Median Observation Period Research Articles

The Impact of Early Indication of Living Donor Liver Transplantation on the Outcomes of Patients With Propionic Acidemia: A Single-Center Experience.

Liver transplantation has been indicated for propionic acidemia (PA) patients with frequent metabolic decompensation and performed as an enzyme replacement therapy. We retrospectively evaluated the outcomes of patients with PA and analyze the appropriate timing of living donor liver transplantation (LDLT). We reviewed 12 children with PA who underwent LDLT, who were divided into early (period from the first episode of metabolic decompensation to LDLT < 1 year; n = 6) and late (> 1 year; n = 6) indication groups depending on the timing of LDLT. The patient and graft survival rates were 100% in 12 children with PA, and the median observation period was 61 months (5-193 months). None of the patients experienced any episodes of metabolic decompensation after LDLT. The timing of LDLT did not influence the incidence of surgical complications. Two patients in the late indication group had episodes of cardiac arrest and long QT syndrome before LDLT, and one patient showed prolongation of QT interval after LDLT. Two of the six patients in the late indication group had findings of metabolic stroke of the brain on MRI before LDLT. Although LDLT improved the findings of metabolic stroke, a decrease in development quotient score was shown in the post-LDLT course. LDLT may be an effective therapeutic option for improving metabolic control. Early LDLT might be help prevent cardiomyopathy and neurological impairment.

Brief Report: Switching to Long-Acting CAB/RPV: Data From an Italian Monocentric Cohort

Background: Cabotegravir (CAB)/rilpivirine (RPV) is the first long-acting injectable (LAI) antiretroviral therapy approved for virologically suppressed adults with HIV-1. Setting: Italian single centre cohort. Methods: We conducted a retrospective observational study to assess the durability, adherence to the prescribed injection schedule, and reasons for discontinuation of CAB/RPV LAI administered every 8 weeks (Q8W). Results: One hundred thirty-eight patients were included with a median observation period of 43 weeks [interquartile range (IQR) 34–47 weeks]. Of these, 32 (23.2%) were female, and the median age was 51 years (IQR 40–58 years). Twelve patients (8.7%) discontinued CAB/RPV LAI treatment with a median time to discontinuation of 21 weeks (IQR 12–35 weeks), and 92.8% of the injections occurred within the CAB/RPV LAI schedule. The most common reason for discontinuation was injection-related pain (5/12). No confirmed virological failure occurred during the period of observation with 3 individuals who experienced virological blips. Conclusions: Our findings showed that CAB/RPV LAI Q8W is tolerated well in clinical practice, with high adherence to the injection schedule and few discontinuations mainly related to injection site–related pain.

Long-term outcomes of active surveillance for low-risk papillary thyroid carcinoma: Progression patterns and tumor calcification.

Active surveillance (AS) for low-risk papillary thyroid carcinoma (PTC) is acknowledged as a valid management strategy. While older age is identified as a favorable factor for progression, long-term evidence is scarce and lifelong monitoring has been deemed essential. This study investigated progression patterns and tumor calcification under long-term AS and explored the possibility of ending follow-up. A total of 650 patients with low-risk PTC who chose AS were enrolled. Progression was defined as either tumor enlargement (≥3mm from initiation) or development of clinically apparent lymph node metastasis. The median observation period was 8years; 45.2% were under surveillance for ≥10years. Overall, 80 patients (12.3%) exhibited progression. Median age and observation period at the time of progression were 55 and 4years, respectively. Only 2 patients showed progression after 15years of follow-up and 5 patients showed progression after reaching 80years old. Among 71 patients experiencing tumor enlargement, surgery was performed immediately in 32 patients. The remaining 39 patients continued surveillance, but only 5 demonstrated ongoing enlargement thereafter. Of 40 surgeries due to progression, 36 were conducted within the first 10years. The degree of calcification correlated with age and observation periods. No progression occurred after the development of rim calcification. Progression during AS was extremely rare in older patients with long-term surveillance and in tumors with rim calcification. It may be feasible to consider ending scheduled surveillance visits for these patients. Instances of progression halting after enlargement are not uncommon.

Clinical characteristics of monoclonal immunoglobulin-associated renal disease: a retrospective cohort study.

Clinical epidemiological data on monoclonal gammopathy of renal significance (MGRS) are lacking. In this retrospective observational study, MGRS was compared with B-cell or plasma cell malignancies (BCM/PCM) with renal involvement to clarify differences in their clinical features. Among the 1408 renal biopsies performed at our hospital, 25 MGRS and 18 BCM/PCM patients were identified. We investigated baseline characteristics and hematologic parameters of MGRS in reference to BCM/PCM using multivariable analysis. Cox proportional hazards analysis was performed for end-stage kidney disease (ESKD) and all-cause mortality. Comparing the MGRS with the BCM/PCM, meandifferences in creatinine level, estimated glomerular filtration rate, and clonal bone marrow plasma cell percentage were -2.76mg/dL, 27.72mL/min/1.73m2, and -18.86%, respectively (all P < 0.001). MGRS group had a predominance of glomerular lesions such as immunoglobulin-associated amyloidosis, cryoglobulinemic GN, and MIDD, and a lower risk of acute kidney injury/acute renal disease compared to BCM/PCM. During a median observation period of 23.7months, clone-directed therapy was performed in 32.0% of patients in the MGRS group, compared to 83.3% of patients in the BCM/PCM group. Compared with BCM/PCM, MGRS had a hazard ratio of 0.66 (95% confidence interval (CI) 0.23-1.92, P = 0.45) for ESKD and 0.33 (95% CI 0.11-1.03, P = 0.06) for death in multivariate logistic regression analysis. The clinical characteristics of MGRS and BCM/PCM with monoclonal immunoglobulin-associated renal disease are disparate. Understanding these differences is crucial for developing tailored clinical approaches and therapeutic strategies to improve patient outcome.

Efficacy of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma in immunotherapy era clinical practice.

Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases. Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74years; male patients, 152; Child-Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C,59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated. The median observation period was 7.2months (interquartile range, 3.2-10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p=0.028) (median PFS: without vs. with=5.6 vs. 2.7months, p<0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p=0.523 and p=0.038, respectively). History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

Interim analysis of robot-assisted radical hysterectomy in Japan: a multicenter, prospective interventional single-arm clinical trial

ObjectiveTo investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.Materials and methodsThis study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.ResultsOverall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.ConclusionRARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.Trial registrationUMIN-CTR: UMIN000022278, registered on 11th May 2016.

Total baseline tumor size predicts survival among patients with advanced small-cell lung cancer receiving chemotherapy plus programmed death-ligand 1 inhibitor as first-line therapy: a multicenter retrospective observational study.

Total baseline tumor size (BTS) is a prognostic factor for programmed death 1 and programmed death-ligand 1 (PD-L1) inhibitor treatments. However, the prognostic value of total BTS for patients with small-cell lung cancer (SCLC) who receive chemotherapy plus PD-L1 inhibitor remains unknown. Thus, in this study, we aimed to determine whether total BTS is associated with prognosis in patients with SCLC who receive chemotherapy plus PD-L1 inhibitor as first-line therapy. This study included patients with extensive-stage SCLC or post-chemoradiotherapy recurrence of limited-stage SCLC who received chemotherapy plus PD-L1 inhibitor as first-line therapy from August 2019 to December 2022. The two lesions with the largest diameter among the measurable lesions in each organ were selected from up to five organs (maximum of 10 lesions), and the sum of all diameters was defined as total BTS. The patients were divided into two groups, large or small, with total BTS using X-tile software. Median survival was analyzed using the Kaplan-Meier method, and the groups were compared using the log-rank test. Univariate and multivariate analyses examined the association between total BTS and prognosis. Fifty patients were included; 14% had large total BTS (>183.2mm) and 86% had small total BTS (≤183.2 mm). The median observation period was 10.5 months. The large total BTS group showed significantly worse overall survival than the small total BTS group (median: 26.8 months vs. 5.7 months, P = 0.0003). The multivariate analysis indicated that large total BTS was an independent negative predictor of overall survival (hazard ratio: 7.14, 95% confidence interval: 1.89-26.96). Total BTS is a potentially useful prognostic factor for patients with advanced SCLC who receive chemotherapy plus PD-L1 inhibitor as first-line therapy.

Risk Assessment for Cardiovascular Events using Achilles Tendon Thickness and Softness and Intima-Media Thickness in Familial Hypercholesterolemia.

This was a retrospective cohort study that aimed to determine cutoff values for major adverse cardiovascular events (MACEs) in patients with heterozygous FH (HeFH) for Achilles tendon (AT) thickness (ATT) measured by ultrasonography (US-ATT) and radiography (Xp-ATT), AT softness, and intima-media thickness of carotid artery (C-IMT), and to examine the effectiveness of these values as well as AT calcification as indexes in assessing risk for MACEs. The subjects were 391 clinically diagnosed HeFH patients. Kaplan-Meier curves were drawn based on the threshold values for the individual indexes calculated from ROC curves, and multivariate analysis was used to examine whether they were predictors of the development of MACEs. The median observation period was 1,239 days (700-1,827 days). Twenty-one subjects (5%) had MACEs during the observation period. The cutoff values for MACEs for US-ATT were 9.9 mm in males and 7.1 mm in females, and those for C-IMT were 1.6 mm in males and 1.5 mm in females. Subjects were classified into two groups according to whether they were above or below the cutoff values and presence of calcification, and we compared MACE rates between them. MACE rates were significantly increased in groups with AT thickening determined by ultrasonography (P＜0.001), AT softening (P＜0.001), presence of calcification in AT (P=0.016) and greater C-IMT (P＜0.001). However, classification according to Xp-ATT revealed no significant difference in MACE rate (P=0.112). These thresholds and examination for AT calcification will help in risk assessment for patients in Japanese FH practice and encourage stricter and more comprehensive management for patients who exceed the thresholds.

Baseline inflammatory status affects the prognostic impact of statins in patients with peripheral arterial disease

BackgroundStatins bring favourable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD. MethodsThis study was a sub-analysis of a multicenter prospective cohort of 2321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1974 patients (1021 statin users and 953 non-users) were classified into four groups depending on CRP levels: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1–0.3 mg/dL), intermediate-high CRP (0.3–1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. ResultsDuring the median observation period of 316 days, the primary composite endpoint occurred in 112 (11.0 %) statin users and 178 (18.7 %) non-users (log-rank test, p < 0.001). However, statin therapy was associated with significantly lower event rates only in the intermediate-high- and high-CRP categories (p = 0.02 and p = 0.008, respectively). Multivariable Cox regression analysis revealed that statin use was independently associated with the primary endpoint only in the high-CRP category (adjusted hazard ratio: 0.64 [95 % confidence interval: 0.41–0.98]). ConclusionStatins may exert favourable prognostic effects in patients with PAD and highly elevated CRP levels.

Recovery from rituximab-associated persistent hypogammaglobulinaemia in children with nephrotic syndrome.

There are limited data on the long-term outcomes and risk factors for non-recovery after development of rituximab (RTX)-associated persistent hypogammaglobulinaemia among children with idiopathic nephrotic syndrome (NS). A nationwide Japanese survey was conducted to determine the prognosis of patients with childhood-onset idiopathic NS who developed persistent hypogammaglobulinaemia after RTX administration. Specifically, predictors of IgG level recovery and risk factors for serious infection were examined. The cohort comprised 118 patients (66.1% boys; median age at initial RTX administration, 7.5 years). Among the 121 patients diagnosed with persistent hypogammaglobulinaemia, only 31 (26.3%) recovered within a median observation period of 2.8 years; approximately 70% of patients continued to exhibit persistent hypogammaglobulinaemia. Among the patients who recovered from hypogammaglobulinaemia, the median time to recovery was 14.1 months. Patients with a history of steroid-resistant NS were less likely to recover from persistent hypogammaglobulinaemia (hazard ratio, 0.28; 95% CI, 0.09-0.87). In addition, of the 118 eligible patients, 18 (15.3%) developed serious infections requiring hospitalization, and the main risk factor for infection during hypogammaglobulinaemia was agranulocytosis (a well-known adverse effect of RTX in children). A significant portion of patients with RTX-associated persistent hypogammaglobulinaemia did not exhibit recovery even after 1 year. Moreover, the data indicate that patients with a history of steroid-resistant NS have a significantly lower probability of recovering from this condition. Agranulocytosis under hypogammaglobulinaemia was significantly associated with an elevated risk of serious infections.

Serum zinc levels as predictors of covert hepatic encephalopathy in patients with liver cirrhosis.

Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions. This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated. CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211days, OHE developed in 18 patients (14.3%). The administration of more than 20mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207). Cirrhotic patients with serum zinc levels below 60µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20mg or more of furosemide.

A novel puzzle ring replacement technique of a lumen-apposing metal stent with a double-pigtail plastic stent to prevent walled-off necrosis recurrence (with video).

Replacing a lumen-apposing metal stent (LAMS) with a double-pigtail plastic stent (DPS) after treatment for walled-off necrosis contributes to the prevention of recurrence. However, the success rate is not very high. To overcome this issue, we devised a novel stent-replacement technique. In the final treatment procedure, a 7-F DPS was placed in the lumen of the LAMS. Subsequently, the walled-off necrosisshrank, and granulation formed over the pigtail portion, which fixed the DPS. The LAMS alone was removed with grasping forceps, leaving the DPS in the lumen of the LAMS (i.e., a puzzle-ring technique; direct or rotary removal technique). Between August 2021 and August 2023, 18 patients were evaluated for recurrence prevention using this novel technique (median duration of LAMS placement, 37 days). In 17 patients (94.4%), the LAMS was successfully replaced with a 7-F DPS (direct technique 14, rotary technique 3; median removal procedure time, 3 min). No recurrence was observed during the median observation period of 385 days. Before using this technique (April 2012 to August 2022), the technical success rate of replacement of LAMS with 7-F DPS was significantly lower (61.8% [42/68, p = 0.02]). Recurrence of pancreatic fluid collection occurred in 15.3% (4/26) of the patients who could not undergo replacement with a 7-F DPS. The novel puzzle ring technique, which improves the success rate of LAMS for DPS replacement, may be useful in reducing recurrence after walled-off necrosistreatment.

A retrospective study of prognostic factors and prostate-specific antigen dynamics in Japanese patients with metastatic hormone-sensitive prostate cancer who received combined androgen blockade therapy with bicalutamide.

This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. The median observation period was 46.4months, and the median age of patients at diagnosis was 71years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2ng/mL in a median time of 4.7months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9months. These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

Clinical significance of intraductal papillary mucinous neoplasms incidentally detected in patients with extrapancreatic gastrointestinal malignancies with a focus on pancreatic cancer development

BackgroundIntraductal papillary mucinous neoplasm is occasionally detected in the preoperative images of patients with gastrointestinal malignancies. Despite numerous studies examining the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasm, limited data exist on the prevalence of intraductal papillary mucinous neoplasm in those with gastrointestinal malignancies. Given that intraductal papillary mucinous neoplasm is a known risk factor for pancreatic cancer, this study aimed to evaluate the prevalence of intraductal papillary mucinous neoplasm in patients who underwent radical surgery for extrapancreatic gastrointestinal malignancies and its impact on pancreatic cancer development. MethodsWe retrospectively reviewed the preoperative computed tomography images of patients who underwent radical surgery for gastrointestinal malignancies between January 2017 and December 2021 for the presence of intraductal papillary mucinous neoplasm. Patients were divided into intraductal papillary mucinous neoplasm and non–intraductal papillary mucinous neoplasm groups, and clinicopathologic features and long-term outcomes, including pancreatic cancer development, were compared between groups. ResultsA total of 814 patients who underwent radical surgery for extrapancreatic gastrointestinal malignancies were included. Among them, 81 patients (10.0%) had intraductal papillary mucinous neoplasm. The median observation period was 39 (0–79) months. Notably, pancreatic cancer developed in 5 patients with intraductal papillary mucinous neoplasm and 1 without. The 5-year cumulative incidences of pancreatic cancer were 8.8% and 0.2% in the intraductal papillary mucinous neoplasm and non–intraductal papillary mucinous neoplasm groups, respectively (P < .001). ConclusionIntraductal papillary mucinous neoplasm is frequently detected in the preoperative images of patients with gastrointestinal malignancies and is associated with a significantly higher risk of developing pancreatic cancer. Consequently, long-term surveillance for pancreatic cancer is crucial in patients with intraductal papillary mucinous neoplasm, particularly those with extrapancreatic gastrointestinal malignancies.

Survival and Endoscopic/Clinical Features of Patients with Colorectal Cancer Resected by Cold Snare Polypectomy: The Importance of Chronic Kidney Disease.

Colorectal polyps resected by cold snare polypectomy (CSP) are rarely diagnosed as colorectal cancer (CRC). We aimed to investigate the prevalence, clinical features, and prognosis of patients with CRC resected by CSP. Patients with colorectal polyps treated with CSP between 2018 and 2022 were enrolled and regularly followed up (median observation period: 30.6 months). Logistic regression analysis and decision tree analysis were employed to investigate the clinical features of the patients. A total of 5,064 colorectal polyps from 2,530 patients were resected by CSP. Of these, 0.24% were diagnosed as CRC; however, no patients died due to CRC. eGFR was an independent risk factor for the presence of CRC (unit 10, OR 0.716, 95%CI 0.525-0.973, P=0.0323) and its optimal cut-off value was 59.9 mL/min/1.73 m2. The decision-tree analysis revealed that 2.03% of patients with creatinine ≥ 1.0 mg/dL had CRC. CRC was diagnosed in 0.24% of the polyps; however, no patients died due to CRC. eGFR <60 mL/min/1.73 m2 and creatinine >1.0 mg/dL were associated with CRC. Thus, colorectal polyps should be carefully examined in patients with chronic kidney disease.

Prevalence of adrenal rest tumors and course of gonadal dysfunction in a clinical sample of men with congenital adrenal hyperplasia - a longitudinal analysis over 10 years

Abstract Background Subfertility is prevalent in men with classic 21-hydroxylase deficiency (21OHD). We sought to characterize the long-term evolution of their gonadal function. Methods Retrospective longitudinal single-center study in 27 men (11 with testicular adrenal rest tissue (TART)); median observation period 12 years; testosterone (T), 11-oxygenated androgens, gonadotropins and inhibin B measurement at each timepoint. Results T concentrations were below the normal range (n.s.) in 43.2% (no TART) and 54.6% (TART) per patient. After accounting for BMI, sex hormone-binding globulin, and age, men with TART exhibited higher T (14.0 ± 0.80 nmol/l) than those without (11.9 ± 0.71 nmol/l). During the observation period, T levels rose in both groups but more in men with TART (from 10.1 ± 1.1 to 17.3 ± 1.9 nmol/l vs. 10.3 ± 1.0 to 12.8± 1.9 nmol/l); this was accompanied by rising luteinizing hormone and diminishing hydrocortisone equivalent dosages (TART: from 38.1± 3.2 to 35.1 ± 1.8 mg/d; vs. no TART: 28.8 ± 2.7 to 28.1 ± 1.6 mg/d) without correlation with any markers of adrenal androgen control. Inhibin B declined in men with large TART over time while TART status remained stable. Conclusion T levels below the normal range are frequent in men with 21OHD, regardless of TART, but change little over time. Besides adrenal androgen control gonadal axis suppression from supraphysiological glucocorticoid dosages needs to be considered. While our results do not endorse regular screening for alterations in TART status among adults, Sertoli cell function should be monitored in men with large TART.

Clinical utility of a comprehensive genomic profiling test for patient with advanced biliary tract cancer.

Biliary tract cancer (BTC) comprises a heterogeneous group of malignancies with poor prognosis because of the limited treatment options. With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests have been widely introduced into daily clinical practice. We performed a retrospective, multicenter, observation cohort study. The genomic and clinical data of 85 BTC patients, who underwent CGP testing from August 2021 to September 2023, were analyzed. There were 62 (73%) cases in which treatment recommendations were raised during expert meetings, including 34 intrahepatic cholangiocarcinoma (ICC), 20 extrahepatic cholangiocarcinoma (ECC) and 8 gall bladder carcinoma (GBC). The drug accessibility rate of the BTC patients was 15.3% (13 cases): ten ICCs, two ECCs, and one GBC. Five ICC patients (three male and two female) with the FGFR2 fusion gene were treated with pemigatinib. Those patients who received a genomically matched therapy had significantly longer median overall survival than those patients who not received. (n = 13; not reached [95% CI not reached-not reached] vs n = 72; 8.6months [95% CI 6.6-10.0]; hazard ratio 0.24 [95% CI 0.12-0.49], p = 0.013). The median observation period of pemigatinib treatment was 15.4months (range 10.1-27.4). The responses were classified as PR in three patients, SD in one patient and PD in one patient. The median progression free survival is 9.0months. No patient had grade 3/4 AEs requiring discontinuation of the treatment. The drug accessibility rate of ICC is high and pemigatinib is effective and well-tolerated in ICC patients harboring FGFR2 gene fusions.

397. TREATMENT OUTCOMES OF IMMUNE CHECKPOINT INHIBITORS AS PRIMARY THERAPY FOR UNRESECTABLE OR RECURRENT ESOPHAGEAL CANCER

Abstract Background For the primary treatment of unresectable or recurrent esophageal cancer, combination therapy with immune checkpoint inhibitors (ICI) such as pembrolizumab (Pem) with CF (cisplatin and 5-fluorouracil), nivolumab (Nivo) with CF, and Nivo with ipilimumab (Ipi) has been shown the significantly improve prognosis compared to standard CF therapy in international collaborative phase III trials. As a result, these ICIs have been approved as primary treatment agents in Japan, with treatment guidelines strongly recommending therapies including ICIs. We evaluated the treatment outcomes at our institute and discussed their utility. Methods We examined the treatment outcomes of 26 esophageal cancer patients who underwent primary treatment with Pem+CF, Nivo+CF, or Nivo+Ipi from January 2018 to January 2023. The median observation period was 7.0 months. Results There were 20 male and 6 female patients, with a median age of 69 years. Histologically, there were 24 cases of squamous cell carcinoma and 2 cases of adenocarcinoma. Of the 26 patients, 9 were postoperative recurrences and 17 were unresectable diseases. They were treated with Pem+CF (12 cases), Nivo+CF (7 cases), or Nivo+Ipi (7 cases) as primary therapy. The initial response was complete response (CR) in 1 case, partial response (PR) in 14 cases, stable disease (SD) in 2 cases, and progressive disease (PD) in 9 cases, resulting in an overall response rate of 57.6%. The median progression-free survival was 5.0 months, and the median overall survival was 15.2 months. There was no significant difference in prognosis according to the regimens. Grade 3 or higher adverse events included neutropenia in 3 cases, pituitary insufficiency in 1 case, and adrenal insufficiency in 1 case. One case with lung metastasis and two cases with para-aortic lymph node metastasis showed disappearance of metastatic lesions after chemotherapy including ICIs, leading to conversion esophagectomy. One case had anastomotic failure, but no other postoperative complications were observed. All patients are currently under observation without recurrence. Conclusion ICIs for unresectable or recurrent esophageal cancer showed a prolongation of prognosis in real-world clinical practice, suggesting their significance as part of a multimodal treatment approach including conversion surgery.

P127 TO INVESTIGATE THE ASSOCIATION BETWEEN BODY MASS INDEX(BMI) AND NECK CIRCUMFERENCE FOR ASSESSING THE RISK OF DEVELOPING HYPERTENSION

Background: This study investigates the association between body mass index (BMI) in combination with neck circumference and the risk of developing hypertension. Methods: Participants (35,000) were selected from the 2021 May Measurement Month participants, comprising normotensive individuals. We categorized participants into four groups based on BMI and neck circumference. Neck circumference was then analyzed for its association with BMI in both females and males. Receiver operating characteristic (ROC) analysis was conducted to determine the best cut-off values for predicting central obesity, and the area under the curve (AUC) was compared between neck circumference and BMI. Results: Following a median observation period of 2.1years, hypertension was diagnosed in 22,400 (64%) participants. Groups 2, 3, and 4 displayed notably elevated hypertension risks compared to Group 1, exhibiting hazard ratios (HRs) of 1.066 (95% CI: 1.025, 1.110), 1.322 (95% CI: 1.235, 1.415), and 1.422 (95% CI: 1.337, 1.512), respectively. Moreover, integrating BMI into a conventional model yielded a more substantial enhancement in hypertension prediction than neck circumference alone. Concurrently assessing BMI and neck circumference further improved hypertension risk estimation accuracy. Neck circumference demonstrated significant correlations with waist circumference in both females and males, with respective b-coefficients of 1.03 (95% CI: 0.85, 1.21) and 0.74 (95% CI: 0.54, 0.70). Receiver operating characteristic (ROC) analysis identified neck circumferences ≥36 cm in females and ≥40 cm in males as optimal thresholds for predicting central obesity. Additionally, the area under the curve (AUC) for neck circumference (0.71; 95% CI: 0.72–0.77) in predicting central obesity surpassed that of BMI (0.77; 95% CI: 0.78–0.82). Conclusion: Individuals with elevated BMI and neck circumference face an increased risk of developing hypertension. While BMI proves to be a predictor of hypertension risk, neck circumference is a superior predictor. Utilizing both measures together enhances hypertension risk prediction accuracy. This underscores the importance of considering both BMI and neck circumference in assessing hypertension risk among individuals.

245. ESOPHAGECTOMY AFTER NEOADJUVANT CHEMOTHERAPY WITH AN INDICATION FOR CONVERSION SURGERY FOR HIGHLY ADVANCED ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA

Abstract Background There is currently no strong evidence for preoperative chemotherapy for advanced esophagogastric junction adenocarcinoma. Furthermore, no curative treatment strategy has been established for advanced junction adenocarcinoma, including Stage IV disease, with no indication for conversion surgery. Subjects and Methods In this study, we retrospectively reviewed nine patients with highly advanced esophagogastric junctional adenocarcinoma, including Stage IV adenocarcinoma, who underwent systemic chemotherapy followed by planned resection at our hospital. Results The participants included 6 males and 3 females, with median age of 64 (range: 45–72) years. Pretreatment stages III, IVA, and IVB, categorized based on UICC TNM classification (esophageal adenocarcinoma), were observed in 1, 4, and 4 cases, respectively, with 1 case of (#104) subclavian lymph node metastases, 1 case of (#16) abdominal para-aortic lymph node metastases, and 2 cases of liver metastases, including multiple lesions. All patients received S-1 plus oxaliplatin (SOX) therapy as preoperative chemotherapy (2–40 courses). Although we observed one patient with unresectable abdomen malingnancies, the others underwent R0 resection, six underwent esophagectomy (with three total gastrectomy and one liver resection), and two open (+ continuous right thoracotomy) lower esophagectomy + total gastrectomy. Pathological stages I, II, III, and IV were observed in two, one, four, and one patients, respectively. Postoperatively, stereotactic irradiation, chemotherapy, and immune checkpoint inhibitors were administered to the patients to treat recurrent brain and liver metastases, and the 1-year survival rate was found to be 71.4% with a median observation period of 17 (range: 0–61) months. Among them, downstage and pN0 cases were relatively promising. Conclusion Even in highly advanced cases, cases with promising prognoses with multidisciplinary treatment, including surgery, were observed. We hope that large-scale clinical trials, such as JCOG2203, will help clarifying the significance of this approach, and advancements in chemotherapy regimens are expected.