Fumio Kijima

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.

Molecular detection of circulating cancer cells during surgery in patients with biliary-pancreatic cancer

BACKGROUND It remains unclear whether surgical treatment for biliary-pancreatic cancers provokes the hematogenous dissemination of cancer cells. The aim of this study was to detect circulating cancer cells in the blood stream before and during tumor resection for biliary-pancreatic cancer. METHODS We analyzed blood samples obtained perioperatively from the portal vein, peripheral artery, and superior vena cava, using a carcinoembryonic antigen (CEA)-specific nested reverse transcriptase-polymerase chain reaction. RESULTS CEA-mRNA expression was detected in the blood of 21 (52.5%) of 40 patients with biliary-pancreatic cancer. The patients with detectable CEA-mRNA expression included 8 (42.1%) of 19 with bile duct cancers and 13 (61.9%) of 21 with pancreatic cancers. CEA-mRNA expression was not detected in blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate of CEA-mRNA of advanced clinical stage (TNM pStage III and IV) showed higher than that of early stage (pStage I and II; P <0.05). Tumor resection increased significantly the positive rates of CEA-mRNA in the blood stream of three kinds of vessel. CONCLUSIONS Surgical procedures provoke the hematogenous dissemination of cancer cells perioperatively. Therefore, new strategies during operations to prevent liver metastases are needed to improve the survival of patients with biliary-pancreatic cancer.

Detection and Clinical Significance of Lymph Node Micrometastasis Determined by Reverse Transcription-Polymerase Chain Reaction in Patients with Esophageal Carcinoma

We investigated micrometastasis in lymph nodes by detecting carcinoembryonic antigen (CEA) mRNA. A total of 400 lymph nodes obtained from 21 patients with esophageal carcinoma were examined by CEA-specific reverse transcription-polymerase chain reaction (RT-PCR). Serial sections of positive lymph nodes were reexamined histologically and immunohistologically. Twenty-seven lymph nodes of 11 patients were diagnosed as being positive by conventional histologic examination. CEA-mRNA positivity was found in 18 of 21 patients. Among 373 histologically negative nodes, 79 (21.2%) were positive for CEA mRNA. Of these, micrometastasis was detected in 2 by histological reexamination and in 11 by immunohistochemical staining using cytokeratin antibody. Two of 6 RT-PCR-positive patients (33.3%) had recurrent disease. Four of 11 patients (36.4%) whose nodal involvement was discovered by routine histological examination also had recurrent cancer. CEA-specific RT-PCR detected micrometastasis in lymph nodes at a higher rate than histological or immunohistochemical analysis of serial sections. Since the incidence of CEA-mRNA positivity is high in the lymph nodes of esophageal cancer patients except for those with early cancer, these patients should be treated with adjuvant therapy.

Mucosal Squamous Cell Carcinoma of the Esophagus: A Clinicopathologic Study of 30 Cases

A clinicopathologic study was carried out on 30 patients with mucosal esophageal cancer (MEC). The depth of cancer invasion was subdivided histologically into three categories: m1 = carcinoma in situ (intraepithelial carcinoma) or carcinoma with questionable invasion beyond the basal membrane; m2 = cancer invasion confined to the lamina propria, and m3 = cancer reaching to or infiltrating into the muscularis mucosae. Lymph node metastases and lymphatic invasion were found only in the tumors reaching or infiltrating the muscularis mucosae (m3). The maximum histologic vertical extent of the tumors was more than 1 mm in 4 of 5 patients with lymph node metastasis or lymphatic invasion. None of the patients died of recurrent esophageal disease, and 3 of the 6 patients who had a second primary tumor died of this other malignancy. It is critical to distinguish between m1, m2 and m3 tumors to plan a treatment strategy, including an endoscopic mucosal resection.

Paraaortic lymph node micrometastasis and tumor cell microinvolvement in advanced gastric carcinoma.

Abstract:Background. Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The purpose of this study was to investigate the incidence and significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in these critical lymph nodes.Methods. A total of 2339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically, using cytokeratin antibody.Results. Lymph node metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine histological examination. MM or TCM was immunohistochemically detected in 45 of the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n = 10). The 5-year-survival rate in the paraaortic node-negative group and cytokeratin-positive group was significantly higher that that of the hematoxilin and eosin-positive group. The total number of lymph node metastases by hematoxylin and eosin staining and the pathological lymph node compartments, by cytokeratin-positive nodes, were prognostic factors by multivariate analysis. Conclusions. We demonstrated a high rate of MM or TCM in the paraaortic lymph nodes and suggest that such harbored metastases are related to the prognosis of patients with advanced gastric carcinoma. On the basis of this study, a multi-institutional study should be considered.

So-called carcinosarcoma of the esophagus: A clinicopathologic, immunohistochemical and DNA flow-cytometric analysis of 6 cases.

Six cases of carcinosarcoma of the esophagus were studied clinicopathologically, immunohistochemically and with DNA flow cytometry. Transitional areas with morphology intermediate between carcinoma and sarcoma were found microscopically in all cases. Immunohistochemically, the carcinomatous areas contained keratin-positive cell components in all cases while vimentin-positive cells were found in sarcomatous areas in 5 cases. By DNA flow analysis of microdissection, the sarcomatous components of the tumors showed an aneuploid pattern with one exception, in contrast the carcinomatous components were diploid in all cases. In these few cases, PCNA, S-phase fraction and the mitotic rate were extremely high, apparently indicating a correlation with malignant behavior. Accordingly, examination by immunohistochemistry and DNA ploidy is useful for the analysis of biological properties in the so-called carcinosarcoma of the esophagus.

Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance

AbstractBackground: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.

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.

Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in the patients with esophageal carcinoma

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Small cystic insulinoma: Value of arterial stimulation venous sampling

Cystic insulinomas are rare, with only three cases having been reported in the literature. It is not difficult to determine the site of such neoplasms, as cystic insulinomas are usually 4–10 cm in diameter. We report a patient with a histologically confirmed cystic insulinoma. This case is unique because of the small size (1.3 cm) of the tumor. Arterial stimulation venous sampling was useful for localizing and distinguishing this tumor from other pancreatic lesions.