Characterization of the Antioxidant Effects of γ-Oryzanol: Involvement of the Nrf2 Pathway.

γ-Oryzanol (ORY) is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS) scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293). The 24 h ORY exposure significantly prevented hydrogen peroxide- (H2O2-) induced ROS/RNS production at 3 h, and this effect was sustained for at least 24 h. ORY pretreatment also enhanced the activity of antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPX). Interestingly, ORY induced the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and upregulation of Nrf2-dependent defensive genes such as NAD(P)H quinone reductase (NQO1), heme oxygenase-1 (HO-1), and glutathione synthetase (GSS) at mRNA and protein levels in both basal condition and after H2O2 insult. Thus, this study suggested an intriguing effect of ORY in modulating the Nrf2 pathway, which is also involved in regulating longevity as well as age-related diseases.

Radiotherapy or chemotherapy for clinical stage IIA and IIB seminoma: a systematic review and meta-analysis of patient outcomes.

BACKGROUND: Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma. PATIENTS AND METHODS: A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus <30 Gy), and PEB/EP regimens only. RESULTS: Thirteen studies have been selected for MA on relapse outcome. No randomized trials compared RT and CT. There were 4 prospective and 9 retrospective studies, with a total of 607 patients receiving RT and 283 patients CT. The pooled relapse rate (RR) was similar between the RT [0.11, 95% confidence interval (CI) 0.08-0.14, P for heterogeneity = 0.096, I(2) = 38%] and CT groups (0.08, 95% CI 0.01-0.15, P for heterogeneity <0.001, I(2) = 82.5%). However, in the sensitivity analysis, the pooled RR for RT in CSIIB was 0.12 (95% CI 0.06-0.17) while it was 0.05 (95% CI 0-0.11) for CT. Long-term side-effects and incidence of second cancers were more frequently reported following RT. The overall incidence of nontesticular second malignancies was 0.04 (95% CI 0.01-0.02) in the RT group and 0.02 (95% CI 0.003-0.04) in the CT group. CONCLUSIONS: Although RT and CT appeared to be equal options in CSIIA and IIB seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size.

High-dose sequential chemotherapy (HDS) versus PEB chemotherapy as first-line treatment of patients with poor prognosis germ-cell tumors: mature results of an Italian randomized phase II study.

BACKGROUND: In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS: From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS: The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ cell tumors: long-term efficacy and safety outcomes.

BACKGROUND: Since 1985, we introduced a modified combination of etoposide, ifosfamide, and cisplatin (PEI) as second-line therapy of adult male germ cell tumors with the aim to reduce toxic effect while maintaining efficacy over the original regimen. PATIENTS AND METHODS: Patients received four cycles of ifosfamide at 2.5 g/m(2) on days 1-2, etoposide, and cisplatin at 100 and 33 mg/m(2), respectively, on days 3-5 every 21 days, followed by surgery. Results were stratified according to the International Germ Cell Consensus Classification Group-2 (IGCCCG-2). RESULTS: From February 1985 to January 2012, 189 patients were treated. 72.6% were IGCCCG-2 intermediate-to-very high risk. Thirty-five patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm-). Median follow-up was 122.1 months (inter-quartile range [IQR]: 71.4-232.0). Two-year progression-free and 5-year overall survival were 34.3% [95% confidence interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively. Survival estimates compared favorably with those obtained by conventional dose chemotherapy (CDCT) regimens in each prognostic category. 70.4% of grade 3-4 neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia, 21.2% anemia, 3.2% neurotoxic effect, and no severe renal toxic effect were recorded. CONCLUSION: Dose-modified Italian PEI should be considered as an appropriate benchmark for CDCT in the first salvage setting.

CT-guided percutaneous cryoablation of renal masses in selected patients.

PURPOSE: We analysed our experience with computed tomography (CT)-guided percutaneous cryoablation (PCA) in patients who were not surgical candidates or refused surgery for small to medium-sized renal masses. MATERIALS AND METHODS: Two freezing cycles were applied and separated by a passive warming cycle using 1.7- and 2.4-mm cryoprobes under either general anaesthesia or sedation based on patient positioning and respiratory status. Postoperative monitoring included haematological and biochemistry evaluation and CT scan 24 h after PCA. Follow-up consisted of a multislice CT scan at 1 month and every 3 months in the first year then every 6 months thereafter. RESULTS: Thirty-seven patients (38 lesions) underwent 40 PCA procedures; 5/37 (13.5%) had a solitary kidney. Median mass size was 35 (range 12-70) mm. No complications occurred during the procedure. Clavien grade ≥2 anaemia occurred in two patients (5.4 %): one patient required 1 U of packed red blood cells; the other required an arterial embolisation. Serum creatinine did not increase in any case. Two patients showed persisting or recurrent disease at 1 and 9 months, respectively, and both could be re-treated with PCA. All other patients showed a hypodense mass 3 months after PCA, with no contrast enhancement. Subsequent examinations showed that lesion sizes decreased and CT densitometry remained stable or increased minimally, also with no contrast enhancement. CONCLUSIONS: PCA proved relatively easy and safe and could be considered an effective alternative for patients who are not surgical candidates or refuse surgery, as well as in patients with medium-sized lesions.

[Retroperitoneal surgery in the treatment of germ-cell tumors of the testis: retroperitoneal lymph node dissection (RPLND)]. / La linfoadenectomia retroperitoneale (RPLND) nel trattamento delle neoplasie germinali del testicolo.

Germ-cell tumors of the testis (GCTT) are rare, but have a high social impact. In fact they represent no more than 1% of male tumors (about 700 new cases per year in Italy), but electively occur in young patients, 20 to 40 years old, during their fully mature social and working life. More than 80% of patients are cured and return to a normal social, sexual, and working life. Improvements achieved both in diagnosis, with the use of scans (CT, MRI, US and recently PET) and of serum tumor markers alpha-fetoprotein (AFP), beta-fraction of human chorionic gonadotropin (b-HCG) and lactate dehydrogenase (LDH), and mainly in treatment, through the amelioration of radiotherapy and surgical techniques and, especially, with the introduction of Cisplatin, Etoposide and Ifosfamide in chemotherapic regimens, have made germ-cell tumor a model of "curable disease". Retroperitoneal lymph node dissection (RPLND) has indications in patients with clinical stage I (CS1) as well as in advanced disease, where it is integrated in the multimodality treatment. Anatomical studies, as well as a long-term experience, have gradually but consistently modified the surgical techniques of RPLND. Currently, "nerve sparing" RPLND represents a safe management of CS1 nonseminomatous germ cell testicular tumor with minimal morbidity and excellent outcomes. Nonetheless, surveillance and adjuvant chemotherapy are as effective as RPLND, but, in our opinion, associated with some discomforts for the patients. Laparoscopic retroperitoneal lymph node dissection (Lap-RPLND) is gaining popularity as a minimally invasive staging procedure for clinical stage I nonseminomatous testicular carcinoma, but its therapeutic role is still under investigation.

[State of the art and controversies in the treatment of testis germ-cell tumors (TGT)].

Many different, intersecting strategies are available for managing germ-cell cancers,particularly in early-stage disease. Which is 'right' remains a matter of debate, and requires balancing efficacy against late effects, bearing in mind the complexity of treatment strategies and the available expertise.

[Effectiveness and side effects of the treatment with propafenone and flecainide for recent-onset atrial fibrillation]. / Efficacia ed effetti collaterali del trattamento con propafenone e flecainide della fibrillazione atriale di recente insorgenza.

BACKGROUND: The authors report their experience in recent-onset atrial fibrillation treated with intravenous flecainide and propafenone, in comparison with the placebo group. METHODS: We randomized 352 (138 in the flecainide group, 164 in the propafenone group and 50 in the control group) consecutive patients (167 males, 185 females, mean age 59 +/- 12 years) with recent-onset atrial fibrillation. The electrocardiogram of all patients was monitored for at least 24 hours. RESULTS: The restoration of sinus rhythm occurred in 72.5, 80.4, 86.2 and 89.8% of patients in the flecainide group; in 54.3, 68.3, 75 and 92.1% in the propafenone group; in 22.2, 27.8, 35.2 and 46.3% in the control group, at 1, 3, 6 and 24 hours respectively. The occurrence of side effects was the same in all treatment groups, and occurred in about 10% of patients in the flecainide and propafenone groups, and in 4% in the control group. In our study population the treatment of recent-onset atrial fibrillation with flecainide was faster in converting the arrhythmia to sinus rhythm (p < 0.005 at 1 hour, p < 0.05 at 3 hours, p = 0.05 at 6 hours). However within 24 hours the efficacy of either flecainide or propafenone was the same (p = NS at 24 hours). CONCLUSIONS: Side effects were similar in both treatment groups. In particular malignant arrhythmias did not occur in the treatment groups and in the control group.

[Uro-andrologic prevention of male infertility]. / La prevenzione uro-andrologica dell'infertilità maschile.

The Authors analyze the more frequent uro-andrological pathologies correlated with male infertility and consider the causes of impoverishment in semen in industrialized countries. They analyze preventing possibilities to maintain the normal physiological level of fertility in young male in various uro-andrological pathologies.

[Activity of purified diosmin in the treatment of hemorrhoids]. / Attività della diosmina pura nel trattamento della malattia emorroidaria.

Several theories on the etio-pathogenesis and physio-pathology of hemorrhoids have been up to now proposed. From the fisio-pathological viewpoint, particular importance is retained by the vascular factor, which in its turn is influenced by mechanical and sphinceric factors, that impair the venous back-flow. In the evidence of an hemorrhoidal crisis, characterized by local oedema, pain and bleeding, the use of bioflavonoid drugs is deemed to be the first choice. We investigated the use of purified diosmin, given at a dose of two 450 mg tablets bid for the first 7 days, then at 1 tablet bid for up to 2 months, in a group of 66 patients suffering from primitive hemorrhoids of grade 1-4. Our results confirmed diosmin efficacy in decreasing both pain and bleeding: reduction rates of 79% and 67%, respectively, were reached in the first treatment week. In the second week, figures were 98% and 86%, respectively. Diosmin tolerability was excellent: this characteristic makes the drug very easy to handle by the general practitioner and also useful to the proctologist in the preparation of patient to further treatments.

[Urgency-frequency syndrome in women: interstitial cystitis and correlated syndromes]. / La sindrome urgenza-frequenza nella donna: cistite interstiziale e sindromi correlate.

In our clinical practice we encountered urgency-frequency syndrome in female patients. Only in the 3.6% is possible to diagnose a typical interstitial cystitis (IC). In the 63.6% we observed only local trigonal squamous metaplasia (leucoplasia), it could be considered a paraphysiological condition present in 50-70% of fertile women, its rigid, not impermeable epithelium may offer an aethiological hypotesis for the dysuric syndrome. In the treatment of this lesion by endoscopic infiltration we had syntomatological results with 47.8% of patients even if only for a short period (one-two years). This treatment is simple and can be repeated, if the patient is responsive. We noticed that the results did not change even if we used different drugs probably due to the role of a physical detachment of leucoplasia from bladder trigon.

[The prognosis of surgery on the elderly. Proposal for a parametric evaluation]. / La prognosi nella chirurgia del paziente anziano. Proposta per una valutazione parametrica.

BACKGROUND AND AIMS: To data there are no preoperative systems of evaluating surgical risk specifically in geriatric patients. Given that it was thought useful to formulate a score-based prognostic system for these patients based on surgical risk, the authors collected a wide range of preoperative data with the aim of identifying the easily determined variables. METHODS: While data from other hospital centres are in the process of being collected, the authors report the data for 122 over 65-year-old patients who underwent elective surgery up until 30-1-1996 out of a total of 329 hospitalized patients. In addition to a wide series of objective, laboratory and instrumental data, the study also took into account the pathology requiring to surgery, any associated morbid conditions, psychic and social conditions, the type of surgery and local and/or general postoperative complications. RESULTS: Hernia of the abdominal wall were found to be the most frequent cause of surgery (41 cases), followed by 27 neoplasias of various organs and biliary lithiasis (20 cases). Cardiovascular diseases were the most common associated pathologies (85 patients). A total of 13 major and 80 medium operations were performed, including 16 cholecystectomies. Among the general complications, an altered acid-base balance was found in 7 patients. Two deaths were recorded within 30 days of surgery. When the data collection is complete, the results will be analysed statistically in order to obtain a numerical calculation of the coefficients of risk correlated to the individual variables. CONCLUSIONS: This will enable the criteria of operability to be broadened, thereby allowing surgery to be performed in those patients who are currently excluded merely on the basis of the personal judgement of the surgeon and anesthetist.

Management of recurrent stricture of appendicostomy in continent neobladder (Indiana pouch) with Memotherm ureteral stent: case report.

The authors report their experience in the treatment of recurrent stricture of the appendiceal stump in continent diversion (Indiana pouch) after cystectomy by means of the Memotherm ureteral stent. The patient presented was treated successfully with this device after failure of repeat cold-knife incisions of the stricture. At 9-months' follow-up from positioning, the stent is in place, covered by mucosa. Self-catheterization of the pouch is easily performed five or six times a day with a 12F catheter.

[Stents in the treatment of stenosis of the entero-urethral junction in continent diversion: case reports]. / Gli stents nel trattamento delle stenosi della giunzione entero-uretrale nelle derivazioni continenti: casi clinici.

Strictures of entero-urethral anastomosis in orthotopic neobladder and of the catheterizable conduit in continent diversion after cystectomy are seldom encountered; they are usually treated with dilation, TUR or cold incision. 3 cases that came to our observation are presented. The first was treated with TUR after neo-bladder neck stricture in orthotopic neobladder; total incontinence occurred after this procedure. The patient at present is waiting for AS800 artificial sphincter implant. The second patient had similar features. After repeat TUR a prostacoil removable stent was placed through the stricture and removed after 5 months. At 12 months from removal the patient is continent and doesn't present clinical evidence of restriction. The third patient underwent cystectomy with Indiana continent pouch. After 4 months increasing problems in self catheterization occurred due to stricture of the catheterization conduit (appendix). He was treated twice with cold incision with early recurrence of the stricture. A permanent Memotherm stent (indicated for urethral strictures) was placed inside the appendix. After one month self catheterization was started again. At a 2 months follow up there is no evidence of stricture. In our experience, even if anecdotal, we have verified that treatment of this kind of strictures with TUR can cause incontinence or expose to further recurrences. 2 of the cases presented were treated with different kind of stents; the outcome is good even if the follow up is still short. We believe that this kind of treatment can be considered in selected cases.

[Conservative treatment of high-risk (T1G3) transitional carcinoma]. / Il trattamento conservativo nel carcinoma transizionale ad alto rischio (T1G3).

OBJECTIVE: This study evaluates the outcome of patients (pts) with primary T1G3 bladder cancer treated by transurethral resection (TUR) alone or followed by intravesical prophylaxis (BCG/Doxorubicin). Cistectomy was considered at disease progression. METHODS: Between 1/89 and 5/95 thirty-one pts with primary T1G3 bladder cancer were treated by TUR, in 24 followed by intravesical prophylaxis (13 with BCG, 11 with Doxorubicin). 7 pts had only TUR. RESULTS: At 42 months median follow up 45.2% pts (14/31) are disease free. The recurrence rate was 25.8% (8/31) and progression of disease was seen in 29.0% (9/31); mortality rate was 22.6% (7/31). In 13/31 pts treated by TUR + BCG 53.8% pts (7/13) are disease free. The recurrance rate was 23.1% (3/13) and progression of disease was seen in 23.1% (3/13) of cases; mortality rate was 23.1% (3/13). In 11/31 pts treated by TUR+Doxorubicin 54.5% pts (6/11) are disease free. The recurrance rate was 18.2% (2/11), progression of disease was seen in 27.3% (3/11) of cases of mortality rate of 9.1% (1/11). In 7/31 pts treated by TUR alone 14.3% pts (1/7) are disease free. The recurrance rate was 42.9% (3/7) and progression of disease was seen in 42.9% (3/7) of cases and mortality rate of 42.9% (3/7). Cistectomy was considered in 4 pts (3 for disease progression and 1 because of no disease free interval). The other pts with progression were not treated surgically because of their poor performance status. CONCLUSION: At a 42 months median follow up 77.4% pts (24/31) are alive (83.3% pts treated by TUR+intravesical prophylaxis). 64.5% pts (20/31) still have their bladder (66.6% pts treated by TUR+intravesical prophylaxis (16/24). We did not find a significative difference between prophylaxis with immunotherapy or chemotherapy. In conclusion we believe that the conservative management of high risk bladder transitional cell carcinoma T1G3 is feasible and allow us to plan cistectomy only in pts with progression or recurrance with no free interval without losing survival.

[Evaluation of cardiac risk in patients undergoing major vascular surgery. Usefulness and limitations of transesophageal atrial pacing]. / Valutazione del rischio cardiaco in pazienti da sottoporre a chirurgia vascolare maggiore. Utilità e limiti del pacing atriale transesofageo.

Patients undergoing vascular surgery are at high risk of developing cardiac events in the perioperative period. The aim of the study was the evaluation of the predictive accuracy of transesophageal atrial pacing (TAP) in identifying patients at higher risk of developing major cardiac events (cardiac death, acute myocardial infarction, unstable angina, heart failure and sustained ventricular tachyarrhythmias). We studied 96 consecutive patients, 80 males and 16 females, median age 63, requiring arterial surgery (aortofemoral or aortoiliac bypass and thromboendoarterectomy, abdominal aneurysm resection and extracranial carotid thromboendoaterectomy). TAP was performed without cardioactive drugs in all patients, but one. After surgery CK and CKMB serial assessment and ECG recording were performed daily until the seventh postoperative day. Preoperatively all patients were admitted to the Intensive Care Unit and submitted to haemodynamic monitoring with Swan-Ganz catheter at least for 72 hours. Three patients did not undergo surgery because of severe ST depression during TAP. Thus, 93 patients (96.8% of the series) were the subject of this report. In the postoperative period only two events (2.1% of the patients) were recorded, one relapsing acute myocardial infarction and one ventricular fibrillation, both in patients with negative TAP. No death occurred. Our study shows a very low prevalence of major cardiac events.(ABSTRACT TRUNCATED AT 250 WORDS)