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Backgrounds Poorly differentiated clusters (PDCs), defined as solid cancer nests comprising ≥ 5 cancer cells lacking tubular formation, may reflect the phenotype of epithelial-mesenchymal transition. The diagnostic utility in pathological practice and clinical significance in pancreatic ductal carcinoma (PDAC) has not been fully explored. This study aimed to investigate the presence of PDCs in PDAC and evaluate their clinical implications. Methods We examined the presence of PDCs in 102 cases with PDAC. Tumor clusters with ≥ 5 clusters were classified as high PDCs and < 5 were classified as low PDCs. The association of pathological parameters and survival was assessed for high and low PDCs. Subgroup analyses were also performed for 37 cases following neoadjuvant chemotherapy (NAT). Results High PDCs were significantly associated with larger tumors, advanced pT category (≥ T3), lymphatic and vascular invasion, positive surgical margins, high tumor budding (TB), elevated CA19-9 levels, and increased recurrence risk ( P  = 0.014, 0.021, 0.011, 0.013, 0.026, < 0.001, 0.016, 0.027, respectively). Moreover, this was associated with worse overall survival and disease-free survival of PDAC, especially in cases following NAT ( P  < 0.001). Additionally, high PDCs in cases following NAT was an independent prognostic factor for shorter overall (Hazard ratio (HR): 9.131, P  = 0.012) and disease-free survival (HR: 3.896, P  = 0.018) in multivariable Cox regression analysis, exceeding TB in prognostic impact. Conclusion PDCs in the actual pathological diagnosis are more useful as a prognostic marker for PDAC than TB. Due to the limited sample size and broad confidence intervals, the findings of this study should be interpreted with caution and require validation in larger, independent cohorts.

Background Cholecystocolonic fistula (CCF) is a rare complication of advanced Mirizzi syndrome (MS) and often presents with chronic watery diarrhea due to abnormal bile entry into the colon. The optimal role of endoscopic treatment in MS with CCF remains uncertain. Case Summary A 63‐year‐old man presented with three months of chronic watery diarrhea. Computed tomography, magnetic resonance imaging, and endoscopic retrograde cholangiopancreatography showed an impacted cystic duct confluence stone, pneumobilia, and contrast passage into the colon, establishing the diagnosis of MS complicated by CCF. A biliary stent improved his symptoms, and peroral cholangioscopy–guided electrohydraulic lithotripsy subsequently enabled complete stone clearance. Cholangioscopy revealed no grossly apparent neoplastic lesions within the gallbladder. The patient subsequently underwent subtotal cholecystectomy with partial colectomy without biliary reconstruction. Histopathology revealed chronic cholecystitis without malignancy, and the postoperative course was uneventful. Conclusion A stepwise approach combining cholangioscopy‐guided lithotripsy with targeted surgery can reduce operative complexity and facilitate safe management of advanced MS with CCF.

Background Long-chain fatty acyl CoA synthetase 4 (ACSL4) is crucial for lipid metabolism, primarily catalyzing the formation of 12–20 carbon chain fatty acids. ACSL4 is upregulated in various cancers and linked to aggressive behavior and poor survival. A bioinformatics study showing ACSL4 upregulation in pancreatic cancer. However, utility for actual pathological diagnosis and clinical significance in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) are unexplored. This study aimed to investigate ACSL4 expression in PDAC and IPMN, and evaluate its clinical implications. Methods We examined ACSL4 expression using immunohistochemistry in 165 patients with PDAC and IPMN. Differences in ACSL4 expression between malignant and benign lesions were evaluated using the Pearson χ2 test. The association between ACSL4 expression, pathological parameters, and survival was assessed through Kaplan-Meier and Cox regression analyses in 96 patients with invasive cancer. Results Compared to normal pancreatic ducts, low-grade pancreatic intraepithelial neoplasm, and intraductal papillary mucinous adenoma (IPMA) (3.3%, 3.4%, and 2.7%, respectively), ACSL4 expression was significantly higher in invasive PDAC, noninvasive intraductal papillary mucinous carcinoma (IPMC), and invasive IPMC (77%, 86.7%, and 93.9%, respectively). In invasive cancers, low ACSL4 expression was associated with a higher frequency of lymphovascular invasion and recurrence and shorter disease-free survival ( P  = 0.006). Additionally, low ACSL4 expression was an independent prognostic factor for shorter disease-free survival in multivariable Cox regression analysis (HR = 2.409, 95% CI: 1.121–5.180, P  = 0.024). Conclusion ACSL4 expression helps differentiate cancerous from precancerous lesions in pancreatic cancer, but low expression is linked to a higher frequency of lymphovascular invasion and shorter disease-free survival in invasive cases. Due to the limited sample size and broad confidence intervals, the findings of this study should be interpreted with caution and require validation in larger, independent cohorts.

Key Clinical Message The characteristics of liver dysfunction due to adult‐onset Still's disease are not specific. Differentiating from autoimmune hepatitis is important in deciding whether to continue corticosteroid therapy, and also in terms of management of cirrhosis and surveillance of hepatocellular carcinoma. Liver biopsy is thought to be the most important determinant for differential diagnosis. Hematoxylin–eosin staining of a section of the liver shows hepatocyte shedding around the central vein (arrowheads) and eosinophil infiltration at the time of the first acute liver injury in October 2017.

Second-line chemotherapy (2L) is recommended after gemcitabine plus nab-paclitaxel (GnP) first-line chemotherapy (1L) for unresectable pancreatic cancer (UR-PC). However, in routine clinical practice, not all patients proceed to 2L. This retrospective study aimed to identify baseline clinical and biological factors associated with 2L eligibility. We retrospectively reviewed the data of 124 consecutive patients with UR-PC who received 1L GnP between 2016 and 2024 at a single center, excluding those with postoperative recurrence. Patients were grouped by 2L receipt [2L( +), n = 63] or non-receipt [2L( -), n = 61]. Ascites was assessed based on baseline imaging findings and additionally classified as none, mild, or moderate-to-severe. Overall survival (OS) was assessed from completion or discontinuation of 1L GnP, and progression-free survival (PFS) was assessed from 1L GnP initiation, using Kaplan-Meier and Cox regression analyses. Cox regression analysis for OS included only baseline variables. The 2L( +) group less frequently had baseline ascites and better Eastern Cooperative Oncology Group performance status. The distribution of ascites severity also differed significantly between the groups. Median OS was 7.1 vs. 1.9 months (p < 0.001) and median PFS was 5.9 vs. 3.0 months (p = 0.004) for 2L( +) vs. 2L( -). Multivariate Cox analysis identified the absence of ascites as an independent factor associated with longer OS (hazard ratio [HR] 0.595, 95% confidence interval 0.367-0.963; p = 0.035). Multivariate logistic regression revealed that the absence of ascites independently predicted 2L eligibility (adjusted odds ratio 4.435, 95% CI 1.583 - 12.423, p = 0.005). Baseline ascites was independently associated with reduced eligibility for 2L after 1L GnP in patients with UR-PC. Nevertheless, patients who received 2L had longer survival than those who did not, including among those with baseline ascites. However, this association should be interpreted cautiously because of the retrospective design and potential treatment-selection bias. These findings may support individualized reassessment and proactive supportive care to maximize opportunities for sequential chemotherapy.

Ionizing radiation (IR)-induced double-strand breaks (DSBs) are primarily repaired by non-homologous end joining or homologous recombination (HR) in human cells. DSB repair requires adenosine-5′-triphosphate (ATP) for protein kinase activities in the multiple steps of DSB repair, such as DNA ligation, chromatin remodeling, and DNA damage signaling via protein kinase and ATPase activities. To investigate whether low ATP culture conditions affect the recruitment of repair proteins at DSB sites, IR-induced foci were examined in the presence of ATP synthesis inhibitors. We found that p53 binding protein 1 foci formation was modestly reduced under low ATP conditions after IR, although phosphorylated histone H2AX and mediator of DNA damage checkpoint 1 foci formation were not impaired. Next, we examined the foci formation of breast cancer susceptibility gene I (BRCA1), replication protein A (RPA) and radiation 51 (RAD51), which are HR factors, in G2 phase cells following IR. Interestingly, BRCA1 and RPA foci in the G2 phase were significantly reduced under low ATP conditions compared to that under normal culture conditions. Notably, RAD51 foci were drastically impaired under low ATP conditions. These results suggest that HR does not effectively progress under low ATP conditions; in particular, ATP shortages impair downstream steps in HR, such as RAD51 loading. Taken together, these results suggest that the maintenance of cellular ATP levels is critical for DNA damage response and HR progression after IR.