一穴肛原癌2例报道与中文文献分析(英文)

Cloacogenic carcinoma is a rare tumor of rectum and anus, which originating from epithelium of the anal transitionzone of embryonic residuals. We described the medical history of two patients with cloacogenic carcinoma of anal canal andreviewed of the Chinese literature (January 1994 to March 2009). In conclusion, cloacogenic carcinoma of anal canal canobtain good results with a abdominoperineal excision (APE).     

Detection of human papilloma virus type 16 E6 mRNA in laryngeal squamous cell carcinoma by in situ hybridization

Objective  

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse. Human papilloma virus (HPV) is an epitheliotropic oncogenic virus that has been detected in a variety of head and neck tumors including LSCC. This retrospective study was to investigate the prevalence of HPV infection in patients with LSCC.     

Synchronous and metachronous colon lesions in squamous cell carcinoma of the anal canal

The charts of 79 patients with a histologic diagnosis of squamous cell carcinoma of the anal canal were reviewed to determine the incidence of synchronous and/or metachronous colon lesions. Forty-six patients underwent an adequate preoperative evaluation of the colon and rectum. Ten patients underwent colonoscopy, 33 patients underwent a barium enema, and three patients underwent colonoscopy and a barium enema. In this group six adenomatous polyps and three hyperplastic polyps were discovered. An adenocarcinoma of the sigmoid colon was found in another patient six months prior to the diagnosis of a squamous cell carcinoma of the anal canal. Twenty-three patients had follow-up evaluation of the large bowel for metachronous lesions following treatment of the squamous cell carcinoma of the anal canal. Ten patients underwent colonoscopy, three patients had a barium enema, and ten autopsies were available for analysis. In this group metachronous lesions consisted of two adenomatous polyps and one hyperplastic polyp.     

Squamous cell carcinoma of the anal canal and anal margin

Squamous cell carcinomas of the anal canal and margin are relatively uncommon neoplasms of the distal gastrointestinal tract and surrounding skin. The major risk factors for tumor development have been defined through various epidemiologic studies. Randomized, phase III trials have defined the standard of care for anal cancer tumors to be a combined modality approach of radiation therapy and chemotherapy. This nonsurgical, organ-sparing regimen results in good anal sphincter function in the majority of patients, and treatment efficacy is favorable when compared with historic surgical series. Anal margin tumors are staged and treated as skin cancers, with a more favorable prognosis.     

Distribution pattern of human papilloma virus 16 genome in cervical neoplasia by molecular in situ hybridization of tissue sections

Using a highly sensitive method with single-stranded RNA probes, we analyzed the distribution pattern of HPV 16 DNA by in situ hybridization in CIN II (10 cases), CIN III (11 cases) and in invasive cervical carcinoma (17 cases). The technique used detected as little as 20-50 viral genomes per cell. This sensitive technique unmasked HPV 16 genomes in the basal cells of all forms of CIN. In CIN III viral genomes were present throughout the entire thickness of the epithelium. There was a striking difference in the distribution of viral DNA in CIN II compared with CIN III and invasive cancer. Variable viral genome distribution was observed in CIN II with the highest copy number in the area of epithelial differentiation. In contrast, CIN III showed a uniform distribution pattern of HPV genomes reflecting the lack of epithelial maturation. The majority of invasive carcinomas showed the same uniform distribution of the HPV 16 genomes as CIN III.     

Benign anal lesions, inflammatory bowel disease and risk for high-risk human papillomavirus-positive and -negative anal carcinoma.

A central role in anal carcinogenesis of high-risk types of human papillomaviruses (hrHPV) was recently established, but the possible role of benign anal lesions has not been addressed in hrHPV-positive and -negative anal cancers. As part of a population-based case-control study in Denmark and Sweden, we interviewed 417 case patients (93 men and 324 women) diagnosed during the period 1991-94 with invasive or in situ anal cancer, 534 patients with adenocarcinoma of the rectum and 554 population controls. Anal cancer specimens (n = 388) were tested for HPV by the polymerase chain reaction. Excluding the 5 years immediately before diagnosis, men, but not women, with anal cancer reported a history of haemorrhoids [multivariate odds ratio (OR) 1.8; 95% confidence interval (CI) 1.04-3.2] and unspecific anal irritation (OR 4.5; CI 2.3-8.7) significantly more often than controls. Women with anal cancer did not report a history of benign anal lesions other than anal abscess to any greater extent than controls, but they had used anal suppositories more often (OR 1.5; CI 1.1-2.0). Patients with hrHPV in anal cancer tissue (84%) and those without (16%) reported similar histories of most benign anal lesions, but anal fissure or fistula was more common among hrHPV-positive cases. Ulcerative colitis and Crohn''s disease, reported by <1% of study participants, were not associated with anal cancer risk. The higher proportion of hrHPV-positive anal cancers among case patients with anal fissure or fistula suggests that such mucosal lesions may provide direct viral access to basal epithelial layers. Since risk associations with benign anal lesions in men may be confounded by unreported sexual behaviour, and since risk associations in women were generally negative, it seems unlikely that benign anal lesions act as promoters in hrHPV-associated anal carcinogenesis. Moreover, benign anal lesions appear not to be linked to an alternative, hrHPV-unassociated causal pathway to anal cancer. Ulcerative colitis and Crohn''s disease were not supported as causal factors for anal cancer.     

Radiation therapy for epidermoid carcinoma of the anal canal, clinical and treatment factors associated with outcome.

BACKGROUND AND PURPOSE: In recent years, treatment with combined chemotherapy and radiation has become the standard of care for epidermoid carcinoma of the anus. However, optimal radiotherapy techniques and doses are not well established. MATERIALS AND METHODS: During the period 1975-1997, 106 patients with epidermoid carcinoma of the anal canal underwent radiation therapy. Treatment policies evolved from radiation therapy alone or with surgery, to combined chemotherapy and radiation followed by surgery, to combined chemotherapy and radiation. RESULTS: Overall 74% of patients were NED (no evidence of disease) at last follow-up. The most important clinical correlate with ultimate freedom from disease (includes the contribution of salvage surgery) was extent of disease. The 5-year ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15% salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001, Tarone-Ware). There was no difference between planned vs. expectant surgery (5-year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The most important correlate with late toxicity was a history of major pelvic surgery (surgical vs. non-surgical group: P=0.013, Fisher's exact test, two-tailed summation). Thirty-three additional malignancies have been seen in 26 patients. The most common additional malignancies were gynecologic (nine cases), head and neck (six cases), and lung cancer (five cases). CONCLUSIONS: For T1/T2N0 disease, moderate doses of radiation combined with chemotherapy provided adequate treatment. T4N0 and N+ lesions are the most appropriate candidates for investigational protocols evaluating dose intensification. T3N0 tumors may also be appropriate for investigation; however, dose intensification may ultimately prove counterproductive if the cure rate is not improved and salvage surgery is rendered more difficult. The volume of irradiated small bowel should be minimized for patients who have a past history of major pelvic surgery or who (because of locally advanced tumors) may need salvage surgery in the future. Because of the occurrence of additional malignancy, patients with anal cancer should receive general oncologic screening in long-term follow-up.     

DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma.

PURPOSE: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. EXPERIMENTAL DESIGN: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. RESULTS: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. CONCLUSIONS: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.     

15例直肠肛管癌放射治疗加化疗的疗效

目的 观察放射治疗加化疗低位直肠癌与肛管癌的疗效与副反应。方法 15例低位直肠癌与肛管癌中4例有腹股沟淋巴结肿大者先行1～3个疗程化疗，其余先行DT40～60Gy外照射治疗。近距离放射治疗包括腔内和肛周组织间插植治疗(8～18Gy)。同时全身以氟尿嘧啶为主的静脉化疗，共3～6个疗程。结果 平均随访49．1个月，15例中14例肛门全部获得保留，局部控制率为60．0％，5年生存率为66．7％。主要急性并发症发生在消化道，腹泻发生占12／15，国际抗癌联盟(UICC)的2级以上腹泻占5／12；2例经保留灌肠治疗缓解；1例因放射性直肠炎慢性便血30个月；2例出现肛门失禁症状，其中1例经外科切除肛门结肠造口。9例出现UICC2级以上骨髓抑制，4例经粒细胞集落刺激因子治疗缓解，其余5例被迫中断化疗。结论 低位直肠肛管癌的全身化疗加放射治疗远期疗效较好，其疗效不比根治性手术差，能保留肛门提高患者生存质量。     

Epstein-barr virus detection in tumors of upper gastrointestinal tract. An in situ hybridization study in Pakistan

To examine the potential role of Epstein-Barr virus (EBV) in the carcinogenesis of upper gastrointestinal tract, we conducted an in situ hybridization assay for EBV-encoded small RNA (EBER) expression in the tumors of 56 oral and 50 esophageal squamous cell carcinoma (SCC) cases, and 52 stomach adenocarcinoma cases diagnosed in the King Edward Medical College and Allama Iqbal Medical College Lahore, Pakistan between 1996-2002. There were no malignancies with positive EBER expression in oral and esophageal SCC. Only one out of the 52 gastric adenocarcinoma cases (1.9%) was positive for EBER expression, and this frequency was relatively low as compared to cases reported worldwide. The case was a 42 year-old male patient and histologically classified as moderately differentiated tubular adenocarcinoma. In conclusion, the frequency of EBV-associated gastric carcinoma was relatively low in Pakistan. The present study could not confirm the involvement of EBV in the carcinogenesis of oral and esophageal SCC.     

Correlation between human papillomavirus infection and clinicopathological parameters in anal canal carcinoma

We evaluated human papillomavirus (HPV) DNA in 17 anal canal tumors and its correlation with symptomatology, tumor extension and prognosis. Five squamous carcinomas and 4 cloacogenic tumors resulted HPV+. Statistical analysis showed no correlation between HPV infection and tumor morphology, lymph node involvement or prognosis, and no significant difference in the duration of symptoms between HPV+ and HPV- patients. HPV are involved in the pathogenesis of the tumors, but are not responsible for an increased neoplastic malignancy. Anoscopy with brushing or biopsy is a suitable screening method to identify HPV.     

A case of squamous cell carcinoma of the anal cancer with associated human immunodeficiency virus

A 62-year-old man with internal piles tested positive for infection with HIV and was admitted to our hospital. He presented with an anal tumor with bilateral inguinal nodal metastasis and pain in the anus; the tumor was diagnosed as stage IIIb (cA1N2M0). The patient's immune system was unstable. Therefore, he was administered chemoradiotherapy [low dose 5-fluorouracil plus cisplatin (FP) and radiotherapy (RT)] following HAART. Chemoradiotherapy resulted in complete response. However, CT performed 2 years after the diagnosis showed a recurrence in the hilar and mediastinal lymph node. The patient was administered chemotherapy with 5-fluorouracil and cisplatin (5-FU/CDDP) to the metastatic lymph node. However, the treatment response was graded as progressive disease, and the treatment was changed from CDDP to mitomycin C (MMC). The patient developed non-hematologic toxicity and died within 3 years of the diagnosis. We report a case of squamous cell carcinoma of the anus with associated HIV infection.     

High-sensitivity human papilloma virus genotyping reveals near universal positivity in anal squamous cell carcinoma: Different implications for vaccine prevention and prognosis

BackgroundCharacterisation of human papilloma virus (HPV) infection in anal squamous cell carcinoma (ASCC) may have dual importance: first, aetiological; second, prognostic, informing outcome after chemo-radiotherapy (CRT). We undertook HPV genotyping, and allelic characterisations, to evaluate the aetiological role of HPV while simultaneously evaluating the impact of HPV genotyping on relapse-free (RFS) and overall survival (OS).MethodDual-primer HPV genotyping (subtypes 6, 11, 16, 18, 31, 33, 45, 52, 58) and DNA sequencing of HPV 16 positive tumours were analysed in 151 consecutively referred ASCCs, previously characterised by immunohistochemistry for p16 expression. In 110 patients treated with CRT, factors influencing RFS and OS were evaluated using univariate and multivariate models.ResultsHPV positivity was observed in 95%. HPV 16 accounted for 89%; of these, 64% harboured the T350G E6 variant. HPV 16 positivity was significantly correlated with improved 5-year RFS (62% versus 40%; p = 0.027) and OS (59% versus 38%; p = 0.019). p16 expression was also significantly correlated with improved 5-year RFS (positive versus negative: 65% versus 16%; p < 0.0001) and OS (63% versus 13%; p < 0.0001). In multivariable models that included HPV 16 status, p16 status, sex, and age, p16 expression remained an independent prognostic factor for RFS (p < 0.0001) and OS (p = 0.002).ConclusionIn ASCC, near-universal HPV detection rates were demonstrated, higher than generally reported in the literature, and supporting the development of multivalent HPV vaccinations for prevention. By contrast, p16 negatively, but not HPV 16 genotype, is an independent adverse prognosticator after chemo-radiotherapy in patients with ASCC.     

Genital human papilloma virus infection in males. A clinico-pathologic study.

From March 1987 to December 1988, 402 male sexual partners of 317 women with human papilloma virus (HPV) infection of the lower genital tract and 85 with HPV-associated cervical and/or vulvar intraepithelial neoplasia (CIN and/or VIN) were submitted to clinical examination and peniscopy. The latter was performed at a 6-15 X magnification after a 3 min exposure to 5% acetic acid solution. Visible lesions were biopsied. Thirty-one patients had clinical evidence of HPV infection in the glans, penile shaft or urethra, and 222 had peniscopic evidence of subclinical aceto-white lesions. Of 31 patients with clinical lesions, 11 showed also aceto-white subclinical lesions. Of 253 peniscopically positive males, 237 were biopsied and 191 of these were histologically ascertained. Three patients had penile intraepithelial neoplasia, one with clinical appearance of a Buschke-L?wenstein tumor. The incidence of HPV infection in male sexual partners of women affected by HPV infection of the lower genital tract associated or not with intraepithelial neoplasia is lower than expected. However, clinically negative males should not be considered disease free; in fact, 12 patients, negative at the first examination, showed histological evidence of HPV infection at subsequent controls. Therefore, follow-up of at least 6 months should be allowed to identify HPV bearing males. The reported low frequency of HPV infection may be due to the fact that the males may harbour the virus in the urethra, prostate or seminal vesicles or penis without any clinical evidence of disease. Although research for HPV-DNA in intraurethral and penile scraping material might be useful for diagnosis, peniscopy with a 5% acetic acid application remains the clinical test for evaluating HPV infection in males. The importance of peniscopy should be viewed with respect to the prevention of infection or reinfection of the female sexual partners, in addition to the specific diagnostic purpose in male patients.     

Synthetic vaccine for the treatment of lesions caused by high risk human papilloma virus

Until recently, therapeutic cancer vaccines only sporadically led to long-term clinical responses. We here report on a novel vaccine modality, characterized by the administration of long (23-45 amino acids) synthetic peptides in incomplete Freund adjuvant (mineral oil-based, Montanide ISA-51), delivered subcutaneously. Such vaccines were first demonstrated to be much more potent in preclinical T-cell response induction and tumor therapy experiments than short major histocompatibility complex class I-binding peptides that have been used extensively in the clinic. A long-peptide vaccine consisting of 13 overlapping peptides, together covering the entire length of the 2 oncogenic proteins E6 and E7 of high-risk human papilloma virus type 16 (HPV16), caused complete regression of all lesions and eradication of virus in 9 of 20 women with high-grade vulvar intraepithelial neoplasia. The nature and strength of the vaccine-induced T-cell response were significantly correlated with the clinical response. This vaccine promises to be of use, not only in patients with premalignant lesions caused by high-risk HPV16, but also in patients with malignant tumors caused by this virus, including HPV16-positive cervical cancer, anal cancer, and head and neck cancer.     

Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.

To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.