent GT with > 15 lymph nodes examined (adjusted HR, 1.55, 95% CI 0.44–5.49; P = 0.499; SHR, 1.47, 95% CI 0.44–4.88; P = 0.532). Conclusions: The ET can be considered in Western pT1acN0M0 gastric adenocarcinoma patients who met the Japanese expanded criteria. However, a prospective study should be warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Tertiary lymphoid structures (TLS) arise in non-lymphoid tissues due to inflammation or cancer and play a key role in adaptive immune responses. In this study, we analyzed the TLS maturity in 78 patients with pathological T4 colorectal cancer (CRC). Mature TLS, identified by organized T (CD3+) and B (CD20+) lymphocytes with Ki-67-positive B cells, have been linked to microsatellite instability and improved cancer-specific and post-recurrence survival. High tumor Ki-67 expression correlated with poorer outcomes. The absence of mature TLS independently predicted poor survival. Tumors with mature TLS showed a higher infiltration of CD3+ T cells, FOXP3+ T cells, and CD86+ immune cells, including M1-like macrophages. Focusing on the Ki-67 expression pattern, the simultaneous evaluation of TLS maturity and tumor proliferation potency is suggested to be a potential prognostic indicator in CRC. Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes and prognostic factors of 127 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from the initiation of ARSI were assessed. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS varied among patients treated with enzalutamide, abiraterone acetate, apalutamide, and darolutamide (27.0, 20.0, 10.0, and 14.0 months, respectively; p = 0.33). Multivariate analysis indicated that a baseline PSA level of ≥3.67 ng/mL (p = 0.002) was significantly associated with poorer OS prognosis. ARSI demonstrated favorable efficacy in nmCRPC patients, with no significant differences in clinical outcomes among different types of ARSI. High baseline PSA of ARSI was found to have a significantly poor prognosis associated with OS. We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. [ABSTRACT FROM AUTHOR]

This study aimed to determine which instrumental activities of daily living (IADL) are associated with health deterioration from the "support level" to the "care level" among users of the long-term care insurance system in Japan. From April 2017 to March 2020, we conducted a retrospective follow-up survey on 178 Japanese community-dwelling older adults (64 men, 114 women) newly certified as support level. Independent variable was 8 IADL items and the outcome defined as the "support level maintenance time." Cox models were used to assess the risk of health deterioration, with adjustments for age group, family composition, dementia status, and frailty status by gender. Dependence on 5 items, "laundry" (hazard ratio [HR] =2.5; 95% confidence interval [CI]: 1.1-5.8), "cooking" (HR = 3.7; 95% CI: 1.1-12.2), "telephone use" (HR = 2.4; 95% CI: 1.2-4.7), "financial management" (HR = 2.5; 95% CI: 1.2-5.0), and "medication management" (HR = 2.4; 95% CI: 1.2-4.8), was independently associated with a worse outcome among men, whereas dependence on "financial management" (HR = 2.6; 95% CI: 1.5-4.7) and "medication management" (HR = 2.0; 95% CI: 1.1-3.5) was independently associated with a worse outcome among women. These findings suggest that difficulties in "financial management" and "medication management" are common factors associated with health deterioration from the support to the care level among both genders. An association with household tasks was also seen among men, indicating that a paradigm shift is needed to increase the participation of men in household tasks. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child–Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child–Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study. [ABSTRACT FROM AUTHOR]

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objectives: Patients undergoing a prior failed attempt of chronic total occlusion‐percutaneous coronary intervention (CTO‐PCI) represent a challenging subgroup across all patients undergoing CTO‐PCI. There are limited data on the effects of a prior failed attempt on the outcomes of subsequent CTO‐PCI. We aimed to compare the procedural results and 24‐month outcomes of prior‐failed‐attempt CTO‐PCI with those of initial‐attempt CTO‐PCI. Methods: Patients who underwent attempted CTO‐PCI between January 2017 and December 2019 were prospectively enrolled. We analyzed the procedural results and 24‐month major adverse cardiac events (MACE) between patients who underwent prior‐failed‐attempt and initial‐attempt CTO‐PCI. MACE was defined as a composite of cardiac death, target vessel‐related myocardial infarction, and ischemia‐driven target vessel revascularization (TVR) during follow‐up. Results: In total, 484 patients who underwent CTO‐PCI (prior‐failed‐attempt, n = 49; initial‐attempt, n = 435) were enrolled during the study period. After propensity score matching (1:3), 147 patients were included in the initial‐attempt group. The proportion of the Japanese‐CTO (J‐CTO) score ≥2 was higher in the patients who underwent prior failed attempt than in those who underwent initial attempt (77.5% vs. 38.8%, p < 0.001). The retrograde approach was more often adopted in the prior‐failed‐attempt group than in the initial‐attempt group (32.7% vs. 3.4%, [P< 0.001). Successful CTO revascularization rates were significantly lower in the prior‐failed attempt‐group than in the initial attempt group (53.1% vs. 83.3%, P < 0.001). The multivariate analysis revealed that J‐CTO score ≥2 [odds ratio (OR), 0.359; 95% confidence interval (CI), 0.159–0.812; P = 0.014], intravascular ultrasound procedure (OR, 4.640; 95% CI, 1.380–15.603; P = 0.013), and prior failed attempt (OR, 0.285; 95% CI, 0.125–0.648; P = 0.003) were the independent predictors for successful CTO revascularization. There were no significant differences in major procedural complications (2.0% vs. 0.7%, p = 0.438) and MACE rates (4.1% vs. 8.8%, p = 0.438) between the groups, mainly due to the TVR rate (4.1% vs. 8.2%, P = 0.522). Conclusions: Compared with initial‐attempt CTO‐PCI, prior‐failed‐attempt CTO‐PCI deserves more attention, since it is associated with a lower successful CTO revascularization rate. Prior failed attempt, J‐CTO score ≥2, and IVUS procedure are the determining factors for predicting successful CTO revascularization. There are no significantly different unfavorable outcomes between patients who undergo prior‐failed‐attempt and initial‐attempt CTO‐PCI. [ABSTRACT FROM AUTHOR]

Background: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. Methods: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with > 600, two with 401–600, five with 201–400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. Results: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401–600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan–Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. Conclusions: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the fifth most prevalent malignancy globally and the fourth major contributor to cancer-related mortality. The comparative effectiveness of robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) at different stages of gastric cancer is unclear regarding surgical and survival outcomes. We compared surgical and survival outcomes between RG and LG in early-stage (cStage I) and advanced (cStage II/III) gastric cancers to elucidate the difference in the efficacy of RG across various stages of gastric cancer. Methods: We identified 299 patients (LG, 170; RG, 129) with cStage II/III disease and 569 (LG, 455; RG, 114) with cStage I disease who underwent either LG or RG. Following propensity score matching for RG and LG, 118 pairs were selected for cStage II/II and 113 pairs for cStage I. Surgical and survival outcomes of LG and RG were separately compared for cStage II/III and cStage I. Results: In cStage II/III, RG showed significantly fewer intra-abdominal complications of Clavien–Dindo (C.D.) Grade ≥ III in the RG group than in the LG group (LG = 8.5 vs. RG = 1.7%, P = 0.033). Multivariate analysis identified LG as an independent risk factor for intra-abdominal complications of C.D. Grade ≥ III (OR 5.69, 95% CI 1.17–27.70, P = 0.031). However, in cStage I, no difference in surgical outcomes between LG and RG was observed. No differences were observed in survival outcomes between LG and RG in both cStage I or cStage II/III. Conclusions: The real benefit of RG was demonstrated in surgical outcomes, especially for advanced-stage gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. Methods: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. Results: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). Conclusions: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required. [ABSTRACT FROM AUTHOR]

Background The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. Methods We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. Results Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. Conclusions Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE. [ABSTRACT FROM AUTHOR]

Aim: Branched‐chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. Methods: During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan–Meier analyses were conducted to examine time‐dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. Results: The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. Conclusions: Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; 24: 603–608. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgery (MIS), such as laparoscopic and robotic surgery for rectal cancer, is performed worldwide. However, limited information is available on the advantages of MIS over open surgery for multivisceral resection for cases clinically invading adjacent organs. Patients and methods: This was a retrospective propensity score-matching study of consecutive clinical T4b rectal cancer patients who underwent curative intent surgery between 2006 and 2021 at the University of Tokyo Hospital. Results: Sixty-nine patients who underwent multivisceral resection were analyzed. Thirty-three patients underwent MIS (the MIS group), while 36 underwent open surgery (the open group). Twenty-three patients were matched to each group. Conversion was required in 2 patients who underwent MIS (8.7%). R0 resection was achieved in 87.0% and 91.3% of patients in the MIS and open groups, respectively. The MIS group had significantly less blood loss (170 vs. 1130 mL; p < 0.0001), fewer Clavien–Dindo grade ≥ 2 postoperative complications (30.4% vs. 65.2%; p = 0.0170), and a shorter postoperative hospital stay (20 vs. 26 days; p = 0.0269) than the open group. The 3-year cancer-specific survival rate, relapse-free survival rate, and cumulative incidence of local recurrence were 75.7, 35.9, and 13.9%, respectively, in the MIS group and 84.5, 45.4, and 27.1%, respectively, in the open group, which were not significantly different (p = 0.8462, 0.4344, and 0.2976, respectively). Conclusion: MIS had several short-term advantages over open surgery, such as lower complication rates, faster recovery, and a shorter hospital stay, in rectal cancer patients who underwent multivisceral resection. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. Methods We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution CT (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. Results Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar haemorrhage, and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLCO), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLCO and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLCO and presence of honeycombing on chest HRCT (termed "MPF model"). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. Conclusions Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) represent a cornerstone in contemporary cancer therapy, yet managing immune-related adverse events (irAEs) remains pivotal. These events, characterized by reinvigorated autoimmune responses against normal tissues, present particular challenges, especially regarding their safety and tolerability in elderly patients. To address this gap, we conducted a multicenter retrospective cohort study focusing on patients with non-small cell lung cancer undergoing ICI therapy. Our findings revealed that irAE incidence, severity, and organ specificity did not significantly differ between elderly patients and their younger counterparts. However, elderly patients tended to transition to the best supportive care following irAE onset. These findings suggest that while age alone may not preclude ICI treatment, irAEs may be less tolerated in certain elderly individuals, potentially impacting patient prognosis. Identifying markers of irAE intolerance, such as frailty, sarcopenia, and cachexia, alongside chronological age, could aid in optimizing patient selection and clinical benefits of ICI treatment in this population. With cancer diagnosis occurring at older ages, the use of immune checkpoint inhibitors (ICIs) has extended to older adults. However, the safety of immune-related adverse events (irAEs) in this population remains unclear and relies on data extrapolated from younger adults. This multicenter retrospective study aimed to examine irAE prevalence and tolerability in older adults. We included 436 patients with non-small lung cancer undergoing ICI therapy and dichotomized them into two age groups (< or ≥75 years). Incidence of any irAE grade, grade ≥3 irAEs, and steroid usage after irAE occurrence was similar between younger (n = 332) and older groups (n = 104). While the younger patients with irAEs showed prolonged overall survival in the 12-month landmark Kaplan–Meier analysis (Hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.38–0.89, p = 0.013), the older cohort did not (HR 0.80, 95% CI 0.36–1.78, p = 0.588). Although no differences were observed with ICI continuation or re-challenge after irAE onset, the elderly cohort had double the irAE cases that required a transition to best supportive care (BSC) (11.3% vs. 22.4%, p = 0.026). In conclusion, although irAE prevalence remains consistent regardless of age, the increased conversion to BSC post-irAE onset in older adults suggests diminished tolerability and the potential absence of favorable prognosis associated with irAEs in this population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Owing to advances in the multidisciplinary treatment of hepatocellular carcinoma (HCC), a conceptualization and definition for borderline resectable (BR) HCC, which carries a high risk of recurrence, is warranted. In this study, we aimed to define BR-HCC using a prognosis-oriented approach. STUDY DESIGN: The study included an original cohort of 221 patients and an independent validation cohort of 181 patients who had undergone primary hepatic resection for HCC. To define biological BR-HCC, we evaluated the risk factors for early recurrence beyond the Milan criteria within 1 year after hepatic resection using multivariable logistic regression models. Subsequently, we developed high-risk scores using the identified risk factors and defined BR-HCC. The utility of high-risk score was validated in the validation cohort. RESULTS: In the original cohort (hepatitis B virus:hepatitis C virus = 20%:29%), recurrence beyond the Milan criteria within 1 year was observed in 28 patients (13%), with a 5-year survival rate of 25%. Multivariable analysis identified risk factors for recurrence beyond the Milan criteria within 1 year, including serum alpha-fetoprotein levels of 12 ng/mL or more (p = 0.02), tumor diameters less than 5 cm (p = 0.02), tumor number 3 or more (p = 0.001), and macrovascular invasion (p = 0.04). BR-HCC was defined as a tumor with 2 or more identified risk factors, and 42 patients (19%) were diagnosed with BR-HCC, with a 5-year survival rate of 51%. In the validation cohort, 45 (25%) patients had BR-HCC, with a 5-year survival rate of 42%. CONCLUSIONS: The prognosis-oriented definition of BR-HCC enabled us to identify patients who are susceptible to early unresectable recurrence and have poor survival after hepatic resection for HCC. For patients with BR-HCC, preoperative systemic therapy may be a viable option to improve postresection outcomes. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. Patients and Methods This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio. Results The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% CI, 0.70-2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61-2.47). Consistent results were obtained for subgroups receiving palbociclib (n  = 177) and abemaciclib (n  = 63) without propensity score matching. Adverse event incidence and severity were similar in both groups. Conclusion The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted. [ABSTRACT FROM AUTHOR]

Background Dual antiplatelet therapy (DAPT) is necessary to prevent thromboembolic complications after stent-assisted coiling (SAC) or flow-diversion (FD) for cerebral aneurysms, but the optimal antiplatelet regimen remains unclear. Objective To determine the optimal DAPT duration in patients with SAC/FD. Methods This multicenter cohort study enrolled patients who received SAC/FD for cerebral aneurysms at seven Japanese institutions between January 2010 and December 2020. The primary outcome was the time from procedure to the occurrence of a composite of target vessel-related thromboembolic events, procedure-unrelated major bleeding events, or death. The cumulative event-free survival rates were analyzed using a Kaplan-Meier curve, and the differences in each outcome between the groups dichotomized by the duration of DAPT were analyzed using the log-rank test. Results Of 632 patients (median observational period, 646 days), primary outcome occurred in 63 patients (10.0%), most frequently within 30 days after the procedure. The cumulative event-free survival rates at 30 days, 1 year, and 2 years after the procedure were 93.3% (91.4 to 95.3%), 91.5% (89.3 to 93.7%), and 89.5% (87.0 to 92.0%), respectively. The cumulative event-free survival rates after switching to monotherapy were similar for the >91 and <90 days DAPT groups in the population limited to patients who were switched from DAPT to monotherapy without major clinical events. Conclusions Thromboembolic events rarely occurred beyond 30 days after SAC/FD. The duration of DAPT may be shortened if patients have a periprocedural period without events. Further prospective studies are warranted to determine the optimal duration of antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is known to have obesity as a risk factor. Body mass index cannot distinguish between lean mass and fat mass. We aimed to examine the association between predicted fat mass, predicted lean mass, predicted percent fat and risk of T2DM in Japanese adults. We also explored whether these three new parameters could predict T2DM better than other obesity markers. Methods: This present study is a secondary data analysis. The study enrolled 20,944 Japanese individuals who participated in the NAGALA medical assessment program between 2004 and 2015. 15,453 participants who are eligible and have complete information were included to our analysis. Through the use of Kaplan-Meier curve, restricted cubic spline and univariate and multivariate Cox regression analysis, the relationship between predicted fat mass, predicted lean mass, predicted percent fat and T2DM risk was examined. The area under the curve method was used to assess the differences between these markers of obesity. Results: A total of 373 cases of T2DM occurred over a median time of 5.4 years. In the male group, we found a U-shaped connection between predicted fat mass, predicted lean mass, and T2DM onset (p value, non-linearity < 0.05). A linear relationship was found between predicted percent fat and T2DM onset. The linear relationship was also found in the female group for predicted fat mass, and predicted percent fat. And for women, predicted lean mass was not an independent predictor. The area under the curve (AUC) for predicted fat mass, predicted lean mass, predicted percent fat in men was 0.673 (95%CI: 0.639 ~ 0.707), 0.598 (95%CI: 0.561 ~ 0.635), 0.715 (95%CI: 0.684 ~ 0.745), respectively. In males, WHtR was the strongest predictor (AUC 0.7151, 95%CI: 0.684 ~ 0.746), followed by predicted percent fat (AUC 0.7150, 95%CI: 0.684 ~ 0.745). In the females, WHtR was also the strongest predictor (AUC 0.758, 95%CI: 0.703 ~ 0.813), followed by body mass index (AUC 0.757, 95%CI: 0.704 ~ 0.811) and predicted percent fat (AUC 0.742, 95%CI: 0.687 ~ 0.798). Conclusion: Predicted fat mass, predicted lean mass, predicted percent fat were strongly connected with an increased risk for developing T2DM in Japanese, particularly in males. WHtR and predicted percent fat had a slightly better discrimination than other common obesity indicators in males. In the females, predicted fat mass and predicted percent fat were associated with T2DM risk, WHtR and body mass index had the slightly higher predictive power. [ABSTRACT FROM AUTHOR]

Introduction: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life‐threatening arrhythmias in patients with BrS. Methods: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life‐threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow‐up period was examined. Results: During the follow‐up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3−10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan–Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p =.032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. Conclusion: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life‐threatening arrhythmias. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinical course of classic Hodgkin lymphoma arising in immune deficiency/dysregulation (CHL-IDD) differs from that of CHL arising in immunocompetent cases and typically exhibits aggressive clinical behaviors. This study investigated the genetic aberration of 9p24.1 and protein expression of PD-L1 and also analyzed the clinicopathological association of these genetic lesions in CHL-IDD. Our findings showed that PD-L1 expression and 9p24.1 copy number alterations were observed in all patients analyzed in this study. Though it is recognized that an increase in 9p24.1 copy number alteration is associated with a more aggressive clinical course in immunocompetent CHL patients, we identified a subset of the 9p24.1 copy gain group, which had less 9p24.1 copy number alteration than the amplification group, exhibited more extensive extranodal lesions and had higher clinical stages in CHL-IDD cases. This finding speculates the presence of a genetically distinct subgroup within CHL-IDD patients, which may explain certain characteristic features. A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. [ABSTRACT FROM AUTHOR]

Background: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) emerge as better alternatives to right ventricular apical pacing (RVAP) in patients with bradycardia requiring permanent cardiac pacing. We aimed to compare the clinical outcomes of LBBAP, HBP, and RVAP in Japanese patients with bradycardia. Methods: A total of 424 patients who underwent successful pacemaker implantation (HBP, n = 53; LBBAP, n = 75; and RVAP, n = 296) were retrospectively enrolled in this study. The primary study endpoint was the cumulative incidence of heart failure hospitalization (HFH) during the follow-up. Results: The success rate for implantation was higher in the LBBAP group than in the HBP group (94.9% and 81.5%, respectively). Capture threshold increase >1V during the follow-up occurred in the HBP and RVAP groups (9.4% and 5.1%, respectively), while it did not in the LBBAP group. The cumulative incidence of HFH was significantly lower in the LBBAP group than the RVAP (adjusted hazard ratio, 0.12 [95% confidence interval: 0.02--0.86]; p = .034); it did not differ between the HBP and RVAP groups (adjusted hazard ratio, 0.48 [95% confidence interval: 0.17-1.34]; p = .16). Advanced age, mean percent right ventricular pacing (per 10% increase), left ventricular ejection fraction <50%, and RVAP were associated with HFH. Conclusions: Compared to RVAP and HBP, LBBAP appeared more feasible and effective in patients with bradycardia requiring permanent cardiac pacing. [ABSTRACT FROM AUTHOR]

Background: Psychological readiness to return to sports (RTS) has been associated with second anterior cruciate ligament (ACL) injury. However, this relationship is controversial because covariates such as anatomic and knee function characteristics have not been adequately considered. Purpose/Hypothesis: To investigate whether psychological readiness in the early postoperative period can predict the occurrence of a second ACL injury within 24 months after primary ACL reconstruction (ACLR) using propensity score analysis. It was hypothesized that patients with high ACL–RSI after injury (ACL-RSI) scores at 3 months postoperatively would have a second ACL injury within the projected postoperative period. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 169 patients who underwent primary ACLR using hamstring tendon autografts between November 2017 and July 2021 and also underwent knee functional assessments at 3 months postoperatively. The ACL-RSI scale was used to assess psychological readiness for RTS. A second ACL injury was defined if ipsilateral or contralateral ACL injury was confirmed by examination within 24 months postoperatively. Based on a previous study showing that 65 was the highest cutoff value for the ACL-RSI score for RTS, we classified patients into 2 groups: those with high ACL-RSI scores (≥65; group H) and those with low ACL-RSI scores (<65; group L). We generated 1-to-1 matched pairs using propensity score analysis and used log-rank testing to compare the rate of second ACL injury between the 2 groups. Results: More patients returned to any sports activities within 12 months in group H than in group L (90% vs 73%; P = .03). A second ACL injury within 24 months postoperatively was identified in 7% of patients (13/169). The rate of second ACL injury was significantly higher in group H than in group L (17.6% vs 3.4%; P = .001). In 43 matched pairs extracted using propensity scoring, the rate of second ACL injury was also higher in group H than in group L (18.6% vs 4.7%; P = .04). Conclusion: Patients with a higher ACL-RSI score at 3 months exhibited a significantly higher incidence of second ACL injury within 24 months after primary ACLR. [ABSTRACT FROM AUTHOR]

Although magnetic resonance imaging (MRI) data of patients with multiple myeloma (MM) are used to predict prognosis, few reports have applied artificial intelligence (AI) techniques for this purpose. We aimed to analyze whole-body diffusion-weighted MRI data using three-dimensional (3D) convolutional neural networks (CNNs) and Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable AI, to predict prognosis and explore the factors involved in prediction. We retrospectively analyzed the MRI data of a total of 142 patients with MM obtained from two medical centers. We defined the occurrence of progressive disease after MRI evaluation within 12 months as a poor prognosis and constructed a 3D CNN-based deep learning model to predict prognosis. Images from 111 cases were used as the training and internal validation data; images from 31 cases were used as the external validation data. Internal validation of the AI model with stratified 5-fold cross-validation resulted in a significant difference in progression-free survival (PFS) between good and poor prognostic cases (2-year PFS, 91.2% versus [vs.] 61.1%, P = 0.0002). The AI model clearly stratified good and poor prognostic cases in the external validation cohort (2-year PFS, 92.9% vs. 55.6%, P = 0.004), with an area under the receiver operating characteristic curve of 0.804. According to Grad-CAM, the MRI signals of the spleen and bones of the vertebrae and pelvis contributed to prognosis prediction. This study is the first to show that image analysis of whole-body MRI using a 3D CNN without any other clinical data is effective in predicting the prognosis of patients with MM. [ABSTRACT FROM AUTHOR]

Objectives Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. Methods We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). Results A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh −0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. Conclusion IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting. [ABSTRACT FROM AUTHOR]

Background: Temporal change in outcomes of heart failure patients receiving cardiac resynchronization therapy with a defibrillator (CRT‐D) is unknown. Methods: We assess outcomes and underlying heart diseases of patients receiving CRT‐D with analyzing database of the Japan cardiac device treatment registry (JCDTR) at the implantation year 2011–2015 and New JCDTR at the implantation year 2018–2021. Results: Proportion of nonischemic heart diseases was about 70% in both the groups (JCDTR: 69%; New JCDTR: 72%). Cardiac sarcoidosis increased with the rate of 5% in the JCDTR to 9% in the New JCDTR group. During an average follow‐up of 21 months, death from any cause occurred in 167 of 906 patients in the JCDTR group (18%) and 79 of 611 patients in the New JCDTR group (13%) (adjusted hazard ratio [aHR] in the New JCDTR group, 0.72; 95% confidence interval [CI]: 0.55–0.94; p =.017). The superiority was mainly driven by reduction in the risk of noncardiac death. With regard to appropriate and inappropriate implantable cardioverter–defibrillator (ICD) therapy, there was a significant reduction in the New JCDTR group versus the JCDTR group (aHR in the New JCDTR group, 0.76; 95% CI: 0.59–0.98; p =.032 for appropriate ICD therapy; aHR in the New JCDTR group, 0.24; 95% CI: 0.12–0.50; p <.0001 for inappropriate ICD therapy). Conclusions: All‐cause mortality was reduced in CRT‐D patients implanted during 2018–2021 compared to those during 2011–2015, with a significant reduction in noncardiac death. [ABSTRACT FROM AUTHOR]

Summary: Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application. [ABSTRACT FROM AUTHOR]

Summary: Background: Part E of the KEYNOTE-011 (NCT01840579) study assessed the safety and antitumor activity of pembrolizumab plus platinum-etoposide chemotherapy in Japanese patients with previously untreated extensive-stage small-cell lung cancer (ES-SCLC). Methods: Patients received 4 cycles of pembrolizumab (200 mg) every 3 weeks in combination with cisplatin (75 mg/m2) and etoposide (100 mg/m2; days 1, 2, 3) in cohort 1; with carboplatin (AUC 5 mg/mL/min) and etoposide (100 mg/m2; days 1, 2, 3) in cohort 2; or with cisplatin/etoposide and pegfilgrastim (3.6 mg; cycle 1, day 4) in cohort 3. Combination therapy was followed by pembrolizumab monotherapy (31 cycles). The primary endpoint was safety and tolerability (including dose-limiting toxicities; DLTs). Results: Fifteen patients were included in the study (cohort 1, n = 6; cohort 2, n = 6; cohort 3, n = 3). Median time from treatment allocation to data cutoff was 22.1 months (range, 4.1‒32.4 months). DLTs occurred in 3 patients in cohort 1 (one patient with grade 4 laryngeal stenosis and grade 3 febrile neutropenia; two patients with grade 3 febrile neutropenia); no patients in cohorts 2 or 3 experienced DLTs. Grade ≥ 3 treatment-related adverse events included leukopenia (67%) and neutropenia (87%). Among all patients, ORR was 67% (95% CI, 38%‒88%) and median DOR was 4.5 months (range, 2.8‒28.8 months). Median PFS was 4.2 months (95% CI, 3.0‒7.8 months) and median OS was 22.1 months (95% CI, 7.4‒25.9 months). Conclusion: Pembrolizumab in combination with platinum-etoposide therapy had manageable toxicity with no new safety signals and was associated with antitumor activity in Japanese patients with ES-SCLC. Trial Registration: ClinicalTrials.gov, NCT01840579. [ABSTRACT FROM AUTHOR]

Background: An increased relative eosinophil count (REC) has potential as a predictive biomarker for a beneficial clinical response and outcome to cancer immunotherapies. Therefore, the present study investigated the impact of an increased posttreatment REC on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods: We retrospectively reviewed all 151 patients diagnosed with NSCLC and treated with ICI monotherapy and blood test data between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Results: A total of 151 patients with a mean age of 69 years were included. REC after 4 weeks of initial ICI monotherapy was higher than pretreatment REC in 87 patients but not in 64. REC after 4 weeks of the ICI treatment with and without an increased REC were 4.4 and 1.8%, respectively (p < 0.001). Disease control rates (DCR) were significantly higher in patients with than in those without an increased REC (84% vs. 47%, p < 0.001). The median overall survival (OS) of lung cancer patients with or without an increased REC were 674 and 234 days, respectively. A Kaplan–Meier univariate analysis revealed a significant difference in OS between the two groups (p < 0.001). A Cox proportional regression analysis identified an increased REC as an independent predictor of OS (p = 0.003). Conclusion: ICI‐treated NSCLC patients with an increased REC after 4 weeks of treatment had a better DCR and prognosis than the other patients examined. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular targeted therapies are very effective as a treatment for postoperative recurrence of non-small cell lung cancer (NCSLC) with driver mutations. On the other hand, the efficacy of local therapies for oligo-recurrence has also been reported. To investigate the optimal treatment strategy for oligo-recurrence in NSCLC patients with driver mutations, we retrospectively evaluated 66 NSCLC patients with driver mutations who were treated with local or molecular targeted therapies as the initial treatment after recurrence. Patients treated with local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival and progression-free survival compared with those treated with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can be curative after recurrence and can delay the start of the administration of molecular targeted therapies. Background: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Methods: Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. Results: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701–2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459–1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Conclusions: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies. [ABSTRACT FROM AUTHOR]

Background: The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. Methods: We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low (< 2.5 mmol/L), middle (≥ 2.5 and < 4.0 mmol/L), and high (≥ 4.0 mmol/L). We compared 28 days mortality and ICU-free and ventilator-free days using multiple linear regression among groups. Results: Of the 422 RESTRIC trial participants, 396 were analyzed, with low (n = 131), middle (n = 113), and high (n = 152) lactate. Across all lactate groups, 28 days mortality was similar between strategies. However, in the low lactate group, the restrictive approach correlated with more ICU-free (β coefficient 3.16; 95% CI 0.45 to 5.86) and ventilator-free days (β coefficient 2.72; 95% CI 0.18 to 5.26) compared to the liberal strategy. These findings persisted even after excluding patients with severe traumatic brain injury. Conclusions: Our results suggest that restrictive transfusion strategy might not have a significant impact on 28-day survival rates, regardless of lactate levels. However, the liberal transfusion strategy may lead to shorter ICU- and ventilator-free days for patients with low initial blood lactate levels. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous implantable cardioverter defibrillators (S‐ICDs) are occasionally used in combination with other cardiac implantable electronic devices (CIEDs). However, whether the incidence of inappropriate shock increases in patients with S‐ICDs and concomitant CIEDs remains unclear. This study aimed to investigate the association between the concomitant use of CIEDs and the incidence of inappropriate shock in patients with current‐generation S‐ICDs. Methods: A total of 127 consecutive patients received an S‐ICD. Patients were assigned to two groups depending on concomitant use of CIEDs at the time of S‐ICD implantation: patients without other CIEDs (non‐combined group, 106 patients) and patients with other CIEDs (combined group, 21 patients). CIEDs included pacemakers, implantable cardioverter defibrillators, cardiac resynchronization therapy pacemakers, and cardiac resynchronization therapy defibrillators. The primary outcome was inappropriate shock, defined as a shock other than ventricular arrhythmia. Hazard ratios and 95% confidence intervals were calculated using a time‐varying Cox proportional hazards model which was adjusted for age because age differed between the groups and could be a confounder. Results: During a median follow‐up period of 2.2 years (interquartile range, 1.0–3.4 years), inappropriate shock events occurred in 17 (16%) and five (19%) patients of the non‐combined and combined groups, respectively. While the age‐adjusted hazard ratio for inappropriate shock was 24% higher in the combined than in the non‐combined group (hazard ratio = 1.24, 95% confidence interval, 0.39–3.97), this difference was insignificant (p =.71). Conclusion: The incidence of inappropriate shock did not differ between patients with and without concomitant use of CIEDs, suggesting that S‐ICDs could potentially be combined with other CIEDs without increasing the number of inappropriate shocks. Further studies are warranted to confirm the safety and feasibility of concomitant use of S‐ICDs and CIEDs. [ABSTRACT FROM AUTHOR]

Introduction: Cryoballoon ablation (CBA) of the left atrial (LA) roof in addition to a pulmonary vein isolation has been expected to improve the clinical outcomes post‐atrial fibrillation (AF) ablation. We demonstrated the characteristics and efficacy of CBA of the LA roof through our experience with a large volume of procedures. Methods: Among 1036 AF ablation procedures with CBA of the LA roof, 834 patients who underwent a de novo ablation were analyzed. Results: Complete LA roof line conduction block was obtained in 767 patients (92.0%) solely by CBA (Group A). Compared with the other patients (Group B), the mean nadir balloon temperature during CBA of the LA roof (−44.5 ± 5.6°C for Group A vs. −40.5 ± 7.5°C for Group B, p <.01) and number of cryoballoon applications during the LA roof ablation with a circular mapping catheter located in the left superior pulmonary vein (1.3 ± 0.8 for Group A vs. 1.6 ± 1.0 for Group B, p =.02) were significantly lower in Group A. A multivariate analysis revealed that those were predictors of a complete LA roof conduction block after only CBA. The 1‐year Kaplan–Meier atrial arrhythmia free rate estimates were 80.6% for Group A and 59.0% for Group B (p <.01). Conclusion: Complete LA roof line conduction block could be obtained with a cryoballoon without touch‐up ablation in most cases. The LA roof CBA with a circular mapping catheter located in the right superior pulmonary vein was preferable to obtaining complete LA roof conduction block, which was important with regard to the clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the efficacy and safety of robot-assisted radical cystectomy (RARC) in older patients with bladder cancer (BCa). Material and methods: We reviewed the clinical and pathological records of 110 patients with BCa who underwent RARC at Gifu University Hospital between February 2019 and January 2023. Older patients were defined as those with BCa aged ≥ 75 years. The enrolled patients were divided into two groups: those aged < 75 years (Group I) and those aged ≥ 75 years (Group II). Oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were the primary endpoints of the study; the secondary endpoints were the surgical and pathological outcomes. Results: A shorter console time, less blood loss, and reduced time to postoperative fluid and food intake in Group II may be attributed to the fact that more patients opted for ureterocutaneostomy in Group II than in Group I. In all patients, the three-year OS and RFS rates were 84.7% and 88.5%, respectively. There were no significant differences in OS or RFS between the two groups. (p =.403, p =.963, respectively). Conclusions: RARC appears to be a safe and useful treatment option for older patients with BCa. [ABSTRACT FROM AUTHOR]

PURPOSE Research studies have demonstrated that comprehensive geriatric assessment (CGA) improves outcomes in older adults with cancer treated with chemotherapy. We compared survival outcomes on older adults with advanced cancer before and after the initiation of a geriatric oncology service (GOS) in a single Japanese cancer center. METHODS This was a comparative study of two groups of consecutive patients 70 years and older with advanced cancer who were referred to medical oncology for first-line chemotherapy before (controls; n = 151, September 2015-August 2018) and after (GOS; n = 191, September 2018-March 2021) implementation of the GOS. When the treating physician requested a consultation from the GOS, a geriatrician and an oncologist performed CGA and provided recommendations for cancer treatment and geriatric interventions. Time to treatment failure (TTF) and overall survival (OS) were compared between the two groups. RESULTS The median age for all patients was 75 (range, 70-95) years, and 85% had GI cancers. In the GOS group, 82 patients received the CGA before a treatment decision and oncologic treatment plans were changed in 49 patients (60%). The overall implementation rate of the CGA-based geriatric interventions was 45%. Two hundred and eighty-two patients received chemotherapy (controls; n = 128 and GOS; n = 154), and 60 patients were treated with best supportive care only (controls; n = 23 and GOS; n = 37). Among patients receiving chemotherapy, TTF event rates for the GOS group compared with the control group were 5.7% versus 14% at 30 days (P = .02) and 13% versus 29% at 60 days (P = .001). The GOS group had longer OS than the control group with a hazard ratio of 0.64 (95% CI, 0.44 to 0.93; P = .02). CONCLUSION In this study, older adults with advanced cancer managed after the implementation of a GOS had improved survival outcomes compared with a historical control of patients. [ABSTRACT FROM AUTHOR]

Background: The net benefit is an effect measure for any type of endpoint, including the time-to-event outcome, and can provide intuitive and clinically meaningful interpretation. It is defined as the probability of a randomly selected subject from the experimental arm surviving by at least a clinically relevant time longer than a randomly selected subject from the control arm. In oncology clinical trials, an intercurrent event such as treatment switching is common, which potentially causes informative censoring; nevertheless, conventional methods for the net benefit are not able to deal with it. In this study, we proposed a new estimator using the inverse probability of censoring weighting (IPCW) method and illustrated an oncology clinical trial with treatment switching (the SHIVA study) to apply the proposed method under the estimand framework. Methods: The net benefit can be estimated using the survival functions of each treatment group. The proposed estimator was based on the survival functions estimated by the inverse probability of the censoring weighting method that can handle covariate-dependent censoring. The simulation study was undertaken to evaluate the operating characteristics of the proposed estimator under several scenarios; we varied the shapes of the survival curves, treatment effect, covariates effect on censoring, proportion of the censoring, threshold of the net benefit, and sample size. We also applied conventional methods (the scoring rules by Péron or Gehan) and the proposed method to the SHIVA study. Results: Our simulation study showed that the proposed estimator provided less biased results under the covariate-dependent censoring than existing estimators. When applying the proposed method to the SHIVA study, we were able to estimate the net benefit by incorporating the information of the covariates with different estimand strategies to address the intercurrent event of the treatment switching. However, the estimates of the proposed method and those of the aforementioned conventional methods were similar under the hypothetical strategy. Conclusions: We proposed a new estimator of the net benefit that can include covariates to account for the possibly informative censoring. We also provided an illustrative analysis of the proposed method for the oncology clinical trial with treatment switching using the estimand framework. Our proposed new estimator is suitable for handling the intercurrent events that can potentially cause covariate-dependent censoring. [ABSTRACT FROM AUTHOR]

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the annual patient report for 2020 and the Annual Treatment Report for 2015, on the outcomes of patients who started treatment in 2015. Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2020 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2015 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests. Results: Treatment was initiated in 2020 for 7689 patients with cervical cancer, 13 113 with endometrial cancer, 8004 with ovarian, tubal, and peritoneal cancer, 2152 with ovarian borderline tumors, and with the others (260 vulvar cancer, 157 vaginal cancer, 464 uterine sarcoma, 50 uterine adenosarcoma, 136 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5‐year survival rates of the patients with cervical cancer were 92.3%, 76.2%, 56.5%, and 32.2% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 93.9%, 87.6%, 71.4%, and 29.3% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 91.7%, 80.6%, 50.8%, and 39.7% for Stages I, II, III, and IV, respectively. Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan. [ABSTRACT FROM AUTHOR]

Objective: We previously reported that dickkopf WNT signaling inhibitor 3 (DKK3) would modulate malignant potential of oral squamous cell carcinoma (OSCC) via activating Akt. Recently, cytoskeleton associated protein 4 (CKAP4) functions as receptor of DKK3, which activates Akt in esophageal squamous cell carcinoma, but its expression and function in OSCC were unclear. Methods: We studied DKK3 and CKAP4 protein expression in OSCC tissue and investigated the correlation between protein expression and clinical data. We also investigated whether antibodies (Ab) for DKK3 or CKAP4 could suppress malignant potential of the cancer cells. Results: DKK3/CKAP4 protein expression was observed in majority of OSCC cases and was associated with significantly higher T‐stage and TNM stage. Multivariate analysis revealed that DKK3 and CKAP4 were independent prognostic biomarkers for overall survival (OS) and disease‐free survival (DFS), respectively. Survival analyses revealed that DKK3‐positive cases and CKAP4‐positive cases showed significantly shorter OS and DFS, respectively, and that DKK3/CKAP4 double‐negative cases showed significantly favorable prognosis. Both anti‐DKK3Ab and anti‐CKAP4Ab could suppress cancer cell proliferation, migration, and invasion. Conclusion: DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal postoperative surveillance protocol after esophagectomy for patients with esophageal cancer has still not been established. We investigated the risk factors for recurrence of esophageal cancer to devise an appropriate surveillance protocol. We focused on the appearance and worsening of symptoms to determine if additional imaging examinations should be performed. STUDY DESIGN: We enrolled 416 patients with esophageal and esophagogastric junctional cancer who had undergone thoracoscopic esophagectomy at Tokai University Hospital. Outpatient visits for the patients are usually scheduled at least 4 times per year with CT imaging and blood biochemical examination. We evaluated the time to recurrence after esophagectomy, especially the correlation of this parameter with the appearance and worsening of symptoms during the postoperative outpatient follow-up. RESULTS: Of the 416 patients, recurrence occurred in 127 patients (30.5%). The median time to recurrence was 6 months after esophagectomy; recurrence occurred within 24 months in 112 patients (88%), and 51 of these patients (40%) developed some new symptom(s) (symptomatic group) before the diagnosis of recurrence. The number of patients who developed recurrence within 6 months was significantly higher in the symptomatic group compared with that in the asymptomatic group (66.7% vs 46.0%, p = 0.02). The overall survival in the symptomatic group was significantly shorter than that in the asymptomatic group (p < 0.001). CONCLUSIONS: We advocate an effective surveillance protocol depending on the appearance and worsening of symptoms to diagnose recurrence of esophageal cancer; we recommend routine imaging examinations every 6 months and clinical outpatient follow-up at even shorter intervals for the first 24 months after esophagectomy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effect of lymphadenectomy around the recurrent laryngeal nerve (RLN) in open esophagectomy has been demonstrated with the efficacy index (EI). However, it remains unclear whether this effect exists for minimally invasive esophagectomy (MIE) in the prone position. The purpose of this study was to clarify whether the upper mediastinal lymphadenectomy contributed to improved prognosis in patients with esophageal squamous cell carcinoma. STUDY DESIGN: This study included 339 patients with esophageal squamous cell carcinoma treated with MIE in the prone position at Kobe University or Hyogo Cancer Center, Japan, from 2010 to 2015. EIs for each station, correlations between metastatic lymph nodes around the left RLN and RLN palsy, and survival of patients with and without upper mediastinal lymphadenectomy were investigated. RESULTS: Among 297 patients treated with upper mediastinal lymphadenectomy, Clavien-Dindo grade = II left RLN palsy occurred in 59 patients (20%). Overall, EIs for the right RLN (7.4) and left RLN (6.6) were higher than EIs for other stations. For patients with upper-third or middle-third tumors, the trend was stronger. Left RLN palsy was more likely in patients with metastatic lymph nodes around the left RLN than in those without (44% vs 15%, p < 0.0001). After propensity score-matching, 42 patients were included in each group with and without upper mediastinal lymphadenectomy. In survival analyses, the 5-year overall survival rates were 55% vs 35% and cause-specific survival rates were 61% vs 43% for the patients with and without upper mediastinal lymphadenectomy respectively. Significant differences were confirmed in survival curves (overall survival: p = 0.03; cause-specific survival: p = 0.04, respectively). CONCLUSIONS: Upper mediastinal lymphadenectomy contributes to improved prognosis with high EIs in MIE in the prone position. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although patient-risk stratification is important for selecting individualized treatment for pancreatic ductal adenocarcinoma (PDAC), predicting the oncologic outcomes after surgery remains a challenge. In this study, we identified a nectin family gene panel (NFGP) that can accurately stratify oncologic outcomes in patients with PDAC. STUDY DESIGN: Comprehensive analysis of the expression of 9 nectin family genes identified the NFGP, which was assessed for predictive performance in 2 independent public cohorts (The Cancer Genome Atlas [TCGA] n = 176; International Cancer Genome Consortium [ICGC] n = 89). It was subsequently trained and validated for the in-house training cohort without neo-adjuvant therapy (NAT, n = 213) and the validation cohort with NAT (n = 307). RESULTS: Using the Cox regression model, NFGP derived from 9 nectin family genes accurately stratified overall survival (OS) in TCGA (p = 0.038) and ICGC (p = 0.005). We subsequently optimized NFGP, which robustly discriminated postoperative prognosis, OS (p = 0.014) and relapse-free survival ([RFS] p = 0.006) in the training cohort. The NFGP was successfully validated in an independent validation cohort (OS: p < 0.001; RFS: p = 0.004). Multivariate analysis demonstrated the NFGP was an independent prognostic factor for OS and RFS in the training (p = 0.028 and 0.008, respectively) and validation (p < 0.001 and 0.013, respectively) cohorts. The subcohort analyses showed that the predictive performance of NFGP is applicable to the patients' subcohort according to resectability or adjuvant therapy status. Additionally, a combination model of NFGP score and CA19-9 level emerged with improved accuracy for predicting prognosis. CONCLUSIONS: This study established the predictive significance of NFGP for oncologic outcomes after surgery in PDAC. Our data demonstrate its clinical impact as a potent biomarker for optimal patient selection for individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Although patients with head and neck squamous cell cancer (HNSCC) often show malnutrition, its effects on immune checkpoint inhibitor (ICI) treatment outcomes in these patients are unclear. To investigate the prognostic influence of nutritional indices in patients with HNSCC treated with ICIs and determine the optimal indices. This retrospective study included 106 patients with HNSCC treated with ICIs between 2017 and 2022. The prognostic influences of body mass index (BMI), geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI) on overall survival (OS) and progression-free survival (PFS) were analysed using the Kaplan–Meier method and Cox-regression models. The 1-year PFS rates in the groups with high and low BMI, GNRI, and PNI were, respectively, 24.2% and 28.4% (p =.731), 29.7% and 14.4% (p =.024), and 30.3% and 13.9% (p =.015). PNI was an independent prognostic factor for both PFS (hazard ratio (HR) = 1.89; 95% confidence interval (CI), 1.08–3.29) and OS (HR = 3.26; 95% CI, 1.66–6.40). PNI can predict ICI outcomes and should be assessed when ICI treatment is considered. [ABSTRACT FROM AUTHOR]

Left atrial (LA) enlargement frequently occurs in atrial fibrillation (AF) patients, and this enlargement is associated with the development of heart failure, thromboembolism, or atrial functional mitral regurgitation (AFMR). AF patients can develop LA enlargement over time, but its progression depends on the individual. So far, the factors that cause progressive LA enlargement in AF patients have thus not been elucidated, so that the aim of this study was to identify the factors associated with the progression of LA enlargement in AF patients. We studied 100 patients with persistent or permanent AF (aged: 67 ± 2 years, 40 females). Echocardiography was performed at baseline and 12 (5–30) months after follow‐up. LA size was evaluated as the LA volume index which was calculated with the biplane modified Simpson's method from apical four‐and two‐chamber views, and then normalized to the body surface area (LAVI). The deterioration of AFMR after follow‐up was defined as a deterioration in severity of mitral regurgitation (MR) by a grade of 1 or more. Multivariate regression analysis demonstrated that hypertension (p =.03) was an independently associated parameter of progressive LA enlargement, as was baseline LAVI. In addition, the Kaplan–Meier curve indicated that patients with hypertension tended to show greater deterioration of AFMR after follow‐up than those without hypertension (log‐rank p =.08). Hypertension proved to be strongly associated with progression of LA enlargement over time in patients with AF. Our findings provide new insights for better management of patients with AF to prevent the development of AFMR. [ABSTRACT FROM AUTHOR]

Objective: This study was identified seeking treatment for hypertension and diabetes among male shift workers. Method: This retrospective cohort study included nine large companies in Japan. Data were collected from health checkup, health insurance records, and self-administered questionnaires in 2017 and 2020. Data were analyzed using Kaplan-Meier curves and Cox regression. Result: Person-days shift workers and day workers seeking treatment for hypertension were 41,604 and 327,301, respectively and, for diabetes, were 7326 and 60,735, respectively. The log ranks were statistically significant. Shift workers were 46% and 56% less likely to seek treatment for hypertension and diabetes, respectively, than day workers were after adjustment for age, marital status, education level, and intention to modify lifestyle (model 2) ( P < 0.01). Conclusions: Male shift workers are less likely to seek treatment for hypertension and diabetes compared with day workers. [ABSTRACT FROM AUTHOR]

Introduction: There are approximately 13 million patients with osteoporosis in Japan; however, only 20% of them receive treatment. This study compared the 4‐year continuation rates of osteoporosis drugs at different dosing intervals across throughout Japan. Materials and methods: Receipt data were analyzed to determine the continuation of osteoporosis medication in patients who began treatment at 210 hospitals throughout Japan between October 2016 and September 2017. Continuation rates were compared using Kaplan–Meier curves and log‐rank tests. Results: The 4‐year continuation rates of daily, weekly, monthly, semi‐annual, and yearly medications nationwide were 8.6%, 16.5%, 13.5%, 31.0%, and 26.0%, respectively. The 4‐year continuation rates for semi‐annual and yearly drugs were significantly higher than daily, weekly, monthly drugs. Conclusion: Throughout Japan, the 4‐year treatment continuation rates of daily, weekly, monthly, semi‐annual, and yearly osteoporosis drugs all decreased over time. However, the continuation rates of semi‐annual and yearly drugs in the fourth year were significantly higher than those for the other dosing regimens. Therefore, injectable drugs with dosing intervals ≥6 months may improve continuation rates of osteoporosis drugs. Geriatr Gerontol Int 2023; 23: 665–670. In various regions of Japan, the 4‐year treatment continuation rates of daily, weekly, monthly, semi‐annual, and yearly drugs of osteoporosis drugs with different dosing intervals decreased over time. However, the continuation rates of semi‐annual and yearly drugs in the fourth year were significantly higher than those of the other drugs. [ABSTRACT FROM AUTHOR]