Effect of anal epidermoid cancer-related viruses on the dendritic (Langerhans') cells of the human anal mucosa.
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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 < 0.001) and the serum HIV load (odds ratio, 4.9; 95% confidence interval, 1.1-21.4 log/ml; P < 0.03) but not the serum CD4 T-lymphocyte rate as a predictive risk factor for having <17 LCs/mm tissue. 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. (+info)
Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus.
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Before the introduction of highly active antiretroviral therapy (HAART), several studies demonstrated a high prevalence of human papillomavirus (HPV) infection and associated anal intraepithelial neoplasia (AIN) in men who have sex with men, particularly in human immunodeficiency virus (HIV)-infected men with low CD4+ cell counts. Similarly high levels of anal HPV infection and AIN have been found in HIV-positive women. HIV-positive men and women are at an increased risk of developing anal cancer compared with the general population. Data suggest that there has been no reduction in the incidence of AIN after the introduction of HAART. Screening efforts have the potential to decrease the incidence of invasive anal cancer, and cost-effectiveness analyses have demonstrated the utility of anal cancer screening in select populations. Treatment for AIN remains challenging, but AIN is easier to treat when the lesions are small, and it is likely that a screening program would identify affected individuals at an earlier stage of disease. (+info)
Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma.
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PURPOSE: To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma. PATIENTS AND METHODS: Between 1989 and 2000, 23 patients with invasive anal-rectal melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two. RESULTS: After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2). CONCLUSION: Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR. (+info)
Microangiopathic hemolytic anemia in a patient with recurrent anal cancer and liver metastasis.
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Microangiopathic hemolytic anemia (MAHA) is a late but fatal complication in advanced cancers (cancer-associated). It may also appear in complete remission after chemotherapy (chemotherapy-related). Mucin-producing adenocarcinoma has been extensively studied in relation to this phenomenon. Squamous cell carcinoma with MAHA, on the other hand, has not often been reported in the English literature. Because of the difficulty of case collection, understanding of the association of MAHA and anal squamous cell carcinoma remains vague. We present a 60-year-old woman with anal cancer and liver metastasis. This patient received chemotherapy (mitomycin C, 5-fluoruracil, and cisplatin) and reached a good partial response. MAHA developed 2 months later, and tumor recurrence with rapid deterioration appeared 5 months later. The patient died 5 months after MAHA was diagnosed. We consider that the MAHA in this patient is chemotherapy-related. However, the possibility of cancer-associated MAHA could not be excluded. (+info)
Colposcopy in the follow-up of women with lower genital tract or perianal carcinoma.
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Colposcopy has gained acceptance in the management of patients with abnormal cytologic smears or visible lesions of the lower genital tract. The well documented potential for the development of multifocal neoplastic disease in these tissues provides the rationale for the suggested use of the colposcope in the follow-up of patients with a previously treated carcinoma of the lower genital or perianal region. The value of colposcopy in such a patient is discussed. (+info)
Malignant melanoma metastatic to bone marrow.
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Bone marrow aspiration and biopsy is a useful means of detecting systemic involvement in patients with non haematological malignancy. Metastases of malignant melanoma may be detected in the bone marrow in a small percentage of patients. Two cases of malignant melanoma, with metastasis to marrow at the time of presentation, are described. In one case, bone marrow was the first site where the malignancy was identified. Subsequent investigations revealed an anal melanoma. In the second case, the patient had widespread dissemination from a tonsillar melanoma to many organs of the body, including bone marrow. (+info)
Cisplatin-based combined modality therapy for anal carcinoma: a wider therapeutic index.
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BACKGROUND: Definitive chemoradiation therapy is the standard of care for anal carcinoma. The chemotherapy regimen comprising 5-fluorouracil (5-FU) and mitomycin-C is the most commonly used among patients with anal carcinoma but causes well documented toxicities. In the current study, the authors evaluated their experience in treating anal carcinoma with combined modality therapy using cisplatin and 5-FU. METHODS: A retrospective analysis was performed of 92 patients with nonmetastatic squamous cell carcinoma of the anus who were treated between 1989 and 1998. The primary tumor and involved lymph nodes received a total dose of 55 grays (Gy) administered in more than 30 daily fractions. Cisplatin (4 mg/m(2)/day) and 5-FU (250 mg/m(2)/day) were given as a continuous infusion, 5 days each week during the entire radiation course. Kaplan-Meier methodology was used to determine local control (LC), disease-free survival (DFS), and overall survival (OS). RESULTS: Ten patients had T1 or Tx, 43 had T2, 27 had T3, and 12 patients had T4 disease. There were 21 male and 71 female patients. Sixty-five patients (71%) were lymph node negative. With a median follow-up duration of 44 months, the actuarial 5-year OS rate was 85%, the DFS rate was 77%, and the colostomy-free survival rate was 82%. Local recurrences occurred in 16 patients (17%). Distant metastases (DM) occurred in eight patients (9%). Advanced T classification (> T2) predicted lower LC and DFS rates. Advanced N classification (> N1) predicted worse DFS, OS, and DM rates. Greater than 90% of patients completed treatment without significant treatment interruption. Only five patients developed acute toxicities of Radiation Therapy Oncology Group (RTOG) Grade 4 or higher and only three patients developed chronic toxicities of RTOG Grade 4 or higher. CONCLUSIONS: Combined modality therapy with continuous infusion of cisplatin and 5-FU is a well tolerated regimen that results in high rates of LC, OS, and sphincter preservation. These rates are comparable to the best results reported with mitomycin-C and 5-FU. Without the normally severe toxicity, cisplatin-based therapy results in a wider therapeutic index. (+info)
Screening for anal dysplasia associated with human papillomavirus.
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Anal dysplasia associated with human papillomavirus (HPV) infection occurs in substantial proportions of HIV-infected men and women and poses risk for anal carcinoma. Whether to routinely screen for HPV-associated anal dysplasia in this population, however, remains a debated question. Anal dysplasia is detectable by Pap screening and colposcopic biopsy; as Pap testing results have relatively low reproducibility, 2 baseline tests may be prudent. Screening should also ascertain risk factors for dysplasia, degree of immunosuppression, and history of prior anal disease. Although treatment options for anal dysplasia are limited by morbidity and high recurrence rates, early detection may permit better tolerance of therapy, and current estimates indicate that routine screening for the condition would be cost-effective. In addition, emerging immunologic therapies offer hope of more effective future treatment. This article summarizes a presentation given by Wm. Christopher Mathews, MD, MSPH, at the November 2002 International AIDS Society-USA course in San Diego. (+info)