Ovarian cancer: etiology, risk factors, and epidemiology

Little is known regarding the early aspects of ovarian carcinogenesis. As a consequence, the identification of women at risk for the disease is based primarily on clinical grounds, with family history being the most important risk factor. In this review, we will discuss the various hypotheses regarding ovarian etiology and pathogenesis. In addition, we will discuss the epidemiology of ovarian cancer, including hereditary, reproductive, hormonal, inflammatory, dietary, surgical, and geographic factors that influence ovarian cancer risk.     

Ovarian cancer and venous thromboembolic risk

OBJECTIVE: To determine the incidence and the prognostic factors of objectively diagnosed deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with epithelial ovarian malignancy. METHODS: We reviewed the records of all patients with epithelial ovarian cancer who were diagnosed, treated, and followed-up at our institution between 1990 and 2001. Data were collected regarding age, body mass index, previous DVT and PE, menopause status, FIGO stage, grade, histology, type of surgery, residual disease, first line chemotherapy, and relapse status. RESULTS: Of the 253 cases, the overall incidence of symptomatic venous thromboembolic events (VTE) was 16.6% (42 patients): 1.6% (4) with PE and 15% (38) with DVT. 8 events (3.2%) were detected before tumor diagnosis, 6 (2.4%) in the postoperative period, 16 (6.4%) during first line chemotherapy and 12 (4.8%) throughout the follow-up period. Risk factors associated with occurrence of VTE were: at diagnosis, history of deep vein thrombosis (P = 0.001); during chemotherapy, older age (P = 0.017), larger body mass index (P = 0.019), FIGO stage 2c-4 (P = 0.004), no surgery (P = 0.003), and presence of residual tumor (P = 0.026). None of the considered risk factors were found to be predictors of VTE postoperatively. The multivariate regression analysis found that residual tumor, age, and body mass index were independent prognostic factors. CONCLUSION: The incidence of VTE throughout the entire history of ovarian malignancy is high. Prognostic factors could be used to establish prophylaxis protocols based on risk stratification.     

Total laparoscopic hysterectomy: indications, techniques and outcomes

PURPOSE OF REVIEW: The indications, techniques and outcomes of laparoscopic associated hysterectomy and especially total laparoscopic hysterectomy are thoroughly reviewed. RECENT FINDINGS: The original technique for total laparoscopic hysterectomy is detailed as it is still applicable. The total laparoscopic hysterectomy operation has not changed to any major degree over the past 15 years. The technique detailed works well and lessens the chance for a ureteral injury. Expansion of the technique has occurred in oncology. Evidence-based studies support the use of vaginal hysterectomy if possible over laparoscopic and abdominal hysterectomy. They also support a laparoscopic approach to hysterectomy over total abdominal hysterectomy. SUMMARY: Despite evidence-based studies, gynecologic surgical specialists have been slow to adopt both laparoscopic and vaginal hysterectomy into their practice. This trend may increase in the near future. Adoption of laparoscopic associated hysterectomy has been extremely slow.     

Ovarian cancer hormonal and environmental risk effect

To understand the influence of hormonal and environmental factors on the risk of ovarian cancer, it is important to remember the established risk factors and postulated mechanisms that lead to the development of ovarian cancer. Several risk factors have been identified as increasing the risk of epithelial ovarian cancer, including low pariety, infertility, early age of menarche, and late age of menopause. This article discusses the different hypotheses and focuses on hormonal and environmental risk factors, as well the chemoprevention of epithelial ovarian cancer.     

Ovarian cancer risk after the use of ovulation-stimulating drugs

OBJECTIVE: To assess the long-term effects of ovulation-stimulating drugs on the risk of ovarian cancer. METHODS: A retrospective cohort study of 12,193 eligible study subjects (median age 30 years) who were evaluated for infertility during the period of 1965-1988 at 5 clinical sites identified 45 subsequent ovarian cancers in follow-up through 1999. Standardized incidence ratios compared the risk of cancer among the infertile patients to the general population, whereas analyses within the cohort allowed the derivation of rate ratios for drug usage compared with no usage after adjustment for other ovarian cancer predictors. RESULTS: The infertility patients had a significantly elevated ovarian cancer risk compared with the general population (standardized incidence ratio 1.98, 95% confidence intervals [CI] 1.4, 2.6). When patient characteristics were taken into account and risks assessed within the infertile women, the rate ratios associated with ever usage were 0.82 (95% CI 0.4, 1.5) for clomiphene and 1.09 (95% CI 0.4, 2.8) for gonadotropins. There were higher, albeit nonsignificant, risks with follow-up time, with the rate ratios after 15 or more years being 1.48 (95% CI 0.7, 3.2) for exposure to clomiphene (5 exposed cancer patients) and 2.46 (95% CI 0.7, 8.3) for gonadotropins (3 exposed cancer patients). Although drug effects did not vary by causes of infertility, there was a slightly higher risk associated with clomiphene use among women who remained nulligravid, based on 6 exposed patients (rate ratio 1.75; 95% CI 0.5, 5.7). CONCLUSION: The results of this study generally were reassuring in not confirming a strong link between ovulation-stimulating drugs and ovarian cancer. Slight but nonsignificant elevations in risk associated with drug usage among certain subgroups of users, however, support the need for continued monitoring of long-term risks. LEVEL OF EVIDENCE: II-2     

Ovarian cancer risk assessment: a tool for preoperative assessment

Objectives

The objective of this pilot study was to determine if the combination of CA 125, menopausal status and prealbumin can be used to accurately predict ovarian cancer in women with pelvic masses.

Study design

Preoperative serum CA 125, prealbumin and menopausal status were prospectively determined. Results were formulated into an ovarian cancer risk assessment (OCRA) score and compared with final surgical pathology.

Results

OCRA was studied in 130 women. No cancers were found in women with a score less than 200. For all cancers, an OCRA score ≥ 200 had a sensitivity of 96%, specificity of 95% and positive predictive value of 95%. When the OCRA score of ≥200 was evaluated for its ability to predict ovarian cancer, the sensitivity, specificity, and positive predictive value were 100%, 83%, and 78%, respectively.

Conclusions

In this pilot study, OCRA was able to predict which women with pelvic masses were more likely to have ovarian cancer. The scoring system easily applied clinically and may help facilitate appropriate referral of women to gynecologic oncologists for optimal care.     

Ovarian tissue cryopreservation for prepubertal girls: indications and feasibility

OBJECTIVE: Survival improvement of children, adolescents and young women with cancer has led to consider with more cautiousness the long time iatrogenic side effects of treatments. Among those, premature ovarian failure has been described even for children. The aim of the study was to evaluate the indications and the feasibility of ovarian tissue cryopreservation for prepubertal girls. PATIENTS AND METHODS: From September 2000 to December 2004, 47 prepubertal girls were referred by oncologists for ovarian tissue cryopreservation. After informed consent, the ovarian tissue was collected and frozen by a slow cooling protocol until the temperature of liquid nitrogen. A histological analysis and a follicular account were performed. RESULTS: The harvest of ovarian tissue was performed for 45 patients. No surgical side effect occurred. The younger girls had a follicular density higher than the older. No metastatic ovarian tumour was found. DISCUSSION AND CONCLUSIONS: Numerous arguments as the follicular density in the ovary, the age of the patient, no surgical side effect, no metastatic ovarian tumour and recent progress in term of birth after ovarian tissue autografting allowed to think it is very important and ethical to propose an ovarian tissue cryopreservation even for children before sterilising treatment.     

Robotic myomectomy: a review of indications and techniques

The primary surgical techniques used in myomectomy are open surgery, laparoscopic surgery, and, recently, robot-assisted ("robotic") surgery. The optimal surgical treatment of myomas is still a subject of debate because of the limitations of minimally invasive techniques and the disadvantages of laparotomy. In this article, the authors discuss the technique and the application of robotic myomectomy in the treatment of uterine fibroids.     

Ovarian dysgerminoma: clinical signs, assessment, and therapeutic indications, with reference to 30 observations

Thirty cases of ovarian seminomas in patients aged for the most part between 10 and 20 years were studied at the Gustave-Roussy Institute between 1957 and 1970. In 10 per cent of cases both ovaries were involved. They were revealed by menstrual disorders, acute cystic twisting, signs of abdomino-pelvic compression, or a change in the general state of health. Lymphograms were made for the 25 most recent cases. They showed pathological signs in 35 per cent of cases. The role of the lymphogram is of prime importance in the suveillance of nonirradiated patients, making it possible for them to have remedial treatment. Surgery ensures excision of the tumour and indicates the degree of abdominal extension. During a second operation, it is possible to transpose a healthy ovary to avoid castration. The methods of ganglion irradiation, which should be systematic, are discussed in relation to the results of the operation and of the lymphogram. In 80 per cent of cases, the patients were alive after two years and slightly more than half of them had maintained ovarian function.     

Ovarian cancer risk associated with varying causes of infertility

OBJECTIVE: To evaluate the risk of ovarian cancer as related to underlying causes of infertility. DESIGN: Retrospective observational cohort study. SETTING: Five large reproductive endocrinology practices. PATIENT(S): A total of 12,193 women evaluated for infertility between 1965 and 1988. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian cancer ascertained through 1999. RESULT(S): With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7). CONCLUSION(S): Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis.     

Ovarian cancer in the proteomics era: diagnosis, prognosis, and therapeutics targets

Abstract.   Boyce EA, Kohn EC. Ovarian cancer in the proteomics era: diagnosis, prognosis, and therapeutics targets. Int J Gynecol Cancer 2005; 15(Suppl. 3): 266–273.
Ovarian cancer is clinically quiet as it plants seeds of metastases in the peritoneal cavity, even during early stages when there is highest potential for cure. The only available biomarker is CA125, which has an unacceptably low sensitivity and specificity for diagnostic use. Highly sensitive and specific tools to further optimize early diagnosis and treatment are needed. We propose that proteomic technologies have an important role to play in the development of these tools. Mass spectrometry platforms, such as surface-enhanced laser desorption/ionization time-of-flight, may be used to mine patient's serum for proteomic signatures that are shed by tumor and stroma. Such signatures could serve as a diagnostic tool during early-stage disease and as a remission-monitoring tool in later-stage disease. Reverse-phase protein microarrays are a new microproteomic tool to profile signaling pathways in ovarian cancer, thus identifying therapeutic targets while simultaneously suggesting prognostic indicators. Proteomic technologies have the capacity to build upon our genomic and clinical understanding of ovarian cancer by moving the focal point to the tumor and its microenvironment. This unique proteomic vantage point allows the creation of tools that will aid clinicians in making rational decisions in the diagnosis and treatment of women with ovarian cancer.     

Autologous and alloplastic breast reconstruction--overview of techniques, indications and results

It is important for any woman undergoing mastectomy to make an informed decision about reconstruction and to be provided with information about the technique, advantages and disadvantages. There is a high degree of patient satisfaction with breast reconstruction, but high levels of preoperative information and psychological support are necessary. Close collaboration between oncological and reconstructive surgeons or management by an oncoplastic breast surgeon, careful patient selection and counseling, and refinements in surgical techniques can provide a range of safe and predictable techniques for breast reconstruction. After modified radical mastectomy breast reconstruction involves replacement of breast skin and breast volume; after skin-sparing mastectomy only the replacement of breast volume is necessary. The most commonly used surgical techniques are tissue expansion, latissimus dorsi myocutaneous flap with or without implants, and the use of lower abdominal tissue. Until today, the pedicled TRAM flap is the standard method for autologous breast reconstruction.     

Ovarian tissue cryopreservation and transplantation: scientific implications

After fresh or frozen ovary transplantation, FSH levels return to normal, and menstrual cycles resume by 150 days, coincident with anti-Müllerian hormone rising to higher than normal levels. AMH then returns to well below normal levels by 240 days, remaining as such for many years with nonetheless normal ovulation and fertility. To date, 20 babies have been born in our program from 11 fresh and 13 cryopreserved ovary transplant recipients with a live baby rate of over 70 % (11 babies from fresh and 9 from frozen). Globally, over 70 live births have been reported for both fresh and frozen ovary transplants with an approximate 30 % live birth rate. Given the rapid rise of AMH after the fall of FSH, with a subsequent AMH decrease with retention of ovarian function, it is tempting to speculate the existence of a shared mechanism controlling primordial follicle recruitment, fetal oocyte meiotic arrest, and recruitment in the adult ovary. With the massive recruitment of primordial follicles observed after human ovarian cortical tissue transplantation, which subsides to an extremely low recruitment rate, we will discuss how this phenomenon suggests a unifying theory implicating ovarian cortical tissue rigidity in the regulation of both fetal oocyte arrest and recruitment of follicles in the adult ovary. As the paper by Winkler-Crepaz et al. in this issue demonstrates, our in vivo results are consistent with the in vitro demonstration that primordial follicles in the fetal cortex are “locked” in development, resulting in meiotic arrest, which spares the oocytes from being rapidly lost all at once (Winkler-Crepaz et al., J Assist Reprod Genet, 1). Winkler-Crepaz et al. demonstrate that follicle loss after ovarian cortex transplantation is unlikely due to ischemic apoptosis, but rather from a “burst” of primordial follicle recruitment. In vivo, primordial follicles are normally resistant to further development or activation to prevent oocyte depletion. The dense fibrous ovarian cortex, through as yet unresolved mechanisms, arrests the further continuation of meiosis and also prevents a sudden depletion of all resting follicles in the adult ovary. Intrinsic tissue pressure is released after cortical tissue transplantation, temporarily resulting in a rapid follicle depletion. These results are consistent with the observation that once the ovarian reserve is reduced in the graft, the rate of recruitment diminishes and the ovarian tissue exhibits a relatively long duration of function.     

超大剂量化疗与外周血干细胞移植治疗卵巢癌

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