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Biomedical subjects

P C de Jong

Publications and source records attributed to P C de Jong.

At least 19 recordsLinked to original sources
PubMed2001

Importance of local aromatase activity in hormone-dependent breast cancer: a review.

The cytochrome P-450 enzyme complex aromatase is the rate-limiting step in the production of oestrogens. It catalyses the conversion of androgens to oestrogens. In the treatment of hormone-dependent breast cancer in postmenopausal women, aromatase is the target for treatment with aromatase inhibitors. Recently registered aromatase inhibitors like anastrozole, letrozole and exemestane have proven to be effective therapy for advanced breast cancer in postmenopausal patients failing to respond to treatment with tamoxifen. Intratumoural aromatase activity has predictive value for response to treatment with aromatase inhibitors. Attempts are being made to find an immunohistochemical technique to determine aromatase in tumour tissue, which may serve as a predictive factor. In situ oestrogen synthesis through local aromatase activity in the tumour and adjacent tissue is probably a very important growth-stimulating system in hormone-dependent breast cancer. This synthesis can be blocked with aromatase inhibitors. The regulation of aromatase activity and the cell types that contribute to this process are the subject of extensive research. There seems to be a complex interaction between malignant cells and adjacent cells in which factors such as IL-6 and its soluble receptor, TNF-alpha and prostaglandin E2 play an important role in stimulating aromatase activity.

Journal Article↗
PubMed1999

New aromatase inhibitors for the treatment of advanced breast cancer in postmenopausal women.

Inhibition of the enzyme aromatase, the rate limiting step in estrogen production, is an effective endocrine treatment of advanced postmenopausal breast cancer. Recently, several new aromatase inhibitors have been developed to improve efficacy and reduce toxicity compared to the prototype aromatase inhibitor aminoglutethimide. Aromatase inhibitors can be divided into two types. The first are the non-steroidal inhibitors that have a mechanism of action similar to aminoglutethimide. The second are the steroidal inhibitors that function as a false substrate for aromatase. Of the non-steroidal aromatase inhibitors, two drugs, anastrozole and letrozole, have recently been registered for the second line endocrine treatment of advanced postmenopausal breast cancer after failure on tamoxifen. The phase III studies of these drugs indicate at least equal efficacy compared to current second line treatment with aminoglutethimide or megestrol acetate. Their toxicity profile, however, is much more favourable. This makes them the drugs of choice for the second line endocrine treatment of advanced breast cancer in postmenopausal patients, who failed during adjuvant or first line treatment with tamoxifen. Of the steroidal aromatase inhibitors, the orally active drug exemestane is still in phase III clinical study; the registration is expected in 1999.

Aminoglutethimide↗
PubMed1997

Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole.

In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.

Aged↗
PubMed1997

[Microscopic tumor embolisms in metastasized breast carcinoma].

In two patients, women of 54 and 46 years old, with metastatic carcinoma of the breast, multiple microscopic tumour emboli in the lungs were found at autopsy. Ante mortem, unexplained respiratory distress in the former and an atypical thrombotic thrombocytopenic purpura-like syndrome in the latter were the most characteristic clinical features. Pulmonary microscopic tumour embolism is a rare diagnosis but it may occur in all types of cancer. Clinically, thrombotic pulmonary emboli are difficult to distinguish from microscopic tumour embolism. Special attention is to be paid to typical findings on radionuclide perfusion lung scanning (multiple subsegmental perfusion defects at the periphery of the bronchopulmonary segments with a normal ventilation named "segmental contour pattern'). Microangiopathic haemolytic anaemia and consumption coagulopathy are associated disorders. Tumour-directed therapy is the treatment of choice.

Breast Neoplasms↗
PubMed1994

A comparison of epidural catheters with or without subcutaneous injection ports for treatment of cancer pain.

The aim of this study was to compare the incidence of technical complications of epidural catheters with subcutaneous injection ports to percutaneous epidural catheters without ports, fixed only by adhesive dressing. We reviewed 149 patients who received 250 epidural catheters for treatment of cancer pain during a 3 1/2-yr period from January 1, 1989, to June 30, 1992. Of the 250 catheters, 52 were provided with subcutaneous injection ports and 198 were percutaneous catheters. Of the 198 percutaneous catheters, 41 were tunneled for a short distance; the remainder entered the skin at the dorsal midline. In the percutaneous group 21% of the catheters became dislodged. In the injection port group, there were no catheter dislodgements. The overall incidence of infections was similar in both groups (13.6%). When we indexed the infection rate to catheter-days, the number of infections per 1000 catheter-days in the injection port group was half that of the percutaneous group (2.86 infections versus 5.97 for percutaneous catheters). No injection port became infected during the first 70 days of treatment, whereas in the percutaneous group infections occurred as early as the first week. Within the percutaneous group the complication rate in the tunneled epidural catheters was as high as in the nontunneled. We conclude that injection ports reduce the complication rate of epidural catheters, particularly catheter dislodgement and early infections.

Adult↗
PubMed1992

T3 laryngeal cancer: a retrospective study of the Dutch Head and Neck Oncology Cooperative Group: study design and general results.

511 Patients with T3 N0-3 M0 squamous cell carcinoma of the larynx, treated in the Netherlands from 1975 until 1984, were retrospectively analysed. Four different treatment policies were followed: primary surgery, planned combination of radiotherapy and surgery, primary radical radiotherapy, and selective radiotherapy. General results are presented. Local control rate was 72%. Regional control rate was 90% for clinically N0 patients and 78% for clinically N+ patients. Salvage therapy was overall successful in 38%. Surgical salvage for local radiation failures (with regional relapse) was successful in 69%, and for regional failures (without local relapse) in 46%. Ultimate locoregional control was 78% and, due to 8% distant metastases, 5-year actuarial corrected survival was 70%. Prognosis did not improve over the years. Corrected survival was independently correlated with tumour extension, involvement of neck nodes and treatment strategy. Corrected survival was similar for primary radiotherapy and primary surgery, but significantly better for planned combined therapy. Multiple primary tumours occurred significantly more often in male (19.5%) than in female patients (7.3%) (P = 0.05), the bronchus being most commonly affected. Cumulative actuarial risk for metachronous tumour was 15% after 5 years and 30% after 10 years so prevention and early detection of these second tumours may play the most important role in improving overall survival rates in the future.

Adult↗
PubMed1991

Validation of a questionnaire on medical drug use during pregnancy.

The validity of a questionnaire on medical drug use during pregnancy was tested against information collected 7 years previously (in 1983-1984) at the University Hospital of Nijmegen, the Netherlands. The study population consisted of women with high-risk pregnancies. The sensitivity for drug categories varied between 0% and 80%. The sensitivity was highest for drugs used during labor (77%) and was extremely low (0%) for some drug categories. Personal characteristics thought to influence the sensitivity, such as parity of the mother and method of data collection (postal questionnaire or personal interview), showed no statistically significant effect. The newly developed questionnaire needs further improvement.

Data Collection↗
PubMed1991

Medication during low-risk pregnancy.

The use of medication during low-risk pregnancy was studied prospectively in a cohort of women supervised by specialist obstetricians at a university hospital (n = 332) and a cohort of women supervised by midwives in private practice (n = 250). More women under supervision of obstetricians/gynaecologists used medication (87.7%) than women supervised by midwives (59.8%). The top-five of medication were analgesics, antacids, vitamins, antibiotics and dermatologic preparations. More research is needed to establish the risks of these medications to the offspring.

Female↗
PubMed1991

Judging speech communication effectiveness in oral cancer patients.

An experiment was conducted to assess the effects of different types of sentences and recording methods on naive judges' evaluations of the speech communication effectiveness of four patients who had undergone surgery for oral cancer. As expected, judges understood patients better if they read meaningful rather than meaningless sentences and if their speech was evaluated under video rather than audio conditions. However, these general findings were qualified because of the powerful influence of individual differences among patients. For example, whereas the intelligibility of three of the patients increased under the audio condition if the sentences being read were meaningful, one patient was poorly understood no matter what type of sentence he read under the same condition. The results suggested that the identification of the unique personality characteristics of patients that are related to their intelligibility merits serious consideration by both researchers and rehabilitation clinicians.

Adolescent↗
PubMed1989

Evaluation of treatment results of squamous cell carcinoma of the buccal mucosa.

Of the 49 patients with squamous cell carcinoma of the buccal mucosa referred to the Rotterdam Radio-Therapeutic Institute (RRTI) and Universital Hospital Dijkzigt Rotterdam (AZD) during 1970-1984, 31 patients had an advanced stage of disease, 21 patients had clinical evidence of lymph node metastasis. Forty patients were treated with curative intention. Treatment modalities were: radiation therapy, preoperative radiation followed by surgery, and primary surgery. Eighteen of the 40 patients (45%) developed a local tumor recurrence; nearly all recurrences occurred within 2 years. The incidence was equal in all treatment groups. Of the 22 patients with initial clinically negative neck, regional relapse occurred in 3 of the 14 patients, of whom the neck was not treated electively by radiation therapy; all three in combination with a local recurrence. None of the 8 patients with electively irradiated necks developed a regional relapse. Eight of the 18 patients with initial clinically enlarged lymph nodes treated either by radiotherapy or surgery, developed a regional relapse, 5 in combination with a local recurrence. Treatment of the clinically positive neck by neck dissection was superior to radiotherapy. Local recurrence carried a poor prognosis. Almost 70% died of their disease. The overall and corrected 5-year survival was 38% and 52% respectively.

Carcinoma, Squamous Cell↗
PubMed1989

Induction chemotherapy with cisplatin and continuous infusion 5-fluorouracil in locally far-advanced head and neck cancer.

Induction combination chemotherapy with cisplatin, 100 mg/m2 i.v. day 1, and 5-fluorouracil, 1,000 mg/m2/24-h infusion days 1-4, was applied in 76 patients with locally far advanced squamous-cell cancer of the head and neck. The treatment program consisted of 3 cycles of chemotherapy, followed by local radiotherapy and/or surgery. Hematologic side effects were leukocytopenia (50%) and thrombocytopenia (35%). Other side effects included renal toxicity (23%), nausea and/or vomiting (86%), alopecia (18%), and phlebitis (45%). Thirteen patients (17%) achieved a complete remission and 37 patients (49%) a partial remission. Median progression-free and overall survival were 8 and 11 months, respectively. Only patients achieving a complete remission had a better prognosis. Although induction chemotherapy may facilitate further local treatment in about half of the patients, on the basis of presently available data, this procedure should not be routinely applied with the aim of better survival.

Adult↗