This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian ...tube, or primary peritoneal cancer.
Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).
A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm.
Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
The most important prognostic factor in the ovarian cancer is optimal cytoreduction. The neoadjuvant chemotherapy, an only optional method of treatment in this case and is still the subject of ...debate. The object of this study was to evaluate the usefulness of markers: CA 125, HE4, YKL-40 and bcl-2 as well as cathepsin L in predicting optimal cytoreduction and response to chemotherapy.
Sera were secured preoperatively. The division into groups was performed retrospectively depending on the method of treatment (surgery vs neoadjuvant chemotherapy) as well as on response to chemotherapy (sensitive vs resistant vs refractory). Comparisons were made between groups, and the diagnostic usefulness of tested proteins was examined.
We found that statistically significant differences between primary operated patients and patients undergoing neoadjuvant chemotherapy were applicable only to the tumour markers (CA125 1206.79 vs 2432.38, p=0.000191; HE4 78.87 vs 602.45, p=0.000004; YKL-40 108.13 vs 203.96, p=0.003991). Cathepsin-L and Bcl-2 were statistically insignificant. The cut-off point values were determined for the CA 125 (345 mIU/ml), HE4 (218.43 pmol/L) and YKL-40 (140.9 ng/ml). The sensitivity, specificity, PPV and NPV were as follows: CA125 (83.3%; 75%; 80.6%; 78.3%), HE4 (86.6%; 91.3%; 92.9%; 84%) and YKL-40 (75%; 83.3%; 84%; 74.1%).
Among the tested proteins the HE4 marker appears to be helpful in forecasting of optimal cytoreduction and possibly also of the prediction of response to platinum analogues used in first-line treatment of ovarian cancer.
Abstract Leptin levels in serum depending on Body Mass Index (BMI) in patients with endometrial hyperplasia and cancer. Objectives Concentrations of leptin, a hormone secreted by white adipose ...tissue, correlate strongly with body mass. Leptin interacts with several other hormones, modifies the activities of some enzymes and proinflammatory cytokines, participates in hematopoiesis, thermogenesis, and angiogenesis, and is involved in the control of carbohydrate and lipid metabolism. This study was undertaken to determine whether serum concentrations of leptin in obese patients with endometrial hyperplasia and cancer deviate from values in patients with normal endometrium. Study design We enrolled 86 obese postmenopausal women, including 40 with endometrial cancer and hyperplasia and 46 with normal endometrium. Depending on BMI, three subgroups were formed: I < 30; II = 30–40; III > 40. Leptin concentrations were measured with immunoenzymatic test kits from IBL. Statistical comparison was done with the chi square ( χ2 ) test and Statistica software package. Results Mean serum concentration of leptin in endometrial cancer and hyperplasia was 16737.1 pg/ml as opposed to 9048.7 pg/ml in patients without endometrial pathology ( p < 0.0001). Significantly, higher concentrations of leptin were noted in every BMI subgroup of patients with endometrial pathology in comparison to controls ( p < 0.005). Conclusions Leptin appears to participate in proliferative processes of the endometrium. Obesity is an important risk factor in endometrial cancer.
The ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the ...peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer.
A total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed.
Differences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients.
On the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin.
Tumors of dysgenetic gonads in Swyer syndrome Zieliñska, Dorota; Zajączek, Stanislaw; Rzepka-Górska, Izabella
Journal of pediatric surgery,
10/2007, Letnik:
42, Številka:
10
Journal Article
Recenzirano
Abstract Background/Purpose The female with Swyer syndrome requires close follow-up because of the high risk of neoplastic transformation in the dysgenetic gonads. The aim of this work was to present ...our experience with tumors in patients with Swyer syndrome. Methods We studied 8 females with Swyer syndrome. At the time of diagnosis, they were 13 to 18 years old. We performed an ultrasound examination of dysgenetic gonads, hormonal (follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone) and genetic ( SRY , karyotype) tests, and histologic analysis of gonads (bilateral gonadectomy was performed in all patients). Results Gonadal tumors were found in 6 patients (3 cases of gonadoblastoma, 1 dysgerminoma, and 2 gonadoblastoma with dysgerminoma). Hormonal activity of gonadoblastoma was noted in 3 patients, with 1 tumor producing androgens. Conclusion Our data suggest that patents with gonadal dysgenesis and 46,XY karyotype should be referred for bilateral gonadectomy because of the high risk of neoplastic transformation. Estrogen-producing gonadoblastoma may mask gonadal dysgenesis and delay the diagnosis of this pathology.
This study was undertaken with regard to the gonadotropin theory of ovarian cancer advocated in the literature and was designed to disclose specific features of ovarian morphology in carriers of the ...BRCA1 gene mutation. We enrolled 171 patients and divided them into two groups: A (n=90)--operated for breast cancer (30 patients with and 60 without the BRCA1 mutation); B (n=81)--with the BRCA1 mutation qualified for preventive adnexectomy. According to the authors' classification described herein, some patients without the BRCA1 mutation retained "signs of estrogenization" in menopausal ovaries, revealing the role of estrogens as a factor promoting mammary carcinogenesis in these patients. A tendency to premature menopause was observed in BRCA1 mutation carriers of groups A and B as evidenced by the final menorrhea appearing at a younger age and almost total absence of "signs of estrogenization" in menopausal ovaries. It is concluded from these findings that earlier menopause in carriers of the BRCA1 mutation is associated with hypergonadotropic activity and may predispose to ovarian cancer at younger age.
Germ cell tumors are the most frequent ovarian neoplasms among girls and young women under the age of 25. Female patients with gonadal dysgenesis are at higher risk of germ cell tumors. Two cases of ...women with pure gonadal dysgenesis were described. A hormonally active tumor secreting estrogens, caused the development of sexual features and genital tract bleeding what imitated premature puberty. It needs to be emphasized that the presence of sexual features does not exclude dysgenesis - a pathology that is connected with an increased risk of gonadal tumors--and that the ultrasound evaluation, during which the presence of follicles in gonads is evaluated, is essential.
Resistant ovary syndrome (ROS) and premature ovarian failure (POF) represent two forms of hypergonadotropic hypogonadism. Principal symptoms include primary or secondary amenorrhea (before the age of ...40 years), low levels of estradiol and elevated FSH (above 40IU/ml) in serum. The main difference is the presence of follicles in ROS which is tantamount to the possibility of pregnancy. We present the case of pregnancy in a 31-year-old patient who was initially diagnosed with POF, which was the basis of the final diagnosis of ROS.
Adnexal torsion belongs to the group of urgent cases in gynecology Early diagnosis and management can prevent the loss of an ovary and the Fallopian tube. The case of the 14.5-year-old girl was ...described by the authors. The symptoms were moderate and caused diagnostics problems. During clinical assessment current literature knowledge, differentiation and treatment of the adnexa were taken into account.
The aim of our study was to evaluate the behaviour of the human epididymis protein 4 (HE4) in the peritoneal fluid encountered in various female genital diseases.
We enrolled 139 patients, 40 with ...ovarian cancer (group I), 82 with benign diseases (group II), and 17 with other malignant neoplasms (group III). The HE4 tumor marker concentrations were determined in serum, in the peritoneal effusion and ovarian cyst/ tumor fluids, CA125 in the serum only. We compared the groups, examined correlations and determined corresponding ROC curves. We evaluated the relationship between the HE4 marker concentration in the peritoneal effusion in the group I, depending on the selected prognostic parameters.
The HE4 median value between the study groups did not differ statistically significantly and were as follows: in group I 3322 pmol/L, in the group II 2150 pmol/L and in the group III 627 pmol/L (p = 0.206376 for the groups I and II, p = 0.05929 for the groups I and III and p = 0.0797 for the groups II and III. In group I there were no differences found in the HE4 concentrations in the peritoneal fluid, depending on the stage, grade, the presence of neoplastic cells and the peritoneal dissemination.
The HE4 marker concentrations in the peritoneal fluid are highly irrespective of the pathology observed in the female sexual organ. Therefore, it seems that its determinations in the peritoneal fluid are completely useless in terms of diagnostics. More research is needed on the role of the HE4 marker, especially the place of its formation and possible use in the targeted therapy.
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