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Case of an anal problem PowerPoint Presentation

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Description : Check out this medical presentation on anal cancer, which is titled "Case of an anal problem", to know about the anal problems like “anal abnormality” with anal leakage and anal cancer etc.

Tags : anal cancer, problem, leakage, anorectal disease in HIV+ patients, Condylomata Acuminata of HPV, Condyloma Lata of 2’ Syphilis, Abscesses, Fistulae, Molluscum Contagiosum, Nodular HSV, Hemorrhoids, Rectal Prolapse, Anal Canal Cancers, Lymphoma, Ddx Anal Mass, anal squamous cell carcinoma, Anal SCC

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Slide 1-

case of an anal problem brought to you by the GI Consult Team
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SHx: caucasian MSM r. clinical psychologist rare EtOH no illicits/IVDU ever ID: 61M HIV+ CD4=256 admitted to psychiatry awaiting LTC placement for HIV-related dementia RFR: “anal abnormality” with anal leakage PMH: HIV HAART since 2007 no known opportunistic infections HIV-related dementia since 2007 remote penile warts & syphilis (treated 1970’s) bipolar depression (quiescent) smoker 40 pkyrs +FHx breast ca (aunt) Meds: Norvir RITONAVIR Truvada TENOFOVIR-EMTRICITABINE Telzir FOSAMPRENAVIR septra prophylaxis olanzapine
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HPI: Admitted for LTC placement Otherwise well, no fevers Constant anal leakage of fecal material ~1yr (+) sensation of discrete episodes of need to evacuate (+) has control over discrete bowel movements (+) formed BMs daily Never pain/bleeding FMD cannot recall doing DRE
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O/E: 120/70 82 RR16-100% RA Tmax 36.6 H+N no icterus, no oral or perioral lesions, no cerv/axill lymphadenopathy CVS normal Resp normal Abdo abdo soft & benign, no HSM (+) 2cm L non-tender inguinal lymph node On rectal exam…
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Photo Courtesy of Alex McDonald, St. Michael’s Hospital Media Centre
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differential diagnosis?
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Ddx New Anal Mass in an HIV+ Pt Infectious condyloma accuminata (HPV), condyloma lata (syphilis) perirectal/perianal abscess, fistulae hypertrophic HSV, VZV, CMV Structural hemorrhoids, skin tags, rectal prolapse, traumatic Neoplast (Malig) anal cancer (squamous-adeno-neuroendo-lymphoma-leiomyosarc) Kaposi’s, Bowen’s, Paget’s, BCC, melanoma mets ( and rarely ) Neoplast (Benign) lipoma, etc. granular cell tumour, etc
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anorectal disease in HIV+ patients
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Epidemiology 59,000 HIV+ adults in Canada 20051 1.2 million HIV+ adults in USA 20051 33.2 million HIV+ adults worldwide2 Anorectal Disease reported to MD by ~1/3 of all HIV+ patients3,4 #1 reason for surgical referral in HIV+4 1. UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance, 2006.2. WHO AIDS Epidemic Update, 2007. 3. Edwards et al. The gastrointestinal manifestations of AIDS. Aust N Z J Med 1990;20:141-8. 4. Miles et al. Surgical management of anorectal disease in HIV-positive homosexuals. Br J Surg 1990;77:869-71.
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Which Anorectal Diseases in HIV? Populations of HIV+ pts with anorectal complaints: n=1860 Nadal et al. Dis Colon Rectum 1999;42:649-54 n=260 Barrett et al. Dis Colon Rectum 1998;41:606-612 n=180 Yuhan et al. Dis Colon Rectum 1998;41:1367-70. n= 148 Puy et al. Int J Colorect Dis 1992;7:26-30. n=88 Retamozo et al. Rev de Soc Brasil Med 40(3):286-9. n=83 Sanchez et al. Rev Gastroenterol Mex 1998;63:89-920. 1 2 3 4 5 6
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Nadal et al., 1999 n=1860 1 2 3 4 5 6 Avg age “30’s to 40’s” “>88%M” (?CD4 ?MSM)Instituto de Infectologia Emiolio Ribas, Sao Paulo anorectal pain bleeding discharge obstipation
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Barrett et al., 1998 n=260 1 3 4 5 6 2 Avg 35yo CD4175 96%M 75%MSMColorectal Clinic, George Washington University 55% anorectal pain 19% mass 16% blood in stools 11% blood PR
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Yuhan et al., 1998 n=180 1 2 4 5 6 3 Avg 34yo CD4160 96%M 55%MSMColorectal Surgery Clinic, Chicago Cook County Hospital 57% anorectal pain 28% mass 12% blood PR 11% discharge
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Puy-Montbrun et al., 1991 n=148 1 2 3 5 6 4 Avg 34yo CD4? 97%M 69%MSMColoproctology Department, Hopital Leopold Bellan, France anorectal pain pruritus discharge mass
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Other Conditions Reported Molluscum, HSV, CMV, M. fortuitum Proctitis Pruritis ani, excoriation, lichenification Anal sinus, rectal stenosis Mucosal prolapse, sphincter atonia Anal Crohn’s disease, ulcerative colitis Various malignancies Traumatic wound
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Anorectal Disease Pre/Post HAART Generally, HAART: Can attenuates some pathologies (i.e. KAPOSI’S, NHL) Can exacerbate some pathologies ~IRIS (i.e. TB, CMV, PCP, JC) Can have no significant effect (i.e. HL, ANAL SCC) Gonzalez et al., 2004
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Anorectal Diseases HIV+ vs. HIV- Instituto de Infectologia de Sao Paolo 1989-1996HIV+ 88% were male aged 30’s-40’s Conjunto Hospitalar Mandaqui 1991-1996HIV-neg male=female, most aged 40’s-50’s 1. Nadal et al. Dis Colon Rectum 1999;42:649-54
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Caveats of Anorectal Disease in AIDS common probs exaggerated/atypical in appearance rare conditions need to be considered in the Ddx treatment complicated by immunosuppression
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infectious DeToma G et al. Eur Surg Res 2006;38:418-22.
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Condylomata Acuminata of HPV Previous photo: Giant Condyloma Acuminatum Marked papillary proliferation Tendency to deep invasion displacing surrounding tissues not verrucous carcinoma No infiltration of BM, lymphatics, blood vessels No distant mets possibly regional variant of verrucous carcinoma? infectious 1. DeToma G et al. Surgical management of perianal giant condyloma acuminatum. Eur Surg Res 2006;38:418-22.
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infectious Begovac J. NEJM 2005;352(7):708.
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Condyloma Lata of 2’ Syphilis Secondary syphilis Rash (one of many manifestations) is usually: symmetrical macular or papular covering entire trunk-extremities-palms-soles in moist areas: condyloma lata broad-based raised flat greyish-white most commonly near 1’ chancre site HIV+ cases of exaggerated condyloma lata described infectious
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infectious Medscape.com
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Abscesses & Fistulae Of 163 HIV+ presenting to Colorectal Surgery Clinic,n=47 “likely infectious etiology” 18 perirectal abscess requiring incision & drainage: 9 usual bowel flora 3 HSV 3 CMV 2 Neisseria gonorrhea 1 M. fortuitum 14 perianal fistulas 1. Goldberg et al. Microbiology of human immunodeficiency virus anorectal disease. Dis Colon Rectum 1994;37:439-43. infectious
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infectious Utdol.com
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infectious Molluscum Contagiosum In HIV, molluscum is associated with larger & more numerous lesions more incidence of polypoid with stalk more resistance to therapy1 decreased incidence with HAART2 1. Koopman et al. Molluscum contagiosum: a marker for advanced HIV infection. Br J Dermatol 1992;126:528. 2. Calista et al. Resolution of disseminated molluscum contagiosum with HAART in patients with AIDS. Eur J Dermatol 1999;9(3):211-3.
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infectious Simonsen et al. Clinics, 2008;63(1):143-6.
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Nodular HSV Previous Photo: 39M MSM HIV on HAART CD4=400painful perianal nodules 3 months Bx: cytoarchitectural alterations c/w HSVimmunohistochemical test (+)HSV-2 Potentially verrucous-like hyperplastic in HIV1: HSV, VZV, molluscum, CMV 1. Simonsen et al. Atypical perianal herpes simplex infection in HIV-positive patients. Clinics, 2008;63(1):143-6. infectious
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structural Hemorrhoids
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http://www.stanford.edu/class/humbio103/ParaSites2002 structural
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Rectal Prolapse This photo: prolapse 2’ to Trichuris trichiura (whipworm) 2nd most common nematode infxn after pinworm worms bury their heads into intestinal walls elastic epithelial loosening rectal prolapse rare -- seen occ in severe pediatric Trichiuriasis structural
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http://www.acthiv.org neoplastic
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Anal Canal Cancers Previous photo: 40MSM CD4=450 on HAARTulcerating lesion biopsied: invasive squamous cell ca neoplastic http://www.acthiv.org
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Rakoto. Annales de chirurgie, 2003;128:265-7.. neoplastic
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Lymphoma Previous photo: Anal Burkitt’s Lymphoma1 Primary anorectal lymphoma rare ~3-6% of GIT lymphomas amongst gen pop3,4but higher incidence in case series of HIV+ patients who develop lymphoma2 1. Ioachim HL et al. EBV-associated anorectal lymphomas in patients with acquired immune deficiency syndrome. Am J Surg Pathol 1997;21:997-1006. 2. Ioachim et al. AIDS-associated lymphomas. Hum Pathol 1991;22:659-73. 3. Saraga et al. Hum Pathol 1981;12:713-23…3/66 4. Papadimitiou et al. Cancer 1985;55:870-9…2/83 neoplastic
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back to our case…
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Ddx Anal Mass in Our HIV+ Patient Infectious condyloma accuminata, condyloma lata perirectal/perianal abscess, fistulae hypertrophic HSV-VZV-CMV-molluscum Structural hemorrhoids, skin tags, rectal prolapse, trauma Neoplast (Malig) anal cancer (squamous-adeno-neuroendo-lymphoma-leiomyosarc) Kaposi’s, Bowen’s, Paget’s, BCC, melanoma mets ( and rarely ) Neoplast (Benign) lipoma, etc. granular cell tumour, etc.
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Investigations Bloodwork: Colonoscopy: 122M84 9.1 208 1364.7 11125 952.5 Ca/Mg/Phos normalbumin 26AST/ALT/bili/ALP norm INR/PTT norm Hard near-circumferential massExtends ?6cm from anal verge Origin ?below dentate No synchronous lesions
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Moderately-Differentiated Invasive Squamous Cell Carcinoma
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Moderately-Differentiated Invasive Squamous Cell Carcinoma
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CT Chest-Abdo-Pelvis
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MRI T2 Weighted
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MRI T2 Weighted
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MRI with Gadolinium
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anal squamous cell carcinomain HIV+ patients
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Background: Anatomy Endoderm Ectoderm Superior rectalveins Inferiorrectalveins Inferior Mesentericvein & lymph nodes Internal Iliac vein & Superficial inguinallymph nodes
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Roughly, Classification is actually histology-based anal adenocarcinomas are really rectal cancers anal squamous cell carcinomaabove dentate line are anal non-keratinizing squamous cell carcinomabelow dentate line are anal keratininzing squamous cell carcinoma anal melanoma other (neuroendocrine, carcinoid, Kaposi’s, leimyosarcoma, lymphoma) Background: Other Anal Cancers “rectal cancer” “anal cancer” 1. Klas et al. Malignant tumours of the anal canal. Cancer 1999;85(8):1686-93.
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Roughly, Classification is actually histology-based anal adenocarcinomas are really rectal cancers anal squamous cell carcinomaabove dentate line are anal non-keratinizing squamous cell carcinomabelow dentate line are anal keratininzing squamous cell carcinoma anal melanoma other (neuroendocrine, carcinoid, Kaposi’s, leimyosarcoma, lymphoma) Background: Other Anal Cancers “rectal cancer” “anal cancer” 1. Klas et al. Malignant tumours of the anal canal. Cancer 1999;85(8):1686-93.
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Epidemiology 1. Jemal et al. Cancer statistics 2007. CA Cancer J Clin 2007;57:43-66. 2. Frisch et al. HPV-associated cancers in HIV-AIDS. J Natl Cancer Inst 2000;92:1500-1510. 3. Klencke et al. Anal cancer: an HIV-associated cancer. Hem Onc Clin N Amer 2003;17(3):859-72. 4. Melbye M et al. High incidence of anal cancer among AIDS patients. Lancet 1994;343:636-9. 5. Diamond et al. Increased incidence of anal cancer among men with AIDS. Sex Trans Dis 2005;32:314-20. 6. Hessol et al. The impact of HAART on non-AIDS-defining cancers. Am J Epidemiol 2007;165:1143-53.
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Clinical Presentation1,2 anal bleeding (freq attrib to hemorrhoids) mass 20% asymptomatic groin pain sometimes assoc /w inguinal LN involvement Risk Factors: HIV, HPV, anoreceptive sex history of cervical cancer or CIN smoking 1. Ryan et al. Carcinoma of the anal canal. NEJM 2000;342:792-800. 2. Ryan et al. Anal carcinoma: histology, staging, epidemiology, treatment. Curr Opin Oncol 2000;12:345-52.
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Background: HPV & Anal SCC HPV DNA commonly present & epidemiologically linked Tumour samples consistently contain viral E6 & E7 proteins E6 & E7 have transforming properties & can interact /w host proteins E6 & E7 expression is necessary to maintain a malignant phenotypein cervical cancer . 1. Hildesheim et al., Persistence of HPV infection among normal women. J Infect Dis 1994;169:235-40.
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Background: HPV & Anal SCC 1.Villiers Virology 2004;324:17-27. Most common among HIV+ Men: 6, 16, 18, 31 Vandersnoek et al., 2005 n=286 HIV+ Men Assoc with 70% of anal cancers in pop-based studies: 16
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Background: HPV & Anal SCC HPV DNA commonly present & epidemiologically linked Tumour samples consistently contain viral E6 & E7 proteins E6 & E7 have transforming properties & can interact /w host proteins E6 & E7 expression is necessary to maintain a malignant phenotypein cervical cancer Molecularly2 : 1. Zur Hausen H. Papillomavirus causing cancer: evasion from host-cell control. J Natl Cancer Inst 2000;92(9):690-8.2. Uptodate.com p53 Proceed to S phase Pause to allowDNA repair after damage E6
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Background: HPV & Anal SCC HPV DNA commonly present & epidemiologically linked Tumour samples consistently contain viral E6 & E7 proteins E6 & E7 have transforming properties & can interact /w host proteins E6 & E7 expression is necessary to maintain a malignant phenotypein cervical cancer Molecularly2 : 1. Zur Hausen H. Papillomavirus causing cancer: evasion from host-cell control. J Natl Cancer Inst 2000;92(9):690-8.2. Uptodate.com p53 Proceed to S phase Pause to allowDNA repair after damage E6
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Background: HPV & Anal SCC HPV DNA commonly present & epidemiologically linked Tumour samples consistently contain viral E6 & E7 proteins E6 & E7 have transforming properties & can interact /w host proteins E6 & E7 expression is necessary to maintain a malignant phenotypein cervical cancer Molecularly2 : 1. Zur Hausen H. Papillomavirus causing cancer: evasion from host-cell control. J Natl Cancer Inst 2000;92(9):690-8.2. Uptodate.com Rb Proceed to S phase E2TF
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Background: HPV & Anal SCC HPV DNA commonly present & epidemiologically linked Tumour samples consistently contain viral E6 & E7 proteins E6 & E7 have transforming properties & can interact /w host proteins E6 & E7 expression is necessary to maintain a malignant phenotypein cervical cancer Molecularly2 : 1. Zur Hausen H. Papillomavirus causing cancer: evasion from host-cell control. J Natl Cancer Inst 2000;92(9):690-8.2. Uptodate.com Rb Proceed to S phase E2TF
Slide 57-

Background: HPV & Anal SCC HPV DNA commonly present & epidemiologically linked Tumour samples consistently contain viral E6 & E7 proteins E6 & E7 have transforming properties & can interact /w host proteins E6 & E7 expression is necessary to maintain a malignant phenotypein cervical cancer Molecularly2 : 1. Zur Hausen H. Papillomavirus causing cancer: evasion from host-cell control. J Natl Cancer Inst 2000;92(9):690-8.2. Uptodate.com Proceed to S phase E2TF Rb
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1. Vernon et al. The HIV-1 tat protein enhances E2-dependent HPV 16 transcription. Virus Res 1993;27(2):133-452. Grulich et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007;370:59-67. Background: Anal SCC & Immune Sys HIV slower HPV clearance & CD4 correlated with HSIL but Increased incidence despite HAART Anal cancer studies no CD4 correlation HIV+ less effective clearance of HPV Other factors at play (i.e. tat up-regulates E6 & E71)
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If Anal Cancer Suspected… Physical exam Size: Inguinal LN: FNAB or biopsy if suspicious1 Women: gyne exam + cervical cancer screening American Joint Commission on CancerAnal Squamous Cell Carcinoma Staging 1. Grade B Recommendation from American Society of Colorectal Surgeons (Level of Evidence IV)
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If Anal Cancer Suspected… Endoscopy + biopsies Colonoscopy if age >50 or any RF for concomitant colorectal ca1 Otherwise could just do sigmoidoscopy or anoscopy1 CT scan chest-abdo for staging (R/O mets) MRI can clarify local spread PET can identify mets missed in 25% of cases 20% of inguinal LN “neg” on exam and CT are (+) on PET2 Cotter 2006: of HIV+ anal cancer patients, 44% +LN on PET 16% +LN on CT 1. Grade B Recommendation from American Society of Colorectal Surgeons (Level of Evidence IV) 2. Trautmann et al. PET for pretreatment staging in cancer of the anal canal. Mol Imaging Biol 2005;7:309-13. 3. Cotter et al. FDG-PT/CT in evaluation of anal carcinoma. Int J Rad Oncol Biol Phys 2006;65:20-5.
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Treatment1 1. National Comprehensive Cancer Network. Anal Carcinoma Practice Guideline v.1.2008, www.nccn.org Before mid-1980’s: everyone APR, 5-yr survival ~40-50% Mid-1990’s: chemorad vs. rad Local failure at 3yrs39% chemorad61% rad only Complete remission 80% chemorad 54% rad only /
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1. National Comprehensive Cancer Network. Anal Carcinoma Practice Guideline v.1.2008, www.nccn.org
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Treatment Points Specific to HIV+ Pre-treatment CD4 count predicts outcome & tolerance of chemoradiation1 CD4 >200 similar to general pop CD4 <200 sig more toxicity from Tx…closer monitoring HAART  better tolerance of chemoradiation2  improved local tumour control2 1. Hoffman et al. Significance of pretreatment CD4 count on outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Rad Oncol Biol Phys 1999;44:127-31. 2. Place et al. Outcome analysis of HIV patients with anal squamous cell carcinoma. Dis Colon Rectum 2001;44:506-12.
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Obviating Anal SCC Risk: Applying Cervical Cancer Concepts Based on biological behaviour: Same nomenclature therefore applied: Anal squamous intraepithelial lesion Cervical squamous intraepithelial lesion ~ ~ www.analcancerinfo.ucsf.edu SquamousCell Carcinoma putatively
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Randomized RCT’s documenting value of screening for ASIL in HIV+: Randomized RCT’s documenting value of screening for CSIL in women: none. none, but large body of evidence accumulated from observational studies Obviating Anal SCC Risk: Applying Cervical Cancer Concepts
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Table from Kreuter et al. Anal intraepithelial neoplasia in HIV infection. JDDG 2008;6:1-9.
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1. Kreuter et al. Anal intraepithelial neoplasia in HIV infection. JDDG 2008;6:1-9.
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Obviating Anal SCC Risk: Applying Cervical Cancer Concepts 1. Kreuter et al. Anal intraepithelial neoplasia in HIV infection. JDDG 2008;6:1-9. (Anoscopy with 3% acetic acid) Normal transformation zone
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Obviating Anal SCC Risk No consensus in favour of screening Sensitivity of anal cytology ~50-80%1 Screening HIV-neg MSM q2-3 yrs “is cost-effective”2 Many feel it is advisable to screen high-risk groups: All MSM even if HIV-neg All HIV+ regardless of sexual practices Known cervical ca, vulvar HSIL or vulvar cancer Transplant recipients 1. Goldie et al. The clinical effectiveness of screening for ASIL and cancer in HIV-neg homosexual men. JAMA 1999;281:1822-1829 2. Kreuter et al. Anal intraepithelial neoplasia in HIV infection. JDDG 2008;6:1-9.
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Obviating Anal SCC Risk No consensus in favour of screening Many experts feel it is advisable to screen high-risk groups: All MSM even if HIV-neg All HIV+ regardless of sexual practices Known cervical ca, vulvar HSIL or vulvar cancer Transplant recipients ?
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the consult team would like to thankMr. CDr. David BellDr. BurnsteinDr. BaldersonAlex McDonaldYvonne from 17CC
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ppt slide no 72 content not found
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Obviating Anal SCC Risk: Anal Paps WHO Criteria for Screening Tests1: Condition sought should be of significant relavence to pop There should be useful intervention if disease is detected Natural history of the disease should be understood There should be a latent or early symptomatic stage Facilities for diagnosis and treatment should be available Treatment started at early stage should be of more benefit than treatment started later Screening should be relatively cost-effective       ? 1. Wilson and Junger. Principles and practice of screening for disease, Public Health Papers No. 34. WHO Geneva 1968, cited by www.nt.gov.au/health/healthdev/health_promotion/bushbook/volume1/bibliography3.html