Paul Meria

Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma

PURPOSE Approximately 50% of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2% of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determine the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease. MATERIALS AND METHODS The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study. RESULTS Significantly elevated levels of chromogranin A were detected in 15% of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55% and 30% of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma. CONCLUSIONS Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs to be active against neuroendocrine tumors.

ENCRUSTED CYSTITIS AND PYELITIS

PURPOSE Encrusted cystitis and pyelitis are chronic inflammations of the bladder and collecting system associated with mucosal encrustations induced by urea splitting bacteria. We review these infectious diseases. MATERIALS AND METHODS A literature search was performed of the MEDLINE database from 1985 to 1997. Additional articles published before 1985 were also selectively included. RESULTS Most of the articles were case reports or short series. During the last 10 years increasing numbers of cases have been diagnosed, especially in immunodepressed patients, and particularly in renal transplant recipients. Many bacteria have been demonstrated in this infection but Corynebacterium group D2 is currently the most frequent. The development of encrusted cystitis or pyelitis requires the presence of specific bacteria with an alkaline urine, a preexisting urological procedure and a clinical context predisposing to infection. Clinical diagnosis can be difficult but the presence of alkaline urine containing abundant calcified mucopurulent debris is highly suggestive. Demonstration of the bacteria requires prolonged cultures in enriched media. Treatment is based on adapted antibiotic therapy, acidification of urine and excision of plaques of calcified encrustation. The consequences of treatment failure are serious and can result in graft nephrectomy in kidney transplant recipients. CONCLUSIONS Early clinical and bacterial diagnosis of encrusted cystitis and pyelitis could improve the prognosis of these infectious diseases.

Management of pelvic stones larger than 20 mm: laparoscopic transperitoneal pyelolithotomy or percutaneous nephrolithotomy?

Large pelvic stones are frequently managed with percutaneous nephrolithotomy (PCNL) but laparoscopic transperitoneal pyelolithotomy (LTP) can be an alternative. We compared PCNL and LTP for the treatment of pelvic stones >20 mm in diameter. Patients and Methods: Between November 1999 and November 2004, 16 consecutive patients, mean age 42, with a single pelvic stone >20 × 10 mm (group I), underwent LTP as first-line treatment or after shockwave lithotripsy failure. They were compared with a similar population of 16 consecutive patients, mean age 45 (group II), who underwent PCNL for the same indication and were assessed retrospectively. We evaluated operative characteristics, complications, and results for each technique. Results: There was no difference between the two groups regarding the characteristics of patients and stones. Operative time duration was significantly longer in group I (129 vs. 75 min; p = 0.001) and conversion was required in 2 patients (12%). The main postoperative complications were urinary leakage (2 patients, 12%) in group I and bleeding (3 patients, 18%) in group II, but only 1 required blood transfusion. Mean hospital stay was respectively 6.5 and 5.6 days in groups I and II (p = 0.17). Stone-free rates were assessed at 3 months and were not different between group I and group II (88 vs. 82%). Conclusions: The operative time of LTP is longer and the results of both techniques are comparable but postoperative morbidity is different. Specific indications of each technique must be determined although PCNL remains the gold standard for most large pelvic stones.

Laser Induced Autofluorescence Diagnosis of Bladder Tumors: Dependence on the Excitation Wavelength

PURPOSE We assessed the ability of laser induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa. MATERIALS AND METHODS Three different pulsed laser excitation wavelengths were used successively: 308 nm. (xenium chloride excimer laser), 337 nm. (nitrogen laser) and 480 nm. (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1 mm. core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Device performance was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings. RESULTS At 337 and 480 nm. excitation wavelengths the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308 nm. excitation wavelength the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm. CONCLUSIONS This spectroscopic study could be particularly useful to design a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.

Stone Formation and Pregnancy: Pathophysiological Insights Gained From Morphoconstitutional Stone Analysis

PURPOSE We examined whether stone composition in pregnant women reflects peculiar pathophysiological conditions. MATERIALS AND METHODS We analyzed in detail the composition of stones from 244 pregnant women 17 to 44 years old and from 5,712 nonpregnant women in the same age range, as recorded between January 1991 and December 2007. Clinical features were also recorded. All stones were analyzed by morphological examination coupled with infrared spectroscopy. The 2 patient groups were compared by clinical and biochemical characteristics. RESULTS Stone episodes in pregnant women manifested mainly in trimesters 2 and 3 (39% and 46%, respectively). Spontaneous passage was noted in 81% of pregnant vs 47% of nonpregnant women (p <0.0001). Calcium phosphate, mainly in the form of carbapatite, was the main stone component in 65.6% of pregnant vs 31.4% of nonpregnant women (p <0.0001). Octacalcium phosphate pentahydrate, a transition phase in calcium phosphate stone formation, was found in a 5-fold higher proportion in carbapatite stones in pregnant than in nonpregnant women, a finding also suggesting recent stone formation during pregnancy. CONCLUSIONS The composition of stones manifesting during pregnancy clearly differs from that of stones formed in nonpregnant women of childbearing age, suggesting a different pathophysiology specific to the pregnant state. In view of the pH dependency of calcium phosphate stones factors that increase the physiological elevation in maternal urinary calcium excretion and pH are likely to have a role in the preferential formation of calcium phosphate stones during pregnancy.

Nephron Sparing Surgery is a Feasible and Efficient Treatment of T1a Renal Cell Carcinoma in Kidney Transplant: A Prospective Series From a Single Center

PURPOSE Renal cell carcinoma in a renal graft is a rare condition whose incidence will increase in the future. To our knowledge no standardized treatment has been established for this disease. We performed a prospective study of nephron sparing surgery for small renal cell carcinoma in renal grafts. MATERIALS AND METHODS From January 2002 to December 2006, 2,050 renal graft recipients were followed at our transplantation center. Of these patients 7 were diagnosed with histologically confirmed renal cell carcinoma in the renal graft, 5 of whom presented with T1a renal cell carcinoma and prospectively underwent nephron sparing surgery. RESULTS Five patients with 15 to 30 mm (median 20) renal cell carcinoma were included in the study and were treated with nephron sparing surgery. Median operative time was 110 minutes (range 60 to 150). Blood loss was less than 200 ml in each case. All tumors were pT1aN0M0 with negative margins. No postoperative complications were observed (hemorrhage, urinary fistulas, renal failure). Preoperative immunosuppressive treatment was not modified postoperatively. At 3 months after nephron sparing surgery and at a mean of 17.4 months of followup (range 5 to 54) no significant impairment of renal function or recurrence was observed. CONCLUSIONS Nephron sparing surgery is a safe and efficient procedure for the treatment of renal cell carcinoma in renal grafts, resulting in the preservation of renal function and in short-term cancer control.

An experimental model of bulbar urethral stricture in rabbits using endoscopic radiofrequency coagulation.

OBJECTIVES To develop an experimental model of endoscopic urethral stricture mimicking the human clinical situation. METHODS Twenty-four New Zealand male rabbits were included. Eighteen animals (study group) underwent videourethroscopy with a pediatric resectoscope, and a 3 to 5-mm-long circumferential electrocoagulation of the bulbar urethra was performed, without postoperative urinary diversion. Six animals underwent the same procedure without application of electrocautery (control group). Each animal was assessed for urethral stricture on day 15 and day 30 by videourethroscopy and voiding cystogram. Among the study group, 8 animals were killed on day 15 and 10 on day 30 for histologic evaluation. All the control animals were killed on day 30 for histologic examination. RESULTS Nine animals (50%) in the study group developed a significant bulbar stricture (reducing the lumen by more than 50%) at day 15. Histologic examination confirmed the presence of hyalin fibrosis mutilating the urethral wall. No spontaneous improvement of the stricture was observed on day 30. None of the controls developed urethral stricture, and histologic examination showed a normal urethra in each case. CONCLUSIONS Endoscopic electrocoagulation of the urethral wall provides a reproducible model of stricture in the rabbit.

A 3 TROCAR TECHNIQUE FOR TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY

PURPOSE Additional trocars and retractor instruments may enhance the risk of iatrogenic injuries during laparoscopic nephrectomy. We describe a modified technique of laparoscopic nephrectomy requiring only 3 ports of entry and no extra instruments instead of the 5 ports, 2 of which are used for retractors, usually required. MATERIALS AND METHODS With the patient in full flank position a 10 mm. trocar is inserted between the umbilicus and subcostal margin, a 5 mm. trocar is placed subcostal in the midclavicular line and a 12 mm. trocar is inserted over the iliac crest in the anterior axillary line. The first step is incision of the line of Toldt and medial reflection of the colon. During the second step of vascular controls the posterosuperior attachments of the kidney are left untouched, keeping the renal vessels stretched, with no need for an extra instrument. The third step consists of severing the remaining posterior and superior attachments of the kidney followed by specimen retrieval. A total of 14 consecutive patients underwent laparoscopic nephrectomy with this technique. RESULTS All 14 procedures were completed without an additional port. There were no intraoperative or postoperative complications, except 1 abdominal wall hematoma. Mean operating time was 120 minutes (range 70 to 230) and mean hospital stay was 5 days (range 3 to 7). CONCLUSIONS Transperitoneal laparoscopic nephrectomy with laparoscopic access limited to 3 trocars is a reliable and safe technique.

Biopsy-confirmed de novo renal cell carcinoma (RCC) in renal grafts: a single-centre management experience in a 2396 recipient cohort

Study Type – Therapy (case series)

Percentage of free serum prostate-specific antigen : a new tool in the early diagnosis of prostatic cancer

Prostate-specific antigen (PSA) is a protease able to bind to serum antiproteases as alpha 1 antichymotrypsin (ACT). Free PSA (FPSA) corresponds to the fraction of total PSA (TPSA) which is unbound to ACT. Specific detection of the FPSA seems to be a valuable tool in the distinction between prostatic cancer (PCa) and benign prostatic hyperplasia (BPH). Our aim was to evaluate retrospectively the FPSA/TPSA ratio in comparison to TPSA or FPSA determination, using two new immunoradiometric assays (PSA-RIACT and FPSA-RIACT, CIS bio international, Gif Sur Yvette, France) in the early diagnosis of PCa. 256 men, with TPSA levels between 0.7 and 44.7 ng/ml (median age = 69 years), including 164 sera obtained from patients with BPH and 92 sera from patients with untreated PCa were assayed. All diagnoses were histologically confirmed and patients tested before any adjuvant treatment. The evaluation of the median FPSA/TPSA ratio in the two groups showed significantly different values (BPH group: 24.2%, PCa group: 12.1%, P < 0.0001). By R.O.C. (Receiver-Operating-Characteristics) analysis, we show that the FPSA/TPSA ratio is the method of choice for discriminating BPH and PCa, since the area under curve is the greatest for the FPSA/TPSA ratio curve, as compared to the TPSA or FPSA curves (P < 0.0001). The best accuracy (number of true positive + true negative/total = 82.4%) was obtained with a FPSA/TPSA ratio < or = 15% with high odds ratio (20.5; confidence interval (CI): 11.2; 37.7). Of interest, similar results were also confirmed even in the subpopulation with serum TPSA levels between 2.5 and 10 ng/ml (161 patients including 99 BPH and 62 PCa). We thus confirm that combined serum measurement of FPSA and TPSA is of particular interest in the early diagnosis of PCa for patients with non-suspicious digital rectal examination and a TPSA value between 2.5 and 10 ng/ml. In those patients, biopsy should be reserved to the cases with FPSA/TPSA below 15%, which allows significant odds ratio (12.8; CI: 5.2; 31.4). Otherwise, to avoid the risk of missing any PCa, usual follow-up with combined TPSA and FPSA determination would be required with the same criteria of biopsy (i.e. FPSA/TPSA ratio < or = 15% when TPSA value is between 2.5 and 10 ng/ml; or TPSA > 10 ng/ml).