Cervical re-injection of indocyanine green to improve sentinel lymph node detection in endometrial cancer.

OBJECTIVES: To evaluate the role of cervical re-injection of indocyanine green (ICG) to increase the detection rate of sentinel lymph node (SLN) in patients with endometrial cancer (EC) who underwent robotic-assisted surgical staging. METHODS: We retrospectively identified consecutive EC patients undergoing robotic-assisted staging with SLN biopsy at our Institution between June 2016 and April 2020. Patients were excluded if they had open abdominal surgical approach, neoadjuvant chemotherapy, and advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] at diagnosis. According to our SLN protocol, in case of either unilateral or no SLN detection, we performed an ipsilateral or bilateral cervical re-injection of ICG. RESULTS: In total, 251 patients meeting inclusion criteria were included in the analysis. At first injection, bilateral detection was achieved in 184 (73.3%), unilateral detection in 57 (22.7%), and no detection in 10 (4.0%) patients. Cervical re-injection was performed in 51 of 67 patients with failed bilateral mapping. After cervical re-injection, bilateral detection rate increased to 94.5% (222/235), while unilateral and no detection were 5.1% (12/235) and 0.4% (1/235), respectively. CONCLUSIONS: Our results suggest that cervical re-injection of ICG, in case of failed bilateral mapping of SLN, brings about a significant improvement in SLN detection rates, therefore reducing the number of side-specific required lymphadenectomies.

The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study.

OBJECTIVE: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. TWEETABLE ABSTRACT: Monochorionicity is associated with adverse perinatal outcomes, but outcomes for preterm twins are comparable irrespective of their chorionicity.

Conservative management of early-stage epithelial ovarian cancer: results of a large retrospective series.

BACKGROUND: To assess the long-term oncological outcome and the fertility of young women with early-stage epithelial ovarian cancer (ES/EOC) treated with fertility-sparing surgery (FSS). PATIENTS AND METHODS: All patients treated with FSS for ES/EOC in two Italian centers were considered for this analysis. Univariate and multivariate analyses were used to test demographic characteristics and clinical features for the association with overall survival (OS), recurrence-free survival (RFS) and fertility. RESULTS: From 1982 to 2010, 240 patients with malignant ES/EOC were treated with FSS in two tertiary centers in Italy. At a median follow-up of 9 years, 27 patients had relapsed (11%) and 11 (5%) had died of progressive disease. Multivariate analysis found only grade 3 negatively affected the prognosis of patients [hazard ratio (HR) for recurrence: 4.2, 95% confidence interval (CI): 1.5-11.7, P=0.0067; HR for death: 7.6, 95% CI: 2.0-29.3, P=0.0032]. Grade 3 was also significantly associated with extra-ovarian relapse (P=0.006). Of the 105 patients (45%) who tried to become pregnant, 84 (80%) were successful. CONCLUSIONS: Conservative treatment can be proposed to all young patients when tumor is limited to the ovaries, as ovarian recurrences can always be managed successfully. Patients with G3 tumors are more likely to have distant recurrences and should be closely monitored.

A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis.

To test the feasibility and efficacy of epirubicin and ifosfamide added to first-line chemotherapy with cisplatin and paclitaxel in a phase II randomised clinical trial. Patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP) or cisplatin/paclitaxel/ifosfamide (CIP) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms and the median number of cycles per patient was six. Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm. Response rates were 85% (95% confidence interval (CI) 77-93%) in the CIP arm and 90% (95% CI 84-96%) in the CEP arm; complete response rates were 48 and 52%. After a median follow-up of 82 months, median overall survival (OS) was 51 and 65 months; 5-year survival rates were respectively 43 and 50%. In this clinical trial, both regimens showed good efficacy, but toxicity was heavier with the CIP regimen. Considering that more than 50% of patients were suboptimally debulked after the first surgery, OS seems to be longer than is commonly reported. This unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach.

A phase II clinical trial of topotecan and carboplatin in patients with newly diagnosed advanced epithelial ovarian cancer.

A phase II clinical trial conducted to evaluate the efficacy and tolerability of topotecan and carboplatin as first-line therapy for women with advanced epithelial ovarian cancer was the objective of this study. Patients had histologically confirmed ovarian epithelial cancer with at least one measurable lesion. Patients received topotecan 1.5 mg/m(2) on days 1-3 and carboplatin at an area under the curve (AUC) of 5 on day 3 every 21 days for six cycles. All 42 patients enrolled were evaluable for response and toxicity. Median number of cycles delivered was six. Overall response rate was 71%, with 19 clinical complete responses (45%) and 11 clinical partial responses (26%). Median survival time was 47 months and 5-year survival was 42%. Myelosuppression was the predominant toxicity, with grade 3 or 4 neutropenia occurring in 100% of patients. However, this toxicity was transient and easily manageable; no patients experienced febrile neutropenia. The combination of topotecan and carboplatin is active in advanced epithelial ovarian cancer. Delay of therapy by 1 week or topotecan dose reduction to 1.25 mg/m(2) is the first-choice option to reduce topotecan toxicity without affecting the efficacy. Moreover, a chemotherapy regimen using weekly topotecan, which is currently being tested, should be considered.

Primary malignant vaginal melanoma treated with adriamycin and ifosfamide: a case report and literature review.

BACKGROUND: Vaginal melanoma is a very rare but highly malignant gynecological disease, usually diagnosed in postmenopausal woman. The prognosis tends to be poor and it is associated with high rate of recurrence and short survival rates. CASE: The following paper describes a case report regarding a 72-year-old woman with a locally advanced malignant melanoma. The previous erroneous histopathological diagnosis was leiomyosarcoma. She underwent chemotherapy with 3 courses of doxorubicin and ifosfamide. The diagnosis of malignant melanoma was obtained after a repeated biopsy and further pathological investigations. She later underwent radical surgery and 2 additional cycles of the same chemotherapy. At present, 7 months after the last cycle, the patient was locally disease-free, but developed brain metastases, requiring chemotherapy treatment. CONCLUSION: In view of poor survival, this chemotherapy regimen may be an interesting alternative to the traditional treatment of vaginal melanoma.

New drugs from the sea.

This paper illustrates some biochemical and pharmacological properties of two natural marine products such as trabectedin (ET-743, Yondelis) and aplidine. Trabectedin has shown clinical antitumor activity in refractory soft tissue sarcoma and ovarian cancer. The lack of cross resistance of trabectedin with other chemotherapeutic drugs is presumably related to its peculiar mode of action, that seems to be related to a promoter-dependent transcription modulation. Aplidine is a potent pro-apoptotic inducer in human leukemia and has antiangiogenic properties. These examples support the view that more research should be carried out to investigate new natural marine products since there are compounds among them with antitumor properties. Some of them appear to act by mechanisms different from those of conventional chemotherapeutic drugs and thus may be effective against tumors for which no active drugs are available.

Novel [1,2]- and [2,3]-Wittig rearrangements of alpha-benzyloxy beta-CF(3)-beta-lactam enolates.

[reaction: see text] alpha-Benzyloxy alpha-CF(3)-beta-lactams are shown to offer the first examples of the enolate [1,2]- and enolate ortho-[2,3]-Wittig rearrangements which provide a unique entry to the alpha-benzyl-alpha-hydroxy lactams and the alpha-aryl-alpha-hydroxy lactams, respectively. Both products are potential precursors of new trifluoromethyl isoserines, and the latter is not accessible via the usual alkylation methodology.

Application of the Monte Carlo integration (MCI) method for calculation of the anisotropy of 192Ir brachytherapy sources.

Source anisotropy is a very important factor in the brachytherapy quality assurance of high-dose rate (HDR) 192Ir afterloading stepping sources. If anisotropy is not taken into account then doses received by a brachytherapy patient in certain directions can be in error by a clinically significant amount. Experimental measurements of anisotropy are very labour intensive. We have shown that within acceptable limits of accuracy, Monte Carlo integration (MCI) of a modified Sievert integral (3D generalization) can provide the necessary data within a much shorter time scale than can experiments. Hence MCI can be used for routine quality assurance schedules whenever a new design of HDR or PDR 192Ir is used for brachytherapy afterloading. Our MCI calculation results are compared with published experimental data and Monte Carlo simulation data for microSelectron and VariSource 192Ir sources. We have shown not only that MCI offers advantages over alternative numerical integration methods, but also that treating filtration coefficients as radial distance-dependent functions improves Sievert integral accuracy at low energies. This paper also provides anisotropy data for three new 192Ir sources, one for the microSelectron-HDR and two for the microSelectron-PDR, for which data are currently not available. The information we have obtained in this study can be incorporated into clinical practice.