The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.
Objectives
To determine if a re-TUR in the presence or absence of muscle at the first TUR in T1-high grade (HG)/G3 bladder cancer patients makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).
Methods
In a large retrospective multi-centre cohort of 2451 T1-HG/G3 patients initially treated with BCG, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in 4 groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the 4 groups.
Results
Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence (HR = 0.67, p = 0.08), progression (HR = 0.46, p = 0.06), CSS (HR = 0.31; p = 0.07) and OS (HR = 0.48, p = 0.05). Re-TUR in the presence of muscle in the primary specimen did not improve the outcome for any of the endpoints.
Conclusions
Our retrospective analysis suggests that re-TUR may not be necessary in T1-HG/G3 patients if muscle is present in the specimen of the primary TUR.
Background
Potential differences in efficacy of different BCG strains are of importance for daily practice, especially in the era of BCG shortage.
Objective
To retrospectively compare the outcome with BCG Connaught and BCG Tice in a large study cohort of pT1 high grade non muscle-invasive bladder cancer (NMIBC) patients.
Design, setting, and participants
Individual patient data were collected for 2451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011.
Outcome measurements and statistical analysis
Using Cox multivariable regression and adjusting for the most important prognostic factors in this non randomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression and the duration of cancer specific (CSS) and overall survival (OS).
Results and limitations
Information on the BCG strain was available for 2099 patients: 957 on Connaught and 1142 on TICE. 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (HR = 1.48, 95% CI: 1.20 – 1.82, p < 0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66, 95% CI: 0.47 – 0.93, p=0.019) with a trend for CSS (HR = 0.36, 95% CI: 0.14 – 0.92, p = 0.033). For time to progression and OS, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall and disease specific, for TICE but not for Connaught.
Conclusions
We found that BCG Connaught results in a lower recurrence rate as compared to BCG Tice when no maintenance is used. However, the opposite is true when maintenance is given.
Patient summary
Since there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this non randomized retrospective comparison in over 2000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG Tice when no maintenance is used, but the opposite is true when maintenance is given.
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