C Müller

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

The mechanism of generating immunoglobulin light chain genes by rearrangement of variable (V), joining (J), and constant (C) gene segments is still unknown. It has been discussed mostly in terms of excision and deletion of the DNA between the recombined V and J gene segments. However, the finding of DNA digests from the mouse myeloma T of a fragment (called f-T) that contains the 3' flank of a V kappa and the 5' flank of a J1 gene segment argued against a simple deletion mechanism [Steinmetz, M., Altenburger, W. & Zachau, H. G. (1980) Nucleic Acids Res. 8, 1709--1720]. The origin of fragment f-T has now been investigated by cloning and determining the sequence of the germ-line V gene segment that apparently participated in its formation. Moreover, analogous fragments containing flanking sequences were isolated from the myelomas MOPC 173 and 41 (f-173 and f-41) and studied by sequence analysis. The f fragments appear to be recombination products of V--J rearrangements reciprocal to rearranged kappa genes but, at least in the cases of f-T and f-173, not of the rearranged V genes present in the same tumor cell. This fact is best explained by a sister chromatid exchange mechanism of V--J recombination because, by this model, the rearranged V genes and the reciprocal flank recombination products would segregate into different cells during the following mitosis. The possibility is suggested that there exists in lymphocyte differentiation more than one mechanism of V--J recombination.

Almost half of our patients admitted with mesenteric infarction (MI) (n = 81) were inoperable. In the group (n = 44) who underwent curative therapy, 45% have survived, 32% died of recurrent MI and 23% from causes other than intestinal ischemia. In view of this high rate of recurrence our therapeutic strategy in MI needs to be reconsidered. Postischemic vasoconstriction may be the main cause of the progression of mesenteric ischemia despite apparently curative treatment. Selective injection of vasodilators in the superior mesenteric artery may improve prognosis.