OBJECTIVES:Positive surgical margins (PSMs) are associated with biochemical recurrence (BCR) following radical prostatectomy (RP). However, their prognostic significance varies, and not all patients with PSMs experience recurrence. This study aimed to evaluate whether detailed analysis of margin characteristics could improve postoperative risk stratification. METHODS:We retrospectively reviewed 1003 patients who underwent RP without neoadjuvant or adjuvant therapy. PSMs were categorized according to total PSM length (≤ 5 mm vs. > 5 mm), maximum PSM length (≥ 3 mm vs. < 3 mm), primary Gleason pattern (pGP) at PSM (pGP3 vs. pGP4-5), multifocality (single vs. multiple), and location (apex-only vs. others). Other pathological factors analyzed pathological T/N stage, ISUP grade group, and intraductal carcinoma of the prostate (IDC-P). RESULTS:PSMs were present in 377 patients (37%), Total PSM length was 5.0 (0.1-66) mm and pGP3 was more common in apex-only PSMs. pGS, IDC-P, and PSM status were significant predictors of BCR in the entire cohort. Among margin parameters, total PSM length and pGP at the PSM were the strongest predictors. In organ-confined disease with PSM, BCR risk was significantly stratified into three groups based on total PSM length > 5 mm and pGP4-5 at the margin (0, 1, or 2; p < 0.001). CONCLUSIONS:A risk classification incorporating total PSM length and pGP at the margin improves postoperative prognostic stratification for localized prostate cancer with PSMs. In cases with multiple PSMs, total PSM length may be more informative than the maximum PSM length European Association of Urology recommended.
BACKGROUND:The t(1;22)(p13;q13) chromosome abnormality is reported in 10%-17% of children with acute megakaryoblastic leukemia (AMKL), leading to the chimeric fusion gene RBM15::MRTFA. Previous studies have revealed that AMKL with t(1;22) exhibits a good prognosis; however, early death has been observed in cases with onset of the disease at birth and liver failure. METHODS:To determine the clinical characteristics and outcomes of AMKL with t(1;22), we conducted a nationwide retrospective survey. RESULTS:AMKL with t(1;22) was diagnosed in 23 children (eight boys and 15 females) from 2000 to 2013. Their median age at diagnosis was 4 months (range: 0-34 months). Hepatosplenomegaly was observed in 17 patients, with three initially misdiagnosed as solid tumors. G-banding revealed t(1;22) in 21 patients, and PCR detected the RBM15::MRTFA fusion gene in two other patients. The 5-year overall survival (OS)/event-free survival (EFS) rates in all patients were 52%/35%. Eight patients aged less than 6 months at diagnosis and had hepatomegaly (≥6 cm under the right hypochondrium) demonstrated significantly lower 5-year OS/EFS rates (25%/0%) than the remaining 15 patients (67% [p = 0.008]/25% [p < 0.001]). Among 16 patients treated with intensive chemotherapy, the 5-year OS/EFS rates were significantly higher (63%/44%) than those of seven patients who did not receive such treatment (29% [p = 0.04]/14% [p = 0.03]). CONCLUSIONS:These findings suggest that previously reported data may have overestimated the prognosis of AMKL with t(1;22). Infants aged less than 6 months with severe hepatosplenomegaly demonstrated poor outcomes, and thus AMKL with t(1;22) should be suspected to initiate appropriate chemotherapy immediately.
T follicular helper (TFH)-derived peripheral T-cell lymphomas (PTCLs) harbor frequent mutations in epigenetic regulators and are sensitive to epigenetic therapies. The histone deacetylase inhibitor tucidinostat demonstrated efficacy in relapsed/refractory PTCL, especially angioimmunoblastic T-cell lymphoma (AITL), in a phase IIb trial; however, the lack of TFH phenotyping has prevented assessment of the predictive value of this phenotype across a broader PTCL spectrum. Therefore, we retrospectively analyzed patients originally diagnosed with AITL or PTCL not otherwise specified (NOS) based on 2008 World Health Organization criteria who participated in the aforementioned trial. TFH phenotype was defined as the expression of ≥ 2 TFH markers. Among the 23 evaluable patients, the TFH group (n = 17) included six with AITL and 11 with PTCL-NOS exhibiting TFH features, and the non-TFH group included six patients with PTCL-NOS. The objective response rate was numerically higher in the TFH group (12/17, 70.6
INTRODUCTION:The importation of infectious diseases has increased dramatically in recent years. The diagnosis of such diseases has traditionally been based on symptoms, as well as blood and biochemical tests. In this study, we developed machine-learning models to diagnose influenza cases among international travellers using information on the number of infected individuals in destination countries and the incubation period, which have not been utilised for diagnosis. METHODS:This study examined cases recorded in Japan Registry for Infectious Diseases from Abroad (https://jrida-jprecor.ncgm.go.jp/en/j-rida/index.html), which included influenza test results and information on travel destination and duration. Multivariable logistic regression and machine-learning methods were used to build diagnostic models, with symptoms and an epidemiological score calculated from information on the number of cases in the destination country and the incubation period serving as explanatory variables. RESULTS:Logistic regression analysis revealed that symptoms such as fever (p < 0.001) and cough (p < 0.001), as well as the epidemiological score (p < 0.001), were significant predictors of influenza infection. The machine-learning models were then developed and tested using training and test data, respectively. The constructed models showed good specificity and high accuracy. Among these models, the neural network had the highest accuracy (93%). DISCUSSION:Adding epidemiological information to the usual clinical information can improve diagnostic accuracy. Machine-learning models capable of handling a wide variety of data would be particularly beneficial for diagnosis. The knowledge gained should also be used to raise awareness among travellers.
Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi). Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165). Findings With a median follow-up of 7.1 years (interquartile range 5.6-8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%-80%) and OS was 78% (95% CI 61%-89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1). Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients. Copyright (c) 2025 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).