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[Title] P16 and Ki67 Immunostains Decrease Intra- and Interobserver Variability in the Diagnosis and Grading of Anal Intraepithelial Neoplasia (AIN).

BACKGROUND: Significant variation is reported in the diagnosis of HPV-associated AIN.

We previously observed that band-like positivity for p16 in >90% of contiguous cells coupled with Ki67 positivity in >50% of lesional cells is strongly associated with high grade AIN.

This study was undertaken to determine if addition of p16 and Ki67 immunostaining would reduce inter- and intraobserver variability in diagnosis and grading of AIN.

DESIGN: H&E stained slides of 60 anal biopsies were reviewed by three pathologists and consensus diagnoses were achieved: 25 negative, 12 low (condyloma and/or AIN I) and 23 high (9 AIN II and 14 AIN III) grade lesions.

The H&E stained slides were diagnosed independently by three additional ("participant") pathologists.

RESULTS: Addition of p16 and Ki67 immunostains reduced intra- and interobserver variability, improved concurrence with consensus diagnoses and reduced two-step differences in diagnosis.

Negative and high grade AIN diagnoses showed the most improvement in concurrence levels.

CONCLUSION: Addition of p16 and Ki67 immunostains is helpful in the diagnosis and grading of AIN.

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(PMID = 21876646.001).

[ISSN] 1178-1181

[Journal-full-title] Clinical medicine. Pathology

[ISO-abbreviation] Clin Med Pathol

[Language] eng

[Publication-type] Journal Article

[Publication-country] New Zealand

[Other-IDs] NLM/ PMC3159996

[Keywords] NOTNLM ; Ki67 / P16 / anal intraepithelial neoplasia (AIN) / condyloma / human papilloma virus (HPV) / interobserver variability / intraobserver variability

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Perianal squamous cell carcinoma with high-grade anal intraepithelial neoplasia in an HIV-positive patient using highly active antiretroviral therapy: case report.

CONTEXT: Highly active antiretroviral therapy (HAART) has turned human immunodeficiency virus (HIV) infection into a chronic condition, and this has led to increased incidence of anal dysplasia among HIV-positive patients.

Routine anal evaluation including the anal canal and perianal area is recommended for this population, especially for patients infected by oncogenic human papillomavirus (HPV) types.

CASE REPORT: A 54-year-old homosexual HIV-positive man presented with a six-year history of recurrent perianal and anal warts.

He presented some condylomatous spreading lesions occupying part of the anal canal and the perianal skin, and also a well-demarcated slightly painful perianal plaque of dimensions 1.0 x 1.0 cm.

Both anal canal Pap smears and biopsies guided by high-resolution anoscopy revealed high-grade squamous intraepithelial lesion.

Biopsies of the border of the perianal plaque also revealed high-grade squamous intraepithelial lesion.

HPV DNA testing of the anus detected the presence of HPV-16 type.

The patient underwent local full-thickness excision of the lesion.

Histological analysis on the excised tissue revealed high-grade squamous intraepithelial lesion with one focus of microinvasive squamous cell cancer measuring 1 mm.

The patient showed pathological evidence of recurrent anal and perianal high-grade squamous intraepithelial lesions at the sixth-month follow-up and required further ablation of those lesions.

However no invasive squamous cell carcinoma recurrence has been detected so far.

[MeSH-major] Antiretroviral Therapy, Highly Active / adverse effects. Anus Neoplasms / pathology. Carcinoma, Squamous Cell / pathology. HIV Seropositivity / drug therapy. Human papillomavirus 16 / isolation & purification. Papillomavirus Infections / pathology

[MeSH-minor] Anal Canal / pathology. Anal Canal / virology. DNA, Viral / analysis. Humans. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Recurrence, Local / diagnosis

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(PMID = 18094898.001).

[ISSN] 1516-3180

[Journal-full-title] São Paulo medical journal = Revista paulista de medicina

[ISO-abbreviation] Sao Paulo Med J

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Brazil

[Chemical-registry-number] 0 / DNA, Viral

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Management of anal cancer in 2010. Part 1: Overview, screening, and diagnosis.

Although anal cancer is a rare disease, its incidence is increasing in men and women worldwide.

Anal cancer is generally preceded by high-grade anal intraepithelial neoplasia (HGAIN), which is most prevalent in human immunodeficiency virus (HIV)-positive men who have sex with men.

Meta-analysis suggests that 80% of anal cancers could be avoided by vaccination against HPV 16/18.

Nearly half of all patients with anal cancer present with rectal bleeding.

Pain or sensation of a rectal mass is experienced in 30% of patients, whereas 20% have no tumor-specific symptoms.

According to the Surveillance Epidemiology and End Results (SEER) database, 50% of patients with anal cancer have disease localized to the anus, 29% have regional lymph node involvement or direct spread beyond the primary, and 12% have metastatic disease, while 9% have an unknown stage.

Clinical staging of anal carcinoma requires a digital rectal exam and a computed tomography scan of the chest, abdomen, and pelvis.

The 5-year relative survival rates are 80.1% for localized anal cancer, 60.7% for regional disease, and 29.4% for metastatic disease.

Part 2 of this two-part review will address the treatment of anal cancer, highlighting studies of chemoradiation.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / prevention & control. Mass Screening

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(PMID = 20464850.001).

[ISSN] 0890-9091

[Journal-full-title] Oncology (Williston Park, N.Y.)

[ISO-abbreviation] Oncology (Williston Park, N.Y.)

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Number-of-references] 94

   

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] BD ProEx C immunostaining in extramammary Paget's disease and perineal melanoma.

The differential diagnosis of perineal biopsies can include squamous intraepithelial lesions, extramammary Paget's disease, and melanoma.

Immunostaining for ProEx C has been validated in cervical cytology and positive staining has also been shown to be strongly associated with human papilloma virus (HPV)-induced cervical and anal intraepithelial neoplasia in biopsies.

We observed positive staining for ProEx C in Paget cells in all of 26 cases of Paget's disease irrespective of tissue site (extramammary, mammary) and in melanoma cells in all of 12 cases of primary perineal melanoma with immunostaining in >50% of malignant cells in 73% of Paget disease cases and 43% of perineal melanoma cases.

Positive staining was heterogeneous and exclusively nuclear in all cases.

Currently neither of these lesions is known to be HPV related although according to the literature the possibility of a role for HPV in melanoma is still unsettled.

[MeSH-major] Antigens, Neoplasm / analysis. Anus Neoplasms / enzymology. Cell Cycle Proteins / analysis. DNA Topoisomerases, Type II / analysis. DNA-Binding Proteins / analysis. Melanoma / enzymology. Nuclear Proteins / analysis. Paget Disease, Extramammary / enzymology. Perineum / pathology. Reagent Kits, Diagnostic. Vaginal Neoplasms / enzymology. Vulvar Neoplasms / enzymology

[MeSH-minor] Adult. Aged. Aged, 80 and over. Alphapapillomavirus / genetics. Alphapapillomavirus / isolation & purification. Biopsy. DNA, Viral / isolation & purification. Diagnosis, Differential. Female. Humans. Immunoassay. In Situ Hybridization. Male. Middle Aged. Minichromosome Maintenance Complex Component 2. Mucous Membrane / enzymology. Mucous Membrane / pathology. Mucous Membrane / virology. Predictive Value of Tests

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(PMID = 18931649.001).

[ISSN] 1530-0285

[Journal-full-title] Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

[ISO-abbreviation] Mod. Pathol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Cell Cycle Proteins; 0 / DNA, Viral; 0 / DNA-Binding Proteins; 0 / Nuclear Proteins; 0 / Reagent Kits, Diagnostic; EC 3.6.4.12 / MCM2 protein, human; EC 3.6.4.12 / Minichromosome Maintenance Complex Component 2; EC 5.99.1.3 / DNA Topoisomerases, Type II; EC 5.99.1.3 / DNA topoisomerase II alpha

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Diagnosis of Sex Chromosome Disorders and Prenatal Diagnosis of Down Syndrome using Interphase Fluorescent In-Situ Hyperidization Technique.

OBJECTIVES: Evaluation of guidelines used for prenatal diagnosis of Down syndrome (DS) as well as sex chromosomal disorders including interphase Fluorescent In Situ Hyperidization (FISH) technique.

METHODS: Enrolled cases were among those presenting to Genetics and Neonatology Units, Mansoura and Ain-Shams University hospitals,(Egypt) during 2002 to 2004.

Groups 2 comprised suspected cases with sex chromosomal disorders including neonates with ambiguous genitalia (64 cases) and adults with primary amenorrhea (69 cases) or infertility (38 cases).

They were subjected to a diagnostic workup including RESULTS: Among the pregnant women group, seven were found to be at a high risk of having DS fetuses including 3 cases with a history of affected off-springs, 2 cases with age above 35 years, and 2 cases with high triple test.

Only one case had positive trisomy 21 on interphase FISH confirmed by karyogram on cultured amniotic cells.

Regarding the other group, 5 cases out of the 9 females were proved to be feminized males, one proved mosaic turner, one proved mixed gonadal dysgenesis and 2 normal females.

On the other hand one out of three males were proved to be verilized female while the other one was a male with incomplete testicular feminization and the last one was a male with infertility diagnosed as Klinefelter syndrome at the age of 26 years.

It adds to the diagnostic utility of routine cytogenetics and its use on interphase nuclei overcomes the difficulty of conventional cytogenetics.

It could be used in the prenatal diagnosis of DS in addition to ultrasonography, and triple test.

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[Cites] Chromosome Res. 2004;12(1):15-23 [14984098.001]

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(PMID = 21475429.001).

[ISSN] 1658-3639

[Journal-full-title] International journal of health sciences

[ISO-abbreviation] Int J Health Sci (Qassim)

[Language] eng

[Publication-type] Journal Article

[Publication-country] Saudi Arabia

[Other-IDs] NLM/ PMC3068641

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Cost-effectiveness of screening high-risk HIV-positive men who have sex with men (MSM) and HIV-positive women for anal cancer.

BACKGROUND: Anal cancer is uncommon and predominantly a disease of the elderly.

Individuals who are human immunodeficiency virus (HIV)-positive are particularly vulnerable to HPV infections, and increasing numbers from this population present with anal cancer.

OBJECTIVE: To estimate the cost-effectiveness of screening for anal cancer in the high-risk HIV-positive population [in particular, men who have sex with men (MSM), who have been identified as being at greater risk of the disease] by developing a model that incorporates the national screening guidelines criteria.

The following electronic bibliographic databases were searched: Applied Social Sciences Index and Abstracts (ASSIA), BIOSIS previews (Biological Abstracts), British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, NHS Database of Abstracts of Reviews of Effects (DARE), NHS Health Technology Assessment (HTA) Database, PsycINFO, Science Citation Index (SCI), and Social Sciences Citation Index (SSCI).

STUDY SELECTION: Published literature identified by the search strategy was assessed by four reviewers.

Papers that met the inclusion criteria contained the following: data on population incidence, effectiveness of screening, health outcomes or screening and/or treatment costs; defined suitable screening technologies; prospectively evaluated tests to detect anal cancer.

Searches identified 2102 potential papers; 1403 were rejected at title and a further 493 at abstract.

RESULTS: The reference case cost-effectiveness model for MSM found that screening for anal cancer is very unlikely to be cost-effective.

The negative aspects of screening included utility decrements associated with false-positive results and with treatment for high-grade anal intraepithelial neoplasia (HG-AIN).

However, combined with higher regression rates from low-grade anal intraepithelial neoplasia (LG-AIN), the lowest expected incremental cost-effectiveness ratio remained at over 44,000 pounds per quality-adjusted life-year (QALY) gained.

Probabilistic sensitivity analysis showed that no screening retained over 50% probability of cost-effectiveness to a QALY value of 50,000 pounds.

The screening model for HIV-positive women showed an even lower likelihood of cost-effectiveness, with the most favourable sensitivity analyses reporting an incremental cost per QALY of 88,000 pounds.

LIMITATIONS: Limited knowledge is available about the epidemiology and natural history of anal cancer, along with a paucity of good-quality evidence concerning the effectiveness of screening.

CONCLUSIONS: Many of the criteria for assessing the need for a screening programme were not met and the cost-effectiveness analyses showed little likelihood that screening any of the identified high-risk groups would generate health improvements at a reasonable cost.

Further studies could assess whether the screening model has underestimated the impact of anal cancer, the results of which may justify an evaluative study of the effects of treatment for HG-AIN.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / economics. HIV Infections / complications. Homosexuality, Male / statistics & numerical data. Mass Screening / economics

[MeSH-minor] Age Factors. Antiretroviral Therapy, Highly Active. Cost-Benefit Analysis. Disease Progression. Female. Humans. Incidence. Male. Marital Status. Papillomavirus Infections / complications. Prognosis. Quality of Life / psychology. Risk Factors. Risk-Taking. United States / epidemiology

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(PMID = 21083999.001).

[ISSN] 2046-4924

[Journal-full-title] Health technology assessment (Winchester, England)

[ISO-abbreviation] Health Technol Assess

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.

OBJECTIVES: Evaluation of anal intraepithelial neoplasia (AIN) is subjective.

Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade.

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.

MATERIALS AND METHODS: Seventy-seven anal specimens were retrieved.

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.

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).

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.

CONCLUSIONS: 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.

[MeSH-major] Anus Neoplasms / diagnosis. Carcinoma in Situ / diagnosis. DNA, Neoplasm / analysis. Gene Expression Regulation, Neoplastic. Genes, p16 / physiology

[MeSH-minor] Adult. Aged. Aged, 80 and over. Antigens, Neoplasm / analysis. Biopsy. Clinical Competence. Diagnosis, Differential. Female. Humans. Male. Middle Aged. Observer Variation. Retrospective Studies

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(PMID = 19550211.001).

[ISSN] 1526-0976

[Journal-full-title] Journal of lower genital tract disease

[ISO-abbreviation] J Low Genit Tract Dis

[Language] eng

[Publication-type] Comparative Study; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / DNA, Neoplasm

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Anal intraepithelial neoplasia].

[Transliterated title] Neoplasia intraepitelial anal.

Human papillomavirus (HPV) is responsible for anal condylomata, anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma.

AIN is a premalignant condition that can progress to invasive carcinoma through different grades of severity of the disease called AIN I, AIN II and AIN III.

This paper looks at the current definition, diagnostic methods and management of AIN.

The incidence of AIN has increased significantly in the last decades.

The groups at risk are mainly patients with infection with human immunodeficiency virus, immunossuppressed patients and patients affected by HPV related diseases (e.g., cervical cancer or anal condyloma).

Accurate diagnosis of AIN lesions consists of accurate grading and disease extension.

Low grade AIN (AIN I) or in extensive lesions, follow-up is advised to determine the possible evolution to anal squamous cell carcinoma.

In cases of more severe and localized lesions (AIN II and AIN III), surgical resection should be considered if the predictive postoperative morbidity is low.

Screening programs for AIN are not currently in place and there might be much effort to study the management of HPV in these patients.

[MeSH-major] Anus Neoplasms / pathology. Carcinoma in Situ / pathology

[MeSH-minor] Anal Canal / pathology. Anal Canal / surgery. Humans

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(PMID = 17198654.001).

[ISSN] 0025-7753

[Journal-full-title] Medicina clínica

[ISO-abbreviation] Med Clin (Barc)

[Language] spa

[Publication-type] English Abstract; Journal Article; Review

[Publication-country] Spain

[Number-of-references] 58

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN). Impact of HPV analysis of anal lesions on diagnosis and prognosis.

BACKGROUND AND AIMS: Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN).

This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN.

METHODS: The study included biopsy samples from 87 patients who had been diagnosed with the following disease patterns: 47 invasive anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions.

RESULTS: In 38 of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the majority of which were HPV 16 (33/38=86.8%).

In 29 of the 33 cases of AIN, HPV DNA was detected (87.9%), most of these in AIN III (15/16=93.8%).

DISCUSSION: In our series, the clinical diagnosis of the invasive anal carcinoma had a high sensitivity of 93.6%, with a specificity of 80%.

The positive predictive value was 84.6%, and the negative predictive value 91.4%.

In contrast, AIN had been detected clinically in none of the cases.

In this situation, especially with high-risk patients, our findings recommend anal HPV screening in combination with anal cytology and anoscopy.

CONCLUSION: Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected.

[MeSH-major] Alphapapillomavirus / genetics. Anus Neoplasms / virology. Carcinoma in Situ / virology. Carcinoma, Squamous Cell / virology. DNA, Viral / analysis

[MeSH-minor] Adult. Aged. Aged, 80 and over. Biopsy. Diagnosis, Differential. Female. Humans. Male. Middle Aged. Polymerase Chain Reaction. Prognosis. Retrospective Studies

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[CommentIn] Int J Colorectal Dis. 2007 Oct;22(10):1289 [16703315.001]

(PMID = 15864603.001).

[ISSN] 0179-1958

[Journal-full-title] International journal of colorectal disease

[ISO-abbreviation] Int J Colorectal Dis

[Language] eng

[Publication-type] Journal Article

[Publication-country] Germany

[Chemical-registry-number] 0 / DNA, Viral

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal intraepithelial neoplasia.

BACKGROUND: Anal intraepithelial neoplasia (AIN) is believed to be a precursor of anal squamous cell cancer and its incidence is rising in high-risk groups, particularly those infected with the human immunodeficiency virus (HIV).

The natural history of AIN is unclear and management strategies are lacking.

METHODS: This review is based on a literature search (Medline and PubMed) with manual cross-referencing of all articles related to AIN.

RESULTS AND CONCLUSIONS: The aetiology of AIN is intricately linked with human papilloma viruses.

The pathological processes involved in the progression of AIN are becoming clearer but the natural history, particularly the rate of progression to invasive cancer, remains unknown.

There is no standard management for AIN and this is mainly due to difficulties in both diagnosis and treatment.

Long-term follow-up of these patients is essential until the natural history of AIN becomes clearer.

[MeSH-major] Anal Canal / pathology. Anus Neoplasms. Carcinoma in Situ. Carcinoma, Squamous Cell

[MeSH-minor] Female. HIV Infections / complications. Humans. Immune Tolerance. Male. Papillomavirus Infections / complications. Precancerous Conditions / etiology. Precancerous Conditions / pathology. Precancerous Conditions / surgery. Risk Factors. Tumor Virus Infections / complications

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[Copyright] Copyright (c) 2005 British Journal of Surgery Society Ltd.

(PMID = 15736144.001).

[ISSN] 0007-1323

[Journal-full-title] The British journal of surgery

[ISO-abbreviation] Br J Surg

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] England

[Number-of-references] 131

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal intraepithelial neoplasia: correlation of grade with p16INK4a immunohistochemistry and HPV in situ hybridization.

Accurate diagnosis and grading of anal intraepithelial neoplasia (AIN) can be problematic, especially in separating AIN from anal transitional-zone epithelium.

To investigate if p16 would help in more accurately diagnosing and grading AIN, particularly when attempting to distinguish benign transitional-zone epithelium from high-grade AIN, we separately assessed these stains in a blinded manner on a large number of consecutive anal biopsies and anal tissues and correlated the findings with the diagnosis and grade of AIN.

One hundred thirty-three consecutive anal tissue specimens, from 128 patients were studied.

One hundred and eight were anal biopsies and 25 were hemorrhoidectomy specimens.

No gold standard was chosen, rather, comparisons between the 3 tests were made and agreement between tests was tested for statistical significance using the kappa value (kappa).

The comparisons included AIN grade (negative, 1, 2, 3) with nuclear intensity of p16 IHC (0 to 3+), AIN grade with IHC nuclear staining patterns (contiguous, patchy/rare), AIN grade with HPV-ISH [negative, low-risk (LR), high-risk (HR)] and, nuclear intensity of p16 IHC with HPV-ISH.

One hundred percent of AIN2 and 3 cases were strongly positive for nuclear p16, whereas 80% of AIN1 were positive.

Yet, 33% of AIN negative cases were positive for nuclear p16, although with less nuclear intensity than for AIN2 or 3.

The kappa value for AIN/nuclear p16 intensity agreement was 0.61 (ie, substantial agreement).

Yet, 12.5% of AIN negative cases were positive for HPV for both LR and HR types.

The kappa value for AIN/HPV agreement was 0.62 (ie, substantial agreement).

The kappa value for HPV/nuclear p16 intensity agreement was 0.56 (ie, moderate agreement).

Of interest, 30 cases were negative for AIN and p16 staining and of these, 2 (7%) were positive for HPV (both LR subtype).

Three cases positive for HR HPV were negative for AIN with only patchy nuclear p16 positivity.

We conclude that the correlation between AIN and p16 and HPV is strong enough to be quite useful in distinguishing true AIN from benign mimics, such as benign transitional-zone epithelium.

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(PMID = 18301250.001).

[ISSN] 1533-4058

[Journal-full-title] Applied immunohistochemistry & molecular morphology : AIMM

[ISO-abbreviation] Appl. Immunohistochem. Mol. Morphol.

[Language] ENG

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / DNA Probes, HPV

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] P16 and Ki67 immunostaining is a useful adjunct in the assessment of biopsies for HPV-associated anal intraepithelial neoplasia.

P16 is a tumor suppressor gene product, shown to be overexpressed in most cervical carcinomas and dysplasias associated with high-risk human papilloma virus (HPV) infection.

HPV is also associated with anal squamous dysplasias and carcinomas.

Significant interobserver and intraobserver variation exists in the interpretation of biopsies for anal intraepithelial neoplasia (AIN).

This study was undertaken to assess the potential role of p16 and Ki67 immunohistochemical expression in refining the diagnosis and grading of AIN.One-hundred and four anal biopsies from 74 patients were retrieved from the surgical pathology files of the department.

After discrepancies were resolved and concurrence was achieved by at least 2 of 3 reviewing pathologists, the diagnoses were as follows: 37 negative, 12 condylomas without overt dysplasia, 14 AIN I, 25 AIN II, and 16 AIN III. p16 and Ki67 expression was evaluated by ABC immunoperoxidase staining whereas the presence of the high-risk subtypes of HPV virus was determined by in situ hybridization on a subset of the biopsies.

Results were reviewed by 2 pathologists and positive and negative staining was correlated with H&E diagnoses.

Nuclear and/or nuclear and cytoplasmic staining was considered as positive for p16 when present in >10% of squamous cells.

A band-like pattern of p16 immunoreactivity was seen in 21.4% AIN I, 80% AIN II, and 87.5% AIN III cases.

None of the condylomas and only 1 of the negative cases showed a band of p16 positive staining.

Spotty p16 immunoreactivity was observed in 8.1% negative, 8.3% condyloma, 14.3% AIN I, 12.0% AIN II, and 12.5% AIN III cases.

More than 50% of nuclei stained positive for Ki67 in 28.6% AIN I, 48.0% AIN II, and 75.0% AIN III cases but in none of the negative or condyloma cases.

On the basis of these results, a band-like pattern of p16 staining and Ki67 positivity in >50% of the squamous cell nuclei were strongly associated with high-grade AIN.

Conversely, absence of a p16 band of positivity coupled with Ki67 positivity in <50% of nuclei was frequently associated with benign lesions.

Most AIN I lesions stained similar to the nondysplastic cases.

A small subset of biopsies studied did not conform to the pattern described above: 4 of 14 (28.6%) AIN I lesions showed a band-like pattern of p16 staining and/or >50% Ki67 positive nuclei.

4 of 25 (16.0%) AIN II lesions comprising 9.8% of the 41 high-grade AINs (AIN II and III) showed spotty p16 positivity and <50% Ki67 positive nuclei.

We conclude that when used together and evaluated in conjunction with H&E stained sections, p16 and Ki67 immunoexpression is a useful adjunct in the diagnosis and grading of AIN.

[MeSH-major] Anus Neoplasms / pathology. Carcinoma in Situ / pathology. Cyclin-Dependent Kinase Inhibitor p16 / metabolism. Ki-67 Antigen / metabolism. Papillomavirus Infections / pathology. Precancerous Conditions / pathology

[MeSH-minor] Adult. Aged. Biomarkers, Tumor / metabolism. Biopsy. Cell Nucleus / metabolism. Cell Nucleus / pathology. DNA, Viral / analysis. Female. Humans. Immunoenzyme Techniques. In Situ Hybridization. Male. Middle Aged. Papillomaviridae / genetics. Papillomaviridae / isolation & purification

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(PMID = 16819320.001).

[ISSN] 0147-5185

[Journal-full-title] The American journal of surgical pathology

[ISO-abbreviation] Am. J. Surg. Pathol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / DNA, Viral; 0 / Ki-67 Antigen

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [HPV type 16-associated anal intraepithelial neoplasia (AIN)].

[Transliterated title] HPV-Typ-16-assoziierte anale intraepitheliale Neoplasie (AIN).

A 25-year-old woman had suffered from a perianal ulcer for approximately 1 year.

Employing virologic and histologic techniques, we confirmed the diagnosis of an intraepithelial neoplasia.

Anal intraepithelial neoplasia (AIN) is induced by carcinogenic human papillomaviruses.

Because of its frequency, AIN is a crucial differential diagnosis for lesions of the anogenital area region failing to respond to standard therapies.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / surgery. Carcinoma in Situ / diagnosis. Carcinoma in Situ / surgery. Human papillomavirus 16 / isolation & purification. Papillomavirus Infections / diagnosis. Papillomavirus Infections / surgery. Skin Neoplasms / diagnosis. Skin Neoplasms / surgery

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(PMID = 19430747.001).

[ISSN] 1432-1173

[Journal-full-title] Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete

[ISO-abbreviation] Hautarzt

[Language] ger

[Publication-type] Case Reports; English Abstract; Journal Article

[Publication-country] Germany

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Clinical spectrum and virologic characteristics of anal intraepithelial neoplasia in HIV infection.

BACKGROUND: Anal intraepithelial neoplasia (AIN) represents a precursor lesion of invasive squamous cell carcinoma with a clear association to high-risk human papillomavirus (HPV) types.

HIV infection is strongly associated with a higher prevalence of genital HPV infection, a higher incidence of AIN, and, consecutively, an increased risk for anal cancer.

OBJECTIVE: The aim of this study was to determine the clinical spectrum of AIN and lesional HPV colonization in a cohort of homosexual men who were HIV positive and had a history of receptive anal intercourse.

RESULTS: Of all patients, 86% had anal HPV infection at their first visit.

AIN was diagnosed in 20 of the 103 patients (19.4%).

High-risk HPV types were present in all AIN cases with up to 7 different high-risk and up to 5 different low-risk types per lesion.

Histologically, 7 (35%), 7 (35%), and 6 (30%) of the patients had AIN grade I, II, or III, respectively.

Four different types of clinical presentation could be distinguished in the 20 patients with AIN: bowenoid (1 case, 5%); erythroplakic (2 cases, 10%); verrucous (6 cases, 30%); and leukoplakic (11 cases, 55%).

All verrucous lesions were graded as high-grade intraepithelial lesions in cytology, whereas 6 of the 11 leukoplakic lesions (55%) were low grade.

All verrucous AIN carried at least 4 different HPV types, always including HPV-16, and the mean number of HPV types was higher in verrucous lesions than in leukoplakic lesions (5.5 vs 3.8, respectively).

CONCLUSION: These data confirm the high incidence and prevalence of AIN in patients who are HPV positive with HIV infection.

Four different clinical types of AIN can be distinguished that might have prognostic implications.

Standardized screening programs for anal cancer prevention and treatment protocols for AIN in patients infected with HIV must be implemented.

[MeSH-major] Anus Neoplasms / virology. Carcinoma in Situ / virology. HIV Seropositivity / complications. Papillomaviridae / isolation & purification

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(PMID = 15793509.001).

[ISSN] 1097-6787

[Journal-full-title] Journal of the American Academy of Dermatology

[ISO-abbreviation] J. Am. Acad. Dermatol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Expression of proliferative biomarkers in anal intraepithelial neoplasia of HIV-positive men.

BACKGROUND: Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent among HIV-infected individuals, especially in men having sex with men (MSM).

Early diagnosis and treatment of AIN might prevent development of anal cancer.

OBJECTIVES: We aimed to evaluate the expression of 8 promising proliferative biomarkers in anal dysplasia and to compare the efficacy of these markers in diagnosing high-grade AIN.

METHODS: Immunohistochemical analysis of minichromosome maintenance proteins (MCM3, MCM4, MCM6, and MCM7), p21, Ki-67, p16, and proliferating cell nuclear antigen (PCNA) was performed in a total of 49 specimens of normal anal mucosa and high- and low-grade anal dysplasia.

HPV typing for 36 high- and low-risk HPVs was performed, and high-risk HPV-DNA loads were determined by real-time polymerase chain reaction (PCR) for HPV-types 16, 18, 31, and 33.

RESULTS: A total of 392 immunohistochemical slides were analyzed in this study.

In the progression from normal epithelium to high-grade dysplasia, we found significant differences in the expression of all biomarkers.

A cutoff of 25% or 50% lesional immunopositivity for the 4 MCMs, Ki-67, and p16 resulted in 100% sensitivity and 100% specificity to diagnose high-grade AIN.

Sensitivity and specificity of PCNA and p21 for a high-grade AIN diagnosis were lower.

HPV-DNA was detectable in 100% of high-grade AIN and 87.5% of low-grade AIN lesions.

All MCMs, p16, Ki-67, and PCNA, but not p21 correlated with cumulative lesional high-grade HPV-DNA loads.

LIMITATIONS: The relatively small number of samples is a limitation, especially for adequate subgroup analyses.

CONCLUSIONS: MCMs, Ki67, and p16 are reliable immunohistochemical adjuncts for diagnosing high-grade AIN.

[MeSH-major] Anus Neoplasms / pathology. Biomarkers, Tumor / analysis. Carcinoma in Situ / pathology. HIV Infections / diagnosis. Proliferating Cell Nuclear Antigen / metabolism

[MeSH-minor] Adult. Aged. Analysis of Variance. Antiretroviral Therapy, Highly Active / methods. Biopsy, Needle. DNA, Viral / analysis. HIV Seropositivity. Homosexuality, Male. Humans. Immunohistochemistry. Intestinal Mucosa / metabolism. Intestinal Mucosa / pathology. Male. Middle Aged. Neoplasm Staging. Papillomavirus Infections / complications. Papillomavirus Infections / diagnosis. Polymerase Chain Reaction / methods. Precancerous Conditions / pathology. Reference Values. Risk Assessment. Sensitivity and Specificity. Viral Load. Young Adult

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[Copyright] Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

(PMID = 20006407.001).

[ISSN] 1097-6787

[Journal-full-title] Journal of the American Academy of Dermatology

[ISO-abbreviation] J. Am. Acad. Dermatol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Viral; 0 / Proliferating Cell Nuclear Antigen

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Irregularly shaped leucoplakic lesion of the anus. Diagnosis: anal intraepithelial neoplasia (AIN).

[MeSH-major] Anus Neoplasms / pathology. Carcinoma in Situ / pathology. Leukoplakia / pathology. Papillomavirus Infections / complications

[MeSH-minor] Adult. Antiretroviral Therapy, Highly Active. Diagnosis, Differential. Homosexuality, Male. Humans. Male. Papillomaviridae / isolation & purification. Precancerous Conditions / pathology. Risk Factors

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(PMID = 17425644.001).

[ISSN] 0307-6938

[Journal-full-title] Clinical and experimental dermatology

[ISO-abbreviation] Clin. Exp. Dermatol.

[Language] eng

[Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal intraepithelial neoplasia in women with genital intraepithelial neoplasia.

OBJECTIVE: To estimate the prevalence of anal intraepithelial neoplasia in heterosexual women with genital intraepithelial neoplasia, and to compare anal cytology with colposcopy for their effectiveness in anal intraepithelial neoplasia screening.

METHODS: Women with confirmed intraepithelial neoplasia on the cervix, vagina, or vulva were referred for gynecologic oncology care.

All patients underwent anal cytology and high-resolution anoscopy.

Wilson score method was used to estimate 95% confidence interval for prevalence.

RESULTS: Women with average age of 39.6 years (range 14 to 83 years) underwent anal cytology and anoscopy (N=205).

Of the 205 patients with genital intraepithelial neoplasia, 25 patients (12.2%) had biopsy-proven anal intraepithelial neoplasia.

Twelve patients (5.9%) had abnormal anal cytology (nine with atypical squamous cells of undetermined significance [ASC-US], three with low-grade squamous intraepithelial lesions [LSIL]).

None of the nine patients with anal ASC-US had biopsy-proven anal intraepithelial neoplasia.

Of the three patients with anal LSIL, two had anal intraepithelial neoplasia II and one had condyloma on biopsy.

However, 78 patients (38%) had abnormal anoscopy findings that resulted in 25 biopsy-proven anal intraepithelial neoplasias (8 anal intraepithelial neoplasia I, 5 anal intraepithelial neoplasia II, 12 anal intraepithelial neoplasia III)), condylomas (n=11), and hyperkeratosis (n=8).

Anoscopy identified 32% (25 patients) with anal intraepithelial neoplasia out of 78 abnormal anoscopic examinations.

In diagnosing anal intraepithelial neoplasia, anoscopy has 100% sensitivity and 71% specificity; anal cytology has 8% sensitivity and 94% specificity.

CONCLUSION: Patients with cervical, vulvar, and vaginal intraepithelial neoplasia have 12.2% prevalence of anal intraepithelial neoplasia and should be screened with high-resolution anoscopy.

In anal intraepithelial neoplasia screening, anoscopy is more sensitive but less specific than anal cytology.

[MeSH-major] Anus Neoplasms / epidemiology. Carcinoma in Situ / epidemiology. Genital Neoplasms, Female / epidemiology

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[CommentIn] Obstet Gynecol. 2010 Sep;116(3):566-7 [20733435.001]

[ErratumIn] Obstet Gynecol. 2010 Nov;116(5):1224

(PMID = 20733438.001).

[ISSN] 1873-233X

[Journal-full-title] Obstetrics and gynecology

[ISO-abbreviation] Obstet Gynecol

[Language] eng

[Publication-type] Comparative Study; Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Human papillomavirus (HPV) viral load and HPV type in the clinical outcome of HIV-positive patients treated with imiquimod for anogenital warts and anal intraepithelial neoplasia.

OBJECTIVE: To evaluate the efficacy of 5% imiquimod in HIV-positive male patients with anogenital warts or anal intraepithelial neoplasia (AIN), and to elucidate whether human papillomavirus (HPV) type and viral load were important for clinical outcome and recurrences.

METHODS: Thirty-seven patients with histologically proven anogenital warts or AIN were enrolled.

Topical 5% imiquimod was applied three times per week for more than 8 h overnight for 16 weeks, although patients were allowed to continue therapy for 4 more weeks if they did not have complete clearance of lesions.

The perianal area was the main lesion location.

Eighteen patients had a histopathological diagnosis of AIN-1.

Clearance was not influenced by patients' CD4 counts, wart location, HIV viral load or HPV viral load.

CONCLUSIONS: The assumption that visible perianal warts are benign lesions in HIV-positive patients has to be reevaluated since an important number of such lesions could correspond to low-grade anal disease, which in turn could progress to high-grade anal disease or cancer.

In addition, our results in this preliminary study indicate that imiquimod appears to be effective in treating AIN in HIV-positive patients.

Further studies are needed to document its utility to prevent high-grade dysplasia and/or anal cancer.

[MeSH-major] AIDS-Related Opportunistic Infections / drug therapy. Adjuvants, Immunologic / therapeutic use. Aminoquinolines / therapeutic use. Anus Diseases / drug therapy. Anus Neoplasms / drug therapy. Condylomata Acuminata / drug therapy. Genital Diseases, Male / drug therapy. Papillomavirus Infections / drug therapy

[MeSH-minor] Administration, Topical. Adult. Carcinoma in Situ / drug therapy. Carcinoma in Situ / virology. Humans. Male. Middle Aged. Papillomaviridae / classification. Polymerase Chain Reaction. Treatment Outcome. Viral Load

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(PMID = 17714124.001).

[ISSN] 0926-9959

[Journal-full-title] Journal of the European Academy of Dermatology and Venereology : JEADV

[ISO-abbreviation] J Eur Acad Dermatol Venereol

[Language] eng

[Publication-type] Clinical Trial; Journal Article

[Publication-country] Netherlands

[Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Aminoquinolines; 99011-02-6 / imiquimod

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Malignant transformation of high-grade anal intraepithelial neoplasia.

BACKGROUND: The natural history of anal intraepithelial neoplasia (AIN) is uncertain.

METHODS: All patients were diagnosed with high-grade AIN (AIN III) between 1994 and 2003.

Diagnosis was by full-thickness biopsy and histopathological examination.

Excision of localized high-grade AIN was carried out in 28 patients with minimal morbidity.

Six patients were systemically immunosuppressed at diagnosis, all of whom had multifocal perianal lesions.

Three immunosuppressed patients developed invasive anal squamous carcinoma during follow-up.

By contrast, no invasive carcinomas were identified among immunocompetent patients with either localized or multifocal perianal disease.

CONCLUSION: AIN III appears to have a relatively low potential for malignant transformation in the immunocompetent patient.

However, immunosuppressed patients are more likely to have extensive AIN III and a greater risk of malignant change.

[MeSH-major] Anus Neoplasms / pathology. Carcinoma in Situ / pathology. Cell Transformation, Neoplastic / pathology

[MeSH-minor] Adult. Carcinoma, Squamous Cell / pathology. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Invasiveness / pathology. Neoplasm Recurrence, Local. Prospective Studies

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[Copyright] Copyright 2005 British Journal of Surgery Society Ltd.

(PMID = 16044425.001).

[ISSN] 0007-1323

[Journal-full-title] The British journal of surgery

[ISO-abbreviation] Br J Surg

[Language] eng

[Publication-type] Journal Article

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia.

Anal intraepithelial neoplasia (AIN) is a human papilloma virus related lesion.

The objective of this study is to correlate p16 expression and cellular proliferation measured by Ki-67 staining with the degree of dysplasia in the anal canal and to determine the efficacy of these markers in diagnosing high-grade AIN.

Seventy-five anal specimens from 55 patients (37 men; 18 women; mean age: 48 y; median: 44 y; range 25 to 96 y) were studied including 35 normal/reactive lesions, 23 low-grade AIN (AIN I and condyloma), and 17 high-grade AIN (AIN II and III).

Expression of p16 in AIN correlated with that of Ki-67 (P<0.001).

High-grade AIN often demonstrated p16 staining in more than one-third of the thickness of the epithelium in a diffuse/continuous fashion. p16 expression in low-grade AIN was often restricted to the lower 1/3 of the epithelium and/or was focal and discontinuous.

The expression of both p16 and Ki-67 correlated with the degree of dysplasia (P<0.01).

When positive p16 staining was defined as the presence of diffuse/continuous staining in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of p16 as a marker for diagnosing high-grade AIN were 76%, 86%, and 84%, respectively.

When positive Ki-67 staining was defined as the presence of nuclear staining in more than 25% of the cells in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of Ki-67 as a marker for diagnosing high-grade AIN were 71%, 84%, and 83% respectively.

Both p16 and Ki-67 are reliable markers for diagnosing high-grade AIN.

[MeSH-major] Anus Neoplasms / diagnosis. Genes, p16. Ki-67 Antigen / metabolism. Papillomavirus Infections / diagnosis. Precancerous Conditions / diagnosis. Tumor Virus Infections / diagnosis

[MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers, Tumor / analysis. Carcinoma, Squamous Cell / diagnosis. Carcinoma, Squamous Cell / metabolism. Carcinoma, Squamous Cell / virology. Female. History, 17th Century. Humans. Immunohistochemistry. Male. Sensitivity and Specificity

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(PMID = 17414102.001).

[ISSN] 0147-5185

[Journal-full-title] The American journal of surgical pathology

[ISO-abbreviation] Am. J. Surg. Pathol.

[Language] eng

[Publication-type] Historical Article; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Ki-67 Antigen

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal intraepithelial neoplasia in HIV infection.

While the immune system eliminates most HPV infections over time in immunocompetent individuals, HPV infections tend to persist in immunodeficient individuals.

In HIV-infected men who have sex with men (MSM), anal HPV prevalence is more than 90% and infections with multiple HPV types are common.

Anal intraepithelial neoplasia (AIN) is a potential precursor lesion of squamous cell carcinoma of the anus.

Like its cervical counterpart, cervical intraepithelial neoplasia (CIN), AIN is causally linked to persistent infections with high-risk HPV types such as HPV16 or HPV18.

As AIN and CIN share distinct biological similar-ities, AIN screenings analogous to Pap smear programs for CIN have been recommended in high-risk populations to reduce the incidence of anal carcinoma.

These screenings include cytological analysis followed by high resolution anoscopy in case of anal dysplasia.

Treatment guidelines for AIN are not yet available.

However, controlled studies on AIN treatment have not been performed.

The impact of HPV vaccination on AIN development will also need to be assessed.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / therapy. HIV Infections / diagnosis. HIV Infections / therapy. Papillomavirus Infections / diagnosis. Papillomavirus Infections / therapy. Skin Neoplasms / diagnosis. Skin Neoplasms / therapy

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(PMID = 18410393.001).

[ISSN] 1610-0387

[Journal-full-title] Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

[ISO-abbreviation] J Dtsch Dermatol Ges

[Language] eng; ger

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review

[Publication-country] Germany

[Number-of-references] 46

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal intraepithelial neoplasia and anal cancer in dermatological practice.

Anal intraepithelial neoplasia is considered to be a precursor lesion of invasive anal cancer.

Human papillomaviruses are considered to be an important aetiological agent in both anal intraepithelial neoplasia and anal cancer.

Dermatologists are likely to encounter these conditions among the differential diagnoses to be considered in high-risk patients presenting with perianal and anal lesions.

Anal cancer rates are also increasing among the HIV-infected and HIV-non-infected population.

The successful treatment of anal intraepithelial neoplasia may reduce the risk of subsequent development of anal cancer.

However, current therapies for anal intraepithelial neoplasia may be associated with treatment-related morbidity and are not well validated.

It is currently not proven that they reduce the likelihood of the development of anal cancer.

Nevertheless, screening for anal intraepithelial neoplasia is being advocated for high-risk groups and may become standard dermatological care for these patients.

In view of recent developments in the understanding of this condition, this article reviews the current understanding of anal intraepithelial neoplasia and its treatment from a dermatological perspective.

[MeSH-major] Anus Neoplasms. Carcinoma in Situ. Carcinoma, Squamous Cell. Papillomavirus Infections

[MeSH-minor] Diagnosis, Differential. HIV Infections / complications. Humans. Papillomaviridae / pathogenicity

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(PMID = 17680964.001).

[ISSN] 0004-8380

[Journal-full-title] The Australasian journal of dermatology

[ISO-abbreviation] Australas. J. Dermatol.

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] Australia

[Number-of-references] 115

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] P16/CDKN2A and Ki-67 enhance the detection of anal intraepithelial neoplasia and condyloma and correlate with human papillomavirus detection by polymerase chain reaction.

The classification of anal intraepithelial neoplasia (AIN) in mucosal biopsies is subject to considerable interobserver variability.

Previous studies have shown that Ki-67 and p16/CDKN2A immunostains aid detection of dysplasia in biopsy samples from the uterine cervix.

The aim of this study was to determine whether Ki-67 and p16/CDKN2A immunolabeling enhanced diagnostic accuracy in the assessment of anal mucosal biopsies from patients with suspected human papillomavirus (HPV) infection.

The study consisted of 75 cases that were originally interpreted to represent normal anal transitional zone (n=15), fibroepithelial polyp (n=10), condyloma accuminatum (n=10), low-grade AIN (AIN1, n=20), and high-grade AIN (n=20), including 10 cases each of AIN2 and AIN3.

Thus, the final study group consisted of 17 samples of normal anal transition zone, 14 fibroepithelial polyps, 6 condylomata accuminata, and 38 cases of AIN (11 AIN1, 16 AIN2, and 11 AIN3).

Each case was tested for the presence of HPV DNA by a SPF10 polymerase chain reaction and LiPA25 genotyping assay and immunostained for Ki-67 and p16/CDKN2A.

A positive Ki-67 result was defined as the presence of a cluster of at least 2 strongly stained epithelial nuclei in the upper two-thirds of the epithelial thickness.

A positive result for p16/CDKN2A was defined as diffuse moderate-to-strong cytoplasmic and nuclear staining.

None of the anal transition zone samples or fibroepithelial polyps showed Ki-67 or p16/CDKN2A staining.

All condylomata and samples of AIN contained HPV DNA and showed positive Ki-67 labeling.

All cases of high-grade AIN showed positive p16/CDKN2A staining.

We conclude that Ki-67 labeling detects anal HPV-related changes with a high degree of sensitivity and specificity, whereas increased p16/CDKN2A staining is strongly associated with high-grade squamous neoplasia.

These results indicate that a combination of these markers may aid interpretation of anal mucosal biopsy samples.

[MeSH-major] Anus Neoplasms / diagnosis. Carcinoma in Situ / diagnosis. Condylomata Acuminata / diagnosis. Cyclin-Dependent Kinase Inhibitor p16 / metabolism. Ki-67 Antigen / metabolism. Papillomaviridae / isolation & purification. Papillomavirus Infections / diagnosis

[MeSH-minor] Adult. Aged. Biomarkers, Tumor / metabolism. Biopsy. Colonic Polyps / metabolism. Colonic Polyps / pathology. Colonic Polyps / virology. DNA Probes, HPV. Female. Humans. Immunohistochemistry. Male. Middle Aged. Precancerous Conditions / diagnosis. Precancerous Conditions / metabolism. Precancerous Conditions / virology. Predictive Value of Tests. Young Adult

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(PMID = 20871219.001).

[ISSN] 1532-0979

[Journal-full-title] The American journal of surgical pathology

[ISO-abbreviation] Am. J. Surg. Pathol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / DNA Probes, HPV; 0 / Ki-67 Antigen

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Anal intraepithelial neoplasia: application of a diagnostic protocol in risk patients using anal cytology].

[Transliterated title] Neoplasia intraepitelial anal: resultados de la aplicación de un protocolo diagnóstico en pacientes de riesgo mediante el uso de citología anal.

INTRODUCTION: Anal intraepithelial neoplasia is a precursor condition of squamous anal carcinoma.

The groups at risk of this lesion are patients with anogenital condylomata, cervical dysplasia, human immunodeficiency virus infection and, in general, patients with HPV infection.

The aim of this study was to analyse the results of a diagnostics protocol of Anal Intraepithelial Neoplasia in high risk population using anal cytology.

PATIENTS AND METHOD: The protocol is based on a visit in the outpatient department, clinical interview, physical examination and anal cytology evaluated by Bethesda criteria.

The cross-sectional observational study was designed to study the anal smear results and their relationship with risk factors.

RESULTS: A total of 64 patients were included from January 2005 to December 2006.

In the overall series, 25 patients have been diagnosed with abnormal anal cytology: 9 atypical squamous cells of undetermined significance (ASCUS), 15 low-grade and 1 high-grade squamous intraepithelial lesions.

There were no significant associations between abnormal cytology results and the presence of anal condyloma (p = 0.22).

CONCLUSIONS: Our diagnostic protocol of anal intraepithelial neoplasia revealed 25% of patients with pre-invasive lesions of squamous anal cancer.

[MeSH-major] Anus Neoplasms / pathology. Carcinoma in Situ / pathology

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(PMID = 19303590.001).

[ISSN] 0009-739X

[Journal-full-title] Cirugía española

[ISO-abbreviation] Cir Esp

[Language] spa

[Publication-type] English Abstract; Journal Article

[Publication-country] Spain

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A dedicated applicator for light delivery and monitoring of PDT of intra-anal intraepithelial neoplasia.

The objective of this study was to develop an applicator for delivery of light and monitoring of photodynamic therapy (PDT) in the anal cavity for treatment of anal intraepithelial neoplasia grade III (AIN III), which can progress to invasive anal cancer.

Forty-eight hours before treatment, patients participating in the study were injected with 0.03 (n=2) or 0.075 (n=2) mg kg(-1) m-THPC.

For light delivery and monitoring of PDT, an applicator based on standard anoscopy equipment was developed which facilitates, in addition to a light treatment fiber, fiber optic probes to monitor blood saturation, blood volume, fluorescence and fluence (rate) at two different locations in situ.

Patients were given a light dose of 10-17 J cm(-2) at a fluence rate of 45-50 mW cm(-2) based on in situ measured light treatment parameters.

We demonstrate that the applicator does not influence the fluence rate profile of the light treatment fiber.

Furthermore this study shows the possibility of monitoring blood saturation, blood volume, fluorescence and fluence (rate) during therapeutic illumination without changing the light treatment protocol.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / drug therapy. Carcinoma in Situ / diagnosis. Carcinoma in Situ / drug therapy. Lighting / instrumentation. Photochemotherapy / instrumentation. Photosensitizing Agents / administration & dosage

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[Copyright] 2010 Elsevier B.V. All rights reserved.

(PMID = 20230986.001).

[ISSN] 1873-1597

[Journal-full-title] Photodiagnosis and photodynamic therapy

[ISO-abbreviation] Photodiagnosis Photodyn Ther

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Netherlands

[Chemical-registry-number] 0 / Photosensitizing Agents

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal intraepithelial neoplasia and other neoplastic precursor lesions of the anal canal and perianal region.

Anal cancer is rare and this helps to explain why anal pre-neoplastic conditions are poorly understood, especially with regard to their natural history and management.

Anal intraepithelial neoplasia is closely linked to human papillomavirus infection and is particularly common in homosexuals and in immunosuppressed patients, especially those with HIV/AIDS.

The high regression rates of low-grade anal intraepithelial neoplasia may simply reflect inconsistent pathologic reporting.

Higher grades of anal intraepithelial neoplasia may remain static for long periods of time in immunocompetent patients, but those with HIV/AIDS show early and rapid malignant transformation.

In general, most anal pre-neoplastic conditions are best diagnosed by biopsy and treated by surgical excision, although local recurrence is a problem.

In anal Paget's disease, it is important to ascertain, at the time of diagnosis, whether it is due to a primary in-situ apocrine-type of neoplasia of the anus or if the disease is secondary to an invasive primary carcinoma of the rectum.

[MeSH-minor] Anal Canal. Diagnosis, Differential. Humans

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(PMID = 17996800.001).

[ISSN] 0889-8553

[Journal-full-title] Gastroenterology clinics of North America

[ISO-abbreviation] Gastroenterol. Clin. North Am.

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Number-of-references] 119

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Anal intraepithelial neoplasia and anal carcinoma: an increasing problem in HIV patients].

[Transliterated title] Anale intraepitheliale Neoplasie und Analkarzinom : Ein zunehmendes Problem bei Menschen mit HIV-Infektion.

Anal dysplasia is common in HIV patients, especially in HIV-positive men having sex with men (MSM).

High-grade anal dysplasia can progress to invasive anal cancer.

As in cervical carcinoma, there is a cause and effect relationship between anal cancer and human papillomavirus (HPV) infection, especially with high-risk types such as HPV16.

Several experts have recommended screening programs for anal cancer, including anal cytology along the lines of the Pap smear in women.

Such screenings should only be performed if pathological findings result in further diagnostic steps and, if necessary, appropriate treatment.

Clinical inspection, lesion biopsy, and treatment of anal dysplasia are performed under high-resolution anoscopy.

Anal cancer is divided into cancer of the anal margin and cancer of the anal canal.

This classification is important because of the difference in treatment regimens.

Early cancer of the anal margin is excised akin to squamous cell cancer of the exposed skin, whereas cancer of the anal canal is treated by radiochemotherapy.

Physicians working in the field of HIV/AIDS should regularly screen their patients for the presence of anal dysplasia and anal cancer.

Basic diagnostic workup includes clinical inspection of the perianal area, digital rectal examination, and anal cytology.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / prevention & control. Carcinoma in Situ / virology. HIV Infections / complications. Precancerous Conditions / diagnosis. Precancerous Conditions / prevention & control

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(PMID = 19967333.001).

[ISSN] 1432-1173

[Journal-full-title] Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete

[ISO-abbreviation] Hautarzt

[Language] ger

[Publication-type] English Abstract; Journal Article

[Publication-country] Germany

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men.

BACKGROUND: Human papillomavirus (HPV)-associated anal cancer is increasing in prevalence and is more common among men who have sex with men and HIV-positive individuals than cervical cancer is among women in the United States.

Cytology screening can detect the anal cancer precursor, anal intraepithelial neoplasia (AIN).

Little is known about self-collected samples for AIN screening, and few community-based AIN estimates exist.

OBJECTIVE: To compare the sensitivity of self-collected versus clinician-collected anal cytology specimens to detect biopsy-confirmed AIN and the prevalence estimate of AIN in a community sample.

DESIGN: Cross-sectional study.

Participants were mailed anal cytology self-collection kits with instructions.

Clinicians repeated anal cytology and performed high-resolution anoscopy with biopsies as the diagnostic reference standard.

MEASUREMENTS: Prevalence of anal HPV and AIN.

Sensitivity and specificity of self-collected and clinician-collected anal cytology specimens to diagnose AIN were calculated.

RESULTS: Biopsy-proven AIN was diagnosed in 57% of HIV-positive and 35% of HIV-negative participants (P = 0.04), and 80% provided adequate self-collected specimens for interpretation.

The sensitivity of cytology to detect AIN in HIV-positive men was 75% (95% CI, 51% to 93%) when self-collected and 90% (CI, 68% to 99%) when clinician-collected; respective values in HIV-negative men were 48% (CI, 26% to 70%) and 62% (CI, 38% to 82%).

The specificity of cytology to detect AIN in HIV-positive men was 50% (CI, 22% to 78%) when self-collected and 64% (CI, 36% to 86%) when clinician-collected; respective values in HIV-negative men were 86% (CI, 71% to 94%) and 85% (CI, 72% to 93%).

LIMITATIONS: The study sample was from a narrowly defined geographical area.

CONCLUSION: In a community-based sample, a high proportion of HIV-positive and HIV-negative men who have sex with men have AIN.

The sensitivity of cytology to detect AIN is higher for clinician-collected versus self-collected specimens and for HIV-positive versus HIV-negative men.

The specificity of cytology to detect AIN is higher in HIV-negative versus HIV-positive men.

However, the probability of AIN in a patient with a negative cytology result may not be low enough (23% for HIV-negative men and 45% for HIV-positive men with a patient-collected specimen) for clinicians to be comfortable recommending no anoscopy for those with a negative cytology result if done as a one-time test.

Given limited resources and the limited number of clinicians trained in anoscopy, cytology screening may be the best current approach to identifying disease in the at-risk population.

[MeSH-major] Anus Neoplasms / pathology. Carcinoma in Situ / pathology. Cytological Techniques / methods. Homosexuality. Papillomavirus Infections / pathology. Specimen Handling / methods

[MeSH-minor] Adult. Aged. Anal Canal / pathology. Biopsy. Endoscopy, Gastrointestinal. HIV Seronegativity. HIV Seropositivity / epidemiology. HIV Seropositivity / pathology. HIV Seropositivity / virology. Humans. Male. Middle Aged. Prevalence. San Francisco / epidemiology. Sensitivity and Specificity

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[CommentIn] Ann Intern Med. 2009 Feb 17;150(4):283-4; author reply 284-5 [19221387.001]

[SummaryForPatientsIn] Ann Intern Med. 2008 Sep 2;149(5):I38 [18765696.001]

(PMID = 18765699.001).

[ISSN] 1539-3704

[Journal-full-title] Annals of internal medicine

[ISO-abbreviation] Ann. Intern. Med.

[Language] eng

[Grant] United States / NCRR NIH HHS / RR / 5 M01-RR-00079; United States / NIAID NIH HHS / AI / K23 AI054157; United States / NIAID NIH HHS / AI / R01 CA/AI 88739; United States / NCI NIH HHS / CA / R01 CA54053; United States / NIMH NIH HHS / MH / R01 MH54320

[Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Anal carcinoma and anal intraepithelial neoplasia in HIV-infections].

[Transliterated title] Analkarzinom und anale intraepitheliale Neoplasie bei HIV-Infektion.

[MeSH-major] Anus Neoplasms / diagnosis. Carcinoma in Situ / diagnosis. HIV Infections / diagnosis. Skin Neoplasms / diagnosis

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(PMID = 16883662.001).

[ISSN] 1610-0379

[Journal-full-title] Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

[ISO-abbreviation] J Dtsch Dermatol Ges

[Language] ger

[Publication-type] Journal Article

[Publication-country] Germany

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Performance characteristics of anal cytology and human papillomavirus testing in patients with high-resolution anoscopy-guided biopsy of high-grade anal intraepithelial neoplasia.

PURPOSE: High-resolution anoscopy is colposcopy of the anus after applying 3 percent acetic acid.

High-resolution anoscopy with biopsy was used as the standard for detecting high-grade anal neoplasia and was compared to detection of high-grade anal neoplasia by anal cytology, human papillomavirus testing, or the combination.

METHODS: A total of 125 men who have sex with men (MSM) were enrolled from a group of MSM identified by random digit dialing: HIV-negative = 85, HIV-positive = 35, and unknown status = 5.

A specimen was taken for anal cytology and human papillomavirus testing, followed by high-resolution anoscopy with biopsy of any lesions.

RESULTS: Ninety-one percent of HIV-positive and 57 percent of HIV-negative MSM had anal human papillomavirus infection.

In HIV-positive men the sensitivity of abnormal cytology to detect high-grade anal neoplasia was 87 percent, and in HIV-negative MSM it was 55 percent.

Among HIV-negative men, 9 of 20 cases of high-grade anal neoplasia would have been missed because cytology was negative, but the addition of human papillomavirus positivity increased sensitivity for the combination to 90 percent.

CONCLUSIONS: Sensitivity and specificity of anal cytology and human papillomavirus testing are different in HIV-positive and HIV-negative MSM for detecting high-grade anal neoplasia when patients have high-resolution anoscopy-guided biopsy of lesions.

High-resolution anoscopy is an effective tool for diagnosing high-grade anal neoplasia.

[MeSH-major] Anal Canal / pathology. Anus Neoplasms / diagnosis. Carcinoma in Situ / diagnosis. Endoscopy, Gastrointestinal. Papillomaviridae / isolation & purification. Papillomavirus Infections / diagnosis

[MeSH-minor] Adult. Aged. Anus Diseases / diagnosis. Anus Diseases / virology. Biopsy. Cytodiagnosis. HIV Seronegativity. HIV Seropositivity / complications. Homosexuality. Humans. Male. Middle Aged. Polymerase Chain Reaction. Precancerous Conditions / diagnosis. Predictive Value of Tests. Sensitivity and Specificity

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(PMID = 19279418.001).

[ISSN] 1530-0358

[Journal-full-title] Diseases of the colon and rectum

[ISO-abbreviation] Dis. Colon Rectum

[Language] eng

[Grant] United States / NCRR NIH HHS / RR / 5 M01-RR-00079; United States / NIAID NIH HHS / AI / K23 AI054157; United States / NIAID NIH HHS / AI / R01 CA/AI 88739; United States / NCI NIH HHS / CA / R01 CA54053; United States / NCRR NIH HHS / RR / UL1 RR024131-01

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Grade 3 vulvar and anal intraepithelial neoplasia in a HIV seropositive child--therapeutic result: case report.

A case report of a HIV seropositive 8-year-old child with vulvar and anal border neoplasia, both grade 3, and the adopted therapeutic management are presented.

The mother reported the history of a progressively growing verrucous lesion in the vulva since the age of three and a half years.

On physical examination a pigmented and elevated lesion was observed in the whole vulvar region extending to the anal region and intergluteal sulcus.

After the first two sessions of laser therapy early relapses occurred.

We conclude that antiretroviral therapy associated with podophyllotoxin and Thuya was not effective regarding regression of the lesions.

[MeSH-major] Anus Neoplasms / therapy. Carcinoma / therapy. HIV Infections / diagnosis. HIV Infections / drug therapy. Vulvar Neoplasms / therapy

[MeSH-minor] Administration, Topical. Aminoquinolines / administration & dosage. Anti-HIV Agents / therapeutic use. Child. Combined Modality Therapy. Female. Follow-Up Studies. HIV Seropositivity. Humans. Immunocompromised Host. Low-Level Light Therapy / methods. Papillomavirus Infections / pathology. Papillomavirus Infections / therapy. Risk Assessment. Treatment Outcome

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(PMID = 16108402.001).

[ISSN] 0390-6663

[Journal-full-title] Clinical and experimental obstetrics & gynecology

[ISO-abbreviation] Clin Exp Obstet Gynecol

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Italy

[Chemical-registry-number] 0 / Aminoquinolines; 0 / Anti-HIV Agents; 99011-02-6 / imiquimod

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Diagnosis and management of HPV-related anal dysplasia.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / therapy. Nurse Practitioners / organization & administration. Papillomavirus Infections / diagnosis. Papillomavirus Infections / therapy. Primary Health Care / methods

[MeSH-minor] AIDS-Related Opportunistic Infections / complications. Algorithms. Biopsy. Cytodiagnosis. Decision Trees. Humans. Mass Screening. Neoplasm Staging. Nursing Assessment. Patient Education as Topic. Primary Prevention. Proctoscopy. Risk Factors. United States / epidemiology

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(PMID = 19390399.001).

[ISSN] 1538-8662

[Journal-full-title] The Nurse practitioner

[ISO-abbreviation] Nurse Pract

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Number-of-references] 65

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Intraoperative high-resolution anoscopy: a minimally invasive approach in the treatment of patients with Bowen's disease and results in a private practice setting.

Anal intraepithelial neoplasia III (AIN III) is a risk factor for anal cancer with poor curative results and high morbidity.

High-resolution anoscopy (HRA) is a minimally invasive means of identifying and treating AIN III early.

We retrospectively reviewed HRA in the treatment of AIN III in a community setting.

From January 2002 through November 2005, 76 patients with AIN III diagnosed by anal Pap smear, colposcopy, or biopsy underwent HRA for diagnosis and treatment.

Twenty-one patients with AIN III on initial HRA underwent follow-up HRA for reassessment and treatment at 6 months.

Recurrence/persistence of disease was recorded and compared with patient characteristics.

Twelve of 21 (57%) had intraanal recurrence/persistence; nine of 21 (43%) had no AIN III.

Three (75%) HIV-negative patients had no recurrence/persistence; one of four (25%) had recurrence; and 11 of 17 (65%) HIV-positive patients had persistence of disease.

HRA is an alternative tool to treat AIN III and can be performed in a community setting yielding results comparable to the university setting.

As the prevalence of AIN III increases, it will be more important for community surgeons to treat AIN III with HRA.

[MeSH-major] Bowen's Disease / pathology. Bowen's Disease / surgery. Endoscopy, Gastrointestinal / methods. Skin Neoplasms / pathology. Skin Neoplasms / surgery

[MeSH-minor] Adult. Aged. Anal Canal. Community Health Services. Follow-Up Studies. Humans. Male. Middle Aged. Private Practice. Retrospective Studies. Treatment Outcome

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(PMID = 18186390.001).

[ISSN] 0003-1348

[Journal-full-title] The American surgeon

[ISO-abbreviation] Am Surg

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Economic burden of anal cancer management in France.

BACKGROUND: The incidence of anal cancer has increased over the last 25 years.

No organized screening exists for the precursors of anal cancer (anal intraepithelial neoplasia and carcinoma in situ) and diagnosis is often delayed.

Treatment for precursor lesions is of limited success, while cancer management is traumatic for the patient.

Like cancers of the cervix, most cases of anal cancer are associated with infection with human papillomavirus (HPV).

With increases in the incidence of anal cancer, and in light of the availability of prevention strategies such as screening and HPV vaccination, it is important, from a public health perspective, to assess the economic burden of anal cancer in France.

METHODS: We performed a retrospective analysis based on data extracted from a French hospital database - the Programme de médicalisation des systèmes d'information (PMSI) - to assess the number and management of patients hospitalized for anal cancer in 2006.

Data on radiotherapy sessions performed in private hospitals were obtained from the Statistiques annuelles des établissements de santé (SAE) database.

Costs of hospitalization, from the healthcare-payer perspective, were obtained from official diagnosis-related group tariffs for public and private hospitals.

RESULTS: In 2006, 3,711 patients with anal cancer were treated in hospitals in France.

The annual cost of hospital treatment for anal cancer was estimated at € 20,326,868.

CONCLUSION: This study, the first to investigate the economic burden of anal cancer in France, shows that the management costs of anal cancer are high and comparable to cervical cancer management costs (€ 44 million).

Prophylactic HPV vaccination could significantly reduce the burden of this disease.

[MeSH-major] Anus Neoplasms / economics. Health Care Costs

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[Copyright] Copyright © 2010 Elsevier Masson SAS. All rights reserved.

(PMID = 20869182.001).

[ISSN] 0398-7620

[Journal-full-title] Revue d'épidémiologie et de santé publique

[ISO-abbreviation] Rev Epidemiol Sante Publique

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] France

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Necrotizing fasciitis: a challenging diagnosis.

The objective of the study was to evaluate our recent experience in diagnosis and management of necrotizing fasciitis.

Records of patients who were diagnosed as having necrotizing fasciitis at Al-Ain Hospital in the period between March 2003 and August 2005 were studied retrospectively with regard to clinical features, risk factors, diagnosis, causative organisms, treatment, and outcome.

The main risk factor was diabetes mellitus in seven patients (64%).

The provisional clinical diagnosis was incorrect in seven patients (64%).

Pure beta-hemolytic streptococcus group A or B was the causative organism in five patients (46%).

High clinical suspicion is essential for the diagnosis of necrotizing fasciitis.

Accurate early diagnosis, aggressive resuscitation, using proper antibiotics, and extensive surgical debridement are essential for a favorable outcome.

[MeSH-major] Fasciitis, Necrotizing / diagnosis. Streptococcal Infections / complications

[MeSH-minor] Adolescent. Adult. Aged. Anti-Bacterial Agents / therapeutic use. Child. Debridement. Diabetes Complications / diagnosis. Diabetes Complications / therapy. Diagnostic Errors. Female. Humans. Length of Stay. Male. Middle Aged. Retrospective Studies. Risk Factors. Social Class. Streptococcus / isolation & purification

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(PMID = 17198329.001).

[ISSN] 0969-9546

[Journal-full-title] European journal of emergency medicine : official journal of the European Society for Emergency Medicine

[ISO-abbreviation] Eur J Emerg Med

[Language] eng

[Publication-type] Journal Article

[Publication-country] England

[Chemical-registry-number] 0 / Anti-Bacterial Agents

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Immunohistochemical staining for p63 is useful in the diagnosis of anal squamous cell carcinomas.

Anal canal carcinomas account for between 1% and 2% of all gastrointestinal carcinomas in the United States.

By far, the most common carcinoma in this site is squamous cell carcinoma, but the differential diagnosis typically includes poorly differentiated adenocarcinoma and well-differentiated neuroendocrine carcinoma or carcinoid tumor.

Because the first diagnostic specimen received in the pathology laboratory is usually a small, sometimes suboptimal biopsy, the distinction of these types of carcinoma can be difficult.

However, accurate diagnosis is imperative, because the treatment differs between squamous carcinoma (chemoradiation) and the other types of carcinoma (surgical therapy).

The p63 protein has been previously shown to be involved in epithelial proliferation and differentiation, and is known to be related to squamous carcinomas in many sites.

Therefore, we undertook to ascertain its usefulness in the diagnosis of squamous carcinomas in the anal canal.

We retrieved 24 anal squamous carcinomas, 68 colorectal adenocarcinomas (including a tissue microarray), and 32 colorectal neuroendocrine carcinomas from the archives at the University of Michigan, and immunostained them for the p63 antigen.

As a result, this immunohistochemical stain had a specificity of 98% and a positive predictive value of 92% for squamous cell carcinoma once invasive carcinoma had been established.

It also stained the dysplastic epithelial cells in adjacent areas of anal intraepithelial neoplasia.

We report that the p63 immunostain is a highly specific and useful tool in the diagnosis of carcinomas of the anal canal.

[MeSH-major] Anal Canal / metabolism. Anus Neoplasms / metabolism. Biomarkers, Tumor / metabolism. Carcinoma, Squamous Cell / metabolism. DNA-Binding Proteins / metabolism. Immunoenzyme Techniques / methods. Trans-Activators / metabolism. Tumor Suppressor Proteins / metabolism

[MeSH-minor] Carcinoid Tumor / diagnosis. Carcinoid Tumor / metabolism. Carcinoma in Situ / metabolism. Carcinoma in Situ / pathology. Carcinoma, Neuroendocrine / diagnosis. Carcinoma, Neuroendocrine / metabolism. Colorectal Neoplasms / metabolism. Colorectal Neoplasms / pathology. Diagnosis, Differential. Humans. Predictive Value of Tests. Tissue Array Analysis. Transcription Factors

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(PMID = 17255774.001).

[ISSN] 0147-5185

[Journal-full-title] The American journal of surgical pathology

[ISO-abbreviation] Am. J. Surg. Pathol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA-Binding Proteins; 0 / TP63 protein, human; 0 / Trans-Activators; 0 / Transcription Factors; 0 / Tumor Suppressor Proteins

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Invasive squamous cell carcinoma arising in refractory perianal Bowen's disease in a HIV-positive individual.

A 54-year-old HIV-positive homosexual man presented with erythematous and pigmented plaques on background erythema in the perianal region, histologically consistent with Bowen's disease.

Perianal Bowen's disease represents high-grade anal intraepithelial neoplasia, which is considered a precursor lesion of invasive anal squamous cell carcinoma.

This patient's anal intraepithelial neoplasia was unresponsive to multiple treatment modalities including cryotherapy, serial curettage and cautery, topical 5-fluorouracil and 5-aminolaevulinic acid photodynamic therapy.

He progressed to develop a poorly differentiated squamous cell carcinoma of the anus three and a half years after the Bowen's disease was diagnosed.

The squamous cell carcinoma was treated with combined chemoradiation.

A recurrence of high-grade anal intraepithelial neoplasia was noted 6 months after completion of chemoradiation.

[MeSH-major] Bowen's Disease / diagnosis. Carcinoma, Squamous Cell / diagnosis. HIV Infections. Neoplasm Recurrence, Local / diagnosis. Skin Neoplasms / diagnosis

[MeSH-minor] Anal Canal. Combined Modality Therapy. Diagnosis, Differential. Homosexuality, Male. Humans. Male. Middle Aged. Neoplasm Invasiveness

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(PMID = 16637809.001).

[ISSN] 0004-8380

[Journal-full-title] The Australasian journal of dermatology

[ISO-abbreviation] Australas. J. Dermatol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Australia

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Sexually transmitted diseases (STDs) are a common public health problem and as such may be more common in a surgical practice than is believed.

This article reviews the presentation and management of the more common perianal STDs including human immunodeficiency virus, as well as the pathogenesis and management of anal intraepithelial neoplasia.

[MeSH-major] Condylomata Acuminata / therapy. Condylomata Acuminata / virology. Genital Diseases, Female / virology. Genital Diseases, Male / virology

[MeSH-minor] Aminoquinolines / administration & dosage. Anti-Bacterial Agents / administration & dosage. Antineoplastic Agents / administration & dosage. Anus Neoplasms / virology. Chancroid. Female. HIV Infections. Herpes Genitalis / diagnosis. Herpesvirus 1, Human. Herpesvirus 2, Human. Humans. Male. Penicillin G / administration & dosage. Proctitis / virology. Rectal Diseases / virology. Sexually Transmitted Diseases / virology. Syphilis / drug therapy. Ulcer

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[Copyright] Copyright 2010 Elsevier Inc. All rights reserved.

(PMID = 20109635.001).

[ISSN] 1558-3171

[Journal-full-title] The Surgical clinics of North America

[ISO-abbreviation] Surg. Clin. North Am.

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Aminoquinolines; 0 / Anti-Bacterial Agents; 0 / Antineoplastic Agents; 99011-02-6 / imiquimod; Q42T66VG0C / Penicillin G

[Number-of-references] 42

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal cytology: is there a role for reflex HPV DNA testing?

There is an increased incidence of anal squamous carcinoma and its precursor lesions (anal intraepithelial neoplasia [AIN]) among persons who engage in anal-receptive sex.

Analogous to cervical cancer screening, anal Papanicplaou (Pap) smears currently are used to screen these high-risk populations.

Human papilloma virus (HPV) has been implicated in anal carcinoma pathogenesis and this study was performed to assess the potential role of HPV DNA testing as an adjunct to anal cytology.

We correlated cytological diagnoses and HPV DNA (Digene Hybrid Capture [HC II] assay) in anal specimens collected in SurePath liquid medium from 118 patients; 54.8% of cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) and 87.8% diagnosed as low-grade squamous intraepithelial lesion (LSIL) or above tested positive for high- risk HPV DNA (B+).

Although a cytological diagnosis of ASC-US or above was a reliable indicator for AIN, cytology frequently did not accurately predict the grade of SIL in subsequent biopsy.

Our findings suggest that reflex HPV DNA testing would be helpful in triaging patients diagnosed with ASC-US.

However, patients diagnosed with LSIL or above should go directly to ansocopic biopsy.

[MeSH-major] Anal Canal / virology. Anus Neoplasms / diagnosis. Carcinoma in Situ / diagnosis. Carcinoma, Squamous Cell / diagnosis. Papillomavirus Infections / diagnosis. Tumor Virus Infections / diagnosis

[MeSH-minor] Adult. Biomarkers, Tumor / analysis. DNA, Viral / analysis. Humans. Male. Mass Screening / methods. Middle Aged. Papillomaviridae / isolation & purification

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[Copyright] Copyright (c) 2005 Wiley-Liss, Inc.

(PMID = 16078257.001).

[ISSN] 8755-1039

[Journal-full-title] Diagnostic cytopathology

[ISO-abbreviation] Diagn. Cytopathol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Viral

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Screening HIV-infected individuals for anal cancer precursor lesions: a systematic review.

Individuals with human immunodeficiency virus (HIV) infection are at increased risk for human papillomavirus-related squamous cell cancer of the anus.

Screening HIV-infected patients for squamous cell cancer of the anus and human papillomavirus-related anal dysplasia may prevent excess morbidity and mortality.

We have conducted a systematic review of the indirect evidence in the literature regarding the utility of anal Papanicolau (Pap) smear screening of HIV-infected individuals in the highly active antiretroviral therapy era.

Although there are no published studies evaluating the efficacy of anal Pap smear screening for preventing squamous cell cancer of the anus or anal intraepithelial neoplasia, we reviewed data regarding the burden of disease, anal Pap smear sensitivity and specificity, the prevalence of anal dysplasia, and 1 cost effectiveness study.

The available evidence demonstrates that HIV-infected individuals have an increased risk for squamous cell cancer of the anus and anal intraepithelial neoplasia.

This review identifies important areas for further study before routine anal Pap smear screening can be recommended.

[MeSH-major] Anus Neoplasms / diagnosis. Carcinoma, Squamous Cell / diagnosis. HIV Infections / complications. Papanicolaou Test. Papillomavirus Infections / diagnosis. Precancerous Conditions / diagnosis. Vaginal Smears

[MeSH-minor] Antiretroviral Therapy, Highly Active. Carcinoma in Situ / diagnosis. Carcinoma in Situ / etiology. Female. Humans. Male. Mass Screening. Papillomaviridae

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(PMID = 16779751.001).

[ISSN] 1537-6591

[Journal-full-title] Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

[ISO-abbreviation] Clin. Infect. Dis.

[Language] eng

[Grant] United States / NIMH NIH HHS / MH / K23MH67505

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review

[Publication-country] United States

[Number-of-references] 100

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The epidemiology of anal human papillomavirus and related neoplasia.

Like cervical cancer, anal cancer is preceded by a series of precancerous changes, raising the possibility that like cervical cancer, anal cancer can be prevented.

Further, given the known risk factors for anal cancer, prevention efforts could be targeted to high-risk groups, providing a unique example of a screening program targeted to high-risk individuals.

This article describes the epidemiology of anal HPV infection, anal intraepithelial neoplasia, and anal cancer among men and women, as well as current efforts to prevent anal cancers.

[MeSH-major] Anal Canal / pathology. Anus Neoplasms / epidemiology. Colonoscopy / methods. Human papillomavirus 11. Papillomavirus Infections / epidemiology. Sexually Transmitted Diseases, Viral / epidemiology

[MeSH-minor] Diagnosis, Differential. Female. Humans. Incidence. Male. Risk Factors. United States / epidemiology

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(PMID = 19344856.001).

[ISSN] 1558-0474

[Journal-full-title] Obstetrics and gynecology clinics of North America

[ISO-abbreviation] Obstet. Gynecol. Clin. North Am.

[Language] eng

[Grant] United States / NCI NIH HHS / CA / R01 CA 085178; United States / NCI NIH HHS / CA / R01 CA 88739; United States / NCRR NIH HHS / RR / UL1 RR02413,1

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review

[Publication-country] United States

[Number-of-references] 49

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Human papillomavirus-associated diseases in HIV-infected men who have sex with men.

This review summarizes recent data on papillomavirus-induced anal intraepithelial neoplasia and anal cancer in these patients.

Moreover, data are provided on penile and oral HPV-associated diseases, for which only limited information is available in the literature.

RECENT FINDINGS: The incidence of anal intraepithelial neoplasia rises in HIV-positive men who have sex with men despite the introduction of highly active antiretroviral therapy.

Increasing evidence indicates that high-grade lesions can progress to anal cancer over time.

Anal cytology has been recommended as the primary screening tool for anal dysplasia in the at-risk population.

Anal cancer has become one of the most common non-AIDS-defining tumors in HIV-infected individuals.

In the era of highly active antiretroviral therapy, the outcome of combined chemoradiotherapy in HIV-positive individuals with anal cancer is similar to that in HIV-negative persons.

Penile and oral HPV-associated diseases seem to be more frequent in HIV-positive men than reported for HIV-negative heterosexual men.

SUMMARY: Diagnostic and therapeutic guidelines should be implemented for at-risk populations for anal dysplasia/anal cancer, such as HIV-positive men who have sex with men.

More study is required to get better insights into the natural history of penile and oral HPV-associated benign and malignant lesions.

[MeSH-major] Anus Neoplasms / epidemiology. Anus Neoplasms / virology. HIV Infections / complications. Papillomaviridae / isolation & purification. Papillomavirus Infections / complications. Papillomavirus Infections / epidemiology

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(PMID = 19276878.001).

[ISSN] 1473-6527

[Journal-full-title] Current opinion in infectious diseases

[ISO-abbreviation] Curr. Opin. Infect. Dis.

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Number-of-references] 40

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Causes of delayed diagnosis of scapular fractures.

OBJECTIVES: To study the causes of delayed diagnosis of scapular fractures in blunt trauma cases, and to advise on early fracture detection.

PATIENTS AND METHODS: Between February 2003 and September 2004, 64 consecutive patients (3 females) with a median (range) age of 35 (8-60) years, treated at Al-Ain Hospital for scapular fractures, were prospectively collected.

Fractures diagnosed after more than 24h from admission were considered missed; 8 people with missed scapular fractures were compared with a control group of 56 who had timely diagnosis, regarding the mechanism and distribution of injury, injury severity score, and type and quality of radiological methods used.

RESULTS: The median (range) abbreviated injury scale scores for the missed scapular fracture group and the control group were 4 (0-5) and 2 (0-2), respectively.

The missed scapular fracture group stayed significantly longer in the intensive care unit compared with the control group, with a median (range) stay of 15 (5-37) days compared with 9 (1-26) days.

If computed tomography did not cover the whole scapula, some fractures might not be shown.

CONCLUSION: Delayed diagnosis of scapular fractures can be due to extensive chest injuries overshadowing the scapula on the chest trauma radiographs, inappropriately performed computer tomography or an unusual mechanism of injury.

[MeSH-minor] Adolescent. Adult. Child. Diagnostic Errors. Female. Humans. Injury Severity Score. Male. Middle Aged. Multiple Trauma / etiology. Multiple Trauma / radiography. Prospective Studies. Time Factors. Tomography, X-Ray Computed

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(PMID = 18243201.001).

[ISSN] 0020-1383

[Journal-full-title] Injury

[ISO-abbreviation] Injury

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Netherlands

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic.

OBJECTIVES: The purpose of this study is to describe our experience with routine anal cancer screening using anal cytology, determine risk factors for abnormal anal cytology, and determine if an association exists between cytology and histology in patients with HIV infection.

RESULTS: Overall, 276 of 560 of the clinic patients received a screening anal cytology during the study period.

Of these patients, 11 were excluded from the analysis and 74 of 265 (27.9%) patients screened had an abnormal anal cytology.

Forty-nine percent were African American, 34% Caucasian, and 17% Hispanic.

They were also more likely to have a lower CD4+ nadir (142 cells/mm3 vs. 223 cells/mm3, P = 0.005) and CD4+ at time of anal cytology (353 cells/mm3 vs. 497 cells/mm3, P <0.001).

Those with an abnormal anal cytology also had higher occurrence of anal disease on perianal visual inspection (30% vs. 9%, P <0.001) and were more likely to have a history of genital warts (23% vs. 12%, P = 0.02) or herpes (35% vs. 22%, P = 0.02).

Two patients had anal intraepithelial neoplasia (AIN) I, 2 AIN II, 3 AIN III, and 2 squamous cell carcinoma in situ on histology.

CONCLUSION: Routine anal cytology screening is a feasible tool to incorporate into HIV care for patients regardless of gender and HIV risk factors.

Its impact on morbidity and mortality warrant further study.

[MeSH-major] Anus Neoplasms / diagnosis. HIV Infections / complications. Neoplasms, Squamous Cell / pathology. Urban Health Services / organization & administration

[MeSH-minor] Adult. Aged. Anal Canal / pathology. Colonoscopy / methods. Female. Follow-Up Studies. Humans. Logistic Models. Male. Middle Aged. Multivariate Analysis

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(PMID = 18216727.001).

[ISSN] 0148-5717

[Journal-full-title] Sexually transmitted diseases

[ISO-abbreviation] Sex Transm Dis

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Anal-rectal cytology: correlation with human papillomavirus status and biopsy diagnoses in a population of HIV-positive patients.

OBJECTIVES: We describe the cytological distribution of disease, correlate cytological diagnoses with human papillomavirus (HPV) DNA status and surgical biopsy diagnoses, determine if CD4 counts correlate with lesion severity, and compare anal-rectal data of HIV-infected patients (primarily men) with cervical data.

MATERIALS AND METHODS: A retrospective search of the computerized database identified 118 HIV-positive patients who had anal-rectal cytology.

Cytology results were compared with available follow-up data including repeat anal-rectal cytology tests, surgical biopsy, CD4 counts, and HPV DNA polymerase chain reaction-based genotyping.

RESULTS: Cytological diagnoses included 3% unsatisfactory for diagnosis, 41% negative for intraepithelial lesion or malignancy (NILM), 23% atypical squamous cells of undermined significance (ASC-US), 31% low-grade squamous intraepithelial lesion (LSIL), and 2% high-grade squamous intraepithelial lesion (HSIL) (ASC-US/squamous intraepithelial lesion, 0.7:1).

Two anal intraepithelial neoplasia (AIN) II, 10 AIN III, and 1 invasive squamous cell carcinoma were histologically detected (11%).

The majority of AIN II was preceded by LSIL, 54%; ASC-US, 15%; and HSIL, 8%.

Sensitivity, specificity, negative predictive value, and positive predictive value were 92%, 8%, 33%, and 67%, respectively.

Of those HPV tested concurrent with the first cytology specimen, 48% NILM, 78% ASC-US, and 100% LSIL were HPV positive.

Mean CD4 counts (per microliter) were lower in patients with HSIL (243 [SD, 65]) compared with LSIL (400 [SD, 261]) and NILM (428 [SD, 232]).

CONCLUSIONS: Anal-rectal cytology is a useful screening test.

A high percentage of AIN II lesions were detected in this at-risk population, and the majority was detected following cytological abnormality.

[MeSH-major] Anal Canal / pathology. HIV Infections / complications. Papillomaviridae / isolation & purification. Papillomavirus Infections / epidemiology. Rectal Neoplasms / epidemiology. Rectum / pathology

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(PMID = 20354415.001).

[ISSN] 1526-0976

[Journal-full-title] Journal of lower genital tract disease

[ISO-abbreviation] J Low Genit Tract Dis

[Language] eng

[Grant] United States / NCI NIH HHS / CA / CA83679

[Publication-type] Journal Article; Research Support, N.I.H., Extramural

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Human papillomavirus and anal neoplasia.

Anal cancer is a rare disease in the general population, but the incidence of anal cancer is higher in certain at-risk groups, such as men who have sex with men (MSM), and immunosuppressed individuals, including those with HIV infection.

Among HIV-positive MSM, the incidence of anal cancer may be as high as 10 times greater than current rates of cervical cancer in the general population of women.

Anal cancer is associated with human papillomavirus (HPV) infection and may be preceded by high-grade anal intraepithelial neoplasia (HGAIN).

HGAIN and anal HPV infection are both highly prevalent in groups at risk for anal cancer.

Current issues include determining the effect of antiretroviral therapy on the natural history of HGAIN and the incidence of anal cancer, optimizing diagnostic and therapeutic approaches to HGAIN, and determining the potential for prophylactic HPV vaccines to prevent anal HPV infection and anal cancer in at-risk groups.

[MeSH-major] Anus Neoplasms. Carcinoma in Situ. Papillomavirus Infections

[MeSH-minor] Anus Diseases / epidemiology. Anus Diseases / virology. Female. HIV Infections / complications. Homosexuality, Male. Humans. Male. Papillomaviridae / isolation & purification

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(PMID = 18510893.001).

[ISSN] 1548-3568

[Journal-full-title] Current HIV/AIDS reports

[ISO-abbreviation] Curr HIV/AIDS Rep

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review

[Publication-country] United States

[Number-of-references] 57

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Improved screening for anal neoplasia by immunocytochemical detection of minichromosome maintenance proteins.

PURPOSE: Early detection of anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (SCC) by screening will improve clinical outcome.

Assessment of anal cytology samples using routine Papanicolaou testing suffers from shortcomings in sensitivity and/or specificity, suggesting that screening tests based on biomarkers may be of value.

EXPERIMENTAL DESIGN: We undertook an initial immunohistochemical study of 54 anal tissue samples and validated our findings using an independent prospective cohort study of 235 anal cytology samples from 144 subjects.

RESULTS: In the progression from normal anal epithelium through AIN to SCC, there was increasing expression of MCM2 and MCM5, including in the superficial epithelial third, the source of the majority of cells collected by anal swab.

The median labeling indices (LI) for MCM2 and MCM5 in the superficial third of AIN2/3 and SCCs combined were 90.2% and 84.0%, respectively.

By immunocytochemistry using a mixture of anti-MCM2 and anti-MCM5 antibodies, immunopositive cells were readily identified in anal cytology samples, even at low magnification.

MCM testing showed sensitivity for AIN2/3 of 84% (95% confidence interval, 75,93) and for AIN1/viral changes of 76% (68, 84), with overall specificity (for any lesion) of 77% (64, 90).

CONCLUSIONS: MCMs are promising biomarkers for improving detection of AIN and SCC in anal cytology samples.

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(PMID = 18843031.001).

[ISSN] 1055-9965

[Journal-full-title] Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

[ISO-abbreviation] Cancer Epidemiol. Biomarkers Prev.

[Language] ENG

[Grant] United Kingdom / Medical Research Council / / MC/ U105359875; United Kingdom / Medical Research Council / / MC/ U105359878; United Kingdom / Cancer Research UK / / ; United Kingdom / Medical Research Council / /

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Cell Cycle Proteins; 0 / Ki-67 Antigen; 0 / MCM5 protein, human; 0 / Nuclear Proteins; EC 3.6.4.12 / Minichromosome Maintenance Complex Component 2

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Immunoreactivity of p16 in anal cytology specimens: histologic correlation.

BACKGROUND: Cytology has been proposed as a potential screening tool in the evaluation of squamous anorectal disease in view of the morphologic similarities between anal and cervical squamous lesions.

Previous studies have demonstrated that p16 overexpression correlates with the degree of dysplasia in the uterine cervix with promising results.

Due to potential diagnostic pitfalls in anal cytology, p16 overexpression in these specimens was studied.

One slide of each case was destained.

RESULTS: Twenty-eight of the 43 cases demonstrated the presence of squamous cells immunoreactive for p16 in cytology specimens.

The p16-positive cells were identified in cases of low-grade squamous intraepithelial lesion (LSIL) (n = 3 cases), high-grade squamous intraepithelial lesion (HSIL) (n = 22 cases), and invasive squamous carcinoma (n = 1 case), and in 2 cases with negative follow-up biopsies.

The sensitivity and specificity of p16 immunoreactivity in the detection of anal intraepithelial neoplasia or carcinoma were 72% and 71%, respectively.

CONCLUSIONS: The presence of p16 immunoreactivity is a good predictor of dysplasia in anal specimens.

However, the sensitivity and specificity of this marker are not high.

[MeSH-major] Anus Neoplasms / pathology. Biomarkers, Tumor / analysis. Carcinoma in Situ / pathology. Neoplasms, Squamous Cell / pathology

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[Copyright] (c) 2006 American Cancer Society.

(PMID = 16404747.001).

[ISSN] 0008-543X

[Journal-full-title] Cancer

[ISO-abbreviation] Cancer

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cyclin-Dependent Kinase Inhibitor p16

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Methylation of human papillomavirus genomes in cells of anal epithelia of HIV-infected men.

Intra-anal malignancies disproportionately affect individuals who engage in anal intercourse because of infection with human papillomaviruses (HPVs), with an increased risk attributed to infection with HIV because of a declining immunity against HPvs. Long-term persistence of HPVs suggests yet other mechanisms that determine the clinical outcome, however.

Because methylation of HPV DNA represses oncogene expression in cervical samples, we investigated whether this mechanism also occurs in HIV-positive men and studied the methylation of CpG dinucleotides overlapping with the HPV-16 enhancer and promoter in 16 anal samples.

In low-grade anal intraepithelial neoplasia (AIN), methylation was high in CpGs overlapping the viral enhancer but rare in promoter positions, whereas methylation was high in promoter regions in high-grade AIN, especially in samples with a high load of viral genomes.

We also detected de novo methylation at methylated (me) CpA, meCpT, and meCpC dinucleotides.

Our study expands the observation and mapping of HPV DNA methylation to anal infections and the HIV-positive patient population.

DNA methylation, taken together with virus load, may be useful to diagnose the emergence of a population of tumor cells.

[MeSH-minor] Anal Canal / virology. Base Sequence. Biopsy. DNA Primers. DNA, Viral / genetics. DNA, Viral / isolation & purification. Dinucleoside Phosphates / analysis. Enhancer Elements, Genetic. Homosexuality, Male. Humans. Male. Polymerase Chain Reaction. Virus Latency. Virus Replication

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(PMID = 15905729.001).

[ISSN] 1525-4135

[Journal-full-title] Journal of acquired immune deficiency syndromes (1999)

[ISO-abbreviation] J. Acquir. Immune Defic. Syndr.

[Language] eng

[Grant] United States / NCI NIH HHS / CA / CA-91964; United States / NCI NIH HHS / CA / R01 CA-91964

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

[Publication-country] United States

[Chemical-registry-number] 0 / DNA Primers; 0 / DNA, Viral; 0 / Dinucleoside Phosphates; 2382-65-2 / cytidylyl-3'-5'-guanosine

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Extensive anal condylomatosis: prognosis in relation to viral and host factors.

OBJECTIVE: To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences.

Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples.

RESULTS: Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included.

There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients.

CONCLUSION: Radical resection resulted in a favourable clinical course.

Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful.

[MeSH-minor] Adult. Aged. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Male. Middle Aged. Prognosis. Retrospective Studies. Young Adult

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[ErratumIn] Colorectal Dis. 2010 Oct;12(10):1072. Mistro, A [corrected to Del Mistro, A]

(PMID = 19508521.001).

[ISSN] 1463-1318

[Journal-full-title] Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

[ISO-abbreviation] Colorectal Dis

[Language] eng

[Publication-type] Comparative Study; Journal Article

[Publication-country] England

[Chemical-registry-number] 0 / DNA, Viral

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The fear factor: drivers and barriers to follow-up screening for human papillomavirus-related anal cancer in men who have sex with men.

Human papillomavirus (HPV)-related anal cancer incidence is rising in men who have sex with men (MSM).

Retrospective chart review identified MSM with anal dysplasia.

From June 2007 to March 2008, subjects completed a questionnaire in-person at the time of screening or via telephone (LTF).

Questionnaires were completed after anal dysplasia diagnosis.

RF were more likely to describe their HPV diagnosis as 'upsetting' (P = 0.003).

MSM with high-grade intraepithelial lesions (HSIL) were more likely to be RF versus those with low-grade intraepithelial lesions (P = 0.001.

Positive predictors for screening compliance include an upsetting experience during the HPV diagnosis, physical symptoms driving the initial visit and HSIL.

Engaging patients in a firm, salient approach may facilitate follow-up compliance.

[MeSH-major] Anus Neoplasms / diagnosis. Anus Neoplasms / psychology. Early Detection of Cancer / psychology. Homosexuality, Male. Papillomavirus Infections / diagnosis. Patient Compliance / statistics & numerical data

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(PMID = 20852198.001).

[ISSN] 1758-1052

[Journal-full-title] International journal of STD & AIDS

[ISO-abbreviation] Int J STD AIDS

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates.

BACKGROUND: Hypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality.

This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae.

Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively.

RESULTS: Both under-diagnosis of hypertension (33%) and under-treatment (76%) were common.

Under-diagnosis of hypertension was more common among foreigners than among nationals.

CONCLUSION: Hypertension, even severe, is commonly under-diagnosed and under-treated in the UAE.

Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population.

[MeSH-minor] Adult. Aged. Cardiovascular Diseases / etiology. Female. Humans. Male. Middle Aged. Risk Factors. United Arab Emirates

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[Cites] N Engl J Med. 2001 Aug 16;345(7):479-86 [11519501.001]

[Cites] BMC Public Health. 2006;6:9 [16423280.001]

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(PMID = 16753071.001).

[ISSN] 1471-2261

[Journal-full-title] BMC cardiovascular disorders

[ISO-abbreviation] BMC Cardiovasc Disord

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Other-IDs] NLM/ PMC1501045

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Hypokalemic periodic paralysis: a case series, review of the literature and update of management.

The objective of this study was to present a case series of patients with hypokalemic periodic paralysis.

We described all patients with diagnosis of hypokalemic periodic paralysis admitted to the Al Ain Hospital (UAE) during the year 2006.

Seventeen patients, all males and mostly Asians, were presented to the Al Ain Hospital over a 12-month period.

In conclusion, clinicians should have a high index of suspicion, especially among Asians presenting with flaccid paralysis and hypokalemia.

[MeSH-major] Hypokalemic Periodic Paralysis / diagnosis

[MeSH-minor] Adult. Emigrants and Immigrants. Fluid Therapy. Humans. Hypokalemia / diagnosis. Hypokalemia / therapy. Male. Middle Aged. Potassium / blood. Potassium / therapeutic use. Seasons. Thyrotoxicosis / complications. United Arab Emirates. Young Adult

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(PMID = 20201128.001).

[ISSN] 1473-5695

[Journal-full-title] European journal of emergency medicine : official journal of the European Society for Emergency Medicine

[ISO-abbreviation] Eur J Emerg Med

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] England

[Chemical-registry-number] RWP5GA015D / Potassium

[Number-of-references] 10

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Complementary roles of prenatal sonography and magnetic resonance imaging in diagnosis of fetal renal anomalies.

OBJECTIVES: This study was designed to assess the role of magnetic resonance imaging (MRI) in refining the diagnosis of prenatally suspected fetal renal abnormalities following screening ultrasound.

PATIENTS AND METHODS: Twenty pregnant women, with suspected fetal renal abnormality detected during screening ultrasound and more than 14 weeks' gestation, were included in this observational prospective study at Ain Shams University Maternity Hospital from March 2004 to March 2005 after informed consent and after approval of the study protocol by the institute ethics committee.

RESULTS: The MRI could diagnose correctly 10 cases of hydronephrosis, one case of polycystic kidney disease (PCKD), one case of RA, two normal case and two cases of intra-abdominal masses (IA Mass) (16 of 18 cases).

The prenatal ultrasound could diagnose correctly eight cases of hydronephrosis, one case of PCKD, one case of renal agenesis, one case of multicystic kidney disease and one case of IA Mass (12 of 18 cases).

The prenatal ultrasound and MRI gave different diagnoses in eight cases and gave the same diagnosis in 12 cases.

The MRI could diagnose the aetiology of congenital renal cysts in 10 of the 20 studied cases (50%).

[MeSH-major] Fetal Diseases / diagnosis. Kidney / abnormalities. Magnetic Resonance Imaging. Ultrasonography, Prenatal. Urogenital Abnormalities / diagnosis

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(PMID = 20618240.001).

[ISSN] 1479-828X

[Journal-full-title] The Australian & New Zealand journal of obstetrics & gynaecology

[ISO-abbreviation] Aust N Z J Obstet Gynaecol

[Language] eng

[Publication-type] Clinical Trial; Journal Article

[Publication-country] Australia

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Acute interstitial nephritis (AIN) represents a frequent cause of acute kidney injury, accounting for 15-27% of renal biopsies performed because of this condition.

By and large, drug-induced AIN is currently the commonest etiology of AIN, with antimicrobials and nonsteroidal anti-inflammatory drugs being the most frequent offending agents.

Pathogenesis is based on an immunologic reaction against endogenous nephritogenic antigens or exogenous antigens processed by tubular cells, with cell-mediated immunity having a major pathogenic role.

A significant proportion of AIN has nowadays an oligosymptomatic presentation, although the presence of specific extrarenal symptoms such as fever, skin rash, arthralgias, and peripheral eosinophilia has an important role to orientate clinical diagnosis.

Identification and removal of the offending drug are the mainstay of the treatment, but recent studies strongly suggest that early steroid administration (within 7 days after diagnosis) improves the recovery of renal function, decreasing the risk of chronic renal impairment.

[MeSH-minor] Acute Disease. Animals. Disease Progression. Humans. Predictive Value of Tests. Recovery of Function. Risk Factors. Steroids / therapeutic use. Time Factors. Treatment Outcome

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[CommentIn] Kidney Int. 2011 Jan;79(1):137-8; author reply 138 [21157464.001]

(PMID = 20336051.001).

[ISSN] 1523-1755

[Journal-full-title] Kidney international

[ISO-abbreviation] Kidney Int.

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Steroids

[Number-of-references] 34

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury.

Many etiologies of AIN have been recognized--including allergic/drug-induced, infectious, autoimmune/systemic, and idiopathic forms of disease.

The most common etiology of AIN is drug-induced disease, which is thought to underlie 60-70% of cases.

Multiple agents from many different classes of drugs can cause AIN, and the clinical presentation and laboratory findings vary according to the class of drug involved.

AIN is characterized by interstitial inflammation, tubulitis, edema, and in some cases, eventual interstitial fibrosis.

A definitive diagnosis of AIN can be established only by kidney biopsy.

Noninvasive tests such as (67)gallium scintigraphy and testing for eosinophiluria have limited diagnostic utility.

The mainstay of therapy for drug-induced AIN is timely discontinuation of the causative agent.

Although the benefits of corticosteroid therapy remain unproven, they do appear to have a positive effect in some patients with drug-induced AIN, especially when treatment is initiated early in the course of the disease.

In general, the prognosis for drug-induced AIN is good, and at least partial recovery of kidney function is normally observed.

Early recognition is crucial because patients can ultimately develop chronic kidney disease.

[MeSH-minor] Biopsy. Diagnosis, Differential. Humans

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(PMID = 20517290.001).

[ISSN] 1759-507X

[Journal-full-title] Nature reviews. Nephrology

[ISO-abbreviation] Nat Rev Nephrol

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Ga-67 scintigraphy in the differential diagnosis between acute interstitial nephritis and acute tubular necrosis: an experimental study.

BACKGROUND: The differentiation between acute interstitial nephritis (AIN) and acute tubular necrosis (ATN) is crucial in patients with acute kidney injury.

Gallium-67 citrate (Ga-67) has been used clinically in the differential diagnosis between these entities, but its efficacy is disputed.

The aim of this study was to evaluate Ga-67 scintigraphy efficacy in the differentiation between experimental models of drug-induced AIN and ATN.

METHODS: Animals were divided into three groups: AIN (n = 8), ATN (n = 8) and control (NL, n = 10).

The AIN group received intraperitoneal puromycin aminonucleoside (single dose, 150 mg/kg).

The ATN group received a single intraperitoneal injection of cisplatin (6 mg/kg).

The NL group did not receive active drugs.

RESULTS: Renal Ga-67 uptake was strikingly more intense in the AIN group when compared to the ATN (P < 0.0001) and NL (P < 0.001) groups.

The ATN group had increased Cr when compared to the NL group (P < 0.001) and lower urinary osmolality vs the NL (P < 0.001) and AIN (P < 0.01) groups.

Renal histology showed severe acute tubular injury in the ATN group and intense interstitial inflammation in the AIN group, and was normal in control animals.

CONCLUSION: Ga-67 scintigraphy was extremely effective in the differentiation between experimental drug-induced ATN and AIN.

[MeSH-minor] Acute Disease. Acute Kidney Injury / radionuclide imaging. Animals. Diagnosis, Differential. Kidney / pathology. Kidney / physiopathology. Male. Rats. Rats, Wistar

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(PMID = 20348147.001).

[ISSN] 1460-2385

[Journal-full-title] Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

[ISO-abbreviation] Nephrol. Dial. Transplant.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Gallium Radioisotopes

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The aim of the present study was to report and analyse the clinical features of 15 patients with acute interstitial nephritis (AIN) and acute renal failure from PPI that were referred to renal services in Auckland over a period of 3 years.

The diagnosis of AIN was made by renal biopsy in 12 cases.

In all patients, the time-course of drug exposure and improvement of renal function on withdrawal suggested PPI were causal.

RESULTS: The median patient age was 78 years.

The mean baseline serum creatinine level was 83 micromol/L, peak level 392 micromol/L, and recovery level 139 micromol/L.

The erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and 12 patients, respectively, where this information was collected (ESR mean 85 mm/h, and C-reactive protein mean 81 mg/L).

AIN occurred at 8 per 100 000 patient years (95% confidence level 2.6-18.7 per 100 000 patient years).

CONCLUSION: PPI are now the most commonly identified cause of AIN in the Auckland area.

Early diagnosis may be facilitated by clinician awareness of the insidious onset of renal failure, and an elevated erythrocyte sedimentation rate and C-reactive protein.

[MeSH-minor] 2-Pyridinylmethylsulfinylbenzimidazoles / adverse effects. Aged. Aged, 80 and over. Anti-Ulcer Agents / adverse effects. Biopsy. Blood Sedimentation. C-Reactive Protein / metabolism. Female. Humans. Male. Middle Aged. Risk Factors

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Hazardous Substances Data Bank. PANTOPRAZOLE .

Hazardous Substances Data Bank. OMEPRAZOLE .

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[CommentIn] Nephrology (Carlton). 2006 Oct;11(5):379-80 [17014548.001]

(PMID = 17014549.001).

[ISSN] 1320-5358

[Journal-full-title] Nephrology (Carlton, Vic.)

[ISO-abbreviation] Nephrology (Carlton)

[Language] eng

[Publication-type] Journal Article

[Publication-country] Australia

[Chemical-registry-number] 0 / 2-Pyridinylmethylsulfinylbenzimidazoles; 0 / Anti-Ulcer Agents; 0 / Enzyme Inhibitors; 0 / Proton Pump Inhibitors; 9007-41-4 / C-Reactive Protein; D8TST4O562 / pantoprazole; KG60484QX9 / Omeprazole

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Automated analysis of fluorescent in situ hybridization (FISH) labeled genetic biomarkers in assisting cervical cancer diagnosis.

The numerical and/or structural deviation of some chromosomes (i.e., monosomy and _polysomy of chromosomes 3 and X) are routinely used as positive genetic biomarkers to diagnose cervical cancer and predict the disease progression.

Among the available diagnostic methods to analyze the aneusomy of chromosomes 3 and X, fluorescence in situ hybridization (FISH) technology has demonstrated significant advantages in assisting clinicians to more accurately detect and diagnose cervical carcinoma at an early stage, in particular for the women at a high risk for progression of low-grade and high-grade squamous intra-epithelium lesions (LSIL and HSIL).

In order to increase the diagnostic accuracy, consistency, and efficiency from that of manual FISH analysis, this study aims to develop and test an automated FISH analysis method that includes a two-stage scheme.

In the first stage, an interactive multiple-threshold algorithm is utilized to segment potential interphase nuclei candidates distributed in different intensity levels and a rule-based classifier is implemented to identify analyzable interphase cells.

In the second stage, FISH labeled biomarker spots of chromosomes 3 and X are segmented by a top-hat transform.

The experimental results of four test cases showed high agreement of FISH analysis results between the automated scheme and the cytogeneticist's analysis including 92.7% to 98.7% agreement in cell segmentation and 4.4% to 11.0% difference in cell classification.

This preliminary study demonstrates the feasibility of potentially applying the automatic FISH analysis method to expedite the screening and detecting cervical cancer at an early stage.

[MeSH-major] Biomarkers, Tumor / analysis. In Situ Hybridization, Fluorescence / methods. Uterine Cervical Neoplasms / diagnosis. Uterine Cervical Neoplasms / genetics

[MeSH-minor] Automation. Cervical Intraepithelial Neoplasia / diagnosis. Cervical Intraepithelial Neoplasia / genetics. Female. Humans. Vaginal Smears

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(PMID = 20441233.001).

[ISSN] 1533-0338

[Journal-full-title] Technology in cancer research & treatment

[ISO-abbreviation] Technol. Cancer Res. Treat.

[Language] eng

[Grant] United States / NCI NIH HHS / CA / R01 CA136700; United States / NCI NIH HHS / CA / R01 CA136700-01; United States / NCI NIH HHS / CA / CA136700

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Biomarkers, Tumor

[Other-IDs] NLM/ NIHMS220245; NLM/ PMC2916642

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND AND OBJECTIVES: The objective of this study was to describe the characteristics of patients with HIV infection and biopsy-proven acute interstitial nephritis (AIN).

Patients who received a diagnosis of AIN without evidence of HIV-associated nephropathy were identified, and their clinical course was reviewed up to 18 months after biopsy.

RESULTS: Of 262 biopsies, 29 (11%) patients who had AIN without evidence of HIV-associated nephropathy were identified.

The mean age at the time of biopsy was 47.5 years (range 28 to 71 years), 17 (59%) were men, and 23 (79%) were black.

Drugs were identified as the cause of AIN in the majority (72%) of cases.

CONCLUSIONS: In our series, AIN was prevalent (11%) and was often drug induced.

AIN should not be excluded from the differential diagnosis on the basis of absence of the classic clinical triad of fever, rash, and pyuria.

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(PMID = 20338962.001).

[ISSN] 1555-905X

[Journal-full-title] Clinical journal of the American Society of Nephrology : CJASN

[ISO-abbreviation] Clin J Am Soc Nephrol

[Language] ENG

[Grant] United States / NIDA NIH HHS / DA / K23 DA015616; United States / NIDA NIH HHS / DA / R01 DA018577; United States / NIDA NIH HHS / DA / R01 DA026770

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Anti-Retroviral Agents

[Other-IDs] NLM/ PMC2863972