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.

Endoscopic Submucosal Dissection Using EndoTrac, a Novel Traction Device.

BACKGROUND: Endoscopic submucosal dissection (ESD) is recognized as a minimally invasive and curative treatment for superficial gastrointestinal (GI) cancers. However, ESD is still challenging and time-consuming with a high risk of adverse events such as bleeding and perforation. Various traction methods have been explored for maintaining good visualization of the submucosal layer during ESD. We developed a novel traction device (the EndoTrac) which can easily tie the thread and has the ability to change the towing direction. The aim of this study is to evaluate safety and feasibility of ESD using the EndoTrac for GI neoplasms. PATIENTS AND METHODS: We retrospectively analyzed 44 patients (45 lesions) with esophageal, gastric, duodenal, and colorectal neoplasms who had undergone ESD using the EndoTrac device between June 2018 and May 2019. Primary outcome measures were preparation time, procedural success using the EndoTrac device, and ease of ability to change towing direction. RESULTS: Mean preparation time was 2 (2-5) min in esophagus, 3 (1-5) min in stomach, 6 (5-9) min in duodenum, and 4 (2-8) min in colorectum. The procedural success rate was 100% (8/8) in esophagus, 100% (21/21) in stomach, 100% (4/4) in duodenum, and 100% (12/12) in colorectum. The rate of successful towing to both proximal and distal sides was 100% (8/8) in esophagus, 100% (21/21) in stomach, 0% (0/4) in duodenum, and 100% (12/12) in colorectum. CONCLUSIONS: Use of the EndoTrac device appears to be a feasible approach to ESD for GI neoplasms.

Vonoprazan vs lansoprazole for the treatment of artificial gastric ulcer after endoscopic submucosal dissection: a prospective randomized comparative study.

Vonoprazan is a potent inhibitor of gastric acid secretion and may have better response than proton pump inhibitors (PPIs) in the treatment of endoscopic submucosal dissection induced artificial ulcers. However, reported outcomes remain controversial. In this study, we conducted a prospective, randomized comparative trial to evaluate healing effects of vonoprazan and lansoprazole on endoscopic submucosal dissection (ESD)-induced ulcers. We enrolled 216 patients who underwent endoscopic submucosal dissection for early gastric neoplasms. They were randomly divided into vonoprazan (20 mg/day) and lansoprazole (30 mg/day) groups. The primary endpoint was the reduction rate of ulcer and complete healing (scar) ratio of ESD-induced ulcers at 4 and 8 weeks. Finally, 101 patients of the vonoprazan group and 95 patients of the lansoprazole group were included in the analysis. There were no significant differences in the reduction rate between the vonoprazan and lansoprazole groups at either timepoint (4 weeks, 94.0 vs 93.4%; 8 weeks, 99.8 vs 99.9%, respectively). The complete healing ratio at 4 and 8 weeks did not differ significantly between the vonoprazan and lansoprazole groups (4 weeks, 11.9 vs 12.6%; 8 weeks, 87.1 vs 86.3%, respectively). In the anti-H. pylori-antibody negative or positive patients, there were no significant differences in the reduction rate and complete healing ratio between the vonoprazan and lansoprazole groups. Regardless of treatment choice, the overall complete healing ratio at 8 weeks was significantly higher in the anti-H. pylori-antibody negative patients than the positive patients (p = 0.006). The healing effects of vonoprazan on ESD-induced ulcers were comparative to those of lansoprazole.

No transformation of a fundic gland polyp with dysplasia into invasive carcinoma after 14 years of follow-up in a proton pump inhibitor-treated patient: A case report.

A fundic gland polyp (FGP) is a common gastric polyp. Intraepithelial neoplasia in FGPs, referred to as FGP with dysplasia, is often seen in patients with familial adenomatous polyposis (FAP). In sporadic FGPs, low-grade dysplasia (LGD) is rare, and high-grade dysplasia (HGD) or carcinoma arising from sporadic FGPs is extremely rare. Because of this rarity, the prognosis and appropriate management of these lesions have not been clarified. In the present case, a sporadic FGP with LGD did not develop into invasive carcinoma, but contained foci of HGD 14 years after diagnosis. The biopsy specimen of the polyp taken at the first esophagogastroduodenoscopy 15 years earlier was diagnosed as FGP without dysplasia. At the second histological examination, LGD was found. Because the polyp increased in size during proton pump inhibitor therapy for 14 years, endoscopic mucosal resection was performed. The pathological diagnosis of the resected specimen was FGP with HGD mixed in LGD, with no invasive carcinoma. Dysplasia in FGPs might have less malignant potential regardless of dysplasia or size.

[A Case of Combined Treatment Approach of Endoscopic Submucosal Dissection and Transanal Minimally Invasive Surgery for Radiation Induced Rectal Cancer].

It is hard to determine treatment strategy for radiation induced carcinoma, because radiation cause fibrosis to adjacent organ.The patient was in the 70's, who underwent 70 Gy radiation therapy for prostate cancer 5 years ago.He visited hospital because of fecal occult blood.Endoscopic examination revealed laterally spreading tumor(LST)in rectal front wall, and he referred to our hospital in purpose of endoscopic submucosal dissection(ESD).We performed ESD for LST, following transanal minimally invasive surgery to suture mucosal defect.He discharged out hospital 9 days after operation without any adverse event except anal pain.Suturing of mucosal defect after ESD might be potent to prevent postoperative complications in radiation induced rectal cancer.

Four-times-daily Dosing of Rabeprazole with Sitafloxacin, High-Dose Amoxicillin, or Both for Metronidazole-Resistant Infection with Helicobacter pylori in Japan.

BACKGROUND: The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. AIM: To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. METHODS: We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a 13 C-urea breath test. RESULTS: Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. CONCLUSION: In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains.

Factors affecting pancreatic hyperamylasemia in patients undergoing peroral single-balloon enteroscopy.

BACKGROUND AND AIM: Acute pancreatitis following balloon-assisted enteroscopy is a rare but serious complication. The causative mechanism is uncertain and prevention strategies are not established. We conducted a retrospective study to clarify the risk factors for pancreatic hyperamylasemia. METHODS: Eighty-four patients undergoing peroral single-balloon enteroscopy (SBE) were enrolled in this study. Serum pancreatic and salivary amylase levels were measured 2 h after endoscopic examination. RESULTS: We experienced three patients with post-SBE pancreatitis. Factors predicting pancreatic hyperamylasemia were: (i) elderly patients; (ii) deeper insertion; and (iii) clockwise insertion. In contrast, younger age at examination was a significant factor observed in salivary hyperamylasemia. CONCLUSIONS: It is important to measure pancreatic amylase and not total amylase after SBE. When carrying out peroral SBE, the distance of insertion should be reduced especially if the scope traces a clockwise loop or the subject is elderly.

Comparison of energy metabolism and nutritional status of hospitalized patients with Crohn's disease and those with ulcerative colitis.

This study aimed to compare the nutritional status and energy expenditure of hospitalized patients with Crohn's disease (CD) and those with ulcerative colitis (UC). Twenty-two hospitalized patients with CD and 18 patients with UC were enrolled in this study. We analyzed nutritional status upon admission by using nutritional screening tools including subjective global assessment, malnutrition universal screening tool, and laboratory tests. We measured resting energy expenditure (mREE) of the patients with indirect calorimetry and predicted resting energy expenditure (pREE) was calculated by using the Harris-Benedict equation. Results presented here indicate no significant difference in nutritional parameters and energy metabolism between CD and UC patients. In UC patients, a significant correlation was observed between mREE/body weight and disease activity detected by the Lichtiger and Seo indices. However, there was no correlation between mREE/body weight and Crohn's disease activity index in CD patients. Inflammatory cytokine interleukin-6 levels correlated with mREE/pREE in CD and UC patients while tumor necrosis factor-α was not. In conclusion, energy expenditure significantly correlated with disease activity in UC patients but not in CD patients. These results indicate that establishing daily energy requirements based on disease activity of UC is imperative for improving the nutritional status of patients.

Changes in energy metabolism after induction therapy in patients with severe or moderate ulcerative colitis.

We investigated the changes in energy expenditure during induction therapy in patients with severe or moderate ulcerative colitis. Thirteen patients (10 men, 3 women; mean age, 36.5 years) with ulcerative colitis admitted to the Shiga University Hospital were enrolled in this study. We measured the resting energy expenditure and respiratory quotients of these patients before and after induction therapy with indirect calorimetry. We analyzed the changes of nutritional status and serum inflammatory cytokine levels and also evaluated the relationship between energy metabolism and disease activity by using the Seo index and Lichtiger index. The resting energy expenditure was 26.3 ± 3.8 kcal/kg/day in the active stage and significantly decreased to 23.5 ± 2.4 kcal/kg/day after induction therapy (p<0.01). The resting energy expenditure changed in parallel with the disease activity index and C-reactive protein and inflammatory cytokine levels. The respiratory quotient significantly increased after induction therapy. Thus, moderate to severe ulcerative colitis patients had a hyper-metabolic status, and the energy metabolism of these patients significantly changed after induction therapy. Therefore, we recommend that nutritional management with 30-34 kcal/kg/day (calculated as measured resting energy expenditure × activity factor, 1.3) may be optimal for hospitalized ulcerative colitis patients.

[Cases of Three Patients with Gastric Cancer and Metastasis to the Skeletal Muscle].

Metastasis to the skeletal muscle from gastric cancer is relatively rare. We report cases of 3 patients undergoing chemotherapy for gastric cancer with metastasis to the skeletal muscle. Case 1: A man in his 70s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the lung, brain, lymph node, and iliopsoas muscle. Case 2: A man in his 60s was diagnosed with advanced gastric cancer (cT3N3M1P0, stage IV), with metastasis to the brain, lung, lymph node, and iliopsoas muscle. Case 3: A man in his 50s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the urinary duct, lymph node, back muscle, and iliopsoas muscle. All 3 patients died within 7-8 months after the diagnosis due to progressive disease despite chemotherapy. The prognosis of these 3 patients was significantly poorer than that of patients in our hospital with metastasis not involving the skeletal muscle (p<0.01). Accordingly, metastasis to the skeletal muscle may be an adverse prognostic factor in gastric cancer.

Predicting Mucosal Healing in Crohn's Disease Using Practical Clinical Indices with Regard to the Location of Active Disease.

BACKGROUND/AIMS: Only a few reports have examined the relationship between balloon-assisted enteroscopy (BAE)-based mucosal lesion severity in Crohn's disease (CD) using clinical variables such as serum levels of disease activity markers and Crohn's Disease Activity Index. We analysed whether clinical variables are useful for predicting mucosal healing (MH) in various CD types. METHODOLOGY: A total of 173 CD patients who underwent BAE were enrolled. Endoscopic findings were assessed using the modified Rutgeerts score (MRS). In this study, all observed samples of intestine, small bowel and large bowel were individually scored. The 'ileum group' included patients with MRS ileum scores greater than or equal to MRS colon scores (n = 139), whereas the 'colon group' included patients who had colon scores greater than or equal to MRS ileum scores (n = 56). RESULTS: Spearman's rank correlation between MRS and practical clinical parameters was stronger in the colon group than in the ileum group. Receiver operating characteristic analysis revealed that the colon group had better correlativity for MH prediction than the ileum group. The MH index using C-reactive protein and serum albumin obtained from logistic regression analysis improved the accuracy of MH prediction by 74.3%. CONCLUSION: A combination of serum albumin and C-reactive protein is useful for MH prediction. However, the reliability of MH prediction can differ depending on the dominant area of the mucosal lesions.

Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction.

BACKGROUND: Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. METHODS: Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. RESULTS: Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). CONCLUSIONS: Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy.

Neutralization of complement component C5 ameliorates the development of dextran sulfate sodium (DSS)-colitis in mice.

The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease, we evaluated the effects of anti-C5 antibodies on the development of dextran sulfate sodium-induced colitis in mice. Dextran sulfate sodium-colitis was induced in BALB/c mice with intraperitoneal administrations of anti-C5 antibodies (1 mg/body [DOSAGE ERROR CORRECTED]) every 48 h. Tissue samples were evaluated by standard histological procedures. The mucosal mRNA expression of the inflammatory cytokines was analyzed by real-time PCR. Body weight loss in the mice was completely blocked by the administration of anti-C5 antibody. The disease activity index was significantly lower in the anti-C5 antibody-treated mice than the dextran sulfate sodium mice. The colonic weight/length ratio, histological colitis score and mucosal myeloperoxidase activity were significantly lower in the anti-C5 antibody-treated mice than the dextran sodium sulfate mice. The administration of the anti-C5 antibody significantly reduced the mucosal expression of mRNAs for tumor necrosis factor-α, interleukin-1ß and interleukin-6. In conclusion, the complement system plays a role in the development of dextran sodium sulfate-induced experimental colitis.

Implantation of sigmoid colon cancer into the endoscopic resection site of intramucosal rectal cancer: A case report.

A 70-year-old woman was diagnosed with intramucosal rectal cancer and advanced sigmoid colon cancer at the same time. First, the intramucosal rectal cancer was curatively resected by endoscopic submucosal dissection, and surgery was subsequently performed for sigmoid colon cancer. After 20 months, a follow-up colonoscopy revealed a tumor growth at the ulcer scar of the endoscopic submucosal dissection. Histological findings and KRAS mutation analysis suggested implantation of sigmoid colon cancer to the post-endoscopic submucosal dissection site of intramucosal rectal cancer.

The severity of dextran sodium sulfate-induced colitis can differ between dextran sodium sulfate preparations of the same molecular weight range.

BACKGROUND: We hypothesized that the severity of dextran sodium sulfate (DSS)-induced colitis could differ between DSS preparations of the same molecular weight, and that this difference may be affected by the sulfur content. To test this, we used three DSS preparations of similar molecular weights but with different sulfur contents. METHODS: Three DSS preparations with molecular weights of 40,000 to 50,000 were tested: MP Biomedicals (MP Bio), USB (USB), and The Lab Depot (The Lab). Epithelial cell lines were used to assess the levels of poly (ADP-ribose) polymerase (PARP) in the presence of 2.0% DSS in vitro. Eight-week-old female C57/B6 mice were fed 2.0% DSS in water for 1 week, and then sacrificed to investigate the effects of the DSS preparations in vivo. RESULTS: In vitro experiments using CaCo-2 and CMT-93 cells revealed decreased PARP levels from all DSS preparations. Notably, the PARP level was significantly decreased in CaCo-2 cells treated with DSS from USB as compared to The Lab Mice treated with The Lab DSS had significantly decreased body weight losses on day 7 as compared to mice receiving DSS from MP Bio and USB. This result was supported by their DAI score, colon weight/length ratio, and histological scores. CONCLUSION: The severity of colitis can differ between similar DSS preparations of the same molecular weight range. This difference in colitogenic properties may be affected by the total sulfur content of each DSS preparation.

Mixed neuroendocrine-non-neuroendocrine neoplasm associated with autoimmune gastritis.

A 60-year-old woman presented with a protruding tumor at the anterior wall of the middle gastric body, and she was positive for anti-parietal cells antibodies with elevated serum gastrin level. Final diagnosis was a mixed neuroendocrine-non-neuroendocrine neoplasm consisting of adenocarcinoma (tub1) and neuroendocrine tumor G2 with autoimmune gastritis.

A case of appendix adenocarcinoma associated with ulcerative colitis.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. Patients with UC have an increased risk of developing colorectal cancer. However, appendix adenocarcinoma associated with UC is extremely rare.

Difference of computed tomographic characteristic findings between gastric and intestinal gastrointestinal stromal tumors.

PURPOSE: We aimed to compare the computed tomography (CT) imaging differences between gastric and intestinal gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: Thirty-eight patients with 38 gastric GISTs and 27 with 31 intestinal GISTs were enrolled. Tumors were classified as small (< 5 cm) or large (≥ 5 cm). Qualitative and quantitative CT imaging characteristics on non-contrast and contrast-enhanced CT were evaluated by two radiologists independently and statistically compared. RESULTS: Early venous return and higher CT number of the draining vein in the arterial phase were more frequent in small-sized intestinal GISTs than in small-sized gastric GISTs (p < 0.001). Small-sized intestinal GISTs demonstrated a wash-out pattern, whereas small-sized gastric GISTs showed a plateau pattern. Contrast enhancement was higher in small-sized intestinal GISTs than in small-sized gastric GISTs (p < 0.001). CT number was inversely proportional to the diameter of intestinal GISTs in both arterial and venous phases but not to that of gastric GISTs. CONCLUSION: Strong enhancement with wash-out pattern and early venous return are characteristic findings of small-sized intestinal GISTs. Radiologists should be aware that CT findings of GISTs have a wide spectrum and may differ according to size and site of origin.

Comparison of characteristic computed tomographic findings of gastrointestinal and non-gastrointestinal stromal tumors in the small intestine.

PURPOSE: We aimed to reveal specific findings of gastrointestinal stromal tumors (GISTs) in the small intestine on contrast-enhanced computed tomography (CT) by comparing GISTs with non-GISTs. METHODS: We enrolled 28 patients with 39 GISTs and 20 patients with 22 non-GISTs who underwent enterectomy with a preoperative diagnosis of small intestinal tumor. All lesions were diagnosed by histopathological examination. Two radiologists independently evaluated internal homogeneity, growth pattern, calcification, intratumoral hemorrhage, degeneration, ulceration, and lymphadenopathy and measured the maximum diameter of the tumor and contrast-enhanced CT (CECT) value of the solid portion as well as the diameter and CT value of the feeding artery and drainage vein on CECT in the arterial and venous phases. RESULTS: Intratumoral hemorrhage was seen in 15.4% and 25.6% of GISTs and in 0% and 0% of non-GISTs (p = 0.079 and 0.010), with good interobserver agreement (κ = 0.715). The drainage vein diameter correlated well with the maximum diameter of the tumor (r = 0.744, p < 0.001). The CT value of the solid tumor part in the arterial and venous phases (p < 0.01) and the CT value of the drainage vein in the arterial phase (p < 0.05) were higher for GISTs than for non-GISTs (p < 0.01). CONCLUSIONS: Strong parenchymal enhancement with the peak in the arterial phase and the CT value of the drainage vein in the arterial phase was characteristics findings of GIST compared with non-GISTs. The diameter of the drainage vein was proportional to the maximum diameter of GISTs.