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.
Few data illustrate the man's reaction to orchidectomy. We investigated long-lasting feelings of loss and uneasiness or shame about the body after removal of a testicle by orchidectomy. We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programmes Swedish-Norwegian Testicular Cancer Group I-IV between 1981 and 2004. We asked the survivors about feelings of loss and uneasiness or shame after having had a testicle removed by orchidectomy. We obtained information from 960 (82%) testicular cancer survivors. We found that 32% of these men miss or previously missed their removed testicle(s) and that 26% have or previously had feelings of uneasiness or shame about their body because of the removed testicle(s). Men who had never been offered a prosthesis reported feelings of loss [relative risk (RR): 2.0; 95% confidence interval (CI): 1.3-3.0] and uneasiness or shame (RR: 2.0; 95% CI: 1.3-3.2) to a higher extent than those who had been offered, but rejected a prosthesis. An orchidectomy may result in long-lasting feelings of loss and uneasiness or shame in some men; offering a testicular prosthesis may hinder this experience.
ObjectivesTo assess penile cancer incidence, stage distribution, adherence to guidelines and prognostic factors in a population-based setting.
Patients and MethodsThe population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. A total of 1 678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study.
ResultsThe mean age-adjusted incidence of penile cancer was 2.1/ 100 000 men, remaining virtually unchanged during the study period. At diagnosis, 14 and 2% of the men had clinical N+ and M+ disease, respectively. Most men were staged pTis (34%), pT2 (19%), or pT1 (18%), while stage information was unavailable for 18% of the men. Organ-preserving treatment was used in 71% of Tis-T1 tumours. Of men with cN0 and ≥pT1G2 disease, 50% underwent lymph node staging, while 74% of men with cN1-3 disease underwent lymph node dissection. The overall 5-year relative survival rate was 82%. Men aged ≥40 years and those with pT2-3, G2-3 and N+ tumours had worse outcomes.
ConclusionsThe incidence of penile cancer in Sweden is stable. Most men presented with localized disease, and the proportion of noninvasive tumours was high. During the period under study, adherence to guidelines was suboptimum. The overall 5-year relative survival rate was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival.
Stromal invasion in the rete testis and tumor diameter >4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.
Low educational level, low disposable income, being divorced or never married, and living in a single-person household, all increase the risk of advanced stage penile cancer, but not lymph node or distant metastases. The assessed indicators of SES did not influence penile CSM. In conclusion, our findings indicates that SES influences the risk and stage of penile cancer, but not survival.
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.
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