Does tumour effraction during robotic partial nephrectomy have any impact on recurrence?

OBJECTIVE: To evaluate the impact of accidental surgical incision into the tumour (ASIT) on oncological outcomes in patients undergoing RPN for a malignant tumour. MATERIALS AND METHODS: A retrospective review of our prospectively maintained database was performed to identify all patients who underwent RPN for a localized RCC between June 2010 and July 2016. We stratified our cohort into two groups according to the presence of an ASIT. Perioperative data were compared between the two groups. Logistic regression analyses were used to assess the variables associated with ASIT. Recurrence-free survival was estimated using the Kaplan-Meier method and compared between groups with the log-rank test. RESULTS: A total of 234 patients were identified. 32 (14%) ASIT were observed. Patients' characteristics were similar in the two groups. Most of intraoperative outcomes were comparable between the two groups, but patients in the ASIT group had greater EBL (475 vs. 300 mL; p = 0.01). In multivariate analysis, tumour size (p = 0.02), RENAL score (p = 0.02), EBL (p = 0.05) and low surgeon experience (p = 0.03) were all predictive factors of ASIT. 15 (6%) of recurrences were observed over a median follow-up of 36 months. There was no difference in recurrence-free survival between the two groups (p = 0.57). CONCLUSIONS: In our experience, accidental surgical incision into the tumour during RPN was a common event that did not appear to compromise oncological outcome.

Does training of fellows affect peri-operative outcomes of robot-assisted partial nephrectomy?

OBJECTIVE: To evaluate the impact of fellows' involvement on the peri-operative outcomes of robot-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: We analysed 216 patients who underwent RAPN for a small renal tumour. We stratified our cohort into two groups according to the involvement of a fellow surgeon during the procedure: expert surgeon operating alone (expert group) and fellow operating under the supervision of the expert surgeon (fellow group). Peri-operative data were compared between the two groups. Linear and logistic regression analyses were performed to assess the impact of fellows' involvement on peri-operative and postoperative outcomes. Trifecta and margins ischaemia complications (MIC) score achievement rates were used to assess the quality of surgery in both the expert and fellow groups. Trifecta was defined as a combination of warm ischaemia time <25 min, negative surgical margins and no peri-operative complications. MIC score was defined as negative surgical margins, ischaemia time <20 min, and absence of complications grade ≥3. RESULTS: Fellows were involved in a total of 89 procedures (41%). Patients' characteristics were similar in the two groups. Operating time and warm ischaemia time (WIT) were longer in the fellow group (180 vs 120 min, P < 0.001, and 18 vs 14 min, P = 0.002, respectively). Length of hospital stay (LOS) was longer in the fellow group (5 vs 4.3 days; P = 0.05) and patients in this group had higher estimated blood loss (EBL; 400 vs 300 mL; P = 0.01), but this had no impact on transfusion rate (14% vs 11%; P = 0.43). Positive surgical margin rates were similar in the fellow and expert groups (2.2% vs 3.1%; P = 0.70). Major complications were more frequent in the fellow group (12.3% vs 6.3%), but the difference was not significant (P = 0.10). In multivariable analysis, fellow involvement was predictive of longer WIT (ß = 0.22; P = 0.003) and operating time (ß = 0.49; P < 0.001), but was not associated with EBL (ß = 0.12, P = 0.09) or LOS (ß = 0.12, P = 0.11). Finally, fellow involvement was associated with a lower rate of trifecta and MIC score accomplishment (odds ratio [OR] 0.53, P = 0.05 and OR 0.46, P = 0.01, respectively). CONCLUSION: Training fellows to perform RAPN is associated with longer operating time and WIT but does not appear to compromise other peri-operative outcomes.

Initial source of heterogeneity in a model for cell fate decision in the early mammalian embryo.

During development, cells from a population of common progenitors evolve towards different fates characterized by distinct levels of specific transcription factors, a process known as cell differentiation. This evolution is governed by gene regulatory networks modulated by intercellular signalling. In order to evolve towards distinct fates, cells forming the population of common progenitors must display some heterogeneity. We applied a modelling approach to obtain insights into the possible sources of cell-to-cell variability initiating the specification of cells of the inner cell mass into epiblast or primitive endoderm cells in early mammalian embryo. At the single-cell level, these cell fates correspond to three possible steady states of the model. A combination of numerical simulations and bifurcation analyses predicts that the behaviour of the model is preserved with respect to the source of variability and that cell-cell coupling induces the emergence of multiple steady states associated with various cell fate configurations, and to a distribution of the levels of expression of key transcription factors. Statistical analysis of these time-dependent distributions reveals differences in the evolutions of the variance-to-mean ratios of key variables of the system, depending on the simulated source of variability, and, by comparison with experimental data, points to the rate of synthesis of the key transcription factor NANOG as a likely initial source of heterogeneity.

Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial.

BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma. METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion <2 cm in size), and no contraindications to selective internal radiation therapy, as assessed by use of a technetium-99m macro-aggregated albumin scan. Patients were randomly assigned (1:1) by use of a permutated block method, with block sizes of four and without stratification, to receive either standard dosimetry (120 ±â€ˆ20 Gy) targeted to the perfused lobe; standard dosimetry group) or personalised dosimetry (≥205 Gy targeted to the index lesion; personalised dosimetry group). Investigators, patients, and study staff were not masked to treatment. The primary endpoint was the investigator-assessed objective response rate in the index lesion, according to European Association for the Study of the Liver criteria, at 3 months after selective internal radiation therapy in the modified intention-to-treat population. Safety was assessed in all patients who received at least one selective internal radiation therapy injection, and analysed on the basis of the treatment actually received (defined by central dosimetry assessment). The trial is registered with ClinicalTrials.gov, NCT02582034, and has been completed. FINDINGS: Between Dec 5, 2015, and Jan 4, 2018, 93 patients were assessed for eligibility. Of these patients, 60 were randomly assigned: 31 to the personalised dosimetry group and 29 to the standard dosimetry group (intention-to-treat population). 56 (93%) patients (28 in each group) were treated (modified intention-to-treat population). In the modified intention-to-treat population, 20 (71% [95% CI 51-87]) of 28 patients in the personalised dosimetry group and ten (36% [19-56]) of 28 patients in the standard dosimetry group had an objective response (p=0·0074). In the safety analysis population, a least one serious adverse event was reported in seven (20%) of the 35 patients who received personalised dosimetry, and in seven (33%) of the 21 patients who received standard dosimetry. The most frequent (ie, occurring in >5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group. INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.

What Is Better for Predicting Morbidity of Robotic Partial Nephrectomy-A Score or Your Clinical Judgement?

BACKGROUND: Little is known about the predictive value of surgeon's judgement to estimate perioperative outcomes following robotic partial nephrectomy (RPN). OBJECTIVE: To evaluate the accuracy of surgeon's intuition to estimate perioperative outcomes of patients undergoing RPN and compare its predictive value with that of objective scoring systems. DESIGN, SETTING, AND PARTICIPANTS: We prospectively analysed 100 consecutive patients who underwent RPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RENAL, PADUA, and MAP scores were calculated based on preoperative imaging. The surgeon gave a subjective estimation of the technical difficulty and the risk of postoperative complications of RPN immediately before and after surgery using a visual analogue scale (VAS). Correlation between scores, VAS, estimated blood loss (EBL), operative time (OT), and warm ischaemia time (WIT) were examined. Logistic regression analyses were performed to identify the best predictors of overall complications. Receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of VAS and scoring systems to predict trifecta achievement. RESULTS AND LIMITATIONS: RENAL, PADUA, and MAP scores significantly correlated with surgeon's pre- and postoperative VAS evaluation, with the RENAL score showing the strongest correlation (r=0.49 and r=0.34, respectively). Pre- and postoperative VAS scores had the strongest correlation with EBL (r=0.48 and r=0.59, respectively), OT (r=0.44 and r=0.65, respectively), and WIT (r=0.37 and r=0.47, respectively). In multivariate analysis adjusted for anticoagulant/antiplatelet treatment, body mass index, surgeon's experience, and Charlson comorbidity index, only surgeon's prediction could significantly predict overall complications (odds ratio=5.42, p <0.001). Finally, surgeon's intuition was better to predict trifecta accomplishment than all radiological scores (ROC areas under the curves were 0.76 and 0.77 for pre- and postoperative VAS scores, respectively). CONCLUSIONS: Surgeon's clinical assessment is a good predictor of perioperative outcomes of RPN and seems to perform better than conventional scores. PATIENT SUMMARY: In this report, we found that surgeon's clinical feeling can better predict perioperative morbidity of robotic partial nephrectomy than conventional radiological scores.

Predicting morbidity after robotic partial nephrectomy: The effect of tumor, environment, and patient-related factors.

PURPOSE: To investigate the effect of tumor and nontumor related parameters on perioperative outcomes of robotic partial nephrectomy (RPN). PATIENTS AND METHODS: Patients who underwent RPN for a localized renal tumor at 2 institutions between June 2010 and November 2016 were reviewed. RENAL and Mayo adhesive probability (MAP) scores were calculated and information on comorbid conditions including ASA score, performance status, Charlson's comorbidity index (CCI), and history of cardiovascular disease was collected. Correlations between each variable and warm ischemia time, estimated blood loss (EBL), operative time, change in estimated glomerular filtration rate, and length of hospital stay were assessed. Logistic regression analyses were performed to identify the best predictors of overall complications, major complications, risk of conversion, and Trifecta achievement. RESULTS: A total of 500 patients were included. RENAL score was found to have a statistically significant (P<0.05) correlation with warm ischemia time, EBL, and change in estimated glomerular filtration rate. MAP score showed significant association (P<0.05) with operative time and EBL. CCI had a significant correlation (P<0.05) with length of hospital stay and postoperative complications. In multivariable analyses, MAP score as a continuous variable (OR = 7.66; P<0.001) and MAP risk group stratification (OR = 3.29; P = 0.005) were independent predictors of the risk of conversion. Major complications were significantly associated with the cardiovascular disease in both univariable (OR = 2.35; P = 0.01) and multivariable analysis (OR = 4.52, P = 0.01). Finally, the MAP score as a continuous variable was an independent factor of Trifecta achievement (OR = 0.56; P = 0.04). CONCLUSION: Patients related factors were the most important determinants of postoperative complications after RPN. RENAL and MAP scores had some influence on intraoperative parameters.