Genitourinary Symptoms-Patient Help-Seeking and General Practitioner Management: An Outpatient Based Survey at a Tertiary Hospital in Southern Italy

Introduction: General knowledge of most common genitourinary diseases is often lacking. In this survey we evaluated the attention given by patients and general practitioners to genitourinary symptoms, and particularly to hematuria and potential early signs of genitourinary cancer. Methods: A structured self-administered questionnaire was administered to outpatients before the urological consultation. The questionnaire consisted of 4 multiple choice questions to record the level of patient awareness of urological symptoms, the importance given to gross hematuria, the interval between the onset and the visit, the regularity of physical examination and the first-level investigations indicated by the general practitioner before the urological consultation. Results: A total of 327 self-administered questionnaires were obtained from 358 consecutive patients for a compliance rate of 91.3%. Asymptomatic gross hematuria was present in 91 cases (27.8%). The first episode of hematuria was not reported by 20% of the patients, with a median delay of 11 months. Only 77 patients (23.6%) in the last 5 years had received a physical examination including the external genitalia. Laboratory and/or imaging investigations were indicated before urological counseling in 172 (52.6%) patients. Conclusions: The majority of patients underestimated urological symptoms. Less than 25% and 50% of patients had a physical examination and first-level investigations performed before urological counseling, respectively. Our survey reveals an important lack of awareness of genitourinary symptoms that could be responsible for delayed diagnosis and inappropriate treatment

Correlation between BMI and the pathological features of prostate cancer at biopsy

Introduction/Aim: Numerous clinical trials investigated the association between obesity and prostate cancer, but they yielded inconsistent results (1). Obesity has been found to be related to prostatic tumors at more advanced stages and higher Gleason grade when compared with normal population (2). An increased number of biopsy cores has been advocated by some Authors in obese and overweight men due to an increased difficulty and delay in cancer detection (3). The main aim of our research was to correlate Body Mass Index (BMI) with the pathological characteristics of prostate cancer at biopsy. Patients and Methods: Patients with positive prostate biopsy performed for palpable prostate nodule and/or elevated PSA levels were considered in the present study. A transrectal prostate biopsy procedure, not less than 12 cores, was performed. The number of specimens was increased in case of re-biopsy (18-24 cores or more). After informed consent, a database has been created, including clinical and pathological data: demographics, PSA, digital rectal examination, transrectal ultrasound and prostate cancer features at biopsy. Patients were divided into four categories according to their BMI as follows: 16-19,9 (underweight), 20.0-24.9 (normal weight), 25.0-29.9 (overweight) and ≥30.0 (obese). The statistical analysis was conducted with Fisher’s exact test for Gleason pattern 4 (<4 or ≥4) and BMI for single weight class and the Pearson’s Chisquared test with Yates’ continuity correction for aggregate BMI classes. Results: Out of 149 patients diagnosed with prostate cancer, the Gleason score was available for 121 (81.2%), ASAP or PIN were found in 5 more patients (3.4%). Twenty-seven (21.4%) patients had a previous negative biopsy. The median age was 71 years (range 45-86). The median BMI was 26.7 kg/m2 (range 17.5-37.4). Two patients (1.3%) were underweight, 43 (28,6%)patients had normal weight (median BMI 23), 70 (47%) were overweight (median BMI 26.8) and 34 (22.8%) were obese (median BMI 35.3). Median PSA was 9.5 ng/ml (range 0,41- 1339). A prostate nodule was palpable in 45 (30.2%) patients. The median prostate volume was 44.5 cc. A Gleason pattern of 4 or more was evident in 49 (40.5%) patients, while it was not detected in the remaining 72 (59.5%) patients. The presence of Gleason pattern 4 did not result in relation to the class of BMI (p-value=0.9814), neither combining different classes: normal weight and overweight men versus obese ones (p-value=0.7696); normal weight versus overweight and obese men (p-value=0.9678). Discussion and Conclusion: Our study, in contrast with some evidence in literature, did not show any significant correlation between BMI and the presence of Gleason pattern 4. However, the small number of patients did not allow to include in our analysis important factors, such as biological, hormonal, environmental and life-style factors, involved in the pathogenesis of prostate cancer. A larger, prospective, multicenter investigation is on going. References 1 Howlader N, Krapcho M, Neyman N et al: SEER Cancer statistics review, 1975-2008. National Cancer Institute, Bethesda,http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission. 2 Nunzio CD, Freedland S, Miano L, Agrò EF, Bañez L and Tubaro A: The uncertain relationship between obesity and prostate cancer: an Italian biopsy cohort analysis. European Journal of Surgical Oncology 37(12): 1025-1029, 2011. 3 Wallner LP, Morgenstern H, McGree ME et al: The effects of body mass index on changes in prostate-specific antigen levels and prostate volume over 15 years of follow-up: implications for prostate cancer detection. Cancer Epidemiol Biomarkers Prev 20(3): 501-508, 2011. Doi: 10.1158/1055-9965. EPI-10-1006. Epub 2011 Jan 17. 3

Towards the Anchovy Biorefinery: Biogas Production from Anchovy Processing Waste after Fish Oil Extraction with Biobased Limonene

Anchovies are among the largest fish catch worldwide. The anchovy fillet industry generates a huge amount of biowaste (e.g., fish heads, bones, tails) that can be used for the extraction of several potentially valuable bioproducts including omega-3 lipids. Following the extraction of valued fish oil rich in omega-3, vitamin D3 and zeaxanthin from anchovy fillet leftovers using biobased limonene in a fully circular process, the solid residue (anchovy sludge) was used as starting substrate for the production of biogas by anaerobic digestion. In spite of the unbalanced carbon to nitrogen (C/N) ratio, typical of marine biowaste, the anchovy sludge showed a good methane yield (about 280 mLCH4·gVS−1), proving to be an ideal substrate for co-digestion along with other carbon rich wastes and residues. Furthermore, the presence of residual limonene, used as a renewable, not-toxic and edible extraction solvent, does not affect the microbial methanogenesis. The results reported in this study demonstrate that anchovy leftovers after the fish oil extraction process can be efficiently used as a starting co-substrate for the production of biogas in a modern biorefinery

PLEOMORPHIC HYALINIZING ANGIOECTATIC TUMOR (PHAT) OF RENAL PARENCHYMA. FIRST CASE REPORTED IN LITERATURE

Introduction: The pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare non-metastatic tumor of soft tissue identified in 1996 (1). In adults, it generally occurs in the subcutaneous tissue of the lower limbs, although reported also in chest wall, buttock and arms. In the literature, only one case of PHAT has been described in the kidney at the level of the hilum but not involving renal pelvis or parenchyma (2). The clinical behavior of PHAT is characterized by a slow growth and a rate of local recurrences higher than 50%. Metastasis has not been reported. Case Report: A 61-year-old Caucasian obese female with a medical history of hypertension and hypercholesterolemia was admitted at the Emergency Unit for recurring gross hematuria since one year, becoming more frequent and severe in the last 3 months. Due to the severe anemia (hemoglobin of 7.7g/dl), the patient was transfused. Computed tomography (CT) scan revealed a parenchymal lesion of 4 cm in diameter of the lower pole of the right kidney. The lesion was only partially capsulated, mixed with a well evident cystic component, in strict contact with the lower calyx suspicious for infiltration. At cystoscopy, a clot emerging from the right ureteral meatus was evident. Urine cytology was negative and no imaging was indicative of transitional upper urinary tract tumor. After written informed consent, a right nephrectomy was performed and the patient was discharged on the 4th day. The histological exam revealed a partially capsulated lesion (3.7 cm in diameter) with a pseudo-cystic structure, including hemosiderin depositions, compressing but not invading the dilated lower calyx. The lesion was characterized by hyalinized clusters of thin-walled ectatic blood vessels within a stroma composed of sheets and fascicles of spindled and pleomorphic atypical cells with intranuclear inclusions. At immunohistochemical analysis, AE1/AE3, EMA, CD31, S100, desmin, actin of smooth muscle, HMB45, ALK resulted negative. The lesion was classified as a PHAT. The patient is maintained in follow-up. Discussion: PHAT is a low-grade mesenchymal neoplasm of uncertain lineage described in soft tissue and characterized by diffusely infiltrative borders, although some do have well-circumscribed margins. The immunohistostaining for S-100 protein, actin, desmin, cytokeratin, CD-31, factor VIII antigens or epithelial membrane antigen are negative. To date approximately 22 cases of PHAT and 40 cases of its precursor, "early PHAT", have been described in the world literature. At least 3 cases of PHAT were reported to progress to high-grade myxofibrosarcoma (1). A case of PHAT arising in the hilum of the kidney, clinically mimicking an infiltrating tumor of the renal pelvis, has been described in 2012 (2). Our case is the second described in retro-peritoneum and the first of the renal parenchyma. In our patient, a partial nephrectomy was not carried out due to the absence of well-defined margins and apparent involvement of the lower calyx, although not confirmed by the pathological exam. If a partial nephrectomy is performed, a strict followup should be considered due to the high percentage of local recurrence characterizing the clinical behavior of PHAT (3). 1 Shi Wei et al: Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts. Human Pathology 43: 121-126, 2012. 2 Muhammad T et al: Pleomorphic hyalinizing angiectatic tumor of renal hilum. Annals of Diagnostic Pathology 16: 489-493, 2012. 3 Folpe AL and Weiss SW: Pleomorphic hyalinizing angiectatic tumor: analysis of 41 cases supporting evolution from a distinctive precursor lesion. Am J Surg Pathol 11: 1417-1425, 2004

VISCERAL FAT TISSUE ACTIVITY DOES NOT CORRELATE TO HIGH GRADE PROSTATE CANCER RISK AT BIOPSY

Introduction/Aim: High-grade prostate cancer (PCa) has been reported in association with metabolic syndrome (MS). In a previous study we found no significant correlation between body mass index (BMI) and prevalence of high Gleason score at biopsy (1). BMI could be not an accurate marker of the endocrine activity of visceral adipose tissue responsible of high plasmatic levels of adipokines promoting PCa aggressiveness. We estimated visceral adiposity dysfunction by the visceral adiposity index (VAI) considering waist circumference (WC), BMI, triglycerides (TG) and high density lipoproteins (HDL) plasma levels of each patient (2). The aim was to correlate VAI values with PCa detection rate and Gleason patterns 4 and 5 at biopsy. Patients and Methods: Patients who underwent prostate biopsy for suspicious digital rectal examination and/or elevated PSA levels were enrolled. After informed consent, a transrectal prostate biopsy, 12 cores at least (24 in case of re-biopsy), was performed. VAI was expressed as: WC/[39.68 + (1.88 × BMI)] × TG/1.03 × 1.31/HDL, assuming VAI=1 in healthy, non obese men with TG and HDL levels within normal limits. PCa detection at biopsy, Gleason score patterns, VAI and BMI were statistically analyzed using the Mann Whitney U-test. Results: Ninety-five patients were entered with a median age of 67 years (range=47-79). The median BMI was 27 kg/m2 (range=17.4-40) and the median VAI was 4.47 (range=1.3-15.6). Median PSA was 7.9 ng/ml (range=0.47- 53). A prostate nodule was palpable in 27 (28.4%) patients. Ten patients (10.5%) had a previous negative biopsy. A prostate cancer was diagnosed in 43 (45.2%) patients, Gleason patterns 4 and 5 were detected in 18 (41.8%) patients. Median BMI and VAI were 27.4 Kg/m2 and 26.3 Kg/m2 (p=0.53) and 4.25 and 4.66 (p=0.28) in patients with positive and negative biopsy, respectively. Median BMI and VAI resulted 27.7 Kg/m2 and 27.3 Kg/m2 and 4.78 and 3.98 in patients with and without Gleason patterns 4 or 5, respectively. No statistically significant difference was highlighted for VAI (p=0.37) or BMI (p=0.85). Discussion and Conclusion: The identification of patients harboring an aggressive PCa remains an important goal. To date the relation between MS and PCa remains contradictory. Moreover, an accurate marker of MS has not yet been determined (3). VAI might be a more accurate marker than BMI in indicating the activity of visceral fat. In spite of VAI adoption, our analysis does not reveal any statistically significant correlation between VAI, PCa detection rate and incidence of Gleason patterns 4 or 5 at biopsy. Diet, race and other environmental and genetic factors, playing a promoting or protective role in PCa, should be also considered in further studies. The statistical support of the GSTU Foundation is acknowledged. 1 Serretta V, Caruana G, Sommatino F, et al: Does exist A correlation between BMI and Gleason patterns 4 and 5 at prostate biopsy? J Cytol Histol 4: 182, 2013. 2 Amato MC, Giordano C, Galia M et al: Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care 33: 920, 2010. 3 Bhindi B, Locke J, Alibhai SM et al: Dissecting the association between metabolic syndrome and prostate cancer risk: analysis of a large clinical cohort. Eur Urol 67(1): 64-70, 2015. Epub 2014 Feb 14

Urological dysfunctions in patients with Parkinson’s disease: clues from clinical and non-invasive urological assessment

Abstract Background Autonomic nervous system dysfunction, common in patients with Parkinson’s disease (PD), causes significant morbidity and it is correlated with poor quality of life. To assess frequency of urinary symptoms in patients with PD, without conditions known to interfere with urinary function. Methods Non-demented PD patients were consecutively enrolled from the outpatients clinic of our department. Scales investigating motor and non-motor symptoms were carried out. Evaluation of urinary dysfunctions was carried out using the AUTonomic Scale for Outcomes in Parkinson’s disease (SCOPA-AUT) questionnaire. Patients underwent noninvasive urological studies (nUS), including uroflowmetry and ultrasound of the urinary tract. Results Forty-eight (20 women, 42%) out of 187 PD patients met the inclusion criteria and were enrolled in the study. Mean SCOPA-AUT score was 14.1 ± 6.9 (urinary symptoms subscore 5.2 ± 3.8). Among those evaluated by the SCOPA-AUT scale, the urinary symptoms were among the most common complaints (93.8%). At nUS mean maximum flow rate (Qmax) was 17.9 ± 9.1 ml/s, and mean postvoid residual (PVR) urine volume was 24.4 ± 44.1 ml. Ultrasound investigation documented prostate hypertrophy in 12 male patients (42.8%). Urinary items of the SCOPA-AUT (SCOPA-U subscore) correlated with measures of disease severity only in female patients. Conclusion Urinary symptoms and abnormal findings in nUS are common in PD. Though nigrostriatal degeneration might be responsible for urinary symptoms also in the early-intermediate stage of the disease, when urinary dysfunction occurs other medical conditions need to be excluded

The Added Value of [18F]Choline PET/CT in Low-Risk Prostate Cancer Staging: A Case Report

In the management of prostate cancer (PCa), correct staging is crucial in order to assess the right therapeutic approach. [18F]Choline PET/CT has been shown to provide more accurate staging information than conventional imaging approaches. The aim of this paper is to provide a real practice demonstration of the impact of [18F]Choline PET/CT on low-risk prostate cancer staging and clinical management. We report a 64-year-old man with biochemical PCa recurrence diagnosis after transurethral resection of the prostate. The patient, after the detection of an increased level of PSA, underwent multi-parametric prostate magnetic resonance imaging (mpMRI) that did not show evidence of disease. The patient was admitted to perform [18F]Choline PET/CT that showed a macroscopic prostate recurrence. Patient underwent photon external beam radiation therapy (EBRT) treatment, and [18F]Choline PET/CT was also used to define treatment volumes. At 3- and 6-month clinical follow-up evaluations, no late toxicity was detected and a significant reduction in PSA value was shown. Therefore, our case highlights the potential usefulness of [18F]Choline PET/CT for the staging of low-risk prostate cancer and its impact on the management and quality of life of such patients. The presented case should urge the scientific community to enhance larger and multicentric studies, assessing more extensively the potential impact of [18F]Choline PET/CT in this clinical scenario

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called &ldquo;lymphocyte miRNA signature&rdquo;, specifically induced in long-responder patients (CR, PR, or SD to nivolumab &gt;18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients