QUIN 2.0 - new release of the QUaternary fault strain INdicators database from the Southern Apennines of Italy.

QUIN database integrates and organizes structural-geological information from published and unpublished sources to constrain deformation in seismotectonic studies. The initial release, QUIN1.0, comprised 3,339 Fault Striation Pairs, mapped on 445 sites exposed along the Quaternary faults of central Italy. The present Data Descriptor introduces the QUIN 2.0 release, which includes 4,297 Fault Striation Pairs on 738 Structural Sites from southern Italy. The newly investigated faults span ~500 km along the Apennines chain, with strikes transitioning from ~SE to ~SW and comprehensively details Fault Striation Pairs' location, attitude, kinematics, and deformation axes. Additionally, it offers a shapefile of the fault traces hosting the data. The QUIN 2.0 release offers a significant geographic extension to the QUIN 1.0, with comprehensive description of local geometric-kinematic complexities of the regional pattern. The QUIN data may be especially relevant for constraining intra-Apennine potential seismogenic deformation patterns, where earthquake data only offer scattered or incomplete information. QUIN's data will support studies aimed at enhancing geological understanding, hazard assessment and comprehension of fault rupture propagation and barriers.

Long-term analysis of microseism during extreme weather events: Medicanes and common storms in the Mediterranean Sea.

In this work, we analyze 12 meteorological events that occurred in the Mediterranean Sea during the period November 2011-November 2021 from a seismic point of view. In particular, we consider 8 Medicanes and 4 more common storms. Each of these events, in spite of the marked differences between them, caused heavy rainfall, strong wind gusts and violent storm surge with significant wave heights usually >3 m. We deal with the relationships between these meteorological events and the features of microseism (the most continuous and widespread seismic signal on Earth) in terms of spectral content, space-time variation of the amplitude and source locations tracked employing two different methods (amplitude decay-based grid search and array techniques). By comparing the positions of the microseism sources with the areas of significant storm surges, we observe that the microseism locations align with the actual locations of the storm surges for 10 out of 12 events analyzed (two Medicanes present very low intensity in terms of meteorological parameters and the microseism amplitude does not show significant variations during these two events). We also perform two analyses that allowed us to obtain both the seismic signature of these events, by using a method that exploits the coherence of continuous seismic noise, and their strength from a seismic point of view, called Microseism Reduced Amplitude. In addition, by integrating the results obtained from these two methods, we are able to "seismically" distinguish Medicanes and common storms. Consequently, we demonstrate the possibility of creating a novel monitoring system for Mediterranean meteorological events by incorporating microseism information alongside with other commonly employed techniques for studying meteorological phenomena. The integration of microseism with the data provided by routinely used techniques in sea state monitoring (e.g., wave buoy and HF radar) has the potential to offer valuable insights into the examination of historical extreme weather events within the context of climate change.

The enigmatic 1693 AD tsunami in the eastern Mediterranean Sea: new insights on the triggering mechanisms and propagation dynamics.

The disastrous earthquake of 1693 AD caused over 60,000 causalities and the total destruction of several villages and towns in south-eastern Sicily. Immediately after the earthquake, a tsunami struck the Ionian coasts of Sicily and the Messina Strait and was probably recorded even in the Aeolian Islands and Malta. Over the last few decades, the event has been much debated regarding the location of the seismogenic source and the possible cause of the associated tsunami. The marine event has been related to both a submarine landslide and a coseismic displacement at the seafloor. To better define the most reliable sources and dynamics of the tsunami, we couple high-resolution marine seismic survey data with hydrodynamic modelling to simulate various scenarios of tsunami generation and propagation. Results from the simulations are compared with geomorphological evidence of past tsunami impacts, described in previous work along the coast of south-eastern Sicily, and within historical chronicles and reports. The most reliable scenario considers the 1693 event composed by two different tsunami waves: a first wave generated by the coseismic fault displacement at the seafloor and a second wave generated by a submarine landslide, triggered by the earthquake shaking. Tsunami modelling shows that a simultaneous movement between fault displacement and submarine mass movement could determine a destructive interference on the tsunami waves, resulting in a reduction in wave height. For this reason, the second tsunami wave probably occurred with a maximum delay of few minutes after the one generated by the earthquake and induced a greater flooding. The double-source model could explain the observation because in the course of other destructive earthquakes in south-eastern Sicily, such as that of 1169 AD, the associated tsunami caused less damages. This implies the need to better map, define and assess the hazard responsible for this type of tsunami events.

Severe systemic disease of the American Society of Anesthesiologists' (ASA) physical status system classification associated with delayed length of hospital stay in 1329 consecutive patients treated with radical prostatectomy for clinical prostate cancer.

BACKGROUND: The investigate the associations of the ASA physical status system with clinical, pathological, and perioperative features of prostate cancer (PCa) patients treated with radical prostatectomy (RP) that eventually associated with pelvic lymph node dissection (PLND). METHODS: We performed a retrospective analysis of prospective collected data from January 2013 to October 2020, including1329 patients. The ASA system was preoperatively assessed for each patient. Evaluated clinical factors were grouped as preoperative, perioperative, and pathological and were statistically associated with the ASA system. Continuous variables were represented as medians with relative interquartile ranges (IQR) and categorical factors were assessed as frequencies (percentages). Associations and risk of each ASA Class with population features were assessed by the multinomial logistic regression model (univariate and multivariate analysis). All tests were two-sided with P<0.05 considered to indicate statistical significance. RESULTS: Postoperative complications at discharge occurred in 27.2%. The distribution of the ASA physical status system was as follows: ASA I 108 patients (8.1%), ASA II 1081 subjects (81.3%) and ASA III 140 cases (10.5%). Median length of hospital state (LOHS) was the same for ASA groups I and II (4 days), but longer (5 days) for the ASA group III. On MVA, the risk of delayed hospital stay was associated only with ASA III patients and was independent from age and BMI. Clavien-Dindo complications greater than 2 did not show any independent association with the ASA system. CONCLUSIONS: The ASA preoperative physical status system predicted the likelihood of longer LOHS.

Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection.

OBJECTIVE: To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N = 0) or with one (N = 1) or more than one metastatic node (N > 1). The risk of multiple pelvic lymph node metastasis (N > 1, mPLNM) was assessed by comparing it to the other two groups (N > 1 vs. N = 0 and N > 1 vs. N = 1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT > 1) and tumor grade group greater than two (ISUP > 2). RESULTS: Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N = 1 and 31 (5%) with N > 1. On multivariate analysis, ET was inversely associated with the risk of N > 1 when compared to both N = 0 (odds ratio, OR 0.997; CI 0.994-1; p = 0.027) as well as with N = 1 cases (OR 0.994; 95% CI 0.989-1.000; p = 0.015). CONCLUSIONS: In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

The bladder-flap ureteral augmentation: An original solution in case of complex distal stricture.

An original surgical solution for complex stenosis of the distal ureter is presented. A young, single-kidney male patient developed a stricture of the pelvic ureter after ureteroscopy and laser lithotripsy. Surgical repair was planned after the failure of conservative management. The ureter was sectioned prevesically and spatulated; a bladder flap with the same dimensions of the ureteral plate was taken from the anterior wall, and used to augment the ureter; finally an omental flap was wrapped around the reconstructed tract. Further radiological and ureteroscopic controls showed a largely patent reconstructed ureter, and follow up proved a regularly maintained kidney function.

Multiple stones in neobladder: Case report and literature review.

INTRODUCTION: Neobladder urolithiasis is a rare but important long-term complication of orthotopic urinary diversion. It may be asymptomatic and can be discovered as an incidental finding on a radiological investigation. However, when symptoms occur, they may include lower abdominal pain, dysuria, hematuria, and lower urinary tract symptoms. CASE DESCRIPTION: We report the case of a 63-year-old male patient with irritative lower urinary tract symptoms, lower abdominal fullness, urinary incontinence, fecaluria, and urinary loss from the left inguinal fold 12 years after a radical cystoprostatectomy with a orthotopic neobladder. Computed tomography scan and urethrocystography showed a distended pouch with multiple large stones, an enterovesical fistula, and neovesicocutaneous fistula. The fistulae were successfully managed conservatively with the placement of a Foley catheter. After 3 months, open cystolithotomy was performed and approximately 50 stones with dimensions varying from 5 mm to 5 cm, with a total weight of 890 g, were removed. After a 1-year follow-up, the patient did not report pain, urinary tract infections, or symptoms suggestive of fistula and imaging evaluation confirmed no recurrence of neobladder stones. CONCLUSION: Neobladder stones may present with various symptoms. Our patient had irritative lower urinary tract symptoms, lower abdominal fullness, urinary incontinence, fecaluria, and urinary loss from the left inguinal fold 12 years after a radical cystoprostatectomy with a orthotopic neobladder. Our experience demonstrates that open cystolithotomy is an effective intervention for the removal of large stones in neobladder.

Low Preoperative Prolactin Levels Predict Non-Organ Confined Prostate Cancer in Clinically Localized Disease.

INTRODUCTION: To evaluate the association between preoperative serum prolactin (PRL) levels and risk of non-organ confined prostate cancer (PCa) in clinically localized disease. MATERIALS AND METHODS: From December 2007 to December 2011, 124 patients with clinically localized PCa were retrospectively evaluated. Non-organ confined disease in the surgical specimen was defined according to extra-capsular extension, seminal vesicle invasion, positive surgical margins, and lymph node invasion. The association between clinical factors and serum levels of pituitary-testis hormones with the risk of non-organ confined disease was evaluated. RESULTS: Perioperative factors associated with non-organ confined disease include prostatic-specific antigen (OR 1.144; p = 0.025), proportion of biopsy positive cores (BPC, OR 36.702; p = 0.007), bioptical Gleason Score > 6 (OR 2.785; p = 0.034), and PRL (OR 0.756, p < 0.0001). The association was strong for BPC (area under the curve [AUC] 0.704; p < 0.0001) and PRL (AUC 0.299; p < 0.0001). When we dichotomized according to median value, PRL ≤7.7 µg/L was an independent predictor of extraprostatic disease (OR 6.571; p < 0.0001) with fair discrimination power (AUC 0.704; p < 0.0001). CONCLUSION: Low preoperative PRL levels predict the risk of non-organ confined PCa in clinically localized disease.

Simultaneous Measurements of Follicle Stimulating Hormone and Total Testosterone and Associations in Clinically Localized Prostate Cancer.

OBJECTIVES: To evaluate the potential relations of simultaneous measurements of basal levels of follicle stimulating hormone (FSH) and total testosterone (TT) in clinically localized prostate cancer (PCa). MATERIALS AND METHODS: The study included 126 patients who had simultaneous measurements of prostate specific antigen (PSA), FSH, and TT before undergoing radical prostatectomy for clinically localized PCa. Correlations and independent associations between clinical and pathological factors were investigated by statistical methods. RESULTS: The tumor volume (TV) was directly correlated to PSA and TT which was inversely related to FSH. Moreover, it was independently associated with both PSA and TT. In a multivariate linear regression model, FSH and TV were simultaneous independent factors associated with TT, and the association was inverse in the former and direct in the latter. In the patient population, the subset with FSH levels above the third quartile was related to lower median levels of TT that were associated with high grade cancer showing a lower TV. In localized PCa, basal levels of TT were associated with tumor parameters and inversely related to FSH levels, and the subset FSH levels above the third quartile were related to lower TT levels that were associated with high grade cancers showing a lower tumor load. CONCLUSION: Preoperative TT was associated with tumor parameters and inversely related to FSH levels. Patient with increased FSH levels was related to lower levels of TT, which was associated with high grade cancer.

High Testosterone Preoperative Plasma Levels Independently Predict Biopsy Gleason Score Upgrading in Men with Prostate Cancer Undergoing Radical Prostatectomy.

PURPOSE: The study aims to investigate the potential associations between preoperative plasma levels of total testosterone (TT) and biopsy Gleason score (bGS) upgrading in prostate cancer (PCA) patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Exclusion criteria were treatment with 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement. Criteria of bGS upgrading were as follows: (i) bGS 6 to pathological Gleason score (pGS) >6, (ii) bGS 7 with pattern 3 + 4 to pGS 7 with pattern 4 + 3 or to pGS >7, (iii) bGS 7 with pattern 4 + 3 to pGS >7. Patients who showed bGS >7 were excluded from the cohort. RESULTS: The study included 209 patients. Tumor upgrading was assessed in 76 (36.4%) cases of the entire cohort, in 51 out of 130 cases (39.2%) of the bGS 6 group and 25 out of 79 patients (31.6%) in the bGS 7 cluster. Logistic regression models showed that independent clinical covariates predicting the risk of bGS upgrading included TT (OR 1.058; p = 0.027) and prostate-specific antigen (PSA) density (OR 23.3; p = 0.008) as well as TT (OR 1.057; p = 0.029) with PSA (OR 1.061; p = 0.023). The model suggests that 1 unit increase in TT plasma levels increases the odds of bGS upgrading by 5.8 or 5.7%. CONCLUSIONS: In summary, we have determined that high TT preoperative plasma levels independently predict bGS upgrading in men with PCA undergoing RP. Preoperative plasma levels of TT might be included as a potential marker for assessing the risk bGS upgrading.

Large Urethro-Vesico-Vaginal Fistula due to a Vaginal Foreign Body in a 22-Year-Old Woman: Case Report and Literature Review.

In the non-industrialized countries of Africa and Asia obstetric fistulas are more frequently caused by prolonged labour, whereas in countries with developed healthcare systems they are generally the result of complications of gynaecological surgery or, rarely, benign pathologies like inflammation or foreign bodies. A 22-year-old woman was brought to the gynaecology clinic because of foul-smelling vaginal discharge. On pelvic examination a ring-like foreign body was impacted between the anterior and posterior vaginal wall. MRI scan confirmed the presence of a cylindrical foreign body in the vagina and the patient revealed that she had 'involuntarily' inserted a plastic bubble bath cap into the vagina. At surgery removal of the cap was difficult and at the end of the manoeuver evidence of a huge urethro-vesico-vaginal fistula occurred. The patient was discharged with bilateral ureteral stents and suprapubic catheter. After 3 months we performed an end-to-end anastomotic urethroplasty to repair the urethral avulsion and restored the bladder/trigonal and vaginal/cervical defects with 3 layers of sutures; 3 months later the patient had no complaints. Complex genital fistulas represent an extremely debilitating morbidity. In our case, a vaginal approach was successful, but the choice between an abdominal or vaginal approach depends on the surgeon's experience and training.

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.

Accuracy of preoperative endo-rectal coil magnetic resonance imaging in detecting clinical under-staging of localized prostate cancer.

OBJECTIVES: To assess the accuracy of intra-rectal coil magnetic resonance imaging (ER-MRI) for staging early prostate cancer (EPC). MATERIALS AND METHODS: ER-MRI was performed with the Magnetom Symphony 1.5 Tesla system. ER-MRI and pathology findings were statistically correlated. RESULTS: One hundred and fifty-four consecutive patients underwent radical prostatectomy (RRP) for EPC (cT1c-2 Nx M0). An average age was 66, mean PSA 11.04 µg/L (median 7.33 µg/L) and mean pathologic Gleason score 6. Pathology detected 97 out of 154 patients (63 %) as EPC and 57 cases (37 %) as extra-prostate extension (EPED) (pT3) with extra-capsular extension (ECE) (pT3a) in 41 (27 %) and seminal vesicle invasion (SVI) (pT3b) in 16 (10 %). ER-MRI staged 100 patients (65 %) as cT2 and 54 (35 %) as EPED with ECE in 37 cases (24 %) and SVI in 17 (11 %). ER-MRI sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy resulted respectively 0.78, 0.96, 0.86, 0.92, 0.91 for ECE as well as 0.88, 0.98, 0.82, 0.99 and 0.97 for SVI. CONCLUSION: ER-MRI was effective in detecting preoperative EPC under-staging. In the next future, multi-parametric 3-Tesla ER-MRI will be the procedure for diagnosing, staging and following-up prostate cancer patients.

Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer and subsequent cluster selection of the patient population undergoing standard radical prostatectomy.

AIM: A preceding exploratory analysis has shown that follicle-stimulating hormone (FSH) was significantly correlated to and predicted by prostate-specific antigen (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of initial diagnosis of prostate cancer in an operated population clustered according to the FSH/PSA ratio. PATIENTS AND METHODS: The study included 93 patients who underwent standard radical prostatectomy. Age, percentages of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH, prolactin hormone (PRL), total testosterone (TT), free testosterone (FT), estradiol (ESR) and PSA were the continuous variables. Category variables were pT and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was clustered according to the FSH/PSA ratio which was computed from empirical data and then ranked for clustering the population as groups A (range 0.13 ≤ FSH/PSA ≤ 0.20), B (range 0.20 < FSH/PSA ≤ 0.50), C (range 0.50 < FSH/PSA ≤ 0.75), D (range 0.75 < FSH/PSA ≤ 1.00), E (range 1.00 < FSH/PSA ≤ 1.25), F (range 1.25 < FSH/PSA ≤ 2.00), G (range 2.00 < FSH/PSA ≤ 2.25), H (range 2.25 < FSH/PSA ≤ 6.40) and I (range 6.40 < FSH/ PSA ≤ 19.40). The model was assessed by simple linear regression analysis and differences between the groups were investigated by analysis of variance (ANOVA) for continuous variables and by contingency tables for category variables. RESULTS: FSH was significantly correlated to and predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p < 0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p = 0.001). Also, clusters (A-I) differed significantly for mean values of FSH (p < 0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed significant different frequency distributions of pGPI (p = 0.02), pGPII (p = 0.0002) and bGPI (p = 0.04). CONCLUSION: The ranking FSH/PSA ratio significantly clustered, along the PTP axis, an operated population diagnosed with prostate cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters expressing different levels of hormonal disorder along the PTP axis and prognostic potential with different risks of progression. As a theory, in the current advancing world, the ranking FSH/PSA model might be considered as an interesting and effective tool for prostate cancer study as well as individualized, risk-adapted approaches of the disease. However, confirmatory studies are needed.

Investigative clinical study on prostate cancer part IX and X: estradiol and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

AIM: To evaluate estradiol (E(2)) physiopathology along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer (PC) and subsequent cluster selection of the patient population. PATIENTS AND METHODS: Records of the diagnosed (n=105) and operated (n=91) patients were retrospectively reviewed. Age, percentage of positive cores at-biopsy (P+), biopsy Gleason score (bGS), E(2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free-testosterone (FT), prostate-specific antigen (PSA), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi), clinical stage (cT), biopsy Gleason pattern (bGP) and pathology stage (pT), were the investigated variables. None of the patients had previously undergone hormonal manipulations. E(2) correlation and prediction by multiple linear regression analysis (MLRA) was performed. At diagnosis, the log E(2)/log bGS ratio clustered the population into groups A (log E(2)/log bGS ≤ 2.25), B (2.25

Investigative clinical study on prostate cancer part VIII: prolactin hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

AIM: To evaluate the prolactin hormone (PRL) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer and the subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables. PATIENTS AND METHODS: Ninety-two operated prostate cancer patients were retrospectively reviewed. No patient had previously received hormonal treatment. The investigated variables included PRL, follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), total prostate specific antigen (PSA), percentage of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi) and age. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population and clustered according to pT (2a/b, 3a, 3b/4) status. The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5< log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+ >2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model and analysis of variance was performed for assessing significant differences between the groups. RESULTS: PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b). Interestingly, PRL was independently predicted by LH (p=0.03) and FSH, TT, FT, PSA, bGS, pGS, V+, Wi and age (all at p=0.01) in advanced stage-disease (pT3b/4). V+ was also significantly correlated (r=0.47) and predicted by P+ (p<0.0001) in the prostate cancer population. PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10)PRL/V+ ratio in group A (p=0.008), B (p<0.0001) and C (p<0.0001). Moreover, the three groups had significantly different mean values of PRL (p<0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p<0.0001), Wi (p=0.03), bGS (p=0.008), pGS (p=0.003); also, groups A, B and C had significant different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions. CONCLUSION: At diagnosis, in an operated prostate cancer population, PRL was significantly correlated and independently predicted along the pituitary testis prostate axis in high-stage disease; V+ was also significantly correlated and predicted by P+. Because of the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10)PRL/V+ ratio into groups A, B and C that, in theory, might be models with prognostic potential and clinical applications in the prostate cancer population. However, confirmatory studies are needed.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57

Investigative clinical study on prostate cancer part VII: prolactin and the pituitary-testis-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate prolactin (PRL) physiopathology along the pituitary-testis-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: The study involved 100 individuals diagnosed with prostate cancer. Age, percentage of positive cores at transrectal ultrasound scan biopsy (P+), biopsy Gleason score (BGS), PRL, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received hormonal manipulations. Correlation and multiple linear regression analysis of the the variables along the pituitary-testis-prostate cancer axis was performed. The prostate cancer population was clustered according to the PRL/P+ ratio into group A (4.20≤PRL/P+ ≤20), B (20

Investigative clinical study on prostate cancer part IV: exploring functional relationships of total testosterone predicting free testosterone and total prostate-specific antigen in operated prostate cancer patients.

OBJECTIVES: To explore, in operated prostate cancer patients, functional relationships of total testosterone (tt) predicting free testosterone (ft) and total PSA. PATIENTS AND METHODS: 128 operated prostate cancer patients were simultaneously investigated for tt, ft and PSA before surgery. Patients were not receiving 5α-reductase inhibitors, LH-releasing hormone analogues and testosterone replacement treatment. Scatter plots including ft and PSA versus tt were computed in order to assess the functional relationship of the variables. Linear regression analysis of tt predicting ft and PSA was computed. RESULTS: tt was a significant predictor of the response variable (ft) and different subsets of the patient population were assessed according to the ft to tt ratio. PSA was related to tt according to a nonlinear law. tt was a significant predictor of PSA according to an inversely nonlinear law and different significant clusters of the patient population were assessed according to the different constant of proportionality computed from experimental data. CONCLUSIONS: In our prostate cancer population, ft was significantly predicted by tt according to a linear law, and the ft/tt ratio was a significant parameter for assessing the different clusters. Also, tt was a significant variable predicting PSA by a nonlinear law and different clusters of the patient population were assessed by the different constants of proportionality. As a theory, we explain the nonlinear relation of tt in predicting PSA as follows: (a) the number of androgen-independent prostate cancer cells increases as tumor volume and PSA serum levels rise, (b) the prevalence of androgen-independent cells producing a substance which inhibits serum LH, and (c) as a result lower levels of serum tt are detected.

Investigative clinical study on prostate cancer Part V: Luteinizing hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate Luteinizing hormone (LH) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: Age, percentages of positive cores at Trans Rectal Ultrasound Scan Biopsy (TRUSB) (P+), biopsy Gleason score (bGS), LH, Total Testosterone (TT), Free Testosterone (FT) and Prostate Specific Antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement treatment. Correlation analysis was performed for the patient population. Correlation analysis, linear regression and analysis of variance was computed in groups and subgroups of the prostate cancer population. RESULTS: Correlation analysis of the patient population showed that LH was significantly correlated to age (p=0.02) and FT (p=0.01). The population was clustered in LH I (LH≤7.5 IU/l) and LH II (LH>7.5 IU/l). Correlation analysis showed significant LH correlations for TT (p<0.0001) and FT (p=0.0004) for LH I; significant LH correlation to FT (p=0.0001) for LH II. Simple linear regression showed that LH was significantly predicted by both TT (p-Value<0.0001) and FT (p-Value=0.0004) in LH I; but only FT (p-Value<0.0001) in LH II. Multiple linear regression showed that LH was significantly predicted by both TT (p-Value=0.0004) and PSA (p-Value=0.03) in LH I; but only by FT (p-Value=0.003) in LH II. Analysis of variance showed that: a) LH and age were significantly lower in LH I than II; b) LH I expressed higher mean FT levels (p=0.08) and lower mean P+ (p=0.07) than LH II. The LH versus PSA plot was computed for LH group I and 3 sub clusters were created: LH I group A (LH/PSA≤0.25), B (0.250.75). Correlation analysis showed that LH was significantly correlated to age (p=0.01), TT (p=0.03) and PSA (p=0.0004) in LH IA; LH was significantly correlated to PSA (p<0.0001) in LH IB; and LH significantly correlated to TT (p=0.005), FT (p=0.01), and PSA (p=0.008) in LH 1C. Multiple linear regression showed that LH was significantly correlated to age (p=0.02) and PSA (p=0.01) in LH IA, to TT (p=0.01) and PSA (p<0.0001) in LH IB, and to PSA (p=0.003) and weakly to TT (p=0.09) in LH IC. The groups differed significantly for mean levels of LH (p=0.0004), TT (p=0.005), FT (p=0.01), PSA (p<0.0001), bGS (p=0.003). Analysis of variance between the subgroups of the patient population (LH IA, LH IB, LH IC, LH II) showed significant differences in mean levels for LH (p<0.0001), age (p=0.004), TT (p=0.009), FT (p=0.02), PSA (p<0.0001), PSA/FT (p<0.0001), bGS (p=0.01), but not for P+ (p=0.10). CONCLUSION: According to LH physiopathology, the prostate cancer population could be clustered into hypo-gonadic and non-hypo-gonadic group at diagnosis. The hypo-gonadic group expresses an aggressive tumor phenotype and might be divided into two more different significant subsets including primary and secondary hypo-gonadic patients: the former (LH II) including older patients with high LH levels, the latter (LH IA) including younger patients with low LH and LH/PSA levels (subgroup LH IA). The non-hypo-gonadic group showed a less aggressive tumor phenotype and according to the LH/PSA ratio might beclustered into LH IB (0.250.75), the former showing a more aggressive tumor phenotype than the latter. Confirmatory studies are necessary.