Search

Background: Management of penile cancer patients has its grey zones. In particular, no strong evidence or recommendations exist regarding the timing of prophylactic lymphadenectomy. Here, we aim to review the impact that the timing of inguinal and pelvic prophylactic lymph node dissection has on patient outcome. Methods: All relevant databases were searched following the preferred reporting items for systematic reviews and meta-analysis guidelines. A narrative review of indications for lymph node dissection and pathological considerations precede a systematic review of the impact of prophylactic lymph node dissection timing on prognosis. The primary endpoint is disease-free and overall survival in patients undergoing early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials, all focusing on the role of inguinal lymph node dissection, are included. Despite the lack of randomized and controlled trials, this review suggests that lymph node dissection should be performed as soon as possible after diagnosis, with 3 months as a realistic cut-off. Conclusions: Survival of penile cancer patients is strictly related to the timing of prophylactic pelvic lymph node dissection. All patients at high risk of nodal metastasis should be offered lymph node dissection within three months of diagnosis, until new predicting tools are validated.

Abstract Background Nivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC. Methods In this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression‐free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated. Results After progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13 months (95% CI: 4‐NR) in actively treated patients and 3 months (95% CI: 2–4) in BSC patients (p = 0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p = 0.03), with no significant differences in PFS (5 and 3 months, 95% CI: 1–6 vs. 2–5; p = 0.6) and OS (12 and 4 months, 95% CI: 3‐NR vs. 2‐NR; p = 0.2). Conclusion After treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC.

Wax models of normal and diseased organs were formerly essential medical teaching tools. The ceroplastic heart models from two 19th century pathology museums at the Universities of Florence (n = 8) and Coimbra (n = 10) were analysed. The Florentine collection comprised congenital malformations as well as infectious and inflammatory disorders. The Coimbra waxworks included congenital defects, cardiac hypertrophy and dilation, valvular pathology and cardiac adiposity. This study focuses on heart diseases and teaching resources in European university hospitals during the 19th century. It also highlights the importance of wax models in medical education both then and today, in an era of informatics and digital photography.

Deleterious aberrations in DNA repair genes are actionable in approximately 25% of metastatic castration-resistant prostate cancers (mCRPC) patients. Homology recombination repair (HRR) is the DNA damage repair (DDR) mechanism most frequently altered in prostate cancer; of note BRCA2 is the most frequently altered DDR gene in this tumor. Poly ADP-ribose polymerase inhibitors showed antitumor activity with a improvement in overall survival in mCRPC carrying somatic and/or germline alterations of HHR. Germline mutations are tested on peripheral blood samples using DNA extracted from peripheral blood leukocytes, while the somatic alterations are assessed by extracting DNA from a tumor tissue sample. However, each of these genetic tests have some limitations: the somatic tests are related to the sample availability and tumor heterogeneity, while the germline testing are mainly related to the inability to detect somatic HRR mutations. Therefore, the liquid biopsy, a non-invasive and easily repeatable test compared to tissue test, could identified somatic mutation detected on the circulating tumor DNA (ctDNA) extracted from a plasma. This approach should better represent the heterogeneity of the tumor compared to the primary biopsy and maybe helpful in monitoring the onset of potential mutations involved in treatment resistance. Furthermore, ctDNA may inform about timing and potential cooperation of multiple driver genes aberration guiding the treatment options in patients with mCRPC. However, the clinical use of ctDNA test in prostate cancer compared to blood and tissue testing are currently very limited. In this review, we summarize the current therapeutic indications in prostate cancer patients with DDR deficiency, the recommendation for germline and somatic-genomic testing in advanced PC and the advantages of the use liquid biopsy in clinical routine for mCRPC.

Although immune checkpoint inhibitors (ICIs) have dramatically revolutionized the field of oncology over the last decade, severe immune-related adverse events (irAEs) are potentially life-threatening. In comparison with toxicities involving the skin, gastrointestinal tract and endocrine system, nephrotoxicity is less common but often underestimated due to difficult diagnosis. Management usually consists of treatment discontinuation and/or corticosteroid use. In this review, we summarize current knowledge of ICI-induced nephrotoxicity, evaluating drawbacks and future perspectives.

BackgroundSudden cardiac arrest (SCA) in young people represents a dramatic event, often leading to severe neurologic outcomes or sudden cardiac death (SCD), and is frequently caused by genetic heart diseases. In this study, we report the results of the Tuscany registry of sudden cardiac death (ToRSADE) registry, aimed at monitoring the incidence and investigating the genetic basis of SCA and SCD occurring in subjects < 50 years of age in Tuscany, Italy.Methods and resultsCreation of the ToRSADE registry allowed implementation of a repository for clinical, molecular and genetic data. For 22 patients, in whom a genetic substrate was documented or suspected, blood samples could be analyzed; 14 were collected at autopsy and 8 from resuscitated patients after SCA. Next generation sequencing (NGS) analysis revealed likely pathogenetic (LP) variants associated with cardiomyopathy (CM) or channelopathy in four patients (19%), while 17 (81%) carried variants of uncertain significance in relevant genes (VUS). In only one patient NGS confirmed the diagnosis obtained during autopsy: the p.(Asn480Lysfs*20) PKP2 mutation in a patient with arrhythmogenic cardiomyopathy (AC).ConclusionSystematic genetic screening allowed identification of LP variants in 19% of consecutive patients with SCA/SCD, including subjects carrying variants associated with hypertrophic cardiomyopathy (HCM) or AC who had SCA/SCD in the absence of structural cardiomyopathy phenotype. Genetic analysis combined with clinical information in survived patients and post-mortem evaluation represent an essential multi-disciplinary approach to manage juvenile SCD and SCA, key to providing appropriate medical and genetic assistance to families, and advancing knowledge on the basis of arrhythmogenic mechanisms in inherited cardiomyopathies and channelopathies.

Urothelial carcinoma of the bladder is one of the most prevalent cancers worldwide, diagnosed as muscle invasive in 25% of cases. Although several studies have demonstrated an overall 5% absolute survival benefit at 5 years with cisplatin-based combination neoadjuvant treatment, administration of chemotherapy prior to radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC) patients is still a matter of debate. This may be due to the perceived modest survival benefit, cisplatin-based chemotherapy ineligibility, or fear of delaying potentially curative surgery in non-responders. However, immunotherapy and novel targeted therapies have shown to prolong survival in advanced disease and are under investigation in the neoadjuvant and adjuvant settings to reduce systemic relapse and improve cure rates. Genomic characterization of MIBC could help select the most effective chemotherapeutic regimen for the individual patient. Large cohort studies on neoadjuvant treatments with immune checkpoint inhibitors (ICIs) and molecular therapies, alone or combined with chemotherapy, are ongoing. In this review, we trace the development of neoadjuvant therapy in MIBC and explore recent advances that may soon change clinical practice.

BackgroundOncocytomas are uncommon benign tumors that arise in various organs and are predominantly composed of oncocytes. Adrenocortical oncocytomas are extremely rare and are generally non-functioning.MethodsWe report the case of a 40-year-old patient with a progressively enlarging left adrenal mass. At the age of 19 he had undergone right adrenalectomy for a cortisol-secreting adenoma. Radiologic features were not typical of an adenoma and positive uptake was detected at 18F-FDG-PET. Because of the uncertain nature of the growing lesion, it was decided to proceed to surgical resection.ResultsThe surgeon managed to remove the left adrenal mass, sparing the normal adrenal gland, and histology was consistent with adrenocortical oncocytoma. Corticosteroid supplementation was prescribed, but at reassessment, adrenal function was found to be preserved and treatment withdrawn.ConclusionsAdrenal oncocytoma is a rare diagnosis, but should be considered in the presence of a growing mass with non-specific radiologic appearance.

Abstract Background ETV4 is one of the ETS proteins overexpressed in prostate cancer (PC) as a result of recurrent chromosomal translocations. In human prostate cell lines, ETV4 promotes migration, invasion, and proliferation; however, its role in PC has been unclear. In this study, we have explored the effects of ETV4 expression in the prostate in a novel transgenic mouse model. Methods We have created a mouse model with prostate-specific expression of ETV4 (ETV4 mice). By histochemical and molecular analysis, we have investigated in these engineered mice the expression of p21, p27, and p53. The implications of our in vivo findings have been further investigated in human cells lines by chromatin-immunoprecipitation (ChIP) and luciferase assays. Results ETV4 mice, from two independent transgenic lines, have increased cell proliferation in their prostate and two-thirds of them, by the age of 10 months, developed mouse prostatic intraepithelial neoplasia (mPIN). In these mice, cdkn1a and its p21 protein product were reduced compared to controls; p27 protein was also reduced. By ChIP assay in human prostate cell lines, we show that ETV4 binds to a specific site (-704/-696 bp upstream of the transcription start) in the CDKN1A promoter that was proven, by luciferase assay, to be functionally competent. ETV4 further controls CDKN1A expression by downregulating p53 protein: this reduction of p53 was confirmed in vivo in ETV4 mice. Conclusions ETV4 overexpression results in the development of mPIN but not in progression to cancer. ETV4 increases prostate cell proliferation through multiple mechanisms, including downregulation of CDKN1A and its p21 protein product: this in turn is mediated through direct binding of ETV4 to the CDKN1A promoter and through the ETV4-mediated decrease of p53. This multi-faceted role of ETV4 in prostate cancer makes it a potential target for novel therapeutic approaches that could be explored in this ETV4 transgenic model.

Objectives: The incidence of prostate cancer in renal transplant recipients (RTRs) is increasing, but few data are available in the literature. In this study, we reviewed the 25-year experience in the management of prostate cancer after kidney transplantation at the Florence Transplant Centre.Methods: We retrospectively reviewed the data from 617 RTR male patients who underwent renal transplantation at our institute between July 1996 and September 2016. Data regarding demographics, renal transplantation, prostate cancer and immunosuppressive treatment were analyzed. The probability of death was estimated by using the Kaplan-Meier method and differences between patients' groups were assessed by the log-rank test.Results: From July 1991 to September 2016, 617 kidney transplantations of male patients were performed at our institute. Among these, 20 patients were subsequently diagnosed with prostate cancer accounting for a cumulative incidence of 3.24%. After a median follow-up of 59 months, 10 patients underwent radical prostatectomy whereas 10 patients underwent primary radiotherapy. A biochemical recurrence was identified in five (25%) patients while a fatal event occurred in 11 (55%) patients. Univariate Cox regression showed that the basal value of PSA >10 ng/ml was the only significant factor negatively affecting the survival of patients.Conclusions: Standard treatments can be proposed to RTR with satisfactory results on both post-operative and oncological outcomes. Further studies are needed to address the issue of prostate cancer screening based on PSA levels and the optimal management of prostate cancer in RTRs.

Fascin-1 (FSCN1) is an actin-bundling protein associated with an invasive and aggressive phenotype of several solid carcinomas, as it is involved in cell cytoskeleton rearrangement and filopodia formation. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by poor prognosis, particularly when metastatic at diagnosis. Radical resection is the only therapeutic option for ACC patients in addition to the adjuvant treatment with mitotane. Novel specific biomarkers suggestive of tumor progression to refine diagnosis and prognosis of patients with advanced ACC are urgently needed. ACC intratumoral FSCN1 has previously been suggested as a valid prognostic marker. In the present study, we identified FSCN1 in the bloodstream of a small cohort of ACC patients (n = 27), through a specific ELISA assay for human FSCN1. FSCN1 can be detected in the serum, and its circulating levels were evaluated in pre-surgery samples, which resulted to be significantly higher in ACC patients from stage I/II and stage III/IV compared with nontumoral healthy controls (HC, n = 4, FI: 5.5 ± 0.8, P

Our understanding of aetiological factors associated with urinary bladder cancer has radically improved over the last decades. Cigarette smoking is considered the most important risk factor, even in the industrialised world, while various occupational and environmental exposures to chemicals are also held responsible. The link between bladder cancer and schistosomiasis, highly prevalent in sub-Saharan Africa, Sudan, Egypt, and Yemen, provides input for investigating and potentially preventing bladder carcinogenesis. Growing concern regarding environmental diseases prompts investigation into the historical milestones that have helped disentangle the relationships between health and environment.

Background: Pheochromocytoma (Pheo) and paraganglioma (PGL) are rare tumors, mostly resulting from pathogenic variants of predisposing genes, with a genetic contribution that now stands at around 70%. Germline variants account for approximately 40%, while the remaining 30% is attributable to somatic variants. Objective: This study aimed to describe a new PHD2 (EGLN1) variant in a patient affected by metastatic Pheo and chronic myeloid leukemia (CML) without polycythemia and to emphasize the need to adopt a comprehensive next-generation sequencing (NGS) panel. Methods: Genetic analysis was carried out by NGS. This analysis was initially performed using a panel of genes known for tumor predisposition (EGLN1, EPAS1, FH, KIF1Bβ, MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, and VHL), followed initially by SNP-CGH array, to exclude the presence of the pathogenic Copy Number Variants (CNVs) and the loss of heterozygosity (LOH) and subsequently by whole exome sequencing (WES) comparative sequence analysis of the DNA extracted from tumor fragments and peripheral blood. Results: We found a novel germline PHD2 (EGLN1) gene variant, c.153G>A, p.W51*, in a patient affected by metastatic Pheo and chronic myeloid leukemia (CML) in the absence of polycythemia. Conclusions: According to the latest guidelines, it is mandatory to perform genetic analysis in all Pheo/PGL cases regardless of phenotype. In patients with metastatic disease and no evidence of polycythemia, we propose testing for PHD2 (EGLN1) gene variants. A possible correlation between PHD2 (EGLN1) pathogenic variants and CML clinical course should be considered.

Background and Objectives: The incidence of urothelial cancer in males is higher than in females; however, females have a higher risk of recurrence and progression. The aim of our study was to report the effect of gender on the oncological outcome in advanced urothelial cancer. Materials and Methods: In our retrospective study, all patients had undergone primary surgical treatment for urothelial cancer and were affected by stage IV disease at the time of chemotherapy. Response to therapy and toxicity were evaluated. Subgroups were analyzed for tumour presentation, first- and second-line treatment response, progression-free survival (PFS) and overall survival (OS). Results. Seventy-five patients, 18 (24%) females and 57 (76%) males, were considered. Investigation into the distribution of individual characteristics according to gender revealed a significant difference only for smoking, with a prevalence of smokers in women (p = 0.029). At the end of follow-up, OS was higher in females (27.5% vs. 17.4%; p = 0.047). Smoking did not significantly influence OS (p = 0.055), while univariate Cox regression analysis confirmed that males had a higher risk of death (HR = 2.28, 95% CI 0.99–129 5.25), with borderline statistical significance (p = 0.053). Men showed higher PFS than women both after first-line (p = 0.051) and second-line chemotherapy (p = 0.018), with a lower risk of progression (HR = 0.29, 95% CI 0.10–0.86; p = 0.026). No differences were found between genders with regard to toxicity. Conclusions. In our series, PFS rates following first- and second-line therapies for advanced urothelial carcinoma confirmed that females have a greater risk of progression than males.

Purpose: The role of Chlamydia trachomatis (CT) infection in chronic bacterial prostatitis (CBP) is well known. What is unclear is whether there are any differences in the course or clinical outcome of the disease when the cause is CT or other uropathogens. Materials and Methods: A series of 311 patients affected by CBP due to CT (cohort A) was compared with a group of 524 patients affected by CBP caused by common uropathogen bacteria (cohort B). All participants completed the following questionnaires: National Institutes of Health Chronic Prostatitis Symptom Index, International Prostate Symptom Score, International Index of Erectile Function-15 erectile function domain (IIEF-15-EFD), Premature Ejaculation Diagnostic Tool (PEDT), and the Short Form 36 (SF-36) Health Survey. All patients were followed with clinical and microbiological evaluations. Results: After a mean follow-up time of 42.3 months, the number of symptomatic episodes was significantly higher in patients in cohort A than in cohort B (4.1±1.1 vs. 2.8±0.8, p

Background: The aim of this study was to perform a literature-based meta-analysis to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in first-line metastatic renal cell carcinoma (RCC), focusing on the predictive role of PD-L1 expression. Methods: The primary outcome was overall survival, and secondary outcomes were progression-free survival (PFS) and objective response. We planned a subgroup analysis for overall survival according to PD-L1 status. Results: Five studies were included in the analysis for a total of 4063 cases. Overall survival was greater in PD-L1 positive tumours (HR = 0.49, 95% CI: 0.36–0.67; p

Objectives: We evaluated the efficacy of sutureless laparoscopic partial nephrectomy (LPN), using a fibrin gel in order to minimize renal ischemia time and preserve kidney function. Materials and Methods: Nineteen patients (mean age 58.3 ± 7.1) undergoing sutureless LPN using a fbrin gel were compared with a control group consisting of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing. Intraand post-operative data for the two groups were compared. The following parameters were recorded: patient demographics, Charlson Comorbidity Index, tumor characteristics according to the RENAL score, warm ischemia and operative times, estimated blood loss, mean hospital stay, post-operative complications referring to the Clavien-Dindo classification, renal function parameters pathologic and follow-up data. The main outcome measure was renal ischemia time and maintenance of kidney function. Results: Median warm ischemia time was 13 minutes (range 11-19) in the group treated with fibrin gel and 19 (range 17- 29) in the control group, with a statistically significant difference (p < 0.001). The two groups were homogeneous in terms of the Charlson Comorbidity Index (4.6 vs 4.8) and RENAL score (9.6 vs 9.4). Median operative time differed significantly in the two groups, 183 minutes (range 145-218) in the group treated with fibrin gel and 201 (range 197-231) in the control group (p < 0.001). A negative surgical margin was reported in 18 patients (94.7%) in the group treated with fibrin gel and in 21 patients (100%) in the control group. No difference in renal function was found between the two groups. Conclusions: Sutureless LPN with fibrin gel can reduce warm ischemia and total operative time while preserving kidney function.

Background and objectives: Angiosarcomas are uncommon and extremely aggressive malignancies derived from vascular endothelial cells. Although they can occur anywhere in the body and at any age, they are more frequently found in the skin of the head and neck regions and in the elderly. Few cases have been recorded in deep soft tissues and in parenchymal organs. Angiosarcomas of the urinary bladder are exceedingly rare. They usually arise in adult patients with a history of radiation therapy, cigarette smoking, or exposure to chemical agents (e.g., vinyl chloride). Despite multidisciplinary treatment approaches combining surgery, radiotherapy, and chemotherapy, prognosis is dismal. Materials and Methods: We describe a case of a 78-year-old Caucasian man presenting with a vesical mass incidentally discovered with abdominal computerized tomography (CT). He underwent transurethral resection of the bladder (TURB), and histology was compatible with angiosarcoma. Results: The patient had been a heavy smoker and his medical history included therapeutic irradiation for prostate cancer eight years previously. Radical cystoprostatectomy was feasible, and pathologic examination of the surgical specimen confirmed angiosarcoma involving the urinary bladder, prostate, and seminal vesicles. Post-operative peritonitis resulted in progressive multi-organ failure and death. Conclusions: Angiosarcoma primary to the urinary bladder is seldom encountered, however, it should be considered in the differential diagnosis of vesical tumors, especially in elderly men with a history of pelvic radiotherapy.

Background: Mutations in genes encoding one of the subunits of succinate dehydrogenase (SDH) are involved in pheochromocytoma (PHEO) and paraganglioma (PGL) development. Over the last few years, such mutations have also been associated with non-chromaffin tumors. However, immunohistochemistry (IHC) on the tumor tissue and a study on the loss of heterozygosity (LOH) aimed at demonstrating the pathogenic role of SDHx genes have only been employed in a few cases. Case report: We describe the case of a 19-year-old Caucasian man with a germline SDHB mutation, who presented with acne vulgaris resistant to medical treatment. His follow-up for chromaffin tumors was negative, while hormonal tests revealed suppressed gonadotropins with testosterone in the upper range of normality and elevated β-human chorionic gonadotropin (β-hCG). At the whole-body enhanced CT scan, a mediastinal lesion suggestive of a germ cell tumor (GCT) was detected. 18FDG-PET (fluorodeoxyglucose-positron emission tomography) imaging showed low glucose metabolism at the mediastinal site. Surgical removal of the mass was uneventful. Pathology confirmed the diagnosis of GCT consisting of cystic teratoma (95%) and seminoma (5%). IHC for SDHB showed normal protein expression, and genetic analysis of the tumor tissue revealed the absence of SDHB LOH. Normalization of the hormonal tests and acne attenuation were achieved after surgery. Conclusion: We report an incidental association of a germinal SDHB mutation and mediastinal GCT in a young Caucasian man. Our paper highlights the importance of IHC and genetic analysis in confirming the etiologic role of SDHx genes in nonchromaffin tumors, thus excluding incidental associations.

PurposeTo investigate the relationship between human papillomavirus (HPV) infection and prostatitis-related symptoms.Materials and MethodsAll young heterosexual patients with prostatitis-related symptoms attending the same Center from January 2005 to December 2010 were eligible for this case-control study. Sexually active asymptomatic men were considered as the control group. All subjects underwent clinical examination, Meares-Stamey test and DNA-HPV test. Patients with prostatitis-related symptoms and asymptomatic men were compared in terms of HPV prevalence. Moreover, multivariable Cox proportional hazards regression analysis was performed to determine the association between HPV infection and prostatitis-related symptoms.ResultsOverall, 814 out of 2,938 patients (27.7%) and 292 out of 1,081 controls (27.0%) proved positive to HPV. The HPV genotype distribution was as follows: HR-HPV 478 (43.3%), PHR-HPV 77 (6.9%), LR-HPV 187 (16.9%) and PNG-HPV 364 (32.9%). The most common HPV genotypes were: 6, 11, 16, 26, 51, 53 and 81. No difference was found between the two groups in terms of HPV infection (OR 1.03; 95% CI 0.88-1.22; p = 0.66). We noted a statistically significant increase in HPV infection over the period 2005 to 2010 (p < 0.001) in both groups. Moreover, we found a statistically significant increase in HPV 16 frequency from 2005 to 2010 (p = 0.002).ConclusionsThis study highlights that prostatitis-like symptoms are unrelated to HPV infection. Secondary, we highlight the high prevalence of asymptomatic HPV infection among young heterosexual men.

Background: Solid-pseudopapillary neoplasms of the pancreas (SPNs) are uncommon tumours usually frequent in young women. Although the pathogenesis of SPNs is uncertain a potential influence of the sex hormone milieu on the biology of these tumours has been suggested. The controversial expression of oestrogen receptors (ERs) in SPNs, provide a rationale for studying the effects of oestrogenic molecules on SPN development.

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues in everyday urological practice that require special attention: the role of ABU in pre-operative prophylaxis and in women affected by recurrent urinary tract infections (rUTIs). Nowadays, this is the time to think over our practice and change our way of thinking. Here, we aimed to summarize the current literature knowledge in terms of ABU management in patients undergoing urological surgery and in patients with rUTIs. In the last years, the approach to patient with ABU has changed totally. Prior to all surgical procedures that do not enter the urinary tract, ABU is generally not considered as a risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a protective role in preventing symptomatic recurrence, particularly when Enterococcus faecalis (E. faecalis) has been isolated.

Metabolic pathologies mainly originate from adipose tissue (AT) dysfunctions. AT differences are associated with fat-depot anatomic distribution in subcutaneous (SAT) and visceral omental (VAT) pads. We address the question whether the functional differences between the two compartments may be present early in the adipose stem cell (ASC) instead of being restricted to the mature adipocytes. Using a specific human ASC model, we evaluated proliferation/differentiation of ASC from abdominal SAT-(S-ASC) and VAT-(V-ASC) paired biopsies in parallel as well as the electrophysiological properties and functional activity of ASC and their in vitro-derived adipocytes. A dramatic difference in proliferation and adipogenic potential was observed between the two ASC populations, S-ASC having a growth rate and adipogenic potential significantly higher than V-ASC and giving rise to more functional and better organized adipocytes. To our knowledge, this is the first comprehensive electrophysiological analysis of ASC and derived-adipocytes, showing electrophysiological properties, such as membrane potential, capacitance and K(+)-current parameters which confirm the better functionality of S-ASC and their derived adipocytes. We document the greater ability of S-ASC-derived adipocytes to secrete adiponectin and their reduced susceptibility to lipolysis. These features may account for the metabolic differences observed between the SAT and VAT. Our findings suggest that VAT and SAT functional differences originate at the level of the adult ASC which maintains a memory of its fat pad of origin. Such stem cell differences may account for differential adipose depot susceptibility to the development of metabolic dysfunction and may represent a suitable target for specific therapeutic approaches.