Nerve Protection During Prostate Cryosurgery.

Cryosurgery is a minimally invasive approach to the treatment of focal prostate cancer (PCa). A major complication is the cryoinjury to the cavernous nerve in the neurovascular bundle (NVB). This nerve cryoinjury halts conduction of action potentials (APs) and can eventually result in erectile dysfunction and therefore diminished quality of life for the patient. Here, we propose the application of cryoprotective agents (CPA) to the regions of the nerves in the NVB, prior to prostate cryosurgery, to minimize non-recoverable loss of AP conduction. We modeled a cryosurgical procedure based on data taken during a clinical case and applied ex-vivo porcine phrenic nerves and rat sciatic nerve with temperature profile of NVB. The APs were measured before and after the CPA exposures and during 3 h of recovery. Comparisons of AP amplitude recovery with various CPA compositions reveal that certain CPAs (e.g., 5% DMSO + 7.5% Trehalose and 5% M22 for porcine and rat nerves, respectively) showed little or no toxicity and effective cryoprotection from freezing (on average 48% and 30% of recovered AP, respectively). In summary, we demonstrate that neural conduction can be preserved after exposure to freezing conditions if CPAs are properly selected and deployed onto the nerve.

Determinants and effects of positive surgical margins after prostatectomy on prostate cancer mortality: a population-based study.

BACKGROUND: The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. METHODS: We included 1'254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990-2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon's caseload. RESULTS: Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage of tumour in the prostate were significantly associated to positive margins. Ten-year prostate cancer-specific survival was 96.6% for the negative margins group and 92.0% for the positive margins group (log rank p = 0.008). In the Cox survival analysis adjusted for tumour characteristics, surgical margin status per se was not an independent prognostic factor while age, pathological T, PSA level and Gleason score remained associated with prostate cancer-specific survival. CONCLUSIONS: More aggressive tumour characteristics were strong determinants for positive margins. Furthermore, surgical margin status per se was not an independent prognostic factor for prostate cancer-specific survival after adjusting by the gravity of the disease in the multivariate analysis.

Impact of socioeconomic status on prostate cancer diagnosis, treatment, and prognosis.

BACKGROUND: The objective of the current study was to evaluate the impact of socioeconomic disparities on prostate cancer presentation, treatment, and prognosis in Geneva, Switzerland, in which healthcare costs, medical coverage, and life expectancy are considered to be among the highest in the world. METHODS: This population-based study included all patients diagnosed with invasive prostate cancer among the resident population between 1995 and 2005. Patients were divided into 3 socioeconomic groups according to their last known occupation. Compared were patient and tumor characteristics and treatment patterns between socioeconomic groups. Cox multivariate regression analysis was used to assess and explain socioeconomic inequalities in prostate cancer-specific mortality. RESULTS: Compared with patients of high socioeconomic class, those of low socioeconomic class were more often foreigners, were found less frequently to have screen-detected cancer, were found to have a more advanced stage of disease at diagnosis, and less often had information regarding disease characteristics and staging. These patients underwent prostatectomy less frequently and were more often managed with watchful waiting. The risk of dying as a result of prostate cancer (hazards ratio [HR]) in patients of a low versus high socioeconomic status was increased 2-fold (95% confidence interval [95% CI], 1.5-2.6). After adjustment for patient and tumor characteristics and treatment, the mortality risk was no longer found to be significantly increased (HR, 1.2; 95% CI, 0.8-1.6). CONCLUSIONS: In the current study, patients of low socioeconomic class were found to be at increased risk of dying as a result of their prostate cancer. This increased mortality is largely attributable to delayed diagnosis, poor diagnostic workup, and less invasive treatments in these individuals.

Adjuvant approaches to enhance cryosurgery.

Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue. This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions. Two important motivations for adjuvant use are: (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site). This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo. The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including: thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators. The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.

Percutaneous cryoablation of small kidney tumours under magnetic resonance imaging guidance: medium-term follow-up.

OBJECTIVE: Minimally invasive treatment of small kidney tumours remains a challenge. Cryoablation has recently been advocated for such neoplasias. However, few series evaluating this therapeutic regimen are as yet available. The goal of this retrospective study was to evaluate the initial clinical experience of magnetic resonance imaging (MRI)-guided percutaneous cryotherapy of small renal tumours. MATERIAL AND METHODS: Seven patients with small renal tumours [mean diameter 21 (11-30) mm] underwent percutaneous renal tumour cryoablation using the Cryo-Hit delivery system. The procedure was performed in an MRI interventional unit, using a 0.23 Tesla open MRI imaging system. Five men and two women were included in the group. The average age was 61.5 (34-84) years. The patients had a solitary kidney (n = 2), renal insufficiency (n = 4) or a kidney graft (n = 1). The intervention was performed under general anaesthesia. Average time for the whole procedure was 235 min with 26 min of effective treatment time. Mean follow-up was 28 (7-43) months. RESULTS: All tumours were successfully ablated. There were no perioperative complications. Mean hospital stay was 2.4 (2-5) days. One patient stayed for 5 days because therapeutic anticoagulation had to be reinitiated. No significant change in the perioperative value of the serum creatinine was noticed. No radiographic evidence of disease recurrence or new tumour development was identified during the follow-up. CONCLUSIONS: In this small group of patients, percutaneous renal tumour cryoablation under MRI guidance was efficient and carried no morbidity. Hospital stay was remarkably shorter than that of surgically treated patients. At medium-term follow-up, no recurrence has been identified, but long-term follow-up is required.

Increased risk of colon cancer after external radiation therapy for prostate cancer.

Radiotherapy can induce second cancers. Controversies still exist regarding the risk of second malignancies after irradiation for prostate cancer. We evaluated the risk of developing colon and rectum cancers after prostate cancer in irradiated and nonirradiated patients. Using data from the population-based Geneva cancer registry, we included in the study all men with prostate cancer diagnosed between 1980 and 1998 who survived at least 5 years after diagnosis. Of the 1,134 patients, 264 were treated with external radiotherapy. Patients were followed for occurrence of colorectal cancer up to 31 December, 2003. We calculated standardized incidence ratios (SIR) using incidence rates for the general population to obtain the expected cancer incidence. The cohort yielded to 3,798 person-years. At the end of follow-up 19 patients had developed a colorectal cancer. Among irradiated patients the SIR for colorectal cancer was 3.4 (95% confidence intervals [CI] 1.7-6.0). Compared to the general population, the risk was significantly higher for colon cancer (SIR = 4.0, 95% CI: 1.8-7.6), but not for rectal cancer (SIR = 2.0, 95% CI: 0.2-7.2). The risk of colon cancer was increased in the period of 5-9 years after diagnosis (SIR = 4.7, 95% CI: 2.0-9.2). The overall SIR of secondary cancer in patients treated with radiotherapy was 1.35 (p = 0.056). Nonirradiated patients did not have any increased risk of rectal or colon cancer. This study shows a significant increase of colon but not rectum cancer after radiotherapy for prostate cancer. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.

Short- and long-term mortality with localized prostate cancer.

BACKGROUND: No clear guidelines exist for managing localized prostate cancer because clinical studies have not yet established which treatment provides the best long-term outcome. We assessed the effect of treatment on prostate cancer-specific mortality considering the determinants of treatment and prognosis. METHODS: The population-based cohort included all 844 patients having a diagnosis of localized prostate cancer between January 1, 1989, and December 31, 1998, in Geneva, Switzerland. Treatments included prostatectomy (n = 158), radiotherapy (n = 205), watchful waiting (n = 378), hormone therapy (n = 72), and other types of therapy (n = 31). We compared survival curves using the log-rank test. With multivariate Cox proportional hazards analysis and propensity score methods, we evaluated the independent effect of treatments on prostate cancer-specific mortality. RESULTS: Treatment options only slightly influenced 5-year prostate cancer-specific mortality but had an important effect on long-term mortality. Ten-year specific survival was 83% (95% confidence interval [CI], 73%-93%), 75% (95% CI, 67%-83%), and 72% (95% CI, 66%-80%) for patients who underwent surgery, radiotherapy, and watchful waiting, respectively (P < .001). At 10 years, patients treated with radiotherapy or watchful waiting had a significantly increased risk of death from prostate cancer compared with patients who underwent prostatectomy (multiadjusted hazard ratio, 2.3 [95% CI, 1.2-4.3] and 2.0 [95% CI, 1.1-3.8], respectively). The increased mortality associated with radiotherapy and watchful waiting was primarily observed in patients younger than 70 years and in patients with poorly differentiated tumors (Gleason score > or = 7; reference, 1 [best]-10 [worst]). Patients who received hormone therapy alone already had an increased risk of prostate cancer-specific mortality at 5 years (hazard ratio, 3.5 [95% CI, 1.4-8.7]). CONCLUSIONS: Our study results suggest that surgery offers the best chance of long-term prostate cancer-specific survival, in particular for younger patients and patients with poorly differentiated tumors. Until clinical trials provide conclusive evidence, physicians and patients should be informed of these results and their limitations.

A comprehensive renal injury concept based on a validated finite element model of the human abdomen.

BACKGROUND: The identification of abdominal injury mechanisms, development of effective countermeasures, and refinement of clinical approach to injury treatment are greatly facilitated by the employment of numerical models that can predict injuries resulting from complicated soft tissue interactions during blunt abdominal impact. METHODS: The present study introduces a detailed three-dimensional finite element model of the human abdomen that was developed specifically for the investigation of renal trauma. The model geometry and materials reflect the complex mechanical environment of the abdomen, and is validated against both published and novel experiments. RESULTS: It is shown that use of the proposed model, in combination with appropriate mechanical organ injury criteria, provides a significant step toward a comprehensive renal injury concept. Specifically, the abdominal model offers the possibility to investigate injury likelihood and identify injury mechanisms over a broad range of impact loading scenarios. CONCLUSIONS: A sophisticated numerical model of renal trauma has been developed that can be used to effectively predict renal injury outcome for lateral impact.

Low-dose versus standard-dose CT protocol in patients with clinically suspected renal colic.

OBJECTIVE: The purpose of our study was to compare a low-dose abdominal CT protocol, delivering a dose of radiation close to the dose delivered by abdominal radiography, with standard-dose unenhanced CT in patients with suspected renal colic. MATERIALS AND METHODS: One hundred twenty-five patients (87 men, 38 women; mean age, 45 years) who were admitted with suspected renal colic underwent both abdominal low-dose CT (30 mAs) and standard-dose CT (180 mAs). Low-dose CT and standard-dose CT were independently reviewed, in a delayed fashion, by two radiologists for the characterization of renal and ureteral calculi (location, size) and for indirect signs of renal colic (renal enlargement, pyeloureteral dilatation, periureteral or renal stranding). Results reported for low-dose CT, with regard to the patients' body mass indexes (BMIs), were compared with those obtained with standard-dose CT (reference standard). The presence of non-urinary tract-related disorders was also assessed. Informed consent was obtained from all patients. RESULTS: In patients with a BMI < 30, low-dose CT achieved 96% sensitivity and 100% specificity for the detection of indirect signs of renal colic and a sensitivity of 95% and a specificity of 97% for detecting ureteral calculi. In patients with a BMI < 30, low-dose CT was 86% sensitive for detecting ureteral calculi < 3 mm and 100% sensitive for detecting calculi > 3 mm. Low-dose CT was 100% sensitive and specific for depicting non-urinary tract-related disorders (n = 6). CONCLUSION: Low-dose CT achieves sensitivities and specificities close to those of standard-dose CT in assessing the diagnosis of renal colic, depicting ureteral calculi > 3 mm in patients with a BMI < 30, and correctly identifying alternative diagnoses.

Abdominal plain film in patients admitted with clinical suspicion of renal colic: should it be replaced by low-dose computed tomography?

OBJECTIVES: To evaluate a low-dose abdominal computed tomography (LDCT) protocol, delivering a radiation dose close to that delivered by an abdominal plain film (APF), in patients with a clinical suspicion of renal colic. METHODS: A total of 139 patients for whom an APF was requested for suspicion of renal colic were randomized into two groups. The patients in group 1 (n = 68) underwent an admission LDCT scan delivering a 2.1-mSv radiation dose to women and 1.6 mSv to men, instead of the APF. Patients in group 2 (n = 71) underwent an APF. Clinical and radiologic follow-up data were obtained for each patient. The number of additional abdominal ultrasound and CT scans performed to reach a confident final diagnosis and determine the proper treatment was compared between the two groups. A mean effective radiation dose was obtained in each group. RESULTS: Of the 68 patients in group 1 (LDCT), 10 (15%) underwent ultrasonography, 9 (13%) conventional abdominal CT, and 2 (3%) both. In group 2 (APF), the corresponding percentages were 27% (19 of 71), 28% (20 of 71), and 23% (16 of 71). Of the 68 patients in group 1, 47 (69%) did not require any additional examinations compared with 16 (23%) of the 71 patients in group 2 (P < 0.0001). The mean effective dose was 3.5 and 6.9 mSv in groups 1 and 2, respectively (P < 0.0001). CONCLUSIONS: In patients with suspicion of renal colic, replacing the admission APF with our LDCT protocol will significantly reduce the need for additional CT or ultrasonography. Also, our LDCT protocol decreases by almost 50% the mean radiation dose per patient.

Cryosurgical changes in the porcine kidney: histologic analysis with thermal history correlation.

Advances in minimally invasive renal cryosurgery have renewed interest in the relative contributions of direct cryothermic and secondary vascular injury-associated ischemic cell injury. Prior studies have evaluated renal cryolesions seven or more days post-ablation and postulated that vascular injury is the primary cell injury mechanism; however, the contributions of direct versus secondary cell injury are not morphologically distinguishable during the healing/repair stage of a cryolesion. While more optimal to evaluate this issue, minimal acute (< or = 3 days) post-ablation histologic data with thermal history correlation exists. This study evaluates three groups of porcine renal cryolesions: Group (1) in vitro non-perfused (n = 5); Group (2) in vivo 2-h post-ablation perfused (n = 5); and Group (3) in vivo 3-day post-ablation perfused (n = 6). The 3.4 mm argon-cooled cryoprobe's thermal history included a 75 degrees C/min cooling rate, -130 degrees C end temperature, 60 degrees C/min thawing rate, and 15-min freeze time. An enthalpy-based mathematical model with a 2-D transient axisymmetric numerical solution with blood flow consideration was used to determine the thermal history within the ice ball. All three groups of cryolesions showed histologically similar central regions of complete cell death (CD) and transition zones of incomplete cell death (TZ). The CD had radii of 1.4, 1.1, and 1.0 cm in the non-perfused, 2-h and 3-day lesions, respectively. Capillary thrombosis was present in the 2-h perfused cryolesions with the addition of TZ arteriolar/venous thrombosis in the 3-day perfused lesions. Thermal modeling revealed the outer CD boundary in all three groups experienced similar thermal histories with an approximately -20 degrees C end temperature and 2 degrees C/min cooling and thawing rates. The presence of similar CD histology and in vitro/in vivo thermal histories in each group suggests that direct cryothermic cell injury, prior to or synchronous with vascular thrombosis, is a primary mediator of cell death in renal cryolesions.