An observational study investigating the association of ultrasonographically assessed machine milking-induced changes in teat condition and teat-end shape in dairy cows.

Mechanical forces during machine milking induce changes in teat condition which can be differentiated into short-term and long-term changes. Machine milking-induced short-term changes in teat condition (STC) are defined as tissue responses to a single milking and have been associated with the risk of new intramammary infection. Albeit, their association with teat characteristics, such as teat-end shape, has not been investigated by rigorous methods. The primary objective was to determine the association of STC, as measured by ultrasonography, with teat-end shape. The second objective was to describe possible differences in the recovery time of teat tissue after machine milking among teats with different teat-end shapes. Holstein cows (n=128) were enrolled in an observational study, housed in free-stall pens with sand bedding and milked three times a day. Ultrasonography of the left front and right hind teat was performed after teat preparation before milking (t-1), immediately after milking (t 0) and 1, 3, 5 and 7 h after milking (t 1, t 3, t 5, t 7). The teat tissue parameters measured from ultrasound scans were teat canal length, teat-end diameter, teat-end diameter at the midpoint between the distal and proximal end of the teat canal, teat wall thickness, and teat cistern width. Teat-end shape was assessed visually and classified into three categories: pointed, flat and round. Multivariable linear regression analyses showed differences in the relative change of teat tissue parameters (compared with t-1) at t 0 among teats with different teat-end shapes, with most parameters showing the largest change for round teats. The premilking values were reached (recovery time) after 7 h in teats with a pointed teat-end shape, whereas recovery time was greater than 7 h in teats with flat and round teat-end shapes. Under the same liner and milking machine conditions, teats with a round teat-end shape had the most severe short-term changes. The results of this observational study indicated that teat-end shape may be one of the factors that contribute to the severity of STC.

Clinical value of digital image analysis in the diagnosis of urinary bladder cancer, particularly in aggressive tumors: a preliminary report.

The aim of the project was to evaluate the clinical value of a computer analysis of cytological specimen images obtained from urine and bladder washing samples. Three sample types (voided urine, catheterized urine and bladder washing) from 59 patients with primary or recurrent tumor were analyzed. All patients underwent cystoscopy and biopsy or resection. The histological results were compared with the results of the image analyzing computer system of collected urine samples. The consistency between the computer diagnosis and the clinical or histological diagnosis both in the presence and absence of cancer was as follows: 77% for voided urine samples, 72.5% for catheterized urine samples and 78% for bladder washing samples. The specificity of the method at the standard pathology level was 71%, and the sensitivity was 83%. The positive and negative predictive values (PPV and NPV) were 87.5% and 63% respectively. The sensitivity for G3 or CIS or T2 or T3 tumors reached nearly 100%. Computer analysis of urine provided correct diagnoses in cancer and control patients with the sensitivity of 83% and specificity of 71% and gave excellent results in aggressive tumors such as T2, T3, G3 and in CIS.

Influence of oligomeric herbicidal ionic liquids with MCPA and Dicamba anions on the community structure of autochthonic bacteria present in agricultural soil.

The aim of this study was to evaluate the impact of selected herbicidal ionic liquids (HILs), which exhibit high efficacy in terms of weed control and low toxicity, but may be persistent due to limited biodegradability, on the community structure of autochthonic bacteria present in agricultural soil. Four different oligomeric HILs (with two types of cations and different ratio of herbicidal anions) were synthesized and characterized by employing (1)H and (13)C NMR. The results of biodegradation assay indicated that none of the tested HILs could be classified as readily biodegradable (biodegradation rate ranged from 0 to 7%). The conducted field studies confirmed that the herbicidal efficacy of the HILs was higher compared to the reference herbicide mixture by 10 to 30%, depending on the dose and weed species. After termination of field studies, the soil treated with the tested HILs was subjected to next generation sequencing in order to investigate the potential changes in the bacterial community structure. Proteobacteria was the dominant phylum in all studied samples. Treatment with the studied HILs resulted in an increase of Actinobacteria compared to the reference herbicidal mixture. Differenced among the studied HILs were generally associated with a significantly higher abundance of Bacteroidetes in case of 1-HIL-Dicamba 1/3 and Firmicutes in case of 2-HIL-Dicamba 1/3.

A personalised approach to prostate cancer screening based on genotyping of risk founder alleles.

BACKGROUND: To evaluate whether genotyping for 18 prostate cancer founder variants is helpful in identifying high-risk individuals and for determining optimal screening regimens. METHODS: A serum PSA level was measured and a digital rectal examination (DRE) was performed on 2907 unaffected men aged 40-90. Three hundred and twenty-three men with an elevated PSA (≥4 ng ml⁻¹) or an abnormal DRE underwent a prostate biopsy. All men were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA and C61G), for four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395 and I157T), for one allele in NBS1 (657del5), for one allele in HOXB13 (G84E), and for nine low-risk single-nucleotide polymorphisms (SNPs). RESULTS: On the basis of an elevated PSA or an abnormal DRE, prostate cancer was diagnosed in 135 of 2907 men (4.6%). In men with a CHEK2 missense mutation I157T, the cancer detection rate among men with an elevated PSA or an abnormal DRE was much higher (10.2%, P=0.0008). The cancer detection rate rose with the number of SNP risk genotypes observed from 1.2% for men with no variant to 8.6% for men who carried six or more variants (P=0.04). No single variant was helpful on its own in predicting the presence of prostate cancer, however, the combination of all rare mutations and SNPs improved predictive power (area under the curve=0.59; P=0.03). CONCLUSION: These results suggest that testing for germline CHEK2 mutations improves the ability to predict the presence of prostate cancer in screened men, however, the clinical utility of incorporating DNA variants in the screening process is marginal.

An inherited NBN mutation is associated with poor prognosis prostate cancer.

BACKGROUND: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. METHODS: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). RESULTS: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ≤ 60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. CONCLUSION: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.

Regional and age-specific patterns of pandemic H1N1 influenza virus seroprevalence inferred from vaccine clinical trials, August-October 2009.

The extent of the H1N1 pandemic has been estimated from case counts and deaths but the proportion of exposed populations with inapparent infections has not been described in detail. We analysed haemagglutination-inhibition (HI) antibody titres of pre-vaccination sera from pandemic vaccine trials conducted in six countries on four continents to provide an indication of A/CA/07/2009(H1N1)-like influenza seroprevalence in those populations. Among 7,962 subjects, ranging in age from 12 months to over 60 years, the proportions with HI antibody titres > or =40 to the H1N1pnd virus in the period from August to October 2009 were, by country: Costa Rica 26.4%, United States (US) 22.5%, Switzerland 16.9%, Germany 12.6%, Belgium 10.1%, and Japan 5.9%. Age-specific seropositivity rates in the samples were higher in children and adolescents in Costa Rica and in the US than in Europe and in Japan. The low proportion of seropositive children in Europe and Japan suggests that little local viral transmission had occurred in those regions even as late as September and October 2009, while in the US and Costa Rica, the greater proportion of previously infected children and young adults suggested that a significant number of asymptomatic infections had occurred during the first pandemic wave. Nevertheless, in all locations, the majority of the population remained susceptible to the pandemic virus at the beginning of the influenza season in the northern hemisphere, justifying the implementation of public health interventions.

MF59-adjuvanted influenza vaccine (FLUAD) in children: safety and immunogenicity following a second year seasonal vaccination.

After priming with two intramuscular doses of MF59-adjuvanted (Sub/MF59) or split influenza vaccines during the 2006/07 season, 89 healthy children received a third booster dose of the respective vaccine (2007/08 Northern Hemisphere formulation) approximately 1 year later, and were followed up for 6 months post-third injection. Immunogenicity was evaluated on 81 of them by a hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. The Sub/MF59 influenza vaccine was safe and well tolerated following the booster vaccination. Pre-booster HI antibody titers were consistently higher in the Sub/MF59 group than in the comparator group, confirming significantly longer persistence of antibodies after priming with Sub/MF59 vaccine. Post-booster immune responses were significantly higher in the Sub/MF59 group compared with the split group, especially vs. the influenza B strain, which is epidemiologically relevant in the pediatric population. Altogether, these data further support the potential use of MF59-adjuvanted influenza vaccine as a safe and highly immunogenic influenza vaccine for young children.

Multiple sclerosis produces significant changes in urinary bladder innervation which are partially reflected in the lower urinary tract functional status-sensory nerve fibers role in detrusor overactivity.

BACKGROUND: Detrusor overactivity is often observed in patients with multiple sclerosis (MS), and neurotoxins are emerging as second-line therapies albeit with different degrees of success per patient basis. OBJECTIVE: To investigate lower urinary tract (LUT) functional status and bladder innervation (calcitonin gene related peptide [CGRP] and substance P [SP] positive nerve fibers) in patients with MS. METHOD: Eighteen MS patients with LUT symptoms underwent urodynamic investigations, and six non-MS patients undergoing cystoscopy due to microscopic hematuria served as controls. Cold cut bladder biopsies were taken from the bladder trigone region. Neurotransmitter expression was determined by individual immunohistochemical staining. RESULTS: Two distinct groups could be distinguished: group 1 with pronounced neurogenic detrusor overactivity and mild outflow obstruction; group 2 with some degree of neurogenic detrusor overactivity, detrusor hypocontractility during voiding, and high degree of an outflow obstruction. The presence of SP and CGRP immunoreactive + fiber density was observed in greater numbers in group 1. CONCLUSION: Density of CGRP and SP positive nerve fibers within the urinary bladder of patients with MS may be suggestive of functional status of the lower urinary tract, namely denser innervation is observed in patients with mild outflow obstruction and strong detrusor overactivity. This observation could be useful when planning second-line treatment (neurotoxins) in these patients. Patients with denser innervation probably will respond better to such a therapy.

Seroprotection against serogroup C meningococcal disease in adolescents in the United Kingdom: observational study.

OBJECTIVE: To determine the persistence of bactericidal antibody titres following immunisation with serogroup C meningococcal glycoconjugate vaccine at age 6-15 years in order to examine changes in persistence of antibodies with age. DESIGN: Observational study. SETTING: Secondary and tertiary educational institutions in the United Kingdom. PARTICIPANTS: Healthy adolescents aged 11-20 years previously immunised between 6 and 15 years of age with one of the three serogroup C meningococcal vaccines. INTERVENTION: Serum obtained by venepuncture. MAIN OUTCOME MEASURES: Percentage of participants with (rabbit complement) serum bactericidal antibody titres of at least 1:8; geometric mean titres of serogroup C meningococcal serum bactericidal antibody. RESULTS: Five years after immunisation, 84.1% (95% confidence interval 81.6% to 86.3%) of 987 participants had a bactericidal antibody titre of at least 1:8. Geometric mean titres of bactericidal antibody were significantly lower in 11-13 year olds (147, 95% confidence interval 115 to 188) than in 14-16 year olds (300, 237 to 380) and 17-20 year olds (360, 252 to 515) (P<0.0001 for both comparisons). Within these age bands, no significant difference in geometric mean titres of bactericidal antibody between recipients of the different serogroup C meningococcal vaccines was seen. More than 70% of participants had received a vaccine from one manufacturer; in this cohort, geometric mean titres were higher in those immunised at aged 10 years or above than in those immunised before the age of 10. CONCLUSIONS: Higher concentrations of bactericidal antibody are seen five years after immunisation with serogroup C meningococcal vaccine at age 10 years or above than in younger age groups, possibly owing to immunological maturation. This provides support for adolescent immunisation programmes to generate sustained protection against serogroup C meningococcal disease not only for the vaccine recipients but also, through the maintenance of herd immunity, for younger children.

Significance of urodynamic assessment of lower urinary tract in dialysis patients before renal transplantation.

INTRODUCTION: Some dialyzed patients suffer from lower urinary tract (LUT) anatomic and functional disturbances. Complete LUT assessment should be performed to decide whether they can be included on the waiting list, because such disorders, if not diagnosed and properly treated before transplant, may lead to graft loss. PATIENTS AND METHODS: Based on data in the medical records of 4170 dialysis patients, 535 were selected for further investigation: 265 patients after undergoing urethrocystography or urethrocystoscopy, were included on the waiting list for transplantation and 145 patients underwent nephroureterectomy owing to reflux, nephrolithiasis, polycystic renal disease, or hydronephrosis. Five patients with urethral or bladder neck stricture underwent urethral dilation or bladder neck incision. These patients were also ultimately listed for transplantation. Twenty-two patients, with serious LUT disease were qualified for kidney transplantation after extra-anatomic urine outflow. Ninety-eight patients underwent a urodynamic study (URD) to assess LUT disturbances. RESULTS: Of 535 studied patients, 460 (86%), including those who underwent surgical or pharmacologic treatment, were ultimately listed for kidney transplantation. Out of 98 patients who underwent a URD, 45 (46%) were included for kidney transplantation, and 47 for transplantation with atypical urinary outflow. Six patients were excluded from transplantation owing to refusal of investigations or serious contraindications. CONCLUSIONS: All potential kidney recipients should undergo proper evaluation of the LUT before being qualified for kidney transplantation. This study allows selection of patients who should undergo surgical and/or pharmacologic treatment before transplantation.

A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.

BACKGROUND: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. PARTICIPANTS AND METHODS: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. RESULTS: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G-->A, 1100delC). CONCLUSION: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.

Impact of corticosteroids on the immune response to a MF59-adjuvanted influenza vaccine in elderly COPD-patients.

The influence of steroids on the antibody response to a MF59-adjuvanted influenza vaccine in elderly COPD patients has not been studied previously. In the influenza season 2001/02 (October-February) elderly COPD patients were recruited at 14 doctor's offices and our 250-bed hospital. Patients were stratified into three groups according to current treatment regimen: (a) > 10 mg of prednisolone/day (SS); (b) inhaled steroids (IS); (c) no steroid treatment (control group, CG). All patients were vaccinated with the MF59-adjuvanted influenza vaccine. Antibodies against the influenza strains A/H1N1, A/H3N2, and B were measured at baseline, 4 and 24 weeks after vaccination by hemagglutination inhibition (HI) assay. One-hundred and sixty-two patients completed the study (CG n = 42; IS n = 87; SS n = 33). Mean age was 71.3 years (range 60-89). Twenty-one percent of all patients reported local reactions; no serious adverse events were observed. Four weeks after vaccination, mean geometric HI titres (GMT) for A/H1N1, A/H3N and B increased significantly in all groups (p < or = 0.05). After 24 weeks, GMTs to A/H1N1 and A/H3N2 returned to baseline, while GMTs to type B remained significantly higher than baseline in all groups. Significant differences between the groups as regards GMTs, seroconversion (56-89%) or seroprotection rates (64-93%) were not observed. Systemic steroids did not influence the antibody response towards the MF59-adjuvanted influenza vaccine. We found that the strains included in the vaccine showed varying long-term immunogenicity.

[The applicability of the ProSeal laryngeal mask airway for laparotomies]. / Die Anwendbarkeit der ProSeal-Larynxmaske bei Laparotomien.

OBJECTIVE: The ProSeal laryngeal mask airway (PLMA) has some design features, which in contrast to the classic LMA allow separation of the respiration from the gastrointestinal canal, a higher leak pressure and a better position assessment. It can be debated if these instrumental improvements justify the application of the PLMA for elective abdominal surgery in cases without aspiration risk. Insertion of airway instruments and gastric tube with regard to insertion time and difficulties and frequency of side effects were to be compared for the tracheal tube and the PLMA. The pharyngolaryngeal morbidity for both methods was also of interest. It was approached with direct and indirect postoperative interview techniques. METHODS: 65 patients were investigated both at the university hospital and at the hospital Neu-Bethlehem in Goettingen. The surgical intervention was a surgical or gynecological laparotomy. Anaesthesia was performed with a standardized application of propofol, alfentanil and rocuronium. Glycopyrroniumbromide was applied to minimize salivation. A total of 34 patients received the PLMA, 31 were intubated. All of them were provided with a gastric tube. RESULTS: The insertion of the PLMA took 70 seconds (21 - 234) on average, the intubation 57 seconds (35 - 145). Endotracheal intubation was accomplished in a shorter time period, but there was no significant difference in comparison with the PLMA-group (p = 0.1924). Insertion of the PLMA was significantly more difficult than oral intubation (p = 0.0006). The base of the tongue and the dorsal pharyngeal wall, but not the vocal cords or the epiglottis were visible in those cases, where the PLMA could not be positioned at all. Here the tip of the cuff was bended. The time period for positioning of the gastric tube was 38 seconds (15 - 75) in the PLMA- and 57 seconds (22 - 219) in the tracheal tube group. With these results the gastric tube positioning was accomplished in a significantly shorter time period in the PLMA-group (p = 0.0267), but not at a significantly higher level of difficulty for endotracheal intubation (p = 0,6247). In one case there was regurgitation through the drainage tube without aspiration before gastric tube placement. At the direct interview 16 patients in the PLMA-group and 23 of the tube group mentioned postoperative throat symptoms. The most frequent symptom was hoarseness (11 PLMA- and 18 intubated patients). There was no significant difference between PLMA- and tracheal tube application with regard to the total number of patients with pharyngolaryngeal morbidity and the frequency of single symptoms. The same is true for the degree of the symptoms. There was a tendency for a longer prevalence of throat symptoms after intubation, but no significant difference. CONCLUSION: In this investigation the PLMA could be successfully applied for elective laparotomies in cases without the risk of aspiration. Proper patient selection and a deep level of anaesthesia are important. The advantage for patients receiving the PLMA is a smooth recovery without cough, but not so much a reduced amount of pharyngolaryngeal morbidity. From this observation it might be concluded that the invasiveness of the surgical intervention might also influence the tolerance for the airway instrument. The disadvantage in this study was the more difficult insertion of the PLMA compared with the oral intubation. Further studies with a larger number of patients must show if these first results of the "Proseal"-LMA for lararotomies are to be confirmed.

Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the most common conditions associated with ageing in men. BPH often presents as lower urinary tract symptoms (LUTS) due to difficulties in voiding and irritability of the bladder. We conducted a retrospective cohort study within the Integrated Primary Care Information (IPCI) database, a general practitioners database in The Netherlands, to assess the incidence of LUTS suggestive of BPH (LUTS/BPH) in the general population. MATERIALS: Our study population comprised all males, 45 years or older who were registered for at least 6 months prior to start of follow-up. The study period lasted from 1 January 1995 to 31 December 2000. Cases of LUTS/BPH were defined as persons with a diagnosis of BPH, treatment or surgery for BPH, or urinary symptoms suggestive of BPH that could not be explained by other co-morbidity. RESULTS: The study cohort comprised 80,774 males who contributed 141,035 person-years of follow-up. We identified 2181 incident and 5605 prevalent LUTS/BPH cases. The overall incidence rate of LUTS/BPH was 15 per 1000 man-years (95% CI: 14.8-16.1). The incidence increased linearly (r(2) = 0.99) with age from three cases per 1000 man-years at the age of 45-49 years (95% CI: 2.4-3.6) to a maximum of 38 cases per 1000 man-years at the age of 75-79 years (95% CI: 34.1-42.9). After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop LUTS/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3% (95% CI: 10.2-10.5). The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%). CONCLUSIONS: The incidence rate of LUTS/BPH increases linearly with age and reaches its maximum at the age of 79 years.

Transurethral microwave thermotherapy: first experiences in Poland.

OBJECTIVE: To present early experiences in Poland with high-energy transurethral microwave thermotherapy (HeTUMT), considered as a serious alternative to surgery in managing benign prostatic hypertrophy (BPH). PATIENTS AND METHODS: Sixty-one patients were treated in two centres using a commercial TUMT system. The patients were assessed at 5-6 weeks, 3 and 6 months after treatment, evaluating subjective complaints, the International Prostate Symptom Score (IPSS), urinary flow rate and postvoid residual volume. RESULTS: A complete follow-up was available in 44 patients; most had symptomatic improvement 3 months after HeTUMT but it was slightly less pronounced after 6 months. The improvement in objective variables increased up to 6 months after HeTUMT. There was > or = 50% improvement in subjective complaints in 43% of the patients, in urinary flow rate in 25% and in residual urine in half. Two patients required re-treatment for a urethral stricture and ineffective HeTUMT. CONCLUSIONS: HeTUMT may be a useful treatment for BPH but the outcome for an individual patient seems to be unpredictable. The indications for TUMT should be reviewed individually for each patient.

Computer identification of neoplastic urothelial nuclei from the bladder.

OBJECTIVE: To introduce computer-based analysis of Feulgen-stained urinary bladder cell nuclei from voided urine to identify neoplastic urothelial nuclei. STUDY DESIGN: Nuclei from 23 healthy people and 33 patients with urinary bladder cancer were analyzed. The nuclei from 9 cancer patients with grade G1 (stage Ta), 17 with grade G2 (stages Ta, T1, T1a and T2) and 7 with grade G3 (stages Cis, Ta + Tis, T1 and T3b) were analyzed. Image analysis was carried out by means of a digital image processing system designed by the authors. Features describing nuclei were selected as the first step of the procedure. Then a multistage classifier was constructed to identify positive and negative cases. RESULTS: The results of this pilot study of a group of 56 patients yielded a 71% correct classification rate in the control group, while a 66% rate was obtained among the cancer patients. The sensitivity of the method was 100% and the specificity was 77%. CONCLUSION: This approach to the identification of neoplastic urothelial nuclei may be sufficiently well developed to be used successfully both in screening high-risk populations and in clinical practice.

Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop?

PURPOSE: We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate biopsy 1. MATERIALS AND METHODS: In this prospective European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies. All patients in whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localized cancer underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Overall, of the patients with clinically localized disease, which was 67% of cancers detected, 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectively. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, there were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), respectively. CONCLUSIONS: Despite differences in location and multifocality, pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar, suggesting comparable biological behaviors. Cancer detected on biopsies 3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.

Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study.

PURPOSE: We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. MATERIALS AND METHODS: In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. RESULTS: Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. CONCLUSIONS: Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.