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A more effective TR systematic biopsy of the prostate associated with power doppler ultrasonography (PDU): technical and morphological aspects.

OBJECTIVES: It is by now ascertained how PDU improves the effectiveness of systematic biopsy of the prostate. We have attempted to find better technical and imaging methods to optimise results. MATERIAL AND METHODS: We associated echo-biopsy with PDU on 131 patients. 64 patients (48.85%) showed prostate Ca. Their age was between 53 and 84 (av. 71.7) with PSA ranging from 1.14 and 59.7 (r. 9.,55 +/- 11.99 ng/ml). We then tried to locate in each sector areas of altered vascularization. RESULTS: In 34 cases (53.12%) we found hypo/hyper/iso reflecting areas surrounded by numerous vessels and crossed by one or more vascular branches (usually 2-3). In 8 cases (12.5%) we found hypo/hyper vascular echogenic virtually avascular, i.e. only a small perforating or surrounding branch. In 13 cases (20%) we found an aspecific and often widespread hyper-vascularization not associated to echographically atypical areas, bilateral in 4 cases. In 9 cases (14%) we did not find evident vascular alterations during PDU. Through the correlation of power Doppler ultrasonography images with histology we noticed that the area of altered vascularization was positive to Ca in 38 patients (59.37%) whereas the same was not true in 5 patients (7.8%), and finally in 21 patients (32.8%) the echo-doppler results (12 hypervascular and 9 "normal") was too aspecific to allow any kind of histomorphologic correlation. DISCUSSION: There are no pathognomonic patterns detectable through PDU for prostate Ca; although in the light of the above data it is safe to assume the existence of PDU detectable vascular alterations that in a good number of cases are not always neoplastic but prostatic disease which often coincide (about 60%) with cancer. The association of systematic biopsy and PDU helps highlight these areas thereby considerably improving diagnoses.

Aged↗

Evaluation of costs and benefits of advances in cytologic technology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Uterine cervical cytology smears are among the most cost-effective cancer prevention interventions available, but they are not infallible, and new or modified technologies have been and will be proposed to improve diagnostic accuracy. Before these new technologies are accepted, their performance attributes will be carefully studied and defined. Equally important in this era of fiscal constraints are cost/benefit analyses, for which we review certain guidelines. CONSENSUS POSITION: In an effort to control rising costs in the health care sector, there has been a strong incentive to move toward a market system, and a variety of forces are acting to drive down expenditures. These same pressures will continue to be brought to bear on the providers of cervical cytology services. It must be emphasized that the technical knowledge required to define cost-effective medical practice lies within the medical profession itself, which must recognize the following: (a) Resources are finite; (b) Elimination of fraud, abuse and waste is not enough to bring health care expenditures down to levels considered acceptable to government and business; (c) The medical profession must take the responsibility to identify the health and economic consequences of the services it provides and make wise recommendations for allocation of resources to optimize health consequences. The analysis of costs and benefits must be viewed from a societal perspective and presented in terms of the marginal impact on current practice. This does not mean that new technologies must reduce cost; on the contrary, improvements in health can be expected to come at a price, but at a price commensurate with value gained in lives saved or in added quality adjusted life years. To be of value, a new technology for cervical cytology must be more effective in preventing cervical carcinoma. Dysplasia is considered a precursor of carcinoma, and detection of dysplasia has been a surrogate for prevention of cervical carcinoma, but dysplasia does not always lead to carcinoma, least of all mild dysplasia, and policy makers ultimately will insist that a favorable change in health outcome be effected by new technology before it is allocated resources. Alternatively, new technologies may lower cost, perhaps by modifying screening or rescreening procedures according to known risk; by improved cytopreparatory techniques that simplify, improve or speed screening; or by monitoring devices that minimize screening error. In each case the performance attributes of the instrument or human instrument process should be evaluated in the intended use environment. ONGOING ISSUES: While current cervical cytology methodology is one of the most effective means of cancer prevention, there continues to be development of new techniques to increase the sensitivity and specificity of this test. With present fiscal constraints, these will be subject to stringent cost/benefit analyses in which the medical profession must play a key role. Such analyses can be quite complicated, considering the additional costs or cost savings of clinical follow-up procedures and the reliability of dysplasias detected by cytology as a surrogate for cervical carcinoma in calculating quality of life years saved.

Attitude of Health Personnel↗

[Defense and illustration of a health examination in adolescents as observed in the course of secondary education].

In France, children's health is carefully looked after by periodical examinations from birth to six years old. But the french children cannot have afterwards a systematic health examination during the course of their compulsory attendance at school, except those preparing a technical teaching. The author suggests that an examination during the first period of adolescence (between 11 and 15 years old) should be a vector of information very useful to subjects themselves and knowledge in Public Health not much documented at this stage. To assert this statement and draw useful conclusions, the Institut Regional pour la Santé de Tours, whose the author is the founder, and the departmental School Health Service have co-ordinated their actions for an examination on 56 classes in second forms (randomised among 321) of 1316 schoolchildren (662 boys-654 girls). This clinical, paraclinical and biological survey pointed out bad habits of nutrition, alcoholic drinks, smoking, excess of corpulence and blood pressure, visual and auditive trouble unknown or neglected, dental caries not treated, statics trouble and high hypercholesterolemia, as well. All these pathological elements are unknown and not taken over on the whole, at the present time. But these discoveries cannot really justify the systematic generalisation of an health examination, if, on the one hand, there is not an efficient follow-up that affects family physicians, pediatricians, local Health Educational Services, and, on the other hand, a short and mean-dated estimation. Such a completed and systematic examination could then be essential both from the individual benefit point of view and to the literature in Public Health (analytical and descriptive epidemiology). The author also refers to a similar study, as productive as the former, led one year before in the first form. Whatever the form--first or second ones--systematization of a good examination must fill the blank: it can be validly made by the coordinated actions of a dynamic School Health Service, a local partnership (bringing logistic, laboratory, data processing and physicians (general practitioners or pediatricians) for a medical and educational follow-up essential not only in the immediate future but with a view to a mean and long-dated prevention.

Adolescent↗

Surveillance of pre-malignant disease of the pancreatico-biliary system.

Technical advancements in ultrasonography, contrast-enhanced computed tomography and magnetic resonance imaging, as well as the wider availability of these ultramodern imaging techniques, have resulted in the early detection and a better classification of various asymptomatic and symptomatic pancreatico-biliary lesions. Pre-malignant biliary and pancreatic lesions are rare disorders, and no clear data are available to define their malignant potential. Because of the lack of controlled epidemiological data, the time span for malignant transformation and its frequency cannot be defined in the majority of these lesions. Adenomyomatosis of the gallbladder and gallbladder polyps larger than 10 mm should be treated by cholecystectomy even in asymptomatic patients because of an increased risk of malignant transformation. Chronic cholangitis, primary sclerosing cholangitis and choledochal cysts are also pre-malignant conditions. The timing of surgery, once it is advised for a pre-malignant condition that is still benign, should, however, be individualized to the particular patient situation. In patients with chronic pancreatitis, surgery may be indicated for disease-related complications. In as much as chronic pancreatitis predisposes to a higher risk of pancreatic cancer, any suspicion of malignancy should warrant a surgical exploration. Intraductal papillary tumours and mucin-producing pancreatic tumours are other pre-malignant pancreatic lesions whose malignant potential cannot be precisely determined pre-operatively. They should be resected in situations where there is a high degree of suspicion even without a clear objective diagnosis. In conclusion, pre-malignant hepato-biliary and pancreatic lesions of uncertain pathology should undergo early resection in view of treatment limitations and the dismal prognosis of established cancers. While hepato-biliary and pancreatic surgery is nowadays performed in specialized centres, with a low post-operative morbidity and mortality, it is equally important to understand that observation alone with regular computed tomography or magnetic resonance imaging control can no longer be recommended in the management of these lesions.

Biliary Tract Neoplasms↗

Testing automated liquid-based cytology samples with a manual liquid-based cytology method using residual cell suspensions from 500 ThinPrep cases.

We report a technical improvement upon a previously disclosed manual liquid-based cytology (MLBC) method; and, we use the improved method to prepare slides from residual ThinPrep specimens in order to see how often ThinPrep diagnoses correspond to diagnoses derived from exhaustive examination of their parent sample suspensions. Residual cell suspensions from 500 ThinPrep cases comprising (1) 20 low-grade squamous intraepithelial lesions (LSILs); (2) 200 high risk (HR) negatives and 20 ASC-US; and (3) 260 screening cytology specimens were studied. Institutional review committee guidelines allowed us to know diagnoses by groups of specimens, but did not allow us to know individual patient diagnoses, so we could not perform case-by-case matched outcome-comparisons. Cells were concentrated by conventional centrifugation and sedimented into a polymer gel that was then vortex-mixed and converted into a viscous cell-rich suspension. The cell suspension was smeared between two clean glass slides, which were air-dried and stained with the Papanicolaou stain. Two study-sets were created, comprising one slide from each case. Each of the two study sets was examined by two cytopathologists, and discordant diagnoses were adjudicated. Because of the ambiguity involved in the "atypical" (ASC-US, ASC-H, AGC) diagnosis categories, only outcomes at the level of LSIL or greater were recorded. All MLBC SILs were digitally imaged and abnormal slides plus digital images were sent to the laboratory that provided the residual automated liquid-based cytology (ALBC) suspensions. The final diagnoses were confirmed by the laboratory that provided the residual ALBC specimens. MLBC slides of the 20 LSIL cases afforded 2 high-grade squamous intraepithelial lesions (HSILs) and 18 LSILs. Those of the 200 HR-Negatives showed 3 HSILs and 30 LSILs; and those of the 20 HR-ASC-US showed 3 HSILs and 9 LSILs. MLBC slides of the 260 screening cytology specimens showed 1 Carcinoma, 3 HSILs and 20 LSILs; affording 3 HSILs and 14 LSILs more than originally diagnosed. The MLBC method of this report is useful for preparing cell suspensions for cytological examination. Our analytical method was exhaustive and used nearly all of the cell material that was provided to us for analysis; therefore, we conclude that this approach is useful for determining how well ALBC instruments represent their parent sample suspensions. It appears that "rare events" may be overlooked when limited sample aliquots are analyzed by ALBC instruments, and this probably accounts for our increased discovery of SILs by the MLBC method. Also, SILs often present as aggregates of cohesive cells which, if overlooked or ineffectively transferred to ALBC slides, would not be diagnosed.

Cytological Techniques↗

Evaluation of molecular techniques in prediction and diagnosis of cytomegalovirus disease in immunocompromised patients.

OBJECTIVES: To evaluate selected molecular tests in diagnosis and screening of cytomegalovirus (CMV) infection in immunosuppressed patients. DESIGN: Clinical and cost-effectiveness were assessed through a prospective two-stage trial of CMV screening regimes in a routine service setting. Different molecular test results were fed back to clinicians in each stage, plus antigenaemia results. The technical performance of the molecular methods was assessed through an independent masked comparison of each molecular test against the established (antigenaemia) test. Scientists performing a particular test were blind to the other test results for that sample. Diagnostic and therapeutic impact were recorded prospectively for all tests, to include any effect on diagnostic certainty, changes to CMV therapy and any other reported impact on patient management. The cost of each test was estimated under different laboratory conditions. Prospective patients undergoing CMV screening were compared with consecutive historical controls in the same unit. Towards the end of the study, a survey of all UK virology laboratories was undertaken to identify current CMV screening practice and test preferences. In addition, all UK renal transplant surgeons and haematology transplant centres were surveyed in order to identify current clinical practice and perceptions of the benefits of CMV screening. SETTING: Study patients were recruited from University Hospital Wales (UHW), Cardiff. Staff in the Cardiff Public Health Laboratory Service virology laboratory performed the tests. PARTICIPANTS: A consecutive series of transplant patients was recruited to the prospective study over a 42-month period, totalling 98 renal and 140 haematology patients. A consecutive series of historical controls was identified, with 199 renal and 136 haematology patients who underwent transplants in the UHW during the 29 months prior to the prospective CMV screening trial. INTERVENTIONS: A predefined CMV screening protocol was applied to all patients in the prospective trial. Renal patients were tested every 4 weeks until 16 weeks post-transplant (five tests in total). Haematology patients were tested every 2 weeks until 12 weeks post-transplant, and then every 4 weeks until 24 weeks (10 tests in total). The assays used for CMV screening were as follows: non-molecular test, (1) pp65 antigenaemia assay; molecular tests, semi-quantitative in-house polymerase chain reaction (PCR), (2) single-round (PCR1) and (3) two-round, nested (PCR2); and qualitative commercial tests, (4) Roche Amplicor Assay (Amplicor) and (5) pp67 NASBA assay (NASBA). MAIN OUTCOME MEASURES: Test failure rates, sensitivity/specificity values and positive predictive value (PPV) and negative predictive value (NPV) were measured for each assay. The laboratory cost of undertaking various CMV tests was measured and other NHS costs associated with false-positive or false-negative test results were estimated. The likelihood of CMV disease and the likely impact of positive or negative test result on therapy and further investigations were recorded. On receipt of the test result, interim outcome measures were recorded to include the impact of test result on diagnostic certainty, changes to planned patient management (e.g. therapy, investigations) and perceived benefit. All definitive diagnoses of CMV disease, prescribing of CMV therapy and interim patient outcome at the end of the screening period were recorded. RESULTS: In haematology and renal transplant patients, all tests had a similar NPV (0.976--0.997 and 0.935--0.995, respectively) when used in CMV screening. PCR1 is the least expensive molecular test (7.80-13.70 UK pounds). Commercial tests, NASBA and Amplicor, are both more expensive (22.50-34.70 UK pounds NASBA; 23.20-29.20 UK pounds Amplicor). Antigenaemia costs 12.50-27.40 pounds depending on staff grade and batch size. Quantitative PCR (COBAS) is the most expensive at around 50 UK pounds per sample. No clear link between screening test results and CMV prescribing was detected; clinicians appear to consider screening results in the context of other factors. There was no evidence that the introduction of CMV screening led to reductions in CMV deaths or improved transplant success rates. For cost per positive test result, PCR1 was the most cost-effective screening test on this indicator (renal patients 116 UK pounds per true positive, haematology patients 518 pounds). Antigenaemia was the least cost-effective screening test (renal patients 643 UK pounds per true positive, haematology patients 2475 pounds). Cost-effectiveness analysis and cost per "beneficial result" (as judged by clinicians) confirmed that PCR1 remained the most cost-effective test. Modelling outputs for targeted screening protocols also supported this. CONCLUSIONS: The study findings offer some evidence that a CMV screening regime is more cost-effective than diagnostic testing alone, based on the cost per true positive detected and interim outcome such as changes in patient management. However, the study was unable to demonstrate any benefits in terms of longer term patient outcomes. If CMV screening is introduced, the use of antigenaemia pp65 is clearly less cost-effective than the use of molecular tests. The study identified the optimum test for CMV screening as an in-house molecular test (single-round PCR test). This test was less costly to perform and also resulted in lower costs linked to false positives and negatives than other tests. The in-house, semi-quantitative test was two to three times more cost-effective than the commercial molecular tests assessed; however changes to European Union legislation may mean that it may not be feasible to use in-house tests. The use of targeted screening (limiting CMV screening to high-risk transplants) as opposed to universal screening offers a significant improvement in the cost-effectiveness ratio for haematology transplant patients, but has limited impact in the case of renal transplants. Economic analyses could be expanded to model the cost-effectiveness of more frequent screening tests (as reported nationally), and screening in other "at risk" groups. Subgroup specific disease groups should be investigated across a larger population to allow more accurate modelling of the impact of CMV screening on disease progression. Further studies of CMV screening programmes should address a range of outcome measures, including patient outcomes.

Biological Assay↗