Giuseppe Del Priore

Effects of Parity on Pregnancy Hormonal Profiles Across Ethnic Groups with a Diverse Incidence of Breast Cancer

Epidemiologic evidence suggests that a full-term pregnancy may affect maternal risk of breast cancer later in life. The objective of this cross-sectional study was to compare circulating levels of maternal hormones affecting breast differentiation (human chorionic gonadotropin and prolactin) and proliferation [α-fetoprotein, insulin-like growth factor I (IGF-I), and estradiol] between women at a low to moderate risk (Asians and Hispanics), as compared with women at a high risk for breast cancer (Caucasians and African-Americans). Between May 2002 and December 2004, a total of 586 pregnant women were approached during a routine prenatal visit. Among them, 450 women (206 Caucasian, 126 Asian, 88 Hispanic, and 30 African-American) met the inclusion criteria and signed the informed consent. Only singleton pregnancies were considered. Blood samples were drawn during the second trimester of pregnancy. Laboratory analyses were done using the IMMULITE 2000 immunoassay system. Gestational age standardized mean levels of estradiol, IGF-I, and prolactin were significantly higher in Hispanic women compared with Caucasian women. Mean concentration of IGF-I was significantly higher in African-American women compared with Caucasian and Asian women. No significant differences in pregnancy hormone levels were observed between Caucasian and Asian (predominantly second-generation Chinese) women in this study. Irrespective of ethnicity, women who had their first pregnancy had substantially higher mean levels of α-fetoprotein, human chorionic gonadotropin, estradiol, and prolactin compared with women who previously had at least one full-term pregnancy. These data suggest that circulating pregnancy hormone levels may explain some of the ethnic differences in breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2123–30)

Oral diindolylmethane (DIM): Pilot evaluation of a nonsurgical treatment for cervical dysplasia

OBJECTIVE Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options. We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions. METHODS Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse). Subjects were evaluated every 3-4 months for 1 year. Analysis of data up to 1 year was assessed including Pap smear, HPV, colposcopy, biopsy and physical examination were performed at follow-up. Central pathology review confirmed all histology diagnoses. RESULTS To date, 64 subjects (mean age 28 years, range 18-61) have been enrolled (45 in the DIM arm, 19 in the placebo arm), with 60 available for analysis. Average follow-up was 6 months. At enrollment, 58% were diagnosed with CIN 2 and 42% with CIN 3, 57% of subjects were Caucasian, 15% African American, 12% Hispanic and 17% Asian. During treatment 2 subjects (3%) complained of nausea (grade 2) at the 3- to 4-month visit. No systemic toxicities were observed (normal CBC, LFTs, comprehensive metabolic). Forty-six subjects had biopsies at first follow-up (77%). Twenty-one subjects (47%) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result. Median time to improvement was 5 months. Improved Pap smear was seen in 49% (22/45) with either a less severe abnormality or normal result. Colposcopy improved in twenty-five subjects in the DIM group (56%). Of these 25 subjects, 21 (84%) had improved colposcopic impression, 13 (52%) had a decrease in involved quadrants and 18 (72%) had a decrease in lesion number. Complete colposcopic response was observed in 4 subjects (9%). Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results. At median follow-up of 6 months, 85% of subjects have not required LEEP based on routine clinical triage of improving global assessment. There was no statistically significant difference in any outcome between the DIM and placebo group. CONCLUSION Oral DIM at 2 mg/kg/day is well tolerated with no significant toxicity. We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial.

Use of abdominal radical trachelectomy to treat cervical cancer greater than 2 cm in diameter

Objective Invasive cervical cancer is one of the most common cancers, with 500,000 new cases diagnosed annually. Fertility preservation has become an important component of the overall quality of life of many cancer survivors. Expert opinion has suggested that fertility-sparing surgery should be limited to those patients diagnosed with cervical cancer less than 2 cm in diameter. Our objective was to report our abdominal radical trachelectomy (ART) experience in the opposite group of patients—those with a cervical cancer more than 2 cm in diameter. Methods Between 1999 and 2006, a total of 45 patients with cervical carcinoma at International Federation of Gynecology and Obstetrics stage IB1-IB2 measuring more than 2 cm in diameter underwent fertility-sparing ART and pelvic lymphadenectomy at the 3 institutions where the authors are based (Budapest, Hungary; London, United Kingdom; New York, United States). They were followed up for more than 5 years. Results For 69% of patients (n = 31), completed ART was considered to have been curative, and no adjuvant treatment was advised. Of those patients, 93.5% (n = 29) were alive at the time of follow-up. Thirty-one percent of patients (n = 14) underwent immediate completion of radical hysterectomy. Three of 8 patients who wished to fall pregnant delivered healthy neonates. Conclusions The 5-year survival rate (93.5%) for this case series is equal (or better) to rates reported in the literature for patient treated with radical hysterectomy. Our survival data seem to support the hypothesis that ART is a safe treatment option for patients with invasive cervical cancer lesions of more than 2 cm.

Elevated and secreted phospholipase A2 activities as new potential therapeutic targets in human epithelial ovarian cancer

Ascites in epithelial ovarian cancer (EOC) promotes tumor development by mechanisms that are incompletely understood. Lysophosphatidic acid (LPA), a major tumor‐promoting factor in EOC ascites, is an enzymatic product of autotaxin (ATX) and phospholipase A2 (PLA2)enzymes. The contribution of PLA2 activities to ovarian tumorigenesis was investigated. The quantitative measurement of PLA2 activities in ascites and tissues, as well as assay conditions selective for PLA2 subtypes, were optimized and validated. PLA2 activities correlated with tumor‐promoting activates in cell‐based and in vivo assays. High activities consistent with both cytosolic and calcium‐independent PLA2 were found in human EOC ascites for the first time. Elevated PLA2 and ATX activities were also observed in EOC compared to benign tumors and normal tissues. Cell‐free and vesicle‐free (S4) human EOC ascites potently promoted proliferation, migration, and invasion of human EOC cells in a PLA2‐dependent manner. LPA mediated a significant part of the cell‐stimulating effects of ascites. S4 ascites stimulated tumorigenesis/metastasis in vivo, and methyl arachidonyl fluorophosphonate was highly effective in inhibiting EOC metastasis in mouse xenograft models. PLA2 activity was found in conditioned media from both EOC cells and macrophages. Collectively, our work implies that PLA2 activity is a potential marker and therapeutic target in EOC.—Cai, Q., Zhao, Z., Antalis, C., Yan, L., Del Priore, G., Hamed, A. H., Stehman, F. B., Schilder, J. M., Xu, Y. Elevated and secreted phospholipase A2 activities as new potential therapeutic targets in human epithelial ovarian cancer. FASEB J. 26, 3306–3320 (2012). www.fasebj.org

Spinal cord stimulator for the treatment of a woman with vulvovaginal burning and deep pelvic pain.

BACKGROUND: Vulvodynia is a chronic pain disorder of the vulva that occurs in the absence of visible infectious, inflammatory, neoplastic, or neurological findings. Multiple treatment modalities are used, often with insufficient results. We report the successful use of a spinal cord stimulator to treat vulvodynia symptoms in a patient who had unsuccessful prior conservative therapies. CASE: A postmenopausal woman presented with 15 years of treatment for vulvar and vaginal burning and deep pelvic pain. She had been taking multiple pain medications with inadequate relief. After successful test stimulation, a permanent spinal cord stimulator was implanted. At 10 months posttreatment, her pain improved by 80%, and the patient no longer requires oral medication. CONCLUSION: The use of spinal cord stimulation was successful in a patient with vulvodynia and unsuccessful multiple prior therapies and whose symptoms were diffuse in nature.

Uterus transplantation: on the edge.

Uterus transplantation for absolute uterus factor infertility is moving closer to human trials. The indication for uterus transplantation is evident as is its potential to ameliorate the social and personal burdens of these patients. The extensive collaborative research efforts between animal works, advancements in transplantation medicine, and immune suppression have culminated in demonstrating its apparent feasibility. As for the concerns regarding its risk, in perspective it is similar to other high-risk pregnancies. Moving uterus transplantation toward clinical applications obviously will require a continued commitment of research and support.

Neoadjuvant Chemotherapy Followed by Simultaneous Robotic Radical Trachelectomy and Reversal of Tubal Sterilization in Stage IB2 Cervical Cancer

Robotic trachelectomy after neoadjuvant chemotherapy with simultaneous tubal anastomosis may be an option in stage IB2 cervical cancer patients.

Successful treatment with nab-paclitaxel after hypersensitivity reaction to paclitaxel and docetaxel

Highlights • First case report of successfully treating severe paclitaxel and docetaxel hypersensitivity reaction with nab-paclitaxel• We demonstrated that nab-paclitaxel is a safe taxane chemotherapy treatment option for patients who could not tolerate paclitaxel or docetaxel.

Experiences in Uterine Transplantation

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Rescue radical trachelectomy for preservation of fertility in benign disease

OBJECTIVES To report a series of patients treated with modified radical abdominal trachelectomy to preserve fertility in benign disease that would normally result in hysterectomy. DESIGN We reviewed all cases of radical abdominal trachelectomy performed for nonneoplastic indications. PATIENT(S) Of the >160 radical abdominal trachelectomies we performed, four cases were performed for benign indications. One patient had a 10-year history of progressive endometriosis with worsening hydronephrosis, failed medical therapy, and infertility. Two myomectomy patients had intraoperative consultation and a third had preoperative consultation for large lower segment/cervical myomas with conversion to trachelectomy rather than hysterectomy. INTERVENTION(S) Modified radical trachelectomy was successfully completed in all patients. MAIN OUTCOME MEASURE(S) We measured the successful completion of the surgery without hysterectomy, complications, and follow-up. RESULT(S) Hysterectomy was avoided in all patients, and all resumed normal menses. There were no intraoperative or postoperative complications. One required hysterectomy for recurrence 1 year later, and the remainder were symptom free at 1-5 years of follow-up. CONCLUSION(S) Although traditionally performed with cervical cancer, radical abdominal trachelectomy can be modified to preserve fertility for benign indications that would otherwise require hysterectomy.