Optimizing Strategies for Sentinel Lymph Node Mapping in Early-Stage Cervical and Endometrial Cancer: Comparison of Real-Time Fluorescence With Indocyanine Green and Methylene Blue.

OBJECTIVE: This retrospective study aimed to compare the sentinel lymph node (SLN) mapping results of methylene blue (MB) and indocyanine green (ICG) in women with early-stage endometrial or cervical cancer. METHODS: From August 2011 to March 2015, all consecutive patients with stage I endometrial or cervical cancer who underwent SLN mapping with intracervical injection of MB or ICG using a 22-gauge spinal needle were included in the study. Radical or simple hysterectomy with bilateral pelvic and/or aortic lymphadenectomy was performed after SLN mapping. RESULTS: Overall, 81 women (64 women with endometrial cancer and 17 women with cervical cancer) underwent surgery, including SLN mapping. Sixty-five patients (80%) underwent minimally invasive surgery. The overall detection rate was 84% (34 of 38) and 100% (43 of 43) for MB and ICG, respectively (P = 0.041). Bilateral SLN detection was higher in the ICG group than in the MB group (88% vs 50; P = 0.002). Eleven patients (13.5%) were found to have positive nodes with at least 1 positive SLN. The sensitivity and negative predictive value of SLN were 100%. CONCLUSIONS: Real-time florescence mapping with ICG shows better overall detection rate and bilateral mapping than MB alone. In our pilot study, the differences are statistically significant. The higher number of bilateral mapping of ICG may increase the quality of life and recovery of women by reducing the need for complete lymphadenectomy.

Treatment of simple and complex endometrial non-atypical hyperplasia with natural progesterone: response rate to different doses.

The aim of this study is to evaluate the response rate to natural progesterone in non-atypical endometrial hyperplasia and to identify the lowest effective dose. A total of 197 patients of childbearing age with simple or complex hyperplasia were retrospectively identified. The women were treated with a cyclic administration of progesterone at different dosages (100 versus 200 versus 300 mg daily). Endometrial biopsies were performed at 6, 12, 18 months. In comparing progesterone to a regimen of no therapy, a significantly higher remission rate was observed in the progesterone group than in the latter (95 versus 75%, p = 0.05 for simple hyperplasia; 89 versus 35%, p < 0.001 for complex hyperplasia). Out of 60 women with simple hyperplasia, remission was observed in 9/11 (81.8%), 40/41 (97.5%) and 8/8 (100%) patients treated, respectively, with progesterone 100, 200 and 300 mg daily. Out of 72 women with complex hyperplasia, remission was observed in 3/5 (60%), 49/53 (92.4%) and 12/14 (85.7%) patients treated with progesterone 100, 200 and 300 mg daily, respectively. There was no statistically significant difference in the response rate in the two groups, neither with simple nor with complex hyperplasia. In conclusion, progesterone increased the regression rate of both simple and complex hyperplasia.

A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian cancer.

PURPOSE: To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses of the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and cytomorphometric biomarkers in cancer cells collected from ascitic fluid before and after treatment. METHODS: Twenty-two naive patients with ascitic ovarian cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area, DNA index, and chromatin texture) were determined in ascitic cells. Drug levels were measured by high-performance liquid chromatography. RESULTS: Doses up to 800 mg/d were well tolerated, and no adverse reactions occurred. There was no effect of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75% of subjects, and cytomorphometric variables, which were assessed in 80% of subjects. Plasma retinol levels were significantly lower in affected women than healthy donors. 4-HPR plasma concentrations increased slightly with increasing doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in malignant ascitic cells and tumor tissue were higher than in plasma but were 50 and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1 micromol/L 4-HPR. CONCLUSIONS: Cell biomarkers can be measured in ascitic cells to assess drug activity. Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention.

Placental site trophoblastic tumor: an overview.

OBJECTIVE: To analyze 15 consecutive cases of placental site trophoblastic tumor seen in a single reference institution for gestational trophoblastic disease, San Gerardo Hospital, Monza, Italy. STUDY DESIGN: Consecutive patients affected by placental site trophoblastic tumors were selected from our computerized database. RESULTS: There were 15 patients with placental site trophoblastic tumor, with a median age of 35 years. The antecedent pregnancy was a term one in 6 cases (40%), a miscarriage in 4 cases (27%), a termination in 2 cases (13%) and a molar abortion in 2 cases (13%). In 1 case the previous pregnancy was unrecognized. The median interval from the last pregnancy was 12 months, and the presenting symptom in 11 cases was vaginal bleeding, in 2 cases amenorrhea, in 1case a nephrotic syndrome and in 1 case, presenting with metastatic disease, hemoptysis. Six patients were treated using neoadjuvant chemotherapy with etoposide/methotrexate/actinomycin-etoposide/ vincristine (EMA-CO) followed in 5 of 6 (83%) cases by hysterectomy. One patient had only medical treatment with EMA-CO because of a strong desire for or childbearing and had a complete response; after 15 months she was free from disease. The last 9 patients underwent surgery as the first therapy. Among these patients 1 had presented with metastatic pulmonary disease and underwent chemotherapy, with complete disappearance of the pulmonary lesions. Two of these 9 patients had a relapse; the mirst patient had a pelvic and bladder relapse, and 14 months after multiple chemotherapy and surgery, she died. The second had a suburethral relapse 2 months after initial surgery; after chemotherapy and surgery she was well and free of disease. CONCLUSION: Our experience suggests that the role of chemotherapy may be reconsidered not only for metastatic disease but als of or uterine disease when choosing conservative management in young, fertile patients who desire childbearing. Chemotherapy may play an important role in avoiding relapse or early metastases even in patients who underwent hysterectomy as primary treatment.

Ovarian Sertoli-Leydig cell tumor, endometrioid-like yolk sac tumor, and Y-chromosomal material.

Sertoli-Leydig cell tumors (SLCTs) are rare neoplasms, accounting for less than 0.2% of ovarian tumors. The endometrioid-like variant of yolk sac tumor (YST) is very rare, and the most extensive series reported only 8 cases. We present a case of ovarian SLCT with endometrioid-like YST in a patient with a 46,XX karyotype with Y-chromosomal material. A 26-year-old woman had undergone a right salpingo-oophorectomy for SLCT with endometrioid-like YST. Chromosomal analysis revealed a 46,XX karyotype with Y-chromosomal material insertion into chromosome 1. The patient's father and sister, and 7 other paternal relatives (4 male and 3 female) presented the same chromosome variant without evidence of cancer. The YST component relapsed to the right side of the uterine wall and then metastasized to the peritoneum and liver, while SLCT was eradicated with primary surgery. Several chemotherapeutic regimens were totally ineffective to control tumor progression. She died of disease progression 54 months after the diagnosis. We adopted the policy of a close surveillance for ovarian neoplasms for the 22-year-old sister of the patient, who presented the same Y-chromosomal material in her karyotype. In very rare tumors, new methods, based on molecular and cytogenetic models, are requested to define recommended management.