Polyglycolic Acid Felt Sealing Method for Prevention of Bleeding Related to Endoscopic Submucosal Dissection in Patients Taking Antithrombotic Agents.

Background and Study Aims. When performing endoscopic submucosal dissection (ESD) for patients on antithrombotic agents, the frequency of delayed bleeding is expected to increase. The endoscopic polyglycolic acid (PGA) felt and fibrin glue sealing method could be a new method for prevention of delayed bleeding. Patients and Methods. The safety and efficacy of the endoscopic tissue sealing method with PGA sheets and fibrin glue for the prevention of post-ESD bleeding were examined in 104 patients taking antithrombotic agents. During the study period, 70 patients taking antithrombotic agents did not undergo the sealing method, 36 patients discontinued antithrombotic agents, and 724 patients had not received antithrombotic therapy. Results. Delayed bleeding rates were 3.8% (4/104) in the sealing group, 12.9% (9/70) in the nonsealing group, 8.3% (3/36) in the discontinuation group, and 4.6% (33/724) in the nonantithrombotic therapy group. Thus, the delayed bleeding rate was significantly lower in the sealing group than in the nonsealing group and comparable to that in the nonantithrombotic therapy group. Conclusions. This PGA felt and fibrin glue sealing method might become a promising post-ESD bleeding prevention method in patients taking antithrombotic agents (UMIN000013990, UMIN000013993).

Oral prednisolone and triamcinolone injection for gastric stricture after endoscopic submucosal dissection.

BACKGROUND: The expansion of the indications for endoscopic submucosal dissection (ESD) to include early gastric cancers has enabled extensive resection. However, post-ESD stenosis after large resections applied to the gastric cardia or pylorus is often difficult to manage. The aim of this study was to evaluate the benefit of oral prednisolone and triamcinolone injection for stenosis after gastric ESD. METHODS: Eight patients who underwent ESD for large neoplastic lesions that extended more than three-fourths of the luminal circumference were enrolled in this study. Four patients underwent ESD for gastric cardia cancer, and four patients were treated for pyloric lesions. To prevent post-ESD stricture, oral prednisolone was started at 30 mg daily on the second day after ESD and then tapered gradually in two cases, while topical injection of 80 mg triamcinolone was performed once immediately after ESD in six cases. Endoscopic balloon dilatation (EBD) was used for stricture-related symptoms or signs including nausea, vomiting, or food residuals observed on endoscopy. EBD was also applied if a 10-mm-diameter endoscope was not able to pass through the lumen. The incidence of stenosis, the frequency and period required for EBD, the duration required for ulcer healing after ESD, and the incidences of post-procedural bleeding and perforation were assessed. RESULTS: One of the eight patients had post-ESD stenosis requiring EBD. The median ulcer healing period after ESD was 87.5 (range, 56-133) days. No patients experienced post-procedural bleeding or perforation. There were no adverse events due to steroid therapy. CONCLUSIONS: The results of the present study showed the safety and usefulness of steroid therapy for management of stenosis after large ESD in the gastric cardia or pylorus.

Early and long-term outcomes of endoscopic submucosal dissection for early gastric cancer in a large patient series.

Endoscopic submucosal dissection (ESD) enables the curative resection of early gastric cancer (EGC); however, little information is available on the long-term outcomes of ESD. This study was conducted to clarify the clinical outcomes of a large number of patients with EGC who underwent ESD. The early outcomes were assessed in 1,209 patients and the long-term outcomes were assessed in 300 patients at a follow-up >5 years after the ESD procedure. The overall survival rates were compared between indication and expanded-indication groups, and between the patients who did or did not undergo additional surgery in an out-of-indication group. Overall survival rates were also compared among different age groups. In total, 617 lesions were classed as the indication group, 507 as the expanded-indication group and 208 as the out-of-indication group. Curative resection rates were 96.6% and 91.5% in the indication and expanded-indication groups, respectively. In terms of the long-term outcomes, 20 of the 146 patients in the indication group, 15 of the 105 patients in the expanded-indication group and one of the 23 patients who underwent additional surgery in the out-of-indication group succumbed due to causes other than gastric cancer. Among the 26 patients who did not undergo additional surgery in the out-of-indication group, 10 mortalities occurred, including one due to gastric cancer. The five-year survival rates were not significantly different between the indication and expanded-indication groups. In the out-of-indication group, the five-year survival rate for the patients who did not undergo additional surgery (65.0%) was significantly lower than that for those who did undergo additional surgery (100%) (P<0.01). The five-year survival rate of patients aged >80 years (67.1%) was significantly lower than that of the younger patients (<60 years, 91.6%; sixties, 93.0%; seventies, 84.5%) (P<0.0001). In conclusion, although expanded-indication of ESD for EGC is appropriate, comorbidities require consideration in elderly patients.

Endocytoscopic findings of lymphomas of the stomach.

BACKGROUND: The gastric lesions of various lymphomas were observed at the cellular level using endocytoscopy. METHODS: Endocytoscopy and magnifying endoscopy with narrow band imaging (NBI) were performed in 17 patients with lymphomas of the stomach. The lesions consisted of 7 with low-grade mucosa-associated lymphoid tissue (MALT), 5 with gastric involvement by adult T-cell leukemia/lymphoma (ATLL), 4 with diffuse large B-cell lymphoma (DLBCL), and 1 with peripheral T-cell lymphoma. RESULTS: On conventional endoscopy, 9 were classified as having superficial spreading type, 7 were mass-forming type, and 1 was diffuse infiltrating type. Anti-H. pylori treatment was given in the 7 MALT lymphoma cases. NBI magnification endoscopy invariably showed dilatation or ballooning and destruction of gastric pits and elongation and distortion in microvessels. Endocytoscopy showed mucosal aggregation of interstitial cellular elements in almost all gastric lymphoma cases. The nuclear diversity in size and configuration was exclusively seen in gastric lymphomas other than MALT lymphoma, whereas the nuclei of MALT lymphoma cells were regular and small to moderate in size. Inter-glandular infiltration by lymphomatous cell elements was frequently observed in MALT lymphoma and DLBCL, but it was uncommon in peripheral gastric T-cell malignancies. Endocytoscopy could identify the disease-specific histology, the lymphoepithelial origin, as inter-glandular infiltration of cellular components in MALT lymphoma and the possibly related DLBCL cases. Complete regression (CR) was observed in 2 of the 7 MALT lymphoma patients. In the 2 patients with CR who underwent repeat endocytoscopy, the ultra-high magnification abnormalities returned to normal, while they were unchanged in those without tumor regression. CONCLUSIONS: On endocytoscopy, intra-glandular aggregation of cellular components was invariably identified in lymphomas of the stomach. Nuclear regularity in size and configuration may indicate the cytological grade, differentiating the indolent low-grade from aggressive lymphoproliferative diseases. The inter-glandular infiltration seen on endocytoscopy can indicate the lymphoepithelial lesions seen in MALT lymphoma and related DLBCL. Endocytoscopy would be applicable for virtual histopathological diagnosis of different lymphoproliferative disorders and their clinical assessment during ongoing endoscopy.

Characteristics of gastrointestinal symptoms and function following endoscopic submucosal dissection and treatment of the gastrointestinal symptoms using rikkunshito.

The aim of the present study was to investigate the gastrointestinal (GI) symptoms and gastric emptying following endoscopic submucosal dissection (ESD), as well as to evaluate a novel treatment strategy using rikkunshito, a traditional Japanese herbal medicine. GI symptoms and gastric emptying were evaluated 6-8 days after ESD as part of the Step I study. In the Step 1 study, the Gastrointestinal Symptom Rating Scale (GSRS) scores of the two groups after 4 and 8 weeks of treatment with either a proton pump inhibitor (PPI; PPI monotreatment group, n=5) or a PPI plus rikkunshito (PPI + rikkunshito group, n=8) were compared against baseline values. Abdominal pain and constipation occurred in the majority of patients after ESD. The mean T-max 6-8 days after gastric emptying was 75.4±13.6 min, which was significantly longer compared with that reported in healthy subjects (43.9±10.3 min). In the Step 2 study, the total GSRS score was significantly improved only in the PPI + rikkunshito group after 8 weeks of treatment. In conclusion, ESD affects gastric emptying and is associated with an increased incidence of upper GI symptoms such as abdominal pain and indigestion. Rikkunshito may be useful as a novel supporting therapeutic drug for the treatment of GI symptoms in patients who have undergone ESD.

Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management.

AIM: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps. METHODS: Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations. RESULTS: NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8. CONCLUSION: We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.

Analysis of the tumor color patterns of early esophageal cancer using an autofluorescence imaging video endoscopy.

BACKGROUND: Using a novel autofluorescence imaging video (AFI) endoscopy system, early esophageal cancers (EECs) appeared purple or brown in green background. However, the factors associated with these color patterns remain unraveled. The aims of this study were to classify the AFI color patterns of EECs and to investigate the correlation between the color patterns and clinicopathologic features of EECs. PATIENTS: From April 2008 to April 2010, 32 patients with 42 EECs who underwent endoscopic submucosal dissection at the Nagasaki University Hospital were enrolled in this study. They consisted of 25 men and 7 women, with the mean age of 64.7 years old (range, 52 to 82 y). METHODS: With AFI endoscopy, we classified 2 color patters in EECs into purple in green patterns (P in G) and brown with purple dots in green patterns (BP in G), and we assessed the association with clinicopathologic factors. These factors included tumor morphology, location, size, histologic depth of invasion, and histologic lymphatic and vessel permeations. RESULTS: The color patterns of EECs were classified into 2 groups: purple in green patterns (P in G) (14%) and brown with purple dots in green patterns (BP in G) (86%). Univariate analysis revealed that only macroscopic type was associated with the EECs color pattern. CONCLUSIONS: This study revealed the association of AFI color patterns with clinicopathologic factors of EECs. Recognition of the color patterns in AFI images might be useful for the detections and diagnosis of EECs as one of the new endoscopic modalities.

Management of esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms en bloc, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD. METHODS: Seven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia. RESULTS: En bloc ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions. CONCLUSIONS: Use of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.

Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial esophageal squamous cell carcinoma. However, postprocedure stricture is common after ESD for extensive tumors, and multiple endoscopic balloon dilation (EBD) is required for recalcitrant cases. OBJECTIVE: To evaluate the effectiveness of oral prednisolone in controlling postprocedure esophageal stricture. DESIGN: Retrospective study. SETTING: Endoscopy department at a university hospital. PATIENTS: Patients who underwent complete circular or semicircular ESD for esophageal squamous cell carcinoma involving more than three fourths of the lumen were treated with either pre-emptive EBD or oral prednisolone. INTERVENTION: Preemptive EBD was started on the third day post-ESD and continued twice weekly for 8 weeks. Oral prednisolone was started at 30 mg/day on the third day post-ESD , tapered gradually, and then discontinued 8 weeks later. An additional EBD was performed on demand in both groups whenever dysphagia appeared. MAIN OUTCOME MEASUREMENT: The incidence of esophageal stricture and number of EBD sessions required to relieve dysphagia. RESULTS: Stricture at 3 months after ESD was found in 7 of 22 patients in the preemptive EBD group but only 1 of 19 in the oral prednisolone group (P < .05). The average number of EBD sessions required was 15.6 in the preemptive EBD group and 1.7 in the oral prednisolone group (P < .0001). After complete circular ESD, 32.7 EBD sessions were needed on average in the preemptive EBD group, whereas fewer were needed in the oral prednisolone group (P < .05). LIMITATIONS: Nonrandomized study. CONCLUSIONS: Post-ESD esophageal strictures were persistent even if treated preemptively with multiple EBD sessions, but oral prednisolone may offer a useful preventive option.

Magnifying chromoendoscopic findings of early gastric cancer and gastric adenoma.

PURPOSE: In the field of colorectal cancer and adenoma, Kudo's classification of pit pattern with magnifying chromocolonoscopy using crystal violet (CV) staining is now accepted. Magnifying endoscopy using narrow band imaging has been used for the diagnosis of gastric carcinoma; the characteristic findings of microvascular patterns have been demonstrated. However, there was limited information on magnified endoscopic findings with CV staining for gastric neoplasms in terms of their pit patterns. METHODS: Magnifying chromoendoscopy with CV was performed in 175 patients with early gastric cancer and 18 with gastric adenoma, prior to treatment. Surface patterns of gastric tumors were classified into five types: (1) long tubular pit pattern, (2) irregular size pit pattern, (3) small round pit pattern, (4) destroyed pit pattern, and (5) non-structural pattern. RESULTS: Long tubular pit pattern was most common in gastric adenoma. Well differentiated adenocarcinoma and papillary adenocarcinoma tended to show different size of pit pattern or destroyed pit pattern. Small round pit pattern was most commonly seen in moderately differentiated adenocarcinoma. Non-structural pattern was most frequently observed in poorly differentiated adenocarcinoma and signet ring cell carcinoma (P < 0.0001). CONCLUSION: For gastric neoplasms, magnifying endoscopy may help predict histopathological type.

Effect of oral prednisolone on esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: a case report.

A 74-year-old man with nausea underwent upper gastrointestinal endoscopy, and a 0-IIb type tumor was found in the middle thoracic esophagus. Histological examination with endoscopic biopsies revealed squamous cell carcinoma (SCC), and chromoendoscopy with iodine staining revealed that the superficial SCC involved nearly the entire circumference of the esophageal lumen. There were neither nodal nor distant metastases. Complete circular endoscopic submucosal dissection (ESD) was successfully achieved with tumor-free margins in an en bloc fashion. The histopathological examination confirmed a diagnosis of intramucosal invasive carcinoma limited to the lamina propria mucosae without angiolymphatic invasion. Oral prednisolone was started with 0.5 mg/kg daily on the 3rd post-ESD day, tapered gradually, and then discontinued 8 weeks later without adverse effects. There were no complaints of dysphagia following ESD. On follow-up endoscopy with iodine staining, which was scheduled at 1, 3 and 6 months after ESD, there was no postprocedural esophageal stricture, and neither recurrent nor metachronous lesions were found. Thus, the patient required no sessions of endoscopic balloon dilatation. At the last outpatient clinic visit 7 months after ESD, he remained well without dysphagia. Oral prednisolone administration may offer an effective therapeutic strategy to prevent the post-ESD esophageal stricture after complete circular ESD.

Proximal extension of backwash ileitis in ulcerative-colitis - associated colon cancer.

BACKGROUND: Extension of the inflammatory process into the terminal ileum in ulcerative colitis is termed backwash ileitis. Ulcerative colitis patients with pancolitis and backwash ileitis may be at increased risk of colorectal carcinoma. A case of ulcerative colitis-associated cancer with backwash ileitis, which extended proximally over time, is described. CASE REPORT: A 67-year-old man was diagnosed with pancolitis; despite prednisolone and mesalazine treatment, he showed no improvement. Although initial endoscopic examination showed no abnormalities in the terminal ileum, a repeat colonoscopy 4 months later revealed erythema, absence of the vascular pattern, mucosal friability, and erosions within 30 cm of the terminal ileum in a continuous fashion from the cecum, and a flat, elevated lesion was found in the transverse colon. On histopathologic examination, the patient had nonspecific, active, chronic inflammation of the ileal mucosa, consistent with backwash ileitis, and colonic adenocarcinoma. Despite additional treatment with leukocytapheresis, the backwash ileitis progressed, with increased severity of mucosal inflammation and extensive erosions, 20 cm proximal to the primarily affected site of the ileum on repeat colonoscopy 2 months later. The patient underwent a proctocolectomy and excision of the terminal ileum with an ileostomy. CONCLUSIONS: Histopathology of the surgical specimen revealed marked backwash ileitis and submucosal, well-differentiated adenocarcinoma. The patient has remained well for 5 years after surgery.

Magnifying endoscopic observation with narrow band imaging for specialized intestinal metaplasia in barrett's esophagus with special reference to light blue crests.

AIM: Barrett's esophagus (BE) with specialized intestinal metaplasia (SIM) is at high risk of esophageal adenocarcinoma. Magnified endoscopy with narrow band imaging (ME-NBI) can be useful for detecting this condition. In addition to pit patterns, light blue crests (LBC), blue-whitish patchy areas on the metaplastic epithelia of the stomach, can predict SIM in BE under ME-NBI observation. METHODS: A total of 54 patients with BE underwent ME-NBI to identify IM pits (tubular and villous pits) and LBC. Biopsy samples were taken for histological evaluation of IM, immunohistochemical staining for CD10, MUC2 and MUC5AC antigen, transmission electron microscopy and real-time polymerase chain reaction (RT-PCR) analysis of CD10 mRNA expression. RESULTS: IM pit pattern with ME-NBI for the diagnosis of IM yielded acceptable sensitivity, specificity and accuracy at 92%, 77% and 83%, respectively. However, the sensitivity, specificity and accuracy of LBC with ME-NBI for IM were comparably high at 79%, 97% and 89%, respectively. Upon immunohistochemistry, all 19 metaplastic epithelia of LBC-positive BE showed immunoreactivity against anti-MUC2 antibody, whereas CD10 antigen was identified in 11 of the 19 LBC-positive BE. Brush borders were seen on IM epithelia using electron microscopy. On real-time PCR analysis, CD10 mRNA levels in the LBC-positive BE were higher compared to those in the LBC-negative BE. CONCLUSION: The appearance of LBC can be an accurate sign to predict SIM in BE and may be associated with high CD10 expression, possibly along with brush borders.

[A case of sacroiliitis complicated with ulcerative colitis which was treated with leukocytapheresis].

A 51-year-old woman was admitted to our hospital because of fever and pain in the right buttock. She had ulcerative colitis. She was given a diagnosis of sacroiliitis complicated with ulcerative colitis, based on a physical examination and magnetic resonance imaging (MRI) . Her sacroiliitis was successfully treated by leukocytapheresis (LCAP) . Sacroiliitis complicated with ulcerative colitis is rare in Japan, and its treatment and pathogenesis remain unclear. We report an unusual case of sacroiliitis complicated with ulcerative colitis, which was successfully treated by LCAP.

Endoscopic submucosal dissection for laterally spreading tumours of the colorectum in 200 consecutive cases.

BACKGROUND: Colorectal laterally spreading tumours (LSTs) are classified into granular (LST-G) and non-granular (LST-NG) type; each type was sub-grouped into LST-G-H (homogenous) and LST-G-M (nodular mixed) type or LST-NG-F (flat elevated) and LST-NG-FD (pseudodepressed) type, respectively. We assessed the clinicopathological factors associated with clinical outcomes of endoscopic submucosal dissection (ESD) for colorectal LSTs, and conducted follow-up after ESD. METHODS: ESD was performed in 196 patients with 204 LSTs that fulfilled the inclusion criteria for colorectal neoplasms. Clinical outcomes including resectability and curability of ESD and perforation were investigated, and factors related to the outcomes were analysed using logistic regression. One hundred thirty-eight patients received endoscopic follow-up for more than 12 months and metastatic surveys in 79 cases of cancerous LSTs. RESULTS: The incidence of submucosal cancer was lower in LST-G type. There were no significant differences in outcomes regarding LST macroscopic types. Overall en bloc, complete and curative resection, and perforation rates were 86.8%, 77.5%, 82.8% and 9.8%, respectively. Logistic regression analysis showed higher risk of non-curative resection in LST-G-M than in LST-G-H type. No other factors were associated with outcomes. During median follow-up of 35.5 months, no locally recurrent or metastatic tumours were observed, and overall survival was still 100%. CONCLUSIONS: ESD provides acceptable resectability for colorectal LSTs by facilitating en bloc resection, irrespective of macroscopic types. The relatively long-term outcomes may be excellent, but further evaluation is needed for appropriate treatment strategy for each type of LST.

Peyer's Patches in the Terminal Ileum in Ulcerative Colitis: Magnifying Endoscopic Findings.

Peyer's patches (PPs), a major component of the gut-associated lymphoid tissue, serve as important antigen entry sites in mucosal immunity. PPs may play a role in the extension of ulcerative colitis (UC) into the terminal ileum. We sought to clarify the magnified endoscopic findings of the PPs in the terminal ileum of UC patients. Eighteen UC patients underwent magnifying chromoendoscopy before initial treatment to evaluate the follicle-associated epithelium (FAE) on the PPs domes and the surrounding villi. In 8 UC patients, as in healthy controls, the PPs' domes were slightly elevated, covered with the regular FAE lining, and surrounded by dense and bulky villi; however, in 10 UC patients, the PPs' domes were irregular, and the surrounding villi were sparse and atrophic. These abnormal findings within the PPs were associated with minimal mucosal lesions but not with backwash ileitis; both electron microscopy and magnifying endoscopy confirmed that these lesions were reversible following remission with prednisolone-mesalazine therapy. Similar to Crohn's disease patients, UC patients commonly had abnormalities in the FAE on PPs' domes and the surrounding villi on magnifying endoscopy.