Off-clamp Versus On-clamp Partial Nephrectomy: Re-envision of a Dilemma.

We contextualize controversial evidence on the impact of warm ischemia on functional outcomes after partial nephrectomy for localized renal tumors and provide a holistic framework for re-envisioning the dilemma of off-clamp versus on-clamp surgery. The focus should shift away from the surgeon towards patient- and kidney-related characteristics.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Role of Bladder Emptying on Outcomes of Transurethral Resection of the Prostate.

OBJECTIVE: To assess the role of bladder emptying on outcomes of males undergoing transurethral resection of the prostate (TURP). MATERIALS AND METHODS: This prospective study involved candidates for TURP (January 2017-2018) with a follow-up of 3 years. Preoperative and follow-up evaluation comprised: UF, simple PVR (S-PVR), PVR-Ratio (PVR-R) as the ratio of PVR to bladder volume (BV: voided volume (VV) + PVR), Bladder voiding efficiency (BE) as the ratio between VV and BV -(voided volume/total bladder capacity) × 100 - and the IPSS. Patients were stratified for S-PVR, PVR-R, and BVE. RESULTS: Patients recruited were 100 (mean ± SD age: 68.8 ± 8.7 years). No patient had severe complications, re-admission, nor needed blood transfusion. At baseline, 38% of the patients showed S-PVR ≤ 50 mL, 62% a S-PVR ≤ 100 mL, and 25% a S-PVR >150 mL. In both pre- and postoperative evaluation there were no significant differences in Qmax and IPSS score among the groups. In each group we found a significant improvement in Qmax, IPSS score, and S-PVR, PVR-R and BVE after TURP (except for PVR in group with lowest preoperative S-PVR). Analysing a preoperative S-PVR threshold >100 mL, PVR-R significantly increased, and BVE significantly decreased after TURP. Conversely, when preoperative S-PVR was >100 mL, PVR-R, and BVE relevantly but non significantly improved after surgery. CONCLUSION: Bladder emptying is only partially related to TURP outcomes and other preperative parameters. Patients with baseline S-PVR lower than 100 mL had the chance of greater recovery of bladder emptying after TURP.

Features of patients referring to the outpatient office due to benign prostatic hyperplasia: analysis of a national prospective cohort of 5815 cases.

BACKGROUND: Evidence on clinical presentation of benign prostatic hyperplasia (BPH) is scarce, and studies involving outpatients are lacking. We aimed to provide an insight into the contemporary Italian scenario of BPH-affected outpatients using symptom scores (International Prostate Symptom Score [IPSS], BPH Impact Index [BII]), and to compare characteristics of patients with known BPH and those first-diagnosed at the visit. METHODS: "IMPROVING THE PATH" project working group designed a questionary prospectively administered to BPH-affected outpatients by urologists. A cross-sectional study was performed. Data were adjusted for patient age as a potential confounding factor. RESULTS: Of 5815 patients enrolled, BPH was already diagnosed in 4144 (71.3%), and not in 1671 (28.7%). Patients with known BPH, compared to newly diagnosed, were older (median 68 versus [vs] 55), had more frequent smoking (smoker 27.2 vs 22.6%, and ex-smoker 16.4 vs 12.5%) and drinking habits (55.4 vs 45.1%), were more frequently affected by hypertension (60.0 vs 42.4%), obesity (15.3 vs 9.6%), diabetes (17.9 vs 12.5%), and cardiovascular diseases (14.2 vs 9.5%), p < 0.001. At IPSS, moderate and severe symptoms correlated with already known BPH (56.1 vs 47.3% and 24.8 vs 7.8%), whereas newly diagnosed patients showed milder symptoms (44.9 vs 19.1%), all p < 0.001. At BII, concern for one's health and time lost due to urinary problems were higher in patients with known BPH (p < 0.001). For these patients, the urologist changes at least one of the ongoing medications in 63.5%. For patients newly diagnosed, supplements/phytotherapeutics, alpha-blockers, and 5-alfa reductase inhibitors were prescribed in 54.6%, 21.6%, and 7.1%, respectively. CONCLUSIONS: Despite medical treatment, natural history of BPH leads to a progressive deterioration of symptoms. This may reflect the difference between newly diagnosed patients and those with known BPH in lifestyle and associated comorbidities. A healthy lifestyle and treatments including local anti-inflammatory agents may delay worsening of symptoms and improve quality of life.

Oncological and safety profiles in patients undergoing simultaneous transurethral resection (TUR) of bladder tumour and TUR of the prostate.

OBJECTIVES: To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory. PATIENTS AND METHODS: Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB-alone patients. Associations between surgery approach with recurrence-free (RFS) and progression-free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size >3 cm). RESULTS: A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien-Dindo Grade ≥III) for the TURB-alone vs TURB+TURP groups, while the latest led to longer operative time (P < 0.001). During a median follow-up of 44 months, there were more recurrences in the TURB-alone (47%) compared to the TURB+TURP group (28%; P < 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB-alone group (55% vs 3%, P < 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29-0.53; P < 0.001), but not PFS (HR 1.63, 95% CI 0.90-2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22-0.49; P < 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28-0.62; P < 0.001). CONCLUSION: In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa.

Oral Health in Breast Cancer Women with Vitamin D Deficiency: A Machine Learning Study.

Breast cancer (BC) survivors treated with aromatase inhibitors (AIs) commonly show several pathological issues, including poor oral health, bone health impairment, and vitamin D deficiency. However, to date, oral health issues in BC survivors treated with AIs have been poorly investigated and their relationship with vitamin D deficiency are far from being understood. This study aimed to evaluate the correlation between oral health and vitamin D status in BC survivors undergoing treatment with AIs through a machine learning approach. In this cross-sectional study, we included post-menopausal BC women with vitamin D deficiency undergoing AIs therapy. The outcome measures were the following: oral health indexes as the Decayed, Missing, and Filled Permanent Teeth Index (DMFT); serum levels of 25(OH)D3; Bone Mineral Density (BMD); and the diagnosis of osteoporosis. We included 41 post-menopausal BC women, mean aged 66.10 ± 8.47 years, with mean serum levels of vitamin D of 14.63 ± 6.62 ng/mL. Furthermore, 56.10% of patients had a diagnosis of osteoporosis and 36.59% were osteopenic. DMFT was significantly related to smoking (p-value = 0.005) and dental floss use (p-value = 0.001). There was a significant correlation between DMFT and vitamin D levels (Pearson's r: -0.73; p-value = 0.001). The regression machine learning model showed that vitamin D status and the use of dental floss were the most relevant variables in terms of correlation with DMFT. In conclusion, vitamin D deficiency, inadequate use of dental floss, and smoking had a negative impact on oral health in BC women. Thus, vitamin D deficiency screening and supplementation and a prompt oral rehabilitation plan should be suggested and implemented in the complex treatment framework of BC survivors undergoing treatment with AIs.

Rates of metastatic prostate cancer in newly diagnosed patients: Numbers needed to image according to risk level.

BACKGROUND: The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown. METHODS: Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed. RESULTS: Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1a-c ), 8920 (4.9%) harbored M1a-c stage: 50 (0.07%), 45 (0.1%), 161 (0.5%), 1290 (5.1%), and 7374 (22.0%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk. These resulted in NNI of 1347, 602, 174, 20, and 5, respectively. CONCLUSIONS: Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids.

Benefits of the omega-3 polyunsaturated fatty acids (PUFA) on a number of clinical disorders, including autoimmune diseases, are widely reported in the literature. One major dietary source of PUFA are fish, particularly the small oily fish, like anchovy, sardine, mackerel and others. Unfortunately, fish (particularly the large, top-predator fish like swordfish) are also a source of pollutants, including the heavy metals. One relevant heavy metal is mercury, a known environmental trigger of autoimmunity that is measurable inside the thyroid. There are a number of interactions between the omega-3 PUFA and thyroid hormones, even at the level of the thyroid hormone transport proteins. Concerning the mechanisms behind the protection from/amelioration of autoimmune diseases, including thyroiditis, that are caused by the omega-3 PUFA, one can be the decreased production of chemokines, a decrease that was reported in the literature for other nutraceuticals. Recent studies point also to the involvement of resolvins. The intracellular increase in resolvins is associated with the tissue protection from inflammation that was observed in experimental animals after coadministration of omega-3 PUFA and thyroid hormone. After having presented data on fish consumption at the beginning, we conclude our review by presenting data on the market of the dietary supplements/nutraceuticals. The global omega-3 products market was valued at USD 2.10 billion in 2020, and was projected to go up at a compound annual growth rate of 7.8% from 2020 to 2028. Among supplements, fish oils, which are derived mainly from anchovies, are considered the best and generally safest source of omega-3. Taking into account (i) the anti-autoimmunity and anti-cancer properties of the omega-3 PUFA, (ii) the increasing incidence of both autoimmune thyroiditis and thyroid cancer worldwide, (iii) the predisposing role for thyroid cancer exerted by autoimmune thyroiditis, and (iv) the risk for developing metabolic and cardiovascular disorders conferred by both elevated/trendwise elevated serum TSH levels and thyroid autoimmunity, then there is enough rationale for the omega-3 PUFA as measures to contrast the appearance and/or duration of Hashimoto's thyroiditis as well as to correct the slightly elevated serum TSH levels of subclinical hypothyroidism.

Advances in pharmacotherapy for advanced thyroid cancer of follicular origin (PTC, FTC). New approved drugs and future therapies.

INTRODUCTION: The most common altered signaling found in aggressive iodine-refractory thyroid cancers derived from follicular cells (RAI-TC) are RTK, MAPK, PI3K, WNT, BRAF, RAS, RET, and TP53. Tyrosine Kinase Inhibitors (TKI) are multi-kinase inhibitors able to act against different pathways, that elicit an anti-neoplastic activity. AREAS COVERED: The aim of this paper is to review recent novel molecular therapies of RAI-TC. Recently, sorafenib and lenvatinib, have been approved for the treatment of aggressive RAI-TC. Other studies are evaluating vandetanib and selumetinib in RAI-TC. Furthermore, preliminary studies have evaluated dabrafenib, and vemurafenib in BRAF mutated RAI-TC patients to re-induce 131-iodine uptake. The interplay between cells of the immune system and cancer cells can be altered by immune checkpoints inhibitors. The expression of PDL1 in RAI-TC was related to tumor recurrence and poor survival. Several clinical trials are investigating a combination of different therapies, such as lenvatinib and pembrolizumab. EXPERT OPINION: Mechanisms of resistance to TKIs inhibitors can be of intrinsic or acquired origin. An acquired resistance to lenvatinib, or sorafenib can be due to upregulation of FGFR; therefore, anti-FGFR agents are evaluated. A new strategy is to combine TKIs with immunotherapy. Several studies are evaluating lenvatinib and pembrolizumab in RAI-TC patients.

Perioperative Outcomes of Holmium Laser Enucleation of the Prostate: A Systematic Review.

INTRODUCTION: The aim of the study was to systematically review the literature and describe perioperative complications of holmium laser enucleation of the prostate (HoLEP), including the Clavien-Dindo classification of surgical complications. METHODS: All English language publications on HoLEP were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines to evaluate PubMed®, Scopus®, and Web of Science™ databases from January 1, 1998, to June 1, 2020. RESULTS: Fifty-seven studies were included, for a total of 10,371 procedures. We distinguished between intra-, peri-, and postoperative complications. Overall, the rate of complications is 0-7%. Intraoperative complications include incomplete morcellation (2.3%), capsular perforation (2.2%), bladder (2.4%), and ureteric orifice (0.4%) injuries. Perioperative complications include postoperative urinary retention (0.2%), hematuria and clot retention (2.6%), and cystoscopy for clot evacuation (0.7%). Postoperative complications include dysuria (7.5%), stress (4.0%), urge (1.8%), transient (7%) and permanent (1.3%) urinary incontinence, urethral stricture (2%) and bladder neck contracture (1%). CONCLUSIONS: HoLEP is a safe procedure, with a satisfactory low complication rate. The most common reported perioperative complications are not severe (Clavien-Dindo classification grades 1-2). Further randomized studies are certainly warranted to fully determine the predictor of surgical complications in order to prevent them and improve this technique.

The Influence of Endogenous Testosterone on Incidental Prostate Cancer after Transurethral Prostate Resection.

OBJECTIVE: The aim of the study was to test the hypothesis that endogenous total testosterone (TT) may relate to incidental prostate cancer (iPCA) in patients with lower urinary tract symptoms (LUTS) associated with prostate enlargement undergoing transurethral resection of the prostate (TURP). METHODS: The hypothesis was tested in contemporary cohort of patients who underwent TURP because of LUTS due to prostate enlargement after excluding the suspect of PCA. In period running from January 2017 to November 2019, 389 subjects were evaluated. Endogenous testosterone was measured preoperatively between 8:00 and 10:00 o'clock in the morning. Relationships between TT and iPCA were evaluated by statistical methods. RESULTS: Overall, iPCA was detected in 18 cases (4.6%) with clinical stage cT1a or International Society of Urologic Pathology (ISUP) < 2 in 11 patients (61.1%). Endogenous testosterone was inversely associated with age and BMI in the study population but not in the subgroup with iPCA in wholly endogenous TT strongly correlated to both number of chips involved by cancer (Pearson's correlation coefficient, r = 0.553; p = 0.017) and ISUP > 2 (r = 0.504; p = 0.033). The positive association of endogenous TT with both tumor load and tumor grade was confirmed by the linear regression model with high-regression coefficients for the former (regression coefficient, b = 0.307; 95% confidence interval, 95% CI: 0.062-0.551; and p = 0.017) as for the latter (b = 5.898; 95% CI: 0.546-11.249; and p = 0.033). CONCLUSIONS: Preoperative endogenous TT is associated with features of iPCA. The influence of iPCA on endogenous testosterone needs to be addressed by a large multicenter prospective trial.

Comparison between thulium laser vapoenucleation and plasmakinetic resection of the prostate in men aged 75 years and older in a real-life setting: a propensity score analysis.

BACKGROUND: Urologists may hesitate to offer transurethral resection of the prostate (TURP) because of increased morbidity in elderly patients. AIMS: We aimed to compare data on postoperative outcomes of elderly men undergoing bipolar transurethral resection of the prostate (B-TURP) as compared to thulium laser vapoenucleation of the prostate (ThuVEP). METHODS: We retrospectively reviewed data of all patients aged ≥ 75 years who underwent benign prostatic hyperplasia surgery. Differences between interventions were estimated using propensity scores (PS) to adjust for different patients characteristics. RESULTS: Between 2017 and 2020, 275 men were included in the analysis. Propensity score retrieved 65 patients in each group. Median age was 78 (4) years in B-TURP group and 78 (6) in ThuVEP group. Median prostate volume was 63 (35) ml and 54 (24) ml in B-TURP group and ThuVEP group, respectively. Only American Society of Anesthesiologists score was significantly higher in ThuVEP group (p = 0.006). Median operation time, catheterization time, and hospital stay were similar in both groups (55 min, 2 and 3 days). Overall, 84.6% of men had no complications, with no significant differences between the groups (p = 0.234). Only one patient in B-TURP group experienced a Clavien grade IIIb complication. By 1 year, there were a statistically significant differences in International Prostate Symptom Score (p = 0.000) in favor of B-TURP group and in maximal urine flow rate (p = 0.000) in favor of ThuVEP group. DISCUSSION AND CONCLUSIONS: Both procedures showed excellent functional improvements one year after surgery with a low rate of major complications in men aged ≥ 75 years with small-to-medium sized prostates.

The Association of Myo-Inositol and Selenium Contrasts Cadmium-Induced Thyroid C Cell Hyperplasia and Hypertrophy in Mice.

Previous studies have demonstrated that, in addition to inducing structural changes in thyroid follicles, cadmium (Cd) increased the number of C cells. We examined the effects of myo-inositol (MI), seleno-L-methionine (Se), MI + Se, and resveratrol on C cells of mice exposed to cadmium chloride (Cd Cl2), as no data are currently available on the possible protective effects of these molecules. In contrast, we have previously shown this protective effect against CdCl2 on the thyroid follicles of mice. Ninety-eight C57 BL/6J adult male mice were divided into 14 groups of seven mice each: (i) 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); (ii) Se (0.2 mg/kg/day per os); (iii) Se (0.4 mg/kg/day per os); (iv) MI (360 mg/kg/day per os); (v) Se (0.2 mg/kg/day) + MI; (vi) Se (0.4 mg/kg/day) + MI; (vii) resveratrol (20 mg/kg); (viii) CdCl2 (2 mg/kg/day i.p.) + vehicle; (ix) CdCl2 + Se (0.2 mg/kg/day); (x) CdCl2 + Se (0.4 mg/kg/day); (xi) CdCl2 + MI; (xii) CdCl2 + Se (0.2 mg/kg/day) + MI; (xiii) CdCl2 + Se (0.4 mg/kg/day) + MI; (xiv) CdCl2 + resveratrol (20 mg/kg). After 14 days, thyroids were processed for histological, immunohistochemical, and morphometric evaluation. Compared to vehicle, Cd significantly decreased follicle mean diameter, increased CT-positive cells number, area and cytoplasmic density, and caused the disappearance of TUNEL-positive C cells, namely, the disappearance of C cells undergoing apoptosis. Se at either 0.2 or 0.4 mg/kg/day failed to significantly increase follicular mean diameter, mildly decreased CT-positive cells number, area and cytoplasmic density, and was ineffective on TUNEL-positive C cells. Instead, MI alone increased significantly follicular mean diameter and TUNEL-positive cells number, and decreased significantly CT-positive cells number, area and cytoplasmic density. MI + Se 0.2 mg/kg/day or MI + Se 0.4 mg/kg/day administration improved all five indices more markedly. Indeed, follicular mean diameter and TUNEL-positive cells number increased significantly, while CT-positive cells number, area and cytoplasmic density decreased significantly. Thus, all five indices overlapped those observed in vehicle-treated mice. Resveratrol improved significantly all the considered parameters, with a magnitude comparable to that of MI alone. In conclusion, the association Myo + Se is effective in protecting the mouse thyroid from the Cd-induced hyperplasia and hypertrophy of C cells. This benefit adds to that exerted by Myo + Se on thyrocytes and testis.

Outcomes of transurethral resection of the prostate in unobstructed patients with concomitant detrusor underactivity.

AIMS: The aim of the study was to evaluate the transurethral resection of the prostate (TURP) outcomes of unobstructed patients with detrusor underactivity (DUA), comparing the surgical results between obstructed and unobstructed males with concomitant DUA, at midterm follow-up. METHODS: This was an observational, prospective, comparative, nonrandomized study. Candidates to TURP underwent preoperative urodynamics (UD), with a diagnosis of DUA, were divided in two cohorts: Group A unobstructed men, group B males with bladder outlet obstruction (BOO). Males were evaluated yearly with uroflowmetry (UF), post-void residual (PVR), and bladder voiding efficiency (BVE), International Prostate Symptom Score (IPSS) questionnaire, visual analogic scale (VAS) for subjective assessment of the quality of life. The degree of the variation of maximum flow rate (Qmax), PVR, BVE, IPSS, VAS between baseline and follow-up (Δ) was evaluated. RESULTS: Patients in group A were 28 and in group B 23. Overall patient's mean ± SD age was 63.37 ± 12.41 years. Preoperative urodynamics characteristics: mean bladder contractility index (BCI) of 61.15 and 76.25 in group A and B, respectively; mean bladder outlet obstruction index (BOOI) of 17.25 and 50.15 in group A and group B, respectively. After surgery, overall patient group, group A, and group B showed a statistical improvement in IPSS score (P < .0001), Qmax (P < .0001), PVR (P < .0008), BVE (P < .03) and VAS (P < .0001). CONCLUSIONS: BOO had an important impact on the degree of improvement of Qmax and PVR/BVE, while had a poor influence on lower urinary tract symptoms amelioration. The most relevant outcomes were found when BOO was associated with DUA, which was not a contraindication to surgery.

Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies.

Nutraceuticals are defined as a food, or parts of a food, that provide medical or health benefits, including the prevention of different pathological conditions, and thyroid diseases, or the treatment of them. Nutraceuticals have a place in complementary medicines, being positioned in an area among food, food supplements, and pharmaceuticals. The market of certain nutraceuticals such as thyroid supplements has been growing in the last years. In addition, iodine is a fundamental micronutrient for thyroid function, but also other dietary components can have a key role in clinical thyroidology. Here, we have summarized the in vitro, and in vivo animal studies present in literature, focusing on the commonest nutraceuticals generally encountered in the clinical practice (such as carnitine, flavonoids, melatonin, omega-3, resveratrol, selenium, vitamins, zinc, and inositol), highlighting conflicting results. These experimental studies are expected to improve clinicians' knowledge about the main supplements being used, in order to clarify the potential risks or side effects and support patients in their use.

Protective Effects of Myo-Inositol and Selenium on Cadmium-Induced Thyroid Toxicity in Mice.

Cadmium (Cd) damages the thyroid gland. We evaluated the effects of myo-inositol (MI), seleno-L-methionine (Se) or their combination on the thyroids of mice simultaneously administered with Cd chloride (CdCl2). Eighty-four male mice were divided into 12 groups (seven mice each). Six groups (controls) were treated with 0.9% NaCl (vehicle), Se (0.2 mg/kg/day), Se (0.4 mg/kg/day), MI (360 mg/kg/day), MI+Se (0.2 mg/kg) and MI+Se (0.4 mg/kg). The other six groups were treated with CdCl2 (2 mg/kg), CdCl2+MI, CdCl2+Se (0.2 mg/kg), CdCl2+Se (0.4 mg/kg), CdCl2+MI+Se (0.2 mg/kg) and CdCl2+MI+Se (0.4 mg/kg). An additional group of CdCl2-challenged animals (n= 7) was treated with resveratrol (20 mg/kg), an effective and potent antioxidant. All treatments lasted 14 days. After sacrifice, the thyroids were evaluated histologically and immunohistochemically. CdCl2 reduced the follicular area, increased the epithelial height, stroma, and cells expressing monocyte chemoattractant protein-1 (MCP-1) and C-X-C motif chemokine 10 (CXCL10). CdCl2+Se at 0.2/0.4 mg/kg insignificantly reversed the follicular and stromal structure, and significantly decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI significantly reversed the thyroid structure and further decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI+Se, at both doses, brought all indices to those of CdCl2-untreated mice. MI, particularly in association with Se, defends mice from Cd-induced damage. The efficacy of this combination was greater than that of resveratrol, at least when using the follicular structure as a read-out for a comparison. We suggest that the use of these nutraceuticals, more specifically the combination of MI plus SE, can protect the thyroid of Cd-exposed subjects.

Endocrine disruptors and thyroid autoimmunity.

Many papers evaluated the effect of the environmental, or occupational endocrine disruptors (ED), on the thyroid gland, that can lead to thyroid autoimmunity. A higher prevalence of autoimmune thyroid diseases (AITD) was observed in people living in polluted areas near to petrochemical plants, and in petrochemical workers, but also in area contaminated with organochlorine pesticides, or with polychlorinated biphenyls, or near aluminum foundries. The exposure to Hg in chloralkali workers, or in swordfish consumers has been also found to increase AITD prevalence. Vanadium has been shown to increase the inflammatory response of thyrocytes. A beneficial effect of omega-3 fatty acids, and of myo-inositol and selenomethionine have been shown to counteract the appearance of AITD in subjects exposed to environmental or occupational ED. More large studies are needed to investigate the potential roles of ED in the induction of AITD, and of agents or habits that are able to prevent them.

Bipolar endoscopic enucleation versus bipolar transurethral resection of the prostate: an ESUT systematic review and cumulative analysis.

PURPOSE: To perform a cumulative analysis of the current evidence on the surgical and functional outcomes of bipolar endoscopic enucleation of the prostate (b-EEP) versus bipolar transurethral resection of the prostate (b-TURP). METHODS: A systematic review of the literature was performed on PubMed, Ovid®, and Scopus® according to Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA Statement). The meta-analysis was conducted using the Review Manager 5.3 software. Parameters of interest were surgical and functional outcomes. Weighted mean difference, and odds ratio with 95% confidence interval were calculated for continuous and binary variables, respectively. Pooled estimates were calculated using the random-effect model. RESULTS: Fourteen comparative studies were included. No statistically significant difference in terms of overall baseline characteristics was found. b-EEP had higher amount of resected tissue (p < 0.0001), shorter catheter time (p = 0.006), lower Hb drop (p = 0.03), and shorter length of stay (p < 0.0001). Equally, overall post-operative complications were lower (p = 0.01) as well as short (p = 0.04), and long-term complication rate (p = 0.04). There was higher re-intervention rate in the b-TURP group (p = 0.02) whereas b-EEP group had smaller residual prostate volume (p = 0.03), and lower post-operative PSA values (p < 0.00001). At long term, b-EEP presented lower IPSS (p = 0.04), higher Qmax (p = 0.002), and lower PVR (p < 0.00001). CONCLUSIONS: b-EEP is an effective and safe surgical treatment for BPO. This procedure might offer several advantages over standard b-TURP, including the resection of a larger amount of tissue within the same operative time, shorter hospitalization, lower risk of complications, and lower re-intervention rate. This was submitted to PROSPERO registry: CRD42019126748.

Treatment paths for localised prostate cancer in Italy: The results of a multidisciplinary, observational, prospective study (Pros-IT CNR).

BACKGROUND: There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study. METHODS: The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method. RESULTS: At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis. CONCLUSIONS: An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.

Myo-inositol in the protection from cadmium-induced toxicity in mice kidney: An emerging nutraceutical challenge.

Cadmium (Cd) induces functional and morphological changes in kidney. Therefore, the effects of a natural nutraceutical antioxidant, myo-inositol (MI), were evaluated in mice kidneys after Cd challenge. Twenty-eight C57 BL/6 J mice were divided into these groups: 0.9% NaCl; MI (360 mg/kg/day); CdCl2 (2 mg/kg/day) plus vehicle; CdCl2 (2 mg/kg/day) plus MI (360 mg/kg/day). After 14 days, kidneys were processed for structural, biochemical and morphometric evaluation. Treatment with CdCl2 increased urea nitrogen and creatinine in serum and augmented tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression. Furthermore, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1) and myo-inositol oxygenase (MIOX) immunoreactivity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells number were significantly higher than control and MI groups. Glutathione (GSH) content and glutathione peroxidase (GPx) activity were reduced and structural changes were evident. The treatment with MI significantly lowered urea nitrogen and creatinine levels, TNF-α and iNOS expression, MCP-1, KIM-1 and MIOX immunoreactivity and TUNEL positive cells number, increased GSH content and GPx activity and preserved kidney morphology. A protection of MI against Cd-induced damages in mice kidney was demonstrated, suggesting a strong antioxidant role of this nutraceutical against environmental Cd harmful effects on kidney lesions.