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.     

Endoscopic findings of adenocarcinoma arising from short-segment Barrett's esophagus

Adenocarcinoma arising from short-segment Barrett's esophagus (SSBE) is rare in Japan, although the incidence of this condition is increasing in Western countries. Four cases of early adenocarcinoma arising from SSBE were diagnosed and treated at Niigata-prefectural Yoshida Hospital. All patients were male, variously 55, 71, 73 and 79 years of age. All four patients had long-term gastroesophageal reflux disease, although one patient had erosive esophagitis and three patients did not have erosive esophagitis. Three patients were diagnosed as having Helicobacter pylori-free stomach. All adenocarcinomas occurred close to the squamocolumnar junction. Patients with SSBE should undergo detailed endoscopic examination of the squamocolumnar junction in order to detect early adenocarcinoma arising from SSBE.     

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma in Barrett＇s esophagus： An Italian experience

AIM: To evaluate endoscopic mucosal resection (EMR) in patients with high-grade dysplasia (HGD) and/or intramucosal cancer (IMC) in Barrett's esophagus (BE). METHODS: Between June 2000 and December 2003, 39 consecutive patients with HGD (35) and/or IMC (4) underwent EMR. BE >30 mm was present in 27 patients. In three patients with short segment BE (25.0%), HGD was detected in a normal appearing BE. Lesions had a mean diameter of 14.8±10.3 mm. Mucosal resection was carried out using the cap method. RESULTS: The average size of resections was 19.7± 9.4×14.6±8.2 mm. Histopathologic assessment post-resection revealed 5 low-grade dysplasia (LGD) (12.8%), 27 HGD (69.2%), 2 IMC (5.1%), and 5 SMC (-12.8%). EMR changed the pre-treatment diagnosis in 10 patients (25.6%). Three patients with SMC underwent surgery. Histology of the surgical specimen revealed 1 T0N0 and 2 T1NO lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy, occurred in four patients (10.3%). After a median follow up of 34.9 mo, all patients remained in remission. CONCLUSION: In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.     

Endoscopic mucosal resection of large hyperplastic polyps in 3 patients with Barrett＇s esophagus

AIM: To report the endoscopic treatment of large hyperplastic polyps of the esophagus and esophago-gastric junction (EGJ) associated with Barrett's esophagus (BE) with low-grade dysplasia (LGD), by endoscopic mucosal resection (EMR). METHODS: Cap fitted EMR (EMR-C) was performed in 3 patients with hyperplastic-inflammatory polyps (HIPs) and BE. RESULTS: The polyps were successfully removed in the 3 patients. In two patients, with short segment BE (SSBE) (<= 3 cm), the metaplastic tissue was completely excised. A 2 cm circumferential EMR was performed in one patient with a polyp involving the whole EGJ. A simultaneous EMR-C of a BE-associated polypoid dysplastic lesion measuring 1 cm multiply 10 cm, was also carried out. In the two patients, histologic assessment detected LGD in BE. No complications occurred. Complete neosquamous re-epithelialization occurred in the two patients with SSBE. An esophageal recurrence occurred in the remaining one and was successfully retreated by EMR. CONCLUSION: EMR-C appears to be a safe and effective method for treating benign esophageal mucosal lesions, allowing also the complete removal of SSBE.     

Endoscopic submucosal dissection compared to endoscopic mucosal resection for early Barrett esophagus neoplasia

Endoscopic resection has become an invaluable diagnostic and therapeutic tool in the evaluation and management of early Barrett esophagus (BE) neoplasia. While endoscopic mucosal resection (EMR) is the current standard of care for the resection of nodular early BE neoplasia, endoscopic submucosal dissection (ESD) has been recently introduced as part of the armamentarium in the treatment of these lesions. The potential advantages of ESD compared to EMR include higher en-bloc and R0 resection rates, decreased local recurrence, and the procurement of large en-bloc specimens that may facilitate pathologic staging. On the other hand, EMR is less time-consuming and has been traditionally associated with a lower incidence of serious adverse events when compared to ESD. At present, the choice of the endoscopic resection technique hinges on operator’s preferences, patient and lesions characteristics and available local expertise. Future high-quality studies comparing clinical outcomes between ESD and EMR are needed to better define their roles in the management of early BE neoplasia.     

Clinical outcome of endoscopic mucosal resection for esophageal squamous cell cancer invading muscularis mucosa and submucosal layer

When a tumor invades the muscularis mucosa and submucosal layer (T1a‐MM and T1b in Japan), esophageal squamous cell cancer poses 10–50% risk of lymph node metastasis. By this stage of esophageal cancer, surgery, although very invasive, is the standard radical therapy for the patients. Endoscopic mucosal resection (EMR) is the absolutely curable treatment for cancer in the superficial mucosal layer. Because of its minimal invasiveness, the indications of EMR may be expanded to include the treatment of T1a‐MM and T1b esophageal carcinoma. To date, the clinical outcomes of EMR for T1a‐MM and T1b patients have not been fully elucidated. Here, the retrospective analysis of the clinical outcomes is reported. Between January 1994 and December 2007, 247 patients underwent EMR at Kanagawa Cancer Center. Of these individuals, 44 patients with 44 lesions fulfilled the following criteria: (i) extended EMR treatment for clinical T1a‐MM and T1b tumor; (ii) diagnosis of clinical N0M0; and (iii) follow up for at least 1 year, and negative vertical margin. These patients were reviewed for their clinical features and outcomes. Statistical analyses were performed by the Kaplan–Meier methods, the Chi‐square test, and the Cox proportional hazard model. P‐value of <0.05 was considered statistically significant. The data were analyzed in February 2009. Based on the informed consent and their general health conditions, 44 patients decided the following treatments immediately after the EMR: 2 underwent surgery, 1 underwent adjuvant chemotherapy, and 41 selected follow up without any additional therapy. Of the 41 patients, 20 selected this course by choice, 12 because of severe concurrent diseases, 2 because of poor performance status, and 7 because of other multiple primary cancers. Twelve patients died; two were cause specific (4.5%), eight from multiple primary cancers, one from severe concurrent diseases, and one from unknown causes. No critical complications were noted. Median follow‐up time was 51 months (12–126). Five patients ultimately developed lymph node metastasis. One patient with adjuvant chemotherapy required surgery, and another was treated with chemotherapy whose subsequent death was cause specific. The other three patients received chemoradiotherapy and have not shown cause‐specific death. Overall and cause‐specific survival rates at 5 years were 67.3% and 91.8%, respectively. Among 41 patients treated by EMR alone, only one died from primary esophageal cancer (2.4%), and overall and cause‐specific survival rates at 5 years were 75.6% and 97.6%, respectively. Multivariate analysis revealed that severe concurrent diseases including multiple primary cancers and the administration of 5‐fluorouracil‐based chemotherapy for multiple primary cancers significantly influenced survival (P= 0.025, hazard ratio [HR] 13.1 [95% confidence interval 1.5–114]) and (P= 0.037, HR 0.213 [95% confidence interval 0.05–0.914]), respectively. Eight and six patients developed metachronous esophageal squamous cell cancer and local recurrence, respectively. With the exception of one patient, they could be retreated endoscopically. EMR is a reasonable option for the patients with T1a‐MM and T1b esophageal carcinoma without clinical metastasis, especially for the individuals with severe concurrent diseases. The prognostic factors for the benefit of EMR in such cases should be further examined.     

Endoscopic mucosal resection for esophageal and gastric cancers

Better outcomes for digestive tract cancers are likely to be possible if the tumors are detected in their earliest stages, particularly when they exist as mucosal lesions without lymph node metastases. Early esophageal squamous cell cancers can be detected with high sensitivity and specificity by iodine staining. Only mucosal cancers are suitable for the curative approach of submucosal resection; the rate of metastasis is 4%, compared to a rate of metastasis of 35% in tumors with submucosal spread. In this review, the history of endscopic mucosal resection is reviewed, including the factors that have refined the technique and technical aspects crucial for effective results. The importance of adequate submucosal injection of dilute epinephrine in saline solution is particularly emphasized. The overall efficacy, low rate of complications and such practical aspects as post-therapeutic care are discussed. In general, mucosal cancers of the gastrointestinal tract have no risk of lymph node metastases and can be curatively managed by refined endoscopic mucosal resection procedures.     

Mucoepidermoid carcinoma of the esophagus treated by endoscopic mucosal resection

Mucoepidermoid carcinoma is a mixed cell tumor with both adenocarcinomatous and squamous components. We report a rare case of superficial mucoepidermoid carcinoma of the esophagus with mucosal gastric cancer. Endoscopic mucosal resection was performed on a 67-year-old man with a slight but defined depressed lesion of the thoracic esophagus and two lesions of mucosal gastric cancer. Histological examination revealed that the lesion of the esophagus was a mucoepidermoid carcinoma and the two lesions of the stomach were well-differentiated adenocarcinoma. Since the mucoepidermoid carcinoma had only slightly invaded the submucosal layer, it was thought to arise from the ductal epithelium of the esophageal gland or the stratified squamous epithelium of the esophagus. Radiation therapy with a total dose of 60 Gy was performed and there has been no recurrence or metastasis to other organs during 36 months of follow-up.     

Primary adenocarcinoma of the cervical esophagus arising from heterotopic gastric mucosa

Received: February 18, 2000 / Accepted: November 17, 2000     

Endoscopic cap resection for treatment of early Barrett''s neoplasia is safe: a prospective analysis of acute and early complications in 216 procedures

This study aimed to prospectively evaluate the safety of endoscopic resection for early neoplasia in Barrett's esophagus (BE) using the endoscopic cap resection (ER cap) technique. All resections performed between September 2000 and March 2006 with the ER-cap technique in patients with BE were included. Complications were classified 'acute' (during the procedure) or 'early' (< 48 h after the procedure). A total of 216 ER-cap procedures were performed in 121 patients, of which 145 were performed with a standard hard cap and 71 with a large flexible cap. Specimens removed with the standard cap had a mean diameter of 20 mm (SD 5.0) versus 23 mm (SD 5.8) for the large cap (P < 0.001). Acute complications occurred in 51 procedures (24%), 49 bleedings and two perforations. All bleedings were effectively treated with hemostatic techniques and classified as mild complications. No patient experienced a drop in hemoglobin levels or required blood transfusions or repeat interventions. The two perforations were classified as severe complications and treated conservatively. Three (1%) early complications, all bleedings, occurred and were effectively treated with endoscopic hemostatic techniques and classified as moderately severe complications. In manova the indication for the resection (high-grade intraepithelial neoplasia or early cancer versus low-grade intraepithelial neoplasia or no dysplasia) was found to be significantly associated with an increased risk of acute bleeding. Endoscopic cap resection in BE is safe. Most complications become apparent immediately during the procedure and can be managed endoscopically. Bleeding after the endoscopic resection procedure and severe acute complications (i.e., perforations) are rare (2%).     

Endoscopic therapy in early adenocarcinomas (Barrett's cancer) of the esophagus

The incidence of early esophageal adenocarcinoma has been increasing significantly in recent decades. Prognosis depends greatly on the choice of treatment. Early cancers can be treated by endoscopic resection, whereas advanced carcinomas have to be sent for surgery. Esophageal resection is associated with high perioperative mortality (1–5%) even in specialized centers. Early diagnosis enables curative endoscopic treatment option. Patients with gastrointestinal symptoms and a familial risk for esophageal cancer should undergo upper gastrointestinal endoscopy. High‐definition endoscopes have been developed with technical add‐on that helps endoscopists to find fine irregularities in the esophageal mucosa, but interpreting the findings remains challenging. In this review we discussed novel and old diagnostic procedures and their values, as well as our own recommendations and those of the authors discussed for the diagnosis and treatment of early Barrett's carcinoma. Endoscopic resection is the therapy of choice in early esophageal adenocarcinoma. It is mandatory to perform a subsequent ablation of all residual Barrett's mucosa to avoid metachronous lesions.     

Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection

Background and Aims: The incidence of early colorectal cancer (ECC) has been increasing. The aim of this study was to evaluate the clinical outcome and prognosis of ECC treated by endoscopic mucosal resection (EMR). Methods: A total of 129 ECC patients who were initially treated by EMR between April 2005 and August 2007 were enrolled. Clinicopathological characteristics and prognoses were evaluated retrospectively. Results: En bloc resection was performed in 85% of ECC patients, and piecemeal resection was performed in 15% of patients. Clear lateral and deep margins were achieved in 86% of cases. Of the 129 patients, 64 were found to have intramucosal cancer and 65 had submucosal cancer. Clinical characteristics were not different between patients with intramucosal cancer and submucosal cancer; however, poor differentiation and the absence of background adenoma showed significant association with submucosal cancer. Seven patients with submucosal cancer underwent subsequent surgical resection; five had lymphovascular invasion or a positive resection margin, one had perforation, and one patient requested surgical resection. Of these seven patients, one had residual cancer and two had lymph node metastasis. All patients with intramucosal cancer had no recurrence during the follow‐up period. Seven patients with submucosal cancer showed adverse outcomes within 3 years, such as residual/recurrence of primary cancer or lymph node metastasis; five showed lymphovascular invasion or a positive deep margin, and two had no histological risk factors. Conclusions: Our results suggest that intramucosal cancer shows good prognosis, and a cure could be expected after EMR; however, adverse outcomes can occur in submucosal cancer. Therefore, meticulous endoscopic follow up is needed in patients with submucosal cancer for at least 3 years after EMR.     

Adenocarcinoma arising in Barrett's esophagus

The main goal of this study was to evaluate the development of adenocarcinoma in patients with Barrett's esophagus. During the period from January 1975 to December 1985, a total of 134 patients had endoscopically severe esophagitis and/or Barrett's esophagus. In these patients, 32 (24%) met the macroscopic and histologic criteria for the diagnosis of Barrett's esophagus. A check-up study of these patients was performed in 1987. Adenocarcinoma developed in three patients during the follow-up period of 166.1 patient-years. Dysplasia in the columnar epithelium was found in two of these patients six and 15 months before the diagnosis of adenocarcinoma. The third patient with adenocarcinoma was detected in endoscopic follow-up in 1987. In addition, the endoscopic examination showed unchanged Barrett's epithelium in all but three patients despite the operative and/or medical treatment 3–12 years (mean 6.7 years) earlier. We conclude that Barrett's esophagus is a potential premalignant condition and careful endoscopic surveillance for dysplasia in the columnar epithelium of the distal esophagus is mandatory in patients with Barrett's esophagus.     

《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...     

Endoscopic diagnosis of early Barrett's neoplasia: Perspectives for advanced endoscopic technology

Barrett's esophagus (BE) is a metaplastic condition that occurs secondary to gastroesophageal reflux disease. BE is also a precursor to esophageal adenocarcinoma, which, although still rare in Japan, is one of the most rapidly increasing cancers in Western countries. However, the prevalence of gastroesophageal reflux disease has increased significantly over the past few decades in Japan, possibly leading to an incremental rise in BE and the associated inherent risk of adenocarcinoma. Given the poor prognosis of advanced‐stage Barrett's adenocarcinoma, endoscopic surveillance is recommended for subjects with BE to detect early neoplasias including dysplasia. However, endoscopic identification of dysplastic lesions is still not sufficiently reliable or subjective, making targeted therapy extremely difficult. Over the past few years, improvements in image resolution, image processing software, and optical filter technology have enabled identification of dysplasia and early cancer in BE patients. We retrieved as many studies on advanced endoscopic technologies in BE as possible from MEDLINE and PubMed. The present review focuses on the emergent clinically available technologies to provide an overview of the technologies, their practical applicability, current status, and future challenges.     

Volumetric laser endomicroscopy in Barrett's esophagus: a feasibility study on histological correlation

Volumetric laser endomicroscopy (VLE) is a novel balloon‐based optical coherence tomography (OCT) imaging technique that may improve detection of early neoplasia in Barrett's esophagus (BE). Most OCT studies lack a direct correlation between histology and OCT images. The aim is to investigate the optimal approach for achieving one‐to‐one correlation of ex‐vivo VLE images of endoscopic resection (ER) specimens with histology. BE patients with and without early neoplasia underwent ER after delineating areas with electrocoagulation markers (ECM). After ER, specimens underwent additional ex‐vivo marking with several different markers (ink, pin, Gold Probe) followed by ex‐vivo VLE scanning. ER specimens were carefully sectioned into tissue blocks guided by the markers. Histology and VLE slides were considered a match if ≥ 2 markers were visible on both modalities and mucosal patterns aside from these markers matched on both histology and VLE. From 16 ER specimens 120 tissue blocks were sectioned of which 23 contained multiple markers. Fourteen histology–VLE matches were identified. ECMs and ink markers proved to be the most effective combination for matching. The last 6/16 ER specimens yielded 9/14 matches, demonstrating a learning curve due to methodological improvements in marker placement and tissue block sectioning. One‐to‐one correlation of VLE and histology is complex but feasible. The groundwork laid in this study will provide high‐quality histology–VLE correlations that will allow further research on VLE features of early neoplasia in BE.