Perioperative management of upper tract urothelial carcinoma in the Nordic countries.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries. METHODS: The electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022. RESULTS: Overall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision. CONCLUSIONS: Adherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent.

IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation.

CD103(+)CD11b(+) dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo function remains unclear. Here we demonstrate that intestinal CD103(+)CD11b(+) DC survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17 (IL-17)-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes (MLN) following immunization. The latter was associated with a selective reduction in CD103(+)CD11b(+) MLN DCs and DC derived IL-6. Immunized Il6(-/-) mice failed to support Th17 cell differentiation in MLN in vivo and CD103(+)CD11b(+) MLN DCs supported IL-6-dependent Th17 cell differentiation in vitro. Together, our results suggest a central role for IRF4-dependent, IL-6 producing CD103(+)CD11b(+) DCs in intestinal Th17 cell differentiation.

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

OBJECTIVES: To investigate the long-term functional outcomes and complications after continent cutaneous diversion with the Lundiana pouch. PATIENTS AND METHODS: Complications, re-operations, renal function, and continence were ascertained from patient charts. Outcome variables were validated by a second and independent review of the patient files. 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.

Clear Cell Adenocarcinoma of the Female Urethra: Four Case Presentations of a Clinical and Pathological Entity Requiring Radical Surgery.

Clear cell adenocarcinoma of the female urethra is a rare tumour of unknown origin. Here, we report 4 patients with such malignancy and argue for proper identification of the disease entity and radical surgery based on the available literature.

Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective: results from a prospective intervention study.

BACKGROUND: The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long. METHODS: We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with macroscopic haematuria. The control group comprised 101 patients diagnosed with bladder cancer in the same catchment area with macroscopic haematuria who underwent regular diagnostic process. RESULTS: In all 275 patients who called 'the Red Phone' hotline were investigated, and 47 of them (17%) were diagnosed with cancer and 36 of those had bladder cancer. Median time from patient-reported haematuria to diagnosis was 29 (interquartile range (IQR) 14-104) days and 50 (IQR 27-165) days in the intervention and the control group, respectively (P=0.03). The median health-care costs were lower in the intervention group (655 (IQR 655-655) EUR) than in the control group (767 (IQR 490-1096) EUR) (P=0.002). CONCLUSIONS: Direct access to urologic expertise and fast-track diagnostics is motivated for patients with macroscopic haematuria to reduce diagnostic intervals and lower health-care expenditures.

Transurethral bladder tumor resection can cause seeding of cancer cells into the bloodstream.

PURPOSE: Transurethral bladder tumor resection is the initial diagnostic procedure for bladder cancer. Hypothetically tumor resection could induce seeding of cancer cells into the circulation and subsequent metastatic disease. In this study we ascertain whether transurethral bladder tumor resection induces measurable seeding of cancer cells into the vascular system. MATERIALS AND METHODS: Patients newly diagnosed with suspected invasive bladder cancer and planned for transurethral resection of bladder tumor in 2012 to 2013 were enrolled in the study. Before transurethral bladder tumor resection a vascular surgeon placed a venous catheter in the inferior vena cava via the femoral vein. Blood samples were drawn before and during the resection from the inferior vena cava and a peripheral vein, and analyzed for circulating cancer cells using the CellSearch® system. The number of circulating tumor cells identified was compared in preoperative and intraoperative blood samples. RESULTS: The circulating tumor cell data on 16 eligible patients were analyzed. In 6 of 7 positive inferior vena cava samples (86%) the number of circulating tumor cells was increased intraoperatively (28 vs 9, 28 vs 0, 28 vs 5, 3 vs 0, 4 vs 0, 1 vs 0), and results were similar, although less conclusive, for the corresponding peripheral vein samples. CONCLUSIONS: Our study confirms that tumor cells can be released into the circulation during transurethral bladder tumor resection. It is currently unknown whether this will increase the risk of metastatic disease.

Toward a molecular pathologic classification of urothelial carcinoma.

We recently defined molecular subtypes of urothelial carcinomas according to whole genome gene expression. Herein we describe molecular pathologic characterization of the subtypes using 20 genes and IHC of 237 tumors. In addition to differences in expression levels, the subtypes show important differences in stratification of protein expression. The selected genes included biological features central to bladder cancer biology, eg, cell cycle activity, cellular architecture, cell-cell interactions, and key receptor tyrosine kinases. We show that the urobasal (Uro) A subtype shares features with normal urothelium such as keratin 5 (KRT5), P-cadherin (P-Cad), and epidermal growth factor receptor (EGFR) expression confined to basal cells, and cell cycle activity (CCNB1) restricted to the tumor-stroma interface. In contrast, the squamous cell cancer-like (SCCL) subtype uniformly expresses KRT5, P-Cad, EGFR, KRT14, and cell cycle genes throughout the tumor parenchyma. The genomically unstable subtype shows proliferation throughout the tumor parenchyma and high ERBB2 and E-Cad expression but absence of KRT5, P-Cad, and EGFR expression. UroB tumors demonstrate features shared by both UroA and SCCL subtypes. A major transition in tumor progression seems to be loss of dependency of stromal interaction for proliferation. We present a simple IHC/histology-based classifier that is easy to implement as a standard pathologic evaluation to differentiate the three major subtypes: urobasal, genomically unstable, and SCCL. These three major subtypes exhibit important prognostic differences.

Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar).

Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.

Tough Times Require Tough People: The Benefits of Grit for Reducing Employee Burnout.

Organizations are facing a serious challenge with employee burnout, which leads to a loss of productivity and employee morale. Despite its importance, there is still a knowledge gap in understanding one of the key features of employee burnout, namely, the personal characteristics of employees. This research aims to determine if grit can alleviate employee burnout in organizations. The study conducted a survey of employees in service companies, and results showed that employee grit was negatively associated with burnout. Moreover, the study revealed that grit does not equally affect all three dimensions of burnout, with emotional exhaustion and depersonalization being the most affected by employee grit. Increasing employee grit is therefore a promising strategy for companies that want to mitigate the risk of employee burnout.

Practice Variation in the Management of Adult Hydroceles: A Multinational Survey.

Background: Although hydrocele is one of the most common urologic pathologies, it is seldom studied, and the major urologic associations have no guidelines for the management of adult hydroceles. Objective: To characterize international practice variation in the treatment of adult hydroceles. Design setting and participants: An international survey was conducted addressing the management of hydroceles among urologists in Belgium, Denmark, Finland, Iceland, Japan, and the Netherlands from September to December 2020. We invited a random sample of 170 urologists from each country (except Iceland). Outcome measurements and statistical analysis: Urologists' treatment options, factors relevant for decision-making, expected patient satisfaction, and outcomes after aspiration versus surgery were assessed. Results and limitations: Of the 864 urologists contacted, 437 (51%) participated. Of the respondents, 202 (53%) performed both hydrocelectomies and aspiration, 147 (39%) performed hydrocelectomies only, and 30 (8%) performed aspiration only. In Belgium (83%), the Netherlands (75%), and Denmark (55%), urologists primarily performed hydrocelectomies only, whereas in Finland (84%), Japan (61%), and Iceland (91%), urologists performed both hydrocelectomies and aspiration. Urologists favored hydrocelectomy for large hydroceles (78.8% vs 37.5% for small), younger patients (66.0% for patients <50 yr vs 41.2% for ≥70 yr), patients with few or no comorbidities (62.3% vs 23.1% with multiple comorbidities), and patients without antithrombotic agents (53.5% vs 36.5% with antithrombotic agents). Most urologists considered patient satisfaction to be highest after hydrocelectomy (53.8% vs 9.9% after aspiration) despite believing that hydrocelectomy is more likely to cause complications (hematoma 77.8% vs 8.8% after aspiration). Estimates varied between countries. Conclusions: We found a large variation in the treatment of adult hydroceles within and between countries. Optimization of hydrocele management globally will require future studies. Patient summary: Our international survey shows that treatment of adult hydrocele varies considerably within and between countries.

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

UNLABELLED: It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now. By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable. OBJECTIVES: To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS: Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS: The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION: Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.

Transition from open to robotically assisted approach on radical prostatectomies in Iceland. A nationwide, population-based study.

OBJECTIVES: In January 2015, radical prostatectomies (RPs) in Iceland changed almost entirely from being performed as open (ORP) to robotically assisted (RARP). This study assesses early surgical and short-term oncological outcome after ORP and RARP and evaluates the safety of transition between the two surgical techniques. METHODS: The study population involved 160/163 (98%) of all radical prostatectomies performed in Iceland between January 2013 and April 2016. Data on patients was collected retrospectively from medical records. Early surgical and short-term oncological outcomes were compared between the two surgical techniques. RESULTS: The ORP and RARP cohorts were comparable with respect to all clinical and pathological variables, except for median prostate volume, which was 45 mL in the ORP cohort and 37 mL in the RARP cohort (p = 0.03). Intraoperative blood loss was higher, hospital stay longer, catheterization time longer, and risk of complications within 30 days of surgery higher after ORP than RARP (p < 0.01). The operative time, positive surgical margin rate and recurrence free survival, within two years, was comparable between the two surgical techniques. CONCLUSIONS: The transition from ORP to RARP in Iceland was safe and resulted in improved early surgical outcome. However, no conclusion can be drawn from this study regarding oncological outcome, due to short follow up and a small sample size.

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

OBJECTIVE: Being able to predict the recurrence or progression of non-muscle-invasive bladder cancer would facilitate effective planning of treatments and follow-up. Biomarkers are needed that can supply prognostic information beyond that provided by clinical and pathological parameters. Tissue microarray (TMA)-based analysis of Ta bladder tumours was used to investigate the prognostic value of expression of several proteins involved in bladder carcinogenesis. MATERIAL AND METHODS: Tumour tissue from 52 patients with Ta bladder cancer was investigated. At least three 0.6 mm punch cores from each tumour were placed in a paraffin array block. Tumour expression of tumour protein 53 (TP53), CDH1 (E-cadherin), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), fibroblast growth factor receptor-3 (FGFR3) and epidermal growth factor receptor (EGFR) was quantified by immunohistochemistry (IHC) and correlated with time to recurrence. Median follow-up time was 3.1 years. Whole-section IHC analysis was performed to validate significant findings. RESULTS: Of all patients, 69% (36/52) experienced recurrence. In univariate analysis, recurrence was associated with multifocality, number of earlier recurrences and a low quantity score for EGFR. In a multivariate model, a low EGFR quantity score was correlated with early recurrence (hazard ratio = 5.5, p = 0.003). However, whole-section IHC results for EGFR differed markedly from the TMA findings (κ = 0.07) and no association with time to recurrence was found (p = 0.65). CONCLUSIONS: Expression of EGFR measured by TMA-IHC, but not by whole-section IHC, was associated with early recurrence. The results suggest that the proteins assessed have no predictive value for recurrences. Concerns are raised regarding the methodology and generalization of results obtained with TMA-IHC.

Operative management in patients with upper tract urothelial carcinoma in Iceland: a population-based study.

OBJECTIVE: Radical nephroureterectomy is the standard treatment of organ-confined upper tract urothelial carcinoma (UTUC). The objective of this study was to investigate survival and bladder recurrence rate in Icelandic patients with UTUC who underwent radical nephroureterctomy (RNU) or other procedures with curative intent. MATERIAL AND METHODS: All patients who were diagnosed with UTUC in Iceland from 2003 to 2016 and treated with curative intent were included in the study. Information on patients was obtained retrospectively from patients' medical records and from the Icelandic Cause of Death Registry. RESULTS: Overall 63 patients underwent a procedure for UTUC with curative intent in Iceland during the study period. The median age was 71 years and the majority were male (65%). In 50 patients (79%), the tumor was a primary UTUC. The most common procedure was RNU (78%) and eight patients (13%) underwent a kidney-sparing procedure. No patient died within 90 d of surgery. Twenty-eight patients (44%) had pathological stage T2 or higher, whereas 35 patients (56%) had pathological stage T1 or lower. The median follow-up time was 98.8 months . During the follow-up time 25 patients (40%) were diagnosed with recurrence in the bladder. Five-year cancer-specific survival (CSS) was 67%. CONCLUSIONS: This population-based study shows that the oncologic outcome in Icelandic patients with UTUC is similar to what has been reported in other countries. Bladder recurrence rate is high and can hopefully be reduced by improvements in surgical and intravesical instillation treatment. Possibly more kidney-sparing surgeries could have been done during the study period; however, careful selection for those procedures is mandatory.

Which data are available in central registries on bladder cancer patients in the five Nordic countries.

OBJECTIVE: The aim of this study was to give a collective overview on all available data sources on bladder cancer patients in the Nordic countries including the amount of detail and coverage. METHODS: National representatives from five Nordic countries were asked to fill out a questionnaire on available information regarding bladder cancer patients from databases in their respective countries. Additional information was retrieved from descriptions of the relevant registries. RESULTS: Non-muscle invasive bladder cancer: from all countries, information on stage and grade at transurethral resection of the bladder (TURB) could be retrieved. Details on procedures (TURB, instillation therapy, photodynamic diagnosis, and perioperative instillation) were varying within different databases. Muscle invasive bladder cancer: in all Nordic countries, detailed information on cystectomy patients could be retrieved but with variable registration of complications. Completeness of available information on oncological treatment (radiation, chemotherapy, and immunotherapy) were varying. Oncological outcome: Information on overall survival was available in all countries whereas recurrence-free survival and cancer-specific survival were available for some but not all patients depending on treatment modality. CONCLUSIONS: Despite limitations, we found that it was possible to retrieve detailed information on diagnostics, treatment, and outcome for most aspects of bladder cancer in the Nordic countries on a population based, non-selected patient cohort.

Clinical markers of morbidity, mortality and survival in bladder cancer patients treated with radical cystectomy. A systematic review.

Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.Objective: To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice.

Preventing Parastomal Hernia After Ileal Conduit by the Use of a Prophylactic Mesh: A Randomised Study.

BACKGROUND: Parastomal hernia (PSH) after urinary diversion with ileal conduit is frequently a clinical problem. OBJECTIVE: To investigate whether a prophylactic lightweight mesh in the sublay position can reduce the cumulative incidence of PSH after open cystectomy with ileal conduit. DESIGN, SETTING, AND PARTICIPANTS: From 2012 to 2017, we randomised 242 patients 1:1 to conventional stoma construction (n = 124) or prophylactic mesh (n = 118) at three Swedish hospitals (ISRCTN 95093825). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was clinical PSH, and secondary endpoints were radiological PSH assessed in prone position with the stoma in the centre of a ring, parastomal bulging, and complications from the mesh. RESULTS AND LIMITATIONS: Within 24 mo, 20/89 (23%) patients in the control arm and 10/92 (11%) in the intervention arm had developed a clinical PSH (p = 0.06) after a median follow-up of 3 yr, corresponding to a hazard ratio of 0.45 (confidence interval 0.24-0.86, p = 0.02) in the intervention arm. The proportions of radiological PSHs within 24 mo were 22/89 (25%) and 17/92 (19%) in the two study arms. During follow-up, five patients in the control arm and two in the intervention arm were operated for PSH. The median operating time was 50 min longer in patients receiving a mesh. No differences were noted in proportions of Clavien-Dindo complications at 90 d postoperatively or in complications related to the mesh during follow-up. CONCLUSIONS: Prophylactic implantation of a lightweight mesh in the sublay position decreases the risk of PSH when constructing an ileal conduit without increasing the risk of complications related to the mesh. The median surgical time is prolonged by mesh implantation. PATIENT SUMMARY: In this randomised report, we looked at the risk of parastomal hernia after cystectomy and urinary diversion with ileal conduit with or without the use of a prophylactic mesh. We conclude that such a prophylactic measure decreased the occurrence of parastomal hernias, with only a slight increase in operating time and no added risk of complications related to the mesh.

MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31.

We analyzed 34 cases of urothelial carcinomas by miRNA, mRNA and genomic profiling. Unsupervised hierarchical clustering using expression information for 300 miRNAs produced 3 major clusters of tumors corresponding to Ta, T1 and T2-T3 tumors, respectively. A subsequent SAM analysis identified 51 miRNAs that discriminated the 3 pathological subtypes. A score based on the expression levels of the 51 miRNAs, identified muscle invasive tumors with high precision and sensitivity. MiRNAs showing high expression in muscle invasive tumors included miR-222 and miR-125b and in Ta tumors miR-10a. A miRNA signature for FGFR3 mutated cases was also identified with miR-7 as an important member. MiR-31, located in 9p21, was found to be homozygously deleted in 3 cases and miR-452 and miR-452* were shown to be over expressed in node positive tumors. In addition, these latter miRNAs were shown to be excellent prognostic markers for death by disease as outcome. The presented data shows that pathological subtypes of urothelial carcinoma show distinct miRNA gene expression signatures.

Extended lymph node dissection in patients with urothelial cell carcinoma of the bladder: can it make a difference?

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.

Extended pelvic lymphadenectomy for prostate cancer: will the previously reported benefits be reproduced in hospitals with lower surgical volumes?

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.