Urological cancers: do early detection strategies exist?

OBJECTIVE: To determine the perceptions of healthcare professionals and the general public about the symptoms, diagnosis and available treatment of urological cancers, and thus the perceived value of screening for their early detection. SUBJECTS AND METHODS: Two questionnaires were developed, based on semi-structured interviews, and distributed to 288 healthcare professionals, comprising 182 general practitioners (GPs), 56 practice nurses and 50 urology nurses, and to 250 members of the general public in three different socio-economic groups. The questionnaires asked about the symptoms, diagnosis and treatment of prostate, bladder and testicular cancer, and whether the respondents considered that screening for these cancers would be useful in ameliorating morbidity or death from these diseases. RESULTS: The response rate was very poor (13 of the GPs, 7%; 34 of the nurses, 32%; and 58 members of the general public, 23%). This severely limited the interpretation of the results, but the responses highlighted areas which need addressing. Obvious symptoms were well understood by all the groups but less well-known symptoms could be missed. No GP supported screening for prostate cancer and only seven of the GPs believed in teaching testicular self-examination, but practice nurses were considerably more active in all aspects of patient education. The general public felt that they needed more information to make decisions about urological cancers, although there was a general feeling that 'screening saved lives'. CONCLUSION: This survey showed that no healthcare professional seems to have a clearly defined role in informing potential patients about screening. The general public, who seem to perceive from the media that early detection is beneficial, are confused by the lack of clarity about policies for urological cancers.     

Target detection: Magnetic resonance imaging-ultrasound fusion–guided prostate biopsy

Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance.     

Is ultrasound really helpful in the detection of rib fractures?

OBJECTIVE: To determine the usefulness of ultrasound in the detection of rib fractures. PATIENTS AND METHODS: A prospective study was performed over a 3-month period. Patients presenting with a high clinical suspicion of rib fracture(s) to the Accident and Emergency Department were referred for radiological work-up with a PA chest radiograph, an oblique rib view and a chest ultrasound. Associated lesions, e.g. pleural effusion, splenic laceration and pneumothorax were recorded. RESULTS: Fourteen patients were radiologically assessed. The mean patient age was 31 years (range 16-55 years) and the M:F ratio 3.7:1 (11 men and 3 women). Ten patients displayed a total of 15 broken ribs. Chest radiography detected 11, oblique rib views 13 and ultrasound 14 broken ribs. Ultrasound findings included discontinuity of cortical alignment in 12 fractures, an acoustic linear edge shadow in nine and a reverberation artifact in six. Concordance with plain film findings, and especially oblique rib views, was good, though better when the rib fractures fragments were markedly displaced. One splenic laceration was detected with an associated small pleural effusion. There were no pneumothoraces. The average time of ultrasound examination was 13 min. CONCLUSION: Ultrasound does not significantly increase the detection rate of rib fractures, may be uncomfortable for the patient and is too time-consuming to justify its routine use to detect rib fractures.     

Are extended biopsies really necessary to improve prostate cancer detection?

The aim of this study is to understand the value of specific sites in extended peripheral and transition zone biopsy schemes in order to define the optimal systematic biopsy regimen correlated with the percentage of positivity of each single bioptic site. A total of 165 consecutive patients underwent transrectal ultrasonography examination to detect prostate cancer followed by a lesion-directed and systematic 14-step biopsy scheme. The detection rate was examined for the lesion-directed and for each zone region biopsy. The frequency of positive biopsies in the various prostate regions was determined to evaluate the diagnostic yield of each biopsy site. Analysis was stratified for prostate-specific antigen (PSA), free-to-total PSA ratio, age, prostate size and digital rectal examination. The biopsy protocol detected 40% of patients (66/165) as positive and 55.1% (91/165) as negative for cancer. Standard sextant biopsy was expected to detect only 51 cancer on 66, lateral peripheral (PZ), transition (TZ) and central zone (CZ) biopsies only 56 cancer on 66, while the combination of sextant, PZ, TZ and CZ biopsies, for a total of 14 zone biopsies, detected 64 on 66 patients with cancer (97%) at recruitment. Sampling only the eight prostate regions with higher frequency of positive cancer biopsy was expected to detect 61 cancer patients against the 64 found with the 14-step scheme. This eight-biopsy regimen outperforms the conventional sextant regimen in cancer detection rate (93 vs 77%) and has an overall detection rate lower by only 3.1% (36.9 vs 40%) compared to the 14-biopsy regimen. This difference in detection rate is even smaller in patients with PSA values <10 ng/ml, age <70 y and prostate size <50 ml. This eight-biopsy scheme, including sampling in PZ and TZ toward the base, should be considered in an initial biopsy scheme to maintain a similar detection rate of an extensive biopsy scheme reducing the number of biopsies.     

Does the patient's position influence the detection of detrusor overactivity?

AIMS: The demonstration of preoperative detrusor overactivity (DO) with associated overactive bladder symptoms (OAB) is known to have an adverse effect on surgery performed for stress incontinence or for prostatic obstruction. The purpose of this review is to examine the best position, when filling the bladder during urodynamics, to demonstrate detrusor overactivity and reproduce the OAB symptoms, when the demonstration of DO might be important. MATERIALS AND METHODS: MEDLINE and PUBMED literature searches were performed, spanning the period from 1956 to August 2005 using the keywords "detrusor overactivity" or "detrusor instability" combined with "posture or position or standing or sitting" and "urodynamics." Other studies were identified by reviewing secondary references in the original citations. RESULTS: Sixteen studies looked at the effect of position on the detection rate of DO. There is good consistency between the studies analyzed. All but two [Ramsden et al., Br J Urol 49:633-9, 1977; Choe et al., J Urol 161:1541-4, 1999] showed a clear effect, with an increase in DO when the patient is filled in the vertical position or is asked to sit or stand, with a full bladder, after being filled supine. Performing the urodynamics (UDS) in the supine position would have missed a large proportion of DO diagnoses ranging from 33% to 100%. CONCLUSIONS: This review confirms that the patient's position is a significant variable during urodynamics and that supine cystometry will fail to detect a significant percentage of patients with DO. We suggest that all patients should be filled sitting or standing, unless physically disabled. It seems desirable for the International Continence Society (ICS) to extend its "Good urodynamic practice guideline" [Schafer et al., Neurourol Urodyn 21:261-74, 2002] to cover this important issue.     

3D Navigo™ versus TRUS-guided prostate biopsy in prostate cancer detection

Introduction

To overcome the limitations regarding transrectal ultrasound (TRUS)-guided biopsies in prostate cancer (PCa) detection, there is a focus on new imaging technologies. The Navigo? system (UC-care, Israel) uses regular TRUS images and electrospatial monitoring to generate a 3D model of the prostate. The aim of this study was to compare cancer detection rates between the Navigo? system and conventional TRUS, in patients without a history of PCa.

Methods

We performed a retrospective study by collecting data from all patients who underwent 12-core prostate biopsies from lateral peripheral zones between September 2013 and February 2015 at the Jeroen Bosch Hospital in ‘s-Hertogenbosch (Netherlands).

Results

A total of 325 patients met our inclusion criteria. 77.8 % of biopsy sessions were performed using the Navigo? system. There was no statistically significant difference in PCa detection (39.9 vs 46.2 % with Navigo? system and TRUS, respectively). Using the Navigo? system for taking prostate biopsies proved not to be associated with the presence of PCa at biopsy, likewise for clinically significant PCa and for both subgroups.

Limitations

The limitations of the study include its retrospective design, the limited number of patients in the conventional TRUS group, the statistically significant different number of biopsy sessions and the ones performed by an advanced physician in both groups.

Conclusion

In our study, there is no added value of 3D TRUS using Navigo? system compared to conventional 2D TRUS regarding PCa detection in biopsy-naive men and men with prior negative biopsy.

     

Dietary habits and prostate cancer detection: a case–control study

Background

Many studies have suggested that nutritional factors may affect prostate cancer development. The aim of our study was to evaluate the relationship between dietary habits and prostate cancer detection.

Methods

We studied 917 patients who planned to have transrectal ultrasonography–guided prostatic biopsy based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. Before receiving the results of their biopsy, all patients answered a self-administered food frequency questionnaire. In combination with pathology data we performed univariable and multivariable logistic regression analyses for the predictors of cancer and its aggressiveness.

Results

Prostate cancer was found in 42% (386/917) of patients. The mean patient age was 64.5 (standard deviation [SD] 8.3) years and the mean serum PSA level for prostate cancer and benign cases, respectively, was 13.4 (SD 28.2) μg/L and 7.3 (SD 4.9) μg/L. Multivariable analysis revealed that a meat diet (e.g., red meat, ham, sausages) was associated with an increased risk of prostate cancer (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.55–4.87, p = 0.027) and a fish diet was associated with less prostate cancer (OR 0.54, 95% CI 0.32–0.89, p = 0.017). Aggressive tumours were defined by Gleason score (≥ 7), serum PSA level (≥ 10 μg/L) and the number of positive cancer cores (≥ 3). None of the tested dietary components were found to be associated with prostate cancer aggressivity.

Conclusion

Fish diets appear to be associated with less risk of prostate cancer detection, and meat diets appear to be associated with a 3-fold increased risk of prostate cancer. These observations add to the growing body of evidence suggesting a relationship between diet and prostate cancer risk.     

How useful is glucose detection in diagnosing cerebrospinal fluid leak? The rational use of CT and Beta-2 transferrin assay in detection of cerebrospinal fluid fistula

BACKGROUND: This report describes the sensitivity and specificity of glucose detection using Glucostix test strips and computed tomography (CT) of the skull base for confirming cerebrospinal fluid (CSF) fistulae in patients with persistent rhinorrhoea or otorrhoea, and comparing them with the beta-2 transferrin assay as the gold standard for CSF detection. METHODS: Fluid samples from the nose were collected from 18 patients with suspected CSF fistulae. The samples were assayed for beta-2 transferrin using the Western blotting and immunostaining technique. CT (5mm axial slice) of the skull base was performed for evidence of skull base fracture. The glucose levels and Glucostix results were compared. RESULTS: Out of the 18 samples, 15 were positive for beta-2 transferrin adn the leaks were validated surgically in 10 patients. Give leaks healed spontaneously with conservative management. Glucostix tests produced three false positive results from blood and nasal mucus contaminated fluid. Glucostix failed to detect another three CSF leaks resulting from false negative tests because of low CSF glucose levels. The Glucostix glucose test was nonspecific and insensitive compared with the beta-2 transferrin assay. CT failed to detect three of the 15 beta-2 transferrin-positive leaks but there were no false positive results. CT produced six negative results, of which three were false negatives. CONCLUSIONS: Glucose detection using Glucostix test strips is not recommended as a confirmatory test due to its lack of specificity and sensitivity. In the presence of a skull bas fracture on CT and a clinical CSF leak, there is no need for a further confirmatory test. In cases where a confirmatory test is needed, the beta-2 transferrin assay is the test of choice because of its high sensitivity and specificity.     

Urinary markers in the detection of bladder cancer: what's new?

PURPOSE OF REVIEW: Bladder cancer is one of the most common genitourinary malignancies and is a potentially life-threatening diagnosis. For many patients, however, the diagnosis of bladder cancer entails a lifetime of vigilant, costly, and invasive surveillance for recurrent and/or progressive disease. In the context of relative limitations of the current standard of cystoscopy and cytology, there has been burgeoning activity in the development of novel molecular urine-based markers for bladder cancer detection. RECENT FINDINGS: A large number of candidate bladder cancer biomarkers have emerged as our understanding of the molecular pathogenesis of the disease has evolved. Many of these are in the relatively earlier phases of development but several have received the approval of the United States Food and Drug Administration for clinical use and are already being applied to patients in clinical practice. SUMMARY: Urine-based markers for bladder cancer detection represent an area of substantial innovation and discovery with potentially profound scientific, clinical, and economic implications. As more of these tests become standardized and undergo evaluation in large multicenter trials, it is conceivable that a novel marker or panel of markers will emerge as a major enhancement to the current standard of care.     

Can complexed prostate specific antigen enhance prostate cancer detection in Japanese men?

BACKGROUNDS: The aim of this study is to ascertain whether Bayer complexed PSA (cPSA) and volume referenced cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 214 Japanese men whose serum total PSA (tPSA) values ranged from 1.2 ng/ml to 4600 ng/ml were enrolled from two institutions. Serum samples for tPSA, free PSA, PSA-alpha-1-antichymotripsin (PSA-ACT) and cPSA (ADVIA-Centaur) were obtained in all cases. In addition, total gland (TGV) as well as transition zone volume (TZV) were determined in all cases who underwent untrasound guided prostate biopsy (sextant and two additional transition zone biopsies). Biopsy outcome was correlated to the following parameters: tPSA, cPSA, PSA-ACT, free to total (F/T) PSA ratio, 2 complex to total (C/T) PSA ratios and 6 volume referenced parameters. RESULTS: Prostate cancer was detected in 85 of 214 patients (40%). The area under the receiver operating characteristic curve in non-volume referenced variables was highest for cPSA (0.736), followed by PSA-ACT (0.735), tPSA (0.722), F/T PSA ratio (0.613) and C/T PSA ratio (0.591). Comparing tPSA with the cutoff value of 4.0 ng/ml, the cutoff value with a 2.8 ng/ml of cPSA detected one more positive biopsy patient, decreasing one more cancer missed case and 8 more false positive cases. At sensitivities of 85% to 95% in men with tPSA between 4.00 and 10.00 ng/ml (n = 116), there were no significant differences in the corresponding specificities between tPSA and cPSA, or between cPSA and PSA-ACT. At sensitivities of 90% to 95%, the corresponding specificities of PSA-ACT adjusted for transition zone volume revealed best performance. As for the performance in men with a tPSA less than 4.0 ng/ml, the specificities of cPSA performed best, and differed significantly from PSA-ACT and F/T PSA at sensitivities of 80% to 90%. CONCLUSION: Bayer cPSA could replace the first screening test by total PSA and can enhance cancer detection, compared with PSA-ACT. However, cPSA did not provide additional value in differentiating cancer from non-cancer cases in men with a tPSA between 4.00 and 10.00 ng/ml.     

HLA-B27 detection – comparison of genetic sequence-based method and flow cytometry assay

Objectives

The presence of human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis. HLA-B27 testing is routinely applied in the diagnosis of this disease. The aim of the present study was to compare two methods of HLA-B27 detection – a genetic sequence-based method and a flow cytometry assay.

Material and methods

Peripheral blood was obtained from 300 individuals with suspected spondyloarthropathy. Expression of HLA-B27 on the T cell surface was analysed by flow cytometry assay using GS145.2 monoclonal antibody specific for HLA-B27. DNA was isolated from the whole blood. Genes coding for HLA-B27, -B40 and -B47:01 were detected by polymerase chain reaction using the MW02/MW09 primer pair. Then, positive samples were sequenced in order to discriminate allelic variations of the HLA-B27 gene. Results of sequencing were analysed using Chromas LITE 2.1.1 software, BLAST software and the IMGT/HLA database. Ambiguous samples were additionally analysed by polymerase chain reaction using E91 and E136 primers amplifying a 135-bp fragment of the human HLA-B27 gene.

Results

Among 300 samples, 76 were HLA-B27-positive on the basis of flow cytometry analysis. Genetic sequence analysis confirmed positivity of 73 from among 76 samples. Two hundred twenty six samples were HLA-B27-negative, whereas the result of one sample analysis was ambiguous. Fifty-three samples were identified as allelic variation 27:05, 19 samples as allelic variation 27:02, and one sample as allelic variation 27:07.

Conclusions

This study shows that the genetic sequence-based method and the flow cytometry assay give consistent results in 99% of cases. The performed genetic analysis proves that the majority of HLA-B27-positive samples belong to the 27:05 allelic variation, which is strongly associated with high risk of ankylosing spondylitis.     

Is there a need for early detection programs for chronic kidney disease?

The aims of this paper are to examine whether early detection programs are needed to assist in detecting and managing chronic kidney disease (CKD). It draws on existing material which indicates that CKD and its precursor risk factors or illnesses such as hypertension, diabetes mellitus and HIV infection are very clearly major challenges faced by health systems worldwide. This paper evaluates whether CKD meets the epidemiological criteria to justify early screening. More compelling evidence is becoming available which indicates that the prevalence of CKD is significant in both developing and developed countries and that CKD can be easily detected and treated with only small changes to existing practice and this may be improved through screening programs. A brief evaluation of the challenges of establishing early detection programs is provided, as well as an examination of the capacity which exists for establishing such programs. It concludes that, despite the lack of randomized studies, these programs appear to provide an opportunity to integrate CKD management with common chronic illnesses and, through this approach, provide clinical and cost-effective management of both CKD and cardiovascular disease.     

Breath analysis by mass spectrometry: a new tool for breast cancer detection?

Breath analysis has received attention as a noninvasive diagnostic tool with increasing research into its potential usefulness. We are investigating the utility of the analysis of breath volatile organic compounds (VOCs) as an effective modality for breast cancer (BC) detection and monitoring by collecting breath samples with a simple portable device to determine whether BC patients have breath VOCs distinct from those in healthy volunteers. We prospectively enrolled 20 healthy volunteers and 20 newly diagnosed stage II-IV BC patients. The study subjects deeply exhaled into a commercially available Teflon/valved breath sampler equipped with a rapid passive diffusive sampler five times at 5-minute intervals trapping alveolar breath VOCs. The exhaled breath samples were analyzed by thermal desorption/gas chromatography/mass spectrometry monitoring 383 VOCs in the breath of both populations. Our results indicate that aggregate low-dimensional summaries and compound quantities result in specific patterns that can confirm BC. We found a definite clustering of the presence of BC from cancer-free points. Overall sensitivity was 72 per cent and specificity was 64 per cent resulting in a correct classification rate of approximately 77 per cent. Our data show promising evidence that BC patients can be differentiated from healthy volunteers through distinct breath VOCs.