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 extraper...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.展开更多
Objective: To evaluate the association between the presence of uterine leiomyomas and three functional single nucleotide polymorphisms (SNPs) of the estrogen receptor alpha (ESR1), catechol- O- methyltransferase (COMT...Objective: To evaluate the association between the presence of uterine leiomyomas and three functional single nucleotide polymorphisms (SNPs) of the estrogen receptor alpha (ESR1), catechol- O- methyltransferase (COMT), and cytochrom P450 17 (CYP17A) genes, which have been described to modify the estrogen metabolism. Design: Prospective case control study. Setting: Academic research institution. Patient(s): One hundred thirty women with clinically and surgically diagnosed uterine leiomyomas and 139 population controls. Intervention(s): Peripheral venous puncture. Main Outcome Measure(s): Polymerase chain reaction and pyrosequencing were performed to genotype women with respect to the ESR1 IVS1- 397 T/C (PvuII), COMT G158A, and the CYP17A 34T→ C SNPs. Result(s): Comparing women with uterine leiomyomas and controls, no statistically significant differences with respect to allele frequency and genotype distribution were ascertained for ESR1 IVS 1- 397 T/C (PvuII) (P=0.9 and P=0.6, respectively), COMT G158A (P=0.3 and P=0.6, respectively), and CYP17A 34T→ C (P=0.1 and P=0.5, respectively). When all two- way interactions of investigated SNPs were ascertained, no significant interactions were observed. In a multivariate model, no SNP was significantly associated with leiomyomas. Conclusion(s): Carriage of the ESR1 IVS1- 397 T/C (PvuII), COMT G158A, and the CYP17A 34T→ C SNPs is not associated with the susceptibility to uterine leiomyoma in a Caucasian population.展开更多
Objective: To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Design: Prospective case-control...Objective: To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Design: Prospective case-control study. Setting: Academic research institution. Patient(s): One hundred thirty-two women with clinically and surgically diagnosed uterine leiomyomas and 280 controls. Intervention(s): Peripheral venous puncture. Main Outcome Measure(s): Genotyping was performed by polymerase chain reaction-based amplification of the Arg and Pro variants at codon 72 of the p53 gene and by restriction fragment length polymorphismanalysis of the G/G and G/A alleles in exon 4 of the ANGPT2 gene. Result(s): Comparing women with uterine leiomyomas and controls, no statistically significant difference with respect to allele frequency and genotype distribution were ascertained for the ANGPT2 polymorphism (P=.2 and P=.5, respectively). However, for the p53 tumor suppressor gene polymorphism, statistically significant differences in terms of a higher Pro allele frequency and a higher prevalence of the Pro/Pro genotype among women with uterine leiomyoma (32.0% vs. 16.0% , respectively, and 21.3% vs. 4.7% , respectively) were ascertained (P=.001, OR 1.74; 95% CI 1.24-2.45, P=.001; OR 3.84, 95% CI 1.81-8.14; respectively). Conclusion(s): Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomyoma.展开更多
文摘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.
文摘Objective: To evaluate the association between the presence of uterine leiomyomas and three functional single nucleotide polymorphisms (SNPs) of the estrogen receptor alpha (ESR1), catechol- O- methyltransferase (COMT), and cytochrom P450 17 (CYP17A) genes, which have been described to modify the estrogen metabolism. Design: Prospective case control study. Setting: Academic research institution. Patient(s): One hundred thirty women with clinically and surgically diagnosed uterine leiomyomas and 139 population controls. Intervention(s): Peripheral venous puncture. Main Outcome Measure(s): Polymerase chain reaction and pyrosequencing were performed to genotype women with respect to the ESR1 IVS1- 397 T/C (PvuII), COMT G158A, and the CYP17A 34T→ C SNPs. Result(s): Comparing women with uterine leiomyomas and controls, no statistically significant differences with respect to allele frequency and genotype distribution were ascertained for ESR1 IVS 1- 397 T/C (PvuII) (P=0.9 and P=0.6, respectively), COMT G158A (P=0.3 and P=0.6, respectively), and CYP17A 34T→ C (P=0.1 and P=0.5, respectively). When all two- way interactions of investigated SNPs were ascertained, no significant interactions were observed. In a multivariate model, no SNP was significantly associated with leiomyomas. Conclusion(s): Carriage of the ESR1 IVS1- 397 T/C (PvuII), COMT G158A, and the CYP17A 34T→ C SNPs is not associated with the susceptibility to uterine leiomyoma in a Caucasian population.
文摘Objective: To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Design: Prospective case-control study. Setting: Academic research institution. Patient(s): One hundred thirty-two women with clinically and surgically diagnosed uterine leiomyomas and 280 controls. Intervention(s): Peripheral venous puncture. Main Outcome Measure(s): Genotyping was performed by polymerase chain reaction-based amplification of the Arg and Pro variants at codon 72 of the p53 gene and by restriction fragment length polymorphismanalysis of the G/G and G/A alleles in exon 4 of the ANGPT2 gene. Result(s): Comparing women with uterine leiomyomas and controls, no statistically significant difference with respect to allele frequency and genotype distribution were ascertained for the ANGPT2 polymorphism (P=.2 and P=.5, respectively). However, for the p53 tumor suppressor gene polymorphism, statistically significant differences in terms of a higher Pro allele frequency and a higher prevalence of the Pro/Pro genotype among women with uterine leiomyoma (32.0% vs. 16.0% , respectively, and 21.3% vs. 4.7% , respectively) were ascertained (P=.001, OR 1.74; 95% CI 1.24-2.45, P=.001; OR 3.84, 95% CI 1.81-8.14; respectively). Conclusion(s): Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomyoma.