Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata.

BACKGROUND/OBJECTIVES: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. METHODS: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. RESULTS: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). CONCLUSIONS: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

Predictors of technical difficulty for complete closure of mucosal defects after duodenal endoscopic resection.

BACKGROUND AND AIMS: It has been reported that the prophylactic closure of mucosal defects after duodenal endoscopic resection (ER) can reduce delayed adverse events; however, under certain circumstances, this can be technically challenging. Therefore, the aim of this study was to determine the predictors of difficulty during the complete closure of mucosal defects after duodenal ER. METHODS: This was a retrospective study of duodenal lesions that underwent ER between July 2010 and May 2020. We reviewed the endoscopic images and analyzed the relationships between the degree of closure or closure time and clinical features of the lesions using univariate and multivariate analyses. RESULTS: We analyzed 698 lesions. The multivariate analysis revealed that lesion location in the medial or anterior wall (odds ratio, 2.8; 95% confidence interval, 1.36-5.85; P < .01) and a large lesion size (odds ratio, 1.4; 95% confidence interval, 1.07-1.89; P = .03) were independent predictors of an increased risk of incomplete closure. Moreover, a large lesion size (ß coefficient, .304; P < .01), an occupied circumference over 50% (ß coefficient, .178; P < .01), intraoperative perforation (ß coefficient, .175; P < .01), treatment period (ß coefficient, .143; P < .01), and treatment with endoscopic submucosal dissection (ß coefficient, .125; P < .01) were independently and positively correlated with a prolonged closure time in the multiple regression analysis. CONCLUSIONS: This study revealed that lesion location in the medial or anterior wall and lesion size affected the incomplete closure of mucosal defects after duodenal ER, and lesion size, occupied circumference, intraoperative perforation, treatment period, and treatment method affected closure time.

External drainage of bile and pancreatic juice after endoscopic submucosal dissection for duodenal neoplasm: Feasibility study (with video).

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for superficial duodenal epithelial tumors (SDETs) is technically difficult and has a high risk of adverse events. Endoscopic nasobiliary and nasopancreatic duct drainage (ENBPD) may reduce the risk of delayed adverse events by preventing exposure of the post-ESD mucosal defect to bile and pancreatic juice. This study was performed to evaluate the safety and feasibility of ENBPD after duodenal ESD. METHODS: Patients who underwent ESD for SDETs from July 2010 to March 2020 were included. We collected data on the success rate of ENBPD, adverse events due to insertion of a side-viewing endoscope, and pancreatitis after ENBPD. We also collected the clinical outcomes of duodenal ESD, including the incidence rate of delayed adverse events (defined as bleeding or perforation found after the endoscopic procedure). RESULTS: Among 70 patients without complete closure of the post-ESD mucosal defect, ENBPD was successfully performed in all 25 patients including 21 cases inserted immediately after ESD and four cases inserted later. There were no adverse events associated with ENBPD procedure intraoperatively, while pancreatitis after ENBPD occurred in four patients (16.0%). No patients who underwent immediate ENBPD required intervention for an intra-abdominal abscess or delayed perforation, whereas 3 of 49 patients (6.1%) who did not undergo immediate ENBPD required surgery or drainage of an abscess. CONCLUSIONS: Endoscopic nasobiliary and nasopancreatic duct drainage is technically feasible and might provide effective prophylaxis for delayed adverse events, even if a large mucosal defect is present after ESD.

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.

Impact of electrical pulse cut mode during endoscopic papillectomy: Pilot randomized clinical trial.

OBJECTIVE: Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. METHODS: This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. RESULTS: Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). CONCLUSIONS: The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. REGISTRY AND THE REGISTRATION NUMBER: The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

Clinical impact of closure of the mucosal defect after duodenal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Delayed adverse events (bleeding or perforation) are major concerns associated with duodenal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of prophylactic closure of the mucosal defect after duodenal ESD. METHODS: This is a retrospective study from a university hospital. One hundred sixty-eight patients (173 lesions) who underwent duodenal ESD between July 2010 and June 2017 were included in this study. The study participants were divided into 3 subgroups according to the degree of closure: complete group, incomplete group, and unclosed group. The proportion of delayed adverse events, maximum serum level of C-reactive protein (CRP), and total length of hospital stay were compared among these subgroups. Moreover, a multivariate logistic regression model was constructed to identify the risk factors for delayed adverse events. RESULTS: The proportion of delayed adverse events in the complete group, incomplete group, and unclosed group were 1.7%, 25%, and 15.6%, respectively. The difference between the complete group and the other groups was significant (P < .01). The maximum serum CRP level was much lower (1.51 ± 2.18 mg/dL vs 6.28 ± 10.0 mg/dL, P < .01), and the length of hospital stay was significantly shorter in the complete group than in the incomplete/unclosed group (median [range] 5 [5-14] days vs 8 [4-59] days, P < .01). Multivariate analysis revealed that complete closure had a significant decrease in delayed adverse events (odds ratio [OR], 0.055; 95% confidence interval [CI], 0.01-0.29; P < .01), and a lesion located distal from the descending part showed a statistical tendency to an increase in delayed adverse events (OR, 4.48; 95% CI, 0.85-23.6; P = .08). CONCLUSION: The present study revealed that complete closure of the mucosal defect after duodenal ESD significantly decreased the number of delayed adverse events and improved other outcomes.

Clinical utility of novel ultrathin single-balloon enteroscopy: a feasibility study.

BACKGROUND: The advent of balloon-assisted enteroscopy (BAE) has facilitated the examination of the entire digestive tract. However, using a rigid sliding tube during the procedure reduces patient acceptance. This study evaluated the clinical application of a newly developed ultrathin single-balloon enteroscope for BAE. METHODS: 28 outpatients underwent enteroscopy with a novel ultrathin single-balloon enteroscope. None of the subjects required therapeutic procedures, such as balloon dilation or hemostasis. The insertability, efficacy, and safety of the ultrathin single-balloon endoscope were evaluated retrospectively. RESULTS: 7 patients underwent transoral enteroscopy and 21 patients underwent transanal enteroscopy under conscious sedation. No adverse events related to the procedure were reported in any patients. Targeted observation and/or targeted biopsy were achieved in all procedures. All transoral procedures allowed evaluation of the jejunum beyond the ligament of Treitz. All transanal procedures allowed intubation of the terminal ileum, despite several patients having severe stenosis of the colon and ileum. CONCLUSION: A novel ultrathin single-balloon enteroscope showed adequate insertability and safety for outpatient surveillance enteroscopy under conscious sedation.

Enteric Glial Dysfunction Evoked by Apolipoprotein E Deficiency Contributes to Delayed Gastric Emptying.

BACKGROUND AND AIM: Diabetes is the main cause of gastroparesis accompanying decreased neuronal nitric oxide synthase (nNOS) in myenteric ganglia of the stomach. Decreased nNOS expression in the stomach also results from defects in apolipoprotein E (ApoE), which is secreted by astrocytes and has neuroprotective effects on the central nervous system. However, the roles of ApoE and enteric glial cells on gastric motility are uncertain. In this study, ApoE and enteric glial cell alterations in gastroparesis were investigated. METHODS: Type 2 diabetic (db/db) mice and ApoE-knockout mice were analyzed. Gastric emptying was measured using the 13C acetic acid breath test. Expression levels of the pan-neuronal marker, protein gene product 9.5 (PGP 9.5), and glial marker, glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. Neural stem cells (NSCs) were injected into the gastric antral wall of ApoE-knockout mice. RESULTS: Delayed gastric emptying was observed in 27% of db/db mice with significant decreases in serum ApoE levels and GFAP expression in the gastric antrum. Gastric emptying was also delayed in ApoE-knockout mice, with a significant decrease in GFAP expression, but no change in PGP 9.5 expression. Transplantation of NSCs improved gastric emptying in ApoE-knockout mice through supplementation of GFAP-positive cells. CONCLUSIONS: Our results suggest that decreased enteric glial cells in ApoE-knockout mice are crucial for development of delayed gastric emptying, and NSC transplantation is effective in restoring myenteric ganglia and gastric motility.

Efficacy of 10-day Sitafloxacin-Containing Third-Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation.

BACKGROUND AND AIM: Sitafloxacin-containing Helicobacter pylori eradication therapy is a promising third-line therapeutic approach, but there is no previous studies between gyrA mutation status of H. pylori strains and the efficacy of 10-day sitafloxacin-containing regimens. Here, we assessed the efficacy of 2 different 10-day sitafloxacin-containing rescue regimens. METHODS: Patients who failed first- and second-line eradication therapies were enrolled. The minimum inhibitory concentrations (MICs) of sitafloxacin, amoxicillin, and metronidazole and the gyrA mutation status of the H. pylori strains were determined before treatment. The patients were randomized to receive a 10-day triple therapy containing either esomeprazole (20 mg, b.i.d.), amoxicillin (500 mg, q.i.d.), and sitafloxacin (100 mg, b.i.d.) (EAS regimen) or esomeprazole (20 mg, b.i.d.), metronidazole (250 mg, b.i.d.), and sitafloxacin (100 mg, b.i.d.) (EMS regimen). Eradication rates were evaluated by the [13C] urea breath test or the H. pylori stool antigen test. RESULTS: All patients with gyrA mutation-negative strains (24 in EAS and 16 in EMS) showed successful eradication, irrespective of the regimen they received. In patients with gyrA mutation-positive strains, we found eradication rates of 70.3% (26/37) and 66.7% (26/39) in the EAS and EMS groups in per-protocol population, respectively (p = .81). According to logistic regression analyses, the MICs of sitafloxacin, which were strongly associated with gyrA mutation status, were independently associated with successful eradication in both groups. This study was registered in the UMIN Clinical Trials Registry as UMIN000006483. CONCLUSION: There is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin-containing rescue therapies.

Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice.

BACKGROUND AND AIM: Basolateral water channel, aquaporin-4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H2R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection. METHODS: Male H2 R knockout mice and their controls (C57BL/6) were used. H. pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H+/K+-ATPase in the gastric mucosa were investigated by fluorescent immunohistochemistry. The mRNA expressions of AQP4, H+/K+-ATPase, sonic hedgehog (Shh), and trefoil factor-2 (TFF2) were investigated by quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In the H2 R knockout mice, the distribution of AQP4-positive parietal cells was extended toward the surface of the fundic glands. Although the mRNA expression levels of AQP4 and H+/K+ATPase were elevated in H2 R knockout mice at the age of 20 weeks, the elevations were not maintained by aging or H. pylori infection. In H2 R knockout mice with H. pylori infection, the expression level of TFF2 mRNA was elevated while the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased compared with the H2 R knockout mice without H. pylori infection. CONCLUSIONS: In the H2 R knockout mice, massive SPEM was induced by H. pylori colonization and the ratio between AQP4 and H+/K+ATPase mRNA expression was decreased.

Successful management of bile duct injury with duodenal perforation using endoscopic naso-pancreatic drainage and fully covered self-expandable metallic stent deployment.

Video 1A case of bile and pancreatic duct injury with duodenal perforation during endoscopic submucosal dissection for superficial duodenal epithelial neoplasia.

Unique bile acid profiles in the bile ducts of patients with primary sclerosing cholangitis.

BACKGROUND: The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC. METHODS: Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13). RESULTS: The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups. CONCLUSIONS: Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.

Biliary findings assist in predicting enlargement of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND & AIMS: There is controversy over the optimal management strategy for patients with branch-duct type intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs), precursors to pancreatic cancer. We aimed to identify factors associated with the presence of BD-IPMNs and changes in their diameter. METHODS: Two separate analyses were conducted in a cohort of patients who underwent magnetic resonance cholangiopancreatography (MRCP) in a single year (2006). MRCP findings and clinical outcomes of these patients were followed for a maximum of 6 years. We evaluated initial MRCP findings and demographics associated with the presence of BD-IPMNs at baseline and increase in BD-IPMN diameter over time. RESULTS: During the follow-up period, 154 patients developed BD-IPMN and 322 patients did not. Older age, diabetes mellitus, gallbladder adenomyomatosis, and absence of gallstones were associated with the presence of BD-IPMNs at baseline. Increases in diameter of BD-IPMNs were associated with 3 baseline factors: BD-IPMN diameter greater than 17 mm, gallbladder adenomyomatosis, and a common bile duct diameter less than 5.5 mm. Patients with BD-IPMNs could be stratified into 4 groups with varying risk for the enlargement of BD-IPMNs over time: those with 3 risk factors (hazard ratio [HR], 11.4; 95% confidence interval [CI], 3.4-37.8), 2 risk factors (HR, 4.7; 95% CI, 1.7-12.8), or 1 risk factor (HR, 3.1; 95% CI, 1.2-8.2) compared with those without risk factors. CONCLUSIONS: For patients with BD-IPMNs, careful follow-up evaluation is particularly important for those with BD-IPMN >17 mm in size, common bile duct diameter <5.5 mm, or gallbladder adenomyomatosis.

Improvement of reflux symptom related quality of life after Helicobacter pylori eradication therapy.

The relationship between Helicobacter pylori (H. pylori) eradication therapy and the risk of developing gastroesophageal reflux disease (GERD) is controversial. We investigated the influence of H. pylori eradication on the risk of GERD by focusing on the quality of life (QOL) and evaluating reflux symptoms. Patients with H. pylori infection were administered triple therapy for H. pylori eradication. At 3 months and 1 year after the eradication therapy, surveys were conducted to determine the health-related QOL by quality of life in reflux and dyspepsia-Japanese version, (QOLRAD-J) and the severity of GERD symptoms by Carlsson-Dent questionnaire (CDQ). Forty patients were included in the analysis. Although no significant changes of these scores were apparent 3 months after H. pylori eradication, the QOLRAD-J and CDQ scores were significantly improved after 1 year. The degree of improvement was even more marked in cases with initially low scores. In conclusion, improved GERD-related QOL and reflux symptoms were noted 1 year after H. pylori eradication therapy. In addition, the degree of improvement was more marked in cases with severe reflux symptoms.

Primary angiosarcoma of the ascending colon diagnosed after the discovery of intraoral tumor.

Here, we report a case of primary angiosarcoma of the ascending colon diagnosed after the discovery of an oral tumor. An 86-year-old woman presented to our hospital with severe anemia. Although she did not report any oral symptoms, an intraoral mass 15 mm in size with ulceration was observed. Since colonic tumors and osteolytic tumors in the maxilla and sacra were also identified by fluorodeoxyglucose (FDG)-positron emission tomography (PET), colonoscopy was performed. A semi-peripheral tumor with ulceration from the cecum to the ascending colon was detected. Biopsies of the oral cavity and colon revealed a poorly differentiated tumor, and multiple additional immunohistochemical stains were performed to confirm the diagnosis of angiosarcoma. Angiosarcoma progresses rapidly and has a very poor prognosis. Hence, although it is rare, angiosarcoma should always be considered in the differential diagnoses of malignancy of the gastrointestinal tract.

Large submucosal hematoma after cold snare polypectomy for colorectal adenoma.

Cold snare polypectomy (CSP), for the treatment of colorectal polyps, has become widespread due to its low incidence of adverse events compared to that of endoscopic procedures such as endoscopic mucosal resection. However, we experienced a case of large hematoma development shortly after CSP for a colorectal adenoma despite no bleeding during the procedure. The patient underwent CSP for a 7-mm type Isp lesion in the ascending colon. She returned the following day because of hematochezia. Computed tomography showed a 70-mm, high-intensity mass in the ascending colon, consistent with the large hematoma that was detected by colonoscopy. Although the patient initially had right-sided abdominal pain, it gradually improved with conservative treatment. The hematoma decreased in size, and she was discharged 20 days after emergency admission. Although CSP can be a favorable alternative to more invasive procedures and is expected to be performed more frequently, adverse events, such as that described in this case, should be anticipated.

Efficacy of sitafloxacin-based rescue therapy for Helicobacter pylori after failures of first- and second-line therapies.

Sitafloxacin-based triple therapy achieved 83.6% (per-protocol) and 78.2% (intention-to-treat) success in eradicating Helicobacter pylori among 78 Japanese patients after clarithromycin-based first-line and metronidazole-based second-line triple therapies failed. Eradication succeeded in 32 out of 43 patients, even with gyrA mutation-positive Helicobacter pylori (per protocol). The position of the gyrA mutation (N87 or D91) was determined to be a better marker than MIC levels for predicting outcomes of sitafloxacin-based treatment.