S. Wyler

Perioperative Morbidity of Laparoscopic Cryoablation of Small Renal Masses with Ultrathin Probes: A European Multicentre Experience

BACKGROUNDnLow morbidity has been advocated for cryoablation of small renal masses.nnnOBJECTIVESnTo assess negative perioperative outcomes of laparoscopic renal cryoablation (LRC) with ultrathin cryoprobes and patient, tumour, and operative risk factors for their development.nnnDESIGN, SETTING, AND PARTICIPANTSnProspective collection of data on LRC in five centres.nnnINTERVENTIONnLRC.nnnMEASUREMENTSnPreoperative morbidity was assessed clinically and the American Society of Anaesthesiologists (ASA) score was assigned prospectively. Charlson Comorbidity Index (CCI) and Charlson-Age Comorbidity Index (CACI) scores were retrospectively assigned. Negative outcomes were prospectively recorded and defined as any undesired event during the perioperative period, including complications, with the latter classed according to the Clavien system. Patient, tumour, and operative variables were tested in univariate analysis as risk factors for occurrence of negative outcomes. Significant variables (p<0.05) were entered in a step-forward multivariate logistic regression model to identify independent risk factors for one or more perioperative negative outcomes. The confidence interval was settled at 95%.nnnRESULTS AND LIMITATIONSnThere were 148 procedures in 144 patients. Median age and tumour size were 70.5 yr (range: 32-87) and 2.6 cm (range: 1.0-5.6), respectively. A laparoscopic approach was used in 145 cases (98%). Median ASA, CCI, and CACI scores were 2 (range: 1-3), 2 (range: 0-7), and 4 (range: 0-11), respectively. Comorbidities were present in 79% of patients. Thirty negative outcomes and 28 complications occurred in 25 (17%) and 23 (15.5%) cases, respectively. Only 20% of all complications were Clavien grade > or = 3. Multivariate analysis showed that tumour size in centimetres, the presence of cardiac conditions, and female gender were independent predictors of negative perioperative outcomes occurrence. Receiver operator characteristic curve confirmed the tumour size cut-off of 3.4 cm as an adequate predictor of negative outcomes.nnnCONCLUSIONSnPerioperative negative outcomes and complications occur in 17% and 15.5%, respectively, of cases treated by LRC with multiple ultrathin needles. Most of the complications are Clavien grade 1 or 2. The presence of cardiac conditions, female gender, and tumour size are independent prognostic factors for the occurrence of a perioperative negative outcome.

Abstract 3384: High ALDH activity is associated with high tumorigenicity in prostate cancer

OBJECTIVE: Tumor initiation and progression might be driven by rare populations of cells endowed with stem-properties, and therefore defined as cancer stem cells (CSC). High Aldehyde dehydrogenase (ALDH) activity has been suggested to selectively identify CSC in several tumor types including breast cancer, and, possibly, prostate cancer (PCA). In this study, we investigated presence and potential CSC characteristics of cells with high ALDH activity (ALDH bright) in PCA cell lines, fresh surgical specimens, and primary cultures. MATERIALS AND METHODS: PC3, Du145, VCaP, and LNCaP PCA cell lines were evaluated. Surgical specimens, including Benign Prostate Hyperplasia (BPH) and PCA, were used directly for gene expression studies. Surgical samples were also enzymatically digested for functional analysis and the establishment of primary cultures. ALDH activity was tested using ALDEFLUOR® technology. Cells were sorted from individual cell lines by flow cytometry and evaluated for CSC properties, including spheroid formation ability, clonogenicity, stemness-related gene expression, ALDH specific isoforms expression, and tumorigenicity upon injection in NOD/SCID mice. RESULTS: PCA cell lines and primary cultures displayed heterogeneous ALDH activity and expression of specific ALDH isoforms. Despite a higher expression of Oct4A and Klf4 stemness associated genes, ALDH bright cells isolated from Du145 and PC3 did not show improved spheroid formation or clonogenic capacity, as compared to their dim counterparts. Interestingly, however, ALDH bright cells were associated with a significantly higher tumorigenic capacity in vivo as compared to ALDH low cells. Nevertheless, ALDH bright cells lost their higher tumorigenic capacity following serial “in vivo” passages. Most importantly, a well defined ALDH bright population could also be detected in cells isolated from PCA specimens (n>20). ALDH activity was consistent with a strong expression of several ALDH specific isoforms in PCA tissues. Notably, a significant increase of defined ALDH isoforms such as ALDH1A3 (p=0.001) was detectable in tissues obtained from patients with PCA as compared to BPH or normal specimens. CONCLUSIONS: ALDH bright subsets can be detected in cells isolated from fresh PCA tissue samples, PCA cell lines and primary cultures. These populations appear to be associated with increased “in vivo” tumorigenicity rather than enhanced “in vitro” stem properties in the cell lines investigated. Importantly, expression of ALDH specific isoforms appears to be increased in clinical PCA as compared to BPH and “normal” samples, thereby suggesting a putative role of ALDH in PCA tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3384. doi:1538-7445.AM2012-3384