PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study, pre-operative recognition of high risk endometrial carcinoma: a multicentre prospective cohort study.

BACKGROUND: Endometrial carcinoma is the most common gynaecologic malignancy in industrialised countries and the incidence is still rising. Primary treatment is based on preoperative risk classification and consists in most cases of hysterectomy with bilateral salpingo-oophorectomy. In patients with serous and clear cell histology a complete surgical staging is mandatory. However, in routine clinical practice final histology regularly does not correspond with the preoperative histological diagnosis. This results in both over and under treatment. METHODS/DESIGN: The aim of this multicentre, prospective cohort study is to select a panel of prognostic biomarkers to improve preoperative diagnosis of endometrial carcinoma in order to identify those patients that need extended surgery and/or additional treatment. Additionally, we will determine whether incorporation of cervical cytology and comorbidity could improve this preoperative risk classification. All patients treated for endometrial carcinoma in the participating hospitals from September 2011 till December 2013 are included. Patient characteristics, as well as comorbidity are registered. Patients without preoperative histology, history of hysterectomy and/or endometrial carcinoma or no surgical treatment including hysterectomy are excluded. The preoperative histology and final pathology will be reviewed and compared by expert pathologists. Additional immunohistochemical analysis of IMP3, p53, ER, PR, MLH1, PTEN, beta-catenin, p16, Ki-67, stathmin, ARID1A and L1CAM will be performed. Preoperative histology will be compared with the final pathology results. Follow-up will be at least 24 months to determine risk factors for recurrence and outcome. DISCUSSION: This study is designed to improve surgical treatment of endometrial carcinoma patients. A total of 432 endometrial carcinoma patients were enrolled between 2011 and 2013. Follow-up will be completed in 2015. Preoperative histology will be evaluated systematically and background endometrium will be classified. This is the first study incorporating immunohistochemistry, cervical cytology and comorbidity to define the optimal panel of prognostic biomarkers that contribute in clinical decision making in the management of endometrial carcinoma. TRIAL REGISTRATION: Netherlands Trial Register number NTR3503.

Selective pulmonary artery perfusion followed by blood flow occlusion: new challenge for the treatment of pulmonary malignancies.

INTRODUCTION: Selective pulmonary artery perfusion (SPAP) is an experimental endovascular technique for the treatment of pulmonary malignancies. This study evaluated blood flow occlusion (BFO) after SPAP and dose-escalation in order to delay washout of gemcitabine from the lung tissue, to augment pulmonary drug exposure and to maintain plasma concentrations equivalent to intravenous administration. MATERIAL AND METHODS: Six groups of pigs underwent left-sided SPAP using gemcitabine in a clinically applied dose of 1-1.5g/m(2) after balloon catheterisation. BFO experiment: four groups (n=4, each) were treated with SPAP with 1g/m(2) of gemcitabine during 2 min followed by BFO for 0, 10, 20 and 30 min, respectively. Dose-escalation experiment: two more groups (n=3, each) received SPAP with 1.25 and 1.5 g/m(2) of gemcitabine during 2 min followed by 30 min BFO. All pigs underwent left thoracotomy with sampling of lung, liver and blood. The animals were sacrificed after 1h. The lung and plasma areas under the curve (AUC) were calculated for each group and ANOVA and t-test was used for comparison. RESULTS: Thirty minutes BFO resulted in the highest lung AUC compared to 0, 10 and 20 min BFO (p<0.001), while no significant differences in plasma AUC and liver levels were observed. Gemcitabine dose-escalation up to 1.25 g/m(2) resulted in significantly higher lung AUC (p=0.02) compared to 1g/m(2), while plasma AUC was equivalent with intravenous treatment. Further dose-escalation to 1.5g/m(2) did not result in significantly higher lung levels compared to 1.25 g/m(2). CONCLUSION: BFO after SPAP delays the washout of gemcitabine from lung tissue. Dose-escalation resulted in higher lung concentrations, while plasma levels were equivalent with intravenous administration. We advocate 2 min of SPAP with 1.25 g/m(2) of gemcitabine followed by 30 min of BFO to be investigated as a new treatment modality for pulmonary malignancies.