In vitro prediction of in vivo absorption of ibuprofen from suspensions through rational choice of dissolution conditions.

Two ibuprofen suspension formulations were investigated for their dissolution in various bicarbonate, phosphate and acetate buffers. Phosphate and acetate gave faster release than bicarbonate at comparable molarities. Nevertheless, mass transport modelling using the reversible non-equilibrium (RNE) approach enabled the calculation of phosphate molarities that gave good matches to physiological bicarbonate in terms of ibuprofen dissolution.

A novel technique for intraduodenal administration of drug suspensions/solutions with concurrent pH monitoring applied to ibuprofen formulations.

Characterization of dissolution of solid suspended drug particles in vivo is important for developing biopredictive in vitro tests. Therefore, methods to gain deeper insights into particle dissolution in vivo are needed. The soft Bioperm intubation method, a well established tool for investigation of permeability, absorption, metabolism, and drug interactions at predefined locations in the gastroinstinal tract, was modified.

Long-term third-party assessment of results after continent cutaneous diversion with Lundiana pouch.

Objectives: To investigate the long-term functional outcomes and complications after continent cutaneous diversion with the Lundiana pouch.

Patients And Methods: Complications, re-operations, renal function, and continence were ascertained from patient charts. Outcome variables were validated by a second and independent review of the patient files.

A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma.

Background: One third of patients with stage T1 urothelial carcinoma (UC) progress to muscle-invasive disease requiring radical surgery. Thus, reliable tools are needed for risk stratification of stage T1 UC.

Objective: To investigate the extent to which stratification of stage T1 tumours into previously described molecular pathologic UC subtypes can provide improved information on tumour progression.

Urinary diversion: how experts divert.

Objective: To determine the rates of the available urinary diversion options for patients treated with radical cystectomy for bladder cancer in different settings (pioneering institutions, leading urologic oncology centers, and population based).

Methods: Population-based data from the literature included all patients (n = 7608) treated in Sweden during the period 1964-2008, from Germany (n = 14,200) for the years 2008 and 2011, US patients (identified from National Inpatient Sample during 1998-2005, 35,370 patients and 2001-2008, 55,187 patients), and from Medicare (n = 22,600) for the years 1992, 1995, 1998, and 2001. After the International Consultation on Urologic Diseases-European Association of Urology International Consultation on Bladder Cancer 2012, the urinary diversion committee members disclosed data from their home institutions (n = 15,867), including the pioneering institutions and the leading urologic oncology centers.

Urostomy and health-related quality of life in patients with lower urinary tract dysfunction.

Objective: Urinary diversion may be an option in patients with disabling lower urinary tract dysfunction (DLUTD), refractory to conservative and minor invasive treatment. The aim of this study was to evaluate whether urostomy improves quality of life and cost of surgery, in terms of complications, loss of kidney function and hospital stay, in these patients.

Material And Methods: This prospective study included 52 consecutive patients (nine men and 43 women) with various benign disorders.

Infiltration of CD3⁺ and CD68⁺ cells in bladder cancer is subtype specific and affects the outcome of patients with muscle-invasive tumors.

Objectives: Urothelial carcinoma (UC) aggressiveness is determined by tumor inherent molecular characteristics, such as molecular subtypes, as well as by host reactions directed toward the tumor. Cell types responsible for the host's response include tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). The aim of the present investigation was to explore the immunological response in relation to UC molecular subtypes and to evaluate the prognostic effect of TIL and TAM counts in tissue sections from muscle-invasive (MI) tumors.

Functional results after orthotopic bladder substitution: a prospective multicentre study comparing four types of neobladder.

Objective: The aim of this study was to evaluate enterocystometry, voiding pattern and urine leakage of four types of orthotopic bladder substitute.

Material And Methods: At eight urological departments, 78 consecutive men were studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)] neobladder. Enterocystometry, determination of residual urine, micturition protocol and 24 h pad weight test were performed 6 and 12 months postoperatively.

Toward a molecular pathologic classification of urothelial carcinoma.

We recently defined molecular subtypes of urothelial carcinomas according to whole genome gene expression. Herein we describe molecular pathologic characterization of the subtypes using 20 genes and IHC of 237 tumors. In addition to differences in expression levels, the subtypes show important differences in stratification of protein expression.

Impact of hospital volume on local recurrence and distant metastasis in bladder cancer patients treated with radical cystectomy in Sweden.

Objective: This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden.

Material And Methods: All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with ≥10 cystectomies/year and a low-volume hospital (LVH) as one with <10 cystectomies/year.

ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion.

Context: A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications.

Objective: To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD).

Evidence Acquisition: An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken.

Preoperative staging of locally advanced bladder cancer before radical cystectomy using 3 tesla magnetic resonance imaging with a standardized protocol.

Objective: The correlation between clinical tumour stage and pathological tumour stage in radical cystectomy specimens in locally advanced bladder cancer is suboptimal. Radiological methods have so far been of limited value in preoperative staging; however, the resolution with magnetic resonance imaging (MRI) has improved with further technical developments of the method. The aim of this study was to compare tumour stage at MRI with pathological tumour stage in the cystectomy specimen.

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.

A molecular taxonomy for urothelial carcinoma.

Purpose: Even though urothelial cancer is the fourth most common tumor type among males, progress in treatment has been scarce. A problem in day-to-day clinical practice is that precise assessment of individual tumors is still fairly uncertain; consequently efforts have been undertaken to complement tumor evaluation with molecular biomarkers. An extension of this approach would be to base tumor classification primarily on molecular features.

The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

Unlabelled: It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now.

A systematic study of gene mutations in urothelial carcinoma; inactivating mutations in TSC2 and PIK3R1.

Background: Urothelial carcinoma (UC) is characterized by frequent gene mutations of which activating mutations in FGFR3 are the most frequent. Several downstream targets of FGFR3 are also mutated in UC, e.g.

Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?

Objective: Being able to predict the recurrence or progression of non-muscle-invasive bladder cancer would facilitate effective planning of treatments and follow-up. Biomarkers are needed that can supply prognostic information beyond that provided by clinical and pathological parameters. Tissue microarray (TMA)-based analysis of Ta bladder tumours was used to investigate the prognostic value of expression of several proteins involved in bladder carcinogenesis.

Pelvic exenteration for advanced and recurrent malignancy.

Background: Improved surgical techniques and oncological treatment render many advanced pelvic tumors amenable to curative resection. We evaluated morbidity, survival, and quality of life (QoL) after extended pelvic procedures.

Methods: From January 2003 to November 2008, 85 patients underwent multivisceral pelvic resection; 87% had colorectal or anal malignancies.

Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome.

In the present investigation, we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes, we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1 in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets.

Prevention and management of complications following radical cystectomy for bladder cancer.

Context: This review focuses on the prevention and management of complications following radical cystectomy (RC) for bladder cancer (BCa).

Objective: We review the current literature and perform an analysis of the frequency, treatment, and prevention of complications related to RC for BCa.

Evidence Acquisition: A Medline search was conducted to identify original articles, reviews, and editorials addressing the relationship between RC and short- and long-term complications.

Urinary diversion after cystectomy for bladder cancer: a population-based study in Sweden.

Objective: To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register.

Material And Methods: Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion).