Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

Purpose  

The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS).     

Conservative treatment of a young patient with thyroid carcinoma in adult ovarian teratoma – case report

The cystic mature teratomas, including dermoid cysts, are one of the most frequently occurring benign ovarian tumors diagnosed in female patients. The process of neoplastic transformation in mature dermoid cysts is applicable only to 1–2% of cases. In our article, we present a rare case of thyroid carcinoma development in adult teratoma in 21-year-old patient. The young age, certain pathomorphological features and clinical data (small size of neoplastic lesion, correct values of tumour markers, unilateral character, regular levels of thyreoglobulin and absence of any significant deviations in imaging examinations), were the basis for attempting to apply the conservative treatment both in the scope of gynecological surgery and in the supplemental endocrinological therapy. In the patient, the one-sided adnexectomy was performed, considering pathological lesions on the adnexa, as well as the other ovary dermoid cyst was enucleated, without the hysteroctomy procedure. Considering the lack of any morphological lesions and functional changes relating to thyroid gland, the treatment was not radicalised in this scope, either. At present, one year after the primary operation treatment, the patient does not manifest any disease symptoms, whereas the other ovary, in the follow-up ultrasound examinations, shows normal size and echostructure. The thyroid-stimulating hormone (TSH) suppression keeps being applied.     

Is there a role for HIPEC in ovarian cancer?

Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack of robust data supporting this. Publicly available evidence addressing the value of HIPEC in EOC is rather inconclusive, revealing contradictory and inconsistent results while some studies even report harm to the patients from a higher morbidity. On this ground, we cannot recommend the implementation and use of HIPEC outside of a randomized clinical trial setting.     

Is there a role for DHEA supplementation in women with diminished ovarian reserve?

Purpose

Poor ovarian reserve and poor ovarian response presents a challenge to IVF centers. Dehydroepiandrosterone (DHEA) supplementation is increasingly being used by many IVF centers around the world in poor responders despite the lack of convincing data. We therefore examined the rationale for the use of DHEA in poor responders, address the relevant studies, present new data, and address its potential mechanisms of action.

Methods

All published articles on the role of DHEA in infertile women from 1990 to April 2013 were reviewed.

Results

Several studies have suggested an improvement in pregnancy rates with the use of DHEA. Potential mechanisms include improved follicular steroidogenesis, increased IGF-1, acting as a pre-hormone for follicular testosterone, reducing aneuploidy, and increasing AMH and antral follicle count. While the role of DHEA is intriguing, evidence-based recommendations are lacking.

Conclusions

While nearly 25 % of IVF programs use DHEA currently, large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.     

Is color Doppler ultrasound useful in diagnosing ovarian cancer?

In summary, the emergence of CDUS presented an interesting new technical approach to the study of neovascularization in ovarian cancers. Techniques for CDUS are technically difficult and plagued with artifacts making correct interpretation difficult. Measures of blood flow (such as the resistive index) overlap significantly between ovarian cancers and benign ovarian tumors. Wide differences in estimates of the sensitivity and specificity of CDUS have been published, and fundamental norms such as resistive index also vary greatly among studies. Explanations for these differences are lacking. Most studies were performed in academic centers with referrals of high risk patients. This limits the ability to generalize results to the community. Data are insufficient to include CDUS in diagnostic protocols for ovarian cancer.     

Is age a barrier to the aggressive treatment of ovarian cancer with paclitaxel and carboplatin?

OBJECTIVE: The objective of this study was to determine whether the toxicities associated with chemotherapy are age related in women treated for ovarian cancer. METHODS: Patients with stage II-IV epithelial ovarian cancer underwent cytoreductive surgery. Adjunctive therapy was given to each patient consisting of intravenous (IV) paclitaxel 175 mg/m(2) over 3 h with a subsequent 30-min IV infusion of carboplatin. Carboplatin dose was calculated to achieve a targeted area under the curve (AUC) of 5.0-7.5. Treatment was repeated at 21- to 28-day intervals for six cycles. Toxicities were graded after each dose of chemotherapy. Results were analyzed using the Wilcoxon rank sum test and log likelihood ratio to compare toxicities in women age <60 years old to women >/=60 years old. RESULTS: Fifty-three women, 22 of whom were >/=60 years old, were treated with 309 cycles of chemotherapy. Forty-eight patients (92%) completed all six cycles. AUC dosing of carboplatin was equivalent for both groups. Carboplatin dose reduction occurred in 75% of patients for grade 4 neutropenia or thrombocytopenia. No patient required a reduction in the paclitaxel dose. Neutropenia was less frequent in women >/=60 years old than in women <60 years old (P = 0.02). There was no difference between women <60 years old and women >/=60 years old in the incidence of anemia, thrombocytopenia, or the use of growth factors. A 68% complete clinical response rate was observed in women >/=60 years old compared to a 74% complete response rate for women under age 60 (P = 0.22). CONCLUSION: Age is not a barrier to the aggressive treatment of ovarian cancer with this regimen of paclitaxel and carboplatin.     

Resumption of ovarian function after 4?years of estro-progestin treatment in a young woman with Crohn’s disease and premature ovarian insufficiency: a case report

Purpose

To report the long-term management of a case of premature ovarian insufficiency of unknown origin in a young woman with Crohn’s disease.

Method

Here is reported the case of a 20 years old woman with Cronh’s disease presenting with two years amenorrhea and FSH and LH levels of 255 mIU/ml and 182 mIU/ml respectively, who received 10 months corticosteroid treatment followed by 7 years of estro-progestin treatment.

Results

Corticosteroid treatment was ineffective in restoring patients gonadotropin levels as well as ovarian volume, while estro-progestins promoted a prompt reduction in gonadotrophin levels, which returned in the normal range after two years of treatment, as well as restoration of ovarian function, which occurred after four years of estrogens administration, as demonstrated by normal ovarian volume and ovulatory follicles at ultrasound, and by the re-establishment of regular menses after estroprogestin discontinuation.

Conclusions

Long-term suppression of the endogenous gonadotropins using estroprogestins may be suggested as a treatment able to restore ovarian responsiveness even in patients with premature ovarian insufficiency showing highly elevated gonadotropin levels.Premature ovarian insufficiency (POI), is defined as secondary amenorrhea with elevated gonadotropin level observed under the age of 40 and affects 1–2 % of women of the general population [7]. POI is highly heterogeneous condition that may have iatrogenic, autoimmune, infective, chromosomal, genetic or idiopathic origin [4]. Post-pubertal onset of ovarian failure represents the large majority of the cases: this is characterized by secondary amenorrhea associated with premature follicular depletion or arrested folliculogenesis [4].Although elevation in gonadotropin serum level may suggest an irreversible impairment of ovarian reserve and function, intermittent follicular function and spontaneous ovulation clearly occur in some POI-affected women [20]. Moreover, POI may either spontaneously resolve or may respond to therapeutic modalities such as glucocorticoids or exogenous estrogen administration, thus indicating that ovarian failure is not always permanent. Immunosuppression with glucocorticoids has been employed for up to 12 months in cases of POI of supposed autoimmune etiology [11], however proof of the efficacy of this treatment has not been forthcoming as the two randomized, placebo-controlled trial using corticosteroid and ovulation induction in POI women demonstrated either no ovulation or a low ovulation rate [2, 21]. On the other hand, either short course or long-term (up to 24 months) estrogen administration have been found to be useful in these patients, as this treatment may overcome ovarian FSH receptor desensitization [18].Here we report the case of a young woman with POI of unknown origin who did not respond to corticosteroid treatment but showed resumption of ovarian function after 4 years of estro-progestin treatment.     

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis

Objective

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC.

Methods

Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and > 12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome.

Results

140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p = 0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p = 0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor.

Conclusion

The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable.     

Is blastocyst transfer useful as an alternative treatment for patients with multiple in vitro fertilization failures?

OBJECTIVE: To determine whether blastocyst transfer is of benefit to patients with multiple IVF failures. DESIGN: Retrospective cohort study. SETTING: The George Washington University Medical Center. PATIENT(S): Patients undergoing IVF between October 1, 1997, and November 30, 1998, who had previously undergone three or more unsuccessful IVF cycles. Patients who had at least three embryos at the 8- to 12-cell stage available on day 3 were eligible for the study. INTERVENTION(S): Patients were given the option of day 3 ET (group A) or blastocyst transfer (group B). MAIN OUTCOME MEASURE(S): Blastocyst-formation rate, clinical pregnancy rate (PR) per transfer, and implantation rate per transfer. RESULT(S): Groups A and B were similar in terms of age, the number of previous failed IVF cycles, fertilization rate, and the number of fertilized oocytes per cycle. The blastocyst-formation rate was 51.0%. Clinical pregnancy and implantation rates per transfer were statistically significantly higher in the blastocyst-transfer group. There were no multiple pregnancies after blastocyst transfer. CONCLUSION: Blastocyst transfer increases implantation rates and PRs in patients with multiple failed IVF cycles, without increasing the risk of multiple pregnancy.     

Is small for gestational age a marker of future fetal survival in utero?

OBJECTIVE: We sought to assess whether small for gestational age is a risk factor for stillbirth of a subsequent sibling. METHODS: The Missouri maternally linked cohort data set, containing data on births from 1978 through 1997, was used. We identified the study group (women who delivered a SGA infant in the first pregnancy) and a comparison group (women who delivered a non-SGA infant in their first pregnancy) and compared the outcome (stillbirth) in the second pregnancy between both groups. RESULTS: We analyzed information on the first and second pregnancies of 402,015 women (43,549 [10.8%] in the study arm and 358,466 [89.2%] in the comparison arm). Of the 1,883 cases of stillbirth in the second pregnancy, 314 cases occurred in mothers with a history of SGA (stillbirth rate 7.2/1,000) and 1,569 in the comparison group (stillbirth rate 4.4/1,000), P < .001. The adjusted risk of stillbirth was 60% higher in women with a prior SGA (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.4-1.8). The risk for stillbirth in the second pregnancy increased with decreasing gestational age at birth of the SGA infant in the first pregnancy (term: OR 1.4, 95% CI 1.2-1.6; preterm: OR 2.8, 95% CI 2.0-3.8; and very preterm: OR 4.2, 95% CI 2.4-7.3), P for trend < .001. CONCLUSION: Small for gestational age is a marker for subsequent stillbirth, and the risk rises with decreasing gestational age of the SGA birth. This information is potentially useful for counseling parents of SGA infants. LEVEL OF EVIDENCE: II-2.     

Is time to recurrence after hysterectomy predictive of survival in patients with early stage endometrial carcinoma?

Purpose/objective(s)

To determine the prognostic significance of time to recurrence (TTR) on overall survival (OS) and disease-specific survival (DSS) following recurrence in patients with stage I-II uterine endometrioid carcinoma.

Materials/methods

After IRB approval, we retrospectively identified 57 patients with recurrent endometrioid carcinoma who were initially treated for FIGO 1988 stages I-II between 1987 and 2009. The Kaplan-Meier approach and Cox regression analysis were used to estimate OS and DSS following recurrence and identify factors impacting outcomes.

Results

Median follow-up times were 54.8 months from hysterectomy and 19.8 months after recurrence. Median time to recurrence was 20.2 months. Twenty-eight (47%) patients had a recurrence < 18 months after hysterectomy and 29 (53%) had a recurrence ≥ 18 months. Both groups were evenly matched regarding initial pathological features and adjuvant treatments. The median OS and DSS in patients with TTR < 18 months was shorter than those with TTR ≥ 18 months, but not statistically significant (p = 0.216). TTR did not impact outcomes after loco-regional recurrence, but for extrapelvic recurrence, a shorter TTR resulted in worse OS and DSS (p = 0.03). On multivariate analysis, isolated loco-regional recurrence (HR 0.28, p = 0.001) and salvage radiation therapy (HR 0.47, p = 0.045) were statistically significant independent predictors of longer OS following recurrence. TTR as a continuous variable or dichotomized was not predictive of OS or DSS.

Conclusions

In our study, the prognostic impact of time to recurrence was less important than the site of recurrence. While not prognostic for the entire cohort or for patients with loco-regional recurrence, TTR < 18 months was associated with shorter OS and DSS after extrapelvic recurrence.     

Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?

PURPOSE OF INVESTIGATION: The aim of this retrospective study was to correlate some patient characteristics at relapse, including also baseline hemoglobin levels, with complete response rate and survival following second-line chemotherapy for recurrent platinum-pretreated ovarian carcinoma. METHODS: The investigation was conducted on 63 patients who received salvage chemotherapy with different agents for clinically detectable recurrent ovarian carcinoma following initial surgery and first-line platinum-based chemotherapy. Some patient characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin level, number of recurrence sites, ascites, platinum-free interval, and treatment-free interval) were related to complete response rate to salvage chemotherapy and survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range, 7.5-15.0 g/dl). RESULTS: Second-line chemotherapy obtained a complete response in 17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients, respectively. By univariate analysis, complete response rate was related to baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and treatment-free interval (p = 0.0048). Multiple logistic regression showed that platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were independent predictors of complete response. Patients with baseline hemoglobin levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when compared to those with lower hemoglobin values. The platinum-free interval was the only independent prognostic variable for survival after recurrence (p = 0.0141), whereas baseline hemoglobin level was not related to survival at univariate nor at multivariate analysis. CONCLUSIONS: Baseline hemoglobin level is an independent predictor of complete response to salvage chemotherapy in patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be paid to anemia correction in these patients, with the aim of improving both the chance of response to salvage treatment and the quality of life.