Yellow mealworm larvae (Tenebrio molitor) inclusion in diets for male broiler chickens: effects on growth performance, gut morphology, and histological findings.

This study evaluated the effects of Tenebrio molitor (TM) larvae meal inclusion in diets for broilers. A total of 160 male broiler chicks (Ross 708) at one-day of age were randomly allotted to four dietary treatments: a control (C) group and three TM groups, in which TM meal was included at 50 (TM5), 100 (TM10), and 150 (TM15) g/kg, respectively. The experimental diets were isonitrogenous and isoenergetic. Each group consisted of five pens as replicates (8 chicks/pen). After the evaluation of growth performance and haematochemical parameters, the animals were slaughtered at 53 days and carcass traits were recorded. Morphometric investigations were performed on duodenum, jejunum, and ileum and histopathological alterations were assessed for liver, spleen, thymus, bursa of Fabricius, kidney, and heart. The live weight (LW) showed a linear (12 and 25 days, P < 0.001 and P < 0.05, maximum with TM15 and TM10) and quadratic (53 days, P < 0.05, maximum with TM5) response to dietary TM meal inclusion. A linear (1 to 12 and 12 to 25 days, P < 0.001, maximum with TM15) and quadratic (12 to 25 days, P = 0.001, maximum with TM15) effect was also observed for the daily feed intake (DFI). The feed conversion ratio (FCR) showed a linear response (25 to 53 and 1 to 53 days, P = 0.001 and P < 0.05, maximum with TM15). Haematological and serum biochemical traits, carcass traits and histopathological findings were not affected by dietary TM meal inclusion (P > 0.05). TM15 birds showed lower villus height (P < 0.05), higher crypt depth (P < 0.05), and lower villus height to crypt depth ratio (P = 0.001) compared with C and TM5. In conclusion, increasing levels of dietary TM meal inclusion in male broiler chickens may improve body weight and feed intake, but negatively affect feed efficiency and intestinal morphology, thus suggesting that low levels may be more suitable. However, no effect on haematochemical parameters, carcass traits, and histological findings were observed in relation to TM meal utilization.

Effects of dietary Tenebrio molitor meal inclusion in free-range chickens.

Insects are currently being considered as a novel protein source for animal feeds, because they contain a large amount of protein. The larvae of Tenebrio molitor (TM) have been shown to be an acceptable protein source for broiler chickens in terms of growth performance, but till now, no data on histological or intestinal morphometric features have been reported. This study has had the aim of evaluating the effects of dietary TM inclusion on the performance, welfare, intestinal morphology and histological features of free-range chickens. A total of 140 medium-growing hybrid female chickens were free-range reared and randomly allotted to two dietary treatments: (i) a control group and (ii) a TM group, in which TM meal was included at 75 g/kg. Each group consisted of five pens as replicates, with 14 chicks per pen. Growth performance, haematological and serum parameters and welfare indicators were evaluated, and the animals were slaughtered at the age of 97 days. Two birds per pen (10 birds/treatment) were submitted to histological (liver, spleen, thymus, bursa of Fabricius, kidney, heart, glandular stomach and gut) and morphometric (duodenum, jejunum and ileum) investigations. The inclusion of TM did not affect the growth performance, haematological or serum parameters. The morphometric and histological features were not significantly affected either, thus suggesting no influence on nutrient metabolization, performance or animal health. Glandular stomach alterations (chronic flogosis with epithelial squamous metaplasia) were considered paraphysiological in relation to free-range farming. The observed chronic intestinal flogosis, with concomitant activation of the lymphoid tissue, was probably due to previous parasitic infections, which are very frequently detected in free-range chickens. In conclusion, the findings of this study show that yellow mealworm inclusion does not affect the welfare, productive performances or morphological features of free-range chickens, thus confirming that TM can be used safely in poultry diets.

Conventional testicular sperm extraction (TESE) and non-obstructive azoospermia: is there still a chance in the era of microdissection TESE? Results from a single non-academic community hospital.

Spermatozoa can be retrieved in non-obstructive azoospermia (NOA) patients despite the absence of ejaculated spermatozoa in their semen because of the presence of isolated foci with active spermatogenesis. Conventional testicular sperm extraction (c-TESE) in patients with NOA has been partially replaced by micro-TESE. It is still under debate the problem regarding the higher costs related to micro-TESE when compared with c-TESE. In this study, we evaluated sperm retrieval rate (SRR) of c-TESE in naive NOA patients. Sixty-three NOA patients were referred to our centre for a c-TESE. For every subject, we collected demographic data, cause of infertility, time to first infertility diagnosis, serum levels of LH, FSH, total testosterone and prolactin. A statistical analysis was conducted to correlate all the clinical variables, the histology and the Johnsen score with the SRR. Sixty-three consecutive NOA patients with a mean age of 37.3 years were included. The positive SRR was 47.6%. No statistical differences were observed between positive vs. negative SRR regarding mean FSH (17.12 vs. 19.03 mUI/mL; p = 0.72), and LH (9.72 vs. 6.92 mUI/mL; p = 0.39) values. Interestingly, we found a statistically significant difference in terms of time to first infertility diagnosis (+SRR vs. -SRR; 44.5 vs. 57 months; p = 0.02) and regarding to age (+SSR vs. -SRR; 40.1 vs. 35.3; p = 0.04). There was a statistically significant decrease in SRRs with the decline in testicular histopathology from hypospermatogenesis to maturation arrest, and SCO. The mean Johnsen score was 5.9 with a mean percentage of Johnsen score ≥8 tubules equal to 19%. The overall pregnancy rate was 26.6%. In our prospective cohort of patients successful SRR with c-TESE was 47.6%. Lower costs and high reproducibility of this technique still support this procedure as an actual reliable option in NOA patients for sperm retrieval.

Drug metabolism enzymes in a steatotic model of rat treated with a high fat diet and a low dose of streptozotocin.

Herein we have characterized CYPs and antioxidant enzymes in a new steatotic rat model induced with a high fat diet (HFD) combined with a low dose of streptozotocin (STZ). This model was recently put forward in order to better replicate the NAFLD human pathology. HFD/STZ rats developed hyperglycemia, hypercholesterolemia and overt steatosis. The treatment also caused liver damage, but not lipid peroxidation, suggesting this damage was due to hepatic fat deposition and excess formation of toxic free fatty acids, rather than to oxidative stress. In the HFD/STZ group, a significant rise in total CYP content was found, in conjunction with increased activity and protein levels of CYP2E1 and CYP4A, the latter also up-regulated at the transcriptional level. A significant decrease of CYP2C11 was observed at the transcriptional and protein level, whereas CYP3A2 did not change in response to HFD/STZ treatment. In our experimental conditions, the activity of the HO-1 and NQO1 enzymes, whose genes are regulated by Nrf2, were not affected, and nor were the antioxidant enzymes SOD and CAT, confirming the lack of oxidative stress. Our HFD/STZ treatment, which established overt steatosis and changes in CYPs expression, but not oxidative stress, likely reflects an early stage of NAFLD.

Feeding a diet contaminated with ochratoxin A for chickens at the maximum level recommended by the EU for poultry feeds (0.1 mg/kg). 1. Effects on growth and slaughter performance, haematological and serum traits.

The European Commission Recommendation 2006/576/EC, suggests that the maximum level of Ochratoxin A (OTA) in poultry feeds should be set at 0.1 mg OTA/kg. Thirty-six one-day-old male Hubburd broiler chickens were divided into two groups, a Control (basal diet) and an Ochratoxin A (basal diet + 0.1 mg OTA/kg) group. The growth and slaughter performance traits were recorded. The liver, spleen, bursa of Fabricius and thymus weights were measured. The erythrocyte and leukocyte numbers were assayed in blood samples, and the heterophils to lymphocytes (H/L) ratio was determined. Alpha-1-acid glycoprotein (AGP), lysozyme, the total protein and the electrophoretic pattern were evaluated in serum samples. Liver enzymes (alanino aminotransferase, ALT and aspartate aminotransferase, AST) and kidney function parameters (uric acid and creatinine) were quantified. The results revealed that feeding a 0.1 mg OTA/kg contaminated diet to chicks caused a decrease in the absolute thymus weight (p < 0.05) and a lower total protein (p < 0.01), albumin (p < 0.01), alpha (p < 0.05), beta (p = 0.001) and gamma (p = 0.001) globulins serum concentration in the Ochratoxin A group. Moreover, the albumin-to-globulin (A/G) ratio of the OTA-treated animals resulted to be higher (p < 0.05). Feeding broiler chickens, a diet contaminated with the maximum level admitted by the European Commission Recommendation (0.1 mg OTA/kg), did not affect the animal performance, slaughter traits, organ weights, haematological parameters, liver enzyme or renal function parameters concentrations but had an overall immunosuppressant effect, with reduction in the thymus weight and of the total serum protein, albumin, alpha, beta and gamma globulins concentration.

Feeding a diet contaminated with ochratoxin A for broiler chickens at the maximum level recommended by the EU for poultry feeds (0.1 mg/kg). 2. Effects on meat quality, oxidative stress, residues and histological traits.

The European Commission Recommendation 2006/576/EC indicates that the maximum tolerable level of ochratoxin A (OTA) in poultry feeds is 0.1 mg OTA/kg. Thirty-six 1-day-old male broiler chicks were divided into two groups, a control (basal diet) and an OTA (basal diet + 0.1 mg OTA/kg) group. The OTA concentration was quantified in serum, liver, kidney, breast and thigh samples. The thiobarbituric acid reactive substances (TBARS) content were evaluated in the liver, kidney, breast and thigh samples. The glutathione (GSH) content, and catalase (CAT) and superoxide dismutase (SOD) activity were measured in the liver and kidney samples. Histopathological traits were evaluated for the spleen, bursa of Fabricius and liver samples. Moreover, the chemical composition of the meat was analysed in breast and thigh samples. In the OTA diet-fed animals, a serum OTA concentration of 1.15 ± 0.35 ng/ml was found, and OTA was also detected in kidney and liver at 3.58 ± 0.85 ng OTA/g f.w. and 1.92 ± 0.21 ng OTA/g f.w., respectively. The TBARS content was higher in the kidney of the ochratoxin A group (1.53 ± 0.18 nmol/mg protein vs. 0.91 ± 0.25 nmol/mg protein). Feeding OTA at 0.1 mg OTA/kg also resulted in degenerative lesions in the spleen, bursa of Fabricius and liver. The maximum tolerable level of 0.1 mg OTA/kg, established for poultry feeds by the EU, represents a safe limit for the final consumer, because no OTA residues were found in breast and thigh meat. Even though no clinical signs were noticed in the birds fed the OTA-contaminated diet, moderate histological lesions were observed in the liver, spleen and bursa of Fabricius.

Effects of N,N-dimethylglycine sodium salt on apparent digestibility, vitamin E absorption, and serum proteins in broiler chickens fed a high- or low-fat diet.

The objective of this study was to assess the effect of supplementation with sodium salt of N,N-dimethylglycine (DMG-Na) on apparent digestibility (AD) in broiler chickens fed low- and high-fat diets. Twenty-eight 1-d-old broiler chickens were fed one of the dietary treatments: a low-fat diet (LF) or a high-fat diet (HF) supplemented with or without 1,000 mg/kg of DMG-Na. Body weight and feed consumption were recorded at 14 and 35 d of age. Average daily growth, daily feed intake, and feed conversion ratio were calculated. The AD of DM, organic matter (OM), CP, total fat (TF), and α-tocopheryl-acetate were assessed by 2 digestibility trials (at 18-21 and 32-35 d, respectively). Serum protein and plasma α-tocopherol concentrations were assessed at 35 d of age. Final BW, feed intake, carcass, breast, and spleen weight were higher in groups fed LF than HF diets (P = 0.048, P = 0.002, P = 0.039, P < 0.001, P = 0.007, respectively). Liver weight was increased in DMG-Na-unsupplemented groups (P = 0.011) for both fat levels. During the first digestibility trial (18-21 d), the AD of DM (P = 0.023), OM (P = 0.033), CP (P = 0.030), and α-tocopheryl-acetate (P = 0.036) was higher in the DMG-Na-supplemented group than control. Digestibility of total fat was increased by DMG-Na supplementation in the LF groups (P = 0.038). A trend for improvement of digestibility was observed during the second digestibility trial (32-35 d) for DM (P = 0.089), OM (P = 0.051), and CP (P = 0.063) in DMG-Na groups. Total serum proteins (and relative fractions) were positively influenced by DMG-Na supplementation both in LF and HF diets (P = 0.029). Plasma α-tocopherol concentration was higher in groups fed LF than HF diets (P < 0.001).

Studying taxis in real time using optical tweezers: applications for Leishmania amazonensis parasites.

Beads trapped by an optical tweezers can be used as a force transducer for measuring forces of the same order of magnitude as typical forces induced by flagellar motion. We used an optical tweezers to study chemotaxis by observing the force response of a flagellated microorganism when placed in a gradient of attractive chemical substances. This report shows such observations for Leishmania amazonensis, responsible for leishmaniasis, a serious disease. We quantified the movement of this protozoan for different gradients of glucose. We were able to observe both the strength and the directionality of the force. The characterization of the chemotaxis of these parasites can help to understand the mechanics of infection and improve the treatments employed for this disease. This methodology can be used to quantitatively study the taxis of any kind of flagellated microorganisms under concentration gradients of different chemical substances, or even other types of variable gradients such as temperature and pressure.

Radical prostatectomy for locally advanced prostate cancer: results of a feasibility study (EORTC 30001).

The aim of this open, non-randomised, 2-stage feasibility study was to determine whether radical prostatectomy (RP) was safe and could provide cure for good prognosis patients with clinical T3 prostate cancer, in a multicentre setting. Cure was defined as a 3 months post-operative of undetectable serum PSA in combination with the presence of pathologically negative margins in the surgical specimen. Forty patients were enrolled of whom 38 were eligible. Six patients (5 pN+ and 1 pNx) did not meet the inclusion criteria and were excluded leaving 32 evaluable pN0 patients of whom 19 (59.4%, SE=4.26) achieved a complete response (CR) and in whom only two serious toxic events (STEs) were observed. The results of the first phase of the study passed the toxicity criteria (<3 STE's) but failed on the cure rate (>20 CRs). This resulted in discontinuation of the study after the first stage. The main reason for failure was the incidence of positive margins in the resected specimen. Although the study was stopped after the first phase, 28 of the 32 pN0 patients (87.5%) had undetectable serum PSA at 3 months. We continue to believe that RP with extensive resection can be beneficial as monotherapy for T3aN0M0 prostate cancer.

Medical therapy of prostate cancer. A review.

Androgen ablation or blockade of androgen action through the androgen receptor (AR) has been the cornerstone of treatment of advanced prostate cancer. The relative merits of monotherapy or combined androgen blockade (CAB) are still the subject of debate. Each treatment strategy/hormonal agent has favourable and unfavourable effects. Patients with advanced prostate cancer will clearly benefit androgen deprivation-based treatment for palliating their symptoms and for improving their quality of life (QOL). However, whether these therapies prolong survival when administered before there are symptoms caused by disease progression remains controversial. Data from multiple recent studies indicate that an earlier treatment in patient's disease course likely leads to better outcome, but it is not easy to predict the best timing of hormonal therapy for asymptomatic advanced disease. For the purpose of delaying the onset of androgen-independent growth of prostate cancer, different regimen of intermittent androgen blockade (IAB) have been applied to patients. The use of IAB is increasing but, despite theoretical advantages in terms of patient QOL, clinical studies have yet to prove superiority over continuous therapy. The role of androgen deprivation in combination with surgery or radiotherapy has been also evaluated. While neoadjuvant hormonal therapy (NHT) can significantly decrease the incidence of positive margins at the time of radical prostatectomy (RP), 3 months of treatment is not long enough to have any significant effect on biochemical recurrence rates. The results of studies investigating longer courses (8 months) of NHT are awaited. High-risk patients should be considered for early adjuvant hormonal therapy (AHT) after surgery, as they may be most likely to benefit. The rationale for the use of NHT in combination with radiotherapy is that it reduces tumour volume and therefore the amount of radiation therapy that is needed to treat the tumour. It has been found that 3-4 months of hormonal treatment reduces prostate volume by 25-50%. Intermediate-risk patients treated with NHT and concomitant hormonal therapy have been found to have a 94% freedom for biochemical failure after 4 years, suggesting that this group is the ideal patient population to receive short-term hormonal therapy in combination with brachytherapy. Several studies suggested the current consensus that patients with clinically localized or locally advanced high-grade tumours benefit from definitive radiation therapy and long-term AHT. The current treatment for advanced prostate cancer remains essentially palliative. However, an increased understanding of the heterogeneous nature of the disease, the mechanisms that lead to hormone-refractory prostate cancer (HRPC) has identified novel therapeutic targets and led to the development of selective new therapies, that may help to prolong survival and maintain QOL for patients with HRPC.

Combination of intravesical chemotherapy and hyperthermia for the treatment of superficial bladder cancer: preliminary clinical experience.

The prevalence of superficial transitional cell carcinoma of the bladder (STCCB) is still increasing in spite of improved adjuvant chemotherapeutic and/or immunoprophylaxis approaches. Thus, there is certainly an urgent need to improve our ability to control this disease. Local hyperthermia has a therapeutical potential for the treatment of many solid tumors, especially when used in combination with other treatments, such as radiation and chemotherapy. In particular, a synergistic or, at least, supra-additive anti-tumor cell killing effect was documented when local hyperthermia was administered in combination with selected cytostatic drugs. Recently, advances in miniaturized technology have allowed the development of a system specifically designed for delivering an endovesical thermo-chemotherapy regimen in humans. In preliminary clinical experiences, insofar mainly carried out as mono-institutional investigations, the combined treatment using this system was demonstrated to be feasible, minimally invasive and safe when performed on out-patient basis. Moreover, the anti-tumoral efficacy seemed to be significantly enhanced when compared with that obtained using intravesical chemotherapy alone for both adjuvant (prophylaxis) and neo-adjuvant (ablative) approaches to superficial bladder cancer.

Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma.

AIMS: To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder, and to establish the likely safety of this procedure. METHODS: Group 1 (n = 12) received 20 mg intravesical MMC plus local hyperthermia, group 2 (n = 13) 20 mg MMC alone, group 3 (n = 16) 40 mg MMC plus local hyperthermia and group 4 (n = 10) 40 mg MMC alone. Patients in groups 1, 2, and 4 underwent post-tumour resection adjuvant treatment, whereas those in group 3 still had tumour present and were treated to eradicate it. Intravesical instillation lasted 60 min, with the solution (50 ml) being replaced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. MMC concentrations in plasma and in urine were determined by h.p.l.c. RESULTS: The highest MMC plasma concentration (67.9 ng ml(-1)) occurred in a patient in group 3. This value was well below the threshold concentration (400 ng ml-1) for myelosuppression. Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30, 45 and 60 min compared with chemotherapy alone (Group 1 vs 2, P < or = 0.008). Systemic exposure to MMC was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered. Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients. CONCLUSIONS: Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown to cause toxicity.

Thermo-chemotherapy and electromotive drug administration of mitomycin C in superficial bladder cancer eradication. a pilot study on marker lesion.

OBJECTIVE: To assess the feasibility and safety of two novel methods for intravesical chemotherapy administration in patients suffering from superficial bladder carcinomas. To draw preliminary considerations concerning the ablative effect on marker lesion using novel approaches compared to standard intravesical chemotherapy. METHODS: Eighty patients suffering from single, recurrent, low-stage, low-grade superficial bladder tumor entered a prospective nonrandomized study. Thirty-six of them were treated by means of mitomycin C instillation as a standard procedure. In 29 patients mitomycin C solution was administered in combination with local microwave-induced hyperthermia and in 15 patients the mitomycin C solution was administered according to the electromotive drug procedure. The treatment was scheduled as a short term neo-adjuvant regimen prior to transurethral resection. Feasibility and safety of the different procedures were evaluated on an outpatients basis. The local toxicity induced by different approaches was defined and compared using a subjective questionnaire. RESULTS: Both intravesical chemotherapy administered in combination with hyperthermia and according to the electromotive drug technique appeared to be feasible and safe. Local toxicity induced by thermo-chemotherapy was more severe than that registered for electromotive drug technique and standard intravesical chemotherapy. Local toxicity was always short and self healing without early or delayed major complications. A higher complete response rate on marker lesion was observed after thermo-chemotherapy compared to other administration methods. CONCLUSION: The intravesical administration of mitomycin C can be safely performed in the form of both thermo-chemotherapy and electromotive drug approach with an increased ablative success rate on small superficial tumor involving only minimal local side effects.

Nerve and seminal sparing radical cystectomy with orthotopic urinary diversion for select patients with superficial bladder cancer: an innovative surgical approach.

PURPOSE: Radical cystectomy is advocated for high risk patients with superficial bladder cancer. To preserve complete urinary continence, normal sexual function and fertility in young patients, we developed an innovative technique based on nerve and seminal sparing radical cystectomy. MATERIALS AND METHODS: Radical cystectomy was recommended for 8 patients with superficial bladder cancer that was not conservatively manageable. Average patient age was 44 years (range 36 to 48), and all patients were extremely anxious to maintain potency and fertility. The surgical procedure consisted of transurethral resection of the prostate, pelvic iliac lymph node dissection and extraperitoneal radical cystectomy performed while preserving the vas deferens seminal vesicles and neurovascular bundles. Urinary diversion was accomplished with a W-shaped ileal reservoir anastomosed to the prostatic capsule. RESULTS: Patients were generally discharged from the hospital 15 days after surgery, and postoperative morbidity was limited. Daytime and nighttime continence was immediate and complete after catheter removal. Normal erectile function was clinically documented in all patients while fertility potential with semen retrieval via urine was recorded in 7. The quality of life, as reported by the patients, was highly satisfactory at 18-month followup. CONCLUSIONS: The surgical approach we describe should be considered in young men with clinical, superficial bladder tumors refractory to conservative treatment who wish to maintain potency and fertility, and to guarantee as good a quality of life as possible. To ensure oncological success scrupulous patient selection is a primary step of this procedure.

Percent of free serum prostate-specific antigen and histological findings in patients undergoing open prostatectomy for benign prostatic hyperplasia.

PURPOSE: To determine which pathologic features of the surgical specimen in men undergoing open prostatectomy for benign prostatic hyperplasia (BPH) correlate with preoperative and postoperative total, free prostate-specific antigen (PSA) levels and the free-to-total PSA ratio. METHODS: Forty-four patients, undergoing open prostatectomy for BPH without evidence of prostate cancer in systematic biopsies and clinical prostatitis, were included in this prospective study. Each prostatectomy specimen was weighed and each slide was evaluated for inflammation (acute prostatitis, chronic-active prostatitis and chronic-inactive prostatitis), prostatic intraepithelial neoplasia, transitional/squamous metaplasia, cystic ductal dilation, leiomyoma-resembling stromal cell proliferation, leakage of prostatic secretion, infarction and prostatic calculi. RESULTS: The mean preoperative (and postoperative) total PSA and free PSA levels were 6.1 +/- 4.3 (1.14 +/- 0.87) and 1.7 +/- 1.6 (0.24 +/- 0.19) ng/ml, respectively. The mean prostatic and transition zone volume was 83.9 +/- 28.4 and 55.4 +/- 27.6 cm(3), respectively. Both total PSA and free PSA levels were correlated with total gland volume (p = 0.0001; p = 0.002) and the volume of the surgical specimen (p = 0.003; p < 0.05) and, upon stepwise logistic analysis, patients with a total gland volume of <50 cm(3) had an odds ratio of 11 (CI 1.6-71.3) for having a free-to-total ratio of <18%. No minimal change pathology or prostatic inflammation were associated with preoperative total or free PSA levels. The free-to-total PSA ratio was higher in the group of patients with histologically acute and moderate to severe chronic-active prostatitis (mean ratio 27 +/- 12%) than in patients with chronic-inactive prostatitis and minimal chronic-active prostatitis (mean ratio 0.19 +/- 13%; p = 0.05), showing an odds ratio of 5 (CI 1.1-22.1) for having a free-to-total PSA ratio of <18%. CONCLUSIONS: Prostate volume and, in particular, transition zone volume seem to influence both free and total PSA levels in men with BPH. The free-to-total PSA ratio seems to be influenced by the presence of histological prostatitis in the surgical specimen. In particular, patients with a prostate volume of <50 cm(3) and an inactive form of prostatitis seem to have a relatively higher risk of having a free-to-total PSA ratio of <18%.

Monitoring the role of oxalate in manganese peroxidase.

The water proton relaxation rate measurements between 0.01 and 50 MHz on water solutions containing the cyanide adduct of the manganese-depleted manganese peroxidase (MnP-CN-) and increasing amounts of Mn2+ have been determined. The proton relaxivity curves have shown evidence of the formation of the protein/Mn2+ complex and have been analyzed in order to obtain spin Hamiltonian parameters and correlation times. Oxalate is shown not to alter the above profiles. This suggests that no protein-Mn2+-oxalate ternary complex is formed and that oxalate does not remove Mn2+ from the protein. On the basis of high-resolution 1H NMR experiments, we propose that Ce3+ and Gd3+ bind at the manganese site, and, on the basis of the charge, we propose that they may mimic Mn3+. The water proton relaxation rates of water solutions containing manganese-depleted MnP-CN- and increasing amounts of Gd3+ have been measured and analyzed. Oxalate is shown to remove the trivalent metal ions. This suggests that trivalent metal ions bind oxalate and diffuse away from the protein presumably as oxalate complexes. Implications for the enzymatic mechanism are discussed.

Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors.

PURPOSE: The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study. MATERIALS AND METHODS: A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system, based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas. RESULTS: After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved. CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.

Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial.

PURPOSE: This study was aimed at assessing prospectively the effect of postoperative intracavernous injections of alprostadil on the recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 30 potent patients with clinically localized prostate cancer (clinical stage B1 or B2, Gleason sum 7 or greater, prostatic specific antigen less than 20 ng./ml.) underwent nerve-sparing radical retropubic prostatectomy and was subsequently randomized to alprostadil injections 3 times per week for 12 weeks (group 1, 15 patients) or observation without any erectogenic treatment (group 2, 15 patients). Patients were assessed at the 6-month followup by sexual history, physical examination, color Doppler sonography of the cavernous arteries and polisomnographic recording of nocturnal erections. RESULTS: In group 1, 12 patients (80%) completed the entire treatment schedule and were evaluated at the long-term followup. Eight patients in this group (67%) reported the recovery of spontaneous erection sufficient for satisfactory sexual intercourse, compared with 3 patients (20%) in group 2. The difference between the 2 groups was statistically significant (p <0.01). In group 1, all but 1 patient reporting normal postoperative erections also showed normal erections at nocturnal testing, whereas color Doppler sonography demonstrated normal penile hemodynamics in all of them. In these patients, failures were the result of cavernous veno-occlusive dysfunction (2 cases, 17%) and cavernous nerve injury (2 cases, 17%). In group 2, patients with normal erections showed both normal nocturnal testing and penile hemodynamics, whereas failures were the result of cavernous veno-occlusive dysfunction (8 cases, 53%), cavernous arterial insufficiency (2 cases, 13%) or cavernous nerve injury (3 cases, 20%). Complications in patients treated with alprostadil injections accounted for 2 cases (13%) of a penile nodule and 1 further case (6%) of prolonged penile erection. Complications were not seen in group 2 patients. CONCLUSIONS: Early postoperative administration of alprostadil injections significantly increases the recovery rate of spontaneous erections after nerve-sparing radical retropubic prostatectomy. It is our belief that programmed vasoactive injections improve cavernous oxygenation, thereby limiting the development of hypoxia-induced tissue damage. The potential complications related to the use of intracavernous injections must be clearly explained to patients.

Pathologic features and clinical outcome after anatomic radical prostatectomy by transcoccygeal approach.

OBJECTIVES: A nonrandomized prospective study was conducted aimed at verifying the clinical outcome and pathologic features of a group of patients submitted to transcoccygeal radical prostatectomy. METHODS: Radical transcoccygeal prostatectomy was performed at our institution in 26 patients after laparoscopic (24 cases) or open surgical (2 cases) pelvic lymphadenectomy. Eighteen patients were selected because they were considered to be at risk for nodal metastases on the basis of preoperative staging (prostate-specific antigen level of 20 ng/mL or greater and/or Gleason score greater than 5); the remaining 8 manifested incidental prostate carcinoma. RESULTS: Intraoperative complications included rectal injury in 1 patient (3.8%) and massive blood loss in another. Transitory leakage at the site of the urethrovesical anastomosis and urethrorectal fistula occurred postoperatively in 2 patients. The rate of positive surgical margins was 26.9%. The mean follow-up time is 27 months (range 3 to 39 months). Total urinary continence was obtained in 21 patients (80.8%); 5 patients (19.2%) still require urinary pads. Four patients (15.4%) have experienced tumor recurrence evidenced only by increased serum prostate-specific antigen levels. Local tumor recurrence with positive biopsy of the urethrovesical junction was diagnosed in 3 patients (11.5%), and 1 (3.8%) experienced systemic tumor recurrence. CONCLUSIONS: Radical transcoccygeal prostatectomy is a safe procedure for the surgical treatment of prostate cancer, both from a clinical and a pathologic point of view. Operative complication as well as pathologic features and clinical outcome reported in this series of patients must be related to selection criteria used in most cases. The exact role of radical transcoccygeal prostatectomy in the clinical setting has yet to be defined. According to these preliminary results, radical transcoccygeal prostatectomy should be further investigated in the treatment of incidental carcinoma after transurethral resection of the prostate or suprapubic prostatectomy and could become an elective indication in such cases.

Dynamic gadolinium-enhanced magnetic resonance imaging in staging of superficial bladder cancer.

PURPOSE: We evaluated the usefulness of dynamic enhanced magnetic resonance imaging (MRI) in the staging of superficial tumors following a bolus administration of gadopentetate dimeglumine. MATERIALS AND METHODS: In 48 patients with proved bladder tummors the results of preoperative plain spin echo T1 (repetition time/echo time 500/20 msec.) and T2 (repetition time/echo time 2,000/40 to 100 msec.)-weighted MRI, dynamic gadolinium-enhanced MRI (repetition time/echo time 200/15 msec.) and late gadolinium-enhanced MRI (repetition time/echo time 500/20 msec.) were compared and correlated with the histopathological findings. RESULTS: Unenhanced spin echo T1 and T2-weighted MRI sequences were able to stage correctly 14 (56%) and 17 (68%) of 25 superficial bladder cancers, respectively. Muscular infiltration (stages pT2 and pT3a) was correctly depicted in 3 (27%) and 6 (54%) of 11 cases respectively, with over staging being the most frequent error. On the basis of the dynamic gadolinium-enhanced T1-weighted MRI appearance, superficial involvement of the bladder wall was correctly assessed in 21 of 25 cases (84%) and muscular infiltration (stages pT2 to pT3a) in 7 of 11 (63%). Delayed enhanced T1-weighted sequences showed a low accuracy rate in staging superficial tumors (44%). The overall accuracy of T1 and T2-weighted, dynamic T1-weighted and delayed T1-weighted MRI in staging bladder cancer was 58, 71, 81 and 56% respectively. CONCLUSIONS: The use of gadolinium improved the accuracy of dynamic enhanced MRI in staging superficial bladder cancer. On the contrary, delayed enhanced MRI was not useful for staging superficial bladder cancer. The degree of bladder distension was a determinant factor in staging superficial tumors.