BackgroundAccumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn’t require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs.MethodsTwelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5–20 × 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care.ResultsNo INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy.ConclusionsOur findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.Trial registrationClinicaltrials.gov identifier: NCT01525017.

PEP has an equal anticancer efficacy to CAD and does not increase cardiovascular mortality. Final evaluation of cardiovascular morbidity is awaiting further analysis and follow-up. PEP is considerably cheaper than CAD.

In a questionnaire survey of urological departments in Sweden, Denmark, Finland and Norway, 20 episodes of perforation of continent urinary pouches were found to have occurred in 18 patients, representing an incidence of 1.5%. This complication occurred with ileal as well as colonic segments, without predilection. In one case there was perforation of an appendiceal outlet. Noticeable findings were (a) a long delay (median 10h) to treatment and (b) that investigational procedures such as enterocystography and enterocystoscopy were not commonly employed. Treatment of this potentially lethal complication was by oversewing the perforation, and there were no subsequent major complications. This complication should be strongly suspected if a patient with continent urinary reconstruction presents with acute abdominal pain.

To evaluate the influence of the volume of 2% lidocaine jelly as an anesthetic during cystoscopy 241 men and women received either 11 or 20 ml. jelly intraurethrally in a randomized, double-blind fashion. Pain was recorded on a visual analogue scale by the patient and on a 3-level scale by the physician. The pain scores according to the visual analogue scale were significantly higher in the patients given 11 ml. jelly than in those given 20 ml. when all patients in the study were analyzed. There was no significant difference in the visual analogue scale between the 2 treatments in women but a significant difference was noted in men, although in men older than 55 years the difference was not statistically significant. There was general agreement between the visual analogue scale results and the physician scores but the visual analogue scale procedure was more sensitive in detecting differences between treatments. It is suggested that approximately 11 ml. 2% lidocaine jelly is the appropriate volume for women and 20 ml. is the appropriate volume for men during cystoscopy but that the lower volume of jelly may be sufficient in older men.

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