Long-term Outcomes of 100 Transobturator Tape Procedures.

Aim Satisfactory short-term outcomes of transobturator tapes (TOTs) are recognized, yet a lack of long-term data exists. We investigated long-term patient-reported outcomes of TOTs. Methods A retrospective review was performed of 100 female patients post TOT insertion by a single surgeon (2005-2010). Results and postoperative complications were identified. At long-term follow-up, patients completed ICIQ-Short Form, PGI-S and PGI-I questionnaires. Results Mean age was 51.7 years (33-75), mean follow-up 9.4 years (7.25 - 12.75). Clinically, 68/100(68%) had mixed and 32/100(32%) pure stress urinary incontinence (SUI). Short-term cure/significant improvement in SUI was seen in 98/100(98%). Grade >2 Clavien-Dindo complications occurred in 10/100(10%) within 6 months of surgery. Long-term questionnaire response rate was 76/100(76%). 62/76 (81.57%) described current urinary condition as "much" or "very much" "better." No new complications emerged at long-term follow-up. Conclusion TOTs demonstrate high success rates in treatment of SUI, with no late-onset complications identified in our study. Recent concerns surrounding use of polypropylene tapes make reporting of long-term outcomes both desirable and necessary.

Predictive value of PI-RADS classification in MRI-directed transrectal ultrasound guided prostate biopsy.

AIM: To correlate the results of transrectal ultrasound (TRUS)-guided targeted prostate biopsies (performed in the setting of at least one previous negative biopsy) with the Prostate Imaging Reporting and Data System (PI-RADS). MATERIAL AND METHODS: Fifty-two patients (mean age 64 years, range 52-76 years), with previous negative prostate biopsy underwent magnetic resonance imaging (MRI)-directed TRUS-guided targeted and sectoral biopsy. A retrospective review of MRI examinations was carried out, blinded to biopsy results. PI-RADS scores (T2, diffusion-weighted imaging [DWI] and overall) were assigned on a per lesion basis, and localised to sextants. The scores were correlated with biopsy results, and the positive predictive values (PPV) of PIRADS scores for positive biopsies were calculated. RESULTS: Overall, biopsies were positive in 23/52 (44.2%) patients. Eighty-one areas were targeted in 52 patients. On a per lesion basis, there was significant correlation between positive targeted biopsy and both T2 and overall PI-RADS score (p<0.001). The correlation between biopsy and DWI score was significant for peripheral zone tumours only, not for transitional zone tumours. The PPV of overall PI-RADS scores of 3, 4, and 5 were 10.6%, 44%, and 100%, respectively. The PPV of T2 PI-RADS scores of 3, 4, and 5 were 19.6%, 60%, and 100%, respectively. The PPV of DWI PI-RADS scores of 3, 4, and 5 were 50%, 27.3%, and 33%, respectively. When transitional tumours were excluded, the PPV of DWI PI-RADS 3, 4, and 5 were 40%, 43%, and 78%. CONCLUSION: The PIRADS score provides an effective framework for determining the likelihood of prostate cancer on MRI. The DWI PI-RADS score correlates well with the presence of peripheral zone tumour on targeted biopsy, but not with transitional zone tumours.

Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers.

OBJECTIVES: The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC. DESIGN: A total of 98 samples were sequenced to a mean depth of 31,642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies. RESULTS: Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. CONCLUSIONS: Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.

A Narrative Review on the Pathophysiology and Management for Radiation Cystitis.

Radiation cystitis is a recognised complication of pelvic radiotherapy. Incidence of radiation cystitis ranges from 23 to 80% and the incidence of severe haematuria ranges from 5 to 8%. High quality data on management strategies for radiation cystitis is sparse. Treatment modalities are subclassified into systemic therapies, intravesical therapies, and hyperbaric oxygen and interventional procedures. Short-term cure rates range from 76 to 95% for hyperbaric oxygen therapy and interventional procedures. Adverse effects of these treatment strategies are acceptable. Ultimately, most patients require multimodal treatment for curative purposes. Large randomised trials exploring emergent management strategies are required in order to strengthen evidence-based treatment strategies. Urologists encounter radiation cystitis commonly and should be familiar with diagnostic modalities and treatment strategies.

Peri-operative management in urinary diversion surgery: A time for change?

INTRODUCTION: Bowel preparation was established as part of the pre-operative course for patients undergoing ileal conduit formation since the late 1970's. Rationales for its use include reduction in infection and wound complications, technically easier anastomosis and earlier return to bowel function. However, recent reports have challenged this practice. Traditionally antibiotics were also administered for several days prior to surgery with the assumption that bacterial load was reduced. Modification of antibiotic protocols resulted from evidence-based findings. Furthermore, publications emphasizing the benefit of Enhanced Recovery Protocols/Programmes (ERP) have become contemporary. METHODS: An online multiple-choice questionnaire (via Monkey Survey) was administered to all consultant urologists in Ireland. This national cross-sectional study evaluated the use of bowel preparation and antibiotic prophylaxis prior to urinary diversion. In addition, we also assessed consultant urologists' awareness of ERP and their views on the introduction and implementation of such a national program. RESULTS: Of the 41 consultant urologists surveyed, 80.4% (n = 33) responded. 63.6% routinely used bowel preparation. Klean Prep was the most commonly used bowel preparation. 80.9% of urologists admit their patient's one-day pre-operatively for bowel preparation, with 87.8% using antibiotic prophylaxis at anesthesia induction, and 18.1% continuing the antibiotics for 24-48 h post-operatively. Although 74% of consultants are aware of ERP, only 66.6% are in favor of their national implementation. CONCLUSION: The majority of Irish urologists use bowel preparation prior to ileal conduit formation. Substantial recent evidence has emerged showing no difference in infective complications or anastomotic leakage when bowel preparation was not used. National guidelines would be beneficial regarding the use of bowel preparation, antibiotic prophylaxis and ERP for urinary diversion surgery.

Correlations between colonic crypt mucin chemotype, inflammatory grade and Desulfovibrio species in ulcerative colitis.

AIM: The colonic mucus gel layer is composed of mucins that may be sulphated or sialyated. Sulphated mucins predominate in health while in ulcerative colitis (UC) sulphation is reduced. These differences result directly from inflammatory events. It may also be hypothesized that they arise in part from alterations in the colonic microbiota, particularly changes in the burden of sulphated mucin-metabolizing species, such as Desulfovibrio (DSV) bacteria. The aim of this study was to correlate colonic mucin chemotypes and inflammatory scores in health and UC and relate these changes to changes in the colonization of colonic crypts by DSV. METHOD: Paired colonic biopsies from 34 healthy controls (HC) and 19 patients with active UC were collected for the purpose of parallel histological and microbiological assessment. High-iron diamine and Alcian blue staining and haematoxylin and eosin of mucosal biopsy specimens were used to assess histological changes within the clinical spectrum of UC. Quantitative real-time polymerase chain reaction analysis was employed to determine the total and DSV copy number within the colonic crypts. RESULTS: Compared with HC, the mucin chemotype in UC was less sulphated and inversely correlated with the degree of mucosal inflammation. A weak but significant negative correlation was found between the abundance of sulphated mucins and DSV burden. CONCLUSION: Mucin composition strongly correlates with the degree of mucosal inflammation, and to a lesser extent with DSV burden. These data suggest that mucin chemotype and DSV burden are linked phenomena and highlight the need to consider changes in mucin chemotype in the setting of microbial dysbiosis occurring within the colitic colon. What does this paper add to the literature? Decreased sulphation of mucins has been associated with inflammation in ulcerative colitis. Currently there are few data describing the relationship between microbial species and changes in mucin chemotype. This study validates previous findings and presents evidence of changes in mucin chemotype occurring in tandem with coherent changes in the microbiota within crypt niches.

Incidentalology: A developing urological sub-specialty.

OBJECTIVE: To identify the incidence and features of significant incidental findings discussed at our departmental multidisciplinary team meeting (MDM). The improved quality of radiological imaging has resulted in increased rates of incidental findings. Although some may be trivial, many have clinical significance and early diagnosis and treatment may be beneficial. METHODS: A retrospective analysis was performed of all cases discussed at the MDM between January 2012 and February 2013. Cases were divided into two groups--Group 1 consisted of patients whose initial imaging was performed for a urological presentation which resulted in a synchronous finding; Group 2 consisted of patients who were referred with a synchronous urological finding for discussion following investigation of an initial benign urological condition or a non-urological condition. RESULTS: 696 patients were discussed at 53 MDMs. 109 (15.7%) patients had incidental findings. 61 (56%) of these were in Group 1. 16 (26.2%) were synchronous malignant diagnoses, 25 (41%) were benign and 20 (32.8%) were indeterminate. 48 (44%) patients in Group 2 - 40 (83.3%) were renal in origin and 30 (75%) of these proceeded to surgery. The median tumour size was 3.2 cm (Range: 1.2 cm-10 cm). One patient had radio-frequency ablation. Two were referred for palliative care. Seven patients are under ongoing surveillance--the median size of these lesions is 3.6 cm (Range: 2.1 cm-8.3 cm). CONCLUSION: A substantial workload is generated from the investigation of incidental findings discussed at MDM--these now represent the majority of the caseload for renal cancer surgery.

The value of appropriate assessment prior to specialist referral in men with prostatic symptoms.

BACKGROUND: Referrals to Urology OPD of men with a likely diagnosis of BPH are common. AIMS: To review referrals to OPD of men with lower urinary tract symptoms (LUTS) to establish how many could have been managed without specialist assessment. METHODS: We reviewed records of 200 male patients referred to OPD with LUTS. We assessed whether the referral source had performed digital rectal examination (DRE), International Prostate Symptom Score (IPSS), Bother Score or PSA level. RESULTS: 74% of patients were referred by GPs. In 31.5% of cases DRE was performed prior to referral. One GP had completed an IPSS, none a Bother Score. 96% had a PSA checked before OPD. Ultimately, 88.5% of our patients were diagnosed with BPH. CONCLUSIONS: With better pre-assessment in the form of DRE, IPSS and Bother Score, allied to a PSA check, many patients with LUTS could be managed in a primary care setting.

Prevalence and characterization of enteric adenoviruses in the South of Ireland.

Enteric adenoviruses have been shown to be a substantial cause of pediatric gastroenteritis in various parts of the world, and are considered to be the second most common cause of viral gastroenteritis, next to rotavirus in young children. Genetic characterization of 95 adenovirus isolates obtained from patients with acute gastroenteritis between 2002 and 2007 from the southern regions of Ireland, were characterized by PCR analysis, restriction endonuclease (RE) analysis and sequencing analysis. All isolates were found to be of adenovirus type 41 origin. Genetic analysis of seven hypervariable regions (HVRs) located within the hexon gene has revealed a high level of amino acid sequence homology in samples over the course of this study, with a very close relationship to the D22 genome type. The D22 genome type has been detected in several other countries, thus suggesting Irish isolates have common genome types with other stains worldwide. This is the first such study undertaken in the south of Ireland, to type and genetically characterize adenoviral gastroenteritis isolates, and has revealed a high level of conservation within the isolated analyzed.

Joseph-Frédéric-Benoît Charrière: master cutler and instrument designer.

Modern surgery owes its development to the innovations and skill of those craftsmen in the early 19th Century. Joseph-Frédéric-Benoît Charrière was a Parisian Cutler of renowned fame. He pioneered many developments in ether administration, urologic and other general surgical instrumentation. He also made profound modifications to the syringe, haemostat and aneurysm clip. Charrière, most importantly, developed the French (Fr) or Charrière (Ch) gauge system used in sizing catheters and endoscopic equipment (1 Charr. = 0.333 mm). His contributions were widespread and are still evident today.

Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes.

Loss-of-function mutations in the cystatin B (Cstb) gene cause a neurological disorder known as Unverricht-Lundborg disease (EPM1) in human patients. Mice that lack Cstb provide a mammalian model for EPM1 by displaying progressive ataxia and myoclonic seizures. We analyzed RNAs from brains of Cstb-deficient mice by using modified differential display, oligonucleotide microarray hybridization and quantitative reverse transcriptase polymerase chain reaction to examine the molecular consequences of the lack of Cstb. We identified seven genes that have consistently increased transcript levels in neurological tissues from the knockout mice. These genes are cathepsin S, C1q B-chain of complement (C1qB), beta2-microglobulin, glial fibrillary acidic protein (Gfap), apolipoprotein D, fibronectin 1 and metallothionein II, which are expected to be involved in increased proteolysis, apoptosis and glial activation. The molecular changes in Cstb-deficient mice are consistent with the pathology found in the mouse model and may provide clues towards the identification of therapeutic points of intervention for EPM1 patients.

A new zinc ribbon gene (ZNRD1) is cloned from the human MHC class I region.

Eleven unique cDNA fragments were identified from YAC B30H3, which spans 330 kb in the human major histocompatibility complex class I region. One fragment (CAT80) was mapped 80 kb telomeric to the HLA-A locus. Using this cDNA fragment as probe, Northern analysis reveals a ubiquitously expressed transcript of about 850 nt in all 16 tissues tested. Based on the cDNA fragment sequence, a full-length cDNA of 858 bp that contains an open reading frame of 378 bp was cloned. Within the putative polypeptide of 126 amino acids, two zinc-ribbon domains were identified: Cx2Cx15Cx2C at the N-terminal and Cx2Cx24Cx2C at the C-terminal. The C-terminal domain is well conserved throughout evolution, including archaea, yeast, Drosophila, nematodes, amphibians, and mammals. The conserved amino acid sequence, CxRCx6Yx3QxRSADEx2TxFxCx2C, is highly homologous to the yeast RNA polymerase A subunit 9 and transcription-associated proteins. Alignment with genomic DNA demonstrates that this gene spans 3.6 kb and consists of four exons and three introns. Cross-species Northern analysis reveals a mouse homolog of a similar size and with an expression profile similar to those of the human gene. We have named this gene ZNRD1 for zinc ribbon domain-containing 1 protein.

Chromosomal localization and genomic structure of the human arsenite-stimulated ATPase (hASNA-I).

The hASNA-I is a novel human arsenite-stimulated ATPase identified as the human paralogue of the ATPase component of the arsenite efflux system in E. coli. The hASNA-I has distinct biochemical properties and a dual nuclear and cytoplasmic distribution. Immunohistochemical staining showed a distinct pattern of hASNA-I expression in cells within normal tissues, and its overexpression in breast cancer. Recently, the yeast two-hybrid system has identified hASNA-I as a cellular partner of metallothionein II suggesting an additional role in Zn homeostasis and cellular detoxification. This report describes the assignment of hASNA-I to human chromosome 19 by somatic-cell hybrid PCR mapping, the isolation of a chromosome 19-specific cosmid clone, and the genomic structure and exon-intron boundaries of hASNA-I. Our results indicate that the coding region of hASNA-I consists of 4 exons spanning 6 kb on band 19q13.3. These data will facilitate molecular analysis of the role of hASNA-I in human disease.

Cloning, sequencing, gene organization, and localization of the human ribosomal protein RPL23A gene.

The intron-containing gene for human ribosomal protein RPL23A has been cloned, sequenced, and localized. The gene is approximately 4.0 kb in length and contains five exons and four introns. All splice sites exactly match the AG/GT consensus rule. The transcript is about 0.6 kb and is detected in all tissues examined. In adult tissues, the RPL23A transcript is dramatically more abundant in pancreas, skeletal muscle, and heart, while much less abundant in kidney, brain, placenta, lung, and liver. A full-length cDNA clone of 576 nt was identified, and the nucleotide sequence was found to match the exon sequence precisely. The open reading frame encodes a polypeptide of 156 amino acids, which is absolutely conserved with the rat RPL23A protein. In the 5' flanking region of the gene, a canonical TATA sequence and a defined CAAT box were found for the first time in a mammalian ribosomal protein gene. The intron-containing RPL23A gene was mapped to cytogenetic band 17q11 by fluorescence in situ hybridization.

The identification of exons from the MED/PSACH region of human chromosome 19.

We have used exon amplification to identify putative transcribed sequences from an 823-kb contig consisting of 28 cosmids that form a minimum tiling path from the interval 19p12-p13.1. This region contains the genes responsible for multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). We have trapped 66 exons (an average of 2.4 exons per cosmid) from pools of 2 or 3 cosmids. The majority of exons (51.5%) show only weak similarity or no similarity (36.3%) to sequences in current databases. Six of 8 exons examined from these groups, however, show cross-species sequence conservation, indicating that many of them probably represent authentic exons. Eight exons show identity or significant similarity to ESTs or known genes, including the human TNF receptor 3 '-flanking region gene, human epoxide hydrolase (EPHX), human growth/differentiation factor (GOF-1), human myocyte-specific enhancer factor 2, the rat neurocan gene, and the human cartilage oligomeric matrix protein gene (COMP). Mutations in this latter gene have recently been shown to be responsible for MED and PSACH.

Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a well characterized dwarfing condition mapping to chromosome 19p12-13.1. Cartilage oligomeric matrix protein (COMP), a cartilage specific protein, maps to the same location within a contig that spans the PSACH locus. Using single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing we have identified COMP mutations in eight familial and isolated PSACH cases. All mutations involve either a single base-pair change or a three base-pair deletion in exon 17B. Six mutations delete or change a well conserved aspartic acid residue within the calcium-binding type 3 repeats. These results demonstrate that mutations in the COMP gene cause pseudochondroplasia.

Physical mapping of sequences homologous to an endogenous retrovirus LTR on human chromosome 19.

The human genome contains multiple copies of sequences related to the HERV-K family of endogenous retroviruses, homologous to the B-type mouse mammary tumour virus. A DNA fragment closely resembling an HERV-K long tandem repeat (LTR) was detected in a library of hncDNA clones enriched for sequences from human chromosome 19. Sites showing homology to the sequence of this fragment have been identified on human chromosome 19 by hybridization to previously mapped chromosome 19 cosmids. Thus the distribution of LTR sequences on a specific human chromosome has been mapped for the first time. We estimate the total number of such sites on human chromosome 19 to be at least 110. Many of these sites are located in the vicinity of known genes. The precise localizations (to specific cosmids) of LTR-homologous sequences on chromosome 19 can serve as a reference source and will automatically provide further insight into LTR-gene relationships as new genes are mapped onto the chromosome.