Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-ß/Smad pathway suppression in hepatic stellate cells.

Transforming growth factor (TGF)-ß/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-ß/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-ß/Smad pathway activity. Human hepatic stellate cells (HHSteCs) were cultured with TGF-ß and multiple miglustat concentrations to examine dose-dependent effects on the expression levels of ECM-related genes and Smad proteins. To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis, followed by combined CCl4 plus miglustat for a further 2 weeks. To examine if miglustat can also prevent fibrosis, mice were treated with CCl4 for 2 weeks, followed by CCl4 plus miglustat for 2 weeks. Miglustat dose-dependently downregulated expression of α-smooth muscle actin and ECM components in TGF-ß-treated HHSteCs. Both phosphorylation and nuclear translocation of Smad2 and Smad3 were also suppressed by miglustat treatment. Sirius-Red staining and hydroxyproline assays of model mouse liver samples revealed that miglustat reduced fibrosis, an effect accompanied by decreased expression of ECM. Our findings suggest that miglustat can both prevent and reverse liver fibrosis by inhibiting TGF-ß/Smad pathway.

Efficacy and Safety of Electrohydraulic Lithotripsy Using Peroral Cholangioscopy under Endoscopic Retrograde Cholangiopancreatography Guidance in Older Adults: A Single-Center Retrospective Study.

Background and objectives: The safety of electrohydraulic lithotripsy (EHL) in older adults remains unclear. We aimed to investigate the efficacy and safety of EHL using peroral cholangioscopy (POCS) under endoscopic retrograde cholangiopancreatography (ERCP) guidance in older adults aged ≥80 years. Materials and Methods: This retrospective clinical study was conducted at a single center. Fifty patients with common bile duct stones who underwent EHL using POCS under ERCP guidance at our institution, between April 2017 and September 2022, were enrolled in this study. The eligible patients were divided into an elderly group (n = 21, age ≥80 years) and a non-elderly group (n = 29, age ≤79 years), and were analyzed. Results: A total of 33 and 40 EHL procedures were performed in the elderly and non-elderly groups, respectively. After excluding cases in which stone removal was performed at other institutions, complete removal of common bile duct stones was confirmed in 93.8% and 100% of the elderly and non-elderly groups, respectively (p = 0.20). The mean number of ERCPs required for complete removal of bile duct stones was 2.9 and 4.3 in the elderly and non-elderly groups, respectively (p = 0.17). In the EHL session, the overall occurrence of adverse events was eight and seven in the elderly (24.2%) and non-elderly (17.5%) groups, respectively; however, the difference was insignificant (p = 0.48). Conclusions: EHL using POCS under ERCP guidance is effective in patients aged ≥80 years and there was no significant increase in adverse event rates compared to those aged ≤79 years.

A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD. The establishment of animal models with these metabolic comorbidities and with the rapid progression of the disease is needed for developing treatments for NAFLD but remains to be archived. In the present study, KK-Ay mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The KK-Ay mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A prominent accumulation of triglycerides and cholesterol in the liver was observed at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12 weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still developed steatohepatitis and fibrosis. In summary, we established a diet-induced murine NAFLD model with the rapid development of steatohepatitis and fibrosis, bearing obesity and insulin resistance. This model could be useful as preclinical models for drug development of NAFLD.

Diagnostic value of peroral cholangioscopy in addition to computed tomography for indeterminate biliary strictures.

BACKGROUND: Peroral cholangioscopy (POCS) has been used to overcome the difficulty in diagnosing indeterminate biliary stricture or tumor spread. However, the value of adding POCS to computed tomography (CT) remains unclear. Our aim was to evaluate the diagnostic value of adding POCS to CT for indeterminate biliary stricture and tumor spread by interpretation of images focusing on the high diagnostic accuracy of visual findings in POCS. METHODS: We retrospectively identified 52 patients with biliary stricture who underwent endoscopic retrograde cholangiography (ERC) at our institution between January 2013 and December 2018. Two teams, each composed of an expert endoscopist and surgeon, performed the interpretation independently, referring to the CT findings of the radiologist. The CT + ERC + POCS images (POCS group) were evaluated 4 weeks after the evaluation of CT + ERC images (CT group). A 5-point scale (1: definitely benign to 5: definitely malignant) was used to determine the confident diagnosis rate, which was defined as an evaluation value of 1 or 5. Tumor spread was also evaluated. RESULTS: In the evaluation of 45 malignant diagnoses, the score was significantly closer to 5 in the POCS group than in the CT group in both teams (P < 0.001). The confident diagnosis rate was significantly higher for the POCS group (92% and 73%) than for the CT group (25% and 12%) in teams 1 and 2, respectively (P < 0.001). We found no significant difference in diagnostic accuracy for tumor spread between the groups. CONCLUSION: Visual POCS findings confirmed the diagnosis of biliary strictures. POCS was useful in cases of indefinite diagnosis of biliary strictures by CT.

Liver cirrhosis is a risk factor for poor prognosis of acute cholangitis caused by choledocholithiasis.

INTRODUCTION AND OBJECTIVES: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear. MATERIALS AND METHODS: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019. RESULTS: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02). CONCLUSIONS: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.

The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells.

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx-overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in ELAVL1-knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.

Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells.

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib.

Analysis of circulating cell-free DNA after endoscopic ultrasound-guided fine needle aspiration in pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: Recently, increase in cell-free DNA (cfDNA) concentration or newly detected KRAS mutation after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy were reported to be related to the occurrence of new distant metastasis. In this study, we investigated whether cfDNA concentration increased with the release of tumor components into the blood after EUS-FNA and whether its increase was related to prognosis. METHODS: Sixty-eight patients underwent EUS-FNA and were pathologically confirmed as having pancreatic ductal adenocarcinoma (PDAC). We measured plasma cfDNA concentration and the copy number of KRAS mutation in 68 patients and circulating tumor cells in 8 before and after EUS-FNA. RESULTS: The average cfDNA concentration after EUS-FNA (672.5 ± 919.6 ng/mL) was significantly higher than that before EUS-FNA (527.7 ± 827.3 ng/mL) (P < 0.001). KRAS mutation in plasma was detected in 8 patients (11.8%), however a significant increase in cfDNA concentration after EUS-FNA was not related to the change in KRAS-mutant copy number. Minimal increase in circulating tumor cells was observed in 3 of 8 patients. New distant metastasis was observed within 286 days to initial metastasis detection in 6 of 12 patients with ≥2-fold increase in cfDNA concentration and 26 of 56 patients with <2-fold increase within 185 days. In 32 patients who underwent surgery, ≥2-fold increase in cfDNA did not affect early recurrence. CONCLUSIONS: The increase in cfDNA concentration after EUS-FNA was not caused by tumor cell components released into blood vessels. Hence, the risk of seeding via the blood stream after EUS-FNA may need not be considered.

Alternate Endpoints for Phase II Trials in Advanced Neuroendocrine Tumors.

BACKGROUND: In phase II trials for neuroendocrine tumors (NETs), the objective response rate (ORR) is traditionally used as a primary endpoint. However, the validity of the ORR as a primary endpoint has never been systematically examined. Therefore, a literature-based analysis of phase II trials for NETs was performed to identify valid alternative endpoints for predicting median progression-free survival (PFS) in clinical trials for NETs. MATERIALS AND METHODS: Phase II trials of medical treatment for advanced NETs were identified based on a systematic search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. RESULTS: A total of 22 trials were identified, and 1,310 patients and 27 treatment arms were included in the analysis. There was no significant relationship between the ORR and median PFS (r = .374; 95% confidence interval [CI], -0.051 to 0.800; p = .085). Conversely, 12-month PFS rates showed very strong correlations with median PFS (r = .929; 95% CI, 0.831-1.027; p < .001). CONCLUSION: The results of the present analysis indicate that the ORR is not significantly correlated with median PFS and suggest that 12-month PFS rates are good alternate endpoints for screening phase II trials for NETs. IMPLICATIONS FOR PRACTICE: Phase II trials are screening trials that seek to identify agents with sufficient activity to continue development. Thus, earlier endpoints are preferable, and the objective response rate (ORR) has been traditionally used as a surrogate endpoint in phase II trials for neuroendocrine tumors (NETs). However, the present study showed that the ORR was not significantly correlated with median progression-free survival (PFS). On the other hand, the 12-month PFS rate showed very strong correlation with median PFS and is considered a good alternate endpoint for screening phase II trials for NETs.

Skill-up study of systemic endoscopic examination technique using narrow band imaging of the head and neck region of patients with esophageal squamous cell carcinoma: Prospective multicenter study.

OBJECTIVE: To evaluate the usefulness of a training program on endoscopic head and neck surveillance for beginner endoscopists. METHODS: This prospective multicenter study included 13 beginner endoscopists from 10 institutions who received training in systematic observation techniques and diagnostic criteria, and the training involved hands-on learning. Between May 2016 and February 2017, enrolled patients with current or previously diagnosed esophageal squamous cell carcinomas underwent head and neck surveillance using narrow band imaging (NBI) endoscopy, and histologically confirmed head and neck squamous cell carcinoma (HNSCC) detection rates, endoscopic image quality, and examination times were compared before (group A) and after (group B) the training program. Maximum possible score for the endoscopic images was 30 points. RESULTS: A total of 330 patients, comprising 181 in group A and 149 in group B, were enrolled. Three patients with HNSCC were detected in group A (1.7%) and in group B (2.0%; P = 1.000). Mean ± standard deviation (SD) examination times were 157 ± 71 s and 174 ± 109 s in groups A and B, respectively, (P = 0.073). Mean ± SD scores of the endoscopic images were 25.04 ± 5.47 points and 27.01 ± 4.35 points in groups A and B, respectively, (P < 0.001). CONCLUSION: The HNSCC detection rate based on the use of NBI on patients with ESCC did not improve after the training program for beginner endoscopists; however, endoscopic image quality improved significantly after the training program.

Penetration of duodenal wall by proximal end of biliary straight plastic stent in a patient with ampullary carcinoma.

A 70-year-old woman presented to our hospital with abdominal discomfort. Gastrointestinal endoscopy revealed an ampullary tumor, while a biopsy revealed a pathological diagnosis of adenocarcinoma. No distant metastases were observed and neoadjuvant chemotherapy and surgical resection were planned. Shortly thereafter, she developed obstructive jaundice due to the ampullary carcinoma. The patient underwent endoscopic retrograde cholangiopancreatography, during which a straight plastic stent was placed in the bile duct. The patient was discharged without complications. Neoadjuvant chemotherapy was initiated. Two months later, she was readmitted for surgery while asymptomatic. Endoscopic retrograde cholangiopancreatography was scheduled to replace the stent with a nasobiliary drainage tube for the surgery. Endoscopic imaging revealed that the proximal end of the stent had penetrated the duodenum on the oral side of the ampullary carcinoma. The distal end of the stent was grasped with forceps and the stent was successfully removed. A catheter was inserted into the bile duct orifice and cholangiography was performed, which revealed that the distal bile duct and the duodenum had formed a fistula. A guidewire was placed in the bile duct via the papilla and a nasobiliary drainage tube was placed. After endoscopic retrograde cholangiopancreatography, the patient exhibited smooth progress without issue. Pancreaticoduodenectomy was performed on the fourth day after the nasobiliary drainage tube placement, and the patient's postoperative course was uneventful. The proximal end of a biliary stent penetrating the duodenal wall is an infrequent phenomenon. This case report highlights a rare but noteworthy adverse event associated with straight biliary plastic stent placement.

Genomic Analysis of Undifferentiated Carcinoma of the Pancreas with Squamous Differentiation: A Case Report.

Pancreatic cancer is an intractable malignancy associated with a dismal prognosis. Undifferentiated carcinoma, a rare subtype, poses a clinical challenge owing to a limited understanding of its molecular characteristics. In this study, we conducted genomic analysis specifically on a case of undifferentiated carcinoma of the pancreas exhibiting squamous differentiation. An 80-year-old male, previously treated for colorectal cancer, presented with a mass with central cystic degeneration in the pancreatic tail. The mass was diagnosed pathologically as undifferentiated carcinoma of the pancreas with squamous differentiation. Despite surgical resection and chemotherapy, the patient faced early postoperative recurrence, emphasizing the aggressive nature of this malignancy. Genomic analysis of distinct histologic components revealed some common mutations between undifferentiated and squamous components, including Kirsten rat sarcoma virus (KRAS) and TP53. Notably, the squamous component harbored some specific mutations in SMARCA4 and SMARCB1 genes that code for members of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. The common mutations in the undifferentiated and squamous cell carcinoma components from this analysis suggest that they originate from a common origin. The discussion also underscores the scarcity of genomic analyses on undifferentiated carcinoma of the pancreas, with existing literature pointing to SWI/SNF complex-related gene mutations. However, our case introduces chromatin remodeling factor mutations as relevant in squamous differentiation. In conclusion, this study provides valuable insights into the genomic landscape of undifferentiated pancreatic carcinoma with squamous differentiation. These findings suggest the importance of further research and targeted therapies to improve the management of undifferentiated carcinoma of the pancreas and enhance patient outcomes.

Clinical outcomes and reintervention after endoscopic retrograde cholangiopancreatography in primary sclerosing cholangitis in absence of cholangitis.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) may help detect cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC), but it may be associated with complications. This study was aimed at determining the prognostic impact of ERCP on patients with PSC without cholangitis. METHODS: Patients with PSC without cholangitis were divided into two groups: those who underwent ERCP within three years after diagnosis (ERCP-performed group) and those who did not (non-ERCP group). These groups were compared in terms of clinical outcomes (liver-related death or liver transplantation, endoscopic treatment requirement and repeated cholangitis) and the composite outcome. RESULTS: Of 99 patients with PSC with detailed medical history, 49 were included in the ERCP-performed group and 21 in the non-ERCP group. In Kaplan-Meier analysis, the non-ERCP group was less likely to achieve the three outcomes and the composite outcome, showing statistical significance (endoscopic treatment requirement; p = 0.017 and composite outcome; p = 0.014). A Cox proportional hazards model indicated that ERCP in the asymptomatic state was a significant predictor of endoscopic treatment requirement (hazard ratio [HR]: 4.37, 95% confidence interval [CI]: 1.03-18.59) and the composite outcome (HR: 4.54, 95% CI: 1.07-19.28). CONCLUSION: ERCP in patients with PSC without cholangitis is likely to require further endoscopic treatment and may be associated with poor prognosis.

Feasibility of Biliary Drainage Using a Novel Integrated Biliary Stent and Nasobiliary Drainage Catheter System for Acute Cholangitis.

Background Acute cholangitis is caused by cholestasis and bacterial infection, and if exacerbated, sepsis may occur and be fatal. Biliary drainage is recommended for acute cholangitis regardless of severity, except in some cases of mild acute cholangitis, in which antibiotics are effective. A novel integrated device comprising a biliary drainage stent and a nasobiliary drainage tube, called the UMIDAS NB stent (UMIDAS Inc., Kanagawa, Japan), was developed. In this study, we evaluated the efficacy and safety of biliary drainage using the UMIDAS NB stent outside type for acute cholangitis in clinical practice. Methods Patients with acute cholangitis with common bile duct stones or distal biliary strictures who underwent biliary drainage with the UMIDAS NB stent outside type at our institution between January 2022 and December 2022 were examined retrospectively. The UMIDAS NB stent outside type was placed transpapillary using endoscopic retrograde cholangiopancreatography (ERCP). Patients with biliary drainage stent placement other than the UMIDAS NB stent outside type on the same ERCP session and patients with acute cholecystitis were excluded. Results A total of 13 patients were included in this study. The severity of cholangitis was mild in four cases, moderate in five, and severe in four. There were eight cases of common bile duct stones and five cases of pancreatic cancer. The stent diameter was 7 French scale (Fr) in five cases and 8.5 Fr in eight cases. The median procedure time was 20 minutes. Clinical success was achieved in all 13 patients (100%). No treatment-related adverse events were observed. Unintended removal of the nasobiliary drainage tube was not observed. There were no cases of biliary drainage stent dislocation with nasobiliary drainage tube removal. Conclusions Although the sample size was small, our study demonstrated that biliary drainage with the UMIDAS NB stent outside type was effective and safe for patients with acute cholangitis who had common bile duct stones or distal biliary strictures, regardless of the severity of cholangitis.

Endoscopic Transpapillary Stenting for Malignant Hilar Biliary Stricture: Side-by-Side Placement versus Partial Stent-in-Stent Placement.

BACKGROUND/AIMS: Endoscopic uncovered metal stent (UMS) placement has been widely performed for unresectable hilar malignant biliary stricture (UHMBS). Two stenting methods are used for the two bile duct branches: side-by-side placement (SBS) and partial stent-in-stent placement (PSIS). However, it remains controversial whether SBS or PSIS is superior. This study aimed to compare SBS and PSIS in UHMBS cases with UMS placement in two branches of the IHD. METHODS: This retrospective study included 89 cases of UHMBS treated with UMS placement through the SBS or PSIS technique using endoscopic retrograde cholangiopancreatography at our institution. Patients were divided into two groups, SBS (n = 64) and PSIS (n = 25), and compared. RESULTS: Clinical success was achieved in 79.7% and 80.0% in the SBS and PSIS groups, respectively (p = 0.97). The adverse event rate was 20.3% and 12.0% in the SBS and PSIS groups, respectively (p = 0.36). The recurrent biliary obstruction (RBO) rate was 32.8% and 28.0% in the SBS and PSIS groups, respectively (p = 0.66). The median cumulative time to RBO was 224 and 178 days in the SBS and PSIS groups, respectively (p = 0.52). The median procedure time was 43 and 62 min in the SBS and PSIS groups, respectively, which was significantly longer in the PSIS group (p = 0.014). CONCLUSIONS: No significant differences were noted in the clinical success rate, adverse event rate, time to RBO, or overall survival between the SBS and PSIS groups, other than the significantly longer procedure time in the PSIS group.

Bile proteome analysis by high-precision mass spectrometry to examine novel biomarkers of primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of unknown etiology that affects the intra- and extrahepatic bile ducts. The present study examined the utility of a bile proteome analysis using a high-sensitivity mass spectrometer to comprehensively screen for novel PSC biomarkers. METHODS: Bile endoscopically collected from patients with PSC, common bile duct stones, and biliary tract cancer were subjected to high-precision liquid chromatography/mass spectrometry. Some of the proteins specifically up-regulated in the bile of the PSC group were re-examined by an enzyme-linked immunosorbent assay. RESULTS: A total of 8094 proteins were successfully identified and 332 were specifically up-regulated in the PSC group. The bioinformatics analysis showed that proteins involved in the proliferation and activation of diverse inflammatory cells were up-regulated in the PSC group. A receiver operating characteristic curve analysis showed good area under the curve values for interleukin-8 and annexin A1 (ANXA1) (0.836 and 0.914, respectively). Immunostaining for ANXA1 revealed its strong expression in inflammatory cells infiltrating the peripheral biliary tract in PSC livers. CONCLUSION: A bile proteome analysis is a useful tool for elucidating the pathogenesis of PSC and developing new diagnostic approaches. Therefore, ANXA1 has potential as a bile biomarker for PSC.

Secondary Sclerosing Cholangitis After Emphysematous Cholecystitis.

A 64-year-old woman was diagnosed with emphysematous cholecystitis. An open cholecystectomy was performed immediately. After the cholecystectomy, jaundice and multiple bile duct strictures that were not present preoperatively appeared. The patient was diagnosed with sclerosing cholangitis secondary to emphysematous cholecystitis. Endoscopic biliary stenting and endoscopic biliary balloon dilatation were performed. However, jaundice did not improve. She developed candidemia 75 days after cholecystectomy. The patient died of multiple organ failures 92 days after cholecystectomy. Although rare, secondary sclerosing cholangitis occurred after emphysematous cholecystitis, and endoscopic treatment was ineffective in this case.

Phase II study comparing nasal pressure monitoring with capnography during invasive endoscopic procedures: a single-center, single-arm trial.

Nasal pressure signal is commonly used to evaluate obstructive sleep apnea. This study aimed to assess its safety for respiratory monitoring during sedation. A total of 45 adult patients undergoing sedation with propofol and fentanyl for invasive endoscopic procedures were enrolled. While both nasal pressure and capnograph signals were continuously recorded, only the nasal pressure signal was displayed. The primary outcome was the incidence of oxygen desaturation below 90%. The secondary outcomes were the ability to predict the desaturation and incidence of harmful events and false alarms, defined as an apnea waveform lasting more than 3 min without desaturation. Of the 45 participants, 43 completed the study. At least one desaturation event occurred in 12 patients (27.9%; 95% confidence interval 15.3-43.7%). In these 12 patients, more than half of the desaturation events were predictable in 9 patients by capnography and 11 patients by nasal pressure monitoring (p = 0.59). In the 43 patients, false alarms were detected in 7 patients with capnography and 11 patients with nasal pressure monitoring (p = 0.427). Harmful events unrelated to nasal pressure monitoring occurred in 2 patients. Nasal pressure monitoring is safe and possibly useful for respiratory monitoring despite false alarms during sedation.

Safety of endoscopic ultrasound-guided fine-needle aspiration for pancreatic solid mass in the elderly: A single-center retrospective study.

AIM: There are few reports on the safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the elderly. In this study, we investigated the safety of EUS-FNA for pancreatic solid masses in patients aged ≥80 years. METHODS: This is a single-center retrospective study. A total of 600 patients with pancreatic solid masses who underwent EUS-FNA under midazolam-based sedation at our institution between September 2016 and December 2022 were enrolled in this study. Eligible patients were divided into two groups: an elderly group aged ≥80 (n = 84), as well as a nonelderly group aged ≤79 (n = 516). These two groups were compared. RESULTS: The elderly group required significantly fewer midazolam doses for sedation (P < 0.001). Adverse events occurred in eight patients (1.3%), including one (1.2%) and seven (1.4%) in the elderly and nonelderly groups, respectively (P = 0.90). There were no cases of early adverse events in the elderly group and six cases (1.2%) in the nonelderly group (P = 0.32). There was one case of late adverse events in both the elderly and nonelderly groups (P = 0.14), and both were needle tract seeding. There was no significant difference between the two groups in the proportion of cases in which percutaneous oxygen saturation decreased to ≤90% during the EUS-FNA. CONCLUSIONS: Our analysis suggests that EUS-FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years. Geriatr Gerontol Int 2023; 23: 836-841.