Background The prognosis and recurrence patterns of early-diagnosed pancreatic ductal adenocarcinoma (PDAC), particularly following surgical resection, remain unclear. Methods This multicenter retrospective study analyzed patients who underwent surgical resection for PDAC between 2005 and 2023. Patients were categorized according to pathological stages 0, I, and II. Recurrence patterns and survival outcomes were compared among the three groups. Multivariate analysis was performed to identify independent risk factors for remnant pancreatic recurrence, including early-stage disease, postoperative follow-up of more than 5 years, and receipt of adjuvant chemotherapy. Results A total of 349 patients were included: 51 with stage 0, 77 with stage I, and 221 with stage II PDAC. The 5-year overall survival rates were 87%, 71%, and 49% for patients with stage 0, I, and II PDAC, respectively. Remnant pancreatic recurrence was observed in 10% of patients with stage 0 PDAC and 18% of patients with stage I PDAC, compared with 5% of those with stage II PDAC. Recurrence was significantly more frequent in stage I (P < 0.001) and tended to be higher in stage 0 (P = 0.062) than in stage II. Multivariate analysis identified pathological stage 0-I and postoperative follow-up of > 5 years as independent risk factors for remnant pancreatic recurrence. Conclusions Patients with early-stage PDAC exhibit a higher risk of remnant pancreatic recurrence than those with stage II disease. These findings underscore the importance of long-term pancreas-focused surveillance in early-stage PDAC to enable timely detection of late recurrence and potentially improve patients outcomes.
BACKGROUND:There is a paucity of data regarding the efficacy and safety of lenvatinib as a second-line treatment following first-line combination immunotherapy with durvalumab and tremelimumab (Dur + Tre). METHODS:This retrospective multicenter study included 14 patients with unresectable hepatocellular carcinoma who received lenvatinib after progression on Dur + Tre therapy, conducted at five institutions, including Hiroshima University. In cases where the multidisciplinary team determined that concurrent transcatheter arterial chemoembolization (TACE) would be beneficial, on-demand TACE was administered concomitantly with lenvatinib. The therapeutic response and safety profile of lenvatinib were evaluated in all enrolled patients, including those who underwent TACE. RESULTS:The objective response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS) for Dur + Tre and subsequent lenvatinib treatment were 14.3%/30.7%, 57.1%/61.5%, and 2.4/2.3 months, respectively. Five patients (35.7%) received combined lenvatinib and TACE therapy. Among these, one patient each with stable disease (SD) and progressive disease (PD) on Dur + Tre improved to partial response (PR) during lenvatinib therapy. Two patients (14.3%) remained on lenvatinib at the time of analysis. Six patients (42.9%) transitioned to subsequent lines of systemic therapy, all receiving atezolizumab combined with bevacizumab. Overall, five patients (35.7%) had died at the data cutoff, with a median overall survival (OS) of 18.4 months. Grade 3 or higher adverse events (AEs) were observed in 7 patients (50%) across both Dur + Tre and lenvatinib treatment phases. CONCLUSIONS:Lenvatinib administered after progression on Dur + Tre demonstrates promising efficacy and an acceptable safety profile in patients who tolerate the therapy. The integration of TACE in suitable candidates warrants further exploration, and timely transition to subsequent systemic therapies should be considered when adverse events or intolerance are encountered.
BACKGROUND:Obesity is a major global health issue. While tirzepatide demonstrates robust weight reduction in clinical trials, data comparing low maintenance doses (2.5 vs. 5 mg) in non-diabetic adults with obesity remain limited. This study evaluated the comparative efficacy and safety of 2.5 versus 5 mg tirzepatide combined with lifestyle intervention. METHODS:This multicentre, prospective, non-randomised cohort study enrolled non-diabetic Japanese adults (18-65 years) with BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with comorbidities. Patients initiated tirzepatide at 2.5 mg weekly; after 4 weeks, the dose was maintained at 2.5 mg or increased to 5 mg based on shared decision-making. All participants received standardised dietary and exercise counselling. The primary outcome was the proportion achieving BMI < 25 kg/m2 or > 15% body weight reduction at 6 months. RESULTS:Of 112 participants analysed (58 on 2.5 mg, 54 on 5 mg), baseline characteristics were well balanced (mean BMI 30.8 kg/m2). At 6 months, the primary outcome was achieved in 62.1% of the 2.5 mg group and 63.0% of the 5 mg group (HR 0.93, 95% CI 0.58-1.49; p = 0.772). Mean percent weight loss was -15.3% and -16.1%, respectively (p = 0.563), with similar reductions in BMI, skeletal muscle mass, and bone mass. Adherence to dietary therapy was excellent in both groups (96.4%), while exercise adherence was 37.5%. Adverse events were more frequent with 5 mg (50% vs. 35%), primarily gastrointestinal symptoms. CONCLUSION:In non-diabetic Japanese adults with obesity, 2.5 and 5 mg tirzepatide combined with lifestyle modification yielded similar weight loss at 6 months, with better tolerability at the lower dose. These findings support the potential utility of low-dose tirzepatide strategies in real-world practice.
Background:Information on long-term outcomes of colorectal endoscopic submucosal dissection (ESD) in real-world clinical practice remains limited. This study aimed to evaluate long-term local recurrence and its predictors after colorectal ESD. Methods:This prospective, multicenter study was conducted at 11 institutions in Hiroshima, Japan, and included all consecutive colorectal ESD cases (1838 lesions from 1732 patients) between 2014 and 2018. The primary outcome was the cumulative local recurrence rate. The secondary outcomes included factors associated with local recurrence, overall survival, and cancer-specific survival. Factors associated with local recurrence were evaluated using cause-specific Cox proportional hazards models using Firth's penalized partial likelihood. Results:The cumulative local recurrence rates at 1, 3, and 5 years were 0.06%, 0.64%, and 0.75%, respectively. The longest interval to recurrence was 52 months. No local recurrence was observed in patients who achieved curative resection. Rectal lesions (hazard ratio [HR] 3.93; P = 0.04), high-risk pathologic features (HR 14.3; P < 0.001), R1 resection (HR 7.59; P = 0.003), and delayed bleeding (HR 7.72; P = 0.009) were associated with local recurrence. The 5-year overall survival and cancer-specific survival rates were 95.3% and 100%, respectively; however, 1/10 patients with local recurrence developed liver and lung metastases and subsequently died 64 months after ESD. Conclusions:Colorectal ESD had a very low long-term local recurrence rate in real-world clinical settings. No recurrence was observed in patients who underwent curative resection. Long-term surveillance is warranted after noncurative resection.
Background: With the growing older adult population in developed countries, the number of older adults with cancer is also rising. Selecting appropriate treatments for these patients is challenging, owing to difficulties in assessing their tolerance to invasive surgery. This study aimed to identify the prognostic factors in octogenarians undergoing first-time hepatectomy for hepatocellular carcinoma (HCC). Methods: We enrolled 229 consecutive patients with resected HCC between 2008 and 2018, excluding three who died within 90 days post-surgery. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and recurrence-free survival (RFS). Results: Participants were aged 80–93 years and included 163 males and 63 females, with the majority having hepatitis C virus. Liver function was well-preserved (Child–Pugh grade A: 215; grade B: 12). Laparoscopic hepatectomy was performed in 34 patients. The following factors showed significant association with OS in the univariate analysis: age-adjusted Charlson comorbidity index (ACCI) ≥ 10, neutrophil-to-lymphocyte ratio ≥ 3, alpha-fetoprotein (AFP) > 100 ng/mL, tumor size > 50 mm, and multiple tumors. Multivariate analysis confirmed ACCI ≥ 10, AFP > 100 ng/mL, tumor size > 50 mm, and multiple tumors as independent risk factors for OS. Regarding RFS, the significant factors identified in the univariate analysis included sex, indocyanine green retention rate at 15 min > 10%, des-gamma-carboxy prothrombin > 500 mAU/mL, intraoperative bleeding, tumor size, multiple tumors, and vascular invasion. Multivariate analysis identified sex, multiple tumors, and vascular invasion as independent risk factors for RFS. Conclusions: Elevated tumor markers, multiple tumors, and ACCI ≥ 10 are risk factors for poor OS in older adults with primary HCC. Both tumor-related factors and ACCI score should be considered when selecting treatment for octogenarian patients with HCC.
