Jarno Riikonen

Decision aids for localized prostate cancer treatment choice: Systematic review and meta-analysis.

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user‐centered design of decision aids that promote shared decision making. CA Cancer J Clin 2015;65: 239–251.

Decision aids for localized prostate cancer treatment choice

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user‐centered design of decision aids that promote shared decision making. CA Cancer J Clin 2015;65: 239–251.

Dose-dependent decrease in glial fibrillary acidic protein-immunoreactivity in rat cerebellum after lifelong ethanol consumption

The effects of aging and lifelong ethanol consumption on astrocytic morphology and glial fibrillary acidic protein-immunoreactivity (GFAP-IR) in the cerebellar vermis obtained from ethanol-preferring Alko, Alcohol (AA) rats were analyzed by using computer-assisted image analysis. The ethanol-consuming animals (both male and female) were given ethanol (10%-12%, vol./vol.) as the only available fluid for 21 months (3-24 months), whereas the young (3 months) and the old (24 months) controls received water. In the male rats, but not in the female rats, an age-related decrease in GFAP-IR was found in folia II, VII, and X of the molecular layer, and in turn, an age-related increase was found in folium X of the granular layer, indicating opposite changes in GFAP-IR for male rats due to aging in adjacent brain regions. In the female rats, 21 months of daily average ethanol consumption of 6.6 g/kg resulted in decreased GFAP-IR in folium VII of the molecular layer, and the decrease in cerebellar GFAP-IR correlated with the average daily ethanol intake (r=-.886, P=.019) when folia II, IV, VII, and X were analyzed together. No effect of ethanol on GFAP-IR was detected in the granular layer or in the central white matter of the female rats. There was no change in GFAP-IR in any of the three cerebellar layers of the male rats with average daily ethanol consumption of 3.2 g/kg. These results indicate that the Bergmann glial fibers are the GFAP-expressing structures of the cerebellum most sensitive to moderate-to-heavy chronic ethanol exposure and that this effect is dose dependent.

Interaction of aging and intermittent ethanol exposure on brain cytochrome c oxidase activity levels

The effects of chronic, intermittent ethanol exposure on brain cytochrome c oxidase (CO) activity levels were studied in young (3- to 4-month-old) and aged (29- to 30-month-old) male Wistar rats. The rats were given highly intoxicating doses of ethanol three times a day by intragastric intubation for four successive days, followed by a 3-day ethanol-withdrawal period. This 4-day ethanol-exposure with 3-day ethanol-withdrawal cycle was repeated five times to simulate the binge drinking of human alcoholics. The histochemical demonstration of CO showed a markedly decreased activity level in the medial prefrontal cortex (especially layer V pyramids and neuropil) of the ethanol-exposed rats of both age groups compared with findings for the respective controls. In the cerebellar vermis, CO activity level was decreased in the Purkinje neurons of the aged ethanol-exposed rats and in the granule cells of both young and aged ethanol-exposed rats. The CO activity level in the locus coeruleus was decreased in both young and old ethanol-exposed rats, but the decrease was more pronounced in the young ethanol-exposed group. Aging per se did not markedly change CO histochemical findings in either prefrontal or cerebellar cortex, but CO activity levels were increased in the locus coeruleus. In summary, results of the current study support our conclusion that CO activity levels were decreased in the cerebral and cerebellar cortices as well as in the locus coeruleus-CNS regions known to be negatively affected by chronic ethanol exposure. Defective energy metabolism due to decreased CO activity levels might compromise neuronal energy stores and thereby contribute to ethanol-induced brain dysfunction and irreversible CNS degeneration.

Survival of AA and ANA rats during Lifelong ethanol exposure

BACKGROUND Study of the long-term effects of chronic alcohol consumption in human populations is confounded by genetic and environmental factors. METHODS The study was intended to investigate the effects on morbidity and survival of lifetime forced ethanol consumption in male and female AA (Alko, Alcohol) and ANA (Alko, Non-Alcohol) rats. The ethanol-exposed rats had 12% ethanol as the only available fluid from 3 to 24 months of age. The control groups had water. Rats that died during the experiment and those that were killed at 24 months of age were all autopsied, and the pathologic findings were recorded. RESULTS Lifelong ethanol consumption did not change the survival rate of the rats, and had no significant effect on the rates of any of the pathologic measures in either the AA or ANA line of rats, suggesting that this may not be a good animal model for studying the detrimental effects of chronic alcohol. An unexpected, highly significant finding was observed: the AA rats, bred for high voluntary ethanol drinking, lived much longer than the ANA rats, bred for ethanol avoidance. The death rate by 24 months in the AA line was less than one-third of that in the ANA line. This difference was found regardless of whether the animals were maintained on alcohol or water, and in both genders. The AA rats had significantly lower rates of kidney disease, benign tumors, and cardiovascular disease than the ANA animals. CONCLUSIONS Lifelong ethanol consumption increased neither the mortality nor the morbidity of AA and ANA line of rats. Genes selected in the development of the high drinking AA line have additional effects producing rats that are healthier and living longer than the ANA rats possessing genes resulting in alcohol avoidance.

Effects of lifelong ethanol consumption on rat sympathetic neurons

In this experiment we studied the effects of aging and lifelong ethanol consumption on rat peripheral sympathetic neurons. The aim was to find out the possible differences in the vulnerability to ethanol-induced neuronal degeneration between rats of both genders, or between the alcohol-avoiding (ANA) and the alcohol-preferring (AA) lines of rat. The superior cervical ganglia (SCG) of 40 male and 41 female AA and ANA rats were analyzed. The ethanol-exposed groups had 12% ethanol as the only available fluid from 3 to 24 months of age. The young (3 months) and old (24 months) control groups had water instead. SCG neuronal density, volume, and total neuron number were measured by unbiased morphometric methods. No gender difference was seen in either the volume of the SCG or in the SCG neuron number. The volume of the ganglion was significantly increased with age, but the total neuron number did not change. Neuronal density was significantly decreased with age, but lifelong ethanol consumption induced no further decrease. SCG neuron number in the ethanol-exposed groups did not differ from the age-matched or young control groups, but a significant negative correlation (r = -0.70, p<0.01) was seen between individual ethanol consumption and the number of SCG neurons in the female rats. The amount of lipopigment in the SCG was increased in the ethanol-exposed male rats. These results suggest that the peripheral sympathetic neurons are rather resistant to ethanol-induced degeneration, and that no major gender or line differences exist in this respect.

Feasibility of prostate PAXgene fixation for molecular research and diagnostic surgical pathology : comparison of matched fresh frozen, FFPE, and PFPE tissues

Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied. Our results suggest that it is feasible to use PFPE tissue for routine robot-assisted laparoscopic prostatectomy surgical pathology diagnostics and immunohistochemistry, with the benefit of significantly improvedDNA and RNA quality and RNA picogram yield per nucleus as compared with FFPE tissue. For fresh frozen, FFPE, and PFPE tissues, respectively, the average Genomic Quality Numbers were 7.9, 3.2, and 6.2, average RNA Quality Numbers were 8.7, 2.6, and 6.3, average DNA picogram yields per nucleus were 0.41, 0.69, and 0.78, and average RNA picogram yields per nucleus were 1.40, 0.94, and 2.24. These findings suggest that where DNA and/or RNA analysis of tissue is required, and when tissue size is small, PFPE may provide important advantages over FFPE. The results also suggest several interesting nuances including potential avenues to improve RNA quality in FFPE tissues and confirm recent suggestions that some DNA sequence artifacts associated with FFPE can be avoided.

Side-fenestrated catheter decreases leakage at the urethrovesical anastomosis after robot-assisted laparoscopic radical prostatectomy.

Abstract Objective. The aim of this study was to analyse whether a side-fenestrated urinary catheter can decrease the frequency of anastomotic leakage after robot-assisted laparoscopic radical prostatectomy (RALP). Material and methods. Two-hundred and fifty patients with localized prostate cancer undergoing RALP were randomized into standard and side-fenestrated catheter groups in a prospective randomized study. The catheter was fenestrated at the site of the anastomosis to improve drainage. A cystogram was taken at 7 ± 2 days postoperatively to verify the watertightness of the anastomosis. The patients were monitored for 3 months. Results. The study included 106 patients with the standard and 108 patients with the fenestrated catheter. Leakage at the urethrovesical anastomosis was found in 13/106 (12.3%) of the standard and 5/108 (4.6%) of the side-fenestrated catheter patients (p = 0.044). Discomfort induced by the catheter and urinary leakage beside the catheter did not differ between the groups. The clinical and pathological characteristics and complications were equal between the groups. Conclusions. The side-fenestrated catheter decreased leakage rates at the urethrovesical anastomosis after RALP.

Prevalence of Complications Leading to a Health Care Contact After Transrectal Prostate Biopsies: A Prospective, Controlled, Multicenter Study Based on a Selected Study Cohort

BACKGROUND Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is typically considered a safe procedure. However, infectious complications have been increasing. OBJECTIVE To determine the contemporary rate of biopsy-related infectious and noninfectious complications after TRUS-Bx, and identify potential risk factors associated with the complications. DESIGN, SETTING, AND PARTICIPANTS This was a prospective multicenter study and a substudy of a trial investigating the role of magnetic resonance imaging (MRI) in prostate cancer diagnosis (multi-IMPROD, NCT02241122). INTERVENTION TRUS-Bx was performed for all patients included in the study. Ciprofloxacin, levofloxacin, or fosfomycin was administered for antibiotic prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS On inclusion, patients completed a detailed questionnaire and underwent MRI scanning. Antibiotic prophylaxis was prospectively recorded. After collection of a rectal swab, TRUS-Bx (total of 14-18 biopsy cores) was performed and. The rectal swabs were cultured and the antimicrobial susceptibility profile of Escherichia coli strains was analyzed. Biopsy complications leading to a visit to a health care unit were recorded and potential risk factors for complications were analyzed. RESULTS AND LIMITATIONS Twelve of the 294 patients (4.1%) had a biopsy-related complication, of which two (0.7%) were infectious and managed in the outpatient setting. Some 11% of the patients had an E. coli strain resistant to the prophylactic antibiotic administered. CONCLUSIONS The risk of an infectious or noninfectious complication after TRUS-Bx is very low, although the FQ resistance rate in the study population was significant. Accordingly, the present TRUS-Bx procedure and antibiotic prophylaxis are efficient in guarding against biopsy complications, but regional resistance rates may affect the generalizability of the results. PATIENT SUMMARY We examined the rate of complications after prostate biopsies in 294 patients. The risk of having a biopsy-related complication was low (4.1%). The rate of infectious complications was reasonably low (0.7%) although antibiotic resistance to the prophylactic antibiotic regimen was significant (11%).

Initiation of robot-assisted radical prostatectomies in Finland: Impact on centralization and quality of care

Abstract Objective The aim of this study was to analyze the impact of introduction of robot-assisted prostate surgery and its quality measures in Finland from 2008 to 2012. Materials and methods Registry data were collected for time trends and national distribution of prostate cancer surgery in Finland, while preoperative, operative and follow-up data were collected for quality measures. Results The number and proportion of robot-assisted laparoscopic radical prostatectomies (RALPs) increased rapidly and they accounted for 68% of all radical prostatectomies in 2012. The number of centers performing prostatectomies diminished from 25 to 20 at the expense of low-volume centers. In total, 1996 patients were operated on in the four RALP centers in 2008–2012. As anticipated, the learning curve was uniform between the centers, as were mean blood loss (212 ml), hospitalization (1.8 days) and catheterization times (10.6 days). At 3 and 12 months, 49.4% and 71.2% of patients, respectively, were totally continent (no pads). After unilateral nerve-sparing surgery, 9.9% and 5.1% had partial or normal erection at 3 months postoperatively and 14.8% and 20.4% at 12 months, respectively. If bilateral nerve sparing was done, the figures were 13.0% and 13.5% at 3 months and 14.6% and 34.9% at 12 months. Clavien–Dindo grade 3, 4 or 5 complications were seen in 0.3%, 0.3% and 0.1% of patients, respectively. Limitations of the study include non-standardized collection of outcome parameters. Conclusions This report shows that the main impact of adoption of RALP on a national level was rapid spontaneous centralization of prostate cancer surgery. The main advantages of minimally invasive prostatectomy, i.e. low blood loss and short hospitalization, are easily achieved, while continuous effort is necessary for improvements in surgical outcomes.