Abstract: Biomarkers of prostate cancer can assess a presence risk or an evolution risk of the disease. The integration of temporal and clinical data during the interpretation of a PSA dosage improves its performance. Trough a performing algorithm, the Phi index (Prostate Health Index) combines the results of total PSA, free PSA, and pro-PSA. The ration of urinary PCA3 and urinary PSA determines a powerful marker to be used in difficult diagnostic situations. Gene fusions in prostate cancer are promising biomarkers and eventual therapeutic targets. The cost of these new biomarkers is limiting their current use to individual situations.
Abstract: CONTEXT: The development of agents targeting androgen signalling holds promise for men with castration-resistant prostate cancer (CRPC). OBJECTIVE: The emerging role of abiraterone acetate (AA), a novel, orally administered androgen synthesis inhibitor, is critically analysed. EVIDENCE ACQUISITION: Data were acquired from critically important original research published in peer-reviewed literature or presented at conferences conducted by the American Society of Clinical Oncology and the European Society of Medical Oncology. EVIDENCE SYNTHESIS: The major findings are addressed in an evidence-based, objective, and balanced fashion. CONCLUSIONS: AA specifically inhibits CYP17 and substantially reduces serum androgen levels without inducing significant adrenal insufficiency. A phase 3 trial reported a significant extension of survival in metastatic CRPC with AA plus prednisone compared to prednisone alone following docetaxel. The primary toxicity of mineralocorticoid excess is manageable. The addition of low-dose corticosteroids to AA may be necessary for controlling symptoms of mineralocorticoid excess.
Abstract: Sphingosine kinase-1 (SphK1) was shown in preclinical models and non-genitourinary cancers to be instrumental in cancer progression, adaptation to hypoxia and in tumour angiogenesis. No data were available in human prostate cancer. The present study was designed to assess SphK1 expression and activity in radical prostatectomy specimens and to research correlations with clinical features.
Abstract: Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.
Abstract: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm.
Abstract: Radiotherapy is widely used as a radical treatment for prostate cancer, but curative treatments are elusive for poorly differentiated tumors where survival is just 15% at 15 years. Dose escalation improves local response rates but is limited by tolerance in normal tissues. A sphingosine analogue, FTY720 (fingolimod), a drug currently in phase III studies for treatment of multiple sclerosis, has been found to be a potent apoptosis inducer in prostate cancer cells. Using in vitro and in vivo approaches, we analyzed the impact of FTY720 on sphingolipid metabolism in hormone-refractory metastatic prostate cancer cells and evaluated its potential as a radiosensitizer on cell lines and prostate tumor xenografts. In prostate cancer cell lines, FTY720 acted as a sphingosine kinase 1 (SphK1) inhibitor that induced prostate cancer cell apoptosis in a manner independent of sphingosine-1-phosphate receptors. In contrast, γ irradiation did not affect SphK1 activity in prostate cancer cells yet synergized with FTY720 to inhibit SphK1. In mice bearing orthotopic or s.c. prostate cancer tumors, we show that FTY720 dramatically increased radiotherapeutic sensitivity, reducing tumor growth and metastasis without toxic side effects. Our findings suggest that low, well-tolerated doses of FTY720 could offer significant improvement to the clinical treatment of prostate cancer.
Abstract: Prostate cancer (CaP) has become the most frequent cancer in France and represents the 4th cause of mortality by cancer. Main risk factors include age, family history, black ethnic origin and carcinogenesis results from interaction between environmental and endogen factors. This work aimed to review main data and strategic trends about evolution of prevention and early diagnosis of CaP. Research topics considered as priorities results from the main objective including definition of most efficient medico-economic strategies according to epidemiology, diagnostic and therapeutic modalities and ethno-sociologic particularities, including in the schema presently used (PSA/biopsies): 1) new markers (genetic, serum and urinary), measurable environmental risk factors and potential prevention actions; 2) functional imaging (new techniques including contrast echography, dynamic MRI, spectro-MRI) in order to avoid unnecessary biopsies (60-70% biopsies are negative); 3) optimization of biopsies technique in identifying tumor zones in order to decrease false negative biopsies (about 15% of CaP < 0,5 cm3 but of high grade are missed in the first set of biopsies) and in improving the representativity of the tumor sample biopsied (discordance of about 40% between biopsy data and complete pathological analysis of prostatectomy specimen); 4) development of predictive models in order to perform individual prediction taking into account several risk factors (clinical and molecular) and genes/environment interactions in order to offer rational help in diagnostic and primary prevention procedures.
Abstract: OBJECTIVES: To evaluate the feasibility and morbidity and mortality of laparoscopic radical cystectomy for bladder cancer in elderly patients. METHODS: Prospective study conducted between January 2003 and May 2009 in 22 patients, one woman and 21 men, who underwent laparoscopic radical cystectomy for bladder cancer. Mean patient age was 76.2+/-4.3 years. The median preoperative ASA score was 2 (1-3). The indication for surgery was an invasive muscle bladder tumour in 18 cases and noninvasive muscle bladder cancer refractory to conservative treatment (chemotherapy, immunotherapy) in four cases. Ileal conduit was carried out in 15 cases. An ileal neobladder was fashioned in six cases using Camey's technique. One bilateral cutaneous ureterostomy was performed. RESULTS: There was one conversion to open surgery. One intraoperative complication was noted (left obturator nerve injury). Mean blood loss was 377.5+/-341.2ml. No perioperative death was observed. Mean time to resumption of oral fluids was 2.4+/-1.6 days and mean time to resumption of solids was 4.5+/-1.6 days. Mean time to resumption of bowel movements was 3.9+/-1.9 days. Mean critical care unit was 4.2+/-1.4 days. Five patients (22.7 %) had postoperative complications. Postoperative narcotic analgesics were necessary in 60 % of cases. Mean hospital stay was 11.0+/-3.0 days. Mean patient follow-up was 46.4+/-20.8 months. CONCLUSIONS: Laparoscopic radical cystectomy for bladder cancer in elderly patients is associated with low morbidity, and a limited hospital stay.
Abstract: OBJECTIVE: To compare both approaches of laparoscopic pyeloplasty, transperitoneal vs retroperitoneoscopy. METHODS: A total of 65 procedures were performed in 62 patients, 36 females and 26 males. Laparoscopic pyeloplasty with Anderson Hynes technique was performed transperitoneal in 34 cases and retroperitoneal in 31 cases. Parameters studied were the operative duration, the rate of conversion to open approach, transposition of crossing vessel, complications and reintervention, results, and the duration of hospitalization. Then, overall success rate for both approaches was evaluated in the presence or absence of crossing vessels, and if transposition of crossing vessel was performed vs without. RESULTS: The overall success rate for both procedures was 85% (87% for the retroperitoneal vs 82% for the transperitoneal approach). The mean operative duration was 231.69 +/- 59.97 and 194.76 +/- 25.37 minutes for the retroperitoneal and transperitoneal approaches, respectively (P = .029). The rate of conversion was 19.35% (6 of 31) and 2.9% (1 of 34) for the retroperitoneal and transperitoneal approaches, respectively (P = .047). No significant statistical difference was noted between both techniques related to the age of patient, the hospital stay, and intraoperative and postoperative complications. Transposition of crossing vessel had no effect on the results (81.25% with transposition and 80% if not, P = .93). CONCLUSIONS: Retroperitoneoscopic approach is associated with longer operative time and more conversion rate than transperitoneoscopy. However, the overall outcomes of laparoscopic transperitoneal pyeloplasty vs retroperitoneoscopic were comparable.
Abstract: OBJECTIVE: To analyze the impact of screening on prostate cancer (PCa) mortality, and to discuss the main points of controversy regarding this screening. METHODS: A bibliographic analysis was made using Medline services (keywords: prostate cancer, screening). Only the randomized studies regarding the impact of PCa screening on specific mortality were taken into account. RESULTS: Two randomized studies, comparing one group of screened men with another group of nonscreened men, were published this year with conflicting results. The American study PLCO included 76,693 men. After a follow-up of 7 years, it did not report a significant difference in terms of specific mortality between both arms: 2/10,000 deaths in the control group versus 1.7/10,000 in the screened arm (RR=1.13; IC 95%: 0.75-1.7). The European study ERSPC included 182,160 men. After 9 years of follow-up, it showed a significant 20% reduction of specific mortality rate in the screened group (RR=0.80; IC 90%: 0.65-0.98; p=0.04). Methodologically, the European study seems to be superior to the American study, in which the control group was biased by a high percentage of preinclusion screening. CONCLUSIONS: This is the first time that a large randomized study shows a benefit of PCa screening regarding specific mortality. However, this issue remains to be clarified, due to the lack of data regarding the risk of "overdiagnosis" and the economic impact of screening.
Abstract: Sphingolipid metabolites are critical to the regulation of a number of fundamental biological processes including cancer. Whereas ceramide and sphingosine mediate and trigger apoptosis or cell growth arrest, sphingosine 1-phosphate promotes proliferation, cell survival and angiogenesis. The delicate equilibrium between the intracellular levels of each of these sphingolipids is controlled by the enzymes that either produce or degrade these metabolites. Sphingosine kinase-1 is a crucial regulator of this two-pan balance, because its produces the pro-survival and pro-angiogenic sphingosine 1-phosphate and decreases the amount of both ceramide and sphingosine, the pro-apoptotic sphingolipids. Moreover, its gene is oncogenic, its mRNA is overproduced in several solid tumors, its overexpression protects cells from apoptosis, and its activity is down-regulated by anti-cancer treatments. Therefore, the sphingosine kinase-1/sphingosine 1-phosphate signaling pathway appears to be a target of interest for therapeutic manipulation.
Abstract: The reduction in the normal level of tissue oxygen tension or hypoxia is a characteristic of solid tumors that triggers the activation of signaling pathways promoting neovascularization, metastasis, increased tumor growth, and resistance to treatments. The activation of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) has been identified as the master mechanism of adaptation to hypoxia. In a recent study, we identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway, which elicits various cellular processes including cell proliferation, cell survival, or angiogenesis, as a new modulator of HIF-1alpha activity under hypoxic conditions. Here, we consider how the SphK1/S1P signaling pathway could represent a very important target for therapeutic intervention in cancer.
Abstract: BACKGROUND: Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer.
Abstract: PURPOSE: We compared the morbidity and mortality of laparoscopic vs open surgery in radical cystectomy for bladder cancer. MATERIALS AND METHODS: This prospective, nonrandomized study was conducted between January 2003 and July 2007 in 68 patients (7 women and 61 men) who underwent radical cystectomy for bladder cancer. A total of 38 cystectomies were performed laparoscopically and 30 by open surgery. Mean patient age was 68.0 +/- 9.0 years. Median preoperative American Society of Anesthesiologists score was 2 (range 1 to 3) in both groups. RESULTS: Intraoperative blood loss and transfusion rate were significantly lower in the laparoscopic surgery group. Postoperatively the incidence of minor complications and mortality were also significantly lower. Postoperative opioid consumption was significantly less in the laparoscopic surgery group in amount and duration. Resumption of oral fluid and solid intake as well as return to normal bowel function were significantly more rapid in the laparoscopic surgery group, and mean hospital stay was significantly shorter. Mean patient followup was 30.5 +/- 17.2 months. CONCLUSIONS: Laparoscopic radical cystectomy for bladder cancer has a lower morbidity rate than cystectomy by open surgery. It allows more rapid resumption of oral fluid and solid intake as well as return to normal bowel function and shorter hospital stay.
Abstract: The objective of this case report is to describe the laparoscopic insertion of an artificial periprostatic urinary sphincter. We report the case of a paraplegic patient in whom an artificial urinary sphincter was inserted in a periprostatic position by way of laparoscopy to treat stress urinary incontinence. In addition to laparoscopy being minimally invasive, its advantages include the excellent quality of retroprostatic dissection and the perfect visualization it gives at the level of cuff positioning with respect to the anatomic landmarks. It is more appropriate to be able to cleave the interprostatorectal space to ensure passage of the cuff under perfectly safe conditions.
Abstract: OBJECTIVE: We recently bioengineered a ureter substitute from a seeded scaffold implanted by open surgery in the omentum. In view of the development of laparoscopy in the treatment of benign conditions of the ureter, obtaining a ureter substitute by minimally invasive techniques would be a desirable objective. However, conflicting results about the biological impact of carbon dioxide insufflation on the microcirculation of intra-abdominal organs prompted us to investigate first whether the results obtained by open surgery, in terms of vascular supply and maturation, could be reproduced laparoscopically. MATERIALS AND METHODS: Bladder full-thickness tissue was harvested laparoscopically from three pigs for urothelial and smooth muscle cell primary cultures subsequently used to seed a small intestinal submucosa (SIS) matrix. After 2 wk, the in vitro seeded constructs were shaped around silicone drains and transferred laparoscopically into the abdomen for omental maturation. Three weeks later, the constructs were harvested for histological, immunohistochemical, and electron microscopic analysis. RESULTS: The laparoscopic procedures were performed successfully in all animals. After omental maturation, the constructs were vascularized and comprised of a well-differentiated multilayered urothelium with umbrella cells, over connective tissue and smooth muscle cells, with no evidence of fibrosis or inflammation. Electron microscopic analysis showed characteristics of a terminally differentiated urothelium. CONCLUSION: As shown by conventional microscopy, immunochemistry, and electron microscopy, carbon dioxide insufflation does not impact cell growth and differentiation. These findings validate the laparoscopic approach for omental maturation of ureter substitutes.
Abstract: We have previously reported that, in prostate cancer, inhibition of the oncogenic sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway is a key element in chemotherapy-induced apoptosis. Here, we show that selective pharmacologic inhibition of SphK1 triggers apoptosis in LNCaP and PC-3 prostate cancer cells, an effect that is reversed by SphK1 enforced expression. More importantly, we show for the first time that the up-regulation of the SphK1/S1P pathway plays a crucial role in the resistance of prostate cancer cells to chemotherapy. Importantly, pharmacologic SphK1 inhibition with the B-5354c compound sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to S1P sphingolipid ratio. To conclude, our study highlights the notion that drugs specifically designed to inhibit SphK1 could provide a means of enhancing the effects of conventional treatment through the prosurvival antiapoptotic SphK1/S1P pathway.
Abstract: Here, we provide the first evidence that sphingosine kinase 1 (SphK1), an oncogenic lipid kinase balancing the intracellular level of key signaling sphingolipids, modulates the transcription factor hypoxia inducible factor 1alpha (HIF-1alpha), master regulator of hypoxia. SphK1 activity is stimulated under low oxygen conditions and regulated by reactive oxygen species. The SphK1-dependent stabilization of HIF-1alpha levels is mediated by the Akt/glycogen synthase kinase-3beta signaling pathway that prevents its von Hippel-Lindau protein-mediated degradation by the proteasome. The pharmacologic and RNA silencing inhibition of SphK1 activity prevents the accumulation of HIF-1alpha and its transcriptional activity in several human cancer cell lineages (prostate, brain, breast, kidney, and lung), suggesting a canonical pathway. Therefore, we propose that SphK1 can act as a master regulator for hypoxia, giving support to its inhibition as a valid strategy to control tumor hypoxia and its molecular consequences.
Abstract: OBJECTIVE: To determine the survival and prognosis criteria of pT3NxM0 prostate tumours (TNM 2002) after radical retropubic prostatectomy (RRP). MATERIAL AND METHODS: Between 1988 and 2000, 606 consecutive RRP were performed for T1-3 tumours, whose 246 (40.6%) specimens were classified pT3, followed in 53 cases by adjuvant radiotherapy and in 71 cases by salvage radiotherapy. Fifty-five patients received postoperative hormonotherapy at the time of biochemical recurrence. Biochemical recurrence was determined by two PSA values greater than 0.2 ng/ml. RESULTS: Mean age of this group was 65 years at surgery. Mean follow-up was 91.4 months. Mean preoperative PSA was 12.8 ng/ml. Distribution of cases was 170 pT3a (69.1%) and 76 (30,9%). At 10 years, the biochemical progression-free, metastasis-free, specific and overall survival was 54, 86, 92 and 75% respectively. Worse biochemical prognostic factors were lymph node extension, high Gleason score, high preoperative PSA, seminal vesicles involvement, positive surgical margins and adjuvant radiotherapy absence. CONCLUSION: This study shows that pT3 tumours treated with therapeutic associations including RRP presents an excellent specific survival at 10 years. The determination of biochemical recurrence prognostic factors could help to select patients who need complementary treatments after surgery.
Abstract: OBJECTIVE: To evaluate the clinical and urodynamic efficacy and duration of efficacy of intradetrusor botulinum toxin A (BTA) injections in patients with neurogenic overactive bladder refractory to anticholinergic therapy. PATIENTS AND METHODS: Between 2004 and 2005, 33 patients (19 men and 14 women), with neurogenic overactive bladder were treated by intradetrusor injections of 300 U of BTA (Botox) in 30 points. All patients were refractory to, intolerant of or presented contraindications to anticholinergic therapy. All patients voided by intermittent self-catheterization. RESULTS: Six weeks after BTA injections, the success rate was 75.8%, with improvement in 12.1% of cases and failure in 9.1% of cases. The mean number of self-catheterizations per 24 h was significantly decreased (6.37 versus 5.2, P=0.02), the maximum voiding volume was increased (321.68 ml versus 536.25 ml, P=0.002), the mean number of episodes of incontinence per 24 h was decreased (7.39 versus 0.03, P<0.0001), the proportion of patients with incontinence was decreased (66.66% versus 6.04%, P<0.0001), the mean maximum cystomanometric capacity was increased (286.75 ml versus 554.16 ml, P=0.002) and the mean maximum intravesical pressure was decreased (54.8 cm H(2)O versus 5.3 cm H(2)O, P<0.0001). After BTA injections, 87.8 % of patients no longer experienced uninhibited contractions. The median duration of clinical efficacy was 7.03 months. At 12 months, injections were still effective clinically in 21.2 % of patients. CONCLUSION: Intradetrusor BTA injections are an effective and well tolerated treatment for neurogenic overactive bladder. Their clinical efficacy persisted for more than 12 months in more than 20% of cases.
Abstract: Estrogens are known to modulate lower urinary tract (LUT) trophicity and neuronal nitric oxide synthase (nNOS) expression in several organs. The aim of this study was to explore the effects of endogenous and supraestrus levels of 17beta-estradiol (E2) on LUT and urethral nNOS expression and function. LUT function and histology and urethral nNOS expression were studied in adult female mice subjected either to sham surgery, surgical castration, or castration plus chronic E2 supplementation (80 microg.kg(-1).day(-1), i.e., pregnancy level). The micturition pattern was profoundly altered by long-term supraestrus levels of E2 with decreased frequency paralleled by increased residual volumes higher than those of ovariectomized mice. Urethral resistance was increased twofold in E2-treated mice, with no structural changes in urethra, supporting a pure tonic mechanism. Acute nNOS inhibition by 7-nitroindazole decreased frequency and increased residual volumes in ovariectomized mice but had no additive effect on the micturition pattern of long-term supraestrus mice, showing that long-term supraestrus E2 levels and acute inhibition of nNOS activity had similar functional effects. Finally, E2 decreased urethral nNOS expression in ovariectomized mice. Long-term supraestrus levels of E2 increased urethral tone through inhibition of nNOS expression, whereas physiological levels of E2 had no effect.
Abstract: We examined the involvement of sphingosine kinase-1 (SphK1), which governs the ceramide/sphingosine-1-phosphate balance, in susceptibility to imatinib of either sensitive or resistant chronic myeloid leukemia cells. Imatinib-sensitive LAMA84-s displayed marked SphK1 inhibition coupled with increased content of ceramide and decreased pro-survival sphingosine-1-phosphate. Conversely, no changes in the sphingolipid metabolism were observed in LAMA84-r treated with imatinib. Overcoming imatinib resistance in LAMA84-r with farnesyltransferase or MEK/ERK inhibitors as well as with cytosine arabinoside led to SphK1 inhibition. Overexpression of SphK1 in LAMA84-s cells impaired apoptosis and inhibited the effects of imatinib on caspase-3 activation, cytochrome c and Smac release from mitochondria through modulation of Bim, Bcl-xL and Mcl-1 expression. Pharmacological inhibition of SphK1 with F-12509a or its silencing by siRNA induced apoptosis of both imatinib-sensitive and -resistant cells, suggesting that SphK1 inhibition was critical for apoptosis signaling. We also show that imatinib-sensitive and -resistant primary cells from chronic myeloid leukemia patients can be successfully killed in vitro by the F-12509a inhibitor. These results uncover the involvement of SphK1 in regulating imatinib-induced apoptosis and establish that SphK1 is a downstream effector of the Bcr-Abl/Ras/ERK pathway inhibited by imatinib but upstream regulator of Bcl-2 family members.
Abstract: OBJECTIVES: To study the effect of botulinum toxin A (BoNTA) injections into the detrusor muscle on the incidence of symptomatic urinary infections in patients with neurogenic detrusor overactivity. METHODS: Between February 2004 and June 2005, 30 patients (18 men, 12 women), mean age 39.4+/-12.1 yr, with neurogenic detrusor overactivity received an injection of 300 U Botox (Allergan Inc., Irvine, CA, USA) into the detrusor. Fifteen patients had multiple sclerosis, 14 had spinal cord injury, and 1 had myelitis. Twenty-two patients had urinary incontinence. Patients were either resistant to anticholinergic medications, had discontinued treatment because of adverse effects, or had contraindications to anticholinergic drugs. Before and 6 wk after injection, each patient kept a bladder diary and underwent urodynamic investigation, retrograde and voiding cystourethrography, and urine culture. All symptomatic urinary infections (pyelonephritis, orchitis, prostatitis) occurring in the 6 mo before and the 6 mo after injection were recorded. RESULTS: Before injection, the mean number of symptomatic urinary infections over 6 mo was 1.75+/-1.87. After injection, the mean was 0.2+/-0.41 (p=0.003), and only 3 patients presented symptomatic urinary infections. These patients were those who showed less improvement in their urodynamic parameters after injection (volume of the first uninhibited contraction, maximum bladder pressure, and maximum cystometric capacity, respectively; p=0.0037, p=0.0002, p=0.0027, ANOVA). CONCLUSIONS: BoNTA injections into the detrusor muscle significantly decreased the incidence of symptomatic urinary infections. This effect seems to be related to improvement in urodynamic parameters, reflecting improved reservoir capacity at low pressure.
Abstract: Renal haemangioma (RH) is a rare congenital vascular lesion that is frequently responsible for macroscopic haematuria. This lesion is difficult to diagnose preoperatively despite progress in imaging techniques. These diagnostic difficulties account for the high rate of radical treatment (nephrectomy or nephro-ureterectomy) due to a suspicion of renal carcinoma or upper urinary tract tumour. However, conservative diagnostic and therapeutic management can be performed by a combination of CT angiography, flexible ureteroscopy and selective embolization.
Abstract: OBJECTIVES: Tissue engineering is very promising in bladder reconstruction. However, one of the main problems is to limit the development of ischaemic fibrosis during tissue maturation. We describe a model using the omentum as an in vivo bioreactor for a previously seeded scaffold. METHODS: Bladder biopsies were taken from five female pigs, from which both urothelial and smooth muscle cells cultures were made. These cultured cells were used to seed a sphere-shaped small intestinal submucosa (SIS) matrix, which was transferred into the omentum after 3 wk of cell growth. The grafts were harvested 3 wk later and histologic, immunohistochemical, and functional studies were performed. RESULTS: We obtained a highly vascularized tissue-engineered construct that contracted in response to acetylcholine stimulation. The wall thickness was 4mm, on average. Histologic and immunostaining analysis of the construct confirmed the presence of a multilayer urothelium on the luminal aspect and deeper fascicles organised tissue composed of differentiated smooth muscle cells and mature fibroblasts without evidence of inflammation or necrosis. Large- and small-diameter vessels were clearly identified histologically in the tissue obtained. CONCLUSION: The omentum permitted in vivo maturation of seeded scaffolds with the development of a dense vascularisation that is anticipated to prevent fibrosis and loss of contractility. This in vivo maturation into the omentum could be the first step before in situ implantation of the construct.
Abstract: OBJECTIVES: To evaluate the morbidity and mortality of laparoscopic cystectomy combined with transileal ureterostomy to treat neurogenic vesicosphincteric disorders. MATERIAL: Prospective study performed between february 2004 and april 2006 on 26 consecutive patients with a mean age of 55.0 +/- 12.7 years treated by laparoscopic cystectomy for neurogenic vesicosphincteric disorders. The underlying neurological disease was multiple sclerosis (MS) in 20 cases, spinal cord injury in 4 cases and transverse myelitis in 2 cases. The median preoperative ASA score was 3 (range: 2-3). RESULTS: No open conversion was necessary. One intraoperative complication was observed (vascular injury). No perioperative death was observed. The nasogastric tube was maintained postoperatively for an average of 8.69 +/- 5.9 hours. The mean time to resumption of oral fluids was 1.4 +/- 0.7 days and mean time to resumption of solids was 2.6 +/- 1.0 days. The mean time to resumption of bowel movements was 3.8 +/- 3.2 days. The mean intensive care stay was 3.9 +/- 1.1 days. Two postoperative complications were observed in the same patient (ileus and bronchial congestion). Postoperative narcotic analgesics were necessary in 60% of cases. The mean hospital stay was 10.3 +/- 4.1 days. Two late postoperative complications were observed in the same patient (two episodes of pyelonephritis). CONCLUSION: Laparoscopic cystectomy has a low morbidity in neurological patients, allowing early return of feeding and a moderate length of hospital stay.
Abstract: OBJECTIVE: Long ureteric defects may theoretically be repaired with the use of tissue-engineered neoureter. However, attempts to construct such a neoureter in animal models have failed because of major inflammatory response. Avoidance of such inflammation requires a well-differentiated urothelium. We investigated whether omental maturation of a seeded construct in a pig model could achieve terminal differentiation of the urothelium to allow construction of a stricture-free neoureter. MATERIAL AND METHOD: Bladder biopsies were taken to allow urothelial and smooth muscle cell cultures. These cultured cells were used to seed small intestinal submucosa (SIS) matrix. After 2 wk of cell growth, the in vitro SIS-seeded construct was shaped around a silicone drain and wrapped by the omentum to obtain neoureters. These neoureters were left in the omentum without any contact with urine, and then harvested 3 wk later for histologic and immunohistochemical studies. RESULTS: Before implantation, the in vitro constructs were composed of a mono- or bilayer of undifferentiated urothelium overlying a monolayer of smooth muscle cells. After 3 wk of omental maturation, these constructs were vascularized and comprised a terminally differentiated multilayered urothelium with umbrella cells over connective tissue and smooth muscle cells, with no evidence of fibrosis or inflammation. CONCLUSION: We obtained, for the first time, with this model of in vivo maturation in the omentum, a mature neoureter composed of a well-differentiated multilayered urothelium.
Abstract: OBJECTIVE: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study. METHODS: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency. RESULTS: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40). CONCLUSIONS: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced.
Abstract: OBJECTIVES: The purpose of our study was to demonstrate, describe, and assess the results of the technique of laparoscopic cystectomy sparing the uterus, fallopian tubes, ovaries, and vagina. PATIENTS AND METHODS: Between July 2004 and December 2005, 13 women with neurogenic vesical dysfunction (mean age: 53.3+/-13.0 yr) underwent laparoscopic cystectomy sparing the uterus, fallopian tubes, ovaries, and vagina. A noncontinent transileal Bricker diversion was performed extracorporeally in each case. Parameters studied were the pre-, peri- and postoperative data. RESULTS: Mean duration of the operation was 325+/-36 min, and mean blood loss was 323.1+/-246.3 ml. No conversion was required. One perioperative complication was observed: a tear in a branch of the right hypogastric vein, which was sutured under laparoscopy. One patient was transfused during surgery (2 units of blood). No early or late postoperative complications were observed. One patient required transfusion of 2 units of red blood cell concentrate on the first day after surgery. None of the patients required opiate analgesia in the postoperative period. The analgesic regimen used was paracetamol and nefopam in all cases. The pain score on an analogic visual scale was less than 4 in all cases. Resumption of transit was not delayed in any of the patients. Mean hospital stay was 11.6+/-1.9 d. Over an average follow-up of 7.4+/-5.4 mo, none of the patients developed late complications. Before surgery, 77% of the women were sexually active; 80% of them were sexually active 4 mo after the surgery. CONCLUSIONS: Laparoscopic cystectomy sparing the uterus, fallopian tubes, ovaries, and vagina is feasible. This operation has low morbidity and requires only a limited stay in hospital.
Abstract: Application to the study of sexuality in a population of 93 French women. OBJECTIVES: This study was designed to linguistically validate the French version of the BISF-W (Brief Index of Sexual Functioning for Women) which provides a quantitative and qualitative assessment of female sexuality according to 7 dimensions. This version was then used to study the impact of recognized factors of sexual dysfunction on a control population. MATERIAL AND METHOD: The BISF-W a self-administered quality of life questionnaire developed by Rosen, was translated and linguistically validated. This questionnaire comprises 22 questions in 7 dimensions investigating all aspects of female sexuality: D1 (desire), D2 (arousal), D3 (frequency of sexual activity), D4 (receptiveness), 05 (pleasure, orgasm), D6 (relational satisfaction), D7 (problems affecting sexuality), Composite Score (CS) D1+D2+D3+D4+D5+D6+07. The French version was administered to a study population of 93 women: 49 derived from gynaecology or urology departments and 44 derived from the general population. We calculated and compared the scores of the various dimensions of the BISF-W according to factors able to modify sexuality, such as menopause, age or parity. RESULTS: The results of our study show an alteration of the various dimensions of sexuality in elderly patients (D2, D5, D6, CS; p<0.05) or postmenopausal patients (D2, D5, D6, CS, p<0.05) and in multiparous women. CONCLUSION: The French version of the BISF-W gives results in line with the literature and demonstrates changes of sexuality as a function of the above mentioned variables.
Abstract: OBJECTIVES: To determine the results of treatment of chronic urinary retention secondary to bladder outlet obstruction complicating retropubic suburethral insertion of Tension-free Vaginal Tape (TVT) by section of this tape. MATERIAL AND METHODS: Between June 2000 and December 2004, 30 women with a mean age of 63.5 +/- 11.6 years underwent a single lateral urethral section of Tension-free Vaginal Tape to treat bladder outlet obstruction secondary to retropubic suburethral TVT insertion. Success was defined by resolution of the symptoms, a maximum urine flow rate greater than 15 ml/s and a post-voiding residual less than 50 ml and failure was defined by persistence of at least one of these three criteria. RESULTS: The mean interval between TVT placement and tape section was 12.7 +/- 14.7 months. The mean follow-up was 25.8 +/- 7.8 months. The cure rate was 70%. One complication (a bladder wound) was observed. Postoperatively, two patients (70%) developed recurrence of stress urinary incontinence. CONCLUSION: The treatment of chronic bladder outlet obstruction after retropubic TVT placement to treat stress urinary incontinence by single lateral urethral section of this tape is a simple and effective technique with low morbidity, accompanied by a very low urinary incontinence recurrence rate.
Abstract: OBJECTIVE: To report the results of laparoscopic live donor nephrectomy (LLDN) and to describe our technique. MATERIAL AND METHODS: We retrospectively reviewed 47 laparoscopic live donor nephrectomies performed between January 1999 and July 2005. Several parameters were studied: donor clinical characteristics, intraoperative and postoperative complications, operating time and warm ischaemia time. This series comprised 26 women (55.31%) and 21 men (44.68%) with a mean age of 48 +/- 20 years. Donor nephrectomy was mainly performed on the left kidney (85.37%). It was performed by lumbar endoscopy in the first 20 cases and by laparoscopy in 27 cases. Kidney extraction was performed via an incision between two trocar orifices for the first cases and via an iliac incision for the last 18 cases. RESULTS: The mean operating time was 189 min with a mean blood loss of 127 ml. Warm ischemia time was 6 minutes. Open conversion was required in two cases: renal vein injury in one case and an obese donor with difficulties of dissection in the other case. Surgical revision was required in only one case (haemoperitoneum secondary to genital vein injury). A trocar orifice abscess was observed in one case and prolonged ileus was reported in 2 cases. In the recipient, a urinary anastomotic fistula was observed secondary to ischaemic necrosis of the distal segment of the ureter. Late complications were essentially vascular (19.14%). A right renal graft was lost due to an error of compatibility. Mean serum creatinine was 132 +/- 6.5 micromol/l at 3 months for the other recipients. CONCLUSION: Our experience confirms the feasibility and efficacy of laparoscopic live donor nephrectomy. Intraoperative and postoperative complications and the conversion rate were low. Renal function was rapidly restored in the recipient. The morbidity of this technique is low, but there is a high risk of vascular complications at the beginning of the operator's experience.
Abstract: PURPOSE: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. MATERIALS AND METHODS: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6 +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. RESULTS: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. CONCLUSIONS: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus Calmette-Guerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.
Abstract: OBJECTIVES: To assess sexual function in young men with spina bifida and myelomeningocele. METHODS: Between November 2003 and February 2004, a cross-sectional study was performed in 55 men older than 18 years of age who had been regularly followed up for myelomeningocele since childhood, between 1961 and 1985, in the Pediatric Internal Surgery Department. The International Index of Erectile Function (IIEF) questionnaire was mailed to each man. RESULTS: The response rate was 72.7%. Of the 40 men who replied, 16 (40%) had had sexual intercourse at least once during the previous month. These were the older men (age 31.9 +/- 5.7 years versus 27.7 +/- 5.5 years, P = 0.027). The IIEF scores for the whole group were erectile function 11.61 +/- 9.44, orgasmic function 3.53 +/- 3.86, sexual desire 6.94 +/- 2.4, intercourse satisfaction 3.7 +/- 4.81, and overall satisfaction 4.7 +/- 3.34. According to the classification of Cappelleri, of the 16 men who had had sexual intercourse during the previous month, 4 had no erectile dysfunction, 3 had mild, 4 mild to moderate, and 5 severe dysfunction. Erectile function was statistically related to the ability to maintain erections (mean IIEF score 4 and 5 for men with no erectile dysfunction versus a mean IIEF score of 4 and 5 for men with erectile dysfunction: 4.75 +/- 0.5 versus 2.00 +/- 1.32, P = 0.011 for IIEF score of 4 and 4.50 +/- 1.5 versus 3 +/- 2, P = 0.040 for IIEF score of 5). CONCLUSIONS: Young adult men with spina bifida and myelomeningocele begin sexual activity late. Moreover, 75% have erectile dysfunction that is related to difficulty in maintaining erections.
Abstract: OBJECTIVES: To compare pulsed duplex ultrasound and cavernometry in the aetiological diagnosis of veno-occlusive erectile dysfunction. MATERIAL AND METHODS: Between September 1995 and January 2005, 81 patients with a mean age of 48.45 +/- 12.35 years consulting for erectile dysfunction were investigated by cavernometry and pulsed duplex ultrasound before and after sensitization by intracavernous injection of 10 microg/ml of prostaglandin. The results of these two examinations were compared by the kappa concordance test. RESULTS: According to pulsed duplex ultrasound, 54 patients presented veno-occlusive incompetence. According to cavernometry, 56 patients presented veno-occlusive incompetence. The concordance between the results of the two examinations was only moderate (kappa = 0.52, p < 0.0001, 95% CI: 0.5886-0.7967). CONCLUSION: Duplex ultrasound is a first-line examination in a case of suspected organic erectile dysfunction due to a vascular cause. However, due to the limited concordance for the aetiological diagnosis of veno-occlusive erectile dysfunction between duplex ultrasound and cavernometry, cavernometry is still indicated in highly selected cases such as preoperative work-up.
Abstract: Systemic chemotherapy was considered of modest efficacy in prostate cancer until the recent introduction of taxanes. We took advantage of the known differential effect of camptothecin and docetaxel on human PC-3 and LNCaP prostate cancer cells to determine their effect on sphingosine kinase-1 (SphK1) activity and subsequent ceramide/sphingosine 1-phosphate (S1P) balance in relation with cell survival. In vitro, docetaxel and camptothecin induced strong inhibition of SphK1 and elevation of the ceramide/S1P ratio only in cell lines sensitive to these drugs. SphK1 overexpression in both cell lines impaired the efficacy of chemotherapy by decreasing the ceramide/S1P ratio. Alternatively, silencing SphK1 by RNA interference or pharmacologic inhibition induced apoptosis coupled with ceramide elevation and loss of S1P. The differential effect of both chemotherapeutics was confirmed in an orthotopic PC-3/green fluorescent protein model established in nude mice. Docetaxel induced a stronger SphK1 inhibition and ceramide/S1P ratio elevation than camptothecin. This was accompanied by a smaller tumor volume and the reduced occurrence and number of metastases. SphK1-overexpressing PC-3 cells implanted in animals developed remarkably larger tumors and resistance to docetaxel treatment. These results provide the first in vivo demonstration of SphK1 as a sensor of chemotherapy.
Abstract: INTRODUCTION: Various routes are used to extract the operative specimen during laparoscopic nephrectomy. The main points are compliance with rules of cancer surgery, when applicable, and minimum wall destruction. The objective of this study was to prospectively evaluate the low iliac approach. MATERIAL AND METHOD: Prospective follow-up of 23 laparoscopic nephrectomies (17 tumours and 6 living donor kidney harvestings) in which the kidney was extracted via a low iliac incision measuring 5 to 7 cm. RESULTS: The mean operating time was 188 +/- 50 min with a mean blood loss of 112 +/- 126 ml. The mean duration of the incision was 10 minutes. In the case of a tumour the mean weight of the operative specimen was 571 +/- 127 g in and the mean diameter of the mass was 5.7 +/- 1.9 cm. All grafted kidneys functioned normally. No surgical conversion was necessary. The mean follow-up was 9.6 +/- 1.2 months. No late postoperative complications were observed. CONCLUSION: Radical nephrectomy or living donor kidney harvesting can be performed via laparoscopy with extraction of the operative specimen via a low iliac incision. This incision ensures extraction of very large specimens while preserving the aesthetic and functional advantages of laparoscopy with no increased cancer risk. They are simple to perform and easily reproducible via a transperitoneal or retroperitoneal approach. Absence of muscle section maintains the integrity of the abdominal wall. No postoperative incisional hernia has been observed.
Abstract: OBJECTIVES: To evaluate, given the central role of the pudendal nerves in erection, the impact of potential infraclinical lesions on male sexual function. After intramedullary femoral fixation, countertraction on the fracture table has sporadically been involved in pudendal neurapraxia. Patients with tibial fractures served as controls. METHODS: A total of 168 patients treated for femoral or tibial shaft fractures by intramedullary nailing were mailed the International Index of Erectile Function questionnaire, which addresses all aspects of male sexual function and permits grading of the severity of erectile dysfunction (ED). Univariate and multivariate analyses were conducted to test for factors associated with ED. RESULTS: Of the 168 patients, 101 (60.1%) returned the questionnaire. A greater proportion of ED was observed in sexually active patients after femoral fracture than after tibial fracture (40.5% versus 12.5%, P <0.01). The differential prevalence of ED in both groups subjected to comparable high-energy trauma suggested that post-traumatic stress disorder was of marginal importance in ED occurring after femoral nailing. Greater intraoperative doses of curare were associated with better sexual functioning in sexually active patients after femoral fracture (10.6 versus 7.5 mg in patients without and with ED, respectively, P = 0.02), suggesting that postoperative ED could be partially prevented by optimal muscle relaxation during fracture reduction. CONCLUSIONS: Erectile dysfunction was shown to be highly prevalent after intramedullary nailing of femoral shaft fractures. Greater intraoperative curare doses, resulting in optimal relaxation and reduced pressure on the pudendal nerves by the perineal post, were associated with better sexual functioning.
Abstract: INTRODUCTION: The aim of this retrospective study was to determine the outcome of third cadaveric renal transplantations performed between 1989 and 2004 among a cohort of 35 patients whose immunosuppression included induction therapy and calcineurin inhibitors. Most patients were highly sensitized with 1 (0-4) HLA (classes I + II) incompatibility between donor and recipient. RESULTS: The median follow-up time was 57 months (range, 1-190). Fourteen patients experienced delayed graft function that required posttransplantation hemodialysis. The current patient and graft survival rates were 91.4% and 82.8%, respectively. At last follow-up, 6 grafts had been lost: 1 due to primary nonfunction; 1 due to an urinary leak (day 45); 2 deaths with functioning grafts; and 2 chronic allograft nephropathies (CAN) at 85 and 60 months posttransplantation, respectively. Among the 10 patients who experienced acute rejection episodes, half were steroid-sensitive, whereas the others required OKT3 therapy. Overall, when excluding the 2 patients who presented with early loss of their grafts, 13 of 33 patients (39.4%) developed CAN, which led to the graft loss in only 2 cases. The mean creatinine clearance was 57 +/- 23 mL/min at year 5. Of the 35 recipients, 12 (34.3%) developed graft/perigraft complications, among whom 10 (83.3%) required treatment. The most frequent complication was lymphocele (M = 4; 11.4%) or infections that led to rehospitalization (n = 17). CONCLUSION: Results from third transplantations were encouraging. Thus, despite the organ shortage, a third graft was worth it!
Abstract: The hypothesis that tumor growth is angiogenesis-dependent has been documented by a considerable body of direct and indirect experimental data. Since the discovery of the vascular endothelial growth factor (VEGF), most attention has been focused on the VEGF system. Although fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) can exert a strong angiogenic activity when they are supplied as a single pharmacological agent, their role in pathological angiogenesis in preclinical models remains controversial. To decipher the contribution of FGF receptors in various models of angiogenesis, we took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for FGFR-1 and FGFR-2 (AIdF-1 and AIdF-2). They mimicked FGF-1 and FGF-2 for receptor binding, signal transduction, proliferation of endothelial cells and differentiation of the bladder carcinoma cell NBT-II which expresses FGFR-2b but not FGFR-1. The constitutive expression of FGFR-1 allowed binding of FGF-2 and AIdF-2 and inhibition of the proliferation of NBT-II cells. AIdF-1 and AIdF-2 induced angiogenesis in the corneal pocket assay. Although FGFR-1 dimerization achieved by AIdF-2 injection led to highly differentiated and smaller NBT-II tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF.
Abstract: OBJECTIVES: To report the long-term impact of two cycles of adjuvant chemotherapy on relapse rates and treatment-related morbidity in high-risk stage I nonseminomatous testicular germ cell tumors (NSGCTT I). MATERIAL AND METHODS: From April 1987 to September 1997, 40 stage I NSGCTT patients with evidence of vascular invasion and/or embryonal carcinoma (EC) in the orchidectomy specimen were treated with two courses of bleomycin, cisplatin, and etoposide (BEP). RESULTS: All patients but one (incidental death) were alive after an extended follow-up (median 113.2 months, range 63-189). No patients relapsed but two patients presented a second cancer in the remaining testis. Short-term toxicity was minimal and no long-term toxicity was observed. CONCLUSION: The present series, with extensive follow-up, demonstrated that the efficacy and toxicity of two cycles of BEP compared well with the results of surveillance strategies or RPLND in high-risk stage I NSGCTT.
Abstract: BACKGROUND: This is the first report of graft function and prostate cancer control in renal transplant recipients subjected to modern conformal radiotherapy. METHODS: Eight kidney transplant recipients were treated with three-dimensional conformal radiotherapy. All patients but one were subjected to transitory hormonal deprivation. A three-dimensional radiotherapy-planning system (Pinnacle, Philips Medical System, Bothell, WA) was used to delineate anatomic contours on pretreatment computed tomography and for dose computation. The clinical target volume encompassed the prostate and was expanded with a 10-mm wide margin in all directions to obtain the planning target volume. The irradiation technique consisted of a nine-field arrangement delivering 70 Gy in 2-Gy fractions, with 18-MV photon beams. Biochemical recurrence was defined as two consecutive increases in prostate-specific antigen (>1.5 ng/mL). Graft function was monitored by creatinine clearance. Excretory profiles were assessed by furosemide-stimulated diethylenetriaminepentaacetic acid renography. All patients were subjected to hip magnetic resonance imaging to assess for avascular hip necrosis. RESULTS: After a mean follow-up of 28 months, two patients showed isolated biochemical recurrence and six patients remained free of recurrence. In seven patients with functional allografts, the creatinine clearance was unimpaired by treatment. However, significant obstruction of the terminal ureter was revealed in two patients by furosemide-stimulated diethylenetriaminepentaacetic acid renograms. The doses delivered to the uretero-neocystostomy were calculated to range from less than 20 Gy to more than 45 Gy depending on bladder repletion. CONCLUSIONS: Adequate cancer control was achieved at the expense of infraclinical ureteral obstruction. The doses delivered to the uretero-neocystostomy may be reduced by having a full bladder at the time of irradiation. No avascular hip necrosis was observed.
Abstract: From July 2003 to February 2004, 13 laparoscopic radical cysto-prostatectomies have been achieved in our department. The technique is describe, the ablation of the bladder and prostate is done through a pure laparoscopic approach when the reconstruction is done trough a small incision under the umbilicus. The uretro-neobladder anastomoses are performed under laparoscopy after re-integration of the bladder. All procedures have been successfully achieved; the mean operative time is 400 minutes, 320 for the cutaneous diversions and 450 for the Camey 2 procedures. Blood loss were 390 ml, blood transfusion was d for only one patient. No major complication was observed, the mean hospital stay was 14.2 days (+3.5). In our experience laparoscopic radical cystectomy is a safe option, associated with shorter hospital stays and gentler postoperative recovery.
Abstract: INTRODUCTION: Many factors degrade the initially favourable results of conservative treatment of T1G3 bladder tumours, leading to a permanent risk of progression and death. On the other hand, immediate radical cystectomy, while ensuring optimal local control of the disease, would be excessive in some patients in part because of its purported impact on quality of life. METHODS: To contribute to the ongoing debate on T1G3 optimal treatment the literature was reviewed to organize evidences in favour of radical cystectomy by focusing on two main issues: the impact of time on the initial results of conservative treatment and quality of life after cystectomy. RESULTS: A critical appraisal of conservative treatment efficacy was structured by comparing survival curves after either conservative treatment or radical cystectomy. It highlighted that after conservative treatment the patients remained under the burden of lifelong risk of progression and death. The positive impact of maintenance BCG and the frequent resort to cystectomy after conservative treatment further illustrated the limits of bladder conservative treatments. On the other hand, evidences were shown that quality of life was not critically affected by radical cystectomy and that surgical techniques could be further adapted to its preservation. The influence of age at cystectomy on functional results was highlighted. However, identifying a prognostic factor for the success of conservative treatment would put an end to the controversy by allowing a tailored attitude to every patient's unique situation. The importance of uropathologist's expert evaluation, including the depth of invasion, was emphasized. CONCLUSION: While ensuring optimal control of the disease, the indiscriminate use of radical surgery would be excessive in a significant minority of patients who do well under conservative treatment. It is suggested to consider as typical cases for immediate surgery, young patients with "deep" T1 tumours (>T1a or >1.5mm in depth) with at least one additional factors of bad prognosis: multifocality, association of carcinoma-in-situ, prostatic involvement, site difficult to resect.
Abstract: PURPOSE: Determine the feasibility of dynamic gadolinium enhanced MRI and spectroscopic imaging in routine clinical practice using standard equipment and its usefulness for patients with negative biopsies and high degree of suspicion of prostate cancer. PATIENTS AND METHODS: Fifty five patients underwent endorectal MRI using T2W spin echo (SE) imaging, dynamic gadolinium enhanced imaging and proton spectroscopic imaging before repeat US-guided transrectal biopsies. The statistical analysis consisted in the correlation of the results obtained with each of the two MRI techniques and the results of the biopsies in the corresponding prostate lobe. RESULTS: 32 patients were included in the analysis. Biopsies revealed cancer for 15 patients. The statistical analysis showed a lack of significant correlation between T2W-SE imaging and biopsy results. A correlation with statistical significance was found between dynamic gadolinium enhanced imaging and biopsies (p=0,0018) and between spectroscopic imaging results and biopsies in the corresponding lobe (p=0,0001). CONCLUSION: Endorectal MRI with a standard clinical equipment using dynamic gadolinium enhanced imaging and spectroscopic imaging may be used in clinical routine to improve detection and localization in prostate cancer compared to T2 weighted spin echo imaging.
Abstract: PURPOSE: We aimed to promote the efficacy of paclitaxel in intracavitary treatment of superficial transitional cell carcinoma of the bladder by designing bio-adhesive microspheres capable of achieving controlled release of the drug at the urothelium/urine interface. MATERIALS AND METHODS: Poly(methylidene malonate 2.1.2) microspheres encapsulating paclitaxel were prepared by a single emulsion method. Bioactivity of the released paclitaxel was confirmed by assessing cytotoxicity on MBT-2, a bladder cancer cell line. Biodistribution of particles after bladder instillation was assessed by confocal microscopy and scanning electron microscopy. In vivo studies were performed in Balb/c mice after bladder cancer was induced by BBN (N-n-Butyl-N-butan-4-ol-nitrosamine) in drinking water. The efficacy of intravesical injections of conventional and microsphere paclitaxel was assessed by histology and survival rates. RESULTS: Spherical 5 microm microspheres with 5% weight per weight paclitaxel loading ensured sustained release of bioactive paclitaxel. After bladder instillation the microspheres adhered to the mucosa and remained in the bladder lumen for at least 48 hours. In the BBN induced bladder cancer model compared with controls the 9-week survival rate was significantly improved by 2 injections of paclitaxel bio-adhesive microparticles. Microscopic evaluation confirmed the lower incidence of carcinoma in situ and high grade transitional cell carcinoma after injections of paclitaxel bio-adhesive microparticles compared with controls and with injections of similar doses of the conventional paclitaxel formulation. CONCLUSIONS: Intravesical administration of poly(methylidene malonate 2.1.2) paclitaxel microspheres is a promising approach for intracavitary chemotherapy of superficial bladder cancer.
Abstract: Ileovesical fistula is a rare inaugural complication of Crohn disease. Current approaches associate antibiotics, total parenteral nutrition and various combinations of immunomodulatory agents. However, only a minority of fistulas subside under conventional treatment, as most of them ultimately require complex surgery to excise and close the structures involved. We report the case of a 31-year-old patient successfully treated by targeting the local production of tumour necrosis factor alpha with infliximab.
Abstract: OBJECTIVES: Evaluation of the results of endoscopic Teflon injections for the treatment of symptomatic vesicoureteric reflux in renal transplant recipients and identification of prognostic factors. POPULATION AND METHODS: Between June 1997 and January 2002, out of a series of 408 renal transplant recipients, 15 patients (8 males, 7 females) with a mean age of 41.9 years were treated for symptomatic vesicoureteric reflux on the transplanted kidney by endoscopic Teflon injection. This treatment was indicated due to the presence of febrile or afebrile infections, possibly associated with deterioration of renal function. Reflux was demonstrated by retrograde cystography. The results of endoscopic treatment were evaluated by cystography at 3 months, and by clinical and laboratory examinations thereafter. RESULTS: The mean interval between renal transplantation and endoscopic treatment was 64.2 +/- 64.7 months. With a mean follow-up of 25 +/- 16.7 months, we observed a 53.3% success rate (8 patients), 13.3% of patients (2 patients) were improved and 33.3% of procedures were considered to be failures (5 patients). A lower number of preoperative infections, reflux < or = grade III and the absence of impaired renal function are predictive factors for the success of endoscopic treatment. The only complication was one case of renal colic due to meatal stenosis at 3 months, which responded favourably to endoscopic treatment alone. CONCLUSION: Endoscopic treatment of symptomatic vesicoureteric reflux on a transplanted kidney by Teflon injection is effective in two-thirds of cases. Due to the low morbidity of this minimally invasive procedure, this treatment should be proposed as first-line management for all cases of symptomatic vesicoureteric reflux on a transplanted kidney.
Abstract: In Wegener's granulomatosis, necrotizing lesions are typically located in the upper and lower respiratory tract and kidneys, and ureteral involvement is uncommon. We report 2 cases in which intrinsic ureteral stenosis was the sole manifestation of this small-vessel vasculitis. Excisional surgery evidenced characteristic granulomatous inflammation that allowed adjuvant elective medical treatment. Urologists, nephrologists, and internists should be aware of this atypical presentation of Wegener's granulomatosis. Thorough clinical and biologic assessments are warranted in the initial workup of isolated intrinsic ureteral stenosis.
Abstract: OBJECTIVES: To evaluate the morbidity and mortality of retroperitoneal laparoscopic nephrectomy for polycystic kidney. MATERIAL AND METHODS: Between June 2000 and March 2002, seven retroperitoneal laparoscopic nephrectomies for polycystic kidney were performed in six patients (three men, three women) with a mean age of 52.8 years. All patients presented end-stage renal failure treated by haemodialysis in five cases and by renal transplantation in one case. The ASA score was 2 in four cases and 3 in two cases. The indication for surgery was preparation for renal transplantation, episodes of macroscopic haematuria and pain in three cases, hypertension poorly controlled by medical treatment in two cases, preparation for renal transplantation in one case and pain associated with restrictive respiratory syndrome due to compression in one case. RESULTS: The mean operating time was 4 hours 35 minutes, and the mean blood loss was 400 ml. There were no intraoperative or perioperative deaths. An early postoperative complication occurred in two cases. The mean hospital stay was 11 days, with a mean stay of 2.4 days in the postoperative intensive care unit. No late complications were observed with a mean follow-up of 14 months. Preoperative pain, episodes of haematuria, hypertension and signs of compression resolved in each case. CONCLUSION: Laparoscopic nephrectomy for polycystic kidney is a technique that can be performed via a retroperitoneal approach without manual assistance and with low morbidity.
Abstract: BACKGROUND: Erectile dysfunction (ED) is common in men with renal failure, but is not always alleviated following kidney transplant. The objective of the present study was to assess the feasibility in renal transplant patients of sildenafil citrate treatment, an agent with proven efficacy in the management of ED. METHODS: This was a phase IV, open, multicentre, 3 month, dose-escalation study. All patients meeting the inclusion criteria were prescribed a dose of 50 mg sildenafil at the first visit. Thereafter the dose could be increased to 100 mg or reduced to 25 mg based on efficacy or tolerability. The primary efficacy parameter assessed the ability of patients to achieve erections sufficient for intercourse and to maintain erections after penetration. Secondary endpoints assessed patient satisfaction with sildenafil and the effect of sildenafil on their quality of life. Patients were carefully monitored throughout the study for adverse events, interactions with immunosuppressive therapy and effect on graft function. RESULTS: The study included 50 patients in the intent-to-treat population. Sildenafil significantly improved patient's erection ability and the frequency of their erection maintenance. Analysis of the secondary efficacy parameters revealed that 66% of patients believed treatment had improved their erections. Patients reported improvements in their sexual life and partner relationships and a high level of satisfaction with treatment. There were no interactions between sildenafil and the immunosuppressive drugs and there was no significant adverse effect of sildenafil on graft function. CONCLUSIONS: Sildenafil is an effective and well-tolerated agent for the treatment of ED in renal transplant recipients.
Abstract: BACKGROUND: There is no consensus regarding prostate cancer in renal-transplant recipients (RTR). A questionnaire evaluating prostate cancer screening after transplantation and assessing the number, diagnostic modalities, treatment, and outcome of prostate cancer cases was mailed to 22 French renal-transplant centers. RESULTS: Among 1,680 RTR in 1998, 11 (0.65%) cases of prostate cancer were diagnosed, and among the 2,338 recipients followed up, 28 (1%) cases of prostate cancer have been diagnosed and treated. Median ages at diagnosis and at transplantation were 63 and 58, respectively. Clinical stages were T1 50% and T2 25%. Eighteen patients had a Gleason score under 7. At 18 months of mean follow-up, 2 men had died from prostate cancer, and in the curative treatment group, 16 of 17 men were alive with no evidence of disease. CONCLUSIONS: The incidence of prostate cancer in RTR appeared to be higher than expected. Prostate specific antigen (PSA) testing should be performed routinely each year in renal transplantation centers.
Abstract: BACKGROUND: Sildenafil (Viagra) improves erection by sustaining Guanosine 3', 5'-cyclic monophosphate (cGMP)-mediated smooth muscle relaxation in the corpus cavernosum. It also induces systemic vasodilation, resulting in a minor decrease in blood pressure. We evaluated the effect of one dose of sildenafil on graft function and hemodynamics in impotent male transplant recipients. METHODS: Two sets of combined lithium, inulin, and p-amino hippurate clearance studies were conducted, with and without sildenafil (100 mg orally) in 11 male kidney transplant recipients (KTRs). RESULTS: Sildenafil increased glomerular filtration rate by 14+/-4 from the baseline value of 55+/-7 ml x min(-1) x 1.73 m2(-1) (P<0.01), whereas calculated renal vascular resistances decreased by 40+/-18 from the baseline value of 247+/-29 mmHg/L x min(-1) x 1.73 m2-1 (P<0.05). CONCLUSIONS: The oral administration of sildenafil in KTRs did not impair the function of the graft. In terms of renal physiology, the observed modifications did not warrant any specific precautions when offering sildenafil to KTRs suffering from erectile dysfunction.
Abstract: PURPOSE: The objective of vascular surgery for erectile dysfunction is to provide long-term improvement of erectile function. We evaluated that claim after deep dorsal vein arterialization by a cross-sectional study of multifaceted male sexual function with the validated International Index of Erectile Function (IIEF). MATERIALS AND METHODS: We performed a mail survey of male sexual function after deep dorsal vein arterialization in 68 consecutive literate men who underwent surgery between 1984 and 1998 for severe erectile dysfunction. The IIEF questionnaire and a questionnaire on patient characteristics were answered in a self-administered and nominative manner. Scores of the responders pertaining to the 5 domains of male sexuality were compared with those of the control groups used for the psychometric validation of the IIEF. RESULTS: Of the patients 38 (55.9%) with a mean age plus or minus standard deviation of 46.5 +/- 11.9 years responded. Mean followup was 61.2 +/- 34.7 months. Compared to controls with erectile dysfunction controls men who underwent deep dorsal vein penile arterialization had significantly higher scores for erectile function, sexual desire, orgasmic function, intercourse satisfaction and overall satisfaction. Conversely compared with normal controls these patients reported significantly lower erectile function, orgasmic function, intercourse satisfaction and overall satisfaction scores, whereas sexual desire scores were similar in the 2 groups. No correlations were noted of the 5 IIEF domains with the duration of followup after arterialization. When erectile function scores were graded, 25.0% and 28.1% of patients reported no and or mild dysfunction, respectively, while 15.6% still complained of severe erectile dysfunction. CONCLUSIONS: Long-term improvement in the various aspects of male sexual function was observed after deep dorsal vein penile arterialization in a significant proportion of patients.
Abstract: OBJECTIVES: To report the perioperative events after radical cystectomy and urinary diversion in bladder cancer in terms of major and minor complications and to seek statistical relationships with patient's characteristics and surgical procedures. METHODS: One hundred and sixty-one radical cystectomies performed in the modern era in two academic hospitals were reviewed. Preoperative patients characteristics (age, sex, hemoglobin, total protein, weight and height) and perioperative data (operative time, type of urinary diversion, associated procedures, blood transfusion, seniority of the surgeon) were recorded. Perioperative morbidity was defined by any adverse event during hospital stay or within 30 days after surgery, those requesting an additional stay of more that 3 days in the intensive care unit or a reoperation being classified as major complications. Significant relationships were sought for classes by Student's t test for comparison of quantitative variables and Yate's corrected chi(2) test for categorical variables. Spearman's rank correlation test was used for comparison of quantitative variables. RESULTS: Major complications were observed in 41 patients (25.5%) and resulted in 14 reoperations (8.7% reoperation rate). Most of them were diversion-related and were statistically related to the ASA score > or =3 (p<0.01, 5.7 odds ratio). Compared to sophisticated means of diversion, cutaneous diversion resulted in minimal operative time and hospital stay. No relationships between age, body mass index, biological parameters, type of diversion, associated procedure, surgeon's experience and postoperative complications could be evidenced. Uneventful recovery resulted in a 16.6 days mean hospital stay, minor complications induced a significant 3.8 days additional stay and major complications resulted in major lengthening of hospital stay (21.2 days mean additional stay). CONCLUSION: ASA scores equal to or greater than 3 were associated with major complications and most specially those related to the type of urinary diversion. Therefore, we recommend special care in the selection of the type of urinary diversion and further preoperative evaluation inclusive of nutritional assessment.
Abstract: OBJECTIVES: To define the clinical, laboratory and histological variables associated with secondary elevation, after an undetectable phase, of PSA after radical prostatectomy. MATERIALS AND METHODS: This was a prospective study of 83 consecutive patients undergoing retropubic radical prostatectomy with an undetectable postoperative PSA at 3 months. The predictive value of five preoperative criteria (age, total PSA, Gleason score on biopsies, positive apical biopsies, clinical stage) and four postoperative criteria (pathological stage, Gleason score on the operative specimen, positive margins, follow-up) for secondary laboratory progression was studied by univariate and multivariate analysis. RESULTS: With a median follow-up of 36 months, the laboratory recurrence rate was 19%. Laboratory recurrence was associated with a biopsy Gleason score greater than or equal to 7 (p = 0.04), a high pathological stage (p = 0.03), a high histological score (Gleason > or = 7) (p < 0.01) and positive margins (p = 0.04). Logistic regression identified a Gleason score on the operative specimen greater than or equal to 7 to be the only element predictive of secondary laboratory progression. CONCLUSION: The concept of positive margins or high pathological stage is insufficient to identify the risk of laboratory progression after radical prostatectomy. The Gleason score, which evaluates tumour aggressiveness, the risk of micrometastases or periprostatic extension, therefore appears to be more useful.
Abstract: OBJECTIVES: To study the efficacy and safety of periurethral collagen injection in the treatment of severe urinary incontinence. PATIENTS AND METHODS: From 1994 to 1998, 25 periurethral collagen injections were performed in 25 women with a mean age of 65 years presenting with urinary incontinence classified as grade III in 17 cases and grade II in 9 cases, under local anaesthesia in 5 cases, spinal anaesthesia in 10 cases and general anaesthesia in 10 cases. Twenty patients were treated for recurrent incontinence. One injection was performed in 20 cases and two injections were performed in 5 cases. None of the patients presented disorders of pelvic muscles. The preoperative urodynamic assessment did not reveal any cases of detrusor instability, and showed a mean urethral closure pressure of 35 cm H2O. A skin test was performed in each case at least 30 days before the injection. RESULTS: The mean hospital stay was 2.75 days. The mean quantity of collagen injected was 5.7 ml. With a mean follow-up of 24 months, 33% of patients were continent, 39% were improved and 28% were considered to be failures. No complications were observed. CONCLUSION: Due to its safety, this method can be proposed in outpatients with good results, in patients of all ages, either as first-line treatment or for recurrent incontinence, as, in the case of failure, this technique does not comprise subsequent treatment by another operation.
Abstract: BACKGROUND: There is a strong body of evidence in favor of influenza virus immunization in solid organ recipients. However, little attention has been devoted to other reservoirs, such as the patients' relatives and, at the time of hospital admission, to the healthcare workers. METHODS: Analysis of the epidemiology of an outbreak of nosocomial influenza A in a solid organ transplant unit. RESULTS: Four cases of influenza A virus infection were reported during a short 4-day outbreak in a 12 single-room transplant unit. None of the patients had been immunized against influenza. Three patients had not been visited by their relatives between admission and influenza infection. Three nurses, among the 27 healthcare workers, presented with clinical flu symptoms at times consistent with nosocomial transmission. CONCLUSIONS: Because the prevention of influenza infection by vaccination warrants a global strategy to target the different reservoirs, we suggest that the modern policy of vaccinating solid organ patients should be extended both to their relatives and to the healthcare workers of transplant units.
Abstract: OBJECTIVES: To assess the multifaceted male sexual function after pelvic ring fracture. METHODS: A cross-sectional study of male sexual function after pelvic ring fractures was conducted, using the International Index of Erectile Function (IIEF). The department of traumatology database was scanned (June 1996 to April 1999) for 30 to 70-year-old male patients with pelvic fracture. Seventy-six consecutive, literate patients were then contacted by mail. IIEF domain scores were calculated for all responders. Cappelleri's method for identification and grading of erectile dysfunction was applied for patients sexually active within the past 4 weeks. Student's t test was used to compare the domain scorings of patients with those of the control population used for the IIEF psychometric validation. Relationships between IIEF results and patient characteristics were sought by Spearman's rank correlation coefficient for quantitative variables and Student's t test for classes. RESULTS: Forty-six patients answered (60.1% response rate). Thirty-seven patients had experienced sexual intercourse in the past 4 weeks during which 11 patients (29.7%) had exhibited various degrees of impaired erection. As a whole, compared with the published controls a significant decrease in overall satisfaction (P <0.05) was demonstrated. Pubic diastasis was further related to impaired erectile function and overall satisfaction; we suggest that cavernosal nerves might be damaged at the time of diastasis. CONCLUSIONS: This study evidenced the impairment of sexual overall satisfaction after pelvic trauma and the specific decrease in erectile function and erection firmness and confidence associated with pubic diastasis. The IIEF questionnaire might be considered at the time of rehabilitation to identify those patients that could benefit from supportive treatments.
Abstract: MATERIALS AND METHODS: A HIV-1 patient database was scanned in March 1998, and 750 patients were identified who had received HAART including indinavir. Of these, 28 cases had nephrolithiasis; and 85 asymptomatic indinavir-treated patients were randomly selected as controls. The characteristics of cases and controls were compared by analysis of variance for quantitative parameters and by Fisher's exact test for classes. RESULTS: We observed a significant increase in the incidence of nephrolithiasis in patients co-infected with HIV-1 and either hepatitis C virus (HCV) (HCV RNA-positive) or hepatitis B virus (HBV) (HBs antigen-positive) (odds ratio and 95% confidence intervals: 2.8 and 1.1-7.7), whereas no significant differences were demonstrated between cases and controls with regard to age (42.4 +/- 8.0 versus 39.8 +/- 9.8 years), sex (male patients 70.4 versus 74.1%), duration of HIV-1 infection (8.6 +/- 3.1 versus 7.7 +/- 4.0 years), duration of indinavir treatment (16.1 +/- 5.8 versus 14.1 +/- 5.4 months), AST increase > or = 1.25 of normal (29.6 versus 25.9%), or ALT increase > or = 1.25 of normal (33.3 versus 22.4%). In co-infected patients, ALT increase (> or = 1.25 of normal), but not AST increase, at the time of indinavir initiation was statistically related to the occurrence of nephrolithiasis. CONCLUSIONS: We found a significant increase of nephrolithiasis incidence in patients co-infected with HIV-1 and HCV or HBV, which suggests that underlying multifactorial hepatic damage may limit liver catabolism of indinavir, and consequently increase its renal excretion and the risk of nephrolithiasis. Caution is therefore advised when initiating indinavir treatment in HIV patients with evidence of HBV or HCV infection.
Abstract: BACKGROUND AND METHODS: A cross-sectional study of multifaceted male sexual function in 323 consecutive kidney transplant recipients was conducted by mail by means of the validated International Index of Erectile Function (IIEF). All five IIEF domains (IIEF-5), i.e., erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction, were scored for each responder. IIEF-5 scoring that conformed to the National Institutes of Health definition of erectile dysfunction (ED) was computed for all patients sexually active within the past 4 weeks. RESULTS: Two hundred and seventy-one patients replied. Compared to the controls used for IIEF psychometric validation, kidney transplant recipients gave lower erectile function (P<0.01) and intercourse satisfaction (P<0.05) scores, despite their being younger. ED, according to the IIEF-5 method, was demonstrated in 55.7% of the sexually active patients (n=212). Age, time on dialysis, and iterative transplants were significantly and negatively related to erectile dysfunction. CONCLUSION: IIEF proved to be a valuable means of unveiling highly prevalent erectile dysfunction in male kidney transplant recipients. The negative impact of the time on dialysis was emphasized in the results.
Abstract: Adverse events following intravesical BCG therapy are related to strain virulence, allergic reactions or to nosocomial urinary tract infections. Low grade fever and irritative symptoms are common side-effects of BCG. They subside within 48 hours and do not require any specific treatment, apart from standard painkillers and antispasmodics. Further instillations should be postponed until symptoms have resolved completely. If symptoms do not resolve, complementary investigations are recommended including urine culture, and isoniazid may be prescribed for 15 days. The BCG dose should be reduced if symptoms increase after subsequent instillations. Complications of BCG infection - either local or systemic - have been reported with an incidence of 10-15%. These complications include: granulomatous prostatitis or epididymitis (treated with isoniazid and rifampicin for 3 months), contracted bladder may occur, mainly during maintenance courses, systemic infection such as granulomatous nephritis and abscesses, pneumonitis, hepatitis, osteomyelitis (treated with isoniazid, rifampicin and ethambutol for 6 months), and life-threatening adverse events may be related to septicaemia or to immunoallergic reactions, the onset of which may be delayed several months after the end of BCG therapy. Such conditions require urgent treatment with standard antituberculous antibiotics and prednisolone. These complications are an absolute contraindication for further BCG instillations. Despite its toxicity, the risk-benefit ratio favours the use of BCG in patients who have moderate- and high-risk tumours. Copyright Copyright 2000 S. Karger AG, Basel
Abstract: Vascular endothelial growth factor (VEGF) binding to the kinase domain receptor (KDR/FLK1 or VEGFR-2) mediates vascularization and tumor-induced angiogenesis. Since there is evidence that KDR plays an important role in tumor angiogenesis, we sought to identify peptides able to block the VEGF-KDR interaction. A phage epitope library was screened by affinity for membrane-expressed KDR or for an anti-VEGF neutralizing monoclonal antibody. Both strategies led to the isolation of peptides binding KDR specifically, but those isolated by KDR binding tended to display lower reactivities. Of the synthetic peptides corresponding to selected clones tested to determine their inhibitory activity, ATWLPPR completely abolished VEGF binding to cell-displayed KDR. In vitro, this effect led to the inhibition of the VEGF-mediated proliferation of human vascular endothelial cells, in a dose-dependent and endothelial cell type-specific manner. Moreover, in vivo, ATWLPPR totally abolished VEGF-induced angiogenesis in a rabbit corneal model. Taken together, these data demonstrate that ATWLPPR is an effective antagonist of VEGF binding, and suggest that this peptide may be a potent inhibitor of tumor angiogenesis and metastasis.
Abstract: OBJECTIVES: A multi-institutional study of 280 radical prostatectomy specimens obtained from three independent academic hospitals was undertaken to validate a nomogram developed for the prediction of specimenconfined protstate cancer after prostatectomy. METHODS: Three preoperative factors - the Gleason score, prostatespecific antigen (PSA) and apical location of positive biopsies - that were identified with a previous logistic regression formula were collected. Links between margin status and preoperative criteria were confirmed by univariate methods. Subsequently, the predictive indexes of positive margins were calculated and compared to the actual margin status in terms of predictive characteristics. RESULTS: This control series, independent of the initial series that was used to identify the relevant preoperative factors, confirmed that positive apical biopsies(p<0.001), PSA (p<0.005) and the Gleason score (p<0.005) were strongly linked to the occurrence of positive margins. Different cutoff values for the predictive index were compared in a receiver operating characteristic curve. A value of 0.5, similar to the one described in the original series, gave an adequate compromise between sensitivity and specificity with respective values of 68 and 73% and a test accuracy of 72%. In practical terms, it was possible to predict 85% of negative margins, and to delineate two groups with different rates of positive margins (14.5 vs. 50%). CONCLUSIONS: We demonstrated that PSA, the Gleason score and apical biopsy status are cumulative risk factors for positive margins. Risk of positive margins increases when it is not possible to obtain a wide excision of periprostatic fascia, as at the apex. This study substantiates the independent prognostic value of positive preoperative apical biopsies for predicting positive surgical margins.
Abstract: OBJECTIVE: To evaluate the efficacy and safety of transurethral resection of the overcorrected posterior lip of the bladder neck in patients with chronic urinary retention after repair of incontinence. MATERIAL AND METHODS: Transurethral bladder neck resection was performed in 26 women with a median age of 59 years. Incontinence repair consisted of a Burch procedure in eight cases, a Raz procedure in eight cases, a Marshall-Marchetti-Krantz procedure in five cases, an aponeurotic sling in three cases and a synthetic sling in two cases. The median preoperative maximum urine flow rate was 11.5 ml/s and the median residual urine was 150 ml. Preoperative cystourethrography and cystoscopy revealed overcorrection of the bladder neck in each case. RESULTS: With a median follow-up of 39 months, 65.5% of patients were cured (resolution of symptoms, maximum urine flow rate greater than 15 ml/s and residual urine less than 50 ml), 23% were improved and 11.5% were considered to be failures. No complications or secondary urinary incontinence were observed. Patients not cured by this technique were treated by urethrolysis in three cases, Uroflow stent in one case and section of a Raz cervicocystopexy suture in one case. CONCLUSION: Transurethral bladder neck resection can be used as first-line treatment for chronic urinary retention after repair of incontinence, as it is an effective, rapid, minimally invasive technique not associated with any morbidity. Urethrolysis can always be performed in the case of failure.
Abstract: It is generally accepted that tumor development requires the secretion by cancer cells of soluble mediators which activate the formation of new vessels, called "Tumor Angiogenic Factors". The intense quest for identifying these factors has recently been confirmed by strong experimental data. The discovery in 1989 of the Vascular Endothelial Growth Factor VEGF and of new proteases had led to the identification of the key actors of tumor angiogenesis. The elucidation of their mechanisms of action allowed to design new therapeutic strategies already confirmed by preclinical trials. There are now almost twenty molecules which are under clinical investigation in man.
Abstract: We report the case of a 52-year-old patient with spina bifida, neurologic bladder, and a history of recurrent urinary tract infections (UTIs) in whom a bladder cancer was incidentally discovered. Cytology, cystoscopy, and cystography showed nonspecific, extensive inflammatory lesions. Cystography demonstrated a complex of diverticulae and cellules. Pathologic examination of a diverticulectomy specimen revealed a grade III pT3b transitional and squamous cell carcinoma. Because of the similar disease causation (recurrent UTIs, stones, and indwelling catheterization), we suggest extension of the guidelines proposed for patients with spinal cord injuries (ie, annual serial bladder biopsies) to patients with nontraumatic neurogenic bladder.
Abstract: PURPOSE: To measure the incidence of second non-germ cell malignancies (SNGCM) in patients treated for a stage I-II testicular seminoma. MATERIALS AND METHODS: From 1970 to 1992, 131 evaluable patients received in the Institut Claudius Regaud a post-orchiectomy treatment for a stage I-II testicular seminoma. The therapeutic modalities, including salvage treatment for six recurrences, were as follows: infradiaphragmatic radiotherapy (IDRT) (n = 55); infra- and supradiaphragmatic radiotherapy (IDRT + SDRT) (n = 64); IDRT + SDRT with chemotherapy (n = 12). The mean follow-up was 11 years. The cumulative incidence of SNGCM was compared to the overall cancer incidence in the general male population on the basis of the Tarn Cancer Registry; the relative risk was expressed as a standardized incidence ratio (SIR). RESULTS: Overall, the cumulative incidence of SNGCM was 10.7% (14/131 cases). The SIR was equal to 2.81 (95% confidence interval (CI) 1.54-4.72; P < 0.001) and increased with follow-up duration. The SIR was significantly increased in 64 patients treated with IDRT + SDRT (SIR = 3.08; 95% CI 1.47-5.66; P = 0.002) but not in 55 patients treated with IDRT alone (SIR = 0.62; 95% CI 0.01-3.43; P = 0.8). The 12 patients who received chemotherapy had an SIR of 26.2 (95% CI 5.48-77.69; P < 0.001), while the SIR was 2.26 in the 119 patients who did not receive any chemotherapy (95% CI 1.13-4.04; P = 0.01 ). Of four hematologic malignancies, three appeared in the 12 patients who received chemotherapy. CONCLUSIONS: An increased risk of SNGCM after SDRT + IDRT has been demonstrated. After IDRT alone, the risk of second cancer is not incremented after a median follow-up of 6 years, but further observation of the patients is necessary to achieve final conclusions. Our results suggest that the risk of second cancer and especially of hematologic malignancy is increased by the association of chemotherapy and radiation.
Abstract: OBJECTIVES: The treatment of vascular erectile insufficiency may require surgery because of the high failure rate of intracavernous injections. Implantation of penile prostheses is a last resort which can be avoided in certain selected patients in whom vascular surgery can be proposed. However, the modalities and results of this type of treatment remain controversial. We therefore evaluated the results of two different techniques. MATERIAL AND METHODS: From 1st January, 1985 to 31st December, 1995, 114 patients were operated for impotence due to pure veno-cavernous incompetence in 23 cases (20%), associated with arterial disease in 38 cases (46%) or purely arterial insufficiency in 39 cases (34%). The mean age was 47.5 +/- 11 years (range: 20 to 74). These patients had suffered from erectile insufficiency for an average of 33.3 +/- 3 years. Pharmacological erection tests achieved rigid erection in only 6 cases. Two surgical techniques were used: end-to-end bypass graft between the epigastric artery and the dorsal artery of the penis (DAP) in 44 cases and arterialisation of the deep dorsal vein of the penis (DVP) in 71 cases. RESULTS: Overall, there were 54 good results (48%), defined by return of normal erections allowing satisfactory sexual intercourse without any complementary treatment, 15 improvements (14%) and 45 failures (38%) with a mean follow-up of 18 months (range: 3 to 120). These results were equivalent in the case of pure veno-cavernous incompetence (65%) of good results) or associated arterial disease (52%) of good results), but poorer results (31% of good results) were obtained in the case of pure arterial disease. The results were not statistically influenced by age or the presence of graft in all 3 types of erectile insufficiency, arterial, veno-cavernous or mixed. However, this difference was only statistically significant for pure veno-cavernous incompetence. The morbidity of arterialisation of the DVP was marked by high-flow syndrome in 21% of cases (n = 15), requiring surgical revision in 77% of cases (n = 11). Interestingly, 85% of good results on erectile function were obtained in this subgroup. CONCLUSION: The results obtained in this series of vascular erectile impotence, regardless of the aetiology of erectile insufficiency, are in favour of the better efficacy of arterialisation of the DVP compared to arterial bypass graft. The biological mechanisms underlying this better result need to be elucidated.
Abstract: OBJECTIVE: To determine the incidence of second non-germ-cell cancers (SNGC) in patients treated for stage I-II testicular seminoma. MATERIAL AND METHODS: This study is based on 131 evaluable patients treated at the Institut Claudius Regaud between 1970 and 1990. Treatment modalities, including salvage therapy for 6 patients developing recurrence, were as follows: infradiaphragmatic irradiation (infraDI) only in 55 cases, infra- and supradiaphragmatic irradiation (infraDI + supraDI) in 64 cases, and irradiation and chemotherapy (IC) in 12 cases. Five patients were lost to follow-up 4 months to 14 years after primary treatment (mean follow-up: 11 years). The cumulative incidence of SNGC was compared to the overall cancer incidence in the age-matched male population reported in the Tarn Cancer Registry. The relative risk was expressed as the Standardized Incidence Ratio (SIR). RESULTS: The cumulative incidence of SNGC was 10.7% (14/131 patients). SIR was equal to 2.81 (p < 0.001) and increased with the duration of follow-up. SIR was significantly increased in 64 patients treated with infraDI + supraDI (SIR) = 3.25; p = 0.002), but not in the 55 patients treated with infraDI only (SIR = 0.62; p = 0.8). The 12 treated patients with IC had an SIR of 26.2 (p < 0.001). Three of the 4 patients who developed a haematological malignancy belonged to the IC group. CONCLUSIONS: The risk of SNGC is increased after infraDI + supraDI. The risk of SNGC after infraDI only is not increased with a median follow-up of 6 years, but this follow-up is too short to allow any definitive conclusions. The risk of SNGC and particularly haematological malignancy appears to be increased by the combination of radiotherapy and chemotherapy.
Abstract: OBJECTIVES: To compare: 1) the incidence of positive resection margins after radical prostatectomy, 2) the incidence of secondary elevation of PSA, in two groups of patients operated before and after May 1994. METHODS: We collected and compared preoperative (PSA, Gleason score on biopsies, positive apical biopsies) and postoperative variables (number and site of positive margins, secondary elevation of PSA) in two historical cohorts of 115 and 67 patients undergoing retropubic radical prostatectomy. RESULTS: We currently operate on tumours characterized by lower PSA values with a smaller proportion of positive apical biopsies. Inversely, the proportion of high Gleason scores appears to be greater, although the difference is not statistically significant. The decreased incidence of positive resection margins and PSA failure rate compared to our initial series reflects the improvement of the oncological results. The respective place of improvement of techniques and changing indications has yet to be defined. CONCLUSION: This study demonstrates the changing operative indications and histological and laboratory results over time. The documented improvement of oncological results is partly related to the progress in surgical indications.
Abstract: BACKGROUND: Prostate-specific antigen (PSA) is the most important tumor marker in prostate cancer diagnosis and follow-up. Its catabolism by the liver has not influenced its use as a prostate marker until the recent report of a significant increase in a man and a woman with acute hepatitis. In addition, PSA was detected in liver tumor extracts, which warranted its evaluation in liver cytolysis and hepatocellular carcinoma. In this study, PSA was evaluated in a cohort of both sexes presenting either acute hepatitis or hepatocellular carcinoima. METHODS: Forty-two patients with acute hepatitis (21 male patients, 21 female patients) and 54 patients with hepatocellular carcinoma (31 male patients, 23 female patients) were tested for PSA by equimolar immunoassay (Abbott AxSYM Total PSA, Abbott Diagnostics, Rungis, France) and for relevant liver biological parameters (alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin rate). RESULTS: PSA was undetectable in all the female patients and was consistent with age in the males (PSA median and range in acute hepatitis, 0.36 microg/l (range, 0.05-1.3); in hepatocellular carcinoma, 0.36 microg/l (range, 0.02-3.9)). It did not correlate with alpha-fetoprotein and aminotransferases. CONCLUSIONS: Our results confirm the well-established reliability of PSA, and show that PSA remains a valid prostate marker in patients with acute hepatitis and hepatocellular carcinoma.
Abstract: An overview is presented of the various steps of angiogenesis, to which an important contributor is Vascular Endothelial Growth Factor (VEGF), a substance capable of increasing both the permeability and the mitosis rate of endothelial cells. VEGF is also a potent vasodilating agent. The beneficial effects of these properties on the ischemic vasculature have been documented in numerous animal models, leading to the concept of angiogenesis-enhancement as a therapeutic tool. The first clinical trials are under way. This area is discussed based on a literature review.
Abstract: BACKGROUND: Following radical prostatectomy, urinary prostate-specific antigen (uPSA) may originate from periurethral glands or from recurrent carcinomatous prostatic cells. We evaluated massage of the urethro-vesical anastomosis as a uPSA-releasing method for the detection of local recurrence. METHODS: PSA was assessed (PSA IMx, Abbott Diagnostic, Rungis, France) in serum and in the first voided urine before and after massage in 59 patients: 7 after cystoprostatectomy for bladder cancer, 22 with prostate in situ, and 30 after radical prostatectomy for prostate cancer. RESULTS: No significant changes of uPSA were induced by the massage in cystoprostatectomy patients and in 4 radical prostatectomy patients with a negative biopsy of the anastomosis. In contrast, a significant increase of uPSA was observed after massage in the patients with prostate in situ and in 6 radical prostatectomy patients with biopsy-proven local relapse. CONCLUSIONS: uPSA before and after massage of the prostatic fossa may constitute a new and efficient tool for the detection of local recurrence, if these preliminary results are confirmed on a larger scale.
Abstract: Medical procedures are performed in the context of a contract between the physician and the patient. Failure to comply with this contract may engage the physician's responsibility. For a long time, the physician's responsibility was engaged because of technical errors or, more rarely, lack of information or consent, which had to be proved by the patient. In the case of litigation, a recent decision by the Court of Appeal (25 February 1997) requires physicians to demonstrate that they have effectively and validly informed the patient. This article studies the content of this information. It suggests a method which, set up under the authority of scientific societies, would allow, in our discipline, the proposal of information forms designed to inform our patients and to preserve our responsibility. Finally, this approach is illustrated by the study of tolerability of materials containing silicone.
Abstract: OBJECTIVE: The concept of therapeutic angiogenesis with vascular endothelial growth factor (VEGF) has been validated in peripheral arterial disease. Its use in myocardial ischemia may be delayed as the result of the description in a porcine model of peripheral vasodilation after intraluminal injections of VEGF resulting in a 50% fatality rate by hypotension. We carried out this study to test whether VEGF-induced hypotension (1) is species specific, (2) is mediated by the receptor mediating angiogenesis, (3) is prevented by inhibition of nitric oxide synthase. METHODS: In the rabbit corneal pocket assay we tested whether a previously published anti-idiotypic antibody (AIA) agonist of the VEGF receptor Flk-1/KDR could elicit angiogenesis. Various doses of recombinant VEGF or AIA were injected into anesthetized normotensive Wistar-Kyoto rats and the mean arterial blood pressure (MABP) was recorded. To test the implication of nitric oxide in VEGF-induced hypotension we treated the animals with a competitive inhibitor of nitric oxide synthase prior to the injection of VEGF. RESULTS: Both VEGF and AIA induce angiogenesis but only intravenous injections of VEGF induced a rapid, transient and dose-dependent decrease in MABP. The ED50 was 0.5 micrograms. The interval between two VEGF injections required to lead to a decrease of MABP was 40 minutes. Nitric oxide synthesis inhibitor prevented, in a reversible fashion, the effect of VEGF. CONCLUSION: VEGF-induced hypotension is not species specific. It is prevented by nitric oxide inhibition. VEGF-induced angiogenesis and hypotension are not mediated in vivo by the same VEGF receptor.
Abstract: PURPOSE: We evaluated the results of microvascular penile revascularization in impotent men and carefully selected those whose vasculogenic impotence was defined as arteriogenic impotence, veno-cavernous leakage or mixed vasculogenic impotence. MATERIALS AND METHODS: Over a period of 11 y, 114 patients were treated for vasculogenic impotence with two surgical procedures: Michal II arterial bypass (44 patients) and modified Furlow-Fisher technique of deep dorsal vein arterialization (DDVA) (70 patients). Initial evaluation included history, physical and neurological examination, hormonal level determination, pharmacological erection test, Rigiscan, duplex ultrasonography, selective pudendal arteriograpy, dynamic cavernosometry and cavernosography. The patients were followed up for a mean period of 17 months and the results were clinically evaluated. RESULTS: The results at the end of one month were considered as good in 69.5% and improved in 12.2% and failed in 18.3%. Follow-up results are good in 47.8%, improved in 14.6% and failed in 37.4%. The best success rate was obtained with patients with pure venogenic impotence treated with DDVA, whereas the worst was observed in patients with pure arteriogenic impotence treated with the Michal II procedure. DDVA seems to provide better results than arterial bypass regardless of the etiology of impotence. CONCLUSIONS: Penile microvascular revascularization is not the best cure for all impotent men but appears to have a place in the treatment for selected patients with vasculogenic impotence. Further studies will be necessary to define parameters able to permit a better understanding and selection of candidates. DDVA is the most effective procedure to treat surgically vasculogenic impotence although the hemodynamic and biologic consequences of this operation are unknown.
Abstract: Impotence affects 10 to 15% of the male population. Organic factors are recognized in 80% of cases. Intracavernosal injections of vasoactive agents (Virag) have provided advances in the physiopathologic understanding of impotence and provide new ways of treating this incapacity. However this option is inaffective in most organic cases: arteriogenic, venogenic or disorders of smooth cavernous muscle. Vasoactive injections for many reasons are abandoned in about 40% of the cases. Two kinds of surgical management can be performed: microrevascularization in order to restore the arterial penile flow or to reduce penile venous flow during erection; implantation of penile prosthesis when other therapeutic possibilities are exhausted. Arterialization of the deep dorsal vein (DDV) appears to be the best procedure in arteriogenic and principally venous impotence. Erectile function in theses case is restored in 60% of our patients. Two types of prostheses can be implanted: semi-rigid with an axial permanent rigidity and inflatable or hydraulic devices with a flaccid aspect after intercourse. These prostheses are technically successful in 75 to 90% of cases, but partner satisfaction does not match surgical success rates.
Abstract: We took advantage of the anti-idiotypic strategy to design circulating probes mimicking the biological effects of VEGF (vascular endothelial growth factor) or FGF2 (fibroblast growth factor 2). The activation of the VEGF receptor KDR/flk-1 induced endothelial cell proliferation but not their migration, whereas that of the FGF receptor FGF-R1 gave opposite results. The long lasting delivery of KDR/flk-1 agonists, but not that of FGF-R1, in nude mice grafted with tumor fragments enhanced the tumor volume. Microscopic examination showed an increase in both the vascularization and the proliferation of cancer cells. In contrast, no difference in cell proliferation was observed within normal tissues.
Abstract: The reactivity of MIB1 antibody on routinely processed paraffin sections was compared with that of Ki-67 antibody on frozen sections of 80 transitional cell carcinomas of the bladder. The percentage of labelled cells was expressed as the labelling index. MIB1 labelling indices were higher than those of Ki-67 but for each case the two values were strongly correlated (r = 0.91). Ki-67 and MIB1 indices were also correlated to tumour grade and stage (P < or = 0.001). MIB1 indices determined after both formaldehyde and ethanol based Bouin's fluid fixatives did not show any significant difference. MIB1 antibody staining after microwave oven heating of tissue sections is a simple technique for assessing the proliferative fraction of bladder tumours on fixed material. The use of MIB1 antibody permits retrospective studies and should determine whether the proliferation index in bladder carcinoma has the same prognostic value as demonstrated in other types of neoplasms.
Abstract: 33 patients underwent a penile deep dorsal vein arterialization (DDVA) (11 venous leak, 8 pure arteriogenic impotence, 14 mixed arterial and venous impotence). The mean follow-up was 12 months. Surgery was considered successful when the patients had permeable anastomosis and were able to achieve satisfactory erections resulting in normal intercourse. 92% of the patients with venous leak, 62.5% of those with arteriogenic impotence and 58% with mixed lesions had a successful results. Due to antithrombotic therapy, there was no graft occlusion. Glans hypervascularity occurred in 3 patients and was treated by arterial banding. The role of DDVA in vascular impotence and its functional mechanism are discussed.
Abstract: In France, therapeutic trials are governed by the so-called Huriet Law of December 20, 1988 concerning the "protection of subjects participating in biomedical research". Urologists must be familiar with this Law to preserve their responsibility. We must make sure that the Sponsor fulfils his obligations and that the information which we give to our patients guarantees the validity of their consent. The authors recall the legal penalties associated with failure to comply with this law.
Abstract: OBJECTIVE: To restore physiological erection by performing microsurgical penile revascularization. PATIENTS AND METHODS: The records of 21 patients with pure arteriogenic impotence were reviewed. Thirteen patients with localized obstruction of the internal pudendal or common penile artery underwent a Michal II arterio-arterial penile revascularization. Eight patients with a more distal arterial obstruction underwent a penile deep dorsal vein arterialization (DDVA). The mean follow-up period was 22 months. Surgery was considered successful when the patients had a permeable anastomosis and were able to achieve satisfactory erections resulting in normal intercourse. RESULTS: Potency was restored in eight of the 13 patients who had a Michal II procedure and in five of the eight patients who had a DDVA. Under antithrombotic therapy graft occlusion occurred in four patients. CONCLUSION: Microsurgical penile revascularization restored erectile function in two-thirds of patients in this study. However, further research must be performed to reach a greater understanding of the revascularization process.
Abstract: Intravesical BCG is the reference adjuvant therapy for superficial urothelial tumours. Its adverse effects and the modalities of follow-up are now clearly established. We treated a female patient by antegrade BCG instillation for a carcinoma in situ discovered in a ureteric stump following cystectomy for generalised CIS. Treatment was well tolerated and no recurrence was observed with a follow-up of 3 years.
Abstract: Impotence of vascular origin may be due to a defect of the arterial blood supply, a cavernous venous leak or a combination of the two phenomena. Several microsurgical techniques have been proposed to restore physiological erectile function, without the use of intracavernous injections of vasoactive drugs or implantation of penile prostheses. We have used this type of surgery in motivated and selected patients for more than 15 years (72 patients treated, 57 patients evaluated after surgery). In patients with impotence of arterial origin, we perform a Michal II arterio-arterial revascularisation in the case of limited proximal or distal lesions with preservation of one of the two dorsal arteries, (13 patients) and arterialisation of the deep dorsal vein of the penis in the case of diffuse distal lesions (8 patients). 62% of positive results were obtained with both forms of revascularisation with a mean follow-up of 22 months. In patients with impotence of venous origin (11 patients), we perform arterialisation of the deep dorsal vein of the penis, with 92% of positive results with a mean follow-up of 12 months. In patients with impotence of arterial and venous origin (25 patients), we carry out a Michal II revascularisation and ligation of the dorsal vein or arterialisation of the dorsal vein achieves 64% and 58% of positive results with a mean follow-up of 12 months and 5 months, respectively. In the light of these results, the authors try to define the place of vascular microsurgery in the treatment of impotence.
Abstract: From February 1971 through February 1989, 51 patients with biopsy proven epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium 192). The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6, N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients without clinical nodal involvement received no treatment to the nodes. Stage N1 and N2 patients had surgery and external irradiation to the inguinal and iliac nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease following therapy. Five of six presented initially with clinical nodal involvement. Seven of fifty-one (14%) developed local recurrence only, requiring surgery (four partial penectomies, three total penectomies). Six of these seven patients are alive and free of disease with a mean follow-up of 5.5 years. Nine of thirty eight (23%) patients with local control developed local necrosis. The treatment consisted of local excision (one patient), partial amputation (six patients) or total amputation (two patients). Partial urethral stenosis was noted in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%) uncircumcised patients. Interstitial irradiation for penile carcinoma provided effective local control rates, especially for T1-T2 patients (91%). Local failures could be treated successfully with surgery. Complications could be treated conservatively in most patients. Local control with penile conservation was achieved in 67% of all patients and 75% of patients with T1-T2 disease.
Abstract: An enquiry by self-filled questionnaire was conducted among 834 employees of the Toulouse Hospital Centre. The 79.6 percent answer rate obtained made it possible to determine the prevalence of hepatitis B virus infection (11.1 percent), the proportion of immunized subjects (42.5 percent) and their distribution among the different professional categories, and the proportion of accidents that could carry a risk infection (64.3 percent). At present, the protective measures are insufficiently known and applied. The information needed should be precise and up-to-date, covering the various aspects of hepatitis B infection; it should be provided before any occupational exposure and thereafter recalled during routine activities.
Abstract: Angiosarcoma of the breast is a rare connective tissue tumour, there having been fewer than 100 cases described. It occurs practically only in women and presents as a phylloid tumour of rapid growth in a young woman. There may be inflammatory phenomena; local trauma is often mentioned. The diagnosis is difficult and relies on the histological examination of biopsy specimens or of the whole specimen removed. The microscopic appearance may be very similar to that of a benign haemangioma. It is necessary to make several cuts and to remember the essential feature of a haemangioma of the breast, namely that it is subclinical and therefore usually discovered microscopically by chance. Treatment consists of simple mastectomy without usually needing to clear the axilla. It is necessary to give polychemotherapy. There is still no agreement on radiotherapy and hormone therapy. The prognosis is very serious because the mean length of survival is around 22 months. We report a recent case of angiosarcoma of the breast in which diagnostic steps were taken in order, and for which expert histological opinion made it possible to diagnose the condition in less than one month. A 37 year old woman had been complaining of the recent appearance of a tumour in her right breast which was growing rapidly because at the first consultation, within one month after her first signs, it measured 50 mm in diameter. It was poorly outlined, multinodular and non-inflammatory.(ABSTRACT TRUNCATED AT 250 WORDS)
