ABSTRACT
BACKGROUND AND PURPOSE: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. MATERIALS AND METHODS: A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. RESULTS: With 48months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor (p<0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3+4=7a, 4+3=7b, and 8-10, respectively. CONCLUSIONS: In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis.
Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Adult , Aged , Humans , Lymph Node Excision , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Prostatectomy , Prostatic Neoplasms/pathology , Recurrence , Retrospective Studies , Risk , Salvage Therapy , Survival RateABSTRACT
PURPOSE: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. MATERIAL AND METHODS: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. RESULTS: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. CONCLUSION: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.
Subject(s)
Acute Kidney Injury/diagnostic imaging , Kidney Cortex/diagnostic imaging , Kidney Medulla/diagnostic imaging , Reperfusion Injury/diagnostic imaging , Tomography, X-Ray Computed/instrumentation , Acute Kidney Injury/diagnosis , Acute Kidney Injury/pathology , Animals , Disease Models, Animal , Image Processing, Computer-Assisted , Kidney Cortex/pathology , Kidney Medulla/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Reperfusion Injury/diagnosis , Reperfusion Injury/pathology , Synchrotrons , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND & AIMS: The risk for small bowel cancer (SBC) is significantly increased in hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC-associated SBCs are poorly characterized. METHODS: Thirty-two SBCs were characterized according to clinical, pathologic, and germline mutation data. Histomorphologic characteristics, microsatellite instability (MSI) testing, mismatch repair (MMR) protein expression, and frameshift mutations of 7 coding mononucleotide repeats were investigated in 17 SBCs. RESULTS: Median age at diagnosis was 39 years. Fifty percent of SBCs were located in the duodenum. The Amsterdam criteria were fulfilled in 50% of patients; 45% of patients had no personal history of previous malignancies. Two patients had a positive family history for SBC. Pathogenic germline mutations were identified in 81%; high MSI was detected in 95% and loss of MMR protein expression in 89% of cases. TGFBR2 , BAX , MSH3 , MSH6 , ACVR2 , AIM2 , and SEC63 frameshift mutations were detected in 69%, 59%, 59%, 35%, 82%, 56%, and 56%, respectively. An expansive growth pattern of the tumor border and an intense intratumoral lymphocytic infiltrate were present in 75%, respectively. CONCLUSIONS: HNPCC-associated SBC often manifests at a young age and may be the first disease manifestation. Endoscopy may detect 50% of tumors. Considering recent data on gastric cancer, we propose endoscopic screening of mutation carriers starting at 30 years of age because clinical criteria cannot define a high-risk group. In addition, our study shows that histopathologic criteria, MSI, and MMR immunohistochemistry are often similar to these features in HNPCC.
