Nonrecurrence Rate of Underwater EMR for ≤20-mm Nonampullary Duodenal Adenomas: A Multicenter Prospective Study (D-UEMR Study).

BACKGROUND AND AIMS: Endoscopic resection of nonampullary duodenal adenoma is often challenging, and its technique has not yet been standardized. To overcome the practical difficulty of conventional endoscopic mucosal resection, underwater endoscopic mucosal resection (UEMR) was recently developed; therefore, we investigated the effectiveness and safety of UEMR for nonampullary duodenal adenoma. METHODS: A multicenter, prospective cohort study was conducted at 21 institutions in Japan. We enrolled patients with no more than 2 nonampullary duodenal adenomas ≤20 mm in size, who were planned to undergo UEMR. After UEMR, follow-up endoscopies were scheduled at 2 and 12 months after the procedure, and biopsy specimens were taken from the post-UEMR scars. The primary endpoint was the proportion of patients with histologically proven nonrecurrence at follow-up endoscopy and biopsy. RESULTS: A total of 155 patients with 166 lesions underwent UEMR. One patient with a non-neoplastic lesion in the resected specimen and 10 patients with 10 lesions who were lost to follow-up were excluded. Finally, 144 patients with 155 lesions who received all follow-up endoscopies were analyzed for the primary endpoint. The proportion of patients with proven nonrecurrence was 97.2% (n = 140 of 144; 95% confidence interval, 92.8%-99.1%) which exceeded the predefined threshold value (92%). Two cases of delayed bleeding (1.2%) occurred and they were successfully managed by clips. All recurrences were successfully treated by additional endoscopic treatment. CONCLUSIONS: This multicenter, prospective cohort study demonstrated effectiveness and safety of UEMR for nonampullary duodenal adenomas ≤20 mm in size. (University Hospital Medical Network Clinical Trials Registry, Number: UMIN000030414).

Depth of the cutting plane with underwater and conventional endoscopic mucosal resection: Post-hoc analysis of a randomized study.

BACKGROUND AND AIM: A multicenter randomized controlled trial reported a better R0 resection rate for intermediate-sized (10-20 mm) colorectal polyps with underwater endoscopic mucosal resection (UEMR) than conventional endoscopic mucosal resection (CEMR). To clarify whether UEMR removes enough submucosal tissue in the removal of unpredictable invasive cancers, we investigated the cutting plane depth with UEMR versus CEMR. METHODS: This was a post-hoc analysis of a randomized controlled trial in which 210 intermediate-sized colorectal polyps were removed in five Japanese hospitals. One pathologist and two gastroenterologists independently reviewed all resected specimens and measured the cutting plane depth. The cutting plane depth was evaluated as (i) maximum depth of submucosal layer and (ii) mean depth of submucosal layer, calculated using a virtual pathology system. RESULTS: We identified 168 appropriate specimens for the evaluation of the cutting plane depth, resected by UEMR (n = 88) and CEMR (n = 80). The median resection depth was not significantly different between UEMR and CEMR specimens, regardless of the measurement method ([i] 1317 vs 1290 µm, P = 0.52; [ii] 619 vs 545 µm, P = 0.32). All specimens in the UEMR and CEMR groups contained substantial submucosa and no muscularis propria. CONCLUSIONS: The cutting plane depth with UEMR was comparable with that with CEMR. UEMR can be a viable alternative method that adequately resects the submucosal layer for the histopathological assessment of unpredictable submucosal invasive cancers.

Guidelines for sedation in gastroenterological endoscopy (second edition).

Sedation in gastroenterological endoscopy has become an important medical option in routine clinical care. Here, the Japan Gastroenterological Endoscopy Society and the Japanese Society of Anesthesiologists together provide the revised "Guidelines for sedation in gastroenterological endoscopy" as a second edition to address on-site clinical questions and issues raised for safe examination and treatment using sedated endoscopy. Twenty clinical questions were determined and the strength of recommendation and evidence quality (strength) were expressed according to the "MINDS Manual for Guideline Development 2017." We were able to release up-to-date statements related to clinical questions and current issues relevant to sedation in gastroenterological endoscopy (henceforth, "endoscopy"). There are few reports from Japan in this field (e.g., meta-analyses), and many aspects have been based only on a specialist consensus. In the current scenario, benzodiazepine drugs primarily used for sedation during gastroenterological endoscopy are not approved by national health insurance in Japan, and investigations regarding expense-related disadvantages have not been conducted. Furthermore, including the perspective of beneficiaries (i.e., patients and citizens) during the creation of clinical guidelines should be considered. These guidelines are standardized based on up-to-date evidence quality (strength) and supports on-site clinical decision-making by patients and medical staff. Therefore, these guidelines need to be flexible with regard to the wishes, age, complications, and social conditions of the patient, as well as the conditions of the facility and discretion of the physician.

Comparison of Underwater vs Conventional Endoscopic Mucosal Resection of Intermediate-Size Colorectal Polyps.

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) with submucosal injection is an established method for removing colorectal polyps, although the en bloc resection rate decreases when polyp size exceeds 10 mm. Piecemeal resection increases local recurrence. Underwater EMR (UEMR) is an effective technique for removal of sessile colorectal polyps and we investigated whether it is superior to conventional EMR (CEMR). METHODS: We conducted a multicenter randomized controlled trial at 5 institutions in Japan. Patients with endoscopically diagnosed, intermediate-size (10-20 mm) sessile colorectal lesions were randomly assigned to undergo UEMR or CEMR. Only the most proximal lesion was registered. The UEMR procedure included immersion of the entire lumen in water and snare resection of the lesion without submucosal injection of normal saline. We analyzed outcomes of 108 colorectal lesions in the UEMR group and 102 lesions in the CEMR group. R0 resection was defined as en bloc resection with a histologically confirmed negative resection margin. The primary endpoint was the difference in the R0 resection rates between groups. RESULTS: The proportions of R0 resections were 69% (95% confidence interval [CI] 59%-77%) in the UEMR group vs 50% (95% CI 40%-60%) in the CEMR group (P = .011). The proportions of en bloc resections were 89% (95% CI 81%-94%) in the UEMR group vs 75% (95% CI 65%-83%) in the CEMR group (P = .007). There was no significant difference in median procedure time (165 vs 175 seconds) or proportions of patients with adverse events (2.8% in the UEMR group vs 2.0% in the CEMR group). CONCLUSIONS: In a multicenter randomized controlled trial, we found that UEMR significantly increased the proportions of R0 resections for 10- to 20-mm sessile colorectal lesions without increasing adverse events or procedure time. Use of this procedure should be encouraged. Trials registry number: UMIN000018989.

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial.

Background: Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP). Objective: To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps. Design: Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355). Setting: 30 Japanese institutions. Patients: Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp. Intervention: Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy. Measurements: The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP). Results: A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group. Limitation: An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously. Conclusion: Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP. Primary Funding Source: Japanese Gastroenterological Association.

Comparison of the Diagnostic Performance of Newly Designed 21-Gauge and Standard 22-Gauge Aspiration Needles in Patients with Solid Pancreatic Masses.

BACKGROUND: Although endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been widely used for the diagnosis of pancreatic tumors, the ability to obtain adequate pancreatic tumor tissue needs to be improved. AIMS: This study was performed to compare a newly designed 21-gauge needle (EUS Sonopsy CY; Hakko Medical, Nagano, Japan) and a standard 22-gauge needle for tissue sampling of solid pancreatic masses. METHODS: Consecutive patients with solid pancreatic masses who underwent EUS-FNA with either the EUS Sonopsy CY or the 22-gauge needle from June 2014 to December 2016 were enrolled. The primary outcome was comparison of the diagnostic yield of the FNA samples. The secondary outcomes were comparison of technical success, diagnostic ability for malignancy, and complications. RESULTS: A total of 93 patients (40.9% female; mean age, 70.1 years) underwent EUS-FNA with the EUS Sonopsy CY (n = 47) or the standard 22-gauge needle (n = 46). The technical success rate was 100% in both groups, and the overall diagnostic accuracy for malignancy was similar between the groups (100% in the EUS Sonopsy CY group vs. 95.7% in the 22-gauge needle group, P = 0.242). Nevertheless, the EUS Sonopsy CY resulted in significantly higher scores for cellularity (P = 0.006) and lower scores for blood contamination (P < 0.001). The procedure-related complication rate was comparable between the groups (P = 0.148). CONCLUSIONS: The EUS Sonopsy CY provided higher-quality specimens for histological evaluation in terms of both sample cellularity and blood contamination for the diagnosis of solid pancreatic masses. TRIAL REGISTRATION: The study was registered in a clinical trial registry, No. UMIN000032598.

A comparison of the resection rate for cold and hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study).

OBJECTIVE: To investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4-9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP). DESIGN: A prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4-9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps. RESULTS: A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI -1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps). CONCLUSIONS: The complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4-9 mm colorectal polyps. (Study registration: UMIN000018328).

The Feasibility of 18-mm-Diameter Colonic Stents for Obstructive Colorectal Cancers.

OBJECTIVES: This study aimed to evaluate the characteristics and the feasibility of 18-mm-diameter stents for obstructive colorectal cancer, comparing the clinical courses with 22- mm-diameter stents. METHODS: We retrospectively compared 33 consecutive cases treated with 18-mm-diameter stents (bridge to surgery [BTS] in 25, palliative therapy [PAL] in 8) with 27 consecutive cases treated with 22-mm-diameter stents (BTS in 21, PAL in 6) for obstructive colorectal cancer between May 2013 and November 2015 in our institution. RESULTS: There were no significant differences between the 18-mm and 22-mm groups in technical success rates (97 and 96%, respectively) and clinical success rates (100 and 100%, respectively). As a BTS, the rates of complications and stoma formation were not significantly different between groups. For PAL, although the rates of complications and stent patency were similar, stent occlusion occurred in 1 patient (12.5%) in the 18-mm group. CONCLUSIONS: The 18-mm-diameter stents were similarly effective when compared with 22-mm-diameter stents. Because 18-mm-diameter stents are easy to handle and produce less mechanical stress, they have the potential to decrease the perforation rate and mitigate the stent's impact on the tumors. 18-mm-diameter stents can be useful and safe, especially as a BTS.

Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group.

AIM: To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice. METHODS: Retrospective analysis was performed of 112 patients who had received interferon (IFN) for treating hepatitis C following treatment of HCC and were registered with the Japanese Red Cross Liver Study Group. Factors that may influence recurrence and survival rates were investigated. RESULTS: Factors involved in prevention of recurrence were: surgical resection as HCC treatment, platelet and α-fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN AFP level. Multivariate analysis showed post-IFN AFP level to be an independent factor. Factors involved in prolonging survival were: IFN adherence, IFN response (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post-IFN AFP level and absence of recurrence. Multivariate analysis showed absence of recurrence to be an independent factor. Although IFN adherence was involved in recurrence and survival, ribavirin adherence was not. IFN was suggested to be involved in preventing recurrence and improving survival due not only to its anti-viral effect, but also its antitumor effect. CONCLUSION: Although complete prevention of HCC recurrence is difficult, the most important factor affecting first recurrence is the AFP level at 6 months after the conclusion of antiviral treatment. The survival rate improves dramatically if the hepatitis C virus is eliminated, but the most important factor for improving survival is absence of recurrence.

[A case of transcatheter arterial embolization for reduction of a hemorrhagic rectal gastrointestinal stromal tumor].

A 91-year-old woman was referred to our hospital with a primary complaint of hematochezia. A rectal submucosal tumor and an acute hemorrhagic rectal ulcer were noted on colonoscopy. After hemostasis was achieved with APC, the patient was diagnosed with a GIST by EUS-FNA. We performed TAE of the middle and inferior rectal artery to secure hemostasis, because these arteries were also observed to be bleeding during hospitalization. A CT scan and colonoscopy revealed that the rectal GIST had reduced and that the acute rectal ulcer had been successfully treated. We report a case in which TAE was used to achieve tumor reduction of a hemorrhagic rectal GIST.

Clinicopathological Features of Methotrexate-associated Lymphoproliferative Disorders in the Gastrointestinal Tract.

Methotrexate may cause methotrexate-associated lymphoproliferative disorder (MTX-LPD); however, this disease is uncommon in the gastrointestinal tract. We examined six patients with MTX-LPD in the gastrointestinal tract at our hospital. All of the lesions were ulcerative. Four cases regressed spontaneously, all of which were positive for Epstein-Barr virus-encoded small RNA by in situ hybridization. Two patients who did not regress were negative for Epstein-Barr virus RNA, one of whom received chemotherapy, and one underwent surgery. The prognosis of this disease is considered to be good. MTX-LPD should considered when ulcerative lesions are observed during endoscopy in patients receiving MTX.

Two cases of esophageal basaloid squamous cell carcinoma which achieved long-term survival by endoscopic submucosal dissection and additional chemoradiotherapy.

Herein, we report two rare basaloid squamous cell carcinoma (BSCC) cases. Esophagogastroduodenoscopy revealed a submucosal tumor-like lesion and a biopsied specimen showed a finding suspected of BSCC in both cases. Both lesions underwent endoscopic submucosal dissection with en bloc resection, and long-term survival was achieved using additional chemoradiotherapy. The standard treatment for BSCC has not been determined, and there are few reports of esophageal BSCC treated using endoscopic resection. Endoscopic submucosal dissection and additional chemoradiotherapy for superficial BSCC may be effective treatment options.

Efficacy of antimicrobial therapy in patients with uncomplicated acute colonic diverticulitis: an updated systematic review and meta-analysis.

The need for antimicrobial therapy for uncomplicated acute diverticulitis of the colon remains controversial. We conducted a systematic review of the efficacy of antimicrobial agents against this disease, including new randomized controlled trials (RCTs) reported in recent years, and evaluated their efficacy using a meta-analytic approach. RCTs were searched using PubMed, EMBASE, Google Scholar, Cochrane Library, Ichushi-Web, and eight registries. Keywords were 'colonic diverticulitis', 'diverticulitis', 'antimicrobial agents', ''antibiotics, 'complication', 'abscess', 'gastrointestinal perforation', 'gastrointestinal obstruction', 'diverticular hemorrhage', and 'fistula'. Studies with antimicrobial treatment in the intervention group and placebo or no treatment in the control group were selected by multiple reviewers using uniform inclusion criteria, and data were extracted. Prevention of any complication was assessed as the primary outcome, and efficacy was expressed as risk ratio (RR) and risk difference (RD). A meta-analysis was performed using 5 RCTs of the 21 studies that were eligible for scrutiny in the initial search and which qualified for final inclusion. Three of these studies were not included in the previous meta-analysis. Subjects included 1039 in the intervention group and 1040 in the control group. Pooled RR = 0.86 (95% confidence interval, 0.58-1.28) and pooled RD = -0.01 (-0.03 to 0.01) for the effect of antimicrobial agents in reducing any complications. Recurrences, readmissions, and surgical interventions did not significantly show the efficacies of using antimicrobial agents. A meta-analysis of recently reported RCTs did not provide evidence that antimicrobial therapy improves clinical outcomes in uncomplicated acute diverticulitis of the colon.

Primary Retroperitoneal Mucinous Cystadenocarcinoma during Long-term Administration of Infliximab for the Treatment of Crohn's Disease.

We herein report a rare case of primary retroperitoneal mucinous cystadenocarcinoma (PRMC) in a 60-year-old man. The patient, who had been treated with infliximab for Crohn's disease of the colon for 13 years, was referred to our hospital for lower back pain. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging revealed multiple cystic lesions in the right retroperitoneum, the calcification of the cyst, and bone lesions. Bone and CT-assisted biopsies of the retroperitoneal lesions revealed poorly differentiated adenocarcinoma. The patient was diagnosed with PRMC with bone metastases using immunohistochemical staining and positron emission tomography/CT.

Dexmedetomidine is safe and effective for reducing intraprocedural pain in colorectal endoscopic submucosal dissection.

Objectives: Endoscopic submucosal dissection (ESD) is effective for the resection of colorectal intramucosal lesions. This study was performed to examine the safety and effectiveness of using dexmedetomidine (DEX) in the anesthesia regimen of patients with colorectal lesions undergoing ESD. Methods: We retrospectively examined 287 consecutive patients who underwent ESD for colorectal lesions in our institution from January 2015 to December 2021. Outcomes including the frequency of intraprocedural pain and adverse events were compared between the DEX and no DEX groups. Moreover, univariate and multivariate analyses were conducted for each clinical factor of intraprocedural pain. Intraprocedural pain was defined as patient-reported abdominal pain or body movement during the procedure. Results: The incidence of intraprocedural pain was significantly lower in the DEX than in the no DEX group (7% vs. 17%, p = 0.02). The incidence of hypotension was also significantly higher in the DEX group (7% vs. 0%, p = 0.01), but no cerebrovascular or cardiac ischemic events occurred. In the univariate analyses, the diameter of the resected specimen, procedure time, no use of DEX, and total midazolam dose was associated with intraprocedural pain. The midazolam dose and DEX administration were significantly negatively correlated and the diameter of resected specimen and procedure time were significantly positively correlated. Multivariate logistic regression showed that no use of DEX was independently associated with intraprocedural pain (p = 0.02). Conclusions: Adding DEX to the anesthesia regimen in patients undergoing colorectal ESD appears to be safe and effective for reducing intraprocedural pain.

Primary Hepatic Neuroendocrine Carcinoma with Thrombocytopenia Due to Diffuse Bone Marrow and Splenic Infiltration: An Autopsy Case.

An 82-year-old man with fever and back pain was referred to our hospital and was thus found to be thrombocytopenic. A bone marrow biopsy revealed the diffuse infiltration of poorly differentiated neuroendocrine carcinoma (NEC). Computed tomography revealed a large hepatic mass. Considering the risk of bleeding due to thrombocytopenia, a needle biopsy was not performed. The patient rapidly deteriorated and died 10 days after presentation. An autopsy confirmed the diagnosis of primary hepatic NEC, with diffuse metastasis to the spleen, bone marrow, and systemic lymph nodes. This is an extremely rare case of NEC presenting with thrombocytopenia due to extensive bone marrow and splenic infiltration.

Longly-attached cap can contribute to en bloc underwater endoscopic mucosal resection of 20-30 mm colorectal intramucosal lesions.

Background and study aims Underwater endoscopic mucosal resection (UEMR) is effective for colorectal intramucosal lesions. The aim of this study was to evaluate whether a longly-attached cap in UEMR improves the en bloc resection rate for 20-30 mm lesions. Patients and methods We performed a retrospective study at a tertiary institute. Candidates for the study were systematically retrieved from an endoscopic and pathological database from October 2016 to December 2020. We assessed the procedural outcomes with UEMR for lesions ≥ 20 mm in size and the clinical factors contributing to en bloc resection. Results A total of 52 colorectal lesions that underwent UEMR were included. The median procedure time was 271 (66-1264) seconds. The en bloc resection rate and R0 resection rate were 75 % and 73 %, respectively. Intraprocedural perforation occurred in one (1.9 %) case, but no bleeding occurred. Delayed bleeding occurred in one (1.9%) case, but no delayed perforation occurred. Regarding tumor size, macroscopic type, tumor location, and the presence or absence of a history of abdominal operation, there was no significant difference between the en bloc resection and piecemeal resection groups. The visibility of the whole lesion, a longly-attached cap, and sessile serrated lesions were more frequently observed in the en bloc resection group than in the piecemeal resection group ( P  < 0.001, P  = 0.01, and P  = 0.04, respectively). Multivariate analysis showed that a longly-attached cap was the only independent factor associated with en bloc resection ( P  = 0.02). Conclusions A longly-attached cap might contribute to en bloc resection.