Outcomes of Endoscopic Intervention Using Over-the-Scope Clips for Anastomotic Leakage Involving Secondary Fistula after Gastrointestinal Surgery: A Japanese Multicenter Case Series.

BACKGROUND: The over-the-scope clip (OTSC) is a highly effective clipping device for refractory gastrointestinal disease. However, Japanese data from multicenter studies for anastomotic leakage (AL) involving a secondary fistula after gastrointestinal surgery are lacking. Therefore, this study evaluated the efficacy and safety of OTSC placement in Japanese patients with such conditions. METHODS: We retrospectively collected data from 28 consecutive patients from five institutions who underwent OTSC-mediated closure for AL between July 2017 and July 2020. RESULTS: The AL and fistula were located in the esophagus (3.6%, n = 1), stomach (10.7%, n = 3), small intestine (7.1%, n = 2), colon (25.0%, n = 7), and rectum (53.6%, n = 15). The technical success, clinical success, and complication rates were 92.9% (26/28), 71.4% (20/28), and 0% (0/28), respectively. An age of <65 years (85.7%), small intestinal AL (100%) and colonic AL (100%), defect size of <10 mm (82.4%), time to OTSC placement > 7 days (84.2%), and the use of simple suction (78.9%) and anchor forceps (80.0%) were associated with higher clinical success rates. CONCLUSION: OTSC placement is a useful therapeutic option for AL after gastrointestinal surgery.

Interventional radiology using endoscopy: Blood supply route-targeted endoscopic injection sclerotherapy with multiple ligations for giant esophagogastric varices.

A case of high-risk giant esophagogastric varices was treated by blood supply route-targeted endoscopic injection sclerotherapy with multiple ligations (EISML). An endoscope was inserted in the left lower semi-lateral position under general anesthesia in the digital subtraction angiography room. The C-arm was rotated to obtain a frontal view for fluoroscopy. Before puncturing the esophageal varices, the balloon attached to the tip of the endoscope was inflated to block the variceal blood flow. At puncture, an intravascular injection was confirmed fluoroscopically, and a total of 18 m of 5% ethanolamine oleate with iopamidol was injected retrogradely at 5-minute intervals from the esophagogastric varices to the root of the left gastric vein, maintaining stagnation for 25 minutes. The variceal site of the injection was ligated immediately after the removal of the needle to prevent variceal bleeding. Multiple variceal ligations were added to stop the variceal blood flow. Contrast-enhanced CT 3 days after EISML showed the thrombus formation in esophagogastric varices and the left gastric vein. The blood supply route-targeted EISML can be a feasible procedure for giant esophagogastric varices.

Non-atrophic gastric mucosa is an independently associated factor for superficial non-ampullary duodenal epithelial tumors: a multicenter, matched, case-control study.

BACKGROUND/AIMS: The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. METHODS: This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. RESULTS: For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p<0.001). Non-atrophic mucosa (C0 to C1) was observed in 96 of 177 (54.2%) patients with SNADETs and 112 of 531 (21.1%) control patients (p<0.001). Conditional logistic regression analysis revealed that non-atrophic gastric mucosa was an independent risk factor for SNADETs (odds ratio, 5.10; 95% confidence interval, 2.44-8.40; p<0.001). CONCLUSION: Non-atrophic gastric mucosa, regardless of H. pylori infection status, was a factor independently associated with SNADETs.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Diagnosis of histological type of early gastric cancer by magnifying narrow-band imaging: A multicenter prospective study.

Objectives: Distinguishing undifferentiated-type from differentiated-type early gastric cancers (EGC) is crucial for determining the indication of endoscopic resection. We aimed to investigate the diagnostic performance of white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) for the histological type of EGC. Methods: In this multicenter prospective study, patients with histologically proven cT1 EGC, macroscopically depressed or flat type, size ≥5 mm, and without erosion/ulcer, were recruited. The diagnostic criterion of WLE for undifferentiated-type EGC was pale color. The M-NBI algorithm was created based on microsurface and microvascular patterns, and lesions with absent microsurface pattern and opened-loop microvascular patterns were diagnosed as undifferentiated-type. The center of the lesion was defined as the evaluation point and was initially evaluated by WLE, then by M-NBI, and a biopsy specimen was taken as a reference standard. The primary and key secondary endpoints were overall diagnostic accuracy and specificity, respectively. Results: In total, 167 lesions (122 differentiated-type and 45 undifferentiated-type EGCs) in 167 patients were analyzed. The overall accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80%, 69%, 84%, and 4.4, respectively, and those of M-NBI were 82%, 53%, 93%, and 7.2, respectively. There was no significant difference in overall accuracy (p = 0.755), but specificity was significantly higher in M-NBI (p = 0.041). Conclusions: The use of M-NBI did not improve the accuracy of WLE for the diagnosis of depressed/flat undifferentiated-type EGCs but improved the specificity. It may reduce surgical overtreatment by preventing misdiagnosis of differentiated-type EGC as undifferentiated-type.

Flexible Magnifying Endoscopy with Narrow Band Imaging for Diagnosing Uterine Cervical Neoplasms: A Multicenter Prospective Study.

We aimed to investigate the diagnostic ability of magnifying endoscopy with narrow band imaging (ME-NBI) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). This was a multicenter prospective study. Eligible patients had positive Pap smear results or follow-up high-grade cytology or CIN3 diagnosed in referring hospitals. Patients underwent ME-NBI by a gastrointestinal endoscopist, followed by colposcopy by a gynecologist. One lesion with the worst finding was considered the main lesion. Punch biopsies were collected from all indicated areas and one normal area. The reference standard was the highest histological grade among all biopsy specimens. The primary endpoint was the detection rate of patients with CIN2+ in the main lesion. The secondary endpoints were diagnostic ability for CIN2+ lesions and patients' acceptability. We enrolled 88 patients. The detection rate of ME-NBI for patients with CIN2+ was 79% (95% CI: 66-88%; p = 1.000), which was comparable to that of colposcopy (79%; p = 1.000). For diagnosing CIN2+ lesions, ME-NBI showed a better sensitivity than colposcopy (87% vs. 74%, respectively; p = 0.302) but a lower specificity (50% vs. 68%, respectively; p = 0.210). Patients graded ME-NBI as having significantly less discomfort and involving less embarrassment than colposcopy. ME-NBI did not show a higher detection ability than colposcopy for patients with CIN2+, whereas it did show a better patient acceptability.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. METHODS: One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. RESULTS: GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. CONCLUSIONS: We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

The Acute Onset of Autoimmune Hepatitis During Pregnancy in the Absence of Hypergammaglobulinemia and Autoantibodies.

The onset of autoimmune hepatitis (AIH) during pregnancy is rare and often poses a diagnostic challenge. A 29-year-old Japanese woman experienced epigastric pain and nausea during the third trimester of her third pregnancy. Three days after the symptom onset, an emergency Caesarean section was performed because of suspected acute fatty liver of pregnancy; however, the patient's liver dysfunction worsened afterward. Despite normal serum IgG concentration and absence of autoantibodies, biopsy-proven severe hepatitis with centrilobular zonal necrosis and good biochemical response to corticosteroids led to a diagnosis of AIH. Therefore, AIH should be included in the differential diagnosis of liver dysfunction during pregnancy.

Quality Assessment of Endoscopic Forceps Biopsy Samples under Magnifying Narrow Band Imaging for Histological Diagnosis of Cervical Intraepithelial Neoplasia: A Feasibility Study.

The current standard for diagnosing cervical intraepithelial neoplasia (CIN) is colposcopy followed by punch biopsy. We have developed flexible magnifying endoscopy with narrow band imaging (ME-NBI) for the diagnosis of CIN. Here, we investigated the feasibility of targeted endoscopic forceps biopsy (E-Bx) under guidance of ME-NBI for the diagnosis of CIN. We prospectively enrolled 32 consecutive patients with confirmed or suspected high-grade CIN undergoing cervical conization. Next to colposcopy, the same patients underwent ME-NBI just before conization. ME-NBI was performed, and 30 E-Bx samples were taken from lesions suspicious for high-grade CIN and 15 from non-suspicious mucosa. We recalled 82 punch biopsy (P-Bx) specimens taken from lesions suspicious for high-grade CIN under colposcopic examination before enrollment. The proportion of sufficient biopsy samples, which had an entire mucosal layer with subepithelial tissue, for the diagnosis of CIN was evaluated by both methods. Performance of targeted E-Bx for the final diagnosis of at least high-grade CIN was calculated. Seventeen P-Bx specimens were unavailable. The proportion of sufficient samples with E-Bx was 84%, which was similar to that with P-Bx (87%) (p = 0.672). The sensitivity, specificity, and accuracy of ME-NBI using E-Bx was 92%, 81%, and 88%, respectively. In conclusion, ME-NBI-guided E-Bx samples were feasible for histological diagnoses of CIN, and further investigation of its diagnostic accuracy is warranted.

Uterine Cervical Neoplasm Diagnosed by Flexible Magnifying Endoscopy with Narrow Band Imaging.

When detected early, uterine cervical cancer is one of the most successfully treatable forms of cancer. The diagnostic accuracy of the standard method, the Pap smear test followed by colposcopy, remains unsatisfactory. To improve detection of early-stage cervical cancer, new diagnostic tools for uterine cervical intraepithelial neoplasm (CIN) need to be developed. Magnifying endoscopy with narrow- band imaging (ME-NBI), which allows the visualization of the micro-structure as well as micro-vascularity of the mucosal surface, has excellent diagnostic ability for early gastrointestinal neoplasms. In our previous investigation, ME-NBI was efficacious for diagnosis of CIN. We herein report two notable cases of CIN3 that were diagnosed by ME-NBI that were not detected by colposcopy. These cases illustrate the usefulness of ME-NBI for diagnosis of early-stage uterine cervical neoplasms.

[A case of pancreatic cancer with clusters of invasive micropapillary carcinoma markedly reduced by chemotherapy].

A man in his 60s was hospitalized with multiple cerebral infarctions and referred for Trousseau's syndrome. Computerized tomography confirmed a 60-mm mass in the pancreatic head and swollen lymph nodes around the abdominal aorta. Fine needle aspiration cytology of the pancreatic lesion and laparoscopic para-aortic lymph node biopsy revealed adenocarcinoma, including clusters of invasive micropapillary carcinoma (IMPC). Chemotherapy (gemcitabine and nab-paclitaxel) markedly decreased the primary and metastatic lesions, and no recurrence was clinically detected 24 months later. To the best of our knowledge, reports of pancreatic IMPCs are rare. Our case was the seventeenth case of pancreatic cancer with IMPC. In this case, chemotherapy was markedly effective.

Characteristic findings of high-grade cervical intraepithelial neoplasia or more on magnifying endoscopy with narrow band imaging.

BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3. METHODS: A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens. RESULTS: The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.

Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial.

BACKGROUND: Accurate delineation of tumor margins is necessary for curative resection of early gastric cancer (EGC). The objective of this multicenter, randomized, controlled study was to compare the accuracy with which magnifying narrow-band imaging (M-NBI) and indigo carmine chromoendoscopy delineate EGC margins. METHODS: Patients with EGC ≥ 10 mm undergoing endoscopic or surgical resection were enrolled. The oral-side margins of the lesions were first evaluated with conventional white-light endoscopy in both groups and then delineated by either chromoendoscopy or M-NBI. Biopsies were taken from noncancerous and cancerous mucosa, each at 5 mm from the margin. Accurate delineation was judged to have been achieved when the histological findings in all biopsy samples were consistent with endoscopic diagnoses. The primary end point was the difference in rate of accurate delineation between the two techniques. RESULTS: Data on 343 patients were analyzed. The accurate delineation rate (95 % confidence interval) was 85.7 % (80.4 - 91.0) in the chromoendoscopy group (n = 168), and 88.0 % (83.2 - 92.8) in the M-NBI group (n = 175; P = 0.63). Lower third tumor location (odds ratio [OR] 2.9; P = 0.01), nonflat macroscopic type (OR 4.4; P < 0.01), and high diagnostic confidence (OR 3.6; P < 0.001) were associated with accurate delineation, whereas use of M-NBI was not (OR 1.2; P = 0.39). Even after adjustment for identified confounders, the difference in accurate delineation between the groups was not significant (OR 1.0; P = 0.82). CONCLUSIONS: M-NBI does not offer superior delineation of EGC margins compared with chromoendoscopy; the two methods appear to be clinically equivalent.

Clinical predictors of histologic type of gastric cancer.

BACKGROUND AND AIMS: Gastric cancer is classified into differentiated and undifferentiated types according to the degree of glandular differentiation. Undifferentiated-type early gastric cancer (EGC) carries a higher risk of lymph-node metastasis than differentiated type, and therefore the indication criteria for endoscopic resection differ. This study aimed to clarify the ability of clinical predictors to distinguish between differentiated-type and undifferentiated-type EGCs. METHODS: This was a post hoc study of a multicenter prospective trial carried out in 5 Japanese hospitals, including 343 patients with cT1 EGC of ≥10 mm. According to the protocol, age, sex, and endoscopic findings of cancer (diameter, location, macroscopic type, and invasion depth) were evaluated, and the final diagnosis was confirmed from resected specimens. We evaluated the associations between these clinical factors and the histologic type of cancer and calculated the ability of the factors to diagnose differentiated-type EGC. The diagnostic ability of forceps biopsy was also calculated as a reference. RESULTS: Multivariate analysis identified older age (≥72 years), male sex, larger tumor size (>30 mm), elevated type, and shallower invasion depth (cT1a) as independent significant predictors for differentiated-type EGC, with elevated type showing the highest positive likelihood ratio. The sensitivity, specificity, accuracy, and positive and negative likelihood ratios of elevated type for differentiated-type EGC were 24%, 99%, 38%, 15.7, and 0.77, respectively, compared with 96%, 86%, 95%, 7.0, and 0.04 for forceps biopsy. CONCLUSIONS: Endoscopic elevated type is a significant predictor for differentiated-type EGC and may exclude undifferentiated-type EGC without the need for forceps biopsy.

Russell body gastritis with Dutcher bodies evaluated using magnification endoscopy.

Russell body gastritis (RBG) is an unusual type of chronic gastritis characterized by marked infiltration of Mott cells, which are plasma cells filled with spherical eosinophilic bodies referred to as Russell bodies. It was initially thought that Helicobacter pylori (H. pylori) infection was a major cause of RBG and that the infiltrating Mott cells were polyphenotypic; however, a number of cases of RBG without H. pylori infection or with monoclonal Mott cells have been reported. Thus, diagnostic difficulty exists in distinguishing RBG with monoclonal Mott cells from malignant lymphoma. Here, we report an unusual case of an 86-year-old-Japanese man with H. pylori-positive RBG. During the examination of melena, endoscopic evaluation confirmed a 13-mm whitish, flat lesion in the gastric antrum. Magnification endoscopy with narrow-band imaging suggested that the lesion was most likely a poorly differentiated adenocarcinoma. Biopsy findings were consistent with chronic gastritis with many Mott cells with intranuclear inclusions referred to as Dutcher bodies. Endoscopic submucosal dissection confirmed the diagnosis of RBG with kappa-restricted monoclonal Mott cells. Malignant lymphoma was unlikely given the paucity of cytological atypia and Ki-67 immunoreactivity of monoclonal Mott cells. This is the first reported case of RBG with endoscopic diagnosis of malignant tumor and the presence of Dutcher bodies.

Evaluation of an e-learning system for diagnosis of gastric lesions using magnifying narrow-band imaging: a multicenter randomized controlled study.

Background and study aim Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness. Participants and methods This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored < 80 % accuracy on Test 1. The primary end point was the difference in accuracy between Test 1 and Test 2 for the two groups. Results A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9 % for the e-learning group and 61.7 % for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively; P < 0.001). Conclusion This study clearly demonstrated the efficacy of the e-learning system in improving practitioners' capabilities to diagnose EGC using M-NBI.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000008569).