Continent urinary tract reconstruction - the Lund experience.

The Department of Urology in Lund, Sweden, has a long association with innovations in reconstructive urology. The authors from that department describe their experience over a long period with orthotopic bladder substitution and continent cutaneous urinary diversion. They conclude that continent urinary tract reconstruction is associated with a high incidence of early and late complications. They also found that for storage and emptying, their Lundiana pouch was superior to the Goldwasser neobladder. OBJECTIVE: To assess the early and late complications and functional results in patients undergoing continent reconstruction of the urinary tract, i.e. orthotopic bladder substitution (OBS) or continent cutaneous diversion (CCD). PATIENTS AND METHODS: The medical records of all patients undergoing OBS (Goldwasser technique) or CCD ('Lundiana' technique) for malignant or benign disease during 1987-1999 and followed to December 2001 were reviewed. There were 67 patients with neobladders, 77 with a Lundiana pouch who had undergone radical cystectomy and 22 with a Lundiana pouch operated for benign disorders. RESULTS: Early complications requiring reoperation occurred in 12% of the cystectomy group, with no difference with type of reconstruction, and in 10% with benign diseases. Four patients (3%) undergoing radical cystectomy died from early cardiovascular complications, two after surgery for intra-abdominal complications. Intestinally related complications and wound dehiscence requiring re-operation occurred in nine and six patients, respectively. The incidence of late complications requiring open surgery was 22% and 23% after cystectomy with OBS and CCD, respectively. The value in patients with benign diseases undergoing CCD was also 23%. Stone formation in the pouch was common, occurring in 12% in patients with OBS and in 10% after CCD. The pouch perforated or ruptured in four patients. The incidence of uretero-intestinal stricture using the Le Duc technique was 2.4% and renal function was well preserved. The incidence of revisional surgery of the Lundiana pouch outlet for incontinence was low and all patients but four were continent. The functional outcome in patients with OBS was less good; some needed pouch augmentation or an artificial urinary sphincter. Most patients used incontinence products and many needed clean intermittent self-catheterization. CONCLUSION: Continent urinary tract reconstruction is associated with a high incidence of early and late complications. For storage and emptying, the CCD Lundiana pouch is superior to the OBS of Goldwasser

A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4-6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism

Oynophagia in patients after dental extraction: surface electromyography study

OBJECTIVES: Surface electromyographic (sEMG) studies were performed on 40 adult patients following extraction of lower third and second molars to research the approach and limitations of sEMG evaluation of their odynophagia complaints. METHODS: Parameters evaluated during swallowing and drinking include the timing, number of swallows per 100 cc of water, and range (amplitude) of EMG activity of m. masseter, infrahyoid and submental-submandibular group. The above mentioned variables (mean + standard deviation) were measured for the group of dental patients (n = 40) and control group of healthy adults (n = 40). RESULTS: The duration of swallows and drinking in all tests showed increase in dental patients' group, in which this tendency is statistically significant. There was no statistically significant difference between male and female adults' duration and amplitude of muscle activity during continuous drinking in both groups (p = 0.05). The mean of electric activity (in μV) of m. masseter was significantly lower in the dental patients' group in comparison with control group. The electric activity of submental-submandimular and infrahyoid muscle groups was the same in both groups. CONCLUSION: Surface EMG of swallowing is a simple and reliable noninvasive method for evaluation of odynophagia/dysphagia complaints following dental extraction with low level of discomfort of the examination. The surface EMG studies prove that dysphagia following dental extraction and molar surgery has oral origin, does not affect pharingeal segment and submental-submandibular muscle group. This type of dysphagia has clear EMG signs: increased duration of single swallow, longer drinking time, low range of electric activity of m. masseter, normal range of activity of submental-submandibular muscle group, and the "dry swalow" aftereffect. The data can be used for evaluation of complaints and symptoms, as well as for comparison purposes in pre- and postoperative stages and in EMG monitoring during treatment of post-surgical oral cavity discomfort and dysphagia

Integrated Genomic and Gene Expression Profiling Identifies Two Major Genomic Circuits in Urothelial Carcinoma

Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21), and BCL2L1 (20q11). We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development

Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition

Previous in vitro and case–control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre‐diagnostic plasma concentrations of IGF‐I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow‐up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre‐diagnostic circulating IGF‐I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66–1.24, ptrend = 0.40) or UCC (n of cases = 776; 0.91, 0.65–1.26, ptrend = 0.40). There was no significant evidence of heterogeneity in the association of IGF‐I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (pheterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF‐I concentrations and bladder cancer risk

Menstrual factors, reproductive history, hormone use, and Urothelial carcinoma risk: A prospective study in the EPIC cohort

Background: Urothelial carcinoma (UC) is the predominant (95%) bladder cancer subtype in industrialised nations. Animal and epidemiological human studies suggest that hormonal factors may influence UC risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort (EPIC). Associations between hormonal factors and incident UC (overall and by tumour grade, by tumour aggressiveness, and by non-muscle invasive UC) risk were evaluated using Cox proportional hazards models. All models were stratified by age at recruitment and study centre, and adjusted for smoking status and intensity, and fruit and vegetable intakes. Results: During a mean of 15 years of follow-up, 529 women developed UC. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT) showed an inverse association between, number of FTP was inversely associated with UC risk (HR≥5vs1=0.48, 0.25-0.90; P-trend in parous women=0.010) and MHT-use (compared to non-use) was positively associated with UC risk (HR=1.27, 1.03-1.57), but no dose-response by years of MHT-use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analysis in never-smokers showed similar HR patterns for number of FTP and no association between MHT-use and UC risk. Association between MHT-use and UC risk only remained significant in current-smokers. No heterogeneity of the risk estimations in the final model was observed by tumour aggressiveness or by tumour grade. A positive association between the MTH-use and non-muscle invasive UC risk was observed. Conclusion: Increasing number of FTP may reduce UC risk. Our results provided limited evidence for a role of MHT-use in UC risk due to residual confounding by tobacco. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells

Do diagnostic delays in cancer matter?

background: The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis. methods: Scoping review of the published studies, with a focus on methodological issues. results: Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings. conclusion: While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods

Two-year changes in quality of life in elderly patients with low-energy hip fractures. A case-control study

<p>Abstract</p> <p>Background</p> <p>The long-term effect of hip fracture on health-related quality of life (HRQOL) and global quality of life (GQOL) has not been thoroughly studied in prospective case-control studies.</p> <p>Aims</p> <p>a) to explore whether patients with low-energy hip fracture regain their pre-fracture levels in HRQOL and GQOL compared with changes in age- and sex-matched controls over a two year period; b) to identify predictors of changes in HRQOL and GQOL after two years.</p> <p>Methods</p> <p>We examined 61 patients (mean age = 74 years, <it>SD </it>= 10) and 61 matched controls (mean age = 73 years, <it>SD </it>= 8). The Short Form 36 assessed HRQOL and the Quality of Life Scale assessed GQOL. Paired samples <it>t </it>tests and multiple linear regression analyses were applied.</p> <p>Results</p> <p>HRQOL decreased significantly between baseline and one-year follow-up in patients with hip fractures, within all the SF-36 domains (<it>p </it>< 0.04), except for social functioning (<it>p </it>= 0.091). There were no significant decreases within the SF-36 domains in the controls. Significantly decreased GQOL scores (<it>p </it>< 0.001) were observed both within patients and within controls between baseline and one-year follow-up. The same pattern persisted between baseline and two-year follow-up, except for the HRQOL domain mental health (<it>p </it>= 0.193). The patients with hip fractures did not regain their HRQOL and GQOL. Worsened physical health after two years was predicted by being a patient with hip fracture (B = -5.8, <it>p </it>< 0.001) and old age (B = -1.0, <it>p </it>= 0.015), while worsened mental health was predicted by co-morbidity (B = -2.2, <it>p </it>= 0.029). No significant predictors of differential changes in GQOL were identified.</p> <p>Conclusion</p> <p>A hip fracture has a long-term impact on HRQOL and is a strong predictor of worsened physical health. Our data emphasize the importance of preventing hip fracture in the elderly to maintain physical health. This knowledge should be included in decision-making and health care plans.</p