笹沼 英紀

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal; however, early-stage cases with improved survival are increasingly detected, underscoring the need for more standardized and clinically applicable histological grading in routine diagnostic practice. Based on 139 resected PDACs without neoadjuvant therapy, including 41 pT1 tumors, we propose a modified CAP-based grading system (mCAP). This system assesses the overall proportion of non-tubular components (NTC) and dense non-tubular clusters (DNTC), the latter defined as ≥ 30 non-tubular clusters within a 0.785 mm² area. DNTC was incorporated to capture focal dense non-tubular morphology not adequately reflected by overall NTC proportion alone. Tumors were classified as G1 (< 10% NTC and DNTC-negative), G2 (10-<50% NTC or < 10% NTC with DNTC positivity), or G3 (≥ 50% NTC). In Kaplan-Meier and log-rank analyses, mCAP showed prognostic stratification for both disease-free survival (DFS) and overall survival (OS). In multivariable Cox analysis for pT1c-pT3 tumors, mCAP G2/G3 remained independently associated with worse prognosis: the adjusted hazard ratios for mCAP G2/G3 versus G1 were 5.23 for DFS (95% confidence interval [CI], 2.58-10.61; P < 0.001) and 3.06 for OS (95% CI, 1.66-5.65; P < 0.001). In grade-only Cox models, mCAP showed the lowest Akaike information criterion (AIC) values for both DFS and OS among the three grading systems, suggesting more favorable model fit for mCAP. In the interobserver reproducibility study, unweighted Fleiss' kappa coefficients were 0.287 for WHO, 0.500 for CAP, and 0.531 for mCAP. Overall, mCAP may refine morphology-based risk stratification in resected PDAC.

Acoustic radiation force impulse (ARFI) imaging is an ultrasound elastography technique that enables quantitative assessment of tissue mechanical properties. However, unlike conventional B-mode imaging, ARFI elastography uses longer and higher-intensity push pulses to induce tissue displacement. This feature raises important questions regarding whether the conventional mechanical index (MI) and thermal index (TI) are sufficient to assess the safety of ARFI exposure. In addition, the acoustic field associated with ARFI push pulses may extend beyond the intended focal region, creating the potential for unintended effects to adjacent vulnerable organs, such as the lung or the heart during liver scanning or breast scanning. This narrative review examines the current evidence on the safety of ARFI, with emphasis on direct experimental studies of ARFI bioeffects and their interpretation in the context of international safety guidance from organizations such as the American Institute of Ultrasound in Medicine (AIUM), the British Medical Ultrasound Society (BMUS), and the World Federation for Ultrasound in Medicine and Biology (WFUMB). Available evidence, derived primarily from animal models, suggests that the prolonged pulse duration of ARFI may lower the threshold for certain mechanical bioeffects, including pulmonary capillary hemorrhage and cardiac rhythm disturbances. Concurrent use of ultrasound contrast agents may increase susceptibility to cardiac mechanical bioeffects, whereas no significant increase in ARFI-induced pulmonary hemorrhage was demonstrated in a rabbit lung model under the tested conditions. In vivo rabbit measurements also showed greater temperature rise at the bone surface than in liver tissue during ARFI exposure. These findings indicate that the safety profile of ARFI cannot be inferred solely from criteria developed for conventional diagnostic ultrasound. ARFI-specific factors, including pulse duration, cumulative exposure, tissue vulnerability, off-target exposure, and contrast-agent use, should be considered in safety assessment and clinical practice.

PURPOSE: There is limited awareness of work-related musculoskeletal disorders (MSDs) in Japan, despite the high ergonomic risks for surgeons. We conducted this study to investigate the prevalence, characteristics, and impact of MSDs on Japanese general surgeons. METHODS: An electronic survey of 136 general surgeons at a Japanese university hospital network used a modified Nordic Musculoskeletal Questionnaire to assess demographics, work factors, MSD symptoms, psychological distress, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and their impact. RESULTS: Based on a 56.6% response rate, we found a high prevalence of chronic (37.7%) and acute (51.9%) MSDs. These disorders frequently impacted surgeons' work (30.0%) and daily life (39.0%), leading to time off (5.2%) and medical intervention (28.6%). Both MSD types correlated significantly with the use of NSAIDs and psychological distress. Notably, neck pain was strongly associated with the use of NSAIDs. The proportion of minimally invasive surgical procedures performed each week was associated significantly with acute, but not chronic, MSDs. CONCLUSIONS: MSDs are highly prevalent among Japanese surgeons, impacting their physical and psychological health. The high symptom prevalence and the strong association between neck pain and NSAID reliance underscore the urgent need for ergonomic interventions and preventive strategies in surgical practice to protect this essential workforce.

<jats:p>Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. While curative resection offers the best chance for long-term survival, the high postoperative recurrence rate suggests a persistent need for effective perioperative therapies. We investigated a multimodal approach, combining sequential lenvatinib with transarterial chemoembolization (TACE), as a presurgical treatment (PST) for resectable HCC. Methods: This retrospective study included 19 patients with technically resectable HCC who underwent the PST protocol followed by surgery between March 2022 and September 2024. The protocol involved four phases: Pre-TACE lenvatinib administration (Pre-LEN), TACE, Post-TACE lenvatinib administration, and surgery. We assessed the feasibility, safety, and pathological response of the protocol. Liver function was evaluated using the albumin-bilirubin (ALBI) score, modified ALBI (mALBI) grade, and tumor response was assessed using the Response Evaluation Criteria in Cancer of the Liver (RECICL). Results: The PST protocol demonstrated high efficacy and safety. The median tumor reduction rate was 22.9%, and the median pathological tumor necrosis rate was 95%. The preoperative overall RECICL response was a complete response in 84.2% of patients. With a median follow-up of 22 months, the 2-year recurrence-free survival rate was 84.6%, and the overall survival rate was 100%. A significant association was found between mALBI grade and the decision to proceed with surgery at two time points: Pre-LEN (p = 0.023) and before surgery (p = 0.006). Conclusion: Presurgical sequential lenvatinib-TACE therapy is a feasible and safe strategy for resectable HCC. This protocol achieved a high pathological response and favorable survival outcomes, suggesting that it may mitigate the risk of early recurrence. Our findings highlight the importance of mALBI grade monitoring for patient selection and provide a rationale for larger, prospective studies.</jats:p>

Fibroblast growth factor receptor (FGFR)2 rearrangements define a distinct molecular subset of intrahepatic cholangiocarcinoma (iCCA) with therapeutic potential using FGFR inhibitors. However, acquired resistance invariably limits long-term efficacy, posing a significant clinical challenge. Sequential targeting with different FGFR inhibitors is an emerging strategy, yet robust evidence, particularly for third-line and beyond, is scarce, and a consensus on optimal sequencing and patient selection remains unreached. Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. This case underscores the sustained dependency on the FGFR pathway and highlights the potential clinical utility of rationally sequenced FGFR-targeted therapy even after multiple lines of treatment. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.