TRENDS IN PSA TESTING, PROSTATE BIOPSIES AND RADICAL PROSTATECTOMY PROCEDURES IN MARCHE REGION

==inizio objective==

Nowadays the use of PSA in clinical practice is a question of matter. In particular PSA is not always tested with accuracy and according to latest reccomendations (1-2). Clinical consequences of PSA testing could be prostate biopsy and radical prostatectomy (2).
In Italy from 2010 reflex PSA is daily used in clinical practice (for PSA value between 2 ng/ml and 10 ng/ml PSA free is automatically computed).
In Marche Region PSA reflex has been used since July 2012 and, starting from late 2014, the Region has provided a reduction of PSA free cost.
Aim of the study was to determine the trend of regional employment of PSA total and free/total ratio testing; to evaluate the effect upon sanitary costs and its consequences in terms of number of prostate biopsy and radical prostatectomy.

==fine objective==

==inizio methodsresults==

We analyzed data coming from Marche Region about the employment of free/total PSA ratio and reflex PSA from 2010 to 2014, divided per age groups. In the same period we analyzed the number of US-guided prostate biopsies and radical prostatectomy performed.

==fine methodsresults==

==inizio results==

The number of total and free PSA testing decreased of 43.5% and 35.3%, respectively, followed by a continuous increasing of reflex PSA up to 44% in the 2011-2014 period.
Even considering the more frequent use of reflex PSA, we observed a reduction of 50000 PSA testing.
On the other hand prostate biopsy showed an increasing of 300 procedures per year until 2014, while during the same period radical prostatectomy performed in Marche Region or in other Italian Region on Marche inhabitants (passive mobility) showed a decreasing of 100 procedures.

==fine results==

==inizio discussions==

The regional trend of PSA testing has been decresing, also because of regional sanitary administration choices; nevetheless the trend could be bettered.
The lack of biopsies decreasing in the 2011-14 period could be due to more accuracy PSA testing.
The decrease of radical prostatectomy procedures could be explained with a better comprehension of prostate cancer biological behavior that leaded to less aggressive and watchful approaches; according to this, PSA testing reduction is only partially involved.

==fine discussions==

==inizio conclusion==

PSA testing has been largely overused especially in age groups in which it should be avoided (2-3-4-5).
Valid conclusions will be obtained by ongoing observation of the trends in years to come.

==fine conclusion==

==inizio reference==

1. Opportunistic prostate-specific antigen screening in Italy: 6 years of monitoring from the italian general practice database G.G. d’Ambrosio, S. Campo, M. Cancian, S. Pecchioli and G. Mazzaglia E.Journal Cancer Prevention 2010, Vol.19 N.6; 413-416

2. EAU Guidelines 2016; Prostate cancer

3. Vedel I, Puts MTE, Monette M, Monette J, Bergman H: The decision-making process in prostate cancer screening in primary care with a prostatespecific antigen: A systematic review. J Geriatr Oncol 2011, 2011. doi:http://dx.doi.org/10.1016/j.jgo.2011.04.001.

4. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, Djulbegovic B, Dahm P: Screening for prostate cancer: systematic review and
meta-analysis of randomised controlled trials. BMJ 2010, 2010. doi:http://dx.doi.org/10.1136/bmj.c4543

5. Doctors’ perspectives on PSA testing illuminate established differences in prostate cancer screening rates between Australia and the UK:
a qualitative study. Pickles K, et al. BMJ Open 2016;6:e011932. doi:10.1136/bmjopen-2016-011932

==fine reference==

MRI-based nomogram predicting the probability of diagnosing a clinically significant Prostate Cancer with MRI-US fusion biopsy

==inizio objective==

Identifying clinically significant prostate cancers is the main objective of prostate cancer diagnosis. The aim of this study was to develop, to internally validate and to calibrate a nomogram to predict the probability of detecting a clinically significant prostate cancer.

==fine objective==

==inizio methodsresults==

Prospectively collected data from 3 tertiary referral center series of 478 consecutive patients who underwent MRI-US fusion biopsy using the UroStation™ (Koelis, France) were used to build the nomogram. A logistic regression model is created to identify predictors of PCa diagnosis with MRI-US fusion biopsy. Predictive accuracy was quantified using the concordance index (CI). Internal validation with 200 bootstrap resampling and calibration plot were performed.

==fine methodsresults==

==inizio results==

Mean age was 66.3 yrs (± 7.98) and mean PSA levels were 9.8 ng/mL (± 7.98). The overall PCa detection rate was 57.4%.
Age, PSA serum levels, PI-RADS score at MRI report, number of targeted and number of systematic cores taken were included in the model (Figure 1).Predictive accuracy was 0.81. On internal validation the CI was 0.81 and predicted probability was well calibrated (Figure 2).
Limitations include the lack of external validation and the absence of patients with races different by Caucasian in the development cohort.

==fine results==

==inizio discussions==

==fine discussions==

==inizio conclusion==

Predicting the risk of a clinically significant PCa is the goal of physicians. This nomogram provides a high accuracy in predicting the probability of diagnosing a clinically significant PCa with MRI-US fusion biopsy. The ease to use makes this nomogram a clinical tool for both patients and physicians.

==fine conclusion==

==inizio reference==

– Prostate cancer detection with magnetic resonance-ultrasound fusion biopsy: The role of systematic and targeted biopsies.
Filson CP, Natarajan S, Margolis DJ, Huang J, Lieu P, Dorey FJ, Reiter RE, Marks LS.
Cancer. 2016 Mar 15;122(6):884-92. doi: 10.1002/cncr.29874.

– Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: multi-institutional retrospective analysis of 389 patients.
Mariotti GC, Costa DN, Pedrosa I, Falsarella PM, Martins T, Roehrborn CG, Rofsky NM, Xi Y, M Andrade TC, Queiroz MR, Lotan Y, Garcia RG, Lemos GC, Baroni RH.
Urol Oncol. 2016 Sep;34(9):416.e9-416.e14. doi: 10.1016/j.urolonc.2016.04.00

==fine reference==

Urinary continence outcomes after peri-urethral suspension according to Patel during Robot Assisted Laparoscopic Radical Prostatectomy (RALP). Results from a case-control study

==inizio objective==

Technical variations of RALP have been proposed by different authors to improve urinary continence with conflicting results, due to the persistence of multiple adjunctive factors such as bladder neck sparing and the patient or disease characteristics. The aim of the present study was to determine the effects of peri-urethral suspension according to Patel on a cohort of consecutive patients who underwent RALP for clinically localized prostate cancer.

==fine objective==

==inizio methodsresults==

Two-hundred and thirty patients who previously underwent RALP were recalled by telephone and subsequently investigated by PSA testing , ultrasound post-voiding residual urine measurement and specifically designed questionnaire to investigate their quality of life and the effects of surgery on urinary continence. 174 of them responded to the telephone recall and were eligible for the study while 56 were considered as drop out (2 deceased for unrelated diseases, 51 refused to respond the questionnaire). 81 out 174 received PUS with polyglecaprone 3-0 suture prior of Van Velthoven vesico-urethral anastomosis ( Group 1) while 93 out 174 received a standard vesico-urethral polyglecaprone 3-0 suture according to Van Velthoven (Group 2). Statistical analysis was performed by Fisher Exact test.

==fine methodsresults==

==inizio results==

Patients presented comparable preoperative characteristics in both groups except for prostate volume, which had a median value greater than 40 cc in 95.3% of Group 1 in comparison to 80.8% in the Group 2 (p<0.001). Pathological analysis demonstrated comparable distribution of progression risk in both groups but a significantly higher number of T3 patients in the control group ( 13.3% vs. 25.6%) (p=0.02). Positive surgical margin rate was comparable between the two groups. Sixty-nine percent of patients in the Group 1 were immediately and totally continent after the urethral catheter removal as well as after a median follow up of 23±17.4 months (period 2011-2016) while only 48.3% in the Group 2 were continent with a median follow up of 30±22.1 months (period 2009-2016). Socially acceptable continence (no pads or a single safety pad a day) was found in 92.58% of the Group 1 and 79.56 of the Group 2 patients respectively (p=0.003). Severe incontinence was found in 4.9% and 15% of the Group 1 and 2 respectively. ==fine results== ==inizio discussions== ==fine discussions== ==inizio conclusion== Periurethral suspension according to Patel during RALP resulted in a statistically significant shorter interval to continence recovery and higher continence rate at a median 23 months follow up time. ==fine conclusion== ==inizio reference== ==fine reference==

FOCAL TREATMENT OF PROSTATE CANCER USING FOCAL ONE DEVICE. ROLE OF FOCAL THERAPY, ONCOLOGICAL AND FUNCTIONAL RESULTS

==inizio objective==

The over-diagnosis and over-treatment of prostate cancer is a reality unequivocally demonstrated by studies with PSA screening [1]. In fact in the United States and Canada it is a recommendation was issued against [2,3] systematic screening. In Europe, however, in agreement with the European Society of Urology, the execution of the PSA in patients without urinary symptoms it should be reserved for patients with a 15 year life expectancy and should focus particularly “cases at risk” or with a family history, hereditary or members of certain ethnic groups [4]. Together with the re-evaluation of the role of PSA and early diagnosis of prostate cancer were introduced into clinical practice of alternative treatment modality to classical radical therapy, surgery or radiation, for low risk of progressing tumors [4]. The need for alternatives to radical therapy derived from the heavy consequences which in fact has on the patient’s quality of life when the benefits, in terms of lifespan gain, are not certain [2,3]. Active surveillance is in fact a deferred treatment of radical therapy [5,6]. The tumor is monitored by repeated checks with PSA, clinical examination of the prostate and prostate biopsies [5,6]. In about 1/3 of cases in active surveillance for a suspected progression, the patient is recommended a radical active treatment [5,6]. Until any radical treatment patients that maintain their quality of life, though psychologically accept “live” with the tumor. The evolution of multiparametric MRI, the ability to perform targeted biopsies (fusion biopsy on mpMRI) [7] and to identify a primary outbreak [8], the so-called “index lesion”, within the prostate, has allowed to introduce into clinical practice the focal therapy that is substantially complementary to the active surveillance and, analogously thereto, ideal for limiting the over treatment of prostate cancer. The focal therapy is associated with a very low probability of affecting the patient’s quality of life, ensuring generally the preservation of continence and sexual activity [9,10]. Nevertheless, treating the primary lesion can cure the patient and avoid potentially radical treatment for all the rest of life [11].

==fine objective==

==inizio methodsresults==

Focal One is a device designed for the focal therapy of Prostate Cancer integrating the ability to visualize, target, treat and validate the focal treatment. Magnetic Resonnance Imaging (MRI) volumes are imported through the hospital’s network into the device so that an elastic fusion can be done between the real time ultrasonography and the MRI where the regions to treat have been previousy drawn, thus allowing to apply limited and targeted HIFU lesions. During the HIFU energy delivery process, the operator sees a live ultrasound image of what is being treated and, if necessary, can readjust the treatment planning. At the end of the treatment process, a Contrast-enhanced Ultrasound volume is acquired showing the de-vascularized areas.
53 patients with mono focal prostate cancer were treated from June 2015 and January 2017.HIFU treatment process was realized with the Focal One device using a 6to 12 mm safety margin around the tumor. Contrast enhanced MRI is performed within 30 day after HIFU and Control biopsies with fusion technique were performed only on suspected mri lesion.
All patients respected inclusion criteria:
Life expectancy ≥10 years
PSA at diagnosis ≤15,
clinical stage cT2NoMo
cancerous lesions identified at mpMRI
Biopsy performed with technical cast of mpMRI image with histopathological positive concordant with suspects mpMRI
Standard cancer biopsy but with acknowledgment to mpMRI (also later executed) and contralateral lobe to mpMRI negative and / or positive in one frustule to 3 mm max
Gleason score 3 + 3 (grade group 1)
presence of tumor for more than 3 mm in the frustule bioptic
presence of cancer in at least two biopsy cores,
cancer mpMRI> ≥10mm
Gleason score 3 + 4 (grade group 2)
Gleason score 4 + 3 (grade 3 group) as a single index lesion or lesion associated depending on the same side or contralateral lesion grade group 1 and 2 present in a frustule only for a maximum of 3 mm

==fine methodsresults==

==inizio results==

The mean age of patients was 65.8±5.5 years. Mean cancer volume was 9 cc (6 to 15 cc)
Mean Prostate Volume was 40±23 cc and no patient required TURP before procedure
Average time of procedure 50 min
Mean Time of Hospitalization 2 Days
Average time of catheterization 5 Days.
none found major postoperative complication
>95% of preservation of continence
>75% of the power preservation
<15% failure rate ==fine results== ==inizio discussions== The over treatments era is finished, the technologies (MRI multi parametric , fusion biopsy) let us to chose patients witch can switch to Active surveillance ore active focal treatments without having to undergo to surgery as first therapy line. Since the early 2000s, two systems have been marketed for this application, and other devices are currently in clinical trials. HIFU treatment can be used either alone or in combination with (before- or after-) external beam radiotherapy (EBRT) (before or after HIFU) and can be repeated multiple times. HIFU treatment is performed under real-time monitoring with ultrasound or guided by MRI. We must look to the past: HISTORICAL INFORMATION FROM PUBLIC WITH HIFU [12-28] With radical curative intent in prostate cancer confined to the gland or locally advanced Age greater than or equal to 70 years Age also less than 70 years in the presence of significant comorbidities Refusal by the patient of the other standard treatments provided by international guidelines (RT, radical prostatectomy, active surveillance) Local recovery of established disease with biopsy after RT, brachytherapy or radical prostatectomy. With palliative intent,HIFU may be indicated even in prostate tumors become hormonotherapy resistant and how local therapy minimally invasive cytoreductive within prostate tumors in metastatic systemic therapy. Only turning his eyes back we will look to the future (29-32) Focal therapy - only treat the micro tumor foci saving the prostate gland and thus improving% of urinary incontinence and erectile dysfunction. The focal treatment therefore involves the ablation of prostatic tumor lesion that has the highest biopsy Gleason Score or the biggest volume (Index Tumor IT). Consensus not to preclude the therapy for multifocal tumors. In the recent past the focal therapy had limitations due to the variability and validity of biopsy mapping; currently with the introduction of Magnetic Resonance Multiparametric and "fusion imaging" that is, the integration of the images obtained by multiparametric MRI and 3D ultrasound was made a major scientific advancement for both diagnosis and for the indications to treat cancer prostate. -Zonal (more tissue treatment than the focal) -Emiablazione (1/2 prostate; right or right lobe) -Multi-zone (both right quadrants that sin, not total) ==fine discussions== ==inizio conclusion== HIFU is an evolving technology perfectly adapted for focal treatment. Thus, HIFU focal therapy is another pathway that must be explored when considering the accuracy and reliability for PCa mapping techniques. HIFU would be particularly suited for such a therapy since it is clear that HIFU outcomes and toxicity are relative to the volume of prostate treated. Focal One device is able to achieve a complete destruction of small prostate cancer using an elastic magnetic resonance-ultrasound (MR-US) registration system for tumor location and HIFU treatment planning. ==fine conclusion== ==inizio reference== 1)Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Schröder FH et all ERSPC Investigators.Lancet. 2014 Dec 6;384(9959):2027-35 2)Moyer VA; U.S. Preventive Services Task Force.Screening for prostate cancer: U.S. Preventive ServicesTask Force recommendation statement. Ann Intern Med2012;157:120-34.Canadian Task Force on Preventive Health Care, Bell N, 3)Connor Gorber S, et al. Recommendations on screening or prostate cancer with the prostate-specific antigen test. CMAJ 2014;186:1225-34. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der 4)Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology Eur Urol. 2014 Jan;65(1):124-37. 5)Klotz L, Zhang L, Lam A, et al. Clinical results of longterm follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010;28:126-31 6)Bul M, Zhu X, Valdagni R, et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Our Urol 2013;63:597-603 7)Assessment of Prospectively Assigned Likert Scores for Targeted Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsies in Patients with Suspected Prostate Cancer. Costa DN, Lotan Y, Rofsky NM, Roehrborn C, Liu A, Hornberger B, Xi Y, Francis F, Pedrosa I. J Urol. 2016 Jan;195(1):80-7. 8)Multiparametric Magnetic Resonance Imaging (MRI) and MRI-Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen. Radtke JP, Schwab C, Wolf MB, Freitag MT, Alt CD, Kesch C, Popeneciu IV, Huettenbrink C, Gasch C, Klein T, Bonekamp D, Duensing S, Roth W, Schueler S, Stock C, Schlemmer HP, Roethke M, Hohenfellner M, Hadaschik BA. Eur Urol. 2016 Jan 19 9)Marien A, Gill I, Ukimura O, Betrouni N, Villers A. Target ablation— image-guided therapy in prostate cancer. Urol Oncol 2014;32: 912–23. 10)Valerio M, Ahmed HU, Emberton M, et al. The role of ocal therapy in the management of localised prostate cancer: a systematic review. Eur Urol 2014;66:732-51. 11)The Effects of Focal Therapy for Prostate Cancer on Sexual Function: A Combined Analysis of Three Prospective Trials. Yap T, Ahmed HU, Hindley RG, Guillaumier S, McCartan N, Dickinson L, Emberton M, Minhas S Eur Urol. 2015 Oct 30 12)Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused Ultrasound: Oncologic Outcomes and Morbidity in 1002 Patients. S. Crouzet et al - 2013 - European Urology 13)Evolution and Outcomes of 3 MHz High Intensity Focused Ul- trasound Therapy for Localized Prostate Cancer During 15 Years.
S. Thüroff et al - 2013 The Journal of Urology 14)Fourteen-year oncological and functional outcomes of high-intensity focused ultrasound in localized prostate cancer.
R. Ganzer et al - 2013 BJU International 15)Locally recurrent prostate cancer after initial radiation therapy: Early sal- vage high-intensity focused ultrasound improves oncologic outcomes. S. Crouzet et al - Radiother Oncol. 2012 16)Single application of high-intensity focused ultrasound as a rst-line therapy for clinically localized prostate cancer: 5-year outcomes. D. Pfeiffer et al - 2012 BJU International 17)Morbidity of Focal Therapy in the Treatment of Localized Prostate Cancer. E. Barret et al - 2012 BJU International 18)High-intensity focused ultrasound (HIFU) for de nitive treatment of pros- tate cancer. E. R. Cordeiro et al - 2012 BJU International 19)Complete high-intensity focused ultrasound in prostate cancer: outcome from the @-Registry. A. Blana et al - 2012 Prostate Cancer and Prostatic Diseases 20)Single-session primary high-intensity focused ultrasonography treatment for localized prostate cancer: biochemical outcomes using third genera- tion-based technology. J. H. Pinthus et al - 2012 BJU International 21)Robotic High-intensity Focused Ultrasound for Prostate Cancer: What Have We Learned in 15 Years of Clinical Use? C. Chaussy et al - Current Urology Report 2011 22)Foca al Therapy with High-Intensity Focused Ultrasound for Pros- tate Cancer in the Elderly. A Feasibility Study with 10 Years Follow-Up. A. B. El Fegoun et al - Brazilian Journal of Urology 2011 23)HIFU as salvage rst-line treatment for palpable, TRUS-evidenced, biop- sy-proven locally recurrent prostate cancer after radical prostatectomy: A pilot study. A. Asimakopoulos et al – Urologic Oncology 2011 24)Correlation of prostate-speci c antigen nadir and biochemical failure after High-Intensity Focused Ultrasound of localized prostate cancer based on the Stuttgart failure criteria – analysis from the @-Registry. R. Ganzer et al – BJU International 2011 25)Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 Patients. S. Crouzet et al - 2010 European Urology 26)Salvage Radiotherapy After High-Intensity Focussed Ultrasound for Recur- rent Localised Prostate Cancer. J. Riviere et al - 2010 European Urology 27)A prospective study of salvage high-intensity focused ultrasound for lo- cally radiorecurrent prostate cancer: Early results. V. Berge et al - 2010 Scandi- navian Journal of Urology 28)High-intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology. X. Rebillard et al - BJU International 2008 29)Eight years’ experience with High-Intensity Focused Ultrasonography for treatment of localized prostate cancer. A. Blana et al Journal of Urology 2008.06.062 30)Comparing High-Intensity Focal Ultrasound Hemiablation to Robotic Radical Prostatectomy in the Management of Unilateral Prostate Cancer: A Matched-Pair Analysis. Albisinni S, Aoun F, Bellucci S, Biaou I, Limani K, Hawaux E, Peltier A, van Velthoven R. J Endourol. 2017 Jan;31(1):14-19. 31)Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients. Rischmann P, Gelet A, Riche B, Villers A, Pasticier G, Bondil P, Jung JL, Bugel H, Petit J, Toledano H, Mallick S, Rouvière O, Rabilloud M, Tonoli-Catez H, Crouzet S. Eur Urol. 2017 Feb;71(2):267-273. 32)Focal High-intensity Focused Ultrasound Targeted Hemiablation for Unilateral Prostate Cancer: A Prospective Evaluation of Oncologic and Functional Outcomes. Feijoo ER, Sivaraman A, Barret E, Sanchez-Salas R, Galiano M, Rozet F, Prapotnich D, Cathala N, Mombet A, Cathelineau X. Eur Urol. 2016 Feb;69(2):214-20 ==fine reference==

CENTRAL AND PERIFERIC PROSTATE DIFFUSION OF Fosfomycin trometamol in men with or without metabolic abnormalities

==inizio objective==

Current evidences show that men with abnormal metabolic parameters are at major risk of harboring a more aggressive prostate cancer [1]. Despite the increased risk of post-procedure complication, infections included, this is the cohort of patients for which prostate biopsy will be particularly useful. Precisely for this reason prophylactic antibiotics in these patients, before they underwent prostate biopsy, plays a predominant role. Fosfomycin trometamol (FT) is a bactericidal, broad-spectrum antibiotic with low profile of resistance and elevated activity against multidrug-resistant bacteria. It is well known FT’ urinary distribution but about prostate diffusion in literature [2] there are only few and old works and none in patients with Metabolic syndrome (METs). This prospective study focuses on the diffusion proprieties of FT in prostatic tissue by comparing its concentration in men with different metabolic abnormalities.

==fine objective==

==inizio methodsresults==

FT was administered 3 to 6 hours before procedure to sixty men with suspected prostate cancer. The diffusion of FT was calculated analyzing the concentration differences in the cores obtained from peripheral and from central prostate biopsies (central zone [C] and peripheral zone [P]). The arithmetic mean of C and P was considered as total prostatic concentration (T). Metabolic features including waist circumference, arterial blood pressure, glycemia, HDL-Cholesterol and triglyceride were recorded in all men. Each obtained value was split into normal or pathologic according to NCEP-ATPIII criteria. The variations of FT concentration among different zones of the gland (C, P and T) and men with or without abnormal metabolic parameters were analyzed by Anova.

==fine methodsresults==

==inizio results==

Over all patients, thirty-one (51.7%) suffered from hypertension, nineteen (31.7%) presented hyperglycemia, twenty-one (35%) were classified with high levels of Triglycerides while two (3.3%) with low levels of HDL-Cholesterol. Ten (16.7%) had a pathologic waist circumference. The table below reports the mean value of FT concentration in different zone of prostate (C, P, T) according to the normal vs abnormal metabolic features.

Central
Peripheral
Total
Blood pressure
Normal
9.02
7.35
8.15

Pathologic
13.09
12.97
13.03

p value
0.032
0.008
0.010
Glycaemia
Normal
10.04
9.16
9.57

Pathologic
14.03
12.65
13.34

p value
0.033
0.080
0.037
Triglycerides
Normal
11.29
10.44
10.87

Pathologic
12.19
11.17
11.58

p value
0.636
0.731
0.705
HDL-Cholesterol
Normal
11.5
10.59
11.01

Pathologic
15.97
15.05
15.51

p value
0.376
0.437
0.379
Waist Circumference
Normal
11.10
9.54
9.79

Pathologic
16.27
14.32
15.29

p value
0.010
0.089
0.026

==fine results==

==inizio discussions==

In literature it is known as METs is correlated with various diseases: oncological, non-oncological and infectious. As also evident in the literature, patients undergoing prostate biopsy, if not treated with appropriate prophylactic antibiotics, are at risk for infectious complications sometimes with series sequele. Especially in patients affected from metabolic disorders, which exhibit increased susceptibility to infection, it is important a suitable prophylactic coverage with a low resistance to common uropathogenic bacteria and broad spectrum antibiotic. FT, a chemoterapic with the mentioned characteristics, in our study seems to be spreading adequately in prostate tissue as to be used in the prophilaxis of prostate biopsy. Moreover it seems to have higher distribution in prostate of patients with diabetes, hypertension dyslipidemia. This evidence could lead to hypothesize that if on one hand the diabetic patients have higher infection risk, on other hand they have at the same time higher concentration of FT in our target tissue. It could be explained as dysmetabolic patients have a generalized inflammatory state that, in the prostate, could increase distribution of fosfomycin in the tissue, making it a suitable drug also for patients suffering from METs.

==fine discussions==

==inizio conclusion==

FT shows a higher concentration rate in the prostate gland of obese, hypertensive and hyperglycemic patients compared to those with non-altered metabolic parameters. For this reason FT can be considered an effective prophylaxis before performing a prostate biopsy, particularly in dysmetabolic men.

==fine conclusion==

==inizio reference==

1. Bhindi B, Xie WY, Kulkarni GS, Hamilton RJ, Nesbitt M, Finelli A, Zlotta AR, Evans A, van der Kwast TH, Alibhai SM, Trachtenberg J, Fleshner NE. Influence of Metabolic Syndrome on Prostate Cancer Stage, Grade, and Overall Recurrence Risk in Men Undergoing Radical Prostatectomy. Urology. 2016 Jul;93:77-85. doi: 10.1016/j.urology.2016.01.041.

2. Rhodes NJ, Gardiner BJ, Neely MN, Grayson ML, Ellis AG, Lawrentschuk N, Frauman AG, Maxwell KM, Zembower TR, Scheetz MH. Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis. J Antimicrob Chemother. 2015 Jul;70(7):2068-73. doi: 10.1093/jac/dkv067.

==fine reference==

ECONOMICAL ASPECTS ABOUT THE COSTS OF ROBOT-ASSISTED LAPAROSCOPIC PROSTATECTOMY (RALP)

==inizio objective==

The aim of this study to report the economic costs related to the RALP procedure in a robotic reference center.

==fine objective==

==inizio methodsresults==

A five years robotic activity is evaluated to determine the costs of RALP by engineers team. The evaluated items are: preoperative, operatory and post-operatory costs.

==fine methodsresults==

==inizio results==

The total amount pro patients is estimated 7852,06 euro:
-111,30 euro for preoperative assesment .
-5693.08 euro for operatory fase (800.86 for medical e paramedical equipe, 3781 euro for medical device and drugs, 1110.40 euro for operating room.

==fine results==

==inizio discussions==

 While potential benefits of robotic technology include decreased morbidity and improved recovery, some have suggested a prohibitively high cost. Because of the last governement resolution for Tuscany the financial balance about the robotic procedure is improved

==fine discussions==

==inizio conclusion==

Robotic technology did not significantly increase hospital costs. While the absolute cost for robotic surgery was higher than conventional techniques after taking into account the institutional cost of the robot, the major driver of cost for robotic procedures will likely continue to decrease. Furthermore we must consider due to the our last regional government resolution the robotic DRG refunded raised from 4234.00 to 9677.00 euro.
This variation leads to a positive balance varing from -3618.06 to +1824.94

==fine conclusion==

==inizio reference==

non ci sono reference

==fine reference==

Salvage lymph node dissection for nodal recurrence after radical prostatectomy

==inizio objective==

the incidence of recurrence after radical treatment of local prostate cancer (PCa) is frequent, occurring in 30-50% after radical prostatectomy and in up to 80% after extracorporal radiotherapy [1]. An increase of PSA indicates a relapse but it cannot help to differenciate between local recurrence and systemic spread of the disease. These patients are normally managed with palliative androgen deprivation therapy (ADT), which is associated with significant toxicity and development of hormone refractory disease. Positron emission tomography with cholin tracer is a promising technique for restaging of these patients before they receive an ADT. The aim of this study is to examine the outcome of salvage lymph node dissection (LND) with evaluation of PSA in patients with only nodal recurrence documented with C-Choline-PET / CT.

==fine objective==

==inizio methodsresults==

Fifteen consecutive patients between 2007 and 2015 with biochemical failure and positive lymph node in C-Choline-PET/CT were retrospectively included in the study. Because of a prostate cancer (PCa), 12 patients had initially undergone a retropubic radical prostatectomy with LND and 3 a perineal prostatectomy without LND. The patients underwent a secondary open extended LAD, performed from 2 of our experienced surgeon. The extended LAD consisted in dissection of lymph nodes from the obturator fossa, the internal and external iliac artery, the paravesical lymph nodes and the common iliac artery. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml 6 weeks after salvage surgery.

==fine methodsresults==

==inizio results==

Mean PSA at the time of C-Choline-PET / CT before salvage LND was 2.1 ng/ml. Definitive histological metastases could be found in 12 of 15 patients but in 3 cases not where these were indicated by C-Choline-PET / CT; in further 3 cases no positive lymph nodes were found at all. All postoperative courses were uneventful without any major complications except in one case, with necessity of surgical reintervention. Median follow up after salvage lymph node dissection was 52 months. A total of 7 patients (46%) achieved a biochemical response. During follow up 3 patients (20%) remained free from recurrence (one of these patients died for another tumor 12 months after LND) while 2 another patients became adjuvant RT and ADT 6 and 72 months after LND and show actually no progression of disease. Only one patient died of disease 6 year after LND. The other 8 patients, who didn’t achieved a biochemical response, are actually managed with ADT.

==fine results==

==inizio discussions==

C-Choline-PET / CT has been proved to be useful for restaging patients with increase of PSA after radical surgery even though its results could be influenced from PSA value [2-3]. Based on the findings of C-Choline-PET / CT, a selected group of patients could benefit of an extended secondary LAD. The current data suggest that about half of patients have an immediate postoperative response and one third of these patients can remain free of relapse for 5 years [4]. Our results are similar to these findings and we believe that these procedure should be offered in highly selected cases.

==fine discussions==

==inizio conclusion==

Salvage LND may represent a therapeutic option for selected patients with biochemical recurrence and nodal pathologic uptake at C-Choline-PET / CT with improving cancer control and reducing the exposure time to ADT.

==fine conclusion==

==inizio reference==

1) Han M, Partin AW, Zahurak M. Biochemical (PSA) recurrence probability following radical prostatectomy for clinical localized prostate cancer. Journal of Urology 2003; 169: 517-523
2) Scattoni V, Picchio M, Suardi N et al. Detection of lymph node metastases with integrated C-Choline-PET / CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open-pelvic retroperitoneal lymphadenectomy. European Urology 2007; 52: 423-429
3) Martini T, Mayr R, Trenti E. The role of C-Choline-PET / CT guided secondary lymphadenectomy in patients with PSA failure after radical prostatectomy: lessons learned from eight cases. Advances in Urology 2012; 1-3
4) Abdollah F, Briganti F, Montorsi F. Contemporary role of salvage lymphadenectomy in patients with recurrence following radical prostatectomy. European Urology 2015; 67: 839-849

==fine reference==

Role of Benique in Single Incision Laparoscopic Prostatectomy. Our Experience

==inizio objective==

Laparoscopic prostatectomy is a well-established and standardized technique to treat patients with localized prostate cancer. Nevertheless, the procedure is continuously in evolution in order to yield better results in cosmesis, pain , convalescence and in order to reduce the risk of the technique manteining the benefits in terms of potency, continence and oncological management.
Aim of this study is to show how the Benique aided single incision laparoscopic prostatectomy (SILP) technique with totally extraperitoneal approach can avoid the ligation of Santorini dorsal venous complex

==fine objective==

==inizio methodsresults==

retrospective study on 262 SILP in the period 2011-2015 : match analysis between surgical and transfusional data
Benique catheter is applied along the urethra after the bladder neck incision allowing : 1) better exposure and mobilization of the prostate during the seminal vesicles plan dissection and endopelvic fascia and puboprostatic ligaments incision; 2) better Santorini plexus exposure and , after Santorini cold cutting by scissors , 3) no stithces to close it; 4) Santorini compression against the pubis bone to avoid bleeding 5) better urethra exposure during the vesico-urethral suture

==fine methodsresults==

==inizio results==

262 patients range of age 45 – 76, submitted to SILP from 2011 to 2015, 19 pat (7,2 %) needed
blood transfusions during hospitalization but only 8 pat (3 %) within the early 12 hours after surgery ,
6 patients had a retropubic hematoma, but no treatment was necessary.
1 paz (0,3%) needed rehospitalization for concomitant hematuria occurring 10 days after discharge
Mean surgery time was 100 minutes , range 75 – 130 minutes

==fine results==

==inizio discussions==

No differences in intra-and / or post-operatively blood loss evidenced in the percentage of patients with hemotransfusion were shown with literature : in fact a systematic review of the literature shows that the weighted mean intra and postoperative transfsion rate for laparoscopic prostatectomy is 6,3 % . This shows the security of the technique
even with the single port approach: furthermore the use of Beniquet may be useful both for hemostatic compression and for the exposure of the urethra during vesico-urethral suture

==fine discussions==

==inizio conclusion==

The ligation of Santorini venous plexus is not necessary during laparoscopic prostatectomy : bleeding can be avoided by the use of a Benique catheter for compression .
This save time without increasing risk of important bleeding; the technique is not influenced performing the single incision procedure

==fine conclusion==

==inizio reference==

De Carlo F., Celestino F., Verri C., Masedu F., Liberati E., Di Stasi S.M. Retropubic, Laparoscopic, and Robot-Assisted Radical Prostatectomy: Surgical, Oncological, and Functional Outcomes: A Systematic Review . Urol Int 2014;93:373-383

==fine reference==

COMPARISON OF TWO TEMPLATES OF LYMPHADENECTOMY IN PATIENTS AFFECTED BY HIGH RISK PROSTATE CANCER

==inizio objective==

High risk prostate cancer treatment considers an extended lymphadenectomy. We have compared two templates of pelvic lymphadenectomy in high risk patients undergone an extraperitoneal or transperitoneal laparoscopic radical prostatectomy.

==fine objective==

==inizio methodsresults==

Two consecutive series of patients affected by high risk prostate cancer underwent laparoscopic radical prostatectomy. In group 1 (116 pts), the procedure was realized by a preperitoneal access with an extended lymphadenectomy including external iliac and obturator nodes; in group 2 (35 pts), access was transperitoneal with a broader lymphadenectomy consisting of common iliac, external iliac, hypogastric and obturator nodes. We have compared perioperative outcomes in terms of number of nodes removed, positive nodes, complications in the two groups of patients. Statistical analysis has been realized using SPSS 24

==fine methodsresults==

==inizio results==

Data on 151 patients were analyzed. Baseline characteristics are reported in table 1. Preoperative data were balanced between two groups of patients except for biopsy Gleason score. Postoperative outcomes are listed in table 2: Group 2 patients presented worse pathological stage, longer operative time, more nodes removed (mean 33.3 vs 16.6, p<0.001) and more positive pathological nodes (22.9 vs 1.7%, p<0.001). Moreover, a wider lymphadenectomy template was not associated to greater risk of complications or lymphocele. ==fine results== ==inizio discussions== Pelvic lymphadenectomy remains the gold standard for providing a diagnosis of lymph node metastasis in prostate cancer patients. A limited lymph¬adenectomy to the obturator fossa was the standard technique until a few years ago when it was replaced by extended lymphadenectomy. We describe our experience in two consecutive series of high risk patients undergone to two lymphadenectomy templates. Preoperative were balanced between two groups of patients except for biopsy Gleason score that resulted higher in the second group. Regarding postoperative outcomes, Group 2 patients presented worse pathological stage, longer operative time, but also more nodes removed (mean 33.3 vs 16.6 p<0.001) and more positive pathological nodes (28.0 vs 1.7%, p<0.001). Moreover, a wider lymphadenectomy template was not associated to greater risk of any complications or lymphocele. Increasing the NLN may have a therapeutic effect on the outcome of prostate cancer, but this feature needs more documentation. Our study cannot evaluate this issue. ==fine discussions== ==inizio conclusion== In our retrospective analysis, atransperitoneal laparoscopic radical prostatectomy with an extended lymphadenectomy template including obturator, external iliac, common iliac and hypogastric nodes allows to remove a greater number of nodes, to obtain a more positive nodes without increasing risk of complications. ==fine conclusion== ==inizio reference== Annals of Oncol 2013; 24: 1459-66 Eur Urol 2014; 65: 20-25 Eur Urol 2009; 55: 1251-65 Eur Urol 2008; 53: 118-125 ==fine reference==

C-MYC COPY NUMBER ANALYSIS IN URINE CELL FREE DNA FROM PRIMARY PROSTATE CANCER PATIENTS: A FEASIBILITY STUDY

==inizio objective==

The amplification of 8q, in particular of the region 8q24 containing c-MYC gene, is a frequent event in primary prostate cancer tissues and maybe associated with biochemical recurrence and worse outcome (1; 2). The possibility to have non invasive biomarkers is an important chance for the early diagnosis and monitoring of prostate cancer patients instead of invasive approaches. While the use of circulating cell free DNA from blood has been intensively studied (3) only few data have been published on the role of urinary cell free DNA (UcfDNA) as a noninvasive marker (4; 5).
In the present study we aimed at evaluating copy number variation (CNV) of c-MYC gene in urinary samples collected after radical prostatectomy in a series of patients consecutively enrolled from 2013 to 2014. Our aim was to determine the feasibility of copy number analysis in urine samples using a Real Time PCR approach and to correlate it with clinical pathological characteristics.

==fine objective==

==inizio methodsresults==

The study was conducted on a total of 49 individuals, 37 with a first diagnosis of prostate cancer and 12 with benign prostatic disease including prostatitis, inflammation, prostatic benign hyperplasia. Participants were enrolled from the Departments of Urology of Morgagni Pierantoni Hospital (Forlì, Italy) and Bufalini Hospital (Cesena, Italy). First-morning voided urine samples were collected and centrifuged at 850 g for 10min and the supernatants were transferred into cryovials and stored at −80 °C until use.
DNA isolation was performed starting from 4 ml of urine supernatant and using Quick-DNA Urine Kit (Zymo Research), following the manifacturer’s instructions. Urine cell free DNA was quantified using Qubit fluorometer.
c-MYC gene amplification was evaluated by duplex TaqMan quantitative Real Time PCR using two different assays: (ID:Hs01764918 located on exon 3 and ID:HS02602824 located on exon 1) and two different reference genes: AGO1 (ID: Hs02320401) and TCC3 (ID: Hs02765308) both located in chromosomal regions not affected by gain or deletions. For each sample, 1.5 ng of DNA was analyzed in triplicate using TaqMan Universal Master Mix and the primers for target and reference sequences. Three urine DNAs from healthy males over 40 years were singly tested, and then pooled and used as a calibrator, a sample with no CNVs of target and reference genes. In the same run the samples were evaluated for the two loci of the target gene and the two reference genes. When the Ct either for c-MYC or for the reference genes was ≥35.5, samples were considered as “not evaluable”. Copy number variation analysis was performed using CopyCaller Software (Applied Biosystems). Final results were calculated as the average between the copy number values of the two gene loci. CNV values >2.6 were considered as amplification while values <1.4 were considered as deletion. ==fine methodsresults== ==inizio results== UcfDNA copy number was feasible on 43 samples. Six samples were considered as “not evaluable” as their Real Time Ct either for c-MYC or for the two reference genes was ≥35.5. Cancer patients had a pathological stage as follows: 2 pT1, 7 pT2a, 17 pT2b, 6 pT3a and 1 pT3b. Eleven patients had a Gleason score ≤6, 25 had a Gleason score >6. Median PSA was 5.87 for cancer patients and 2.46 for individuals with urological benign pathologies.
Copy number value for c-MYC gene varied from 1.3 to 3.1 in prostate cancer patients with a median value of 2.1 and from 1.1 to 2.4 in patients with benign diseases with a median value of 1.8.
c-MYC gene was gained in 8 of 31 evaluable prostate cancer patients (25.6 %), while it was normal for all individuals with benign pathologies except for two deletions.
Samples with c-MYC copy number gain had all T2 stage tumors. No gain was detected either in T1 or in T3 tumors. Regarding the pathological Gleason score, patients with amplification of c-MYC were: 4 Gleason score 6, 3 Gleason score 7, 1 Gleason score 9. Patients follow-up was available for 24 patients and only two patients experienced a biochemical recurrence until now (one with c-MYC gain).
To date the number of analyzed cases are too low to statistically CNV values with clinical -pathological characteristics or follow-up information.

==fine results==

==inizio discussions==

UcfDNA takes its origin either directly from dying cells exfoliated in urine (also prostatic cells) or from the circulation, for this reason it could be a good source of biomarkers especially for urological cancers such as prostate or bladder ones.
In the present study we demonstrated that copy number analysis could be easily performed in cell free DNA isolated from urine supernatant and that no amplification was found in healthy individuals or individuals with benign pathologies.
We found a 26% frequency of copy number gain for c-MYC gene in UcfDNA from prostate cancer patients with different pathological stages and grades. This amplification frequency is in line with those reported in papers previously published regarding 8q24 gain in primary prostate cancer tissues (1; 2). We strangely found no amplification in T3 patients but the number of cases analyzed is still too low to draw any statistical conclusion. The case series will be implemented in the next future.
It will be necessary for prostate cancer patients to analyze CNV of c-MYC in primary tissue and compare the results with those obtained in urine to establish the UcfDNA CNV sensitivity and to eventually adjust the cut off values.

==fine discussions==

==inizio conclusion==

We demonstrated that copy analysis of c-MYC gene is feasible in cell free DNA isolated from urine supernatant. We found that 26% of prostate cancer samples had a gain for c-MYC while all individuals with benign pathologies had normal copy number.
In the next future we will enlarge the case series and compare results with those obtained in the corresponding tissues to test assay sensitivity and correlate with clinical pathological features.

==fine conclusion==

==inizio reference==

We demonstrated that copy analysis of c-MYC gene is feasible in cell free DNA isolated from urine supernatant. We found that 26% of prostate cancer samples had a gain for c-MYC while all individuals with benign pathologies had normal copy number.
In the next future we will enlarge the case series and compare results with those obtained in the corresponding tissues to test assay sensitivity and correlate with clinical pathological features.

==fine reference==