Today there are no established techniques to image positive surgical margins (PSM) intraoperatively in endoscopic extraperitoneal radical prostatectomy (EERPE). The intention of this study was to ...describe the specific technique of photodynamic diagnosis (PDD) in patients undergoing EERPE and report on the potential to detect PSM under PDD.
Twenty-four patients with clinically organ-confined prostate cancer received 5-aminolevulinic acid 20 mg/kg body weight orally 3 hours prior to nonnerve-sparing EERPE. An endoscopic PDD system (Karl Storz, Tuttlingen, Germany) including a Tricam PDD 3-chip camera head linked with a straight 10-mm telescope and a D-light C system was used. During EERPE, visualization of the surgical margins was performed by means of both white light and PDD at specific steps during standardized prostatectomy in all patients. Positive PDD areas on the prostate specimen were marked with white ink and consequently processed in pathology.
In white light endoscopy, no suspicion of a PSM was raised. Six out of the eight PSM were detected by PDD. In two cases, areas of positive PDD findings were free of prostate cancer and two PSM were not detected by PDD ( one bladder neck, one lateral). The overall sensitivity and specificity were 75% and 88.2%, respectively.
Laparoscopy offers an appropriate setting for the use of PDD in prostate cancer to visualize possible PSM. Although imaging of PSM by PDD is promising with the technique being feasible and safe, larger series are needed to prove the reproducibility of our results.
Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of ...limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2r gamma (null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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