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.     

Endoscopic predictive factors associated with local recurrence after gastric endoscopic submucosal dissection

Objective: Endoscopic submucosal dissection (ESD) has been accepted as the treatment of choice for gastric epithelial neoplasia. Endoscopic characteristics of the primary lesion and post-ESD scars may be informative to predict the possibility of local recurrence.

Methods: Between November 2008 and July 2015, a retrospective study was conducted in a single-tertiary referral hospital. Consecutive patients who underwent ESD for early gastric cancer (EGC) or high-grade dysplasia were analyzed to evaluate the incidence of local recurrence and associated endoscopic characteristics.

Results: A total of 639 lesions were analyzed. The rates of en-bloc and complete resection were 98.1% and 95.5%, respectively. A total of 15 local recurrent lesions were found (2.3%). The endoscopic findings of primary lesions associated with local recurrence were a lesion size ≥20?mm (odds ratio, OR, 4.408; 95% confidence interval, CI, 1.369–14.186, p?=?.013) and incomplete endoscopic resection (OR 17.059, 95% CI 4.887–59.551, p?Conclusion: Lesions with larger size (≥ 20?mm) and incompletely resected lesions had higher risk of local recurrence. Endoscopic forceps biopsy is unnecessary for even-flat ESD scar without erythematous changes.     

《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...     

Clinical impact of Epstein-Barr virus status on the incidence of lymph node metastasis in early gastric cancer

Epstein-Barr virus-positive gastric cancer (EBVGC) comprises approximately 9% of all gastric cancers and is associated with a low prevalence of lymph node metastasis (LNM). Given that limited data concerning LNM in EBV-related early GC are available, EBV status is not considered an indicator for endoscopic submucosal dissection (ESD). In this review, we focused on pT1 EBVGC and on gastric carcinoma with lymphoid stroma (GCLS), and discuss expanded ESD indications and curative resection criteria. In pT1b EBVGC, the incidence of LNM was low (6/180 patients, 3.3%; 95% confidence interval [CI] 1.2–7.1), especially in lymphovascular invasion-negative EBVGC (1/109 patients, 0.9%). No patients with pT1a EBVGC had LNM (0/38 patients, 0%; 95% CI 0–7.6), even those who did not meet the current curative ESD criteria. Although the frequency of LNM in GCLS was low (5.0–10.6%), the incidence of LNM in non-EBV GCLS was relatively high (10.0–20.0%); therefore, EBV status can be considered a more important factor than GCLS. In summary, the clinicopathological characteristics of EBVGC differ from those of conventional GC, and EBV negativity is a risk factor for LNM in early GC. Therefore, patients in this group are likely to be promising candidates for ESD, and we recommend that EBV status evaluation be included in early GC treatment guidelines.     

Long-term use of proton pump inhibitors does not affect ectopic and metachronous recurrence of gastric cancer after endoscopic treatment

Abstract

Objective: Long-term administration of proton pump inhibitors (PPIs) after eradication of Helicobacter pylori infection has been reported to increase the risk for development of gastric cancer (GC). We investigated whether long-term administration of PPI affects ectopic and metachronous recurrence of GC after endoscopic treatment.

Methods: Participants were 687 patients who underwent endoscopic treatment for GC from January 2005 to March 2018. Questionnaire surveys and medical record reviews of medications, including PPIs, H₂ receptor antagonists and low-dose aspirin (LDA) were conducted for all patients. The influence of PPI in ectopic and metachronous recurrence of GC was evaluated with Cox’s proportional hazard analysis.

Results: Patients who did not respond to the questionnaire and those who underwent additional treatment after endoscopic treatment were excluded from analyses; 418 patients were included. During an average observation period of 1608 days (range, 375–4993 days), 136 patients (32.5%) took PPIs for more than 1 year and 94 took PPIs for more than 3 years; of those, 40 had ectopic and metachronous recurrences. Cox’s proportional hazards analysis revealed that long-term use of PPIs (for both 1 year and 3 years) was not a risk factor for recurrence. In addition, age, severity of gastric atrophy, long-term use of LDA, current infection with H. pylori, and cure achieved with the first endoscopic treatment were also not risk factors for recurrence.

Conclusions: Long-term use of PPIs does not affect ectopic and metachronous recurrence of GC after endoscopic treatment.     

Laparoscopic and endoscopic cooperative surgery for full-thickness resection and sentinel node dissection for early gastric cancer

The endoscopic submucosal dissection (ESD) technique has become the gold standard for submucosal tumors that have negligible risk of lymph node metastasis (LNM), due to its minimal invasiveness and ability to improve quality of life. However, this technique is limited in stage T1 cancers that have a low risk of LNM. Endoscopic full thickness resection can be achieved with laparoscopic endoscopic cooperative surgery (LECS), which combines laparoscopic gastric wall resection and ESD. In LECS, the surgical margins from the tumor are clearly achieved while performing organ-preserving surgery. To overcome the limitation of classical LECS, namely the opening of the gastric wall during the procedure, which increases the risk of peritoneal tumor seeding, non-exposed endoscopic wall-inversion surgery was developed. With this full-thickness resection technique, contact between the intra-abdominal space and the intragastric space was eliminated.     

Lymph node metastasis in differentiated-type early gastric cancer: a single-center retrospective analysis of surgically resected cases

Background. Lymph node metastasis (LNM) from early gastric cancer (EGC) is rare, especially for differentiated-type EGC. However, LNM has been reported in a few cases after endoscopic curative resection of differentiated-type EGC. This study aimed to evaluate LNM risk factors to identify those that should be considered during the preoperative evaluation of differentiated-type EGC. Patients and methods. A total of 976 EGC patients who underwent radical gastrectomy were reviewed in this study. Univariate and multivariate analyses were used to analyze the predictive factors for LNM based on the histology of the differentiated-type EGC cases. Results. Differentiated-type EGC was observed in 59% of the cases. The rate of LNM was 6.6% (38/576 patients) in the differentiated-type EGC cases. Macroscopic shape, ulcers, tumor size, deeper invasion and lymphovascular invasion were shown to be related to LNM in differentiated-type EGC. Multivariate analysis revealed that size, depth, ulceration and lymphovascular invasion were independent predictors of LNM in differentiated-type EGC. When lymphovascular invasion was absent, the presence of one or more of the risk factors of ulcer lesions, tumor size >30 mm and submucosal invasion increased the rate of LNM. Thirteen patients who underwent radical gastrectomy were shown to have differentiated-type EGC with LNM that met the standard and expanded criteria of endoscopic submucosal dissection. Conclusions. As endoscopic resection is widely used, it is important to clarify the clinical significance of LNM in differentiated-type EGC and to screen for LNM with this incidence in mind and to follow the clinical courses of such cases, especially in China.     

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.     

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.     

Histomorphologic features of early gastric carcinoma treated by endoscopic submucosal dissection: relation to efficiency of endoscopic resection

Objective: Early gastric cancer (EGC) is defined as cancer invasion confined to the mucosa or submucosa, irrespective of lymph node metastasis. Recently endoscopic submucosal dissection (ESD) has been widely accepted for the treatment for dysplasia and EGC without lymph node metastases. While the method has been advanced in Far East countries, ESD is still being developed in Europe and has not gained enough popularity although it has been recommended as the treatment of choice for superficial gastric neoplastic lesions by European Society of Gastrointestinal Endoscopy (ESGE) in 2015.

Methods: The aim of the study was to perform a retrospective analysis of clinical and histomorphologic features of 58 cases of EGCs removed by ESD in a university hospital in Western Pomerania in Poland and to evaluate factors related to the efficiency of ESD resection.

Results: With univariate analysis, indications for ESD with the highest R0 rate were found in EGCs limited to mucosa (T1a, small mucosal, M), without muscularis mucosa invasion, localised in the middle/lower part of stomach and intestinal type in histological examination. The R0 complete resection rate was significantly (p?Conclusions: Our data showed that in EGCs with favourable histomorphologic characteristics, ESD seemed to be a totally efficient and safe method of treatment in a European small-volume centre. R0 resection rate reached 81.1% of cases and median time of the ESD procedure was 61.5?min.     

Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer

BACKGROUND Endoscopic submucosal dissection(ESD) has been routinely performed in applicable early gastric cancer(EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis(LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial.AIM To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC.METHODS We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262(10.1%) EGC patients were eligible forinclusion in this study. Data on the patients' clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses.RESULTS LNM was observed in 182(14.4%) patients. No LNM was detected in the patients who met the absolute indications(0/90). LNM occurred in 4/311(1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium(20-30 mm)and large(30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion(SM1 and SM2), poor differentiation,lymphovascular invasion(LVI), perineural invasion, and diffuse and mixed Lauren's types. Multivariate analysis demonstrated SM1 invasion(odds ration[OR] = 2.285, P = 0.03), SM2 invasion(OR = 3.230, P 0.001), LVI(OR = 15.702, P 0.001), mucinous adenocarcinoma(OR = 2.823, P = 0.015), and large lesion size(OR = 1.900, P = 0.006) to be independent risk factors.CONCLUSION The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.     

Bleeding after endoscopic submucosal dissection of gastric lesions

Endoscopic submucosal dissection (ESD) is generally used to treat gastric mucosal and submucosal lesions. Nevertheless, ESD is more difficult and complicated to perform than a traditional endoscopic mucosal resection, which can increase the incidence of various complications including hemorrhage, perforation and infection. Hemorrhage is a major post‐ESD complication. Prevention and early diagnosis of post‐ESD bleeding for gastric lesions are closely associated with the efficacy and safety of the operation. Many studies have reported the risks of and the preventative measures for hemorrhage after gastric ESD, but there remain some issues to be solved. We thus reviewed the risk factors, precautions and treatments for hemorrhage after ESD of gastric lesions.     

Endoscopic submucosal dissection vs endoscopic mucosal resection for early gastric cancer: A meta-analysis

AIM: To compare endoscopic submucosal dissection(ESD) and endoscopic mucosal resection(EMR) for early gastric cancer(EGC).METHODS: Computerized bibliographic search was performed on PubMed/Medline, Embase, Google Schol-ar and Cochrane library databases. Quality of each included study was assessed according to current Co-chrane guidelines. Primary endpoints were en bloc re-section rate and histologically complete resection rate. Secondary endpoints were length of procedure, post-treatment bleeding, post-procedural perforation and re-currence rate. Comparisons between the two treatment groups across all the included studies were performed by using Mantel-Haenszel test for fixed-effects mod-els(in case of low heterogeneity) or DerSimonian and Laird test for random-effects models(in case of high heterogeneity).RESULTS: Ten retrospective studies(8 full text and 2 abstracts) were included in the meta-analysis. Overall data on 4328 lesions, 1916 in the ESD and 2412 in the EMR group were pooled and analyzed. The mean operation time was longer for ESD than for EMR(stan-dardized mean difference 1.73, 95%CI: 0.52-2.95, P =0.005) and the "en bloc " and histological complete re-section rates were significantly higher in the ESD group [OR = 9.69(95%CI: 7.74-12.13), P 0.001 and OR = 5.66,(95%CI: 2.92-10.96), P 0.001, respectively]. As a consequence of its greater radicality, ESD provided lower recurrence rate [OR = 0.09,(95%CI: 0.05-0.17), P 0.001]. Among complications, perforation rate was significantly higher after ESD [OR = 4.67,(95%CI, 2.77-7.87), P 0.001] whereas the bleeding incidences did not differ between the two techniques [OR = 1.49(0.6-3.71), P = 0.39].CONCLUSION: In the endoscopic therapy of EGC, ESD showed a superior efficacy but higher complication rate with respect to EMR.     

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.