PubMed Health⌕ Search

Biomedical subjects

M Kouri

Publications and source records attributed to M Kouri.

At least 19 recordsLinked to original sources

1H MRS studies in the Finnish boron neutron capture therapy project: detection of 10B-carrier, L-p-boronophenylalanine-fructose.

This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.

Adult↗

Design and construction of shoulder recesses into the beam aperture shields for improved patient positioning at the FiR 1 BNCT facility.

Improvements have been made at the FiR 1 BNCT facility to ease the positioning of the patient with a tumor in the head and neck region into a lateral neutron beam. Shoulder recesses were constructed horizontally on both sides of the beam aperture. When shoulder recesses are not needed, they are filled with neutron attenuating filling blocks. MCNP simulations using an anthropomorphic human model BOMAB phantom showed that the main contribution to the increase in the effective dose to the patient's body due to the shoulder recesses was from the neutron dose of the arm. In a position when one arm is inside the shoulder recess, the maximal effective dose of the patient was estimated to be 0.7Sv/h. Dose measurements using the twin ionization chamber technique showed that the neutron dose increased on the sides as predicted by the MCNP model but there was no noticeable change in the gamma doses. When making the recesses into the lithium containing neutron shield material tritium contamination was confined using an underpressurized glove box and machine tools with local exhaust. The shoulder recesses give space for more flexible patient positioning and can be considered as a significant improvement of the Finnish BNCT facility.

Boron Neutron Capture Therapy↗

Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients.

OBJECTIVE: To study the long-term effects of radiotherapy on cognitive function in adult patients operated on for low-grade glioma. METHODS: A cohort of 160 patients who underwent surgery for low-grade gliomas of cerebral hemisphere between 1980 and 1992 in a single institution serving a defined population was studied. At a mean follow-up time of 7 years, 28 of the 101 patients who had postoperative irradiation (and no second surgery or chemotherapy) were still alive and eligible for MRI and neuropsychological study. Twenty-three of 59 patients who did not have radiotherapy, second surgery, or chemotherapy were alive and eligible at a mean of 10 years. RESULTS: The group that had postoperative irradiation performed significantly worse than the group that did not in cognitive tests. This difference was not accounted for by histologic diagnosis; location, extent of removal, or progression of the tumor; or any patient factor. Leukoencephalopathy was more severe in the group that had postoperative irradiation than in the group without radiotherapy, and correlated to poor memory performances only in the postoperative radiotherapy group. Average Karnofsky performance scale score was significantly lower in the group that had postoperative irradiation than in the group that did not. CONCLUSION: In adults with low-grade glioma, postoperative radiotherapy poses a significant risk of long-term leukoencephalopathy and cognitive impairment.

Adult↗

Biweekly dose escalation in curative accelerated hyperfractionation for advanced head and neck cancer: a feasibility study.

PURPOSE: To study the feasibility of a dose-escalated accelerated hyperfractionation schedule for patients with advanced head and neck cancer. MATERIALS AND METHODS: Twenty-nine previously untreated patients with advanced squamous cell carcinoma were treated with the following biweekly dose-escalated accelerated hyperfraction schedule: during the first 2 weeks 1.2 Gy twice a daily (bid) up to 24 Gy, thereafter during the next following 2 weeks 1.4 Gy bid to 28 Gy in 20 fractions, and thereafter 22.4 Gy in 1.6 Gy bid fractions during 1 1/2 weeks. Thus, the the total dose was 74.4 Gy in 54 fractions given in 5 1/2 weeks. RESULTS: The planned total dose was given within the planned time to 19 (66%) patients. For seven patients the treatment time was prolonged with 1 to 6 days because of department closure for holidays or machine-down days, and in three cases the treatment time was prolonged more than 8 weeks. When the tumor responses were evaluated at 3 months after given radiotherapy, 27 (93%) patients showed complete tumor clearance, 1 patient had a recidual focus, and 1 patient showed progressive disease. The ultimate 1-, 2-, and 3-year local control rates were: 87, 71, and 60%. Four patients had a salvage laryngectomy. The 1-, 2-, and 3-year survival rates for all patients were as follows: 96, 81, and 73%. All patients developed confluent mucositis, 15 patients were hospitalized for nutritional support, and 11 patients had moist desquamation. However, all acute reactions healed completely, and no serious late complications were observed. CONCLUSIONS: This is a safe and effective treatment schedule for patients with advanced head and neck cancer.

Adult↗

Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer.

A phase III randomised study, comparing treatment with fluorouracil, epidoxorubicin and methotrexate (FEMTX) with the best supportive care, was conducted in patients with unresectable or metastatic gastric cancer. During the period from July 1986 to June 1992, 41 patients were randomised to receive FEMTX or best supportive care. MTX was given in a dose of 1500 mg m-2 intravenously (i.v.) followed after 1 h by 5-FU 1500 mg m-2 i.v. on day 1; leucovorin rescue was started after 24 h (30 mg orally every 6 h for 48 h) and epidoxorubicin 60 mg m-2 i.v. was administered on day 15. In addition both groups received tablets containing vitamins A and E. Response rates for FEMTX were as follows: complete response (CR), 19% (4/21); partial response (PR), 10% (2/21); no change (NC), 33% (7/21); and progressive disease (PD), 24% (5/21). Response rates in the control group were: NC, 20% (4/20); and PD, 80% (16/20). Increased pain was observed in one patient in the treated group and in 11 patients in the control group within the first 2 months. WHO grade III/IV toxicity in the chemotherapy group was as follows: nausea/vomiting 40%, diarrhoea 10%, stomatitis 15%, leucopenia 50% and thrombocytopenia 10%. One possible treatment-related death was due to sepsis. The median time to progression in the FEMTX group was 5.4 months [95% confidence interval (CI) 3.1-11.7 months], but only 1.7 months in the control group (95% CI 1.2-2.7 months) (P = 0.0013). Similarly, the FEMTX group displayed significantly (P = 0.0006) prolonged survival compared with the control group, i.e. median survival 12.3 months (95% CI 7.1-15.6 months) vs 3.1 months (95% CI 1.6-4.6 months). In conclusion, FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival. It can be used as a reference treatment in testing new investigational combinations.

Adult↗

Poor prognosis associated with elevated serum CA 19-9 level in advanced colorectal carcinoma, independent of DNA ploidy or SPF.

DNA ploidy, S-phase fraction (SPF) for the tumours, serum tumour markers such as carcinoembryonic antigen (CEA) and serum CA 19-9 and major clinical parameters were analysed as prognostic factors in 105 patients with advanced colorectal carcinoma. All 105 were treated with a three-drug schedule including low dose epirubicin and sequential methotrexate, 5-fluorouracil, followed by leucovorin rescue. In univariate analysis, gender, Karnofsky index, extent of metastases, presence of abdominal metastases, CEA and CA 19-9 correlated with survival. Age, presence of liver or of lung metastases, DNA ploidy or SPF were not significantly associated with survival. In stepwise multivariate analysis an elevated serum CA 19-9 level, a poor Karnofsky index and multiple sites of metastases were independent adverse prognostic factors. Based on the multivariate analysis, patients were grouped in three categories. Group 1 consisted of 32 patients with Karnofsky > or = 80, with a normal serum CA 19-9 level and a single site of metastases. Group 2 consisted of 48 patients with Karnofsky > or = 80 and with an elevated serum CA 19-9 level or multiple sites of metastases. Group 3 consisted of 14 patients with Karnofsky < or = 70. This classification gave a highly significant correlation with survival (chi 2 = 45.52, P < 0.001, log rank test). The median survival in group 1, group 2 and group 3 was 30.1 months, 13.5 months and 3.9 months, respectively. Based on these results we suggest that trials involving advanced colorectal cancer should include the measurement of serum CA 19-9 levels as one of the most important prognostic factors, but also include documentation of other independent prognostic factors.

Antigens, Tumor-Associated, Carbohydrate↗

DNA ploidy of colorectal carcinoma by tumour site, gender and history of noncolorectal malignancies.

DNA ploidy was analysed by flow cytometer from frozen samples of 205 colorectal carcinomas. Sixty-two percent of the tumours had an abnormal DNA stemline. Forty-eight percent of carcinomas in the right colon, 62% of carcinomas in the left colon and 74% of carcinomas in the rectum were aneuploid (p = 0.007). Sixty-nine percent of tumours in males and 55% of tumours in females were aneuploid (p = 0.029). The difference in frequency of aneuploidy between females and males was greatest in tumours of the right colon, where 37% of the tumours in females and 62% of the tumours in males were aneuploid (p = 0.047). The percentage of diploid colorectal carcinomas was higher (55%) in patients with a history of noncolorectal malignancy than in others (34%, p = 0.031). These results suggest that flow cytometry may be helpful in understanding the development of colorectal carcinomas.

Aged↗

Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma.

Tumor markers such as carcinoembryonic antigen (CEA) and CA19-9 were analyzed as response indicators and prognostic factors in advanced colorectal carcinoma. Eighty-five patients participated in a phase II chemotherapy study from October 1984 to July 1990. A three-drug schedule was administered including low dose epirubicin and sequential methotrexate 5-fluorouracil, followed by leucovorin rescue. Serum specimens for CEA and CA19-9 were obtained prior to the initiation of chemotherapy, and subsequently at 4-6 weeks' intervals. In univariate analysis Karnofsky, the site of the primary tumor, the extent of metastases, the presence of abdominal or liver metastases, serum CEA (cut-off of 20 micrograms/l), and CA19-9 levels correlated with survival. In stepwise multivariate analysis an elevated CA19-9 level, a poor Karnofsky, and the presence of liver metastases were independent adverse prognostic factors. Tumors originating from the left colon had a better prognosis than the others. This was related to a higher response rate in this patient group. Serum CA19-9 level was the most significant prognostic factor whether it was entered as a continuous or as a dichotomized variable into the model. The median survival of patients with a normal CA19-9 level was 30.0 months (lower 95% confidence interval: 16.4 months; upper limit was not calculable), and with an elevated CA19-9 value 10.3 months (8.0-12.6 months, 95% confidence interval). Five of 85 patients had a complete response and 20 a partial response, the overall response rate being 29%. When compared with tumor shrinkage, "CEA response" and "CA19-9 response" had a sensitivity of 84% and 88% and specificity of 77% and 67%, respectively. In conclusion, serum CEA value seems to be the best tumor marker for response prediction, while CA19-9 level is one of the best available prognostic indicators in advanced colorectal carcinoma.

Adult↗

Disease stabilization by leukocyte alpha interferon and survival of patients with metastatic melanoma.

Thirty-one patients, 13 males and 18 females, with metastatic malignant melanoma were treated with human leukocyte interferon (IFN) alpha. The dose was 3 x 10(6) IU daily s.c. for 6 weeks followed by 6 x 10(6) IU/day 3 times a week. Only 1 patient (3%) achieved a partial response (PR) while 14 patients (45%) had disease stabilization for 2-8 months. Three patients experienced mixed responses, where some of the metastases responded, while the others were only stabilized. Interestingly, 1 patient showed regression of lung and disappearance of liver metastases after termination of IFN treatment. Two female patients are still alive without evidence of disease. After IFN they were treated with radiotherapy or surgery. The median survival for all the patients was 48 weeks. Our conclusion is that in IFN therapy long-term follow-up is indicated even in the absence of objective responses. In spite of poor response rate IFN may contribute beneficially to survival in a proportion of patients.

Adult↗

Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study.

PURPOSE: The aims of this study were to assess the effect of adjuvant chemotherapy on overall survival, disease-free survival, and relapse pattern, as well as its toxicity in patients who underwent radical surgery for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred ten patients with T1-3N0 (World Health Organization [WHO] 1981) NSCLC underwent radical surgery during the period of 1982 through 1987. After surgery, the patients were randomized to receive adjuvant chemotherapy (n = 54) (cyclophosphamide 400 mg/m2, doxorubicin 40 mg/m2, and cisplatin 40 mg/m2 [CAP] for six cycles) or no active treatment (n = 56). RESULTS: After 10 years from the start of the study, 61% of patients were alive in the chemotherapy group and 48% were alive in the control group (P = .050). Seventeen patients (31%) in the CAP group and 27 patients (48%) in the control group had a recurrence during the follow-up period (P = .01). The 5-year survival rate was 67% in the chemotherapy group and was 56% in the control group (P = .050). The patients in the chemotherapy group who completed the planned treatment had a slightly better 5-year survival than those whose chemotherapy was discontinued (72.5% v 50.3%; P = .15). Chemotherapy-related gastrointestinal toxicity grade 3 to 4 (WHO) occurred in 63% and was the main reason why patients refused further planned therapy. CONCLUSION: Our results suggest that patients with NSCLC at pathologic stage I who have undergone radical surgery benefit from adjuvant chemotherapy.

Adult↗

Serum carcinoembryonic antigen and DNA ploidy in colorectal carcinoma. A prospective study.

We have analysed the relationship between carcinoembryonic antigen (CEA) and DNA ploidy prospectively in 130 colorectal carcinoma patients. CEA was elevated preoperatively significantly more often in patients with DNA-aneuploid tumours than in DNA-diploid or DNA-tetraploid tumours--that is, in 48% (36 of 75) of patients with aneuploid tumours, in 34% (14 of 41) of patients with diploid tumours, but only in 14% (2 of 14) of patients with tetraploid tumours (p less than 0.05). Aneuploid tumours had an elevated CEA level in 38% of stage A-B disease and in 61% of stage C-D disease. The elevated CEA values (greater than or equal to 5.0 micrograms/l) correlated with tumour stage in patients with aneuploid tumours but not in patients with diploid tumours. Whereas CEA is a suitable marker for aneuploid carcinomas, other more sensitive tumour markers should be sought for diploid and also for tetraploid tumours. If such markers are found, flow cytometry could provide the most important information in selecting individual follow-up programmes for colorectal cancer patients.

Adult↗

The effect of fractionated irradiation on cell kinetics.

The effects of single and split-dose irradiation were compared by in vitro experiments on HeLa cells. Changes in rate of cell proliferation were detected by flow cytometry, simultaneously determining the DNA content and the bromodeoxyuridine incorporation of individual cells. Cell cultures were irradiated with either a single dose of 1-6 Gy or with a corresponding dose divided into multiple fractions given at 1-6-h intervals. A dose-dependent accumulation of cells in G2/M phase was observed. The method was sensitive enough for the detection of G2/M block even after 1 Gy. The block disappeared completely within a 24-h follow-up time at dose levels up to 3 Gy. Interestingly, no differences in cell kinetics were observed between the single and split-dose regiments. This approach proves to be valuable in evaluating novel fractionation models and the effects of radiation on the cell kinetics of human tumor cells.

Cell Division↗

Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry.

Fifty-nine colorectal carcinomas of patients with verified cancer family syndrome (CFS) were analyzed for DNA ploidy using flow cytometry. Sixty-eight percent of the tumors were diploid, and 32% were aneuploid. The aneuploid tumors had a median DNA index of 1.24 (range, 1.12-1.97). In 90% of all tumors the DNA index was less than 1.27. This predominance of diploid/near-diploid tumors was seen both in primary and in metachronous carcinomas. In 21 cases a cell cycle analysis was possible. Tumors with the S-phase fraction (SPF) greater than or equal to 9.8% had a worse prognosis than tumors with the SPF of less than 9.8%. These findings suggest that the predominance of diploid/near diploid DNA values is one of the characteristics of colorectal carcinomas in CFS. This might signify the existence of two or more pathogenetically different subgroups of colorectal carcinoma and explain the proposed better prognosis of colorectal carcinoma in CFS compared with other colorectal carcinomas.

Adult↗

The prognostic value of DNA-ploidy in colorectal carcinoma: a prospective study.

One hundred and fifty-seven patients with usual colorectal cancer were analysed prospectively for DNA-ploidy, DNA-index and S-phase fraction (SPF) using flow cytometry. An abnormal DNA-stemline was observed in 68% of tumours. The patients have been followed for a median of 36 months. In univariate analysis, tumour stage was the most significant prognostic factor. After excluding patients with stage D disease, DNA-aneuploidy was significantly associated with a shorter survival and a shorter disease free survival. SPF, however, did not correlate with prognosis. In multiple samples from the same tumour there was on average a 29% difference between the highest and the lowest SPF indicating considerable heterogeneity in proliferative activity within the tumours. In diploid tumours the variation was even higher. Patients with proximal tumours as well as female patients had DNA-diploid tumours more often than the others. This may indicate that there are different, so far unknown, aetiological factors leading to different types of ploidy pattern.

Adult↗