Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. RESULTS: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. CONCLUSION: Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer.

Using proteomic analysis of the nuclear matrix (NM), we found that heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family with pleiotropic functions, was differentially expressed in prostate cancer (PCa) tissues. This study aimed to characterise the expression of hnRNP K and its subcellular localisation in PCa, utilising immunohistochemical and quantitative western blot techniques. Furthermore, the hnRNP K expression was studied in human PCa cell lines in order to determine its modulation by bicalutamide, the anti-androgen widely used in PCa therapy. Immunohistochemical staining of paraffin-embedded tissues showed that hnRNP K was overexpressed in PCa, where it was localised both in the cytoplasm and in the nucleus. Staining of non-tumour tissues showed exclusively nuclear localisation and a less intense or absent signal. Immunoblot analysis demonstrated that the hnRNP K level within the NM was higher in PCa compared with non-tumour tissues and closely correlated with Gleason score (P=0.008). Higher expression within the NM was significantly (P=0.032) associated with poor prognosis. In two-dimensional western blot analysis hnRNP K presented several isoforms; the one with pI 5.1 was the most differently expressed between non-tumour and PCa tissues. Preliminary results indicate that hnRNP K can be modulated in vitro by a non-steroidal anti-androgen. Taken together, our findings suggest that hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in PCa.

Biopsia guiada por ecografía: el diagnóstico clave del cáncer de próstata / Sonographically guided biopsy: the key diagnosis of prostate cancer

La biopsia sextante de la próstata guiada por ecograiía transrectal (ETR) representa la técnica más difundida en el diagnóstico del cáncer de próstata. La ETR aislada no es una herramienta adecuada para el diagnóstico de cánceres de próstata tempranos. Se discute el momento apropiado de practicar biopsia sextante en un paciente. Se discuten también los problemas asociados con la repetición de las biopsias, dándose también pautas para la realización de biopsias de repetición. Se discute con profundidad cuál es la técnica más idónea de practicar la biopsia y se compara la biopsia por sextantes clásica con las nuevas modalidades como la biopsia sistemática en 5 regiones, la biopsia prostática extendida de 11 muestras o la biopsia 'en abanico'. En la práctica clínica parece recomendable realizar siempre la biopsia sextante estándar y añadir progresivamente muestras en las zonas de mayor incidencia de cáncer: los cuernos laterales, la zona media y periférica, y la zona transicional. Todas ellas deben considerarse en las biopsias de repetición si se mantiene la sospecha clínica de cáncer (AU)

Horseshoe-shaped marlex mesh for the treatment of pelvic floor prolapse.

OBJECTIVE: Pelvic prolapse results from weakness or damage to the normal pelvic-support systems. The main support for the pelvic viscera is provided by the pelvic fascia, which is naturally reinforced by urethra-pelvic ligaments, cardinal ligaments and uterosacral ligaments. A polypropylene mesh (Marlex-Bard) was used as a genitourinary and rectal support in order to substitute the damaged pelvic fascia. METHODS: Sixteen consecutive females suffering from severe genitourinary prolapse entered the study. Using the HWS (Baden-Walker) classification 10 patients presented a grade-IV and 6 patients a grade-III cystocele, 7 patients a grade-III and 1 a grade-IV rectocele. Hysterocele of grade IV was present in 2 patients and in 5 patients grade III. No enterocele was present at the pre-operative visit. Twelve patients suffered from stress incontinence; one had obstructive urinary symptoms with postvoiding residual urine of >200 ml. All patients underwent urodynamic tests and pre-operative cystography. The primary aim was prolapse reduction and continence. The operation, under general anesthesia, consisted of insertion and fixation of a horseshoe-shaped Marlex mesh between pubis and sacrum to close the area between the pelvic viscera and inferior pelvic hiatus. Three patients underwent hysterectomy. RESULTS AND CONCLUSIONS: The follow-up ranged between 12 and 29 months. In 15 patients the prolapse was completely resolved and 13 were dry at follow-up. One patient presented a complete recurrence at the 3-month follow-up. Nine cases of pre-operative constipation were recovered after surgery. This technique seems to give promising results in the repair of genitourinary prolapse and stress incontinence.

[Prostate biopsy: assessment of current indications and techniques]. / La biopsia prostatica: valutazione delle indicazioni e delle tecniche attuali.

Following pulmonary carcinoma, prostate cancer in the second leading cause of death due to neoplastic diseases and accounts for approximately 10% of all malignant neoplasms in the european male population. This disease is strictly and age related pathology and as such destined to be increasingly relevant in an ageing general population. The preventive measures and strategies being developed and refined are aimed at diagnosing tumours at an earlier stage and as a consequence increasing life. At this moment in time ultrasound (US) guided transrectal prostate sextant biopsies, described by Hodge as early as 1989, represent the most diffusely employed technique for the diagnosis of prostate cancer. Even if transrectal ultrasound (TRUS) markedly increases the US resolution capacity with respect to those obtainable transperineally or suprapubically, initial enthusiasm associated in performing biopsies of hypoechogenic zones for the diagnosis of early prostate cancers weaned after follow-up studies of this technique became available. Studies from different authors reveal how TRUS is inadequate in precisely pin-pointing prostate cancers above all early ones. According to the data published in the literature between 30 and 57% of hypoechogenic lesions discovered at US are not tumours but rather non-neoplastic prostatic tissue diseases such as acute or chronic infections/inflammations, atrophy, infarcts or prostatic intraepithelial neoplasms (PIN). Furthermore, Chang et al. have shown how sextant biopsies have a greater specificity in diagnosing prostate cancer with respect to single biopsies aimed at hypoechogenic areas, these values being 76 and 50% respectively. Having observed how many repeat prostate biopsies revealed the presence of a prostatic carcinoma following an initial negative prostate biopsy in patients with pre-existing elevated prostate specific antigen (PSA) levels has induced many authors to exceed the number samplings, as suggested by Hodge, performed during biopsies. Different diagnostic results obtained by biopsy sampling in different positions and in different numbers (up to a maximum of 18) have recently been compared in different studies. This concept follows the principle that increasing the number of samplings will invariably be associated by an increased diagnostic potential of prostate carcinomas, above all in those "grey zone" patients with PSA values less than 10 ng/ml, thus identifying the prostatic cancer at an earlier stage reducing morbility and correlated mortality, increasing specificity and reducing the quote of unnecessary biopsies.

Primary endoscopic treatment of ureteric calculi. A review of 378 cases.

AIM OF THE STUDY: In the post-ESWL period, ureteroscopy represented the solution giving a second choice in the treatment of ureteral calculi in case of failure of extracorporeal lithotripsy. The aim of this study is to review a wide series of ureteral stones in which ureteroscopy combined with endoscopic lithotripsy can be chosen as the first approach for the treatment of ureteral calculi. METHODS: Between January 1994 and September 1997, 378 patients underwent ureteroscopy and endoscopic lithotripsy for ureteral stones with a miniscope associated with either a pneumatic or electropneumatic lithotriptor. Three different miniscopes were used: Olympus (8 Fr), Wolf (7 Fr) and Circon Acmi (7.7 Fr). 238 patients were male and 140 were female. The stones were localized in the upper tract of the ureter in 62 cases (16.4%), 96 (25.3%) in the mid ureter and 220 (58. 3%) in the lower ureter. RESULTS: A complete stone fragmentation with spontaneous expulsion of the fragments occurred in 354 patients (93.6%). In 22 patients (5.8%) the stones were accidentally pushed up and successfully underwent ESWL. In 38 patients (10%) the fragments were completely removed by basket. A single J polyethylene catheter was placed in 21 (5.5%) and a JJ stent in 147 patients (38. 8%). The operative time ranged from 10 to 60 min, with an average time span of 32. In 22 cases (5.8%) an iterative ureteroscopy for stenosis or incomplete fragmentation was needed. Five cases (1.3%) of ureteral perforation were successfully treated by JJ stent, and only 1 case of ureteral avulsion (upper ureter) was treated by open surgery. In the attempt of overcoming an ureteral stenosis, we had 1 case (0.2%) of ureteral reimplantation. One patient (0.2%) underwent ureterolithotomy for an extremely narrow stenosis just before the ureteropelvic junction. No relevant complication was recorded in the postoperative period. Patients were dismissed after 1- 4 days (average 1.9). Up until now, no case of postoperative ureteral stricture has been observed, although we were not able to carry out a specific follow-up in all our patients. CONCLUSIONS: Ureteroscopy with miniscopes has a high success rate (93.6%) with low morbidity and can be given as a primary approach in the management of ureteral calculi. In the lumbar ureter (especially in women) this technique can represent a good alternative to ESWL in the treatment of obstructing stones (which need stenting) or when the patient asks for a 'one-shot' treatment.

Results of rebiopsy for suspected prostate cancer in symptomatic men with elevated PSA levels.

AIM OF THE STUDY: To develop indications for repeat biopsy in patients with suspected prostate cancer and first negative biopsy. MATERIALS AND METHODS: 148 consecutive patients, submitted to two or more biopsies for suspected prostate cancer, were extracted from our database on prostatic diseases. Patients were stratified according to the results of the last biopsy (benign or carcinoma) considering the results of the first and of the last biopsy when more than two biopsies had been performed. PSA velocity was calculated when the interval between PSA obtained before the initial and the final biopsy was at least 6 months; PSA velocities were annualized and absolute changes between the two groups were analyzed. RESULTS: Prostatic carcinoma was detected in 60 of the 148 patients (40.5%), including 19 of 41 (46.4%) with prostatic intraepithelial neoplasia (PIN) and 45 of 107 (42.1%) with normal tissue or prostatic epithelial atrophia on initial biopsy. 20% of patients (4 of 20) with low-grade PIN and 71.1% (15 of 21) with high-grade PIN had cancer at repeat biopsy. The mean PSA value of patients with carcinoma on the repeat biopsy was higher than that of patients without carcinoma (13.3 vs. 10.7 ng/ml). However, this difference was not statistically significant (p = 0.37). Mean PSA velocity increased for patients with a final diagnosis of carcinoma versus those without evidence of carcinoma (+0.3 vs. +1.4 ng/ml/year); this difference was statistically significant (p = 0.002). CONCLUSIONS: According to these results, patients with either PIN II-III, or high PSA and PIN I on initial biopsy, and/or with elevated PSA velocity (more than 1 ng/ml/year) should undergo repeat prostate needle biopsy, being at high risk of prostate carcinoma.