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Biomedical subjects

C W Burger

Publications and source records attributed to C W Burger.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of estrogens and hormone replacement therapy on breast cancer risk and on efficacy of breast cancer therapies.

This review summarises preclinical and clinical data on effects of endogenous and exogenous estrogens on probability of breast cancer diagnosis, and on the course and efficacy of breast cancer therapies. The data indicate that higher endogenous estrogen exposure (e.g. pregnancy, early menarche and late menopause, estrogen levels in future breast cancer patients, obesity) or exogenous estrogens (oral contraceptives; hormone replacement therapies) may be associated with an increased probability of breast cancer diagnosis. However, there is little evidence that estrogens have deleterious effects on the course of breast cancer. Moreover, increased incidence of breast cancer diagnosis after prolonged hormone replacement therapy (HRT) use seems to be associated with clinically less advanced disease. In studies assessing both diagnosis and mortality, HRT is frequently associated with reduced mortality compared to never users. The interaction of progestagens and estrogens on the probability of breast cancer diagnosis is complex and dependent on type of progestagens and regimens employed. Efficacy of current treatment modalities for breast cancer (surgery, irradiation, adjuvant therapy or chemotherapy) is not negatively influenced by estrogens at concentrations considerably higher than those attained with current HRT preparations. Although it cannot be excluded that estrogens increase the probability of breast cancer diagnosis, available data fail to demonstrate that, once breast cancer has been diagnosed, estrogens worsen prognosis, accelerate the course of the disease, reduce survival or interfere with the management of breast cancer. It may therefore be concluded that the prevalent opinion that estrogens and estrogen treatment are deleterious for breast cancer, needs to be revisited. However, results of ongoing prospective, randomised clinical trials with different HRT regimens in healthy women or breast cancer survivors are needed to provide more definite conclusions about risks and benefits of HRT.

Breast Neoplasms↗
PubMed2000

Sentinel node detection in cervical cancer.

BACKGROUND: For superficial tumors such as melanoma, breast, and vulvar cancer, sentinel node detection prevents unnecessary extensive lymph node dissections. Sentinel node detection has not yet proved feasible in tumors, such as cervical cancer, that drain to deep pelvic lymph nodes. TECHNIQUE: We injected technetium-99m colloidal albumin around the tumor allowing preoperative lymphscintigraphy and intraoperative gamma probe detection of sentinel nodes. For visual detection, blue dye was injected at the start of surgery. EXPERIENCE: In six of 10 eligible women who had Wertheim-Meigs operations for cervical cancer stage Ib, one or more sentinel nodes could be detected by scintigraphy. Intraoperative gamma probe detection was successful in eight of ten women, whereas visual detection found sentinel nodes in only four. They were found as far as the common iliac level. One woman had positive lymph nodes, of which one was a sentinel node. CONCLUSION: Identification of sentinel nodes using radionuclide is possible in women with cervical cancer and potentially identifies women in whom lymph node dissection can be avoided.

Adult↗
PubMed2000

Cancer risk associated with subfertility and ovulation induction: a review.

OBJECTIVE: Over the past decades the use of fertility drugs (FDs) has greatly increased. Recently, the possible association between the use of FDs and risk of cancer has aroused great concern. In this paper, we critically review the available epidemiologic studies. METHODS: We identified papers published between 1966 and 1999 that examined FDs and specific causes of subfertility in relation to the risks of cancers of the ovary, breast, endometrium and thyroid, and melanoma. RESULTS: Although present insights into the pathogenesis of hormone-related malignancies suggest a possible association between the use of FDs and the risk of specific cancers, this has not been convincingly demonstrated in epidemiologic studies. With regard to cancer risk in relation to the cause of subfertility, the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on FDs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal. The most important sources of bias are inadequate confounder control for both parity and causes of subfertility. CONCLUSIONS: To discriminate between the possible carcinogenic effects of various ovulation induction regimens, subfertility disorders, and reproductive characteristics associated with subfertility, future studies should include large populations of subfertile women with sufficient follow-up time. In such cohort studies the cause of subfertility should be measured adequately (based on medical records) and information about reproductive characteristics should be collected for all cohort members. Such studies should also include a group of subfertile women with an indication for FD use but not so treated.

Adolescent↗
PubMed2000

Oestrogen, progesterone, and androgen receptors in ovarian neoplasia: correlation between immunohistochemical and biochemical receptor analyses.

AIM: To investigate the correlation between immunohistochemical and biochemical steroid receptor analyses by measurement of oestrogen, progesterone, and androgen receptor status in ovarian neoplasia. METHODS: Tissue samples were obtained from 27 ovarian neoplasms, including two borderline tumours. Immunohistochemical staining of the tissue slides was scored semiquantitatively, incorporating the intensity and percentage of positive staining (histo-score). Tumours with a histo-score of 10 or more were considered steroid receptor positive. The epithelial and stromal fractions of the tumours were analysed separately. To study the uniformity of receptor expression throughout a tumour, up to four samples were analysed. RESULTS: Immunohistochemical histo-scores of the oestrogen receptor in the epithelial fractions were significantly correlated with the biochemical oestrogen receptor values (r = 0.408). Androgen receptor status in the epithelial fraction was correlated with that in the stromal fraction (r = 0.741), while androgen receptor histo-scores in the epithelial fraction correlated with the biochemical assay values (r = 0.463). On biochemical analysis, 17 of the 27 ovarian tumours were oestrogen receptor positive and seven were progesterone receptor positive. On immunohistochemical analysis, eight tumours were oestrogen receptor positive and two were progesterone receptor positive. Biochemical analysis showed that 14 of the 26 tumours were slightly androgen receptor positive (10-50 fmol/mg protein), while all the others were negative. On immunohistochemical analysis, seven of the 26 tumours were androgen receptor positive. When two or more specimens from one tumour were analysed, marked differences in steroid status were found, especially in progesterone receptor and androgen receptor expression. Some parts of a tumour were steroid receptor positive, while other parts were negative owing to heterogeneity of expression. CONCLUSIONS: Immunohistochemical and biochemical analysis of steroid receptors in ovarian tumours correlated weakly or not at all. Heterogeneity of expression within a tumour and the presence of progesterone and androgen receptors in the stromal fraction partly accounted for this observation. Biochemical and immunohistochemical androgen receptor status was much lower than in previous reports.

Biochemical Phenomena↗
PubMed2000

The problems of surgical training in gynaecologic oncology.

During the late 60s and early 70s it was recognised that the surgical training for residents in Obstetrics and Gynaecology was inadequate to comprehensively acquire the surgical skills necessary in managing women with gynaecologic cancers. Gynaecologic Oncology (Gynae-Oncology) has three important goals: 1) to maintain the highest standards for patients with gynaecologic cancer, 2) to provide the trainee with clinical skills and structural clinical research after his/her surgical completion, and 3) to acknowledge clinical training centers for the trainees in Gynae-Oncology. For women trainees careful family planning, good communication, flexibility from the program director and faculty, support from co-workers, and, most important, participation and support from the spouse of the trainee are the ingredients of successful childbearing and family care during training programs. These problems have to be faced and dealt with before they become insurmountable problems. International standards are needed for training programs of trainees in Gynae-Oncology, with special emphasis on surgical skills.

Canada↗
PubMed1999

Postmenopausal hormone replacement in the woman with a reproductive risk factor for breast cancer.

OBJECTIVE: to assess the interaction between postmenopausal hormone replacement therapy (HRT) and various reproductive risk factors for breast cancer such as early menarche, late menopause, late first delivery and nulliparity. DESIGN: three cohort studies and fourteen case control studies, published between 1975 and 1997, provided relative risks (RRs) of HRT use in women with, as well as in those without, a reproductive risk factor for breast cancer. METHODS: using an additive RR model reported before, we investigated whether the RR for breast cancer in women with a combination of HRT and a given reproductive risk factor result from a simple addition of RRs of HRT on the one hand, and of the pre-existing reproductive risk factor on the other hand, or that synergism between both risk factors occurs. RESULTS: simple addition of RRs was shown in the case of early menarche and late menopause. Less increase of risk, suggesting antagonism, was found for both late first delivery and nulliparity in combination with HRT use. CONCLUSION: we could not observe any synergistic effect of the combined risks of any of the following reproductive risk factors for breast cancer: early menarche, late menopause, late first delivery or nulliparity on the one hand, with the risk resulting from HRT use on the other hand. Therefore, as far as the risk of breast cancer is concerned, the use of HRT appears not to be highly detrimental in women with a reproductive breast cancer risk factor, as it results in not more than a simple addition of risks at the most.

Breast Neoplasms↗
PubMed1999

Hormone replacement therapy in women treated for gynaecological malignancy.

Can we prescribe hormone replacement therapy (HRT) safely for women, with postmenopausal complaints who were treated for a gynaecological malignancy? Only three retrospective studies have investigated this issue in endometrial cancer patients. No recurrences or deaths occurred in these treated groups. However, the physician introduced bias through the selection of favourable groups. At present, combined estrogen and progestogen therapy is probably not contra-indicated in endometrial cancer stage I and probably also not in stage II, although so far there is only circumstantial evidence. Squamous cell cancers of the cervix, vulva, and vagina are unlikely to be influenced by HRT. In the only study available of women with ovarian cancer, < or = 50 years, estrogen replacement therapy did not have a negative influence on (disease-free) survival. According to the data currently available, no evidence exists that HRT adversely influences survival and overall survival after treatment for ovarian cancer. In general, adenocarcinomas of the cervix and leiomyosarcomas of the uterus may be managed such as the adenocarcinomas of the uterus. During the last 25 years, HRT has been shown to substantially reduce the risk of cardiovascular diseases, osteoporotic fractures and colon carcinoma. On the other hand there is a significant increase of the risk in breast cancer with prolonged use of > 5 years. Re-evaluation of the current view that HRT should no be given to women treated for a gynaecological malignancy is strongly warranted after evaluating the advantages and the disadvantages of HRT use in each individual patient. Long-term HRT in women treated for a gynaecological cancer must be based on the medical history of the individual patient (and her family).

Contraindications↗
PubMed1999

Micturition complaints in postmenopausal women treated with continuously combined hormone replacement therapy: a prospective study.

OBJECTIVES: To study parameters of the micturition pattern in postmenopausal women and the effect of an oral continuously combined HRT-regimen. METHODS: Hormone therapy consisted of 2 mg 17 beta-oestradiol in combination with either 2.5, 5, 10 or 15 mg dydrogesterone, orally once a day. The baseline assessment was done just before starting hormone replacement therapy, the second assessment took place after 6 months of hormone therapy. Data were collected using a standardized questionnaire and focused on diurnal urinary frequency, nocturnal urinary frequency and urinary incontinence as parameters of the micturition pattern. Furthermore, bacteriuria was assessed. RESULTS: One hundred and two women entered the study and 95 women completed 6 months of hormone replacement therapy. Urinary incontinence was reported by 44.1% of the women, in 19.6% of the women it occurred more than twice a week. Both diurnal frequency and nocturnal frequency was reported by 28.4% of the women. For women with frequency or nocturia, the number of voids significantly decreased after 6 months hormone replacement therapy. Nocturia disappeared in 65.4% of the women after treatment and 23.3% reported to be cured of their urinary incontinence. Bacteriuria was present in the same seven women before and after hormone treatment. Dydrogesterone dose did not influence treatment outcomes. CONCLUSIONS: Postmenopausal women report improvement on urinary incontinence and nocturia after 6 months of a continuously combined hormone replacement therapy regimen. The improvement was most outspoken with regard to nocturia. Bacteriuria was not influenced. Different doses of dydrogesterone did not effect these findings.

Administration, Oral↗
PubMed1999

Clostridium septicum myonecrosis and ovarian cancer: a case report and review of literature.

A case report of lethal distant myonecrosis with gas gangrene is presented. Cultures from blood and suppuration of our patient revealed Clostridium septicum. At obduction the patient appeared to have a necrotic metastasis of a known ovarian carcinoma in the cecum wall. Predisposing conditions for this type of infection are hematologic malignancies, colon carcinoma, neutropenia, diabetes mellitus, and disruption of the bowel mucosa. Clostridium septicum is highly associated with the presence of a malignancy, either known or occult at the time infection occurs. Occult tumors are mostly situated in the cecal area of the bowel. Clinical symptoms of the syndrome and therapeutic options are discussed.

Female↗
PubMed1998

Cytogenetics of a malignant ovarian germ-cell tumor.

Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ-cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor, revealed a highly abnormal chromosomal pattern. We found a chromosome number in the hypertriploid/hypotetraploid range, and several clonal structural abnormalities, including 2 copies of an isochromosome 12p. We showed that the chromosomal pattern of this ovarian tumor is very similar to that of testicular germ-cell tumors. This finding, together with reported cytogenetic data of malignant ovarian germ-cell tumors, supports the hypothesis that ovarian and testicular germ-cell tumors are strongly related entities that may have a similar origin and pathogenetic pathway.

Adult↗
PubMed1998

Postmenopausal hormone replacement therapy and cancer of the female genital tract and breast.

Taking into account data from recent case-control and cohort studies, this review addresses anew the controversial issue of a possible relationship between hormone replacement therapy and an increased risk of female cancer. The adequate addition of a progestogen reduces considerably the significantly increased risk of endometrial cancer seen in current and in past long-term estrogen replacement therapy (ERT) users. However, a small risk increase might still be present with combined estrogen-progestogen replacement therapy (EPRT), and with low-dose continuous combined treatment. Whether long-term hormone replacement therapy increases the risk of breast cancer remains controversial. All four recent case-control studies report a small, marginally significant risk increase of about 20-30%, while two recent cohort studies are very reassuring. Sequential addition of a progestogen does not seem to influence breast cancer risk. Unfortunately, no data are available on the both practically and theoretically interesting option of continuous combined hormone replacement therapy. It can be concluded from the present data that hormone replacement therapy can be safely prescribed for periods of less than five years to women with climacteric symptoms. Short-term hormone replacement therapy for climacteric complaints in women who have been treated for the above-mentioned cancers should not be considered to be absolutely contraindicated as the available but scanty new data do not indicate any detrimental effect in such women.

Breast Neoplasms↗
PubMed1997

[Postmenopausal hormone replacement therapy and cancer of the female genitalia and breast].

Oestrogen replacement therapy (ORT) significantly increases the relative risk (RR) of endometrial cancer, especially long-term oestrogen use (RR: 9.5; 95% confidence interval (CI): 7.4-12.3). Addition of a progestin to ORT reduces this increased risk completely or largely. The risk of breast cancer is increased after ORT of 5 years or longer (RR: 1.23; 95% CI: 1.08-1.40). Addition of a progestin does not reduce this increased risk. The possibility cannot be excluded that long-term ORT increases the risk of epithelial ovarian cancer. No significant association between ORT and cervical cancer has been demonstrated. It is safe to prescribe ORT for a period shorter than 5 years for women with menopausal symptoms. Addition of a progestin is indicated when the uterus is in situ. Hormonal supplementation therapy is to be discouraged in women treated for breast cancer, may be considered in young women previously treated for endometrial or ovarian cancer with a good prognosis and severe menopausal symptoms and is justified in women previously treated for cervical cancer.

Aged↗
PubMed1997

Hormone replacement therapy and breast cancer morbidity, mortality and recurrence.

The effects of short-term and long-term HRT (in its various forms, unopposed oestrogens, sequentially combined HRT and continuous combined HRT) on the female breast are reviewed. The question is addressed whether HRT will increase the risk of breast cancer as well as the risk of dying from breast cancer in healthy women, and whether or not women who already run an increased risk on the basis of a positive family history, use of DES during pregnancy or because of the presence of premalignant epithelial abnormalities in the breast, increase their risk for breast cancer further. The risks of HRT and the options for HRT in patients who have a history of breast cancer are discussed and alternative treatment modalities for climacteric complaints (e.g. clonidine, paced-respiration) or for preventive HRT (e.g. tamoxifen, tibolone) are reviewed.

Breast Neoplasms↗
PubMed1997

Experience with intraperitoneal cisplatin and etoposide and i.v. sodium thiosulphate protection in ovarian cancer patients with either pathologically complete response or minimal residual disease.

BACKGROUND: High-dose platinum-based regimens can produce responses in patients not responding to standard chemotherapy. As in many ovarian cancer patients the disease remains confined to the peritoneal cavity, intraperitoneal (i.p.) chemotherapy has been applied as an alternative approach to increase drug exposure. The delivery of cytotoxic agents to the peritoneal cavity can lead to high drug concentrations intraperitoneally with less systemic toxicity. This study aimed at evaluating the efficacy and toxicity of high-dose i.p. cisplatin plus etoposide and intravenous sodium thiosulphate protection in ovarian cancer. PATIENTS AND METHODS: Patients with either a pathologically complete response (pCR) after first-line treatment or with persistent disease after first-line platinum-based chemotherapy or abdominal recurrences were eligible. All intraabdominal lesions had to be < 2 cm at the start of i.p. treatment. The treatment consisted of etoposide 350 mg/m2 i.p. followed by cisplatin 200 mg/m2 i.p. with intravenous sodium thiosulphate (4 g/m2 bolus, followed by 12 g/m2 over six hours) protection. Four courses of i.p. treatment were administered in case of pCR and 6 courses otherwise, at four-weekly intervals. RESULTS: The study comprised 29 patients, six patients with pCR, 17 patients with persistent disease and six patients with abdominal recurrences. They received a total of 105 courses of treatment (65% of the scheduled number of courses). Twelve patients completed scheduled treatment, illustrating its feasibility. In 17 patients treatment had to be prematurely stopped because of inflow obstruction (seven patients), bowel perforation (two patients), renal toxicity (two patients), neurotoxicity (two patients), or malaise and vomiting (four patients). One patient with bowel perforation died of this complication. Severe nausea and vomiting occurred in 51% of cycles. Leukopenia and thrombopenia grade 3 and 4 occurred in 30% and 6% of cycles, respectively. Ototoxicity of cisplatin was measured by serial tone audiography in 23 patients: only eight patients (35%) showed significant audiographic changes, although none of them developed clinical hearing loss. Fifteen patients were evaluable for response: four pCR, five PR, two SD, four PD. The median duration of freedom from progression was 616 days and the median overall survival 1065 days from the start of treatment. CONCLUSIONS: High-dose i.p. treatment with cisplatin and etoposide can be associated with significant toxicities. Major clinical problems are nausea, vomiting, and the formation of intraabdominal adhesions. Intravenous sodium thiosulphate effectively reduces the systemic toxicity of high-dose cisplatin. The value of high-dose i.p. treatment is uncertain and its routine use cannot be recommended.

Adult↗
PubMed1996

LHRH agonist treatment of breast cancer and gynecological malignancies: a review.

Since 1982 LHRH agonists have been used as a treatment modality in patients with disseminated breast cancer and gynecologic malignancies, based on the assumption of steroid dependence of these cancers. They have been successfully used in the treatment of premenopausal women with breast cancer; response rates reported are 31-63%. Less optimistic results have been reported in postmenopausal breast cancer patients as well as in the treatment of women suffering from ovarian cancer. Response rates for treatment of postmenopausal breast- and ovarian cancer patients appear to be up to 22% and 29%, respectively. Studies using LHRH agonists to treat endometrial and cervical intra-epithelial neoplasia are still rare and, until now, no data about the efficacy of LHRH agonists in treating these malignancies have been reported. This paper reviews clinically important studies of LHRH agonists, including a rationale for the use of LHRH agonists in breast cancer and gynecological cancer treatment. In view of the changed endocrine state in postmenopausal women on the one hand and alterations in endocrine metabolism in breast cancer tissue on the other hand, it is concluded that it might be more effective to use a combination of LHRH agonists and other endocrine modalities to treat disseminated breast cancer and gynecological malignancies.

Breast Neoplasms↗
PubMed1996

Identification of the major chemokines that regulate cell influxes in peritoneal dialysis patients.

To investigate which members of the recently discovered family of chemotactic cytokines (chemokines) are important in leukocyte recruitment to a bacterial inflammation site, four different chemokines in the effluent of peritoneal dialysis patients suffering from acute bacterial peritonitis were measured. The presence of two neutrophil-attracting chemokines, interleukin-8 and human melanoma growth-stimulating activity (huGRO alpha), and two monocyte-attracting members of the chemokine superfamily, monocyte chemotactic protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES), was investigated in patient effluents just before, during, and after a peritonitis episode. This was studied in seven peritonitis effluents of five patients by using chemokine-specific enzyme-linked immunosorbent assays. Cell populations in the dialysates were differentiated on cytocentrifuge preparations. The contribution of the detected chemokines to neutrophilic and monocytic cell influxes in the inflamed peritoneal cavity was analyzed by correlating concentrations of chemokines to the relevant cell numbers present in the dialysates of these patients. The detection of the neutrophil-attracting chemokine interleukin-8 during peritonitis was in accordance with other studies. Moreover, a second neutrophil chemoattractant, huGRO alpha, was identified in vivo. Both were elevated during inflammation (P < 0.02) and contributed significantly to the neutrophilic cell influx (P < 0.05). One of the monocyte-attracting chemokines, RANTES, could not be detected in any of the effluents, whereas the other, MCP-1, was significantly elevated during peritonitis (P < 0.02). In contrast to the other chemokines measured, MCP-1 concentration was relatively high in steady-state peritoneal dialysates. An absolute correlation between dialysate MCP-1 concentration and the number of macrophages in these effluents was absent. However, in a 48-well chemotaxis assay, monocyte migration toward peritonitis, as well as steady-state patient dialysates, could be blocked with antibodies to MCP-1. It was concluded, therefore, that MCP-1 is the most important monocyte chemoattractant in peritoneal dialysis steady-state and peritonitis patients; whereas, besides interleukin-8, huGRO alpha was identified as a major neutrophil-attracting chemokine in the peritonitis situation.

Acute Disease↗
PubMed1995

[Favorable results of paclitaxel (Taxol) in patients with ovary carcinoma pretreated with platinum].

OBJECTIVE: To assess the anti-tumour and side effects of paclitaxel in patients with ovarian carcinoma, after prior treatment with al least one platinum-containing chemotherapy regimen. DESIGN: Phase II study. SETTING: Academic Hospital of the Free University, Amsterdam. METHOD: Fourteen of 55 patients with progressive ovarian carcinoma were treated with 135 mg/m2 and 41 with 175 mg/m2 paclitaxel. 9 patients by 24-hour and 46 by 3-hour intravenous infusion. RESULTS: In 9/55 (16%) patients an objective tumour response was obtained, which was complete in 1 patient. In 19/55 (35%) patients the disease stabilised. The serum CA 125 level was increased in 52 patients. In 33% of the patients the course of the serum CA 125 was an indication of the tumour response. The median duration of response was 8 months (range 4.1-13.1) and the median duration of survival was 11.3 months (range 0.3-28.2). Side effects of paclitaxel treatment were hair-loss, arthralgia and myalgia and neutropenia of short duration. In 76% of patients pre-existing neurosensory symptoms increased mildly or developed de novo. The neurotoxic effect appeared reversible in most instances after discontinuation of the paclitaxel treatment. CONCLUSION: In this rather unfavourable patient population, paclitaxel induced only 16% objective response. However, more than 50% of the patients did benefit from paclitaxel treatment, as a much larger group had long lasting disease stabilisation without symptoms or had reduction of symptoms. The treatment was well tolerated by most patients.

Adult↗