Japanese Gastric Cancer Association Research Articles

Development trend of assessment system in gastric cancer based on evolution of staging criteria

There are two major stage classification systems for gastric cancer: the tumor-node-metastasis (TNM) staging by the International Union against Cancer (UICC)/the American Joint Committee on Cancer(AJCC) and the Japanese Classification of Gastric Carcinoma by the Japanese Gastric Cancer Association(JGCA). The evolution of these two systems showed the advancement of gastric cancer treatment. The independence of TNM and JGCA staging system is not conducive to global communication and cooperation. The integration of 2010 Japan's 14th edition of the General Rules for Gastric Cancer Study and the 7th edition of UICC/AJCC TNM staging formed an internationally unified clinical staging system. TNM staging determined by the N factor according to the number of lymph node metastasis more accurately stratified the survival curves of different stages. On January 1, 2018, the 8th edition of the TNM staging system for gastric cancer was officially implemented. The 8th edition of TNM staging provided a new definition of the staging criteria for esophagogastric junction cancer. On the basis of a single staging system, clinical TNM staging(cTNM) and neoadjuvant treatment staging (ypTNM) were added. N3a and N3b were seperately staged, and adjustments were made to the histological grading. A comprehensive treatment plan was determined by accurate clinical staging in the model of multidisciplinary diagnosis and treatment for gastric cancer. Comprehensive application of endoscopic ultrasonography (EUS), multi-slice spiral CT(MDCT), positron computed tomography combined with CT(PET-CT), and staging laparoscopy can improve the accuracy of preoperative staging of gastric cancer. The emergence of ypTNM staging is a highlight of the 8th edition of the staging, but due to insufficient case data for cTNM and ypTNM staging, the staging criteria are relatively broad, and more data validation, refinement and revision are required in the future. The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer. The new version of the staging can guide clinicians to develop treatment plans more rationally, evaluate the treatment more scientifically, and assess the prognosis more accurately. New lymph node staging methods such as metastatic rate(rN), log odds of positive lymph nodes (LODDS), and a new staging system based on the anatomical range of lymph node metastasis can also better predict the prognosis of patients. At present, molecular type of gastric cancer has little significance for prognosis guidance, and may be rewritten or supplemented with TNM staging of gastric cancer in the future. This article discusses the history, current status and research progress of gastric cancer staging.

Features of clinicopathology and blue laser imaging combined with magnification endoscopy of patients with early gastric cancer

Objective To study the clinical and pathological characteristics of early gastric cancer (EGC) and to evaluate the value of blue laser imaging combined with magnification endoscopy (BLI-ME) in the diagnosis of EGC. Methods A retrospective study was conducted on data of 255 patients with EGC diagnosed in Huashan Hospital from January 2014 to January 2017, including 33 cases of preoperative BLI-ME intensive examination. According to the Japanese classification of gastric carcinoma of Japanese Gastric Cancer Association, the EGCs were histopathologically divided into differentiated and undifferentiated subtypes. Clinical characteristics, endoscopic features, pathological type, lymph node metastasis, and lesion characteristics of BLI-ME were analyzed. Results Among the 255 cases of EGC, 164 cases (63.31%) were male, 242 cases (94.90%) were over 40 years old, 182 cases (71.37%) belonged to differentiated type, 93 cases (36.47%) were located in gastric antrum, 92 cases (36.08%) were type 0-Ⅱc under endoscopy, and 37 cases (14.51%) had lymph node metastasis. Comparative analysis showed that the lymph node metastasis rate was significantly lower in mucosal carcinoma compared to submucosal carcinoma[5.04% (7/139) VS 25.86% (30/116), χ2=22.109, P=0.000], lower in differentiated carcinoma compared to undifferentiated carcinoma[9.89% (18/182) VS 26.03% (19/73), χ2=10.938, P=0.002], and lower in tumors with maximum diameter of lesion≤2.0 cm compared to maximum diameter of lesion>2.0 cm[9.88% (16/162) VS 22.58% (21/93), χ2=7.687, P=0.009]. Among the 33 cases undergoing BLI-ME, differentiated EGC was mainly fine-network pattern (13.64%, 3/22), intralobular loop pattern (ILL)-1 (59.09%, 13/22) and ILL-2 (22.73%, 5/22), whereas undifferentiated subtype patients were characterized as ILL-2 (45.45%, 5/11) and corkscrew pattern (54.55%, 6/11). Conclusion The incidence of EGC is higher in male with age over 40 years. Gastric lesions occur most frequently in the antrum, and the most common microscopic morphology is 0-Ⅱc type. Tumor>2.0 cm or invasion of submucous layer, and undifferentiated carcinoma are prone to lymph node metastasis. The assessment of mucosal microvascular pattern and micro surface structure under BLI-ME facilitate to determine the pathological type of EGC. Key words: Retrospective studies; Early gastric cancer; Blue laser imaging combined with magnification endoscopy; Pathological type

Impact of the Number of Lymph Nodes Examined on Differences in Survival for Surgically Treated Gastric Cancer Patients Between the US and Japan Using Nationwide Databases

Background: Although incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. The international collaborative study for cancer survival using population-based cancer registry showed that the survival of GC was higher in Korea and Japan than other countries, including the United States of America (US). Aim: We examined the determinant factors of the high survival in Japan, compared with the US, with particular focus on the impact of the number of lymph nodes (LNs) examined for surgically treated patients. Methods: We obtained data on 88,447 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007. We also obtained 18,995 GC cases from US population-based cancer registry data from the Surveillance, Epidemiology, and End Results Program (SEER), diagnosed from 2004-2010. We estimated five-year relative survival and applied a multivariate excess hazard model to compare the two countries. We considered the effect of LNs examined on differences in survival. Results: Five-year relative survival in Japan was 79.8%, compared with 40.1% in the US. After controlling for confounding factors, we still observed significantly higher survival in Japan. The distribution of number of LNs examined showed notable differences between two countries. In over 50% of patients in the US, only 1 to 15 LNs were examined. A higher number of LNs examined showed better survival in both countries. The differences in excess death from cancer between countries were reduced in the category when more than 30 LNs were examined. Conclusion: Although it is difficult to remove biases to compare the two countries, stage migration, related to the more detailed retrieving strategy for LNs in Japan, is a key explanation for high survival in Japan.

Anatomical analysis of gastric lymph nodes in cancer-free individuals.

Lymphadenectomy is a crucial part of the surgical therapy for gastric cancer. The number of normal lymph nodes could indicate the number of nodes that need to be retrieved during the procedure. The aim of this study is to analyze the number of lymph nodes in cadavers without gastric cancer according to the Japanese Gastric Cancer Association guidelines. Twenty fresh adult cadavers (14 males, mean age 55, range 24-93 years) were used. Abdominal lymph nodes were dissected and classified according to the Japanese Gastric Cancer Association. For total gastrectomy, the median number of lymph nodes that comprised D1 + dissection was 27 (range 15-42). The median and mean number of lymph nodes that comprised D2 dissection was 33, ranging from 18 to 50. For distal gastrectomy, the D1 + level comprised a median of 21 lymph nodes (range 11-38), and the D2 level 22 lymph nodes (range 11-39). In conclusion, considering gastrectomy + D2 lymphadenectomy as the standard treatment for gastric cancer, our results show that adequate lymphadenectomy must encompass around 30 lymph nodes. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.

RA08.03: LYMPH NODE METASTASIS RISK IN SUPERFICIAL ESOPHAGOGASTRIC JUNCTIONAL ADENOCARCINOMA

Abstract Background We have reported that lymph node metastasis risk in cases of superficial Barrett's esophageal cancer (BC) was of submucosal invasion within 500μm without other risk factors (lymphovascular involvement, a poorly differentiated component, and lesion size) through a multicenter retrospective study in 13 facilities. Cardiac cancer (CC) was included in the gastric cancer criteria of the Japanese Gastric Cancer Association. Since BC and CC near the esophagogastric junction (EGJ) show almost the same biological behavior, we elucidated the metastasis risk factors in patients with EGJ adenocarcinoma. Methods Patients who underwent ESD for superficial EGJ adenocarcinoma as Siewert typeII between January 2011 and April 2017 were included. Results A total of 120 patients were analyzed. Fifty-three patients (44.1%) had BC and 67 patients (55.8%) had CC. Of the 120 lesions, the median size was 16.7 ± 8.5 mm; 10 (8.3%; 4 BC, 6 CC) were greater than 30 mm in size. Thirty-five (29.1%; 17 BC, 18 CC) were submucosal (SM) cancers. Twenty-one (17.5%; 13 BC, 8 CC) had poorly differentiated components and 19 (15.8%; 14 BC, 5 CC) had lymphovascular involvement. Of the 19 cases with lymphovascular involvement, 11/22 (50%) were SM cancers with > 200μm of invasion, and 8/98 (8.1%) were mucosal (M)/SM cancers within SM200μm of invasion. Of the BCs with DMM invasion, 7/17 (41.1%) had lymphovascular involvement. Of the patients initially treated through ESD, 33 (27.5%) had lymphovascular involvement, positive horizontal/vertical margins, or SM > 200μm of invasion. Of these, 26 were treated with additional surgery. Metastasis was confirmed from 2 patients. Both were BCs, with SM > 501μm of invasion, positive lymphovascular involvement, and with poorly differentiated components. One was > 30 mm in size. Metastasis was not identified in CC and in cases with SM < 200μm of invasion. Conclusion For superficial esophagogastric cancer, we did not identify metastasis in patients with SM > 501 μm of invasion. There were no cases of metastasis in patients without risk factors. ESD might be indicated for lesions within SM 500μm of invasion without risk factors. Among DMM cases of BC, lymphovascular involvement was highly frequent. Therefore, histopathological surveillance for lymphovascular involvement is important. Disclosure All authors have declared no conflicts of interest.

Clinicopathological characteristics and prognostic factor analysis of carcinoma in remnant stomach cancer at Peking University Cancer Hospital

To investigate the interval time to canceration, clinicopathological characteristics and prognostic factors of carcinoma in remnant stomach (CRS) in patients with primary benign diseases or primary malignant tumors. Based on the criteria of the definition of CRS proposed by Japanese Gastric Cancer Association in 2017, a retrospective analysis was conducted on clinicopathological characteristics of patients diagnosed with CRS at Peking University Cancer Hospital from March 1992 to March 2017. Between patients with primary benign diseases (CBS-B group) and primary malignant tumors (CBS-M group), continuous variables were compared using the Student's t-test or the Mann-Whitney U test; categorical variables were compared using the chi-square test or Fisher's exact test. Spearmen-Rho was used to examine correlation. Survival was estimated and compared using Kaplan-Meier methods. Cox proportional hazards regression was applied to identify independent prognostic factors. Area under ROC curve(AUC) was used to evaluate and compare prediction accuracy. A total of 89 patients were included in the study with a male: female ratio of 5.4 to 1.0. The male: female ratio in CRS-B (n=46) and CRS-M (n=43) group was 14.3 to 1.0 and 2.9 to 1.0 respectively with significant difference (χ2=6.091, P=0.019). The interval time to canceration in CRS-B and CRS-M group was 342(36-576) months and 47(12-360) months respectively with significant difference (t=8.887, P=0.000). The interval time to canceration was correlated with the first operative procedure in CRS-B group (r=0.398, P=0.006), while interval time to canceration was correlated with the age at the first operation in CRS-M group (r=0.337, P=0.027). After differentiating the pathological findings of the first operative sample and the second operative sample, 27 patients presented recurrence and 15 patients had new cancer, and the corresponding interval time to canceration was 46(12-132) months and 60(12-360) months respectively with significant difference (t=5.652, P=0.023). In CRS-B group, location of stump carcinoma in gastric intestinal anastomosis, gastric anastomosis, and non-anastomosis area was found in 60.9%(28/46), 23.9%(11/46) and 15.2%(7/46) respectively, and the corresponding percentage in CRS-M group was 39.5%(17/43), 16.3%(7/43) and 44.2%(19/43) respectively without significant difference (χ2=4.726, P=0.096). Among 77 patients with radical gastrectomy, the overall surgical complication rate was 20.8%(16/77), including 8 cases of infection and 7 cases of respiratory system diseases. The 3-year survival rate was 78.4% and 62.6% in CRS-B and CRS-M group respectively with significant difference (χ2=3.969, P=0.046), indicating better prognosis of CRS-B patients. The AUC for the lymph nodes ratio and N staging was 0.725 and 0.639 respectively. Multivariate analysis showed the pathological T staging was an independent risk factor of prognosis (HR=1.192, 95%CI:1.032-1.376, P=0.017). Men have more CRS than women. The interval time to canceration is correlated to the first operative procedure for CRS-B patients, while it is correlated to the age at the first operation for CRS-M patients. The major location of CRS is in the gastrointestinal anastomosis for CRS-B patients and in non-anastomosis area for CRS-M patients. Main postoperative complications include respiratory and infectious complications. Pathological T staging is an independent prognostic risk factor for CRS patients.

Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

AIMTo investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODSWe proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.RESULTSWe identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSIONNAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.

Determinant Factors on Differences in Survival for Gastric Cancer between the US and Japan Using Nationwide Databases: The Impact of Number of Lymph Nodes Examined

Background: Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international collaborative study reported much higher survival in Korea and Japan than other countries, including the US. We examined the determinant factors of the high survival in Japan, compared with the US. Methods: We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 GC cases from the Surveillance, Epidemiology, and End Results Program (SEER), a US population-based cancer registry data from 2004-2010. We estimated five-year relative survival and applied a multivariate excess hazard model to compare the two countries. We considered the effect of number of lymph nodes (LNs) examined on differences in survival. Findings: Five-year relative survival in Japan was 81.0%, compared with 45.0% in the US. After controlling for confounding factors, we still observed significantly higher survival in Japan. The effect of number of LNs examined showed different trends according to TNM-N categories. N0 and N1 patients showed much wider gaps between the two countries. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. Interpretation: The wide differences in gastric cancer survival between Japan and US can be largely explained by differences in the stage at diagnosis, which were related to early detection in Japan, mainly due to the screening system and greater awareness of gastric cancer. Stage migration, which is related to differences in the number of retrieved and examined LNs, also helps explain the wide gap in gastric cancer survival between the two countries. Funding Statement: Ministry of Health, Labour and Welfare, Japan Declaration of Interests: The authors have no conflict of interest.

Prof. Takeshi Sano: early detection contributes to cure of gastric cancer

Prof. Sano is a council member of the Japanese Gastric Cancer Association and Secretary General of the International Gastric Cancer Association ( Figure 1 ).

The Incidence of Lymph Node Metastasis in Submucosal Early Gastric Cancer (EGC) According to the Expanded Criteria of the Japanese Gastric Cancer Association (JGCA): A Systematic Review

Introduction: Japanese criteria for curative endoscopic resection of early gastric cancer initially included non-ulcerated, well-differentiated mucosal lesions ≤2 cm in diameter, known as the absolute criteria. Subsequently, these indications were expanded to include non ulcerated differentiated lesions < 3 cm with submucosal invasion (SM1) μm. Whether patients meeting the expanded criteria can be safely managed without gastrectomy and lymph node dissection has been controversial. There are conflicting results regarding the risk of lymph node metastasis in patients with submucosal gastric lesions who met the expanded criteria. We performed a systemic review to evaluate the incidence of Lymph Node Invasion (LNM) in patients met the expanded criteria for SM1 lesions. Methods: We comprehensively searched main reference databases (MEDLINE, EMBASE, CINHAL) for any study that included patients who underwent gastrectomy and lymph node dissection for early gastric cancer through December 10, 2016. Patients with submucosal lesions that met the expanded criteria were included in the final analysis. We followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA). Article review was done by “MA” and “MB” and the final review was done by “MO.” Relative risk was used to compare the incidence of LNM in each group. CI of 95 and p Results: Our search yielded 1,775 studies, of which 1,705 studies were excluded after abstract or method, and result sections were reviewed. A total of 70 full-text articles were reviewed. 54 articles were excluded due to missing data on LN. 16 manuscripts (1 prospective and 15 retrospectives) from Japan, Korea, and China were included. 1392 patients with SM early gastric cancer met the expanded indication were included in the final analysis. The search strategy is summarized in Figure 1. The incidence of LNM was 41 out of 1392 patients (2.9%) table 1.FigureConclusion: The incidence of LNM for submucosal lesions met the expanded criteria is (2.9%). This is higher than the results in the landmark study by Gottoda et al. The increased risk of LNM should be considered in discussing surveillance versus surgical gastrectomy in patients who underwent Endoscopic Submucosal Dissection for EGC with SM1 invasion.Figure

Prof. Takeshi Sano: early detection contributes to cure of gastric cancer

Prof. Sano is a council member of the Japanese Gastric Cancer Association and Secretary General of the International Gastric Cancer Association ( Figure 1 ).

Long-Term Outcomes of Using Endoscopic Submucosal Dissection to Treat Early Gastric Cancer.

Endoscopic submucosal dissection (ESD) is becoming the main procedure for the resection of early gastric cancer (EGC). The absolute indications for treating EGC with endoscopic resection were established by the Japanese Gastric Cancer Association and have been generally accepted. However, the absolute indications for treating EGC are rather strict, and expanded indications have been developed. Many studies have reported favorable long-term outcomes for patients who received curative resection for the expanded indication. ESD preserves the stomach, thereby improving patients’ quality of life compared to surgery; however, a generally higher incidence of metachronous gastric cancer has been reported after ESD for EGC. Therefore, clinicians must pay careful attention during surveillance endoscopy, even after a curative ESD.

P-122 - The long-term prognosis and risk factors for splenic hilar lymph node metastasis in patients with gastric cancer: a systematic review and meta-analysis

Introduction: The Japanese Gastric Cancer Association guidelines stipulate that D2 gastrectomy is required for treating advanced gastric cancer. However there is controversy regarding lymph node dissection around the splenic artery and hilum in advanced gastric carcinoma. The purpose of this study was to investigate the long-term prognosis and risk factors for splenic hilar lymph node metastasis(SHM) in patients with gastric cancer. Methods: A systematic search of PubMed, EMBASE, and Web of Science from January 1994 to June 2016 was conducted. All original studies comparing splenic hilar lymph node metastasis(metastasis group) to the non-metastasis(non-metastasis group) were included by critical appraisal. The following evaluated endpoints were assessed: prevalence of splenic hilar lymph node metastasis rate, 5 year overall survival rate and risk factors of SHM.Data synthesis and statistical analysis were carried out using R environment 3.0.1 software. Results: a total of 10 studies were included, representing 1,910 individuals. The pooled prevalence of lymph node metastasis at the splenic hilus was 16% (95% confidence intervals (CI): 5, 26%),in advanced proximal third gastric carcinoma. Compared with non-metastasis group, metastasis group had worse long-term prognosis [HR = 0.34, 95%CI(0.29, 0.42);P<0.05]. And our meta-analysis showed that, tumor located at greater curvature [RR = 0.49, 95%CI(0.37,0.65); P < 0.05],proximal third gastric carcinoma[RR = 0.49, 95%CI(0.29,0.83); P < 0.05], Borrmann IV [RR = 0.31, 95%CI(0.16,0.63); P < 0.05], depth of invasion T4 [RR = 0.31, 95%CI(0.22,0.43); phatic invasion [RR = 0.64, 95%CI(0.49,0.86); P < 0.05] and vascular invasion [RR = 0.44, 95%CI (0.22,0.87); P < 0.05] were statistically significantly associated with splenic hilar lymph node metastasis. Conclusion: The long-term prognosis of gastric cancer patients who had SHM was worse than those who had non-metastasis of splenic hilar lymph node. We identified risk factors consistently associated with SHM in patients with gastric cancer. These factors help to offer doctors postoperative clinical treatment for SHM in patients with gastric cancer.

Prognosis of Stage IIB Early Gastric Cancer Has a Unique and Dismal Property Putatively Requiring Postoperative Adjuvant Chemotherapy

Pathological T1 (pT1) gastric cancer showed excellent prognosis; however, lymph node metastasis sometimes reflects patients with dismal prognosis. In this study, we investigated prognosis of pT1 gastric cancer with lymph node metastasis to identify prognostic factors. Among 1442 gastric cancer patients between 2002 and 2010, 73 (5%) of pT1 with lymph node metastasis were identified. Univariate prognostic factors were applied to multivariate Cox proportional hazards model. First, among the 1442 patients, pT1 was composed of 333 patients with pT1a and 423 patients with pT1b, which included 9 (2.7%) and 64 cases (15.1%) with lymph node metastasis, respectively. Secondly, 10 (13.7%) patients of the 73 patients with lymph node metastasis showed tumor relapse. Univariate negative prognostic factors were tumor size (P = 0.03), intraoperative bleeding (P = 0.03), and perioperative transfusion (POT; P = 0.001), as well as 14th JGCA (Japanese Gastric Cancer Association) Stage (P &amp;lt; 0.0001), and multivariate analysis identified 14th JGCA Stage (P = 0.0004) and POT (P = 0.03) as independent prognostic factors. Third, pT1 gastric cancer representing pN3 (Stage IIB) was rare (n = 4) and unique entity from a prognostic point of view, exhibiting dismal prognosis (0% at 5 years). We thereafter identified 17 such cases from 5204 gastric cancer cases including the earliest cases. Prognosis of the 17 patients was unique in that recurrences occurred even 5 years after curative operation, and the frequent recurrent sites were bone. pT1 gastric cancer prognosis is robustly affected by pN3 and POT, and Stage IIB disease showed unique prognosis requiring special attention even after 5 years of operation.

Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007).

The aim of this retrospective study was to investigate the tumor characteristics, surgical details, and survival distribution of surgically resected cases of gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. Data from 118,367 patients with primary gastric carcinoma who underwent resection between 2001 and 2007 were included in the survival analyses. The 5-year survival rates were calculated for various subsets of prognostic factors. The median age of the patients was 67years. The proportions of patients with pathological stage (Japanese Gastric Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%, 11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30days of operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who were treated by resection was 71.1%. The 5-year overall survival rates of patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were 91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease-specific survival rates in the patients with pT1 (mucosa) disease after D1+dissection of lymph node station no. 7 (D1+α), D1+dissection of lymph node station nos. 7, 8, and 9 (D1+β), and D2 lymphadenectomy were 99.4%, 99.6%, and 99.1% respectively. The 5-year disease-specific survival rates in the patients with pT1 (submucosa) disease after D1+α, D1+β, and D2 lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. Detailed analyses of the data from more than 100,000 patients show the recent trends of the outcomes of gastric cancer treatment in Japan and provide baseline information for use by medical communities around world.

Comparison of five tumor regression grading systems for gastric adenocarcinoma after neoadjuvant chemotherapy: a retrospective study of 192 cases from National Cancer Center in China

BackgroundNeoadjuvant chemotherapy has been increasingly practiced on gastric cancer (GC), and histological evaluation to predict outcome is urgent in clinical practice. There are five classic tumor regression grading (TRG) systems, including Mandard-TRG system, the Japanese Gastric Cancer Association (JGCA)-TRG system, College of American Pathologists (CAP)-TRG system, China-TRG system and Becker-TRG system.MethodsTotally, 192 patients of gastric adenocarcinoma (including adenocarcinoma of the esophagogastric junction) treated by neoadjuvant chemotherapy and surgery were evaluated using the above five TRG systems. The clinicopathological characteristics were also assessed. The correlation among TRG systems, clinicopathological characteristics and prognosis were analyzed.ResultsAll the five TRG systems were significantly correlated with differentiation, postsurgical T category, postsurgical N category, American Joint Committee on Cancer (AJCC) stage, lymph-vascular invasion, perineural invasion, as well as tumor size. All the five TRG systems were statistically significant in univariate Cox survival analysis. However, only postsurgical T category, postsurgical N category and R0 resection were independent in multivariate Cox survival analysis. The tight correlation between the TRG systems and other characteristics such as postsurgical stage might affect the independent prognostic role of the TRG systems. As compared with other TRG systems, the hazard ratio of no/slightly response in both Mandard TRG system and JGCA TRG system revealed higher hazard of death and disease progression than that of severe response when using univariate Cox survival analysis. The median survival time of complete response and nearly complete response were much longer than that of partial response, all classified by Mandard-TRG system. This could help clinicians predict prognosis more reasonably than JGCA-TRG which does not have the category of nearly complete response.ConclusionWe recommend Mandard-TRG system for GC after neoadjuvant chemotherapy due to its better prediction of prognosis.

Surgical anatomy of gastric lymphatic drainage.

The lymphatic system of the stomach is a multidirectional and complex network composed of lymphatic nodes and vessels. Lymph node metastasis is the most important prognostic factor in curable gastric cancer and lymph node dissection is one of the main areas of surgical research in gastric cancer. Therefore the anatomical classification and embryological development of the gastric lymphatic system have been well described in the literature. The current description of the gastric lymphatic system of the stomach has a surgical orientation and follows the recommendations of the Japanese Gastric Cancer Association. A thorough knowledge of the lymphatic system surrounding the stomach proves to be invaluable to surgeons treating patients with gastric cancer. The aim of this paper is to provide a concise review about surgical anatomy of the gastric lymphatic drainage.

Classification of nodal stations in gastric cancer.

The lymphatic drainage from the stomach is anatomically elaborate and it is very hard to predict the pattern of lymph node (LN) metastases from gastric cancer (GC). However, there are LN stations metastases that are more frequently observed depending on the tumor location. Furthermore, the incidence of metastasis to various regional LN stations depends on the depth of gastric-wall invasion. The Japanese Gastric Cancer Association (JGCA) classifies the regional LNs draining the stomach into 33 regional lymphatic stations. These are distinguished into three (N1-N3) groups with respect to the location of the primary tumor. The aim of this classification is to provide a common language for the clinical, surgical, and pathological description of GC.

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy.

AIMTo evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer.METHODSOne hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined.RESULTSAdvanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator.CONCLUSIONA high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer.

EARLY GASTRIC CANCER: THE MODERN OPINION

The review presents the clinical and morphological characteristics of early gastric cancer. According to the most recent concepts, early gastric cancer is considered as endoscopically resectable cancer with good prognosis. Currently, early gastric cancer is defined as non-invasive high-grade intraepithelial neoplasia (severe dysplasia) and well-differentiated adenocarcinoma with intramucosal (T1a) and/or minor submucosal (T1b1) invasion as well as poorly cohesive carcinoma, including signet-ring cell carcinoma, confined to the gastric mucosa (≤ 3 cm) without ulceration. Most authors consider that early gastric cancer should be characterized by the absence of regional lymph nodes (N0) and distant metastasis (M0). Early gastric cancer should be classified according to the macroscopic criteria proposed by the Japanese Society of Gastroenterological Endoscopy or the revised version of the Paris classification of superficial neoplastic lesions in the digestive tract as well as according to the World Health Organization classification and the recommendations of the Japanese Gastric Cancer Association. It is important to evaluate lymphovascular invasion in all early gastric cancer cases because of high risk of local metastases. Moreover, cases with mixed-type early gastric cancer (differentiated and undifferentiated components) need to be carefully examined, as they are high-metastatic potential lesions. The review considers predictive criteria for assessing the risk of regional metastasis in early gastric cancer. Cases of hereditary diffuse gastric cancer caused by CDHI gene mutations have been also analyzed. A literature review have allowed us to give recommendations on the risk stratification and the choice of an adequate treatment in patients with early gastric cancer