Tochigi Cancer Center

Colorectal serrated lesions (SLs) are recognized as precursors of colorectal cancer (CRC); however, their detection rates and prevalence remain inadequately defined. We aimed to assess their detection rates and estimate their prevalence in the Asia-Pacific, as well as to examine their associated factors. This was a multicenter prospective study in the Asia-Pacific. Asymptomatic individuals aged 40-74 years undergoing first-time colonoscopy for CRC screening were prospectively enrolled. To ensure precise prevalence estimates, colonoscopy procedures involved repeated proximal colon inspection using pan-chromoendoscopy with indigo carmine dye. Detection rates of proximal SLs and sessile serrated lesions (SSLs) were calculated. Mixed-effects logistic regression analyses, accounting for institution-level variability, were performed to identify factors associated with proximal SL and SSL detection. Associations between SLs and synchronous advanced colorectal neoplasia (ACN) were evaluated. Among 965 participants, detection rates of proximal SLs and SSLs were 16.1% (95% confidence interval [CI], 13.8-18.5) and 8.6% (6.9-10.6), respectively. Institutional differences affected detection of proximal SLs (adjusted median OR, 1.44; 95% CI, 1.25-1.79) and SSLs (1.34; 1.18-1.62). A family history of CRC was associated with higher SSL detection (adjusted odds ratio [OR], 2.36; 95% CI, 1.29-4.33). Detection of proximal SLs was associated with synchronous ACN (OR, 1.94; 95% CI, 1.24-3.02 and 1.90; 1.18-3.07, respectively). This multicenter study demonstrates that detection rates and estimated prevalence of SLs are higher than previously reported in the Asia-Pacific and highlights the impact of institutional differences, challenging the notion of their low regional prevalence. UMIN-CTR number, UMIN 000042890.

The mechanisms of peritoneal dissemination in pancreatic ductal adenocarcinoma (PDAC) remain unclear partly owing to the lack of patient-derived models that recapitulate this process. This study aimed to establish an orthotopic model of PDAC peritoneal dissemination and to uncover the transcriptional and regulatory programs underlying this process. Organoids were established from primary pancreatic tumors and malignant effusions of patients with PDAC and orthotopically transplanted into the pancreas of immunodeficient mice to generate patient-derived orthotopic xenograft (PDOX) models. Subsequently, the organoids were rederived from pancreatic and peritoneal lesions of a representative model (PDOX12) and orthotopically reimplanted to assess the dissemination capacity. Single-nucleus RNA sequencing (snRNA-seq) and single-cell ATAC sequencing (scATAC-seq) were performed to analyze the tumors from these models. The organoids that were derived from malignant effusions reproducibly generated peritoneal metastases after orthotopic implantation. To dissect this process more precisely, we focused on one representative model (PDOX12) and rederived organoids from its pancreatic and peritoneal lesions. These organoids generated matched PDOX models that differed only in dissemination potential when reimplanted orthotopically. The results of snRNA-seq revealed a distinct subpopulation enriched in the high-dissemination model, which was characterized by the coordinated activation of genes involved in cytoskeletal dynamics, extracellular matrix remodeling, and plasticity-related signaling—suggesting a dissemination-primed state. Integration with scATAC-seq identified STAT3, SMAD3, and SOX2 as potential upstream regulators of this gene program. This study established PDOX models that isolate the peritoneal dissemination phenotype and reveal the transcriptional and regulatory programs driving this process.

This study aimed to examine the effects of concomitant use of proton-pump inhibitors (PPIs) on the survival outcomes in patients with endocrine-sensitive chemotherapy-naïve advanced breast cancer (BC) treated with palbociclib or abemaciclib. This multicenter, retrospective study was conducted at five hospitals in Japan. Data were collected from consecutive patients treated with palbociclib or abemaciclib in combination with endocrine therapy as first-line treatment for endocrine-sensitive chemotherapy-naïve advanced BC between December 2017 and August 2022. Associations between concomitant PPI use and survival outcomes were analyzed. Among 202 patients, 38 (19%) were concomitant PPI users. In the palbociclib population (n = 123), concomitant PPI use was associated with a trend toward decreased progression-free survival (PFS) and a significant reduction in overall survival (OS; crude hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.86–3.00 and crude HR, 3.51; 95% CI, 1.53–7.64, respectively). In multivariable analyses, consistent results were obtained (adjusted HR, 1.29; 95% CI, 0.66–2.53 and adjusted HR, 3.23; 95% CI, 1.28–7.67, respectively). In contrast, concomitant PPI use did not significantly affect either PFS or OS in the abemaciclib group (n = 79). Concomitant PPI use decreased the efficacy of palbociclib regardless of the formulation, with no such impact observed with abemaciclib.

Eribulin is an approved treatment option for soft tissue sarcomas (STSs) in Japan; however, real-world data regarding its safety, efficacy, and optimal dosing strategies across heterogeneous patient populations remain limited. Thus, this study aimed to evaluate clinical outcomes, treatment tolerability, and prognostic factors in patients with STS treated with eribulin. We retrospectively reviewed 50 patients with STS who received eribulin at a single institution between 2018 and 2024. Clinical variables, dosing schedules, tumor responses, survival outcomes, and adverse events (AEs) were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method; group comparisons were performed with the log-rank test. The cohort had a median age of 66 years, and eribulin was administered as first-line therapy in 24 patients. The disease control rate was 62%; one patient achieved complete response and one achieved partial response. Median PFS and OS were 4 and 19 months, respectively. Hematologic toxicities were the most common Grade ≥3 AEs, with no treatment-related cardiac events observed. Dose modifications included a bi-weekly schedule or a regimen consisting of two administrations followed by a 2-week rest period with pegfilgrastim support. No treatment discontinuations due to AEs occurred in either reduced-intensity schedule; the latter regimen demonstrated the longest treatment duration. Survival outcomes were comparable across age groups, treatment lines, histological subtypes, and tumor locations. Patients aged ≥70 years achieved a median OS of 16 months, generally consistent with previously reported outcomes in elderly sarcoma populations. Eribulin demonstrated favorable tolerability and durable disease control across diverse patient subgroups, including elderly and comorbid patients who are often ineligible for anthracycline therapy. Although no significant prognostic factors were identified, bi-weekly dosing and two-administration/2-week rest schedules were feasible, with the latter offering the advantage of pegfilgrastim support. These findings support the integration of eribulin into individualized treatment strategies for advanced STS and highlight the need for prospective studies to refine patient selection and optimize dosing approaches.

We identified an effective chemotherapy regimen in patients refractory to standard chemotherapy. We included patients with unresectable colorectal liver metastases who underwent hepatic artery infusion chemotherapy and systemic chemotherapy between January 2015 and December 2022. This study was a retrospective analysis conducted at a single center. The patients received either biweekly oxaliplatin and 5-fluorouracil through hepatic artery infusion chemotherapy as well as bevacizumab and leucovorin injected intravenously (HAIC-FOLFOX-B) or biweekly irinotecan and 5-fluorouracil by hepatic artery infusion chemotherapy and bevacizumab and leucovorin injected intravenously (HAIC-FOLFIRI-B). Of the 42 patients, 20 underwent HAIC-FOLFOX-B while 22 underwent HAIC-FOLFIRI-B treatment with response rates of 25% and 4.5%, respectively. The median overall survival and progression-free survival were 12.9 and 4.7 months and 17.4 and 7.7 months in patients undergoing HAIC-FOLFOX-B and HAIC-FOLFIRI-B, respectively. The overall incidence of grade 3/4 toxicity was 23.8%. However, no treatment-related deaths occurred. Functional catheter-associated problems occurred in 9.5% of the patients. Hepatic arterial occlusion occurred in three patients (7.1%); catheter-associated infection occurred in one (2.4%) patient. However, these occurrences were not life-threatening complications. HAIC-FOLFOX-B and HAIC-FOLFIRI-B might improve survival in patients with unresectable colorectal liver metastases and in those who underwent both systemic oxaliplatin-based and irinotecan-based chemotherapies and were refractory to them. HAIC FOLFOX-B and FOLFIRI-B regimens might be effective therapeutic options in patients with unresectable colorectal liver metastases refractory to standard systemic chemotherapy.

Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) and nab-paclitaxel + gemcitabine are recommended as first-line treatments for metastatic pancreatic cancer. S-1, irinotecan, and oxaliplatin (S-IROX) demonstrated activity in a phase Ib trial in this population. Therefore, these three regimens were directly compared. This randomized phase II/III trial was performed at 45 centers in Japan. Eligible patients age 20-75 years with an Eastern Cooperative Oncology Group performance status of 0 or 1 and pathologically confirmed metastatic or recurrent pancreatic cancer were randomly assigned (1:1:1) to receive mFOLFIRINOX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes, l-leucovorin 200 mg/m2 over 2 hours, each once daily on day 1, and fluorouracil 2,400 mg/m2 over 46 hours on days 1-3, every 2 weeks), S-IROX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes on day 1, and S-1 80 mg/m2/day administered orally twice daily on days 1-7, every 2 weeks), or nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) on days 1, 8, and 15 every 4 weeks. The primary end point was overall survival (OS). A total of 527 patients were enrolled, with 426 included in the planned interim analysis. The median OS was 14.0 months (hazard ratio [HR], 1.31 [95% CI, 0.97 to 1.77]) and 13.6 months (HR, 1.35 [95% CI, 1.00 to 1.82]) in the mFOLFIRINOX and S-IROX groups, respectively, as compared with 17.1 months in the nab-paclitaxel + gemcitabine group. The predictive probability of achieving superiority in the final analysis was <1% in both groups. Thus, the trial was terminated owing to its futility. Grade 3 to 4 anorexia was more frequent in the mFOLFIRINOX (23.3%) and S-IROX (27.5%) groups than in the nab-paclitaxel + gemcitabine group (5.0%). Neither mFOLFIRINOX nor S-IROX appeared to be superior compared with nab-paclitaxel + gemcitabine as the first-line treatment for metastatic or recurrent pancreatic cancer.

We report a rare case of hepatic segmental atrophy that was initially suspected to be hepatocellular carcinoma (HCC). An 80-year-old man presented with a new 3 cm hepatic lesion that met LI-RADS-5 criteria. However, follow-up CT performed 1 month later showed loss of arterial hyperenhancement, progressive delayed peripheral enhancement, and a reduction in lesion size. MRI subsequently demonstrated high signal intensity on T2-weighted and diffusion-weighted images, without true diffusion restriction. Based on these imaging features, spontaneous necrosis of scirrhous-type HCC was suspected, and surgical resection was undertaken. Histopathological examination revealed hepatic segmental atrophy with no evidence of malignancy. Segmental atrophy can closely mimic HCC on imaging, potentially leading to misdiagnosis and unnecessary surgery. Careful evaluation of atypical features—such as the absence of true washout, lack of restricted diffusion, disproportionate capsule-like structures, and progressive morphological changes—may assist in distinguishing segmental atrophy from malignancy.

Background Tumor differentiation is recognized as a prognostic predictor in certain malignancies such as gastric cancer. Although some studies have indicated a prognostic role for tumor differentiation in esophageal squamous cell carcinoma (ESCC), that is not widely known. Therefore, in this study, we retrospectively investigated the prognostic value of tumor differentiation in ESCC. Methods This study investigated the prognostic value of tumor differentiation by using data from patients who underwent radical esophagectomy for ESCC. The characteristics of patients with well differentiated, moderately differentiated, and poorly differentiated ESCCs were investigated and compared Survival analysis was conducted using Kaplan–Meier analysis and the Cox proportional hazards model. Results This study included 226 ESCC patients. The frequencies of each ESCC type were as follows: well-differentiated ESCC, 49 cases (21.7%); moderately differentiated ESCC, 149 cases (65.9%); and poorly differentiated ESCC, 28 cases (12.4%). Although Kaplan–Meier analysis showed no statistical significance for overall survival (OS) or recurrence (p = 0.083 and p = 0.36, respectively), Cox regression analysis demonstrated that tumor differentiation, particularly poorly differentiated ESCC, was a statistically significant factor for survival both in univariable and multivariable analyses (p = 0.03 and p < 0.01, respectively). Conclusions Our findings suggest that tumor differentiation in ESCC may be a useful predictor of survival. However, owing to the small sample size, especially in patients who received preoperative treatment, further studies are required to establish definitive evidence.