A right colon pouch with a novel efferent channel concept: long-term results of the Turin pouch.

PURPOSE: To report stoma stenosis rates and efferent channel (EC) complications at long term follow-up for Turin pouch (TP). METHODS: This is a retrospective analysis of the prospectively maintained database of patients who underwent TP between March 2006 and May 2018. The TP is a U-shaped right colon pouch. The EC was conceived by the tubularization of 5 cm of the colon wall with the use of a stapler and sutured to the skin (EC-cutaneostomy). The ureters are sutured separately to the last 10 cm of ileum before the ileocecal valve. In literature, catheterization problems have been described on average in 20.3% of patients and stoma stenosis in 19.5% of the patients with flap valve systems. RESULTS: Thirty-eight consecutive patients underwent a TP procedure. The median age was 55 years (IQR: 52-60). Median operative time was 201 min (IQR: 170-210), median reconstructive time was 61 min (IQR: 55-65) and the blood loss was 244 ml (IQR: 150-300) and 4 patients (10.5%) needed blood transfusions. The median follow-up was 52 months (IQR: 37-92). Complete 24h continence was achieved in 34 (89%) patients. Seven (18.4%) patients reported difficulties in EC catheterization and 4 (10.5%) patients had stoma stenosis. This study is limited by the relatively small number of patients. CONCLUSION: In relation to similar systems, the TP seems to offer comparatively good functional results but EC and stoma complications were lower than other pouch variants in literature.

Evaluación de la biopsia de fusión elástica vs. biopsia sistemática para la detección del cáncer de próstata: resultados de un estudio multicéntrico en 1.119 pacientes / Elastic fusion biopsy versus systematic biopsy for prostate cancer detection: Results of a multicentric study on 1.119 patients

Objetivos: Evaluar la precisión de las biopsias guiada y sistemática para la detección del cáncer de próstata (CP) y CP clínicamente significativo (CPCS) en la práctica diaria, analizando el requerimiento de biopsias sistemáticas adicionales en el momento de la biopsia guiada. Pacientes y métodos: De nuestra base de datos multicéntrica que incluye 2.115 pacientes sometidos a biopsia de fusión con el sistema Koelis(TM) entre 2010 y 2017, seleccionamos 1.119 pacientes que recibieron biopsias guiadas (una mediana de 3 por cada lesión), con posterior muestreo sistemático (12 a 14 núcleos). Se evaluó la tasa de detección de cáncer (TDC) global y clínicamente significativa de las biopsias de fusión de Koelis(TM), comparando la biopsia guiada con la sistemática. Como objetivo secundario, está la identificación de los predictores de detección de CP. Resultados: La TDC de la biopsia guiada fue del 48% para todos los tipos de cáncer y del 33% para el CPCS. El muestreo de próstata sistemático adicional mejoró la TDC global en un 15% y en un 12% para CPCS. Se detectó CP en el 35, 69 y 92% de los pacientes con lesiones calificadas como PI-RADS 3, 4 y 5, respectivamente. Una puntuación elevada de PI-RADS y un examen rectal digital positivo fueron factores predictores de CP, y la condición «biopsia naïve» se asoció con CPCS. Conclusión: En la práctica diaria, la biopsia guiada con Koelis(TM) logra una buena TDC para todos los CP y CPCS, y mejora significativamente con el muestreo sistemático posterior de la próstata. Los excelentes resultados de la biopsia por fusión se confirman también en pacientes naïve. La puntuación PI-RADS elevada y el examen rectal digital positivo están altamente asociados con la presencia de CP

Objectives: To assess the accuracy of targeted and systematic biopsies for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in the everyday practice, evaluating the need for additional systematic biopsies at the time of targeted biopsy. Patients and methods: From our multicentric database gathering data on 2,115 patients who underwent fusion biopsy with Koelis(TM) system between 2010 and 2017, we selected 1,119 patients who received targeted biopsies (a median of 3 for each target), followed by systematic sampling of the prostate (12 to 14 cores). Overall and clinically significant cancer detection rate (CDR) of Koelis(TM) fusion biopsies were assessed, comparing target and systematic biopsies. Secondary endpoint was the identification of predictors of PCa detection. Results: The CDR of targeted biopsies only was 48% for all cancers and 33% for csPCa. The performance of additional, systematic prostate sampling improved the CDR of 15% for all cancers and of 12% for csPCa. PCa was detected in 35%, 69%, and 92% of patients with lesions scored as PI-RADS 3, 4 and 5, respectively. Elevated PI-RADS score and positive digital rectal examination were predictors of PCa, whereas biopsy-naïve status was associated with csPCa. Conclusion: In the everyday practice target biopsy with Koelis(TM) achieves a good CDR for all PCa and csPCa, which is significantly improved by subsequent systematic sampling of the prostate. The outstanding outcomes of fusion biopsy are confirmed also in biopsy-naïve patients. Elevated PI-RADS score and positive digital rectal examination are strongly associated with presence of PCa

Elastic fusion biopsy versus systematic biopsy for prostate cancer detection: Results of a multicentric study on 1,119 patients. / Evaluación de la biopsia de fusión elástica vs. biopsia sistemática para la detección del cáncer de próstata: resultados de un estudio multicéntrico en 1.119 pacientes.

OBJECTIVES: To assess the accuracy of targeted and systematic biopsies for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in the everyday practice, evaluating the need for additional systematic biopsies at the time of targeted biopsy. PATIENTS AND METHODS: From our multicentric database gathering data on 2,115 patients who underwent fusion biopsy with Koelis™ system between 2010 and 2017, we selected 1,119 patients who received targeted biopsies (a median of 3 for each target), followed by systematic sampling of the prostate (12 to 14 cores). Overall and clinically significant cancer detection rate (CDR) of Koelis™ fusion biopsies were assessed, comparing target and systematic biopsies. Secondary endpoint was the identification of predictors of PCa detection. RESULTS: The CDR of targeted biopsies only was 48% for all cancers and 33% for csPCa. The performance of additional, systematic prostate sampling improved the CDR of 15% for all cancers and of 12% for csPCa. PCa was detected in 35%, 69%, and 92% of patients with lesions scored as PI-RADS 3, 4 and 5, respectively. Elevated PI-RADS score and positive digital rectal examination were predictors of PCa, whereas biopsy-naïve status was associated with csPCa. CONCLUSION: In the everyday practice target biopsy with Koelis™ achieves a good CDR for all PCa and csPCa, which is significantly improved by subsequent systematic sampling of the prostate. The outstanding outcomes of fusion biopsy are confirmed also in biopsy-naïve patients. Elevated PI-RADS score and positive digital rectal examination are strongly associated with presence of PCa.

A multicentric study on accurate grading of prostate cancer with systematic and MRI/US fusion targeted biopsies: comparison with final histopathology after radical prostatectomy.

OBJECTIVE: To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing histopathology between systematic biopsies (SB), targeted biopsies (TB) and the combination of both (SB + TB) with the final histopathologic outcomes of radical prostatectomy specimens. MATERIALS AND METHODS: Retrospective, multicentric study of 443 patients who underwent SB and TB using MRI/US fusion technique (Urostation® and Trinity®) prior to radical prostatectomy between 2010 and 2017. Cochran's Q test and McNemar test were conducted as a post hoc test. Uni-multivariable analyses were performed on several clinic-pathological variables to analyze factors predicting histopathological concordance for targeted biopsies. RESULTS: Concordance in ISUP (International Society of Urological Pathology) grade between SB, TB and SB + TB with final histopathology was 49.4%, 51.2%, and 63.2% for overall prostate cancer and 41.2%, 48.3%, and 56.7% for significant prostate cancer (ISUP grade ≥ 2), respectively. Significant difference in terms of concordance, downgrading and upgrading was found between SB and TB (ISUP grade ≥ 2 only), SB and SB + TB, TB and SB + TB (overall ISUP grade and ISUP grade ≥ 2) (p < 0.001). Total number of cores and previous biopsies were significant independent predictive factors for concordance with TB technique. CONCLUSION: In this retrospective study, combination of SB and TB significantly increased concordance with final histopathology despite a limited additional number of cores needed.

C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

Trends in the use of partial nephrectomy for cT1 renal tumors: Analysis of a 10-yr European multicenter dataset.

AIM: Although extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors. METHODS: 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups. RESULTS: Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03). CONCLUSIONS: We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered.

Stapled orthotopic ileal neobladder after radical cystectomy for bladder cancer: Functional results and complications over a 20-year period.

AIMS: To present the long term-results and complications of a large series of stapled ileal orthotopic neobladders. MATERIALS AND METHODS: From 1992 to 2012 we performed 606 radical cystectomies with stapled orthotopic neobladder substitution in male patients. The median patient age was 65 years (interquartile range [IQR]: 58-71). RESULTS: Median operative time was 205 min (IQR: 180-225). The overall survival rates at 5, 10, 15, and 20 yr were 68% (336 of 494), 55% (207 of 376), 38% (98 of 259), and 23% (14 of 62), respectively, and the disease specific survival rates were 75% (371 of 494), 59% (222 of 376), 50% (130 of 259), and 35% (22 of 62), respectively. After a median follow-up of 81 months (IQR: 30-144), a total of 147 early (less than 90 days) complications (38 diversion related, 109 diversion unrelated) occurred in 144 patients (24%); 163 late complications (141 diversion related, 22 diversion unrelated) affected 141 patients (23%). At 60 months, daytime and nighttime continence was complete in 96% and 72% of cases, respectively. Urodynamic studies showed that maximum capacity, residual volume, maximum flow rate, pressure at maximum capacity, and maximum outlet closure pressure were not statistically different at 12 and 60 months postoperatively. CONCLUSIONS: The use of a stapler when performing orthotopic neobladders significantly reduces the operating time, and offers good functional results with acceptable complication rates. Our results could encourage the use of a stapler when performing an ileal neobladder during laparoscopic and robotic radical cystectomies.

A microRNA code for prostate cancer metastasis.

Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-ß and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.

Benefits and shortcomings of superselective transarterial embolization of renal tumors before zero ischemia laparoscopic partial nephrectomy.

AIMS: To report feasibility, safety and effectiveness of "zero-ischemia" laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. METHODS: We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. RESULTS: Mean patients age was 68 years (range 56-74), mean tumor size was 3.5 cm (range 2.2-6.3 cm). STE was successfully completed in 16 patients 12-15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a "zero-ischemia" approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5-22). Mean operative time was 123 min (range 115-130) and mean intraoperative blood loss was 250 mL (range 20-450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. CONCLUSIONS: STE is a viable option to perform "zero-ischemia" LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases.

BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial-mesenchymal transition.

Prostate cancer is one of the leading causes of cancer-related death in men. Despite significant advances in prostate cancer diagnosis and management, the molecular events involved in the transformation of normal prostate cells into cancer cells have not been fully understood. It is generally accepted that prostate cancer derives from the basal compartment while expressing luminal markers. We investigated whether downregulation of the basal protein B-cell translocation gene 2 (BTG2) is implicated in prostate cancer transformation and progression. Here we show that BTG2 loss can shift normal prostate basal cells towards luminal markers expression, a phenotype also accompanied by the appearance of epithelial-mesenchymal transition (EMT) traits. We also show that the overexpression of microRNA (miR)-21 suppresses BTG2 levels and promotes the acquisition of luminal markers and EMT in prostate cells. Furthermore, by using an innovative lentiviral vector able to compete with endogenous mRNA through the overexpression of the 3'-untranslated region of BTG2, we demonstrate that in prostate tumor cells, the levels of luminal and EMT markers can be reduced by derepression of BTG2 from microRNA-mediated control. Finally, we show that the loss of BTG2 expression confers to non-tumorigenic prostate cells ability to grow in an orthotopic murine model, thus demonstrating the central role of BTG2 downregulaton in prostate cancer biology.

Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial.

BACKGROUND: The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days. RESULTS: At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms. CONCLUSION: The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer.

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.

Seminal sparing cystectomy and ileocapsuloplasty: long-term followup results.

PURPOSE: The efficacy of nerve sparing techniques to save potency in cystoprostatectomy is about 50%. This radical surgery may be proposed to young men with normal sexual function. We report the results of a 13-year experience with our innovative seminal sparing cystectomy and bladder replacement to maintain sexual function in such patients. MATERIALS AND METHODS: Seminal sparing cystectomy is a modification of standard radical cystectomy in which the posterior bladder dissection is anterior to the seminal vesicle plane to preserve the vasa deferens, seminal vesicles, prostatic capsule and neurovascular bundles. Ablation of the whole bladder and the prostatic urothelium with surrounding hypertrophic tissue is guaranteed, and injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa is avoided. From April 1990 to December 2002 we performed 68 procedures in 63 patients (7 of whom were lost to followup) with superficial bladder cancer resistant to conservative therapies (18 patients with stage T1G2 disease, 13 TaG2, 11 T1G3 and 14 TaG3) and in 5 patients with invasive bladder cancer (T2G3) which was monofocal and away from the bladder neck. All patients had normal sexual function. A complete clinical evaluation (with prostate specific antigen [PSA], digital rectal examination and transrectal ultrasound) to exclude concomitant prostate cancer was performed. Average patient age was 49 years and mean followup was 68 months. RESULTS: Normal erectile function was preserved in 58 patients (95%). Complete daytime continence was reached in 58 patients (95%) and nighttime continence was reached in 19 patients (31%). The early postoperative complication rate was 18% and the delayed complication rate was 26.2%. A total of 55 patients (90.2%) are alive and 6 patients (9.8%) died, 5 of cancer progression. High grade prostatic intraepithelial neoplasia was noticed in prostatic specimens in 3 patients and prostatic cancer was noted in 1 patient. These patients had a normal PSA before operation and a serum PSA less than 0.2 ng/ml at a mean followup of 19 months. No positive margins were identified on permanent histological analysis of the specimens, nor were local pelvic recurrences observed. CONCLUSIONS: Our innovative technique is safe, effective and easy to perform. The oncological and functional results obtained with a long followup justify seminal sparing cystectomy as an excellent surgical procedure which can be proposed to some oncological and nononcological cases.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Conservative treatment of iatrogenic urinary fistulas: the value of cyanoacrylic glue.

Once previously attempted conservative maneuvers have failed, iatrogenic persistent urinary fistulas usually require difficult repeated operations. We describe 3 patients in whom cyanoacrylic glue was used to repair endoscopically persistent urinary fistulas occurring after major pelvic surgery. At a mean follow-up of 21 months, all patients were free of urinary leakage and had no evidence of recurrent urinary fistulas. This approach may represent a safe and effective way to repair postoperative urinary fistulas.

A novel germline mutation of the MEN1 gene, L259del, in a patient with sporadic multiple endocrine neoplasia type 1 (MEN1).

A Japanese woman was treated for insulinoma when she was 29 years old. Ten years later, heperparathyroidism and non-functioning adrenal tumor were found and she was diagnosed as having multiple endocrine neoplasia type 1 (MEN1). No other family members have developed MEN-related lesion(s). Genomic DNA of the patient was analyzed by sequencing for the MEN1 gene and a novel, three-base in-frame deletion resulting in deletion of an amino acid Leu259 was identified. Her two children showed a wild-type sequence at this codon.

Radical retropubic prostatectomy using endoscopic gastrointestinal anastomosis staplers.

OBJECTIVE: To investigate whether the use of the endoscopic gastrointestinal anastomosis (GIA) stapler for hemostasis of the dorsal vein complex during radical retropubic prostatectomy saves operation time and blood loss together with therapeutic efficacy. MATERIALS AND METHODS: From April 1990 to December 1998, a total of 296 patients underwent radical retropubic prostatectomy for prostate cancer in clinical stages T1, T2 and T3. In 157 patients we evaluated the efficacy of the endoscopic GIA stapler in order to minimize blood loss from the dorsal vein complex and to reduce mean operative time. RESULTS: The mean total operative time decreased an average of 35 min and the mean blood loss fell from 850 to 400 cm(3) using the stapling technique. Although complications are seen with traditional methods, we noted a net increase in anastomotic strictures with this new technique. CONCLUSIONS: Even if this technical trick is effective in reducing blood loss, a higher incidence of anastomotic strictures has to be taken into account when using staplers close to the anastomotic site.

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

OBJECTIVES: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS: Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS: This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

Adjuvant-induced improvement of glucose intolerance in type 2 diabetic KK-Ay mice through interleukin-1 and tumor necrosis factor-alpha.

We reported that administration of complete Freund's adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls. The hypoglycemic effect of insulin was significantly, but partially, potentiated in the CFA-treated mice compared with the controls, suggesting that CFA stimulated insulin-mediated and non-insulin-mediated glucose disposal. Improvement in the GTT with CFA was partially transferable to nontreated mice by peritoneal exudative cells, but not spleen or lymph node cells. Pretreatment with anti-interleukin (IL)-1 alpha and -1 beta antibodies or anti-tumor necrosis factor (TNF)-alpha antibody significantly abrogated the improvement in the GTT with CFA. The results indicate that CFA-induced improvement in glucose intolerance in KK-Ay mice was mediated at least by IL-1 and TNF-alpha.