Background and MethodsCirculating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs.ResultsThe mean CTC counts were 4.6 CTCs [range, 0–8] in patients with localized PCa, 16.8 CTCs [range, 10–25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0–98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively.ConclusionOur results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1–29.39). This proof of concept was required for the approval of the use of the CellCollector in a clinical study for the in vivo isolation of CTCs from the blood stream of PCa patients by the Federal Institute for Drugs and Medical devices (Germany, BfArM).
OBJECTIVE
To compare the oncological outcomes of laparoscopic radical nephroureterectomy (LNU) vs open NU (ONU) for upper urinary tract transitional cell carcinoma (TCC).
PATIENTS AND METHODS
Between July 1999 and January 2003, we performed 70 LNUs and 70 ONUs for TCC of the upper urinary tract. ONU was reserved for patients with previous abdominal surgery or with severe cardiac and/or pulmonary problems. Demographic data, tumour staging and histological grading and rates of metastasis were recorded and compared.
RESULTS
For LNU and ONU the mean operative durations were 240 min and 190 min, respectively. The definitive pathology showed a high incidence of tumour stage pT2 G2 in both LNU and ONU groups. The median follow‐up was 60 months. In the LNU group, the 5‐year disease‐free survival (DFS) was 75%: 100% for pTa, 88% for pT1, 78% for pT2, and 35% for pT3 (P < 0.001). In the ONU group, the 5‐year DFS was 73% (LNU vs ONU, P = 0.037): 100% for pTa, 89% for pT1, 75% for pT2 and 31% for pT3 (P < 0.001).
CONCLUSION
The results of our long‐term controlled study support the use of LNU as an effective alternative to ONU in the therapy of upper urinary tract urothelial cancer.
This study showed that annular enlargement in patients with IMR affects the different annular regions to the same extent. An ideal surgical repair of IMR should be individually tailored after quantitative assessment measurement of geometry and function of each single component of the mitral valve complex.
Twenty-three patients, 11 men and 12 women, with a mean age of 64 (range, 34 to 78) underwent aortic valve replacement (AVR) with a CarboMedics "Top Hat" supraannular prosthesis between March 1993 and August 1994. The top hat supraannular prosthesis, a standard bileaflet valve with the cuff transferred to the valve inflow level, allowed implantation of 21-mm, 23-mm, and 25-mm valves, where a standard 19-mm or 21-mm valve would have usually been placed. One patient who had been in preoperative cardiogenic shock died in the perioperative period. Another had an intraoperative cerebral embolism with permanent impairment. Follow-up on 22 of 23 patients over a mean period of 9 months revealed mean Doppler gradients of 18 +/- 6 mmHg, 15 +/- 2.8 mmHg, and 11 mmHg, for the 21-mm, 23-mm, and 25-mm valves, respectively. Functional improvement was noted, with 17 patients in New York Heart Association (NYHA) Class I and 6 in NYHA Class II, postoperatively, compared with 0 in Class I, 9 in Class II, 10 in Class III, and 4 in Class IV, preoperatively. One patient showed reduced postoperative ventricular function with fractional shortening below 25%. Pandiastolic regurgitation intrinsic to the valve graded as slight was noted in all patients. Other postoperative complications included one patient with anticoagulant-related gastrointestinal bleeding and one other with prosthetic valve endocarditis successfully treated with antibiotics. The CarboMedics top hat valve allows a gain in prosthesis size of 2 mm to 4 mm in the aortic position over standard prostheses, resulting in favorable postoperative hemodynamics.
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