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Biomedical subjects

D Denschlag

Publications and source records attributed to D Denschlag.

8 recordsLinked to original sources

Prognostic factors and outcome in women with uterine sarcoma.

OBJECTIVES: A retrospective analysis of patients with uterine sarcoma was undertaken to assess prognostic factors and treatment related outcomes. PATIENTS AND METHODS: Ninety-four patients (median age: 60years, range: 20-93years) with a histologically verified uterine sarcoma treated at the McGill University Health Centre (MUHC) between 1989 and 2004 were identified from the tumor registry and pathology database. RESULTS: Twenty-eight patients had an endometrial stromal sarcoma (ESS), 30 had a leiomyosarcoma (LMS), and 36 had mixed muellerian tumors (MMT). According to FIGO classification, Stage I, II, III, and IV tumors were identified in 49, 7, 20, and 18 patients, respectively. At the time of analysis, 55.5% of patients (52/94) were dead due to progressive sarcoma disease; 8.5% of the patients (8/94) were alive with disease recurrence, and 36.2% (34/94) were alive without disease recurrence, with a median survival of 35months. Univariate analysis demonstrated a statistically significant association between overall survival and histology in favor of patients with ESS (p<0.001). Analyzing each of the histological subtypes separately, adjuvant treatment with chemotherapy and/or hormonal treatment had no demonstrable impact on overall survival. In multivariate analysis age and advanced stage, remained a significant predictor for overall survival in patients with LMS and MMT, but not in patients with ESS. Regarding adjuvant treatment, radiotherapy had a significant impact on overall survival only in patients with MMT (p=0.002). CONCLUSIONS: In patients with uterine sarcoma, in comparison to LMS and MMT, ESS tends to present as a less aggressive disease with a favorable outcome. Furthermore, reflected by an improved overall survival after radiotherapy only in patients with MMT, it seems to be mandatory to differentiate between these histological subtypes.

Adult↗

Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma.

PROBLEM: To investigate the association between the occurrence of uterine leiomyoma and two SNPs of the CYP 2A13 and CYP 1A1 genes. METHOD OF STUDY: Prospective case control study with 132 women with clinically and surgically diagnosed uterine leiomyoma and 260 controls. Genotyping was performed by polymerase chain reaction (PCR) based amplification of CYP 2A13 and CYP 1A1 genes, and restriction fragment length polymorphism (RFLP) analysis. RESULTS: Comparing women with uterine leiomyoma and controls, we demonstrate statistical significant differences of allele frequency and genotype distribution for the CYP 1A1 polymorphism (P = 0.025 and P = 0.046, respectively). Furthermore, for the CYP 2A13 polymorphism we found a significant difference concerning allele frequency (P = 0.033). However, for the genotype distribution, only borderline significance was observed (P = 0.064). CONCLUSIONS: The CYP 2A13 and CYP 1A1 SNPs are associated with uterine leiomyoma in a Caucasian population and may contribute to the understanding of the pathogenic mechanisms of uterine leiomyoma.

Adult↗

Evaluation of patients after extraperitoneal lymph node dissection for cervical cancer.

OBJECTIVE: The presence of nodal metastases is an important prognostic factor in patients with cervical cancer. To adjust our therapy to the anatomic extent of the disease, we performed a surgical staging with extraperitoneal lymph node dissection (EPLND). The goal of our study was to evaluate the clinical outcome and side effects of the combined treatment approach of EPLND and either radical hysterectomy in case of early stage cervical cancer (FIGO Ia/b and IIa) and negative nodes, or pelvic radiotherapy/extended field radiotherapy with concomitant chemotherapy in case of positive nodes or advanced stage cervical cancer (FIGO IIb, III, and IVa). PATIENTS AND METHODS: Fifty-nine patients with primarily diagnosed invasive cervical cancer underwent EPLND. The value of this procedure as a diagnostic tool for evaluating the extent of disease was determined. Additionally, treatment-related complications and clinical outcomes were monitored. RESULTS: A total of 983 lymph nodes were removed during EPLND (mean 16.7). According to the results of EPLND, radical hysterectomy was abandoned due to histopathologically confirmed lymph node involvement by frozen section in 11 out of 36 patients with early stage cervical cancer (31%). The most common adverse effects directly related to surgery in general (EPLND or combined EPLND and radical hysterectomy) were lymph cysts in seven patients (12%). Only in the group of patients who received EPLND followed by radical hysterectomy, 2 out of 25 patients (8%) developed a severe ileus postoperatively (WHO Grade 3 toxicity). The treatment approach of combined EPLND followed by radio- and chemotherapy was without major complications (WHO Grade 3 or 4 toxicity). After a mean follow up of 28 months (range 6-60), 44 out of 58 patients (one patient lost to follow up) are without evidence of disease (76%), 2 patients have progressive disease (3%), and 12 patients died of their disease (21%). Using Kaplan-Meier analysis, the estimated 5-year overall survival rate for all patients is 64% (SD +/- 9%). Performing the Cox proportional regression analysis, in contrast to clinical FIGO staging (P = 0.24; ns), lymph node involvement was the only significant independent predictor for overall survival (P = 0.04). CONCLUSION: Our data support the approach of pretherapeutic surgical staging by performing EPLND as a diagnostic tool with a low complication rate. This allows an individualized treatment for cervical cancer patients.

Adult↗

[Hystero-salpingo-contrast-sonography with 3-d-ultrasound -- a pilot study].

UNLABELLED: Hystero-salpingo-contrast sonography (HyCoSy) is a sensitive method of assessing tubal patency but cannot completely substitute diagnostic laparoscopy with blue dye and hysteroscopy. Three-dimensional sonography has new imaging facilities which could lead to a reduction of invasive diagnostic procedures. AIM: The aim of this pilot study was to analyse the feasibility of HyCoSy by 3D- and 3D-Doppler-sonography. METHODS: In a prospective setting conventional (2D) HyCoSy was performed in 21 patients with an ultrasound device designed for 3D-ultrasound. After the completion of the 2D procedure, 3D-ultrasound was carried out. In five patients an additional 3D-Doppler-HyCoSy was performed. The generated 3D-volumina were then examined. Laparoscopy with blue dye was performed immediately after the ultrasound examination. RESULTS: A total of 42 Fallopian tubes was assessed. On 2D-ultrasound, visibility of the tubes was excellent in 28 and limited in seven tubes. Of the seven tubes not visible on 2D-ultrasound, four were not patent on laparoscopy. On 3D-ultrasound, visibility of the tubes was excellent in 15 and limited in twelve tubes. 15 tubes were not visible on 3D-ultrasound. 3D-Doppler-HyCoSy revealed excellent assessment in eight of ten tubes, even in one of those with limited visibility on 2D- and 3D-HyCoSy. In 19 patients the assessment of the uterine cavity was excellent by 2D- and 3D-HyCoSy, whereas it was limited in two patients. CONCLUSION: It is possible to visualise the full length of the tubes in a very detailed way from the uterine cavity to the fimbrial end in some patients, but the diagnostic power of HyCoSy is not improved by adding 3D-imaging. The accuracy of 3D-ultrasound seemed to be improved by 3D-Doppler-ultrasound.

Fallopian Tubes↗

The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage.

Endothelial damage, impaired microvascularization and immune maladaptation have been described as aetiological factors in recurrent miscarriages. We investigated the relationship between idiopathic recurrent miscarriage (IRM) and a (GT)(n) repeat microsatellite polymorphism of the gene encoding haem oxygenase 1 (HO-1), known to modulate immune functions such as T-helper (TH) cell function and to be associated with cardiovascular disease. We investigated 162 women with IRM and 129 healthy, post-menopausal controls. The length of the HO-1 (GT)(n) microsatellite was assessed by PCR and direct sequencing in all women. Results were correlated with clinical data. The distribution of genotypes was in Hardy-Weinberg equilibrium. The HO-1 (GT)(n) microsatellite repeat numbers ranged from 13 to 37, with (GT)(23) and (GT)(30) being the most common alleles in both groups. We compared alleles consisting of < or =27 GT repeats, termed class S (short) alleles and alleles consisting of >28 GT repeats, termed class L (long) alleles. Seventy per cent of women with IRM had an S allele either in heterozygous (L/S) or homozygous (S/S) form, compared to 56% of controls (P = 0.02; OR 0.54; 95% CI 0.32-0.90). With respect to S allele frequencies, we found no significant difference among women with IRM and controls [P = 0.3; odds ratio (OR) 1.23, 95% confidence interval (CI) 0.86-1.76]. Comparing women with primary and secondary IRM, no difference with respect to the length of the HO-1 (GT)(n) microsatellite was ascertained. In summary, this is the first report on a HO-1 (GT)(n) microsatellite polymorphism among women with IRM, demonstrating that the investigated polymorphism is associated with IRM in a relatively large Caucasian population.

Abortion, Habitual↗

[The corpus luteum].

The primary function of the corpus luteum is secretion of progesterone for maintenance of pregnancy. The development and function of the corpus luteum from residual follicular granulosa and theca cells after ovulation is induced by the midcyclic peak of LH secretion followed by further pulsatile LH release. Due to this stimulation the follicular granulosa and theca cells are converted to large and small luteinized cells with high proliferation rate. During this process Vascular-Endothelial-Growth Factor (VEGF) plays a major role as a potent stimulator of neo-angiogenesis. Formation of new blood vessels is essential to ensure supply of LDL-Cholesterol as substrate for steroidogenesis. If pregnancy does not occurs, the corpus luteum must regress to initiate another cycle. Luteal regression seems to be initiated by PGF2 alpha which is secreted from the uterus. PGF2 alpha, reduces luteal blood flow and progesterone synthesis. Furthermore it is a potent inducer of apoptosis. If pregnancy occurs, sustained secretion of progesterone and other substances like estradiol and relaxin are required to provide an appropriate uterine environment for maintenance of pregnancy. In that case the corpus luteum is further stimulated by hCG secreted by the blastocyst and the trophoblast-cells until 8/9 weeks of gestational age, when synthesis and secretion of steroids is taken over by the placenta.

Corpus Luteum↗

Topotecan as a continuous infusion over 14 days in recurrent ovarian cancer patients.

OBJECTIVE: In recurrent ovarian cancer the topoisomerase-1 inhibitor topotecan shows activity after prior treatment with platinum and taxanes. Overall response rates of up to 38% in combination with an acceptable toxicity profile have been reported. We performed a pilot study to evaluate the therapeutic efficacy and toxicity profile of a low-dose continuous infusion protocol of topotecan. PATIENTS AND METHODS: Twelve patients with recurrent ovarian cancer and a measurable lesion received a continuous infusion of topotecan (0.4 mg/m2/d) over 14 days, repeated every 28 days. All patients had at least one prior platinum-containing regimen of chemotherapy (range 1-7). Responses were evaluated by ultrasound, computed tomography (CT) scans and/or magnetic resonance imaging (MRI). RESULTS: A total of 57 (median 5, range 1-12) topotecan treatment cycles were administered. The overall response rate was 2/12 (17%). Four patients had stable disease (33%), among them two patients with platinum-refractory tumors. The median time to progression was 26 (range 20-100) weeks. No grade 3 or 4 hematological toxicities were observed. However, one patient developed a grade 2 allergy leading to discontinuation of topotecan. CONCLUSION: Treatment of recurrent ovarian cancer with low-dose continuous infusion of topotecan over 14 days demonstrated response rates comparable to other dosing schedules with minimal toxicity in a preliminary series of 12 patients.

Aged↗