Shigeru Okamoto

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

Background. Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique.n Methods. Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII.n Results. The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis.n Conclusions. All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis.

Hand-assisted laparoscopic surgery for a large gastrointestinal stromal tumor of the stomach.

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach that were successfully treated by hand-assisted laparoscopic surgery (HALS). Two patients, a 56-year-old woman and a 60-year-old man, were admitted to our department for the treatment of a large submucosal tumor of the stomach. After gastrointestinal endoscopy, ultrasonography, computed tomography, and magnetic resonance imaging, we suspected that the masses, measuring 7.0u2009cm and 8.0u2009cm in diameter, respectively, were GISTs in the stomach. However, preoperatively, we could not rule out the possibility of malignant neoplasms, because they had been bleeding or gradually growing. Hand-assisted laparoscopic wedge resection was safely performed for the diagnosis and treatment of the submucosal tumor of the stomach. The immunohistochemical diagnosis in both patients was GIST of the stomach with intermediate-grade malignancy. HALS may be a good indication for large GISTs of the stomach that are difficult to diagnose preoperatively, whether they are malignant or benign, because it is safe and minimally invasive, promoting rapid recovery.

ESTABLISHMENT OF A HUMAN ANAPLASTIC THYROID CANCER CELL LINE SECRETING GRANULOCYTE COLONY-STIMULATING FACTOR IN RESPONSE TO CYTOKINES

SummaryA human anaplastic thyroid cancer cell line K-119, derived from a 77-yr-old woman who had developed marked neutrophilia and underwent surgery for anaplastic thyroid cancer, has been established. The spindlelike and polygonal cells in shape are stably proliferating since the beginning of its culture 2 yr ago. The cells grow rapidly and the population doubling time is 26 h. The chromosomes show many abnormalities and many marker chromosomes have been observed. Heterotransplantation of the cells into nude mice has resulted in the formation of tumors that are histologically interpreted as anaplastic cancer. The most noteworthy characteristics of the cell line are the many Ki-67-positive cells (86.3%) and that the cell line spontaneously secretes granulocyte colony-stimulating factor (G-CSF) and releases increased amounts of G-CSF in response to the stimulation of tumor necrosis factor, interleukin 1α, and interleukin 1β. The conditioned medium obtained from K-119 cells contains an autocrine factor stimulating the proliferation of themselves.

Adenocarcinoma Arising Below an Ileoanal Anastomosis After Restorative Proctocolectomy for Ulcerative Colitis: Report of a Case

We report a case of adenocarcinoma developing in remnant rectal mucosa below a hand-sewn ileal pouch–anal anastomosis (IPAA) after restorative proctocolectomy for ulcerative colitis (UC). To our knowledge, this is the first such case to be reported from Japan. A 60-year-old man with a 13-year history of UC underwent proctocolectomy with a hand-sewn IPAA and mucosectomy for anal stenosis and serious tenesmic symptoms. About 7 years later, a follow-up endoscopy showed a flat elevated malignant lesion, 2u2009cm in diameter, below the ileoanal anastomosis. He was treated by abdominoperineal resection of the pouch and anus with total mesorectal excision. Histopathological examination of the resected specimen confirmed the presence of a well-differentiated adenocarcinoma but there were no metastatic lymph nodes. He recovered uneventfully and remains well without evidence of recurrent disease 2 years and 3 months after his last operation.

Multiple colorectal carcinomas and colorectal carcinoma associated with extracolonic malignancies

In this study, we analyzed 149 surgical cases of colorectal cancer between January 1983 and August 1989. Thirteen cases (8.7 per cent) of colorectal primary cancer associated with extracolonic primary malignancy of 14 lesions and 10 cases (6.7 per cent) of multiple primary colorectal cancers were included. Among the 14 lesions of extracolonic primary malignancy, there were 6 gastric carcinomas, 2 endometrial carcinomas, 2 urinary bladder carcinomas, and one each in the esophagus, liver, bile duct and jejunum. The second tumor was not detected preoperatively in 3 of 4 cases of synchronous multiple primary colorectal carcinoma. A curative resection was done in 10 (77 per cent) out of 13 cases of colorectal cancer associated with extracolonic malignancy, while 7 (88 per cent) out of 8 cases of multiple colorectal cancers had a curative resection. Nine patients (69 per cent) with colorectal cancer associated with extracolonic malignancy were disease-free for 2 months to 14 years. Seven patients (88 per cent) with multiple colorectal cancers were disease-free for one to 22 years. We recommend, therefore, that in any patient with colorectal cancer, the entire large bowel should be thoroughly searched for any other primary tumors, by taking the existence of extracolonic tumors into account. A curative resection should be performed, and the follow-up period should be life-long.

An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection.

Abstract.We encountered a patient with advanced gastric cancer, with Virchows lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchows lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100u2009mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchows and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchows lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug.

Hand-assisted laparoscopic splenectomy for splenic vascular tumors: report of two cases.

We report 2 cases of splenic vascular tumors that were successfully treated by hand-assisted laparoscopic splenectomy. Two patients, a 41-year-old woman and a 33-year-old man, were admitted to our department for investigation of a splenic tumor. After ultrasonography, computed tomography, and magnetic resonance imaging, we suspected that the masses were hemangioma or inflammatory pseudotumor in the spleen. However, we preoperatively could not rule out the possibility of a malignant neoplasm because they each had previously undergone surgical treatment, one for cervical cancer of the uterus and the other for testicular seminoma. Hand-assisted laparoscopic splenectomy was safely performed for the diagnosis and treatment of the splenic tumors. A histologic diagnosis was venous hemangioma and littoral cell angioma, respectively. Hand-assisted laparoscopic splenectomy may be a good indication for splenic vascular tumors that are difficult to diagnose preoperatively whether they are malignant or benign.

Efficacy of combination treatment — (TAE with adriamycin and ethanol) — for hepatocellular carcinoma

SummaryAmong 44 patients with hepatocellular carcinoma (HCC), combination treatment with both transhepatic arterial embolization (TAE) and ethanol injection therapy (EIT) was performed in 10 patients. Only two had tumors measuring less than 3 cm in diameter. In all, eight patients had solitary tumors and two had multiple tumors. The tumor was classified as stage I in one patient, stage II in six subjects, stage III in two patients, and stage IV in one subject prior to TAE, but one stage II case was changed to stage III after laparotomy. The clinical stage was I in two patients, II in six subjects and III in two patients. Five patients with tumors of stages I and II achieved either a complete response (CR) or partial response (PR). However, three patients with tumors of stages III and IV showed progressive disease (PD). Thus, the response rate (CR+PR) was 50%. For tumor stages I and II, the 1-, 2-, and 3-year survival values were 100%, 100%, and 83%, respectively. For tumor stages III and IV, the 1- and 2-year survival values were 75% and 25%, respectively. Combination treatment of HCC appears to be efficacious for tumor stages I and II.

Use of flow cytometry for evaluating breast cancer cell proliferation after chemotherapy

Abstract We studied the change in cell proliferation after preoperative oral administration of an anticancer drug using flow cytometry for aspirated breast cancer cell specimens. Thirty-six patients with breast cancer received 400 mg/d of oral UFT (a 1:4 mixture of tegafur and uracil) for 1 to 2 weeks preoperatively. Cells aspirated from the tumor using a fine needle were evaluated for changes before and after administration of the drug. Ki-67, a nuclear-associated proliferation related antigen, staining and DNA ploidy were studied using flow cytometry and compared with cytologic and histologic (mastectomy specimen) changes. After administration of UFT, the number of cells stained with Ki-67 antigen decreased (from 69.2 ± 21.0 to 47.7 ± 28.6), but DNA ploidy was unchanged. The decreasing number of Ki-67-stained cells was well correlated with cell and tissue damage ( P = 0.0170 and P = 0.0090, respectively). These results suggest that flow cytometry is a simple and effective method for evaluating changes in cell proliferation after chemotherapy. This method also would be useful for selecting an effective anticancer drug for postoperative adjuvant chemotherapy.

Importance of the retro-mammary space as a route of breast cancer metastasis

BackgroundThere are many cases of breast cancer with axillary lymph node metastases without lymphatic invasion. We hypothesized that in these cases cancer cells may pass through the retro-mammary space (RS) into lymph nodes and that axillary lymph node metastases may correlate with the tumor invasion of the RS.MethodsA total of 127 patients who had undergone radical operation between April 1997 and April 2001 were studied. Whether or not the tumor had invaded the RS was histologically examined with hematoxylin and eosin staining of sections made at the point where the distance between the tumor and the fascia of the major pectoral muscle was the shortest.ResultsEighty-five cases did not have lymphatic invasion. Twenty-nine of these 85 cases had RS invasion and 56 cases did not. Among the 29 cases with RS invasion, 14 cases had lymph node metastases. In contrast, of 56 cases without RS invasion only 3 cases had lymph node involvement. Of the 85 cases without lymphatic invasion, the relationship between RS invasion and lymph node invasion was statistically significant (RS(+) vs. RS(-),p < 0.0001,X2 test). For all 127 cases, if cases showing either lymphatic invasion or RS invasion were diagnosed with lymph node involvement, the sensitivity, specificity, accuracy, and negative predictive value were 93.5%, 65.4%, 75.6% and 94.6%, respectively.ConclusionThese data suggest that lymph node metastases may occur via the tumor cell migration through lymphatic vessels and the RS.