Recent advances in endoscopic management of gastric neoplasms

The development and clinical application of new diagnostic endoscopic technologies such as endoscopic ultrasonography with biopsy, magnification endoscopy, and narrow-band imaging, more recently supplemented by artificial intelligence, have enabled wider recognition and detection of various gastric neoplasms including early gastric cancer (EGC) and subepithelial tumors, such as gastrointestinal stromal tumors and neuroendocrine tumors. Over the last decade, the evolution of novel advanced therapeutic endoscopic techniques, such as endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection, along with the advent of a broad array of endoscopic accessories, has provided a promising and yet less invasive strategy for treating gastric neoplasms with the advantage of a reduced need for gastric surgery. Thus, the management algorithms of various gastric tumors in a defined subset of the patient population at low risk of lymph node metastasis and amenable to endoscopic resection, may require revision considering upcoming data given the high success rate of en bloc resection by experienced endoscopists. Moreover, endoscopic surveillance protocols for precancerous gastric lesions will continue to be refined by systematic reviews and meta-analyses of further research. However, the lack of familiarity with subtle endoscopic changes associated with EGC, as well as longer procedural time, evolving resection techniques and tools, a steep learning curve of such high-risk procedures, and lack of coding are issues that do not appeal to many gastroenterologists in the field. This review summarizes recent advances in the endoscopic management of gastric neoplasms, with special emphasis on diagnostic and therapeutic methods and their future prospects.     

Current role of minimally invasive approaches in the treatment of early gastric cancer

Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing approximately 50%of newly detected gastric cancer cases in Asian countries.Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis.Laparoscopic and robotic resections for early gastric cancer,including function-preserving resections,have propagated through advances in technology and surgeon experience.The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer.     

Endoscopic surveillance strategy after endoscopic resection for early gastric cancer

Early detection of early gastric cancer(EGC)is important to improve the prognosis of patients with gastric cancer.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and high-frequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection,a therapeutic option for gastric intraepithelial neoplasia.Consequently,short-term outcomes of endoscopic resection(ER)for EGC have improved.Therefore,surveillance with endoscopy after ER for EGC is becoming more important,but how to perform endoscopic surveillance after ER has not been established,even though the follow-up strategy for more advanced gastric cancer has been outlined.Therefore,a surveillance strategy for patients with EGC after ER is needed.     

Endoscopic advances in the management of gastric cancer and premalignant gastric conditions

Gastric cancer is the fifth most common cancer and in 2018, it was the third most common cause of cancer-related deaths worldwide. Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions. In this review, we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs late-stage gastric cancer outcomes. We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions. This includes the implementation of different imaging modalities such as narrow-band imaging, chromoendoscopy, confocal laser endomicroscopy, and other experimental techniques. We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer. We then discuss the endoscopic advances made in the treatment of these conditions, including endoscopic mucosal resection, endoscopic submucosal dissection, and hybrid techniques such as laparoscopic endoscopic cooperative surgery. Finally, we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.     

胃癌术前分期的研究现状

准确的胃癌术前分期是胃癌综合治疗方案实施的需要.早期胃癌,特别是黏膜内癌,可以行内镜下切除以避免不必要的外科手术;为了获得局部进展期胃癌R0切除,新辅助治疗备受关注并已展开探索.随着内镜超声检查(endoscopic ultrasonography,EUS)、经腹超声检查(transabdominal ultrason...     

Outcome after endoscopic submucosal dissection for early gastric cancer in Korea

Endoscopic treatment,such as endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD),has been established as one of the treatment options for selected cases with early gastric cancer(EGC).Most studies on this topic have been carried out by researchers in Japan.Recently,the experience in EMR/ESD for EGC outside Japan is increasingly reported.In Korea,gastric cancer is the most common malignant disease,and the second leading cause of cancer death.Currently,EMR for EGC is widely performed i...     

早期胃癌内镜治愈性切除的影响因素

目的分析影响早期胃癌内镜治愈性切除的危险因素,提高内镜治愈性切除早期胃癌的可能性。方法收集2008年10月至2013年3月行内镜切除治疗的早期胃癌（包括高级别上皮内瘤变）患者的临床资料;分析性别、年龄、病灶位置、病灶直径、病灶内镜形态学分型及伴有溃疡形成6个因素对内镜切除术（ER）整块切除及治愈性切除的影响;同时分析非治愈性切除的主要原因。结果纳入早期胃癌共94例包含94个病灶,其中高级别上皮内瘤变病灶20个,黏膜内癌病灶70个,黏膜下浅层浸润癌（距黏膜肌层500斗m以内）病灶4个。其中5个病灶经EMR切除,89个病灶经ESD切除。ER整块切除率为95．7％（90／94）,治愈性切除率为79．8％（75／94）。直径〉3．0cm的病灶治愈性切除率显著低于直径≤2．0em的病灶（P=0．022,OR=0．108,95％C1：0．016—0．721）,伴有溃疡形成的病灶治愈性切除率显著低于不伴有溃疡形成的病灶（P=0．047,OR=0．149,95％CI：0．023～0．971）。非治愈性切除的主要原因是侧缘肿瘤细胞的残留。结论病灶直径〉3．0cm、伴有溃疡形成是影响早期胃癌ER治愈性切除的危险因素。     

Management of complications following endoscopic submucosal dissection for gastric cancer

Endoscopic treatment should be considered for early gastric cancer(EGC)and gastric precancerous lesions.Endoscopic submucosal dissection(ESD)was developed for en bloc removal of a large gastric neoplasm and has been developed following improvements in electrical equipment for hemostasis and dissection and with advances in various knives,hemostatic forceps and endoscopic equipment.ESD is currently the treatment of choice for precancerous lesions or EGC showing mucosal invasion.Hemorrhage and perforation are major complications of ESD for EGC.We describe the complication of ESD procedures in gastric lesions for endoscopists who are relatively inexperienced in ESD and who may lack optimal access to ESD education and facilities.     

食管早期癌和癌前病变超声内镜诊断及内镜下食管黏膜切除术的临床研究

目的探讨食管早期癌和癌前病变超声内镜诊断价值及内镜下食管黏膜切除术的临床治疗价值。方法 61例食管早期癌和癌前病变行超声内镜检查探测病变浸润深度,位于黏膜层及黏膜肌层的食管早期癌和癌前病变行内镜下食管黏膜切除术（EMR）,位于黏膜下层的食管早期癌行外科手术治疗。EMR术28例,外科手术33例。比较超声内镜和术后病理判断病变浸润深度。结果超声内镜判断食管黏膜内癌的特异性和敏感性为94.1%（48/51）、98.0%（48/49）;黏膜下癌的特异性和敏感性为80.0%（8/10）、72.7%（8/11）;鉴别黏膜内癌及黏膜下癌浸润深度准确率为91.8%（56/61）。28例EMR术后病理：14例食管早期癌和12例食管黏膜中重度异型增生完全切除,完全切除成功率为92.9%（26/28）,观察3～45个月无复发。结论超声内镜能较准确鉴别食管早期癌和癌前病变浸润深度,黏膜切除术治疗食管早期癌和癌前病变是安全有效的内镜治疗方法。     

Efficacy of Helicobacter pylori eradication for the prevention of metachronous gastric cancer after endoscopic resection for early gastric cancer

Helicobacter pylori(H.pylori)plays an important role in gastric carcinogenesis,as the majority of gastric cancers develop from H.pylori-infected gastric mucosa.The rate of early gastric cancer diagnosis has increased in Japan and Korea,where H.pylori infection and gastric cancer are highly prevalent.Early intestinal-type gastric cancer without concomitant lymph node metastasis is usually treated by endoscopic resection.Secondary metachronous gastric cancers often develop because atrophic mucosa left untreated after endoscopic treatment confers a high risk of gastric cancer.The efficacy of H.pylori eradication for the prevention of metachronous gastric cancer remains controversial.However,in patients who undergo endoscopic resection of early gastric cancer,H.pylori eradication is recommended to suppress or delay metachronous gastric cancer.Careful and regularly scheduled endoscopy should be performed to detect minute metachronous gastric cancer after endoscopic resection.     

Endoscopic submucosal dissection and surgical treatment for gastrointestinal cancer

Endoscopic submucosal dissection (ESD) is widely usedin Japan as a minimally invasive treatment for earlygastric cancer. The application of ESD has expanded tothe esophagus and colorectum. The indication criteriafor endoscopic resection (ER) are established for eachorgan in Japan. Additional treatment, including surgery with lymph node dissection, is recommended when pathological examinations of resected specimens donot meet the criteria. Repeat ER for locally recurrent gastrointestinal tumors may be difficult because of submucosal fibrosis, and surgical resection is required inthese cases. However, ESD enables complete resectionin 82%-100% of locally recurrent tumors. Transanal endoscopic microsurgery (TEM) is a well-developed sur-gical procedure for the local excision of rectal tumors.ESD may be superior to TEM alone for superficial rectaltumors. Perforation is a major complication of ESD,and it is traditionally treated using salvage laparotomy.However, immediate endoscopic closure followed byadequate intensive treatment may avoid the need forsurgical treatment for perforations that occur during ESD. A second primary tumor in the remnant stomach after gastrectomy or a tumor in the reconstructedorgan after esophageal resection has traditionally required surgical treatment because of the technical difficulty of ER. However, ESD enables complete resectionin 74%-92% of these lesions. Trials of a combination ofESD and laparoscopic surgery for the resection of gastric submucosal tumors or the performance of sentinellymph node biopsy after ESD have been reported, butthe latter procedure requires a careful evaluation of itsclinical feasibility.     

Optimal management of biopsy-proven low-grade gastric dysplasia

Gastric adenocarcinoma generally culminates via the inflammation-metaplasia-dysplasia-carcinoma sequence progression. The prevalence of gastric adenomas shows marked geographic variation. Recently, the rate of diagnosis of low-grade dysplasia(LGD) has increased due to increased use of upper endoscopy. Many investigators have reported that gastric highgrade dysplasia has high potential for malignancy and should be removed; however, the treatment for gastric LGD remains controversial. Although the risk of LGD progression to invasive carcinoma has been reported to be inconsistent, progression has been observed during follow-up. Additionally, the rate of upgraded diagnosis in biopsy-proven LGD is high. Therefore, endoscopic resection(ER) may be useful in the treatment and diagnosis of LGD, especially if lesions are found to have risk factors for upgraded histology after ER, such as large size, surface erythema or depressed morphology. Fatal complications in endoscopic submucosal dissection(ESD) are extremely low and its therapeutic and diagnostic outcomes are excellent. Therefore, ESD should be applied preferentially instead of endoscopic mucosal resection.     

胃癌癌前病变的研究进展及防治对策

胃癌癌前病变(precancerous lesions of gastric cancer,PLGC)是胃癌发生和发展过程中的一个重要阶段,早期发现和干预是防控胃癌的重要手段.在PLGC的形成过程中,DNA甲基化、微卫星不稳定性、p53以及幽门螺杆菌(Helicobacter pylori,H.pylori)感染等占有重要位置.鉴于胃癌的高度恶性,且其病因发病机制尚未完全阐明,实施针对病因的一级预防比较困难.本文就目前PLGC发病机制、防治对策等问题进行总结,以便于临床医师对胃癌前病变进行密切的监测及有效的干预.     

Early gastric cancer: A challenge in Western countries

Early gastric cancer(EGC)is an invasive carcinoma involving only the stomach mucosa or submucosa,independently of lymph node status.EGC represents over 50%of cases in Japan and in South Korea,whereas it accounts only for approximately 20%of all newly diagnosed gastric cancers in Western countries.The main classification systems of EGC are the Vienna histopathologic classification and the Paris endoscopic classification of polypoid and non-polypoid lesions.A careful endoscopic assessment is fundamental to establish the best treatment of EGC.Generally,EGCs are curable if the lesion is completely removed by endoscopic resection or surgery.Some types of EGC can be resected endoscopically;for others the most appropriate treatment is surgical resection and D2 lymphadenectomy,especially in Western countries.The favorable oncological prognosis,the extended lymphadenectomy and the reconstruction of the intestinal continuity that excludes the duodenum make the prophylactic cholecystectomy mandatory to avoid the onset of biliary complications.     

早期胃癌内镜下切除日本指南的历史和未来展望

日本胃癌治疗指南首次发表于2001年,其目的是为了明确不同治疗方案的适应证,从而减少不同医疗机构间治疗方式的差异。随着病例的积累及内镜黏膜下剥离术(ESD)的发展,早期胃癌(EGC)内镜下切除(ER)的适应证和治愈性范围有所扩大,但是,仍有部分问题亟待解决。使用风险评分系统(eCura system)评估淋巴结转移(LNM)的情况,可能有助于确定不符合内镜切除标准的EGC患者的治疗方案。对于不符合内镜切除标准的EGC患者,即最新指南中的eCura C-2分期的患者,尽管他们的LNM风险较高,但对于很多患者来说,追加胃切除联合淋巴结清扫术仍然是过度的治疗。而保留功能的低侵入性手术,如内镜下非开放式胃壁反转切除术联合腹腔镜前哨淋巴结活检,有可能会解决该问题。此外,对于拒绝追加胃切除术的患者,可采取更多的低侵入性治疗方式,如ER联合化疗。     

Unveiling lymph node metastasis in early gastric cancer

With respect to gastric cancer treatment,improvements in endoscopic techniques and novel therapeutic modalities[such as endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)]have been developed.Currently,EMR/ESD procedures are widely accepted treatment modalities for early gastric cancer(EGC).These procedures are most widely accepted in Asia,including in Korea and Japan.In the present era of endoscopic resection,accurate prediction of lymph node(LN)metastasis is a critical component of selecting suitable patients for EMR/ESD.Generally,indications for EMR/ESD are based on large Japanese datasets,which indicate that there is almost no risk of LN metastasis in the subgroup of EGC cases.However,there is some controversy among investigators regarding the validity of these criteria.Further,there are currently no accurate methods to predict LN metastasis in gastric cancer(for example,radiologic methods or methods based on molecular biomarkers).We recommend the use of a 2-step method for the management of early gastric cancer using endoscopic resection.The first step is the selection of suitable patients for endoscopic resection,based on endoscopic and histopathologic findings.After endoscopic resection,additional surgical intervention could be determined on the basis of a comprehensive review of the endoscopic mucosal resection/endoscopic submucosal dissection specimen,including lymphovascular tumor emboli,tumor size,histologic type,and depth of invasion.However,evaluation of clinical application data is essential for validating this recommendation.Moreover,gastroenterologists,surgeons,and pathologists should closely collaborate and communicate during these decisionmaking processes.     

Endoscopic mucosal resection and endoscopic submucosal dissection for early gastric cancer: Current and original devices

Compared with endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR) is easier to perform and requires less time for treatment. However, EMR has been replaced by ESD, because achieving en bloc resection of specimens > 20 mm in diameter is difficult with EMR. The technique of ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precise histological diagnosis and can also reduce the rate of recurrence, but has a high level of technical difficulty, and is consequently associated with a high rate of complications, a need for advanced endoscopic techniques, and a lengthy procedure time. To overcome disadvantages in both EMR and ESD, various advances have been made in submucosal injections, knives, other accessories, and in electrocoagulation systems.     

Upgrade of Lesions Initially Diagnosed as Low-Grade Gastric Dysplasia upon Forceps Biopsy Following Endoscopic Resection

Background/Aims

Gastric dysplasia is generally accepted to be the precursor lesion of gastric carcinoma. Approximately 25% to 35% of histological diagnoses based on endoscopic forcep biopsies for gastric dysplastic lesions change following endoscopic resection (ER). The aim of this study was to determine the predictive endoscopic features of high-grade gastric dysplasia (HGD) or early gastric cancer (EGC) following ER for lesions initially diagnosed as low-grade dysplasia (LGD) by a forceps biopsy.

Methods

To determine predictive variables for upgraded histology (LGD to HGD or EGC). The lesion size, gross endoscopic appearance, location, and surface nodularity or redness as well as the presence of a depressed portion, Helicobacter pylori infection, and intestinal metaplasia were retrospectively investigated.

Results

Among 251 LGDs diagnosed by an initial forceps biopsy, the diagnoses of 100 lesions (39.8%) changed following the ER; 56 of 251 LGDs (22.3%) were diagnosed as HGD, 39 (15.5%) as adenocarcinoma, and 5 (2.0%) as chronic gastritis. In a univariate analysis, large lesions (>15 mm), those with a depressed portion, and those with surface nodularity were significantly correlated with a upgraded histology classification following ER. In a multivariate analysis, a large size (>15 mm; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.46 to 5.43) and a depressed portion in the lesion (OR, 2.7; 95% CI, 1.44 to 5.03) were predictive factors for upgraded histology following ER.

Conclusions

Our study shows that a substantial proportion of diagnoses of low-grade gastric dysplasias based on forceps biopsies were not representative of the entire lesion. We recommend ER for lesions with a depressed portion and for those larger than 15 mm.     

Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication

The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori(H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection(ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies.The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy(NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritislike"appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H.pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.     

经口牵引辅助下内镜黏膜下剥离术治疗早期胃癌及癌前病变的临床研究（含视频）

目的评估经口牵引辅助下内镜黏膜下剥离术（ESD）治疗早前胃癌及癌前病变的疗效和价值。方法2013年7月至2014年8月经胃镜及超声胃镜检查判断局限于黏膜层、未侵及固有肌层的早期胃癌及癌前病变患者44例,其中22例采用经口牵引辅助下ESD治疗（牵引组）,22例采用常规ESD治疗（对照组）,评估2组在病灶开始标记至完整剥离时间、黏膜暴露至完整剥离时间、单位时间切除率、操作困难部位切除时间、一次性整块切除率、一次性完整切除率、出血发生率、穿孔发生率等情况。结果牵引组较对照组,病灶开始标记至完整剥离时间[（48．13±14．65）min比（65．07±29．07）min,P〈0．05]、黏膜暴露至完整剥离时间[（37．47±14．17）min比（54．93±28．16）min,P〈0．05]、操作困难部位切除时间[（33．17±10．65）min比（54．53±46．92）min,P〈0．05]均明显缩短,单位时间切除率[（23．60±14．73）mm。／min比（13．62±8．11）mm。／min,P〈0．05]明显提高。2组一次性整块切除率、一次性完整切除率、出血发生率、穿孔发生率及容易操作部位切除时间相似（P〉0．05）,随访均未见局部复发。结论经口牵引辅助下ESD治疗早期胃癌及癌前病变可提高切除效率,对治疗早期胃癌及癌前病变具有较好的应用价值。