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Endoscopic submucosal dissection (ESD) is a new endoluminal therapeutic technique involving the use of cutting devices to permit a larger resection of the tissue over the muscularis propria. The major advantages of the technique in comparison with polypectomy and endoscopic mucosal resection are controllable resection size and shape and en bloc resection of a large lesion or a lesion with ulcerative findings. This technique is applied for the endoscopic treatment of epithelial neoplasms in the gastrointestinal tract from the pharynx to the rectum. Furthermore, some carcinoids and submucosal tumors in the gastrointestinal tract are treated by ESD. To determine the indication, two aspects should be considered. The first is a little likelihood of lymph node metastasis and the second is the technical resectability. In this review, practical guidelines of ESD for the gastrointestinal neoplasms are discussed based on the evidence found in the literature.

Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it: injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en-bloc resection compared to endoscopic mucosal resection (EMR). Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects: (1) the possibility of nodal metastases of the lesion, (2) technical difficulty such as location, ulceration and operator’s skill, and (3) organ characteristics.

Successful Endoscopic EN Bloc Removals of Colorectal Tumors By Endoscopic Submucosal Dissection Using a Flex Knife and a Mixture of High-Molecular-Weight Hyaluronic Acid and a Glycerin Plus Sugar Solution Mitsuhiro Fujishiro, Naohisa Yahagi, Naomi Kakushima, Shinya Kodashima, Masanori Nakamura, Hideyuki Miyoshi, Yoshikazu Moriyama, Nobutake Yamamichi, Ayako Tateishi, Katsuya Kobayashi, Takuhei Hashimoto, Keiji Ogura, Masao Omata Background: Endoscopic submucosal dissection (ESD) is a novel therapeutic technique of gastrointestinal tumors. The technique has been developed further by ourselves as a new ESD method using a flex knife (Flexknife , Olympus Co., Tokyo, Japan) and a mixture of 1% high-molecular-weight (1900 KDa) hyaluronic acid (Suvenyl , Chugai Pharmaceutical Co., Tokyo, Japan) and a glycerin plus sugar solution (Glyceol , Chugai Pharmaceutical Co., Tokyo, Japan). The purpose of this study is to investigate our results of ESD for colorectal tumors. Methods: We retrospectively investigated 122 ESD-indicated lesions (a mean tumor size of 27.8 (range: 5-100) mm) in 113 patients those were treated by ESD with our technique at the University Hospital between June 2000 and October 2004. Those underwent ESD because of patients’ desire, etc, even if the lesions were extra-indicated for ESD preoperatively had been excluded beforehand in the data. The 122 lesions were classified into 12 Is-type tumors, 59 laterally spreading tumors with granular type (LSTs-G), 38 LSTs with non-granular type (LSTs-NG), 9 scarring tumors due to previous intensive biopsy or endoscopic therapy, and 4 carcinoid tumors. From the data, we analyzed an en bloc resection rate, final histology, complication, and recurrence. Complication was defined as a life-threatening event such as hemorrhage needed blood transfusion or perforation needed surgical rescue. Results: An overall en bloc resection rate was 92% (113/122) (Is 92%, LST-G 92%, LST-NG 95%, scarring tumors 89%, carcinoid 100%) and all of the tumors could be evaluated by histology. Post-ESD histology revealed 63 adenomas, 44 intramucosal cancers, 11 submucosal invasive cancers, and 4 carcinoid tumors. Three cancers with massive submucosal invasion were additionally treated by surgery with lymph node dissection. No complication needed blood transfusion or surgical rescue occurred. As recurrence, only one rectal adenoma of LST-G with multi-fragmental resection was treated by argon plasma coagulation 2 months after ESD due to Abstracts

The incidence of adenocarcinoma of the gastric cardia has shown an increase in recent years in the West, and obesity has been reported to have relation to its increased risk. In Japan, however, the majority of gastric cancer are situated in the body and distal stomach which appear to have a different etiology, and cardia cancer is recognized as extemely rare. The purpose of the study is to evaluate the relation of body mass index (BMI) between patients with cardia and distal cancer at an early stage, and to compare clinico-pathological findings of each cancer. A total of 3144 patients with early gastric cacner (EGC) were examined, who underwent surgery in the period from 1962 to 1997 at National Cancer Center Hospital Tokyo (NCCH). Among these, only 70 cases (2%) were adenocarcinoma of gastric cardia, which were located within 20mm from esophagogastric junction, and 2949 cases (94%) were early distal cancer. 34.3 percent of the early cardia cancer showed the macroscopically elevated type, and this occurs in less than 13.7% of the distal cancer. Eight nine percent (62/70) cardia cancer revealed differentiated adenocarcinoma histologically. The male:female ratio of cardia cancer cases was about 2.7:1, which was much higher than that in patients with distal cancer. Proportion of submucosal invasion (53%) was significantly higher in cardia cancer than distal cancer. When BMI of the patients with cardia cancer were compared with 344 cohorts matched for age and sex selected from the patients with early distal cancer, there was no difference in BMI. Conclusions- There were several singnificant differences in clinicopathological characteristics between cardia cancer and distal cancer at an early stage. However, the incidence of early cardia cancer was very low in Japan, and obesity would not relate to its occurrence as reported in the West.

Background and aim: Squamous cell carcinoma of the esophagus is frequently associated with multiple other primary cancers. As recent advances in endoscopic diagnosis increase the cases of superficial esophageal cancer (SEC) of which prognosis is relatively good, we should pay more attention to subsequent other primary cancers (SOPC) or subsequent multiple esophageal cancers (SMEC) after the treatment of esophageal cancer. The present study was designed for determining the clinical features of SOPC and SMEC after the resection of SEC. Subjects: The study included 368 patients with SEC who underwent surgical resection or endoscopic mucosal resection (EMR) in our institute and were followed a median period of 56 months (range; 7~154 months). Surgical resection was performed in 267 patients, and EMR in 101. The presence of the past history of antecedent and/or synchronous multiple other primary cancers was noted in 149 patients. Result: Among the 368 patients, SOPC occurring after the resection of SEC were found in 43 (12%) patients. The most frequent sites of SOPC were the stomach (11 cases) and the hypopharynx (11 cases), followed by the lung (7 cases) and the colon (6 cases). SOPC were diagnosed a mean period of 47.2A}28.9 months after the resection of SEC, and the 5-year cumulative complication rate of SOPC was 14.8%. All cases of gastric cancers and 4 cases of hypopharingeal cancers were detected by endoscopy in postoperative follow up, and all of them were T1 tumor. In comparison with patients without SOPC, SOPC were significantly more frequent in patients who were heavy smokers and those who had the past history of antecedent and/or synchronous multiple other primary cancers (p

Background: Along with advances in endoscopy and diagnostic techniques, superficial esophageal cancers have been detected and treated with endoscopic mucosal resection (EMR). However, indication of EMR is limited to node-negative cancer, which invasion is confined to proper mucosal layer without vessel permeation. Gross appearance is one of good indicators to predict the depth of invasion. The protruding or excavated type suggests submucosal cancer, but the slightly depressed or flat elevated type is widely distributed from carcinoma in situ to submucosal cancer. Patients & Methods: The relationship between nodular changes and depth of invasion in the slightly depressed type of esophageal cancers, 177 surgically resected lesions and 100 lesions resected by EMR, were investigated. Furthermore, the frequencies of lymph node metastasis we investigated using surgically resected specimens. Results: Among 277 lesions, submucosal invasion was observed in 112 lesions (40%). Nodular changes existed in 40 lesions (14%). The frequencies of submucosal cancers in the groups with and without nodular changes were 83% (33/40) and 33% (79/237), respectively (p

Purpose: It is well accepted that most of gastric low-grade MALT lymphoma (L-MALT) disappears after H.pylorieradication. However, some cases relapse and do not response in spite of a cure from H.pyloriinfection. This study was to evaluate the efficacy of endoscopic findings and molecular biology markers in the series of long followed up L-MALT. Patients:Twenty-six patients with L-MALT after eradication of H. pyloriobserved for more than one year (median 31 months, range 13-63 months) between1993 and1999 were evaluated. Method: After eradication, they were classified histologically into 3 groups according to the Wotherspoon s grading; (A) improved group (Grade0-2), (B) boundary group (Grade3), and (C) immutable or progressed group (Grade4- 5). Before and after eradication, we evaluated endoscopic findings as follows, (1) erosion/ulcer, (2) protrusion, (3)cobble stone like appearance, (4)edematous or swelling, (5) IIc like depression,(6)small white spot, and (7)atrophic discolored change. All patients were followed by every 3 month of endoscopy and every 6 month of CT, EUS examination. Molecular biology markers were investigated about trisomy3, IgH rearrangement, p53 and Ki67. Result: After eradication, 19 patients (73%), 4(15%) and 3(12%) were classified into (A), (B) and (C) groups, respectively. In (A) group, the endoscopic (1)-(5) findings were completely disappeared and in 13 of them (63%) finding (7) appeared. However, in (C) group, these findings are also immutable, especially in 1 patients had protruding tumor it progressed and metastasized to para-aortic lymph nodes. Eight patients were referenced IgH rearrangement before and after eradication. And 5/8 patients showed monoclonality before eradication. The frequency of IgH rearrangement (monoclonality-polyclonality) was 5/6(83%) in (A) group, however, in both(C) and(B) group, only monoclonalitymonoclonality change was detected. In other markers (trisomy3, p53, Ki67), detection frequency was quite low and there was no remarkable difference. Conclusion: Endoscopic changes corresponded to the results of histological outcome. The atrophic discolored finding would indicate the endoscopic cure of MALT lymphoma after eradication. IgH rearrangement is useful for evaluation compared with histological results. However, the low frequency of the detection is a problem.

Background. Endoscopic mucosal resection (EMR) has been employed for treatment of early gastric cancer (EGC) in the world, and especially in Japan from the beginning of the 1980s. It has an advantage over surgical gastrectomy in patient's quality of life. However, there is some possibility of complications, such as perforation of the gastric wall and active bleeding. Especially, up to now, a surgical operation has been required to treat perforation and it causes the deterioration of the patient's QOL. In this study, we introduce how to manage and rescue the patients from perforation after EMR without surgical treatment from our experience. Methods. We had 618 patients with 780 cancers or severe dysplasias. They received EMR from October 1987 to August 1999 at the National Cancer Center Hospital, Tokyo, Japan. From 1994, we tried to suture the holes of the stomach using clips endoscopically, with insertion of a nasogastric tube for one day. Results. Perforation occurred in 44 patients (7%). In the early period from 1987 to 1993, all 4 patients with perforation underwent surgical treatment. Of the 40 patients with endoscopic sutures, 39 patients (97.5%) except for one patient, who had a perforation hole of more than 40 mm in size, succeeded in recovering without surgical treatment. Conclusions. Our data suggest that endoscopic suture using clips is a good procedure to rescue from perforation after EMR.

Backgrounds: Eradication of Helicobacter pylori (HP) has been reported to result in regression of gastric low-grade MALT lymphoma (LG-MALT) in 60 to 92% of cases. However, It is controversial on which timing and by which wayan additional treatment should be started in cases of persistent lymphoma. Aims: In order to know the optimal timing of additional treatments after eradication, we investigated the time course of the histological and endoscopic changes in LG-MALT. Patients & Methods: From December 1993 to October 1999, 45 patients (mean age: 55 y.o., M!F: 22/23) with LG-MALT and positive HP were treated with two weeks triple therapy (Iansoprazole: 30 mg/day, clarithromycin: 400 mg/day and arnoxicillin: 1500 mg/day). Endoscopic examinations were performed I and 3 months after eradication and then every 3 months (median follow-up duration: 18 months, range I to 66 montbs). Histological evaluation of biopsy was graded according to Wotherspoon AC et al (Lancet 1993;342: 575-77) and persistent lymphoma was defined as grade 4 and 5 and disappearance as grade 0 to 2. Results: HP was eradicated successfully in all patients. Lymphoma has disappeared histologically in 32 patients (71%) (the median duration between eradication and disappearance of lymphoma is 6 months, range I to 45 months). Histological persistence on endoscopic regression has been observed in 6 patients, in none of whom new lesions have appeared without additional treatments (median follow-up duration: 6 months, range 3 to 45 months). An Additional surgery was performed in 3 patients with persistent lymphoma on endoscopic progression 12, 12 and 34 months after eradication, respectively. The latter patient resulted in the appearance of paraaortic lymph node involvement and an additional chemotherapy had to be performed. The other 4 patients have been followed with histological grade 3 on endoscopic regression. Conclusions: We did not find the optimal timing of an additional treatment for persistent lymphoma. Histological evaluation alone is not enough to decide whether an additional treatment should be performed. To watch until endoscopic progression, on the other hand, may make the optimal timing lost like the matastatic case we experienced. To know the optimal timing, a new predictive maker possible to evaluate on the molecular level is needed.

Background & Aims: In Japan, EMR is generally accepted as the curative treatment for differentiated histological type mucosal cancer with minimum probability of lymph node metastasis. Although many EMR techniques are reported, a standard method has not been established. As to surgical operation, the tumor is usually removed by an en-bloc resection. In EMR, however, the piecemeal resection is often performed because of technical difficulties. To clarify whether the piecemeal resection for EGC is permited or not, we compared and evaluated clinical outcomes (curability, local recurrence) and tumor characteristics (size, location) between en-bloc and piecemeal resection. Patients: Through January 1995 and June 1999 at National Cancer Center Hospital, 402 cancers (372 patients, M/F:298/74, mean age:65.9 y) were treated by EMR according to our endoscopic applications: (1) differentiated-type adenocarcinoma by biopsy, (2) macroscopically I, IIa and IIc types and (3) absence of ulcerative and invasive findings. In the resected specimen, when the above applications including no lymph-vascular involvement and free margins are histologically confirmed, the resection was regarded as “curative”. The resected specimen with difficulty for accurate histological examination was regarded as “not evaluable”. Results: 1. Of 340 intramucosal cancers, 197 (58%) were resected by en-bloc and 143 by piecemeal, though 62 (15%) of 402 lesions invaded submusal layer. 2. Curative resection rate was 93 percent (183/197) by en-bloc and 59 (84/143) by piecemeal. Two cases developed local recurrence after piecemeal resection, but not after en-bloc resection. 3. Two (4/197) and 10 percent (14/143) was histologically not evaluable, respectively. 4. The number of tumor more than 20mm in diameter was 16 lesions (8%) in en-bloc group in contrast with 31 (22%) for piecemeal group. 5. Twenty-six lesions (13%) were located in the upper third of the stomach in en-bloc group and 29 (21%) for piecemeal group. Conclusion: The curative resection rate by en-bloc was much higher than that by piecemeal, and local recurrence rate was lower for en-bloc group. Forthermore the rate of “not evaluable” was low for en-bloc resection. These results suggest that EGC should be removed by en-bloc for curability and accurate histological examination. Therefore, development of new instrument would be needed to resect the lesions located in upper third and larger lesions by en-bloc.

Background The extent of node dissection in esophageal cancer surgery is usually estimated by the number of resected nodes, irrespective of the area of dissection. The efficacy of lymph node dissection by area was evaluated according to the location of the primary tumor. Methods The study group comprised the 3827 patients who underwent R0 esophagectomy with three-field lymph node dissection for squamous cell carcinoma, registered in a nationwide registry in Japan. The areas of lymph node were classified into zones according to AJCC Staging Manual. The Efficacy Index (EI) calculating the frequency and patient survival of metastases to each zone was investigated according to tumor location. Results The EI was high in supraclavicular and upper mediastinal zones in patients with upper esophageal tumors, highest in upper mediastinal zone followed by supraclavicular and perigastric zones in patients with middle esophageal tumors, and highest in perigastric zone followed by upper and lower mediastinal zones in patients with lower esophageal tumors. In patients with middle and lower esophageal cT1 tumors, the EIs of upper mediastinal and perigastric zones were higher than middle and lower mediastinal zones. Conclusion The EIs of each zone were differed by tumor location. The extent of lymph node dissection should be estimated by the dissected zones and modified by the tumor location. Supraclavicular dissection is indispensable for patients with upper esophageal tumors, and recommended for patients with middle esophageal tumors. Upper mediastinal dissection is recommended for all patients with thoracic esophageal squamous cell carcinoma, irrespective of the location.

These data were first made available on January 2016, as the Comprehensive Registry of Esophageal Cancer in Japan, 2009. Not all the tables and figures are reprinted here. The authors were members of the Registration Committee for Esophageal Cancer, the Japan Esophageal Society, and made great contributions to the preparation of this material.

Background: Due to the remarkable progress of endoscopic resection techniques, endoscopic submucosal dissection (ESD) has been widely performed for larger mucosal tumors that would result in large artificial ulcers. The healing process of peptic ulcers has been previously studied in detail; however, no precise investigation for artificial ulcers after ESD has been reported. To confirm the validity of the treatment from the aspect of wound healing, we aimed to clarify the healing process of large gastric artificial ulcers after ESD. Methods: Seventy patients with gastric mucosal tumors treated by ESD were enrolled. The size, location and time of scar formation of the ulcers were reviewed using endoscopic pictures taken from the same view and angle. Follow-up endoscopy was performed at 1, 4, 8 and 12 weeks after ESD. For postoperative medication, all patients received normal doses of proton pump inhibitors and sucralfate for 8 weeks. Results: The average size of the resected specimen was 34.7 mm (20–90 mm). Irrespective of ulcer size and location, all of the cases healed up to scarring stages within 8 weeks. Conclusions: Gastric artificial ulcers after ESD healed within 8 weeks regardless of size and location using normal doses of medication as peptic ulcers. The fact that even giant ulcers after ESD heal within 8 weeks could be helpful information for candidates for ESD and for postoperative management of patients after ESD.

An 89-year-old Japanese woman on continuous ambulatory peritoneal dialysis presented with an obstructed peritoneal catheter (both inflow and outflow) 8 weeks after the initiation of dialysis. To investigate the cause of the catheter obstruction, we adapted a gastrofiberscope for percutaneous endoscopic gastrostomy (FP-7RBS, HOYA-Pentax, Tokyo, Japan) whose outer diameter is 2.4 mm, which is comparable to that of a Tenckhoff catheter. Endoscopic examination revealed that the catheter was obstructed with a red-colored tissue (Figure 1), suggesting a visceral organ (intestine, colon, or fallopian tube). The prolapsed tissue was gently reduced back into the peritoneal cavity under direct vision from the side hole of the Tenckhoff catheter. The catheter subsequently functioned properly and she was able to resume peritoneal dialysis. Although catheter obstruction is a frequent and serious complication in peritoneal dialysis, the available non-invasive methods for the diagnosis are limited to date. Endoscopic approach can provide us accurate diagnostic information and another strategy for the treatment of peritoneal catheter obstruction.