Intralesional steroid infusion using a spray tube to prevent stenosis after endoscopic submucosal dissection of esophageal cancer.

BACKGROUND/AIMS: Intralesional steroid injections have been administered as prophylaxis for stenosis after esophageal endoscopic submucosal dissection. However, this method carries a risk of potential complications such as perforation because a fine needle is used to directly puncture the postoperative ulcer. We devised a new method of steroid intralesional infusion using a spray tube and evaluated its efficacy and safety. METHODS: Intralesional steroid infusion using a spray tube was performed on 27 patients who underwent endoscopic submucosal dissection for superficial esophageal cancer with three-quarters or more of the lumen circumference resected. The presence or absence of stenosis, complications, and the number of endoscopic balloon dilations (EBDs) performed were evaluated after treatment. RESULTS: Although stenosis was not observed in 22 of the 27 patients, five patients had stenosis and dysphagia requiring EBD. The stenosis in these five patients was relieved after four EBDs. No complications related to intralesional steroid infusion using the spray tube were observed. CONCLUSION: Intralesional steroid infusion using a spray tube is a simple and safe technique that is adequately effective in preventing stenosis Clinical trial number (UMIN000037567).

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer.

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.

Epstein-Barr virus-associated gastric carcinomas developed after successful eradication of Helicobacter pylori.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) can develop in gastric mucosa affected by Helicobacter pylori (H. pylori)-induced atrophic gastritis. However, it is unclear whether EBVaGC can develop in gastric mucosa after successful eradication of H. pylori. We report 3 cases of EBVaGC discovered more than 5 years after successful eradication of H. pylori. All 3 cases are men with a history of smoking. The periods from successful eradication to development of EBVaGC were 18, 8, and 9 years, respectively. Their tumors were mainly depressed lesions located in the gastric corpus. Two patients had intramucosal cancer and the other had advanced gastric cancer. Mucosal atrophy was present in the background gastric mucosa of all of three, and the anti-H. pylori antibody titer in each patient had fallen to < 3 U/mL. These cases indicate that EBVaGC can occur after successful eradication of H. pylori.

Invasive inflammatory fibroid polyp of the stomach: a case report and literature review.

BACKGROUND: Inflammatory fibroid polyps (IFPs) are rare mesenchymal lesions that affect the gastrointestinal tract. IFPs are generally considered benign, noninvasive lesions; however, we report a case of an invasive gastric IFP. To the best of our knowledge, this is only the second case report of an invasive gastric IFP. CASE PRESENTATION: A 62-year-old woman presented with complaints of epigastric pain and vomiting. Computed tomography showed a 27-mm, hyper-enhancing tumor in the prepyloric antrum. Upper endoscopy also showed a submucosal tumor causing subtotal obstruction of the gastric outlet. Because a gastrointestinal stromal tumor was suspected, distal gastrectomy was performed. Histopathological examination revealed spindle cell proliferation in the submucosal layer. The spindle cells had invaded the muscularis propria layer and extended to the subserosal layer. The tumor was finally diagnosed as an IFP based on immunohistochemical findings. No mutations were identified in the platelet-derived growth factor receptor alpha (PDGFRA) gene via molecular genetic analysis. DISCUSSION AND CONCLUSIONS: After the discovery that IFPs often harbor PDGFRA mutations, these growths have been considered neoplastic lesions rather than reactive lesions. Based on the present case, IFPs might be considered not only neoplastic but also potentially invasive lesions.

Treatment Using the SpyGlass Digital System in a Patient with Hepatolithiasis after a Whipple Procedure.

An 89-year-old man was referred to our hospital for treatment of hepatolithiasis causing recurrent cholangitis. He had undergone a prior Whipple procedure. Computed tomography demonstrated left-sided hepatolithiasis. First, we conducted peroral direct cholangioscopy (PDCS) using an ultraslim endoscope. Although PDCS was successfully conducted, it was unsuccessful in removing all the stones. The stones located in the B2 segment were difficult to remove because the endoscope could not be inserted deeply into this segment due to the small size of the intrahepatic bile duct. Next, we substituted the endoscope with an upper gastrointestinal endoscope. After positioning the endoscope, the SpyGlass digital system (SPY-DS) was successfully inserted deep into the B2 segment. Upon visualizing the residual stones, we conducted SPY-DS-guided electrohydraulic lithotripsy. The stones were disintegrated and completely removed. In cases of PDCS failure, a treatment strategy using the SPY-DS can be considered for patients with hepatolithiasis after a Whipple procedure.

Image quality of a novel light-emitting diode (LED)-illuminated colonoscope.

BACKGROUND AND STUDY AIMS: Light-emitting diodes (LEDs) are used widely for their high luminous efficiency and durability. We developed a novel prototype high definition endoscope with white LEDs and evaluated the image quality it produced against a commercial endoscope with conventional light source. PATIENTS AND METHODS: The specifications of both colonoscopes were identical, except for the LED light source at the tip of the prototype. We examined 20 patients with rectal or sigmoid colon lesions and the image quality was evaluated in 40 images (one image from the LED colonoscope and one from the conventional colonoscope for each lesion) by three endoscopists. We additionally evaluated the 17 videos recorded with the LED colonoscope that were available. Image quality, mucosal and vascular color, and luminous distribution and intensity were scored on a 5-point scale. RESULTS: The mean score for vascular color given by one evaluator was significantly higher using the LED colonoscope than using the conventional colonoscope. The mean scores for mucosal color and luminous intensity from another evaluator were significantly lower with the LED colonoscope than with the conventional colonoscope. There were no significant differences in the luminous distribution scores for any of the evaluators. The image quality of the videos was evaluated as being similar with both colonoscopes. CONCLUSIONS: Image quality from the LED and conventional colonoscopes were similar, although the luminous intensity of the LEDs is inferior to that of the conventional light source at the present time.

Preliminary study of photodynamic diagnosis using 5-aminolevulinic acid in gastric and colorectal tumors.

AIM: To investigate the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) to detect gastric/colorectal tumors. METHODS: This prospective single-center study investigated inter-subject variability in patients with early-stage gastric/colorectal tumor indicated for endoscopic resection. Subjects were patients with gastric or colorectal tumors who had undergone endoscopic resection between November 2012 and November 2013. Selection criteria included age 20-80 years, either sex, and provision of informed consent. Patients were orally administered 20 mg/kg of 5-ALA enteric-coated capsules (SBI ALApromo Co., Tokyo, Japan). Administration of 5-ALA was followed by endoscopic resection of gastric or colorectal tumors, and the resected specimens were examined using a video autofluorescence processor and a fluorescence endoscope (SAFE-3000 and EB-1970AK, respectively; Pentax, Tokyo, Japan). The primary endpoint was the presence of fluorescence in tumors. Endoscopic, macroscopic, and histopathologic findings of tumors were assessed. We also evaluated adverse events of the present procedure as a secondary endpoint and examined each patient for the presence of known adverse effects of 5-ALA, namely, hematocytopenia, liver dysfunction, hypotension, nausea, and photosensitivity. RESULTS: We enrolled 10 patients (7 men, 3 women) (n = 13 lesions: 10 gastric/3 colorectal tumors). Fluorescence was detected in 7/13 (53.8%) lesions. No significant differences in sex (male: 55.6% vs female: 50.5%, P = 1.00), age (67.1 ± 1.9 years vs 65.0 ± 2.0 years, P = 0.45), tumor color (reddish: 60.0% vs discolored: 33.3%, P = 0.56), tumor diameter (15.0 ± 2.1 mm vs 14.2 ± 2.3 mm, P = 0.80), macroscopic type (protruded: 70.0% vs depressed 0%, P = 0.07), histologic type (differentiated type: 58.3% vs 0%, P = 0.46), invasion depth (mucosal layer: 55.6% vs submucosal layer: 33.3%, P = 1.00), lymphatic invasion (present: 33.3% vs absent: 50.0%, P = 1.00), venous invasion (present: 0% vs absent: 54.5%, P = 1.00) or procedure time of endoscopic resection (36.3 ± 8.3 min vs 36.7 ± 9.0 min, P = 0.98) were observed between the patients with and without fluorescence. Fluorescence detection rate tended to be high for elevated lesions. Liver dysfunction developed in 4/10 (40.0%) patients. The extent of the liver dysfunction was a slight increase in transaminases and total bilirubin levels, which spontaneously improved in the patients. None of the patients developed photosensitivity. CONCLUSION: Results of this preliminary study suggest the utility of PDD using 5-ALA for screening of gastric and colorectal cancers.

Efficacy of i-Scan Imaging for the Detection and Diagnosis of Early Gastric Carcinomas.

We determined comparative efficacy of i-Scan for detection and diagnosis of gastric cancer. Ten patients diagnosed with early gastric cancer based on histopathological findings were analyzed. White light and i-Scan moving images recorded from these patients in twin mode were separated into white light and i-Scan. Twelve endoscopists (three different skill levels) blinded to patient information evaluated the images. Correlation between demarcation accuracy and lesion brightness on still images was investigated. No significant differences were found in diagnostic accuracy between white light and i-Scan moving images for tumor detection rate (91.7% versus 90.8%, P = 0.777). Diagnostic accuracy of tumor size was comparable between novice and experienced endoscopists for i-Scan moving images (65.7% versus 71.1%, P = 0.528), whereas it was significantly lower for white light moving images (41.2% versus 79.5%, P = 0.019). Tumor demarcation accuracy was significantly better with white light than i-Scan still images (71.0% versus 65.8%, P = 0.033). Correlations between demarcation accuracy and brightness reached highs of 0.75 for white light and 0.89 for i-Scan imaging. Efficacy of i-Scan over that of white light imaging for detecting and diagnosing gastric cancer was not shown; however, the diagnostic capability of i-Scan can be improved if imaging conditions are optimized.

Efficacy of endoscopic submucosal dissection for cancer of the operated stomach.

PURPOSE: Cancer can develop in the operated stomach after partial gastrectomy and in the reconstructed gastric tube after surgery for esophageal cancer. It is considered that endoscopic therapy is more safe and suitable for the early gastric cancer developed in such stomach than operation. We investigated the efficacy of endoscopic submucosal dissection (ESD) for cancer of the operated stomach. METHODS: Subjects were 669 gastric cancer patients who underwent ESD: 22 patients (23 lesions) had surgically altered gastric anatomy, whereas 647 patients (727 lesions) had normal gastric anatomy. In the altered gastric anatomy group, 13 patients, 6 patients, and 3 patients had previously undergone distal gastrectomy, gastric tube reconstruction, and proximal gastrectomy, respectively. Rates of complete en bloc resection and curative resection were compared between the two groups. Influence of an anastomotic site and/or a suture line on ESD outcomes was examined in the altered gastric anatomy group. RESULTS: The rate of complete en bloc resection by ESD was 82.6% (19/23 lesions) in the altered gastric anatomy group and 92.3% (671/727 lesions) in the normal gastric anatomy group. The rate of curative resection and incident rates of complications were not significantly different between the groups. In the altered gastric anatomy group, the rate of complete en bloc resection was significantly lower when a lesion had spread across an anastomotic site and/or a suture line (P = 0.0372). Furthermore, duration of ESD was significantly longer (P = 0.0276), and resection efficiency was significantly lower (13 mm(2)/min, P = 0.0283), when treating lesions with an anastomotic site and/or a suture line than when treating isolated lesions. CONCLUSIONS: Outcome of ESD for cancer of the operated stomach compares with that in normal stomach anatomy. Anastomotic site/suture line within a lesion influenced the ESD procedure.

Endoscopic Resection is Infeasible for Early Gastric Cancers with Undifferentiated Components.

BACKGROUND/AIMS: Aim of this study is to find subgroup of early gastric cancer with lymph node metastasis for which successive further surgical operation is needed after endoscopic resection. METHODOLOGY: A total of 559 lesions of early gastric cancer, which had undergone curative gastrectomy, were enrolled in this study. We retrospectively investigated 10 clinicopathological factors predictive of lymph node metastasis by univariate and multivariate analysis. We showed the frequency of lymph node metastasis of subgroups in combination of independent factors selected by multivariate analysis. RESULTS: Lymph node metastases were detected in 57 lesions (10.2%). Univariate analysis revealed that lesion size > 30 mm, undifferentiated components, sm massive invasion, lymphatic invasion and venous invasion were factors significantly correlated with lymph node metastasis. By multivariate analysis, risk factors for lymph node metastasis were lesion size > 30 mm, undifferentiated components, sm massive invasion, and lymphatic invasion, with odds ratios of 2.17, 2.30, 5.88 and 8.24, respectively. In lesions with undifferentiated components, LNM were found in all subgroups. CONCLUSIONS: When we treat early gastric cancers contained undifferentiated components, even if they are predominantly differentiated-type intramucosal lesions, an additional surgical procedure should be considered or careful follow-up is required.

New method for detection of gastric cancer by hyperspectral imaging: a pilot study.

We developed a new, easy, and objective method to detect gastric cancer using hyperspectral imaging (HSI) technology combining spectroscopy and imaging A total of 16 gastroduodenal tumors removed by endoscopic resection or surgery from 14 patients at Yamaguchi University Hospital, Japan, were recorded using a hyperspectral camera (HSC) equipped with HSI technology Corrected spectral reflectance was obtained from 10 samples of normal mucosa and 10 samples of tumors for each case The 16 cases were divided into eight training cases (160 training samples) and eight test cases (160 test samples) We established a diagnostic algorithm with training samples and evaluated it with test samples Diagnostic capability of the algorithm for each tumor was validated, and enhancement of tumors by image processing using the HSC was evaluated The diagnostic algorithm used the 726-nm wavelength, with a cutoff point established from training samples The sensitivity, specificity, and accuracy rates of the algorithm's diagnostic capability in the test samples were 78.8% (63/80), 92.5% (74/80), and 85.6% (137/160), respectively Tumors in HSC images of 13 (81.3%) cases were well enhanced by image processing Differences in spectral reflectance between tumors and normal mucosa suggested that tumors can be clearly distinguished from background mucosa with HSI technology.

Outcomes of endoscopic submucosal dissection for early gastric cancer and factors associated with incomplete resection.

BACKGROUND/AIMS: The introduction of endoscopic submucosal dissection for the treatment of early gastric cancer has enabled en bloc resection of lesions that cannot be treated with conventional endoscopic mucosal resection. Despite expansion of indications for endoscopic treatment, a considerable number of patients still require additional treatment. The objective of this study was to summarize the outcomes of endoscopic submucosal dissection performed on patients with early gastric cancer and to identify factors associated with incomplete resection and non-curative resection. METHODOLOGY: This study examined 605 lesions in 533 patients with early gastric cancer who underwent endoscopic submucosal dissection. Evaluation of treatment outcome was based on the rates of complete resection and curative resection. Factors associated with incomplete resection and non-curative resection were retrospectively identified. RESULTS: Of the 605 lesions, 562 (92.9%) and 510 (84.3%) were diagnosed as complete resection and curative resection, respectively. Factors identified as associated with incomplete resection were tumor size ≥30 mm, location in the U region, undifferentiated carcinoma, sm2 invasion and ulceration. Factors identified as associated with non-curative resection were tumor size ≥30 mm, location in the U region and ulceration. CONCLUSIONS: Incomplete and non-curative resection appears to be associated with preoperative diagnosis of lesions and technical difficulty.

Role of DNA methylation in the development of Epstein-Barr virus-associated gastric carcinoma.

The frequencies of DNA methylation of certain tumor-related genes are higher in Epstein-Barr virus (EBV)-associated gastric carcinomas than in EBV-negative gastric carcinomas. EBV-associated gastric carcinomas have distinct clinicopathological features; however, there are no case-control studies comparing methylation frequency between EBV-associated gastric carcinomas and controls that have been adjusted according to the clinicopathological features of EBV-associated gastric carcinomas. This study evaluated 25 EBV-associated gastric carcinomas that were positive for EBV-encoded small RNA 1 (EBER-1) by in situ hybridization and 50 EBV-negative gastric carcinomas that were matched with the EBV-associated gastric carcinomas by age, sex, histology, depth of tumor invasion, and stage. Methylation status of 16 loci associated with tumor-related genes was analyzed by methylation-specific polymerase chain reaction (PCR) to identify genes in which DNA methylation specifically occurred in EBV-associated gastric carcinomas. Methylation frequencies of 12 of the 16 genes were higher in EBV-associated gastric carcinomas than in EBV-negative controls, and the frequency of methylation of 6 specific loci (MINT2, MINT31, p14, p16, p73, and RUNX3) was significantly higher in EBV-associated gastric carcinomas than in EBV-negative controls. There were no significant differences in the methylation frequencies of the other genes. The mean methylation index in EBV-associated gastric carcinomas was significantly higher than that in EBV-negative controls. DNA methylation of tumor suppressor genes that regulate the cell cycle and apoptosis specifically occurred in EBV-associated gastric carcinomas. Aberrant DNA methylation might lead to the development and progression of EBV-associated gastric carcinoma.

[A case of enteric muco-submucosal elongated polyp].

A woman in her seventies was admitted because of black stool. Esophagogastroduodenoscopy and colonoscopy revealed no bleeding lesions. Balloon endoscopy showed a long and slender polyp. The polyp was covered with normal mucosa and accompanied with ulcerations. The long polypoid lesion was found to be located in the duodenojejunal flexure by a small bowel series. We performed endoscopic polypectomy. The polyp was composed of edematous mucosa and submucosa with dilated blood vessels and lymphangiectasia. The histologic findings of resected specimen were compatible with colonic muco-submucosal elongated polyp. The polyp was considered to be classified as enteric muco-submucosal elongated polyp.

Risk factors for delayed bleeding from endoscopic submucosal dissection of gastric neoplasms.

OBJECTIVE: Delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) of gastric neoplasms. We aimed to clarify risk factors for delayed bleeding from ESD. MATERIAL AND METHODS: This study included 447 patients in whom 544 gastric neoplasms were resected by ESD between April 2006 and March 2011 in Yamaguchi University Hospital. We analyzed risk factors for delayed bleeding from ESD in relation to various clinical and pathological factors. RESULTS: En bloc resection rate was 95.4% (519/544), and curative resection rate was 87.8% (477/544). Delayed bleeding occurred in 7.0% (38/544) and perforation occurred in 1.8% (10/544) of patients. Univariate analysis revealed platelet count (Plt) <15 × 104/µl (p = 0.013), prothrombin time (PT) <70% (p = 0.044), resected size ≥ 50 mm (p = 0.038), and positive/indeterminate lateral margin (p = 0.012) to be risk factors for delayed bleeding. Multivariate analysis showed that Plt <15 × 104/µl (odds ratio [OR], 2.62; 95% confidence interval [CI]: 1.17-5.53, p = 0.020) and positive/indeterminate lateral margin (OR, 5.45; 95% CI: 1.39-17.95, p = 0.018) were independent risk factors for delayed bleeding. CONCLUSIONS: Low Plt, low PT, large resected size, and positive/indeterminate lateral margin were significant risk factors for delayed bleeding from ESD. Patients with these risk factors must be carefully observed for signs of delayed bleeding.

Usefulness of magnifying endoscopy with narrow-band imaging for determining gastric tumor margin.

BACKGROUND AND AIM: Magnifying endoscopy with narrow-band imaging (ME-NBI) enhances images of the irregular mucosal structures and microvessels of gastric carcinoma, and could be useful for determining the margin between cancerous and non-cancerous mucosa. We evaluated the usefulness of ME-NBI for determining the tumor margin compared with indigocarmine chromoendoscopy (ICC). METHODS: The subjects were 110 patients (with 118 lesions) who underwent endoscopic submucosal dissection for gastric tumors. They were randomized into ME-NBI and ICC groups. Marking was carried out by electrocautery with the tip of a high-frequency snare at the tumor margins determined by each observation. The distance from the marking dots to the tumor margin was measured histopathologically in the resected specimens. Marking was diagnosed as accurate if the distance was less than 1 mm. RESULTS: Of the 118 gastric lesions, 55 were allocated to the ME-NBI group, and 63 to the ICC group. Seventeen lesions in the ME-NBI group and 18 lesions in the ICC group were excluded because the distance from the marking dots to the tumor margin was immeasurable histopathologically. Thirty-eight lesions in the ME-NBI group and 45 lesions in the ICC group were evaluated. The rate of accurate marking of the ME-NBI group was significantly higher than that of the ICC group (97.4% vs 77.8%, respectively; P-value = 0.009). CONCLUSION: Magnifying endoscopy with narrow-band imaging can identify gastric tumor margins more clearly than ICC.

Fine-tuning the criteria for strip biopsy and endoscopic submucosal dissection improves the outcome of early gastric carcinoma treatment.

BACKGROUND AND AIM: Strip biopsy and endoscopic submucosal dissection (ESD) have been developed as a local treatment for early gastric cancer (EGC). However, the lesion criteria for the use of ESD, rather than strip biopsy, remain to be elucidated. METHODS: On the basis of reviews of literature and our observations concerning the outcome of strip biopsy, we set the criteria for selecting strip biopsy and ESD as follows. The indications for strip biopsy were lesions less than 10 mm in size and located in the anterior wall or greater curvature of the lower and middle stomach. ESD was indicated for all other lesions. The validity of the criteria was then analyzed prospectively in 156 patients. The rate of en bloc R0 resection and local recurrence were evaluated. RESULTS: Subsequently, 156 lesions were divided according to the criteria and were endoscopically resected by strip biopsy (n = 13) or ESD (n = 143). The en bloc R0 resection rates for the whole group and the strip biopsy and ESD groups was 93.5% (146/156), 92.3% (12/13), and 93.7% (134/143), respectively. None of the patients had suffered from local recurrence in either the strip biopsy or ESD groups. CONCLUSION: The validity of our criteria for selecting strip biopsy and ESD was verified. Our criteria exploit the advantages of both procedures and obtain better endoscopic therapy outcomes for EGC.

[A case of effective photodynamic therapy for local recurrence after definitive chemoradiotherapy for esophageal cancer].

We performed a photodynamic therapy for local recurrence after chemoradiotherapy for esophageal cancer. The patient was a 60s man, who presented dysphasia. Esophagoscopy, CT and FDG-PET revealed an advanced esophageal cancer with mediastinal lymph node metastasis. He rejected a surgical treatment and underwent chemoradiotherapy, then achieved CR once. Subsequent FDG-PET, however, showed slightly FDG uptake at primary focus of the esophagus. Endoscopic biopsy specimen from Lugol's unstained lesion of the esophagus revealed squamous cell carcinoma, and he was diagnosed as a recurrence of the esophageal cancer. He underwent chemotherapy again, but the recurrent lesion enlarged. Because the control of the metastatic lesion was excellent and the recurrent lesion was considered as a superficial cancer, he was performed photodynamic therapy. Two months after photodynamic therapy, the esophagoscopy and FDG-PET showed no findings of the recurrence of the esophageal cancer. It was suggested that photodynamic therapy for local recurrence after definitive chemotherapy for esophageal cancer was effective and relatively safe.