Irreversible electroporation, a new modality in Focal Therapy for prostate cancer.

The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols.

Follow-up after focal therapy in renal masses: an international multidisciplinary Delphi consensus project.

PURPOSE: To establish consensus on follow-up (FU) after focal therapy (FT) in renal masses. To formulate recommendations to aid in clinical practice and research. METHODS: Key topics and questions for consensus were identified from a systematic literature research. A Web-based questionnaire was distributed among participants selected based on their contribution to the literature and/or known expertise. Three rounds according to the Delphi method were performed online. Final discussion was conducted during the "8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer" among an international multidisciplinary expert panel. RESULTS: Sixty-two participants completed all three rounds of the online questionnaire. The panel recommended a minimum follow-up of 5 years, preferably extended to 10 years. The first FU was recommended at 3 months, with at least two imaging studies in the first year. Imaging was recommended biannually during the second year and annually thereafter. The panel recommended FU by means of CT scan with slice thickness ≤3 mm (at least three phases with excretory phase if suspicion of collecting system involvement) or mpMRI. Annual checkup for pulmonary metastasis by CT thorax was advised. Outside study protocols, biopsy during follow-up should only be performed in case of suspicion of residual/persistent disease or radiological recurrence. CONCLUSIONS: The consensus led to clear FU recommendations after FT of renal masses supported by a multidisciplinary expert panel. In spite of the low level of evidence, these recommendations can guide clinicians and create uniformity in the follow-up practice and for clinical research purposes.

Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study.

PURPOSE: Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. MATERIALS AND METHODS: Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. RESULTS: The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. CONCLUSIONS: Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone.

The role of imaging in the active surveillance of small renal masses.

Up to 66 % of renal cell carcinomas are detected as small renal masses before the presence of clinical symptoms. Small renal mass treatment has evolved from the exclusive use of radical nephrectomy to the use of nephron sparing procedures where possible. An increase in elderly and comorbid patients, together with the notion that just 20 % of small renal masses show high malignant potential, has prompted interest in active surveillance as a treatment option. Modern imaging techniques provide objective follow-up parameters, namely size, invasion of collecting system or perirenal fat and enhancement patterns, with minimal complication risks or patient discomfort. This review evaluates recent developments in the field of active surveillance for small renal masses. Special focus is placed on the role of imaging in the primary decision making and subsequent follow-up during active surveillance.

Pyrotechnic shock response predictions combining statistical energy analysis and local random phase reconstruction.

Numerous pyrotechnic devices are used on satellites to separate structural subsystems, deploy appendages, and activate on-board operating subsystems. The firing of these pyrotechnic mechanisms leads to severe impulsive loads which could sometimes lead to failures in electronic systems. The objective of the present investigation is to assess the relevance of a method combining deterministic calculations and statistical energy analysis to predict the time overall shock environment of electronic equipment components. The methods are applied to the low- and high-frequency ranges, respectively, which may be defined using a modal parameter based on the effective transmissibility. Initially, in order to address the problem of the low-frequency content of the mechanical shock pulse, the linear dynamic response of the equipment was calculated using direct time integration of a finite element model of the structure. The inputs in the form of the accelerations measured in all three directions at each of the four bolted interfaces were injected into the model. The high-frequency content of the shock response is taken into account by considering the intrinsic dynamic filtering of the equipment. This frequency filter magnitude is extrapolated from the transfer function given by statistical energy analysis between the different imposed accelerations and the response accelerations. Their associated phases are synthesized by considering pseudo-modal phase variations around the group velocity of the structural flexural waves. Combining the effects of the high-frequency filter outputs and the low-frequency finite element calculations yields good predictions of the equipment shock time response over the whole frequency range of interest.

Early discharge with home antibiotic therapy in the treatment of neonatal infection.

OBJECTIVE: To determine the feasibility and cost of home antibiotic therapy for a select group of neonates. METHODS: A cohort of neonates at a university hospital who met criteria for home antibiotic therapy at discharge were prospectively followed (November 1995 to October 1997) for type and duration of antibiotic therapy as well as for hospital readmission. RESULTS: During the study period, 95 infants diagnosed with sepsis, presumed sepsis, pneumonia, or uncomplicated meningitis (having received > 10 days of in-hospital therapy) met prior, established, criteria for home antibiotic therapy. The mean +/- SD birth weight of the cohort was 3160 +/- 526 gm, with a mean gestational age of 38.4 +/- 2.1 weeks. A total of 59 infants (62%) received antimicrobial therapy for a clinical presentation consistent with sepsis or presumed sepsis, and 24 infants (25%) were treated for pneumonia. Ampicillin and gentamicin were prescribed for 56% of the cohort, and ceftriaxone was prescribed for 21% of the cohort. Four of those infants were switched from intravascular ampicillin/gentamicin therapy to intramuscular ceftriaxone after discharge due to loss of intravascular access. With a bilirubin level of > 8, four additional infants were changed from ceftriaxone back to ampicillin and gentamicin to complete coverage. The mean age at discharge was 5.2 days, with a mean hospitalization cost of $6121 for that period. There were no rehospitalizations or emergency department visits secondary to a worsening clinical course. CONCLUSION: In this cohort of neonates who met early discharge and defined home antibiotic therapy criteria, there were no serious complications or treatment failures reported; in addition, there were fewer costs compared with continued inpatient treatment.

Research in the clinical area: the ethical issues.

Healthcare professionals have a duty to undertake research, say the authors of this article, yet the patient's perspective is rarely considered. Here, they review the ethical aspects of clinical research.

Characterization of the avian GLUT1 glucose transporter: differential regulation of GLUT1 and GLUT3 in chicken embryo fibroblasts.

Vertebrate cells that are transformed by oncogenes such as v-src or are stimulated by mitogens have increased rates of glucose uptake. In rodent cells, the mechanisms whereby glucose transport is up-regulated are well understood. Stimulation of glucose transport involves an elevation in mRNA encoding the GLUT1 glucose transporter that is controlled at the levels of both transcription and mRNA stability. Cloning and sequencing of chicken GLUT1 cDNA showed that it shares 95% amino acid sequence similarity to mammalian GLUT1s. Nevertheless, unlike mammalian GLUT1 mRNA, it was not induced by v-src, serum addition, or treatment with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate in chicken embryo fibroblasts. Rather, the induction of glucose transport in chicken embryo fibroblasts by v-src, serum, and 12-O-tetradecanoylphorbol 13-acetate was associated with induction of GLUT3 mRNA level and GLUT3 transcription. Rat fibroblasts were also found to express both GLUT1 and GLUT3 isoforms, but v-src induced GLUT1 and not GLUT3. This suggests that animal cells require both a basal and an upregulatable glucose transporter and that these functions have been subsumed by different GLUT isoforms in avian and mammalian cells.

Rapid and inexpensive microcapillary immunodiffusion assay technique.

A simple, rapid, and inexpensive single-gel immunodiffusion technique requiring but 1 mul of sample for analysis and an incubation period of only 2 h is described.