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PubMed1987

ICMSF methods study. XVII. An international comparative study of the direct plate and hydrophobic grid-membrane filter methods for enumeration of Escherichia coli in foods. International Commission on Microbiological Specifications for Foods.

Eight laboratories compared counts of Escherichia coli from naturally or artificially contaminated ground beef, other meats and poultry, vegetables, fish and shellfish, cheese, and diverse sources such as swabs, by the Anderson-Baird-Parker direct plate (DP) and a hydrophobic grid-membrane filter (HGMF) method. For five of the eight laboratories overall counts by HGMF were significantly low (51-83%) compared with those by DP. Counts by HGMF tended to be lower for naturally contaminated samples; several possible causes were investigated. In a subsidiary study, analyst variation in counting HGMF ranged from 0.8-7.3%, with little evidence of effects from counting positive versus negative grid cells or from the fullness of growth or staining intensity.

Bacteriological Techniques↗
PubMed2000

Comparison of an LH-RH analogue (Goeserelin acetate, 'Zoladex') with combined androgen blockade in advanced prostate cancer: final survival results of an international multicentre randomized-trial. International Prostate Cancer Study Group.

OBJECTIVE: The aim of this study was to compare the effects of the nonsteroidal antiandrogen flutamide plus the LH-RH analogue goserelin acetate (combined androgen blockade [CAB]) with goserelin acetate alone in patients with advanced prostate cancer. The original analyses at 25 and 56 months of follow-up have been reported previously, and here we report the final survival analysis after 10 years of follow-up. METHODS: 589 patients with advanced prostate cancer (55% with metastatic [M1] and 45% with locally advanced [M0] disease) were randomized to receive goserelin acetate 3.6 mg either alone or in combination with flutamide (250 mg three times daily). RESULTS: A total of 583 patients were included in the analysis. There was a small, but nonsignificant, benefit for CAB compared with goserelin acetate alone in all patients with respect to survival (hazard ratio 0.88, 95% CI 0.73, 1.06). Subgroup analysis of M0 and M1 patients showed similar results (M0: hazard ratio 0.92, 95% CI 0.68, 1.25; M1: hazard ratio 0.85, 95% CI 0.66, 1. 08). The treatment effect was not significantly different for M0 and M1 patients (p = 0.685). CONCLUSIONS: In this large randomized trial containing significant numbers of M0 patients, after 10 years there was a small but nonsignificant benefit for CAB over castration alone.

Aged↗
PubMedDate not supplied

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Adenocarcinoma↗
PubMedDate not supplied

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. ONGOING ISSUES: We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

Cell Biology↗
PubMedDate not supplied

Colposcopy, cervicography, speculoscopy and endoscopy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The colposcope was developed in 1925 and is well established in clinical gynecologic practice for defining and delineating cytologically detected lesions mainly of the cervix but also the vagina and vulva. Additionally, various endoscopic procedures in gastroenterology, pulmonary and urologic lesions enhance the cytologic detection and histologic verification of precancerous and cancerous lesions. The cost-effectiveness of all these devices and their applicability, particularly in countries with a limited health budget, is a major issue. This task force considered aspects of the present state of the art and the challenges in the 21st century. CONSENSUS POSITION: Automated cytology can interface with colposcopic examination in a number of significant ways. Automated cytologic analysis of conventional cervical smears can potentially direct colposcopic examination by predicting the nature of a lesion, assist in determining which patients should receive colposcopy and, in some settings, thereby reduce the number of colposcopies. Potentially, various combinations of automated cytology and colposcopy may be used to generate screening protocols that might result in more effective and inexpensive screening. The role of cervicography, or high-resolution cervical photography, as a screening device remains to be defined. Sensitivity for high grade lesions is generally no greater than that in cytology, and specificity appears lower. The interpretation of cervical photographs in triage of mildly abnormal cytology may prove to be useful in countries with established cytology programs. In areas of the world where cytology screening programs are not in place, the interpretation of cervical photographs may have its most dramatic effect. Cost-effectiveness analyses are needed. There are, at present, insufficient data for the evaluation of speculoscopy, a procedure using chemiluminescent illumination of the cervix for visualization of acetowhite areas. Basic training in colposcopy should be integrated into the residency programs of obstetrics and gynecology. Criteria for the adequate training of colposcopists should be developed. Continuing education programs in colposcopy should be developed when they are not already in existence. The cost-effectiveness of integrating colposcopy as a primary screening technique should be evaluated. Following a high-grade squamous intraepithelial lesion (HSIL) cytology result, colposcopically directed punch biopsy should be taken with or without endocervical curettage. This generally should precede the loop electrosurgical excision procedure (LEEP); however, in certain circumstances direct LEEP may be indicated. LEEP under colposcopic vision is an efficient way to treat an HSIL lesion of the cervix because the histologic extent and margins can be determined, unlike with laser surgery or cryosurgery. It is also more cost-effective than cold knife conization because general anesthesia and an operating room are unnecessary. Following LEEP, the endocervical canal should be examined colposcopically for any evidence of involvement. Lesions in the endocervix can then be removed with a different-shaped loop. Further research into Raman spectroscopy as a diagnostic aid in cervical pathology is needed, as is the use of micrococolpohysteroscopy for in vivo cytologic analyses, especially of the endocervical canal and transformation zone. Hysteroscopy is the most direct method for the diagnosis and treatment of intrauterine diseases. Hysteroscopic endometrial biopsy is more accurate than conventional biopsy methods. Cervical invasion of endometrial cancer can be detected by hysteroscopy. The depth of invasion, however, is more accurately determined by magnetic resonance imaging or computed tomography. ONGOING ISSUES: Many topics for ongoing research and/or implementation are mentioned under "Consensus Position," above. (ABSTRACT TRUNCATED)

Automation↗
PubMedDate not supplied

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs. CONSENSUS POSITION: 1. Based on the available molecular, clinical and epidemiologic data, a subset of HPVs are unequivocally the etiologic agents for cervical cancers and their precursors. 2. Different mucosotropic HPVs have varying neoplastic potential. However, the great majority of cervical HPVs have oncogenic potential. Since oncogenic HPV-induced epithelial transformation to a high grade lesion or cancer is rare relative to the rate of infection, the term high risk is discouraged. 3. HPV's interaction with host cells has two principal biologic consequences: a) All anogenital HPVs induce low grade squamous lesions, which are the morphologic correlate of a productive infection. b) Rarely, HPVs induce a proliferative epithelial phenotype that pathologists recognize as a high grade lesion and that is the proximate cytohistologic precursor of invasive cervical carcinoma. 4. HPV biology and issues of practical clinical management should be reflected in the classification systems used for cytologic and histologic diagnosis. ONGOING ISSUES: The molecular identification of HPVs (HPV testing) potentially may be very useful for primary screening or secondary triage of patients with certain lesions. However, the technology available to the practicing clinician is still evolving. Optimization of type spectrum, sensitivity, specificity and ease of use is under development. Data regarding these factors as well as a clear cost benefit analysis are sparse or pending in several large trials. Until such data are available, caution in clinical implementation of HPV testing is warranted.

Adenocarcinoma↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Medicolegal affairs. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Increasing litigation over alleged false negative cervical cytologic (CC) smears threatens the viability of this test for cervical cancer detection. The problem appears to be largely American but is beginning to appear in some other countries. In the vast majority of cases there is either a settlement or jury verdict for the plaintiff based largely on the testimony of expert witnesses. Cases are judged on an individual basis without significant consideration of the general performance of the CC smear in laboratories operating in compliance with a wide array of laboratory regulations and with documented and comprehensive quality control practices in place. It is acknowledged that there are problem laboratories and cytology practitioners. There is an emerging issue of automated preparation and screening devices and issues of informed patient consent. CONSENSUS POSITION: Cytology professionals have done an extraordinary and commendable job of educating the public about the benefits of the CC smear. We have been less successful and conscientious about explaining and defining the limitations of the CC test. There is a need for public and professional education as to the benefits and limitations of the CC smear for cervical cancer detection. The process suggested is to work with women's groups, public health agencies, government agencies, and state and national legislatures and to coordinate professional committees working on liability issues. Contextual information could be included with the CC smear report to indicate that a negative report confers a low probability of developing cervical cancer. It is suggested that appropriate language and a menu of statements be developed. Increased efforts should be directed to physician education with respect to informed consent concerning the benefits and limitations of CC smear testing and the application of new technology to improve smear accuracy. The process should include development of appropriate statements on the use of alternative technology. The profession should develop "process guidelines" for review of CC smears in the context of possible litigation, including standardized methods for blind slide review of smears that reduce or eliminate context and outcome bias. It is suggested that review panels be anonymous, that the process be standardized and that there be limitations on liability for participating organizations. Professional cytopathology and pathology societies should formulate acceptable guidelines for expert witnesses. The standards should be applicable to both defendant and plaintiff experts. All materials to the extent practical, including consultant opinions, should be available for peer review. Professional cytopathology and pathology societies should monitor expert testimony for objectivity and scientific accuracy. ONGOING ISSUES: For the near future, litigation will continue to focus on false negative CC smears on a case-by-case basis. Laboratories and individuals can reduce the risk of malpractice liability by directing their attention to proactive quality control and quality assurance methods. In the final analysis, consumer education about the benefits and limitations of the test is key to limiting malpractice claims. To stem the tide of continued medicolegal challenges to the integrity of cytology practice, the cytology community has now focused its efforts on developing and utilizing standards that convey to patients, attorneys and cytologists the contemporary status of and reasonable expectations for the practice of cytology. Guidelines such as those for uniform reporting terminology and clinical management of cervical abnormalities form the basis of cytology practice standards on which legal standards of practice can be based. Consensus conference reports, clinical management trials and scientifically valid studies of false negative rates that analyze the type, frequency and cause of missed cases represent sounder methods of establishing defensible

Cell Biology↗
PubMedDate not supplied

Quality assurance/control issues. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: General definitions of quality assurance and quality control (QA/C) have existed in many forms for decades, and a new discipline guides their application to diverse industrial and recently medical processes without much fanfare. However, in the field of cervical cytology screening, the range of QA/C options has recently broadened and become controversial. With the advent of new systems of terminology, larger-scale laboratories and new technologies--plus strong governmental and legal pressures in some nations--the range of extremely difficult and sometimes expensive QA/C choices our community faces is greater than ever. CONSENSUS POSITION: At our conference, the basic definitions of QA/C posed little difficulty. Presentation of the range of methods in use today and of those based on new technologies where use is proposed or has just begun also was achieved with little or no dispute. However, there was lack of consensus on exactly how QA/C methods are to be assessed. Indeed, there was little consistency in the use of different outcome measures with which we can judge success or failure of specific QA/C options. In addition, the tension between pressure to adopt sometimes uncertain or expensive method enhancements and pressure to maintain affordability and the widest possible access for populations that most need cervical cytology screening is greater than ever. ONGOING ISSUES: More data are required that would enable assessment of QA/C options with the clearest possible understanding of cost/benefits and current or new assumptions of risk. Other task forces, such as medicolegal, cost/benefit and those devoted to new technologies, are our essential partners in meeting the challenges described above.

Centers for Medicare and Medicaid Services, U.S.↗