Laparoscopy for living donor left nephrectomy: Comparison of three-dimensional and two-dimensional vision.

The main objective of this preliminary study was to evaluate the feasibility and safety of 3-D laparoscopic living donor left nephrectomy (LDLN). The secondary objective was to compare intraoperative and postoperative outcomes between 3-D and 2-D laparoscopic LDLN. All patients who underwent a laparoscopic LDLN from January 2015 to April 2018 in a university center were included. All surgeries were performed by three experienced surgeons. Seventy three patients were included the following: 16 underwent a 3-D laparoscopic LDLN (3-D group), and 57 underwent a 2-D laparoscopic LDLN (2-D group). Operative time and warm ischemia time (WIT) were significantly lower in the 3-D group (operative time: 80.9 ± 10.2 vs 114.1 ± 32.3 minutes in the 3-D and 2-D groups, P = .0002) (WIT: 1.7 ± 0.6 vs 2.3 ± 0.9 minutes in the 3-D and 2-D groups, P = .02). No conversion to open surgery occurred in both groups. Length of hospital stay was significantly shorter in the 3-D group. No major postoperative complications (Clavien ≥ III) occurred. One-year postoperative GFR was similar to 3-D and 2-D groups. Our preliminary study demonstrates that 3-D laparoscopic LDLN is a feasible and safe surgical procedure. Intraoperative and postoperative outcomes were similar in both 2-D and 3-D vision systems, but 3-D vision systems allow reduction in WIT and operative time.

Estetrol, a Fetal Selective Estrogen Receptor Modulator, Acts on the Vagina of Mice through Nuclear Estrogen Receptor α Activation.

The genitourinary syndrome of menopause has a negative impact on quality of life of postmenopausal women. The treatment of vulvovaginal atrophy includes administration of estrogens. However, oral estrogen treatment is controversial because of its potential risks on venous thrombosis and breast cancer. Estetrol (E4) is a natural estrogen synthesized exclusively during pregnancy by the human fetal liver and initially considered as a weak estrogen. However, E4 was recently evaluated in phase 1 to 2 clinical studies and found to act as an oral contraceptive in combination with a progestin, without increasing the level of coagulation factors. We recently showed that E4 stimulates uterine epithelial proliferation through nuclear estrogen receptor (ER) α, but failed to elicit endothelial responses. Herein, we first evaluated the morphological and functional impacts of E4 on the vagina of ovariectomized mice, and we determined the molecular mechanism mediating these effects. Vaginal epithelial proliferation and lubrication after stimulation were found to increase after E4 chronic treatment. Using a combination of pharmacological and genetic approaches, we demonstrated that these E4 effects on the vagina are mediated by nuclear ERα activation. Altogether, we demonstrate that the selective activation of nuclear ERα is both necessary and sufficient to elicit functional and structural effects on the vagina, and therefore E4 appears promising as a therapeutic option to improve vulvovaginal atrophy.

Long-term oncological outcomes after robotic partial nephrectomy for renal cell carcinoma: a prospective multicentre study.

PURPOSE: This study aimed at reporting the long-term oncological outcomes of robotic partial nephrectomy (RPN) for renal cell carcinoma (RCC). METHODS: Data from all consecutive patients who underwent RAPN for RCC from July 2009 to January 2012 in three departments of urology were prospectively collected. Overall survival (OS), cancer-specific survival (CSS) and disease free-survival (DFS) were estimated using the Kaplan-Meier method. Prognostic factors associated with CSS were sought in univariate analysis. The log-rank test was used for categorical variables and the Cox model for continuous variables. RESULTS: 110 patients were included with a median follow-up of 64.4 months [95% CI = (61.0-66.7)]. Median age was 61 years (29-83) with 62.7% of men and 37.3% of women. Median RENAL score was 6 (4-10) with elective indications accounting for 95% of cases. Out of 27 patients (24.5%) who experienced peri-operative complication, 12 patients (10.9%) had a major complication (Clavien-Dindo grade ≥ 3). The TRIFECTA achievement rate was 52.7%. Three patients (2.7%) experienced local recurrence and seven patients (6.4%) progressed to a metastatic disease. 5-year OS, CSS, DFS were 94.9, 96.8, 86.4%, respectively. In univariate analysis, no pre/peri-operative characteristic was associated with DFS. No port-site metastasis was observed and there was one case of peritoneal carcinomatosis. CONCLUSION: In this multicenter series, long-term OS, DFS and CSS after RPN appeared comparable to large series of open partial nephrectomy, with no port-site metastasis and one case of peritoneal carcinomatosis.

Comparison of 1800 Robotic and Open Partial Nephrectomies for Renal Tumors.

BACKGROUND: Only a few studies have compared the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN). This study aimed to compare perioperative and oncologic outcomes of RPN and OPN. METHODS: The data of all patients who underwent partial nephrectomy from 2006 to 2014 in six academic departments of urology were retrospectively collected. Perioperative outcomes were compared between OPN and RPN patients. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The study included 1800 patients: 937 who underwent RPN and 863 who underwent OPN. The patients in the robotic group had smaller tumors (33.1 vs. 39.9 mm; p < 0.001) but comparable RENAL scores (6.8 vs. 6.7; p = 0.37). The complication rate was higher in the OPN group (28.6 vs. 18 %; p < 0.001). The OPN patients had greater estimated blood loss (359.5 vs. 275 ml; p < 0.001) and more frequent hemorrhagic complications (12.1 vs. 6.9 %; p < 0.001). The robotic approach was associated with a shorter warm ischemia time (WIT 15.7 vs. 18.6 min; p < 0.001) and a shorter hospital of stay (4.7 vs. 10.1 days; p < 0.001). In the propensity score-weighted analysis, the inverse probability of treatment weighting adjusted odds ratio for the risk of complication after OPN versus RPN was 2.11 (95 % confidence interval, 1.53-2.91; p < 0.001). After a median postoperative follow-up period of 13 months for OPN and 39 months for RPN (p < 0.001), CSS and RFS were similar in the two groups. In the multivariate analysis, RPN showed an impact on the occurrence of a complication but had no effect on WIT or RFS. CONCLUSION: In this study, RPN was less morbid than OPN, with lower complications, less blood loss, and a shorter hospital of stay. The intermediate-term oncologic outcomes were similar in the two groups.

Laparoscopic nephrectomy for polycystic kidney: comparison of the transperitoneal and retroperitoneal approaches.

PURPOSE: To evaluate and compare perioperative outcomes in patients undergoing either transperitoneal (TP) or retroperitoneal (RP) laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD). METHODS: All patients with ADPKD who underwent unilateral laparoscopic nephrectomy between 2000 and 2012 in two academic departments were retrospectively included. The perioperative parameters were compared between the TP and RP groups. RESULTS: A total of 82 patients were included, 43 patients in the TP group and 39 in the RP group. The patients' characteristics were similar between TP set and RP set, except for the time from dialysis onset to nephrectomy (p = 0.02). Complication rates (25.6 vs 33.3 %, p = 0.44), transfusion rates (11.6 vs 20.5 %, p = 0.27) and conversion to open surgery (4.6 vs 7.7 %, p = 0.56) were similar between the TP and RP groups, respectively. Operative time was shorter for TP procedures (171.6 vs 210.5 min, p = 0.002), but there was no difference between the two approaches after 20 surgeries (p = 0.06). Patients in TP group had a shorter length of hospital stay (5.3 ± 1.9 vs 7.2 ± 2.5 days, p = 0.002). However, there was a trend towards shorter return of bowel function in the RP group (2.1 ± 0.9 vs 2.4 ± 0.8 days, p = 0.09). CONCLUSION: TP and RP laparoscopic nephrectomies provide good outcomes in patients with ADPKD. The choice of a TP route could decrease the length of hospital stay and the operative time during the beginning of the learning curve period.

Biochemical recurrence-free survival and pathological outcomes after radical prostatectomy for high-risk prostate cancer.

BACKGROUND: We propose to improve the prognostic assessment after radical prostatectomy (RP) by dividing high-risk prostate cancer (hrPCa) (according to the d'Amico classification) into subgroups combining 1, 2 or 3 criteria of aggressiveness (cT2c-T3a, PSA >20 ng/ml, Gleason score (GS) > 7). METHODS: Data from 4795 hrPCa patients who underwent RP in two French university hospitals from 1991 to 2013 were analyzed. Subgroups were formed to determine whether an increasing number (1, 2 or 3) of criteria of tumor aggressiveness was associated with poorer oncological results and early biochemical recurrence (BCR) (PSA > 0.2 ng/ml). These results were compared using Fisher's exact test and BCR was compared according to the Kaplan-Meier method. RESULTS: Eight hundred fifteen patients were treated by RP for hrPCa (8 %). Four hundred eleven patients (79.5 %) presented 1 RF (Risk Factor), 93 (18.0 %) 2 RF and 13 (2.5 %) 3 RF. Lymph node invasion and positive margin rates were 12.4 and 44.1 %, respectively. The prognostic sub-stratification based on these 3 factors was significantly predictive for adverse pathologic features and for oncologic outcomes. BCR free survival was respectively 56.4, 27.06 and 18.46 % for 1RF, 2RF and 3RF (p < 0.0001). However, no predominant negative criterion was found. CONCLUSION: Oncologic results after RP are heterogenous within the hrPCa risk group. Sub-stratification based on three well-defined criteria leads to a better identification of the most aggressive cancers. On the other hand, RP provides both effective cancer control and satisfactory survival rates in patients with only one risk factor.

External validation of the Briganti nomogram to estimate the probability of specimen-confined disease in patients with high-risk prostate cancer.

OBJECTIVE: To establish an external validation of the updated nomogram from Briganti et al., which provides estimates of the probability of specimen-confined disease using the variables age, prostate-specific antigen (PSA), clinical stage and biopsy Gleason score in preoperatively defined high-risk prostate cancer (PCa). PATIENTS AND METHODS: The study included 523 patients with high-risk PCa, as defined by d'Amico classification, undergoing radical prostatectomy (RP) and bilateral lymph node dissection in one of two academic centres between 1990 and 2013. Specimen-confined disease was defined as pT2-pT3a node-negative PCa with negative surgical margins. The receiver-operator characteristic (ROC) curve was obtained to quantify the overall accuracy (area under the curve [AUC]) of the model in predicting specimen-confined disease. A calibration curve was then constructed to illustrate the relationship between the risk estimates obtained by the model (x-axis) and the observed proportion of specimen-confined disease (y-axis). The Kaplan-Meier method was used to assess biochemical recurrence (BCR)-free survival. RESULTS: Patients' median age and PSA level were 64 years and 21 ng/mL, respectively. The definition of high-risk PCa was based on PSA level only in 38.3%, a biopsy Gleason score >7 in 34.5%, a clinical stage >T2b in 6.9%, or a combination of these two or three factors in 20.3% of patients. Positive surgical margins were observed in 43.6%, with a rate of 14.8% in pT2 cancers and lymph node metastasis in 12.1% of patients. pT stage was pT0 in 0.9%, pT2 in 28.9%, pT3a in 37.5% and pT3b-4 in 32.7% of patients. Overall, 44.4% of patients (N = 232) had specimen-confined disease. PSA and cT stage were independently predictive of specimen-confined disease. The median (range) 2-, 5-, and 8-year BCR-free survival rates were significantly higher in specimen-confined disease as compared with non-specimen-confined disease: 80.87 (73.67-86.29) vs 37.55 (30.64-44.44)%, 63.53 (52.37-72.74) vs 26.93 (19.97-34.36)% and 55.08 (41.49-66.74) vs 19.52 (12.50-27.70)%, respectively (P < 0.001). The ROC curve analysis showed relevant accuracy of the model (AUC 0.6470, 95% CI 0.60-0.69) although the calibration plot suggested that, for risks ranging from 0.3 to 0.5, the odds of extracapsular extension were underestimated. CONCLUSIONS: This external validation of the Briganti nomogram shows relevant accuracy, although the relative imprecision for intermediate risk may limit its clinical relevance. Our follow-up findings confirm the large proportion of specimen-confined PCa with good oncological outcomes in this heterogeneous subgroup of patients with high-risk PCa.

External Validation of a Predictive Model to Estimate Renal Function After Living Donor Nephrectomy.

BACKGROUND: Transplantation from living donor nephrectomy (LDN) is the best treatment for end-stage renal disease but observed decrease in donor renal function is a major concern. The aim of this study was to externally validate a predictive model to estimate 1-y postdonation estimated glomerular filtration rate (eGFR) and risk of chronic kidney disease (CKD) in living donors. METHODS: All LDN performed at Necker Hospital from January 2006 to May 2018 were retrospectively included. Observed eGFR (using CKD-EPI formula) at 1-y post LDN was compared with the predicted eGFR calculated with a formula developed at Toulouse-Rangueil and based on predonation eGFR and age. Pearson correlation, receiver operating characteristics curve (ROC curve), and calibration curve were used to assess external validity of the proposed prognostic model to predict postoperative eGFR and occurrence of CKD in donors. RESULTS: Four hundred donors were evaluated with a mean postoperative eGFR of 62.1 ± 14 mL/min/1.73m2. Significant correlation (Pearson r = 0.66; P < 0.001) and concordance (Bradley-Blackwood F = 49.189; P < 0.001) were observed between predicted and observed 1-y eGFR. Area under the receiver operating characteristic curve of the model relevant accuracy was 0.86 (95% CI, 0.82-0.89). CONCLUSIONS: This study externally validated the formula to predict 1-y postdonation eGFR. The calculator could be an accurate tool to improve the selection of living kidney donor candidate.

Living-donor kidney transplantation: comparison of sequential and simultaneous surgical organizations.

PURPOSE: The objective of this study was to compare living-donor kidney transplantation (LDKT) performed either sequentially, in one operating room, leading to extended cold ischemia time (CIT) or simultaneously, in two different operating room, with shorter CIT. METHODS: We retrospectively included all living-donor nephrectomies and kidney transplantations, performed from March 2010 to March 2014, in three French university centers. In the first one (C1), LDKTs were performed in sequential manner (Sequential group) and in C2 and C3, LDKTs were performed in simultaneous manner (Simultaneous group). RESULTS: A total of 324 LDKT were performed: 176 LDKT in Sequential group and 148 LDKT in Simultaneous group. Patients characteristics were equivalent between groups, except nephrectomy side, ABO mismatch rate and previous kidney transplantation rate. CIT, rewarming time, transfusion and delayed graft function (DGF) were significantly higher in Sequential group. Overall survival and graft survival of kidney transplant recipients were similar in the Sequential and Simultaneous groups. 5-year eGFR was similar between groups. In univariate analysis, number of graft arteries, recipient BMI, previous kidney transplantation status and CIT were significant predictors of DGF. Only previous kidney transplantation status was an independent predictive factor of DGF in the multivariate analysis. CONCLUSIONS: Sequential surgical organization results in the same functional results as simultaneous surgical organization. DGF was higher for LDKT performed sequentially but at 5-year overall survival, graft survival and eGFR were similar between these two types of transplant organizations.

Predictive model of 1-year postoperative renal function after living donor nephrectomy.

OBJECTIVE: Kidney transplantation from a living donor nephrectomy (LDN) is the best treatment for end-stage renal disease, but decrease in donor renal function is often revealed. The aim of this study was to evaluate the association between preoperative factors and postoperative estimated glomerular filtration rate (eGFR) and test a predictive model to estimate postoperative eGFR, 1 year after LDN. PATIENTS AND METHODS: We reviewed 226 records of consecutive patients who underwent laparoscopic live donor nephrectomy between 2006 and 2014 in a single tertiary center. Of these, complete data on 202 patients were analyzed. A training (2/3 of the whole population) and a validation set (1/3) were randomized. A multivariate regression model was used to identify predictors and a formula to estimate of 1-year postoperative eGFR in the training set, using the CKD-EPI formula. Then, the formula was subjected to internal validation using the validation set using receiver operating characteristic (ROC) curves. RESULTS: Two hundred and two LLDN were evaluated with a mean preoperative eGFR of 94.1 ± 15.5 ml/min/1.73 m2 and postoperative eGFR of 64.6 ± 14.5 ml/min/1.73 m2 (p < 0.0001). In multivariable analysis, age and preoperative eGFR were independent predictors of postoperative eGFR in the training set. A formula to estimate postoperative eGFR was generated with Pearson r = 0.70 in the training cohort and 0.65 in the validation cohort (both p < 0.0001). Area under the ROC curve of the formula was 0.89 in the training cohort and 0.83 in the validation cohort (both p < 0.0001). CONCLUSIONS: Preoperative eGFR and age are predictors of postoperative eGFR after LDN. The internally validated predictive model of postoperative eGFR developed could be an accurate tool to improve the selection of LDN candidates.

Effect of chronic estradiol plus progesterone treatment on experimental arterial and venous thrombosis in mouse.

Postmenopausal hormone replacement therapy (HRT) with estrogen plus progestogens is the first line therapy to treat menopausal symptoms. The progestogen is added to estrogen to reduce or eliminate the excess risk of endometrial cancer due to the unopposed effect of estrogen. Whereas progestin clearly opposes the proliferative and deleterious long-term actions of estrogen on the endometrium, the interference of progestin on the other estrogen action remains unclear. We previously reported that chronic subcutaneous 17α-estradiol (E2) in mice decreases platelet responsiveness, prolongs the tail-bleeding time and protects against acute thromboembolism. Here, we report the tissue-specific interference of progesterone (P4) on the action of E2 in ovariectomized mice. We first confirm that, in our experimental conditions, P4 attenuates the proliferative action of E2 on the uterus and the effects of E2 on vagina weight and lubrication. We then studied the effect of E2 combined with P4 on hemostasis and thrombosis in vivo in mice and found that P4 did not interfere with the main actions of E2 on platelets, bleeding time and arterial and venous thrombosis. Thus, whereas activation of progesterone receptor interferes with the action of E2 on its classic sex targets, P4 appears to have minimal effect on the hemostasis and thrombosis actions of E2, supporting the prominent role of estrogens and the accessory role of natural progestin on the extra-reproductive cells and tissues involved in thrombosis.

[Association of estrogens and selective estrogens receptors modulators: towards a renewal of the hormonal treatment?]. / L'association estrogènes et modulateurs sélectifs du récepteur des estrogènes: un renouveau du traitement hormonal?

The life expectancy of women has risen in the past century from 48years to more than 80. The decline of endogenous estrogen production (in particular, the principal circulating physiological hormone, 17ß-estradiol) at menopause (which occurs at an average of 51years) is often accompanied by a series of functional disorders that affect quality of life (QoL). This estrogen deficiency affects different tissues and results in an increase in the prevalence of various disorders, including but not limited to osteoporosis and cardiovascular disease. Hormone therapy for menopause is a relatively recent biomedical challenge, which underwent a downturn after the Women Health Initiative study of older postmenopausal women. We will summarize the WHI findings in the first part of this article. At Inserm unit 1048, we are working on understanding the protective effects of estrogen against the development of atherosclerosis and type 2 diabetes in murine models. We have also focused in recent years on modeling the impact of estrogen in thrombosis models, to attempt to clarify the complex relation between estrogen and thrombotic risk. In part II of this article, we will describe a new strategy of hormone therapy for menopause, combining estrogens and selective estrogen receptor modulators (SERM). We review the scientific underpinnings of this strategy, which may enable the renewal of hormone therapy for menopause.