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

________________________________________________________________________

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

________________________________________________________________________

*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

________________________________________________________________________

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*

_______________________________________________________________________

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.

可以翻译合成中文的吗？？谢谢。

 　新的TNM的胃癌
　适当的临床分期癌症可以选择合适的治疗策略、可靠的评估和预测结果的疾病管理、统一文档癌症病例。虽然有几个分类体系,癌症分期胃癌手册开发由美国联合委员会关于癌症(AJCC)的大力支持下,国际癌症控制(UICC),美国癌症协会,美国外科医师协会、美国临床肿瘤学协会、国际联盟对抗癌症,是公认的分类系统。这个cancer-staging标准已经连续精制而成的,在1959年以来医学界相结合,对多个医疗和肿瘤组织。最新版(第七版)的AJCC癌症分期操作手册也被刊登在2010年初。在新版本,AJCC和UICC使用大型数据集和新兴的证据来支持改变癌症分期标准,他们使用的数据集来自亚洲,欧洲和美国在特定胃癌分期系统。
　　
　　
　　
　　在新版本的AJCC分期,肿瘤产生的手册,或由EGJ在近5厘米(贲门胃的延伸到EGJ),正在使用或食道腺癌的TNM系统的食管。所有其他的癌症与中点胃里躺在床上,超过5厘米EGJ远端,或那些在5厘米,但不是EGJ伸向EGJ或食道、正在使用胃癌分期系统。
　　
　　
　　
　　TNM的定义
　　
　　TNM分级描述解剖学特征主要有三种:1)位置肿瘤原发肿瘤,延长的,2)有无淋巴结累及,和(3)有无遥远的肿瘤转移。这些特征的评估可以通过体检,影像学检查、病理的评价。所有癌症,虽然,应确认在组织学上。
　　
　　
　　
　　病理分期之前,应努力鉴别主要胃癌晚期的癌症,它是由不寻常的事件。之后建立了基本胃癌、胃癌归类。多数胃癌是腺癌。其组织学亚型的胃癌都列在表1。
　　
　　表1。其组织学亚型的胃癌
　　
　　腺癌(90%以上)。
　　
　　Adenosquamous癌,
　　
　　降结肠
　　
　　乳头状癌
　　
　　戒指细胞癌
　　
　　鳞状细胞癌
　　
　　管状腺癌
　　
　　未分化癌,
　　
　　在病理上,肿瘤的程度需要仔细地评估。病理分期取决于数据一起在临床上及后续研究的手术切除标本。
　　TNM分级的注意,这个建议只适用于癌。肉瘤、淋巴瘤,神经内分泌肿瘤细胞分化肿瘤(类)的除外。神经内分泌癌腺体/混合使用应举行胃癌分期系统与神经内分泌肿瘤细胞分化肠胃。
　　

    指定的原发性胃癌的地位
　　
　　胃腺癌的主要依赖于扩建的深度和渗透的原发肿瘤。组织学上,墙上的胃粘膜有五层,黏膜下层、肌。此例,浆膜结缔组织,浆膜表面。
　　
　　一个主要的变化对T指示胃癌在第7版的AJCC癌症分期手册是T范畴被修改,以符合这个类别,为癌症的小肠和大肠病。确切地说,T1病变有被细分成T1a和T1b,定义为肿瘤侵入肌与肿瘤侵袭黏膜下层,分别;T2被定义为一种肿瘤侵入了固有肌;T3被定义为一种肿瘤侵入了浆膜结缔组织(原T2b在AJCC癌症分期手册,第六版);和T4被定义为一种肿瘤侵入绒毛膜“(内脏腹膜,原名T3期AJCC癌症分期手册,第六版)或相邻的结构。T(原发肿瘤)指定胃癌是列在表2。
　　表2。原发性肿瘤(T)胃癌
　　
　　________________________________________________________________________
　　
　　德克萨斯州的原发性肿瘤无法评定
　　
　　没有证据表明,每原发肿瘤
　　
　　这肿瘤上皮原位癌:固有层没有入侵
　　
　　T1肿瘤侵入固有层、肌、或粘膜下层
　　
　　T1a肿瘤侵入固有层或肌层
　　
　　T1b粘膜下肿瘤侵入
　　
　　此例中肿瘤侵入层是
　　
　　T3肿瘤穿透浆膜结缔组织无侵犯内脏腹膜或邻近建筑物
　　
　　肿瘤侵入serosa(体重)或相邻建筑物内脏手术
　　
　　T4a肿瘤侵入serosa(内脏腹膜)。
　　
　　T4b肿瘤侵入邻近建筑物
　　
　　
　　
　　毗邻构筑物的胃的包括脾脏、结肠、肝脏、胰腺、隔膜,腹壁、肾上腺、肾脏、小肠和腹膜后腔。
　　
　　
　　指定区域淋巴结的地位
　　
　　这个区域淋巴结的胃大致分为两大类:1)perigastric节点的节点,其中包括在大曲率的胃和节点在较小的胃的曲率,和(2)局部节点胰脏、脾区。
　　
　　适当的区域淋巴结区域解剖是很重要的,确保适当的pN称谓和期末举办。为病理性评估、区域淋巴结清除组织学检查评估总人数的淋巴结以及含有转移瘤的数量。氮类已经被修改的新AJCC分期指南》,N1 = 1-2积极淋巴结、氮气= 3-6积极淋巴结(N1在第六版的AJCC分期手册)和误= 7或更积极的淋巴结。此外,转移性结节的脂肪临近,没有证据显示胃癌淋巴组织的剩余的,被认为是区域淋巴结转移。虽然它已经被建议病理学专家评估至少16淋巴结,可以指定pN测定的基础上进行了实际的节点。N(区域淋巴结)指定胃癌是列在表3。
　　表3。局部淋巴结(N)胃癌
　　
　　________________________________________________________________________
　　
　　NX区域淋巴结(s)不能被评估
　　
　　没有任何区域淋巴结转移
　　
　　在1-2 N1转移的淋巴结
　　
　　氮气转移3-6淋巴结
　　
　　在7个或更多误转移的淋巴结
　　
　　N3a 7-15区域淋巴结转移
　　
　　在16区或更N3b转移的淋巴结
　　
　　________________________________________________________________________
　　
　　
　　
　　注:指示性pN0可以用在所有检查淋巴结阴性,无论总数的拆卸和检查。
　　
　　
　　
　　指定远处转移的地位。
　　
　　
　　
　　两种称谓中的转移包括在第7版的AJCC癌症分期手册,即M0:没有远处转移和M1:远处转移。注意,没有Mx指定在第7版的AJCC癌症分期手册。
　　
　　
　　
　　远处转移意味着肿瘤散布到遥远的淋巴结或一个遥远的器官系统。遥远的淋巴结胃癌,hepatoduodenal,para-aortic包括retropancreatic、门静脉腹膜后,肠系膜。这些腹内淋巴结累及为远处转移。其他转移包括遥远的器官(肝脏,肺,中枢神经系统)和腹膜面(肿瘤植入)。阳性腹水细胞学正在为转移性疾病(M1)。一份的远端转移性肿瘤是指定列在表4。
　　
　　
　　
　　表4。指定的远端转移性肿瘤(M1)。
　　
　　————————————————————————————————————————————————————————
　　
　　在遥远的淋巴结转移癌
　　
　　Hepatoduodenal
　　
　　肠系膜
　　
　　Para-aortic
　　
　　入口
　　
　　Retropancreatic
　　
　　徒腹腔
　　
　　在远处器官转移癌
　　
　　肝
　　
　　肺
　　
　　CNS
　　
　　其他较常见的器官的地点
　　
　　在腹膜面转移癌
　　
　　在腹水细胞学转移癌
　　
　　————————————————————————————————————————————————————
　　
　　
　　
　　
　　
　　指定解剖的阶段
　　
　　
　　
　　期末分组(分期)胃癌是依赖于适当的称谓中的氮、T、解剖阶段,基于当前的AJCC癌症分期手册,是列在表5。注意,如果存在不确定性,关于适当的教师,或被指定,较低的(高级)范畴应按照一般规则的分期。
　　
　　
　　
　　表5解剖阶段胃癌
　　
　　
　　
　　_______________________________________________________________________
　　
　　0这没有M0阶段
　　
　　舞台IA T1没有M0)
　　
　　舞台IB T2没有M0)
　　
　　T1 N1 M0)
　　
　　IIA期没有M0阶段
　　
　　T2 N1 M0)
　　
　　T1 N2 M0)
　　
　　T4a IIB阶段没有M0)
　　
　　T3 N1 M0)
　　
　　T2 N2 M0)
　　
　　T1误M0)
　　
　　IIIA期T4a N1 M0)
　　
　　T3 N2 M0)
　　
　　T2误M0)
　　
　　用户T4b渺茫M0阶段
　　
　　T4b N1 M0)
　　
　　T4a N2 M0)
　　
　　T3误M0)
　　
　　T4b N2期IIIC M0)
　　
　　T4b误M0)
　　
　　T4a误M0)
　　
　　第四阶段
　　
　　任何不AnyN M1
　　
　　________________________________________________________________________
　　
　　
　　
　　从AJCC癌症分期*手册、7版。

大家凑合着看吧，在线翻译的，不行就请翻译组的改改哈。

原发性胃癌的分期评估   

    原发性胃腺癌的分期依赖于原发肿瘤的浸润范围和深度。组织学上，胃壁分为5层：黏膜层、黏膜下层、肌层、浆膜下结缔组织和浆膜面。

 AJCC癌症分期手册第7版有关胃癌T的命名中一个主要的变化是T分类被修改并对应于食管和大小肠癌的T分类。特别是T1病变被分为T1a和T1b，分别定义为肿瘤侵犯黏膜肌层和黏膜下层；T2定义为肿瘤侵犯到肌层；T3被定义为肿瘤侵犯到浆膜下结缔组织（AJCC癌症分期手册第6版位T2b）T4定义为肿瘤侵犯到浆膜（脏层腹膜，AJCC癌症分期手册第6版为T3）或邻近结构。胃癌T分类见表2

表2  胃癌原发肿瘤（T）

________________________________________________________________________

TX      原发肿瘤不能评价

T0      无原发肿瘤

Tis     原位癌：上皮内肿瘤无固有层侵犯

T1      肿瘤侵犯固有层、粘膜肌层或黏膜下层

T1a     肿瘤侵犯固有层或黏膜肌层

T1b     肿瘤侵犯黏膜下层

T2     肿瘤侵犯肌层

T3     肿瘤穿透浆膜下结缔组织但无侵犯脏层腹膜或邻近结构*

T4     肿瘤侵犯浆膜（脏层腹膜）或邻近结构*

T4a     肿瘤侵犯浆膜（脏层腹膜）

T4b     肿瘤侵犯邻近结构

________________________________________________________________________

*胃的邻近结构包括脾脏、横结肠、肝脏、膈肌、胰腺、腹壁、肾上腺、肾脏、小肠和腹膜后

局部淋巴结状态的命名

   胃局部淋巴结大概主要分为2组：1）胃周淋巴结，包括胃大弯和胃小弯淋巴结；2）胰腺和脾脏区域的局部淋巴结。

这些部位淋巴结充分取材对恰当的pN评价和最后的分期非常重要。病理上主要是评价切除的局部淋巴结，从组织学上确定全部淋巴结数目以及含有转移性肿瘤的淋巴结数目。新的AJCC分期手册中对N分类进行了修改，N1为1-2个阳性局部淋巴结，N2为3-6个阳性局部淋巴结（在第6版AJCC分期手册中为N1），N3为7个或以上阳性局部淋巴结。另外，邻近胃癌的脂肪中的转移性结节，虽无残留的淋巴结组织，但应看作局部淋巴结转移。尽管建议要求病理医生至少要评价16个局部淋巴结，但pN的评定可根据镜下评价的实际淋巴结数量来确定。胃癌N（局部淋巴结）分类见表3。

 表3  胃癌局部淋巴结分类（N）

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

________________________________________________________________________

NX      局部淋巴结不能评价

N0      无局部淋巴结转移*

N1      1-2个局部淋巴结转移

N2      3-6个局部淋巴结转移

N3      7个或以上局部淋巴结转移

N3a     7-15个局部淋巴结转移

N3b    16个或以上局部淋巴结转移

________________________________________________________________________

 远处转移状态的确定

 在第7版AJCC癌症分期手册中确定了2种远处转移状态。M0：无远处转移；M1有远处转移。注意的是，在第7版AJCC癌症分期手册中没有提到Mx的命名。

    远处转移意思是指肿瘤扩散到远处淋巴结或远处器官。胃癌远处淋巴结包括胰后、肝十二指肠、主动脉旁、门静脉、后腹膜和肠系膜淋巴结。腹腔内淋巴结累及应作为远处转移。其他转移部位包括远处器官（肝、肺和中枢神经系统）和腹膜表面（肿瘤种植）。腹水细胞学阳性现已视为远处转移（M1）。远处转移的命名概述于表4。

 表4 远处转移（M1）命名

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远处淋巴结转移性癌

       肝十二指肠

       肠系膜

       主动脉旁

        门静脉

        腹膜后

       远处器官转移性癌

       肝

       肺

       中枢神经系统

       其他少见器官

腹膜表面转移性癌

腹腔细胞学转移性癌

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 解剖学分期的命名

胃癌的最终分组（分期）取决于T、N和M的恰当命名。基于目前的AJCC癌症分期手册的解剖学分期见表5。值得注意的是，如果T、N和M分类中难以明确归类，按照分期一般原则，则应使用较低（低进展性）分类

 表5  胃癌解剖学分期*

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0期                   Tis                   N0                   M0

IA期                  T1                    N0                   M0

IB期                  T2                    N0                   M0

                        T1                   N1                     M0

IIA期                T3                  N0                      M0

                        T2                   N1                     M0

                        T1                   N2                      M0

IIB 期               T4a                  N0                      M0

                        T3                   N1                      M0

                        T2                   N2                       M0

                        T1                   N3                      M0

IIIA期              T4a                   N1                      M0

                        T3                    N2                      M0

                        T2                    N3                      M0

IIIB期              T4b                    N0                      M0

                        T4b                   N1                       M0

                        T4a                   N2                       M0

                        T3                    N3                       M0

IIIC期              T4b                    N2                       M0

                        T4b                    N3                      M0                  

                        T4a                    N3                       M0

IV期              任何T                任何N                      M1

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 * 来自于第7版AJCC分期