The utility of endoscopic ultrasonography and endoscopy in the endoscopic mucosal resection of early gastric cancer

OBJECTIVE: To clarify the usefulness of endoscopic ultrasonography (EUS) and endoscopy in the endoscopic mucosal resection (EMR) of early gastric cancer. Patients/Methods-EMR was performed in 61 patients with early gastric cancer over the past five years. The accuracy of the assessment of the depth of cancerous invasion was studied in 49 patients who had EUS before EMR. Forty eight patients were treated with endoscopy alone; in these patients, EUS and endoscopic findings correlated with the clinical course. RESULTS: Forty six patients showed no changes in the submucosal layer or deeper structures on EUS. Pathologically these included 37 patients with mucosal cancer and nine with submucosal cancer showing very slight submucosal infiltration. Three patients showed diffuse low echo changes in the submucosal layer on EUS; pathologically, these included two with submucosal cancer and one with mucosal cancer with a peptic ulcer scar within the tumour focus. Of 48 patients receiving endoscopic treatment alone, 45 showed no tumour recurrence or evidence of metastases on EUS and endoscopy. Three cases of recurrence were observed. Two of these patients had a surgical gastrectomy, and one was re-treated endoscopically. In the former cases, the surgical results correlated well with assessment by EUS and endoscopy. In addition, the latter patient who was re-treated endoscopically after evaluation with EUS and endoscopy has so far had no recurrence. CONCLUSION: The combined use of EUS and endoscopy is effective in diagnosing the depth of cancerous invasion in patients undergoing EMR as well as in clarifying changes both within and between anatomic levels during follow up.     

A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer

BACKGROUND/AIMS: Endoscopic ultrasonography is expected to be useful for invasion depth staging of early gastric cancer. A prospective blind study of the staging characteristics of endoscopy and endoscopic ultrasonography for early gastric cancer was performed. METHODS: Findings of endoscopy and endoscopic ultrasonography using a 20 MHz thin ultrasound probe were independently reviewed and the results of 52 early gastric cancer lesions analysed. RESULTS: The overall accuracy rates in invasion depth staging of early gastric cancer were 63% for endoscopy and 71% for endoscopic ultrasonography. No statistically significant differences were observed in overall accuracy. Endoscopic ultrasonography tended to overstage, and lesions that were classified as mucosal cancer by endoscopic ultrasonography were very likely (95%) to be limited to the mucosa on histological examination. All 16 lesions staged as mucosal cancer independently but coincidentally by both methods were histologically limited to the mucosa. CONCLUSIONS: Endoscopic ultrasonography is expected to compensate for the understaging of lesions with submucosal invasion that are endoscopically staged as mucosal cancer.     

Endoscopic ultrasonography for diagnosis of submucosal invasion in early gastric cancer

Endoscopic ultrasonography (EUS) is considered to be useful for deciding the treatment course for early gastric cancer. To determine reliable indications suggesting submucosal tumor invasion, we retrospectively analyzed EUS images of the hyperechoic third layer, which corresponds to the submucosa. The subjects enrolled in this study were 75 patients, with 78 gastric cancers (diagnosed as mucosal cancer without ulcerous changes on endoscopy and as histologically differentiated adenocarcinoma on biopsy), who were also examined by EUS. We retrospectively classi-fied EUS features of the third layer (submucosa) into five groups: (1) irregular narrowing, (2) budding sign, (3) multiple echo-free spots, (4) unclear, and (5) no changes. In endoscopically diagnosed gastric mucosal cancer, 16 of the 78 lesions were associated with histologic submucosal invasion. EUS features that were associated with a high incidence of histological submucosal tumor invasion were irregular narrowing (submucosal invasion, 60.0%) and the budding sign (85.7%), and 90.9% of lesions with either of these features had submucosal invasion of tumors when tumorous changes in the third layer exceeded 1 mm in depth. Endosonographic irregular narrowing and a budding sign of more than 1 mm in depth in the third layer are useful for the diagnosis of submucosal invasion in gastric cancers that are diagnosed as mucosal cancers without ulcerous change on endoscopy. Received: March 29, 1999 / Accepted: November 26, 1999     

Endoscopic mucosal resection for treatment of early gastric cancer

BACKGROUND: In Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented. METHODS: EMR was applied to patients with early cancers up to 30 mm in diameter that were of a well or moderately histologically differentiated type, and were superficially elevated and/or depressed (types I, IIa, and IIc) but without ulceration or definite signs of submucosal invasion. The resected specimens were carefully examined by serial sections at 2 mm intervals, and if histopathology revealed submucosal invasion and/or vessel involvement or if the resection margin was not clear, surgery was recommended. RESULTS: Four hundred and seventy nine cancers in 445 patients were treated by EMR from 1987 to 1998 but submucosal invasion was found on subsequent pathological examination in 74 tumours. Sixty nine percent of intramucosal cancers (278/405) were resected with a clear margin. Of 127 cancers without "complete resection", 14 underwent an additional operation and nine were treated endoscopically; the remainder had intensive follow up. Local recurrence in the stomach occurred in 17 lesions followed conservatively, in one lesion treated endoscopically, and in five lesions with complete resection. All tumours were diagnosed by follow up endoscopy and subsequently treated by surgery. There were no gastric cancer related deaths during a median follow up period of 38 months (3-120 months). Bleeding and perforation (5%) were two major complications of EMR but there were no treatment related deaths. CONCLUSION: In our experience, EMR allows us to perform less invasive treatment without sacrificing the possibility of cure.     

Evaluation of endoscopic ultrasonography as an indicator for surgical treatment of gastric cancer

BACKGROUND AND METHODS: Clinicopathological analysis of 346 patients with gastric cancer was made retrospectively and new criteria for the indication of a limited operation using endoscopic ultrasonography (EUS) was developed. Suggested new criteria for selecting gastric cancer patients for the limited operation were: (i) the cancer is located in the mucosa and the lymph nodes are not involved as indicated by EUS examination; (ii) the maximum size of the tumour is less than 2.0 cm; (iii) there are no multiple gastric cancers or simultaneous abdominal cancers; and (iv) the mucosal cancer of elevated type less than 2.0 cm is excluded because there are good indications for endoscopic mucosal resection. RESULTS AND CONCLUSIONS: We applied these new criteria to 262 patients and found that the patients who had limited operation had the same prognosis and a better quality of life compared with patients who had the conventional operation.     

Ulcerous change decreases the accuracy of endoscopic ultrasonography diagnosis for the invasive depth of early gastric cancer

Background With the development of endoscopic submucosal dissection, an expansion of the criteria for local treatment was suggested for lesions with ulcerous changes or undifferentiated-type adenocarcinoma. Aim of the Study To determine the efficacy of endoscopic ultrasonography for such lesions, we retrospectively analyzed factors that influenced accurate diagnosis by endoscopic ultrasonography of the depth of tumor invasion. Methods We investigated 267 gastric adenocarcinomas for which histopathological results were obtained by endoscopic mucosal resection or gastrectomy. The lesions were divided into four groups by histological type and the presence of ulcerous changes. Five clinicopathological factors were assessed for their possible associations with incorrect diagnosis. Results The positive predictive value (PPV) for cancer limited within the mucosa (endoscopic ultrasonography, EUS-M) and cancer invaded into the submucosal layer (EUS-SM) were 88.0% (125 of 142 lesions) and 60.0% (30 of 50 lesions), respectively. The lesions diagnosed as EUS-M/SM borderline (37 lesions) included 19 lesions (51.4%) of M cancer and 17 lesions (45.9%) of SM cancer. In logistic analysis, ulcerous changes (p < 0.0001) and macroscopic classification (p = 0.0284) were factors that caused incorrect diagnosis by endoscopic ultrasonography. In the group having differentiated-type adenocarcinoma with ulcerous changes, the PPV of EUS-SM was 25% (3 of 12), and there was a significant difference (p < 0.05) between the EUS-SM of this group and that of the differentiated-type adenocarcinoma without ulcerous changes. Conclusion The accuracy of endoscopic ultrasonography tumor staging was not sufficient for the lesions with ulcerous changes in our study. Therefore, we should be careful to perform endoscopic submucosal dissection for lesions with ulcerous changes.     

Clinical role of endoscopic ultrasonography for the diagnosis of early colorectal cancer and selecting the treatment procedure

Background: Accurate evaluation of the depth of tumor invasion, including the degree of submucosal invasion, is a prerequisite to selecting the treatment procedure for early colorectal cancer (CRC). The purpose of the present study was to evaluate the significance of endoscopic ultrasonography (EUS) for diagnosing the depth of invasion of early CRC and selecting the treatment procedure. We concurrently estimated the usefulness of three‐dimensional EUS (3‐D‐EUS) compared with that of conventional EUS. Methods: We studied 413 consecutive early CRC for which the depth of invasion was examined by EUS. They consisted of 239 lesions of mucosal cancers and 174 lesions of submucosal cancers (sm cancers). We divided sm cancers into two groups, sm‐slight cancers (38 lesions) and sm‐massive cancers (136 lesions), according to the degree of infiltration in the vertical direction in the submucosa. The diagnostic accuracy of the depth of cancerous invasion by EUS and the characteristics of tumors that were difficult to image by EUS were examined. For 59 lesions, the depth of invasion was concurrently evaluated by 3‐D‐EUS to compare the clinical usefulness of this diagnostic tool with that of conventional EUS. Results: In 364 lesions (88%) of early CRC, we could diagnose the depth of invasion by EUS. Differentiation between mucosal or sm‐slight cancers, which were generally treated by endoscopic resection or local excision, and sm‐massive cancers, which were suitable for radical operation, was possible in 90%. A total of 49 lesions (12%) could not be imaged by EUS. Difficulty in imaging often occurred with lesions located proximally to the transverse colon and with protruded‐type lesions. The accuracy rate of 3‐D‐EUS for differentiating between mucosal or sm‐slight cancers and sm‐massive cancers, including difficult‐to‐image lesions, was 86%. This figure was slightly, but not significantly higher, than the accuracy rate of 73% for conventional EUS (P = 0.07). However, the concurrent application of 3‐D‐EUS was considered useful in 31 of the 59 lesions (53%) evaluated by both techniques. Conclusion: EUS is useful for evaluating the depth of tumor invasion and selecting the treatment procedure for early CRC. The concurrent use of 3‐D‐EUS may further improve diagnostic accuracy and decrease the number of difficult‐to‐image lesions.     

Is endoscopic one‐piece mucosal resection essential for early gastric cancer?

Background: Endoscopic mucosal resection (EMR) is widely accepted as a minimally invasive treatment for early gastric cancer (EGC) in Japan. However, the criteria for EMR must be strictly adhered to otherwise patients will miss the chance for additional therapy. We assess the important factor in expanding the indication of EMR. Methods: We investigated 1101 EGCs that had been resected by EMR at the National Cancer Center Hospital (NCCH), Tokyo, Japan, according to the indication recommended by Japanese Gastric Cancer Association (JGCA) and the expanded indication proposed by NCCH. Curability and local recurrence of the EMRs were assessed related to the applied indication and the number of resected specimens. Results: The recurrence rate of non‐evaluable resection was higher than that of evaluable resection (P < 0.0001). Eighty‐three lesions among 772 lesions in the JGCA group were non‐evaluable. Thirty‐seven leisons among 329 lesions in the NCCH group were non‐evaluable. There was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.8329). However, the rate of curative resection was lower in the NCCH group than in the JGCA group (P = 0.0009). In piecemeal resection, there was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.0527). In one‐piece resection, the rate of non‐evaluable resection was lower in the NCCH group than the JGCA group (P = 0.0137). Conclusion: Based on our series of cases, we propose one‐piece resection as a gold standard for EMR because it enables accurate histological evaluation, even in the EMR, according to the expanded indication.     

《早期胃癌内镜黏膜下剥离术和内镜黏膜切除术治疗指南(第二版)》的更新与解读

2014年日本胃肠内镜学会与日本胃癌学会联合发布了基于循证医学原则的《早期胃癌内镜黏膜下剥离术和内镜黏膜切除术治疗指南》。然而由于当时该领域的许多证据级别较低,部分准则只能通过专家共识来建立。近年来,设计规范的临床研究数量激增。基于这些新的证据,日本胃肠内镜学会发布了上述治疗指南的修订第二版。本文将基于新版指南中更新和...     

Clinicopathological study of lymph-node metastasis in 1,389 patients with early gastric cancer: assessment of indications for endoscopic resection

BACKGROUND: The endoscopic resection of early gastric cancers (EGC) is a standard technique in Japan and is increasingly used throughout the world. Further experience in the treatment of EGC and a clearer delineation of the factors related to lymph‐node metastasis would permit a more accurate assessment of endoscopic resection. METHODS: The study group comprised 1389 patients with EGC who underwent gastrectomy with lymph‐node dissection. We evaluated the relations of lymph‐node metastasis to clinicopathological factors. RESULTS: Of the 718 patients with intramucosal carcinomas, 14 (1.9%) had lymph‐node metastasis. All cases of lymph‐node metastasis were associated with ulceration. No lymph‐node metastasis was found in patients with intramucosal carcinomas without ulceration, irrespective of tumor size and histological type. Lymph‐node metastasis was present in 14 (4.7%) of the 296 patients who had cancer with a submucosal invasion depth of less than 500 μm (sm1). Significantly increased rates of lymph‐node metastasis were associated with undifferentiated types, ulcerated lesions and lymphatic invasion. No lymph‐node metastasis was found in patients with differentiated sm1 carcinomas 30 mm or less in diameter without ulceration. Lymph‐node metastasis occurred in 29% of the patients who had cancer with a submucosal invasion depth of 500 μm or more (sm2). CONCLUSION: This large series of patients with EGC provides further evidence supporting the expansion of indications for endoscopic treatment, as well as warns against potential risks.     

Predictive factors for lymph node metastasis and endoscopic treatment strategies for undifferentiated early gastric cancer

Background and Aim: Although more than 80% of undifferentiated early gastric cancers (EGC) are not associated with lymph node metastasis, endoscopic mucosal resection is not generally accepted as a means of curative treatment because of an abundance of conflicting data concerning clinicopathological characteristics and prognoses. The aim of this study was to define a subgroup of undifferentiated EGC that could be cured by endoscopic treatment without the risk of lymph node metastasis. Method: A total of 591 patients surgically resected for undifferentiated EGC between January 1999 and March 2005 were reviewed. Associations between various clinicopathological factors and the presence of lymph node metastasis were analyzed to identify the risk factors of lymph node metastasis. Results: Lymph node metastasis was found in 79 patients (13.4%). By multivariate logistic regression analysis, a tumor diameter 2.5 cm or larger, invasion into the middle third of the submucosal layer or deeper, and lymphatic involvement were identified as independent risk factors of lymph node metastasis (P < 0.001, respectively). Lymph node metastasis was not found in any patient with undifferentiated EGC smaller than 2.5 cm confined to the mucosa or upper third of the submucosal layer without lymphatic involvement. Conclusions: Undifferentiated intramucosal EGC smaller than 2.5 cm without lymphatic involvement was not associated with lymph node metastasis. Thus, we propose in this circumstance that endoscopic mucosal resection could be considered a definitive treatment without compromising the possibility of cure.     

Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition)

In response to the rapid and wide acceptance and use of endoscopic treatments for early gastric cancer, the Japan Gastroenterological Endoscopy Society, in collaboration with the Japanese Gastric Cancer Association, produced “Guidelines for Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection for Early Gastric Cancer” in 2014, as a set of basic guidelines in accordance with the principles of evidence‐based medicine. At the time, a number of statements had to be established by consensus (the lowest evidence level), as evidence levels remained low for many specific areas in this field. However, in recent years, the number of well‐designed clinical studies has been increasing. Based on new findings, we have issued the revised second edition of the above guidelines that cover the present state of knowledge. These guidelines are divided into the following seven categories: indications, preoperative diagnosis, techniques, evaluation of curability, complications, long‐term postoperative surveillance, and histology.     

History and future perspectives in Japanese guidelines for endoscopic resection of early gastric cancer

Japanese guidelines for gastric cancer treatment were first published in 2001 for the purpose of showing the appropriate indication for each treatment method, thereby reducing differences in the therapeutic approach among institutions, and so on. With the accumulation of evidence and the development and prevalence of endoscopic submucosal dissection (ESD), the criteria for the indication and curability of endoscopic resection (ER) for early gastric cancer (EGC) have expanded. However, several problems still remain. Although a risk-scoring system (eCura system) for predicting lymph node metastasis (LNM) may help treatment decision in patients who do not meet the curative criteria for ER of EGC, which is referred to as eCura C-2 in the latest guidelines, additional gastrectomy with lymphadenectomy may be excessive for many patients, even those at high risk for LNM. Less-invasive function-preserving surgery, such as non-exposed endoscopic wall-inversion surgery with laparoscopic sentinel node sampling, may overcome this problem. In addition, further less-invasive treatment, such as ER with chemotherapy, should be established for patients who prefer not to undergo additional gastrectomy.     

Guidelines for endoscopic diagnosis of early gastric cancer

The Japan Gastroenterological Endoscopy Society developed the Guideline for Endoscopic Diagnosis of Early Gastric Cancer based on scientific methods. Endoscopy for the diagnosis of early gastric cancer has been acknowledged as a useful and highly precise examination, and its use has become increasingly more common in recent years. However, the level of evidence in this field is low, and it is often necessary to determine recommendations based on expert consensus only. This clinical practice guideline consists of the following sections to provide the current guideline: [I] Risk stratification of gastric cancer before endoscopic examination, [II] Detection of early gastric cancer, [III] Qualitative diagnosis of early gastric cancer, [IV] Diagnosis to choose the therapeutic strategy for gastric cancer, [V] Risk stratification after endoscopic examination, and [VI] Surveillance of early gastric cancer.     

Preoperative staging of gastric cancer by endoscopic ultrasonography and multidetector‐row computed tomography

Background and Aim: The aim of this study was to determine the accuracy of endoscopic ultrasonography (EUS) and multidetector‐row computed tomography (MDCT) for the locoregional staging of gastric cancer. EUS and computed tomography (CT) are valuable tools for the preoperative evaluation of gastric cancer. With the introduction of new therapeutic options and the recent improvements in CT technology, further evaluation of the diagnostic accuracy of EUS and MDCT is needed. Methods: In total, 277 patients who underwent EUS and MDCT, followed by gastrectomy or endoscopic resection at Bundang Hospital, Seoul National University, from July 2006 to April 2008, were analyzed. The results from the preoperative EUS and MDCT were compared to the postoperative pathological findings. Results: Among the 277 patients, the overall accuracy of EUS and MDCT for T staging was 74.7% and 76.9%, respectively. Among the 141 patients with visualized primary lesions on MDCT, the overall accuracy of EUS and MDCT for T staging was 61.7% and 63.8%, respectively. The overall accuracy for N staging was 66% and 62.8%, respectively. The performance of EUS and MDCT for large lesions and lesions at the cardia and angle had significantly lower accuracy than that of other groups. For EUS, the early gastric cancer lesions with ulcerative changes had significantly lower accuracy than those without ulcerative changes. Conclusions: For the preoperative assessment of individual T and N staging in patients with gastric cancer, the accuracy of MDCT was close to that of EUS. Both EUS and MDCT are useful complementary modalities for the locoregional staging of gastric cancer.     

A study of metachronous cancer after endoscopic resection of early gastric cancer

Abstract

Objective. Endoscopic resection is commonly used for early gastric cancer (EGC) in Korea and Japan. There are only a few reports of metachronous cancer after endoscopic resection. The aim of this study was to identify clinical factors associated with metachronous gastric cancer after endoscopic resection. Methods. A total of 176 patients with EGC who had underwent endoscopic submucosal dissection (ESD) were periodically followed-up with endoscopic examinations from January 2004 to December 2007. The incidence and variable factors of metachronous gastric cancer were investigated in a retrospective study. Results. The median interval between the diagnosis of primary cancer and the diagnosis of the first metachronous cancer was 30 months (range 18–42 months). Metachronous gastric cancer had developed in nine patients (5.1%) during follow-up period and seven patients (4.0%) had synchronous gastric cancer lesions within 1 year of the initial endoscopic treatment. Annual incidence rate of metachronous cancer was approximately 3.3%. Antrum atrophy and old age were significantly associated with the incidence of metachronous cancer. The status of Helicobacter pylori, size, location and gross finding of lesion had no significant relationship with metachronous occurrence. Conclusions. We should examine more carefully older patients who have atrophic gastritis because secondary cancer including metachronous cancer might occur in remnant stomach after initial successful endoscopic resection. And prospective study will be needed for the optimal endoscopic surveillance interval.