The first two reviews are from the same unit in Germany and describe the well‐known but still much discussed ways of improving the prognosis of patients undergoing cystectomy for bladder cancer. The authors review the roles of lymph node dissection and perioperative chemotherapy, and draw conclusions which will be of help for patients having this form of therapy. In a further review, authors from Egypt debate the requirement for a refluxing or non‐refluxing uretero‐ileal anastomosis in low‐pressure reservoirs, drawing on their extensive experience in this field. The optimum treatment for patients with muscle‐invasive bladder cancer remains a matter of intense debate; some authors still question the role of radical cystectomy (RC) per se, as it can be a potentially mutilating procedure with subsequent impairment in quality of life. However, the impairment has not been investigated using validated quality‐of‐life studies. By contrast, it is commonly accepted that no alternative treatment yields similar long‐term survival data to RC. However, survival rates after RC are far from satisfying, particularly for patients with ≥ pT3 and/or pN+ disease. Therefore, various strategies were introduced to improve survival in these patients, i.e. extension of lymph node dissection during radical surgery and perioperative chemotherapy. Both strategies are analysed and discussed in two mini‐reviews, based on data from current publications and from theoretical considerations.

In this review we analyse the current status of perioperative systemic chemotherapy in the treatment of transitional cell carcinoma (TCC) of the bladder; instead of summarizing each neoadjuvant or adjuvant clinical trial we focus on the advantages and disadvantages of both strategies on the basis of theoretical considerations, and outline a rationale for a better design of future studies to confirm the efficacy of perioperative chemotherapy in TCC.

You have accessJournal of UrologyDiscussed Poster, Monday, May 22, 2006, 9:00 am - 12:00 pm1 Apr 2006640: Activated Neutrophil Granulocytes Orchestrate Monocyte and CD4+ T Cell Trafficking During BCG-Immunotherapy of Superficial Bladder Cancer Henrik Suttmann, Dominik Schmaltz, Dieter Jocham, Michael Stöckle, Andreas Böhle, Bad Schwartau, and Sven Brandau Henrik SuttmannHenrik Suttmann More articles by this author , Dominik SchmaltzDominik Schmaltz More articles by this author , Dieter JochamDieter Jocham More articles by this author , Michael StöckleMichael Stöckle More articles by this author , Andreas BöhleAndreas Böhle More articles by this author , Bad SchwartauBad Schwartau More articles by this author , and Sven BrandauSven Brandau More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)32886-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "640: Activated Neutrophil Granulocytes Orchestrate Monocyte and CD4+ T Cell Trafficking During BCG-Immunotherapy of Superficial Bladder Cancer." The Journal of Urology, 175(4S), p. 206 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 206 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Henrik Suttmann More articles by this author Dominik Schmaltz More articles by this author Dieter Jocham More articles by this author Michael Stöckle More articles by this author Andreas Böhle More articles by this author Bad Schwartau More articles by this author Sven Brandau More articles by this author Expand All Advertisement Loading ...

Immunotherapy for treatment of solid cancer mostly is an experimental treatment. In contrast, intravesical immunotherapy of superficial bladder cancer with bacille Calmette-Guerin (BCG) is clinically well established and accepted worldwide because of better results compared to topical chemotherapy. BCG is currently regarded as the most successful immunotherapy of cancer. Unfortunately the mechanism of action has not yet been fully clarified. This article gives an overview on the complex research on the mechanisms of action-highly successful therapy.

We present a rare case of mesonephroid adenocarcinoma arising from mesonephroid metaplasia of the urinary bladder. For the first time, the unique histopathologic features in this patient provide evidence for the theory that vesical mesonephroid adenocarcinoma might be a highly aggressive metaplastic variant of urothelial carcinoma that should be treated accordingly.

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 1:00 - 5:00 pm1 Apr 2005756: Neutrophil Granulocytes are Essential During BCG Immunotherapy of Superficial Bladder Cancer Henrik Suttmann, Josef Riemensberger, Andreas Böhle, Dieter Jocham, and Sven Brandau Henrik SuttmannHenrik Suttmann More articles by this author , Josef RiemensbergerJosef Riemensberger More articles by this author , Andreas BöhleAndreas Böhle More articles by this author , Dieter JochamDieter Jocham More articles by this author , and Sven BrandauSven Brandau More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34925-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "756: Neutrophil Granulocytes are Essential During BCG Immunotherapy of Superficial Bladder Cancer." The Journal of Urology, 173(4S), p. 205 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 205 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Henrik Suttmann More articles by this author Josef Riemensberger More articles by this author Andreas Böhle More articles by this author Dieter Jocham More articles by this author Sven Brandau More articles by this author Expand All Advertisement PDF downloadLoading ...

PURPOSE:Natural killer (NK) cells are of crucial importance for bacillus Calmette-Guerin (BCG) mediated antitumor effects. We defined the mechanisms of BCG mediated NK cell activation in vitro.MATERIALS AND METHODS:A standard Cr release assay was used to measure the cytotoxicity of BCG activated NK cells. Using the MACS system (Miltenyi Biotec, Bergisch-Gladbach, Germany) we depleted various immune cell subpopulations from BCG stimulated peripheral blood mononuclear cells to phenotype activated NK cells. During the stimulation process anticytokine antibodies and recombinant cytokines were added to define their role in NK cell activation. For costimulation studies peripheral blood mononuclear cells were separated into lymphocytes and monocytes by counterflow-centrifugation (elutriation). Inhibitory NK cell receptor expression on activated NK cells was measured by flow cytometry by antiCD3, antiCD56 and anti-inhibitory NK cell receptor triple staining.RESULTS:The accessory function of monocytes was indispensable for BCG mediated NK cell activation. However, the stimulatory potential of monocytes did not require direct cell-cell contact to NK cells or major histocompatibility complex dependent antigen presentation to T cells. Monocyte derived interleukin (IL)-12 and to a lesser extent interferon (IFN)-alpha were key mediators for stimulating BCG induced NK cell cytotoxicity and IFN-gamma production. In contrast, IL-10 inhibited NK cell cytotoxicity and IL-18 did not show any effect. Exogenous recombinant IFN-alpha and IL-12 enhanced BCG mediated secretion of IFN-gamma and yet BCG induced NK cell cytotoxicity remained unchanged. While the CD158a and CD158b subsets did not have a significant role, NKG2A cells represented the predominant cytolytic subset in BCG activated NK cells.CONCLUSIONS:Following BCG stimulation the monocyte derived TH1 cytokines IL-12 and IFN-alpha activate tumor cytotoxic CD3/CD56/NKG2A NK cells. Our results elucidate NK activating mechanisms that are operative during BCG immunotherapy for bladder cancer and are relevant for an early, innate antimycobacterial immune response.

ABSTRACTPolymorphonuclear neutrophil granulocytes (PMN) have been implicated in the early inflammatory response against mycobacteria besides monocytes/macrophages. Yet, little is known about the interaction of mycobacteria with PMN. We investigated the potential ofMycobacterium bovisbacillus Calmette-Guérin (BCG) to stimulate and influence PMN phenotype, gene expression profile and spontaneous apoptosis. Flow cytometric analyses revealed an upregulation of the function-associated molecules Fcγ receptor III (FcγR III) and II (CD16 and CD32) as well as MAC-1 (CD11b and CD18) on BCG-stimulated PMN. As determined by cDNA microarrays and multiplex reverse transcriptase PCR, stimulation with BCG alters the expression of various genes for proinflammatory cytokines/chemokines or receptors in PMN. We detected an upregulation or de novo synthesis of interleukin 1α (IL-1α), IL-1β, IL-8, macrophage inflammatory protein 1α (MIP-1α), MIP-1β, GRO-α, transforming growth factor β, MCP-1, IL-2 receptor γ (IL-2Rγ), IL-10Rα, and IL-6R. Genes for IL-9, IL-12α, IL-15, IL-5Rα, and IL-13Rα1were found to be downregulated or switched off. Furthermore, Giemsa and annexin V-propidium iodide double staining demonstrated an inhibition of spontaneous PMN apoptosis following BCG stimulation. Changes in phenotype and inhibition of apoptosis did not depend on direct mycobacterial stimulation alone, but were a result of an autocrine-paracrine stimulation mechanism. Our findings support the hypothesis that PMN become activated at the site of mycobacterial infections and that this activation might set the stage for a subsequent antimycobacterial immune response.

Immunotherapy with Bacillus Calmette-Guérin (BCG) is clinically established in the treatment of superficial bladder cancer. In our attempt to clarify the underlying immunological mechanism, we could previously show that stimulation of PBMC with BCG leads to the generation of cytotoxic BCG-activated killer (BAK) cells. Among others, these BAK cells as well as lymphokine-activated killer (LAK) cells have been suggested as possible effector cells during BCG therapy. To understand BCG-induced activation of effector lymphocytes more precisely, we investigated the lytic pathways of human BAK cells and compared BAK cell cytotoxicity with LAK cell cytotoxicity. Perforin and Fas ligand (FasL) are the major cytolytic molecules of cytotoxic lymphocytes. Our results demonstrate that BAK and LAK cells showed an increased expression of perforin and FasL as compared with unstimulated controls. Killing of T-24 bladder tumor as well as Jurkat cells by BAK and LAK cells was predominantly mediated via perforin as demonstrated by a drastically reduced lysis in the presence of concanamycin A and EGTA/MgCl2, respectively. In contrast, lysis (radioactive release assay) and membrane disintegration (Annexin V binding) of both targets by BAK and LAK cells could not be blocked with an inhibitory anti-FasL monoclonal antibody (NOK-1). Nevertheless, T-24 and Jurkat were susceptible to killing by recombinant soluble FasL and by Chinese hamster ovary cells expressing membrane-bound FasL. We conclude that cellular mediators of BCG effector mechanisms, such as BAK and LAK cells, kill their targets via perforin and independent of the FasL pathway. Because we also found increased numbers of perforin-expressing lymphocytes in patients after BCG therapy, our findings have potential clinical relevance because BCG therapy would not be impaired by FasL resistance of target cells, which recently has been described for some tumors.