Recurrence in early gastric cancer--presence of micrometastasis in lymph node of node negative early gastric cancer patient with recurrence.

BACKGROUND/AIMS: There are cases of recurrence even after curative resection in early gastric cancer. METHODOLOGY: Seven hundred and sixty-five patients with early gastric cancer who underwent curative gastrectomy were analyzed to identify the prognostic factor. Micrometastases within lymph nodes were determined by immunohistochemistry using anti-cytokeratin antibody in node-negative early gastric cancer patients with recurrence. RESULTS: The recurrence was observed in 17 patients. Hematogenous recurrence was observed most frequently (47.1%), followed by peritoneal recurrence (23.5%). Of 17 patients with recurrence, 6 (35.3%) patients died more than 5 years after operation. The prognosis was poorer when the patients were older, and the depth of invasion was greater, lymph node metastasis, lymphatic involvement, and vascular involvement were present, and lymph node dissection was limited. The independent prognostic factors were lymph node metastasis, lymph node dissection, and age by multivariate analysis using Cox proportional hazards. Micrometastases within lymph nodes were confirmed in 3 of 6 node-negative patients with recurrence. CONCLUSIONS: When patients have lymph node metastases or are older, close and long-term follow-up and careful planning of postoperative adjuvant therapy might be necessary to avoid recurrence. The detection of micrometastases by anti-cytokeratin antibody might be useful for predicting the possibility of recurrence in early gastric cancer.

Prediction of sites of recurrence in gastric carcinoma using immunohistochemical parameters.

BACKGROUND AND OBJECTIVES: To improve prognosis of patients with gastric cancer, it is important to detect recurrences at an early stage following surgery. If the site of recurrence can be predicted, recurrent disease can be easier detected at an early stage. However, this is difficult to achieve using normal clinicopathological factors. We aimed to predict sites of recurrence in patients with advanced gastric carcinoma who underwent curative resection. METHODS: Expressions of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ss1, and p53, together with density of microvessels (MVs), and dendritic cell (DC) infiltration were examined by immunohistochemistry to evaluate their relationships with recurrence patterns in patients with advanced gastric carcinoma (n = 92). RESULTS: All immunohistochemical parameters closely correlated with prognosis (TGF-ss1, P = 0.008; VEGF, P < 0.001; p53, P = 0.028; MV, P < 0.001; DC, P < 0.001). Multivariate analysis showed that DC infiltration (P = 0.02; HR, 2.52; 95%CI, 1.16-5.48), MV density (P = 0.023; HR, 2.48; 95%CI, 1.13-5.44), VEGF expression (P = 0.002; HR, 3.27; 95%CI, 1.52-7.05), and lymph node metastasis (P < 0.0001; HR, 2.09; 95%CI, 1.49-2.93) were independent prognostic factors. A multivariate logistic regression analysis indicated that DC infiltration (P = 0.004; Odds ratio, 4.25; 95%CI, 1.51-11.96) and lymph node metastasis (P = 0.01; Odds ratio, 3.37; 95%CI, 1.31-8.66) provided significant estimates of relative risks for development of peritoneal recurrence. Upon development of hematogenous recurrence, VEGF expression significantly indicated relative risks (P < 0.001; Odds ratio, 7.26; 95%CI, 1.41-37.3). Moreover, p53 expression closely correlated with lymph node recurrence (P = 0.042; Odds ratio, 11; 95%CI, 1.26-95.7). CONCLUSIONS: Assessment of immunohistochemical parameters can predict sites of recurrence in gastric carcinomas, and thus contributes to improve prognosis.

Laparoscopic-assisted intraperitoneal chemotherapy for patients with scirrhous gastric cancer.

BACKGROUND: The prognosis for patients with scirrhous gastric cancer (SGC) is extremely poor. To improve the patients' prognosis, laparoscopic-assisted intraperitoneal chemotherapy (IPC) was introduced for SGC. In this study, we analyzed whether IPC reduced the number of cancer cells in the peritoneal cavity of patients or changed the gene expression levels of cytokines in the peritoneal cavity. We also investigated whether IPC improved the prognosis of patients with SGC. METHODS: Total RNA was extracted from 50 ml of peritoneal wash from 11 SGC patients before and after cisplatin-based IPC. The gene expression levels of survivin, c-myc, transforming growth factor-beta (TGF-beta), interleukin-2 (IL-2), IL-6, and IL-12 were analyzed using real-time reverse transcription-polymerase chain reaction (RT-PCR) assays. Also, carcinoembrionic antigen (CEA) messenger RNA (mRNA) was used to identify the number of gastric cancer cells in peritoneal washes by the real-time RT-PCR method. The gene expression levels of cytokines and the number of cancer cells in the peritoneal cavity were compared before and after cisplatin-based IPC treatment. RESULTS: Before IPC, the gene expression of IL-2 from peritoneal washes of patients was significantly suppressed compared to the controls (p = 0.029); however, other gene expression levels did not differ. In 7 cases, more than 90% of the cancer cells were removed from the peritoneal cavity after cisplatin-based IPC. These 7 cases were named the IPC effective group, and the remaining 4 cases were named the IPC ineffective group. In the IPC effective group, elevated IL-2 and IL-6 genes were detected in 5 (71%) and in 6 (86%) after IPC. The correlation between IPC effectiveness and elevated gene expression after IPC (IL-2: p = 0.137, and IL-6: p = 0.044) was observed. However, the 50% survival period of the IPC effective group (9 months) was not different from that of that of the IPC ineffective group (6 months, p = 0.267). CONCLUSION: IPC effectiveness may correlate with elevation of gene expression of inflammatory cytokines, such as IL-2 and IL-6 in the peritoneal cavity after IPC. However, the prognostic benefits of IPC for SGC patients remain unclear.

Lymph node metastasis of gastric cancer: comparison of Union International Contra Cancer and Japanese systems.

BACKGROUND: The pN classification of gastric cancer (GC) in the Japanese system (Japanese Gastric Cancer Association; JGCA) is based on the site and distance of metastatic nodes from the primary tumour. Union International Contra Cancer (UICC) has recently proposed a classification system based on the number of nodes involved (TNM-1997). The aim of the present study is to assess which classification system is more suitable for providing a prognosis in advanced GC with lymph node metastasis. METHODS: A total of 224 patients who underwent curative gastrectomy (R0: UICC-TNM and Resection A and B: JGCA) and D2 lymphadenectomy between 1990 and 1999, and diagnosed as pT2, pT3 and pT4 GC were enrolled. Patients were followed until the end of 2002. The disease-free survival rates of patients were compared between the two-stage systems (UICC-TNM and JGCA). RESULTS: Using the JGCA system, there was a significant difference between the two survival curves (pN0 and pN1, P = 0.025; pN1 and pN2, P < 0.001; pN2 and pN3, P = 0.031), but the 5-year survival rate of 27 pN2 patients (32.7%) was not significantly different from that of 14 pN3 patients (34.3%, P = 0.994) using the UICC-TNM. In 47 patients with JGCA pN2, the 5-year survival rate of 18 patients with UICC-TNM pN1 (42.9%) was not significantly different from that of 18 patients with UICC-TNM pN2 (25.2%, P = 0.422) or from that of 11 patients with UICC-TNM pN3 (24.2%; P = 0.383). CONCLUSIONS: The JGCA system is more suitable for estimating the prognosis of Japanese patients with advanced GC than the UICC-TNM.

Gene expression levels of cytokines in peritoneal washings from patients with gastric cancer.

Peritoneal seeding is frequently detected in patients with gastric cancer. The peritoneal cavity is a compartment in which the immunologic host-tumor interaction can occur. Here, we investigated the gene expression levels of cytokines, and compared these gene expressions with the progression of gastric cancer. Total RNA was extracted from 50 ml of peritoneal washings from 78 patients with gastric cancer and 11 noncancerous patients. The gene expression levels of transforming growth factor-beta (TGF-beta), interleukin (IL)-2, IL-6 and IL-12 were analyzed by real-time reverse transcription-polymerase chain reaction. The gene expression levels of TGF-beta and IL-12 in 16 patients with peritoneal seeding (peritoneal metastasis or free cancer cells) did not differ from those in controls (n = 11) and stage I and II (n = 43) patients. However, the relative gene expression level of IL-2 in patients with peritoneal seeding (0.9) was lower than that in controls (1.4, p = 0.066) and stage I and II patients (1.4, p = 0.036). In contrast, the relative gene expression level of IL-6 in patients with peritoneal seeding (3.3) was higher than that in control (2.4, p = 0.064) and stage I and II patients (2.6, p = 0.065). Low IL-2 gene and high IL-6 gene expressions in the peritoneal cavity may correlate with cancer development in the peritoneal cavity in patients with gastric cancer.

Detection of cancer cells in the peripheral blood of gastric cancer patients.

The existence of occult metastasis in peripheral blood has been reported in various tumors. However, in gastric cancer (GC), this metastasis has not been well analyzed. In the present study, to identify circulating cancer cells in patients with GC, peripheral blood samples from GC patients were investigated. Total RNA was extracted from 1.5 ml peripheral blood from 55 patients with GC, from 34 non-cancer patients, and from 10 healthy volunteers. Carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and 20 (CK20) messenger RNA (mRNA) were used as probes to detect GC cells in the blood samples using real-time reverse transcriptase polymerase chain reaction (RT-PCR). CEA and CK19 mRNA expression were not detected in the 40 healthy volunteers and non-cancer patients, while 2 of the 40 showed CK20 mRNA expression. In 55 patients with GC, CK19 mRNA was not detected and CEA mRNA was detected in only one case (1.8%) with stage IV. While CK20 mRNA expression was observed in 15 cases (27.3%) and even in stage I, 8 of 24 (33.3%) showed CK20 mRNA expression. Thus, the specificity of CK20 marker may be low. Even though the sensitivity of CEA marker is low, CEA may be a more reliable marker than cytokeratins for detection of cancer cells in GC patient's peripheral blood.