==inizio objective==

Prostate biospyis the gold standard procedure to diagnose prostate cancer. The techniqueisusuallyperformed under transrectalultrasound (TRUS) guidance with transrectal or transperinealapproach. Everyyear more than 1 milionpof procedure are realized in Europe. Complication rate isquitelow; howeverfearsomeinfectiouscomplications are increasing. Wehaveretrospectivelyevaluatedcomplication rate in our database and wehaveanalyzedpredictivefactor of complications

==fine objective==

==inizio methodsresults==

From database of ourinstitution we have evaluated complications of patients undergone transrectal random prostate biopsy for suspicion of prostate cancer. Complications were classified as bleeding more than 3 days after biopsy (hematuria, hematospermia, rectal bleeding), infection defined as fever more than 38°C, acute urinary retention (RUA). Hospitalization due to complication was ha salso been recorded. We have correlated every complication with age, prostate volume, PSA, PSAD, BMI, number of cores, cancer detection, diabetes mellitus, previous urinary or genital infection, BPCO, previous urological surgery, previous or concomitant tumor. Statistical analysis was performed using Chi square test, Mann Whitney, logistic regression test, as appropriate (SPSS 19).

==fine methodsresults==

==inizio results==

Data on 2.106 patients were collected. Patients characteristics are reported in table 1. Complications occurred in 6.4% of the patients (table 2). Multivariate analysis revealed correlation only for infection with previous history of urinary or genital infection (p0.001, OR 0.012 – CI0.001-0.162) (table 3). A minority of patients (15 out of 2.106 0.7%) requiredhospitalizationbecause of complications (11 for infection, 2 for hematuria, 1 for rectalbleeding, 1 for AUR).However 11.2% (15 of 134) of patients with complicatonsneeded hospital admisison.Previousurinary or genitalinfectionwas the onlyfactorassociated with hospitalization (p0.001 – 0.005 0.000-0.125).

Table 1. patientscharacteristics

Pts (n) 2.106
Age (y) 69.4 ±8.0
BMI 27.3 ±8.2
+ve DRE (%) 37.2
PSA (ng/ml) 14.6 ±39.0
Prostate volume (cc) 59.7 ±30.7
PSAD 0.28 ±0.79
Coresnumber (n) 12.6 ±3.2
PCa (%) 46.8
Diabetes (%) 12.2
BPCO (%) 3.4
UTI (%) 2.0
Urologicalsurgery (%) 3.7
Urologicaltumors (%) 3.4
Othertumors (%) 2.9
Neurologicaldisease (%) 2.5
Anyconcomitantdisease (%) 23.7

Table 2. Complications of prostate biopsy
%
Infection 2.1
Hematuria 2.2
Hematospermia 19.8
Rectalbleeding 0.2
Acute urinaryretention 0.9
Hospitalization 0.7
Overallcomplications 24.7

Table 3. Multivariate analysis of complications
Infection hematuria hematospermia Rectalbleeding AUR hospitalization
Age 0.11 0.49 0.26 0.16 0.41 0.47
BMI 0.67 0.67 0.97 0.84 0.89 0.59
PSA 0.32 0.84 0.19 0.36 0.24 0.93
Prostate volume 0.09 0.85 0.86 0.54 0.98 0.09
PSAD 0.28 0.95 0.50 0.32 0.31 0.90
Diabetes 0.88 0.99 0.46 0.99 0.98 0.98
BPCO 0.78 0.99 0.64 0.98 0.99 0.36
infections 0.001 0.97 0.98 0.98 0.99 0.001
0.005
0.000-0.125
Previousurologicalsurgery 0.31 0.98 0.69 0.97 0.99 0.09
Urologicaltumors 0.99 0.62 0.75 0.45 0.97 0.98
Othertumors 0.11 0.97 0.83 0.97 0.98 0.99
Neurologicaldisease 0.99 0.98 0.29 0.96 0.98 0.08
Anyconcomitantdisease 0.28 0.98 0.76 0.98 0.98 0.98
Coresnumber 0.23 0.82 0.79 0.43 0.11 0.86
PCa 0.38 0.83 0.31 0.96 0.86 0.15

==fine results==

==inizio discussions==

==fine discussions==

==inizio conclusion==

Transrectal random prostate biopsyis a common and safe procedure. Complications rate isgenerallylow (6.4%); hematospermiais more frequentcomplication (4.7%). Hospitalizationisrarelyneeded (0.7%). Howeverfearsome and lifethreateninginfectiouscomplicationsare maincausesof hospital admission

==fine conclusion==

==inizio reference==

==fine reference==

==inizio objective==

Random prostate biopsy is still the gold standard procedure to detect prostate cancer. Multiparametric MRI has been introduced to guide target prostate biopsy to improve detection of clinically significant prostate cancer. Today is debated whether primary biopsy should be performed with random or target approach. We evaluated outcomes of patients undergone first transrectal random prostate biopsy. We also evaluated predictive factors of prostate cancer diagnosis.

==fine objective==

==inizio methodsresults==

Patients with suspicious of prostate cancer based on PSA, DRE, ultrasound findings underwent a TRUS guided transrectal biopsy. Procedure was performed under local anaesthesia or intravenous sedation as indicated. Clinical and pathological data were prospectively collected from May 2010 to September 2017 in our database. We calculated cancer detection rate and we identified predictive factors of cancer. Statistical analysis was performed using Chi square test, Mann Whitney, logistic regression test, as appropriate (SPSS 19).

==fine methodsresults==

==inizio results==

Data on 1974 patients were available. Patients characteristics are reported in table 1.Indications for biopsy are reported in table 2. Prostate cancer has been diagnosed in 46.4% of the patients (table 3). There is an increasing trend in cancer detection rate per year (table 4). Positive patients presented ≥3 positive cores or Gleason ≥3+4 in 78,5% and 86,7%, respectively. At multivariate analysis, age, PSA, DRE, prostate volume, number of cores, and year of biopsy are predictive of cancer diagnosis.

Table1.patientscharacteristics

Age (y) 66.3
Bmi (n) 27.4 8.4
Psa (ng/ml) 14.9 39.8
Prostate volume (cc) 60.8 3.3
PSA density 0.28 0.79
Coresnumber (n) 12.7 2.8
+ve DRE (%) 37.9

Table 2. Indication for biopsy

%
PSA 70.7
PSA+ER 27.3
PSA+TRUS 0.2
ER 1.7
TRUS 0.1

Table 3. Prostate biopsyresults

Result %
IPB 40.0
ASAP 4.3
HGPIN 9.3
Cancer 46.4

Table 4. per yearcancerdetection rate
Year pts (n) Cancerdetection rate (%)
2010 176 39.2
2011 266 41.7
2012 303 37.6
2013 309 46.9
2014 239 50.9
2015 307 53.1
2016 205 54.2
2017 169 49.1

Table5. multivariate analysis for cancerdetection rate.
Variable P value OR 95 CI
Age 0.002 1.034 1.012-1.056
BMI 0.13 1.019 0.994-1.044
+DRE <0.001 0.293 0.212-0.407 PSA <0.001 0.939 0.909-0.971 Prostate volume <0.001 0.986 0.977-0.994 Coresnumber <0.001 0.874 0.816-0.937 Year of biopsy <0.001 1.101 1.055-1.149 ==fine results== ==inizio discussions== ==fine discussions== ==inizio conclusion== Random transrectal prostate biopsy identified cancer in 46% of all patients. In the last three years, cancer detection rate is more than half of the patients. More than three quarters of patients presented a clinically significant cancer. Age, PSA, positive DRE, prostate volume and number of cores are correlated with presence of cancer ==fine conclusion== ==inizio reference== ==fine reference==

==inizio objective==

We need to identified only the significant Prostate cancer. PSA is not enough sensible to rule out latent PC. Pro2PSA and PHI (prostate health index ) can help us in the diagnosis but also here there is a grey zone (1-4). To-day Multi-parametric MRI (mp-MRI) may have a role in ruling-out clinically significant prostate cancer (5-8). We decided to offer to the patients with PSA between 4 and 10 ng/ml the test of PHI and who had PHI under 40 were evaluated with mpMRI.

==fine objective==

==inizio methodsresults==

185 consecutive men between January and December 2015 with a mean age 67 years (range 40 to 76y.) and mean PSA 6.2ug/L (range 4.1 to 10) were evaluated., after PHI the Mp-MRI (T1/T2, dynamic contrast enhancement and diffusion weighting, 1.5Tesla, pelvic phased array) was performed each mp-MRI was reported with knowledge of PSA and patient age, by two uro-radiologists expert in prostate MRI. Each prostate was divided into 4 regions of interest (ROI) and a score of 1 to 5 assigned to each ROI (PIRADS 2 score : 1 – ˜no cancer, 5 – highly suspicious.
120 patients which a negative mpMRI entered in a follow – up program. 65 underwent a TRUS fusion guided biopsy for suspicious lesions (12 mapping and target lesion sample and 4 only in the target lesion).

==fine methodsresults==

==inizio results==

In the 65 mpMRI lesion we found 49 tumors (36 Gleason 7 and 13 Gleason 8) at biopsy . The other enter in follow up (no PSA event in 18 months). Between the 120 pts with normal mpMRI 110 had PSA and DRE stable at more than 18 months, but in 10 the PSAv went up and we performed TRUS biopsy. In 6 of 10 a significant Gleason 6 cancer were found.

==fine results==

==inizio discussions==

The data obtained in our study are comparable to others published in the literature; phi appears to be the best marker for prostate cancer screening to date followed by %p2PSA.
The study has shown that phi outperforms tPSA and fPSA, when used alone or in combination, and appears to be more accurate than both markers in excluding prostate cancer before biopsy. Therefore, it helps clinicians to avoid unnecessary biopsies, particularly in patients with gray-zone tPSA level. Phi is the strongest marker that correlates proportionally with GS; making it useful in predicting the aggressiveness of the disease (1-4). Our experience suggests that mp-MRI may have a role in ruling-out clinically significant prostate cancer, sparing a considerable number of invasive prostate biopsy. This finding also can be used to address the over-diagnosis burden from PSA screening by using mp-MRI as a triage test to identify men who can avoid a prostate biopsy (5-8).A prospective study of MRI and MRI guided biopsy (not ultrasound fusion) demonstrated improved cancer detection in biopsy-naïve men (9). Cost estimates for the addition of MRI to the initial diagnostic algorithm of prostate cancer have ranged widely and often more closely reflect local market forces than actual resource utilization (8,10,11).

==fine discussions==

==inizio conclusion==

In this setting, mpMRI can help to manage low risk patients , PSA < 10 and PHI > 40 , The high negative predictive value for clinically
significant cancer as defined suggests that mp-MRI may have a role in ruling-out clinically significant prostate cancer. This finding could be used to address the over-diagnosis burden from PSA screening by using mp-MRI as a triage test to identify men who could avoid a prostate biopsy

==fine conclusion==

==inizio reference==

1) Huang Y-Q, Sun T, Zhong W-D, Wu C-L. Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the detection and management of prostate cancer. Am J Clin Exp Urol 2014. Dec;2(4):343-350.
2) Fuchsova R, Topolcan O, Windrichova J, Hora M, Dolejsova O, Pecen L, et al. PHI in the Early Detection of Prostate Cancer. Anticancer Res 2015. Sep;35(9):4855-4857.
3) Boegemann M, Stephan C, Cammann H, Vincendeau S, Houlgatte A, Jung K, et al. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years. BJU Int 2016. Jan;117(1):72-79
4) Loeb S, Sanda MG, Broyles DL, Shin SS, Bangma CH, Wei JT, et al. The prostate health index selectively identifies clinically significant prostate cancer. J Urol 2015. Apr;193(4):1163-1169.
5) Costa DN, Pedrosa I, Roehrborn C, et al. Multiparametric magnetic resonance imaging of the prostate: technical aspects and role in clinical management. Top Magn Reson Imaging 2014;23:243-57.
6) Bjurlin MA, Meng X, Le Nobin J, et al. Optimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment. J Urol 2014;192:648-58. 10.1016/j.juro.2014.03.117 [PMC free article] [PubMed] [Cross Ref]
7) Weinreb JC, Barentsz JO, Choyke PL, et al. PI-RADS Prostate Imaging-Reporting and Data System:2015,Version 2. Eur Urol 2016;69:16-40 10.1016/j.eururo.2015.08.052 [PubMed] [Cross Ref]
8) de Rooij M, Hamoen EH, Fütterer JJ, et al. Accuracy of multiparametric MRI for prostate cancer detection: a meta-analysis. AJR Am J Roentgenol 2014;202:343-51. 10.2214/AJR.13.11046
9) Pokorny MR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol 2014;66:22-9.
10) de Rooij M, Crienen S, Witjes JA, et al. Cost-effectiveness of magnetic resonance (MR) imaging and MR-guided targeted biopsy versus systematic transrectal ultrasound-guided biopsy in diagnosing prostate cancer: a modelling study from a health care perspective. Eur Urol 2014;66:430-6. 10.1016/j.eururo.2013.12.012 [PubMed] [Cross Ref]
11) Lotan Y, Haddad AQ, Costa DN, et al. Decision analysis model comparing cost of multiparametric magnetic resonance imaging vs. repeat biopsy for detection of prostate cancer in men with prior negative findings on biopsy. Urol Oncol 2015;33:266.e9-16.

==fine reference==

==inizio objective==

SERPINB3, also known as Squamous Cell Carcinoma Antigen-1 or SCCA1 is a member of the family of serine-protease inhibitors. SERPINB3 protects cells from oxidative stress conditions, but in chronic damage this serpin may lead to cancerous lesions through different strategies, including inhibition of apoptosis, induction of epithelial to mesenchymal transition and decrease of desmosomal junctions, cell proliferation and invasiveness. The aim of the present study was to investigate the protein expression of SERPINB3 in a series of prostate cancer specimens and benign prostatic hyperplasia (BPH) following transurethral resection of the prostate (TURP).

==fine objective==

==inizio methodsresults==

Sixty prostate specimens were investigated. Fifty specimens were diagnosed as prostate carcinoma and 15 as benign prostate hyperplasia. The samples were fixed in 10% formaldehyde and paraffin-embedded. Two-micrometer thick sections were cut and processed for immunohistochemistry with primary antibodies raised against SERPINB3 (Proteintech, Rosemont, IL, USA). This was followed by 30 min incubation with the Envision system (Dako). 3,3’-Diaminobenzidine tetrahydrochloride was used as a chromogen to yield brown reaction products.

==fine methodsresults==

==inizio results==

SERPINB3 expression was detected in a high percentage of prostate cancer tissues (80%), but to a much lesser extent in adjacent non-malignant tissues (20%) or tissue affected by benign prostatic hyperplasia (p <0.001). High levels of SERPINB3 expression were found in advanced prostate tissue specimens. ==fine results== ==inizio discussions== The levels of SERPINB3 transcripts or proteins from biological samples have been used in numerous studies to predict disease stage and response to therapy. Detailed histological analysis revealed that SERPINB3 is normally expressed in squamous epithelial cells of tongue, esophagus, tonsils, epidermal hair follicles, lung and uterus, while becoming highly up-regulated in squamous carcinomas of these organs anyway SERPINB3 levels have also been shown to coincide with tumor infiltration and frequency of lymph node metastasis in both cervical and esophageal squamous cell carcinomas. Recent evidence also suggests that SERPINB3 expression is not limited to cancers of squamous origin but also extends to adenocarcinoma of the lung, breast, and pancreas, as well as hepatocellular carcinoma. In addition to being a biomarker, SERPINB3 have been found to associate with several oncogenic processes, suggesting that they are bona fide oncoproteins. Ectopic expression of SERPINB3 leads to oncogenic transformation of the non-tumorigenic mammary epithelial cells . The positive association of elevated SERPINB3 with more advanced malignancy as well as poor prognosis suggests that SERPINB3 may have a positive impact on tumorigenesis and/or tumor progression. The pro-tumorigenic role of SERPINB3 has been largely attributed to their anti-cell death function. SERPINB3 has been shown to protect cancer cells from apoptosis induced by UV irradiation and anti-cancer therapy . SERPINB3 has also been found to localize to the mitochondrial inner membrane to interact with Complex I and suppress mitochondrial ROS generation. Elevated SERPINB3 expression correlates with resistance to platinum combined treatment in non-small cell lung carcinoma and poor prognosis of anthracyclin based chemotherapy in breast cancer. Suppression of SERPINB3 using antisense RNA or short-hairpin RNA leads to decreased growth of a SCC cell line and a number of breast and pancreatic cancer cells. Nonetheless, detection methods with better specificity and higher sensitivity are needed for a more empirical practice of using SERPINB3 as biomarkers [1]. ==fine discussions== ==inizio conclusion== These results suggest that SERPINB3 may be a potential prognostic marker for prostate cancer and that the down-regulation of SERPINB3 may be a therapeutic target in the suppression of prostate cancer growth. ==fine conclusion== ==inizio reference== 1.Yu Sun, Namratha Sheshadri, Wei-Xing Zong, SERPINB3 and B4: from biochemistry to biology Semin Cell Dev Biol. 2017 Feb; 62: 170–177 ==fine reference==

==inizio objective==

To evaluate the best strategy for the correct “detection rate” of significant prostate cancer (PC) in patients who must undergoing re biopsy. Saturation 24 sample in no MRI lesion against target biopsy with fusion technique in finding of Pirads 3-5 lesions.

==fine objective==

==inizio methodsresults==

In the period 1.2014- 12.2016 we performed consecutively mp-MRI in 221 high risk patients (62aa mean age (range 50 – 74), average
PSA 13.53 ng/ml , (range 4.6 – 23), negative DRE)
who need rebiopsy. 112 Negative mp-MRI underwent “saturation biopsy” . 109 mp-MRI with lesion Pirads 3-5 underwent target fusion biopsy .
Each patient had already been subjected to at least one previous set biopsy with a number average of 12 samples . This indication was previous diagnosis of PIN
/ ASAP in 24 (16 pts PIN / ASAP 8 patients) or abnormal increase in the PSA.
Each procedure, performed outpatient basis, was conducted by transrectal way, patients with negative mp-MRI underwent saturation with peripheral block, using
a schema biopsy default to 24 withdrawals. Patients with positive mp-MRI (Pirads 3-5) underwent target biopsy , 4 sample for each lesion, using Toshiba Aplio
500 fusion sofware

==fine methodsresults==

==inizio results==

112 patients saturation biopsy 36 PC (31 Gleason 6 – 5 Gleason >= 7) 76 BPH.
109 patients target biopsy 64 PC ( 6 Gleason 6 – 58 Gleason >= 7) – 45 BPH
29 patients underwent surgery in saturation group ; 2 pT3 and 27 pT2 , no significant variation in Gleason Score.
58 patients underwent surgery in target fusion biopsy 53 pT3 and 5 pT2, no significant variation in Gleason Score

==fine results==

==inizio discussions==

The indication for which there appears to be the best evidence for cost efficacy in prostate MRI is in the man with a negative prior ultrasound-guided prostate biopsy and continued clinical suspicion for prostate cancer (1). In the past clinical nomograms provided information about likelihood of repeated biopsies being positive, but did not provide guidance for localization of repeat biopsy (2). Similarly, additional tests and biomarkers have been shown to improve the performance of PSA in men with prior negative biopsy (3). Studies of MR guided biopsy in men with prior negative ultrasound biopsy have shown an increased rate of detection of high grade tumors, especially in the anterior prostate, a region often poorly sampled in ultrasound-guided biopsy (4). A study from 2015 showed both cost savings in using MRI to inform repeat biopsy and that a large portion of repeat biopsies could be avoided (5). In patients undergoing MR-guided biopsy after negative prior biopsy the possibility of avoiding systematic (non-targeted) biopsies as a cost saving measure has been raised. This approach should be used with caution as it appears that systematic biopsies still add value and detect some clinically relevant cancers in this setting (6). As MRI techniques continue to refine and MRI use in prostate cancer management grows, MRI before repeat prostate biopsy is likely to become increasingly common.
Until recently, prostate biopsy for the detection of prostate cancer has been performed transrectally and in an untargeted sampling fashion. Consequently, the procedure has suffered a small but significant risk of severe morbidity through infection, and low diagnostic accuracy, with undergrading and missed diagnosis being common. MRI is revolutionizing prostate cancer diagnosis by improving detection accuracy via targeted biopsy (7).
In fact, there is now a growing evidence in the literature that (a) saturation PBx (>20 cores) (SPBx) might be indicated in patients with PSA <10 ng/ml or low PSA density or large prostate and (b) an individualized approach with more than 12 cores according to the clinical characteristics of the patients may optimize cancer detection in the single patient. Moreover, in the era of multi-parametric MRI (mpMRI), EPBx or SPBX may be substituted by mpMRI-targeted biopsies (8) ==fine discussions== ==inizio conclusion== After a negative mp-MRI of the prostate running extended mapping biopsy ("saturation biopsy") has a detection rate of less than 30% but of Gleason 6 tumors, and nowadays probably is not recommended to rule out significant (high risk) prostate cancer. The correct scheme of sample with a positive mp-MRI is under discussion, we think that , after previous negative prostate mapping biopsy, target samples could be sufficient to find potentially lethal prostate cancer. Detection rate is up to more than 60% and about all significant cancer. ==fine conclusion== ==inizio reference== 1) Gayet M, van der Aa A, Beerlage HP, et al. The value of magnetic resonance imaging and ultrasonography (MRI/US)-fusion biopsy platforms in prostate cancer detection: a systematic review. BJU Int 2016;117:392-400. 2) Lopez-Corona E, Ohori M, Scardino PT, et al. A nomogram for predicting a positive repeat prostate biopsy in patients with a previous negative biopsy session. J Urol 2003;170:1184-8; discussion 1188. 3) Boegemann M, Stephan C, Cammann H, et al. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years. BJU Int 2016;117:72-9 4) Radtke JP, Boxler S, Kuru TH, et al. Improved detection of anterior fibromuscular stroma and transition zone prostate cancer using biparametric and multiparametric MRI with MRI-targeted biopsy and MRI-US fusion guidance. Prostate Cancer Prostatic Dis 2015;18:288-96. 5) Lotan Y, Haddad AQ, Costa DN, et al. Decision analysis model comparing cost of multiparametric magnetic resonance imaging vs. repeat biopsy for detection of prostate cancer in men with prior negative findings on biopsy. Urol Oncol 2015;33:266 6) Salami SS, Ben-Levi E, Yaskiv O, et al. In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy? BJU Int 2015;115:562-70. 7) Grummet J : How to Biopsy: Transperineal Versus Transrectal, Saturation Versus Targeted, What's the Evidence? Urol Clin North Am. 2017 Nov;44(4):525-534 8) Scattoni V, Maccagnano C, Capitanio U, Gallina A, Briganti A, Montorsi F. : Random biopsy: when, how many and where to take the cores? World J Urol. 2014 Aug;32(4):859-69. ==fine reference==

==inizio objective==

It is now recognized that the evolution of cancer cells is dependent by genetic or epigenetic alterations. However, this concept has recently been challenged by another mode of nucleotide alteration, RNA editing, which is frequently upregulated in cancer. RNA editing is a biochemical process in which either Adenosine or Cytosine is deaminated by a group of RNA editing enzymes including ADAR (Adenosine deaminase; RNA specific) The result of RNA editing is usually adenosine to inosine (A-to-I) or cytidine to uridine (C-to-U) transition, which can affect protein coding, RNA stability, splicing and microRNA-target interactions. The aim of this study was to preliminarily investigate the expression of ADAR1 in a series of prostate cancer specimens and benign prostatic hyperplasia (BPH) following transurethral resection of the prostate (TURP).

==fine objective==

==inizio methodsresults==

Sixty prostate specimens were investigated. Fifty specimens were diagnosed as prostate carcinoma and 15 as benign prostate hyperplasia. The samples were fixed in 10% formaldehyde and paraffin-embedded. Two-micrometer thick sections were cut and processed for immunohistochemistry with primary antibodies raised against ADAR1 (SantaCruz Biotechnology, Dallas, TX, USA) or CD8+ T-lymphocytes (Dako, Milan, Italy). This was followed by 30 min incubation with the Envision system (Dako). 3,3’-Diaminobenzidine tetrahydrochloride was used as a chromogen to yield brown reaction products. To quantify the surface covered by infiltrating CTLs each histological section was digitized using an automated image analysis system with incorporated ad hoc constructed image analysis software. The system automatically selected the surface covered by the CTL on the basis of red, green and blue (RGB) color segmentation.

==fine methodsresults==

==inizio results==

ADAR1 up-regulation was heterogeneously detected in a high percentage of prostate cancer tissues, but to a much lesser extent in adjacent non-malignant tissues or tissue affected by BPH (p <0.001). Prostate cancers with high ADAR1 expression exhibited high tumor-infiltrating CD8 + T lymphocyte. ==fine results== ==inizio discussions== Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. With the growing understanding of the functions of noncoding sequences and their impacts on human diseases, the role of ADAR1 in disease development is increasingly appreciated. Swift improvements in sequencing technologies have also facilitated bioinformatics studies that reveal the editing targets of ADAR1. Although we are still far from fully understanding the mechanistic aspects of ADAR1′s action, including how the dsRNA-binding domains on ADAR1 are used, the full structure of ADAR1, and the editing targets of ADAR1 that are precluded from sequencing studies, the present knowledge of ADAR1′s impacts in human pathologies may provide new possibilities for treatments and preventive measures. For instance, the levels of RNA editing by ADAR1 could serve as new tools for diagnosis in cancer stem cell-related illnesses. In situations where ADAR1 overexpression contributes to disease progression, as seen in several cancers, or where ADAR1 interacts with other proteins in editing-independent manners, inhibition of ADAR1 could potentially be another strategy in treatment [1]. ==fine discussions== ==inizio conclusion== ADAR expression is associated with several diseases including cancer, neurological disorders, metabolic diseases, viral infections, and autoimmune disorders. This study first shows that ADAR1 is highly expressed in a high percentage of prostate cancer tissues, but to a much lesser extent in adjacent non-malignant tissues or tissue affected by benign prostatic hyperplasia. Additionally, prostate cancers with high ADAR1 expression exhibited high tumor-infiltrating CD8 + T lymphocyte. Our findings indicated that ADAR1 might play an important role in the occurrence, progression, and prognosis of prostate cancer, and open new ways for the development of new and more effective immunological therapeutical strategies. ==fine conclusion== ==inizio reference== Chunzi Song, Masayuki Sakurai, Yusuke Shiromoto, Kazuko Nishikura Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases Genes (Basel) 2016 Dec; 7(12): 129 ==fine reference==

==inizio objective==

It is now ascertained that stromal-epithelial interactions play a crucial and poorly understood role in carcinogenesis and prostate cancer progression. Tumor stroma is a complex and dynamic set of cells that includes a fibroblastic component often referred to as cancer-associated fibroblasts and a collagenic and non-collagenic extracellular reactive matrix. In the present study we investigate the collagenic extracellular reactive matrix in a series of prostate cancer biopsy specimens and benign prostatic hyperplasia (BPH) following transurethral resection of the prostate (TURP). Particularly the study focused on the type of collagen composition and its spatial organization.

==fine objective==

==inizio methodsresults==

Sixty prostate specimens were investigated. Fifty specimens were diagnosed as prostate carcinoma and 15 as benign prostate hyperplasia. The samples were fixed in 10% formaldehyde and paraffin-embedded. Two-micrometer thick sections were cut and stained with picric acid-sirius red staining to distinguish type I and III collagen using a polarized light microscopy. The ratios of collagen I/III were automatically evaluated using a computer-aided image analysis system. The spatial organization was evaluated on unstained tissue sections by combining a multi-photon microscopy and an open-source MATLAB software framework that includes two separate but linked packages “CurveAlign” and “CT-FIRE”. All of the data were analyzed using Statistica software (StatSoft, Inc., Tulsa, OK, USA) and GraphPad Prism 5 (San Diego, California, USA). P-values of ≤ 0.05 were considered to be statistically significant.

==fine methodsresults==

==inizio results==

By observing the stained sections with Picro-Sirius Red we found different conformations of the collagenic extracellular matrix. Collagen matrix is characterized by a set of highly irregular fragments with different size, size and roughness. In particular, the tumor microenvironment consists of thin collagen fibers while dense plaques have been observed in the microenvironment that characterizes BPH status. Additionally, we found that in BPH type III collagen is less represented if compared to the low and high-grade tumoral tissues. A statistically significant difference was identified between BPH and biopsies of patients with low-grade tumor and in whose fragment no neoplastic cells were observed (p<0.001). In addition, the alignment of collagen fibers is much more pronounced in biopsy of prostate cancer patients than in tissues of patients with BPH. ==fine results== ==inizio discussions== Prostate stroma is a complex dynamical framework, which involves multiple pathways that are dependent on the homeostatic balance between several growth factors. The topographical organization of collagen within the tumor microenvironment has been implicated in modulating cancer cell migration and independently predicts progression to metastasis. It’s known that collagen matrices with small pores and short fibers, triggers a conserved transcriptional response and subsequent motility switch in cancer cells resulting in the formation of multicellular network structure. An initial step in cancer metastasis is the migration of tumor cells through the extracellular matrix and into the lymphatic or vascular systems. Several features of the tumor ECM have been associated with progression to metastasis. In particular, regions of dense collagen are co-localized with aggressive tumor cell phenotypes in numerous solid tumors, including breast, ovarian, pancreatic and brain cancers. However, sparse and aligned collagen fibers at the edges of tumors have also been reported to correlate with aggressive disease. It remains unclear whether and how collagen architectures have a role in driving metastatic migration programs or if they simply correlate with progression of the tumor [1]. ==fine discussions== ==inizio conclusion== Collagen type (type I versus type III) composition and its spatial organization i.e. alignment is different when evaluated in tumoral versus inflammatory state. Given the dynamical process of tissue matrix remodeling, our findings first demonstrated that stromal collagen alignment might provide additional, clinically-relevant information about prostate cancer and underscores the importance of stroma-cancer interactions. ==fine conclusion== ==inizio reference== 1. Velez DO, Tsui B, Goshia T, Chute CL, Han A, Carter H, Fraley S. 3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry. Nat Commun. 2017 Nov 21;8(1):1651. ==fine reference==

==inizio objective==

Robotic surgery could lead to improved continence outcome in terms of early recovery because of the magnified 3Dvision and the possibility to reach spaces other way not reachable. Age, scars in the rhabdosphincter, length of urethra and postoperative sphincter insufficiency have been considered as possible causes of temporary or definitive urinary incontinence.
We describe a modification of the anastomotic RALP technique that overcomes caudal retraction, reconstructs the posterior fibrous raphe, reconstructs the sphincter, “urethralizes” the levator-ani muscles and restores the anterior support.
Aim of the study is to compare retrospectively the new anastomotic RALP technique with standard technique performing Van Velthoven stitch with and without Rocco stich.
Primary endpoint is continence rate at different time; secondary endpoint is evaluation of urine leakage and anastomosis stenosis rates related to the technique.

==fine objective==

==inizio methodsresults==

From June 2015 to June 2017, 190 patients with localized prostate cancer underwent RALP new anastomosis (group 1) and were retrospectively compared with 200 patients (cT1-3,cN0, cM0) undergone Van Velthoven with Rocco stich (group 2) and 200 patients (cT1-3,cN0, cM0) undergone Van Velthoven without Rocco stich (group 3).
New surgical technique: the posterior semi-circumference of the sphincter is joined to the residuum of Denonvilliers’ fascia using a V-Lock 23 cm long continue suture including laterally part of levator-ani muscle; successively this suture is fixed to the posterior bladder wall 1 cm cranial and dorsal to the new bladder neck before completing the vesicourethral anastomosis with the aim to avoid caudal retraction of the urethrosphincteric complex. Vesicourethral anastomosis is subsequently performed with care taken not to involve the neurovascular bundles. To enlarge the concept of total anatomical reconstruction of Porpiglia we also “urethralize” the right and left levator- ani towards the anastomosis and restore the anterior support.
Pre, intra and postoperative and pathological variables were analyzed.
The same surgeon performed all RALP.
Continence was analyzed preoperatively and 24 hours, 1, 4 , 12 and 24 weeks after catheter removal.

==fine methodsresults==

==inizio results==

600 patients were analyzed. In group 1 the continence rate at catheter removal and at 1, 4, 12, and 24 weeks was 60.5%, 63.0%, 68.0%,69.0% and 71.0%, respectively.
In group 2 it was 52.0%, 52.5%,59.5%, 61.0% and 69.5%.
In group 3 it was 51.0%, 52.0%, 58.5%, 60.5% and 68.0%

Acute urinary retentions in group 1 was 2.5% (3 % in group 2 and 2.0% in group 3) and urine leakage was 1% (2% in group 2 and 3).

==fine results==

==inizio discussions==

The presence of urinary incontinence after RP can significantly impact patient quality of life, the desire to reduce the invasiveness of open surgery and the search for better functional results have been driving factors for the popularity of laparoscopic techniques. Optical magnification has been considered one of the strongest advantages of laparoscopy, and this is particularly true in the case of surgery for prostate cancer. Robotic technology provides further advantages, including binocular three-dimensional visualization with magnification, physiologic tremor of the surgeon’s hand filtration with demultiplication of movements, and wristed instrumentation. Meticulous, precise, and accurate surgical movements are fundamental for minimizing perioperative complications and preserving the key anatomical structures that are involved in urinary continence (1).
Indeed, many published papers have shown the advantages of robotics in terms of functional results (2-5).
Although the mechanism of continence recovery after surgery is complex and not wholly understood, it is universally accepted that the main aim of the surgeon must be to preserve the anatomical structures involved in continence and to precisely conduct reconstruction phase. In recent years, several technical modifications aimed to improve postoperative continence after RP have been proposed, including bladder neck preservation, intussusception of the bladder neck, approximation of anterior supporting structures with sparing or reconstruction of the puboprostatic ligaments, creation of posterior urethral support (posterior reconstruction of the rhabdosphincter), and variations of suspension
sutures . According to Patel et al (6), anterior support provides anatomical support for the urethra, which allows the urethral length to be maximized during apex dissection and either the urethra or the rhabdosphincter to be stabilized in their anatomical position.
Rocco et al (7) proposed a posterior fixation of the anastomosis; this technical modification has been widely used by RARP surgeons even if Menon et al (8) did not find any improvement in the early continence.

In the present study, we reported a RALP anastomosis technique that aimed to restore the anterior and posterior supports to the sphincter. Firstly, we believe that the preservation of pubo-prostatic ligaments is crucial because it allows for better apex dissection; secondly, incision of the bladder necks may be performed in a bloodless way and posterior aspect of the bladder neck should be anchored to the median raphe to reinforce the posterior reconstruction. Then prostatic apex should be done step-by-step, with meticulous dissection of muscular fibers limiting the use of cauterization as much as possible to preserve the anatomical structures that are involved in the support of the urethra and to maximize urethral length. The urethralization of levator ani muscle, as described by Porpiglia [5], do provide an improvement in the continence process as it is provided by ProACT ballons. During the anterior reconstruction, in our technique an apron will be restored and reanchored to the muscular fibers that arise from the anterior aspect of the rhabdosphincter. In summary, the three cornerstones of our technique are the anatomical dissection of the prostatic apex the restoration of the anatomy of the peri-urethral structures by protecting the anastomosis using three posterior layers and two anterior layers, which allows for “tension-free” anastomosis and finally the urethralization of the levator ani muscle.

==fine discussions==

==inizio conclusion==

There is no difference between the group 2 and group 3, anyway the new anastomotic technique (group 1) seems to be promising as it results in the early recovery of urinary continence.

==fine conclusion==

==inizio reference==

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Patel, V.R., Stolzenburg, J.U., Van der Poel, H., Wilson, T.G., Zattoni, F., and Mottrie, A. Systematic
review and meta-analysis of studies reporting urinary continence recovery after robot-assisted
radical prostatectomy. Eur Urol. 2012; 62: 405–417
2) Tewari, A., Srivasatava, A., and Menon, M. Members of the VIP Team. A prospective comparison of
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205–210
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Santoro, L., Detti, S., and de Cobelli, O. Robotic vs open prostatectomy in a laparoscopically naive
center: a matched-pair analysis. BJU Int. 2009; 104: 991–995
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comparing consecutive series of open retropubic and robot-assisted laparoscopic radical
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and Fiori, C. Randomized controlled trial comparing laparoscopic and robot-assisted radical
prostatectomy. Eur Urol. 2013; 63: 606–614
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laparoscopic radical prostatectomy: description of the technique and continence outcomes.
Eur Urol. 2009; 56: 472–478
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G., and Consonni, D. Early continence recovery after open radical prostatectomy with restoration of
the posterior aspect of the rhabdosphincter. Eur Urol. 2007; 52: 376–383
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1023

==fine reference==