[Neuroendocrine small-cell bladder cancer: our experience]. / Carcinoma neuroendocrino a piccole cellule della vescica; nostra esperienza.

INTRODUCTION: Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of 0.35-0.70% of all bladder tumors. The small-cell carcinoma represents the most frequent histologic variant described. Small-cell carcinoma is an epithelial tumor associated with a more aggressive behavior and poorer prognosis than transitional cell bladder carcinoma. The overall survival rate at 5 years does not exceed 8%. At the time of presentation 59% of patients have clinical stage >T2 and 56% show metastatic disease. In 50% of the patients, fatal progression occurs within 6 months. Local recurrence after radical surgery occurred in 50-70% of cases. PATIENTS AND METHODS: We report three cases of pure neuroendocrine small-cell bladder cancer. Hematuria was the most common presenting symptom. Local advanced disease was present in all the cases with stage >T2, metastatic disease in 1 case, lymph node involvement and ureteral bilateral obstruction in 2. Two patients were treated by radical cystectomy, bilateral pelvic limph node resections and urinary derivation. Platinum-based adjuvant chemotherapy was proposed but only two patients received the treatment. One patient with liver metastasis was managed only by extensive TUR and support regimen. RESULTS: In 2 patients residual or relapsed cancer reappered within 2 months after surgery. All of the three patients died of metastatic disease at 5, 7, and 13 months. Median overall survival was 7 months. The most common site of relapse and spread of disease was the peritoneum and intestinal tract, and the reason of death was uncontrolled acute hemorrhage from gastro-intestinal district. CONCLUSIONS: In the absence of a prospective study, and because of the rarity of the disease, the best treatment for small-cell bladder cancer remains uncertain. Neoadjuvant chemotherapy with platinum regimen plus aggressive surgical approach will be the treatment of choice. The association of chemotherapy and radiotherapy should also be considered.

[RIRS through semi-rigid ureteroscope and holmium laser in the treatment of ureteral stones retropulsion]. / La RIRS di necessità con ureteroscopio semirigido e laser ad olmio nel trattamento della calcolosi ureterale retropulsa.

Retrograde displacement of ureteral stones into the renal cavities during ureteroscopic lithotripsy represents a frequent and adverse event that leads to additional procedures (ESWL, PCNL, Retrograde Intra-renal lithotripsy with flexible instruments, DJ stent placement and subsequent EWSL) to obtain full clearence of calculi. All these procedures require a further time of treatment. Between 1/2008 and 3/2009, a total of 48 patients harbouring proximal (21 cases) and distal (27 cases) ureteral stones underwent Holmium Laser lithotripsy. In 3 patients previous percutaneous nephrostomy was performed to drain the excretory way. In 12 cases (25%) stone retropulsion occurred; in 3 patients in the upper calix and in 5 in the renal pelvis. Only in 4 cases the stone migrated in the lower or medium calix. In 8 cases we attempted the immediate treatment of intrarenal displaced stones by advancing the semi-rigid instrument into the renal cavities. In 2 cases the treatment aborted because of the shortness of ureteroscope. The instillation of lubricating lidocaine jelly prevented in 3 cases furher displacement of stone. Washing with saline solution through nephrostomic catheter allowed an effective mobilization of stone and an easy lasertripsy. RIRS was successful in 4 cases. When flexible devices or immediate ESWL are not available, rigid or semi-rigid retrograde lithotripsy with holmium laser immediately performed after ureteral stone displacement represents a safe and effective method to treat displaced stones. Several tricks are required to obtain a good stone-free rate.

[Urethral recurrence of invasive carcinoma following BCG treatment for bladder Ca in situ]. / Recidiva uretrale di Ca infiltrante dopo trattamento con BCG per Ca in situ vescicale.

CIS is a flat, high-grade, non-invasive microscopic urothelial carcinoma. It is considered a precursor of invasive bladder cancer. CIS is classified as primary, secondary or concurrent, when occurred as isolated CIS without cuncurrent papillary tumors, or detected during the follow-up of patients with a previous papillary tumor, or finally in the presence of bladder neoplasm. BCG is widely established as the treatment of choice for CIS with a success rate of approximately 70%. BCG reduces the risk of progression of CIS into invasive carcinoma in 30 to 50% of cases. Direct and prolonged contact between the urothelium and BCG is a prerequisite for successful therapy. Discovery of CIS in the prostatic or membranous urethra represents an ominous sign. CIS may be present only in the epithelial lining of the prostatic urethra or in the ducts, or in the worst case it may be found in the prostatic tissue stroma. Urethral involvement by CIS is at high risk of tumor progression and development of metastases due to reduced thickness of lamina propria and absence of muscolaris mucosa. 83 patients, enrolled from 1/1996 to 12/2005 at our urological department with CIS: primary (focal and multifocal) in 25, secondary in 7 and cuncurrent in 51 (associated with T1bG3 cancer in 37 cases), and urethral CIS in 5 and conservatively treated by TUR and intravescical instillations of BCG, 4 developed afterwords only invasive cancer of the urethra in the absence of bladder involvement. In 2 cases cancer arised from the prostatic fossa after TURP, in 1 from membranous urethra and in the last from prostatic ducts. Among the 4 patients, 3 were treated by cystoprostatourethrectomy and Platinum-based chemotherapy, 1 refused surgical treatment. Two patients died for disseminated disease. 1 patient is alive at 60-month's follow-up. In the last patient cancer relapsed at 36-month's follow-up. We conclude that prostatic/urethral involvement during follow-up after successful intravesical treatment with BCG in CIS represents a high risk of developing invasive and incontrolled cancer. A careful watch is recommended in these patients.

Transcoronary sinus administration of autologous bone marrow in patients with chronic refractory stable angina Phase 1.

PURPOSE: Based on our preclinic studies with autologous unfractionated bone marrow (AUBM) via coronary sinus with transitory occlusion, a clinic study in patients with chronic stable angina was designed. The objectives were to evaluate safety, tolerance and feasibility. METHODS AND MATERIALS: A multicenter prospective study with inclusion and exclusion criteria defined by an Independent Clinical Committee was carried out. Fourteen patients underwent transcoronary sinus administration of freshly aspirated and filtered AUBM (60-120 ml). Safety and tolerance were evaluated. Feasibility was evaluated with Seattle Angina Questionnaire (SAQ), Canadian Cardiovascular Society (CCS) angina classification (baseline-Day 180), myocardial perfusion (baseline-Day 90) with independent core laboratory and coronary angiography (baseline and Day 30). RESULTS: There were no changes in the safety and tolerance parameters. Preliminary clinical efficacy at Day 180 disclosed a significant improvement of 38%, evaluated by the SAQ. The CCS angina classification shows that the mean angina class was 3.0+/-0.55 at baseline and improved to 2.0+/-0.00 at Day 180 (P <.001). Semiquantitative radionuclide perfusion imaging (core lab) showed a significant improvement at Day 90 in 13/14 patients, with a mean improvement of 24% at rest (P <.01) and 33% at stress (P <.05). Coronary angiography showed more collateral vessels in 9/14 patients. CONCLUSIONS: We can conclude that AUBM via coronary sinus with transitory occlusion is tolerable and safe. Significant improvement in the myocardial perfusion at Day 90 and in the quality of life at Day 180 was observed.

[Transurethral resection of the prostate: when?]. / La resezione transuretrale della prostata: quando?

Over a period of 5 years (from 1989 to 1993) 410 patients with benign prostatic hypertrophy (BPH) were treated by transurethral resection of the prostate (TURP). A retrospective study was conducted by the Authors to evaluate indications, surgical approaches and results. The Authors' experience is compared with literature reports.

Rapid induction of cytolytic T cells via CD28 stimulation for cellular immunotherapy.

One approach to adoptive cancer immunotherapy is based on the use of bispecific monoclonal antibodies (mAb) capable to redirect ex vivo generated cytolytic T lymphocytes (CTL) onto tumour cells. The efficiency of the CD28 T-cell activation pathway to induce CD3-dependent cytolytic activity was investigated while avoiding modulation of the TCR/CD3 complex needed for targeting by bispecific mAb. When used e.g. in conjunction with anti-CD2 antibodies or diacylglycerol derivatives, the in vitro stimulation of T cells with anti-CD28 mAb resulted within 36 h in high levels of CD3-dependent cytolysis (tested on a FcR+ target in the presence of anti-CD3 mAb) and sustained lymphokine production, such as TNF alpha, IFN gamma and IL-2, which may affect tumour growth when delivered locally by the transferred T cells. Rapid activation may reduce costly in vitro procedures, preserve homing capacities of retransfused T cells, and thus facilitate implementation of clinical trials based on the use of bispecific antibodies.

Comparison between bladder wall's strain analysis and CMG in clinical urodynamics: preliminary report.

On the basis of data obtained in previous experimental investigations, the application of a new physical entity, "strain" (sigma), was evaluated in bladder dynamics. In this preliminary study 12 cases of urodynamically evaluated subjects are reported; the significance of the traditional P(V) curves is critically compared with the new sigma (V) curve, proposed by the authors.