Modulation of d-galactosamine/lipopolysacharride-induced fulminant hepatic failure by nilotinib.

This investigation was undertaken to test the effect of nilotinib against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF). Male Swiss albino mice were orally treated with nilotinib for 3 days prior to GalN/LPS challenge. The results revealed that administration of GalN/LPS caused elevation in the mortality rate. GalN/LPS-induced severe hepatic injury was manifested by increased serum transaminases and alkaline phosphatase (ALP) levels as well as histopathological hepatic necrosis and inflammation. In addition, GalN/LPS increased the hepatic oxidative stress as indicated by increased malondialdehyde level, decreased glutathione content, and superoxide dismutase (SOD) activity. Furthermore, GalN/LPS increased nuclear factor kappa-B activation and the levels of tumor necrosis factor-alpha and interleukin-1ß. These biochemical and histopathological changes were markedly ameliorated by nilotinib pretreatment. On the other hand, the level of toll-like receptor-4 was increased upon GalN/LPS challenge, which was not alleviated by nilotinib pretreatment. These data demonstrate that nilotinib has hepatoprotective activity against GalN/LPS-mediated FHF in mice via anti-oxidative and anti-inflammatory effects.

Preservation of the internal genital organs during radical cystectomy in selected women with bladder cancer: a report on 15 cases with long term follow-up.

PURPOSE: To prospectively present the technique, functional and oncological outcome of internal genitalia sparing cystectomy for bladder cancer in 15 selected women. PATIENTS AND METHODS: Between January 1995 and December 2010, 305 women underwent orthotopic neobladder after radical cystectomy. Of these, 15 cases with a mean age of 42 years underwent genitalia sparing. Inclusion criteria included stage (T2b N0 Mo or less, as assessed preoperatively, unifocal tumors away from the trigone, sexually active young women and internal genitalia free of tumor. Cystectomy with preservation of the uterus, vagina and ovaries and Hautmann neobladder were performed. Oncological, functional, urodynamic and sexual outcome using Female Sexual Function Index (FSFI) were evaluated. RESULTS: Definitive histopathology showed advanced stage not recognized preoperatively in 2 patients, who developed local recurrence and bony metastasis after 3-4 months. A third patient developed bony metastasis after 15 months. No recurrence developed in the retained genital organs. The remaining 12 patients remained free of disease with a mean follow-up of 70 months. Among women eligible for functional evaluation, daytime and nighttime continence were achieved in 13/13 (100%) and 12/13 (92)%, respectively. Chronic urinary retention was not noted. The urodynamic parameters were comparable to those in other patients without genital preservation. Sexual function (FSFI) was better in these patients than in others without genital preservation. CONCLUSIONS: Genital sparing cystectomy for bladder cancer is feasible in selected women. It provides a good functional outcome, better sexual function and the potential for fertility preservation. So far, the oncological outcome is favorable.

Xylometazoline pretreatment reduces nasotracheal intubation-related epistaxis in paediatric dental surgery.

BACKGROUND: Epistaxis is the most common complication encountered during nasotracheal intubation (NTI) in children. The aim of this study was to test the efficacy of prophylactic intranasal admixture of xylometazoline and local anaesthetic gel in reducing epistaxis after NTI in children. METHODS: Children presenting for dental procedures requiring NTI were randomly allocated into two groups: Group 1 (xylometazoline group, n=53) and Group 2 (control group, n=51). After sevoflurane inhalation induction, the more patent nostril in each subject was lubricated with lidocaine 2% (1 ml) jelly, followed by 0.6 ml of either xylometazoline hydrochloride 0.1% nasal drops (Group 1) or sodium chloride 0.9% (Group 2). The presence and extent of bleeding occurring during intubation, extubation, or both and navigability through the nasal passage were assessed. RESULTS: The incidence and severity of bleeding were significantly reduced between the study group (7.5%) compared with the control group (27.5%; P<0.01). Navigability was similar in both groups. CONCLUSIONS: Admixture of intranasal xylometazoline 0.1% drops and lidocaine 2% jelly reduced the incidence and severity of epistaxis after NTI in preschool children.

Outcome of patients with continent urinary reconstruction and a solitary functioning kidney.

OBJECTIVE: To evaluate the outcome of patients with continent urinary diversions who had a solitary functioning kidney at the time of surgery. PATIENTS AND METHODS: In all, 62 patients with continent urinary reservoirs and a solitary functioning kidney were reviewed (51 men and 11 women). The indications for surgery were bladder cancer in 54 and a contracted bladder in eight. The surgical procedures included an orthotopic ileal neobladder in 36 patients, a continent cutaneous ileal reservoir in 13 and rectal diversion in 13. Kidneys were evaluated using serum creatinine level, ultrasonography, intravenous urography and other radiological studies. RESULTS: The follow-up was 6-173 months; 44 renal units (71%) remained stable during this period. Serum creatinine was increased in four patients with an orthotopic neobladder, with no evidence of obstruction or reflux, in one with preoperative renal impairment and one with voiding dysfunction, reflux and bacteriuria. Six renal units deteriorated because of uretero-intestinal strictures; of these patients, two were treated endoscopically, two with open ureteric reimplantation, one with conversion from a rectal reservoir to an ileal loop conduit, and one was maintained on JJ stenting. Six patients with a rectal diversion had renal deterioration because of chronic pyelonephritis. CONCLUSIONS: A regular follow-up of renal function is mandatory in patients with a continent urinary diversion. Rectal diversion is associated with a higher risk of renal deterioration (54%) than are orthotopic (28%) and cutaneous reservoirs (8%).

The urethral Kock pouch: long-term functional and oncological results in men.

OBJECTIVE: To evaluate our experience with men who underwent radical cystectomy and urethral Kock pouch construction between January 1986 and January 1996. PATIENTS AND METHODS: Complications were classified as early (within the first 3 months after surgery) or late. Continence was assessed by interviewing the patient; they were considered continent if they were completely dry with no need of protection by pads, condom catheter or medication. The patients were followed oncologically and Kaplan-Meier survival curves constructed. Urodynamic studies were used to define the possible causes of enuresis. RESULTS: Three patients died after surgery from pulmonary embolism. There were 67 early complications in 63 patients. The mean (SD) follow-up was 87.8 (49.1) months. There were 111 treatment failures from cancer; of these, four men only had an isolated local recurrence in the urethra. Late complications included 72 pouch stones in 55 patients, and 36 deteriorated renal units caused by reflux (17), uretero-ileal stricture (11), nipple valve eversion (four) or stenosis (four). Interestingly, 65 renal units that were dilated before surgery improved significantly afterward. Ileo-urethral strictures occurred in seven men and anterior urethral strictures in six. Nine patients were totally incontinent and two had chronic urinary retention. Daytime continence was complete in 94% of men, with nocturnal enuresis in 55; the latter had significantly more residual urine, and a higher amplitude and duration of phasic contractions. CONCLUSIONS: Orthotopic bladder substitution after cystectomy for cancer is feasible, with good functional and oncological outcomes in properly selected patients. Nevertheless, the use of a hemi-Kock pouch is associated with many valve-related complications.

Prognostic significance of tumour angiogenesis in schistosoma-associated adenocarcinoma of the urinary bladder.

OBJECTIVE: To report on tumour angiogenesis and its relationship with morphological variables and prognosis in adenocarcinoma of the urinary bladder associated with schistosomiasis. PATIENTS AND METHODS: Fifty-five vesical adenocarcinomas were evaluated from 30 men and 25 women (mean age 47.2 years, sd 8.7, range 30-65) who were followed up after radical cystectomy and urinary diversion for a mean (sd, range) of 61 (43.5, 2.7-159.5) months. Vessels were stained immunohistochemically using an antibody to the platelet endothelial cell-adhesion molecule CD31. Microvessels were counted in active areas of angiogenesis within the tumours (at x250) and the microvessel density (MVD) quantified using the mean of three counts. Treatment failure was defined as death from cancer or the development of local recurrence or distant metastasis. Kaplan-Meier survival curves and Cox's proportional hazard model were used to assess survival. RESULTS: The overall 5- and 10-year survival rates were 57% and 51%, respectively. The presence of lymph node metastasis and high mean vascular density (> 26) were significantly associated with a poor prognosis. The 5-year survival for patients with negative lymph nodes was 66% while no patients with positive nodes survived for 5 years (P < 0.001); the survival was 72% for patients with a low MVD and 33% for those with a high MVD (P = 0.0016). From individual results plotted against vascularity in lymph node-negative patients, there was a significantly better outcome for those with a low MVD (< or = 26; P = 0.0099); this significance was maintained on multivariate analysis. However, there was no significant relationship between angiogenesis and the different clinicopathological factors apart from the grade (P = 0.03); tumour stage, grade and DNA profile had no significant effect on survival in these patients. CONCLUSIONS: These findings suggest that assessing angiogenesis using the MVD provides an independent predictor of survival in patients with adenocarcinoma of the urinary bladder.

Nocturnal enuresis in men with an orthotopic ileal reservoir: urodynamic evaluation.

PURPOSE: We evaluated the urodynamic features of enuretic and continent patients with an orthotopic neobladder. MATERIALS AND METHODS: Included in our study were 100 men with an orthotopic hemi-Kock or W neobladder and a minimum followup of 1 year. Of the patients 50 were completely continent day and night, and 50 had enuresis without evidence of an underlying organic etiology, such as stones, reflux or urethral stricture. RESULTS: Univariate analysis showed significantly higher pressure and a larger volume of post-void residual urine in the men with enuresis. In addition, maximum urethral pressure, maximum flow and compliance were decreased in the enuretic group compared to the continent group. Multivariate analysis revealed that post-void residual urine volume, frequency and maximum amplitude of uninhibited contractions are the most critical parameters affecting nocturnal continence. CONCLUSIONS: The cystometric parameters significantly associated with nocturnal enuresis in patients with an orthotopic reservoir are post-void residual urine volume, frequency and maximum amplitude of uninhibited contractions. Urethral pressure and flow parameters did not sustain significance on multivariate analysis.

Urological complications of Cadaveric Renal Transplantation.

Urological complications in 211 consecutive primary and secondary cadaveric renal transplants, performed t our institution between March 1993 and December 1996, were encountered in 13 patients (6.2%). The complications included urine leakage in four cases (1.9%)., obstruction of the upper urinary tract in seven (3.3%), urethral strictures in two (1%) and stone formation in one. Successfully treated complications amounted to 86%. Associated infection and urinary leak resulted in the loss of two grafts.

Primary nonurachal adenocarcinoma in the bilharzial urinary bladder: deoxyribonucleic acid flow cytometric and morphologic characterization in 93 cases.

OBJECTIVES: To characterize adenocarcinomas of the urinary bladder by their DNA profiles and their proliferative properties. METHODS: Primary nonurachal adenocarcinomas, found in 93 patients with bilharzial bladder carcinomas, were studied using DNA flow cytometry. Tumor ploidy and S-phase fraction were related to tumor grade, stage, cell type, and lymph node status. RESULTS: Aneuploidy with high S-phase fractions, found in 90% of the tumors, demonstrates the high malignancy potential of these tumors, the majority of which were found to be muscle-infiltrative. There were no relationships between ploidy or S-phase fraction and tumor grade and stage. Lymph node metastases, present in 24% of the 93 patients, were found exclusively in nontetraploid aneuploid tumors with high S-phase fractions exceeding 100%. Paraffin-embedded tissues compared with fresh material gave the same information on ploidy, whereas bladder washing did not provide adequate information. CONCLUSIONS: The high aggressiveness of adenocarcinomas in the biharzial bladder is confirmed and can be explained by their proneness to develop gross chromosomal aberrations combined with high cell proliferation.

Incidence and types of malignant tumors in renal transplant recipients: a single center experience.

We reviewed the incidence and types of de novo malignancies which developed in 792 renal transplant recipients who received their grafts between 1979 and 1996 and followed up for an average period of 5.6 years. There were 56 malignant tumors detected in 54 patients, representing an overall incidence of 6.8%. These tumors occurred in a relatively young group of patients whose average age was 33.4 years at the time of transplantation and 40 years at the time of diagnosis of malignancy. The average latency period between transplantation and malignant disease was 7.4 years for solid tumors and 16 months for Kaposi's sarcoma. Tumors included 39 Kaposi's sarcomas, four malignant lymphomas, three hepatomas, two bladder cancers, one renal cell carcinoma of the allograft, two colorectal cancers, two thyroid cancers, one adenocarcinoma of unknown primary, one nasopharyngeal carcinoma and one leiomyosarcoma of the uterus. Kaposi's sarcoma was the most common malignancy and comprised 70% of all tumors in this study. It is imperative for renal transplant recipients to have diligent follow-up at regular intervals for early detection of cancer.

Orthotopic bladder substitutes: histopathologic risk factors.

Prostate glands from 150 patients with carcinoma of the bilharzial bladder who underwent cystoprostatectomy were studied histopathologically by step sections. Prostatic urethral involvement by urothelial carcinoma was noted in 13 out of 96 (13.5%) and 5 out of 40 (12.5%) squamous and transitional cell tumors, respectively. None of the 12 adenocarcinomas and the two undifferentiated tumors showed involvement. Prostatic urethral involvement was as high as 19% in basal tumors and 26.7% in multifocal tumors compared to only 6.5% when the tumors occupied the bladder body. There was a significant increase in the incidence of prostatic urethral involvement from 9.5 to 35% when the prostate gland was involved. Prostate gland was involved in 20 out of 150 (13.3%). The bladder tumor was basal and infiltrating the prostate in 18 such cases. Seminal vesicles were infiltrated in 6 cases from the adjacent basal bladder tumors. We conclude that patients with basal or multifocal tumors are risky regarding bladder substitution and we recommend routine diagnostic transurethral prostatic biopsies and frozen sections from the site of urethral transection during cystoprostatectomy whenever bladder substitution controlled by the urethral sphincter is considered.

Role of cytomegalovirus in inducing congenital anomalies.

Sixty eight infants and newborns were included in the present study being consisted of 55 cases with congenital anomalies and 13 cases of apparently healthy infants acting as controls. Three types of congenital anomaly cases were studied; 17 cases of microcephaly, 17 cases of cerebral palsy and 21 cases with jaundice. All serum samples were tested for cytomegalovirus IgM antibodies (CMV IgM) by microassay ELISA technique to explore the role of CMV infection in inducing congenital anomalies. Six out of the 68 serum samples were found to be positive for CMV IgM. Four of them were detected among the congenital cases (5 our to 55; 7.3%), while 2 cases were among the controls (2 out of 13; 15.4%). The microcephalic group showed 5.9% positivity (one out of 17). The jaundiced infants showed 14.3% positivity (3 out of 21), while all the cerebral palsy cases were negative for CMV IgM. Such a high percentage of CMV IgM in the control group may be attributed to asymptomatic infection, with liability for long term sequelae, particularly hearing loss or ocular abnormalities by 2 years of age. So, continuous follow-up of such asymptomatic cases is essential to control any possible congenital abnormality as early as possible.

Digital subtraction angiography in potential live-kidney donors: a study of 1000 cases.

Intravenous digital subtraction angiography (IV-DSA) combined with excretory urography (IVU) were utilized to study the renal anatomy of 1000 potential live-kidney donors. In the entire series, 712 donors (71.2%) had bilateral single renal arteries, whereas 255 (25.5%) had unilateral multiple, 26 (2.6%) had bilateral multiple, and 7 (0.7%) had unilateral hypoplastic or absent renal arteries determined by IV-DSA. Major renal abnormalities that might be potentially significant for safe renal donation were detected in 76 donors (7.6%) by combined IV-DSA and IVU studies. In 10% of the potential donors, intraarterial digital subtraction angiography (IA-DSA) was required because of the equivocal results of IV-DSA. Of the 1000 potential donors, 700 underwent nephrectomy and the number of renal arteries at nephrectomy was compared with both IV-DSA and IA-DSA reports. Analysis of data revealed a sensitivity of 96% vs 95%, a specificity of 57% vs 75% and an overall accuracy 93% vs 90% for IV-DSA and IA-DSA, respectively, both IV-DSA and IA-DSA were accurate enough in identification of single renal arteries. However, the accuracy of IA-DSA was better than that of IV-DSA in visualization of double (84% vs 64%) and triple (66% vs 33%) renal arteries. It is concluded that IV-DSA combined with IVU is an effective technique for the evaluation of potential kidney donors. In cases where IV-DSA is equivocal, we recommend confirming IA-DSA.

Urethral controlled bladder substitution: a comparison between the intussuscepted nipple valve and the technique of Le Duc as antireflux procedures.

A urethral controlled bladder substitute was constructed from a detubularized, double folded ileal segment in 40 male patients following cystoprostatectomy for bladder cancer. For reflux prevention patients were prospectively randomized to receive either an intussuscepted nipple valve or the ureters were implanted by the Le Duc mucosal trough technique. All patients had normal upper tracts preoperatively. Mean patient age, performance status and stage of cancer were comparable in both groups. Patients were evaluated 6 to 18 months postoperatively. In addition to history taking, assessment included excretory urography, ascending cystography and voiding cystourethrography. During the observation period all patients with nipple valves had normal radiographic appearance of the upper tracts without evidence of reflux. On the other hand, following the Le Duc procedure 12 of 38 renal units (31%) showed evidence of radiographic dilatation. Of the 12 units 11 had stenotic ureters and 1 had reflux. We conclude that nipple valves are more effective in reflux prevention and protection of the upper urinary tract in patients for whom an ileal neobladder is indicated.

Prognostic significance of flow-DNA analysis and cell surface isoantigens in carcinoma of bilharzial bladder.

Flow cytometric DNA analysis and ABO(H) cell surface antigen expression were studied in 46 patients with cystectomies for carcinoma of bilharzial bladder. The most significant prognostic indicators were the DNA index and the status of the pelvic lymph nodes at operation. Diploid tumors were associated with a low metastatic potential (7.7%) and a better five-year survival (54%) in contrast to aneuploid cases that had a higher metastatic potential (45.5%) and a low five-year survival (21%). The ABO(H) isoantigen status did not correlate with pathologic parameters or the clinical course of these invasive bilharzial bladder tumors as was previously reported.

Further experience with the urethral Kock pouch.

In 185 men a urethral Kock pouch was constructed as a bladder substitute after radical cystectomy for cancer. A total of 117 patients was followed for a minimum of 1 year and is fully evaluable. Of the patients 108 (92%) are completely continent during the day, while 85 (73%) are dry at night. Also, 8 patients had an excellent response to imipramine hydrochloride. Stability or improvement in the configuration of the upper tract was noted in 210 renal units (90%). A total of 24 renal units showed evidence of deterioration due to reflux (16) and an anastomotic stricture (8). Stability of the antireflux nipple valve was ensured by creation of a window in the mesentery of the corresponding bowel segment and by anchoring the valve to the wall of the pouch by an additional row of staples. On the basis of this favorable outcome the procedure is recommended for male patients for whom cystectomy is indicated and in whom the urethra can be preserved.