Taole Mokoena DPhil FRCS Professor of Surgery University of Pretoria Kalafong Hospital 16 TH ANNUAL UP CONTROVERSIES IN SURGERYSYMPOSIUM

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1 Ethical Challenges in Surgical Management of Non-AIDS Defining Malignancies Taole Mokoena DPhil FRCS Professor of Surgery University of Pretoria Kalafong Hospital 16 TH ANNUAL UP CONTROVERSIES IN SURGERYSYMPOSIUM

2 INTRODUCTION HIV pandemic has changed epidemiology of cancer worldwide Some cancers are AIDS defining: Kaposi, Non-Hodgkins Lymphoma, Uterine Cervix SCC Some are Non-AIDS defining: emerged in the HAART era Hodgkins, Anal SCC, Hepatoma, Lung CA Deficient tumour immune surveillance and immune response are primary cause Longer survival after HAART gave rise to Non-AIDS defining cancers Many cancers are associated with viral aetiology

3 TABLE I: Interrupted CD4 level based HAART carries more risk for cancer compared to continuous HI Viral Suppression Therapy Rate per 1000 py Malignancy No. Pts IT CT pvalue ADM or NADM ADM NADM AIDS Defining Kaposi sarcoma Lymphoma NI Cervix Ca Non-Aids Defining Skin Lung Anal squamous Hepatocellular HI=human immunodeficiency; ADM=AIDS-defining malignancy; NADM=AIDS-defining malignancy IT= interrupted therapy; CT=Continuous therapy; py=patient year Modified from SMART Trial Results: Silverberg et al 2007

4 Table II: Similarities of Increase in Malignacies in the HIV Infected and in Transplant Recipients Similar Increased Incidence EBV related cancer Hodgkins lymphoma Non-Hodgkins lymphoma HHV-8-related cancer Kaposi Sarcoma HBV/HCV related cancer Liver cancer H.pylori-related cancer Stomach cancer HPV-related cancer Uterine cervix Valva and vagina Penis Anus Oral/pharynx Possibly HPV-related cancer non-melanoma skin cancer lip oesophagus larynx eye other kidney multiple myeloma leukaemia Melanoma EBV=Epstein-Barr virus; HHV=human herpes virus;hbv=hepatitis B virus; HCV=hepatitis C virus; HPV=human papilloma virus * most data from renal transplant: constructed from Grulich 4 et al 2007

5 Squamous Cell Carcinoma of Anus Anal SCC is relatively rare in general population Recent increase in HIV era homosexual men women practising anal sex Human Papilloma Virus infection a risk factor Comparable to uterine cervix SCC Management approach in principle follows cervix SCC Screening with PAP smear in high risk patient population Mainstay of treatment is chemoradiation Surgery reserved for the very early intra-epithelial neoplasia and salvage in failed chemoradiation HPV vaccination in high risk populations new option

6 Table VII: Pathologic evaluation of intraoperative biopsies of anal cancer at the time of first surgery Pathologic Diagnosis Number (%) Normal or Inflammatory changes 10 (5) LSIL 26 (14) HSIL 138 (73) Superficially invasive SCC 9 (5) Invasive SCC 5 (3) Total 188 L/HSIL= low/high grade squamous intra-epithelial lesion Pineda 8 et al 2008

7 Table VIII: Incidence of recurrence of anal cancer according to disease extent Disease extent Incidence of recurrence (percent) Circumferential 64 Extensive 62 Limited 37 P value Pinenda et al 2008

8 Management of Gastric Carcinoma in HIV/AIDS Setting Increase in mucosa associated lymphoid tumour (MALT) associated with Helicobacter pylori infection. Reported more increasingly in HIV infected individuals. Treatment is primarily non-surgical. Eradication of H.pyloric and chemotherapy gives good results.

9 Gastric Adenocarcinoma in HIV/AIDS Patients Less common association of gastric neoplasm with HIV infection is adenocarcinoma Treatment of choice is surgical resection

10 Management of Complications of Cancer in the HIV/AIDS Setting Many of the ADM and NADM may present for the first time with GIT complications or develop these during their non-surgical cancer treatment. The more common ADM to afflict the GIT are Kaposi and NHL. These may present with haemorrhage, obstruction or perforation. Such complications should be treated according to their own merits. However in a moribund patient with full blown AIDS it may be more humane to allow the patient to die with dignity

11 Conclusion HIV/AIDS pandemic has changed epidemiology of cancer Many have viral aetiology Primary treatment is chemoradiation Role of Surgery limited diagnostic treatment of complications palliative rarely primarily curative Most patients will need HAART prior to elective Px More humane to let the moribund die with dignity

12 References 1. Spano J-P, Costagliola D, Katlama C et al. AIDS-related malignancies: State of the art and therapeautic challenges. J Clin Oncol 2008;26: Angeletti PC, Zhang L, Wood C. The viral aetiology of AIDS-associated malignancies. Advances in Pharmacol 2008; 56: Silverberg MJ, Neuhaus J, Bower M et al. Risk of cancers during interrupted antirectroviral therapy in the SMART study. AIDS 2007; 21: Grulich A, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancer in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta analysis Lancet 2007; 370: Berretta M, Cinelli R, Martellotta F et al. Therapeautic approaches to AIDS-related malignancies. Oncogene 2003; 22: Abbasakoor F, Boulos PB. Anal intra-epithelial neoplasia. Br J Surg 2005; 92: Uronis HE, Bendell JC. Anal cancers: an overview. The Oncologist 2007;12: Pineda CE, Berry JM,Jay N, Palefsky JM, Welton ML. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intra-epithelial lesions: A ten-year experience. Dis Colon Rectum 2008; 51: Cleator S, Fife K, Nelson M et al. Treatment of HIV-associated invasive anal cancer with combined chemoradiation. Eur J Cancer 2000, 36: Manfredi R, Sabbatani S, Fasulo G. HIV-associated early gastric adenocarcinoma sussessfully cured with surgery, and followed up over eight years. Internat J STD & AIDS, 2007,18: Yequez JF, Martinez SA, Sands DR, Sands LR, Hellinger MD. Colorectal malignancies in HIV-positive patients. Am Surgeon 2003;69:

13 Thank you Audience for your Attention