Prognostic value of apoptosis-regulating protein expression in anal squamous cell carcinoma.
(49/430)
PURPOSE: This study evaluated the prognostic value of pro and antiapoptotic protein expression, as well as that of spontaneous apoptosis, in anal carcinoma patients treated by radiotherapy (RT) with or without chemotherapy. EXPERIMENTAL DESIGN: Ninety-eight patients with available pretreatment biopsy specimens were studied. Patients had been treated with split-course RT: 30-40 Gy fractionated external beam, followed by a 20-22-Gy boost using interstitial or external RT. Fifty-one patients also received concomitant mitomycin-C and 5-fluorouracil. Median follow-up for surviving patients was 124 months. Tissue sections were examined immunohistochemically for expression of proapoptotic proteins (Bax, p53), antiapoptotic proteins (Bcl-2, Mcl-1), and spontaneous apoptosis (M30). Except for M30, staining of less than 5% of tumor cells was considered negative. Protein expression was correlated with local tumor control (LC) and disease-free survival (DFS) outcomes. The Kaplan-Meier method was used for the monovariate analysis and the Cox proportional hazard models for the multivariate analysis. RESULTS: For LC, beside advanced T- and N-categories and longer overall treatment time (OTT), lack of Bcl-2 expression was associated with poorer 5-year outcome (62 versus 84%, P = 0.009). For DFS, advanced T- and N-categories, longer OTT, and the lack of Bcl-2 expression correlated significantly with lower rates. In the multivariate analysis, N-category (P = 0.0026), OTT (P = 0.04), Bcl-2 (P = 0.0015), and M30 (P = 0.035) expressions were significant factors for LC. For DFS, age (P = 0.049) an N-category (P < 0.0001), as well as expression of Bcl-2 (P = 0.001), p53 (P = 0.003), and M30 (P = 0.03), were found to be independent significant variables. Patients with Bcl-2(+)/p53(-) tumors had a significantly higher 5-year LC compared with patients whose tumors were Bcl-2(-)/p53(+) (93 versus 53%, P = 0.004). CONCLUSIONS: Bcl-2 and particularly the combination of p53 and Bcl-2 expression may prove to be useful predictors of tumor response to RT or radiochemotherapy in anal carcinomas. Patients having tumors that are Bcl-2(-) and p53(+) may require intensified radiochemotherapy or adoption of an alternative therapeutic approach. (+info)
Surgical salvage therapy of anal cancer.
(50/430)
AIM: To evaluate the results of salvage resection in the management of persistent or locally recurrent anal canal cancer. METHODS: Details of all patients with anal canal cancer treated from 1978 to 1994 at Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) were reviewed retrospectively. Sixteen patients who presented with persistent or locally recurrent anal canal cancer received salvage surgery. Before surgery all of the patients had received radiotherapy alone as their primary treatments. RESULTS: Of the 16 patients, 14 received salvage abdominoperineal resection (APR) and two had transanal local excision. There were no deaths attributable to operation. Delayed healing of the perineal wound occurred in eight patients. Complications unrelated to the perineal wound were found in five patients. The median follow-up time was 120 (range 5-245) months after salvage surgery. Nine patients died of disease progression, with a median survival time of 16 (range 5-27) months. Six patients had a long-term survival. CONCLUSION: Salvage resection after radiotherapy can yield a long-time survival in selected patients with anal canal cancer. However it offers little hope to patients with T4 and/or N(2-3) tumors. (+info)
Implantation anal metastases after out-patient treatment of haemorrhoids.
(51/430)
Viable exfoliated colorectal cancer cells may be implicated in some cases of suture line recurrence. Whether they can implant and grow on raw surfaces is debatable. Two cases of anal implantation metastases after out-patient haemorrhoidal treatment are described. (+info)
Biochemotherapy in patients with metastatic anorectal mucosal melanoma.
(52/430)
BACKGROUND: Patients with metastatic anorectal melanoma generally have an unfavorable prognosis, but no effective systemic therapy has been reported. METHODS: The authors retrospectively evaluated the medical records of all patients with metastatic anorectal melanoma treated with biochemotherapy between January 1991 and December 2001 at the University of Texas M. D. Anderson Cancer Center (Houston, TX). RESULTS: The search yielded 18 patients. Of these patients, 14 had undergone treatment with cisplatin (CDDP), vinblastine (VB), dacarbazine (DTIC), interferon alpha-2b (IFN), and interleukin 2 (IL-2); 2 had undergone treatment with CDDP, VB, DTIC, and IFN; 1 had undergone treatment with CDDP, IFN, and IL-2; and 1 had undergone treatment with CDDP, VB, temozolomide, IFN, and IL-2. All IL-2 treatments were administered intravenously. The median follow-up time was 12.2 months (range, 3.5-43.7 months). Eight patients (44%) had major responses, including two (11%) complete responses (CRs). Three patients were lost to follow-up evaluation after the completion of treatment. The median time to progression among the 15 remaining patients was 6.2 months. Four patients, including 1 with a CR, were alive at their last documented follow-up visits (survival: 14.0, 20.7, 31.3, and 43.7 months, respectively). The median overall survival was 12.2 months. Among 13 patients who received biochemotherapy as first-line systemic therapy, 6 patients (46%) had major responses, including two (15%) CRs. The median time to progression for this group was 6.2 months, and the median overall survival was 12.9 months. CONCLUSIONS: Biochemotherapy had substantial activity against metastatic anorectal melanoma and should be considered for use in the treatment of metastatic disease from primary anorectal melanoma. (+info)
Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination.
(53/430)
PURPOSE: The purpose is to study the immunogenicity of heterologous prime-boost human papillomavirus (HPV) oncogene vaccination in patients with anogenital intraepithelial neoplasia (AGIN). EXPERIMENTAL DESIGN: Twenty-nine women with high-grade AGIN received three i.m. doses of TA-CIN (HPV-16 L2/E6/E7 protein) at four weekly intervals followed by a single dermal scarification of vaccinia HPV-16/18 E6/E7 and were followed up for 12 weeks. Immunity to HPV-16 was assessed by lymphoproliferation, IFN-gamma enzyme-linked immunospot (ELISPOT), and ELISA. RESULTS: The patient group significantly responded to TA-CIN and not to the control antigen HPV-6 L2/E7 at all postvaccination time points when compared with baseline responses (P < or = 0.05). Ten of the patients showed at least a 3-fold increase in TA-CIN-specific proliferation at one or more time points after vaccination. Comparison of stimulation with HPV-16 E6- or E7-GST fusion proteins showed that proliferative responses were biased to HPV-16 E6. This bias was also seen by IFN-gamma ELISPOT using overlapping peptides, with HPV-16 E6- or E7-specific T cells being detected in 9 and 2 patients, respectively. In addition, vaccination resulted in the induction of antibodies against the HPV-16 oncoproteins. Of the 6 clinical responders, 2 patients showed both a proliferative TA-CIN-specific response and an E6-specific IFN-gamma response, whereas 3 other patients displayed E6-specific reactivity only. Stable disease was recorded in 19 patients, 8 of whom showed a concomitant TA-CIN-specific proliferative and/or E6-specific T-cell response. Of the 4 progressors, 2 failed to make a T-cell response and 2 responded by either proliferation or E6 ELISPOT alone. CONCLUSIONS: The prime-boost regimen is immunogenic in AGIN patients (humoral and cellular immunity), but there is no simple relationship between induction of systemic HPV-16-specific immunity and clinical outcome. Other factors that may play a role in the eradication of long-term established AGIN lesions need to be determined to identify the patient group that would benefit from immunotherapy with the vaccines used in this study. (+info)
High resolution anoscopy findings for men who have sex with men: inaccuracy of anal cytology as a predictor of histologic high-grade anal intraepithelial neoplasia and the impact of HIV serostatus.
(54/430)
We compared the pathological diagnoses obtained by anal Papanicolaou (Pap) smear with those obtained by anal biopsy or by surgical excision for 153 men who have sex with men (MSM). Analysis of these paired specimens showed that anal Pap smears were an inaccurate predictor of high-grade anal dysplasia, regardless of human immunodeficiency virus (HIV) serostatus. The presence of any abnormal anal cytological finding indicates a potential for high-grade dysplasia on histological examination of MSM. (+info)
Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer.
(55/430)
BACKGROUND: The incidence of anal cancer has increased among both men (160%) and women (78%) from 1973 to 2000 in the U.S. The authors conducted a population-based case-control study of anal cancer to examine factors that may account for this increase. METHODS: Men (n = 119 patients) and women (n = 187 patients) who were diagnosed with anal cancer between 1986 and 1998 in the Seattle area were ascertained through the local Surveillance, Epidemiology, and End Results registry. Control participants (n = 1700) were ascertained through random-digit telephone dialing. Participants were interviewed in person and provided blood samples. Archival tumor tissue was tested for human papilloma virus (HPV) DNA, and serum samples were tested for HPV type 16 (HPV-16). RESULTS: Overall, 88% of tumors (all histologies) in the study were found to be positive for HPV. HPV-16 was the most frequent HPV type detected (73% of all tumors), followed by HPV-18 (6.9%), regardless of gender. However, 97.7% of tumors from men who were not exclusively heterosexual contained HPV DNA. The risk of anal cancer increased among men (odds ratio [OR], 5.3; 95% confidence interval [95% CI], 2.4-12.0) and women (OR, 11.0; 95% CI, 5.5-22.1) who had > or = 15 sexual partners during their lifetime. Among men who were not exclusively heterosexual and women, receptive anal intercourse was related strongly to the risk of anal cancer (OR, 6.8 [95% CI, 1.4-33.8] and OR, 2.2 [95% CI, 1.4-3.3], respectively). Current smokers among men and women were at particularly high risk for anal cancer, independent of age and other risk factors (OR, 3.9 [95% CI, 1.9-8.0] and OR, 3.8 [95% CI, 2.4-6.2], respectively). CONCLUSIONS: The high proportion of tumors with detectable HPV suggests that infection with HPV is a necessary cause of anal cancer, similar to that of cervical cancer. Increases in the prevalence of exposures, such as cigarette smoking, anal intercourse, HPV infection, and the number of lifetime sexual partners, may account for the increasing incidence of anal cancer in men and women. (+info)
Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000.
(56/430)
BACKGROUND: Anal cancer is a rare malignancy of the anogenital tract that historically has affected women at a greater rate than men. METHODS: The authors analyzed changing trends in incidence rates and 5-year relative survival percentages for patients with anal cancer. The publicly available data used in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program, a system of population-based tumor registries in the United States. RESULTS: The incidence of anal cancer was similar for men and women between 1994 and 2000 (2.04 per 100,000 and 2.06 per 100,000, respectively), the most recent period for which data were available, whereas men had lower rates than did women between 1973 and 1979 (1.06 per 100,000, compared with 1.39 per 100,000), the earliest period for which data were available. In addition, recently, black men had higher incidence rates than did other race-specific and gender-specific groups (2.71 per 100,000). From the earliest period for which data were available to the most recent period, relative 5-year survival improved from 59% to 73% among women, was unchanged among men ( approximately 60%), and decreased from 45% to 27% among black men. Eighteen percent of patients who had distant disease were alive at 5 years, compared with 78% of patients who had localized disease. CONCLUSIONS: The incidence of anal cancer in the United States increased between 1973 and 2000, particularly among men. There were higher incidence rates and lower survival rates for black men compared with other race-specific and gender-specific groups. Later disease stage was inversely associated with the survival rate, indicating that earlier detection may improve the survival of patients with anal cancer. (+info)