Kobe Medical Center

We evaluated the prognostic significance and implications of a major pathologic response (MPR) after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). Preoperative treatment is increasingly used for PDAC to improve oncologic outcomes. The pathologic response represents a potential indicator of treatment efficacy; however, its prognostic value in PDAC remains unclear. We retrospectively analyzed 739 patients who underwent pancreatectomy for PDAC after preoperative treatment at 21 institutions in Japan. The pathologic response was graded using Evans' classification, with MPR defined as Evans grade III/IV. Survival outcomes and prognostic factors were evaluated, and factors associated with achieving MPR were analyzed to develop a predictive model. MPR was achieved in 11.5% of patients. The MPR group had a significantly longer median overall survival (71.5 vs. 40.9mo) and recurrence-free survival (55.5 vs. 15.2mo) than the non-MPR group. Multivariate analysis identified MPR as an independent prognostic factor for overall survival. In the MPR subgroup, neither overall nor recurrence-free survival differed according to adjuvant chemotherapy administration; multivariate analysis did not identify adjuvant therapy as an independent prognostic factor. Predictive factors for achieving MPR included chemoradiotherapy, preoperative duration ≥6 months, normal carbohydrate antigen 19-9 after preoperative treatment, and complete or partial radiologic response. Finally, we developed a simplified predictive model for achieving MPR. MPR was independently associated with favorable survival in PDAC. The prognostic impact of adjuvant chemotherapy was not observed among patients who achieved MPR, suggesting that MPR may inform individualized postoperative management and warrants prospective validation.

Skin thinning over cardiac implantable electronic devices (CIEDs) is frequently observed; however, its clinical implications and temporal progression remain unclear. This study aimed to investigate the clinical significance of skin thickness over CIEDs by examining its association with adverse outcomes, including all-cause mortality and device-related infections, and evaluating its temporal changes and associated clinical factors. This study included 96 patients who underwent ultrasonographic measurement of skin thickness over CIEDs between June 2020 and June 2021. Adverse outcomes were monitored through August 2023. Of those, 34 patients had follow-up ultrasonography to assess temporal changes in skin thickness. Among 34 patients with repeated measurements, skin thickness significantly declined over a median of 42 (IQR: 41-44) months (p = 0.001), and thinning was correlated with changes in hemoglobin levels (r = 0.392, p = 0.024). During a median follow-up of 32 (IQR: 11-34) months, patients with skin thickness ≤ 3.3mm (thin group) had significantly higher all-cause mortality than those with a thickness > 3.3mm (normal group) (log-rank p < 0.001). In multivariable Cox regression analysis, skin thickness ≤ 3.3mm remained an independent predictor of mortality (HR 2.42; 95% CI, 1.01-5.80; p = 0.046). Device-related infections were more frequent in the thin group (8%) than in the normal group (2%), but the difference was not statistically significant. Skin thickness over CIEDs progressively declined over time and was significantly correlated with hemoglobin levels. In addition, skin thickness ≤ 3.3mm was independently associated with increased all-cause mortality.

Summary: CBRNE disasters cause severe social disruption and require a special medical response. The Center has prepared a CBRNE disaster response manual in advance of the 2019 Rugby World Cup in Kobe. The Center has similarly held several table-top drills in the neighborhood of the city center to simulate a terrorist attack, but the number of participants was about 20-30 people each time. Therefore, an exercise scenario of multiple patients injured by an accident at a nearby chemical plant was proposed. Before the exercise, a series of study sessions were practiced to deepen the staff’s understanding of CBRNE, including an outline of CBRNE, decontamination tent set-up, and so on. A scenario was developed in which multiple walk-in patients, after dermal or inhalation contamination by chemical agents, collapsed at the hospital entrance, and the initial response was made by multi-professional staff, including a reception clerk, ER nurses, and physicians. On the day of the drill, more than 70 people participated. In the post-drill questionnaire, there were many favorable comments on the drill itself. Many of the participants requested that the next training should be based on an explosion, which could occur in a neighbor’s. As for CBRNE disasters, especially chemical disasters, there have been no mass casualties from terrorist attacks in Japan since the two Sarin gas incidents in 1994 and 1995. On the other hand, chemical disasters such as suicides, accidents, and factory disasters while using toxic agents occur routinely; if the number of the injured/contaminated was too large, or the cause was a terrorist attack in the simulation scenario, participants could hardly view it as realistic. In this CBRNE disaster drill, we believe that the use of “highly probable and realistic training scenarios” raises the sense of urgency and attracts more staff.

Abstract Background: Tumor-infiltrating lymphocytes (TILs) reflect host immune response and are associated with prognosis and treatment response in HER2-positive and triple-negative breast cancer (TNBC). While the International Immuno-Oncology Biomarker Working Group recommends evaluating stromal TILs in tumor areas, intratumoral heterogeneity and small sample size in core needle biopsy (CNB) specimens limit consistent assessment. It remains unclear whether central tumor (CT) or invasive margin (IM) regions should be prioritized and what cut-off values are clinically relevant. Ultrasonographic (US) features may also reflect the immune microenvironment. We previously proposed a TILs-US score based on three US features that predicts lymphocyte-predominant breast cancer (LPBC). This study evaluated the clinical utility of TILs assessment from CT and IM regions, appropriate cut-off values for predicting response in HER2-positive and TNBC using CNB, and explored optimal biopsy targeting through pathologic and US comparisons. Methods: In this multicenter retrospective study, we analyzed 239 patients (124 HER2-positive, 115 TNBC) with cT1-3/cN0-2 breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC). TILs were evaluated using CNB specimens obtained before NAC and assessed separately in the central tumor (CT) and invasive margin (IM) regions. The IM was defined as a 1-mm-wide area centered on the interface between the tumor and surrounding stroma, while the CT was defined as the remaining intratumoral area within the IM boundary. TILs were analyzed using binary cut-offs of 30% and 50%, as well as a three-tier classification: low (0-10%), intermediate (11-49%), and high (≥50%). Pre-treatment ultrasound (US) findings included tumor shape (scored 0-2), internal echo (0-2), and posterior echo (0-3), which were used to calculate a composite TILs-US score ranging from 0 to 7. Associations between TIL levels, US features, and pathological complete response (pCR) were analyzed. Results: Overall, 104 patients achieved pCR (HER2-positive: 39; TNBC: 65). Using a 30% cut-off, TILs were evenly distributed both CT and IM, while ≥50% cases were relatively rare especially CT (CT: 10%; IM: 20%). CT TILs ≥30% was significantly associated with pCR (p=0.001), whereas the ≥50% cut-off was not (p=0.128). In contrast, both 30% and 50% cut-offs in the IM region were predictive of pCR (p&amp;lt;0.001 and p=0.009, respectively). Subtype analysis revealed that in TNBC, TILs ≥30% in both CT and IM regions were significantly correlated with pCR. In HER2-positive cases, however, only IM TILs ≥30% was predictive of pCR. Similar trends were observed with the three-tier classification. Among US features, a small lobulated shape was associated with high TILs levels in both CT and IM regions, while an enhanced posterior echo was correlated with high TILs in the IM region. Conclusion: Our findings suggest that TILs assessment should include the IM in addition to the CT, especially in CNB specimens as provide valuable information. Given the limited tissue area available in CNB specimen, using a 30% cut-off for TILs may offer a clinically meaningful threshold to predict treatment response. In cases where US findings suggest central fibrosis, targeting only the tumor center may result in sampling fibrotic areas with sparse immune and tumor cells, potentially hindering proper evaluation. Therefore, selecting the biopsy target based on US imaging is essential. Especially in HER2-positive breast cancer, as well as TNBC, it is important for operators to consider the optimal needle insertion angle and sampling site to ensure appropriate sampling of viable tumor tissue and immune microenvironment for accurate pathological and immunological evaluation. Citation Format: Y. Kimura, R. Yamaguchi, K. Fukui, A. Kanou, M. Noma, S. Akashi-Tanaka, K. Arihiro, N. Iwamoto, Y. Ohta, T. Okuno, S. Kashiwagi, Y. Kamei, Y. Tanada, S. Nakano, A. Nagata, A. Murakami, Y. Mochitomi, A. Yamakawa, M. Yamaguchi, H. Shima, A. Emi. Ultrasound-guided biopsy-based tils assessment at tumor margins as a predictive biomarker of neoadjuvant treatment response in early her2-positive and triple-negative breast cancer: a multicenter study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-18.

Currently, hormonal therapyis the main treatment option for advanced prostate cancer; however, a certain number of cases progress to metastatic, castration-resistant prostate cancer. Therefore, we designed in vitro and in vivo studies of a new molecular targeted therapy using alpha-tomatine (α-tomatine), a glycoalkaloid extracted from tomatoes, for the growth inhibition of both castration-sensitive human LNCaP and castration-resistant mouse TRAMP-C2 and metastatic human C4-2B prostate cancer cell lines. In vitro, α-tomatine supplementation showed a dose-dependent decrease in the proliferation potential of all prostate cancer cells at concentrations ranging from 1.0 to 5.0 μg/mL, as well as a decrease in migration and invasion abilities at concentrations ranging from 1.0 to2.5 μg/mL, which was sustained throughout the 72 hours post-treatment (p <0.050). Furthermore, flow cytometry demonstrated that α-tomatine at 2.5 μg/mL enhanced the incidence of apoptosis in TRAMP-C2 cells at 48 hours post-treatment (p <0.010). In vivo, TRAMP-C2 cells were subcutaneously implanted in C57BL/6 mice. Then, at a 10-mm diameter, single-time intratumoral injection of 1.0 µg/body α-tomatine was performed. Longitudinal follow-up identified a time-dependent tumor growth inhibition at 3-4 (p< 0.050), 5-7 (p < 0.010), and 8-10 (p < 0.001) days after the administration of α-tomatine. In summary, α-tomatine has the potential to block the proliferation, migration, and invasion of both castration-sensitive and castration-resistant prostate cancer (CRPC) types, even with metastatic cell lines. Further investigation is warranted to clarify the pharmacological action and molecular mechanism of α-tomatine's effects on prostate cancer cells.

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis, for which radical surgery, including lymph node (LN) dissection, remains the only potentially curative treatment. However, the optimal extent of LN dissection has yet to be sufficiently established. The present study sought to evaluate different LN dissection strategies by analyzing the patterns of LN metastasis and calculating the lymph node dissection efficacy index (EI) for each nodal station. A retrospective analysis was conducted on 42 patients with GBC who underwent gallbladder bed resection or more extensive procedures with LN dissection. The prognostic outcome of each LN dissection was assessed using the EI. LN metastases and recurrence were identified in 12 and 14 patients, respectively. Among the four patients with negative metastasis in the hepatoduodenal ligament (LN#12) and positive metastasis in the posterosuperior pancreatic LN (LN#13a), one case remained recurrence-free. Compared with LN along the common hepatic artery (LN#8, 2.94) and LN#12 (4.76), the highest EI value (5.88) was obtained for LN#13a, thereby highlighting its utility in surgical management. Overall, LN#13a might be considered regional nodes for GBC, and should accordingly be dissected, and even in cases in which intraoperative sampling reveals no metastasis in LN#12, dissection of LN#13a warrants consideration.

Altered tumor metabolism has renewed interest in ketogenic strategies, despite limited clinical evidence in glioma. Whereas the ketogenic diet (KD) alone elevates intratumoral amino acids, bevacizumab (BEV) co-administration suppresses these metabolites and curtails tumor growth, pointing to a synergistic therapeutic potential. We conducted a clinical pilot study to evaluate the combination of KD and standard therapy, combining BEV, in patients with malignant glioma. A standardized modified ketogenic diet (mKD) regimen was implemented: carbohydrate intake was restricted to 10 g/day in the first week, 20 g/day in the following 2 months, and ≤30 g/day thereafter. MCT oil was administered at ≥50 mL/day, and ketone formula supplements were provided as needed. The primary endpoint was to assess safety and feasibility. 10 patients were enrolled. The duration of mKD ranged from 63 to 1,954 days, with a median of 185 days. All patients showed a rapid increase in serum ketone levels and achieved therapeutically adequate glucose-ketone index values. All participants met the predefined safety criteria, and no severe adverse events were reported. One patient discontinued the diet owing to moderate abdominal pain. The objective response rate was 50%, and notably, one patient remained on mKD for more than 5 years without tumor recurrence. The median progression-free survival from mKD initiation was 9.5 months, and the median overall survival was 31 months. The combination of mKD and standard therapy with BEV was safe and feasible in patients with malignant glioma. Larger clinical trials are needed to determine its anti-tumor efficacy and clinical benefit.

IntroductionIn this study, we re-evaluated the diagnostic utility of CSF biomarkers, including IL-10, sIL-2R, and β2-microglobulin (β2-MG), and investigated their clinical significance as potential biomarkers for PCNSL.MethodsWe analyzed patients who underwent CSF analysis for IL-10, sIL-2R, and β2-MG between May 2020 and June 2025. The diagnostic sensitivity and specificity of each biomarker were calculated. In PCNSL patients, we further evaluated the correlation of biomarker levels with tumor volume, proximity to the ventricles, recurrence status, and overall survival.ResultsA total of 100 patients were included, 32 PCNSL cases and 68 non-PCNSL cases. The average CSF levels in PCNSL cases were: IL-10: 463 pg/ml, sIL-2R: 840 U/ml, and β2-MG: 5046 μg/l. In contrast, in non-PCNSL cases, the average levels were IL-10: 2 pg/ml, sIL-2R: 107 U/ml (range 30-1726), and β2-MG: 5046 μg/l. The sensitivity and specificity for each marker were as follows: IL-10: 97% sensitivity, 96% specificity, sIL-2R: 65% sensitivity, 89% specificity, β2-MG: 87% sensitivity, 86% specificity Consistent with previous reports, IL-10 demonstrated the highest diagnostic accuracy. Correlation analysis between tumor volume and CSF marker levels revealed a significant correlation for sIL-2R, but not for β2-MG or IL-10. Regarding the tumor’s anatomical relationship with the ventricles, elevated β2-MG levels were significantly associated with ventricular involvement, while IL-10 and sIL-2R were not. Among the 32 PCNSL patients, 10 experienced recurrence or refractory disease. When comparing CSF biomarker levels between recurrent/refractory and non-recurrent cases, β2-MG was significantly higher in the recurrent/refractory group, whereas IL-10 and sIL-2R were not significantly different.ConclusionCSF IL-10 is a highly sensitive and specific biomarker for the diagnosis of PCNSL and is useful in differentiating it from other neurological conditions. However, β2-MG may be more relevant as a prognostic indicator, particularly in predicting recurrence or refractory disease.

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