New strategy for immunomodulation by ex vivo removal of an interleukin-2 inhibitor.
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Biomedical subjects
Publications and source records attributed to K Orita.
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Endoscopic RI-lymphography was performed in 29 patients, with single photon emission computed tomography (SPECT) also performed in 19 of them. The lymph flow from the cardia was directly evaluated in lymphograms and compared with the RI uptake of each lymph node and the incidence of lymph node metastasis of previously resected carcinoma of the cardia in patients according to the location of the lymph node. Endoscopic RI-lymphography performed in combination with SPECT was considered to be highly useful for imaging lymph flow of the cardiac region. SPECT and RI-lymphography indicated rich lymph flow from the cardia to the periaortic region, and this finding was consistent with the incidence of lymph node metastasis according to the location of the lymph node in patients who had previously undergone resection of cancer of the cardia. Careful examination for metastasis to lymph nodes around the abdominal aorta was considered to be necessary, especially in patients with carcinoma of the cardia.
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Apoptosis, programmed cell death, was immunohistochemically determined in 55 samples of oesophageal squamous cell carcinoma using the BM1 Mab. Sections from patients not treated (group 1, n = 12) or preoperatively treated by chemotherapy (group 2, n = 11), radiation (group 3, n = 13) or both (group 4, n = 8), and 11 additional cases of high-grade dysplasia or early cancer were examined. Most of the apoptotic cells were BM1-positive and checked by TUNEL proved to be nick end positive. They accounted for 7 (11%), 19 (29%), 21 (32%) and 26 (38%) cells per field in those 4 groups respectively. Chemotherapy and/or radiation significantly increased the number of apoptotic cells as compared to controls (p = 0.029 and p = 0.029, respectively). To assess the implications of the oncogene expression in the apoptotic pathway, additional section stained with bcl2 and p53 were negative for bcl2 and were positive for p53 in 16 samples (37%). Overall, positive cases for p53 mutation showed a significantly decreased incidence of apoptotic cells (p = 0.03). These results suggest that in situ assessment of apoptotic response better correlates to the apoptosis induced by radiation than that by chemotherapy, that abnormalities of the p53 protein decrease the apoptotic response in oesophageal carcinoma, and that immunohistochemical analysis of p53 protein helps to determine the sensitivity to these anticancer agents.
The specific bindings of insulin and glucagon to 4 x 10(4) g pellets containing hepatic plasma membrane were measured at 1 and 2 weeks after bile-duct ligation and 1 week after reduction of jaundice. At 1 week of jaundice, insulin binding was not decreased compared to control rats, however, glucagon binding 30(6)% was significantly lower than that 43(8)% in control rats (p < 0.01). At 2 weeks of jaundice, insulin binding 35(3)% was significantly lower than that 40(5)% in control rats (p < 0.05), and glucagon binding 26(4)% was also significantly lower compared to control rats 42(4)% (p < 0.01). The decreased insulin and glucagon receptors returned to nearly the levels of controls after 1 week's reduction of jaundice. These results suggested that the measurement of receptor binding may be useful as an indicator of the severity of hepatocyte injury.
We estimated the time of occurrence of metachronous liver metastasis in colorectal cancer patients from tumor diameter and doubling time. Micro-metastasis was present prior to operation in most patients and a few metastatic cases could have been initiated by the surgical procedure. Portal chemotherapy is more effective against liver metastasis than intravenous infusion because a higher drug concentration in the liver can be obtained. This efficacy of portal chemotherapy on survival was also observed in a rat model. Thus perioperative adjuvant treatment should be undertaken for metastasis which already existed before the operation and adjuvant chemotherapy via portal vein is the treatment of choice. The no touch isolation technique is also needed to avoid spreading of tumor cells during surgery.
Three patients with colorectal cancer after irradiation for cervical cancer are described. One patient had two colorectal cancers. Three of the four cancers in these patients were located in the rectum and one in the sigmoid colon; all were within the irradiation field. Microscopic radiation proctocolitis was observed in all specimens. The interval between irradiation and the diagnosis of colorectal cancer was 20-24 years. It is important to consider patients who have undergone pelvic irradiation as being in a high risk group for the development of colorectal cancer. Close and long-term surveillance may be useful in these patients.
We have investigated the interaction between Cepharanthine (CEP), a multi-functional alkaloid that has the capacity to stabilize the cell membrane, and 5-fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788) transplanted into nude mice. Their anti-tumor effects were assessed in a group of 7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day) during a 3-week treatment. The results were compared with a control and a 5-FU group, which received saline solution and 5-FU alone, respectively. The tumors were harvested 2 h after 5-FU administration. On an additional 4 groups of 5 mice, the intratumoral concentration of 5-FU was assessed by a high performance liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg) injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30 mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g, 0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and the three other groups treated with CEP, respectively. This concentration was about twice as high in mice simultaneously treated with CEP compared to those treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to 4 h following 5-FU injection in mice treated with CEP than in those injected only with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)
A 48-year-old woman with a nonresectable pancreatic tumor received combination chemotherapy with cytokines (IFN-a plus TNF-a) and 5-FU. Since partial response was confirmed after seven months, she underwent re-exploration, and received a pancreatico-duodenectomy. Histologically, the tumor was an adenosquamous carcinoma of the pancreas. She recovered uneventfully. However, the tumor rapidly recurred, and she died five months after surgery. Despite the poor result, the survival of the patient with advanced pancreatic cancer for twelve months after the staring of the treatment suggests that combined chemotherapy with cytokines and 5-FU may be a therapeutic modality for advanced pancreatic cancer.
Eight patients undergoing hepatectomy received 15 x 10(4) U of ulinastatin during and after surgery and then twice daily for 4 days, and 11 hepatectomized patients served as untreated controls. Between-group differences in age, duration of surgery, volume of blood loss and transfusion, weight of resected liver, and results of preoperative liver function tests were not significant. On postoperative day 1, mean (+/- SD) polymorphonuclear leukocyte elastase levels were significantly lower in the treated patients than in the controls (310 +/- 69 micrograms/L vs 519 +/- 382 micrograms/L; P < 0.05); interleukin 6 levels also tended to be lower in the treated patients than in controls (42.4 +/- 34.0 pg/mL vs 63.3 +/- 43.1 pg/mL). The results indicate that ulinastatin has beneficial effects on host defenses after surgery.
We report a 62-year-old man with five primary cancers. He underwent nephrectomy for a right renal cell carcinoma and removal of malignant meningioma and 6 years later was diagnosed as having a rectal cancer and hepatocellular carcinoma. He died of respiratory failure and a gastric cancer was found at autopsy.
Three hundred and seventy-two patients with colorectal tumours treated by curative resection between January 1982 and January 1992 were reviewed in order to determine the role of colonoscopy and the outcome of patients with multiple tumours. Thirty (8.1%) of them with a mean age of 57 (35-79) years (20 males, 10 females) had synchronous (19 cases) or metachronous (11 cases) lesions. Rectum and sigmoid colon were the most frequent site of multiple lesions, accounting for 73% of all lesions. Accurate pre-operative diagnosis was performed in 14 of the 19 patients with synchronous lesions, and in the remaining 5 cases failure to perform an intra-operative colonoscopy was the cause of missing the lesions. Three of them had over-looked lesions on the previous barium enema. Synchronous lesions has the tendency to be less invasive as compared to metachronous ones. Five-year survival rates (Kaplan-Meier method) were 45% and 58% for patients with multiple and single lesions respectively (not significant). For patients with colorectal carcinoma a thorough examination of the whole colon by intra-operative colonoscopy should be accomplished in order to rule out the possibility of associated lesions as well as to decrease the incidence of "early" metachronous lesions.
This paper reports a case of complete regression of a liposarcoma in a 62-year-old Japanese man who, in August 1986, presented with a giant subcutaneous tumor of the right anterior chest wall. Local radiotherapy and conventional chemotherapy were initially performed; however, the tumor did not respond at all. He then received cytokine treatment (interferon-alpha and tumor necrosis factor-alpha). Nineteen months after cytokine treatment, the mass disappeared totally. The patient has been in complete remission for five years without recurrence and with no additional treatment. This suggests that the use of interferon-alpha and tumor necrosis factor-alpha in combination may be an effective and promising modality for liposarcomas which are refractory to the conventional anticancer treatments.
We have previously reported that interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blocked the cell cycle progression of cancer cells at the S to G2 transition, causing a synergistic antitumor effect. In this study, the combined effects of both these cytokines and 5-fluorouracil (FUra) on tumor growth and cell cycle progression were investigated in a human colon cancer cell line, RPMI 4788, transplanted in CD-1 nude mice. Daily administration of IFN-alpha and TNF-alpha for 21 days markedly suppressed the tumor growth and induced cytokinetic alterations in which S phase cells were increased and cells in G2/M phase were decreased. FUra added to these cytokines further suppressed tumor development but did not affect the cytokinetics further. Combination of FUra and cytokines in a low dose, either of which alone had no effect, suppressed the tumor growth. These findings demonstrate that IFN-alpha, TNF-alpha and FUra have a distinct antitumor effect in combination.
BACKGROUND/AIMS: This is a comparative study of the relationship between. MATERIAL AND METHODS: Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured by ELISA assay in four patients with chronic hepatitis (CH), 16 with liver cirrhosis (LC), 38 with hepatocellular carcinoma (HCC), and in nine healthy controls. RESULTS: No significant difference in cICAM-1 levels was observed between LC and HCC. The cICAM-1 level in HCC did not correlate with tumor markers but correlated well with tumor size. cICAM-1 level in HCC Stage III + IV was significantly higher than that of Stage I, and was higher in HCC with liver metastasis as opposed to HCC without metastasis. Furthermore, the cICAM-1 level of HCC decreased significantly after hepatectomy. CONCLUSION: These findings showed a close relationship between cICAM-1 and the progress of intrahepatic metastasis of HCC, indicating a possibility for using cICAM-1 as a prognostic marker.
BACKGROUND/AIMS: The clinicopathological features of 34 cases of gastric cancer in the remnant stomach were examined. PATIENTS AND METHODS: Twenty-three patients who underwent primary gastrectomy for benign gastric disease (Group I) and 11 patients who received gastrectomy because of primary gastric cancer (Group II) were studied. RESULTS: The median age at diagnosis of gastric remnant cancer was 62.2 years in Group I and 63.7 years in Group II. The median time interval between the primary operation and the appearance of gastric cancer was 12.6 years in Group I and 6.5 years in Group II. Almost all patients were symptomatic; presenting epigastralgia and constriction. The first diagnostic procedure for these patients was barium examination of the remnant stomach except one patient diagnosed by emergency gastroscopy for hematemesis. Seventy percent of patients in Group I had advanced gastric cancer, most of which were invasive to seromuscular layers, whereas in Group II early gastric cancer was dominant (55%). The prognostic evaluation after the second surgery showed that patients with early stages of cancer had longer survival in both Groups. CONCLUSIONS: These results suggest that early detection of gastric cancer in the remnant stomach by periodical follow up is important and that the application of aggressive surgery for this disease will provide better patient survival.
Cancer spread along the needle tract following fine needle biopsy is reported to be a rare complication. We report a case of subcutaneous implantation of hepatocellular carcinoma (HCC) following ultrasonically (US)-guided fine needle liver biopsy. The patient, a 53-year-old male was found to have a HCC at the medial segment of the liver confirmed by fine needle biopsy. Three year and four months after segmentectomy, the patient felt a subcutaneous growing lump at the previous biopsy site. The tumor was resected and confirmed histologically as HCC. We herein document other reports of such an occurrence following fine needle biopsy of HCC in Japan and consider this problem in liver biopsies.
BACKGROUND/AIMS: We reviewed 17 cases of patients with interrupted hepatic arterial blood flow to determine the effect of such an interruption. MATERIALS AND METHODS: In 17 patients undergoing radical resection of pancreaticobiliary carcinoma with simultaneous hepatic artery excision (n=15) or intraoperative hepatic artery obstruction (n=2), morbidity and mortality were reviewed. Nine hepatic artery anastomoses were performed in 7 of these patients, and postoperative patency was obtained for 5 anastomoses. The patients were classified into the following groups: group I was 6 patients with complete interruption of hepatic arterial flow to the whole liver or the remnant liver, group II was 6 patients with interruption of hepatic arterial flow to a lobe of the liver, and group III was 5 patients with preservation of hepatic arterial flow. RESULTS: Disruption of the bilioenteric anastomosis occurred in all 6 patients from group I versus none of those in groups II and III (p<0.05). Liver abscess and liver failure developed in 1 patient each from group I, but the mortality rate in this group was not high. CONCLUSIONS: Hepatic artery reconstruction in patients with complete interruption of hepatic arterial blood flow appears to be necessary to avoid ischemic breakdown of the bilioenteric anastomosis.