BACKGROUND:The metabolic landscape of biliary tract cancer (BTC) remains poorly characterized. This study aimed to identify tumor-specific metabolic alterations in BTC using paired tumor and adjacent normal tissues. METHODS:Metabolomic profiling was performed on paired tumor and adjacent normal tissues from 71 patients with BTC using capillary electrophoresis time-of-flight mass spectrometry. Differential metabolites were identified using paired statistical analysis with false discovery rate correction. Pathway enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes database. RESULTS:Seventeen metabolites were significantly altered between tumor and normal tissues. Pathway analysis identified glycerophospholipid metabolism as the most enriched pathway, driven by water-soluble precursor and intermediate metabolites, including phosphorylcholine, CDP-choline, and ethanolamine phosphate. Hierarchical clustering demonstrated partially distinct metabolic patterns between tumor and normal tissues, with substantial inter-sample variability observed among tumor samples. Metabolites related to amino sugar and nucleotide sugar metabolism were also increased in tumor tissues. Additional pathways, including nicotinate and nicotinamide metabolism and arginine and proline metabolism, were also enriched. Principal component analysis showed partial separation between tumor and normal samples, indicating global metabolic differences between the two groups. These findings indicate metabolic alterations across multiple pathways in BTC. CONCLUSIONS:Paired tissue metabolomics revealed coordinated metabolic alterations in BTC involving choline phospholipid precursor metabolism, amino sugar and nucleotide sugar metabolism, and additional amino acid-related pathways. These results highlight the presence of broad metabolic reprogramming in BTC and underscore the importance of tissue-based metabolomic profiling for characterizing tumor metabolism.

IntroductionInflammatory bowel diseases (IBD), especially ulcerative colitis, are associated with a high risk of carcinogenesis. D-allose, a D-glucose epimer, exhibits antioxidant and antitumor activities. This study aimed to examine the effects of D-allose on colitis-associated carcinogenesis.MethodsA mouse model of colitis-associated carcinogenesis was established followed by treatment with D-allose. In vitro, ER stress and mitochondrial function in RAW 264.7 macrophages and the migration and proliferation of Caco-2 cells were analyzed to elucidate the underlying mechanisms. Colonic tissues obtained from IBD patients with were subjected to analyze ER stress in macrophages.ResultsD-allose administration significantly reduced the tumor number, hemorrhage, inflammation score, and macrophage infiltration in the AOM/DSS model. D-allose suppressed ER stress signal and mitochondrial dysfunction in LPS treated RAW 264.7 macrophages. D-allose suppressed ER stress marker Bip and CHOP expression in thapsigargin treated RAW 264.7. In IBD patient’s colon, ER stress marker Bip and CHOP positive macrophage infiltration was detected in both inflammatory and tumor areas. The level of fluorescence labeled M6~G1M9 oligosaccharides increased in the LPS-treated RAW 264.7 macrophages, while thapsigargin or D-allose had no effect. In Caco-2 cells, D-allose suppressed phosphorylated AMPK expression, reduced migratory activity. D-allose inhibited glycolysis, and decreased cell proliferation through TXNIP upregulation.ConclusionD-allose suppressed inflammation and tumor development in a colitis-associated carcinogenesis model. D-allose restoring macrophage ER stress and mitochondrial dysfunction, and inhibiting colon cancer cell migration and proliferation. Therefore, D-allose may represent as a promising therapeutic and preventive agent for IBD and inflammation-associated carcinogenesis.

PURPOSE:This study investigated the prognostic value of the preoperative tumor-to-blood pool standardized uptake value ratio (TBR) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients undergoing pancreatoduodenectomy (PD) for distal bile duct and ampullary cancers. METHODS:We retrospectively reviewed 100 patients who underwent PD between January 2011 and December 2024. TBR was calculated as tumor SUVmax divided by the SUV of the descending aorta. The optimal cutoff for overall survival (OS) was determined using time-dependent ROC curve analysis. Survival outcomes were evaluated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS:A TBR cutoff of 2.30 was identified. Patients with high TBR (≥ 2.30) had significantly higher preoperative bilirubin, C-reactive protein, and CA19-9 levels, more frequent lymph node metastasis, poorer differentiation, and longer operation time than those with low TBR. High TBR was associated with worse OS and recurrence-free survival (RFS) (both p < 0.001). Multivariate Cox regression confirmed high TBR as an independent predictor of poor OS (Hazard Ratio: 2.88, p = 0.044). CONCLUSIONS:Preoperative TBR on FDG-PET/CT was associated with adverse pathological features and inferior survival in patients undergoing PD for distal bile duct and ampullary cancers. These findings suggest that TBR may be useful as an adjunctive PET-derived marker for preoperative risk stratification.

BACKGROUND/AIM:This study aimed to evaluate the preventive effect of anti-adhesive materials (AAMs) on the incidence of small bowel obstruction (SBO) and to investigate the risk factors for SBO within five years after gastrectomy for gastric cancer. PATIENTS AND METHODS:This multicenter cohort study included 2,077 patients with gastric cancer who underwent total gastrectomy (TG) or distal gastrectomy (DG). Patients were followed for five years after surgery. Clinical characteristics associated with AAM use and risk factors for postoperative SBO were analyzed. RESULTS:Among the included patients, 959 received AAMs and 1,118 did not. Intraoperative blood loss and operative time were greater in the AAM group. Open surgery and drain placement were more frequently performed in the AAM group. SBO occurred in 4.8% of patients in the AAM group and 4.7% in the non-AAM group. A higher incidence of postoperative intra-abdominal abscess was observed in the AAM group than in the non-AAM group (6.6% vs. 3.7%, p=0.003). Multivariate analysis identified TG [odds ratio (OR)=1.81, p=0.004], postoperative ileus (OR=2.61, p=0.043), and reoperation (OR=4.88, p<0.001) as independent risk factors for SBO within five years after gastrectomy. CONCLUSION:The use of AAMs did not demonstrate a significant preventive effect on postoperative SBO after radical gastrectomy for gastric cancer and may be associated with an increased risk of postoperative intra-abdominal abscess.

Complete resection remains the only potentially curative treatment for localized intrahepatic cholangiocarcinoma (iCCA), yet postoperative recurrence is common, particularly in patients with high-risk disease. Neoadjuvant systemic therapy may permit earlier control of occult micrometastatic disease, optimize the delivery of systemic treatment, and provide an in vivo assessment of tumor biology prior to major hepatectomy. These potential benefits must be balanced against treatment-related toxicity, surgical delay, and the risk of disease progression precluding resection. Early evidence was primarily derived from retrospective studies, which yielded inconsistent survival outcomes and exhibited substantial vulnerability to confounding and treatment-selection bias. The single-arm NEO-GAP trial subsequently demonstrated the feasibility of administering neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel followed by surgical resection. More recently, the randomized phase II–III ZSAB-neoGOLP trial showed that neoadjuvant gemcitabine–oxaliplatin, lenvatinib, and toripalimab followed by surgery prolonged median event-free survival compared with upfront surgery (median: 18.0 vs. 8.7 months) without substantially compromising surgical feasibility. However, the interim overall survival analysis was inconclusive, and the generalizability of these findings beyond selected, medically fit patients treated at Chinese centers remains uncertain. This narrative review critically appraises the evolving evidence, discusses patient selection and perioperative treatment, and identifies priorities for future research. Current evidence supports the selective consideration of neoadjuvant therapy in medically fit patients with technically resectable but oncologically high-risk iCCA, rather than its routine use in all resectable cases.

BACKGROUND:Germline pathogenic variants (GPVs) in cancer predisposition genes increase cancer risk, but their population-level prevalence in Japan remains unclear. AIM:To estimate the prevalence of GPV carriers of hereditary cancer predisposition syndromes (HCPSs) in the Japanese population. DATA SOURCE AND METHODS:A cross-sectional analysis of the Tohoku Medical Megabank Organization datasets was conducted to assess allele frequencies of rare GPVs, estimate carrier prevalence, and describe variant distribution. RESULTS:The cumulative allele frequency of rare GPVs of cancer predisposing genes was 1.47% for autosomal dominant and 3.20% for autosomal recessive diseases. The estimated prevalence of GPV carriers was 2.90% (1 in 35 individuals) and 0.10% (1 in 977 individuals) for autosomal dominant HCPSs and autosomal recessive HCPSs, respectively; ~6.19% of the population (1 in 16 individuals) were carriers. Variant types differed across genes, and hotspot variants had a significant impact on allele frequencies. Moreover, 47 structural variants (0.28%) having the potential to cause structural disruption were identified. CONCLUSIONS:Allele frequency analysis of rare GPVs of cancer predisposition genes offered valuable insight into the prevalence of GPV carriers of HCPSs in the Japanese population. Hotspot variants may represent founder mutations within specific ethnic groups, and their presence or absence could affect gene-specific allele frequencies.

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and limited therapeutic options. Cellular senescence contributes to persistent inflammation through the senescence-associated secretory phenotype (SASP), suggesting that modulation of senescence may represent a novel therapeutic strategy. Here, we investigated the therapeutic effects of probiotic Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) treatment and genetic senolysis on dextran sulfate sodium (DSS)-induced colitis, using p16Ink4a-CreERT2-tdTomato (PT) mice to trace senescent cells and p16Ink4a-CreERT2-DTR-tdTomato (PD) mice to selectively eliminate p16+ cells after diphtheria toxin (DT) treatment. For metagenomic analysis, fecal DNA was evaluated to assess microbial diversity, taxonomic composition, and functional pathways. In PT mice, DSS induced colon shortening, splenomegaly, mucosal inflammation, and signal transducer and activator of transcription 3 (STAT3) activation with tdTomato+ senescent cell accumulation in α-smooth muscle actin (α-SMA)-, cluster of differentiation 31 (CD31)-, platelet-derived growth factor receptor α (PDGFRα)-, and c-Kit-positive compartments. Probio-M9 alleviated these changes, reduced senescent cell burden, and suppressed SASP-associated inflammation, without altering p21 or p53 expression. Metagenomic analysis showed Probio-M9 reshaped microbial composition and metabolic pathways, including selective enrichment of beneficial taxa. In PD mice, DT-mediated senolysis reduced SASP expression, STAT3 phosphorylation, and p21 levels, while increasing p53 and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. DT intervention significantly changed inter-bacterial interaction networks. Both probiotic intervention and genetic senolysis alleviated DSS-induced colitis by reducing the accumulation of p16+ senescent cells. Furthermore, analyses of human IBD specimens and independent public transcriptomic datasets demonstrated increased senescence-associated signatures in inflamed tissues and enrichment of senescence signatures in myeloid immune cells, supporting the clinical relevance of our findings. Together, these results identify inflammation-associated cellular senescence as a therapeutic target in IBD and suggest that Probio-M9 alleviates intestinal inflammation by modulating the microbiota–metabolism–senescence axis.

Robotic distal pancreatectomy (RDP) is being adopted increasingly, but its impact on clinically relevant postoperative pancreatic fistula (CR-POPF) compared with that of open distal pancreatectomy (ODP) remains unclear. We compared the incidences of CR-POPF after RDP vs. ODP, focusing on postoperative inflammation and drain bacterial contamination. The subjects of this retrospective analysis were 125 patients who underwent stapler-based distal pancreatectomy at a single center between 2013 and 2025 (RDP, n = 50; ODP, n = 75). Propensity score matching yielded 32 matched patients in each group. Outcomes included CR-POPF, postoperative C-reactive protein, drain amylase levels, and drain fluid cultures on postoperative days (PODs) 1 and 3. Multivariable analysis was performed to identify the factors associated with CR-POPF. After matching, it was evident that the RDP group had less blood loss (median 95 vs. 573 mL, p < 0.001) and fewer transfusions (3

Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.

Neoadjuvant chemoradiotherapy (NACRT) is increasingly used for pancreatic ductal adenocarcinoma (PDAC), yet the optimal regimen remains unclear. This phase II trial evaluated the feasibility and efficacy of a short-course NACRT regimen comprising gemcitabine, S-1, and hypofractionated radiotherapy in patients with resectable (R) or borderline resectable (BR) PDAC. Patients received NACRT with gemcitabine (1000 mg/m2 on days 1 and 8), oral S-1 (60 mg/m2/day for 14 days), and hypofractionated radiotherapy (30 Gy in 10 fractions over 2 weeks). The primary endpoint was the R0 resection rate. Secondary endpoints included treatment completion, adverse events, tumor response, and survival. In total, 54 patients were enrolled. Treatment completion ranged from 87 to 98

Although pancreatic islet transplantation outcomes have improved, further refinements are required to extend the insulin withdrawal period. The present study examined whether intravenous D-allose administration improves insulin secretion when pancreatic islets are transplanted into type 1 diabetes model mice. Alterations in casual blood glucose levels, intraperitoneal glucose tolerance test (IPGGT) results, the number of apoptotic cells in the engrafted cells, and caspase 3, heme oxygenase 1 and nitric oxide synthase 2 (NOS2) expression in the engrafted cells were examined using the following groups of type 1 diabetic model mice with transplanted pancreatic islets: Mice that received an intravenous injection of D-allose (D-group) and those that received physiological saline as a control (C-group). The mice in the D-group had significantly lower casual blood sugar levels for a longer duration than those in the C-group. Regarding IPGGT, mice treated with D-allose exhibited smaller changes in blood glucose levels compared with untreated mice. Consequently, the incremental area under the curve of glucose in D-allose-treated mice was significantly lower than that in D-allose-untreated mice. No difference was observed in the number of engrafted cells between the groups. NOS2 mRNA expression in the engrafted cells of the D-group tended to be higher than that in the C-group. In conclusion, intravenous administration of D-allose significantly improved hyperglycemia and maintained stable blood glucose levels in type 1 diabetic mice after islet transplantation. Since there was no difference in the number of engrafted cells or apoptotic cells with or without intravenous D-allose administration, D-allose was considered to be effective in maintaining the cellular function of insulin secretion.

Subsequent to a medical examination, a 61-year-old male was referred to our hospital with jaundice. He was diagnosed with intrahepatic cholangiocarcinoma involving the hepatic hilum and was referred to our department to undergo a left trisectionectomy of the liver, extrahepatic bile duct resection, and regional lymphadenectomy. He was discharged on postoperative day 39 without liver failure. Two months postoperatively, positron-emission tomography/computed tomography(PET/ CT)indicated recurrences in the bone, and paraaortic lymph node. Gemcitabine and cisplatin combination first-line therapy was administered. Disease progression occurred after 4 courses of therapy. Gene panel testing was performed and the patient was switched to pembrolizumab owing to high microsatellite instability. After 2 courses of pembrolizumab, notable shrinkage of the paraaortic lymph node recurrence was confirmed on computed tomography as well as a partial response. PET-CT revealed disappearance of abnormal accumulation in all lesions at 20 months postoperatively. This has been sustained for 24 months following surgery without remarkable immune-related side-effects.

BACKGROUND:Based on molecular characteristics, deficient DNA mismatch repair (dMMR) solid tumors are largely divided into three categories: somatically MLH1-hypermethylated tumors, Lynch syndrome (LS)-associated tumors, and Lynch-like syndrome (LLS)-associated tumors. The incidence of each of these conditions and the corresponding pathogenic genes related to LLS remain elusive. METHODS:We identified dMMR tumors in 3609 tumors from 9 different solid organs, including colorectal cancer, gastric cancer, small-bowel cancer, endometrial cancer, ovarian cancer, upper urinary tract cancer, urinary bladder cancer, prostate cancer, and sebaceous tumor, and comprehensively summarized the characterization of dMMR tumors. Characterization of dMMR tumors were performed as loss of at least one of MMR proteins (MLH1, MSH2, MSH6, and PMS2), by immunohistochemistry, followed by MLH1 promotor methylation analysis and genetic testing for MMR genes where appropriate. Somatic variant analysis of MMR genes and whole exome sequencing (WES) were performed in patients with LLS. RESULTS:In total, the incidence of dMMR tumors was 5.9% (24/3609). The incidence of dMMR tumors and the proportion of the three categorized dMMR tumors varied considerably with different tumor types. One to three likely pathogenic/pathogenic somatic MMR gene variants were detected in 15 out of the 16 available LLS tumors. One patient each from 12 patients who gave consent to WES demonstrated non-MMR germline variants affect function (POLQ or BRCA1). CONCLUSIONS:Our data regarding the LS to LLS ratio would be useful for genetic counseling in patients who are suspected to have LS, though the genetic backgrounds for the pathogenesis of LLS need further investigation.

BACKGROUND:/Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs.METHODS:We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups.RESULTS:Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group.CONCLUSIONS:The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.

Background: Despite a strong association between nutritional indices and disease prognosis, evidence regarding the evaluation of nutritional indices after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC) is insufficient. We evaluated the clinical significance of the prognostic nutritional index (PNI) in patients with resectable (R-) and borderline resectable (BR-) PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by pancreatic resection. Methods: We assessed 153 patients with R- and BR-PDAC who underwent NACRT followed by curative resection between 2009 and 2022. We evaluated the association between preoperative PNI after NACRT and short- and long-term outcomes. Results: The median preoperative PNI value after NACRT was 42.1, and the optimal cutoff value from the time-dependent receiver operating characteristic curve was 38.6. The low PNI group (PNI < 38.6, n = 44) exhibited significantly worse inflammatory parameters, surgical outcomes, and prognoses than the high PNI group (PNI >= 38.6, n = 109). Multivariate analysis identified preoperative PNI <= 38.6 (hazard ratio [HR]: 2.32, 95% confidence interval [CI]: 1.00-5.38, p = .049), blood loss >= 1642 mL (HR: 3.05, 95% CI: 1.65-5.64, p < .001), node positive pathology (HR: 2.10, 95% CI: 1.32-3.34, p = .002), and lack of postoperative adjuvant chemotherapy (HR: 3.55, 95% CI: 2.05-6.15, p < .001) as significant predictors of overall survival. Conclusions: For patients with R- and BR-PDAC receiving preoperative treatment, it is imperative to closely monitor their nutritional status when determining the optimal surgical procedure timing.

BACKGROUND:A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach. CASE PRESENTATION:We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space. CONCLUSION:Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence.