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result(s) for
"Gacci, M"
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Meta-analysis of metabolic syndrome and prostate cancer
2017
Background:
Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features.
Methods:
A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4–5 according to the novel prostate cancer grading system). Also the association between MetS and individual MetS components with pathological Gleason Score⩾8, extra-capsular extension, seminal vesicle invasion, positive surgical margins and biochemical recurrence (defined as two consecutive PSA values ⩾0.2 ng ml
−1
after radical prostatectomy) was evaluated.
Results:
24 studies were selected including a total of 132 589 participants of whom 17.35% had MetS. There was a slight association between MetS and PCa incidence (odds ratio (OR)=1.17 (1.00–1.36),
P
=0.04) and between high-grade PCa and MetS (OR= 1.89 (1.50–2.38),
P
<0.0001) but the studies were statistically heterogeneous. No association was found between MetS components and PCa risk except for hypertension. MetS was significantly associated with pathologic Gleason Score⩾8 (OR= 1.77 (1.34–2.34);
P
<0.01), extra-capsular extension (OR=1.13 (1.09–1.18);
P
<0.01), seminal vesicle invasion (OR=1.09 (1.07–1.12);
P
<0.01), positive surgical margins (OR=1.67 (1.47–1.91);
P
<0.01) and biochemical recurrence (OR=1.67 (1.04–2.69);
P
<0.01).
Conclusions:
The presence of MetS is associated with worse oncologic outcomes in men with PCa, in particular with more aggressive tumor features, and biochemical recurrence.
Journal Article
Carbonic anhydrases III and IX are new players in the crosstalk between adrenocortical carcinoma and its altered adipose microenvironment
2023
Purpose
Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC.
Results/methods
CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (
n
= 14) (fold increase FI = 7.4 ± 0.1,
P
< 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06,
P
< 0.001), compared with lower stages (
n
= 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11,
P
< 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1,
P
< 0.01, respectively).
Conclusion
Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.
Journal Article
Metabolic syndrome and lower urinary tract symptoms: the role of inflammation
2013
Background:
Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities.
Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens.
Methods:
A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker.
Results:
Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm
3
(hazard ratio (HR)=3.268,
P
<0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (
Q
max
): 8.6 vs 10.1,
P
=0.008 and average flow rate (
Q
ave
): 4.6 vs 5.3,
P
=0.033, respectively), and higher obstructive urinary symptoms score (
P
=0.064). A positive correlation among both IS–GD and IPSS Score was also observed (adjusted
r
=0.172,
P
=0.008 and adjusted
r
=0.128,
P
=0.050).
Conclusions:
MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.
Journal Article
Prostatic inflammation: a potential treatment target for male LUTS due to benign prostatic obstruction
2018
BackgroundThe purpose of this narrative review is to evaluate the role of prostatic inflammation as a treatment target for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) and provide an update on the available therapies.MethodsAn extensive literature search was conducted for studies on established and investigational treatments with anti-inflammatory mechanism of action that has been assessed for the management of male LUTS due to BPO.ResultsData on phosphodiesterase 5 inhibitors, nonsteroidal anti-inflammatory drugs, vitamin D3 receptor analogs, phytotherapy, statins, and lifestyle changes have been reviewed and analyzed. Preclinical evidence has shown the anti-inflammatory effect of these treatments on prostate. However, there is a wide variation in the degree of mature of each therapy. In addition, there are significant differences between the studies in terms of design, number of patients, and duration of follow-up.ConclusionsSeveral drugs classes have been investigated for their impact on prostatic inflammation and improvement of male LUTS. The reviewed data support the rationale for use of agents that may alter and improve the inflammatory environment in the prostate in men with LUTS, but further high-quality long-term studies are required for the exact positioning of the new drugs in daily practice.
Journal Article
A review of label-free photonics-based techniques for cancer detection in the digestive and urinary systems
2025
For a long time, it has been known that optics can provide a broad range of tools for addressing clinical needs, particularly diagnostics. Optical techniques can help in identifying diseases and detecting pathological tissues with non/minimally invasive and label-free methods. Given the current limitations of standard clinical procedures, such an approach could provide a powerful tool in detecting gastrointestinal and bladder cancers. However, each technique has serious limitations regarding one or more of the following features: biomarker sensitivity, penetration depth, acquisition times, or adaptation to the clinical environment. Hence there is an increasing need for approaches and instruments based on the concept of multimodality; in this regard, we review the application of different imaging/spectroscopy tools and methods operating in the first two optical windows (SHG, SPEF, TPEF, THG, 3PEF, CARS, Raman and reflectance) for tumour detection in the digestive and urinary systems. This article also explores the possibility of exploiting the third bio-tissue transmission window (1600–1900 nm) by reviewing state of the art in ultrafast laser sources development. Finally, we summarize the most recent results in developing multiphoton endoscopes—a key element for clinical in vivo translation of photonics-based diagnostics.
Journal Article
Metabolic abnormalities linked to an increased cardiovascular risk are associated with high-grade prostate cancer: a single biopsy cohort analysis
2016
Background:
Smoking, hypertension, abdominal obesity and metabolic abnormalities have been considered individual factors involved in prostate cancer (PCa) pathogenesis. All of these factors are used to define the individual cardiovascular risk (CVR). The aim of our study was to evaluate the association between CVR and PCa diagnosis and grade among a consecutive series of men undergoing prostate biopsy.
Methods:
From 2010 onwards, consecutive patients undergoing 12-core prostate biopsy were enrolled. Body mass index was measured before the biopsy. Blood samples were collected and tested for: PSA, fasting glucose, triglycerides and high-density lipoproteins. Blood pressure was also recorded. Metabolic syndrome was defined according to the Adult Treatment Panel III and CVR according to the European Association of Cardiologist Guidelines. We evaluated the association between CVR and PCa biopsy Gleason score using logistic regression analyses.
Results:
Five hundred and eighty-four patients were enrolled. Four hundred and six patients (70%) presented a moderate/high CVR. Two hundred and thirty-seven (40.6%) patients had cancer on biopsy; 157 with moderate/high CVR and 80 with low/no CVR (
P
=0.11). Out of the 237 patients with PCa, 113 had a Gleason score 6 and 124 a Gleason score ⩾7. Out of them, 92/124 (75%) presented a moderate/high CVR (
P
=0.004). Moderate/high CVR was not associated with an increased risk of PCa (odds ratio (OR): 0.741, confidence interval (CI): 0.474–1.156;
P
=0.186) but with an increased risk of Gleason score ⩾7 (OR: 2.154, CI: 1.076–4.314;
P
=0.030).
Conclusions:
In our study, a moderate/high CVR is associated with an increased risk of a high-grade Gleason score when PCa is diagnosed on biopsy. Although these results should be confirmed in multicentre studies, patients with moderate/high CVR should be carefully evaluated for PCa diagnosis.
Journal Article
Management of Benign Prostatic Hyperplasia: Role of Phosphodiesterase-5 Inhibitors
by
Maggi, M.
,
Sebastianelli, A.
,
McVary, K. T.
in
Adrenergic alpha-Antagonists - administration & dosage
,
Adrenergic alpha-Antagonists - adverse effects
,
Adrenergic alpha-Antagonists - therapeutic use
2014
Several studies have highlighted a strong association between benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED), particularly in elderly men. Many epidemiological trials, such as in vitro and in vivo studies, have reported the emerging role of metabolic syndrome, including abdominal obesity, impaired glucose metabolism, hypertriglyceridemia, low high-density lipoprotein cholesterol, and hypertension, in the development and progression of urinary and sexual symptoms. Moreover, many authors have focused their studies on the identification of all the shared pathogenetic mechanisms of LUTS/BPH and ED, including alteration of cyclic guanosine monophosphate and RhoA-ROCK pathways or vascular and neurogenic dysfunction. All these are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Therefore, several trials have recently been designed to evaluate the role of PDE5-Is alone or in combination with conventional treatment for BPH, such as α-adrenergic blockers, in men affected by LUTS/BPH, with or without ED. Different PDE5-Is are in clinical use worldwide and currently six of them are licensed for the oral treatment of ED. All these compounds differ in pharmacokinetic factors, with influence on drug action, and subsequently in the overall safety and efficacy profile.
Journal Article
Hypofractionation in Prostate Cancer : Radiobiological Basis and Clinical Appliance
by
Desideri, I.
,
Paiar, F.
,
Gacci, M.
in
Biomedical research
,
Cancer therapies
,
Care and treatment
2014
External beam radiation therapy with conventional fractionation to a total dose of 76–80 Gy represents the most adopted treatment modality for prostate cancer. Dose escalation in this setting has been demonstrated to improve biochemical control with acceptable toxicity using contemporary radiotherapy techniques. Hypofractionated radiotherapy and stereotactic body radiation therapy have gained an increasing interest in recent years and they have the potential to become the standard of care even if long-term data about their efficacy and safety are not well established. Strong radiobiological basis supports the use of high dose for fraction in prostate cancer, due to the demonstrated exceptionally low values of α/β. Clinical experiences with hypofractionated and stereotactic radiotherapy (with an adequate biologically equivalent dose) demonstrated good tolerance, a PSA control comparable to conventional fractionation, and the advantage of shorter time period of treatment. This paper reviews the radiobiological findings that have led to the increasing use of hypofractionation in the management of prostate cancer and briefly analyzes the clinical experience in this setting.
Journal Article
Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer
2010
The aim of the present study was to evaluate how serum testosterone level (
T
) can affect urinary continence and erectile function in patients undergoing radical prostatectomy (RP). We included 257 patients with clinically localized prostate cancer, those who had filled out preoperative quality of life questionnaires (University of California, Los Angeles Prostate Cancer Index, International Index of Erectile Function (IIEF)), and those who had
T
and total PSA sampled the day before surgery. We calculated correlations between
T
and age, body mass index (BMI), PSA, urinary function or bother (UF, UB) and sexual function or bother (SF, SB) and IIEF-5 in the whole population and in sub-populations with normal (⩾10.4 nmol l
−1
) and low (<10.4 ng ml
−1
)
T
using Pearson's and Spearman's correlation coefficients. We evaluated differences in these parameters between patients with low and normal
T
using the unpaired samples
t
-test and Mann–Whitney test, and finally the correlation between UF and SF, UB and SB, and between PSA and
T
in the overall population, and separately in patients with low and normal
T
using the Pearson's correlation coefficient. Mean preoperative
T
was 13.5 nmol l
−1
and 23.7% of patients presented a low
T
. Mean age, mean BMI and mean preoperative total PSA at RP were 64.3 years, 25.9 kg m
−2
and 9.0 ng ml
−1
, respectively. BMI was negatively correlated with
T
in the overall population (
r
=−0.266;
P
=0.02); moreover, patients with normal
T
presented lower BMI compared with patients with low
T
(25.7 vs 27.6:
P
=0.02). We found a significant correlation between SF scores and
T
in patients with normal
T
(
r
=0.1777:
P
=0.05). SF was significantly higher in patients with normal
T
compared with those with low
T
(74.8 vs 64.8:
P
=0.05). Furthermore, UF and UB were significantly correlated with SF (
r
=0.2544:
P
<0.01) and SB (
r
=0.2512:
P
=0.01), respectively, in men with normal
T
. Serum
T
was significantly correlated with PSA in men with low
T
(
r
=0.3874:
P
=0.0029), whereas this correlation was missed in the whole population and in men with normal
T
. The correlation between preoperative PSA and
T
in men with low
T
is in agreement with the ‘saturation’ model proposed by Morgentaler. The correlation between basal
T
and preoperative erectile function and urinary continence underlines the importance of assessing
T
before RP.
Journal Article
Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study
by
Li Marzi, Vincenzo
,
Marzocco, Michele
,
Gacci, M.
in
Angioplasty
,
Blood Flow Velocity
,
Blood Pressure
2018
Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs.
Journal Article