Publications by authors named "Giovanni Muto"

57 Publications

How uro-oncology has been affected by COVID-19 emergency? Data from Piedmont/Valle d'Aosta Oncological Network, Italy.

Urologia 2021 Feb;88(1):3-8

Division of Urology, Molinette Hospital-Città della Salute e della Scienza di Torino, University of Turin, Torino, Italy.

Introduction: Coronavirus disease 2019 (COVID-19) pandemic has dramatically hit all Europe and Northern Italy in particular. The reallocation of medical resources has caused a sharp reduction in the activity of many medical disciplines, including urology. The restricted availability of resources is expected to cause a delay in the treatment of urological cancers and to negatively influence the clinical history of many cancer patients. In this study, we describe COVID-19 impact on uro-oncological management in Piedmont/Valle d'Aosta, estimating its future impact.

Methods: We performed an online survey in 12 urological centers, belonging to the Oncological Network of Piedmont/Valle d'Aosta, to estimate the impact of COVID-19 emergency on their practice. On this basis, we then estimated the medical working capacity needed to absorb all postponed uro-oncological procedures.

Results: Most centers (77%) declared to be "much"/"very much" affected by COVID-19 emergency. If uro-oncological consultations for newly diagnosed cancers were often maintained, follow-up consultations were more than halved or even suspended in around two out of three centers. In-office and day-hospital procedures were generally only mildly reduced, whereas major uro-oncological procedures were more than halved or even suspended in 60% of centers. To clear waiting list backlog, the urological working capacity should dramatically increase in the next months; delays greater than 1 month are expected for more than 50% of uro-oncological procedures.

Conclusions: COVID-19 emergency has dramatically slowed down uro-oncological activity in Piedmont and Valle d'Aosta. Ideally, uro-oncological patients should be referred to COVID-19-free tertiary urological centers to ensure a timely management.
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http://dx.doi.org/10.1177/0391560320946186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917571PMC
February 2021

Health-related quality of life 24-month after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

Minerva Urol Nefrol 2021 Jan 13. Epub 2021 Jan 13.

Urology Unit, Azienda Socio-Sanitaria Territoriale Lariana, Sant'Anna Hospital, Como, Italy.

Background: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study.

Methods: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), radiotherapy plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain.

Results: Overall, 1 537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, p<0.001 and - 19.7, p<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, p=0.02) and RT plus ADT groups at 12 months (-10.3, p=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, p<0.001, -37.8, p<0.001, -20.4, p<0.001, respectively).

Conclusions: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.
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http://dx.doi.org/10.23736/S0393-2249.20.04032-1DOI Listing
January 2021

The waiting time for prostate cancer treatment in Italy: analysis from the Pros-IT CNR study.

Minerva Urol Nefrol 2020 Nov 17. Epub 2020 Nov 17.

National Research Council (CNR), Neuroscience Institute, Aging Branch, Padua, Italy.

Background: Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established.

Methods: Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated.

Results: The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT >90 days. At 6 months from diagnosis the mean SF-12 score for the emotionalpsychological component was significantly lower in WT ≥ 90 days group (p=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups.

Conclusions: In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT > 90 days. WT might have no impact on functional and oncological outcome.
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http://dx.doi.org/10.23736/S0393-2249.20.03925-9DOI Listing
November 2020

How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

World J Urol 2020 Aug 1. Epub 2020 Aug 1.

Aging Branch, National Research Council (CNR), Neuroscience Institute, Padua, Italy.

Purpose: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy.

Methods: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND).

Results: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies.

Conclusions: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.
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http://dx.doi.org/10.1007/s00345-020-03350-5DOI Listing
August 2020

En-bloc endoscopic enucleation of the prostate: a systematic review of the literature.

Minerva Urol Nefrol 2020 Jun 30;72(3):292-312. Epub 2020 Jan 30.

Department of Urology, Careggi Hospital, University of Florence, Florence, Italy.

Introduction: Transurethral resection of the prostate (TURP) remains the gold standard for treatment of benign prostatic hyperplasia (BPH). Yet, the introduction of lasers for the treatment of LUTS due to BPO has dramatically changed the surgical landscape of benign prostatic obstruction (BPO) treatment. Recently, "en-bloc" techniques have shown to prove advantageous in terms of better visualization, more prompt identification of the surgical capsule and the correct plane to dissect. Herein we provide a comprehensive overview of available series of en-bloc enucleation of the prostate, focusing on surgical techniques, perioperative and functional outcomes.

Evidence Acquisition: A systematic review of the literature was performed according to PRISMA recommendations and was conducted on surgical techniques and perioperative outcomes of minimally invasive en-bloc surgery for prostate adenoma detachment.

Evidence Synthesis: Overall, 16 studies with 2750 patients between 2003 and 2019 were included. Specific technical nuances have been described to maximize perioperative outcomes of en-bloc prostatic enucleation, including early apical release, horse-shape incisions, inverted U-shape tractions and low power. Overall, regardless of the energy employed, en-bloc prostatic enucleation achieved favorable outcomes including low risk of major complications and quality of life improvement. However, a great heterogeneity of study design, patients' inclusion criteria, prostate volume and en-bloc surgical strategy was found.

Conclusions: En-bloc endoscopic enucleation of the prostate has been shown to be technically feasible and safe, with potential technical advantages over the classic three-lobe technique. Larger comparative studies are needed to evaluate the ultimate impact of the en-bloc approach on postoperative outcomes, in light of the surgeon's learning curve.
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http://dx.doi.org/10.23736/S0393-2249.20.03706-6DOI Listing
June 2020

Accuracy of magnetic resonance imaging to identify pseudocapsule invasion in renal tumors.

World J Urol 2020 Feb 25;38(2):407-415. Epub 2019 Apr 25.

Department of Urology, Humanitas "Gardenigo" University, Turin, Italy.

Purpose: To evaluate accuracy of MRI in detecting renal tumor pseudocapsule (PC) invasion and to propose a classification based on imaging of PC status in patients with renal cell carcinoma.

Methods: From January 2017 to June 2018, 58 consecutive patients with localized renal cell carcinoma were prospectively enrolled. MRI was performed preoperatively and PC was classified, according to its features, as follows: MRI-Cap 0 (absence of PC), MRI-Cap 1 (presence of a clearly identifiable PC), MRI-Cap 2 (focally interrupted PC), and MRI-Cap 3 (clearly interrupted and infiltrated PC). A 3D image reconstruction showing MRI-Cap score was provided to both surgeon and pathologist to obtain complete preoperative evaluation and to compare imaging and pathology reports. All patients underwent laparoscopic partial nephrectomy. In surgical specimens, PC was classified according to the renal tumor capsule invasion scoring system (i-Cap).

Results: A concordance between MRI-Cap and i-Cap was found in 50/58 (86%) cases. ρ coefficient for each MRI-cap and iCap categories was: MRI-Cap 0: 0.89 (p < 0.0001), MRI-Cap1: 0.75 (p < 0.0001), MRI-Cap 2: 0.76 (p < 0.0001), and MRI-Cap3: 0.87 (p < 0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and AUC were: MRI-Cap 0: Se 97.87% Spec 83.3%, PPV 95.8%, NPV 90.9%, and AUC 90.9; MRI-Cap 1: Se 77% Spec 95.5%, PPV 83.3%, NPV 93.5%, and AUC 0.86; MRI-Cap 2- iCap 2: Se 88% Spec 90%, PPV 79%, NPV 95%, and AUC 0.89; MRI-Cap 3: Se 94% Spec 95%, PPV 88%, NPV 97%, and AUC 0.94.

Conclusions: MRI-Cap classification is accurate in evaluating renal tumor PC features. PC features can provide an imaging-guided landmark to figure out where a minimal margin could be preferable during nephron-sparing surgery.
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http://dx.doi.org/10.1007/s00345-019-02755-1DOI Listing
February 2020

Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases.

Cell Death Dis 2019 02 27;10(3):201. Epub 2019 Feb 27.

IRCCS, Regina Elena National Cancer Institute, Rome, Italy.

The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.
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http://dx.doi.org/10.1038/s41419-019-1453-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393468PMC
February 2019

Correction: Metabolic syndrome increases the risk of upgrading and upstaging in patients with prostate cancer on biopsy: a radical prostatectomy multicenter cohort study.

Prostate Cancer Prostatic Dis 2019 Sep;22(3):491

Department of Urology, Ospedale Sant'Andrea, "La Sapienza" University, Rome, Italy.

The original version of this Article contained an error in the spelling of the authors Cosimo De Nunzio, Aldo Brassetti, Giuseppe Simone, Riccardo Lombardo, Riccardo Mastroianni, Devis Collura, Giovanni Muto, Michele Gallucci and Andrew Tubaro, which were incorrectly given as De Nunzio Cosimo, Brassetti Aldo, Simone Giuseppe, Lombardo Riccardo, Mastroianni Riccardo, Collura Devis, Muto Giovanni, Gallucci Michele and Tubaro Andrea. This has now been corrected in both the PDF and HTML versions of the Article.
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http://dx.doi.org/10.1038/s41391-019-0132-7DOI Listing
September 2019

Accuracy of elastic fusion biopsy in daily practice: Results of a multicenter study of 2115 patients.

Int J Urol 2018 12 5;25(12):990-997. Epub 2018 Sep 5.

Department of Surgical Sciences - Urology, University of Turin, Turin, Italy.

Objectives: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice.

Methods: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables.

Results: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer.

Conclusions: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate.
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http://dx.doi.org/10.1111/iju.13796DOI Listing
December 2018

Renal cancer: new models and approach for personalizing therapy.

J Exp Clin Cancer Res 2018 Sep 5;37(1):217. Epub 2018 Sep 5.

IRCCS, Regina Elena National Cancer Institute, Rome, Italy.

Background: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be the best efficacious approach for the majority of patients. However, a consistent fraction (30%) of cases progress after surgery with curative intent. It is currently largely debated the use of adjuvant therapy for high-risk patients and the clinical and molecular parameters for stratifying beneficiary categories. In addition, the treatment of advanced forms lacks reliable driver biomarkers for the appropriated therapeutic choice. Thus, renal cancer patient management urges predictive molecular indicators and models for therapy-decision making.

Methods: Here, we developed and optimized new models and tools for ameliorating renal cancer patient management. We isolated from fresh tumor specimens heterogeneous multi-clonal populations showing epithelial and mesenchymal characteristics coupled to stem cell phenotype. These cells retained long lasting-tumor-propagating capacity provided a therapy monitoring approach in vitro and in vivo while being able to form parental tumors when orthotopically injected and serially transplanted in immunocompromised murine hosts.

Results: In line with recent evidence of multiclonal cancer composition, we optimized in vitro cultures enriched of multiple tumor-propagating populations. Orthotopic xenograft masses recapitulated morphology, grading and malignancy of parental cancers. High-grade but not the low-grade neoplasias, resulted in efficient serial transplantation in mice. Engraftment capacity paralleled grading and recurrence frequency advocating for a prognostic value of our developed model system. Therefore, in search of novel molecular indicators for therapy decision-making, we used Reverse-Phase Protein Arrays (RPPA) to analyze a panel of total and phosphorylated proteins in the isolated populations. Tumor-propagating cells showed several deregulated kinase cascades associated with grading, including angiogenesis and m-TOR pathways.

Conclusions: In the era of personalized therapy, the analysis of tumor propagating cells may help improve prediction of disease progression and therapy assignment. The possibility to test pharmacological response of ccRCC stem-like cells in vitro and in orthotopic models may help define a pharmacological profiling for future development of more effective therapies. Likewise, RPPA screening on patient-derived populations offers innovative approach for possible prediction of therapy response.
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http://dx.doi.org/10.1186/s13046-018-0874-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126022PMC
September 2018

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study.

Health Qual Life Outcomes 2018 Jun 13;16(1):122. Epub 2018 Jun 13.

Policlinico di Abano Terme, Padova, Italy.

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed.

Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12).

Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis.

Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.
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http://dx.doi.org/10.1186/s12955-018-0952-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001046PMC
June 2018

Metabolic syndrome increases the risk of upgrading and upstaging in patients with prostate cancer on biopsy: a radical prostatectomy multicenter cohort study.

Prostate Cancer Prostatic Dis 2018 09 4;21(3):438-445. Epub 2018 Jun 4.

Department of Urology, Ospedale Sant'Andrea, "La Sapienza" University, Rome, Italy.

Backround: Recently metabolic syndrome has been associated to an increased risk of advanced disease. Aim of our study is to investigate the association of metabolic syndrome (MetS) with the risk of prostate cancer (PCa) upgrading and upstaging after radical prostatectomy (RP).

Methods: From 2012 and 2016, 400 consecutive men underwent RP at three referral centers in Italy and were enrolled into a prospective database. Blood pressure, body mass index and waist circumference were measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Logistic regression analyses were used to assess the association between MetS, defined according to Adult Treatment Panel III, and the risk of upgrading and upstaging), using the new Prognostic Grade Group (PGG) classification system.

Results: Overall 148/400 (37%) men were diagnosed with MetS and most of these reported up-grading (54.5%) and up-staging (56.8%). These events were significantly more common in this population and MetS was a risk factor for up-staging and up-grading on multivariable analysis. Patients with MetS presented worst accuracy (72 vs. 84%; p = 0.001) and worst kappa coefficient of agreement (k = 0.439 ± 0.071 vs. k = 0.553 ± 0.071) between needle biopsy and radical prostatectomy specimens when compared to patients without MetS.

Conclusions: MetS represents a significant risk factor for upgrading and upstaging. Accuracy of PGG system on biopsy is poor in patients with MetS, therefore results should be evaluated carefully in this population.
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http://dx.doi.org/10.1038/s41391-018-0054-9DOI Listing
September 2018

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients.

Eur J Surg Oncol 2018 06 9;44(6):835-839. Epub 2018 Jan 9.

Department of Urology, "Sant'Andrea" Hospital, "La Sapienza" University, Rome, Italy. Electronic address:

Purpose: To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates.

Materials And Methods: Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value.

Results: The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007).

Conclusions: The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management.
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http://dx.doi.org/10.1016/j.ejso.2017.12.003DOI Listing
June 2018

Quality of Life After Prostate Cancer Diagnosis: Data from the Pros-IT CNR.

Eur Urol Focus 2017 10 13;3(4-5):321-324. Epub 2017 Nov 13.

National Research Council (CNR), Neuroscience Institute, Aging Branch, Padua, Italy.

Pros-IT CNR study provides a real-life report on changes in quality of life 6 mo after the diagnosis of prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2017.10.009DOI Listing
October 2017

Primary Malignant Melanoma of the Bladder.

Skinmed 2017;15(5):395-397. Epub 2017 Oct 1.

Department of Dermatology, Campus Bio-Medico University, Rome, Italy;

A 81-year-old man was admitted to our university for a second opinion after diagnosis of bladder melanoma in December 2014. His medical history included arterial hypertension, hypothyroidism, peripheral arterial disease treated with a bypass, and corneal transplantation. His medical history was negative for malignant melanoma. He experienced gross hematuria in the absence of any other clinical manifestations, and urine cytology identified atypical cells. The patient underwent transurethral resection of the bladder with diagnosis of melanoma.
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July 2019

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

Radiol Med 2018 Feb 10;123(2):143-152. Epub 2017 Oct 10.

Department of Radiology, University of Rome "Campus Bio-medico", Via Alvaro del Portillo, 21-00128, Rome, Italy.

Aims And Objectives: To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis.

Materials And Methods: 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test.

Results: There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml).

Conclusion: mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.
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http://dx.doi.org/10.1007/s11547-017-0814-yDOI Listing
February 2018

Multiparametric magnetic resonance imaging of the prostate with computer-aided detection: experienced observer performance study.

Eur Radiol 2017 Oct 6;27(10):4200-4208. Epub 2017 Apr 6.

Department of Radiology at the Candiolo Cancer Institute, FPO, IRCCS, Strada Provinciale 142 km 3.95, 10060, Candiolo, Turin, Italy.

Objectives: To compare the performance of experienced readers in detecting prostate cancer (PCa) using likelihood maps generated by a CAD system with that of unassisted interpretation of multiparametric magnetic resonance imaging (mp-MRI).

Methods: Three experienced radiologists reviewed mp-MRI prostate cases twice. First, readers observed CAD marks on a likelihood map and classified as positive those suspicious for cancer. After 6 weeks, radiologists interpreted mp-MRI examinations unassisted, using their favourite protocol. Sensitivity, specificity, reading time and interobserver variability were compared for the two reading paradigms.

Results: The dataset comprised 89 subjects of whom 35 with at least one significant PCa. Sensitivity was 80.9% (95% CI 72.1-88.0%) and 87.6% (95% CI 79.8-93.2; p = 0.105) for unassisted and CAD paradigm respectively. Sensitivity was higher with CAD for lesions with GS > 6 (91.3% vs 81.2%; p = 0.046) or diameter ≥10 mm (95.0% vs 80.0%; p = 0.006). Specificity was not affected by CAD. The average reading time with CAD was significantly lower (220 s vs 60 s; p < 0.001).

Conclusions: Experienced readers using likelihood maps generated by a CAD scheme can detect more patients with ≥10 mm PCa lesions than unassisted MRI interpretation; overall reporting time is shorter. To gain more insight into CAD-human interaction, different reading paradigms should be investigated.

Key Points: • With CAD, sensitivity increases in patients with prostate tumours ≥10 mm and/or GS > 6. • CAD significantly reduces reporting time of multiparametric MRI. • When using CAD, a marginal increase of inter-reader agreement was observed.
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http://dx.doi.org/10.1007/s00330-017-4805-0DOI Listing
October 2017

Pros-IT CNR: an Italian prostate cancer monitoring project.

Aging Clin Exp Res 2017 Apr 24;29(2):165-172. Epub 2017 Feb 24.

CNR, Aging Branch, Neuroscience Institute, Via Giustiniani 2, 35128, Padova, Italy.

Aims: The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life.

Methods: Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naïve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient's health status, the treatment carried out, and the quality of life will be made. A third assessment, evaluating the treatment follow-up and the quality of life, will be made 12 months after the initial diagnosis. The 4th, 5th, 6th and 7th assessments, similar to the third, will be completed 24, 36, 48 and 60 months after the initial diagnosis, respectively, and will include also a Food Frequency Questionnaire and the Physical Activity Scale for the Elderly.

Discussion: The study will provide information on patients' quality of life and its variations over time in relation to the treatments received for the prostate cancer.
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http://dx.doi.org/10.1007/s40520-017-0735-6DOI Listing
April 2017

An Unusual Cause of Hematuria: Primary Bladder Melanoma in an Older Man.

J Am Geriatr Soc 2016 10 29;64(10):e122-e123. Epub 2016 Sep 29.

Unit of Geriatrics, Department of Medicine, Campus Bio-Medico di Roma University, Rome, Italy.

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http://dx.doi.org/10.1111/jgs.14407DOI Listing
October 2016

Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study.

BMC Cancer 2016 07 7;16:407. Epub 2016 Jul 7.

Department of Urology, "Sant'Andrea" Hospital, "La Sapienza" University, Rome, Italy.

Background: Prostate cancer (PCa) is the most common non-skin cancer in USA and the second leading cause of cancer death in Western Countries. Despite the high mortality associated with PCa, the only established risk factors are age, race and family history. A possible association between metabolic syndrome (MetS) and PCa was firstly described in 2004 and several subsequent studies in biopsy cohorts have shown conflicting results. Aim of our multicentre prospective study was to investigate the association between MetS and PCa in men undergoing radical prostatectomy (RP).

Methods: From January 2012 to June 2015, 349 consecutive men undergoing RP for PCa at three centres in Italy were enrolled into a prospective database. Body Mass Index (BMI) as well as waist circumference was measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Blood pressure was also recorded. We evaluated the association between MetS, defined according to Adult Treatment Panel III, PCa stage (advanced stage defined as pT ≥ 3 or N1) and grade (high grade defined as Gleason Score ≥ 4 + 3) using logistic regression analyses.

Results: Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7 ng/ml (IQR: 5-10), respectively. Median BMI was 26.12 kg/m(2) (IQR 24-29) with 56 (16 %) obese (BMI ≥ 30 kg/m(2)) patients and 87 (25 %) patients with MetS. At pathological evaluation, advanced PCa and high-grade disease were present in 126 (36 %) and 145 (41.5 %) patients, respectively. MetS was significantly associated with advanced PCa (45/87, 51 % vs 81/262, 31 %; p = 0.008) and high-grade disease (47/87, 54 % vs 98/262, 37 %; p = 0.001). On multivariable analysis, MetS was an independent predictor of pathological stage ≥ pT3a or N1 (OR: 2.227; CI: 1.273-3.893; p = 0.005) and Gleason score ≥ 4 + 3 (OR: 2.007, CI: 1.175-3.428; p = 0.011).

Conclusions: We firstly demonstrated in a European radical retropubic prostatectomy cohort study that MetS is associated with an increased risk of high-grade and advanced prostate cancer. Further studies with long term follow-up should evaluate the impact of Mets on PCa survival.
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http://dx.doi.org/10.1186/s12885-016-2442-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936238PMC
July 2016

Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma.

Oncotarget 2016 May;7(22):33381-90

Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.

Purpose: We retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma.

Results: 37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms.

Conclusions: The prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients.
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http://dx.doi.org/10.18632/oncotarget.8302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078103PMC
May 2016

Development and external validation of nomograms predicting disease-free and cancer-specific survival after radical cystectomy.

World J Urol 2015 Oct 27;33(10):1419-28. Epub 2014 Dec 27.

Department of Urology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.

Purpose: To develop two nomograms predicting disease-free survival (DFS) and cancer-specific survival (CSS) and to externally validate them in multiple series.

Methods: Prospectively collected data from a single-centre series of 818 consecutive patients who underwent RC and PLND were used to build the nomogram. External validation was performed in 3,173 patients from 7 centres worldwide. Time to recurrence and to cancer-specific death were addressed with univariable and multivariable analyses. Nomograms were built to predict 2-, 5- and 8-year DFS and CSS probabilities. Predictive accuracy was quantified using the concordance index.

Results: Age, pathologic T stage, lymph-node density and extent of PLND were independent predictors of DFS and CSS (p < 0.05). Discrimination accuracies for DFS and CSS at 2, 5 and 8 years were 0.81, 0.8, 0.79 and 0.82, 0.81, 0.8, respectively, with a slight overestimation at calibration plots beyond 24 months. In the external series, predictive accuracies for DFS and CSS at 2, 5 and 8 years were 0.83, 0.82, 0.82 and 0.85, 0.85, 0.83 for European centres; 0.73, 0.72, 0.71 and 0.80, 0.74, 0.68 for African series; 0.76, 0.74, 0.71 and 0.79, 0.76, 0.73 for American series.

Conclusions: These nomograms developed from a contemporary series are simple clinical tools and provide optimal oncologic outcome prediction in all external cohorts.
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http://dx.doi.org/10.1007/s00345-014-1465-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473822PMC
October 2015

High-intensity focused ultrasound for the treatment of prostate cancer: A prospective trial with long-term follow-up.

Scand J Urol 2015 8;49(4):267-74. Epub 2014 Dec 8.

University of Perugia, Urology Department, Ospedale Santa Maria della Misericordia, Sant'Andrea delle Fratte , Perugia , Italy.

Objective: High-intensity focused ultrasound (HIFU) is a minimally invasive treatment for prostate cancer. Data from the literature show promising oncological outcomes with a favourable side-effect profile. The aim of this study was to re-evaluate and bring up to date the follow-up of a previously published, prospective trial on HIFU as the primary treatment for prostate cancer.

Materials And Methods: Between 2004 and 2007, 163 consecutive men with T1-T3N0M0 prostate cancer underwent HIFU with the Sonablate 500. Follow-up included prostate-specific antigen (PSA) tests every 3 months after treatment and a random prostate biopsy at 6 months. Failure was defined according to positive findings at the 6 month biopsy and biochemical failure was defined according to the Phoenix criteria. Biochemical-free survival, metastasis-free survival and cancer-specific survival were calculated by Kaplan-Meier curves.

Results: Median follow-up was 72.0 months. Of the 160 evaluable patients, 104 (65%) were biochemically disease free; in low- to intermediate-risk disease, on Kaplan-Meier analysis the 8 year biochemical-non-evidence of disease (bNED), metastasis-free survival and cancer-specific survival rates were 69.6%, 81.3%, 100% and 40.5%, 60.6%, 100%, respectively. A PSA nadir below 0.40 ng/ml and risk stratification have an independent predictive value for bNED and metastasis-free survival.

Conclusions: A long-term favourable outcome of HIFU is associated with careful patient selection, with low- to intermediate-risk disease being the ideal case. A low postoperative PSA nadir is a predictor of long-term bNED.
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http://dx.doi.org/10.3109/21681805.2014.988174DOI Listing
April 2016

Thulium:yttrium-aluminum-garnet laser for en bloc resection of bladder cancer: clinical and histopathologic advantages.

Urology 2014 Apr 16;83(4):851-5. Epub 2014 Feb 16.

Department of Urology, San Giovanni Bosco Hospital, Turin, Italy. Electronic address:

Objective: To determine whether thulium:yttrium-aluminum-garnet laser resection of bladder tumor (TmLRBT) may offer advantages over classic resection.

Materials And Methods: From April 2011 to September 2012, 55 consecutive patients newly diagnosed with clinical stage ≤T2 bladder cancer were enrolled in a prospective study on TmLRBT. Neoplasm was removed en bloc in all cases. When the tumor size was >3 cm, it was necessary to incise longitudinally and/or across the lesion and the bladder wall at its the base into 2 or more parts. All cases of non-muscle-invasive bladder cancer underwent second look in 30-90 days.

Results: Pathology reported urothelial carcinoma with Ta low grade in 31 patients (56.4%), T1 high grade in 18 (32.7%), and T2 high grade in 6 (10.9%). Histopathologic evaluation showed that the bladder detrusor was provided in all cases. Hemostasis was excellent, and no postoperative hematuria was reported. In a case of T1 G3, endoscopic re-evaluation showed a focal infiltration of the bladder detrusor, so the patient underwent radical cystectomy. To date, with a mean follow-up of 16 months (range, 8-25), the recurrence rate in patients with superficial disease is 14.5%. All recurrences were outside the site of first resection, and there was no progression in tumor grade.

Conclusion: TmLRBT is a simple method that seems to overcome the "incise and scatter" problem associated with traditional transurethral resection of bladder tumor. Our initial data on staging accuracy and reduction of the local recurrence rate are encouraging.
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http://dx.doi.org/10.1016/j.urology.2013.12.022DOI Listing
April 2014

Seminal-sparing cystectomy: technical evolution and results over a 20-year period.

Urology 2014 Apr 30;83(4):856-61. Epub 2014 Jan 30.

Department of Urology, San Giovanni Bosco Hospital, Turin, Italy. Electronic address:

Objective: To demonstrate the oncologic and functional results of seminal-sparing cystectomy (SSC) in patients with bladder cancer (BC) and to describe the evolution of our surgical technique over a 20-year period.

Methods: From 1990 to 2009 we performed SSC in 88 patients with non-muscle-invasive BC and in 10 patients with muscle-invasive BC away from the bladder neck. Sixty-one of the 98 patients (1990-2002) underwent cystoadenomectomy with ileocapsuloplasty (ICP), consisting of the anastomosis between the Camey II ileal reservoir and the upper edge of the prostatic capsule. This technique was affected by a relevant percentage of anastomotic stricture (11%). From 2003 to 2009, we performed the endocapsular ileourethral anastomosis (EIUA) in 30 patients, on the basis of the direct anastomosis between the ileal reservoir and the urethral stump inside the prostatic apex. Seven patients were lost to follow-up.

Results: After a mean follow-up of 102 months, 81 patients (89%) were alive, and 10 patients (11%) had died (8 of disease progression). Early and late complication rates were 25% and 24%, respectively. Complete daytime continence was obtained in 87 patients (95.6%), and nighttime continence was achieved in 34 patients (37%). In the ICP group, stricture of the prostatic fossa affected 7 patients (11%), whereas no neobladder-urethral anastomosis stricture was noticed in the EIUA group. Normal erectile function was preserved in 87 patients (95.6%).

Conclusion: SSC offers good oncologic and functional results in carefully selected patients. EIUA represents an evolution from ICP because EIUA reduces the risk of stenosis.
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http://dx.doi.org/10.1016/j.urology.2013.08.093DOI Listing
April 2014

Reply: To PMID 24485359.

Urology 2014 Apr 30;83(4):862. Epub 2014 Jan 30.

University Campus Biomedico, Rome, Italy.

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http://dx.doi.org/10.1016/j.urology.2013.08.095DOI Listing
April 2014

Huge anterior sacral meningocele simulating bladder retention.

Urology 2013 Feb;81(2):e9-10

Department of Urology, San Giovanni Bosco Hospital, Turin, Italy.

Anterior sacral meningocele (ASM) is a rare congenital disorder involving herniation of the dural sac through a defect in the anterior surface of the sacrum. We report the case of a young patient with an enormous ASM that simulated bladder retention in terms of symptoms as well as on physical examination and at ultrasonography. After introducing a catheter that excluded urinary retention, computed tomography (CT) scan and magnetic resonance imaging (MRI) showed the ASM. The patient underwent surgical repair of the ASM through a sacral laminectomy and recovered normal lower urinary tract function.
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http://dx.doi.org/10.1016/j.urology.2012.11.015DOI Listing
February 2013

Salvage external beam radiotherapy for recurrent prostate adenocarcinoma after high-intensity focused ultrasound as primary treatment.

Urol Int 2013 30;90(3):288-93. Epub 2013 Jan 30.

University of Torino, Department of Oncology, Radiation Oncology Unit, Turin, Italy.

Introduction: The main objective was to evaluate feasibility, toxicity and biochemical control rates of salvage external beam radiotherapy (EBRT) in recurrent localized prostate cancer after high-intensity focused ultrasound (HIFU) as primary therapy.

Patients And Methods: A total of 24 patients who underwent salvage EBRT after 1 or 2 HIFU sessions and with a minimum post-treatment follow-up of 24 months were retrospectively evaluated. Primary endpoints were toxicity and biochemical disease-free survival (bDFS, defined according to the ASTRO Phoenix definition).

Results: Median follow-up was 40.3 months. Gastrointestinal toxicity was low. Acute genitourinary (GU) toxicity grade ≤II rate was 45.8%, with only few patients presenting grade III (8.3%) and grade IV (4.2%) toxicity. Late grade ≥III GU toxicity was registered in 16.7% of patients. The 3-year bDFS rate was 77.8%. Patients achieving a nadir prostate-specific antigen (nPSA) of ≤0.35 ng/ml after EBRT had significantly higher bDFS (3-year bDFS: 87.7 vs. 50%, respectively; p = 0.001). Achieving nPSA ≤0.35 ng/ml was the only factor independently associated to long-term bDFS both on univariate (p = 0.01) and multivariate analysis (HR 7.06, p = 0.039).

Conclusions: Salvage EBRT after HIFU failure is feasible and allows to obtain satisfactory biochemical control rates, especially in patients attaining a nPSA ≤0.35 ng/ml after EBRT.
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http://dx.doi.org/10.1159/000345631DOI Listing
November 2013

The Turin pouch: a new technique of ileocecal cutaneous continent urinary diversion.

Urology 2013 Mar 21;81(3):663-8. Epub 2013 Jan 21.

Department of Urology, San Giovanni Bosco Hospital, Turin, Italy.

Objective: To evaluate the functional results of a new cutaneous continent reservoir, the Turin pouch (TP), consisting of an ileocolonic pouch with an innovative efferent channel (EC).

Methods: Since 2006, we have performed the TP on 14 patients in whom the appendix was absent. The distal ileum (10 cm) and right colon (40 cm) were isolated. The cecum and right colon were folded to obtain a U-shaped pouch through a stapler detubularization. An artificial EC was created by separating with a stapler a 5-cm tubularized flap of colonic wall and anastomosing this to the umbilicus.

Results: After a mean follow-up of 45 months (range, 12-72 months), 13 patients were alive and 1 died of bladder cancer progression. Early and late complications occurred in 3 and 4 patients, respectively. Daytime continence was 100% and nighttime continence was 93%. No patient has reported stenosis or difficulties in catheterization. Urodynamic studies (12 months postoperatively) showed a mean maximal pouch capacity of 520 mL (range, 360-720 mL), mean end-filling pressure of 23 cm H2O (range, 18-30 cm H2O), and mean EC closing pressure of 65 cm H2O (range, 52-75 cm H2O).

Conclusion: The TP offers good functional results and could be applied in patients undergoing continent, heterotopic, urinary diversion.
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http://dx.doi.org/10.1016/j.urology.2012.11.040DOI Listing
March 2013