Proton pump inhibitor after endoscopic resection for esophageal squamous cell cancer: multicenter prospective randomized controlled trial.

BACKGROUND: Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. METHODS: We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI therapy (the non-PPI group, n = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. RESULTS: No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. CONCLUSION: PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

Clinical outcomes of endoscopic submucosal dissection for early gastric cancer in remnant stomach or gastric tube.

BACKGROUND AND STUDY AIMS: Little information exists regarding the optimal treatment of early gastric cancer (EGC) in a remnant stomach or gastric tube. The aim of this study was to assess the feasibility and clinical outcomes of endoscopic submucosal dissection (ESD) for EGC in a remnant stomach and gastric tube. PATIENTS AND METHODS: Between September 2002 and December 2009, ESD was performed in 62 lesions in 59 patients with EGC in a remnant stomach (48 lesions) or gastric tube (14 lesions). Clinicopathological data were retrieved retrospectively to assess the en bloc resection rate, complications, and outcomes. Treatment results were assessed according to the indications for endoscopic resection, and were compared with those of ESD performed in a whole stomach during the same study period. RESULTS: The en bloc resection rates for lesions within the standard and expanded indication were 100 % and 93 %, respectively. Postoperative bleeding occurred in five patients (8 %). The perforation rate was significantly higher (18 %, 11 /62) than that of ESD in a whole stomach (5 %, 69 /1479). Among the perforation cases, eight lesions involved the anastomotic site or stump line, and ulcerative changes were observed in five lesions. The 3-year overall survival rate was 85 %, with eight deaths due to other causes and no deaths from gastric cancer. CONCLUSION: A high en bloc resection rate was achieved by ESD for EGC in a remnant stomach or gastric tube; however, this procedure is still technically demanding due to the high complication rate of perforation.

Risk factors for recurrence of artificial gastric ulcers after endoscopic submucosal dissection.

It has been reported previously that artificial gastric ulcers caused by endoscopic submucosal dissection (ESD) would heal within 8 weeks, irrespective of their size and location. The aim of this retrospective study was to describe long-term outcomes of gastric ESD ulcers. Check-up of ulcers was performed by periodic endoscopy. The rate of ESD ulcer recurrence and clinicopathological factors that may relate to recurrence were assessed. During the median observation period of 33 months, a benign ulcer recurrence occurred in 10 lesions in 10 patients (2.1%). Univariate analysis showed that Helicobacter pylori infection and presence of pathological ulcer findings within the ESD specimen were significantly related to the risk of ESD ulcer recurrence. Although the frequency is low, there is a possibility of ESD ulcer recurrence in patients with H. pylori infection and in patients who undergo ESD for a lesion with ulceration.

Feasibility of electrocautery snaring as the final step of endoscopic submucosal dissection for stomach epithelial neoplasms.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a novel endoluminal technique that permits the resection of gastric neoplasms. AIM: To analyse the feasibility of snaring as the final step of ESD. PATIENTS AND METHODS: One hundred and ninety-nine consecutive gastric neoplasms resected by four ESD experts from January 2004 to May 2007 were investigated. Forty-five (22.6%) were finally resected finally using a snare. Rates of en bloc resection, complete (R0 plus en bloc) resection, mean operation time, and complications were assessed between the snaring and the non-snaring groups. RESULTS: En bloc resection rate was significantly lower and delayed bleeding rate was significantly higher in the snaring group than in the non-snaring group (91.1% [41/45] vs. 100% [154/154], 11.1% [5/45] vs. 1.9% [3/154], respectively), although complete resection rate (86.7% [39/45] vs. 92.9% [143/154]) and mean operation time (70.2 min vs. 75.8 min) were not significantly different between the two groups. Six perforation cases (3 [6.7%] in the snaring group, 3 [1.9%] in the non-snaring group) were observed, but snaring did not lead to perforation in any case. When the subjects were divided into small (< or = 2 cm) and large (> 2 cm) tumours, en bloc resection rate in large tumours was still significantly different between the groups (76.9% [10/13] vs. 100% [67/67]), whereas in small tumours it was no longer significantly different (96.9% [31/32] vs. 100% [87/87]). CONCLUSIONS: Snaring may facilitate successful ESD for smaller tumours, but multiple-piece resection should be taken into account especially for larger tumours.

Efficacy and safety of endoscopic submucosal dissection for gastric cancer in patients with liver cirrhosis.

Endoscopic submucosal dissection (ESD) has become a widely accepted method for treating gastrointestinal cancer. The aim of this study was to evaluate the efficacy and safety of ESD for gastric cancer in patients with liver cirrhosis. A total of 18 gastric cancers were treated by ESD in 15 patients with cirrhosis. The rate of en bloc resection was 88.9% (16/18). En bloc resection with tumor-free lateral/basal margins (R0 resection) was 77.8% (14/18). Three patients had postoperative bleeding and underwent emergency gastroscopy for hemostasis. No recurrence was observed during the median follow-up of 21.4 months, excluding three patients in whom additional endoscopic resection or surgery was carried out. ESD can be safely performed for gastric cancer in patients with cirrhosis, resulting in a high en bloc resection rate.

Detailed comparison between endocytoscopy and horizontal histology of an esophageal intraepithelial squamous cell carcinoma.

Endocytoscopy allows the real-time microscopic observation of living cells. Unlike the cross-sectional images obtained by conventional histology, endocytoscopy provides cellular images in a plane parallel to the surface of the mucosa. However, there is little knowledge about the endocytoscopic diagnosis of carcinomas. Using a specimen obtained by the endoscopic submucosal dissection of an intraepithelial esophageal squamous cell carcinoma, a detailed comparison between endocytoscopic and horizontal histological images was made, revealing the similarity between the images. Sharp lateral borders between atypical and normal epithelium and differences in cellularity and the sizes and shapes of the nuclei were clearly identified by endocytoscopy. Further horizontal histological investigations of this case also showed the variety of endocytoscopic images in non-cancerous and cancerous epithelia.

Endoscopic submucosal dissection as a staging measure may not lead to worse prognosis in early gastric cancer patients with additional gastrectomy.

BACKGROUND: Endoscopic submucosal dissection is a novel endoluminal technique that enables resection of early stage gastrointestinal malignancies in an en bloc fashion. AIM: To assess whether preceding endoscopic submucosal dissection affected the prognoses of patients who underwent additional gastrectomy with lymph node dissection due to suspicion of nodal metastasis from endoscopic submucosal dissection specimens. PATIENTS AND METHODS: Thirty-one patients with early gastric cancer who underwent gastrectomy after endoscopic submucosal dissection were retrospectively investigated in terms of their survival and tumour recurrence. Additional gastrectomy was performed when histology of the endoscopic submucosal dissection specimens revealed that the tumours did not meet the criteria for node-negative cancers. RESULTS: Twenty-three (74%) and eight (26%) patients had undergone endoscopic submucosal dissection previously due to clinical diagnoses of node-negative cancers and possible node-positive cancers, respectively. Histology of the resected stomachs and lymph nodes revealed residual carcinoma of the stomach in two (6.5%) patients and nodal metastases in four (13%) patients. All patients remain alive without recurrence (median follow-up, 3.4 years; range, 0.6-5.2 years). CONCLUSIONS: Based on the histology of endoscopic submucosal dissection specimens, preceding endoscopic submucosal dissection itself had no negative influence on a patient's prognosis when additional gastrectomy was performed. It may be permissible to resect some early gastric cancers by endoscopic submucosal dissection as a first step to prevent unnecessary gastrectomy, if technically resectable.

Ex vivo pilot study using computed analysis of endo-cytoscopic images to differentiate normal and malignant squamous cell epithelia in the oesophagus.

BACKGROUND AND STUDY AIMS: An endo-cytoscopy system allows acquisition of optical biopsies that are quite similar to conventional histology. To simplify discrimination between normal and malignant tissue in the oesophagus using endo-cytoscopy system, we analysed the nuclear (dark staining) area in the obtained images with the goal of an accurate, automatic diagnosis. PATIENTS AND METHODS: Ex vivo endo-cytoscopic observation was performed using endoscopically or surgically resected oesophagus from 10 enrolled patients. Oesophageal tissues were stained using 1% methylene blue, and endo-cytoscopic images were obtained at normal and malignant areas (two areas of each) in each oesophagus. The centre of each image (4x10(-2) mm(2)) was processed by computer, and the area occupied by the total nuclei in each selected field and its ratio to the entire field were calculated. RESULTS: The mean area of the total nuclei was 0.10x10(-2)+/-0.03x10(-2) mm(2) (range 0.05x10(-2) to 0.18x10(-2) mm(2)) in the normal group and 0.40x10(-2)+/-0.06x10(-2) mm(2) (range 0.33x10(-2) to 0.55x10(-2) mm(2)) in the malignant group (P<0.001). The mean ratio of total nuclei to the entire selected field was 6.4+/-1.9% (range 3.1-11.3%) in the normal tissues and 25.3+/-3.8% (range 20.5-34.5%) in the malignant samples (P<0.001). CONCLUSIONS: Endo-cytoscopy system allowed automatic differentiation of normal and malignant tissues in the oesophagus, which could simplify endo-cytoscopic diagnosis. Further study will elucidate whether such analysis is applicable to inflammatory or pre-malignant epithelia in the oesophagus or other gastrointestinal organs.

Endoscopic submucosal dissection of stomach neoplasms after unsuccessful endoscopic resection.

BACKGROUND: Endoscopic submucosal dissection is a novel endoluminal endoscopic surgery that enables resection of pre-malignant and early-stage malignant gastrointestinal neoplasms in an en bloc fashion. AIM: To assess the feasibility of endoscopic submucosal dissection of stomach neoplasms with submucosal fibrosis caused by unsuccessful endoscopic resection. PATIENTS AND METHODS: Stomach endoscopic submucosal dissection was performed in ten consecutive patients who had unsuccessful endoscopic tumour resection at another hospital between 2003 and 2006. Seven patients had recurrent tumours after complete endoscopic resection, and three patients had incomplete resections due to complications or technical difficulties. Technical feasibility and follow-up data were collected from the patients' reports. RESULTS: All tumours were resected by endoscopic submucosal dissection in one piece without complications. R0 resection (en bloc resection with tumour-free margins) was achieved in nine patients (90%). One patient received additional surgery (gastrectomy) because of submucosal deep invasion with vascular infiltration of the cancer. All patients, including the patient with gastrectomy, have survived without recurrence during a mean follow-up period of 21.4 months (range 3-36 months). CONCLUSIONS: Endoscopic submucosal dissection is an effective and safe method for resection of stomach neoplasms after unsuccessful endoscopic resection.

Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy.

BACKGROUND AND STUDY AIMS: Endocytoscopy allows the observation of living cells in the gastrointestinal tract. Consistently clear views are essential for clinical application of the technique, but these are not always obtained. The aim of this study was to determine an appropriate staining regimen for endocytoscopy. MATERIALS AND METHODS: This was an ex-vivo animal study in which we stained freshly resected porcine esophagus, stomach, and colon with different concentrations of three dyes (1%, 0.5%, and 0.25% crystal violet; 5%, 2.5%, and 1% methylene blue; and 1%, 0.5%, and 0.25% toluidine blue) and assessed them after different exposure times (10 seconds, 30 seconds, 60 seconds, and 90 seconds). The images obtained were evaluated according to the staining status of the cytoplasm and the nucleus, and the contrast between the cytoplasm and the nuclei, and the optimal staining conditions for each organ were determined. Additionally, freshly resected human esophagus, stomach, and colon tissues were tested under the dye/exposure conditions that were found to be the most appropriate in the animal study. RESULTS: After intensive mucus removal, high-quality images were obtained using methylene blue and toluidine blue. The optimum conditions for endocytoscopic observation were obtained after staining with 1% methylene blue in the esophagus and with 0.25% toluidine blue in the stomach and the colon, after 60 seconds of exposure to the dye. This was confirmed in the human specimens. CONCLUSIONS: This study provides important information on appropriate staining conditions for endocytoscopy. Further ex-vivo and in-vivo studies are necessary before this technique comes into standard use, however.

A learning curve for endoscopic submucosal dissection of gastric epithelial neoplasms.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has become a widely accepted method for treating gastrointestinal neoplasms. The objective of our study was to assess the learning curve for ESD of gastric epithelial neoplasms. PATIENTS AND METHODS: Clinicopathological data were retrospectively collected from 383 ESD procedures for gastric epithelial neoplasms that were performed over a 5-year period. Thirteen endoscopists were involved as operators during this period. In study 1, the performance of the two principal operators was assessed every 25 patients. In study 2, the performance of all 13 operators was assessed according to their experience. RESULTS: In study 1, the caseloads of the two principal operators were 188 and 118 ESD procedures. There were no significant differences found between successive groups of 25 patients with regard to en-bloc resection rate and bleeding and perforation complication rates. The size of the lesions and the resected specimen diameter increased significantly as the number of treated cases increased, whereas the average procedure time decreased significantly. In study 2, the operators' caseloads ranged from 1 to 188 cases, with 11/13 operators having experience of fewer than 30 cases. There was no significant difference in treatment efficacy and complication rates between the operators throughout the study period. The lesions were mainly located in the lower part of the stomach in the procedures performed by the 11 less experienced endoscopists. The procedure times shortened as experience in the method increased. CONCLUSIONS: Constant rates of both treatment efficacy and complications were achieved over a 5-year period of experience with ESD. A decrease in procedure time was found to be a marker of proficiency in this technique.

Successful nonsurgical management of perforation complicating endoscopic submucosal dissection of gastrointestinal epithelial neoplasms.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. PATIENTS AND METHODS: We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. RESULTS: Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 degrees C, the mean white blood cell count was 9733/mm3, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). CONCLUSION: Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer.

The correlation between serum pepsinogen (PG) levels and the gross types was investigated in 128 consecutive patients with early gastric cancer. Although there was no significant difference in age, gender, cancer location, or cancer depth among gross appearances, the distribution of histological type was significantly different between polypoid and depressed cancers: all polypoid cancers except one were intestinal type, whereas nearly a third of depressed cancers were diffuse type. All the patients in whom Helicobacter pylori status was investigated had Helicobacterpylori infection. Combination of gross appearances and histology (polypoid cancer with intestinal type, depressed cancer with intestinal type and depressed cancer with diffuse type) showed a clear difference in distribution of serum PG levels and a ratio between levels of PG I and PG II (I/II ratio). In polypoid cancer with intestinal type, a PG I level and a I/II ratio were significantly lower than those of the others. In depressed cancer with diffuse type, PG I and PG II levels were significantly higher. These findings revealed that backgrounds such as intragastric acidity and extent of gastric atrophy might differ among early gastric cancers with different morphology and histology.

Endoscopic submucosal dissection for gastric neoplasia: experience with the flex-knife.

Although the standard treatment for gastric neoplasia is still surgical resection, endoscopic resection has been accepted for some of these lesions in an early stage. Among several methods of endoscopic resection, endoscopic submucosal dissection has been developed to remove the lesions in an en bloc fashion regardless of size, shape, coexisting ulcer, and location. However, indication of endoscopic submucosal dissection is strictly confined by two aspects; those are the possibility of nodal metastases and technical difficulty. Nowadays, several knives for endoscopic submucosal dissection are available and each of them has some merits and demerits. We describe how to perform endoscopic submucosal dissection in the stomach by using the flex-knife, a new endoscopic device specifically designed for submucosal dissection, emphasizing its special features from our experience.

Endoscopic submucosal dissection for rectal epithelial neoplasia.

BACKGROUND AND STUDY AIMS: The technique of endoscopic submucosal dissection (ESD) has recently been developed for en-bloc resection of gastric tumors. For oncological reasons and in order to improve the patients' quality of life, it may be desirable to use the same technique for rectal neoplasia. PATIENTS AND METHODS: Thirty-five consecutive patients with rectal neoplasia who had a preoperative diagnosis of large intraepithelial neoplasias with submucosal fibrosis or located on the rectal folds were enrolled. ESD was carried out with the same technique previously described for the stomach, with some modifications. The efficacy, complications, and follow-up results of the treatment were assessed. RESULTS: The rates of en-bloc resection and en-bloc plus R0 resection were 88.6 % (31 of 35) and 62.9 % (22 of 35), respectively. Hemoglobin levels did not drop by more than 2 g/dl in any of the patients after ESD. None of the patients had to receive blood transfusions or undergo emergency colonoscopy due to bleeding during ESD or hematochezia after ESD. Perforation during ESD occurred in two patients (5.7 %), who were managed with conservative medical treatment after endoscopic closure of the perforation. Excluding three patients in whom additional surgery was carried out, all but one of 32 patients were free of recurrence during a mean follow-up period of 36 months (range 12 - 60 months). The exception was a patient in whom a multiple-piece resection was required; the recurrent (residual) tumor, found 2 months after ESD, was a small adenoma that was again treated endoscopically. CONCLUSIONS: ESD is applicable in the rectum with promising results, but the technique is still at a developmental stage and patients should be informed of the potential risks.

Histopathologic characteristics of gastric ulcers created by endoscopic submucosal dissection.

BACKGROUND AND STUDY AIM: We have previously reported that gastric ulcers artificially created by endoscopic submucosal dissection (ESD) would heal within 8 weeks regardless of size and location. The details of the healing process remain unclear, and we aimed to clarify the mechanism by histopathological investigation. PATIENTS AND METHODS: 21 post-ESD ulcers were examined histopathologically, using surgically resected specimens from patients who had subsequently undergone gastrectomy due to submucosal invasion and/or lymphovascular infiltration by the tumor. The grade of ulcer, appearance of regenerative mucosa, scar formation, and extent of fibrosis were evaluated. RESULTS: Fibrosis and wall thickening were observed from 2 weeks after ESD, but regenerative mucosa was not observed until 5 weeks. Among 12 patients who underwent gastrectomy later than 8 weeks after ESD, a mucosal defect was still observed in two patients. In these two patients the lesion was associated with severe fibrosis due to previous peptic ulcer or submucosal invasion by the lesion. CONCLUSION: Size reduction in these ulcers occurs by contraction in the early phase, then regenerative mucosa covers the remaining mucosal defect within 8 weeks. If there is fibrosis under the lesion before ESD, there is a possibility that the artificially created ulcer will not heal within 8 weeks.

Efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction.

BACKGROUND AND STUDY AIMS: The esophagogastric junction (EGJ) has been considered a difficult location for endoscopic treatment of tumors, due to its narrow lumen and sharp angle. Endoscopic submucosal dissection (ESD) is a method of endoscopic resection, capable of removing large tumors in an en bloc fashion. The aim of this study was to evaluate the efficacy and safety of ESD for EGJ tumors. PATIENTS AND METHODS: For 30 lesions of EGJ tumors treated by ESD, the size of the lesions and resected specimens, the en bloc resection rate, complications, and local recurrence were assessed. RESULTS: The average maximum diameters of the lesions and resected specimens were 22.4 mm and 40.6 mm respectively. The complete en bloc resection (R0) rate was 97% (29/30). Histological evaluation of the resected specimens revealed five cases of angiolymphatic invasion and five cases of submucosal invasion deeper than 500 microm. Perforation occurred in one case but was safely managed by rotatable clips and administration of antibiotics for 3 days. Local recurrence was not observed in any patient during follow-up (mean 14.6 months, range 6-31 months). CONCLUSIONS: ESD can be safely performed for EGJ tumors, with a high en bloc resection rate. For lesions with no apparent submucosal invasion findings, ESD is a curative and diagnostic treatment option that may be considered before open surgery.