Hypofractionated Postoperative Radiotherapy in Prostate Cancer with Ialuril Soft Gels®: Toxicity and Efficacy Analysis on a Retrospective Series of 305 Patients.

Aim: To evaluate the impact of Ialuril soft Gels® (HA) in reducing acute genito-urinary (GU) toxicity in patients treated with adjuvant or salvage radiotherapy for a prostate cancer relapse. Material and Methods: The data of 305 patients were retrospectively collected. One hundred and five patients underwent adjuvant radiotherapy (aRT), while 200 a salvage treatment (sRT). GU toxicity was evaluated according to CTCAE v5.0. Every patient received RT combined with HA. Results: Grade 1-2 GU toxicity during RT was represented by: urgency (36%), dysuria (23%), increased urinary frequency (12.1%), and urinary retention (11.8%). Nevertheless, the majority of symptoms were present at the baseline. Grade 3 severe toxicity was represented by 10 (3.2%) cases of incontinence and 3 (1%) cases of urgency. The incidence of any-grade RT-related GU toxicity was significantly higher in the aRT group than the salvage group (esRT + sRT) (83.8% versus 64.5%). When comparing the incidence of any-grade RT-related GU toxicity in the aRT, esRT, and sRT groups we observed a significant correlation favoring sRT, over esRT, and aRT. Conclusion: Postoperative hypofractionated radiotherapy is safe and not correlated with increase of unexpected toxicity when administered with oral hyaluronic acid. A prospective study is necessary to confirm these results.

Postoperative moderately hypofractionated radiotherapy in prostate cancer: a mono-institutional propensity-score-matching analysis between adjuvant and early-salvage radiotherapy.

AIM: To evaluate the impact of moderately hypofractionated postoperative radiotherapy (RT) in prostate cancer (PCa). MATERIALS AND METHODS: The data of 304 surgically resected PCa patients were analyzed. One hundred and five patients underwent adjuvant RT (aRT), 77 early-savage RT (esRT), and 123 salvage RT (sRT). Biochemical relapse-free survival (BRFS), progression-free survival (PFS) and toxicity were analyzed. A propensity score matching (PSM) was performed to account for potential confounders between aRT and esRT groups. RESULTS: The median follow-up was 33 months. Three-year BRFS and PFS were 82 and 85.2%, respectively, in the overall population. At the multivariate analysis, Gleason score and hormone therapy were factors independently correlated with BRFS and PFS. After PSM, there was no difference in BRFS and PFS between aRT and esRT patients. Severe toxicity was represented by grade 3 urinary incontinence (3.5%) and urgency (1%), and aRT correlated with increased any-grade acute toxicity. Severe grade 3 gastrointestinal late toxicity occurred in 1.3% of cases. CONCLUSION: Postoperative moderately hypofractionated RT achieved acceptable disease control rate and demonstrated no increased or unexpected toxicity. Future prospective studies should evaluate the role of postoperative RT in patients with unfavorable disease characteristics.

Impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5 T MR-guided stereotactic body radiotherapy.

BACKGROUND: The assessment of organ motion is a crucial feature for prostate stereotactic body radiotherapy (SBRT). Rectal spacer may represent a helpful device in order to outdistance rectal wall from clinical target, but its impact on organ motion is still a matter of debate. MRI-Linac is a new frontier in radiation oncology as it allows a superior visualization of the real-time anatomy of the patient and the current highest level of adaptive radiotherapy. METHODS: We present data regarding a total of 100 fractions in 20 patients who underwent MRI-guided prostate SBRT for low-to-intermediate risk prostate cancer with or without spacer. Translational and rotational shifts were computed on the pre- and post-treatment MRI acquisitions referring to the delivery position for antero-posterior, latero-lateral and cranio-caudal direction, and assessed using the Mann-Whitney U-Test. RESULTS: All patients were treated with a five sessions schedule (35 Gy/5fx) using MRI-Linac for a median fraction treatment time of 50 min (range, 46-65). In the entire study sample, median rotational displacement was 0.1° in cranio-caudal, - 0.002° in latero-lateral and 0.01° in antero-posterior direction; median translational shift was 0.11 mm in cranio-caudal, - 0.24 mm in latero-lateral and - 0.22 mm in antero-posterior. A significant difference between spacer and no-spacer patients in terms of rotational shifts in the antero-posterior direction (p = 0.033) was observed; also for translational shifts a positive trend was detected in antero-posterior direction (p = 0.07), although with no statistical significance. We observed statistically significant differences in the pre-treatment planning phase in favor of the spacer cohort for several rectum dose constraints: rectum V32Gy < 5% (p = 0.001), V28 Gy < 10% (p = 0.001) and V18Gy < 35% (p = 0.039). Also for bladder V35 Gy < 1 cc, the use of spacer provided a dosimetric advantage compared to the no-spacer subpopulation (p = 0.04). Furthermore, PTV V33.2Gy > 95% was higher in the spacer cohort compared to the no-spacer one (p = 0.036). CONCLUSION: In our experience, the application of rectal hydrogel spacer for prostate SBRT resulted in a significant impact on rotational antero-posterior shifts contributing to limit prostate intra-fraction motion. Further studies with larger sample size and longer follow-up are required to confirm this ideally favorable effect and to assess any potential impact on clinical outcomes.

Total laparoscopic bladder resection in the management of deep endometriosis: "take it or leave it." Radicality versus persistence.

BACKGROUND: Bladder endometriosis (BE) is the most common external site of deep-infiltrating endometriosis (DIE) affecting the urinary tract. Frequently associated with other DIE lesions, it can be strongly related to a ventral spread of adenomyosis. Possible symptoms are urinary frequency, tenesmus and hematuria, and they are frequently related to DIE of the posterior and lateral compartment. Hormonal therapy can be used in non-symptomatic patients; conversely, in other cases surgical treatment is the management of choice. METHODS: Retrospective cohort study of a series of consecutive patients treated between September 2004 and December 2017 in a tertiary care referral center. Only full-thickness detrusor involvement was considered as BE. All patients underwent laparoscopic bladder resection with concomitant radical excision of DIE. RESULTS: BE was found in 264 patients and was associated with simultaneous bowel DIE requiring bowel resection in 140 patients (53%). Twenty-five patients (9.5%) had associated obstructive ureteral signs requiring ureteroneocystostomy. Mean hospital stay and time of catheter removal were 9.7 and 9.1 days, respectively. Postoperative major complications (< 28 days) were observed in 19 patients (7.2%). Follow-up was performed at 1, 6 and 12 months after surgery, with a 2.3% recurrence rate observed. CONCLUSIONS: Laparoscopic partial cystectomy for BE is a feasible and safe technique, and experienced laparoscopic surgeons should consider it the gold standard treatment. Surgical eradication leads to excellent surgical outcomes in terms of reduction of symptoms and recurrence rates, considering the need to maintain an adenomyotic uterus for fertility purposes.

Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single-Center Experience of 160 Consecutive Patients.

STUDY OBJECTIVE: To investigate the efficacy of laparoscopic ureteroneocystostomy in patients with deep infiltrating endometriosis (DIE) with ureteral, parametrial, and bowel involvement. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: Tertiary referral center for endometriosis care. PATIENTS: One hundred sixty patients with DIE underwent laparoscopic radical eradication and ureteroneocystostomy between January 2009 and December 2016. INTERVENTIONS: Laparoscopic nerve-sparing radical treatment with ureteroneocystostomy, parametrectomy, and, if necessary, segmental bowel resection. MEASUREMENTS AND MAIN RESULTS: Surgical eradication was radical, and ureteral endometriosis was histologically confirmed in all patients (45.6% intrinsic and 54.4% extrinsic). In 58.7% of patients ureteroneocystostomy was performed with the psoas hitch technique. Bowel resection was performed in 121 patients (75.6%), and 115 of them had a concomitant ileostomy (71.9%). Unilateral parametrectomy was performed on the left side in 61.9% of patients and on the right side in 30% of patients, respectively, whereas bilateral parametrectomy was completed in 33 patients (20.6%). Postoperative complications were infrequent: 7 patients underwent reoperation (4.4%), 8 patients experienced fever (5%), 4 patients required blood transfusion (2.5%), 3 patients had intestinal fistulas (1.9%), and 24 patients experienced impaired bladder voiding (15%) after 6 months. Mean follow-up time was 20.5 months (range, 1-60). The study reported good clinical and surgical results, with a regression of symptoms (p < .001) and recurrence of parametrial endometriosis of 1.2% that required opposite-side ureteroneocystostomy. CONCLUSION: This is the largest documented series of patients with DIE undergoing laparoscopic radical eradication and ureteroneocystostomy. The collected data show that in patients with ureteral endometriosis, this technique is feasible, effective, and safe and provides good results in terms of relapses and symptoms' control.

Phase II study of accelerated Linac-based SBRT in five consecutive fractions for localized prostate cancer.

AIM: The goal was to evaluate feasibility, side effects and biochemical no evidence of disease (bNED) after stereotactic body radiation therapy (SBRT) delivered on 5 consecutive days for localized prostate cancer (PC). METHODS: The study was approved by the ethical committee and started in March 2014. Inclusion criteria were age ≤85 years, WHO performance status ≤2, histologically proven adenocarcinoma, low-intermediate risk, no previous surgery (except transurethral resection of the prostate), and a pre-SBRT International Prostatic Symptoms Score of 0-7. The radiotherapy regimen consisted of 35 Gy for low-risk and 37.5 Gy for intermediate-risk PC in 5 consecutive fractions. RESULTS: At the time of the analysis, 52 patients were recruited to the study (median age 73 years, range 55-83 years; median follow-up 34 months, range 12-49 months; 34 patients low-risk and 18 intermediate risk). The median initial prostate-specific antigen (PSA) was 5.9 ng/ml (range 1.8-15.7). Acute genitourinary (GU) toxicity was G0 (grade 0) 36/52 (69%), G1 11/52 (21%), G2 5/52 (10%), while acute rectal (GI) toxicity was G0 43/52 (83%), G1 8/52 (15%), G2 1/52 (2%). No acute toxicity ≥G3 was recorded. At the time of analysis late GU and GI toxicities were as follows: GU-G0 43/52 (83%), GU-G1 7/52 (13%), GU-G2 2/52 (4%); GI-G0 48/52 (92%), GI-G1 2/52 (4%), GI-G2 2/52 (4%). No late toxicities ≥G3 were recorded. bNED was 98%. One patient with intermediate PC had distant progression. CONCLUSIONS: Accelerated SBRT for low-intermediate PC is feasible and well tolerated with comparable oncological outcome as described for other series with the same RT technique but treatment delivery on every other day. Longer follow-up is needed to the assess late toxicity profile and long-term clinical outcome.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

AIM: To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). MATERIALS AND METHODS: 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT. RESULTS: Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). CONCLUSIONS: Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

Moderate Hypofractionated Postprostatectomy Volumetric Modulated Arc Therapy With Daily Image Guidance (VMAT-IGRT): A Mono-institutional Report on Feasibility and Acute Toxicity.

INTRODUCTION: The aim of this study was to evaluate the acute toxicity profiles of a moderate hypofractionated regimen with volumetric modulated arc therapy (VMAT) in patients with prostate cancer (PC) who underwent radical prostatectomy. MATERIAL AND METHODS: From December 2012 to February 2016, 125 patients, previously having undergone radical prostatectomy, received adjuvant (64 patients) or salvage (61 patients) radiotherapy (RT) inside an institutional protocol of moderate hypofractionation schedule using the VMAT technique (Varian RapidArc, Palo Alto, CA). Eligible patients were < 85 years old, with an Eastern Cooperative Oncology Group performance status of 0 to 2, histologically proven adenocarcinoma of the prostate without distant metastases, and pathologic stage pT2-4 N0-1, with at least 1 of the following risk factors: capsular perforation, positive surgical margins, seminal vesicle invasion, and/or postoperative prostate-specific antigen > 0.2 ng/mL. Patients were stratified into low (1%), intermediate (9%), and high-risk (90%) groups. The median age was 68 years. The median doses were 66 Gy (range, 65.5-71.4 Gy) to the prostatic bed and 52.5 Gy (range, 50.4-54 Gy) to the pelvic lymph nodes, in 28 or 30 fractions. The acute genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Common Terminology Criteria for Adverse Events, v4. RESULTS: All 125 patients completed the planned treatment, with good tolerance. After RT, the median follow-up was 18 months. Acute toxicities were recorded for the GU (G0, 45/125 [36%]; G1, 63/125 [50.4%]; G2, 16/125 [12.8%]; G3, 1/125 [0.8%]) and the GI (G0, 42/125 [33.6%]; G1, 72/125 [57.6%]; G2, 11/125 [8.8%]; no G3). Analyzing data according to RT intent, a higher rate of GU toxicity ≥ 2 was found in the adjuvant setting (17.1%) with respect to the salvage group (9.8%); P = .01 with the Fisher exact text. Furthermore, at statistical analysis, no difference was found between the type of surgery (robotic, laparoscopic, or open) and incidence of urinary incontinence (P = .8). The actuarial Kaplan-Meier rates for biochemical disease-free survival were 94% and 77% for adjuvant and salvage RT, at 36 months. CONCLUSIONS: Moderate hypofractionated postoperative RT with VMAT was feasible and safe with acceptable acute GU and GI toxicities. Longer follow-up is needed to assess late toxicity and clinical outcomes.

Association between postoperative thromboembolism prophylaxis and complications following urological surgery.

Thromboembolism represents the most significant complication and cause of non-surgical mortality in major urological surgery. The aim of the present study was to assess the association between the type of pharmacological thromboembolism prophylaxis and the postoperative complication rate in a cohort of patients undergoing major urological surgery. All consecutive patients treated with major urological surgery between December 2011 and March 2013 were evaluated. For each patient, clinical and demographic data, as well as information on the post-surgical complications and the type of pharmacological thromboembolism prophylaxis, were collected. In total, 453 patients (mean age, 63.36±12.05 years) were recruited (43.5% for prostate surgery, 33.1% for renal surgery, 12.1% for bladder surgery and 11.3% for other surgery). Postoperative blood transfusions were required in 50 cases (11.0%). A total of 32 patients (7.1%) underwent re-intervention due to the occurrence of grade ≥3 complications, with a readmission rate of 2.0%. According to the Clavien-Dindo Classification, the complications were grade 1 in 36.0% of the cases, grade 2 in 19.4%, grade 3 in 6.0%, grade 4 in 2.0% and grade 5 (mortality) in 0.7%. Only 1 case of deep venous thrombosis not associated with pulmonary thromboembolism was observed. Univariate analyses showed a significant negative association (higher risk of complications) between the use of >4,000 IU enoxaparin as the thromboembolism prophylaxis and postoperative blood transfusion rate (P=0.045), re-intervention rate (P=0.001) and the occurrence of grade ≥3 complications (P<0.001). Multivariate analysis confirmed the significant association between the use of >4,000 IU enoxaparin and both re-intervention rate (P=0.013) and occurrence of grade ≥3 complications (P=0.002). High doses of enoxaparin (>4,000 IU) may lead to an increased risk of re-intervention and severe postoperative complications following major urological surgery. Randomised, controlled trials comparing the effect of different types of pharmacological thromboembolism prophylaxis on postoperative complications following major urological surgery are required.

Impact of Ialuril Soft Gels in reducing urinary toxicity during radical hypofractionated radiotherapy in prostate cancer: a preliminary experience.

BACKGROUND: The aim of this study was to evaluate the impact of Ialuril Soft Gels in reducing acute genito-urinary (GU) toxicity in patients with prostate cancer treated with volumetric-modulated arc radiotherapy. METHODS: Forty patients were prospectively recruited. A moderate hypofractionation in 28 fractions ("hypo-moderate") was prescribed in 20 patients, while an extreme hypofractionation ("hypo-extreme") in 5 fractions was prescribed in 20 patients. The International Prostate Symptom Score (IPSS) questionnaire was administered in all cases before and after radiotherapy (RT). GU toxicity was evaluated according to CTCAE v4.0. Patients of each group ("hypo-moderate" and "hypo-extreme") were randomized (1:1) to receive RT alone or RT combined with Ialuril Soft Gels. RESULTS: In "hypo-moderate" patients treated with Ialuril Soft Gels the following GU toxicity was reported: G0 3, G1 6, G2 1, G3 0. In the arm treated without Ialuril Soft Gels: G0 0, G1 7, G2 2, G3 1. In "hypo-extreme" arm treated with Ialuril Soft Gels the following GU toxicity was recorded: G0 7, G1 2, G2 1, G3 in 0; while in the arm treated without Ialuril Soft Gels: G0 5, G1 2, G2 2, G3 1. IPSS was unchanged in "hypo-moderate" and "hypo-extreme" groups and patients treated with Ialuril Soft Gels, with a median value of 6 and 5 respectively. In patients treated without Ialuril Soft Gels an increased IPSS was reported in "hypo-moderate" and "hypo-extreme" from 6 to 8 and from 3.5 to 4.5, respectively. At statistical analysis (Fisher's exact text) Ialuril Soft Gels was associated with IPSS improvement (P=0.03). CONCLUSION: Ialuril Soft Gels seems to have a beneficial role in reducing GU toxicity without worsening the IPSS.

Robotic-assisted radical prostatectomy is less stressful than the open approach: results of a contemporary prospective study evaluating pathophysiology of cortisol stress-related kinetics in prostate cancer surgery.

The objective of this study was to investigate the effects of prostate cancer (PCA) surgery on the stress system and to identify potential independent factors associating with stress recovery. The design of the study was prospective and PCA surgery included robot-assisted radical prostatectomy (RARP) or retro pubic radical prostatectomy. Between February and December 2013, 151 consecutive patients were evaluated. The effects of PCA surgery on the stress system were measured by cortisol serum levels before and after surgery on post-operative day (POD) 0, 1, 3, 5 and 45. Statistical methods were applied. RARP was performed in 71% of cases. PCA surgery triggered the stress system which immediately (POD 0) responded by cortisol overproduction which induced the negative feedback mechanism that started on POD 1, continued on POD.

Impact of 18F-Choline PET/CT in the Decision-Making Strategy of Treatment Volumes in Definitive Prostate Cancer Volumetric Modulated Radiation Therapy.

INTRODUCTION: Aim of the study is to evaluate the impact of Cho-PET/CT in decision-making strategy of patients with localized prostate cancer (PC) eligible to definitive radiotherapy (RT). MATERIALS AND METHODS: Sixty patients Cho-PET/CT before RT were prospectively enrolled. All patients were treated with volumetric modulated arc therapy with simultaneous integrated boost in 28 fractions. Androgen deprivation therapy was prescribed according to National Comprehensive Cancer Network (NCCN) risk classification. Therapeutic strategy based on the Cho-PET/CT evaluation was compared with the strategy that would have been proposed in case of PET not available and/or not strictly indicated, according to international and national PC guidelines. RESULTS: Cho-PET/CT was positive in 57 cases (95%): T in 45 (79%); T in combination with N in 8 (14%); and M (bone) in combination with T or N, or both, in 4 (7%). After Cho-PET/CT, patients were stratified as follows: 26 (43%) low risk, 10 (16%) intermediate risk, and 24 (41%) high risk. Cho-PET/CT shifted treatment indication in 13 cases (21%). The changes regarding radiation treatment volumes were as follows: 6 intermediate risk (10%) shifted to high risk and consequently were irradiated on prostate, seminal vesicles, and pelvic nodes PTVs; in 7 high risk (11%), the Cho-PET/CT showed bone and/or N uptake, and consequently, a simultaneous integrated boost on PET positive sites was prescribed. CONCLUSIONS: Cho-PET/CT seems to be a promising diagnostic tool in patients who are candidates for radical RT and supporting the decision making in treatment planning, in particular in intermediate-high risk.

Outcomes and Postoperative Complications of Robot-Assisted Laparoscopic Hysterosacropexy: Initial Experience.

BACKGROUND: Pelvic organ prolapse is a common condition, affecting about 50% of women with children. The aim of our study was to evaluate results and complication rates in a consecutive series of female patients undergoing robot-assisted laparoscopic hysterosacropexy (RALHSP). MATERIALS AND METHODS: We performed a medical record review of female patients with uterine prolapse who had consecutively undergone RALHSP from February 2010 to 2013 at our department. RESULTS: Fifteen patients were included in the analysis. All patients had uterine prolapse stage ≥ II and urodynamic stress urinary incontinence. The mean age was 58.26 years. According to the Clavien-Dindo system, 4 out of 15 patients (26.6%) had grade 1 early complications and 1 patient had a grade 2 complication. At a median follow-up of 36 months, there was a significant prolapse relapse rate of 20% (3/15). CONCLUSION: In our hands RALHSP is easy to perform, with satisfying mid-term outcomes and a low complication rate.

Prostate volume index and chronic inflammation of the prostate type IV with respect to the risk of prostate cancer.

BACKGROUND: Benign prostatic hyperplasia and prostate cancer (PCA) alter the normal growth patterns of zonal anatomy with changes of prostate volume (PV). Chronic inflammatory infiltrates (CII) type IV are the most common non-cancer diagnosis of the prostate after biopsy. OBJECTIVE: To evaluate associations of both PV index (PVI), i.e. the ratio of transitional zone volume (TZV) to peripheral zone volume (PZV), and CII with PCA in patients undergoing biopsy. SUBJECTS AND METHODS: Between January 2007 and December 2008, 268 consecutive patients who underwent prostate biopsy were retrospectively evaluated. PV and TZV were measured by transrectal ultrasound. PZV was computed by subtracting the PV from the TZV. CII were evaluated according to standard criteria. Significant associations of PVI and the presence of CII (CII+) with PCA risk were assessed by statistical methods. RESULTS AND LIMITATIONS: We evaluated 251 patients after excluding cases with painful rectal examinations, prostate-specific antigen (PSA) >20 µg/ml and metastases. The PCA detection rate was 41.1%. PVI was a negative independent predictor of PCA. A PVI ≤1.0 was directly [odds ratio (OR) = 2.36] associated with PCA, which was detected more frequently in patients with a PVI ≤1.0 (29.1%) than in those with a PVI >1.0 (11.9%). CII+ was inversely (OR = 0.57) and independently associated with PCA, which was detected less frequently in cases with CII (9.9%) than in those without CII (21.1%). Potential study limitations might relate to the fact that PV was not measured by prostatectomy specimens and there was PSA confounding for CII and PCA. CONCLUSIONS: Low values of PVI are directly associated with risk of PCA, which was almost 2.5 times higher in patients with a PVI ≤1.0. The PVI might be an effective parameter for clustering patients at risk of PCA. CII+ was inversely associated with risk of PCA and decreased the probability of detecting PCA by 43%. The role of the PVI and CII in PCA carcinogenesis needs further research.

Upgrading and upstaging in prostate cancer: From prostate biopsy to radical prostatectomy.

Prostate cancer (CaP) is the most common malignancy in men and the second cause of cancer-related mortality after lung cancer. Several studies have evaluated the correlation between bioptic and pathological Gleason score (GS), documenting a correlation ranging between 30 and 60%. The aim of this study was the evaluation of the association between bioptic and pathological GS in a series of patients undergoing prostate needle biopsy and subsequent radical prostatectomy. We also aimed to evaluate the possible prognostic factors of upgrading and upstaging. We prospectively collected and retrospectively reviewed data from 300 consecutive patients who underwent radical retropubic or robot-assisted prostatectomy at our Institution. Patients who underwent prostate needle biopsy, transrectal or transperineal, with a minimum of 5 samples, were included in this study. Upgrading and downgrading were defined as increase or decrease, respectively, from one prognostic grade group to another, similar to up- or downstaging. The mean age of the patients was 62.97 years and the mean prostate-spesific antigen (PSA) level was 7.83 ng/ml. A total of 51.3% of the population underwent a transperineal prostate biopsy. The most frequently represented bioptic GS was 3+3 (64.0%) followed by 3+4=7 (15.6%); the most frequent pathological Gleason score was 3+4 (44.3%), followed by 3+3 (31.0%). With reagard to the bioptic GS 4-5-6 group, approximately half of the specimens (46.7%) were subsequently upgraded to GS 3+4, and 5.3% to 4+3. With regards to the bioptic GS 3+4 group, 57.4% was confirmed in the surgical specimen. In the 4+3 group, 23.5% of the cases was downgraded to 3+4 and 35.3% was confirmed. With regards to stage, ~39.7% of the patients received an upstaging on the pathological specimen. We evaluated the correlations between preoperative serum PSA level, prostate volume, digital rectal examination and biopsy type and none of the variables considered exhibited a correlation with any upgrading (P>0.05). Moreover, we evaluated the correlations between the aforementioned variables and upstaging and, at the multivariate analysis, only a serum PSA <4 ng/ml was found to be an independent variable predictive of upstaging (P=0.017). Therefore, new tools are required to predict upgrading and upstaging of our patients, in order to ensure better counseling for optimal treatment planning.

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer.

BACKGROUND: Chronic inflammatory infiltrate (CII) might be involved in prostate cancer (PCA) and benign hyperplasia (BPH); however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. OBJECTIVE: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. DESIGN, SETTING, AND PARTICIPANTS: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years) and PSA (ug/l); moreover, CII+, glandular atrophy (GA+), glandular hyperplasia (GH+), prostate Intraepithelial neoplasm (PIN+), atypical small acinar cell proliferation (ASAP+) and PCA positive cores (P+) were evaluated as categorical and continuous (proportion of positive cores). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of CII+ and PCA risk were assessed by statistical methods. RESULTS AND LIMITATIONS: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8) resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26) and HGPCA (P = 0.0005; OR = 0.05). Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. CONCLUSIONS: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in PCA carcinogenesis remains controversial and needs further research.

Prognostic role of substaging in T1G3 transitional cell carcinoma of the urinary bladder.

This study was conducted to test a new substaging system in a population of patients with stage T1 bladder cancer (BC) at diagnosis and assess its prognostic role in terms of disease progression and disease-specific survival (DSS). Patients with primary stage T1G3 urothelial carcinoma of the bladder were stratified according to the following models: i) T1a [the tumour does not infiltrate the muscularis mucosae-vascular plexus, (MM-VP)]; T1b (the tumour partially infiltrates the MM-VP); and T1c (the tumour infiltrates and invades the MM-VP). ii) T1m (diameter of tumour infiltrating the lamina propria ≤0.5 mm under a high-resolution microscope; and T1e (diameter of tumour infiltrating the lamina propria >0.5 mm). Age, gender, tumour size and multifocality were not found to be of statistical significance. Using the T1a/T1b/T1c system, patients with stage T1a disease exhibited a 5- and 10-year progression rate of 13.3 and 20%, respectively, without reaching statistical significance. Moreover, patients with stage T1a disease exhibited a 5- and 10-year DSS of 93.3 and 73.3%, respectively, which was higher compared to T1b and T1c but not statistically significant. Using the T1m/T1e system, patients with stage T1m disease exhibited a disease progression rate of 8.3 and 16.7% at 5 and 10 years, respectively, which was not statistically significant. Moreover, patients in group T1m presented with DSS rates of 91.7 and 83.3% at 5 and 10 years, respectively, which were higher compared to those in the T1e group (71.4 and 60.7%), although not reaching statistical significance. In conclusion, in our study, neither of the two substaging systems of stage T1 BC reached the prognostic conventional significance level for tumour progression or DSS.

Adenocarcinoma of the paraurethral glands: a case report.

Adenocarcinoma of the paraurethral glands represents a very rare neoplasm of the urinary tract. Due to the rarity of this disease, there is no standard therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old woman, presenting with abnormal serous vaginal discharges. The radiologic examination revealed a 5-cm mass around the urethra, which underwent surgical resection. After surgical resection, the histology revealed a moderately differentiated adenocarcinoma, probably arising from the paraurethral glands. One month later, a pelvic recurrent mass was radiologically diagnosed; consequently, an anterior pelvic exenteration with lymph node dissection was performed. Histological examination revealed a moderately differentiated adenocarcinoma, with glandular and micropapillary architecture, with multiple lymph node metastases. The absence of modifications such as urethritis cystic glandularis on the urethral mucosa, as well as the lack of a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3 and S100p, suggested that the adenocarcinoma originated from the paraurethral glands rather than from the urethral mucosa. Post-surgery CT scans revealed no evidence of metastatic disease. The patient received 6 courses of adjuvant chemotherapy with carboplatin and paclitaxel. One year after the pelvic exenteration, because of inguinal lymph node progression, an inguinal lymphadenectomy was performed. Four months later, a TC-PET revealed a multidistrectual lymph node and a lung micronodule disease progression. Invasive micropapillary carcinomas have been characterized as a rare distinctive variant of carcinomas in several anatomic sites and are distinguished by a marked tendency to lymphovascular invasion, justifying the association with high-stage disease and poor prognosis. In the present case, both the poor prognosis connected with micropapillary structure and the lymph node involvement, encouraged adjuvant cisplatinum-based chemotherapy.

Associations of pretreatment serum total testosterone measurements with pathology-detected Gleason score cancer.

BACKGROUND AND OBJECTIVE: Prostate cancer is an endocrine-dependent tumor which is still under-investigated for physiopathology factors related to its natural history. The association of pretreatment total testosterone (TT) serum levels with prostate cancer is still a controversial topic. The objective of this study was to investigate potential associations and functional relationships of preoperative TT serum level and pathology-detected Gleason score (pGS). MATERIALS AND METHODS: Pretreatment and pathological variables of 220 patients operated with radical prostatectomy were retrospectively reviewed. Age, prostate-specific antigen (PSA), percentage of positive biopsy cores (P+), biopsy Gleason score (bGS), pGS, TT and free testosterone were the continuous variables, while clinical stage (cT: cT1c, cT2/3), biopsy Gleason pattern (bGP: ≤3+3, 3+4, >3+4), pathology Gleason pattern (pGP: ≤3+3, 3+4, >3+4), pathology stage (pT: pT2, pT3a, pT3b), pathology nodal staging (pN: pN0, pN1, pNx) and surgical margin invasion by cancer (R-, R+) were the categorical variables. Statistical methods were computed for assessing associations of TT and pGS; moreover, simple and multiple linear regression analysis (SLRA and MLRA) were used for assessing functional relationships of TT and pGS. RESULTS: High-grade tumors (pGS ≥8.0) were associated with bGS >6.0 (p < 0.0001), pGP ≥3+4 (p < 0.0001), P+ >0.31% (p = 0.006), cT2/3 (p = 0.01), TT >15.5 nmol/l (p = 0.0004) and, to a lesser extent, PSA >6.27 µg/l (p = 0.06). The odds ratio (OR) ranked as follows: 2.01 (PSA >6.27 µg/l), 2.88 (cT2/3), 3.23 (P+ >0.31%), 5.53 (TT >15.5 nmol/l) and 12.09 (pGP ≥3+4 and pGS ≥8.0). On SLRA, pGS variation was significantly predicted by bGS (p < 0.0001), P+ (p < 0.0001), PSA (p = 0.0005) and TT (p = 0.02); on MLRA, pGS variation was still significantly predicted by bGS (p < 0.0001), P+ (p = 0.04), PSA (p = 0.03) and TT (p = 0.002). When bGS, P+, PSA and TT were dichotomized to their median value, only bGS (p < 0.0001) and TT (p = 0.001) showed independence in predicting pGS variation. The best model for predicting pGS variations was by dichotomizing TT above its median (>15.5 nmol/l) because the predictive coefficient increased to 0.32, which means that patients with TT >15.5 have a significantly higher estimated risk for high-grade pGS than patients with TT ≤15.5 nmol/l (OR = 1.31). CONCLUSION: In a patient population undergoing radical prostatectomy, increased pretreatment serum measurements of TT are associated with and functionally related to high-grade pGS; moreover, baseline TT together with bGS and PSA are important factors for predicting pGS and assessing high-grade tumors. Baseline TT serum levels might have prognostic potential for assessing treatment response for continuous as well as intermittent androgen deprivation therapy.