Fesoterodine Ameliorates Autonomic Dysreflexia While Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals With Spinal Cord Injury: A Prospective Phase IIa Study.

The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). Twelve participants (four females, eight males; median age 42 years) completed this study and underwent urodynamics, 24-h ambulatory blood pressure monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. Compared with baseline, fesoterodine improved lower urinary tract (LUT) function, that is, increased cystometric capacity (205 vs. 475 mL, p = 0.002) and decreased maximum detrusor pressure (44 vs. 12 cm H2O, p = 0.009). NDO was eliminated in seven (58%) participants. Severity of AD events during urodynamics (40 vs. 27 mm Hg, p = 0.08) and 24-h ABPM (59 vs. 36 mm Hg, p = 0.05) were both reduced, yielding a large effect size (r = -0.58). AD Frequency (14 vs. 3, p = 0.004) during 24-h ABPM was significantly reduced. Urinary incontinence-related QoL improved (68 vs. 82, p = 0.02), however, cognitive (p = 0.2) and bowel function (p = 0.4) did not change significantly. In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.

Method for simultaneous tracking of thousands of unlabeled cells within a transparent 3D matrix.

Three-dimensional tracking of cells is one of the most powerful methods to investigate multicellular phenomena, such as ontogenesis, tumor formation or wound healing. However, 3D tracking in a biological environment usually requires fluorescent labeling of the cells and elaborate equipment, such as automated light sheet or confocal microscopy. Here we present a simple method for 3D tracking large numbers of unlabeled cells in a collagen matrix. Using a small lensless imaging setup, consisting of an LED and a photo sensor only, we were able to simultaneously track ~3000 human neutrophil granulocytes in a collagen droplet within an unusually large field of view (>50 mm2) at a time resolution of 4 seconds and a spatial resolution of ~1.5 µm in xy- and ~30 µm in z-direction. The setup, which is small enough to fit into any conventional incubator, was used to investigate chemotaxis towards interleukin-8 (IL-8 or CXCL8) and N-formylmethionyl-leucyl-phenylalanine (fMLP). The influence of varying stiffness and pore size of the embedding collagen matrix could also be quantified. Furthermore, we demonstrate our setup to be capable of telling apart healthy neutrophils from those where a condition of inflammation was (I) induced by exposure to lipopolysaccharide (LPS) and (II) caused by a pre-existing asthma condition. Over the course of our experiments we have tracked more than 420.000 cells. The large cell numbers increase statistical relevance to not only quantify cellular behavior in research, but to make it suitable for future diagnostic applications, too.

Intradetrusor OnabotulinumtoxinA Injections Ameliorate Autonomic Dysreflexia while Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals with Cervical and Upper Thoracic Spinal Cord Injury.

Pilot data of our phase IV clinical trial (pre/post study design) highlighted a beneficial effect of intradetrusor onabotulinumtoxinA (200 IU) injections to reduce autonomic dysreflexia (AD) in individuals with chronic spinal cord injury (SCI) at T6 or above. After trial completion, we assessed whether our primary expectation (i.e., decrease of AD severity in 50% of participants during urodynamics [UDS]) was met. Secondary outcome measures were reduction of spontaneous AD in daily life as well as amelioration of AD-related and urinary incontinence-related quality of life (QoL). In addition, we conducted injury-level-dependent analysis-i.e., cervical and upper thoracic-to explore group-specific treatment efficacy. Post-treatment, AD severity decreased in 82% (28/34) of all participants during UDS and in 74% (25/34) in daily life assessed with 24-h ambulatory blood pressure monitoring. In addition, urinary incontinence-related QoL was improved, cystometric capacity was increased, and maximum detrusor pressure during storage was reduced (all p < 0.001). Further, the treatment was well tolerated, with only minor complications (grade I [n = 7] and II [n = 7]) in accordance with the Clavien-Dindo classification recorded in 11 individuals (cervical n = 9, upper thoracic n = 2). Injury-level-dependent analysis revealed lower incidence (cervical n = 15/23, upper thoracic n = 6/11) and lesser severity (cervical p = 0.009; upper thoracic p = 0.06 [Pearson r = -0.6, i.e., large effect size]) of AD during UDS. Further, reduced AD severity in daily life, improved urinary incontinence-related QoL, greater cystometric capacity, and lower maximum detrusor pressure during storage (all p < 0.05) were found in both groups post-treatment. Intradetrusor onabotulinumtoxinA injections are an effective and safe second-line treatment option that ameliorates AD while improving lower urinary tract function and urinary incontinence-related QoL in individuals with cervical and upper thoracic SCI.

Protocol for a phase II, open-label exploratory study investigating the efficacy of fesoterodine for treatment of adult patients with spinal cord injury suffering from neurogenic detrusor overactivity for amelioration of autonomic dysreflexia.

INTRODUCTION: Managing and preventing risk factors associated with cardiovascular and cerebrovascular impairment is well studied in able-bodied individuals. However, individuals with spinal cord injury (SCI) at or above the spinal segment T6 are prone to experience autonomic dysreflexia (AD) but also to suffer from neurogenic detrusor overactivity (NDO). Treatment of NDO would not only improve lower urinary tract function but could also reduce the severity and frequency of life-threatening episodes of AD. Fesoterodine, an antimuscarinic drug, has been successfully employed as a first-line treatment for detrusor overactivity in individuals without an underlying neurological disorder. Thus, our aim is to investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with SCI. METHODS AND ANALYSIS: This phase II, open-label exploratory, non-blinded, non-randomised, single-centre study will investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with chronic SCI at or above T6. During screening, we will interview potential candidates (with a previous history of NDO and AD) and assess their injury severity. At baseline, we will perform cardiovascular and cerebrovascular monitoring (blood pressure (BP), heart rate and cerebral blood flow velocity) during urodynamics (UDS) and 24-hour ambulatory BP monitoring (ABPM) during daily life to assess severity and frequency of AD episodes (ie, maximum increase in systolic BP). The primary outcome is a reduction of artificially induced (during UDS) and spontaneous (during daily life) episodes of AD as a display of treatment efficacy. To answer this, we will repeat UDS and 24-hour ABPM during the last cycle of the treatment phase (12 weeks overall, ie, three cycles of 4 weeks each). At the end of each treatment cycle, participants will be asked to answer standardised questionnaires (AD symptoms and quality of life) and present bladder and bowel diaries, which will provide additional subjective information. ETHICS AND DISSEMINATION: The University of British Columbia Research Ethics Boards (H15-02364), Vancouver Coastal Health Research Institute (V15-02364) and Health Canada (205857) approved this study. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials and CONsolidated Standards Of Reporting Trials statements. TRIAL REGISTRATION NUMBER: NCT02676154; Pre-results.

Reduction in Bladder-Related Autonomic Dysreflexia after OnabotulinumtoxinA Treatment in Spinal Cord Injury.

Bladder-related events, including neurogenic detrusor overactivity, are the leading cause of autonomic dysreflexia in spinal cord injured individuals. Self-reported autonomic dysreflexia is reduced following onabotulinumtoxinA treatment for neurogenic detrusor overactivity; however, none of these trials have assessed autonomic dysreflexia events using the clinical cutoff of an increase in systolic blood pressure ≥20 mm Hg. This study used a prospective, open-labelled design from 2013 to 2014 to quantitatively assess the efficacy of one cycle 200 U intradetrusor-injected onabotulinumtoxinA (20 sites) on reducing the severity and frequency of bladder-related autonomic dysreflexia events and improving quality of life. Twelve men and five women with chronic, traumatic spinal cord injuries at or above the sixth thoracic level, and concomitant autonomic dysreflexia and neurogenic detrusor overactivity, underwent blood pressure monitoring during urodynamics and over a 24 h period using ambulatory blood pressure monitoring pre- and 1 month post-treatment. Post-onabotulinumtoxinA, autonomic dysreflexia severity was reduced during urodynamics (systolic blood pressure increase: 42 ± 23 mm Hg vs. 20 ± 10 mm Hg, p < 0.001) and during bladder-related events across the 24 h period (systolic blood pressure increase: 49 ± 2 mm Hg vs. 26 ± 22 mm Hg, p = 0.004). Frequency of 24 h bladder-related autonomic dysreflexia events was also decreased post-onabotulinumtoxinA (4 ± 2 events vs. 1 ± 1 events, p < 0.001). Autonomic dysreflexia and incontinence quality of life indices were also improved post-onabotulinumtoxinA (p < 0.05). Intradetrusor injections of onabotulinumtoxinA for the management of neurogenic detrusor overactivity in individuals with high level spinal cord injuries decreased the severity and frequency of bladder-related episodes of autonomic dysreflexia, and improved bladder function and quality of life.

LPS-Stimulated Human Skin-Derived Stem Cells Enhance Neo-Vascularization during Dermal Regeneration.

High numbers of adult stem cells are still required to improve the formation of new vessels in scaffolds to accelerate dermal regeneration. Recent data indicate a benefit for vascularization capacity by stimulating stem cells with lipopolysaccharide (LPS). In this study, stem cells derived from human skin (SDSC) were activated with LPS and seeded in a commercially available dermal substitute to examine vascularization in vivo. Besides, in vitro assays were performed to evaluate angiogenic factor release and tube formation ability. Results showed that LPS-activated SDSC significantly enhanced vascularization of the scaffolds, compared to unstimulated stem cells in vivo. Further, in vitro assays confirmed higher secretion rates of proangiogenic as well as proinflammatoric factors in the presence of LPS-activated SDSC. Our results suggest that combining activated stem cells and a dermal substitute is a promising option to enhance vascularization in scaffold-mediated dermal regeneration.

Transperineal approach to complex rectourinary fistulae.

INTRODUCTION: We sought to present our experience and outcomes in patients with complex rectourethral fistulae (RUF) treated using the transperineal approach with gracilis muscle flap interposition. Complex RUF was defined as having prior radiation, failed repair attempts, and large size (>2 cm). METHODS: A retrospective review identified 10 patients presenting with complex RUF between July 2009 and November 2013. Three were excluded due to large fistula defects managed with urinary diversion. Seven patients met inclusion criteria and underwent reconstruction. RESULTS: Six of 7 patients had prostate cancer, and one patient had colon cancer treated with low anterior resection with adjuvant radiation. The primary modality of prostate cancer therapy was brachytherapy (n=3), external beam radiotherapy (n=2) and radical retropubic prostatectomy (RRP) (n=1). Three patients had salvage cancer therapy, including RRP (n=1), cystoprostatectomy with ileal conduit (n=1), and cryotherapy (n=1). One patient developed RUF post-primary RRP without radiation. Mean fistula size was 2.8cm (2-4 cm). No fistulas recurred at mean follow-up 11.4 months (6-20 months). Three patients have had colostomy reversal, one is pending reversal and three have permanent colostomies. Five patients have stress urinary incontinence, with two managed with one to four pads per day, one managed with a condom catheter, and two waiting for artificial urinary sphincter (AUS). One patient developed a perineal wound infection and one developed a pulmonary embolus treated medically. CONCLUSION: Complex RUF defects are effectively treated with transperineal repair using gracilis muscle interposition. The procedure has low morbidity and high success. Concomitant stress incontinence and bladder outlet contracture are prevalent in this population and may require ongoing management.

A simple implantation method for flexible, multisite microelectrodes into rat brains.

A long term functional and reliable coupling between neural tissue and implanted microelectrodes is the key issue in acquiring neural electrophysiological signals or therapeutically excite neural tissue. The currently often used rigid micro-electrodes are thought to cause a severe foreign body reaction resulting in a thick glial scar and consequently a poor tissue-electrode coupling in the chronic phase. We hypothesize, that this adverse effect might be remedied by probes compliant to the soft brain tissue, i.e., replacing rigid electrodes by flexible ones. Unfortunately, this flexibility comes at the price of a low stiffness, which makes targeted low trauma implantation very challenging. In this study, we demonstrate an adaptable and simple method to implant extremely flexible microprobes even to deep areas of rat's brain. Implantation of flexible probes is achieved by rod supported stereotactic insertion fostered by a hydrogel (2% agarose in PBS) cushion on the exposed skull. We were thus able to implant very flexible micro-probes in 70 rats as deep as the rodent's subthalamic nucleus. This work describes in detail the procedures and steps needed for minimal invasive, but reliable implantation of flexible probes.

Photonic crystal slabs for surface contrast enhancement in microscopy of transparent objects.

In optical microscopy the contrast of transparent objects achieved with conventional methods is often not satisfactory, for example for the automated recognition of cells. In this paper we present a nano-optical label-free approach for contrast enhancement based on photonic crystal slabs (PCS) as the specimen holder. Quasi-guided modes inside these structures cause an intrinsic color of the PCS, which strongly depends on the wavelength and the quality factor of the optical mode. Objects on the surface of the PCS experience a significant color and intensity contrast enhancement, as they change properties of the optical modes.

A novel validation algorithm allows for automated cell tracking and the extraction of biologically meaningful parameters.

Automated microscopy is currently the only method to non-invasively and label-free observe complex multi-cellular processes, such as cell migration, cell cycle, and cell differentiation. Extracting biological information from a time-series of micrographs requires each cell to be recognized and followed through sequential microscopic snapshots. Although recent attempts to automatize this process resulted in ever improving cell detection rates, manual identification of identical cells is still the most reliable technique. However, its tedious and subjective nature prevented tracking from becoming a standardized tool for the investigation of cell cultures. Here, we present a novel method to accomplish automated cell tracking with a reliability comparable to manual tracking. Previously, automated cell tracking could not rival the reliability of manual tracking because, in contrast to the human way of solving this task, none of the algorithms had an independent quality control mechanism; they missed validation. Thus, instead of trying to improve the cell detection or tracking rates, we proceeded from the idea to automatically inspect the tracking results and accept only those of high trustworthiness, while rejecting all other results. This validation algorithm works independently of the quality of cell detection and tracking through a systematic search for tracking errors. It is based only on very general assumptions about the spatiotemporal contiguity of cell paths. While traditional tracking often aims to yield genealogic information about single cells, the natural outcome of a validated cell tracking algorithm turns out to be a set of complete, but often unconnected cell paths, i.e. records of cells from mitosis to mitosis. This is a consequence of the fact that the validation algorithm takes complete paths as the unit of rejection/acceptance. The resulting set of complete paths can be used to automatically extract important biological parameters with high reliability and statistical significance. These include the distribution of life/cycle times and cell areas, as well as of the symmetry of cell divisions and motion analyses. The new algorithm thus allows for the quantification and parameterization of cell culture with unprecedented accuracy. To evaluate our validation algorithm, two large reference data sets were manually created. These data sets comprise more than 320,000 unstained adult pancreatic stem cells from rat, including 2592 mitotic events. The reference data sets specify every cell position and shape, and assign each cell to the correct branch of its genealogic tree. We provide these reference data sets for free use by others as a benchmark for the future improvement of automated tracking methods.

Isolation and in vitro cultivation turns cells from exocrine human pancreas into multipotent stem-cells.

Several research groups have reported on the existence and in vitro characterization of multipotent stem-cells from the pancreas. However, the origin of these cells remains largely unexplained. Here, we report that in vitro culturing itself can turn adult cells from human exocrine pancreas into a cell population with typical stem cell characteristics. A simple, yet reliable method enabled us to track cell fates: Combining automated continuous observation using time-lapse microscopy with immunocytochemical analyses, we found that a significant fraction of the pancreatic cells ( approximately 14%) can survive trypsination and displays a drastic change in the protein expression profile. After further cultivation, these cells give rise to a heterogeneous cell population with typical multipotent stem cell characteristics; i.e. they proliferate over long time periods and continuously give rise to specialized cells from at least two germ layers. Although we cannot exclude that a rare pre-existing stem cell-type also contributes to the final in vitro-population, the majority of cells must have been arisen from mature pancreatic cells. Our findings indicate that multipotent cells for regenerative medicine, instead of being laboriously isolated, can be generated in large amounts by in vitro de-differentiation.

The use of glandular-derived stem cells to improve vascularization in scaffold-mediated dermal regeneration.

Clinical success in tissue regeneration requires improvements in vascularization capacity of scaffolds. Several efforts have been made in this field including cellular and acellular technologies. In this work we combined the use of stem cells derived from pancreas or submandibular glands expressing green fluorescent protein (GFP(+)) with a commercially available scaffold for dermal regeneration. Cells were isolated, characterized and seeded in a scaffold for dermal regeneration. Scaffolds containing cells were used to induce dermal regeneration in a full skin defect model. After 3 weeks of in vivo regeneration, tissues were harvested and vascularization was analyzed. Results showed that gland-derived stem cells displayed stem cell features and presented multipotential differentiation capacity because they were able to differentiate in cell types representing the 3 different germ layers. After seeding, cells were homogeneously distributed and formed focal adhesions with the scaffold. Metabolic assays showed that cells can be cultured for at least 3 weeks in the scaffold. In vivo, the presence of pancreatic or submandibular stem cells significantly enhanced the vascularization compared to empty scaffolds. Presence of gland-derived stem cells in the regenerating tissue was confirmed by the detection of GFP expression in the wound area. In order to explore the possible mechanisms behind the improvement in vascular regeneration, in vitro experiments were performed, showing that gland-derived stem cells could contribute by angiogenic and vasculogenic mechanisms to this process. Our results suggest that the combined use of stem cells derived from glands and scaffold for dermal regeneration could be a rational alternative to improve vascularization in scaffold-mediated dermal regeneration.

Cryobanking of viable biomaterials: implementation of new strategies for conservation purposes.

Cryobanking, the freezing of biological specimens to maintain their integrity for a variety of anticipated and unanticipated uses, offers unique opportunities to advance the basic knowledge of biological systems and their evolution. Notably, cryobanking provides a crucial opportunity to support conservation efforts for endangered species. Historically, cryobanking has been developed mostly in response to human economic and medical needs - these needs must now be extended to biodiversity conservation. Reproduction technologies utilizing cryobanked gametes, embryos and somatic cells are already vital components of endangered species recovery efforts. Advances in modern biological research (e.g. stem cell research, genomics and proteomics) are already drawing heavily on cryobanked specimens, and future needs are anticipated to be immense. The challenges of developing and applying cryobanking for a broader diversity of species were addressed at an international conference held at Trier University (Germany) in June 2008. However, the magnitude of the potential benefits of cryobanking stood in stark contrast to the lack of substantial resources available for this area of strategic interest for biological science - and society at large. The meeting at Trier established a foundation for a strong global incentive to cryobank threatened species. The establishment of an Amphibian Ark cryobanking programme offers the first opportunity for global cooperation to achieve the cryobanking of the threatened species from an entire vertebrate class.

Glandular stem cells are a promising source for much more than beta-cell replacement.

Glandular stem cells (GSCs) can be obtained from exocrine glands such as pancreas or salivary glands using well-established cell culturing methods. The resulting cell populations are characterized by a high proliferative capacity and an unusually high plasticity. Cells from pancreas have been demonstrated to differentiate into a multitude of cell types and even into oocyte-like cells. It has been found that the preparation method for GSCs can be applied to many vertebrates, including fishes and birds. Since the cells are excellently cryopreservable, this finding has been utilized to establish a new stem cell bank for preserving living cells of rare and wild animals. Apart from these advances, this mini-review also points out that GSCs from pancreas must not be confused with beta-cell progenitors but constitute a distinct cell type.

Towards a pragmatic strategy for regenerating infarcted myocardium with glandular stem cells.

We have recently reported that the in vitro differentiation of human glandular stem cells into cardiac-like cells can be enhanced by co-culture with small myocardial biopsies. These results suggest that implantation of such cells directly into infarcted myocardium may facilitate the regeneration of the heart. As a preliminary to testing this approach in a goat model, pilot in vitro tests for these experiments have been performed and are presented here. Stem cells, isolated from the glandula submandibularis of Boer goats (SuSCs), have been co-cultured either directly or indirectly with heart biopsies from various species (Boer goat, rattus norwegicus, human) or heart conditioned medium for 48h. We found a substantial increase in the number of cells expressing heart-specific marker proteins (Troponin I, Troponin T, sarcomeric myosin) regardless of the source organism of the heart biopsy. The proliferation of SuSCs also increased significantly under co-culture conditions. To benefit from these results in vivo, the stem cells must be delivered to the infarcted region in the heart and held securely in place over lengthy periods of time. Therefore, we repeated the co-culture experiments with SuSCs grown on biodegradable Vicryl-meshes. The cells demonstrated good proliferation on the meshes and likewise, the expression of heart-specific marker proteins could be enhanced through co-culture with heart biopsies.

Complications of the catheterizable channel following continent urinary diversion: their nature and timing.

PURPOSE: We reviewed the incidence, nature and timing of complications related to the catheterizable channel following continent urinary diversion. MATERIALS AND METHODS: We retrospectively reviewed the records of 67 patients who underwent continent urinary diversion at British Columbia Children's Hospital from 2000 to 2006. Catheterizable channels included 54 Mitrofanoff appendicovesicostomies and 13 ileovesicostomies. Medical records were reviewed for predetermined complications and their timing, that is early -12 months or less, or late - more than 12 months. RESULTS: At a median followup of 28 months (range 3 to 62) a total of 17 complications were identified in 14 patients (21%). Superficial cutaneous stenosis developed in 4 of 67 cases (6%) as an early and as a late complication. These cases were initially treated with operative dilation and surgical revision as necessary. Channel stricture, which developed in 4 of 67 patients (6%) as an early and as a late complication, was treated with operative revision in 2 and endoscopic resection in 2. Three patients (5%) had stomal prolapse, which was generally a late occurrence and required operative revision in all. Channel leakage developed in 6 of 67 patients, presenting as an early complication in 50%. Endoscopic injection of bulking agents was attempted in 4 of these patients and it was successful in 2. Overall 82% of complications were successfully managed by endoscopic or superficial procedures. CONCLUSIONS: Complications of the catheterizable channel are a frequent and challenging problem. They appear to occur throughout the life of the channel with most developing within the first 2 years. Further followup is required to assess the performance and durability of continent catheterizable channels in children as patients progress to adulthood.

Ureteral access sheath use and stenting in ureteroscopy: effect on unplanned emergency room visits and cost.

PURPOSE: We studied the impact of stented and unstented ureteroscopy on unplanned emergency room (ER) return visits, medical costs, and whether use of a ureteral access sheath precluded uncomplicated ureteroscopy. PATIENT AND METHODS: A series of 161 consecutive patients undergoing ureteroscopy for renal or ureteral stones was evaluated retrospectively. We examined sex, age, stone size, stone location, use of a ureteral access sheath, use of a ureteral stent, unplanned ER visits, unplanned imaging, and interventions. Medical costs were calculated according to British Columbia Medical Services Plan rates. RESULTS: In the 107 stented and 54 unstented patients, the mean stone sizes were 9 and 7 mm, respectively (P = 0.01), and ureteral access sheaths were used in 55% and 35% (P = 0.002). Stent use did not differ by patient age or sex or stone location. The ER return rates were 17% v 22% for the stented and unstented patients, respectively (P = 0.40), with emergency CT scans being performed in 28% v 75% of the returning patients (P = 0.02), hospital readmission in 22% v 58% (P = 0.05), and urgent decompression in 0 v 25% (P = 0.04). Among patients who were not stented, 37% of those treated using ureteral access sheaths v 14% treated without access sheaths returned to the ER (P = 0.04). The median costs were CDN dollars 1212 for stented and CDN dollars1071 for unstented patients (P < 0.0001). CONCLUSIONS: The unplanned ER return rate is similar whether patients are stented or unstented after ureteroscopy. The median cost saving for unstented patients is approximately CDN dollars140. Use of a ureteral access sheath precludes uncomplicated ureteroscopy, and a ureteral stent should be placed in these cases.

Urachal-sigmoid fistula associated with diverticular disease.

BACKGROUND: Urachal anomalies rarely present in adulthood. We report the second known case of urachal-sigmoid fistula associated with diverticular disease. METHOD: We performed a case report and literature review. We searched MEDLINE and PubMed using the search words "urachus," "urachal fistula," "sigmoid colon" and "diverticulosis." RESULTS: Our literature review revealed 1 previous report of urachal-sigmoid fistula associated with diverticular disease. We reviewed other publications with respect to pathophysiology, diagnosis and management of urachal disease. CONCLUSION: Urachal disease that presents in an adult is usually the result of some complication of a urachal anomaly. Various modes of imaging may help confirm the diagnosis, although CT sinography has been recommended and was key in the present case. Management includes eradication of infection and, usually, surgical intervention.

Adult pancreatic stem/progenitor cells spontaneously differentiate in vitro into multiple cell lineages and form teratoma-like structures.

Cells isolated from pancreas have a remarkable potential for self-renewal and multilineage differentiation. We here present a comprehensive characterisation of stem/progenitor cells derived from exocrine parts of the adult rat pancreas. Using purified cells from either single colonies or even single-cell clones, we specifically demonstrate: (i) the cells contain the typical stem/progenitor cell markers alkaline phophatase, SSEA-1, Oct-4, CD9, Nestin, Pax6, CD44, a-Fetoprotein and Brachyury, demonstrated by immunocytochemistry and RT-PCR; (ii) the cells have the potential to differentiate into lineages of all three germ layers in vitro; (iii) a clonal analysis revealed that even cell lines derived from a single cell have stem/progenitor cell properties such as self-renewal and spontaneous differentiation into various cell lineages; (iv) the cells have the propensity to form three-dimensional, teratoma-like structures in vitro, which contain cells of different lineages; and (v) external stimuli can activate the generation of certain cell types. For instance, cells treated with retinoic acid show an increased expression of alpha-smooth muscle actin. These results suggest that exocrine glands, such as pancreas may be a potential source of adult stem/progenitor cells, suitable for cell therapy of degenerative diseases.

The challenge of pediatric continent urinary diversion.

OBJECTIVE: Continent urinary diversion (CUD) may be required for refractory incontinence in children with various malformations. We review our experience with CUD to identify determinants of success and ongoing challenges. METHODS: Retrospective chart review of 43 consecutive patients undergoing CUD since 1991 at British Columbia Children's Hospital. RESULTS: Our preferred surgery was intestinal cystoplasty and either appendicovesicostomy (77%) or ileal-vesicostomy. Concomitant bladder neck surgery was performed in 67%. Mean follow-up was 2.5 years. There was a 16% revision rate for persistent leakage, the most common being cystoscopic injection of bulking agents. Continence was ultimately achieved in 88%. Early major and minor postoperative complications each occurred in 21% of cases. Delayed minor complications requiring surgical intervention occurred in 30% including stomal stenosis in 6 patients and stomal prolapse in 2. Urolithiasis required intervention in 5 patients. CONCLUSIONS: Pediatric CUD is a challenging endeavor. Most patients achieve continence although many require additional minor procedures to do so. Early major and minor complications are common. A significant minority of patients require reoperation for delayed minor complications. Patients and families should be informed of these frustrations as part of their preoperative counseling. A high degree of family motivation and commitment is essential.