Showing papers in "International Journal of Gynecological Cancer in 2009"
TL;DR: Cancer can be successfully treated during pregnancy in collaboration with a multidisciplinary team, optimizing maternal treatment while considering fetal safety, and despite limited evidence-based information, cancer treatment during pregnancy can succeed.
Abstract: Cancer in pregnancy presents a rare coincidence which demands intensive interdisciplinary care. Among this, gynecologic cancer is a special challenge because cancer or treatment may not only affect the pregnant women in general but involve the reproductive tract and fetus directly. Currently, there are no guidelines on how to deal with this special coincidence. An international consensus meeting on staging and treatment of gynecologic malignancies during pregnancy including systematic literature search, interpretation, and preparation followed by a physical meeting of all participants with intensive discussion. In the absence of large trials and randomized studies, recommendations were based on available literature data and personal experience, thus representing a low but best achievable level of evidence. Randomized trials and prospective studies on cancer treatment during pregnancy are lacking. Gynecologic cancer during pregnancy is a demanding problem and multidisciplinary expertise should be available. Counseling both parents on the maternal prognosis and fetal risk is needed. When there is a firm desire to continue the pregnancy, gynecologic cancer can be treated in selected cases. The staging and treatment should follow the standard approach as much as possible. Guidelines for safe pelvic surgery during pregnancy are presented. Mainly in cervical and ovarian cancer, chemotherapy and an alternative surgical approach need to be considered. Administration of chemotherapy during the second or third trimester may probably not increase the incidence of congenital malformations. Until now, the long-term outcome of children in utero exposed to oncological treatment modalities is poorly documented, but preterm birth on its own is associated with cognitive impairment. Delivery should be postponed preferably until after a gestational age of 35 weeks.
260 citations
TL;DR: New screening programs in Ghana should address barriers and increase screening cues to the public to address the knowledge and beliefs of female university college students in Ghana.
Abstract: Background: Cervical cancer is the most incident cancer and the leading cause of cancer mortality in women in Ghana. Currently, little is known about Ghanaian women9s knowledge and beliefs about cervical cancer screening, yet this information is essential to the success of cervical cancer screening programs. Therefore, the purpose of this study was to describe the knowledge and beliefs of female university college students in Ghana. Methods: A cross-sectional survey among college women in a university in Ghana elicited information about sociodemographics, knowledge and beliefs, and acceptability of cervical cancer screening, screening history, and sexual history. Bivariate analyses were conducted to identify factors associated with screening. Results: One hundred forty women were recruited; the age range was 20 to 35 years. The prior Papanicolaou (Pap) screening rate was 12.0%. The women were unaware of local screening initiatives, and only 7.9% were aware of the link between human papillomavirus and cervical cancer. The most prevalent barriers were lack of awareness that the purpose of Pap screening is to diagnose cancer, concerns about what others may think, and lack of information about how to obtain screening services. Although women perceived the benefits of screening, only about half perceived themselves to be at risk. Women received few screening cues. Three barriers were negatively associated with screening in bivariate analyses: lack of belief that cancer is diagnosed by cervical screening, belief that Pap test is painful, and belief that the test will take away virginity. Conclusion: New screening programs in Ghana should address these barriers and increase screening cues to the public.
203 citations
TL;DR: A theory that inflammation in the tube, caused by menstrual cytokines or infection, is critical to the genesis of pelvic high-grade serous carcinoma is put forward and a change in surgical practice is recommended, with salpingectomy at the time of simple hysterectomy.
Abstract: Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancy, and most of epithelial cancers are of serous type. The site of origin of pelvic high-grade serous carcinoma has been the subject of debate for 60 years. This paper reviews the evidence that pelvic serous carcinoma originates from the fallopian tube mucosa and puts forward a theory that inflammation in the tube, caused by menstrual cytokines or infection, is critical to the genesis of these tumors. Other risk factors for pelvic serous carcinoma will be reviewed, including oral contraceptive use, parity, infertility, and tubal ligation.Studies were identified for this review by searching the English language literature in the MEDLINE database between the years 1995 and 2007 using the following keywords: fallopian tube neoplasia, ovarian serous adenocarcinoma, pregnancy, oral contraceptive, infertility, pelvic inflammatory disease, cytokines, menstruation, and tubal ligation, followed by an extensive review of bibliographies from articles found through the search.The clinical implications of this theory are discussed, and a change in surgical practice is recommended, with salpingectomy at the time of simple hysterectomy. This theory also has implications for the development of new methods of screening for pelvic serous carcinomas, as there are no screening methods that are currently available to find this form of cancer in an early stage. Inflammatory markers could be detected in the vagina from the fallopian tube indicating possible chronic inflammation and a risk factor for mutagenesis leading to serous carcinoma.
190 citations
TL;DR: The authors set out to determine whether pelvic lymphadenectomy could improve the survival of women with endometrial cancer and concluded that it could not be recommended; furthermore, it could be associated with a worse outcome the more lymph nodes are removed.
Abstract: To the Editor: The authors set out to determine whether pelvic lymphadenectomy could improve the survival of women with endometrial cancer. They included patients with endometrial cancer thought preoperatively to be confined to the corpus yet did not exclude patients with radiological evidence suggesting node enlargement. They concluded that pelvic lymphadenectomy could not be recommended; furthermore, lymphadenectomy could be associated with a worse outcome the more lymph nodes are removed. From a surgical perspective, we take issue with these conclusions for the following reasons: 1. In the United Kingdom, there was a large number of contributing hospitals and surgeons. Most of the hospitals were not cancer centers, and a substantial number of surgeons would not have been experienced in pelvic and/or para-aortic lymphadenectomy. This explains why 35% of the patients in the lymphadenectomy arm had fewer than 10 nodes harvested, why only 40% of the patients had more than 14 nodes harvested, why the median node count was 12, and why more than 50% of the operations took less than 90 minutes. Furthermore, only 6% of the patients had laparoscopic surgery. In the study by Panici et al, who also used term systematic in the title, at least 20 pelvic lymph nodes had to be identified histologically before the term systematic could be used. 2. There was no central pathology review, and in each arm of the study, about 20% of the patients had a nonendometrioid histologic diagnosis, including aggressive subtypes with a known propensity for nodal metastasis, pelvic and para-aortic. 3. The preoperative evaluation of endometrial cancer regarding histologic grade and stage is unreliable when compared with the final histologic diagnosis. The decision for the use of adjuvant treatment or not was based on the final International Federation of Gynecology and Obstetrics stage and histologic subtype. Furthermore, 45% of the cases were welldifferentiated stage IA or IB where the risk of nodal metastasis is 3% to 5%, as acknowledged by the authors. In contrast, Panici et al specifically excluded these low-risk patients by preoperative grade and intraoperative frozen section. 4. Fifty-seven of the patients received adjuvant radiotherapy, most of whom were node negative. As such, any potential benefit of lymphadenectomy would have been masked by radiotherapy.
168 citations
TL;DR: Similarities in histology, metastasis, and stages of hen OVCA to those of humans demonstrate the feasibility of the hen model for additional delineation of the mechanism underlying ovarian carcinogenesis, preclinical testing of new agents for the prevention, and therapy of this disease.
Abstract: The high mortality rate due to ovarian cancer (OVCA) is attributed to the lack of an effective early detection method. Because of the nonspecificity of symptoms at early stage, most of the OVCA cases are detected at late stages. This makes the access to women with early-stage disease problematic and presents a barrier to development and validation of tests for detection of early stage of OVCA in humans. Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Laying hen is the only available animal that develops OVCA spontaneously; however, detailed information on ovarian tumor histology is not available. The goal of this study was to determine the histological features of malignant ovarian tumors in laying hens. A total of 155 young and old (1-5 years of age) laying hens (Gallus domesticus) were selected randomly and evaluated grossly and microscopically for the presence of ovarian tumors. Histological classification of tumors with their stages and grades was determined with reference to those for humans. Similar to humans, all 4 types including serous, endometrioid, mucinous, and clear cell or mixed carcinomas were observed in hen ovarian tumors. Some early neoplastic as well as putative ovarian lesions were also observed. Similarities in histology, metastasis, and stages of hen OVCA to those of humans demonstrate the feasibility of the hen model for additional delineation of the mechanism underlying ovarian carcinogenesis, preclinical testing of new agents for the prevention, and therapy of this disease.
145 citations
TL;DR: In patients with stage I LMS, primary surgery involving tumor injury seems to be associated with a worse prognosis than total hysterectomy as a primary intervention.
Abstract: Background: Uterine leiomyosarcoma (LMS) has a poor prognosis even after early-stage diagnosis. Because there are no accurate diagnostic tools for preoperatively distinguishing LMS from uterine leiomyoma, surgeons might opt for partial surgical procedures such as myomectomy or subtotal hysterectomy. We sought to determine whether a surgical procedure that cuts through the tumor influences prognosis. Materials and Methods: Demographic and clinical data of consecutive patients with stage I LMS treated between 1969 and 2005 were reviewed. The study population was divided into group A: patients whose first surgical intervention was total hysterectomy (n = 21); and group B: patients who underwent procedures involving tumor injury, for example, myomectomy, laparoscopic hysterectomy with a morcellator knife, or hysteroscopic myomectomy (n = 16). Survival rates were analyzed and compared. A Cox proportional hazards model was used to assess the association between variables of interest and prognosis. Results: The median age at diagnosis was 50 years (range, 30-74 years). Median follow-up duration was 44 months. The 2 groups did not differ significantly in age at diagnosis, menopausal status, gravidity, parity, postoperative radiotherapy, or time to last follow-up. Kaplan-Meier curves showed significantly better survival rates (P = 0.04) and a significant advantage in recurrence rate (P = 0.03) for group A compared with group B. Survival in group A was 2.8-fold better than that in group B (95% confidence interval, 1.02-7.67). These estimates remained stable after adjustment for age, menopausal status, and radiotherapy. Conclusions: In patients with stage I LMS, primary surgery involving tumor injury seems to be associated with a worse prognosis than total hysterectomy as a primary intervention.
140 citations
TL;DR: The conclusions were that the impact of postoperative brachytherapy on even the locoregional recurrence rate seems to be limited in patients with low-risk endometrial carcinoma.
Abstract: The purpose of the study was to compare postoperative vaginal irradiation with surgery alone in low-risk International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB endometrial carcinoma. The study was a prospective, randomized trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European gynecologic cancer centers. All tumors were in FIGO stage IA-IB, of endometrioid histological type, and FIGO grade 1-2. High-dose-rate afterloading equipments (iridium [Ir] 192 or cobalt [co] 60) were used at 5 centers, and low-dose-rate (LDR) afterloading equipment (cesium [Cs] 137) at 1 center. Perspex vaginal applicators or ovoids were normally used, and the dose was specified at 5 mm from the surface of the applicator. Three to 6 fractions (3.0-8.0 Gy) were given, and the overall treatment time was 4 to 15 days. A total of 319 patients were treated with surgery plus vaginal irradiation (treatment group), and 326 patients with surgery alone (control group).Twenty-six recurrences (4.0%) were recorded in the complete series. The locoregional recurrence rate was 2.6%, whereas distant metastases occurred in 1.4%. The rate of vaginal recurrences was 1.2% in the treatment group versus 3.1% in the control group. The difference was not statistically significant (P = 0.114). Side effects were few and mild (grade 1-2). Dysuria, frequency, and incontinence were slightly more common after vaginal irradiation (2.8% vs 0.6%, respectively). Late intestinal problems were few and similar in the 2 groups. The conclusions were that the impact of postoperative brachytherapy on even the locoregional recurrence rate seems to be limited in patients with low-risk endometrial carcinoma. The overall recurrence rate and survival were similar in the 2 groups.
137 citations
TL;DR: In case of an ovarian tumor, metastatic disease should always be considered to avoid pitfalls in diagnosis and therapy, and the gastrointestinal tract is the most likely location of the primary tumor, followed by breast and endometrium.
Abstract: Objective: To evaluate the frequency of metastatic tumors among malignant ovarian neoplasms, the site distribution of the primary malignancies that give rise to ovarian metastasis and the clinicopathologic features of metastatic tumors. Methods: We analyzed a total number of 116 patients diagnosed with metastasis to the ovary between 1985 and 2007 at the Radboud University Nijmegen Medical Centre. The medical records of the patients were reviewed for age at diagnosis, medical history, menopausal state, clinical manifestation, primary tumor, intraoperative findings, and prognosis. The pathology reports were reviewed for macroscopic appearances and histopathologic features. Results: Metastasis to the ovary accounted for 15% of all ovarian malignancies identified in the 22-year period at the Radboud University Nijmegen Medical Centre. The gastrointestinal tract was the most common primary site (39%), followed by breast (28%) and endometrium (20%). There were 22 metastases to the ovary that mimicked a primary ovarian tumor at first clinical presentation, of which the single greatest number of cases (36%) originated from a primary tumor of the large intestine. Ovarian cysts were present in 71% of patients, and most ovaries with metastatic disease were 10 cm in diameter or less. Bilateral ovarian involvement was present in 69% of the patients, including all patients with tumors of the stomach. Conclusion: In case of an ovarian tumor, metastatic disease should always be considered to avoid pitfalls in diagnosis and therapy. The gastrointestinal tract is the most likely location of the primary tumor, followed by breast and endometrium.
105 citations
TL;DR: Erlotinib is inactive as monotherapy in patients with recurrent squamous cell carcinoma of the uterine cervix, with the most common drug-related adverse events being gastrointestinal toxicities, fatigue, and rash.
Abstract: Objectives: To determine the proportion of patients with tumor response, the proportion who survived progression-free for at least 6 months (progression-free survival ≥ 6 months), and the frequency and severity of toxicities of patients with recurrent squamous cell carcinoma of the uterine cervix treated with erlotinib. Methods: This was a multicenter, open-label, single-arm trial evaluating the toxicity and efficacy of oral erlotinib at an initial dosage of 150 mg daily until progressive disease or adverse effects prohibited further therapy. Results: Twenty-eight patients with squamous cell carcinoma were enrolled onto this trial. Twenty-five patients were evaluable. There were no objective responses, with 4 (16%) patients achieving stable disease; only 1 patient had a progression-free survival of 6 months (4%) or more. The 1-sided 90% confidence interval for response was 0.0% to 8.8%. The 2-sided 90% confidence interval for the proportion of patients surviving progression-free for at least 6 months is 0.2% to 17.6%. Erlotinib was well tolerated, with the most common drug-related adverse events being gastrointestinal toxicities, fatigue, and rash. Conclusions: Erlotinib is inactive as monotherapy in patients with recurrent squamous cell carcinoma of the uterine cervix.
102 citations
TL;DR: Conservative treatment with progestin can be considered a good therapeutic option in patients with well-differentiated early-stage endometrioid endometrial adenocarcinoma who wish to preserve their uteri or become pregnant.
Abstract: Introduction: The purpose of this study was to evaluate the efficacy of conservative treatment with progestin and pregnancy outcomes in women with early-stage endometrial cancer. Methods: We retrospectively analyzed the medical records of 35 patients with endometrial adenocarcinoma, who were treated with progestin from January 1996 to December 2006. Women with early-stage grade 1 endometrioid endometrial adenocarcinoma, who wanted to receive conservative treatment or preserve fertility, were included. All women were treated with medroxyprogesterone acetate or megestrol acetate, with regular dilation and curettage performed. Complete remission (CR) was defined as no evidence of endometrial adenocarcinoma or hyperplasia. Partial remission was diagnosed when the patient developed endometrial hyperplasia, and persistent disease was defined as residual endometrial adenocarcinoma by pathologic confirmation. Results: The median age was 31 years (range, 21-43 years), and the median follow-up period was 39 months (range, 5-108 months). Complete remission was achieved in 22 patients (62.9%), partial remission was achieved in 1 patient (2.9%), and 12 patients (34.3%) had persistent disease. The median time to CR was 9 months (range, 2-12 months). Of the 22 patients with CR, 9 (40.9%) had recurrent disease, and the median time to recurrence was 12 months (range, 8-48 months). Ten (83.3%) of the 12 patients with CR who tried to conceive were successful, and 8 of the 10 pregnancies resulted in live births. There were no congenital anomalies in babies associated with progestin treatment. Conclusions: Conservative treatment with progestin can be considered a good therapeutic option in patients with well-differentiated early-stage endometrioid endometrial adenocarcinoma who wish to preserve their uteri or become pregnant.
100 citations
TL;DR: Ovarian cancer survivors who were meeting physical activity guidelines reported more favorable outcomes of fatigue, peripheral neuropathy, sleep, and psychosocial functioning.
Abstract: Purpose: Physical activity has been associated with better health-related outcomes in several cancer survivor groups but very few data exist for women with ovarian cancer. The purpose of this study was to investigate the associations between physical activity and health-related outcomes in ovarian cancer survivors and to examine any dose-response relationship. Patients and Methods: A cross-sectional postal survey of ovarian cancer survivors on and off treatment identified through the Alberta Cancer Registry was performed. Participants completed self-report measures of physical activity, cancer-related fatigue, peripheral neuropathy, depression, anxiety, and happiness, as well as demographic and medical variables. Results: A total of 359 ovarian cancer survivors participated (51.4% response rate) of whom 31.1% were meeting the public health physical activity guidelines of the Centers for Disease Control and Prevention. Those meeting guidelines reported significantly lower fatigue than those not meeting guidelines (mean difference, 7.1; 95% confidence interval, 5.5-8.8; d = 0.87; P Conclusions: Ovarian cancer survivors who were meeting physical activity guidelines reported more favorable outcomes of fatigue, peripheral neuropathy, sleep, and psychosocial functioning.
TL;DR: The addition of multiphase 3-dimensional DCE-MRI to T2WI can effectively assess the depth of myometrial invasion in endometrial carcinoma and may be a useful tool to guide the surgical approach.
Abstract: Aim: To assess the added value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting advanced stage disease in patients with endometrial carcinoma. Materials and Methods: Fifty patients with endometrial carcinoma underwent preoperative MRI assessment in a single gynecological cancer center during a 2-year period. Magnetic resonance imaging examinations included high-resolution sagittal, axial, and axial-oblique T2-weighted images (T2WI) of the pelvis, and axial T1-weighted images (T1WI) of the pelvis and upper abdomen followed by DCE-MRI using a multiphase 3-dimensional gradient refocused echo T1WI sequence. The T2W images were evaluated initially, and local and overall staging was assigned according to the FIGO classification. An identical scoring system was used to evaluate the combination of DCE-MRI and T2WI. The presence of potential pitfalls in the accurate assessment of depth of myometrial invasion (leiomyoma, adenomyosis, loss of junctional zone definition, polypoid tumor, poor tumor-to-myometrium contrast, and tumor extension to uterine cornu) was also recorded. Surgical histology constituted the standard of reference. Results: The depth of myometrial invasion was correctly determined in 78% (39/50) of the cases on T2WI alone, increasing to 92% (46/50) with the addition of DCE-MRI (95% confidence interval for improvement, 4.4%-23.6%, P = 0.016). The addition of DCE-MRI led to the correct detection of deep myometrial invasion in all cases. Tumor extension to uterine cornu was the only variable significantly associated (P = 0.014) with incorrect estimation of depth of myometrial invasion. Conclusions: The addition of multiphase 3-dimensional DCE-MRI to T2WI can effectively assess the depth of myometrial invasion in endometrial carcinoma and may be a useful tool to guide the surgical approach.
TL;DR: The lack of Ep-CAM expression on the chelomic epithelium in the peritoneal cavity, combined with the recent development of fully human monoclonal antibodies against this surface molecule, suggest Ep- CAM as a promising target for antibody-mediated therapies in ovarian carcinoma patients harboring tumors refractory to standard treatment modalities.
Abstract: To evaluate the potential of epithelial cell adhesion molecule (Ep-CAM/TROP-1)-specific immunotherapy against epithelial ovarian carcinomas (EOCs), we have analyzed the expression of Ep-CAM at RNA and protein level in patients harboring primary, metastatic, and chemotherapy-resistant/recurrent EOC. Epithelial cell adhesion molecule expression was evaluated by real-time polymerase chain reaction and immunohistochemistry in 168 fresh-frozen biopsies and paraffin-embedded tissues. In addition, Ep-CAM surface expression was evaluated by flow cytometry in several freshly established ovarian carcinoma cell lines derived from patients harboring tumors resistant to chemotherapy in vivo as well as in vitro. Epithelial cell adhesion molecule transcript was found significantly overexpressed in primary, metastatic, and recurrent EOC when compared with normal human ovarian surface epithelium cell lines and fresh-frozen normal ovarian tissue (P < 0.001). Similarly, by immunohistochemistry, Ep-CAM protein expression was found significantly higher in primary, metastatic, and recurrent EOC when compared with normal ovarian tissues. Of interest, metastatic/recurrent tumors were found to express significantly higher levels of Ep-CAM protein when compared with primary ovarian carcinomas (P < 0.001). Finally, a high surface expression of Ep-CAM was found in 100% (5/5) of the chemotherapy-resistant ovarian carcinoma cell lines studied by flow cytometry. These results demonstrate high Ep-CAM overexpression in ovarian carcinoma, especially in metastatic and recurrent/chemotherapy-resistant ovarian disease. The lack of Ep-CAM expression on the chelomic epithelium in the peritoneal cavity, combined with the recent development of fully human monoclonal antibodies against this surface molecule, suggest Ep-CAM as a promising target for antibody-mediated therapies in ovarian carcinoma patients harboring tumors refractory to standard treatment modalities.
TL;DR: Bivalent and quadrivalent HPV vaccines significantly reduced the rate of lesions in the cervix, vulva, vagina, and anogenital region, with efficacy of 93% and 62% respectively, when compared with the control groups according to intention to treat.
Abstract: Human papillomavirus (HPV) types cause approximately 70% of cervical cancer worldwide. Two vaccines have been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co, Inc, Whitehouse Station, NJ). We have performed a systematic review of all randomized controlled trials in which vaccines against HPV were compared with placebo regarding efficacy, safety, and immunogenicity. Six studies met the inclusion criteria, which included 47,236 women. The first objective in this systematic review was to assess vaccine efficacy in the prevention of cytologically and/or histologically proven lesions. And the secondary objective was the evaluation of safety and vaccine immunogenicity. Bivalent and quadrivalent HPV vaccines significantly reduced the rate of lesions in the cervix, vulva, vagina, and anogenital region, with efficacy of 93% (95% confidence interval [CI], 87-96) and 62% (95% CI, 27-70), respectively, when compared with the control groups according to intention to treat. Regarding safety, we found more symptoms in the bivalent vaccine group (35%; 95% CI, 5-73) when compared with the control groups. In regard to vaccine immunogenicity, there was seroconversion in the group that received the vaccine when compared with the placebo group in the bivalent and quadrivalent vaccines. Prophylactic vaccination can prevent HPV infection in women aged 9 to 26 years not previously infected with the HPV subtypes covered by the vaccines. To evaluate cervical cancer incidence and mortality, a longer follow-up is necessary.
TL;DR: To identify the most important trials for women with endometrial carcinoma and uterine carcinosarcoma, both those already underway or to be done, for which the Gynecological Cancer Intergroup might facilitate international cooperation.
Abstract: There is a pressing need to improve our understanding of endometrial cancer (EC) and uterine carcinosarcoma and to develop new treatment strategies to improve outcomes. In recognition of this, a State of the Science meeting on EC was held last November 28 and 29, 2006, in Manchester, United Kingdom. The meeting was cosponsored by the National Cancer Research Institute (UK), the National Cancer Institute (US), and the Gynecological Cancer Intergroup. The objectives of the meeting were as follows: 1. To review current knowledge and understanding of EC and its treatments. 2. To identify key issues for translational research and clinical trials. 3. To identify the most important trials for women with endometrial carcinoma and uterine carcinosarcoma, both those already underway or to be done, for which the Gynecological Cancer Intergroup might facilitate international cooperation.
TL;DR: In conclusion, inhibin B and AMH are both useful serum markers for diagnosis and especially for follow-up of patients with a GCT, and there is no evidence-based preference for inhibition B or AMH as tumor marker.
Abstract: The peptide hormones inhibin and antimullerian hormone (AMH), both produced by the granulosa cells, are potential candidates for diagnosis and follow-up of granulosa cell tumors (GCTs). The objective was to evaluate the usefulness of serum levels of inhibin B and AMH in the diagnosis and follow-up of GCT. The review summarizes and discusses the value and limitations of the laboratory tests of these hormones by investigating the performance characteristics of the serum analyses. A search in PubMed database was accomplished to find articles describing serum inhibin and/or AMH as a diagnostic test or for follow-up of GCT. The literature search included articles published between 1989 and September 2008. The sensitivity of inhibin B and AMH for diagnosing patients with a progressive disease is rather equivalent. Antimullerian hormone is a more specific serum parameter than inhibin, because inhibin may also increase in some (mucinous) epithelial ovarian tumors. Nowadays, specific and ultrasensitive assays are commercially available as well for inhibin B as for AMH, so that early detection of GCT might be possible. For patients with elevated levels of inhibin B and/or AMH at initial diagnosis of GCT, inhibin B and/or AMH seemed to be reliable markers during follow-up for early detection of residual or recurrent disease. Elevated concentrations of these hormones predict relapse earlier than clinical symptoms, which leads to less morbidity of the patients. In conclusion, inhibin B and AMH are both useful serum markers for diagnosis and especially for follow-up of patients with a GCT. Currently, there is no evidence-based preference for inhibin B or AMH as tumor marker.
TL;DR: Neither did adjuvant RT correlate with improved survival within any FIGO stage nor did it alter survival for low- or high-grade tumor groups.
Abstract: Introduction: Endometrial stromal sarcoma (ESS) is a rare uterine malignancy characterized by cells resembling proliferative-phase endometrial stroma. Standard treatment is total hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). The roles of radiation therapy (RT) and lymphadenectomy (LAD) remain unclear. Using a large population database, we retrospectively evaluated the addition of RT and LAD to surgery for survival impact. Methods: We identified 1010 women with ESS between 1983 and 2002 from the National Cancer Institute9s Surveillance, Epidemiology, and End Results Program. Kaplan-Meier method was used to estimate overall survival (OS) and cause-specific survival (CSS). Outcomes for patients treated by TAH-BSO alone and surgery plus RT were compared using Cox proportional hazards regression model. A multivariate analysis controlling for age, International Federation of Gynecology and Obstetrics (FIGO) stage, LAD, race, year of diagnosis, and tumor grade was performed. Univariate analyses were performed for individual FIGO stages, low- and high-grade tumors, and surgery with and without LAD. A literature review was performed to compile studies showing LAD data for ESS. Results: The median follow-up was 54 months (range, 1-248 months). The 5-year OS and CSS for patients undergoing surgery plus RT were 72.2% and 80.1% and 83.2% and 90.7% for surgery alone, respectively. Worse prognoses were associated with increasing FIGO stage, tumor grade, and age. Neither did adjuvant RT correlate with improved survival within any FIGO stage nor did it alter survival for low- or high-grade tumor groups. Adding lymphadenectomy to TAH-BSO did not change survival.
TL;DR: Fertility-sparing surgery is a reasonable alternative treatment for young women with stage I epithelial ovarian cancer desiring fertility preservation and five-year survival data showed no significant difference in the recurrence-free survival of the fertility- Sparing and standard surgery groups or overall survival.
Abstract: Objective: To determine the long-term results of fertility-sparing surgery in the treatment of early-stage invasive epithelial ovarian cancer. Methods: A retrospective review of 123 patients who underwent surgical staging for FIGO stage I epithelial ovarian cancer from November 1982 to July 2002. Demographics, stage, histopathology, adjuvant therapy, recurrence, and survival were compared for patients who had fertility-sparing surgery and for those having standard surgical staging. Results: Twenty patients, with a median age of 27 years, had preservation of the uterus and contralateral ovary at the time of surgical staging. Platinum-based chemotherapy was administered to 50% of these patients postoperatively. Three patients (15%) recurred in the retained ovary at 9, 20, and 22 months, and all died of their disease. One patient was diagnosed with primary endometrial cancer at 15 months and was salvaged with hysterectomy. At a median follow-up of 122 months, 17 (85%) of 20 patients treated with fertility-sparing surgery were alive without disease. Of the 103 patients treated with removal of the uterus and both ovaries, 72% received adjuvant platinum chemotherapy. Twenty (19%) of the patients in the standard surgery group have recurred, and 17 have died of disease. At a median follow-up of 113 months, 78 (76%) of 103 patients treated with standard surgery were alive without disease. Five-year survival data showed no significant difference in the recurrence-free survival of the fertility-sparing and standard surgery groups (84% vs 78%) or overall survival (84% vs 82%). Conclusion: Fertility-sparing surgery is a reasonable alternative treatment for young women with stage I epithelial ovarian cancer desiring fertility preservation.
TL;DR: Nodal status on PET was the major predictor of outcome in locally advanced cervix cancer treated with chemoradiation and was superior to FIGO staging, and tumor volume measured from MRI appears to be an important predictor of loco-regional relapse.
Abstract: Purpose: The aim of this retrospective analysis was to assess whether parameters derived from magnetic resonance imaging (MRI) and positron emission tomography (PET) provide incremental prognostic value compared with International Federation of Gynecology and Obstetrics (FIGO) stage in cervix cancer patients treated with curative intent using concurrent chemoradiotherapy. Materials and Methods: This was a retrospective study of patients with locoregionally advanced cervical cancer staged by examination under anesthesia and pretreatment MRI and PET. Potential prognostic factors examined were derived from either clinical evaluation (age, FIGO stage, clinical diameter, histology), MRI (corpus invasion, tumor volume), or PET (lymph node metastasis). Outcome measures examined were overall survival, relapse-free survival, time to failure, local failure, nodal failure, and distant failure. Results: There were 206 eligible patients. The mean potential follow-up was 4.4 years. At 5 years, for all patients, overall survival rate was 59%. For all outcome measures apart from local failure, for which adenocarcinoma histology was the most powerful adverse prognostic factor (HR, 4.29; P Conclusions: Nodal status on PET was the major predictor of outcome in locally advanced cervix cancer treated with chemoradiation and was superior to FIGO staging. Tumor volume measured from MRI appears to be an important predictor of loco-regional relapse.
TL;DR: It appears that hydroxyl radical- derived oxidative stress, but not nitric oxide radical-derived oxidative Stress, plays a significant role in ovarian carcinogenesis.
Abstract: Objectives: Previous studies have suggested the importance of reactive oxygen species in all the steps of carcinogenesis. Antioxidant enzymes are considered as the most specific and efficient way to protect cells from reactive oxygen species. The purpose of the current study was to identify the role of oxidative stress and major antioxidant enzymes in ovarian carcinomas. Methods: The material consisted of 68 invasive ovarian carcinomas which were studied by immunohistochemistry with antibodies to antioxidant enzymes peroxiredoxins (Prxs) I-VI and thioredoxin and oxidative stress markers nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG). Both the intensity and the extent of the stainings were assessed, and the nuclear and cytoplasmic expressions were evaluated separately. Results: The study revealed the hydroxyl radical-derived oxidative stress marker in DNA, 8-OHdG, to be a powerful prognostic factor in ovarian carcinoma (Kaplan-Meier survival log-rank-analysis P = 0.003; risk of death to ovarian carcinoma 2.69; 95% confidence interval 1.35-5.35. 8-OHdG was also associated with poor differentiation (P = 0.053), higher stage (P Conclusions: To conclude, it appears that hydroxyl radical-derived oxidative stress, but not nitric oxide radical-derived oxidative stress, plays a significant role in ovarian carcinogenesis. Immunohistochemical assessment of 8-OHdG could provide a useful prognostic marker in ovarian cancer.
TL;DR: The importance of complete removal of the fallopian tubes and ovaries and the rigorous systematic pathological examination of these specimens are demonstrated in this case series supports emerging evidence that the fimbrial end of theFallopian tube is an important site of genesis of cancer in BRCA1/2 mutation carriers.
Abstract: Objective: To determine the rate of occult malignancy in patients undergoing prophylactic bilateral salpingo-oophorectomy in Northern Sydney. Methods: A retrospective case series of 45 consecutive patients who underwent prophylactic bilateral salpingo-oophorectomy between 2004 and March 2008. Results: Five (11%) cases of occult neoplasia were found in 45 patients. This included 3 cases of micro-invasive serous carcinoma of the fallopian tube, 1 case of in situ carcinoma in the fallopian tube and 1 case of metastatic breast cancer in the ovary. All cases of primary neoplasia were in the fimbrial end of the fallopian tube. Conclusions: The importance of complete removal of the fallopian tubes and ovaries and the rigorous systematic pathological examination of these specimens are demonstrated in this case series. It supports emerging evidence that the fimbrial end of the fallopian tube is an important site of genesis of cancer in BRCA1/2 mutation carriers
TL;DR: Differentiated-type VIN is significantly more associated with vulval squamous cell carcinoma than usual- type VIN, and the numbers of women with prior, synchronous, or subsequent vulval Squamous Cell carcinoma were 44 (25.7%) and 53 (31.7%), respectively.
Abstract: Objective: To assess the potential malignant risk of vulval premalignant conditions, in particular, to investigate whether there is a difference in the cancer risk between women with the 2 types of vulval intraepithelial neoplasia (VIN). Methods: All vulval biopsy specimens taken for any reason in a single center for a 5-year period were identified. The histologic reports of 1309 biopsy specimens from 802 women were reviewed, and all pathologic conditions present were recorded for each woman. Reports of patients with biopsy specimens containing usual-type VIN, differentiated-type VIN, lichen sclerosus, and squamous hyperplasia were selected and analyzed for the presence of metachronous or subsequent carcinoma to give a proportional risk for each condition. Results: Five hundred eighty women were identified with premalignant vulval conditions: 171 had usual-type VIN, 70 had differentiated-type VIN, 191 had lichen sclerosus, 145 had squamous hyperplasia, and 3 had other conditions not included in this analysis. Within these groups, the numbers of women with prior, synchronous, or subsequent vulval squamous cell carcinoma were 44 (25.7%), 60 (85.7%), 53 (27.7%), and 53 (31.7%), respectively (P = 0.000). Conclusions: Differentiated-type VIN is significantly more associated with vulval squamous cell carcinoma than usual-type VIN.
TL;DR: Surgical outcome was improved with experience, and the complication rate related to operation of group 1 was higher than that of group 2, and there was no significant difference in survival between the 2 groups.
Abstract: Background: To compare the surgical and oncological outcomes and morbidity of the first 50 cases treated by laparoscopic radical hysterectomy with those of the second 50 cases. Methods: Between October 1994 and January 2004, we retrospectively reviewed the charts of 100 consecutive patients (International Federation of Gynecology and Obstetrics stages IA2 [n = 12], IB1 [n = 56], IB2 [n = 15], IIA [n = 15], and IIB [n = 2]) who underwent laparoscopic radical hysterectomy with pelvic and/or para-aortic lymphadenectomy. One hundred patients were divided into the first 50 cases (group 1) and second 50 cases (group 2). Results: Operating time, length of hospital stay, time to normal residual urine, and transfusion rate significantly decreased, and the acquired number of pelvic nodes significantly increased when comparing group 1 with group 2. The intraoperative and postoperative complication rates profoundly decreased in group 2 as compared with group 1. After a median follow-up of 66.5 months, 10 patients had a recurrence, 9 of whom died. The 5-year overall survival rates were 96% in group 1 and 90% in group 2, and 5-year disease-free survival rates were 92% in group 1 and 90% in group 2. Conclusions: Laparoscopic radical hysterectomy is a feasible and safe treatment modality in early and even locally advanced cervical cancer without decreasing survival. Surgical outcome was improved with experience, and the complication rate related to operation of group 1 was higher than that of group 2. There was no significant difference in survival between the 2 groups.
TL;DR: A positive association between positive ERCC1 protein expression and clinical resistance to platinum-based chemotherapy is suggested.
Abstract: Objective: Although platinum-based chemotherapy remains the cornerstone for treatment of ovarian cancer, some patients are resistant to the treatment and will therefore not benefit from the standard platinum-based chemotherapy. Preclinical and clinical data have suggested a potential use of excision repair cross-complementation group 1 enzyme (ERCC1) as a molecular predictor of clinical resistance to platinum-based chemotherapy. Excision repair cross-complementation group 1 enzyme is a key enzyme in the nucleotide excision repair pathway which is involved in the DNA repair mechanisms in tumor cells damaged by treatment with platinum agents. The primary aim of the present study was to investigate if immunohistochemical expression of ERCC1 protein was associated with resistance to standard combination carboplatin and paclitaxel chemotherapy in newly diagnosed ovarian cancer patients. Methods: Formalin-fixed, paraffin-embedded tissue sections from 101 patients with newly diagnosed ovarian cancer were used for immunohistochemical staining for the ERCC1 protein. All patients received carboplatin-paclitaxel combination chemotherapy. Results: Excision repair cross-complementation group 1 enzyme protein overexpression was found in 13.9% of the tumors. Platinum resistance was found in 75% of the tumors with positive ERCC1 protein expression compared with 27% among the patients with negative tumor staining for ERCC1 (P = 0.0013). These findings translated into a significant difference in progression-free survival in both univariate (P = 0.0012) and in multivariate analysis (P = 0.006). Conclusions: The data presented suggest a positive association between positive ERCC1 protein expression and clinical resistance to platinum-based chemotherapy.
TL;DR: Fertility cannot be preserved because of positive cranial margins or involved lymph nodes in almost one third of patients originally referred for radical trachelectomy, which is one of the fertility-sparing procedures in women with early-stage cervical cancer.
Abstract: Background: Abdominal radical trachelectomy (ART) is one of the fertility-sparing procedures in women with early-stage cervical cancer. In comparison with vaginal radical trachelectomy, the published results of ART are so far limited. Methods: Enrolled were women referred for ART either by laparoscopy or laparotomy. The main inclusion criterion was stage IA2 or IB1 with a cranial extent that allows for preservation of at least 1 cm of the endocervical canal. Results: A total of 24 women were referred for the procedure, but fertility could not be preserved in 7 (29%) of them. Four women underwent immediate completion of radical hysterectomy because of a positive cranial surgical margin (n = 2) or sentinel node macrometastasis (n = 2) on frozen section. We found no correlation between tumor volume and inability to preserve fertility. A positive sentinel node was identified in 4 patients (17%); there were no false-negative results. Of the 9 women (53%) who have tried to conceive so far, 6 (67%) have conceived and 5 given birth, 2 of which were premature deliveries. Conclusions: Fertility cannot be preserved because of positive cranial margins or involved lymph nodes in almost one third of patients originally referred for radical trachelectomy. The main criterion for the selection of suitable patients should be the cranial extent of the tumor. Abdominal radical trachelectomy allows for achievement of satisfactory obstetrical outcomes.
TL;DR: There was no survival difference between asymptomatic and symptomatic patients at the time of relapse, and therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol did not seem to improve the clinical outcome of patients who ultimately developed recurrent disease.
Abstract: The aim of this retrospective investigation was to assess the pattern of failures of 412 patients with recurrent ovarian cancer followed up with different surveillance protocols. Time to recurrence was less than 6 months in 98 women (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212 women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the 331 asymptomatic patients, the surveillance procedure that raised the suspect of recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90 (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique in 115 (34.7%). At univariate analysis, survival from initial diagnosis was related to stage (P = 0.004), residual disease after initial surgery (P
TL;DR: The transition away from platinum doublets toward nonpl platinum combinations and emerging data on antiangiogenesis therapy in this setting are outlined and the term platinum sensitive should probably be replaced by chemotherapy sensitive, particularly as new nonplatinum agents and combinations are identified as active in this set.
Abstract: Objectives: The optimal treatment for women with recurrent epithelial ovarian cancer is evolving. The objective of this review is to outline the transition away from platinum doublets toward nonplatinum combinations and review emerging data on antiangiogenesis therapy in this setting. Materials and Methods: Recently published and presented data as well as ongoing clinical trials are discussed. Results: Current clinical practice largely harmonizes with a paradigm that outlines a treatment algorithm for recurrent ovarian cancer based on the duration of platinum-free exposure. In this model, patients whose penultimate platinum compound exposure (platinum-free interval [PFI]) is longer than 6 months are generally offered a platinum agent or a platinum-containing doublet; those with a shorter interval are usually treated with a single nonplatinum agent. This is based on the simple contention that better clinical outcomes will be realized with platinum in those deemed platinum sensitive (PFI >6 months). However, it is becoming clear from various phase II and phase III clinical studies that the performance of many nonplatinum chemotherapeutic agents is also influenced by this parameter (PFI). Indeed, although definitive comparisons of nonplatinum drugs to novel cytotoxic agents are lacking, the clinical activity of these compounds might approach or exceed that of platinum agents. Although recognized by clinicians, the dichotomy that determines therapy based on PFI has not been formally accepted by the US Food and Drug Administration in all cases of drug labeling. For instance, whereas the combination of gemcitabine and carboplatin is now approved for patients with platinum-sensitive recurrent ovarian cancer, traditionally used platinum-resistant (PFI Conclusions: The term platinum sensitive should probably be replaced by chemotherapy sensitive, particularly as new nonplatinum agents and combinations are identified as active in this setting. Nonplatinum doublets are effective in treating platinum-sensitive recurrent disease, and adding antiangiogenesis agents to these combinations is a research priority.
TL;DR: The HNF-1β-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of C CC to anticancer agents.
Abstract: Problem: Clear cell carcinoma (CCC) of the ovary has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC. Method of study: This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology. Results: Recent studies based on genome-wide expression analysis technology have noted specific expression of hepatocyte nuclear factor-1β (HNF-1β) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1β-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents. Conclusions: This review summarizes recent advances in the HNF-1β and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.
TL;DR: The results of this study show that, when an initial response is not achieved or when disease recurs, use of 320 mg/d seems to be associated with a better therapeutic response.
Abstract: Background: There are therapeutic dilemmas regarding fertility-preserving treatment among young women with well-differentiated endometrial carcinoma. Materials and Methods: Twenty-one patients with stage IA well-differentiated endometrial adenocarcinoma were enrolled in a prospective study. The treatment initiated with 160 mg/d of megestrol acetate. The patients underwent dilatation and curettage and hysteroscopy after 3 months, and in cases of normal pathology, the therapy continued for another 3-month period. In patients who did not respond to treatment, the dosage of the drug was doubled (320 mg/d), and the therapy continued for another 3 months. At the second time, patients who did not respond to treatment were recommended for hysterectomy, and in patients who responded to treatment, an additional 3 months of treatment with megestrol acetate (320 mg/d) was administered. Results: Our results showed a response rate of 85.71% (18 patients), and 3 patients underwent hysterectomy. The mean (SD) treatment duration was 8.85 (2.00) months (range, 6Y12 months). The response to therapy was observed in 5 patients (27.78%) with a dosage of 160 mg/d, and the remaining patients with 320 mg/d. Pregnancy occurred in 5 patients (27.78%). Recurrence happened in 3 (16.67%) of 18 patients who responded to treatment who did not give a permit to undergo hysterectomy and received medication again. Two (66.67%) of these patients experienced remission again, whereas the other one was candidate for hysterectomy. Conclusions: The results of this study show that, when an initial response is not achieved or when disease recurs, use of 320 mg/d seems to be associated with a better therapeutic response. Furthermore, serious complications were not observed with this dosage.
TL;DR: Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor for OS in the whole group and early-stage group.
Abstract: Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 × 10−15). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.