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1.
BMJ Open ; 14(1): e080639, 2024 01 12.
Article in English | MEDLINE | ID: mdl-38216189

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study. METHODS AND ANALYSIS: CONSIDERING-AF is a randomised, controlled, siteless, non-blinded diagnostic superiority trial with four parallel groups and a primary endpoint of identifying AF during a 6-month study period set in Region Halland, Sweden. In each group, 740 individuals aged≥65 years will be included. The primary objective is to compare the intervention of AF screening enrichment using a risk prediction model (RPM), followed by 14 days of a continuous ECG patch, with no intervention (standard care). Primary outcome is defined as the incident AF recorded in the Region Halland Information Database after 6 months as compared with standard care. Secondary endpoints include the difference in incident AF between groups enriched or not by the RPM, with and without an invitation to 14 days of continuous ECG recording, and the proportions of oral anticoagulation treatment in the four groups. ETHICS AND DISSEMINATION: This study has ethical approval from the Swedish Ethical Review Authority. Results will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: NCT05838781.


Subject(s)
Atrial Fibrillation , Heart Failure , Stroke , Humans , Atrial Fibrillation/complications , Sweden/epidemiology , Stroke/etiology , Research Design , Heart Failure/complications
2.
PLoS One ; 13(11): e0206475, 2018.
Article in English | MEDLINE | ID: mdl-30419021

ABSTRACT

Patients with bladder cancer need frequent controls over long follow-up time due to high recurrence rate and risk of conversion to muscle invasive cancer with poor prognosis. We identified cancer-related molecular signatures in apparently healthy bladder in patients with subsequent muscular invasiveness during follow-up. Global proteomics of the normal tissue biopsies revealed specific proteome fingerprints in these patients prior to subsequent muscular invasiveness. In these presumed normal samples, we detected modulations of proteins previously associated with different cancer types. This study indicates that analyzing apparently healthy tissue of a cancer-invaded organ may suggest disease progression.


Subject(s)
Disease Progression , Muscles/pathology , Proteomics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/genetics
3.
Lakartidningen ; 1152018 01 26.
Article in Swedish | MEDLINE | ID: mdl-29381183

ABSTRACT

The TARGIT-A (TARGeted Intraoperative radioTherapy) multicentre study of early breast cancer compared intraoperative radiotherapy with external radiotherapy. While the intraoperative radiotherapy was standardised, the external postoperative comparison treatment followed established routines in the participating treatment centres resulting in substantial variations in dosages and treatment durations. The uncertainties in the interpretation of the study results created by the design of the TARGIT-A study constitute substantial obstacles to the possible introduction of intraoperative radiotherapy for early breast cancer.


Subject(s)
Breast Neoplasms/radiotherapy , Intraoperative Care/methods , Radiotherapy/methods , Breast Neoplasms/economics , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Cost-Benefit Analysis , Female , Humans , Intraoperative Care/economics , Multicenter Studies as Topic , Neoplasm Recurrence, Local/epidemiology , Patient Satisfaction , Radiotherapy/economics , Randomized Controlled Trials as Topic
4.
BJU Int ; 120(4): 530-536, 2017 10.
Article in English | MEDLINE | ID: mdl-28370930

ABSTRACT

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. RESULTS: A complication of Clavien-Dindo grade ≥III, including unscheduled re-admissions, occurred in 45/193 patients (23%) at ≤90 days of surgery. At a median follow-up of 13 years, 105/193 patients (54%) had undergone at least one re-operation, with uretero-intestinal stricture being the most prevalent cause [28 patients (15%)]. Re-operations were more prevalent in patients operated during the first half of the study period than during the second half (2000-2007; 62% vs 47%; P = 0.03), and they were also more frequent in patients who underwent surgery for benign causes than in patients who underwent surgery for malignancy (60% vs 51%; P = 0.04). Continence was achieved in 172/188 patients (91%). In all, 16% of all patients required revisional surgery of the outlet to remain continent with an easily catheterisable pouch or to address stomal stenosis. The mean decrease in estimated glomerular filtration rate was more pronounced in patients with benign indications for urinary diversion than in those with malignancies, even after adjusting for younger age at surgery and longer follow-up in the former group (22 vs 11 mL/min/1.73 m2 ; P < 0.006). A disinterested third-party assessment revealed 10 postoperative complications, 17 re-operations during follow-up, and seven occasions of hospitalisation due to pyelonephritis (included in data above) not recorded at the primary data review. CONCLUSIONS: The Lundiana pouch is associated with a high risk of re-operation, although the functional results are good. Independent review by a third party increased the validity of the outcome data.


Subject(s)
Carcinoma, Transitional Cell/surgery , Reoperation/statistics & numerical data , Urinary Bladder Neoplasms/surgery , Urinary Reservoirs, Continent/adverse effects , Aged , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Cohort Studies , Cystectomy/methods , Female , Follow-Up Studies , Hospitals, University , Humans , Linear Models , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Reoperation/methods , Reproducibility of Results , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Rate , Sweden , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Urinary Incontinence/prevention & control
5.
Scand J Urol ; 48(1): 99-104, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23889158

ABSTRACT

OBJECTIVE: This study aimed to reveal the late results of rediversion after urinary diversion. MATERIAL AND METHODS: From 1985 to 2009, 28 patients underwent rediversion at the Department of Urology, Lund University Hospital, Sweden. Median follow-up after rediversion was 147 months (range 7-300 months, interquartile range 63-214). The following rediversions were performed: ileal conduit, cutaneous ureterostomy, ureterosigmoidostomy and rectal bladder to continent cutaneous diversion (group I, n = 17); cutaneous ureterostomy to neobladder (group II, n = 1); ileal conduit and cutaneous ureterostomy to gastric conduit (group III, n = 2); and continent cutaneous diversion and neobladder to ileal conduit (group IV, n = 8). RESULTS: In group I, reoperations were necessary after rediversion in nine of the 17 patients. Excellent functional results were obtained in 14 patients. Two patients, both with Kock pouches, underwent multiple operations and finally required rediversion to an ileal conduit. The sole patient in group II had a ureteric reimplantation owing to ureterointestinal stricture and is now continent but performs clean intermittent catheterization. Both patients in group III underwent reoperations owing to ureteric strictures and renal stones. In group IV, one patient had ureteric stenosis, and one died owing to complications related to later surgery for small bowel obstruction. CONCLUSIONS: Complications are common after urinary rediversion, and several of the present patients required reoperations for a variety of reasons. Modern techniques for continent cutaneous diversion can provide excellent functional results. Patients with difficulties in accepting a urostomy bag pose special problems and need extensive information and counselling.


Subject(s)
Urinary Diversion/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Young Adult
6.
Eur Urol ; 63(1): 67-80, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22995974

ABSTRACT

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. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. EVIDENCE SYNTHESIS: Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. CONCLUSIONS: RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.


Subject(s)
Cystectomy/standards , Urinary Bladder Neoplasms/surgery , Urinary Bladder/surgery , Urinary Diversion/standards , Urinary Reservoirs, Continent/standards , Cystectomy/adverse effects , Female , Humans , Male , Quality of Life , Recovery of Function , Reoperation , Treatment Outcome , Urinary Bladder/pathology , Urinary Bladder/physiopathology , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/physiopathology , Urinary Diversion/adverse effects , Urinary Incontinence/etiology , Urinary Incontinence/physiopathology , Urinary Reservoirs, Continent/adverse effects
7.
Scand J Urol ; 47(2): 108-12, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22989110

ABSTRACT

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. MATERIAL AND METHODS: Prospectively, 53 patients with invasive bladder cancer were preoperatively investigated with 3 tesla (3T) MRI using a standardized protocol. 3T MRI was performed at a standardized bladder volume. Clinical tumour stage, tumour stage at MRI and pathological tumour stage groups (Ta, Cis, T1/T2a, T2b/T3a, T3b/T4a), were compared, and sensitivity and specificity for organ-confined and non-organ-confined disease (stage T3a or above or lymph-node metastases) were analysed. RESULTS: MRI overestimated tumour stage in 23 out of 47 patients (49%), whereas six patients (13%) were understaged. In the three groups of patients (those with the same stage group at MRI as in the cystectomy specimen, overestimated tumour stage and understaged patients), the time interval between transurethral resection of the bladder (TURB) and MRI did not differ significantly. CONCLUSIONS: Preoperative MRI overestimated tumour stage in almost half of the patients investigated in this study. Postoperative changes could have contributed to such overstaging with MRI.


Subject(s)
Carcinoma, Transitional Cell/diagnosis , Cystectomy/methods , Magnetic Resonance Imaging/methods , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging/methods , Urinary Bladder Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/surgery , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Preoperative Period , Reproducibility of Results , Urinary Bladder Neoplasms/surgery
8.
Eur Urol ; 57(2): 293-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19913351

ABSTRACT

BACKGROUND: Fluorescent light (FL)-guided cystoscopy induced by 5-aminolevulinic acid (5-ALA) has been reported to detect more tumours compared with standard white-light (WL) cystoscopy. Most reports are from single centres with relatively few patients. OBJECTIVE: To evaluate whether 5-ALA-induced FL and WL cystoscopy at transurethral resection (TUR) is superior compared with standard procedures under WL only with respect to tumour recurrence and progression in patients with non-muscle-invasive bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: This randomised, multicentre, observer- and pathologist-blinded, prospective phase 3 clinical trial enrolled 300 patients, and of those patients, 153 were randomised to FL cystoscopy and 147 were randomised to standard WL cystoscopy. INTERVENTION: All patients were first inspected under WL and all lesions were recorded. Patients randomised to FL underwent a second inspection. TUR was carried out in both groups. MEASUREMENTS: Control cystoscopy under WL was performed in all patients every 3 mo during the first year after randomisation and biannually thereafter. RESULTS AND LIMITATIONS: At the first TUR, the mean number of resection specimens per patient was 2.5 (FL: 2.5; WL: 2.4; p=0.37) and the resulting mean number of resected tumours was 1.7 with FL and 1.8 with WL (p=0.85). More patients were diagnosed with carcinoma in situ (CIS) in the WL group (13%) than in the FL group (4.2%). Within-patient comparison of FL patients only showed that FL detected more lesions than WL. Tumour lesions solely detected by FL cystoscopy that would not otherwise be detected by WL cystoscopy included 52% dysplasia, 33% CIS, 18% papillary neoplasms, 13% pT1, and 7% pTa. Outcome at 12 mo did not show any difference between groups with regard to recurrence-free and progression-free survival rates. CONCLUSIONS: In this prospective, randomised, multi-institutional study, we found no clinical advantage of FL cystoscopy compared with WL cystoscopy and TUR.


Subject(s)
Aminolevulinic Acid , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Cystectomy/methods , Cystoscopy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Aged , Double-Blind Method , Female , Fluorescence , Humans , Male , Prospective Studies
9.
Scand J Psychol ; 51(1): 31-7, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19392945

ABSTRACT

The Empathy- and Systemizing Quotients (EQ and SQ, respectively; Baron-Cohen, 2003) were determined in a Swedish sample consisting mainly of university undergraduates. Females had significantly higher EQ than males, who in turn scored higher on the SQ inventory. Gender explained 12-14% of the variation. Males were strikingly overrepresented in the group defined by a high SQ/low EQ profile or by a large SQ - EQ difference; females dominated among people with a low SQ/high EQ profile or by a large EQ - SQ difference. Students majoring in the natural sciences had higher SQs than psychology majors, but in both groups the gender difference in SQ and EQ was strong. For each participant a weighted composite score was generated by multivariate processing of the EQ and SQ data (Partial Least Square Discriminant Analysis). These scores were associated in a sex-linked fashion to a biometric measure reflecting prenatal testosterone exposure, i.e. the ratio between index (2D)- and ring (4D) finger lengths. In males a high (female-typical) 2D:4D ratio predicted an enhanced tendency to empathize and a reduced tendency to systemize; in women, by contrast, the 2D:4D ratio was unrelated to these traits. The present research confirms earlier work of a gender difference in EQ and SQ. The difference appears robust as it appears as large in Sweden (a country with high cultural gender-equality) as in countries with considerably lower gender-equality.


Subject(s)
Empathy/physiology , Fingers/anatomy & histology , Adolescent , Adult , Analysis of Variance , Female , Humans , Male , Middle Aged , Multivariate Analysis , Personality Inventory , Sex Characteristics , Sweden
10.
Scand J Urol Nephrol ; 43(6): 437-41, 2009.
Article in English | MEDLINE | ID: mdl-19707953

ABSTRACT

OBJECTIVE: In the European Association of Urology guidelines on prostate cancer an extended pelvic lymphadenectomy (ePLND) is now recommended, instead of a dissection limited to the obturator fossae (lPLND). This recommendation relies on studies reporting that metastatic disease is identified twice as often with ePLND as with lPLND, with only moderately increased complications. However, these studies were from high-volume centres. This study investigated whether these results could be repeated in a hospital with lower surgical volume, more typical for the Nordic countries. MATERIAL AND METHODS: From January 2002 to September 2007 172 patients underwent radical prostatectomy and PLND at the University Hospital of Lund, 108 with ePLND and 64 with lPLND. Perioperative complications and the number of lymph-node metastases found were registered. RESULTS: A median of 17 lymph nodes was identified with ePLND compared with seven with lPLND. Metastases were identified in four out of 64 patients in the lPLND group (6%), versus 22 out of 108 in the ePLND group (20%). In the ePLND group 10 of the patients with metastases had such exclusively outside the obturator fossae. Complications were significantly more common after ePLND (p=0.007): lymphoceles (18 vs 9%), pulmonary embolism (4.6 vs 1.6%), deep venous thrombosis (1 vs 1.5%) and other (haematomas and infectious including sepsis (8 vs 0%). CONCLUSIONS: Almost half of the patients with metastases are misclassified by lPLND. Complications are significantly more common after ePLND. This implies that ePLND should be performed, but in selected patients and by high-volume surgeons only.


Subject(s)
Lymph Node Excision/methods , Lymph Node Excision/statistics & numerical data , Lymphatic Metastasis/diagnosis , Prostatectomy/methods , Prostatectomy/statistics & numerical data , Prostatic Neoplasms/surgery , Clinical Competence , Humans , Lymph Node Excision/adverse effects , Lymphocele/epidemiology , Male , Middle Aged , Neoplasm Staging , Norway , Prostatic Neoplasms/pathology , Pulmonary Embolism/epidemiology , Retrospective Studies , Risk Factors , Treatment Outcome , Venous Thrombosis/epidemiology
11.
World J Urol ; 27(4): 521-6, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19145436

ABSTRACT

OBJECTIVE: We compared extended and limited lymph node dissections performed during radical cystectomy with regard to impact on survival and time to recurrence in bladder cancer patients. METHODS: We analyzed 170 patients who underwent radical cystectomy for urothelial carcinoma between January 1997 and December 2005. From 1997 to 2000, 69 of the patients were subjected to limited lymph dissection that included perivesical nodes and nodes in the obturator fossa. In 2001-2005, the remaining 101 patients underwent extended lymph dissection that included perivesical nodes; nodes in the obturator fossa; the internal, external, and common iliac nodes; and the presacral nodes. RESULTS: Tumors penetrating the bladder wall (pT3 and pT4a) were more common in the extended than in the limited dissection group (48 and 33%, respectively). The median numbers of lymph nodes removed in the two groups were 37 and 8, respectively. Lymph node metastases were detected in 38% of the extended dissection patients but only in 17% of the limited dissection patients. There was no significant difference in survival or time to recurrence between the two groups. Subgroup analyses showed a significantly longer time to recurrence (HR 0.45, 95% CI 0.22-0.93; P = 0.032) in patients with non-organ-confined disease who underwent extended lymph node dissection. In a multivariate analysis adjusting for tumor stage, lymph node status, age, sex, and adjuvant chemotherapy, there was a significantly improved survival (HR 0.47, 95% CI 0.25-0.88; P = 0.018) and time to recurrence (HR 0.42, 95% CI 0.23-0.79; P = 0.007) in the patients with extended lymph node dissections. CONCLUSIONS: Extended lymph node dissection did not improve disease-specific survival, but was in multivariate analysis related to significantly improved disease-specific survival and prolonged time to recurrence in radical cystectomy patients. These results should be interpreted cautiously, since they might have been affected by stage migration and the shorter follow-up in the extended dissection group.


Subject(s)
Carcinoma/diagnosis , Carcinoma/surgery , Cystectomy , Lymph Node Excision/methods , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma/mortality , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis/prevention & control , Neoplasm Recurrence, Local/prevention & control , Prognosis , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Urothelium
12.
Eur Urol ; 55(4): 773-80, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19153001

ABSTRACT

BACKGROUND: To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours. OBJECTIVE: To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of saline intravesically within 24 h of TUR or no further treatment after TUR. MEASUREMENTS: The primary end point was time to first recurrence. RESULTS AND LIMITATIONS: A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of > or = 3 were 81% and 85%, respectively (p=0.35). CONCLUSIONS: A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Epirubicin/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Administration, Intravesical , Aged , Combined Modality Therapy , Female , Humans , Male , Neoplasm Invasiveness , Postoperative Care , Prospective Studies , Time Factors , Urologic Surgical Procedures/methods
14.
J Exp Med ; 205(9): 2139-49, 2008 Sep 01.
Article in English | MEDLINE | ID: mdl-18710932

ABSTRACT

A functionally distinct subset of CD103(+) dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3(+) T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and alpha4beta7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103(+) DCs. CD103(+) SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI-LP. BrdU pulse-chase experiments suggested that most CD103(+) DCs do not derive from a CD103(-) SI-LP DC intermediate. The majority of CD103(+) MLN DCs appear to represent a tissue-derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8(+) and CD4(+) T cells. In contrast, most CD103(-) MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103(+) DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103(+) MLN DCs isolated from SB Crohn's patients. Thus, small intestinal CD103(+) DCs represent a potential novel target for regulating human intestinal inflammatory responses.


Subject(s)
Antigens, CD/biosynthesis , Dendritic Cells/metabolism , Integrin alpha Chains/biosynthesis , Animals , Cells, Cultured , Conserved Sequence , Dendritic Cells/immunology , Flow Cytometry , Humans , Integrins/metabolism , Intestinal Mucosa/metabolism , Intestine, Small/metabolism , Lymph Nodes/metabolism , Mice , Mice, Inbred BALB C , Receptors, CCR/metabolism , T-Lymphocytes/metabolism
15.
Scand J Urol Nephrol ; 42(3): 205-12, 2008.
Article in English | MEDLINE | ID: mdl-18432527

ABSTRACT

OBJECTIVE: In the treatment of reduced bladder capacity, matrix grafts have been used as a scaffold into which cell elements from the native bladder grow, eventually forming a new bladder segment. Functioning motor nerve endings in such segments in the rat have been demonstrated, although little is known about nerve distribution. We compare the pattern of nerve distribution in scaffold-augmented rat bladders with that in bladders regrown after subtotal cystectomy and that in control bladders. MATERIAL AND METHODS: Female Sprague-Dawley rats were either subtotally cystectomized (n=7) or had a part of the bladder dome replaced by an acellular collagen (small intestinal submucosa) matrix graft (n=10). Fourteen age-matched, unoperated animals were used as controls. Two and a half to 10 months after surgery the bladders were stained for acetylcholinesterase and studied in wholemounts. RESULTS: No ganglion neurons were observed in any of the bladders. On their ventral side the control bladders showed longitudinal nerve trunks, running in parallel along the longitudinally oriented muscle bundles, while on the lateral and dorsal aspects the nerves were thinner, more irregularly arranged and frequently branched. In the bladders regrown after subtotal cystectomy, the ventral nerves were seen running obliquely to the still longitudinally oriented muscle bundles, resembling the pattern of the normal bladder base; the pattern of the dorsolateral nerves was the same as that in the controls. In the matrix bladders, the muscle and nerve patterns in the native part were the same as those in controls. Muscle bundles were growing into the matrix, accompanied by nerves, which showed limited branching when entering the matrix, usually running in parallel to the muscle, but then branching within the matrix. CONCLUSIONS: The nerves in the matrix grafts and the regrown parts of the subtotally cystectomized bladders derive from preexisting nerves in the bladder. In neither case does the nerve trunk or muscle bundle arrangement fully attain the pattern found in normal bladders.


Subject(s)
Cystectomy , Nerve Regeneration/physiology , Tissue Scaffolds , Urinary Bladder/innervation , Animals , Female , Rats , Rats, Sprague-Dawley
16.
Scand J Urol Nephrol ; 41(4): 290-6, 2007.
Article in English | MEDLINE | ID: mdl-17763219

ABSTRACT

OBJECTIVES: To prospectively evaluate the incidence of transitional cell carcinoma (TCC) in the prostatic urethra and prostate in the cystoprostatectomy specimen, investigate characteristics of bladder tumours in relation to the risk of involvement of the prostatic urethra and prostate and examine the sensitivity of preoperative loop biopsies from the prostatic urethra. MATERIAL AND METHODS: Preoperatively, patients were investigated with cold cup biopsies from the bladder and transurethral loop biopsies from the bladder neck to the verumontanum. The prostate and bladder neck were submitted to sagittal whole-mount pathological analysis. RESULTS: The incidence of TCC in the prostatic urethra and prostate in the cystoprostatectomy specimen was 29% (50/175 patients). Age, previous bacillus Calmette-Guérin treatment, carcinoma in situ (Cis) in the cold cup mapping biopsies and tumour grade were not associated with the risk of TCC in the prostatic urethra/prostate. Cis, multifocal Cis (> or = 2 locations) and tumour location in the trigone were significantly more common in cystectomy specimens with TCC in the prostatic urethra and prostate: 21/50 (42%) vs 32/125 (26%), p=0.045; 20/50 (40%) vs 27/125 (22%), p=0.023; and 20/50 (40%) vs 26/125 (21%), p=0.01, respectively. Preoperative resectional biopsies from the prostatic urethra in the 154 patients analysed identified 31/47 (66%) of patients with TCC in the prostatic urethra/prostate, with a specificity of 89%. The detection of stromal-invasive and non-stromal involvement was similar: 66% and 65%, respectively. CONCLUSIONS: The incidence of TCC in the prostatic urethra and prostate was 29% (50/175) in the cystoprostatectomy specimen. Preoperative biopsies from the prostatic urethra identified 66% of patients with such tumour growth. Our findings suggest that preoperative cold cup mapping biopsies of the bladder for detection of Cis add little extra information with regard to the risk of TCC in the prostatic urethra and prostate.


Subject(s)
Carcinoma, Transitional Cell/pathology , Prostatic Neoplasms/pathology , Urethral Neoplasms/pathology , Age Factors , Aged , BCG Vaccine/therapeutic use , Biopsy , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/surgery , Cystectomy , Humans , Male , Middle Aged , Prospective Studies , Prostatectomy , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , Urethral Neoplasms/diagnosis , Urethral Neoplasms/surgery , Urinary Bladder Neoplasms/pathology
17.
Neurourol Urodyn ; 25(3): 259-267, 2006.
Article in English | MEDLINE | ID: mdl-16408259

ABSTRACT

AIMS: The functional integration of the smooth muscle of enterocystoplasties into the detrusor muscle was investigated in an awake-rat cystometry model and in vitro. METHODS: The upper fourth of the bladder was removed, and a detubularized appendiceal segment (7 x 7 mm), with preserved vasculature, was incorporated into the bladder. After 1 or 3 months, a catheter was fixed to the top of the bladders. After a 3-day recovery, cystometries were performed. In separate experiments, agonist and nerve-induced responses were evaluated on isolated bladder strips. RESULTS: Cystometries revealed reduced basal pressure and micturition pressure in enterocystoplasty (ECP) bladders. Bladder capacity and micturition volume were increased. Threshold pressure (pressure immediately before micturition) was significantly lower at 1 month, but not at 3 months. Bladder compliance was significantly higher in the operated at 1 month but not at 3 months. Threshold tension did not differ between control and corresponding operated groups. Residual urine was significantly higher in the operated groups. ECP strips showed increased maximal contractions to nerve stimulation, to levels similar to those of detrusor strips. Maximal responses to carbachol increased to levels between those of intestine and detrusor. The inhibitory effect of scopolamine on nerve induced contractions increased to levels similar to those for detrusor. Purinergic activation had no effect on intestinal or ECP strips, but contracted detrusor muscle. CONCLUSIONS: The smooth muscle of the bowel segment in rat ECP bladders underwent a partial change in the response to nerve stimulation from that of intestine towards that of detrusor. The cystometry experiments suggested a partial functional integration of the ECP segment into the detrusor.


Subject(s)
Appendix/transplantation , Muscle, Smooth/physiology , Muscle, Smooth/surgery , Urinary Bladder/physiology , Urinary Bladder/surgery , Animals , Female , In Vitro Techniques , Manometry , Rats , Rats, Sprague-Dawley , Urologic Surgical Procedures/methods
18.
J Urol ; 175(1): 84-8; discussion 88-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16406877

ABSTRACT

PURPOSE: We evaluated intraoperative SN detection in patients with invasive bladder cancer during radical cystectomy in conjunction with extended lymphadenectomy. MATERIALS AND METHODS: A total of 75 patients with invasive bladder cancer underwent radical cystectomy with extended lymphadenectomy. SNs were identified by preoperative lymphoscintigraphy, intraoperative dynamic lymphoscintigraphy and blue dye detection. An isotope (70 MBq (99m)Tc-nanocolloid) and Patent Blue(R) blue dye were injected peritumorally via a cystoscope. Excised lymph nodes were examined ex vivo using a handheld gamma probe. Identified SNs were evaluated by extended serial sectioning, hematoxylin and eosin staining, and immunohistochemistry. RESULTS: At lymphadenectomy an average of 40 nodes (range 8 to 67) were removed. Of 75 patients 32 (43%) were lymph node positive, of whom 13 (41%) had all lymph node metastases located only outside of the obturator spaces. An SN was identified in 65 of 75 patients (87%). In 7 patients an SN was recognized when the nodal basins were assessed with the gamma probe after lymphadenectomy and cystectomy. Of the 32 lymph node positive cases 26 (81%) had a positive (metastatic) SN. Thus, the false-negative rate was 6 of 32 cases (19%). Five false-negative cases had macrometastases and/or perivesical metastases. In 9 patients (14%) the SN contained micrometastases (less than 2 mm), in 5 of whom the micrometastasis was the only metastatic deposit. CONCLUSIONS: SN detection is feasible in invasive bladder cancer, although the false- negative rate was 19% in this study. Extended serial sectioning and immunohistochemistry revealed micrometastases in SNs in 9 patients and radio guided surgery after the completion of lymphadenectomy identified SNs in an additional 7. We believe that the technique that we used in this study improved nodal staging in these 16 of 65 patients (25%).


Subject(s)
Sentinel Lymph Node Biopsy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Aged , Aged, 80 and over , Female , Humans , Intraoperative Period , Lymph Node Excision , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging
19.
Eur Urol ; 49(4): 691-7, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16442699

ABSTRACT

OBJECTIVES: The primary aim was to compare the working capacity in patients with continent urinary diversion with a control group. Secondary aims were to assess the changes in electrolyte and acid-base homeostasis and the functional status during strenuous physical activity, and finally, the well-being in the two groups. METHODS: Eleven patients who had undergone radical cystectomy and continent cutaneous diversion using an ileocolonic segment participated. The control group consisted of 12 men, matched for age and activity level. Working capacity was assessed by ergospirometry on an exercise bicycle. Venous blood samples were taken before the test, when the expiratory exchange ratio (RER) was about 1.0 and immediately after completion of the test. SF-36 was used to evaluate the subject's functional status and well-being. RESULTS: The median working capacity in the patient group was 155 (85-190) W and 155 (125-215) W in the control group (n.s.) corresponding to 72 (43-97) % and 80 (59-97) % respectively of predicted values. Peak oxygen uptake was somewhat low in both groups when compared to P-O Astrands norms. Blood tests revealed that patients developed a slight metabolic hyperchloremic acidosis, not seen in the control group. There were no differences between the groups as assessed with SF-36. CONCLUSION: Patients with a continent urinary diversion have a working capacity equal to a control group despite a slight metabolic hyperchloremic acidosis. Quality of life was similar in the two groups and corresponded well with the norms for the general Swedish population aged 65 to 74.


Subject(s)
Cystectomy , Health Status Indicators , Physical Exertion/physiology , Urinary Bladder Neoplasms/surgery , Urinary Diversion , Urinary Reservoirs, Continent , Acid-Base Equilibrium , Aged , Case-Control Studies , Exercise Test , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Oxygen Consumption/physiology , Quality of Life , Spirometry , Statistics, Nonparametric , Urinary Bladder Neoplasms/physiopathology
20.
Urol Oncol ; 21(1): 7-9, 2003.
Article in English | MEDLINE | ID: mdl-12684120

ABSTRACT

OBJECTIVE: To describe our experience with the nested variant of urothelial carcinoma (UC-NV) of the bladder, by characterization of the clinical picture and the prognostic implications of this rare form of bladder neoplasm. MATERIALS AND METHODS: Three cases of UC-NV of the bladder treated in our institutions were revised and data compared with previously published case-reports. RESULTS: Three patients presented with advanced muscle-invasive UC-NV, of which two had lymph node metastasis at cystoprostatectomy. The histopathology in the latter two cases showed the same picture in the lymph node metastasis as in the primary tumor with nests of tumor cells with mild-moderate atypia. In all three cases the tumor involved a ureteric orifice or the bladder neck. CONCLUSION: UC-NV is a rare but important histopathologic entity. It has a poor prognosis. At early stage, tumors might be difficult to differentiate from benign conditions and awareness of the condition is of outermost importance.


Subject(s)
Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/pathology , Aged , Carcinoma, Transitional Cell/classification , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/epidemiology , Diagnosis, Differential , Disease Progression , Humans , Lymphatic Metastasis , Male , Middle Aged , Muscle, Smooth/pathology , Neoplasm Invasiveness , Prognosis , Sex Distribution , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/epidemiology , Urothelium/pathology
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