Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel

We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.     

Response of the primary lesion in gastric cancer to chemotherapeutic trials

Background We wish to clarify some points in the evaluation of primary tumors in gastric cancer trials, particularly the response rate and patient survival. Methods This study includes 226 patients with advanced gastric cancer who had no prior treatment except surgery, and who had been enrolled into 1 of 4 Japan Clinical Oncology Group trials. The regimens for these 226 patients were tegafur and mitomycin C in 50 a combination of tegafur and uracil and mitomycin C in 39, 5′-deoxy-5-fluorouridine and cisplatin in 49, etoposide, doxorubicin, and cisplatin in 42, and 5-fluorouracil and cisplatin in 46 patients. Antitumor responses were evaluated by the Japanese evaluation criteria. Results Of the 226 patients, 192 (85%) had primary cancers. Only 57 of 192 had roentgenographically measurable tumors. The response rate of the primary cancers was significantly lower than that of measurable metastatic lesions (P<0.01). Forty-five overall responders who had both primary and metastatic tumors were divided into 31 responders and 14 nonresponders, with reference to primary cancers. The 31 patients who had a response in the primary cancer lived significantly longer (P<0.05) than the 14 nonresponders, even though there was no significant difference in patient backgrounds between the 2 groups. This difference in survival became even more remarkable after 1 year. Conclusions Although some questions remain unresolved, evaluation of primary cancer can be meaningful, and the response of primary cancers may be an indicator for long-term survival.     

Clinical Trial of Continuous Infusion of 5-Fluorouracil Using an Ambulatory Pump for Metastatic Colorectal Cancer

A clinical trial was conducted in order to evaluate the anti-tumoreffect and toxicity of a continuous ifusion of 5-fluorouracil(5-FU) for metastati colorectal cancer. Two-hundred and fiftymg/m²/day 5-FU was administered as a continuous infusion throughan indwelling central venous catheter with ambulatory pump.Twenty patients with metastatic colorectal cancer which couldbe measured or evaluated were enrolled in the trial. The objectiveresponse rate was 35% (95% confidence interval, 14–56%).The response rates by site were 33% in liver, 17% in lung, 60%in lymph nodes, 50% in adrenal gland and 50% in primary lesion.The major toxicity was stomatitis (50%; grades 2 and 3 on EasternCooperative Oncology Group (ECOG) criteria) and hand-foot syndrome(40%; grades 2 and 3 on ECOG criteria). The sequence of toxicitywas stomatitis first, followed by hand-foot syndrome. The mediancumulative dose of 5-FU from the initiation of therapy to theonset of toxicity was 7125 mg in stomatitis and 17,875 mg inhand-foot syndrome. These toxicities were mild and reversibleafter a short interruption to the 5-FU infusion. Neither hematologicaltoxicity nor serious catheter-related complications were observed.We concluded that continuous infusion of 5-FU was a feasibletreatment for the patient with metastatic colorectal cancer,and manageable on an out-patient basis     

Pharmacological Correlation between Total Drug Concentration and Lactones of CPT-11 and SN-38 in Patients Treated with CPT-11

The pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were examined to establish the pharmacokinetic variability of the active lactones of CPT-11 and SN-38 in comparison with that of the total (lactone and carboxylates) plasma CPT-11 and SN-38. Twelve patients with malignancies were entered in the study. All received 100 mg/m² of CPT-11 by intravenous drip infusion over 90 min. Blood was sampled at 10 time points in heparin-containing syringes. Analysis by high-performance liquid chromatography showed that the ratio of CPT-11 lactone to total CPT-11 concentration was highest (66%) just after the end of infusion and gradually decreased to 30% at 24 h. Almost 70% of SN-38 lactone was detected after the end of infusion and this decreased to 50% within 24 h. The standard errors of percent lactone of CPT-11 or SN-38 to total drug concentration at each sampling point were less than 12%. The area under the concentration-time curve (AUC) of total CPT-11 and that of total SN-38 were significantly correlated with the AUCs of the lactone CPT-11 and those of lactone SN-38, respectively. We conclude that, for practical purposes, monitoring of total CPT-11 and SN-38 has essentially the same clinical significance as monitoring of lactone CPT-11 and SN-38.     

Experiments with tissue cultures from a human ovarian serous cystadenocarcinoma producing cancer antigen 125 (CA125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA)

Summary The patient was a 57-year-old woman with ovarian serous cystadenocarcinoma in FIGO clinical stage IV. Cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) were immunohistochemically demonstrated in tumor cells, and the variations of serum CA125 and TPA levels reflected the clinical course. The tumor tissue obtained at exploratory laparotomy was minced with scissors, and transplanted subcutaneously into female nude mice for in vivo maintenance. The tumor cells from 5th generation nude mice were dispersed in Eagle's minimal essential medium supplemented with 10% fetal calf serum, and incubated in Falcon tissue culture dishes at 37°C in 5% CO₂ in air for in vitro maintenance. The results were as follows: Histopathologically the tumor transplanted into nude mice showed a cystadenocarcinoma, which closely resembled the original human tumor. Immunohistochemically CA125, TPA and CEA were demonstrated in the tumor transplanted into nude mice as well as in the original human tumor. From the growth curve in nude mice, the doubling time was estimated to be about 3.5 days. Serum TPA levels in nude mice were increased in proportion to the tumor growth after transplantation, but serum levels CA125 and CEA were normal. The concentrations of CA125 and TPA were increased in the conditioned media compared with the control media, although the elevated values were decreased with subsequent passages. CEA concentrations in the conditioned media were unchanged.     

The cerebellar and thalamic degeneration in Fukuyama-type congenital muscular dystrophy

We report a male autopsy case of Fukuyama-type congenital muscular dystrophy (FCMD), with unusual neuropathological findings. The patient was a Japanese man aged 26 years at the time of death. He had shown severe psychomotor retardation and muscular dystrophy since early infancy, and was diagnosed as having FCMD at the age of 5 years. He died of respiratory failure. The main neuropathological finding was extensive cerebral and cerebellar cortical dysplasia, characteristic of this disorder. In addition, degeneration of the cerebellar efferent pathway, including the dentate nucleus, superior cerebellar peduncle, and red nucleus, and that of the lateral thalamic nucleus were observed. These findings suggest the possibility that the long survival can clarify the latent neurodegeneration in the cerebellum and thalamus in FCMD, in addition to congenital malformations. The system degeneration should be carefully evaluated in the pathological examination of this disorder. Received: 1 March 1999 / Revised, accepted: 5 July 1999     

High-resolution ultrasound of the thyroid in patients with Graves' disease

The thyroid glands in 53 patients with Graves' disease were scanned with 10-MHz high-resolution ultrasound. Homogeneous echo pattern was noted in 21 patients (39.6%), and heterogeneous echo pattern was noted in 31 patients (60.4%). Each mean value of the serum triiodothyronine (T3), thyroxine (T4), and free thyroxine (Free T4) in patients with heterogeneous-echo thyroid was noted higher than that of the group with homogeneous-echo thyroid. (p less than 0.05) However, between the two groups, there is no significant difference in mean age and mean duration of treatment with antithyroid drugs. The heterogeneous echo pattern is strongly suggested to be correlated with the severity of hyperthyroidism.     

Embolization of a thoracic aortic aneurysm; The straddling coil technique: Technical note

Occlusion of a patent postligated aortic aneurysymwas performed percutaneously with modified use of giant steel coils in a 50-year-old man. Steel coils were placed across the short, narrowed segment of the aorta. Successful thrombosis of entire aortic aneurysm was accomplished. No complications occurred.     

Differential inhibition by TAK-044 of the inotropic effects of endothelin-1 and endothelin-3

The influence of a nonselective antagonist of endothelin receptors, TAK-044 (cyclo-[d-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-l-alanyl-l-alpha-aspartyl-d-2-(2-thienyl)glycyl-l-leucyl-d-tryptophyl] disodium), on the positive inotropic effect of endothelin-1 and endothelin-3 was investigated in isolated rabbit myocardium. While TAK-044 produced a concentration-dependent rightward shift of the concentration-response curve for endothelin-1 and endothelin-3, the effect of endothelin-3 was hundred times more sensitive to TAK-044 than that of endothelin-1. The combination of FR139317 ([2-(R)-[2(R)-[2(S)-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-methylpentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl] amino-3-(2-pyridyl)propionic acid]) and BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-l-gamma-methylleucyl-d-1-methoxycarbonyltryptophanyl-d-norleucine) mimicked the inhibitory action of TAK-044 on the positive inotropic effect of endothelin-3 but enhanced the effect of endothelin-1. In a receptor-binding assay, TAK-044 was four times more potent in antagonizing the specific binding of endothelin-1 than that of endothelin-3. Endothelin-1 may activate receptor subtypes that trigger both positive and negative inotropic effects, the latter being more susceptible to the antagonistic action of TAK-044, which may explain in part the differential antagonistic action of TAK-044 on the inotropic effect of endothelin-1 and endothelin-3.