Uncertainties persist regarding the allocation of apical lymph nodes in colorectal cancer, the approaches to lymph node dissection and mesocolic excision, which may contribute to inconsistent surgical practices. The aim of this study is to assess surgeons' practices in lymph node dissection and mesocolic excision approaches and to identify areas lacking standardization. A multinational pilot survey of 22 colorectal surgeons from 6 countries was conducted during the FICARE colorectal meeting. The survey consisted of 21 Likert-scale questions on surgical practices and lymph node allocation in colorectal cancer surgery. Majority of the respondents (90.9%) recognized conceptual differences in apical lymph node stratification between right- and left-sided colon cancers, whereas D3 LND for left-sided cancer should include mesocolic tissue along the inferior mesenteric artery from its origin to the last sigmoid artery. Complete lymph node dissection requires excision of mesocolic tissue along inferior mesenteric artery for left colon cancer and superior mesenteric artery for right colon cancer according to 81.8% of respondents. At the same time, 95.5% agreed that intermediate and paracolic lymph nodes are located within a 10-cm resection margin proximally and distally from tumor, while 81.9% of respondents supported the concept of tumor-specific mesocolic excision to be sufficient enough for adequate paracolic and intermediate lymph node dissection. A multinational snapshot showed an existing contraindication in surgeons' perception of lymph node stratification and the variability in mesocolic excision and LND. Further Delphi consensus is needed to prove the suggested concepts.

Hereditary colorectal cancer (HCRC), arising from pathogenic germline variants, accounts for 5-10% of all CRCs. The widespread clinical adoption of next-generation sequencing (NGS) and multigene panel testing (MGPT) has fundamentally transformed the diagnostic paradigm for this genetic predisposition. This review summarizes the latest epidemiological data on genetic predisposition to CRC and examines the essential practical changes required for genomics-based precision medicine. Recent large-scale genomic cohort studies have consistently revealed a higher prevalence of pathogenic/likely pathogenic germline variants (PGVs) in unselected CRC populations than previously recognized, ranging from 3.3 to 15.5%. This proportion is dramatically elevated in patients with early onset CRC (EOCRC), defined as a diagnosis before age 50, where prevalence consistently exceeds 15%. Notably, MGPT has expanded the etiological spectrum far beyond Lynch syndrome (LS)-related genes, demonstrating a significant contribution from non-LS and high- and moderate-penetrance genes, particularly those associated with homologous recombination deficiency (HRD). Consequently, the management of genetic predisposition to CRC is rapidly shifting from single syndrome-based diagnoses to individualized precision medicine guided by gene-specific lifetime cancer risks. To realize clinical benefits, two imperatives must be addressed: (1) the implementation of universal genomic screening for all patients with EOCRC and (2) the development of proactive medical-contact approach models in cascade screening for at-risk relatives. Nevertheless, the viability of this proposal varies considerably between Europe, America, and Asia. Considerable uncertainty surrounds implementation in Asia, where a plethora of challenges must be overcome to facilitate the integration of genomic medicine within the Asian context.

Early detection of cancer and precise recurrence monitoring remain major unmet needs in oncology. Conventional screening is limited to a few cancer types, leaving nearly half of cancers without established programs. Multi-cancer early detection (MCED) tests based on circulating tumor biomarkers have shown promise, but sensitivity for early-stage remains a challenge. In parallel, detection of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) has emerged as a powerful prognostic and predictive tool, though current assays remain limited in sensitivity and specificity. This study aims to integrate multi-omics data to develop more refined and highly sensitive MCED and MRD assays. This study leverages clinical information and biospecimens from patients with cancer and cancer-naïve individuals. Samples from patients with cancers will be derived from the MONSTAR-SCREEN-3 study, while those from cancer-naïve individuals will be obtained from the Tohoku Medical Megabank Project. Comprehensive analyses will include whole-genome sequencing (WGS), whole-exome sequencing (WES), whole-transcriptome sequencing (WTS), proteomics, metabolomics, and microbiome profiling using stool and saliva. Artificial intelligence (AI)-based multi-omics integration will be performed to develop novel MCED and MRD assays and to evaluate their clinical performance. The primary endpoints are the sensitivity and specificity of MCED and MRD assays. This is the first large-scale study to integrate comprehensive multi-omics profiling with AI for MCED and MRD assay development. The findings are expected to advance precision oncology by improving early diagnosis and recurrence monitoring. UMIN000053815, approved by the Institutional Review Board of the National Cancer Center Hospital East.

Pelvic lymph-node dissection is performed across multiple surgical specialties. However, inconsistent terminology and unclear anatomical boundaries hinder standardization. This study established a multidisciplinary team with a shared anatomical understanding, with the aim to prospectively evaluate standardized pelvic lymph-node dissection, focusing on the dorsal region of the obturator nerve. A prospective observational study was conducted at a single institution from November 2022 to 2025. A team of urology, gastrointestinal surgery, gynecology, and pathology specialists received standardized anatomical training. A total of 106 patients undergoing pelvic lymph-node dissection for pelvic cancers were enrolled. Pelvic regions were predefined into seven areas. Data on surgical outcomes, lymph-node yield, complications, operative time, and quality of life were collected. Central pathology review and photographic scoring were performed. Over 90% of surgeons rated the anatomical classification as clear. Planned lymphadenectomy was completed in over 95% of cases. The obturator region was consistently dissected. Dissection of the dorsal obturator nerve region did not increase the number of retrieved or positive lymph nodes but extended operative time by 15min per side. No lymphadenectomy-related complications were observed in 96% of patients. Quality of life declined at 1week postoperatively and stabilized by 1month. A multidisciplinary, standardized approach to pelvic lymph-node dissection is feasible and facilitates implementation across specialties. Dissection of the dorsal obturator nerve region increases operative time without demonstrating additional oncological advantage in this study. Standardized anatomical frameworks may facilitate safer and more consistent practice.

The purpose of this study was to compare the diagnostic performance of radiolabeled prostate-specific membrane antigen-targeted positron emission tomography/computed tomography (PSMA-PET/CT) with 18F, whole-body magnetic resonance imaging (WB-MRI), including diffusion-weighted imaging (DWI) and a combination of conventional computed tomography and bone scintigraphy (CT/BS) for the detection of recurrent lesions in patients with prostate cancer with rising PSA levels following initial definitive treatment. This retrospective study used part of the dataset from a previous phase 2 study conducted between February 2019 and March 2022, which evaluated the detection efficacy of 18F-FSU-880 PSMA-PET/CT in 72 patients with suspected recurrent prostate cancer after definitive treatment. Of these, 35 patients (age 56-82years, PSA level 0.24-40.00ng/ml) who underwent both PSMA-PET/CT and WB-MRI were reviewed by six radiologists. Sensitivity, specificity, and overall accuracy were compared using McNemar's test, and positive predictive value was compared using Fisher's exact test. Total 132 true-positive prostate cancer lesions were detected in 23 of 35 patients (66%). The sensitivity of PSMA-PET/CT (100%) was significantly higher than those of both WB-MRI (57%) and CT/BS (32%) in the per-patient analysis (p = 0.002 and p < 0.001, respectively). In the per-lesion analysis, the sensitivity of PSMA-PET/CT (88%) was significantly higher than those of WB-MRI (44%) and CT/BS (6%) (p < 0.001 and p < 0.001, respectively). 18F-FSU-880 PSMA-PET/CT showed a more favorable diagnostic performance, especially in terms of sensitivity, than WB-MRI and CT/BS in detecting recurrent disease in patients with prostate cancer after definitive treatment.

Lisocabtagene maraleucel (liso-cel), an anti-CD19 CAR T cell therapy, has demonstrated efficacy in relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, real-world data from commercial settings outside the United States remain limited. To evaluate the safety and effectiveness of commercial-use liso-cel in Japan, we conducted a single-center retrospective study of patients with R/R LBCL who received commercial-use liso-cel at our institution between November 2021 and November 2024. 56 patients received liso-cel infusion. The median age was 66.5years, and 55.4% had primary refractory disease. Liso-cel was administered as second-line therapy in 14 patients (25.0%) and as third-line or later therapy in 42 patients (75.0%). The best overall response rate was 80.4%, with a complete response rate of 78.6%. At a median follow-up of 12.3months, 1year progression-free survival (PFS) and overall survival rates were 69.5% and 86.4%, respectively. The 1year PFS rates were 68.5% for diffuse large B cell lymphoma not otherwise specified, 100% for primary mediastinal large B cell lymphoma (PMBCL), and 30% for high-grade B cell lymphoma (HGBCL). Grade ≥ 3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were observed in one patient each. Multivariate analysis identified HGBCL subtype and higher pre-infusion metabolic tumor volume as independent adverse factors for PFS. Commercial-use liso-cel demonstrated high response rates and favorable safety in Japanese patients with R/R LBCL. Patients with PMBCL had excellent outcomes, whereas those with HGBCL showed poorer prognosis, indicating a need for further therapeutic strategies.

This retrospective study compared the outcomes of radiotherapy (RT) and chemoradiotherapy (CRT) in patients with T2N0 hypopharyngeal cancer. We analyzed patients with T2N0 hypopharyngeal squamous cell carcinoma treated with RT or CRT between 2011 and 2016 using data from the Head and Neck Cancer Registry of Japan. Among 53,512 patients, 457 with T2N0 disease received RT (n = 165) or CRT (n = 292; median follow-up, 41.8months; median age, 70years). Tumor sites included the pyriform sinus (72.9%), postcricoid region (12.3%), posterior wall (11.8%), and unknown (3.1%). The groups differed in terms of age and alcohol use. Before weighing, CRT was associated with longer PFS and a lower cumulative incidence of locoregional recurrence compared with RT. However, in the IPTW-adjusted analysis, CRT did not significantly improve OS (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.59-1.62) or PFS (HR, 0.79; 95% CI, 0.53-1.16) compared with RT. PFS was associated with alcohol/smoking history, performance status, and primary site of the tumor. In T2N0 hypopharyngeal cancer, CRT reduced the locoregional recurrence compared to RT. However, CRT did not confer a significant OS or PFS advantage over RT after adjustment for baseline imbalances. RT alone may, therefore, be a reasonable definitive treatment option for selected patients.

Proton pump inhibitors (PPIs) have received considerable attention as inducers of gut dysbiosis through gastric acid suppression. PPI-induced gut dysbiosis is associated with a poor prognosis in patients with non-small cell lung cancer and urothelial cancer treated with immune checkpoint inhibitors (ICIs), but not in those with hepatocellular carcinoma (HCC). Although vonoprazan, which showed more powerful acid suppression than PPIs, tended to decrease efficacy in non-small cell lung cancer and urothelial cancer, its effect on ICIs therapy for HCC remains unknown and was evaluated in this study. This multicenter retrospective study included patients aged ≥ 18years with HCC who received atezolizumab plus bevacizumab (Atz/Bev) between September 2020 and December 2023 at five hospitals. The primary and secondary endpoints were differences in progression-free survival (PFS) and overall survival (OS), respectively. Of the 354 eligible patients, 115 received PPIs, 55 received vonoprazan, and 184 received neither vonoprazan nor PPIs (non-gastric acid suppression [GAS] group). In the multivariate analysis, compared to vonoprazan group, there were no significant differences in the PFS of the PPI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.73-1.53; P = 0.77) and non-GAS groups (HR, 0.93; 95% CI, 0.65-1.32; P = 0.67). Similarly, there were no significant differences in the OS of PPI (HR, 0.94; 95% CI, 0.59-1.48; P = 0.78) and non-GAS groups (HR, 0.75; 95% CI, 0.48-1.17; P = 0.20). Vonoprazan was not associated with worse PFS and OS in patients with HCC treated with Atz/Bev than in those who did not receive PPIs and neither.

Immune checkpoint inhibitors (ICIs) improve cancer survival but can induce immune-related adverse events (irAEs). Pre-existing autoantibodies, particularly antinuclear antibodies (ANAs), have been suggested as predictive biomarkers for irAE development. However, prior studies have yielded mixed results. Furthermore, the predictive value of specific ANA staining patterns has remained unexplored. We aimed to investigate the relationship between baseline autoantibody levels and irAE development. This retrospective observational study included 626 patients with cancer receiving ICI therapy between November 2020 and August 2024 at the Tottori University Hospital. irAEs were graded using Common Terminology Criteria for Adverse Events v5.0, with grade ≥ 2 considered clinically significant. Logistic regression analysis assessed the association between baseline factors and irAE development. Receiver operating characteristic (ROC) curve analysis evaluated model performance. Elevated ANA titers (≥ ×40), speckled ANA staining pattern, and combination ICI therapy were significantly associated with an increased risk of grade ≥ 2 irAEs in both univariable and multivariable analyses. The predictive performance of the area under the ROC curve for the multivariable models using either elevated ANA titers or the speckled pattern was similar (approximately 0.617). Baseline ANA titer and speckled ANA pattern are potential predictive biomarkers for grade ≥ 2 irAEs, particularly in patients receiving combination ICI therapy. Comprehensive ANA testing may improve risk stratification and inform personalized irAE management.