Clinical Factors of Delayed Perforation after Endoscopic Submucosal Dissection for Gastric Neoplasms.

BACKGROUND: Delayed perforation is a rare but severe complication of endoscopic submucosal dissection (ESD) for early gastric neoplasm (EGN). The aim of this study was to clarify clinical factors related to delayed perforation after ESD. METHODS: A total of 1158 consecutive patients with 1199 EGNs underwent ESD at our hospital between January 2000 and December 2015. Univariate analysis was used to identify clinicopathological factors related to delayed perforation. Moreover, duration of cautery needed for hemostasis was measured by comparison between perforated and nonperforated points in patients with delayed perforation. RESULTS: Delayed perforation occurred in 5 of 1158 consecutive patients with 1199 EGNs who underwent ESD (0.42%). All cases were diagnosed within 24 h after ESD and recovered with conservative management. On univariate analysis, location in the upper stomach was the factor most significantly associated with delayed perforation (P < 0.01). Duration of cautery needed for hemostasis was significantly longer at perforated points (9 s) than at nonperforated points (3.5 s) in five patients. CONCLUSIONS: Location in the upper stomach was the risk factor most prominently associated with delayed perforation after ESD for EGNs. In addition, delayed perforation appears associated with excessive electrocautery for hemostasis.

Polypoid leiomyosarcoma of the esophagus treated by endoscopic submucosal dissection.

We report a rare case of polypoid leiomyosarcoma of the esophagus that was treated by endoscopic submucosal dissection (ESD). A 63-year-old man with complaints of progressive dysphagia was referred to Hyogo Cancer Center for treatment of esophageal tumor. Esophagoscopy revealed a polypoid tumor 25 mm in diameter on the left side of the upper esophagus. Despite several biopsy specimens, the diagnosis could not be confirmed. Computed tomography showed a protruded, homogeneously enhancing mass in the upper esophagus, but no lymph node enlargement or metastasis. After 1.5 months, the esophagogram showed a filling defect 47 mm in diameter in the upper esophagus. Given this rapid tumor growth, en bloc resection was done by ESD for therapeutic diagnosis. After this treatment, the tumor seemed to grow larger, showing a short stalk and occupying the esophageal lumen. Histopathologically, the tumor comprised pleomorphic spindle cells with mitosis. Tumor invasion involved the lumina propria mucosae and contact with the muscularis mucosae, but not involving the submucosa. Immunohistochemical examination showed positive staining for smooth muscle actin and HHF35, but negative for desmin, caldesmon, CD34, c-kit, DOG1, ALK, S-100 protein and cytokeratin. These histopathological findings were compatible with a diagnosis of esophageal leiomyosarcoma derived from the muscularis mucosae.

Constrictive pericarditis caused by a pericardial-occupying tumor due to esophageal cancer.

A 61-year-old female was admitted to our hospital for esophageal cancer treatment. Esophagectomy with 2-field lymphadenectomy was performed. Postoperative findings revealed the lesion was a poorly differentiated squamous cell carcinoma invading into the diaphragm and there were no carcinoma cells on the surgical margins. Eight months after surgery, a recurrence was suspected by the presence of tumors at the pericardia, right axillary lymph node and around the descending aorta. The patient was re-admitted for chemotherapy and administrated fluorouracil and cisplatin 4 days after admission. After 7 days, she complained of dysphagia. Esophagogastroduodenoscopy showed no abnormal lesion that could cause the symptom. Computed tomography revealed massive progression of the pericardial tumor, bilateral pleural effusion and congested liver. Echocardiography showed the diffuse pericardial tumor caused restriction of ventricular dilation and hemodynamics of constrictive pericarditis. The patient died 29 days after re-admission. Autopsy revealed squamous cell carcinoma involving the mediatinum and pericardium. The pericardium was completely full of cancer tissue but no fluid. We concluded that the direct cause of death was neoplastic constrictive pericarditis.

1,635 Endoscopic submucosal dissection cases in the esophagus, stomach, and colorectum: complication rates and long-term outcomes.

BACKGROUND: Endoscopic submucosal dissection (ESD) enables en bloc resection of early gastrointestinal neoplasms; however, most ESD articles report small series, with short-term outcomes performed by multiple operators on single organ. We assessed short- and long-term treatment outcomes following ESD for early neoplasms throughout the gastrointestinal tract. METHODS: We performed a longitudinal cohort study in single tertiary care referral center. A total of 1,635 early gastrointestinal neoplasms (stomach 1,136; esophagus 138; colorectum 361) were treated by ESD by single operator. Outcomes were complication rates, en bloc R0 resection rates, and long-term overall and disease-specific survival rates at 3 and 5 years for both guideline and expanded criteria for ESD. RESULTS: En bloc R0 resection rates were: stomach: 97.1 %; esophagus: 95.7 %; colorectum: 98.3 %. Postoperative bleeding and perforation rates respectively were: stomach: 3.6 and 1.8 %; esophagus: 0 and 0 %; colorectum: 1.7 and 1.9 %. Intra criteria resection rates were: stomach: 84.9 %; esophagus: 81.2 %; colorectum: 88.6 %. Three-year survival rates for lesions meeting Japanese ESD guideline/expanded criteria were for all organ-combined: 93.4/92.7 %. Five-year rates were: stomach: 88.1/84.6 %; esophagus: 81.6/57.3 %; colorectum: 94.3/100 %. Median follow-up period was 53.4 (range, 0.07-98.6) months. Follow-up rate was 94 % (1,020/1,085). There was no recurrence or disease-related death. CONCLUSIONS: In this large series by single operator, ESD was associated with high curative resection rates and low complication rates across the gastrointestinal tract. Disease-specific and overall long-term prognosis for patients with lesions within intra criteria after curative resection appeared to be excellent.

Endoscopic submucosal dissection for gastric neoplasm in patients with co-morbidities categorized according to the ASA Physical Status Classification.

BACKGROUND: Endoscopic submucosal dissection (ESD) has come to be widely performed for reduced invasiveness; however, its safety in patients with co-morbidities is not fully examined. We aimed to evaluate the safety and efficacy of gastric ESD with co-morbidities categorized according to ASA Physical Status Classification. METHODS: Two hundred and forty patients of ASA 1 (no co-morbidities), 268 of ASA 2 (mild), and 19 of ASA 3 (severe) were treated by ESD for gastric neoplasms. We retrospectively compared clinicopathological features and treatment results of these three groups. RESULTS: Cases (by percent) treated with anticoagulant/platelet agents were more common in the higher ASA grades (ASA 1, 5.8%; ASA 2, 29.1%; ASA 3, 31.6%; P < 0.0001). There were no significant differences in case numbers treated under guideline criteria, curative resection (ASA 1, 79.6%; ASA 2, 79.9%; ASA 3, 78.9%), or complications related to the ESD procedure (e.g., postoperative bleeding, perforation, thermal injury). By a patient risk prediction model on surgery, i.e., P-POSSUM, morbidity was halved, and no patients died compared to a predicted death rate of 0.5-2%; however, total and complications unrelated to ESD procedure (e.g., aspiration pneumonia, ischemic heat attack) were more common in higher ASA grades (ASA 1, ASA 2, ASA 3: 15.4, 23.9, 26.3%, respectively, P = 0.014; 0.4, 7.1, 0%, respectively, P = 0.00087). Deviation rates from clinical pathway were more frequent and hospital stay (days) longer in higher ASA grades (ASA 1, ASA 2, ASA 3: 11.3, 17.9, 26.3%, respectively, P = 0.014; 8, 8, 9%, respectively, P = 0.0053). CONCLUSIONS: ESD is an efficient treatment for gastric neoplasms with co-morbidities. However, additional caution is required because co-morbidity is a risk factor for both total complications and complications unrelated to the ESD procedure, and may cause deviations in the clinical course and prolonged hospital stay.

Surveillance after colorectal polypectomy; comparison between Japan and U.S.

BACKGROUND: Recently, early detection and early treatment of the colorectal cancer have been enabled by the improvement of endoscopic diagnosis and introduction of new techniques. In Japan, although Japan Polyp Study is running, there is no standard strategy concerning the post-polypectomy colonoscopic surveillance yet. Post-polypectomy colonoscopic surveillance is so far entrusted to each institute or each gastroenterologist at present. MATERIAL AND METHOD: To analyze the present states of the surveillance after polypectomy in Japan, we performed questionary survey and compared them with the results in U.S. and U.S. Multisociety Task Force on colorectal Cancer. A simple random sample of 132 doctors who engaged in a digestive organ disease in plural institutes was obtained. RESULT: Many doctors recommend surveillance every around 1 year regardless of the kind of the polyp. Doctors in Japan tend to recommend postpolypectomy colonoscopic surveillance more frequently than that recommended U.S. Multisociety Task Force on colorectal Cancer. Furthermore in all types of polyps except for 12 mm tubular adenoma with high grade dysplasia, the majority of doctors in Japan recommend post-polypectomy colonoscopic surveillance more frequently than American doctors. Significant difference was found in surveillance of hyperplastic polyp among doctors with 1 to 5 years experience and those with more than 6 years. CONCLUSION: It has been shown that surveillance intervals varies substantially in each doctor. The agreement of the surveillance program in Japan is necessary to standardize the strategy for the post-polypectomy surveillance of the colon.

Association between adherence to evidence-based guidelines for the prescription of non-steroidal anti-inflammatory drugs and the incidence of gastric mucosal lesions in Japanese patients.

OBJECTIVE: Recently, guidelines for the treatment and prevention of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) were established. This study investigated the association between the current adherence to the guidelines and the incidence of gastric mucosal lesions caused by NSAIDs. METHODS: This study included 254 NSAIDs users (128 regular and 126 on-demand users) who had undergone upper gastrointestinal endoscopy. The patients were characterized as high risk based on the following: age 65 years or older, history of peptic ulcers, concurrent use of corticosteroids or anticoagulants, and high-dose NSAIDs use. Adherence was defined as the prescription of NSAIDs with proton pump inhibitors, prostaglandin analogues, or high-dose histamine 2 receptor antagonists in high-risk NSAIDs user. The severity of gastric mucosal lesions was evaluated using the modified LANZA score (MLS). RESULTS: Seventy-nine (61.7%) of the regular NSAIDs users and 65 (51.6%) of the on-demand NSAIDs users met our definition of high-risk patients. Adherence in the regular NSAIDs users and on-demand NSAIDs users was 25 (31.7%) and 16 (24.6%), respectively. The incidence of gastric mucosal lesions (MLS ≧ 1) was significantly higher in the nonadherence group than in the adherence group for both regular NSAIDs users (59.3 vs. 28.0%, P = 0.01) and on-demand NSAIDs users (63.3 vs. 25.0%, P = 0.01). Gastric ulcers in the regular NSAIDs users were more frequently observed in the nonadherence group than in the adherence group (29.6 vs. 4.0%, P < 0.01). CONCLUSION: Nonadherence was associated with a high prevalence of NSAIDs-induced gastric mucosal lesions.

Prescreening of a high-risk group for gastric cancer by serologically determined Helicobacter pylori infection and atrophic gastritis.

BACKGROUND: Though gastric cancer screening by X-ray examination has been confirmed to be effective for reducing gastric cancer mortality, decreases in efficiency have been pointed out. Establishment of an effective screening system, focusing on high-risk status such as Helicobacter pylori infection and atrophic gastritis, is desirable. To date, combined use of serum anti-Helicobacter pylori antibodies and pepsinogen measurement has been assessed prospectively in participants in opportunistic and workplace health check-ups; however, there are no reports of population-based cohort study. AIMS: To clarify the population-based risk of Helicobacter pylori infection and atrophic gastritis for gastric cancer, a cohort study was conducted in rural towns in Kyoto Prefecture. METHODS: Subjects were 1,011 males and 1,848 females recruited in a health check-up in 1987. Their serum was examined for anti-Helicobacter pylori antibodies and pepsinogen I and II. Gastric cancer cases were assessed from the cancer registry of those towns. RESULTS: Up to the end of 1996, 33 males and 28 females developed gastric cancer. A sex- and age-adjusted hazard ratio was calculated by Cox's proportional model. Helicobacter pylori infection increased the risk of gastric cancer even when the subjects had no atrophy (hazard ratio =4.20; 95% confidence interval, 0.96-18.40). The risk increased further when they had both Helicobacter pylori infection and atrophy (hazard ratio =11.23; 95% confidence interval, 2.71-46.51). Subjects with atrophy but negative for anti-Helicobacter pylori antibodies had the highest risk (hazard ratio =14.81; 95% confidence interval, 2.47-88.80). CONCLUSIONS: A high-risk group for gastric cancer can be selected by serological prescreening.

Endoluminal MR imaging of porcine gastric structure in vivo.

BACKGROUND AND AIMS: Recently, several new endoscopic instruments have been developed. However, even with the full use of current modalities, the safety of endoscopic surgery is not guaranteed. Information regarding factors such as fibrosis and the blood vessels under the mucosa is very important for avoiding procedure-related complications. The aim of this study was to define the detailed anatomy of the gastric wall structure in vivo using original endoluminal radiofrequency coils for safer endoscopic therapy. METHODS: Swine were used as the subjects and controlled with general anesthesia. Anatomical images were obtained with T1-weighted fast spin echo (T1FSE) and T2-weighted fast spin echo (T2FSE). Dynamic magnetic resonance (MR) angiography was also obtained with three-dimensional T1-weighted fast spoiled gradient recalled acquisition in the steady state (3D-DMRA) following the injection of hyaluronic acid sodium into the submucosal layer. RESULTS: Porcine gastric wall structure was visualized, and four layers were discriminated in the T1FSE and T2FSE images. The vascular structure was clearly recognized in the submucosa on 3D-DMRA. CONCLUSION: Endoluminal MR imaging was able to visualize the porcine stomach with similar quality to endoscopic ultrasonography imaging. Additionally, it was possible to visualize the vascular structures in the submucosal layer. This is the first report to show that blood vessels under the gastric mucosa can be depicted in vivo.

Validation of the pepsinogen test method for gastric cancer screening using a follow-up study.

BACKGROUND: Serum pepsinogen (PG) measurement has been used for gastric cancer screening since the 1990s. However, there are no reports comparing the screening validity of the PG test method with that of conventional X-ray examination directly in the same population, using a follow-up study. METHODS: From April 2000 to March 2001, 12 120 residents of Osaka Prefecture, who underwent opportunistic screening at a medical checkup organization in Osaka city (hereafter, "the organization"), were enrolled. They received both a barium meal examination and PG test simultaneously. All the participants were followed up for a 1-year period after the screening. For the participants advised to undergo endoscopic examination, the results of those who were examined at the organization were tallied. The other participants were checked using the Osaka Cancer Registry (hereafter, "the registry"). RESULTS: Of the 12 120 participants, 493 (4.1%) were positive with the PG method and 728 (6.0%) were positive with the X-ray method. Fifty-four (0.4%) were positive for both methods. Thirteen gastric cancer cases were diagnosed by successive esophagogastroduodenoscopies at the organization. Six additional gastric cancer cases were identified by record linkage with the registry. The sensitivity, specificity, and positive predictive values of the PG method with a PGI cutoff level of

The new resources of treatment for early stage colorectal tumors: EMR with small incision and simplified endoscopic submucosal dissection.

INTRODUCTION: Early stage colorectal tumors can be removed by endoscopic mucosal resection (EMR) but larger tumors (> or =20 mm) may require piecemeal resection. The development of endoscopic submucosal dissection (ESD) has enabled en-bloc resection of lesions regardless of size and shape. However ESD of colorectal tumor is technically difficult. As the resources, we perform EMR with small incision (EMR with SI) for more reliable EMR, and also ESD with snaring (simplified ESD) for easier and safer ESD. AIM & METHODS: The aim of the study was to retrospectively compare the treatment results of the following 3 methods (EMR with SI/ simplified ESD/ ESD). We treated 24/44/468 colorectal tumors, and examined the tumor size, resected specimen size, procedure time, en-bloc resection rate, complication rate. RESULT: The median tumor size (mm) (EMR with SI/simplified EMR/ESD) was 20/17/30 (EMR with SI vs simplified ESD: P = n.s, simplified ESD vs ESD: P < 0.0001). The median resected specimen size (mm) was 22.5/26/41 (EMR with SI vs simplified ESD: P = 0.0018, simplified ESD vs ESD: P < 0.0001). The procedure time (min.) was 19/27/60 (EMR with SI vs simplified ESD: P = n.s, simplified ESD vs ESD: P < 0.0001) The en-bloc resection rate (%) was 83.3/90.9/98.9. The complication rate (post-operative bleeding rate/perforation rate) was 0/0, 2.3/4.5, 1.5/1.5 (simplified ESD vs ESD: P = n.s). CONCLUSION: Endoscopic mucosal resection with small incision (EMR with SI) and ESD with snaring (simplified ESD) are a good option to fill the differences between conventional EMR and ESD, and also considered to become nice steps to the introduction of ESD.

Role of Fc Receptors as a therapeutic target.

It has been forty years since the discovery of Fc Receptors and their function. Fc Receptors include the IgG receptors (FcgammaR), high-affinity IgE receptor (FcepsilonRI), IgA and IgA/IgM receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the FcgammaRs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Both positive and negative regulatory function has ascribed to Fc receptors and FcgammaRs in particular which serve to establish a threshold for immune cell activation. In other cases, Fc receptors such as FcRn possess a novel structure and function by playing a major role in the transport of IgG across polarized epithelial barriers at mucosal surfaces and in the regulation of IgG half-life. These diverse functions highlight the potential effectiveness of targeting Fc receptors for therapeutic purposes. This review summarizes new information available in the therapeutic applications of this biology.

Fcgamma receptor regulation of Citrobacter rodentium infection.

Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the colon utilizing attaching and effacing lesions to adhere specifically to the surfaces of intestinal epithelial cells and cause mucosal inflammation. CD4+ T cells, B cells, and immunoglobulin G (IgG), but not secretory IgA or IgM, play a critical role in eradicating this pathogen. Consistent with the importance of IgG in C. rodentium eradication, IgG transport by the neonatal Fc receptor for IgG within the intestinal epithelium also has a critical role in the regulation of C. rodentium infection. It remains to be determined, however, whether Fcgamma receptors (FcgammaRs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of FcgammaRs during C. rodentium infection. Fc receptor common gamma chain (FcRgamma)-deficient mice were more susceptible to C. rodentium-induced colitis. This occurred through decreased efficiency of FcR-mediated endocytosis and maturation of dendritic cells and consequently T-cell activation of antigen-specific T cells. Moreover, in the absence of FcgammaRs, phagocytosis by macrophages was significantly diminished. Therefore, activating FcgammaRs play an important role in defending against C. rodentium infection, indicating that the critical role played by IgG in this infection is not mediated by IgG alone but is dependent upon this class of receptors.

[Case of primary malignant fibrous histiocytoma of the diaphragm discovered by liver function disorder].

We present the case of a 67-year-old man with primary malignant fibrous histiocytoma (MFH) of the diaphragm. He was admitted to our hospital with anorexia and loss of body weight. High serum levels of AST, ALT, ALP and gamma-GTP were observed. Several imaging studies disclosed a large tumor on the right side of the diaphragm to the right lobe of the liver. The entire tumor was resected, and histopathological examination of the specimen revealed the characteristics of MFH. MFH originating from the diaphragm is very rare, and we present the case of this patient in addition to a discussion of previous literature.