Japanese classification of gastric carcinoma: 3rd English edition

To evaluate discrepancies between biopsy and resected specimens using the Japanese Classification of Gastric Carcinoma (JCGC) and tumor-node-metastasis (TNM) classification. A total of 376 consecutive paired samples from biopsy and resected gastric specimens, which were derived from curative gastrectomy for gastric cancer between 2008 and 2011, were retrospectively analyzed. (1) Discrepancies in the histologic type were observed between biopsy and resected specimens; 11.7% (44/376) in the JCGC and 18.1% (68/376) in TNM. In specimens diagnosed as the differentiated type from biopsy specimens, 14.4% (28/195) in the JCGC and 41.1% (67/163) in TNM were finally diagnosed as the undifferentiated type from resected specimens; and (2) the incidence of mixed-type gastric cancer was significantly higher in specimens with discrepancies than in those without in both the JCGC and TNM (both P < 0.0001); 93.2% (41/44) of specimens with discrepancies in the JCGC and 97.1% (66/68) of specimens with discrepancies in TNM were mixed-type gastric cancers. Mixed-type gastric cancer was associated with a high incidence of histologic discrepancies between biopsy and resected specimens in both the JCGC and TNM definitions. Care should be taken in deciding treatments based on diagnosis of the histologic type for mixed-type gastric cancer from biopsy specimens.

In 1962, according to the results concluding from specimens of gastric cancer, the Japanese Gastric Cancer Association produced the first edition of Japanese Classification of Gastric Carcinoma (JCGC), in which lymph nodes (LNs) associated with metastasis of gastric cancer (GC) were anatomically divided into groups. This clarified the gastric lymphatic circulation system in detail. The classification laid the theoretical foundation of systematic lymph node dissection for GC and also propelled its surgical treatment into a new era. Researchers in Japan had worked to ensure that the standard set by the JCGC realistically reflected the approach and extent of lymph node metastasis (LNM), to guide the reasonable extent of lymph node dissection. The JCGC has been steadily revised since 1962 with new understandings from continuously practices by Japanese researchers; they kept observing and summarizing the regularities of the distribution of positive metastatic LNs. In 2010 the 14th edition of the JCGC was published. It described the lymphatic system of the stomach from the perspective of anatomy and further revealed the regularity of LNM of GC and the method for evaluating the extent of LNM. Moreover, it established the integrated theoretical framework for systemic lymphadenectomy, in which the extent of lymph node dissection was verified by the stage of cancer. The TNM staging system of the Union for International Cancer Control (UICC) is another important international appraisal system for GC, which evaluates the extent of metastasis with only the number of metastatic LNs. It reflected the relationship between the number of metastatic LNs and the prognosis of the patient. However, with respect to the regularity of LNM, this system cannot reflect well. It can only be regarded as a way for assessing the postoperative outcomes but not as a guide for determining the extent of surgery. Therefore, controversies on the extent of lymphadenectomy for GC almost center on the JCGC.

The clinical impact of the directionality of lymph node (LN) metastasis was assessed in comparison with the staging by the Japanese Classification of Gastric Carcinoma (JCGC), a numerical LN staging system. Two hundred forty-one gastric cancer patients who were diagnosed pathologically to have LN metastasis, and 54 patients who underwent preoperative multidetector-row computed tomography (MDCT) with an image thickness of 1 mm were classified into three groups (unidirectional [Uni-], bidirectional [Bi-], and tridirectional [Tri-] groups) depending on the directionality of their LN metastasis. The prognosis of the Uni-group was better than that of the Bi- or the Tri-group when assessed on the basis of the pathological findings of metastatic LN and also the preoperative MDCT findings. The exact preoperative evaluation was 70.2 % for the directionality system and 61.7 % for the JCGC system, respectively. The stages were less frequently underestimated by the directionality system than the JCGC system (P < 0.02, 19.1 vs. 34.0 %), and the staging could be more precisely performed by both systems in combination. More precise preoperative evaluation of disease stage could be obtained by the directionality system and the JCGC system in combination.

T-stage and N-stage have been proven to be the most important factors influencing survival in gastric cancer patients, and have been accepted for use in the Japanese Classification of Gastric Carcinoma (JCGC) and the Union International Cancer Control (UICC-TNM) staging systems. The purpose of this study was to compare the prognostic values of the different N classification systems in gastric cancer patients without serosal invasion. We retrospectively compared the clinicopathological results of 1,115 patients with primary gastric cancer who underwent curative gastric resection. Serosal invasion was identified in 212 of 1,115 patients (19.0%), and it was associated with lymph node metastasis according to the JCGC(13th) (P<0.001) and TNM(7th) (P<0.001) systems. The 5-year survival rate for the serosal invasion-negative patients (78.2%) was significantly higher than that for the serosal invasion-positive patients (31.1%) (P<0.001). Multivariate Cox regression survival analysis showed that depth of invasion (P=0.013), 13(th) JCGC PN stage (P<0.001), and 7(th) TNM PN stage (P<0.001) were independent prognostic factors for serosal invasion-negative gastric cancer patients. The prognosis of gastric cancer patients with serosal invasion is very poor. Both the 13(th) JCGC and 7(th) TNM N-staging systems were able to accurately estimate the prognosis of gastric cancer patients, but the 7(th) TNM system was simpler and easier to use.

The Japanese Classification of Gastric Carcinoma was established by the Japanese Research Society for Gastric Cancer in 1962. The latest 15th edition was published in 2017. One of its main features is that lymph nodes are numbered as stations. The number of groups has increased from 16 to 36 in 55years. Seven groups (nos. 1, 2, 5, 7, 9, 10, and 15) were retained from the original classification. Nine groups (nos. 3, 4, 6, 8, 11, 12, 13, 14, and 16) were sub-divided into two or more groups. Furthermore, seven groups (nos. 17, 18, 19, 20, 110, 111, and 112) were added in the 6th, 11th, and 12th editions. This numbering system helps surgeons recognize the exact lymph nodes that need to be dissected. However, the numbering system has become extremely complicated. It is necessary to organize the historical background of each lymph node station and share the definitions clearly. This review focuses on nine anatomical zones around the stomach and summarizes the history of lymph node stations in the Japanese Classification of Gastric Carcinoma. Lymph node stations will continue to be modified in the future, and the historical background may be useful in future revisions.

Gastric carcinoma is the fourth most common carcinoma in the world, with an estimated one million new cases every year, and it is the second most common cause of death from carcinoma (Ferlay et al., 2010). Surgery is the mainstay of treatment of gastric carcinoma. Despite recent advances in surgical treatment, the overall prognosis of patients with gastric carcinoma has not improved significantly because the neoplasm is often diagnosed at an advanced stage of the disease. Local and systemic recurrences are common, even after complete resection of the primary tumour and regional lymph nodes. Multimodality therapy, consisting of surgery with adjuvant or neoadjuvant radiotherapy, chemotherapy or both, has been used recently as a means to improve the survival rate of patients with gastric carcinoma. Current data suggest that this carcinoma is best managed with a tailored therapeutic regimen based on thorough preoperative staging of the tumour and an understanding of established prognostic factors (Stein et al., 2000). The International Union Against Cancer (Unio Internationalis Contra Cancrum: UICC) TNM Classification of Malignant Tumours, 7th edition (Sobin et al., 2009), provides the latest, internationally agreed-upon standards to describe and categorise cancer stages and progression. Staging of gastric carcinoma was performed according to the UICC TNM staging for the T stage, N stage and M stage. The T stage refers to the depth of the invasion of the primary tumour, the N stage refers to the number of metastatic lymph nodes and the M stage indicates the presence or absence of systemic metastases (Table 1). For the N stage, the UICC TNM staging detailed in the 7th edition (Sobin et al., 2009) is a classification system based on the number of metastatic lymph nodes, a variable that has proved to be an independent prognostic factor in gastric carcinoma. In contrast, the Japanese Classification of Gastric Carcinoma (JCGC), 13th edition, provides lymph node station numbers for anatomically separate sites of regional lymph nodes (Japanese Gastric Cancer Association [JGCA], 1998). This classification is based on the study of lymphatic flow and surgical results. There was a difference in the two classification systems, particularly regarding lymph node metastasis, but near standardization was reached in 2010. For the year 2011, not enough data have been collected based on the new standards. We describe lymph node metastasis based on the JCGC, 13th edition, which classifies lymph node metastasis according to the anatomic sites of metastatic lymph nodes (Table 2). Current preoperative staging techniques, such as endoscopy, barium studies, computed tomography (CT) and endoscopic ultrasonography (EUS), are of limited accuracy, and invasive procedures often are used for better assessment of the stage of the disease. Positron emission tomography (PET) has been evaluated recently in the staging of gastric carcinoma.

Implications for restaging in gastric cancer with peritoneal metastasis based on the 15th Japanese Classification of Gastric Carcinoma: An analysis from a comprehensive center

Background This study was designed to evaluate the clinical significance of undifferentiated component in differentiated T1/T2 gastric adenocarcinoma. Methods Two hundred thirty-one patients who underwent curative gastrectomy were diagnosed pathologically as differentiated type T1/T2 gastric cancer according to Japanese Classification of Gastric Carcinoma (JCGC). The patients were divided into subgroups, pure differentiated type (pure D group, 181 patients) and differentiated-predominant mixed type (D > U group, 51 patients). The clinicopathological features of D > U group were compared with those of pure D group, and also those of undifferentiated-predominant type (U > D group). Results Patients in D > U group were more likely to have larger and deeper tumors with lymphatic invasion and metastases than pure D group. However, there was no significant difference in clinicopathological factors between D > U and U > D groups, except for depth of tumor invasion. The postoperative 5-year survival rate of D > U group was significantly poorer than that of pure D group (88% and 98%, P = 0.011). Multivariate analysis revealed the presence of undifferentiated component was an independent prognostic factor. Conclusions The presence of undifferentiated component in differentiated T1/T2 gastric cancer is associated with tumor progression. Therefore, the decision criterion of histological mixed type in TNM classification is better suited than JCGC in T1/T2 gastric cancer. J. Surg. Oncol. 2012; 105:800–804. © 2012 Wiley Periodicals, Inc.

This study was designed to evaluate the clinical significance of undifferentiated component in differentiated T1/T2 gastric adenocarcinoma. Two hundred thirty-one patients who underwent curative gastrectomy were diagnosed pathologically as differentiated type T1/T2 gastric cancer according to Japanese Classification of Gastric Carcinoma (JCGC). The patients were divided into subgroups, pure differentiated type (pure D group, 181 patients) and differentiated-predominant mixed type (D > U group, 51 patients). The clinicopathological features of D > U group were compared with those of pure D group, and also those of undifferentiated-predominant type (U > D group). Patients in D > U group were more likely to have larger and deeper tumors with lymphatic invasion and metastases than pure D group. However, there was no significant difference in clinicopathological factors between D > U and U > D groups, except for depth of tumor invasion. The postoperative 5-year survival rate of D > U group was significantly poorer than that of pure D group (88% and 98%, P = 0.011). Multivariate analysis revealed the presence of undifferentiated component was an independent prognostic factor. The presence of undifferentiated component in differentiated T1/T2 gastric cancer is associated with tumor progression. Therefore, the decision criterion of histological mixed type in TNM classification is better suited than JCGC in T1/T2 gastric cancer.

The prognosis for patients with stage Ib (second English edition of the Japanese classification of gastric carcinoma) gastric cancer is promising, with an expected 5-year survival of 90%. Despite this relatively high survival rate, the outcome for patients who experience recurrence is poor. To date, however, prognostic and recurrence factors for stage Ib gastric cancer are poorly understood, and appropriate adjuvant chemotherapy protocols have not been developed. We retrospectively analyzed data from 86 stage Ib gastric cancer patients who underwent curative gastrectomy to determine the rates and predictive factors of recurrence. Eleven patients showed recurrence, with a 12.8% 5-year cumulative recurrence rate. Nearly all of these patients were initially histologically diagnosed with poorly differentiated adenocarcinoma. Based on univariate analyses, recurrence was associated with gender and histological type. Multivariate analyses revealed that the only independent risk factor for recurrence was histologically undifferentiated-type adenocarcinoma. The 5-year survival rate of patients with undifferentiated-type adenocarcinoma was 84%. The predominant recurrence pattern was peritoneal dissemination, and was typically observed 1-3years post-resection. This retrospective study identified undifferentiated-type adenocarcinoma as the only risk factor for recurrence in stage Ib gastric cancer patients. Although randomized controlled studies are necessary, stage Ib gastric cancer patients with this identified recurrence risk factor would be candidates for adjuvant chemotherapy.

In the era of pre- or perioperative therapy for gastric cancer, clinical staging before treatment appears to be increasingly important for prognosis, yet there are no data on the subject for resectable gastric cancer patients. To evaluate the prognostic role of preoperative locoregional staging in gastric cancer patients undergoing curative resection. We reviewed 1964 gastric cancer patients who underwent curative resection without preoperative therapy from 2001 to 2005. We performed computed tomography and clinical staging according to both the International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) (sixth edition) classification system, which bases N stage on the number of involved nodes, and the Japanese Classification of Gastric Carcinoma (JCGC) system, which bases N stage on node location. The 5-year survival rates for patients with clinical T1, T2, T3, and T4 disease were 94.5%, 83.6%, 57.7%, and 35.5%, respectively (P < 0.001). The 5-year survival rates were 89.4% and 68.3%, respectively, for patients with clinical UICC/AJCC N0 and N1 disease (P < 0.001) and 89.4%, 72.4%, 61.0%, and 41.9%, respectively, for patients with clinical JCGC n0, n1, n2, and n3 disease (P < 0.001). When the JCGC system was applied within the UICC/AJCC N1 category, the 5-year survival rates significantly decreased, going from n1 (72.4%) to n2 (61.0%) to n3 (38.2%) (P < 0.001). In multivariate analysis, clinical T and N stage remained significant prognostic factors for overall survival. Clinical stage is an independent predictor of long-term survival in the preoperative setting. It should be incorporated as a stratification factor in a randomized clinical trial of preoperative therapy for gastric cancer patients.

Background: Neoadjuvant chemotherapy for advanced gastric cancer is expected to improve prognoses. However, as there is no method to evaluate neoadjuvant chemotherapeutic efficacy before gastrectomy, some patients at high risk for a poor prognosis undergo gastrectomy. The aim of the present study was to investigate whether endoscopy could be useful for assessing the efficacy of neoadjuvant chemotherapy. Methods: In this retrospective study, we analyzed the data of 41 patients who received neoadjuvant chemotherapy followed by gastrectomy at our institution to investigate whether responsiveness to neoadjuvant chemotherapy, as assessed with endoscopy, can serve as a surrogate marker for histological grades 1b or higher in the Japanese Classification of Gastric Carcinoma (JCGC) scheme. Results: There were 32 (78.0%) responders and 9 (22.0%) nonresponders to neoadjuvant chemotherapy, as observed in endoscopic evaluations. Among the endoscopic responders, 24 (75.0%) had cancer of histological grade 1b or higher, and 15 (46.9%) had cancer of grade 2 or higher. Among the endoscopic nonresponders, 1 (11.1%) patient had histological grade 1b cancer. Compared with endoscopic nonresponders, endoscopic responders were more likely to show a histological response (chi-square test: p = 0.0005 for JCGC grade 1b or higher; p = 0.0099 for JCGC grade 2 or higher). Conclusions: Most endoscopic responders showed JCGC histological responses. Evaluation of neoadjuvant chemotherapeutic efficacy by endoscopy in gastric cancer may be useful before gastrectomy. As this was a retrospective study, further investigations are required. The protocol was approved by the ethics review committee at Osaka Medical College (No. 2422) and was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033088).

Recent studies reported that the histological mixed-type, which consists of differentiated and undifferentiated components, was related to the aggressive clinical features of gastric cancer as well as its poor outcomes. This study was designed to investigate the influences of the mixed-type on lymph node metastasis in patients with submucosal gastric cancer. We analyzed a total of 239 consecutive patients who underwent curative gastrectomy for submucosal gastric cancer between 2004 and 2012 from their hospital records. The overall prevalence of histological mixed-type in submucosal gastric cancer was 46.9% (112/239). The histological mixed-type correlated more strongly with lymph node metastasis (P = 0.0016; 25.0% (28/112)) than the undifferentiated type in the Japanese classification of gastric carcinoma (JCGC) (P = 0.2779; 20.5% (17/83)) and 7th tumor-node-metastasis (TNM) (P = 0.0476; 20.7% (31/150)) classifications. Univariate and multivariate logistic regression analyses identified a tumor size of 25mm or greater (P = 0.0003, OR 4.51 (95% CI 1.95-11.9)) and the histological mixed-type (P = 0.0316, OR 4.02 (95% CI 1.12-19.2)) as independent risk factors for lymph node metastasis. The incidence of lymph node metastasis was high in patients with both these factors (33.8% (23/68)) and low in patients without both factors (3.0% (2/67)). These results suggest that the histological mixed-type correlated more strongly with lymph node metastasis than the undifferentiated type in the JCGC and TNM classifications and highlight its usefulness as a risk factor for lymph node metastasis in submucosal gastric cancer.

Clinical Significance of the Metastatic Lymph-Node Ratio in Early Gastric Cancer

Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared. We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with para-aortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short- and long-term survivors were estimated. In JCOG0210 (n=49), HR was 0.54 in JCGC responders (P=0.059) and 0.40 in histological responders (P=0.005). The difference in response rates between short- and long-term survivors using histological criteria (34%, P=0.023) was greater than that using JCGC criteria (24%, P=0.15). In JCOG0405 (n=51), HR was 0.67 in RECIST responders (P=0.35) and 0.39 in histological responders (P=0.030). In short- and long-term survivors, respectively, RECIST response rates were 62 and 67% (P=0.77), whereas histological response rates were 33 and 63% (P=0.048). Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.