Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history.

BACKGROUND AND AIMS: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.

Total bile acids levels as a stratification tool for screening portopulmonary hypertension in patients with decompensated cirrhosis.

AIM: Echocardiography is necessary for portopulmonary hypertension diagnosis, and identifying patients with cirrhosis who require it is challenging. In this study, we aimed to investigate the utility of the total bile acid (TBA) levels as a screening tool for identifying patients with decompensated cirrhosis who should undergo echocardiography for portopulmonary hypertension diagnosis. METHODS: We evaluated 135 patients with decompensated cirrhosis who underwent liver transplantation. Subsequently, factors contributing to tricuspid regurgitation pressure gradient (TRPG) elevation (≥30 mmHg) were analyzed using preoperative data, including the TBA levels. RESULTS: The median age of patients was 58 years (61 women), and 45 and 90 patients had Child-Turcotte-Pugh grades of B and C, respectively. The median TRPG level was 21 mmHg, and 17 patients (12.6%) showed TRPG elevation. Multiple logistic regression analysis revealed that elevated TBA (odds ratio 4.322; p = 0.013) and main pulmonary artery diameter ≥33 mm (odds ratio 4.333; p = 0.016) were significantly associated with TRPG elevation. The TBA cut-off value (167.7 µmol/L) showed a high diagnostic performance, with 70.6% sensitivity and 64.4% specificity. Ursodeoxycholic acid (UDCA) administration increased the TBA levels dose-dependently. Analysis stratified by UDCA use revealed that in patients not taking UDCA (n = 59), elevated TBA levels and younger age significantly contributed to TRPG elevation. However, in those taking UDCA (n = 76), this contribution disappeared, suggesting that UDCA consumption reduced TBA levels' efficiency in diagnosing TRPG elevation. CONCLUSIONS: The TBA levels may be a potential screening tool for TRPG elevation; however, caution is warranted when interpreting cases treated with UDCA.

[Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report].

A 62-year-old male patient underwent pancreaticoduodenectomy with modified Child reconstruction for distal cholangiocarcinoma. After eight years, a contrast-enhanced computed tomography (CT) revealed a recurrent lesion at the biliojejunal anastomosis, and a biliary stent was placed for obstructive cholangitis in the right posterior segment of the liver. A right hepatectomy was planned for a local recurrent lesion;thus, percutaneous transhepatic portal embolization was performed on the portal vein's right branch to enlarge the left liver. However, he was referred to our department for endoscopic retrograde biliary drainage for the subsequent cholangitis and liver abscess appearance. A double-balloon enteroscope under CO2 insufflation was used to reach the bile duct-jejunal anastomosis. After removing the bile duct stent with grasping forceps, his general condition suddenly deteriorated, causing cardiopulmonary arrest. He was diagnosed with air embolism based on the findings of air in the heart, aorta, and brain on CT after the return of spontaneous circulation. Treatment for the air embolism and subsequent complications continued in the intensive care unit, but he eventually died 114 days after the onset of the air embolism due to his deteriorating general condition. Pathological autopsy revealed cholangiocarcinoma that extends from the porta hepatis to the posterior segment. Additionally, the proximity between the bile duct and vein extended by the adenocarcinoma and the fibrous obstruction of the vein were revealed, indicating the possibility of a bile duct-vein shunt.

EUS-guided fine-needle biopsy sampling of solid pancreatic tumors with 3 versus 12 to-and-fro movements: a multicenter prospective randomized controlled study.

BACKGROUND AND AIMS: A novel EUS-guided fine-needle biopsy sampling (EUS-FNB) needle enabled physicians to obtain sufficient pathologic samples with fewer to-and-fro movements (TAFs) within the lesion. We compared the diagnostic yields of EUS-FNB with 3 and 12 TAFs at each puncture pass. METHODS: The primary endpoint of this multicenter, noninferiority, crossover, randomized controlled trial involving 6 centers was diagnostic sensitivity. Secondary endpoints were diagnostic accuracy and quantity and quality evaluation of EUS-FNB specimens. Length of the macroscopically visible core (MVC) and microscopic histologic quantity were used for quantitative evaluation. Macroscopic visual and microscopic histologic evaluations were performed for qualitative evaluation. RESULTS: Among 110 patients (220 punctures, 110 for 3 TAFs and 12 TAFs each), 105 (210 punctures) had malignant histology. Diagnostic sensitivity for malignancy of 3 TAFs (88.6%) was not inferior to that of 12 TAFs (89.5%; difference, -.9%; 95% confidence interval, -9.81 to 7.86). Diagnostic accuracy for malignancy was 92.7% for 3 TAFs and 94.6% for 12 TAFs. Overall median MVC length was 13.5 mm in both groups. The 3-TAF group had a significantly higher rate of score ≥3 on macroscopic visual quality evaluation than the 12-TAF group (71.8% vs 52.7%, P = .009). No significant intergroup differences existed in microscopic histologic quantity and quality evaluations (quantity evaluation, 88.2% for 3 TAFs vs 83.6% for 12 TAFs; quality evaluation, 90.0% for 3 TAFs vs 89.1% for 12 TAFs). CONCLUSIONS: Diagnostic sensitivity and accuracy of EUS-FNB with 3 TAFs were not inferior to those with 12 TAFs for solid pancreatic lesions. The 3-TAF group showed significantly less blood contamination in sampled tissues than the 12-TAF group. (Clinical trial registration number: UMIN000037309.).

Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial.

BACKGROUND: Nasal high flow (NHF) may reduce hypoxia and hypercapnia during an endoscopic retrograde cholangiopancreatography (ERCP) procedure under sedation. The authors tested a hypothesis that NHF with room air during ERCP may prevent intraoperative hypercapnia and hypoxemia. METHODS: In the prospective, open-label, single-center, clinical trial, 75 patients undergoing ERCP performed with moderate sedation were randomized to receive NHF with room air (40 to 60 L/min, n = 37) or low-flow O2 via a nasal cannula (1 to 2 L/min, n = 38) during the procedure. Transcutaneous CO2, peripheral arterial O2 saturation, a dose of administered sedative and analgesics were measured. RESULTS: The primary outcome was the incidence of marked hypercapnia during an ERCP procedure under sedation observed in 1 patient (2.7%) in the NHF group and in 7 patients (18.4%) in the LFO group; statistical significance was found in the risk difference (-15.7%, 95% CI -29.1 - -2.4, p = 0.021) but not in the risk ratio (0.15, 95% CI 0.02 - 1.13, p = 0.066). In secondary outcome analysis, the mean time-weighted total PtcCO2 was 47.2 mmHg in the NHF group and 48.2 mmHg in the LFO group, with no significant difference (-0.97, 95% CI -3.35 - 1.41, p = 0.421). The duration of hypercapnia did not differ markedly between the two groups either [median (range) in the NHF group: 7 (0 - 99); median (range) in the LFO group: 14.5 (0 - 206); p = 0.313] and the occurrence of hypoxemia during an ERCP procedure under sedation was observed in 3 patients (8.1%) in the NHF group and 2 patients (5.3%) in the LFO group, with no significant difference (p = 0.674). CONCLUSIONS: Respiratory support by NHF with room air did not reduce marked hypercapnia during ERCP under sedation relative to LFO. There was no significant difference in the occurrence of hypoxemia between the groups that may indicate an improvement of gas exchanges by NHF. TRIAL REGISTRATION: jRCTs072190021 . The full date of first registration on jRCT: August 26, 2019.

Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: A nationwide survey in Japan.

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. METHODS: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. RESULTS: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037). CONCLUSIONS: NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

Impact of the COVID-19 pandemic on endoscopic retrograde cholangiopancreatography: a single center experience.

BACKGROUND: the COVID-19 pandemic has impacted on several aspects of health care services worldwide. The aim of the study was to determine its influence on the case volume, success rate and complication rate of endoscopic retrograde cholangiopancreatography (ERCP). METHOD: all patients who underwent ERCP one-year before and after applying COVID-19 safety measures at the Qena University Hospital were included. Data were collected from the patients' records, analyzed and compared. RESULTS: a total of 250 patients underwent ERCP between April 1st, 2019 and March 31st, 2021, and the mean age of participants was 52 ± 18 years. There was a 5 % increase in case volume after applying COVID-19 safety measures (128 vs 122) and the total procedure time was significantly shorter (42 vs 46 minutes, p = 0.04). There was no significant difference in the overall success rate and complication rate. Procedure success significantly correlated with cannulation attempts and total procedure time in both groups, and serum bilirubin and cannulation time in the pre-COVID-19 patients and alkaline phosphatase (ALP) in post-COVID patients. ERCP-related complications significantly correlated with cannulation attempts in both groups, and ALP, international normalized ratio (INR), cannulation time and total procedure time in pre-COVID-19 patients, and platelet count and amylase in post-COVID patients. Two patients were confirmed COVID-19 cases at the time of ERCP; therapeutic targets were achieved in both with a smooth post-ERCP recovery. Three out of nine ERCP team members caught a mild to moderate COVID-19 infection and recovered after receiving proper management. CONCLUSION: our result show that there was no negative impact of using COVID-19 safety measures and precautions on the case-volume, indications, overall outcome or complication rate of ERCP.

Comparison of a 22-gauge Franseen-tip needle with a 20-gauge forward-bevel needle for the diagnosis of type 1 autoimmune pancreatitis: a prospective, randomized, controlled, multicenter study (COMPAS study).

BACKGROUND AND AIMS: Histologic diagnosis of autoimmune pancreatitis (AIP) using EUS-guided FNA (EUS-FNA) is difficult. To address this issue, new fine-needle biopsy (FNB) needles were recently developed. Here, we prospectively evaluated 2 newly designed EUS-FNB needles for histologic evaluation in patients with type 1 AIP. METHODS: This was a prospective, randomized, multicenter trial comparing biopsy specimens obtained with a 22-gauge Franseen needle or a 20-gauge forward-bevel needle in patients with suspected type 1 AIP. AIP was diagnosed according to international consensus diagnostic criteria. The primary endpoint was the sensitivity of EUS-FNB needles, and secondary endpoints were the amount of specimen obtained, histology of the pancreas based on evaluation of lymphoplasmacytic sclerosing pancreatitis (LPSP), and contribution of histologic findings to the diagnosis of AIP. RESULTS: One hundred ten patients were randomly assigned to the Franseen group (22-gauge Franseen needle) or the forward-bevel group (20-gauge forward-bevel needle). EUS-FNB sampling was successful in all patients. Nine patients were excluded because of diagnoses other than AIP. Compared with the forward-bevel needle, the Franseen needle obtained a significantly greater number of high-power fields. Of 101 patients, 39 patients (78%) in the Franseen group and 23 patients (45%) in the Forward-bevel group were diagnosed with level 1 or 2 LPSP (P = .001). Thirty-six patients could not be diagnosed with type 1 AIP without EUS-FNB specimen results. CONCLUSIONS: The 22-gauge Franseen needle should be routinely used for histologic diagnosis of type 1 AIP. (Clinical trial registration number: UMIN 000027668.).

Sevoflurane has postconditioning as well as preconditioning properties against hepatic warm ischemia-reperfusion injury in rats.

PURPOSE: Ischemia-reperfusion (IR) injury is inevitable after liver transplantation and liver resection with inflow occlusion. Sevoflurane has been widely used during hepatobiliary surgery and was reported to exhibit preconditioning (PreC) properties against hepatic IR injury; however, its postconditioning (PostC) properties remain unknown. This study examined whether a clinically applicable dose of sevoflurane has PostC and PreC properties against hepatic IR injury and roles of heme oxygenase-1 (HO-1). METHODS: Warm ischemia was induced in male Wistar rats, excluding the sham group, for 1 h, followed by 3 h of reperfusion. Group C received propofol from 60 min before ischemia until the end of the experimental procedure. In the SPreC and SPostC groups, propofol was replaced by 2.5% sevoflurane for 30 min from 35 min before ischemia in the SPreC group and for 30 min from 5 min before reperfusion in the SPostC group. The SPreC+Z and SPostC+Z groups received a HO-1 inhibitor, zinc protoporphyrin (Znpp), 60 min before ischemia, and sevoflurane PreC and PostC were induced. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, and histological damage scores in the SPreC and SPostC groups were significantly lower than those in group C. Inhibiting HO-1 with Znpp partially blocked these protective effects of sevoflurane. Sevoflurane PreC and PostC significantly increased the number of HO-1-positive Kupffer cells in comparison with group C, and Znpp prevented sevoflurane-induced HO-1 expression. CONCLUSION: PostC and PreC by sevoflurane at a clinically applicable dose have equally protective effects against hepatic IR injury by increasing HO-1 expression.

The role of pancreatic juice cytology in the diagnosis of pancreatic intraductal papillary mucinous neoplasm.

BACKGROUND AND AIM: pancreatic juice cytology (PJC) is an important predictor of malignant intraductal papillary mucinous neoplasm (IPMN). This study aimed to determine the role of PJC for the prediction of malignant IPMN (intraductal papillary mucinous cancer [IPMC]). METHODS: medical records of IPMN patients who underwent surgery between 2012 and 2016 at the Nagasaki University Hospital were reviewed. Patients who underwent preoperative PJC were classified as high risk stigmata (HRS), worrisome features (WF) and no-criteria, based on imaging criteria. PJC class III or higher was considered as positive and only invasive IPMN was defined as IPMC. PJC was validated in each group with regard to sensitivity, specificity, accuracy with the corresponding 95% confidence intervals (95% CI) and area under receiver operating curve (AUROC) analysis. A p-value of < 0.05 was considered as statistically significant. RESULTS: preoperative pancreatic juice was obtained in 33/52 IPMN patients; only patients with adequate aspirate for cytology (n = 29) were included. In the HRS group (n = 9), 4/6 non-IPMC had a negative PJC and 3/3 IPMC had a positive PJC. In the WF group (n = 17), 9/11 non-IPMC had a negative PJC and 3/6 IPMC had a positive PJC. Adding PJC to imaging results improved the AUROCs of HRS and WF from 0.63 and 0.62 to 0.83 and 0.66, respectively. PJC was negative in all no-criteria cases (n = 3; one IPMC and two non-IPMC). In all 29 patients, PJC sensitivity was 60% (95% CI: 26%-88%), specificity was 79% (95% CI: 54%-94%), accuracy was 72% (95% CI: 63%-89%) and the AUROC was 0.69 (p = 0.03). CONCLUSION: PJC is a statistically significant IPMC predictor that can improve the validity of imaging for IPMC prediction.

Sequential occurrence of acute hepatitis B among members of a high school Sumo wrestling club.

A 17-year-old male was admitted to our hospital and diagnosed with acute hepatitis B. Six weeks later, a 15-year-old male was admitted with acute hepatitis B as well. They were Sumo wrestling players in the same club. A detailed survey in the club revealed that a 28-year-old male coach was a hepatitis B surface antigen carrier with high-level viremia. The consistency of hepatitis B virus (HBV) DNA in the infected players was revealed by analyzing the complete HBV genome sequences. Sumo players are more likely to get injured, including cuts and bleeding, compared with players of other sports because of the characteristic wrestling style. Several past reports have suggested that highly viremic HBV carriers have high HBV DNA titers in both their blood and other body fluids such as sweat. In our cases, percutaneous HBV transmission through the bleeding wounds was the most probable infection route. We conclude that a universal HBV immunization program should be introduced urgently in Japan, similar to those implemented in other countries worldwide.

Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis.

Gallbladder (GB) disease is classified into two broad categories: GB wall-thickening and protuberant lesions, which include various lesions, such as adenomyomatosis, cholecystitis, GB polyps, and GB carcinoma. This review summarizes recent advances in the differential diagnosis of GB lesions, focusing primarily on endoscopic ultrasound (EUS) and related technologies. Fundamental B-mode EUS and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of GB diseases because they can evaluate the thickening of the GB wall and protuberant lesions in detail. We also outline the current status of EUS-guided fine-needle aspiration (EUS-FNA) for GB lesions, as there have been scattered reports on EUS-FNA in recent years. Furthermore, artificial intelligence (AI) technologies, ranging from machine learning to deep learning, have become popular in healthcare for disease diagnosis, drug discovery, drug development, and patient risk identification. In this review, we outline the current status of AI in the diagnosis of GB.

Are transmembrane 6 superfamily member 2 gene polymorphisms associated with steatohepatitis after pancreaticoduodenectomy?

Aim: After pancreaticoduodenectomy, 20-40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin-like phospholipase domain-containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear. Methods and Results: Forty-three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real-time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver-to-spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis-4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046). Conclusion: The TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.

Significance of hepatitis B virus core-related antigen and covalently closed circular DNA levels as markers of hepatitis B virus re-infection after liver transplantation.

BACKGROUND AND AIM: Currently, hepatitis B virus (HBV) re-infection after liver transplantation (LT) can be almost completely suppressed by the administration of HBV reverse transcriptase inhibitors and hepatitis B immunoglobulins. However, after transplantation, there is no indicator of HBV replication because tests for the serum hepatitis B surface antigen and HBV-DNA are both negative. Therefore, the criteria for reducing and discontinuing these precautions are unclear. In this study, we examined the serum HBV core-related antigen (HBcrAg) and intrahepatic covalently closed circular DNA (cccDNA) in order to determine if these could be useful markers for HBV re-infection. METHODS: Thirty-one patients underwent LT for HBV-related liver disease at Nagasaki University Hospital from 2001 to 2010. Of these, 20 cases were followed up for more than 1 year (median follow-up period, 903 days). We measured serum HBcrAg and intrahepatic cccDNA levels in liver tissue. In addition, in nine cases, we assessed the serial changes of HBcrAg and intrahepatic cccDNA levels from preoperative periods to stable periods. RESULTS: We examined serum HBcrAg and intrahepatic cccDNA levels in 20 patients (35 samples). HBcrAg and cccDNA levels were significantly correlated with each other (r = 0.616, P < 0.001). From a clinical aspect, the fibrosis stage was significantly lower in both HBcrAg- and cccDNA-negative patients than in HBcrAg- or cccDNA-positive patients. CONCLUSIONS: HBcrAg and cccDNA were useful as HBV re-infection markers after LT. Keeping patients' HBcrAg and cccDNA negative after LT might contribute to long-term graft survival.

Frequency of elevated biomarkers in patients with cryptogenic hepatocellular carcinoma.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated a-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC. MATERIAL/METHODS: A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients. RESULTS: Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C. CONCLUSIONS: DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.

[A case of a patient with splenic arteriovenous fistula associated with portal hypertension who developed refractory ascites and diarrhea as initial symptom].

A 55-year-old woman was admitted to our hospital because of diverse symptoms of portal hypertension, such as refractory ascites, diarrhea, and general malaise. Blood test revealed liver and renal dysfunction and glucose tolerance. Contrast enhancement computed tomography revealed splenic arteriovenous fistula with dilated splenic artery and vein, causing portal hypertension. The splenic arteriovenous fistula was successfully treated by percutaneous transarterial embolization, resulting in the complete recovery of the patient. Herein, we report a case of arteriovenous fistula which was successfully treated with the aid of interventional radiology.

Evans' syndrome induced by atezolizumab plus bevacizumab combination therapy in advanced hepatocellular carcinoma.

An 86-year-old man presented with recurrence of hepatocellular carcinoma (HCC) after surgery. Atezolizumab plus bevacizumab was initiated. After the third course of atezolizumab plus bevacizumab therapy, petechial purpura appeared on the extremities and trunk. Laboratory tests revealed isolated severe thrombocytopenia without evidence of combined coagulopathy. He was diagnosed with immune thrombocytopenic purpura (ITP), and high-dose immunoglobulin and Helicobacter pylori eradication therapies were administered. Improvement in thrombocytopenia was observed; however, 20 days after the onset of ITP, laboratory data revealed hemolytic anemia. Both direct and indirect Coombs tests were positive, and he was diagnosed with Evan's syndrome complicated by ITP and autoimmune hemolytic anemia (AIHA) induced by immune-related adverse events (irAEs). After treatment with prednisolone, the hemoglobin level increased, and hemolytic findings improved on blood tests. We encountered a rare case of Evans' syndrome due to atezolizumab plus bevacizumab therapy for HCC. In atezolizumab plus bevacizumab therapy, hematologic toxicities are not rare adverse events and attention is required.

Examination of stabilization of sedation by Nasal High Flow in patients with endoscopic retrograde cholangiopancreatography during sedation using Dexmedetomidine.

INTRODUCTION: Dexmedetomidine is used for the sedation method in the case of endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of relieving patient anxiety. It has been reported that CO2 accumulated during sedation causes an arousal reaction, so how to normalize CO2 during sedation can be improved by administration of the minimum necessary sedative.Nasal High Flow oxygen therapy (NHF) uses a mild positive pressure load that improves carbon dioxide washout and reduces rebreathing to improve respiratory function and therefore is widely used to prevent hypoxemia and hypercapnia. In this study, we will investigate whether the upper airway patency would be maintained and the hypercapnia and hypoxemia during sedation would be prevented, by applying NHF as a respiratory management method to patients undergoing ERCP under sedation. METHODS/DESIGN: In a randomized comparative study of 2 groups, the NHF device use group and the nasal cannula use group, for adult patients who visited the Nagasaki University Hospital and underwent ERCP examination under sedation. For sedation, Dexmedetomidine will be used in combination with and Midazolam and evaluation by anesthesiologist. In addition, as an analgesic, pethidine hydrochloride was administered intravenously. The total dose of the analgesic pethidine hydrochloride used in combination is used as the primary endpoint. As a secondary evaluation item, the percutaneous CO2 concentration is evaluated with a TCO2 monitor to examine whether it is effective in preventing hypercapnia. Furthermore, we will evaluate the incidence of hypoxemia with a percutaneous oxygen saturation value of 90% or less, and examine whether the use of equipment is effective in preventing the occurrence of hypercapnia and hypoxemia. DISCUSSION: The purpose of this study was to obtain evidence for the utility of NHF as a potential therapeutic device for patients undergoing an ERCP under sedation, assessed by determining if the incidence rates of hypercapnia and hypoxemia decreased in the NHF device group, compared to the control group that did not use of this device.