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.

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.

Association of direct oral anticoagulant and delayed bleeding with pharmacokinetics after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Pharmacokinetic parameters, such as drug plasma level at trough, time to maximum plasma concentration (Tmax), and coagulation factor Xa (FXa) activity generally predict factors for the anticoagulant effects of direct oral anticoagulants (DOACs). Although GI bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacologic parameters. This study aimed to evaluate pharmacologic risk factors for post-ESD bleeding in patients taking DOACs. METHODS: We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions and investigated the association with post-ESD bleeding and pharmacologic factors, including plasma concentration and FXa activity at trough and Tmax. RESULTS: The incidence of post-ESD bleeding was 12.8% (14 of 109; 95% confidence interval [CI], 7.2-20.6). Although plasma DOAC concentration and plasma level/dose ratio at trough and Tmax varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893; P < .001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR], 1.192; 95% CI, 1.020-1.392; P = .027) and high anticoagulant ability analyzed by FXa activity at trough and Tmax (OR, 6.056; 95% CI, 1.094-33.529; P = .039). CONCLUSIONS: The incidence of post-ESD bleeding in patients taking DOACs was high, especially in older patients and with high anticoagulant effects of DOACs. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding.

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.

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.

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.

Association between antispasmodics and detection of lesions by screening esophagogastroduodenoscopy.

Background and Aim: Whether administration of antispasmodics as a component of premedication contributes to detection of lesions by screening esophagogastroduodenoscopy (EGDS) remains unclear. Our primary aim was to investigate this possibility. Methods: The cohort in this retrospective study comprised consecutive asymptomatic individuals who had undergone screening EGDS as part of a health check-up at the Japanese Red Cross Wakayama Medical Center from October 2015 to September 2020. The investigated lesions comprised esophageal squamous cell carcinoma or adenocarcinoma, gastric adenoma or adenocarcinoma, and duodenal adenoma or adenocarcinoma. Results: Targeted lesions were detected in 72 of 31 484 participants (0.23%), 18 260 and 13 224 of whom had received and not received pre-procedure antispasmodics, respectively. The rates of detection of lesions in these groups were 0.21% (38/18260) and 0.26% (34/13224), respectively (P = 0.40). Multivariate logistic regression analysis showed no association between administration of antispasmodics and rates of detection of targeted lesions [P = 0.24, Odds ratio (95% CI): 1.46 (0.78-2.75)]. Conclusions: Antispasmodics, which were administered to more than half of the study cohort, did not improve the rate of detection of targeted lesions.

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.

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.

Artificial intelligence for the detection of esophageal and esophagogastric junctional adenocarcinoma.

BACKGROUND AND AIM: Conventional endoscopy for the early detection of esophageal and esophagogastric junctional adenocarcinoma (E/J cancer) is limited because early lesions are asymptomatic, and the associated changes in the mucosa are subtle. There are no reports on artificial intelligence (AI) diagnosis for E/J cancer from Asian countries. Therefore, we aimed to develop a computerized image analysis system using deep learning for the detection of E/J cancers. METHODS: A total of 1172 images from 166 pathologically proven superficial E/J cancer cases and 2271 images of normal mucosa in esophagogastric junctional from 219 cases were used as the training image data. A total of 232 images from 36 cancer cases and 43 non-cancerous cases were used as the validation test data. The same validation test data were diagnosed by 15 board-certified specialists (experts). RESULTS: The sensitivity, specificity, and accuracy of the AI system were 94%, 42%, and 66%, respectively, and that of the experts were 88%, 43%, and 63%, respectively. The sensitivity of the AI system was favorable, while its specificity for non-cancerous lesions was similar to that of the experts. Interobserver agreement among the experts for detecting superficial E/J was fair (Fleiss' kappa = 0.26, z = 20.4, P < 0.001). CONCLUSIONS: Our AI system achieved high sensitivity and acceptable specificity for the detection of E/J cancers and may be a good supporting tool for the screening of E/J cancers.

Bone metastasis as a recurrence of early papillary adenocarcinoma of the stomach.

Papillary adenocarcinomas of the stomach are rare and associated with a high rate of lymphovascular invasion and distant metastasis. However, the association between papillary adenocarcinoma and bone metastasis in gastric cancer remains largely unexplored. We report a rare case of bone metastasis as a recurrence of early papillary adenocarcinoma of the stomach after curative surgery. A 75-year-old man with a pedunculated polyp at the pylorus of the stomach was diagnosed with papillary adenocarcinoma after biopsy of the lesion, and the polyp was surgically resected. Pathohistological examination revealed intramucosal cancer without lymphovascular invasion or lymph node metastasis. Eight months after surgery, imaging studies showed osteolysis in the right sacrum, and the lesion was diagnosed as a bone metastasis after biopsy. The patient received palliative chemotherapy and radiotherapy for the bone metastasis, which resulted in relief of his leg pain. Subsequently, he was provided supportive care when his condition deteriorated, and he died 8 months after the diagnosis of bone metastasis. Our case shows that bone metastasis should not be overlooked, even though it is rare in gastric cancer patients. Papillary adenocarcinoma of the stomach should be carefully followed up through imaging examinations, even after curative resection.

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.

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.

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.

[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.

Autoimmune polyglandular syndrome III in a patient with idiopathic portal hypertension.

A 42-year-old woman with a history of idiopathic portal hypertension (IPH) developed type 1A diabetes and was found to have chronic thyroiditis. The concurrence of IPH and type 1A diabetes has been previously reported in only one case. This is the second known case, and our patient was classified as having autoimmune polyglandular syndrome (APS) III. The patient's HLA DR and DQ alleles were determined to be susceptible to autoimmune thyroid diseases but resistant to type 1A diabetes.