Utility of pemafibrate in nonalcoholic steatohepatitis model mice induced by a choline-deficient, high-fat diet and dextran sulfate sodium.

Aim: The purpose of this study was to examine the effect of pemafibrate in a murine model of non-alcoholic steatohepatitis (NASH). Methods: Forty-two, 19-week-old, male, C57BL/6J mice were divided into three groups: a Control group (n = 14), a dextran sulfate sodium (DSS) group (n = 14), and a DSS + PEM group (n = 14). All mice were given a standard rodent diet for the first week, followed by a choline-deficient, high-fat diet (CDHF) for the next 12 weeks. The 22nd day after the animals arrived was taken as Day 1 of the experiment. The Control group continued the CDHF diet and MilliQ water. The DSS group continued the CDHF diet, but starting on Day 1, the group received 0.8 % DSS to drink for 7 consecutive days, followed by MilliQ water for 10 days; this was taken as one course, and it was repeated on the same schedule until autopsy. The DSS + PEM group received the CDHF diet with PEM 0.1 mg/kg/day. Their drinking water was the same as that of the DSS group. On Seven animals from each group were autopsied on each of Day 50 and Day 120, and histopathological and immunohistochemical examinations, as well as quantitative RNA and cytokine measurements, of autopsied mice were performed. Results: Pemafibrate improved hepatic steatosis (decreased steatosis area), improved liver inflammation enhanced by DSS (decreased aspartate transaminase and alanine aminotransferase), improved hepatic fibrosis promoted by DSS (decreased fibrotic areas and a marker of fibrosis), inhibited tumorigenesis, and decreased intestinal inflammation in the NASH model mice. Conclusions: In a murine model of NASH, mixing PEM 0.1 mg/kg/day into the diet inhibited disease progression and tumor formation.

Post-embolization syndrome-like symptoms due to shedding of necrotic material of hepatocellular carcinoma into the bile duct following transcatheter arterial chemoembolization: an instructive case.

Fever, abdominal pain, and liver dysfunction are almost inevitable complications of transcatheter arterial chemo embolization (TACE) for hepatocellular carcinoma, but these symptoms may also be due to bile duct obstruction caused by shedding of necrotic tumor material into the bile duct. A 68-year-old man presented with persistent fever, liver dysfunction, and abdominal pain after TACE. Computed tomography revealed stone-like hyperdensities in the bile duct. Endoscopic retrograde cholangiopancreatography revealed these structures to be necrotic material from hepatocellular carcinoma. We believe this is an instructive case of an often overlooked situation.

Single-pigtail plastic stent made from endoscopic nasobiliary drainage tubes in endoscopic ultrasound-guided gallbladder drainage: a retrospective case series.

Technical failure of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is often attributed to device failure. To rectify this problem, we developed a single-pigtail plastic stent (SPPS) for EUS-GBD. We retrospectively reviewed the cases of four patients who underwent EUS-GBD for acute cholecystitis. To prepare the SPPS, a 7.5-Fr endoscopic nasobiliary drainage tube was cut to an appropriate length. The use of SPPS during EUS-GBD was successful from both technical and clinical standpoints. The SPPS spontaneously detached 57 days after the procedure in patient 4 and 412 days after the procedure in patient 1. Patient 1 developed cholecystitis after 426 days and was managed with antibiotics. The other three patients did not develop any complications after surgery. In conclusion, we designed a new SPPS dedicated to EUS-GBD and established its technical feasibility and clinical effectiveness.

An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

Utility of ultrasonography in a mouse model of non-alcoholic steatohepatitis induced by a choline-deficient, high-fat diet and dextran sulfate sodium.

Background: Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that can progress to cirrhosis and hepatocellular carcinoma. The prevalence of NASH is increasing year by year. However, the etiology and progression of NASH, along with the processes leading to carcinogenesis, remain poorly understood. A range of animal models are used in research, but investigators have been unable to establish a model that results in tumorigenesis from a stable disease state. The present study aimed to create a stable, low-mortality model of NASH using abdominal ultrasonography (US) to assess NASH stage and diagnose liver tumors. Methods: Thirty-four 19-week-old male C57BL/6J mice were fed a choline-deficient, high-fat (CDHF) diet. Twenty animals were given seven courses of 0.8 % dextran sulfate sodium (DSS) for 7 days followed by 10 days of MilliQ water (CDHF+DSS group). The remaining 14 animals drank only MilliQ water (CDHF group). All animals were weighed weekly and US was performed on Days 35 and 120. After necropsy, samples were taken for biochemical analysis and histopathological evaluation. Results: The CDHF+DSS group had significantly lower body weight on Days 35 and 120, and significantly higher liver/body weight (%) on Day 35 compared to the CDHF group. US on Days 35 and 120 revealed significantly shorter long intestine and higher colonic histological score in the CDHF+DSS group compared to the CDHF group. IL-1ß and IL-6 levels in the large intestinal tissue were significantly higher in the CDHF+DSS group. Conclusions: A stable, low-mortality model of NASH was created with a CDHF diet and intermittent 0.8 % DSS. Abdominal US can assess the degree of fatty degeneration and evaluate liver tumorigenesis without necropsy. This assessment procedure will reduce the number of mice killed unnecessarily during experiments, thereby contributing to animal welfare.

Hepatic invasion of a gastric ulcer confirmed by endoscopy and surgery.

A 66-year-old woman who had been suffering from chronic anorexia for two years was transported to the hospital after being unable to consume food for three days. She had no hematemesis or abdominal pain and had no history of taking nonsteroidal anti-inflammatory drugs. Blood tests showed marked anemia with hemoglobin of 3.3 g/dL, and esophagogastroduodenoscopy revealed a large ulcer lesion in the lesser curvature of the gastric body and a liver-like mass protruding from the ulcer base. Biopsy of the mass showed proliferation of cells showing irregular cord-like structures, suggestive of normal liver tissue or hepatocellular carcinoma. Computed tomography scan showed no obvious free air in the abdomen. Despite conservative treatment, the patient developed hematemesis and progressive anemia, and surgery was performed (total gastrectomy with partial hepatectomy). Surgical specimen showed an ulcer lesion with fibrosis and loss of wall structure in all layers of the stomach, and liver adhesion with fibrosis deep in the ulcer, but no malignant findings. With the advent of powerful gastric acid secretion inhibitors, gastric ulcer invasion into the liver is now very rare, and this case is thus a valuable example showing very clear images.

Efficacy of endoscopic ultrasound-guided pelvic abscess drainage for pelvic abscesses: A case series study.

BACKGROUND AND STUDY AIM: This is a retrospective study to evaluate the safety and efficacy of endoscopic ultrasound-guided pelvic abscess drainage (EUS-PAD) in a single hospital setting. PATIENTS AND METHODS: The referral criteria for EUS-PAD included patients with a pelvic abscess (PA) that was amenable for the procedure. A total of 14 patients with PA treated with EUS-PAD were included in this study. The mean patient age was 57.4 years, and male-to-female ratio was 7:7. Overall, there were six cases of appendiceal perforation, five of rectal cancer and one case each of the diverticular perforation, perianal abscess, and walled-off necrosis. RESULTS: Overall, 100% of procedures were successful. Clinical success was achieved in 11 patients and they were discharged after EUS-PAD within 21.4 days on an average and the average duration of stent placement before removal was 27.0 days. Of all, six patients achieved complete improvement status where the cause was appendiceal perforation while two and one of the patients were recovered where the causes were post-curative operation for carcinoma and walled-off necrosis, respectively. Eight out of eleven patients who exhibited appendiceal perforation or underwent radical rectal cancer surgery were discharged after an average of 9.4 days post EUS-PAD. Although two patients showed temporary improvement, with perianal abscess and controlled rectal carcinoma, the PA worsened as the primary disease intensified. The PA drainage was ineffective in three patients where two of them had uncontrolled rectal cancer and one had diverticular perforation. CONCLUSION: Conclusively, the EUS-PAD is not only a reliable, safe, and efficient alternative to surgical and percutaneous drainage but also a valuable procedure with a high success rate for patients with acute infections, such as those who have had an appendiceal perforation or curative surgery. Poor indications and contraindications for EUS-PAD include uncontrolled gastrointestinal perforation and direct tumor invasion.

EFFECTIVENESS OF INTRA-SCOPE CHANNEL PLASTIC STENT RELEASE IN ENDOSCOPIC ULTRASOUND-GUIDED PELVIC ABSCESS DRAINAGE.

Abscess endoscopic ultrasound pelvic abscess drainage plastic stent; rectal carcinoma.

Colonic perforation after esophagogastroduodenoscopy: complications with self-expanding metallic stents.

An 83-year-old man was admitted to the emergency room with abdominal pain and bloating. Abdominal computed tomography (CT) revealed a sigmoid colon obstruction caused by colonic carcinoma involving a short segment with circumferential luminal narrowing. The patient underwent endoscopy with colonic self-expanding metallic stent (SEMS) placement as a bridge to surgery. Six days after SEMS placement, the patient was prepared for esophagogastroduodenoscopy for screening. Although screening revealed no complications, 8 h later, the patient complained of sudden abdominal pain. Emergency abdominal CT revealed that the SEMS was about to burst out of the colon. An emergency operation with sigmoidectomy and colostomy was performed, and operative findings revealed a colonic perforation by the SEMS at the proximal side of the tumor. The patient was discharged from the hospital without major problems. This case is a very rare complication of colonic SEMS insertion. It is possible that increased intraluminal bowel movement and/or CO2 pressure during the esophagogastroduodenoscopy caused colonic perforation. Endoscopic placement of a SEMS is an effective alternative to surgical decompression for treating colon obstruction. To avoid unexpected and unnecessary perforations, tests that could increase the intraluminal pressure within the intestine after SEMS insertion should be avoided.

A case of a rare foreign object found in the stomach - A Hem-o-Lok clip after laparoscopic distal pancreatectomy.

We assessed an 81-year-old woman who underwent laparoscopic distal pancreatectomy for a large branched-type intraductal papillary mucinous neoplasm. An enlarged and infected 60-mm cyst was found adjacent to the resection margin one month after surgery. The non-absorbable polymer clip (NAPC: Hem-o-Lok), which was used for ligation of the splenic artery, could also be visualized. We performed endoscopic ultrasound guided-cyst drainage (EUS-CD) for controlling the enlarged and infected cyst. Further, we planned to remove the tube endoscopically after 6 months. During esophagogastroduodenoscopy six months later, the post-EUS-CD scar could be detected without the EUS-CD tube. However, a white artifact could be seen protruding from the outside of the gastric wall into the stomach. Despite the difference in color and morphology, we thought the EUS-CD tube might have been torn at first. We grasped the artifact with endoscopic forceps, and the object was identified as an NAPC. We considered that the fragility and inflammation of the pancreas and surrounding tissues led to the collection of necrotic pancreatic fluid, resulting in an inflammatory response. Upon tearing the puncture hole little by little following EUS-CD, the NAPC was dislodged as an unanticipated foreign body.

The efficacy and safety of colonoscopy in nonagenarians: A multicenter study.

INTRODUCTION: The number of colonoscopy (CS) for the elderly is increasing. There are only a few reports focusing on CS among the very elderly aged ≥ 90-y. We aimed to analyze the efficacy of CS and of colorectal cancer (CRC) for patients aged ≥ 90-y. METHODS: We retrospectively analyzed consecutive patients aged ≥ 90-y receiving CS at eight institutions from October 2016 to September 2017. Bowel preparation, complications, and endoscopic diagnosis were analyzed. The non-elderly group aged between 50-y and 64-y and elderly group aged between 65-y and 79-y were compared to very-elderly group aged ≥ 90-y. Through propensity score matching of sex and CS indications (symptomatic or asymptomatic), the number of CRC and the treatment in each group were analyzed. RESULTS: We analyzed 125 patients receiving 154 colonoscopies (0.9%) in the very-elderly group from among 16,968 cases. Among 92 cases who received bowel-cleansing solution, good preparations were achieved in 94.5%. The rate of CS-related complications was 1.3% (2/154). The rate of CRC in the very-elderly group was 27.2% (34/125), higher than the non-elderly group (7.2%, 9/125, p < 0.01) and elderly group (8.8%, 11/125, p < 0.01). Therapeutic interventions for CRC in the very-elderly group were performed in 73.5% (24/34) patients. The mean survival of 12 patients with CRC resection was 788 days. CONCLUSIONS: CS could be performed safely for the very elderly aged ≥ 90-y with careful considerations. CRC was confirmed to be more frequent in this group with over 70% of patients receiving appropriate therapeutic intervention.

Hyposensitization trial using salazosulfapyridine in a case of mesalamine intolerance.

A 47-year-old Japanese man was diagnosed with pancolitis-type ulcerative colitis. He was treated with mesalamine in a pH-dependent release form. On day 16 of administration, he was admitted because of fever and abdominal pain. We diagnosed his symptoms to be the side effects of mesalamine. Hyposensitization using unmodified and a time-dependent release form mesalamine was performed. On day 7 of mesalamine hyposensitization, a colonoscopy was performed. The patient presented with the same allergic symptoms 9 h after the administration of an oral sodium phosphate solution. Eventually, he was orally administered a course of salazosulfapyridine (SASP) at an initial dose of 2.5 mg/day, which was increased to 2000 mg/day. It is generally recognized that SASP intolerance is an indication to switch from SASP to mesalamine. The need to switch treatment from mesalamine to SASP is, therefore, rare because allergic reactions to mesalamine do not occur frequently. We report a very rare case which was presented with abdominal pain and myalgia because of intolerance to mesalamine in whom hyposensitization with and introduction of SASP were successful.

Multicenter Study of the Hemorrhage Risk after Endoscopic Mucosal Resection Associated with Direct Oral Anticoagulants.

BACKGROUNDS AND AIMS: Recently, direct oral anticoagulants (DOACs) have become widely used for preventing thromboembolism. However, postoperative hemorrhage (POH) is a major complication associated with endoscopic mucosal resection (EMR) for colorectal lesions. In this multicenter study, we analyzed the incidence of POH after EMR associated with DOACs and explored the associated risk factors. MATERIALS AND METHODS: This study was a multicenter retrospective cohort study conducted at 8 Japanese institutions. A total of 2062 cases that underwent EMR for colorectal lesions at these 8 institutions from October 2016 to September 2017 were analyzed. The cases were divided into 4 groups: the DOAC group (63 cases), warfarin group (34 cases), antiplatelet group (185 cases), and no antithrombotics group (1780 cases). In all lesions of the DOAC and warfarin groups, endoscopic clipping was performed after EMR. The rate of POH in the DOAC group, patients' clinical characteristics, the risk factors of POH, and the rate of thromboembolism due to stopping DOACs were compared with other groups. RESULTS: The rates of POH were 7.9%∗ (5/63), 2.9% (1/34), 3.2% (6/185), and 0.6%∗∗ (11/1780) in the DOAC, warfarin, antiplatelet, and no antithrombotics groups, respectively (∗ vs. ∗∗, p < 0.001). Regarding risk factors, the tumor size with POH (mm) was significantly bigger than that without POH (16.2 ± 8.3 vs. 7.2 ± 4.9, p < 0.001). There were no significant differences in the rates of POH based on the type of DOAC. In addition, no thromboembolisms occurred due to stopping of DOAC treatment. CONCLUSIONS: Patients receiving DOACs had significantly higher rates of POH after EMR than those without antithrombotics.

Usefulness of the modified clip-with-line method for endoscopic mucosal treatment procedure.

Endoscopic submucosal dissection (ESD) might be difficult to perform in some cases even for experienced endoscopists. Recently, various traction methods have been introduced to facilitate ESD procedures, such as clip-with-line (CL), external forceps, clip and snare, internal traction, double scope, and magnetic anchor. The traction procedure using the CL method enhances the visibility of the operation field during ESD. The original CL method is performed as follows: the clip with the line (e.g., dental floss) is attached to the edge of the lesion. Traction can be produced by pulling the line gently, thus achieving a sufficient visualization of the submucosal layer to identify an accurate cutting line. Herein, we present a useful modified two-CL method by pulling the appropriate normal mucosa to enhance the visibility of the operation field during ESD procedure. Thus, the traction methods, including our modified CL technique, might reduce the procedure time and complications.