Biomedical subjects

J Michael Berry

Publications and source records attributed to J Michael Berry.

8 recordsLinked to original sources

PubMed2006

A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals.

OBJECTIVES: To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals. DESIGN: A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR. SETTING: University-based research clinic. PARTICIPANTS: Thirteen HIV-positive men and two HIV-positive women with HG-AIN. RESULTS: There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 microg cohorts regressed to AIN 1 and one of five participants in the 1000 microg cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02). CONCLUSIONS: SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.

Adult↗

PubMed2006

High resolution anoscopy and targeted treatment of high-grade squamous intraepithelial lesions.

PURPOSE: The purpose of this video is to illustrate the use of high resolution anoscopy in the diagnosis and treatment of anal high-grade squamous intraepithelial lesions. METHODS: Five patients with anal dysplasia were examined in the operating room with acetic acid and the operative microscope. Lugol's solution was used selectively. Acetic acid is generously applied to aide in the recognition of high-grade squamous intraepithelial lesions. Acetowhite regions are examined under the operative microscope to further distinguish lesions as either low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions. Acetowhite lesions with specific vascular characteristics like punctuate vessels or honeycomb patterns are highly suggestive of high-grade disease. These lesions are selectively destroyed under direct visualization with an effort to maintain normal mucosa and skin to prevent stenosis. Some pigmented lesions contain high-grade squamous intraepithelial lesions; the operative microscope is used in this setting to look for the vascular characteristics of high-grade disease. RESULTS: The video reports five male patients treated for high-grade squamous intraepithelial lesions with the aide of high resolution anoscopy. There were no intraoperative or postoperative complications. All lesions suspicious for high-grade squamous intraepithelial lesions based on observed vascular patterns were confirmed as such with permanent histopathology. CONCLUSION: The use of acetic acid and the operative microscope with selective use of Lugol's solution accentuates the visual characteristics of high-grade lesions, enhancing the surgeon's ability to target treatment to high-grade squamous intraepithelial lesions. High resolution anoscopy is useful in the targeted treatment of high-grade squamous intraepithelial lesions.

Anus Neoplasms↗

PubMed2005

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

OBJECTIVES: The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. DESIGN AND METHODS: A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. RESULTS: Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. CONCLUSIONS: The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

AIDS-Related Opportunistic Infections↗

PubMed2005

Home study course: summer 2005.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management, or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1-hour Category I credit of the Physician's Recognition Award of the American Medical Association and 1-hour Category I credit of the ASCCP's Program for Continuing Professional Development. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

Adult↗

PubMed2004

Self-collected versus clinician-collected anal cytology specimens to diagnose anal intraepithelial neoplasia in HIV-positive men.

BACKGROUND: Anal intraepithelial neoplasia (AIN) is common in men who have sex with men (MSM) and may be diagnosed by anal cytology screening. METHODS: One hundred two MSM with clinician-collected anal cytology and histopathology specimens were assessed from a cohort study of AIN at the University of California at San Francisco. The men were given a cytology self-collection kit with written instructions for use and requested to collect the sample 1 month after the clinic visit. RESULTS: Ninety-one percent of self-collected and 99% of clinician-collected anal cytology samples were adequate for interpretation. The sensitivity of abnormal anal cytology to detect AIN by histology was 68% in self-collected samples and 70% in clinician-collected samples, and the sensitivity to detect AIN 2 or AIN 3 was 71% and 74%, respectively. Cytologic results did not differ by grade between self-collected and clinician-collected samples. Among MSM diagnosed with AIN 2 or 3 by biopsy, 33% of self-collected and 39% of clinician-collected cytology samples were high-grade. The sensitivity of both self-collected and clinician-collected samples to detect AIN 2 or 3 was higher among HIV-positive MSM than among HIV-negative MSM. CONCLUSIONS: MSM with biopsy-proven AIN can self-collect anal cytology samples with sensitivity comparable with that of experienced clinicians. This may facilitate screening for AIN.

Adult↗

PubMed2004

Anal cancer and its precursors in HIV-positive patients: perspectives and management.

Anal cancer is an increasing problem among HIV-infected persons. Although patients are living longer and with better quality of life because of treatment with HAART, they remain at risk for invasive anal cancer and its precursor, anal HSIL. Given the substantial numbers of patients with anal HSIL, further studies need to be done to determine the efficacy and optimal mode of treatment of HSIL, to define the optimal method for screening patients at risk, to define the best way to follow up patients with documented HSIL to ensure early detection, to define prognostic factors for progression to invasive cancer, and to determine the progression rate of HSIL to invasive cancer. Although patients with good functional status and immunologic function seem to do relatively well with standard CMT for anal cancer, there are less fortunate patients who experience substantial morbidity from therapy and have a poorer outcome. It is difficult to draw definitive conclusions about the therapy of HIV-positive patients with anal cancer based on the available literature because of the retrospective nature of the analyses, the small number of patients, and the heterogeneity of the patients reported with regard to tumor size, pretreatment immunologic status, and the variety of treatments received by patients in some series. Identifying patients who develop invasive anal cancer as early as possible will improve results to some degree, but prospective, controlled, multi-institutional trials evaluating the treatment of anal cancer in HIV-infected persons are required to accurately define ways to improve outcome with less morbidity. The results of ongoing therapeutic HPV vaccine trials are eagerly awaited. Improvement may come by the following, determining ways to more accurately stage patients, such as endoanal ultrasound, sentinel lymph node sampling, or positron emission tomography scans; defining the role of cisplatin and whether it is indeed less toxic and equally or more effective; consideration of continuous protracted infusion of low-dose 5-FU; the optimum use of growth factors; and an evaluation of the role of conformal radiotherapy or the use of radio-protectants, such as amifostine. Meanwhile, the best way to treat anal cancer in HIV-infected persons may be to prevent it from occurring by screening persons at risk and treating HSIL, or at a minimum, following up patients carefully and detecting cancers, if they occur, at the earliest possible time.

Acquired Immunodeficiency Syndrome↗

PubMed2003

A review of human papillomavirus vaccines: from basic science to clinical trials.

Human papillomavirus (HPV) infection leads to a spectrum of disease from genital warts to precancerous lesions to cervical and anal cancer and is a worldwide public health problem of epidemic proportions. Unique to HPV-related neoplasia, the presence of specific viral antigens such as the L1 capsid structural protein and the oncoproteins E6 and E7 provide opportunities for vaccine therapy. Although difficult to precisely define, the natural immune response to HPV is vitally important and defects in cell mediated immunity correlate with increased risk of disease and cancer. In preclinical animal models, both prophylactic and therapeutic vaccines have effectively induced HPV-specific cell mediated immune responses protecting animals from viral challenge or eliminating established tumors. Most prophylactic vaccines are virus-like particles (VLP) composed of the L1 structural protein. Phase I trials have demonstrated safety and immunogenicity, but limited efficacy data are available. Therapeutic vaccine trials are reviewed including E6 and E7 vaccines comprised of peptides, fusion proteins, encapsulated plasmid DNA, and recombinant vaccinia virus. All of the vaccines appear to be safe, well tolerated, and preliminary data indicates that most are clinically effective. Multiple trials are in progress and more mature data are expected within the next few years.

Animals↗

PubMed2002

Surgical treatment of high-grade anal squamous intraepithelial lesions: a prospective study.

PURPOSE: The prevalence of anal squamous intraepithelial lesions is high among human immunodeficiency virus-positive homosexual males and, to a lesser extent, among human immunodeficiency virus-negative homosexual males. Furthermore, the incidence of high-grade squamous intraepithelial lesions, the putative precursor lesion to invasive cancer, is also high. We report the first prospective study of high-resolution anoscopy-directed surgical treatment of high-grade squamous intraepithelial lesions. METHODS: A prospective study of patients undergoing surgical treatment of high-grade squamous intraepithelial lesions (excision/cauterization of lesions visualized with high-resolution anoscopy) was performed. Follow-up anoscopy with biopsy and Papanicolaou smear was performed every three to six months. RESULTS: Patients diagnosed with high-grade squamous intraepithelial lesions during the course of their participation in a prospective cohort study of anal squamous intraepithelial lesions were identified. From this group, 37 patients who were treated surgically between 1995 and 1999 were studied. Of these, 29 had tested positive for human immunodeficiency virus and 8 were negative for the virus. Mean patient age was 45 +/- 8 years. Mean duration of follow-up was 32.3 +/- 20.6 months in the human immunodeficiency virus-negative group and 28.6 +/- 12.9 months in the human immunodeficiency virus-positive group. No human immunodeficiency virus-negative patient developed recurrent high-grade squamous intraepithelial lesions. Twenty-three of 29 human immunodeficiency virus-positive patients had persistent or recurrent high-grade squamous intraepithelial lesions (P = 0.003; mean time to recurrence, 12 months). Six patients underwent reoperation for high-grade squamous intraepithelial lesions (4 recurred by 6 months). No patients developed incontinence, stenosis, postoperative infection, or significant bleeding after surgical treatment. CONCLUSIONS: Surgical intervention directed by high-resolution anoscopy is safe and eliminates high-grade squamous intraepithelial lesions in human immunodeficiency virus-negative patients. The high persistence or recurrence rate in human immunodeficiency virus-positive patients suggests that multiple staged procedures and continued surveillance may be necessary.

Adult↗