Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.     

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.     

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...     

Endoscopic treatments for small gastric subepithelial tumors originating from muscularis propria layer

Minimally invasive endoscopic resection has become an increasingly popular method for patients with small (less than 3.5 cm in diameter) gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer. Currently, the main endoscopic therapies for patients with such tumors are endoscopic muscularis excavation, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection. Although these endoscopic techniques can be used for complete resection of the tumor and provide an accurate pathological diagnosis, these techniques have been associated with several negative events, such as incomplete resection, perforation, and bleeding. This review provides detailed information on the technical details, likely treatment outcomes, and complications associated with each endoscopic method for treating/removing small gastric SETs that originate from the MP layer.     

Endoscopic submucosal tunnel dissection salvage technique for ulcerative early gastric cancer

Endoscopic submucosal dissection is an effective treatment modality for early gastric cancer (EGC), though the submucosal fibrosis found in ulcerative EGC is an obstacle for successful treatment. This report presents two cases of ulcerative EGC in two males, 73- and 80-year-old, with severe fibrosis. As endoscopic ultrasonography suggested that the EGCs had invaded the submucosal layer, the endoscopic submucosal tunnel dissection salvage technique was utilized for complete resection of the lesions. Although surgical gastrectomy was originally scheduled, the two patients had severe coronary heart disease, and surgeries were refused because of the risks associated with their heart conditions. The endoscopic submucosal tunnel dissection salvage technique procedures described in these cases were performed under conscious sedation, and were completed within 30 min. The complete en bloc resection of EGC using endoscopic submucosal tunnel dissection salvage technique was possible with a free resection margin, and no other complications were noted during the procedure. This is the first known report concerning the use of the endoscopic submucosal tunnel dissection salvage technique salvage technique for treatment of ulcerative EGC. We demonstrate that endoscopic submucosal tunnel dissection salvage technique it is a feasible method showing several advantages over endoscopic submucosal dissection for cases of EGC with fibrosis.     

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.     

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.     

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目的提高对胃异位胰腺的诊断及治疗水平。方法2000-2004年对解放军总医院消化科241例胃黏膜下肿物进行超声内镜(EUS)检查,回顾分析胃异位胰腺的图像特征。结果EUS诊断良性间质瘤105例,恶性间质瘤23例,脂肪瘤48例,异位胰腺45例,囊肿20例。异位胰腺EUS图像特点:(1)黏膜下层病变39例,6例与固有肌层无分界;(2)边界清37例;(3)42例为不均匀、形状不规则中强回声,3例为不均匀低回声;(4)32例中心有小的不规则液性回声。内镜电切26例,无出血穿孔等并发症。结论超声内镜对胃异位胰腺的诊断有一定价值,内镜切除是安全有效的治疗方法。     

Cutting edge of endoscopic full-thickness resection for gastric tumor

Recently,several studies have reported local full-thickness resection techniques using flexible endoscopy for gastric tumors,such as gastrointestinal stromal tumors,gastric carcinoid tumors,and early gastric cancer(EGC). These techniques have the advantage of allowing precise resection lines to be determined using intraluminal endoscopy. Thus,it is possible to minimize the resection area and subsequent deformity. Some of these methods include:(1) classical laparoscopic and endoscopic cooperative surgery(LECS);(2) inverted LECS;(3) combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique; and(4) non-exposed endoscopic wall-inversion surgery. Furthermore,a recent prospective multicenter trial of the sentinel node navigation surgery(SNNS) for EGC has shown acceptable results in terms of sentinel node detection rate and the accuracy of nodal metastasis. Endoscopic full-thickness resection with SNNS is expected to become a treatment option that bridges the gap between endoscopic submucosal dissection and standard surgery for EGC. In the future,the indications for these procedures for gastric tumors could be expanded.     

内镜下胃间质瘤检出情况探讨

目的探讨首都医科大学附属北京友谊医院消化内镜中心胃间质瘤内镜下的检出率。方法对2004年5月～2010年5月于首都医科大学附属北京友谊医院消化内镜中心行胃镜检查发现胃黏膜下隆起性病变而进行超声检查的病例进行回顾性分析,计算胃间质瘤检出的阳性率。结果6年间胃镜检查共计52368例,胃黏膜下隆起病变461例。其中240例行超声内镜检查,怀疑胃间质瘤161例,其中切除治疗36例,术后病理证实33例。估计胃间质瘤的内镜下检出率约为0．5％。结论消化内镜及超声内镜是胃间质瘤重要的诊断方法,对选择合适的治疗方案具有指导意义。     

Endoscopic prediction of tumor margin and invasive depth in early gastric cancer

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer‐related deaths in the world. The prognosis of GC is clearly associated with the tumor stage, with a 5‐year overall survival rate for early gastric cancer (EGC) exceeding 90%, which is significantly higher than that of advanced gastric cancer. Endoscopic resection, including endoscopic mucosal resection and endoscopic submucosal dissection, has been adopted in recent decades as the first treatment option of EGC in many countries for its minimal invasion and high curative rate. However, the horizontal and vertical margins are related to the curative resection of EGC and the prognosis of patients. Thus the accurate prediction of the tumor boundary and its invasive depth before treatment counts for much in planning the most appropriate treatment strategy and promising curative resection. To date, various endoscopic techniques have been identified to play a role in pretreatment evaluation, such as white light endoscopy, chromoendoscopy, narrow band imaging and endoscopic ultrasonography. This article aimed to summarize the diagnostic methods, applications and limitations of these different endoscopic techniques for identifying tumor horizontal and vertical margins in EGC, helping to increase preoperative evaluation of capabilities and to improve the curative resection rate of EGC.     

早期胃癌内镜下切除术后复发的相关因素分析

目的 探讨早期胃癌内镜下切除术后复发的相关性因素.方法 回顾性分析解放军总医院169例早期胃癌经内镜下切除治疗并定期随访患者的临床病理资料.结果 随访时间13～57个月(中位时间24.5个月),169例患者中12例出现胃癌复发,总复发率为7.10%,复发时间为3～36(28±23)个月,中位时间18个月,0.5、1、2、3年的复发率分别为1.18%(2/169)、3.55%(6/169)、9.91%(11/111)、12.24%(12/98).12例复发患者有11例发生在2年以内,其中组织分化不良(低分化腺癌和印戒细胞癌)、浸润至黏膜下层、有淋巴管浸润的早期胃癌容易出现术后复发(P＜0.05).结论 早期胃癌内镜下切除术后的复发多出现在2年以内.组织分化不良、肿瘤浸润至黏膜下层及有淋巴管浸润是术后复发的危险因素,严谨的内镜随访对于这些患者尤为重要.

Abstract：

Objective To investigate the related factors of recurrence of early gastric cancer (EGC) after endoscopic resection. Methods Clinicopathologic data of 169 patients with EGC who underwent endoscopic resection and periodically followed up by the Chinese PLA General hospital were analyzed retrospectively. Results During a follow-up of 13-57 months (median time 24. 5 months), 12patients had gastric cancer again and the recurrence rate was 7. 1% (12/169). The recurrence time varied from 3 to 36 (28 ± 23)months and the median time was 18 months. The recurrence rates of 0.5 year, 1st year, 2nd year and 3rd year were 1.18% (2/169), 3.55% (6/169), 9.91% (11/111) and 12.24%(12/98), respectively. Eleven patients had gastric cancer again within 2 years after resection.Undifferentiated histology (including poorly differentiated carcinoma and signet ring cell carcinoma),submucosal infiltration and lymphovascular invasion of the primary lesion of EGC were related to thepostsurgical recurrence ( all P ＜ 0. 05). Conclusion Most recurrence of EGC occurred within 2 years afterendoscopic resecton and is related with undifferentiated histology, submucosal infiltration andlymphovascular invasion. It is important for these patients to receive endoscopy follow up.     

Treatment modalities for early gastric cancer

Different treatment modalities have been proposed in the treatment of early gastric cancer (EGC). Endoscopic resection (ER) is an established treatment that allows curative treatment, in selected cases. In addition, ER allows for an accurate histological staging, which is crucial when deciding on the best treatment option for EGC. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become alternatives to surgery in early gastric cancer, mainly in Asian countries. Patients with “standard” criteria can be successfully treated by EMR techniques. Those who meet “expanded” criteria may benefit from treatment by ESD, reducing the need for surgery. Standardized ESD training system is imperative to promulgate effective and safe ESD technique to practices with limited expertise. Although endoscopic resection is an option in patients with EGC, surgical treatment continues to be a widespread therapeutic option worldwide. In this review we tried to point out the treatment modalities for early gastric cancer.     

Ever-changing endoscopic treatment for early gastric cancer: Yesterday-today-tomorrow

Endoscopic resection has been an optimal treatment for selected patients with early gastric cancer (EGC) based on advances in endoscopic instruments and techniques. As endoscopic submucosal dissection (ESD) has been widely used for treatment of EGC along with expanding ESD indication, concerns have been asked to achieve curative resection for EGC while guaranteeing precise prediction of lymph node metastasis (LNM). Recently, new techniques including ESD or endoscopic full-thickness resection combined with sentinel node navigation enable minimal tumor resection and a laparoscopic lymphadenectomy in cases of EGC with high risk of LNM. This review covers the development and challenges of endoscopic treatment for EGC. Moreover, a new microscopic imaging and endoscopic techniques for precise endoscopic diagnosis and minimally invasive treatment of EGC are introduced.     

Endoscopic ultrasound-guided deep and large biopsy for diagnosis of gastric infiltrating tumors with negative malignant endoscopy biopsies

AIM: To assess the diagnostic yield and safety of adeep and large biopsy technique under the guidance of endoscopic ultrasound(EUS) for diagnosis of gastric infiltrating tumors with negative malignant endoscopy biopsies.METHODS: From January 2009 to March 2014, 36 patients in whom gastric infiltrating tumors had been diagnosed by EUS received negative results for malignancy after endoscopic biopsies. The deep and large biopsy technique combined bite-on-bite technique with or without endoscopic mucosal resection(EMR) to obtain submucosal tissue from lesions. EUS was used to select the appropriate biopsy sites. If the lesion protruded into the cavity, EMR was performed for removal of the overlying mucosa and then bite-onbite technique was conducted in the resected area to obtain submucosal tissue. If the lesion appeared to be flat or was difficult to lift by injection, the bite-on-bite technique was directly used.RESULTS: Twenty-eight of the 36 patients were treated by EMR followed by bite-on-bite technique, while 8 patients only underwent bite-on-bite technique. Histological results showed 23 of the 36 lesions were poorly differentiated adenocarcinomas, 2 diffuse large B cell lymphomas, 4 mucosa-associated lymphoid tissue-type lymphomas, and 7 undiagnosed. The deep and large biopsy technique provided a definitive and conclusive diagnosis in 29(80.6%) of the 36 patients. The 12 gastric linitis plastica and 6 lymphoma patients received chemotherapy and avoided surgery. Minor oozing of blood in 2 mucosal resection wounds was managed by argon plasma coagulation and in 5 cases after deep biopsies by epinephrine(0.001%). Neither severe hemorrhage nor perforation occurred in any patient.CONCLUSION: The deep and large biopsy technique is superior to ordinary endoscopic biopsy for achieving an accurate diagnosis of gastric infiltrating tumors.This procedure guided by EUS is an effective and safe diagnostic method for gastric infiltrating tumors in which endoscopic biopsy results were negative for malignancy.     

Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection

An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection(ESD) for early gastric cancer(EGC).Two years after the initial ESD, a 0-Ⅱc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum.The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma.ESD was performed for this lesion and en bloc resection with negative margins was achieved.Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer(1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection.Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection.Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD.Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known.The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.     

Advantages of endoscopic submucosal dissection over conventional endoscopic mucosal resection

BACKGROUND: Endoscopic mucosal resection is an established method for treating intramucosal gastric neoplasms. Conventional endoscopic mucosal resection has predominantly been performed using strip biopsy, but local recurrence sometimes occurs due to such piecemeal resection. Endoscopic submucosal dissection has recently been performed in Japan using new devices such as an insulation-tip diathermic knife. The efficacy and problems associated with endoscopic submucosal dissection were evaluated by comparison with conventional endoscopic mucosal resection. METHODS: Treatment consisted of conventional endoscopic mucosal resection for 48 lesions from January 1999 to October 2002, and endoscopic submucosal dissection for 59 lesions from November 2002 to June 2005. Endoscopic submucosal dissection was performed using an insulation-tip diathermic knife and flex and hook knives, as appropriate. RESULTS: For lesions >or=11 mm in size, en bloc resection rates were significantly higher with endoscopic submucosal dissection than with conventional endoscopic mucosal resection, but treatment time was significantly longer. En bloc resection rates were higher with endoscopic submucosal dissection than with conventional endoscopic mucosal resection in all areas. Treatment of lesions in the upper one-third of the stomach took a long time using endoscopic submucosal dissection, and intraoperative bleeding was frequent. However, en bloc resection rates and intraoperative bleeding with endoscopic submucosal dissection were improved using various knives. CONCLUSIONS: Endoscopic submucosal dissection can take a long time, but is superior to conventional endoscopic mucosal resection for treating intramucosal gastric neoplasms.     

Resection of early esophageal neoplasms: The pendulum swings from surgical to endoscopic management

Esophageal cancer is a highly lethal disease and is the sixth leading cause of cancer related mortality in the world. The standard treatment is esophagectomy which is associated with significant morbidity and mortality. This led to development of minimally invasive, organ sparing endoscopic therapies which have comparable outcomes to esophagectomy in early cancer. These include endoscopic mucosal resection and endoscopic submucosal dissection. In early squamous cell cancer, endoscopic submucosal dissection is preferred as it is associated with cause specific 5-year survival rates of 100% for M1 and M2 tumors and 85% for M3 and SM1 tumors and low recurrence rates. In early adenocarcinoma, endoscopic resection of visible abnormalities is followed by ablation of the remaining flat Barrett's mucosa to prevent recurrences.Radiofrequency ablation is the most widely used ablation modality with others being cryotherapy and argon plasma coagulation. Focal endoscopic mucosal resection followed by radiofrequency ablation leads to eradication of neoplasia in93.4% of patients and eradication of intestinal metaplasia in 73.1% of patients.Innovative techniques such as submucosal tunneling with endoscopic resection are developed for management of submucosal tumors of the esophagus. This review includes a discussion of various endoscopic techniques and their clinical outcomes in early squamous cell cancer, adenocarcinoma and submucosal tumors. An overview of comparison between esophagectomy and endoscopic therapy are also presented.     

Endoscopic submucosal dissection of early gastric cancer

Gastric cancer is the most common cancer worldwide. The proportion of early gastric cancer (EGC) cases at diagnosis has increased because of the use of mass screening endoscopy in older adults. Endoscopic mucosal resection has become the standard treatment for EGC in cases with standard indications because of its low risk of lymph node metastasis. A new endoscopic method, endoscopic submucosal dissection, has recently become available. This method allows en bloc resection without limitation of the size of the lesion. The goal of this article is to review the history and methods of endoscopic treatment with EGC, the conventional and extended indications, the therapeutic outcomes, and the complication rates.     

Technical issues and new devices of ESD of early gastric cancer

Endoscopic submucosal dissection(ESD) is a highly refined technique compared to conventional endoscopic mucosal resection.It enables complete resection of early gastric cancer(EGC) which has no possibility of lymph node metastasis.Indication for ESD of EGC generally entails early gastric cancer confined to the mucosa with well differentiated histology,though there are clinically suitable expanded criteria.As ESD requires specific skill and expertise,endoscopists need to be familiarized with basic methods an...