Duodenitis associated with ulcerative colitis and pouchitis after total colectomy successfully treated with upadacitinib: A case report.

A 27-year-old man had ulcerative colitis (UC) 1 year prior and underwent a colectomy and two-stage ileal pouch-anal anastomosis for medically refractory UC 6 months ago. He visited our department with epigastric pain and discomfort, increased stool frequency, and bloody diarrhea. Esophagogastroduodenoscopy revealed continuous diffuse friable mucosa, erosions, and edema in the duodenum, and pouchoscopy revealed multiple ulcers and purulent mucus adhesions. Based on endoscopic and pathological findings, the patient was diagnosed with duodenitis associated with UC and pouchitis, for which he received oral prednisolone (40 mg/day) and ciprofloxacin. The frequency of stools and occurrence of bloody diarrhea reduced, and epigastric pain and discomfort improved after 2 weeks. However, when prednisolone was discontinued, the symptoms worsened, albumin level decreased, and C-reactive protein level increased. Following this, we administered a 20 mg prednisolone sodium phosphate enema once daily, and the patient's symptoms improved. However, the symptoms relapsed when the enema was discontinued. Assuming that the patient had steroid-dependent duodenitis associated with UC and pouchitis, we initiated upadacitinib. His symptoms improved within a few days, and biomarkers returned to normal after 1 month. Nine months after initiating the upadacitinib treatment, endoscopic remission was achieved in the mucosa of the duodenum and pouch. The patient has been in clinical remission for 1 year without any adverse events.

Recurrence rates and risk factors in obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding (OGIB), defined in 2010, involves bleeding from the GI tract that remains unexplained after standard diagnostic procedures. OGIB, which accounts for about 5% of all GI bleeds, poses diagnostic and management challenges, particularly due to the anatomical features of the small intestine. Advances in capsule endoscopy (CE) and balloon-assisted endoscopy have improved the diagnostic and therapeutic landscape for small intestinal lesions. Objective: To determine the recurrence rate and identify risk factors for recurrence following diagnostic and therapeutic interventions using CE and balloon-assisted endoscopy in patients with OGIB. Methods: A retrospective cohort study at Gifu University Hospital analyzed CE procedures for patients with OGIB from 2008 to 2022. Patients underwent CE with subsequent treatments based on the findings. Statistical analyses, including Kaplan-Meier and Cox proportional hazards models, were used to estimate cumulative recurrence rates and identify recurrence risk factors. Results: Out of 417 patients, 65.2% had positive CE findings, leading to therapeutic interventions in 16.3% of cases. The cumulative recurrence rates at 12, 24, and 36 months were 4.3%, 9.0%, and 13.9%, respectively. Liver cirrhosis (hazard rate: 4.15, 95% confidence interval 1.88-9.18, p < 0.01) was identified as a significant risk factor for recurrence. Conclusions: A significant recurrence rate in OGIB patients, with liver cirrhosis being a major risk factor. Despite diagnostic and therapeutic advances, a comprehensive approach including careful follow-up and consideration of risk factors is essential for management.

Transformed follicular lymphoma with laryngeal edema requiring tracheal intubation after tisagenlecleucel treatment: A case report.

RATIONALE: Cytokine release syndrome (CRS) is a common adverse event of chimeric antigen receptor T (CAR-T) cell therapy. CRS is generally a systemic inflammatory reaction, but in rare cases, it can occur in specific body areas and is referred to as "local CRS (L-CRS)." A case of laryngeal edema due to L-CRS that required tracheal intubation because of the lack of response to tocilizumab (TCZ) and dexamethasone (DEX) is reported. PATIENT CONCERNS: A 67-year-old woman with relapsed transformed follicular lymphoma was treated with CAR-T cell therapy. Although she had been given TCZ and DEX for CRS, neck swelling appeared on day 4 after infusion. DIAGNOSES: Laryngoscopy showed severe laryngeal edema, which was presumed to be due to L-CRS, since there were no other apparent triggers based on history, physical examination, and computed tomography. INTERVENTIONS: Tracheal intubation was performed because of the risk of upper airway obstruction. Ultimately, 4 doses of tocilizumab (8 mg/kg) and 6 doses of dexamethasone (10 mg/body) were required to improve the L-CRS. OUTCOMES: On day 7, laryngeal edema improved, and the patient could be extubated. LESSONS: The lessons from this case are, first, that CAR-T cell therapy may induce laryngeal edema in L-CRS. Second, TCZ alone may be ineffective in cervical L-CRS. Third, TCZ, as well as DEX, may be inadequate. In such cases, we should recognize L-CRS and manage it early because it may eventually progress to laryngeal edema that requires securing the airway.

Successful Surgical Resection of Pancreatic Arteriovenous Malformation Complicated by Acute Pancreatitis: A Case Report.

A 73-year-old man presented with left hypochondral pain. Dynamic computed tomography (CT) revealed abnormal vessels surrounding the pancreas, leading to a suspected diagnosis of pancreatic arteriovenous malformation (PAVM). At the time of the initial examination, dynamic CT revealed mild acute pancreatitis, and PAVM was diagnosed based on the findings of dynamic CT. Although repeated abdominal pain was observed after the improvement of pancreatitis, distal pancreatectomy was performed. At >1 year after surgery, no recurrence of PAVM was observed. Surgical resection should be considered in patients with symptomatic PAVM.

EL4 Murine-Lymphoma-Stromal-Cell Fusion Hybrids Observed With Multiple Distinct Morphologies in the Primary Tumor and Metastatic Organs of a Syngeneic Mouse Model.

BACKGROUND/AIM: We and others have previously shown that cell fusion plays an important role in cancer metastasis. Color coding of cancer and stromal cells with spectrally-distinct fluorescent proteins is a powerful tool, as pioneered by our laboratory to detect cell fusion. We have previously reported color-coded cell fusion between cancer cells and stromal cells in metastatic sites by using color-coded EL4 murine lymphoma cells and host mice expressing spectrally-distinct fluorescent proteins. Cell fusion occurred between cancer cells or, between cancer cells and normal cells, such as macrophages, fibroblasts, and mesenchymal stem cells. In the present study, the aim was to morphologically classify the fusion-hybrid cells observed in the primary tumor and multiple metastases EL4 formed from cells expressing red fluorescent protein (RFP) in transgenic mice expressing green fluorescent protein (GFP), in a syngeneic model. MATERIALS AND METHODS: RFP-expressing EL4 murine lymphoma cells were cultured in vitro. EL4-RFP cells were harvested and injected intraperitoneally into immunocompetent transgenic C57/BL6-GFP mice to establish a syngeneic model. Two weeks later, mice were sacrificed and each organ was harvested, cultured, and observed using confocal microscopy. RESULTS: EL4 intraperitoneal tumors (primary) and metastases in the lung, liver, blood, and bone marrow were formed. All tumors were harvested and cultured. In all specimens, RFP-EL4 cells, GFP-stromal cells, and fused yellow-fluorescent hybrid cells were observed. The fused hybrid cells showed various morphologies. Immune cell-like round-shaped yellow-fluorescent fused cells had a tendency to decrease with time in liver metastases and circulating blood. In contrast fibroblast-like spindle-shaped yellow-fluorescent fused cells increased in the intraperitoneal primary tumor, lung metastases, and bone marrow. CONCLUSION: Cell fusion between EL4-RFP cells and GFP stromal cells occurred in primary tumors and all metastatic sites. The morphology of the fused hybrid cells varied in the primary and metastatic sites. The present results suggest that fused cancer and stromal hybrid cells of varying morphology may play an important role in cancer progression.

Prognostic impact of shift to low visceral fat mass after neoadjuvant chemotherapy in patients with esophageal cancer.

BACKGROUND: Based on the JCOG1109 trial, it is suggested that the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) could potentially become a standard neoadjuvant chemotherapy regimen, alongside the conventional 5-fluorouracil and cisplatin (CF) therapy, for esophageal cancer. However, there are few reports on the impact of body composition changes associated with neoadjuvant chemotherapy on prognosis. AIM: Our study aimed to explore the effect of different neoadjuvant chemotherapy regimens on body composition during treatment and the impacts of body composition changes on their prognosis. METHODS AND RESULTS: This is a retrospective study of 215 patients with advanced thoracic esophageal cancer who had surgery after neoadjuvant chemotherapy from 2013 to 2019. Computed tomography scans were performed before and after neoadjuvant chemotherapy to assess body composition. Skeletal muscle mass index (SMI) was calculated by dividing total skeletal muscle mass at the 3rd lumbar level by the square of height, while visceral and subcutaneous fat masses were measured at the level of umbilicus. Patients in the lowest 25% of both sexes were classified into the low visceral fat and low subcutaneous fat groups, respectively. Of the patients enrolled, 178 were male and 37 were female. Among them, 91 had clinical Stage II disease, and 124 had clinical Stage III disease. Additionally, 146 patients received neoadjuvant chemotherapy CF, and 69 received neoadjuvant chemotherapy DCF. Comparing the DCF and CF groups, the DCF group consisted of significantly younger patients (p < .01), a higher proportion of males (p = .03), and a greater number of clinical Stage III cases (p < .01). However, although percent change in SMI and visceral fat mass was not significantly different between two regimens, percent change in subcutaneous fat mass was significant in the DCF group. The major prognostic factors for patients undergoing surgery after neoadjuvant chemotherapy for thoracic esophageal cancer were clinical Stage III, transition to low visceral fat, and response rating (SD/PD), while the specific neoadjuvant chemotherapy regimen did not significantly influence the outcomes. CONCLUSION: This study suggests that prevention of the shift to low visceral fat throughout the neoadjuvant chemotherapy process should improve patient outcomes.

Endoscopic ultrasound-guided rendezvous techniques for difficult biliary cannulation: Technical review.

Endoscopic retrograde cholangiopancreatography (ERCP) is the standard procedure for the diagnosis and treatment of biliary diseases. However, selective biliary cannulation, the essential first step in ERCP, can sometimes fail due to anatomical variations or technical limitations. In these cases, the endoscopic ultrasound-guided rendezvous technique (EUS-RV) offers a valuable salvage option. Nevertheless, it is crucial to be aware of potential adverse events associated with bile duct puncture. To optimize the success rate and safety of EUS-RV, understanding the basic techniques, technical tips for each procedural step, and troubleshooting strategies for potential difficulties is essential. This review article summarizes the clinical outcomes and technical considerations of EUS-RV, including a comprehensive analysis of the current evidence.

Dexamethasone-sparing strategies in anthracycline and cyclophosphamide-based chemotherapy with a focus on 5-HT3 receptor antagonists: a network meta-analysis.

Background: The effectiveness of a dexamethasone-sparing strategy in the treatment of breast cancer with anthracycline-cyclophosphamide therapy when combined with first-generation 5-HT3 receptor antagonists (RAs) and neurokinin-1 RAs is unclear. This is attributable to a lack of evidence from direct comparison of multiple doses of DEX to a single dose of DEX in combination with first-generation 5-HT3 RAs in anthracycline-cyclophosphamide therapy. Our goal was to clarify the impact of dexamethasone-sparing strategies that involve both first-generation 5-HT3 RAs and palonosetron when combined with neurokinin-1 RAs, using a network meta-analysis. Materials and methods: A literature search was conducted on PubMed/Medline for articles published up to July 4, 2023. We included randomized controlled trials which assessed the efficacy of antiemetic regimens which combined 5-HT3 RAs and dexamethasone, with or without neurokinin-1 RAs, for the initial dose in anthracycline-cyclophosphamide therapy for patients with breast cancer. The primary outcome was the proportion of patients achieving a complete response during the delayed phase (CR-DP). Results: The difference in the proportion of patients achieving CR-DP between multiple and single doses of dexamethasone was 0.1% (95%CI: -12.4 to 12.5) with palonosetron and neurokinin-1 RAs, compared to 5.3% (95%CI: -13.4 to 23.0) with a single dose of a first-generation 5-HT3 receptor antagonist. Additionally, the difference was 12.7% (95% CI: -2.8 to 28.2) when comparing palonosetron against first-generation 5-HT3 RAs in combination with a single dose of dexamethasone and neurokinin-1 RAs. Conclusion: Palonosetron is recommended rather than a single dose of first-generation 5-HT3 RAs in dexamethasone-sparing strategies for anthracycline-cyclophosphamide therapy.

High-Fat Diet Delays Liver Fibrosis Recovery and Promotes Hepatocarcinogenesis in Rat Liver Cirrhosis Model.

More effective treatments for hepatitis viral infections have led to a reduction in the incidence of liver cirrhosis. A high-fat diet can lead to chronic hepatitis and liver fibrosis, but the effects of lipid intake on liver disease status, including hepatitis C virus and alcohol, after elimination of the cause are unclear. To investigate the effects, we used a rat cirrhosis model and a high-fat diet in this study. Male Wistar rats were administered carbon tetrachloride for 5 weeks. At 12 weeks of age, one group was sacrificed. The remaining rats were divided into four groups according to whether or not they were administered carbon tetrachloride for 5 weeks, and whether they were fed a high-fat diet or control diet. At 12 weeks of age, liver fibrosis became apparent and then improved in the groups where carbon tetrachloride was discontinued, while it worsened in the groups where carbon tetrachloride was continued. Liver fibrosis was notable in both the carbon tetrachloride discontinuation and continuation groups due to the administration of a high-fat diet. In addition, liver precancerous lesions were observed in all groups, and tumor size and multiplicity were higher in the high-fat diet-fed groups. The expression of genes related to inflammation and lipogenesis were upregulated in rats fed a high-fat diet compared to their controls. The results suggest that a high-fat diet worsens liver fibrosis and promotes liver carcinogenesis, presumably through enhanced inflammation and lipogenesis, even after eliminating the underlying cause of liver cirrhosis.

Effect of Vitamin D and Skeletal Muscle Mass on Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0-27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77-2.5] for a low SMI and 3.2 [95% CI 1.8-5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

Alcohol-associated liver disease increases the risk of muscle loss and mortality in patients with cirrhosis.

BACKGROUND: Rapid skeletal muscle loss adversely affects the clinical outcomes of liver cirrhosis. However, the relationships between the annual changes in skeletal muscle area (ΔSMA/year) and the etiology of cirrhosis, factors associated with muscle loss, and risk of mortality remains unclear. METHODS: A total of 384 patients who underwent multiple computed tomography (CT) scans between March 2004 and June 2021 were enrolled in this study (median age, 67 years; 64% men; median model for end-stage liver disease score, 9). Body composition and ΔSMA/year were estimated using a 3D image analysis system and data from at least two distinct CT scans. Differences in ΔSMA/year among different etiologies of cirrhosis, factors associated with rapid muscle loss (defined as ΔSMA/year ≤ - 3.1%), and the association between ΔSMA/year and mortality were examined. RESULTS: Patients with alcohol-associated liver disease (ALD) cirrhosis experienced more rapid muscle loss (ΔSMA/year, - 5.7%) than those with hepatitis B (ΔSMA/year, - 2.8%) and hepatitis C cirrhosis (ΔSMA/year, - 3.1%). ALD cirrhosis was independently associated with ΔSMA/year ≤ - 3.1% after adjusting for age, sex, and liver functional reserve. Over a median follow-up period of 3.8 years, ALD cirrhosis, ΔSMA/year ≤ - 3.1%, and low subcutaneous adipose tissue level were found to be significantly associated with reduced survival. ALD cirrhosis (hazard ratio [HR], 2.43; 95% confidence interval [CI] 1.12-5.28) and ΔSMA/year ≤ - 3.1% (HR, 3.68; 95% CI 2.46-5.52) were also predictive of mortality. CONCLUSIONS: These results suggest that ALD cirrhosis increases the risk of rapid muscle loss and mortality in affected patients.

Vitamin D deficiency stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis: A retrospective cohort study.

BACKGROUNDS & AIMS: This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis. METHODS: This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL. The associations between 25-OHD and CHE, OHE occurrence, and mortality were assessed using logistic regression, Fine-Gray competing risk regression, and Cox proportional hazards regression models, respectively. RESULTS: Of 428 eligible patients, 75% had vitamin D deficiency and 23% had CHE. The prevalence of CHE was higher in patients with vitamin D deficiency than in those without vitamin D deficiency (28% vs. 13%, p = 0.002). During the median follow-up period of 2.3 years, 14% of the patients developed OHE and 27% died. Patients with vitamin D deficiency had a higher incidence of OHE (p = 0.002) and mortality (p = 0.006) than those without vitamin D deficiency. After adjustment for potential covariates, multivariate analyses showed that 25-OHE was associated with CHE (odds ratio, 0.95; 95% confidence interval [CI], 0.91-0.99; p = 0.023), OHE occurrence (sub-distribution hazard ratio, 0.92; 95% CI, 0.86-0.98; p = 0.013) and mortality (hazard ratio, 0.96; 95% CI, 0.93-0.99; p = 0.020) in patients with cirrhosis. CONCLUSIONS: Vitamin D deficiency is highly prevalent and is associated with CHE, OHE, and mortality in patients with cirrhosis. Evaluation of vitamin D is essential to predict the outcomes of patients with cirrhosis.

Safety and Efficacy of Covered Self-Expandable Metallic Stent for Choledochojejunal Anastomotic Stricture: A Multi-Center Retrospective Cohort Study.

BACKGROUND: Benign choledochojejunal anastomotic stricture (CJS) is a complication of pancreaticoduodenectomy and choledochojejunostomy. Typically managed with endoscopic balloon dilatation, CJS has a high recurrence rate. Covered metallic stent (CMS) placement is a potential alternative; however, a comprehensive evaluation is lacking. OBJECTIVES: The aim of this study was to evaluate the treatment outcomes of CMS placement in patients with CJS. METHODS: We retrospectively analyzed patients who underwent balloon dilation via endoscopic retrograde cholangiopancreatography using a double-balloon endoscope for CJS between October 2010 and October 2023. The study outcomes included technical and clinical success rates, adverse event rates, choledochojejunal anastomotic stricture recurrence rates, and time to recurrence for balloon dilation and CMS treatment for CJS. RESULTS: There were 43 patients, 55 procedures (40 balloon dilation and 15 CMS placement). The technical and clinical success rates were 100% for both treatments. Recurrence of CJS was observed in 35% (14/40) of the patients in the balloon dilation group. The recurrence rate was significantly higher in the balloon dilation group than in the CMS group (35% vs. 0%, p = 0.006). The time to CJS recurrence was significantly shorter in the balloon dilation group than in the covered metallic stent group (NR vs. NR, p = 0.03). CONCLUSION: Placement of CMS for treating patients with CJS was demonstrated to be an effective and safe method with a lower recurrence rate than balloon dilation.

Exosome Transfer Between Different Co-implanted Human Pancreatic Cancer Cell Lines Occurs in the Primary Tumor and Multiple Metastatic Sites of Nude Mice But Not in Co-Culture In Vitro.

BACKGROUND/AIM: Exosome exchange between cancer cells or between cancer and stromal cells is involved in cancer metastasis. We have previously developed in vivo color-coded labeling of cancer cells and stromal cells with spectrally-distinct fluorescent genetic reporters to demonstrate the role of exosomes in metastasis. In the present study, we studied exosome transfer between different pancreatic-cancer cell lines in vivo and in vitro and its potential role in metastasis. MATERIALS AND METHODS: Human pancreatic-cancer cell lines AsPC-1 and MiaPaCa-2 were used in the present study. AsPC-1 cells contain a genetic exosome reporter gene labeled with green fluorescent protein (pCT-CD63-GFP) and MiaPaCa-2 cells express red fluorescent protein (RFP). Both cell lines were co-injected into the spleen of nude mice (n=5) to further study the role of exosome exchange in metastasis. Three weeks later mice were sacrificed and tumors at the primary and metastatic sites were cultured and observed by confocal fluorescence microscopy for exosome transfer. RESULTS: The primary tumor formed in the spleen and metastasized to the liver, as observed macroscopically. Cells were cultured from the spleen, liver, lung, bone marrow and ascites. Transfer of exosomes from AsPC-1 to MiaPaCa-2 was demonstrated in the cultured cells by confocal fluorescence microscopy. Moreover, cell fusion was also observed along with exosome transfer. Exosome transfer did not occur during in vitro co-culture between the two pancreatic-cancer cell lines, suggesting a role of the tumor microenvironment (TME) in exosome transfer. CONCLUSION: The transfer of exosomes between different pancreatic-cancer cell lines was observed during primary-tumor and metastatic growth in nude mice. This cell-cell communication might be a trigger of cell fusion and promotion of cancer metastasis. Exosome transfer between the two pancreatic-cancer cell lines appears to be facilitated by the TME, as it did not occur during in vitro co-culture.

Implantation cyst appearing more than 30 years after gastrectomy.

Implantation cyst is often reported to be a delayed complication after colorectal surgery. This report presents a 70-year-old man undergoing gastrectomy 33 years earlier for an acute gastric ulcer. His endoscopic finding showed a submucosal tumor about 20 mm in diameter at the gastro-jejunal anastomosis. Endoscopic ultrasonography showed that the tumor was a cystic mass that was continuous from the third layer, but there were no existences of internal substantial nodules, indicating that the tumor was diagnosed as implantation cyst. This is the first report showing that implantation cyst can occur at gastro-jejunal anastomosis. We should take into account the occurrence of implantation cyst, when we encounter a submucosal tumor at gastro-jejunal anastomosis after surgery even if a long period has passed.

Acute kidney injury development is associated with mortality in Japanese patients with cirrhosis: impact of amino acid imbalance.

BACKGROUND: Acute kidney injury (AKI) is a serious complication of cirrhosis. This study analyzed the prognostic effect of AKI in patients with cirrhosis and its risk factors, particularly in relation to amino acid imbalance. METHODS: This retrospective study reviewed 808 inpatients with cirrhosis at two institutes in Gifu, Japan. AKI was diagnosed according to the recommendations of the International Club of Ascites. Amino acid imbalance was assessed by measuring serum branched-chain amino acid (BCAA) levels, tyrosine levels, and the BCAA-to-tyrosine ratio (BTR). Factors associated with mortality and AKI development were assessed using the Cox proportional hazards regression model with AKI as a time-dependent covariate and the Fine-Gray competing risk regression model, respectively. RESULTS: Of the 567 eligible patients without AKI at baseline, 27% developed AKI and 25% died during a median follow-up period of 4.7 years. Using a time-dependent covariate, AKI development (hazard ratio [HR], 6.25; 95% confidence interval [CI], 3.98-9.80; p < 0.001) was associated with mortality in patients with cirrhosis independent of potential covariates. In addition, alcohol-associated/-related liver disease, metabolic dysfunction-associated steatohepatitis, Child-Pugh score, and BTR (subdistribution HR 0.78; 95% CI 0.63-0.96; p = 0.022) were independently associated with AKI development in patients with cirrhosis. Similar results were obtained in the multivariate model that included BCAA and tyrosine levels instead of BTR. CONCLUSIONS: AKI is common and associated with mortality in Japanese patients with cirrhosis. An amino acid imbalance is strongly associated with the development of AKI in patients with cirrhosis.

Usefulness of health checkup-based indices in identifying metabolic dysfunction-associated steatotic liver disease.

Aims: The application of indices in the context of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unexplored. We aimed to validate the ability of alanine aminotransferase (ALT), fatty liver index (FLI), and hepatic steatosis index (HSI) to identify MASLD during health checkups. Methods: We recruited 627 participants and utilized their health checkup data and ultrasound to assess the potential of using ALT, FLI, and HSI as indices for MASLD; this was indicated by the area under the curve (AUC) and restricted cubic spline (RCS) model. The optimal, rule-out (sensitivity ≥90%), and rule-in (specificity ≥90%) cutoff values of each index for identifying MASLD were reported. Results: Among participants with a median age of 46 years, the prevalence of MASLD was 28% in total (38% in males and 18% in females). RCS models confirmed a linear association between indices and MASLD. ROC analyses indicated that the AUC of ALT in identifying MASLD was 0.79 for the total cohort, 0.81 for males, and 0.69 for females. The optimal, rule-out, and rule-in cutoff values for ALT were 21, 13, and 29, respectively. Similarly, the AUC of FLI/HSI in identifying MASLD was 0.90/0.88 for the total cohort, 0.86/0.85 for males, and 0.93/0.90 for females. Considering the reference cutoff values, distinct cutoff values were observed between the sexes for FLI, while HSI had similar cutoff values. Conclusion: This study demonstrated that ALT > 30 IU/L is a reasonable cutoff value to rule-in MASLD. ALT, FLI, and HSI are reliable indices for identifying MASLD during health checkups.

Possibility of Cell Block Specimens from Overnight-Stored Bile for Next-Generation Sequencing of Cholangiocarcinoma.

The identification of anticancer therapies using next-generation sequencing (NGS) is necessary for the treatment of cholangiocarcinoma. NGS can be easily performed when cell blocks (CB) are obtained from bile stored overnight. We compared NGS results of paired CB and surgically resected specimens (SRS) from the same cholangiocarcinoma cases. Of the prospectively collected 64 bile CBs from 2018 to 2023, NGS was performed for three cases of cholangiocarcinoma that could be compared with the SRS results. The median numbers of DNA and RNA reads were 95,077,806 [CB] vs. 93,161,788 [SRS] and 22,101,328 [CB] vs. 24,806,180 [SRS], respectively. We evaluated 588 genes and found that almost all genetic alterations were attributed to single-nucleotide variants, insertions/deletions, and multi-nucleotide variants. The coverage rate of variants in SRS by those found in CB was 97.9-99.2%, and the coverage rate of SRS genes by CB genes was 99.6-99.7%. The NGS results of CB fully covered the variants and genetic alterations observed in paired SRS samples. As bile CB is easy to prepare in general hospitals, our results suggest the potential use of bile CB as a novel method for NGS-based evaluation of cholangiocarcinoma.