Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p = .03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Surgical complications risk in obese and overweight recipients for kidney transplantation: a predictive morphometric model based on sarcopenia and vessel-to-skin distance.

PURPOSE: Sarcopenia or adipose tissue distribution within obese and overweight renal transplanted have been poorly evaluated. Our objective was to evaluate morphometric markers to predict surgical complications in kidney transplantation. METHODS: We retrospectively included patients with a BMI > 25 kg/m2 undergoing kidney transplantation from 2012 to 2017. Following measurements were performed on CT-scan sections: Sub-cutaneous Adipose Tissue surface (SAT), Visceral Adipose Tissue surface (VAT), Vessel-to-Skin distance (VSK), Abdominal Perimeter (AP), and Psoas surface. A multivariable logistic regression model with BMI was compared to a model containing morphometric variables to determine the best predictive model for surgical complications. RESULTS: 248 patients were included, 15 (6%) experienced transplant nephrectomy, 18 (7.3%) urinary leakage, and 29 (11.7%) subcapsular renal hematoma. Multivariable logistic regression evidenced that sarcopenia and VSK were risk factors of surgical complication within a year post-transplantation (respectively, OR = 0.9, 95%CI (0.8-0.9), p = 0.04 and OR = 1.2, 95%CI (1.1-1.3), p = 0.002). Area under the curve for a predictive model including VSK, age and psoas surface was 0.69, whereas BMI model was 0.65. CONCLUSION: Combined morphometric parameters of obesity were associated with surgical complications in kidney transplantation. Morphometric threshold may provide a more accurate and objective criteria than BMI to evaluate kidney transplantation outcomes. External validation is needed.

The male external urethral sphincter is autonomically innervated.

INTRODUCTION: The aim of the present study was to describe autonomic urethral sphincter (US) innervation using specific muscular and neuronal antibody markers and 3D reconstruction. MATERIAL AND METHODS: We performed en-bloc removal of the entire pelvis of three male human fetuses between 18 and 40 weeks. Serial whole mount sections (5 µm intervals) were stained and investigated. The sections were stained with Masson's trichrome and Eosin Hematoxylin, and immunostained with: anti-SMA antibody for smooth muscle; anti-S100 antibody for all nerves; and anti-PMP22 antibody, anti-TH antibody, anti-CGRP antibody, anti-NOS antibody for somatic, adrenergic, sensory and nitrergic nerve fibers, respectively. The slides were digitized for 3D reconstruction to improve topographical understanding. An animated reconstruction of the autonomic innervation of the US was generated. RESULTS: The external and internal US are innervated by autonomic nerves of the inferior hypogastric plexus (IHP). These nerves are sympathetic (positive anti-TH antibody), sensory (positive anti-CGRP antibody), and nitrergic (positive anti-NOS antibody). Some autonomic fibers run within the neurovascular bundles, posterolaterally. Others run from the IHP to the posteromedial aspect of the prostate apex, above an through the rectourethral muscle. The external US is also innervated by somatic nerves (positive anti-PMP22 antibody) arising from the pudendal nerve, joining the midline but remaining below the rectourethral. CONCLUSIONS: This study provides anatomical evidence of an autonomic component in the innervation of the external US that travels in the neurovascular bundle. During radical prostatectomy, the rectourethral muscle and the neurovascular bundles are to be preserved, particularly during apical dissection.

IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?

Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15's renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-ß (TGF-ß)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD.

Temporary contraindication of obese recipients in kidney transplantation: A new morphometric tool for decision support.

BACKGROUND: Morbid obesity, based on body mass index (BMI) and/or clinical examination, can be a temporary contraindication (TCI) of kidney transplantation. However, BMI alone does not evaluate the intra- or extra-peritoneal distribution of fatty tissue, and clinical examination alone is subjective. The objective was to evaluate the interest of morphometric criteria to ensure reproducible and consensual decision of TCI. METHODS: We retrospectively included patients with a BMI >30 transplanted or temporarily contraindicated because of their weight from 2012 to 2017. The following measurements were performed on CT scan sections using a semiautomatic Hounsfield density detection software: subcutaneous adipose tissue surface (SAT), visceral adipose tissue surface (VAT), vessel-to-skin distance (VSK), abdominal perimeter (AP), and psoas index. Performance of morphometric measures to predict TCI was assessed through ROC analysis. RESULTS: Ninety-seven patients were included: 76 kidney transplant recipients and 21 on the TCI list. The area under the curve (AUC, 95%CI) for the BMI model to predict TCI was 0.81 (0.72-0.90). A 5-variable model including BMI, VAT, VSK, AP, and age gave an AUC of 0.88 (0.78-0.98). CONCLUSIONS: Morphometric obesity parameters are associated with TCI decision-making for kidney transplantation: When combined with BMI in a "morphometric tool," they were predictive of a TCI decision.

Epidemiology, biology and treatment of sarcomatoid RCC: current state of the art.

Long recognized to confer an extremely poor prognosis, sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) is a tumor phenotype that is finally beginning to be better understood on the molecular and genetic levels. With an overall incidence that ranges from 1 to 32% depending on associated RCC subtype, the survival of sarcomatoid RCC patients rarely exceeds 2 years. The main reasons for its poor outcome include its aggressive biology, its tendency to present at an advanced or metastatic stage at the time of diagnosis, its high rate of tumor recurrence after nephrectomy, and its limited response to systemic therapies. Molecular pathology studies suggest that sarcomatoid dedifferentiation originates from a focal epithelial-mesenchymal transition (EMT) arising in the carcinomatous component of the tumor. It is hoped that the growing understanding of the molecular biology of sRCC will soon make it possible to adapt treatments based on the identification of actionable tumor alterations. The deliberate inclusion of these patients in the multicenter clinical trials of immune, targeted and combination therapies is a necessary next step in pioneering future treatment strategies.

Renal outcome after simultaneous heart and kidney transplantation.

Simultaneous heart-kidney transplant (HKTx) is a valid treatment for patients with coexisting heart and renal failure. The aim of this study was to assess renal outcome in HKTx and to identify predictive factors for renal loss. A retrospective study was conducted among 73 HKTx recipients: Donors' and recipients' records were reviewed to evaluate patients' and renal transplants' survival and their prognostic factors. The mean follow-up was 5.36 years. Renal primary non-function occurred in 2.7%, and complications Clavien IIIb or higher were observed in 67.1% including 16 (22%) postoperative deaths. Five-year overall survival and renal survival were 74.5% and 69.4%. Among survivors, seven returned to dialysis during follow-up. The postoperative use of ECMO (HR = 6.04, P = 0.006), dialysis (HR = 1.04/day, P = 0.022), and occurrence of complications (HR = 31.79, P = 0.022) were independent predictors of postoperative mortality but not the history of previous HTx or KTx nor renal function prior to transplantation. History of KTx (HR = 2.52, P = 0.026) and increased delay between the two transplantations (HR = 1.25/hour, P = 0.018) were associated with renal transplant failure. HKTx provides good renal transplant survival and function, among survivors. Early mortality rate of 22% underlines the need to identify perioperative risk factors that would lead to more judicious and responsible allocation of a scarce resource.

Detailed muscular structure and neural control anatomy of the levator ani muscle: a study based on female human fetuses.

BACKGROUND: Injury to the levator ani muscle or pelvic nerves during pregnancy and vaginal delivery is responsible for pelvic floor dysfunction. OBJECTIVE: We sought to demonstrate the presence of smooth muscular cell areas within the levator ani muscle and describe their localization and innervation. STUDY DESIGN: Five female human fetuses were studied after approval from the French Biomedicine Agency. Specimens were serially sectioned and stained by Masson trichrome and immunostained for striated and smooth muscle, as well as for somatic, adrenergic, cholinergic, and nitriergic nerve fibers. Slides were digitized for 3-dimensional reconstruction. One fetus was reserved for electron microscopy. We explored the structure and innervation of the levator ani muscle. RESULTS: Smooth muscular cell beams were connected externally to the anococcygeal raphe and the levator ani muscle and with the longitudinal anal muscle sphincter. The caudalmost part of the pubovaginal muscle was found to bulge between the rectum and the vagina. This bulging was a smooth muscular interface between the levator ani muscle and the longitudinal anal muscle sphincter. The medial (visceral) part of the levator ani muscle contained smooth muscle cells, in relation to the autonomic nerve fibers of the inferior hypogastric plexus. The lateral (parietal) part of the levator ani muscle contained striated muscle cells only and was innervated by the somatic nerve fibers of levator ani and pudendal nerves. The presence of smooth muscle cells within the medial part of the levator ani muscle was confirmed under electron microscopy in 1 fetus. CONCLUSION: We characterized the muscular structure and neural control of the levator ani muscle. The muscle consists of a medial part containing smooth muscle cells under autonomic nerve influence and a lateral part containing striated muscle cells under somatic nerve control. These findings could result in new postpartum rehabilitation techniques.

Functional and structural microanatomy of the fetal sciatic nerve.

INTRODUCTION: The ultrastructure of a nerve has implications for surgical nerve repair. The aim of our study was to characterize the fascicular versus fibrillar anatomy and the autonomic versus somatic nature of the fetal sciatic nerve (SN). METHODS: Immunohistochemistry for vesicular acetylcholine transporter, tyrosine hydroxylase, and peripheral myelin protein 22 was performed to identify cholinergic, adrenergic, and somatic axons, respectively, in the human fetal SN. Two-dimensional (2D) analysis and 3D reconstructions were performed. RESULTS: The fetal SN is composed of one-third stromal tissue and two-thirds neural tissue. Autonomic fibers are predominant over somatic fibers within the neural tissue. The distribution of somatic fibers is initially random, but then become topographically organized after intra- and interfascicular rearrangements have occurred within the nerve. CONCLUSIONS: The fetal model presents limitations but enables illustration of the nature of the nerve fibers and the 3D fascicular anatomy of the SN. Muscle Nerve 56: 787-796, 2017.

Neural supply of the male urethral sphincter: comprehensive anatomical review and implications for continence recovery after radical prostatectomy.

PURPOSE: To review the anatomical facts of urethral sphincter (US) innervation discovered over the last three decades and to determine the implications for continence recovery after radical prostatectomy (RP). METHODS: Using the PubMed® database, we searched for peer-reviewed articles in English between January 1985 and September 2015, with the following terms: 'urethral sphincter,' 'urethral rhabdosphincter,' 'urinary continence and nerve supply' and 'neuroanatomy and nerve sparing.' The anatomical methodology, number of bodies examined, data, figures, relevant facts and text were analyzed. RESULTS: Seventeen articles on 254 anatomical subjects were reviewed. Coexisting pathways were described in every article. Dissection, histology, simulation or electron microscopy evidence supported arguments for somatic and autonomic pathways. From the most to the least substantiated, somatic sphincteric fibers were described extra- or intrapelvic as: direct from the distal pudendal nerve (PuN), recurrent from the dorsal nerve of the penis, from the proximal PuN with an intrapelvic course, extrapudendal somatic fibers dispersed among autonomic pelvic fibers. From the pelvic plexus, or from the neurovascular bundles, autonomic fibers to the US have been described in 13 of the reviewed articles, with at least each of the available anatomical methods. CONCLUSION: Because continence depends on a number of factors, it is challenging to delineate the specific impact of periprostatic nerve sparing on continence, but the anatomical data suggest that RP surgeons should steer toward the preservation and protection of these nerves whenever possible.

Origin and nature of pelvic ureter innervation.

AIMS: Innervation of the pelvic ureter traditionally comes from the pelvic plexus. This innervation is independent: adrenergic and cholinergic. The purpose of this study was to describe more precisely the origin and nature of its innervation (adrenergic, cholinergic, nitrergic, and somatic). METHODS: Six specimens of normal human fetal pelvis (four male and two female) from 20 to 30 weeks gestation were studied. The sections of these fetuses, carried out every 5 µm without interval, were treated with Hematoxylin Eosin (HE), with Masson's trichrome (TriM), immunolabeling of smooth muscle cells with smooth anti-actin, of nerves with anti-S100 protein, anti-tyrosine hydroxylase, anti-VAChT, anti-nNOS, and with anti- peripheral myelin protein 22 (PMP 22). The slides were scanned and two-dimensional images reconstructed in 3D, and analyzed. RESULTS: The terminal pelvic ureter travels above and inside the inferior hypogastric plexus (IHP). The nerve fibers that innervate the ureterovesical junction come mainly from the superior hypogastric plexus (SHP) which gives off the hypogastric nerves and pelvic branches of the sacral plexus that form the IHP. Most nerve fibers meet below the ureter, behind the bladder to form an ascending bundle, which innervates the pelvic ureter. Immunohistochemical analysis shows that the nerves of the pelvic ureter consist of adrenergic, cholinergic, and nitrergic fibers. CONCLUSION: The innervation of the distal ureter depends mainly on the SHP. This innervation is adrenergic, cholinergic, and nitrergic. It innervates the pelvic ureter in an ascending manner. This anatomical information can change rectal resection and ureteral reimplantation techniques and drug treatments for pelvic ureter stones. Neurourol. Urodynam. 36:271-279, 2017. © 2015 Wiley Periodicals, Inc.

Levator ani muscle innervation: Anatomical study in human fetus.

AIMS: To characterize the nature and function of the levator ani muscle innervation pathways and to perform a comprehensive three-dimensional reconstruction of female pelvic innervation. METHODS: A computer-assisted anatomical dissection protocol was applied to seven female human fetuses, after approval from the national biomedicine agency. Specimens were serially sectioned and immunostained for overall (antibody against protein S100), somatic (antibody against peripheral myelin protein 22), adrenergic (antibody against tyrosine hydroxylase), cholinergic (antibody against vesicular acetylcholine transferase), and nitrergic (antibody against the neural isoform of nitric oxide synthase) nerve fibers. Slides were digitized for three-dimensional reconstructions using WinSurf®. RESULTS: Three main nerve pathways to the levator ani muscle were observed: the levator ani nerve, the pudendal nerve, and the inferior hypogastric plexus. The pudendal nerve was both somatic and autonomic, located below the levator ani muscle (infralevator pathway), supplying innervation to the inferior aspect of the levator ani muscle. The levator ani nerve was solely somatic, located above the levator ani muscle (supralevator pathway), supplying innervation to the superior aspect of the levator ani muscle. The inferior hypogastric plexus nerve fibers were solely autonomic, located in between the levator ani muscle and pelvic organs (endolevator pathway), supplying innervation to the medial portion of the levator ani muscle. CONCLUSIONS: Our study provides a new representation of levator ani muscle innervation with three nerve pathways, and the levator ani muscle itself as an anatomical landmark.

The male bulbospongiosus muscle and its relation to the external anal sphincter.

PURPOSE: The bulbospongiosus muscle is part of the superficial muscular layer of the perineum and pelvic floor. Its morphology remains controversial in the literature. Therefore, we reinvestigated the fascial arrangement and fiber courses of the bulbospongiosus muscle and its topographical relation to the external anal sphincter. MATERIALS AND METHODS: The perineum was dissected in 9 male cadavers (mean ± SD age 78.3 ± 10.7 years). Select samples were obtained for histology and immunohistochemistry. In 43 patients (mean age 60.7 ± 12 years) the topographical relation between the bulbospongiosus muscle and the external anal sphincter was determined by magnetic resonance imaging. RESULTS: The perineum contains several fascial layers consisting of elastic and collagen fibers as well as bundles of smooth muscle cells. The bulbospongiosus muscle was subdivided into a ventral and dorsal portion, which developed in 4 variants. The ventral insertion formed a morphological unity with the ischiocavernous muscle while the dorsal origin had a variable relation to the external anal sphincter (5 variants). A muscle-like or connective tissue-like connection was frequently present between the muscles. However, in some cases the muscles were completely separated. CONCLUSIONS: We suggest a concept of variations of bulbospongiosus muscle morphology that unifies the conflicting literature. Its ventral fiber group and the ischiocavernosus muscle form a functional and morphological unity. While the bulbospongiosus muscle and the external anal sphincter remain independent muscles, their frequent connection might have clinical implications for perineal surgery and anogenital disorders.

Are urologists and radiologists equally effective in determining the RENAL Nephrometry score?

BACKGROUND: The RENAL nephrometry score (RNS) allows description of the anatomy and the complexity of renal masses. This study aimed to investigate the interobserver reproducibility of the RNS between a radiologist and a urologist. METHODS: The computed tomography (CT) scans of patients undergoing partial nephrectomy in the authors' department between June 2010 and June 2013 were analyzed for determination of the RNS by a urologist and a radiologist blinded to the medical records. Cohen's kappa coefficient was used for interobserver reproducibility assessment. Correlations with per- and postoperative complication rates and renal function were assessed. RESULTS: The study included 52 consecutive patients with a mean age of 55 years. The average score was 7.4 ± 1.7 for the urologist and 7.3 ± 1.5 for the radiologist. The Cohen's kappa was 0.81 for R, 0.47 for E, 0.63 for N, 0.28 for A, and 0.21 for L. The Pearson's coefficient for the total RNS was 0.70. The operative time and the occurrence of major complications were significantly correlated with the complexity assessed by the score of both observers. In the univariate analysis, the RNS, the American Society of Anesthesiologists score, and the patient's age were significantly associated with major complication rates. In the multivariate analysis, the RNS remained significantly associated with major complications. No significant difference in postoperative renal function according to complexity group was found by either the urologist or the radiologist. CONCLUSIONS: The reproducibility of the RNS between the radiologist and the urologist was not very good, especially for some items referring to the location of the tumor, although the major complication rates were significantly associated with the RNS for both observers.

The visceromotor and somatic afferent nerves of the penis.

INTRODUCTION: Innervation of the penis supports erectile and sensory functions. AIM: This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. METHODS: Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). MAIN OUTCOME MEASURES: The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. RESULTS: Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. CONCLUSIONS: There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment.

Are warm ischemia and ischemia time still predictive factors of poor renal function after partial nephrectomy in the setting of elective indication?

PURPOSE: To evaluate renal function and to identify factors associated with renal dysfunction in the elective indications setting of nephron-sparing surgery (NSS). METHODS: We retrospectively reviewed operative data and glomerular filtration rate (GFR) of 519 patients treated by NSS in an elective indications setting between 1984 and 2006 in eight academic institutions. A GFR decrease under the thresholds of 60 or 45 ml/min at last follow-up was considered a significant renal dysfunction. Univariate and multivariate regression models were used to assess multiple factors of renal function. RESULTS: Median age, tumor size, preoperative, and final GFR were 59.5 years (27-84), 2.7 cm (0.9-11), 79 (45-137), and 69 ml/min (p < 0.0001), respectively, with a median follow-up of 23 months (1-416). Hilar clamping was performed in 375 procedures (72.3 %). Significant GFR decrease was observed in 89 patients (17.1 %). Median operating time, hilar clamping duration, and blood loss were 137 min (55-350), 22 min (0-90), and 150 ml (0-4150), respectively. At univariate analysis, age (p = 0.002), preoperative GFR (p = 0.001), pedicular clamping (p = 0.01), and ischemia time (p = 0.0001) were associated with renal dysfunction. Age (p = 0.004; HR 1.2), pedicular clamping (p = 0.04; HR 1.3), and ischemia time (p = 0.0001; HR 1.8) remained independent risk factors for renal function deterioration in multivariate analysis. CONCLUSION: Non- or time-limited clamping techniques are associated with preservation of renal function in the elective indications setting of NSS.

DNA comparison between operative and biopsy specimens to investigate stage pT0 after radical prostatectomy.

PURPOSE: The aim was to eliminate, by DNA comparison, any identity mismatch between operative and biopsy specimens and to analyse the determinants of all pT0 prostate cancers occurred in a single institution. METHODS: All prostate pT0 cases in a single institution over 20 years were investigated. None of the patients had been diagnosed after a transurethral resection of the prostate nor had they received neoadjuvant hormonal treatment. The biopsies performed in other centres had been referred for a centralized pathologic re-analysis. DNA analysis was performed in samples from operative and biopsy specimens, and pairs of tissues were blindly constituted. Correct matching was verified in each pair and compared to the original database in order to comment on the occurrence of identity mismatches in the series. RESULTS: Nineteen patients (0.77 %) had been diagnosed as having pT0 prostate cancer among the 2,462 RP procedures performed over 19 years. The biopsy re-analysis invalidated the initial diagnosis of prostate cancer in one biopsy set performed elsewhere. Among 12 entirely processed cases, the biochemistry procedure evaluated as "very unlikely" the occurrence of an error in tissue identification in the biopsy setting, during the surgical procedure or the pathological analysis. No identification error of tissue samples was established in this first verified pT0 series. CONCLUSIONS: Although it must be suspected, specimen identification error was not a cause for pT0 prostate cancer. Only after a full pathological and DNA verification, the pT0 stage remains a sole entity, unexplained in most cases.

Local recurrence after radical nephrectomy for kidney cancer: management and prediction of outcomes. a multi-institutional study.

BACKGROUND: Local recurrence (LR) after radical nephrectomy (RN) for kidney cancer is uncommon. Our objectives were to analyse characteristics and therapeutic options of LR after RN and to identify survival prognostic factors. MATERIALS AND METHODS: From a multi-institutional retrospective database, we identified 72 patients who experienced LR after RN. RESULTS: Mean time to LR was 26.5 ± 3.3 months. The location of the recurrence was renal fossa, regional lymph node, homolateral adrenal and both renal fossa and regional lymph node for 43 (59.7%), 27 (37.5%), 9 (12.5%) and 7 (9.7%) patients, respectively. Patients were treated by surgery, systemic therapies, combination of therapies and palliative treatment in 24 (33.3%), 18 (25%), 24 (33.3%) and 6 (8.4%) cases, respectively. Within a mean follow-up of 26.4 ± 3.3 months from the date of local recurrence, 12 (16.6%) patients were alive without disease, 30 (41.7%) patients were alive with disease, 30 patients (41.6%) died including 28 (38.8%) from the disease. In multivariate analysis, time to recurrence <1 year (P < 0.001; HR: 4.81) and surgical treatment (P = 0.027; HR: 0.33) were predictive factors. CONCLUSIONS: Local recurrence after radical nephrectomy is associated with poor prognosis. The time to recurrence and the completeness of the surgical treatment are major prognostic factors.

Subcostal TAP block: one or two sequential injections? A cadaveric study.

BACKGROUND AND OBJECTIVES: The subcostal transversus abdominis plane block (scTAPB) provides analgesia to the anterior abdominal wall but analgesic spread following a single injection remains modest and variable. The oblique scTAPB, which is performed with a continuous injection during needle progression into the TAP along the oblique subcostal line, may extend the block to the whole anterior abdominal wall but needle progression by hydrodissection may be difficult, explaining why this block is not widely used. This study investigated if two sequential scTAPB injections (2scTAPI) may reach more nerves than a single scTAPB (1scTAPI). METHODS: After institutional approval and under ultrasound guidance, a single injection of 20 mL of blue dye was performed in 16 cadaveric subjects into the TAP along the costal margin and lateral to the semilunaris line (1scTAPI). On the opposite side, a 20 mL of green solution was split into two injections (2scTAPI), using one injection medial and one lateral to the semilunaris line. Dye spread was assessed via gross anatomical dissection using an indirect method to quantify the involvement of the anterior cutaneous branches of the intercostal nerves with each technique. A nerve was considered stained if the dye was observed in the TAP, reaching the costal margin aligned with the bony extremity of its corresponding rib. RESULTS: According to the spread to the costal margin, the estimated median number of consecutive nerves reached by dye after 2scTAPI was 5 (IQR 5-6) vs 3 (IQR 3-4) for 1scTAPI (p=0.00001). Spread after 2scTAPI suggested coverage of nerves originating from T8 to T12 in 85% of the subjects, and from T7 to T12 in 5 out of 17 cases. Spread following the 1scTAPI suggested coverage of nerves from T9 to T11 in most cases. CONCLUSIONS: In a cadaveric model, a larger spread at the costal margin was obtained after 2scTAPI, suggesting a greater coverage of anterior branches of abdominal wall nerves compared with 1scTAPI. Clinical studies are needed to confirm these results.