p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.
ABSTRACT Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.
Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.
Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone.
Interobserver agreement for diagnosis of AIN was fair when based solely on H&E preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with H&E, Ki-67, and H&E/p16/Ki-67 combined.
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ABSTRACT: HPV-Infektionen spielen eine wichtige Rolle bei der Entstehung des Analkarzinoms. Sowohl der Infektionsweg als auch die sich anschließende Transformation der infizierten Epithelzellen ähnelt sehr den Mechanismen, über die auch andere HPV-assoziierte Karzinome entstehen. Die molekulare Analyse der einzelnen Schritte, die für die maligne Transformation erforderlich sind, führte zur Identifizierung von Markern, durch die eindeutig und mit höherer Präzision die HPV-transformierten Zellen nachgewiesen werden können. Da seit der Einführung der wirksamen antiretroviralen Therapie die Überlebenszeiten von HIV-infizierten Personen, die ein besonders hohes Risiko haben, an HPV-assoziierten Tumoren zu erkranken, deutlich angestiegen sind, sind gerade auch für die praktizierenden Dermatologen und Proktologen diese Entwicklungen zunehmend von praktischem Interesse. In dieser Übersicht beschreiben wir kurz die grundlegenden Mechanismen und einige klinische Anwendungsbeispiele dieser Forschung. HPV infections have been implicated in the pathogenesis of anal cancers. The mode of infection and subsequent transformation resembles very much the pathogenesis of cervical and other HPV-associated cancers. The molecular dissection of individual steps required to achieve cellular transformation within an HPV-infected cell led to the identification of novel biomarkers that make it possible to identify HPV-transformed cells with substantially higher precision in comparison to conventional methods. Since effective antiretroviral therapy allows for possible long-term survival of HIV-infected individuals who are at very high risk to develop HPV-associated cancers in the anogenital tract, these new developments have become increasingly relevant for practicing dermatologists and proctologists. We here briefly review the basic concepts and some clinical applications of this recent research.Der Hautarzt 01/2010; 61(1):13-20. DOI:10.1007/s00105-009-1809-y · 0.54 Impact Factor
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ABSTRACT: To examine levels of persistence and compliance as well as the economic impact of extended-release tolterodine (tolterodine ER) versus immediate- and extended-release oxybutynin (oxybutynin IR or oxybutynin ER) among commercially-insured patients with overactive bladder (OAB). Patients with OAB who initiated tolterodine ER, oxybutynin IR, or oxybutynin ER between January 2001 and December 2002 were identified from the PharMetrics Patient-Centric database; the first medication used in this timeframe was used for treatment group assignment (ie, patients were only in 1 group). Exploratory assessment of persistency and compliance was conducted among all treated patients: subjects were matched 1:1 based on the estimated propensity score for tolterodine ER in remaining analyses. Measures included patient characteristics as well as levels of medication, outpatient and inpatient resource utilization, and costs. Primary comparisons were made descriptively; costs were evaluated using generalized linear models with a gamma distribution and log-link function. Compliance did not differ between tolterodine ER (77.4%) and oxybutynin ER (74.3%), but was lower for oxybutynin IR (60.9%). Mean (+/- standard deviation) duration of therapy was higher for tolterodine ER (139 +/- 132 days) versus oxybutynin ER (115 +/- 122) and oxybutynin IR (60 +/- 85). Totals of 7257 and 5936 matched pairs were available for tolterodine ER versus oxybutynin ER and oxybutynin IR comparisons, respectively. The mean age was 54 years in all groups; the majority was women. Utilization of outpatient and inpatient medical services was consistently lower among tolterodine ER patients in both comparisons. Total costs were slightly lower for tolterodine ER versus oxybutynin ER (dollar 8303 +/- dollar 18 802 vs dollar 8862 +/- dollar 18 684) and oxybutynin IR (dollar 9975 +/- dollar 24860 vs dollar 10521 +/- dollar 22 602); differences were significant after multivariate adjustment. Use of tolterodine ER results in comparable compliance to oxybutynin ER and longer duration of use relative to either form of oxybutynin. In addition, tolterodine ER may be cost-effective relative to oxybutynin IR or oxybutynin ER among commercially-insured persons with OAB.The American journal of managed care 08/2005; 11(4 Suppl):S140-9. DOI:10.1016/S1098-3015(10)67383-4 · 2.17 Impact Factor
Article: Anal–rectal cytology: A review[Show abstract] [Hide abstract]
ABSTRACT: The incidence of invasive anal squamous cell carcinoma, a human papilloma virus (HPV) related cancer, is on the rise, especially in HIV positive men who have sex with men (MSM). Like cervical cancer, anal cancer is associated with precursor lesions detectable on exfoliative cytology as squamous intraepithelial lesions and on biopsy as intraepithelial neoplasia. Anal–rectal cytology screening programs, similar to cervical cytology screening programs, have been developed in an effort to detect and to eradicate precursor lesions prior to progression to invasive squamous cell carcinoma. Either conventional or liquid-based anal–rectal cytology specimens are acceptable, but liquid-based specimens are preferred. Specimens may be collected by health care professionals or by patients. A minimum of 2,000–3,000 nucleate squamous cells should comprise adequate specimens. Diagnostic terminology as defined by the Bethesda System for Reporting Cervical Cytology (TBS 2001) should be used. Sensitivity and specificity of a single anal–rectal cytology specimen is comparable with that of a single cervical cytology test, but cytological interpretations do not always correlate with lesion severity. Patients with atypical squamous cells of undetermined significance (ASC-US) or worse should be referred for anoscopy. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc.Diagnostic Cytopathology 07/2009; 38(7):538 - 546. DOI:10.1002/dc.21242 · 1.52 Impact Factor