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.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Early and long-term outcomes of endoscopic submucosal dissection for early gastric cancer in a large patient series.

Endoscopic submucosal dissection (ESD) enables the curative resection of early gastric cancer (EGC); however, little information is available on the long-term outcomes of ESD. This study was conducted to clarify the clinical outcomes of a large number of patients with EGC who underwent ESD. The early outcomes were assessed in 1,209 patients and the long-term outcomes were assessed in 300 patients at a follow-up >5 years after the ESD procedure. The overall survival rates were compared between indication and expanded-indication groups, and between the patients who did or did not undergo additional surgery in an out-of-indication group. Overall survival rates were also compared among different age groups. In total, 617 lesions were classed as the indication group, 507 as the expanded-indication group and 208 as the out-of-indication group. Curative resection rates were 96.6% and 91.5% in the indication and expanded-indication groups, respectively. In terms of the long-term outcomes, 20 of the 146 patients in the indication group, 15 of the 105 patients in the expanded-indication group and one of the 23 patients who underwent additional surgery in the out-of-indication group succumbed due to causes other than gastric cancer. Among the 26 patients who did not undergo additional surgery in the out-of-indication group, 10 mortalities occurred, including one due to gastric cancer. The five-year survival rates were not significantly different between the indication and expanded-indication groups. In the out-of-indication group, the five-year survival rate for the patients who did not undergo additional surgery (65.0%) was significantly lower than that for those who did undergo additional surgery (100%) (P<0.01). The five-year survival rate of patients aged >80 years (67.1%) was significantly lower than that of the younger patients (<60 years, 91.6%; sixties, 93.0%; seventies, 84.5%) (P<0.0001). In conclusion, although expanded-indication of ESD for EGC is appropriate, comorbidities require consideration in elderly patients.

Management of esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms en bloc, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD. METHODS: Seven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia. RESULTS: En bloc ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions. CONCLUSIONS: Use of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.

Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial esophageal squamous cell carcinoma. However, postprocedure stricture is common after ESD for extensive tumors, and multiple endoscopic balloon dilation (EBD) is required for recalcitrant cases. OBJECTIVE: To evaluate the effectiveness of oral prednisolone in controlling postprocedure esophageal stricture. DESIGN: Retrospective study. SETTING: Endoscopy department at a university hospital. PATIENTS: Patients who underwent complete circular or semicircular ESD for esophageal squamous cell carcinoma involving more than three fourths of the lumen were treated with either pre-emptive EBD or oral prednisolone. INTERVENTION: Preemptive EBD was started on the third day post-ESD and continued twice weekly for 8 weeks. Oral prednisolone was started at 30 mg/day on the third day post-ESD , tapered gradually, and then discontinued 8 weeks later. An additional EBD was performed on demand in both groups whenever dysphagia appeared. MAIN OUTCOME MEASUREMENT: The incidence of esophageal stricture and number of EBD sessions required to relieve dysphagia. RESULTS: Stricture at 3 months after ESD was found in 7 of 22 patients in the preemptive EBD group but only 1 of 19 in the oral prednisolone group (P < .05). The average number of EBD sessions required was 15.6 in the preemptive EBD group and 1.7 in the oral prednisolone group (P < .0001). After complete circular ESD, 32.7 EBD sessions were needed on average in the preemptive EBD group, whereas fewer were needed in the oral prednisolone group (P < .05). LIMITATIONS: Nonrandomized study. CONCLUSIONS: Post-ESD esophageal strictures were persistent even if treated preemptively with multiple EBD sessions, but oral prednisolone may offer a useful preventive option.

Magnifying chromoendoscopic findings of early gastric cancer and gastric adenoma.

PURPOSE: In the field of colorectal cancer and adenoma, Kudo's classification of pit pattern with magnifying chromocolonoscopy using crystal violet (CV) staining is now accepted. Magnifying endoscopy using narrow band imaging has been used for the diagnosis of gastric carcinoma; the characteristic findings of microvascular patterns have been demonstrated. However, there was limited information on magnified endoscopic findings with CV staining for gastric neoplasms in terms of their pit patterns. METHODS: Magnifying chromoendoscopy with CV was performed in 175 patients with early gastric cancer and 18 with gastric adenoma, prior to treatment. Surface patterns of gastric tumors were classified into five types: (1) long tubular pit pattern, (2) irregular size pit pattern, (3) small round pit pattern, (4) destroyed pit pattern, and (5) non-structural pattern. RESULTS: Long tubular pit pattern was most common in gastric adenoma. Well differentiated adenocarcinoma and papillary adenocarcinoma tended to show different size of pit pattern or destroyed pit pattern. Small round pit pattern was most commonly seen in moderately differentiated adenocarcinoma. Non-structural pattern was most frequently observed in poorly differentiated adenocarcinoma and signet ring cell carcinoma (P < 0.0001). CONCLUSION: For gastric neoplasms, magnifying endoscopy may help predict histopathological type.

Endoscopic submucosal dissection for laterally spreading tumours of the colorectum in 200 consecutive cases.

BACKGROUND: Colorectal laterally spreading tumours (LSTs) are classified into granular (LST-G) and non-granular (LST-NG) type; each type was sub-grouped into LST-G-H (homogenous) and LST-G-M (nodular mixed) type or LST-NG-F (flat elevated) and LST-NG-FD (pseudodepressed) type, respectively. We assessed the clinicopathological factors associated with clinical outcomes of endoscopic submucosal dissection (ESD) for colorectal LSTs, and conducted follow-up after ESD. METHODS: ESD was performed in 196 patients with 204 LSTs that fulfilled the inclusion criteria for colorectal neoplasms. Clinical outcomes including resectability and curability of ESD and perforation were investigated, and factors related to the outcomes were analysed using logistic regression. One hundred thirty-eight patients received endoscopic follow-up for more than 12 months and metastatic surveys in 79 cases of cancerous LSTs. RESULTS: The incidence of submucosal cancer was lower in LST-G type. There were no significant differences in outcomes regarding LST macroscopic types. Overall en bloc, complete and curative resection, and perforation rates were 86.8%, 77.5%, 82.8% and 9.8%, respectively. Logistic regression analysis showed higher risk of non-curative resection in LST-G-M than in LST-G-H type. No other factors were associated with outcomes. During median follow-up of 35.5 months, no locally recurrent or metastatic tumours were observed, and overall survival was still 100%. CONCLUSIONS: ESD provides acceptable resectability for colorectal LSTs by facilitating en bloc resection, irrespective of macroscopic types. The relatively long-term outcomes may be excellent, but further evaluation is needed for appropriate treatment strategy for each type of LST.

Endoscopic submucosal dissection for colorectal epithelial neoplasms.

PURPOSE: Endoscopic submucosal dissection permits removal of colorectal epithelial neoplasms en bloc, but long-term clinical outcomes remain unknown. METHODS: Endoscopic submucosal dissection was performed in 282 patients having 296 colorectal tumors that fulfilled the inclusion criteria, which included lesions greater than 20 mm in size for which en bloc resection would be difficult with endoscopic mucosal resection, lesions with fibrotic scar due to previous endoscopic treatment or biopsies, locally residual lesions after endoscopic resection, or invasive carcinoma with slight submucosal penetration. En bloc or piecemeal resection, complete (en bloc with tumor-free lateral/basal margins) or incomplete resection, and complications were assessed, and factors related to each were analyzed using logistic regression. Patients with early colon cancer received endoscopic follow-up and metastatic surveys for a median of 34 months. RESULTS: En bloc resection was achieved in 89.2% (264/296) and 234 lesions (79.1%) were deemed to have undergone complete resection. A right-side colonic location was the significant contributor to incomplete resection. Perforation was seen in 24 cases (8.1%) in association with tumor size and the presence of fibrosis. There was 1 case of locally recurrent tumor with incomplete resection, whereas neither recurrence nor residual disease was observed in the complete resection group. Neither cancer-related nor cancer-unrelated death was observed. CONCLUSIONS: Precise assessment of curability with successful en bloc resection may reduce tumor recurrence after endoscopic submucosal dissection. The prognosis of early colorectal cancer in patients treated by endoscopic submucosal dissection is likely to be excellent, although further longer follow-up studies are warranted.

Clinical outcomes of endoscopic submucosal dissection in elderly patients with early gastric cancer.

OBJECTIVES: Endoscopic submucosal dissection (ESD) has advantages over conventional endoscopic mucosa resection. The number of elderly patients (more than 75 years old) with early gastric cancer (EGC) has been steadily increasing. We sought to assess clinical outcomes of ESD for EGC in elderly. METHODS: ESD was performed for patients with EGC, who fulfilled the criteria for ESD: mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings 3 cm or less in diameter; and minute submucosal invasive cancer 3 cm or less in size. Two hundred and sixty elderly patients (> or =75 years old) with 279 lesions, and 401 non-elderly patients with 434 lesions were enrolled to this study. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 6-89 months (median: 30 months). Resectability (en-bloc or piecemeal resection), curability (curative or noncurative resection), completeness (complete or incomplete resection), complications, and survival rates were assessed. RESULTS: The one-piece resection rate was significantly lower in elderly patients (93.9%) than in non-elderly patients (97.9%). The complete resection rate was significantly lower in elderly patients (87.4%) than in non-elderly patients (96.6%). Pneumonia, but not bleeding or perforation, developed in association with ESD more frequently in the elderly patients by 2.2%. Local tumor recurrence was quite rare, and the overall and disease-free survival rates were acceptable irrespective of age. CONCLUSION: En-bloc and complete resections were achieved less frequently in elderly patients, but the long-term outcomes in elderly EGC patients may be excellent, and ESD is a feasible treatment in the elderly.

Endoscopic submucosal dissection for rectal carcinoid tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) has an advantage over endoscopic mucosa resection (EMR) by enabling removal of gastrointestinal neoplasms en bloc. The ESD procedure is the treatment of choice for rectal carcinoids that have classic histologic architecture with minimal cellular pleomorphism and sparse mitoses, but it has not been applied for such tumors. METHODS: The ESD procedure was performed for patients with colorectal tumors that fulfilled the inclusion criteria specifying tumor with a diameter of 10 mm or less, no muscular layer invasion, and no metastases to the lymph nodes or distal organs. The ESD procedure was performed for patients with rectal carcinoids but no node or distal metastasis. RESULTS: This study enrolled 20 rectal carcinoid tumors from 20 consecutive patients. The mean tumor size was 7.6 mm (range, 3-16 mm). En bloc removal was achieved for all the tumors, and the complete resection (en bloc with tumor-free lateral/basal margins) rate was 90% (18/20). The two cases in which the margins were not evaluable due to burn effects still are free of recurrence and metastasis at this writing. Perforation was seen in one case, which was managed nonsurgically. CONCLUSIONS: Precise histolopathogic assessment of the specimens resected en bloc by ESD may reduce tumor recurrence and metastasis after ESD. As the treatment of choice for small rectal carcinoids, ESD is associated with nominal risks of metastatic disease.

A new thin endoscopic method of transanal drainage tube insertion for acute colonic obstruction due to colorectal cancer.

AIM: Insertion of a transanal drainage tube is effective in the management of obstructing colorectal cancer. We devised a new method of inserting the transanal drainage tube safely and quickly using a thin endoscope. METHODS: Sixteen patients (seven men and nine women) with obstructive left-sided colorectal cancer were treated by inserting a transanal drainage tube using a thin endoscope. We inserted a transanal drainage tube for 32 patients (21 men and 11 women) with left-sided colorectal cancer using the conventional method. RESULTS: Drainage tube placement by the conventional method was successful in 29 (90.6%) of 32 patients, while via the new method, it was successful in all 16 patients without major complications. Moreover, median insertion time was significantly shortened (34 minutes for the new method compared with 42 minutes for the conventional method). CONCLUSION: Management of acute colorectal obstruction by transanal drainage tube insertion using the thin endoscope was effective and safe.

Clinical outcomes of endoscopic submucosal dissection for early gastric cancer by indication criteria.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) can remove early gastric cancer (EGC) en bloc. We sought to assess the feasibility and efficacy of ESD and the clinical outcomes based on the indication criteria. PATIENTS AND METHODS: 551 patients with 589 EGC lesions were divided into the guideline criteria group (elevated lesion < or =20 mm in diameter and depressed lesion < or =10 mm without ulceration) and the expanded criteria group (mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings < or =3 cm in diameter; and minute submucosal invasive cancer < or =3 cm in size). RESULTS: En bloc, complete and curative resection were achieved in 98.6 and 93.0, 95.1 and 88.5, and 97.1 and 91.1%, for the guideline and expanded criteria lesions, respectively; the differences between the 2 groups were significant for each. The expanded criteria lesions were at significantly higher risk of ESD-associated bleeding and perforation. Overall survival was adequate irrespective of the indications, and the disease-specific survival rates were 100% in both. CONCLUSION: ESD for EGCs that met the expanded criteria was acceptable, though the resection rates and safety were decreased compared to those for the guideline criteria lesions.

Factors related to the curability of early gastric cancer with endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) yields substantially high rates for curative resection of early gastric cancer (EGC). It is suggested that larger, ulcerative, or upper EGCs may prevent successful ESD. A detailed analysis of factors associated with the curability of ESD was performed. METHODS: Endoscopic submucosal dissection was performed for patients with EGC that fulfilled the expanded criteria, which specified mucosal cancer without ulcer findings irrespective of tumor size, mucosal cancer with ulcers 3 cm in diameter or smaller, and minute submucosal invasive cancer 3 cm or smaller. Resectability (en bloc or by piecemeal resection), curability (curative or non-curative), and complications were assessed, and logistic regression analysis was used to analyze the related factors. RESULTS: Ulcerative EGCs showed a significantly higher risk associated with ESD on multivariate analysis. When the risk factors (tumor size, location, and ulcer findings) were combined, the larger EGCs (>30 mm) located in the upper third or ulcerative tumors located in the upper and middle portion of the stomach were at significantly higher risk of non-curative resection. Such lesions also were associated with increased risk of procedure-related perforation. CONCLUSIONS: When risk factors including positive ulcer findings and larger size and upper location of tumors are combined, ESD should be performed more carefully.

A case of Cronkhite-Canada syndrome: remission after treatment with anti-Helicobacter pylori regimen.

A 67-year-old man with nausea, appetite loss, frequent diarrhea and severe weight loss presented with alopecia, skin hyperpigmentation and onychodystrophy. Laboratory investigations showed mild anemia, hypoproteinemia and hypoalbuminemia. Colonoscopy identified the numerous, hyperemic and sessile polyps with mucous exudation of various sizes throughout the colorectum. The ileocecal valve was substantially swollen. Magnified chromoendoscopy revealed sparsely distributed crypt openings with widening of the preicryptal space without destruction in the affected lesions. Upper gastrointestinal endoscopy revealed multiple small, reddish, and sessile polyps in the duodenum and Helicobacter pylori-associated gastritis. Histopathological examination of the colonic polyps revealed cystic dilatation and elongation of scattered glands with epithelial hyperplasia and stromal edema and inflammatory cell infiltrates. Thus, a diagnosis of Cronkhite-Canada syndrome was made. The patient was given clarithromycin, amoxicillin and lansoprazole, resulting in negative (13)C-urea breath tests. Three months later, his clinical symptoms and edema of the legs resolved with normalization of serum total protein and albumin levels and return to his previous body. The ectodermal abnormalities were resolved 8 months later. On repeat colonoscopic examinations, there was progressive remission of the duodenal and colorectal polyposis, leaving scattered pedunculated polyps in the transverse and ascending colon and on the almost normal-appearing ileocecal valve. At the follow-up magnifying endoscopic examination 8 months later, small round or round-oval pits were densely and regularly distributed.

Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency.

A 56-year-old woman with a 29-year history of rheumatoid arthritis (RA) was admitted to the hospital, complaining of high fever, abdominal pain and severe bloody diarrhea. Colonoscopy revealed friable and edematous mucosa with spontaneous bleeding, diffuse erosions and ulcers extending from the rectum to the distal transverse colon. Histopathological findings of rectal biopsies were compatible with ulcerative colitis (UC). Being diagnosed as having severe active left-side UC, she was successfully treated with intravenous methylprednisolone followed by prednisolone and leukocytapheresis. Laboratory tests revealed low serum and saliva IgA levels, which might play a role in the development of UC. To our knowledge, this is the first case of UC occurring during the course of RA, accompanied by selective IgA deficiency.

Successful treatment with cyclosporin in adult-onset Still disease manifesting as acute hepatitis with marked hyperferritinemia.

A 48-year-old woman was admitted because of spiking high fever, sore throat, and jaundice. A diagnosis was made of adult-onset Still disease (AOSD) presenting with acute hepatitis and very high serum ferritin levels (32,240 ng/mL), and she was treated with 2 courses of pulse therapy of methylprednisolone (2 g/day for 3 days) followed by 40 mg/day prednisolone. Subsequently, the serum level of ferritin decreased, but serum total bilirubin increased to 17.3 mg/dL. Therefore, cyclosporin was administered orally. Within the next 3 months, results of liver function tests, as well as serum levels of ferritin, soluble interleukin-2 receptor, interferon-gamma, interleukin-6, and tumor necrosis factor-alpha gradually returned to within normal limits, and cyclosporin administration was subsequently reduced gradually. The clinical presentation suggests that AOSD should be considered when liver dysfunction is accompanied with high fever and extreme hyperferritinemia, and that treatment with cyclosporin or other immunosuppressive drugs that selectively suppress cytokine production by helper T cells is a valuable option in the treatment of AOSD with very high serum ferritin levels.