Peri-operative, functional and early oncologic outcomes of salvage robotic-assisted radical prostatectomy after high-intensity focused ultrasound partial ablation

BACKGROUND: Partial ablation of the prostate using high-intensity focussed ultrasound (HIFU-PA) is a treatment option for localised prostate cancer. When local recurrence occurs, salvage robot-assisted radical prostatectomy is a treatment option for selected patients, but there is a paucity of data on the peri-operative safety, functional and oncologic outcomes of sRARP.. The objective of this study was therefore to describe peri-operative safety, functional and early oncologic outcomes following salvage robot-assisted radical prostatectomy (sRARP) for local recurrence after HIFU-PA. METHODS: Retrospective analysis of a prospective database of 53 consecutive men who underwent sRARP after HIFU-PA from 2012 to 2018. Continence and erectile-function were reported pre-HIFU, pre-sRARP, 3-months post-sRARP and 12-months post-sRARP. Complications, PSMs and need for subsequent ADT/radiotherapy were assessed. RESULTS: 45 men were suitable for inclusion and had sufficient data for analyses. Median duration from HIFU to sRARP was 30.0 months and median follow-up post-sRARP was 17.7 months. Median age, PSA and ISUP group were 63.0 yrs., 7.2 ng/mL and 2; 88.9% were cT2. Median operative-console time, blood loss and hospital stay were 140 min, 200 ml and 1 day respectively. Clavien-Dindo grade 1, 2 and 3 complications 90d) complications occurred in 13.2%. At sRARP pathology, ISUP 3-5 occurred in 51.1%, pT3a/b in 64.5%, and PSMs in 44.4% (37.5% for pT2, 48.3% for pT3). Of men with > 3-months follow-up after sRARP, 26.3% underwent adjuvant radiotherapy/ADT for residual disease or adverse pathologic features; 5.3% experienced BCR requiring salvage ADT/radiotherapy. Freedom from ADT/radiotherapy was 66.7% at 12-months. Pad-free rates were 100% pre-HIFU, 95.3% post-HIFU, 29.4% 3-months post-sRARP, and 65.5% 12-months post-sRARP. Median IIEF-5 scores pre-HIFU, post-HIFU, 3- and 12-months post-sRARP were 23.5, 16, 5 and 5, respectively. Potency rates were 81.8, 65.5, 0 and 0%, respectively. Bilateral/unilateral nerve sparing were feasible in 7%/22%. CONCLUSION: Salvage RARP was safe with acceptable but sub-optimal continence and poor sexual-function and poor oncologic outcomes. One in three men required additional treatment within 12-months. This information may aid men and urologists with treatment selection and counselling regarding primary HIFU-PA vs primary RARP and when considering salvage RARP

Salvage Hemiablation High Intensity Focused Ultrasound for unilateral radio-recurrent prostate cancer|Hémiablation prostatique de sauvetage par des ultrasons focalisés à haute intensité pour des récidives unilatérales après radiothérapie prostatique

Objective. - To report the oncological and functional outcomes of salvage hemiablation high-intensity focused ultrasound (HIFU) in patients with unilateral radio-recurrent prostate cancer.Patients and methods. - Patients with biochemical recurrence (BCR) after primary radiation therapy and evidence of unilateral organ confined recurrence based on a complete match between mpMRI and MRI targeted biopsies were included. Patients with distant metastasis were excluded. Patients were followed with serial serum PSA determinations. BCR were defined using the Phoenix criteria. Complications were graded according to the Clavien score. IIEF-5 question-naire was used to assess erectile dysfunction. Urinary incontinence was reported using physician reported rates.Results. - A total of 10 consecutive patients (median age: 71 years, IQR: 69-76) were prospectively enrolled. The median pre-treatment PSA and post-treatment PSA nadir were 3.1 ng/mL (IQR: 1.54-8.59) and 1.52 ng/mL (IQR: 0.76-2.2), respectively. At a median follow-up of 41.5 (IQR: 18-58) months, 50% of patients experience BCR. BCR free-survival rates at 24 and 36 months were 75% (CI95%: 31-93) and 60% (CI95%: 20-85), respectively. Urinary in continence grade II occurred in two patients and the remaining patients were pad-free. One patient developed de novo erectile dysfunction requiring PDE5I. The erectile function scores decreased from a mean of 10.1 to 8.7.Conclusion. - Hemiablation HIFU is an alternative to whole gland therapy in patients with unilateral radio- recurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves functional outcomes. (C) 2019 Elsevier Masson SAS. All rights reserved

The role of perilesional and multiparametric resonance imaging-targeted biopsies to reduce the risk of upgrading at radical prostatectomy pathology: A retrospective monocentric study

Purpose: To evaluate histopathologic upgrading between biopsy methods and whole-mount prostatectomy specimens in International Society of Urological Pathology grade group.Methods: Overall, 134 patients, including 175 magnetic resonance imaging (MRI)-suspicious lesions, diagnosed on MRI-targeted (TB) and systematic (SB) biopsies before radical prostatectomy were retrospectively analyzed from a prospectively maintained database. Perilesional (PLB) and "extended" perilesional (ePLB) biopsies were defined as those taken within a circumferential zone of 5 and 10 mm around magnetic resonance imaging (MRI)-suspicious lesion respectively. Proportion of upgrading at prostatectomy pathology were compared between TB, TB + PLB, TP + ePLB and TB + SB. Uni- and multivariable logistic regressions assessed predictors of upgrading for TB + ePLB method.Results: Focusing on index lesion, median (interquartile range) number of cores taken was 4 (3-4) for TB, 5 (4-6) for TB + PLB, 6 (5 -8) for TB + ePLB and 12 (12-15) for TB + SB. A higher upgrading proportion was detected upon comparing TB and TB + PLB methods to TB + SB (32 vs. 19%, P = 0.001, 26 vs. 19%, P = 0.04, respectively). Conversely, no significant difference was found between TB + ePLB compared to TB + SB (23 vs. 19%, P = 0.2). Proportion of downgrading was similar regardless of biopsy method (all P > 0.1). At multivariable analysis, Prostate Imaging-Reporting and Data System Steering score, total number of positive ePLB cores and International Society of Urological Pathology Grade Group were independent predictors of upgrading (all P = 0.03). Similar results were found by adding data from non-index lesions.Conclusion: Our finding suggest that MRI-targeted biopsies associated with perilesional sampling in a circumferential zone of 10 mm reduced upgrading proportion and showed similar accuracy as the current gold standard combination. Further prospective studies comparing biopsy methods are expected to validate this diagnostic strategy. (C) 2022 Elsevier Inc. All rights reserved

Constitutive androstane receptor (Car)-driven regeneration protects liver from failure following tissue loss

Background & Aims Liver can recover following resection. If tissue loss is too excessive, however, liver failure will develop as is known from the small-for-size-syndrome (SFSS). The molecular processes underlying liver failure are ill-understood. Here, we explored the role and the clinical potential of Nr1i3 (constitutive androstane receptor, Car) in liver failure following hepatectomy. Methods Activators of Car, various hepatectomies, Car-/- mice, humanized CAR mice, human tissue and ex vivo liver slice cultures were used to study Car in the SFSS. Pathways downstream of Car were investigated by in vivo siRNA knockdown. Results Excessive tissue loss causing liver failure is associated with deficient induction of Car. Reactivation of Car by an agonist normalizes all features associated with experimental SFSS. The beneficial effects of Car activation are relayed through Foxm1, an essential promoter of the hepatocyte cell cycle. Deficiency in the CAR-FOXM1 axis likewise is evident in human SFSS. Activation of human CAR mitigates SFSS in humanized CAR mice and improves the culture of human liver slices. Conclusions Impaired hepatic Car-Foxm1 signaling provides a first molecular characterization of liver that fails to recover after tissue loss. Our findings place deficient regeneration as a principal cause behind the SFSS and suggest CAR agonists may bear clinical potential against liver failure. Lay summary The unique regenerative capacity of liver has its natural limits. Following tissue loss that is too excessive, such as through extended resection in the clinic, liver failure may develop. This is known as small-for-size-syndrome (SFSS) and represents the most frequent cause of death due to liver surgery. Here we show that deficient induction of the protein Car, a central regulator of liver function and growth, is a cause of liver failure following extended resection; reactivation of Car through pharmacological means is sufficient to prevent or rescue the SFS

Radiomics of liver MRI predict metastases in mice

Background The purpose of this study was to investigate whether any texture features show a correlation with intrahepatic tumor growth before the metastasis is visible to the human eye. Methods Eight male C57BL6 mice (age 8-10 weeks) were injected intraportally with syngeneic MC-38 colon cancer cells and two mice were injected with phosphate-buffered saline (sham controls). Small animal magnetic resonance imaging (MRI) at 4.7 T was performed at baseline and days 4, 8, 12, 16, and 20 after injection applying a T2-weighted spin-echo sequence. Texture analysis was performed on the images yielding 32 texture features derived from histogram, gray-level co-occurrence matrix, gray-level run-length matrix, and gray-level size-zone matrix. The features were examined with a linear regression model/Pearson correlation test and hierarchical cluster analysis. From each cluster, the feature with the lowest variance was selected. Results Tumors were visible on MRI after 20 days. Eighteen features from histogram and the gray-level-matrices exhibited statistically significant correlations before day 20 in the experiment group, but not in the control animals. Cluster analysis revealed three distinct clusters of independent features. The features with the lowest variance were Energy, Short Run Emphasis, and Gray Level Non-Uniformity. Conclusions Texture features may quantitatively detect liver metastases before they become visually detectable by the radiologist