Tapeworm Infection Diagnosed after Campylobacter jejuni-induced Enteritis.

A 35-year-old man with fever and diarrhea visited our hospital because of white string-like fecal excretion. Based on a morphological examination of the excreted object, a Diphyllobothrium infection was suspected. Additionally, Gram staining of a fecal sample revealed Campylobacter infection. After the intraduodenal administration of meglumine/diatrizoate sodium, the tapeworm was excreted. A polymerase chain reaction-based DNA sequence analysis demonstrated that the tapeworm excreted in this case was Diphyllobothrium nihonkaiensis. This report presents a rare case of coinfection with Diphyllobothrium nihonkaiensis and Campylobacter jejuni. Therefore, it is important to consider the coexistence of other intestinal infections when diagnosing parasitic infections in patients with fever.

Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is a standard approach for management of locally advanced esophageal squamous cell carcinoma (ESCC). Patients who do not respond well to NAC have a poor prognosis. Despite extensive research, the mechanisms of chemoresistance in ESCC remain largely unknown. Here, we established paired tumor organoids-designated as PreNAC-O and PostNAC-O-from one ESCC patient before and after NAC, respectively. Although the two organoids did not exhibit significant differences in proliferation, morphology or drug sensitivity in vitro, the tumorigenicity of PostNAC-O in vivo was significantly higher than that of PreNAC-O. Xenografts from PreNAC-O tended to exhibit keratinization, while those from PostNAC-O displayed conspicuous necrotic areas. The tumorigenicity of PostNAC-O xenografts during the chemotherapy was comparable to that of PreNAC-O without treatment. Furthermore, the gene expression profiles of the xenografts suggested that expression of genes involved in the EMT and/or hypoxia response might be related to the tumorigenicity of PostNAC-O. Our data suggested that the tumorigenicity of residual cancer had been enhanced, outweighing the effects of chemotherapy, rather than being attributable to intrinsic chemoresistance. Further studies are required to clarify the extent to which residual cancers share a common mechanism similar to that revealed here.

Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report.

RATIONALE: Tocilizumab, a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, is used for the treatment of adult-onset Still disease (AOSD). Despite its efficacy in many clinical situations, concerns have been raised regarding intestinal mucosal injury in patients receiving tocilizumab. PATIENT CONCERNS: A 64-year-old woman with a history of AOSD was admitted to our hospital with hematochezia. She had AOSD for 15 years and underwent treatment with biweekly tocilizumab 9 months prior to admission. Colonoscopy revealed a large punched-out ulcer in the terminal ileum. On pathological evaluation, nonspecific enteritis with lymphocytes and eosinophils were seen. Based on the location and shape of the lesion, we suspected intestinal Behçet's disease. However, the ulcer reduced in size over time by discontinuation of tocilizumab without additional drug treatment, indicating that it was a drug-induced ulcer. DIAGNOSIS: The patient was diagnosed with tocilizumab-induced small intestinal ulcer. INTERVENTIONS: The patient treated with the discontinuation of tocilizumab. OUTCOMES: The discontinuation of tocilizumab resulted in ulcer scarring. There was no recurrence of hematochezia. LESSONS: Tocilizumab can cause deep ulcerative lesions in the terminal ileum, which may resemble intestinal Behçet's disease. It is important to continuously monitor abdominal symptoms during tocilizumab therapy and aggressively perform colonoscopy when hematochezia or abdominal pain is observed.

Comparison of the improvement in gastric mucosal tissue after Helicobacter pylori eradication between young and elderly people.

BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) infection has been clearly shown to be a cause of gastric cancer, and the incidence of gastric cancer has been shown to decrease with eradication. However, few reports have described the utility of eradication therapy in elderly people. Thus, an investigation focusing on how much actual histological improvement is obtained with eradication therapy in elderly people was conducted. PATIENTS AND METHODS: This was a retrospective study conducted using medical information of patients diagnosed with H. pylori-associated gastritis and who underwent eradication therapy. The histological improvement was assessed based on changes in the atrophy and intestinal metaplasia scores of the Updated Sydney system from before to after eradication. We investigated the rates of histological improvement in atrophy and intestinal metaplasia one year after and long term more than five years after H. pylori eradication in an elderly group and a younger group. RESULTS: This study included 221 patients (elderly group 123, younger group 98). In histological atrophy, higher rates of improvement were seen in the corpus than in the antrum, and the rates of cure in the antrum were lower in elderly group than in younger group (p = 0.0282). With regard to intestinal metaplasia, the rates of improvement in the antrum were lower in elderly group than in younger. In long term observation, although the rates of cure in the antrum were lower in elderly, improvements were seen in atrophy scores in most of the patients and intestinal metaplasia scores in about half of patients. CONCLUSION: Though there is more obvious improvement in the gastric mucosa when H. pylori eradication therapy is performed at a young age, some mucosal improvement can be expected in about half of patients after eradication, even in elderly people.

Randomized controlled trial comparing conventional and traction endoscopic submucosal dissection for early colon tumor (CONNECT-C trial).

OBJECTIVES: Endoscopic submucosal dissection (ESD) is a widely used treatment for early gastrointestinal cancer. However, colon ESD remains challenging. Previous studies on colon ESD using the traction method used a small sample, single-center design, providing insufficient evidence of this procedure's efficacy. We thus aimed to investigate the efficacy and safety of the traction method in colon ESD in this multicenter randomized trial. METHODS: We conducted a prospective, multicenter, randomized, two-arm controlled trial at 10 facilities in Japan. A 1:1 allocation was conducted for the conventional ESD (C-ESD) and traction ESD (T-ESD) groups. The primary end-point was ESD procedure time. RESULTS: We included 128 C-ESD and 123 T-ESD cases from April 2020 to August 2021. The median procedure times for C-ESD and T-ESD were 61 (40-100) and 53 (40-76) min (P = 0.18), respectively, and no significant differences were observed between the groups. Subgroup analysis showed that the median procedure times for patients with a lesion diameter of ≥30 mm in the C-ESD and T-ESD groups were 89 (57-80) and 69 (50-104) min (P = 0.05), respectively, and for nonexpert operators were 81 (62-120) and 64 (52-109) min (P = 0.07), respectively. CONCLUSIONS: The traction method did not contribute to a significantly shortened ESD procedure time. However, this method may be useful when the tumor diameter is large or if the procedure is conducted by nonexpert endoscopists.

Acute Cholecystitis Associated with Eosinophilic Granulomatosis with Polyangiitis That Responded to Glucocorticoid Therapy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by tissue eosinophilic infiltration and vasculitis. Although EGPA causes multiple organ damage, it causes cholecystitis less frequently. We herein report a case of acute cholecystitis associated with EGPA in which successful treatment with glucocorticoid therapy allowed surgery to be avoided. EGPA can present as acute cholecystitis. It is important not to overlook acute cholecystitis associated with EGPA in patients with abdominal pain with peripheral eosinophilia. Furthermore, in cases of mild cholecystitis associated with EGPA that are diagnosed preoperatively, cholecystectomy might be avoided with conservative glucocorticoid treatment.

Endoscopic hand suturing for mucosal defect closure after gastric endoscopic submucosal dissection may reduce the risk of postoperative bleeding in patients receiving antithrombotic therapy.

OBJECTIVES: Endoscopic hand suturing (EHS) is expected to decrease the risk of post-endoscopic submucosal dissection (ESD) bleeding by closing mucosal defects. We investigated the efficacy of EHS after gastric ESD in patients with antithrombotic agents. METHODS: In this prospective single-arm trial, patients taking antithrombotic agents for cardiovascular disease, arrhythmia, cerebrovascular disease and/or peripheral arterial disease and having <3-cm gastric neoplasms were recruited. The mucosal defects after ESD were closed by EHS in which the needle was delivered through an overtube, and the mucosal rim of the defect was continuously sutured in a linear fashion by manipulating the needle grasped with the needle holder, followed by cutting the remnant suture and retrieval of the needle. The primary endpoint was the incidence of postoperative bleeding within 4 weeks after ESD. RESULTS: Twenty-two lesions in 20 patients (continuing antiplatelet agents in 11, anticoagulant agents in eight, both in one) underwent ESD followed by EHS. All defects (median size, 30 mm; range, 12-51 mm) were completely closed by EHS and remained closed on postoperative day 3. The median number of stitches was six (range, 4-8) and median suturing time was 36 (range, 24-60) min. There were no adverse events during/after EHS or postoperative bleeding. CONCLUSIONS: Postoperative bleeding was not observed in patients taking antithrombotic agents without perioperative cessation. EHS appears to be useful for prevention of post-gastric ESD bleeding in high-risk patients. (Clinical registration number: UMIN000024184).

Differences in Regression Patterns of Complete and Incomplete Intestinal Metaplasia at Ten Years after Helicobacter pylori Eradication.

This study was conducted to reveal the reversibility of subtype of intestinal metaplasia (IM) and Paneth cells after H. pylori eradication (HPE). Among 75 patients, we retrospectively examined the proportions of patients with complete type of IM (CIM), incomplete type of IM (IIM) and Paneth cells in their biopsy specimens obtained from the greater curvature of the antrum (A2) and the greater curvature of the middle corpus (B2) before and during a follow-up period of 10 years after HPE. Immunohistochemistry was used to determine IM type. Compared to before HPE, the proportion of patients with CIM did not decrease significantly during the 10-year follow-up after HPE both in A2 (32% vs. 21.3%, P = 0.13) and in B2 (6.7% vs. 2.7%, P = 0.60). IIM rates in A2 was significantly lower during this time (26.7% vs. 10.7%, P = 0.04), whereas no patients showed IIM in B2 before HPE. The proportion of patients with Paneth cells decreased significantly in A2 after 3, 8, and 9 years of HPE and in B2 after 4, 6 and 9 years of HPE (P < 0.05 for all). Thus, IIM and Paneth cells regressed during a period of 10 years after HPE.

Efficacy of endoscopic preventive procedures to reduce delayed adverse events after endoscopic resection of superficial nonampullary duodenal epithelial tumors: a meta-analysis of observational comparative trials.

BACKGROUND AND AIMS: Although various procedures have been used to prevent serious adverse events after endoscopic resection of the duodenum, their effectiveness has not been determined. In this study, we conducted a systematic review and meta-analysis to determine whether endoscopic preventive procedures reduce delayed adverse events. METHODS: Studies on endoscopic treatment for superficial nonampullary duodenal tumors were selected. We compared the following 2 groups: the closure group, which underwent mucosal sutures and coverage of mucosal defects after resection, and the unclosed group, which did not. The primary outcome was the rate of delayed adverse events, including perforation and bleeding. The pooled risk ratios (RRs) of all outcomes investigated, the 95% confidence intervals (CIs), and P values were calculated. RESULTS: A total of 438 patients from 4 studies were included in the meta-analysis. The pooled overall adverse event rates in the closure group and unclosed group were 3.6% and 21.1%, respectively. This rate was significantly lower in the closure group (RR, 0.19; 95% CI, 0.10-0.38; P < .01; I2 = 0%), and the rate of delayed bleeding was significantly lower in the closure group (RR, 0.14; 95% CI, 0.06-0.33; P < .01; I2 = 0%). Regarding delayed perforation, the RR in the closure group was 0.39 (95% CI, 0.12-1.32; P = .13; I2 = 0%). CONCLUSIONS: Preventive procedures significantly reduced the risk of delayed adverse events by more than 80%. After endoscopic resection of the duodenum, the implementation of preventive procedures, including mucosal sutures and coverage of mucosal defects, to delay adverse events is strongly recommended.

Water pressure method for duodenal endoscopic submucosal dissection (with video).

BACKGROUND AND AIMS: Duodenal endoscopic submucosal dissection (ESD) is considered technically challenging and has a high risk of adverse events. However, we recently made some progress with the ESD technique and device by introducing 2 features: a water pressure (WP) method and a second-generation ESD knife (DualKnife) with a water jet function (DualKnife J). The present study aimed to assess whether these changes improved the clinical outcomes of duodenal ESD. METHODS: This was a retrospective observational study. Among all patients who underwent ESD for superficial duodenal epithelial tumors from June 2010 to December 2018, patients in whom a single expert performed the procedure were included in this study. Various factors, including the use of the WP method and ESD devices (DualKnife or DualKnife J) and the treatment phase (early, mid, and late), were analyzed to determine whether they were associated with intraprocedural perforation and procedure time. Treatment phase was assigned by dividing the study population equally into 3 subgroups according to the treatment phase. RESULTS: The procedure time was significantly shorter, and the proportion of patients with intraprocedural perforations was the lowest in the late phase. Multivariate analysis of the use of the WP method revealed that it significantly decreased the intraprocedural perforation rate (odds ratio, 0.39; 95% confidence interval, 0.16-0.96), and analysis of the use of both the WP method (ß coefficient, -0.40; P < .01) and the DualKnife J (ß coefficient, -0.10; P = .032) revealed they were independently and negatively correlated with procedure time. CONCLUSION: The present study reveals that the WP method significantly reduced the intraprocedural perforation rate and that both the WP method and the DualKnife J significantly shortened procedure times for duodenal ESD.

Endoscopic suturing promotes healing of mucosal defects after gastric endoscopic submucosal dissection: endoscopic and histologic analyses in in vivo porcine models (with video).

BACKGROUND AND AIMS: Endoscopic suturing of mucosal defects after endoscopic submucosal dissection (ESD) is expected to prevent postoperative adverse events. We aimed to endoscopically and histologically evaluate the healing process of post-ESD mucosal defects closed with endoscopic hand suturing (EHS) in in vivo porcine models. METHODS: Twelve mucosal defects (2 cm in size) were created in 2 pigs (6 defects per pig). Initially, 2 defects were created: one was closed with EHS (sutured group) and the other was kept open (control group). On postoperative days (PODs) 7 and 14, 2 additional defects were created in each session, and they were treated in the same manner as in the initial procedure. On POD 21, the entire stomach, with the 6 lesion sites, was extracted for histologic evaluation after endoscopic observation. RESULTS: Endoscopically, all sutured sites remained closed in all sessions (PODs 7, 14, and 21). Histologically, on POD 14, the epithelium and muscularis mucosae were appropriately connected. The mucosae were covered with the epithelium without inversion of the mucosal edge in the sutured group, whereas the ulcer bed was exposed in the control group. Furthermore, the degree of neovascularity and fibroblasts in the submucosa was smaller in the sutured group than that in the control group. CONCLUSIONS: Our findings suggest that endoscopic suturing promotes healing of post-ESD mucosal defects histologically in in vivo porcine models. Thus, endoscopic mucosal closure after ESD might be clinically useful for the prevention of delayed perforation/bleeding if secure suturing is performed endoscopically.

Feasibility of endoscopic submucosal dissection for colorectal neoplasia at anastomotic sites: a retrospective study.

BACKGROUND: Metachronous colorectal lesions sometimes occur at anastomotic sites following colorectal surgery, which increases the risk of developing colorectal cancer. However, these lesions are difficult to treat even with minimally invasive methods such as endoscopic submucosal dissection (ESD). Thus, we aimed to evaluate the outcomes of ESD for colorectal lesions at anastomotic sites following colorectal surgery. METHODS: We retrospectively investigated 11 patients with post-surgical colorectal lesions at anastomotic sites who later underwent ESD from May 2010 to April 2019 at Keio University Hospital, Tokyo, Japan. We examined the patients' background (tumor location, macroscopic type, tumor size, histological type, and depth of invasion) and treatment outcomes (procedure duration, en bloc resection rate, R0 resection rate, and adverse events). RESULTS: The patients' mean age was 66 years. There were two lesions in the transverse colon, six in the rectum, one in the anal canal, and two in the ileal pouch. The median tumor size was 25 mm. The macroscopic types were the protruded type (1 lesion) and the flat or depressed type (10 lesions). The pathological diagnoses were adenoma (4 lesions), intramucosal cancer (corresponding to high-grade dysplasia) (6 lesions), and muscularis propria cancer (1 lesion). The median procedure duration was 50 min; en bloc resection rate was 88.9% and R0 resection rate was 66.7%. The only adverse event was delayed post-ESD bleeding. CONCLUSIONS: A high en bloc resection rate without perforation was achieved with ESD for lesions at anastomotic sites. Although ESD for lesions at anastomotic sites is a technically challenging procedure because of severe submucosal fibrosis, this approach could prevent the need for repeated surgical resection.

How I do it: Endoscopic diagnosis for superficial non-ampullary duodenal epithelial tumors.

There are no reports on detailed endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADET) except for relatively small case series. Herein, we conducted a prospective observational study to investigate the relationship between endoscopic findings and histopathological diagnosis of SNADET. A total of 163 SNADET diagnosed using magnified endoscopic examination with image-enhanced endoscopy (IEE-ME) were prospectively registered in this study. We investigated location, size, macroscopic type, color, and IEE-ME findings including surface structure (closed- or open-loop) and presence of white opaque substance (WOS) in SNADET. We analyzed association between these findings and histopathological diagnosis of SNADET based on the Vienna classification (VCL) using logistic regression analysis. In univariate analysis, lesion size, superficial structure, and WOS deposition showed statistical significance, and the oral side of the lesion location showed statistical tendency for association with VCL C4/5. In multivariate analysis, lesion size (odds ratio [OR], 2.92; 95% CI, 1.94-4.39; P < 0.05) and negative WOS (OR, 5.59; 95% CI, 1.72-18.1; P < 0.05) were significantly associated with VCL C4/5 lesions. Superficial structures with a closed-loop pattern on the surface showed statistical tendency for predicting VCL C4/5 lesions (OR, 2.15; 95% CI, 0.86-5.37; P = 0.10). Based on these findings, we concluded that negative WOS by IEE-ME and lesion size were independent predictors of VCL C4/5 SNADET. These factors may help us to understand of pathophysiology of SNADET and to select appropriate therapeutic strategies.

Management of perforation related to endoscopic submucosal dissection for superficial duodenal epithelial tumors.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is being performed more frequently as a local treatment for superficial duodenal epithelial tumors (SDETs). However, ESD for SDETs is technically difficult because of specific anatomic features that increase the risk of perforation and often require surgery. This study was performed to evaluate the management of ESD-related perforation in patients with SDETs. METHODS: Patients who underwent ESD for SDETs from July 2010 to December 2018 were studied. We collected data on complete closure, insertion of endoscopic nasobiliary and pancreatic duct drainage (ENBPD) tubes, and additional interventions. We also evaluated clinical outcomes, including the fasting period, hospital stay, and maximum serum C-reactive protein level. RESULTS: ESD was completed in 264 patients with SDETs. Perforation was observed in 36 patients, including 4 patients with delayed perforation. Among 32 patients with intraoperative perforation, complete closure was achieved in 13 patients. Compared with patients without complete closure, the fasting period and hospital stay were significantly shorter and the maximum serum C-reactive protein level was significantly lower in patients with complete closure, which were equivalent to those in patients without perforation. In patients without complete closure for mucosal defect, no additional interventions were required when an ENBPD tube was inserted, whereas 2 patients without ENBPD tube insertion underwent additional interventions such as percutaneous drainage and a surgical operation. CONCLUSIONS: Perforation associated with ESD for SDETs required complex conservative management with complete closure or insertion of an ENBPD tube.

Predictors of technical difficulty with duodenal ESD.

Background and study aims Duodenal endoscopic submucosal dissection (ESD) is still considered technically challenging; however, few studies have objectively analyzed predictors of the technical difficulty. Therefore, the aim of the current study was to elucidate predictors of the technical difficulty of duodenal ESD. Patients and methods This was a retrospective observational study. From June 2010 to June 2017, a total of 174 consecutive patients with superficial duodenal epithelial neoplasia who underwent ESD were included in this study. We tried to identify predictors for technical difficulty of ESD by defining technical difficulty as either procedure time > 100 minutes or intraprocedural perforation. Moreover, we constructed a scoring system consisting of factors that were significant in the multivariate analysis. Results The proportion of patients with technical difficulty was 34.5 %. In the multivariate analysis, lesion location in flexural part [odds ratio (OR), 2.61; 95 % confidence interval (CI), 1.02 - 6.68], larger lesion size (> 40 mm) (OR, 5.26; 95% CI, 2.15 - 12.9), and occupied circumference > 50 % of the duodenum (OR, 5.80; 95 % CI, 1.83 - 18.4) were associated with technical difficulty. Conclusion A lesion location in flexural part, lesion size >40 mm and occupied circumference > 50 % were risk factors for technical difficulty of duodenal ESD.

Diagnostic Accuracy of Latex Agglutination Turbidimetric Immunoassay in Screening Adolescents for Helicobacter pylori Infection in Japan.

BACKGROUND/AIMS: Serologic tests are commonly used for screening Helicobacter pylori infection because they not only provide quick results but also are inexpensive. A new latex agglutination serum antibody assay (LZ test) has been developed and it is expected to be as effective as conventional assays. This study aimed to calculate a reliable cutoff value for the LZ test and to estimate the sensitivity and specificity of the cutoff value in screening adolescents for H. pylori infection in Japan. METHODS: We screened junior high school students in Akita Prefecture, Japan, for H. pylori infection. We used the data of 213 such students who underwent H. pylori stool antigen (HpSA) tests in 2016. The students who had positive results with HpSA tests were diagnosed with H. pylori infection. Of the 213 students, 209 underwent the LZ test. RESULTS: The prevalence rate of H. pylori infection was 3.8% (8/209). The area under the curve for the LZ test was 0.88. The cutoff value of the LZ test was determined to be 3.1 U/mL. At this value, the sensitivity and specificity were 87.5 and 91.5%, respectively. CONCLUSION: The accuracy of the LZ test in adolescents was well balanced for sensitivity and specificity as well as for tolerable results.

Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation.

PRIP (phospholipase C-related, but catalytically inactive protein) is a novel protein isolated in this laboratory. PRIP-deficient mice showed increased serum gonadotropins, but decreased gonadal steroid hormones. This imbalance was similar to that for the cause of bone disease, such as osteoporosis. In the present study, therefore, we analyzed mutant mice with special reference to the bone property. We first performed three-dimensional analysis of the femur of female mice. The bone mineral density and trabecular bone volume were higher in mutant mice. We further performed histomorphometrical assay of bone formation parameters: bone formation rate, mineral apposition rate, osteoid thickness, and osteoblast number were up-regulated in the mutant, indicating that increased bone mass is caused by the enhancement of bone formation ability. We then cultured primary cells isolated from calvaria prepared from both genotypes. In mutant mice, osteoblast differentiation, as assessed by alkaline phosphatase activity and the expression of osteoblast differentiation marker genes, was enhanced. Moreover, we analyzed the phosphorylation of Smad1/5/8 in response to bone morphogenetic protein, with longer phosphorylation in the mutant. These results indicate that PRIP is implicated in the negative regulation of bone formation.