Preoperative staging for gastric cancer

Siewert JR, Sendler A.

For decades, the gold standard for evaluating patients with symptoms of peptic ulcer disease was barium upper gastric intestinal radiography. The ability to biopsy an abnormal finding under direct vision has now placed video-endoscopy at the top of the diagnostic algorithm. Through improved flexible endoscopy equipment and more accurate tissue diagnosis with multiple biopsy samples, esophago-gastro-duodenoscopy is now been chosen as the initial diagnostic test for dyspepsia. In the Patient Care Study of the American College of Surgeons, diagnosis of gastric cancer was established in 94% of the patients by endoscopy and biopsy [12].

Following diagnosis, preoperative evaluation to determine whether a tumor and its lymphatic drainage system is completely resectable, plays the crucial role in the decision-making process for or against a primary operation. Only if a complete (UICC R0) resection is to be expected, the prognosis of the patient can be improved by surgery. If surgery alone is considered to be the sole useful therapeutic modality, only patients with tumors determined to be unresectable will really benefit from often time consuming and expensive diagnostic procedures. However, if multimodal treatment strategies are used in gastric cancer, a stage dependent therapy has to be the goal of such diagnostic procedures [9].

Following the rules of the International Union Against Cancer (UICC) and the American Joint Commission on Cancer (AJCC) staging of gastric cancer is done according the TNM system (table I) [11]. Staging is the exact evaluation of the tumor stage, which means in gastric cancer the depth of tumor infiltration into the organ wall (T category), the lymph node status (N category) and the presence of distant metastases (M category). Staging in gastric cancer extends beyond exact physical examination, careful history and basic investigations such as endoscopy, biopsy or sonography. It includes in centers endoluminal ultrasound (EUS) and surgical laparoscopy to inspect the whole abdominal cavity and to obtain an abdominal lavage.

Table I. TNM/R staging according to the UICC, 1997.

Table I

TNM/R staging according to the UICC, 1997.

There is no specific serum tumor marker for gastric cancer. However, carcinoembryonic antigen levels and CA 72-4 are frequently elevated in patients with extensive disease and may be used as a marker in monitoring the progress during treatment.

Primary tumor, T-category

Using endoscopy and biopsy, the location of the tumor and its macroscopic appearance should be clarified. Early gastric cancer (fig. 1) and advanced gastric cancer (Borrmann classification, fig. 2) are classified differently according to the Japanese Gastric Cancer Association[2].

Figure 1. Endoscopic classification of early gastric cancer according to the Japanese Research Society for Gastric Cancer: Type I: protruded, Type IIa: superficial elevated, Type IIb: superficial flat, Type IIc: superficial depressed, Type III: exulcerated.

Figure 1

Endoscopic classification of early gastric cancer according to the Japanese Research Society for Gastric Cancer: Type I: protruded, Type IIa: superficial elevated, Type IIb: superficial flat, Type IIc: superficial depressed, Type III: exulcerated.

Figure 2. Classification of advanced gastric cancer according to Borrmann: Type I: polypoid fungating, Type II: ulcerative with elevated distinct borders, Type III: ulcerative with indistinct borders, Type IV: diffuse, indistinct borders.

Figure 2

Classification of advanced gastric cancer according to Borrmann: Type I: polypoid fungating, Type II: ulcerative with elevated distinct borders, Type III: ulcerative with indistinct borders, Type IV: diffuse, indistinct borders. Type I and II: localized (more...)

The localization of the tumor is crucial, as it determines different surgical strategies:

Carcinoma of the proximal gastric third can frequently not be differentiated from the true carcinoma of the cardia. In addition, these tumors must be distinguished from adenocarcinoma of the distal esophagus (the socalled Barrett's carcinoma). In our experience, these 3 tumor entities can be best discriminated based on the location of the tumor center [10]. The diagnosis of a Barrett's carcinoma is usually easy, because the accompanying columnar type epithelium can be documented in 75–85% of patients. At least two thirds of the tumor mass must be located in the tubular esophagus to classify a tumor as Barrett's carcinoma. To classify a tumor as proximal gastric carcinoma the tumor center must be aboral of the anatomic cardia. Tumors whose center is located within 2 cm oral or aboral of the anatomic cardia consequently represent the true carcinomas of the cardia. With regard to therapy, it is only necessary to definitely differentiate Barrett's carcinoma from the other two entities. This is because a Barrett's carcinoma must be treated as esophageal cancer, while the therapeutic principles are similar for the true carcinoma of the cardia and tumors of the proximal gastric third (fig. 3).

Figure 3. Definition of the adenocarcinoma of the esophago-gastric junction (AEG).

Figure 3

Definition of the adenocarcinoma of the esophago-gastric junction (AEG). For details see text.

The first biopsies will determine the histopathologic type of the tumor. Gastric cancer is predominantly adenocarcinoma. Gastric lymphoma (MALT) has to be excluded before beginning treatment because this entity is treated completely different. The histopathologic subclassification according to the Laurén classification of tumor growth (intestinal versus non-intestinal type) must also be determined since this provides additional important information about the necessary luminal extent of the surgical resection. The grade of differentiation (G 1–3, i.e. well to poor, G 4: undifferentiated), should also be reported in these first biopsies. In future times, biological classification of malignant tumors using molecular-biological methods will be possible. Using this approach, therapy of gastric cancer could be based on a more scientific and individual basis.

Since the depth of infiltration is one of the most important prognostic factors in gastric cancer, endoluminal ultrasound (EUS) is the next step for further diagnostic planning. The overall diagnostic accuracy of staging the T category using EUS is about 85% (table II) [6]. Problems still arise in the differentiation of T2 (subserosal invasion) from the T3 stage. This distinction is crucial, since it separates local from the locally advanced tumor growth. The use of EUS is still hampered by the problem of over- or understaging. It is often difficult, especially in ulcerated gastric cancer, to differentiate between carcinoma, inflamed surrounding soft tissue or even fibrosis. Furthermore, EUS can not detect micro-invasive cancer [5]. In this context it has to be mentioned, that the use of EUS is strongly dependent on the training and experience of the investigator. The excellent results published in various studies are obtained by very well trained, specialized “endosonographists”. Until now, the use of EUS has been restricted to centers which have already accumulated sufficient experience with this sophisticated technique. Further evaluation of the method must be carried out with respect to clinical consequences and it's value in daily routine praxis. EUS is still far superior to CT for the determination of the overall T category. Lightdale et al. [3] reported a concordance of 92% between EUS and surgical pathology and only 42% concordance for CT scan.

Table II. Accuracy of EUS locoregional staging in gastric cancer by stage (TNM 1992).

Table II

Accuracy of EUS locoregional staging in gastric cancer by stage (TNM 1992).

Nodal involvement, N-category

Using EUS, the diagnostic accuracy of determining the N-category according to the old TNM classification (up to 1997) in gastric cancer is reported to be 65–87%. The diagnosis of lymph node metastases is problematic due to a low rate of detected lymph nodes and a high rate of false-positive findings. EUS can only visualize lymph nodes in close proximity to the gastric wall. As with other imaging methods, EUS can only detect enlarged lymph nodes. Nodes that are invaded but not enlarged can not be detected. Furthermore it is not possible to count lymphnodes by EUS. Therefore it is recommended to stage the nodal status only as N positive (+) or negative.

However, there is a distinct correlation between the T category and the number and localization of invaded lymph nodes. T3 tumors have a possibility of 88% positive lymph nodes (fig. 4). Overall, EUS is still more accurate than percutaneous ultrasound or CT for the evaluation of N stage.

Figure 4. Relationship between depth of tumor infiltration and consecutive lymph node metastasation in patients with gastric cancer.

Figure 4

Relationship between depth of tumor infiltration and consecutive lymph node metastasation in patients with gastric cancer.

Distant metastases - M-category

Due to the embryonic rotation of the stomach, gastric cancer metastasizes not only into the lymph nodes of the greater and lesser omentum, but also into the lymph nodes around the celiac axis and the retroperitoneal space along the large abdominal vessels. The tumor itself can reach “per continuitatem” liver, pancreas, small and large bowel and sometimes the spleen. Seldom, in about 3% of the cases, the tumor metastases primarily to the bone marrow. In female patients metastases at the ovary are a possible additional finding (Krukenberg tumors).

The different subtypes of the Laurén classification have different patterns of metastasation. While the intestinal type metastasizes preferentially to the liver and lymph nodes, the diffuse type spreads into the peritoneum [13]. Taking these routes of tumor spread into account, CT-examination of the whole abdominal cavity is necessary. However, a very crucial region for distant spread of gastric cancer, the peritoneum, can only be visualized using CT scanning when ascites is present.

Conventional ultrasonography (US), CT scanning, and MRI are the methods of choice for detecting liver metastases. Small metastases (< 1 cm in diameter) pose a serious problem because they often evade established diagnostic methods, and are the predominantly size of metastases which are found. The sensitivity of US and CT for detecting the presence or absence of metastatic disease in the liver is about 85% [7]. However, for the identification of individual lesions the sensitivity of these techniques is considerably lower. About one in three lesions is missed, usually lesions under 1 cm in diameter.

The described pitfalls in staging can be overcome by surgical laparoscopy. Peritoneal spread of a tumor is easily visualized and confirmed by a videoguided biopsy. In an own study, peritoneal carcinosis was found in 23% of 111 patients with gastric cancer during laparoscopy, which was undetected after conventional staging. Intra-laparoscopic ultrasound furthermore even makes possible the detection of small (< 1 cm) liver metastases [1]. In addition, laparoscopy provides the possibility of obtaining an abdominal lavage to detect so called free tumor cells in the abdominal cavity. With the use of immunohistochemical staining, the cytological evaluation of lavage fluid provides even more valuable information.

Of particular interest is, that the possibility of lymph node involvement and the prediction of the individual prognosis of gastric cancer, can be predicted with the help of a validated and well established computer program [4].

The staging is completed with a bone scintigram (for T3/T4 tumors) and a chest X-ray.

Figure 5 displays a diagnostic approach to gastric cancer based on preoperative staging. This approach allows the identification of a group of patients with locally advanced gastric carcinoma who may benefit from preoperative chemotherapy [8].

Figure 5. Flow diagram illustrates the diagnostic evaluation for patients with gastric cancer in oncologic centers prepared to provide multimodal treatment (PF - prognostic factors, CTx - chemotherapy).

Figure 5

Flow diagram illustrates the diagnostic evaluation for patients with gastric cancer in oncologic centers prepared to provide multimodal treatment (PF - prognostic factors, CTx - chemotherapy).

References

1.
Feussner H, Kraemer S J M, Siewert J R. Staging-Laparoskopie. Chirurg. (1997);68:201. [PubMed: 9198560]
2.
Japanese Research Society for Gastric Cancer. The general rules for the gastric cancer study in surgery and pathology I: Clinical classification. Jpn J Surg. (1981);11:127. [PubMed: 7300058]
3.
Lightdale C J. Endoscopic ultrasonography in the diagnosis, staging and follow- up of esophageal and gastric cancer. Endoscopy. (1992);24 (suppl 1):297. [PubMed: 1633769]
4.
Maruyama K, Gunven P, Okabayashi K, Sasako M. et al. Lymph node metastases of gastric cancer. General pattern in 1931 patients. Ann Surg. (1989);210:596. [PMC free article: PMC1357792] [PubMed: 2818028]
5.
Pollack B J, Chak A, Sivak M V Jr. Endoscopic ultrasonography. Semin Oncol. (1996);23:336. [PubMed: 8658217]
6.
Rösch T. Endosonographic staging of gastric cancer: a review of literature results. Gastrointest Clin North Am. (1995);3:549. [PubMed: 7582581]
7.
Saini S. Imaging of the hepatobiliary tract. N Engl J Med. (1997);336:1889. [PubMed: 9197218]
8.
Sendler A, Dittler H J, Feussner H, Nekarda H. et al. Preoperative staging of gastric cancer as precondition for multimodal treatment. World J Surg. (1995);19:501. [PubMed: 7676691]
9.
Siewert J R, Fink U, Sendler A, Becker K. et al. Gastric cancer. Curr Probl Surg. (1997);43:837.
10.
Siewert J R, Stein H J. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. (1998);85:1457. [PubMed: 9823902]
11.
UICC (1997) TNM classification of malignant tumors. In: Hermanek, P, Hutter RVP, Sobin LH, Wagner G, Wittekind Ch (eds) 4th Ed. Springer, Berlin Heidelberg New York .
12.
Wanebo H J, Kennedy B J, Chmiel J, Steele G Jr. et al. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. (1993);218:583. [PMC free article: PMC1243028] [PubMed: 8239772]
13.
Weiss M, Eder M, Bassermann R. Charakterisierung verschiedener Magenkarzinomtypen mit unterschiedlicher Metastasierung in Leber, Peritoneum und Knochen. Pathologe. (1993);14:260. [PubMed: 8415435]