New TNM  in the Staging of Gastric Cancer

Dongfeng Tan, MD

Introduction

    Properly staging cancer allows the clinician to choose the appropriate treatment modalities, reliably evaluate and predict outcomes of disease management, and uniformly document cancer cases worldwide. Although there are several classification systems for gastric cancer, the Cancer Staging Manual developed by the American Joint Committee on Cancer (AJCC) with support from International Union for Cancer Control (UICC), the American Cancer Society, American College of Surgeons, American Society of Clinical Oncology, and International Union against Cancer, is the generally accepted classification system. The cancer-staging criteria have been continually refined since 1959, with the combined efforts of medical community, and multiple medical and oncology organizations. The latest edition (7^th edition) of the AJCC Cancer Staging Manual was published in early 2010. In the new edition, the AJCC and UICC used large datasets and emerging evidence to support changes in the cancer staging criteria in general, and they used data sets from Asia, Europe, and the United States for the gastric cancer staging systems in particular.

    In the new edition of the AJCC staging manual, tumors arising at the EGJ, or arising within the proximal 5 cm of the stomach (cardia) that extends into the EGJ or esophagus, are staged using the TNM system for adenocarcinoma of the esophagus. All other cancers with a midpoint in the stomach lying more than 5 cm distal to the EGJ, or those within 5 cm of the EGJ but not extending into the EGJ or esophagus, are staged using the gastric cancer staging system.

DEFINITIONS OF TNM

    TNM staging describes three major anatomic characteristics of cancer: 1) the location and extension of the primary tumor, 2) the presence or absence of lymph node involvement, and 3) the presence or absence of distant tumor metastasis. These features can be evaluated by physical examination, imaging studies, and histopathologic evaluation. All cancers, though, should be confirmed histologically.

    Before pathologic staging, efforts should be made to differentiate primary gastric cancer from metastatic disease, which is not an uncommon event. After the primary gastric cancer is established, gastric cancer should be classified. Majority of gastric cancer is adenocarcinoma. The histological subtypes of gastric cancer are listed in Table 1. 

            Adenocarcinoma (more than 90%)

            Adenosquamous carcinoma

            Mucinous adenocarcinoma

            Papillary adenocarcinoma

            Signet ring cell carcinoma

            Squamous cell carcinoma

            Tubular adenocarcinoma

    Pathologically, the extent of the tumor needs to be carefully assessed. Pathologic staging depends on data acquired clinically together with findings on subsequent gross and microscopic examination of the surgically resected specimen.

    Of note, the TNM staging recommendations apply only to carcinomas. Lymphomas, sarcomas, and carcinoid tumors (well-differentiated neuroendocrine tumors) are excluded. Mixed glandular/neuroendocrine carcinomas should be staged using the gastric carcinoma staging system for well-differentiated gastrointestinal neuroendocrine tumors.

Designation of primary gastric cancer status     

    Staging of primary gastric adenocarcinoma is dependent on the extension and depth of penetration of the primary tumor. Histologically, the wall of the stomach has five layers: mucosa, submucosa, muscular propria, subserosal connective tissue, and serosal surface.

    One of the major changes to the T designation for gastric cancer in the 7^th edition of the AJCC Cancer Staging Manual is that the T categories have been modified to correspond to the T categories for cancers of the esophagus and small and large intestine. Specifically, T1 lesions have been subdivided into T1a and T1b, which are defined as tumor invades muscularis mucosae and tumor invades submucosa, respectively; T2 is defined as a tumor that invades the muscularis propria; T3 is defined as a tumor that invades the subserosal connective tissue (formerly T2b in AJCC Cancer Staging Manual, 6^th edition); and T4 is defined as a tumor that invades the serosa (visceral peritoneum, formerly T3 in AJCC Cancer Staging Manual, 6^th edition) or adjacent structures. The T (primary tumor) designation of gastric cancer is listed in Table 2.

Table 2.    Primary Tumor (T) of Gastric Cancer

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TX        Primary tumor cannot be assessed

T0        No evidence of primary tumor

Tis       Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria

T1        Tumor invades lamina propria, muscularis mucosae, or submucosa

T1a      Tumor invades lamina propria or muscularis mucosae

T1b      Tumor invades submucosa

T2        Tumor invades muscularis propria

T3        Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures *

T4        Tumor invades serosa (visceral peritoneum) or adjacent structures *

T4a      Tumor invades serosa (visceral peritoneum)

T4b      Tumor invades adjacent structures

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*The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum.

Designation of regional lymph node status

    The regional lymph nodes of the stomach are roughly divided into two major groups: 1) the perigastric nodes, which include nodes in the greater curvature of the stomach and nodes in the lesser curvature of the stomach, and 2) the local nodes in the pancreatic and splenic area.

Adequate dissection of these regional nodal areas is important to ensure the appropriate pN designations and final staging. For pathologic assessment, the regional lymph nodes are removed and examined histologically to evaluate the total number of lymph nodes as well as the number that contain metastatic tumors. N categories have been modified in the new AJCC staging manual, with N1=1-2 positive regional lymph nodes, N2=3-6 positive regional lymph nodes (N1 in the 6^th edition of AJCC staging manual) and N3=7 or more positive regional lymph nodes. In addition, metastatic nodules in the fat adjacent to a gastric carcinoma, without evidence of residual lymph node tissue, are considered regional lymph node metastases. Although it has been suggested that pathologists assess at least 16 regional lymph nodes, a pN determination may be assigned on the basis of the actual number of nodes evaluated microscopically. The N (regional lymph node) designation of gastric cancer is listed in Table 3.

Table 3.  Regional Lymph Nodes (N) of Gastric Cancer

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NX       Regional lymph node(s) cannot be assessed

N0       No regional lymph node metastasis*

N1       Metastasis in 1-2 regional lymph nodes

N2       Metastasis 3-6 regional lymph nodes

N3       Metastasis in seven or more regional lymph nodes

N3a      Metastasis in 7-15 regional lymph nodes

N3b      Metastasis in 16 or more regional lymph nodes

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*Note: A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.

Designation of distant metastasis status:

    Two designations of metastatic status are included in the 7^th edition of the AJCC Cancer Staging Manual, namely, M0: No distant metastasis, and  M1:Distant metastasis. Note, no Mx designation was mentioned in the 7^th edition of the AJCC Cancer Staging Manual.

    Distant metastasis means that the tumor has disseminated to distant lymph nodes or a distant organ system.    The distant lymph nodes of gastric cancer include retropancreatic, hepatoduodenal, para-aortic, portal, retroperitoneal, and mesenteric. Involvement of these intra-abdominal lymph nodes is classified as distant metastasis. Other metastatic sites include distant organs (liver, lungs, and central nervous system) and peritoneal surfaces (tumor implants). Positive peritoneal cytology is now classified as metastatic disease (M1). A summary of designation of distal metastatic tumor is listed in Table 4.

Metastatic carcinoma in distant lymph nodes

        Hepatoduodenal

        Mesenteric

        Para-aortic

        Portal

        Retropancreatic

        Retroperitoneal

Metastatic carcinoma in distant organs

        Liver

        Lungs

        CNS

        Other less common organ sites

Metastatic carcinoma in peritoneal surfaces

DESIGNATION OF ANATOMIC STAGE

    The final grouping (staging) of gastric cancer is dependent on the appropriate designations of T, N, and M.  The anatomic stage, based on the current AJCC Cancer Staging Manual, is listed in Table 5. Of note, if there is uncertainty concerning the appropriate T, N, or M designation, the lower (less advanced) category should be assigned, in accordance with the general rules of staging.

Table 5   Anatomic Stage of Gastric Cancer*

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Stage 0                                     Tis                               N0                               M0

Stage IA                                   T1                                N0                               M0

Stage IB                                   T2                                N0                               M0

                                                T1                                N1                               M0

Stage IIA                                 T3                                N0                               M0

                                                T2                                N1                               M0

                                                T1                                N2                               M0

Stage IIB                                  T4a                               N0                               M0

                                                T3                                N1                               M0

                                                T2                                N2                               M0

                                                T1                                N3                               M0

Stage IIIA                                T4a                               N1                               M0

                                                T3                                N2                               M0

                                                T2                                N3                               M0

Stage IIIB                                T4b                               N0                               M0

                                                T4b                               N1                               M0

                                                T4a                               N2                               M0

                                                T3                                N3                               M0

Stage IIIC                                T4b                               N2                               M0

                                                T4b                               N3                M0                  

                                                T4a                               N3                               M0

Stage IV                         

                   Any   T           AnyN                          M1

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* from the AJCC Cancer Staging Manual, 7^th Edition.

胃癌新的TNM分期系统

谈东风

引言

对癌症进行恰当的分期不仅有助于临床医生选择合适的治疗方案，预测疾病处理的后果，也有助于全世界对癌症研究有一个统一的标准，以便于更好地比较。尽管有几种胃癌分类系统，但由美国抗癌联合会（AJCC）制定的癌症分期手册得到了国际防癌联盟（UICC）、美国癌症学会、美国外科医师学会、美国临床肿瘤学会和国际抗癌联盟的支持，称为一种广泛接受的分类系统。癌症分期标准自从1959年以来就不停地修订，综合了医学团体、多家医疗和肿瘤机构的共同努力。最新版（第7版）AJCC癌症分期手册于2010年初出版。在这个新的版本中，AJCC和UICC使用了大量数据和新出现的证据来支持这个癌症分期标准的变化，特别是胃癌，他们还特地使用了来自于亚洲、欧洲、美洲的胃癌资料。

在新版的AJCC分期手册内，发生自食管胃连接处的肿瘤或距离胃近端5cm的（贲门）并延伸入EGJ或食管的肿瘤，推荐使用食管腺癌的TNM分期系统。所有位于胃的重点且距离EGJ 5cm以上的胃癌或距离EGJ 5cm以内但未累及EGJ或食管的癌则建议按照胃癌分期系统进行分期。

TNM的定义

  TNM分期描述了癌的3种主要的解剖学特征：1）原发肿瘤的部位和范围，2）淋巴结累及的有无和3）是否有远处肿瘤转移。这些特征能通过体格检查、影像学和组织病理学检查来评估。虽然所有的癌症都应通过组织学来证实。

    在病理分期前，应区分是原发性胃癌还是转移性癌，后者比较少见。一旦确定为原发性胃癌，就应该对癌进行分类。大多数胃癌是腺癌。胃癌的组织学亚型见表1

表1  胃癌的组织学亚型

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 腺癌（90%以上）

腺鳞癌

黏液性腺癌

乳头状腺癌

印戒细胞癌

鳞状细胞癌

小管状腺癌

未分化癌

            -------------------------------------------------------

   病理上，肿瘤的范围需要认真评估。病理分期依赖于临床上获得的资料并结合随后的手术切除标本的大体和镜检结果。

   值得注意的是，TNM分期系统仅适用于癌，淋巴瘤、肉瘤和类癌性肿瘤（高分化神经内分泌肿瘤）不适用于本TNM分期。混合型腺性/神经内分泌癌应使用高分化胃肠道神经内分泌肿瘤的胃癌分期系统进行分期。

今天翻译到这里，明天继续

谢谢！

肿瘤TNM分级，对国际化，标准化医疗服务很重要.

XieXie!  I just summarized the major points of the new TNM manual with my short introduction.

 Sections of colorectal cancer and liver cancer will follow.

 Thank you.

 谢谢，很好的文章

想问一下，谈老师是那里人，很崇拜您。