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 with the combination of a scissor-type knife and novel traction method for colonic neoplasm involving a diverticulum.

Video 1A 35-mm laterally spreading tumor partially infiltrated the interior portion of the diverticular orifice in the ascending colon. Glycerol and hyaluronate solution were injected into the submucosa to maintain adequate mucosal elevation. Mucosal incision and submucosal dissection were performed using a DualKnife and insulation-tipped knife from the anal side; however, safe submucosal dissection was challenging with these knives because of severe fibrosis and abundant blood vessels in the diverticulum. Therefore, to improve the visibility of the submucosa, a scissor-type knife and a multiloop traction device was used to facilitate the submucosal dissection. Finally, en bloc resection was achieved in 117 minutes without adverse events. A part of the diverticular defect after endoscopic submucosal dissection was clipped to prevent delayed perforation.

Case Report: Coexistence of Multiple Myeloma and Auricular Chondritis in VEXAS Syndrome.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an inflammatory disorder caused by somatic UBA1 variants, which are sometimes associated with hematological disorders, including myelodysplastic syndrome (MDS). VEXAS syndrome often overlaps with rheumatic diseases, including relapsing polychondritis. Here, we describe a case of VEXAS syndrome with auricular chondritis and exceptional multiple myeloma (MM). An 83-year-old man was diagnosed with MM, which was treated once by lenalidomide hydrate obtaining a partial response, but the patient did not desire further aggressive therapy. Although the treatment was effective, progressive macrocytic anemia and inflammation of both the ears emerged over the following 2 months. The histological examination of the auricle skin revealed that the perichondrial area was infiltrated by inflammatory cells, leading to the diagnosis of auricular chondritis. He was treated with oral prednisolone 40 mg/day, and his symptoms rapidly resolved. The re-evaluation of the histopathological bone marrow findings revealed vacuoles in the myeloid precursor cells without myelodysplasia-related changes. Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood leukocytes and revealed a somatic variant (c.122T>C:p.Met41Thr) consistent with VEXAS syndrome. This demonstrates that patients with chondritis can have complications with MM despite the absence of underlying MDS. A strong association exists between UBA1 variants and the risk of MDS; however, it remains elusive whether somatic UBA1 variants contribute to the development of plasma cell dyscrasia without MDS. Hence, we discuss the possible relationship between auricular chondritis and MM on a background of VEXAS syndrome.

Colonic Endoscopic Submucosal Dissection for a Granular Cell Tumor with Insufficient Endoscopic Manipulation in the Hepatic Flexure.

This report describes a granular cell tumor (GCT) with insufficient endoscopic manipulation in the hepatic flexure (HF) of the colon, which was treated by endoscopic submucosal dissection (ESD) using a splinting tube and the spring S-O clip traction method. A 44-year-old man presented with a 10 mm subepithelial tumor in the HF near the ascending colon on colonoscopy. The lesion had a smooth surface without erosion. The histology of biopsied specimen from the lesion was suspected as a GCT. Most GCTs are considered low-grade malignant, but ESD was chosen to treat the lesion due to the patient's insistence on endoscopic treatment. Because the lesion was located in the HF, it was assumed that the scope manipulation during ESD would be difficult. During ESD, a splinting tube was utilized to stabilize endoscopic manipulation and the spring S-O clip traction method to keep clear visualization of the submucosa, and the procedure was completed without adverse events. An 8 × 7 mm lesion with negative margins was removed by ESD. Hematoxylin and eosin staining showed atypical cells with round-to-oval nuclei and acidophilic vesicles, and immunohistochemical staining for S-100 protein was strongly positive with a Ki-67 labeling index of 5%. The lesion was pathologically confirmed as a GCT. This case showed the usefulness and safety of ESD for GCT with insufficient endoscopic manipulation in the HF.

Evaluation of the relationship between the spleen volume and the disease activity in ulcerative colitis and Crohn disease.

ABSTRACT: Inflammatory bowel disease (IBD) is caused by the activation of an abnormal immune response in the intestinal mucosa; the spleen is involved in the main immune response. Ulcerative colitis (UC) and Crohn disease (CD) have different inflammatory mechanisms; this study aimed to quantitatively measure and compare the spleen volumes between patients with UC and CD and examine the relationship between spleen volume and disease activity in both.We retrospectively analyzed 44 patients with IBD aged 30-60 years (UC group, n = 24; CD group, n = 20). The control group comprised 19 patients with pancreatic cysts that did not affect the spleen volume. All patients underwent computed tomography (CT) between April 2014 and March 2019. Using the Image J software, spleen volumes in the UC, CD, and control groups were measured accurately from the CT images and adjusted for the body weight.No significant differences in the sex, age, or body weight were noted between the UC and CD groups and the control group. The spleen volumes, adjusted for the body weight, were 2.2 ±â€Š1.0 cm3/kg, 2.0 ±â€Š1.0 cm3/kg, and 3.6 ±â€Š1.7 cm3/kg in the control, UC, and CD groups, respectively. The volumes differed significantly between the CD and control groups (P = .01), but not between the UC and control groups (P = .43). Furthermore, a significant strong correlation was found between the disease activity and the body weight-adjusted spleen volume in patients with CD (P < .01).The spleen volume, adjusted for the body weight, was significantly larger in patients with CD than in the controls and was also strongly correlated with the CD activity. These results suggest that the immune response in CD may affect the spleen volume.

Trichuris trichiura Incidentally Detected by Colonoscopy and Identified by a Genetic Analysis.

Although trichuriasis, a zoonotic disease, has recently become rare in Japan due to improved environmental hygiene, we herein report a 79-year-old man in whom a worm was incidentally found in the ascending colon during colonoscopy for positive fecal occult blood and was endoscopically removed. A genetic analysis identified the worm as Trichuris trichiura possessing mixed sequences from non-human primate and human origins. Despite controversy regarding Trichuris trichiura infection originating from Japanese macaques, according to some studies, it originates primarily from humans. This report suggests the efficacy of a genetic analysis for identifying infection sources.

Optimal selection of endoscopic resection in patients with esophageal squamous cell carcinoma: endoscopic mucosal resection versus endoscopic submucosal dissection according to lesion size.

En bloc resection is essential for accurate pathological evaluation in patients with superficial esophageal squamous cell carcinoma (SESCC). This retrospective study aimed to clarify optimal treatment selection of endoscopic resection according to lesion size. A total of 760 patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) between January 2011 and December 2015. Among them, this retrospective study included 196 solitary index SESCC lesions ≤20 mm, with the deepest invasion to the mucosa or superficial submucosa endoscopically. The lesions were classified according to size measured via endoscopy as follows; group A: lesions ≤10 mm, group B: lesions ≥11 mm but ≤15 mm, and group C: lesions ≥16 mm but ≤20 mm. The short- and long-term outcomes were investigated for EMR and ESD subgroups. In patients undergoing EMR and ESD, en bloc resection rates for group A and B were not different (98.8 vs. 100%, 93.3 vs. 100%, respectively). However, the en bloc resection rate was significantly lower in EMR than that in ESD for group C (64.3 vs. 100%, P < 0.001). Furthermore, the use of adjunctive ablative therapy rate was significantly higher in EMR than that in ESD in group C (35.7 vs. 0%, P < 0.001). The 5-year cumulative local recurrence rate of group C was significantly higher than that of group A + B after EMR (P < 0.01). EMR was an adequate treatment for SESCC lesions ≤15 mm. On the other hand, ESD could be necessary to achieve en bloc resection for lesions ≥16 mm to avoid local recurrence.

Upregulation of complement C1q reflects mucosal regeneration in a mouse model of colitis.

Confirming mucosal healing is important in inflammatory bowel disease treatment. Complement C1q-mediated Wnt signaling activation has recently been suggested to mediate tissue repair and mucosal regeneration. We investigated the involvement of complement C1q and Wnt signaling in intestinal mucosal regeneration using a murine colitis model. The colitis model was established by providing C57BL/6J mice with 4% dextran sodium sulfate (DSS) for 1 week (inflammation phase) followed by regular water for 2 weeks (recovery phase). After 3 weeks, we investigated the relationship between C1q in serum and colonic tissue during the inflammation and recovery phases. We assessed Wnt signaling activity by evaluating ß-catenin expression in mouse intestinal tissue. Serum C1q levels were elevated during the recovery phase. C1q-specific staining indicated high C1q expression in pathological intestinal tissue during the inflammation and recovery phases. C1q mRNA and protein expression was increased during both phases. Interestingly, C1q-expressing cells were consistent with macrophages (F4/80-positive cells). Moreover, the expression of ß-catenin increased in the colonic tissues during the recovery phase of DSS-induced colitis but decreased during the inflammation phase of DSS-induced colitis. C1q expression may mediate Wnt signaling activity and intestinal epithelial regeneration.

A novel endoscopic hand-suturing technique for defect closure after colorectal endoscopic submucosal dissection: a pilot study.

BACKGROUND: This study aimed to demonstrate the feasibility of endoscopic hand-suturing (EHS) and attainability of sustained closure after colorectal endoscopic submucosal dissection (ESD). METHODS: EHS was defined as uninterrupted endoscopic suturing of the mucosal defect after colorectal ESD using an absorbable barbed suture and a through-the-scope needle holder. Following individual EHS training using an ex vivo porcine colonic model, two experienced endoscopists performed EHS. Repeat colonoscopy was performed on the third or fourth day after ESD to examine the EHS site. The primary end point was the complete EHS closure rate, and secondary end points were sustained closure and post-ESD bleeding rates. RESULTS: 11 lesions were included. Median size of the mucosal defect was 38 mm (range 25 - 55 mm) and the lesion characteristics were as follows: lower rectum/upper rectum/ascending colon/cecum = 3/3/2/3, and 0-IIa/0-Is + IIa/others = 5/4/2. EHS was not attempted in two patients owing to difficulty in colonoscope reinsertion after ESD and intraoperative perforation, respectively. EHS was performed for nine lesions, and the complete EHS closure rate was 73 %. Median procedure time for suturing was 56 minutes (range 30 - 120 minutes) and median number of stitches was 8 (range 6 - 12). Sustained closure and post-ESD bleeding rates were 64 % and 9 %, respectively. CONCLUSIONS: EHS achieved complete and sustained closure in the colorectum. However, EHS is not currently clinically applicable given the long procedure time. Further modifications of the technique and devices are desirable.

Anisakiasis in the Small Intestine with Excessive Bleeding That Was Difficult to Diagnose Endoscopically.

Anisakiasis involves the stomach in most cases and occurs rarely in the small intestine. Anisakiasis in the small intestine is associated with abdominal pain and obstruction and is rarely associated with intestinal bleeding. Unlike in the stomach, anisakiasis in the small intestine is difficult to diagnose anatomically. The patient in this case study developed hypovolemic shock due to excessive bleeding and underwent emergency surgery. With the recent increase in the consumption of raw fish around the world, this report provides an important finding of bleeding in the small intestine due to an unknown cause.

Delayed perforation after endoscopic submucosal dissection for mucosal colon cancer: A conservatively treated case.

A 66-year-old man was diagnosed from colonoscopy as having a 40-mm elevated tumor in the cecum. With a preoperative diagnosis of intramucosal carcinoma, endoscopic submucosal dissection (ESD) was performed. The tumor was resected en bloc, yielding a specimen with a 66-mm diameter. No perforation was detected during the operation.Although neither abdominal pain nor fever was observed immediately after ESD, abdominal pain developed on the following day. Two days after ESD, the abdominal pain ceased. The patient was managed conservatively with fasting and intravenous antibiotic treatment. Four days after ESD, abdominal X-ray revealed marked gas retention. Computed tomography revealed pneumoperitoneum and a pelvic abscess, leading to a diagnosis of delayed perforation after colonic ESD and paralytic intestinal obstruction. A decompression tube was then inserted transnasally into the small intestine. Because a gradual decrease occurred in intestinal gas, the decompression tube was removed. Oral ingestion was resumed 13 days post-ESD.Delayed perforation after colonic ESD often requires emergency surgery. The present case was managed conservatively, despite paralytic intestinal obstruction. This approach is rarely employed for this condition and is therefore worth reporting.

Evaluation of Brain Activity Using Near-infrared Spectroscopy in Inflammatory Bowel Disease Patients.

Depression is implicated as a risk factor for the recurrence of inflammatory bowel disease (IBD). Near-infrared spectroscopy (NIRS) and brain-derived neurotrophic factor (BDNF) are useful tools for evaluation of brain activity and a depressive state, respectively. The aim of this study was to clarify the association between brain activity or depressive symptoms and IBD using NIRS and BDNF. This study included 36 ulcerative colitis (UC) patients, 32 Crohn's disease (CD) patients, and 17 healthy controls (HC). Center for Epidemiologic Studies Depression Scale (CES-D) scores were determined, NIRS was performed, and serum BDNF levels were measured in all subjects. NIRS showed that the mean oxygenated hemoglobin concentration was significantly lower in the frontal lobe in the UC group than in the HC group (HC 167 ± 106 vs. UC 83.1 ± 85.3, p < 0.05). No significant difference was seen between the HC and CD groups. There were also no significant differences in CED-D scores and BDNF levels among the groups. Changes in the NIRS values of the UC group may indicate decreased brain activity and a fundamental difference between UC and CD, which are often lumped together as two types of IBD.

An autopsy of intravascular large B-cell lymphoma with hemophagocytic syndrome.

Intravascular large B-cell lymphoma presents with highly variable symptoms caused by the occlusion of small vessels by neoplastic cells in a variety of organs.

Primary rectal mucosa-associated lymphoid tissue lymphoma in a patient with previously identified primary biliary cirrhosis and secondary Sjögren's syndrome.

An 83-year-old female began treatment with prednisolone and ursodeoxycholic acid at 62 years of age, following a diagnosis of primary biliary cirrhosis (PBC) and secondary Sjögren's syndrome (SjS). With persisting bloody stools, the patient underwent colonoscopy at 83 years of age. Histopathological evaluation revealed mucosa-associated lymphoid tissue (MALT) lymphoma. The elevated rectal lesion resolved with rituximab treatment. We report this case because although patients with SjS are at increased risk of malignant lymphoma, primary rectal MALT lymphoma is very uncommon in association with PBC and secondary SjS.

Characterization of economic requirements for a "carbon-debt-free country".

In recent years, greenhouse gas emission controls that incorporate the supply chains of products and services, thereby emphasizing the role of consumers rather than producers, have been drawing increasing attention. A country's consumption-based emissions, including those due to global supply chains, reflect the total emissions on which the national economy relies. To design effective emissions control strategies there is therefore an urgent need for countries to elucidate the structural relationship between their domestic economy and emissions occurring through global supply chains. Here we consider the structural characteristics of consumption-based emissions in Japan, which in 2005 totaled 1675 Mt CO(2)eq. Outside the country the Japanese economy generated global emissions of 541 Mt CO(2)eq, 35.7% of which were UNFCCC Annex I emissions and 64.3% were non-Annex I and other emissions. This figure of 64.3% reveals that Japan is actually relying to a considerable degree on emissions that are subject to no international obligations. We identify key economic contributors to consumption-based emissions at the commodity level and specify items of household expenditure that are effective options for both financial savings and emissions reduction. We then discuss the importance of emissions control for evolving toward a "carbon-debt-free country".