Evolution of the neobladder: A critical review of open and intracorporeal neobladder reconstruction techniques

Orthotopic neobladder is an attractive alternative to the ileal conduit following radical cystectomy. Robotic cystectomy is gaining popularity although the uptake of neobladder reconstruction is low, with the majority of cases being constructed extracorporeally via a mini-laparotomy. Minimally invasive cystectomy using the robotic platform facilitates intracorporeal neobladder reconstruction and several techniques have been described. This review discusses issues relating to patient selection, and describes existing techniques of open surgical neobladder reconstruction and their evolution to suit an intracorporeal approach. A Medline search for publications from January 1970 to September 2015 with the following keyword search criteria was performed: radical cystectomy, robotic cystectomy, intracorporeal, neobladder, orthotopic bladder reconstruction, surgical technique, patient selection and ureteric–ileal anastomosis

Treatment compliance and effectiveness of a cognitive behavioural intervention for low back pain : a complier average causal effect approach to the BeST data set

Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance. Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment. Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation. Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance

Port-site metastases following robotic radical cystectomy: A systematic review and management options

BACKGROUND: Port-site metastases (PSM) are a rare occurrence in robotic surgery. For robot assisted radical cystectomy (RARC), isolated cases have been reported but management has not been described previously. We present a case of PSM that occurred after RARC and perform the results of our systematic review of previously reported port site metastases, and describe treatment options. METHODS: We describe a case of a PSM in a 55-year old gentleman who underwent intracorporeal RARC. We performed a systematic review of MEDLINE and EMBASE databases for previously reported PSMs, detailing the stage and grade of the primary tumour, time to presentation of PSM, treatment offered and outcomes for the identified cases. RESULTS: We identified four cases of PSMs following RARC in the literature, and included our case for analysis. All five cases had muscle invasive bladder cancer at time of cystectomy (>T2) and three of them had local lymph node positive disease. Our aggressive treatment of chemotherapy, wide surgical excision of PSM and radiotherapy has provided the patient a two-year disease-free status. CONCLUSION: PSMs are a rare event in RARC, with only four other cases described in the literature. Outcomes have are not well reported for all of these cases, and we propose that a multi-modality treatment consisting of salvage chemotherapy, surgery and radiotherapy should be considered, but concessions have to be made taking patient factors into account

A simple and robust method for connecting small-molecule drugs using gene-expression signatures

Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

Automated Brainstem Segmentation Detects Differential Involvement in Atypical Parkinsonian Syndromes

OBJECTIVE: Brainstem segmentation has been useful in identifying potential imaging biomarkers for diagnosis and progression in atypical parkinsonian syndromes (APS). However, the majority of work has been performed using manual segmentation, which is time consuming for large cohorts. METHODS: We investigated brainstem involvement in APS using an automated method. We measured the volume of the medulla, pons, superior cerebellar peduncle (SCP) and midbrain from T1-weighted MRIs in 67 patients and 42 controls. Diagnoses were corticobasal syndrome (CBS, n = 14), multiple system atrophy (MSA, n = 16: 8 with parkinsonian syndrome, MSA-P; 8 with cerebellar syndrome, MSA-C), progressive supranuclear palsy with a Richardson’s syndrome (PSP-RS, n = 12), variant PSP (n = 18), and APS not otherwise specified (APS-NOS, n = 7). RESULTS: All brainstem regions were smaller in MSA-C (19–42% volume difference, p < 0.0005) and in both PSP groups (18–33%, p < 0.0005) than in controls. MSA-P showed lower volumes in all regions except the SCP (15–26%, p < 0.0005). The most affected region in MSA-C and MSA-P was the pons (42% and 26%, respectively), while the most affected regions in both the PSP-RS and variant PSP groups were the SCP (33% and 23%, respectively) and midbrain (26% and 24%, respectively). The brainstem was less affected in CBS, but nonetheless, the pons (14%, p < 0.0005), midbrain (14%, p < 0.0005) and medulla (10%, p = 0.001) were significantly smaller in CBS than in controls. The brainstem was unaffected in APS-NOS. CONCLUSION: Automated methods can accurately quantify the involvement of brainstem structures in APS. This will be important in future trials with large patient numbers where manual segmentation is unfeasible

Exceptional river gorge formation from unexceptional floods

An understanding of rates and mechanisms of incision and knickpoint retreat in bedrock rivers is fundamental to perceptions of landscape response to external drivers, yet only sparse field data are available. Here we present eye witness accounts and quantitative surveys of rapid, amphitheatre-headed gorge formation in unweathered granite from the overtopping of a rock-cut dam spillway by small-moderate floods (~100–1,500 m3 s−1). The amount of erosion demonstrates no relationship with flood magnitude or bedload availability. Instead, structural pattern of the bedrock through faults and joints appears to be the primary control on landscape change. These discontinuities facilitate rapid erosion (>270 m headward retreat; ~100 m incision; and ~160 m widening over 6 years) principally through fluvial plucking and block topple. The example demonstrates the potential for extremely rapid transient bedrock erosion even when rocks are mechanically strong and flood discharges are moderate. These observations are relevant to perceived models of gorge formation and knickpoint retreat

Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study

BACKGROUND: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Mapping the genetic architecture of gene expression in human liver

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process. © 2008 Schadt et al