Ureteroscopic biopsy of upper tract urothelial carcinoma and role of urinary biomarkers

Ureteroscopic biopsy is an integral part of diagnosis of urothelial carcinoma of the upper urinary tract. It can be a technical challenge, but diagnostic rates have improved remarkably with refinements in surgical technique and specimen processing. Cytology aids with diagnosis and other urinary biomarkers continue to evolve, which may help further stratify patients for treatment. The current literature on the ureteroscopic biopsy and role of urinary biomarkers is reviewed and summarized below

Characterizing Distances of Networks on the Tensor Manifold

At the core of understanding dynamical systems is the ability to maintain and control the systems behavior that includes notions of robustness, heterogeneity, or regime-shift detection. Recently, to explore such functional properties, a convenient representation has been to model such dynamical systems as a weighted graph consisting of a finite, but very large number of interacting agents. This said, there exists very limited relevant statistical theory that is able cope with real-life data, i.e., how does perform analysis and/or statistics over a family of networks as opposed to a specific network or network-to-network variation. Here, we are interested in the analysis of network families whereby each network represents a point on an underlying statistical manifold. To do so, we explore the Riemannian structure of the tensor manifold developed by Pennec previously applied to Diffusion Tensor Imaging (DTI) towards the problem of network analysis. In particular, while this note focuses on Pennec definition of geodesics amongst a family of networks, we show how it lays the foundation for future work for developing measures of network robustness for regime-shift detection. We conclude with experiments highlighting the proposed distance on synthetic networks and an application towards biological (stem-cell) systems.Comment: This paper is accepted at 8th International Conference on Complex Networks 201

Universal Health Care Coverage in Massachusetts: A Follow-up on the Effects on Neurosurgical Practice

Background: It has been four years since the introduction of universal health care coverage in Massachusetts. Our initial assessment performed from 2007-2008 demonstrated largely positive results. Objectives: We performed a follow-up study to assess the long term financial impact of universal health care on hospital charges associated with neurosurgical operative cases at our institution. Methods: The billing records from July 1, 2009 – June 30, 2010 were compared to those from 2007 and 2008. Records were analyzed for length of stay, case mix, patient age, hospital charge, reimbursement, and procedure. Results: Case volume increased by 31% and mean acuity increased from 2.3 to 3.1 (p \u3c 0.005). Hospital stays lengthened by 1 day (p \u3c 0.005). Payor mix changed over this time with Commonwealth Care and Medicaid comprising 2.9% and 12.4%, respectively, of neurosurgical inpatients; neither had significantly different acuity or lengths of stay. Despite an increase in case volume by 31% and significantly increased acuity in 2010, revenue increased 14% over early reform data. When volume was normalized, extrapolations of pre-reform and early reform coverage on current financials demonstrated that the change in payor mix alone had decreased revenue by 30% and 24%, respectively. When modifying 2010 financials by considering 2007 reimbursement rates and 2007 payor mix, these changes together resulted in a revenue reduction of 36%. Conclusions: Taken together, our data suggests that revenue associated with hospital charges for neurosurgical inpatients has decreased significantly since health care reform went into effect

Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men

The significance of functional renal obstruction in predicting pathologic stage of upper tract urothelial carcinoma.

BACKGROUND AND PURPOSE: Assessing the severity of upper tract urothelial carcinoma (UTUC) has been difficult because of inadequate biopsy specimens. Additional predictive parameters of disease stage would be useful when deciding a treatment plan; it has been suggested that preoperative hydronephrosis can be a surrogate. We examined the relationship between preoperative ipsilateral renal obstruction identified by imaging with final pathologic stage after nephroureterectomy (NU) for UTUC. We then analyzed those patients with ipsilateral renal obstruction and examined if tumor location is associated with an advanced pathologic stage. METHODS: Patients who underwent NU for UTUC between the years 2001 to 2013 were analyzed and relevant staging studies and pathology were reviewed. Criteria for ipsilateral renal obstruction were defined by the presence of a delayed nephrogram on CT scan, renal cortical atrophy with associated hydronephrosis on cross-sectional imaging, and/or \u3e10% split function discrepancy on nuclear renal scintigraphy with associated hydronephrosis. RESULTS: Eighty-two patients met inclusion criteria; 26/82 (31.7%) had locally advanced disease (pT3/T4), while 56/82 (63.4%) had organ-confined (≤pT2) disease. Of the patients with pT3/T4 disease, 10/26 (38.5%) demonstrated radiographic evidence of functional obstruction of the ipsilateral renal unit; similarly, in patients with ≤pT2 disease, 21/56 (37.5%) demonstrated ipsilateral renal obstruction (P=0.93). Of the patients with ipsilateral renal obstruction, in those patients with pT3/T4 disease, 7/10 (70.0%) had ureteral tumor involvement while 9/21 (42.9%) patients with ≤pT2 disease had tumor in the ureter (P=0.25). CONCLUSIONS: This study suggests that renal obstruction by radiographic analysis does not always predict advanced stage. In addition, there is a trend toward advanced stage when a patient has radiographic evidence of ipsilateral renal dysfunction and a ureteral tumor

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

The Minimally Invasive Management of Ureteropelvic Junction Obstruction in Horseshoe Kidneys

Purpose: Data regarding the treatment of ureteropelvic junction obstruction (UPJO) in horseshoe kidneys are limited. We performed a retrospective analysis of our experience with minimally invasive treatment of UPJO in patients with this anomaly. Methods: Between March of 1996 and March 2008, 9 patients with horseshoe kidneys were treated for UPJO at our institution. Of these patients, 6 were managed with retrograde endopyelotomy, 2 with laparoscopic pyeloplasty, and one by robotic pyeloplasty. Outcomes of these procedures were retrospectively reviewed. Results: A total of nine patients were available for analysis. Four of six patients who underwent endopyelotomy had available follow-up, with a mean of 56 months. The success rate for these patients was 75%. Two of three patients (67%) in the laparoscopic/robotic cohort were successfully treated with a mean follow-up of 21 months. Conclusions: UPJO in horseshoe kidneys can pose a therapeutic dilemma. The minimally invasive treatment of these patients is feasible with good success rates for both endopyelotomy and laparoscopic/robotic pyeloplast

A Genomic Pathway Approach to a Complex Disease: Axon Guidance and Parkinson Disease

While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics). The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance) predisposed to a complex disease (Parkinson disease [PD]). We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs) that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 × 10−38), survival free of PD (hazards ratio = 19.0, p = 5.43 × 10−48), and PD age at onset (R2 = 0.68, p = 1.68 × 10−51). By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers