Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.

PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis.

PURPOSE: To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. MATERIALS AND METHODS: Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. RESULTS: All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. CONCLUSIONS: Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option.

Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells.

Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

Modified S-ileal neobladder for continent urinary diversion: functional and urodynamic results after 20 years of follow-up.

OBJECTIVE: To report continence and urodynamic findings after radical cystectomy and urinary diversion with modified S-ileal neobladder between January 1993 and January 2013. PATIENTS AND METHODS: 181 patients were enrolled. Continence status, reservoir sensation, compliance, capacity and activity were assessed. RESULTS: Daytime continence was reported by 88.0, 98.4 and 99.2%, while nighttime continence was reported by 70.2, 94.0 and 95.8% of our patients at 6 months, 5 years and 20 years, respectively. Enterocystometric capacity and maximum reservoir pressure were 366 vs. 405 ml and 502 ml, and 29 vs. 18 and 11 cm H2O, at 6 months, 5 years and 20 years, respectively. Median post-void residual urine volume was 32 ml at 6 months, 50 ml at 5 years and 120 ml at 20 years. CONCLUSIONS: The modified S-ileal neobladder technique has a very good long-lasting functional outcome, with high day- and nighttime continence levels as well as high acceptability rates from our patients.

Is there a role for hyberbaric oxygen as primary treatment for grade IV radiation-induced haemorrhagic cystitis? A prospective pilot-feasibility study and review of literature.

PURPOSE: To examine the safety and efficacy of hyperbaric oxygen as the primary treatment for Grade IV radiation-induced haemorrhagic cystitis. MATERIALS AND METHODS: Hyperbaric oxygen was prospectively applied as a primary treatment option in 11 patients with Grade IV radiation cystitis. Primary endpoint was the incidence of complete and partial response to treatment. Secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. RESULTS: All patients completed therapy without complications for a mean follow-up of 17.82 months (range 3 to 34). Mean number of sessions needed was 32.8 (range 27 to 44). Complete and partial response rate was 81.8% and 18.2%, respectively. However, in three patients the first treatment session was not either sufficient or durable giving a 72.7% rate of durable effect. Interestingly, all 9 patients with complete response received therapy within 6 months of the haematuria onset compared to the two patients with partial response who received therapy at 8 and 10 months from the haematuria onset, respectively (p = 0.018). The need for blood transfusion (p = 0.491) and the total radiation dose (p = 0.259) were not correlated to success-rate. One patient needed cystectomy, while all patients were alive at the end of follow-up. CONCLUSIONS: Early primary use of hyperbaric oxygen to treat radiation-induced grade IV cystitis is an effective and safe treatment option.

Acceptance of Artificial Intelligence in Supporting Cancer Patients.

ASCAPE Project is a study aiming to implement the advances of Artificial Intelligence (AI), to support prostate cancer survivors, regarding quality of life issues. The aim of the study is to determine characteristics of patients who accepted to join ASCAPE project. It results that participants of the study mainly originate from higher-educated societies that are better informed about the potential benefits of AI in medicine. Therefore, efforts should be focused on eliminating patients' reluctancy by better informing them on the potential benefits of AI.

Percutaneous nephrolithotomy in horseshoe kidneys: factors affecting stone-free rate.

PURPOSE: We report a 2-center study of factors affecting the stone-free rate after percutaneous nephrolithotomy in horseshoe kidneys. MATERIALS AND METHODS: The postoperative stone-free rate after percutaneous nephrolithotomy was evaluated in 47 male and 11 female patients with horseshoe kidneys. All data were collected prospectively. Patient and procedure related factors predicting the stone-free rate were analyzed by univariate and multivariate tests. RESULTS: The mean ± SD stone burden was 7.62 ± 7.18 cm(2) (range 1 to 45) and the stone was larger than 10 cm(2) in 14 patients (24.1%). Complex stones and staghorn stones were present in 21 (36.2%) and 19 patients (32.7%), respectively. The overall stone-free rate was 65.5%. Complex stones (p = 0.01), stone burden greater than 5 cm(2) (p = 0.013), stone burden greater than 10 cm(2) (p = 0.012), multiple stones (p = 0.006) and staghorn stones (p <0.001) were related to adverse outcomes on univariate analysis. Logistic regression analysis revealed that staghorn calculi was the only factor that significantly predicted the stone-free rate (p = 0.002). A patient with staghorn calculi in the horseshoe kidney was 45 times more likely to have a lower stone-free rate after percutaneous nephrolithotomy than a patient without staghorn calculi in the horseshoe kidney. CONCLUSIONS: Stone parameters are important when treating calculi in horseshoe kidneys. Staghorn calculi are associated with a lower stone-free rate after percutaneous nephrolithotomy.

Tamsulosin versus transurethral resection of the prostate: effect on nocturia as a result of benign prostatic hyperplasia.

Our objective was to compare the effect of tamsulosin versus transurethral resection of the prostate (TURP) for the management of nocturia in previously untreated men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and no other predisposing factors for nocturia. The study group included 66 patients (mean age 68.9 years, range 52-81) randomized to receive either tamsulosin 0.4 mg per os daily (n = 33) or TURP (n = 33). Nocturia was assessed at baseline, after 3 months and after 1 year, by the number of nocturnal awakenings and hours of undisturbed sleep (HUS) obtained from a 72-h Frequency Volume Chart (FVC). Furthermore, the International Prostate Symptom Score (IPSS), the International Consultation on Incontinence Questionnaire Nocturia (ICIQ-N) and the International Consultation on Incontinence Questionnaire Nocturia Quality of Life (ICIQ-NQoL) were recorded. At baseline, there were no statistically significant differences between the two groups. ICIQNQoL and ICIQ-N scores correlated with the number of awakenings and HUS, respectively. Both tamsulosin and TURP improved all examined parameters during the follow up. TURP was associated with a statistically significant improvement in the number of nocturnal awakenings and in the IPSS, ICIQ-N and ICIQ-NQol scores in comparison with tamsulosin. HUS increased in both groups, but without any statistically significant difference. In conclusion, TURP is superior in comparison with tamsulosin for the management of BPH-related nocturia.

Referral for "Neoadjuvant Chemotherapy" for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes.

BACKGROUND: Utilization of neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer in everyday practice differs from that of clinical trials. We describe the patterns of referral for "neoadjuvant chemotherapy", treatment and outcomes in a multidisciplinary tumor board. METHODS: This was an observational study. Patients referred for neoadjuvant chemotherapy received 4 cycles of dose-dense gemcitabine/cisplatin and were then assessed for definitive local therapy. Patients had a minimum follow-up of 2 years. Primary objective was a 3-year disease-free survival rate. RESULTS: Forty-six patients (clinical stages II: 28, IIIA: 9, IIIB: 4, IVA: 3, missing: 2) were included. Following chemotherapy, 30 underwent radical cystectomy, 8 radiotherapy and 8 no further therapy. Pathological downstaging was observed in 14 (46.6%) of the 30 patients who underwent radical cystectomy; clinical TNM staging was correlated with disease-free survival in the whole population, while clinical and pathological stages, as well as pathological downstaging, were correlated with disease-free survival in patients undergoing radical cystectomy. Three-year disease-free survival rates for the whole cohort and for patients undergoing radical cystectomy were 67.3% (95% confidence interval [CI]: 51-79.2) and 65.2 (95% CI: 44.9-79.6), respectively. CONCLUSION: Real-world muscle invasive bladder cancer patients who receive neoadjuvant chemotherapy are characterized by more advanced diseases and less frequent radical surgery than those included in clinical trials. Nevertheless, outcomes were comparable and, therefore, offering patients with stage II-IVA muscle invasive bladder cancer neoadjuvant chemotherapy after assessment by multidisciplinary tumor boards should be strongly encouraged.

ERCC1 19007 Polymorphism in Greek Patients with Advanced Urothelial Cancer Treated with Platinum-Based Chemotherapy: Effect of the Changing Treatment Paradigm: A Cohort Study by the Hellenic GU Cancer Group.

We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.

The novel prostate cancer antigen 3 (PCA3) biomarker.

PCA3 is a prostate specific, nonprotein coding RNA that is significantly over expressed in prostate cancer, without any correlation to prostatic volume and/or other prostatic diseases (e.g. prostatitis). It can now easily be measured in urine with a novel transcription-mediated amplification based test. Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies with a higher specificity rate in comparison to PSA. Several studies have demonstrated that PCA3 can be used as a prognostic marker of prostate cancer, especially in conjunction with other predictive markers. Novel PCA3-based nomograms have already been introduced into clinical practice. PCA3 test may be of valuable help in several PSA quandary situations such as negative prostatic biopsies, concomitant prostatic diseases, and active surveillance. Results from relevant clinical studies, comparative with PSA, are warranted in order to confirm the perspective of PCA3 to substitute PSA.

Indications, prediction of success and methods to improve outcome of shock wave lithotripsy of renal and upper ureteral calculi.

OBJECTIVES: To clarify the current indications, factors influencing outcome and methods to predict and improve the results of shock wave lithotripsy for the treatment of renal and upper ureteral calculi. MATERIAL AND METHODS: English literature on the Medline and MeSH databases was reviewed. Key words used for search included shock wave lithotripsy, calculi, stones, renal, kidney, ureter, efficacy, prediction, improvement and guidelines. RESULTS: Shock wave lithotripsy still has certain indications for renal and upper ureteral stones. Major impact on outcome has the stone size, with a diameter of less than 20 mm being the cutoff point. Shock wave monotherapy should not be used for larger stones and should be combined with other treatment modalities such as percutaneous nephrolithotomy or ureteroscopy. Other factors influencing outcome include stone number, composition and location, existence of congenital abnormalities, obesity and bleeding diathesis. Nomograms, artificial neural networks and computed tomography are useful adjuncts in predicting the outcome. Potential methods of improvement are the decrease of shock wave rate, the progressive increase in lithotripter output, the use of two simultaneous or sequential pulses and the use of expulsive and chemolytic treatment. CONCLUSION: Shock wave lithotripsy continues to be a significant part in the urologists armamentarium for the treatment of renal and upper ureteral stones.

Detection of circulating tumor cells in prostate cancer patients: methodological pitfalls and clinical relevance.

Disseminated malignancy is the major cause of prostate cancer-related mortality. Circulating tumor cells (CTCs) are essential for the establishment of metastasis. Various contemporary and molecular methods using prostate-specific biomarkers have been applied to detect extraprostatic disease that is undetectable by conventional imaging techniques, assessing the risk for disease recurrence after therapy of curative intent. However, the clinical relevance of CTC detection is still controversial. We review current literature regarding molecular methods used for the detection of CTCs in the peripheral blood and bone marrow biopsies of patients with prostate cancer, and we discuss the methodological pitfalls that influence the clinical significance of molecular staging.

Short- and long-term complications of open radical prostatectomy according to the Clavien classification system.

OBJECTIVE: To assess the use of the Clavien classification system in documenting the complications related to open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: The medical records of 995 patients, who had open RRP during a period of 7 years, were reviewed retrospectively. Short- and long-term complications were classified according to the recently revised Clavien classification system. We also compared the results with a recently reported series of laparoscopic and robotic RRP. RESULTS: The overall complication rate was 26.9%; Grade I, Id, II, IIIa, IIIb and V complications were recorded in 3.4%, 3.9%, 12.8%, 2.6%, 3.8% and 0.3% of cases, respectively. Rectal injuries (10) and postoperative wound infections (24) were included in the Grade I category. Anastomotic leakage was recorded in 39 patients and rated as Grade Id. Grade II included cases of deep vein thrombosis (11), urinary tract infections (42), lymphorrhoeas (22) and haemorrhage requiring transfusion (53). Anastomotic strictures (26) and incisional hernias (38) were included in Grade IIIa and IIIb, respectively. Pulmonary embolism was fatal for three patients (0.3%) of Grade IV and V. CONCLUSIONS: To avoid incoherence in reporting morbidity data, a reproducible and practical classification system is necessary. The Clavien system could provide, after refinement and validation, a common language among urologists.

Penile fractures: immediate surgical approach with a midline ventral incision.

OBJECTIVES: To present our experience with immediate surgical treatment of penile fractures, using a midline ventral incision, as the choice of either immediate surgical or conservative treatment in penile fractures, as well as the type of surgical incision, remains controversial. PATIENTS AND METHODS: In a period of 5 years (2002-2006) eight patients were treated in our department for a penile fracture. The diagnosis was established by a history and clinical examination. In six patients ultrasonography before surgery located the fracture in the right corpus cavernosum, distally from the penoscrotal junction. All patients had immediate surgery using a midline ventral incision and were followed for a mean of 1 year. RESULTS: All patients presented with a penile haematoma, while five and two had concomitant scrotal and perineal haematomas, respectively. Penile urethral rupture was associated with corporal cavernosal rupture in one patient. In all patients a 5-cm midline ventral incision was made at the penile raphe. There was unilateral rupture of the corpus cavernosum in seven patients and bilateral rupture with concomitant urethral rupture in one. The fascial defect was sutured in all patients and an end-to-end anastomosis made if there was urethral rupture. The early and late periods after surgery were uneventful. Erectile function was unaffected during the follow-up. CONCLUSION: Immediate intervention for penile fractures, using a midline ventral incision, achieves good early and late results. Our technique has the advantage of direct access to both corpora cavernosa and the anterior urethra, with a minimal skin incision.

Current status of ureteroscopic treatment for urolithiasis.

Intracorporeal treatment of urolithiasis is characterized by continuous technological evolution. In this review we present updated data upon the use of ureteroscopy for the management of urolithiasis. Novel digital flexible ureteroscopes are used in clinical practice. Ureteroscopic working tools are revolutionized resulting in safer and more efficient procedures. Special categories of stone patients such as pregnant women, children and patients on anticoagulation medication can now undergo uneventful ureteroscopy. Routine insertion of stents and access sheaths as well as bilateral ureteroscopy is still a controversial issue. Future perspectives include smaller and better instruments to visualize and treat a stone, while robotic ureteroscopy is becoming a fascinating reality.

Problems faced by relatives caring for cancer patients at home.

The care of patients suffering from advanced cancer is not limited in the hospital setting. It continues at home where the burden of care is borne by specific individuals. The aim of the present study was to survey and record the various problems faced by those who care for cancer patients at home. The study was conducted in our hospital during the summer of 2007. All participants completed, during a personal interview, a questionnaire which covered pathologic, social, psychological, spiritual/religious and financial problems. Seventy-six carers returned fully completed questionnaires. The most frequent problems reported were: anxiety regarding the patient's future (61.8%), troublesome symptoms such as pain (54%), increased economic burden-financial difficulty (51.3%), problems with patient's feeding (50%), unhappiness or depression (48,7%), emotional upset (47.4%), worsening of the patient's behaviour and personality (38.2%), difficulty of establishing a positive attitude regarding their current status (34.2%), transport to hospital (32.9%), assistance from the wider family circle (25%). Taking care of cancer patients at home creates several problems among carers. Many of them remain undetected. The acknowledgement and recognition of these problems by health-care professionals might contribute to finding solutions in order to assist the difficult task of these individuals.

Reducing the number of sutures for vesicourethral anastomosis in radical retropubic prostatectomy.

OBJECTIVES: To prospectively evaluate the outcome of using a two-suture technique for the vesicourethral anastomosis (VUA) during radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: Two groups of 50 patients each underwent nerve-sparing RRP for localized prostate cancer by one surgeon. In one group, the vesicourethral anastomosis was performed using 2 Vicryl 2-0 stitches placed at the 3- and 9-o'clock positions and in the other group 6 Vicryl 2-0 stitches were placed at the 2-, 4-, 6-, 8-, 10- and 12-o'clock positions. The intraoperative and perioperative parameters analyzed were time to perform the VUA, time to remove the drain and hospitalization. The rate of incontinence, anastomotic stricture and erectile function were included in the outcome analysis. RESULTS: The anastomotic time differed statistically between the 2 groups (mean 3.3 minutes for the 2-suture group and 10.5 minutes for the 6-suture group, p < 0.0001) with similar periods of drain removal (mean 3.12 days for the 2-suture group and 3.45 days for the 6-suture group; p = 0.13) and hospitalization (mean 4.66 days for the 2-suture group and 5.3 days for the 6-suture group; p = 0.09). The functional outcome was excellent for the 2-suture group with no patient suffering from incontinence or anastomotic strictures 1 year postoperatively, while in the 6-suture group there were 2 patients (4%) suffering from incontinence (2 underwent sling procedure) and 1 patient suffered from anastomotic stricture. CONCLUSION: The low number of sutures in the 2-suture VUA technique reduces operating times, does not influence perioperative and intraoperative parameters and results in excellent functional outcome.

Inverse association of leptin levels with renal cell carcinoma: results from a case-control study.

OBJECTIVE: Leptin is primarily produced in adipose tissue and appears to play a modulatory role between metabolism and immunity. Given that obesity, a state of chronic inflammation, is an established risk factor for Renal Cell Carcinoma (RCC), we investigated the association between plasma leptin levels and RCC risk. DESIGN: This case-control study included 70 patients with newly diagnosed, histologically confirmed RCC and 280 age-, gender- and district of residence-matched controls. Anthropometric data, socio-demographic variables, medical history, lifestyle habits and dietary data were derived from a personal interview. Serum leptin and adiponectin levels were determined using standard commercial kits. Adjusted odds ratios for RCC risk were derived through multiple logistic regression analyses. RESULTS: Leptin levels were inversely associated with RCC risk (OR: 0.53, CI: 0.28- 0.99, p = 0.05), even after controlling for potential confounding factors, such as Body Mass Index (BMI), recent weight change, history of diabetes mellitus and other obesity related hormones, notably adiponectin. CONCLUSIONS: The precise mechanism linking obesity with RCC remains unclear; however, the inverse association of leptin with RCC might be attributed, at least in part, to hormonal cross-talk with complex neuron-endocrine and immune circuits. These findings, if confirmed in prospective and interventional studies, might further elucidate the underlying mechanisms.