Koki Tokuda

Surgical Maneuvers Enhance Molecular Detection of Circulating Tumor Cells During Gastric Cancer Surgery

ObjectiveTo evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. Summary Background DataSeveral studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase–polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. MethodsBlood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. ResultsCEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. ConclusionsA high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

CD3‐ζchain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients

Impaired or reduced CD3 zeta chain (CD3‐ζ) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The clinical significance of CD3‐ζ chain expression in tumor‐infiltrating lymphocytes (TILs) in gastric carcinoma remains unclear.

Disseminated cancer cells in the blood and expression of sialylated antigen in gastric cancer

BACKGROUND In gastric cancer, disseminated cancer cells (DCC) can be detected in peripheral blood using bio-molecular techniques. It is known that patients having DCC exhibit a high occurrence of postoperative relapse in gastrointestinal cancer. However, more than half of gastric cancer patients having positive DCC do not show cancer relapse. Sialylated Lewis antigens are considered to be crucial molecules in the metastasis of disseminated cancer. The current study investigated whether combination analysis of DCC and sialylated Lewis antigen are useful in estimating the recurrence risk of gastric cancer. PATIENTS AND METHODS Subjects were 106 consecutive gastric cancer patients who underwent curative gastrectomy. DCC in the peripheral blood were detected using the carcinoembryonic antigen (CEA)-mRNA by RT-PCR method. Sialylated Lewis antigen expression (sLeA and sLeX) of the primary tumor was assessed immunohistochemically. RESULTS Of 106 gastric cancer patients, 43 (40%) were positive for DCC. Immunohistochemically, 53 (50%) and 49 (46%) patients were positive for sLeA and sLeX, respectively. The presence of DCC did not correlate with sLeA and sLeX expression in gastric cancer. Postoperative tumors were present in 19 patients (7 hematogenous and 12 non-hematogenous), 12 of which were positive for DCC. Six sLeA-positive patients (26%) with DCC and 13 sLeX-positive patients (57%) with DCC suffered from postoperative recurrence of gastric cancer. The p value of CEA-mRNA and sLeX combination analysis was more significant (p<0.01) than that of CEA-mRNA alone (p=0.02). CONCLUSION Analyzing both DCC and sLeX expression in gastric cancer may enable more accurate prediction of postoperative recurrence.

Intraoperative Pleural Lavage in Esophageal Carcinoma

Background: Cytological examination of intraoperative pleural or peritoneal lavage specimens is useful for predicting outcomes for patients with various carcinomas. There have been few reports regarding cytological examination of pleural lavage fluid in esophageal carcinoma.Methods: Intraoperative pleural lavage fluid was collected before and after esophagectomy and was examined by Papanicolaou and Giemsa staining for 78 patients with esophageal carcinoma.Results: Although epithelial cells were found for 29 patients, only blood cells were detected for 48. The remaining one patient exhibited no cells in the specimen. For 4 of 78 (5.2%) patients, tumor cells were detected in the pleural lavage fluid after esophagectomy. Three of these four patients had T4 tumors.Conclusions: Positive cytological findings for pleural lavage fluid, using Papanicolaou and Giemsa staining, is correlated with regrowth of residual tumor and poor prognosis in esophageal carcinoma.

Micrometastasis of Gastric Cancer

Even patients with gastric cancer who undergo complete resection and have no histological evidence of lymph node metastasis sometimes experience recurrence after operation [1–3]. Why do cancers recur despite the performance of macroscopically and histologically radical resections? This recurrence is probably caused by micrometastasis to the lymph nodes, circulating blood, and abdominal cavity [4,5]. It is known that occult lymph node micrometastases have been identified by detailed histological examination in additional sections [6,7]. In recent years, the development of sensitive immunohistochemical technique and reverse transcription-polymerase chain reaction (RT-PCR) has led to the detection of micrometastases [4,5]. The concept of isolated tumor cells (ITC) has been introduced in the TNM classification [8]. In this issue, ITC was defined as single tumor cells or small clusters of cells not more than 0.2 mm in greatest dimension that are usually detected by immunohistochemistry or molecular methods, but which may be verified with hematoxylin and eosin (H&E) stains. The clinical significance of ITC or micrometastasis is still unknown in gastric cancer patients. Since 1996, our laboratory has pursued gene diagnosis to detect lymph node micrometastasis,free cancer cells in the circulating blood,and disseminated cancer cells in the abdominal cavity in patients with gastric cancer. In the present chapter, we demonstrate the current results of micrometastasis,including ours,and discuss the role, significance, and problem of perioperative gene diagnosis in gastric cancer surgery.