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Stephen M. Kralovic - One of the best experts on this subject based on the ideXlab platform.
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Phase I study demonstrates safety and tolerability of radiofrequency ablation (RFA) of the Anal Mucosa.
Hiv Clinical Trials, 2020Co-Authors: A. George Smulian, Diana M. Moore, Jaime C. Robertson, Stephen M. KralovicAbstract:Background: Anal carcinoma is increasing in high-risk populations. Dysplasia is often distributed throughout the Anal Mucosa, and focal ablative techniques have high rates of recurrence. Methods: With the goal of eradicating dysplasia from the entire Anal Mucosa, we conducted a phase I dose-ranging study to determine the safety and tolerability of radiofrequency ablation (RFA). HIV-infected individuals with high-grade Anal intraepithelial neoplasia underwent RFA of the Anal Mucosa. Patient-reported procedural and postprocedural symptoms were recorded, and Mucosal healing was visually assessed. Results: Four groups of 3 subjects each were treated with incrementally increasing numbers of RF pulses (1–3) applied to a single area of Anal Mucosa. Two or three doses of 12 J/cm 2 were found to have acceptable patient tolerance and healing of the Mucosa within 4 weeks of ablation. Using these doses, 2 groups underwent ablation of 180° of contiguous Mucosa. Subjects experienced a loss of 1 to 3 days of daily activities of living, 7 to 14 days of postprocedure symptoms, and Mucosal healing within 4 weeks. One subject in the fi rst treatment group had the procedure aborted due to severe procedural pain. Conclusions: The study provides evidence of the safety and tolerability of Anal RFA of 180° of contiguous Mucosa in a single procedure and will allow future RFA effi cacy studies in the treatment of Anal dysplasia. Key words: Anal carcinoma, Anal dysplasia, human papillomavirus
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phase i study demonstrates safety and tolerability of radiofrequency ablation rfa of the Anal Mucosa
Hiv Clinical Trials, 2014Co-Authors: George A Smulian, Diana M. Moore, Jaime Robertson, Stephen M. KralovicAbstract:Background Anal carcinoma is increasing in high-risk populations. Dysplasia is often distributed throughout the Anal Mucosa, and focal ablative techniques have high rates of recurrence. Methods Wit...
Jean Claude Soule - One of the best experts on this subject based on the ideXlab platform.
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Anal carcinoma: incidence and effect of cumulative infections.
AIDS, 2004Co-Authors: Iradj Sobhani, Francine Walker, Laurent Abramowitz, Dominique Henin, Françoise Roudot-thoraval, Hubert Johanet, Jean-charles Delchier, Jean Claude SouleAbstract:INTRODUCTION: Human papilloma virus (HPV) causes Anal condyloma that is a risk factor for Anal carcinoma. The incidence and mechanism of invasive Anal carcinoma in patients with Anal condyloma are prospectively determined. PATIENTS AND METHODS: From 1993 to 2002, 228 consecutive patients (164 HIV positive) with Anal cAnal condylomas were included in the study, after curing of their lesions. They were asked to attend follow-up visits at 3- or 6-month intervals. We checked for Anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus, cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells (LC) in Anal Mucosa at baseline and during follow up. We cured and Analysed relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads and CD4 T-lymphocyte counts were determined at each visit and the densities of LC in consecutive specimens from patients with cancers were compared with that for a matched control group (n = 23). RESULTS: Analysis of 199 patients showed high-grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV positive) patients developed invasive carcinoma after 13-108 months and 112 (56%) patients relapsed condylomas. HIV and Anal co-infection were identified as independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in Anal Mucosa were lower in patients with invasive carcinoma than in controls. CONCLUSION: The risk of invasive carcinoma in HPV-infected patients is increased by HIV and Anal co-infection. Decreases in LC numbers in Anal Mucosa may favour this outcome.
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effect of Anal epidermoid cancer related viruses on the dendritic langerhans cells of the human Anal Mucosa
Clinical Cancer Research, 2002Co-Authors: Iradj Sobhani, Francine Walker, Thomas Aparicio, Laurent Abramowitz, Dominique Henin, Anne Claude Cremieux, Jean Claude SouleAbstract:Purpose: The incidence of Anal cancer is high in patients with Anal condyloma. HIV increases this risk. We Analyzed Anal Mucosa from normal individuals and individuals with condyloma. Experimental Design: Normal Anal Mucosa from 155 consecutively recruited patients (102 HIV-positive and 53 HIV-negative) with Anal condyloma was compared with that obtained from 30 HIV-negative patients after hemorrhoid surgery (controls). Langerhans’ cells (LCs), T lymphocytes, and viruses [EBV, cytomegalovirus, herpes simplex virus 1, and human papillomavirus (HPV) types] in Anal Mucosa and HIV load and CD4 T-lymphocyte counts in the serum were characterized. Results: None of the control individuals had Anal squamous intraepithelial lesion or HPV versus 19 HIV-positive and 4 HIV-negative patients with Anal condyloma ( P = 0.07). The number of LCs/mm in Anal tissue was significantly higher in HIV-negative patients with condylomata (median, 30; range, 2–130) than in HIV-positive patients (median, 15; range, 0–100) or in controls (median, 17; range, 4–35). In HIV-negative individuals, the occurrence of condylomata was linked with a higher number of LCs. Significant differences were observed between HIV-positive and HIV-negative patients with Anal condylomata:number of LCs/mm Anal tissue, oncogenic HPV (26% versus 8%), other current infections (35.6% versus 5%), being male (93% versus 74%). Multivariate regression Analysis found HIV as the only risk factor for a decrease in the number of LCs (odds ratio, 6; 95% confidence interval, 2.28–16.1; P P Conclusion: HPV increases the number of LCs in Anal Mucosa in HIV-negative individuals. HIV alters Anal dendritic cells, likely leading to an increase in Anal cancer risk.
Iradj Sobhani - One of the best experts on this subject based on the ideXlab platform.
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FoxP3 overexpression and CD1a+ and CD3+ depletion in Anal tissue as possible mechanisms for increased risk of human papillomavirus-related Anal carcinoma in HIV infection
Colorectal Disease, 2010Co-Authors: Mohammad Yaghoobi, S. Le Gouvello, N. Aloulou, C. Duprez Dutreuil, F. Walker, Iradj SobhaniAbstract:AIM: We Analysed local cellular and humoral immunity factors in the Anal Mucosa in an attempt to explain how HIV infection increases the risk of Anal cancer in HPV-infected patients. METHOD: HIV-positive cases and matched HIV-negative controls with more than one recurrence of condylomas were included in a prospective study following treatment of the initial lesions. Patients were followed every 3 to 6 months for the development of Anal intraepithelial neoplasia (AIN3) and cancer for up to 60 months. Tissue CD1a(+), CD3(+), CD4(+), CD8(+) cells and mRNAs of selected cytokines and chemokines were quantified and compared in patients with or without AIN3 or cancer using morphometric or immunohistochemistry Analysis and qRT-PCR. RESULTS: Sixty-six individuals (22 patients and 44 controls) were included. In the case group, CD1a(+) and CD3(+) cell counts were significantly lower in biopsies from AIN3 and cancer specimens compared with those from AIN 1-2 or normal biopsies (P < 0.0001). A CD1a(+) count of < 10/mm was predictive of AIN3 and cancer (Odds ratio = 9.4, 95% CI: 5.4-18.3, P < 0.0001). IL-8 and IL23 levels were significantly higher in cancer than in non-cancer tissues regardless of HIV status (P = 0.02). FoxP3 expression was significantly higher in HIV-infected cases than in controls with AIN3/cancer (P < 0.04). CONCLUSION: Depletion of CD1a(+) and CD3(+) cells and overexpression of FoxP3 in the Anal Mucosa appear likely to contribute to the risk of HPV-related Anal cancer in HIV-infected patients. Furthermore, overexpression of IL-8 and IL-23 in the Anal Mucosa might be responsible for the development of this cancer regardless of HIV status.
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Anal carcinoma: incidence and effect of cumulative infections.
AIDS, 2004Co-Authors: Iradj Sobhani, Francine Walker, Laurent Abramowitz, Dominique Henin, Françoise Roudot-thoraval, Hubert Johanet, Jean-charles Delchier, Jean Claude SouleAbstract:INTRODUCTION: Human papilloma virus (HPV) causes Anal condyloma that is a risk factor for Anal carcinoma. The incidence and mechanism of invasive Anal carcinoma in patients with Anal condyloma are prospectively determined. PATIENTS AND METHODS: From 1993 to 2002, 228 consecutive patients (164 HIV positive) with Anal cAnal condylomas were included in the study, after curing of their lesions. They were asked to attend follow-up visits at 3- or 6-month intervals. We checked for Anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus, cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells (LC) in Anal Mucosa at baseline and during follow up. We cured and Analysed relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads and CD4 T-lymphocyte counts were determined at each visit and the densities of LC in consecutive specimens from patients with cancers were compared with that for a matched control group (n = 23). RESULTS: Analysis of 199 patients showed high-grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV positive) patients developed invasive carcinoma after 13-108 months and 112 (56%) patients relapsed condylomas. HIV and Anal co-infection were identified as independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in Anal Mucosa were lower in patients with invasive carcinoma than in controls. CONCLUSION: The risk of invasive carcinoma in HPV-infected patients is increased by HIV and Anal co-infection. Decreases in LC numbers in Anal Mucosa may favour this outcome.
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effect of Anal epidermoid cancer related viruses on the dendritic langerhans cells of the human Anal Mucosa
Clinical Cancer Research, 2002Co-Authors: Iradj Sobhani, Francine Walker, Thomas Aparicio, Laurent Abramowitz, Dominique Henin, Anne Claude Cremieux, Jean Claude SouleAbstract:Purpose: The incidence of Anal cancer is high in patients with Anal condyloma. HIV increases this risk. We Analyzed Anal Mucosa from normal individuals and individuals with condyloma. Experimental Design: Normal Anal Mucosa from 155 consecutively recruited patients (102 HIV-positive and 53 HIV-negative) with Anal condyloma was compared with that obtained from 30 HIV-negative patients after hemorrhoid surgery (controls). Langerhans’ cells (LCs), T lymphocytes, and viruses [EBV, cytomegalovirus, herpes simplex virus 1, and human papillomavirus (HPV) types] in Anal Mucosa and HIV load and CD4 T-lymphocyte counts in the serum were characterized. Results: None of the control individuals had Anal squamous intraepithelial lesion or HPV versus 19 HIV-positive and 4 HIV-negative patients with Anal condyloma ( P = 0.07). The number of LCs/mm in Anal tissue was significantly higher in HIV-negative patients with condylomata (median, 30; range, 2–130) than in HIV-positive patients (median, 15; range, 0–100) or in controls (median, 17; range, 4–35). In HIV-negative individuals, the occurrence of condylomata was linked with a higher number of LCs. Significant differences were observed between HIV-positive and HIV-negative patients with Anal condylomata:number of LCs/mm Anal tissue, oncogenic HPV (26% versus 8%), other current infections (35.6% versus 5%), being male (93% versus 74%). Multivariate regression Analysis found HIV as the only risk factor for a decrease in the number of LCs (odds ratio, 6; 95% confidence interval, 2.28–16.1; P P Conclusion: HPV increases the number of LCs in Anal Mucosa in HIV-negative individuals. HIV alters Anal dendritic cells, likely leading to an increase in Anal cancer risk.
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quantitative Analysis of the immune cells in the Anal Mucosa
Pathology Research and Practice, 1995Co-Authors: E Gervaz, Iradj Sobhani, Ch M Daugegeffroy, Ch Vissuzaine, M Mignon, G Benhamou, F PotetAbstract:Summary The prevalence o f anoperineal diseases, i.e. sexual transmitted infections, is increasing particularly in AIDS, a fact which is likely due to the alteration o f Mucosal immunity. However, no data were available on normal Anal status. In order to study Anal immunity in man, we characterized lymphocytes subtypes and Langerhans' cells (LC) using quantitative morphometric Analysis and immunohistochemistry. Anal normal Mucosal samples obtained from surgical specimens o f 45 patients (30 suffering from hemorrhoids and 15 from fissurations) were Analyzed. Immunohistochemistry was performed on frozen sections with antibodies recognizing CD1a (LC), CD3 (T lymphocytes), CD4 (T4), CD8 (T8) and CD22 (B -lymphocytes). Immunostained cells were counted per square millimeter of Mucosal epithelium. The surface o f CD1a cells was measured using a computerized software program and a percentage o f CD1 a immunostained area was calculated in comparison to the whole Mucosal surface. LC and T -Lymphocytes were found in the squamous epithelium in all Analyzed samples. The mean values o f L C number were 84.13 ± 9.6 and 64.77 ± 9.8 in hemorroid- and fissure-patients, respectively. The mean values o f LC area (% o f CD1a stained area over total Mucosal surface) were 3.89 ± 0.44 and 4.84 ± 0.64, respectively. In the two groups, the number o f intraepithelial CD8 lymphocytes was higher than that o f CD4 lymphocytes. These data suggest for the first time that Anal Mucosa could be considered as a part o f MALT system.
Ruth Holm - One of the best experts on this subject based on the ideXlab platform.
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hpv 16 infection in a patient with two primary squamous cell carcinomas of the uterine cervix and the Anal Mucosa
Apmis, 1997Co-Authors: Aasmund Berner, Sixten Franzen, Ruth HolmAbstract:: A 43-year-old woman presented with metrorrhagia and a polypoid Anal tumor. Cervical dilatation and endocervical curettage and resection of the Anal tumor revealed two primary squamous cell carcinomas: of the uterine cervix and the Anal Mucosa. HPV 16 was identified in both tumors using an in situ hybridization technique with probes against HPV 6, 11, 16, 18, 31 and 33. The cervical carcinoma was weakly positive for p53 protein, whereas the Anal tumor was p53 protein negative. Five years later a recurrence of the cervical carcinoma was diagnosed and a hysterectomy was performed. Of 3,013 patients with squamous cell carcinoma of either the cervix or the anus registered in our files, only one had a primary carcinoma in both locations. It was concluded hat HPV-16-induced squamous cell carcinoma may occur simultaneously in the cervix and the anus, and carcinoma in either of the two locations has to be ruled out when dealing with HPV infection in the anogenital tract.
Diana M. Moore - One of the best experts on this subject based on the ideXlab platform.
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Phase I study demonstrates safety and tolerability of radiofrequency ablation (RFA) of the Anal Mucosa.
Hiv Clinical Trials, 2020Co-Authors: A. George Smulian, Diana M. Moore, Jaime C. Robertson, Stephen M. KralovicAbstract:Background: Anal carcinoma is increasing in high-risk populations. Dysplasia is often distributed throughout the Anal Mucosa, and focal ablative techniques have high rates of recurrence. Methods: With the goal of eradicating dysplasia from the entire Anal Mucosa, we conducted a phase I dose-ranging study to determine the safety and tolerability of radiofrequency ablation (RFA). HIV-infected individuals with high-grade Anal intraepithelial neoplasia underwent RFA of the Anal Mucosa. Patient-reported procedural and postprocedural symptoms were recorded, and Mucosal healing was visually assessed. Results: Four groups of 3 subjects each were treated with incrementally increasing numbers of RF pulses (1–3) applied to a single area of Anal Mucosa. Two or three doses of 12 J/cm 2 were found to have acceptable patient tolerance and healing of the Mucosa within 4 weeks of ablation. Using these doses, 2 groups underwent ablation of 180° of contiguous Mucosa. Subjects experienced a loss of 1 to 3 days of daily activities of living, 7 to 14 days of postprocedure symptoms, and Mucosal healing within 4 weeks. One subject in the fi rst treatment group had the procedure aborted due to severe procedural pain. Conclusions: The study provides evidence of the safety and tolerability of Anal RFA of 180° of contiguous Mucosa in a single procedure and will allow future RFA effi cacy studies in the treatment of Anal dysplasia. Key words: Anal carcinoma, Anal dysplasia, human papillomavirus
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phase i study demonstrates safety and tolerability of radiofrequency ablation rfa of the Anal Mucosa
Hiv Clinical Trials, 2014Co-Authors: George A Smulian, Diana M. Moore, Jaime Robertson, Stephen M. KralovicAbstract:Background Anal carcinoma is increasing in high-risk populations. Dysplasia is often distributed throughout the Anal Mucosa, and focal ablative techniques have high rates of recurrence. Methods Wit...
