Tamar Perri

Uterine leiomyosarcoma: does the primary surgical procedure matter?

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.

Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma

OBJECTIVES Ovulation-related inflammation is suspected to have a causal role in ovarian carcinogenesis, but there are no human models to study the molecular pathways. Our aim is to develop such an ex-vivo model based on human fallopian tube (FT) epithelium exposed to human follicular fluid (FF). METHODS FT epithelium was dissociated from normal surgical specimens. FF was obtained from donors undergoing in-vitro fertilization. The cells were cultured on collagen-coated Transwells and incubated with FF for various periods of time. The transcriptomic changes resulting from FF treatment were profiled using Affymetrix expression arrays. Specific characteristics of the FT pre-cancerous lesions were studied using immunohistochemistry, immunofluorescence, RT-PCR and XTT assay. RESULTS We show that FF exposure causes up-regulation of inflammatory and DNA repair pathways. Double stranded DNA breaks are induced. There is a minor increase in cell proliferation. TP53, which is the hallmark of the precursor lesion in-vivo, is accumulated. Levels of expression and secretion of Interleukin-8 are significantly increased. CONCLUSIONS Our model addresses the main non-genetic risk factor for ovarian cancer, namely the impact of ovulation. This study demonstrates the biological implications of in-vitro exposure of human FT epithelial cells to FF. The model replicates elements characterizing the precursor lesions of ovarian cancer, and warrants further investigation of the linkage between repeated exposure to ovulation-related damage and accumulation of neoplastic changes.

Prolonged conservative treatment of endometrial cancer patients: more than 1 pregnancy can be achieved.

Background: Preserving reproductive function in young patients with early endometrial cancer is an accepted concept today. The safety and feasibility of long-term conservative treatment, allowing more than 1 pregnancy, remain to be ascertained. Methods: This study was a retrospective chart review of a 27 women with endometrioid adenocarcinoma of the endometrium, who were treated conservatively at 2 tertiary-care institutions. Treatment comprised oral high-dose progestins with or without a levonorgestrel-releasing intrauterine device. Endometrial biopsy was repeated every 2 to 3 months. Results: Over 7.8 to 412 months (median, 57.4 months), tumors regressed completely in 24 (89%) of 27 patients and partially in 2 patients, with 79% responding within 1 to 17 months. Of the complete responders, 15 (62%) of 24 had a recurrence; 4 underwent hysterectomy, and 11 underwent subsequent progestational treatment. All 11 responded, and 3 subsequently conceived. After 2 to 4 years, 5 patients again had a recurrence, of whom 3 underwent hysterectomy. Overall, 2 patients developed ovarian adenocarcinoma. All patients are currently disease-free. Conception occurred in 14 (51.8%) of 27 patients, in 5 more than once. There were 17 live births, and 2 patients are pregnant. Conclusions: According to our data, prolonged progestational therapy for early-stage endometrial adenocarcinoma, allowing women to conceive, is feasible and apparently does not alter clinical outcome. Patients should be advised of the high recurrence rate and possible concomitant ovarian malignancy.

Promising effect of aromatase inhibitors on recurrent granulosa cell tumors.

Recurring adult-type granulosa cell tumors of the ovary are usually treated by surgical resection followed by chemotherapy or radiation. However, the results of such treatment are disappointing. We describe 4 patients in whom recurrent ovarian granulosa cell tumors were treated with an aromatase inhibitor, with promising results.

BRCA mutation carriers show normal ovarian response in in vitro fertilization cycles

OBJECTIVE To evaluate the association between carriage of BRCA1/2 mutations and ovarian performance, as demonstrated by in vitro fertilization (IVF) outcomes. DESIGN Retrospective cohort study. SETTING Two tertiary IVF centers. PATIENT(S) BRCA mutation carriers undergoing IVF for preimplantation genetic diagnosis (PGD) or fertility preservation were compared with non-BRCA PGD or fertility preservation patients, matched by age, IVF protocol, IVF center, and cancer disease status. INTERVENTION(S) In vitro fertilization cycles for PGD and fertility preservation. MAIN OUTCOME MEASURE(S) Outcome of IVF: oocyte yield, poor response rate, number of zygotes, pregnancy rates. RESULT(S) A total of 62 BRCA mutation carriers and 62 matched noncarriers were included; 42 were fertility preservation breast cancer patients, and 82 were PGD non-cancer patients. Mean (± SD) age of patients was 32 ± 3.58 years. Number of stimulation days and total stimulation dose were comparable between carriers and noncarriers. Their cycles resulted in comparable oocyte yield (13.75 vs. 14.75) and low response rates (8.06% vs. 6.45%). Number of zygotes, fertilization rates, and conception rates were also comparable. CONCLUSION(S) Both healthy and cancer-affected BRCA mutation carriers demonstrated normal ovarian response in IVF cycles.

Effect of treatment delay on survival in patients with cervical cancer: a historical cohort study.

Objective The objective of this study was to evaluate the effect of treatment delay on prognosis in patients with cervical cancer. Methods The study group of this historic cohort study comprised 321 patients newly diagnosed with cervical cancer between 1999 and 2010. Time from diagnosis to treatment was analyzed both as a continuous variable and as a categorical variable in 3 groups that differed in waiting time between diagnosis and treatment initiation: 30 days or less (group 1, n = 134), 30 to 45 days (group 2, n = 86), and more than 45 days (group 3, n = 101). Associations between waiting time group, patients’ characteristics, and disease outcome were investigated using t tests, analyses of variance and Cox regression analyses, Kaplan-Meier survival analysis, and log-rank (Mantel-Cox) tests. Results Time from diagnosis to treatment initiation, when analyzed as a continuous variable, was not a significant factor in survival. There were no between-group differences in age, smoking rate, marital status, gravidity, parity, tumor histology, or lymph node involvement. Early-stage disease and small tumor diameter were diagnosed most frequently in group 3. However, there was no significant between-group difference in 3-year survival rates (74.6%, 82.2%, and 80.8% in groups 1, 2, and 3, respectively; P = 0.38). On multivariate analysis, only stage, histology, and lymph node involvement were significant prognostic factors for survival. Before starting treatment, 28 patients underwent ovarian preservation procedures. Conclusions Longer waiting time from diagnosis to treatment was not associated with worse survival. Our findings imply that if patients desire fertility or ovarian preservation procedures before starting treatment, it is acceptable to allow time for them.

Safety of ovarian conservation and fertility preservation in advanced borderline ovarian tumors

OBJECTIVE To assess the impact of a fertility-sparing approach on disease recurrence in women with advanced borderline ovarian tumors. DESIGN Historic cohort study. SETTING A tertiary referral center for gynecological oncology patients and a university teaching hospital. PATIENT(S) Consecutive patients with advanced borderline ovarian tumors defined as stage IC and above, treated at a single institution during a span of 30 years. INTERVENTION(S) Data on surgical approach (e.g., fertility sparing, ovarian conserving) as well as histopathology, disease stage, CA-125 level, and use of chemotherapy were collected from the medical records, and their impact on disease recurrence was assessed. MAIN OUTCOME MEASURE(S) Recurrence-free interval. Its association with the type of surgery and with other clinical and pathological features was assessed using the Kaplan Meier and Cox proportional hazards methods. RESULT(S) Fifty-nine patients with advanced disease were identified. Median follow-up was 55.3 months. Mean age at diagnosis was 35 years. Most of the tumors (51, 84.4%) had serous histology. Twenty-seven patients (45.8%) developed recurrences and 6 (10%) died of their disease. Mean time to recurrence was 30.6 months. Of 44 women ≤40 years, 33 (75%) had a fertility-sparing procedure. Fertility preservation was not associated with disease recurrence. A total of 34 pregnancies and 26 live births were documented among 21 patients attempting conception. CONCLUSION(S) Borderline ovarian tumors carry a favorable prognosis, even at an advanced stage. Fertility preservation was not found to be associated with an increased risk of relapse in young patients with advanced disease, and may be reasonably considered.

Abdominopelvic cytoreduction rates and recurrence sites in stage IV ovarian cancer: Is there a case for thoracic cytoreduction?

OBJECTIVE We report the rates of optimal abdominopelvic cytoreduction and the sites of recurrence in stage IV ovarian cancer patients, with particular attention to the potential impact of thoracic cytoreduction on treatment results in patients with intra-thoracic spread. METHODS A historic cohort study of all stage IV ovarian cancer patients diagnosed between 1994 and 2010 and underwent abdominopelvic cytoreductive surgery. Controls were stage IIIc patients. Statistical analyses included χ(2) test, Cox proportional hazards regression models and Kaplan-Meier curves with log-rank tests. RESULTS Group 1 included 76 stage IV patients, 55% with thoracic spread. Group 2 included 142 stage IIIc patients. Age, histology, primary peritoneal tumor and ascites rates were similar for the two groups. Respective rates of optimal abdominopelvic cytoreduction were 68% vs. 83.5% (p<0.05), median time to progression 5.3 vs. 12.3 months (p<0.01) and overall survival 27.2 vs. 46.1 months (p<0.01). Optimal cytoreduction and survival rates were similar for all group 1 patients regardless of spread location. Sites of recurrence in stage IV were abdomen (59.3%), thorax (6.8%), both (28.8%) or other (5.1%). The four patients with thoracic recurrence alone were all initially diagnosed with malignant pleural effusion. Three of them developed abdominal recurrence within 15‒6 months. CONCLUSIONS Optimal abdominopelvic cytoreduction was achievable in stage IV patients, although in significantly fewer patients than in stage IIIc. Sites of recurrence were rarely thorax alone, implying that thoracic debulking is likely to change the course of disease in only few patients and thus should be carefully individualized.

Villoglandular papillary adenocarcinoma of the uterine cervix: A diagnostic challenge

Villoglandular papillary adenocarcinoma (VGA) is a rare subtype of cervical adenocarcinoma. It tends to appear in younger women and its indolent behavior permits fertility‐preserving treatments. Pathologically, VGA presents a diagnostic challenge. The aim of our study was to evaluate the reliability of histological assessment for pre‐treatment diagnosis of VGA. The data from the outpatient files of 12 patients in whom VGA had been diagnosed were reviewed. Median age at diagnosis was 38.8 years (range 27–65). Final pathology results confirmed VGA in nine patients. Of these, only two had been correctly diagnosed preoperatively, while in three, the initial biopsies were benign or pre‐malignant. In four patients, the biopsy results had been interpreted as an invasive malignant tumor necessitating hysterectomy. The final histological report on the remaining three patients was invasive cervical adenocarcinoma. We conclude that pre‐treatment diagnosis should not be based solely on a simple punch biopsy because of its low rate of diagnostic accuracy.

Bowel obstruction in recurrent gynecologic malignancies: Defining who will benefit from surgical intervention

AIM To define factors that could help select, in a cohort of gynecologic cancer patients with malignant gastro-intestinal obstruction, those most likely to benefit from palliative surgery. METHODS In this retrospective study of patients with malignant gastro-intestinal obstruction who underwent palliative surgery in our institute over 7 years, outcome measures were oral intake, chemotherapy, and 30-day, 60-day and overall survival. Based on Cox proportional-hazards regression models and Kaplan-Meier curves with log-rank tests, a prognostic score was developed to identify those most likely to benefit from surgery. RESULTS Sixty-eight palliative surgeries were performed in 62 patients with ovarian (69.1%), primary-peritoneal (8.8%), cervical (11.8%) or uterine (10.3%) malignancies. Procedures were colostomy (26.5%), ileostomy (39.7%), colonic stent (1.5%), gastrostomy (7.3%), gastroenterostomy (5.9%) and bypass/resection and anastomosis (19.1%). Eighteen patients died prior to discharge, within 3-81 days (median 25 days). The 30-day and 60-day mortality rates were 14.7% and 29.4%, respectively. Postoperative oral-intake and chemotherapy rates were 65% and 53%, respectively, with albumin level identified on multivariate analysis as the only significant predictor of both. Median postoperative survival was 106 days (3-1342). Bypass/resection and anastomosis was associated with improved survival. Ascites below 2 L, younger age, ovarian primary tumor, and higher blood albumin correlated with longer postoperative survival. A prognostic index based on these factors was found to identify patients with increased 30-day and 60-day mortality. CONCLUSIONS Our proposed prognostic index, based on age, primary tumor, albumin and ascites, might help select those gynecological cancer patients most likely to benefit from palliative surgery.