Advanced Insights into Human Uterine Innervation: Implications for Endometriosis and Pelvic Pain.

(1) Background: Understanding uterine innervation, an essential aspect of female reproductive biology, has often been overlooked. Nevertheless, the complex architecture of uterine innervation plays a significant role in conditions such as endometriosis. Recently, advances in histological techniques have provided unprecedented details about uterine innervation, highlighting its intricate structure, distribution, and density. The intricate nature of uterine innervation and its influence on pathologies such as endometriosis has garnered increasing attention. (2) Objectives: This review aims to compile, analyze, and summarize the existing research on uterine innervation, and investigate its implications for the pathogenesis of endometriosis and associated pain. (3) Methods: A systematic review was conducted in line with PRISMA guidelines. Using the PubMed database, we searched relevant keywords such as "uterine innervation", "endometriosis", and "pain association". (4) Results: The initial literature search yielded a total of 3300 potential studies. Of these, 45 studies met our inclusion criteria and were included in the final review. The analyzed studies consistently demonstrated that the majority of studies focused on macroscopic dissection of uterine innervation for surgical purposes. Fewer studies focused on micro-innervation for uterine innervation. For endometriosis, few studies focused on neural pain pathways whereas many studies underlined an increase in nerve fiber density within ectopic endometrial tissue. This heightened innervation is suggested as a key contributor to the chronic pain experienced by endometriosis patients. (5) Conclusions: The understanding of uterine innervation, and its alterations in endometriosis, offer promising avenues for research and potential treatment.

Young urologists and kidney transplantation training: A survey designed by the French Transplantation Committee of the French Association of Urology (CTAFU) and the French Association of Urologists in training (AFUF).

OBJECTIVE: In France, kidney transplantations (KT) are mainly performed by urologist. Young urologists and residents are involved in this activity mostly performed in emergency. How do they feel about KT training? Is KT an attractive part of the urologist activity? METHODS: This survey has been designed in the form of a questionnaire by the French Committee of Kidney Transplantation (CTAFU) and the French Association of Urologists in training (AFUF). It has been sent by e-mail to all the AFUF members. Interest in KT and performance of the training were evaluated. RESULTS: In total, 126 members filed the form. Among the residents, 51.5% feel secure to perform KT at the end of their residency. KT is considered as an interesting surgery for 92.1% of the participants: 76.5% are willing to get involved in KT during their residency/fellowship. Among the participants, 44% are willing to continue a long-term involvement. Among the residents, 65.9% consider their practical training insufficient: 56.8% have been supervised for a KT performance during their residency and 86% declare a lack of practical training and had a patient-based learning. Among the residents, 92.1% declare an insufficient theorical training. Among the residents, 33.3% say the schedules of transplantation limit their interest in KT. Among the participants, 34.4% receive a transplant bonus in addition to the usual on-call salary. CONCLUSION: Young urologists wish to continue their involvement in KT activity, but improved theoretical and practical training are essential. In addition, the conditions under which this activity is performed and remunerated are a matter of concern.

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.

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.

An optimized electrotransformation protocol for Lactobacillus jensenii.

Engineered bacteria are promising candidates for in situ detection and treatment of diseases. The female uro-genital tract presents several pathologies, such as sexually transmitted diseases or genital cancer, that could benefit from such technology. While bacteria from the gut microbiome are increasingly engineered, the use of chassis isolated from the female uro-genital resident flora has been limited. A major hurdle to implement the experimental throughput required for efficient engineering in these non-model bacteria is their low transformability. Here we report an optimized electrotransformation protocol for Lactobacillus jensenii, one the most widespread species across vaginal microflora. Starting from classical conditions, we optimized buffers, electric field parameters, cuvette type and DNA quantity to achieve an 80-fold improvement in transformation efficiency, with up to 3.5·103 CFUs/µg of DNA in L. jensenii ATCC 25258. We also identify several plasmids that are maintained and support reporter gene expression in L. jensenii. Finally, we demonstrate that our protocol provides increased transformability in three independent clinical isolates of L. jensenii. This work will facilitate the genetic engineering of L. jensenii and enable its use for addressing challenges in gynecological healthcare.

Updated National Study of Functional Graft Renal Cell Carcinomas: Are They a Different Entity?

OBJECTIVE: To analyze de novo graft carcinoma characteristics from our updated national multicentric retrospective cohort. METHODS: Thirty-two transplant centers have retrospectively completed the database. This database concerns all kidney graft tumors including urothelial, and others type but excludes renal lymphomas over 31 years. RESULTS: One hundred and fifty twokidney graft carcinomas were diagnosed in functional grafts. Among them 130 tumors were Renal Cell Carcinomas. The calculated incidence was 0.18%. Median age of the allograft at diagnosis was 45.4 years old. The median time between transplantation and diagnosis was 147.1 months. 60 tumors were papillary carcinomas and 64 were clear cell carcinomas. Median tumor size was 25 mm. 18, 64, 21 and 1 tumors were respectively Fuhrman grade 1, 2, 3 and 4. Nephron sparing surgery (NSS) was performed on 68 (52.3%) recipients. Ablative therapy was performed in 23 cases (17.7%). Specific survival rate was 96.8%. CONCLUSION: This study confirmed that renal graft carcinomas are a different entity: with a younger age of diagnosis; a lower stage at diagnosis; a higher incidence of papillary subtypes.

Anatomic and functional mapping of human uterine innervation.

OBJECTIVE: To better understand the physiology of pain in pelvic pain pathological conditions, such as endometriosis, in which alterations of uterine innervation have been highlighted, we performed an anatomic and functional mapping of the macro- and microinnervation of the human uterus. Our aim was to provide a 3-dimensional reconstruction model of uterine innervation. DESIGN: This was an experimental study. We dissected the pelvises of 4 human female fetuses into serial sections, and treated them with hematoxylin and eosin staining before immunostaining. SETTING: Academic Research Unit. PATIENTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Detection of nerves (S100 +) and characterization of the types of nerves. The slices obtained were aligned to construct a 3-dimensional model. RESULTS: A 3-dimensional model of uterine innervation was constructed. The nerve fibers appeared to have a centripetal path from the uterine serosa to the endometrium. Within the myometrium, innervation was dense. Endometrial innervation was sparse but present in the functional layer of the endometrium. Overall innervation was richest in the supravaginal cervix and rarer in the body of the uterus. Innervation was rich particularly laterally to the cervix next to the parametrium and paracervix. Four types of nerve fibers were identified: autonomic sympathetic (TH+), parasympathetic (VIP+), and sensitive (NPY+, CGRP1+ and VIP+). They were found in the 3 portions and the 3 layers of the uterus. CONCLUSIONS: We constructed a 3-dimensional model of the human uterine innervation. This model could provide a solid base for studying uterine innervation in pathologic situations, in order to find new therapeutic approaches.

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.

Pre-transplant morphometry by computed tomography scan and post-transplant dialysis risk in overweight or obese kidney transplant recipients.

PURPOSE: Adipose distribution and sarcopenia could better assess kidney transplantation outcomes than body mass index (BMI) and have been poorly evaluated among obese and overweight recipients. We aimed to evaluate morphometric radiologic markers to predict post-operative dialysis within this population. METHODS: We conducted a retrospective study including patients with a BMI > 25 kg/m2 undergoing kidney transplantation during 5 years. Subcutaneous adipose tissue surface (SAT), visceral adipose tissue surface (VAT), and psoas surface were measured on CT scans sections. A model predictive of post-transplantation dialysis was elaborated through a multivariable logistic regression and was compared to a model including only BMI. RESULTS: Overall, 248 patients were included whom mean (SD) BMI and age were, respectively, 29.7 kg/m2 (3.6) and 56 years (12.7). Of them, 83 (33.5%) needed dialysis: 14 (5.7%) for primary kidney failure and 69 (27.8%) for delayed kidney function. On multivariable analysis, SAT, VAT and deceased donor were significantly associated with post-operative dialysis (respectively, OR [95%CI]:1.6 [1.1-2.6], 1.6[1.1-2.6], and 7.5 [1.6-56]). The area under the curve of this predictive model was 0.70 versus 0.64 for a BMI-based model. CONCLUSION: High VAT and SAT were associated with post-transplantation dialysis. A predictive model based on these morphometrics could provide a better appreciation of graft recovery after transplantation among obese and overweight recipients. External validation is needed.

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.

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.

De novo renal carcinoma arising in non-functional kidney graft: a national retrospective study.

AIM: Characteristics of renal carcinoma arising in non-functional graft in renal transplant recipients (RTR) are unknown. We studied a large national retrospective cohort to analyze circumstances of diagnosis, treatment and outcome compared to the literature. METHODS: Study included all RTR presenting with kidney graft tumors irrespective of the histology, except those with lymphoma and including those tumors arising in non-functional renal graft. Between January 1988 and December 2018, 56,806 patients had renal transplantation in the 32 centers participating in this study. Among this cohort, 18 renal graft tumors were diagnosed in non-functional grafts. RESULTS: The median patient age at the time of diagnosis was 42.1 years (31.7-51.3). Median age of kidney grafts at the time of diagnosis was 56.4 (23.2-63.4). Eight (44.4%) tumors were discovered fortuitously on renal graft histologic analysis. Fourteen tumors (77.8%) were papillary carcinomas. Two patients had clear cell carcinomas and one patient had a pTa high-grade multifocal urothelial carcinoma in the graft of the upper tract with an in situ carcinoma. CONCLUSION: Renal carcinomas in non-functional grafts are rare entities and most of them are diagnosed fortuitously. Despite the fact that these tumors are small, low grade and with a good prognosis, regular monitoring of non-functional grafts should be performed with at least an annual ultrasonography.

Thoracic paravertebral block: comparison of different approaches and techniques. A study on 27 human cadavers.

BACKGROUND AND OBJECTIVES: The success rate and spread of thoracic paravertebral block (TPVB) are variable and difficult to predict. It is now recommended that an ultrasound guidance technique should replace the traditional landmark technique. The objective was to compare anatomical outcomes of both techniques on cadavers. METHODS: A landmark technique (loss of resistance technique [LOR]) and a USG technique (three approaches: sagittal, transversal in-plane, transverse out-of-plane) were performed on 27 thawed non-embalmed cadavers. Each of the four approaches was performed in each body (T3-T5 and T9-T11 × right and left). A coloured solution (13 mL, saline 0.9%) was injected in the targeted thoracic paravertebral space (TPVS). A successful thoracic paravertebral injection (TPVI) was defined by the presence of dye in at least one TPVS during anatomical dissection. RESULTS: In 104 TPVIs analysed, the overall success rate was 78%. Factors associated with success were: USG versus LOR technique (85% vs. 52%, P < 0.0007), sagittal versus both transversal approaches (93%/81%/83%, P < 0.0007) and right side (86% vs. 66%). The median spread was 2 TPVS (min - max 1-5) with a median cephalad-caudal spread of 5 cm (min - max 1-18). By multivariate analysis, the sagittal approach was an independent factor of success (OR 2.75). Dye spread and pleural entry were influenced by neither the approach nor the site of injection. CONCLUSIONS: Paravertebral spread of TPVI is variable. USG technique has higher anatomical success rates than the LOR technique, the sagittal USG approach being the most successful.

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.

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.

BK virus-associated collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft recipient.

BK polyomavirus (BKV) nephropathy is a major concern in renal transplantation. Its main consequence is graft loss, which occurs in more than 50% of the cases. De novo renal cell carcinoma in renal allograft is a very rare event. Most of these tumors are papillary or clear cell carcinomas. We report herein the first case of collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft adult recipient. Collecting duct carcinoma occurs long after the cure of a BKV nephropathy. At this time, BKV viremia and viruria were negative as well as the immunostaining for SV40 in the non-tumor kidney. The viral oncoprotein Tag persists only in the tumor cells. To preserve pancreas graft function, we maintained immunosuppression levels. After a 9-months follow-up, the evolution was free from clinical and radiological progression. The oncogenic role of BKV remains controversial in human cancers. However, strong experimental data have shown an association between BKV infection and urologic neoplasms. Further works might precise the exact role of polyomaviruses in renal carcinogenesis. In the meantime, clinical vigilance for early diagnostic of these tumors is mandatory after BKV nephropathy.

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.