今日の臨床サポート

直腸肛門部腫瘤

著者: 金城謙太郎 帝京大学医学部総合診療科、帝京大学大学院公衆衛生学研究科

監修: 井村洋 飯塚病院

著者校正/監修レビュー済:2017/01/20
患者向け説明資料

概要・推奨   

  1. 問診(リスクファクターの聴取や、発生時期、症状(悪性を疑う体重減少等含む)の有無等。推奨度1)を行い、視診・触診(直聴診含む。推奨度1)、必要であれば血液検査を行う(推奨度2)。もし、腫瘤であれば、更なる検査として専門医にコンサルトするのが望ましい(推奨度1)
  1. 専門医による視診、触診(直腸診)、肛門鏡や大腸鏡による病変の確認(推奨度2)と、生検により病理組織学的診断(推奨度2)や、多臓器病変の精査として画像検査(造影CT,PET-CT等。推奨度2)の適応を考慮して診断を行う。また、専門医による診断のもと治療を行う(推奨度1)
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
金城謙太郎 : 研究費・助成金など(ファイザーヘルスリサーチ振興財団)[2022年]
監修:井村洋 : 未申告[2022年]

改訂のポイント:
  1. レビューと最新の情報を上記ガイドラインにて改訂を行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 直腸肛門部腫瘤は、外痔核、内痔核、直腸肛門部コンジローマ(肛門陰部疣贅)、肛門周囲膿瘍、直腸脱、ポリープ、直腸癌、肛門癌(上皮内含む)、ベーチェット病、メラノーマ、ボーエン病、痔瘻などを念頭に置いて診断、治療する[1]
  1. 高齢者、炎症性腸疾患・大腸直腸癌の家族歴、治療にもかかわらず出血が続く場合、体重減少、鉄欠乏性貧血など悪性を疑われる場合は、大腸鏡による精査、生検が必要である[1]
  1. 肛門上皮内悪性腫瘍は、ヒトパピローマウイルス(HPV)感染により生じ、肛門癌へ移行する。HPVによる子宮頚部癌の発展様式と同様である[2]
  1. 大腸癌(肛門癌含む)はわが国において、癌部位別総患者数151万8000人中、23万5000人である(他の消化器癌としては、胃癌21万3000人、肝・肝内胆管癌6万6000人)[3]。肛門がんは、全悪性腫瘍の0.1%、大腸がんの中でも2%程度、2016年の罹患者は1098人と報告がある。日本では腺がんが最も多く、扁平上皮癌は2割程度である[4]
  1. 肛門癌は米国において、消化器癌の2%を占め、2020年に推定される肛門がん、肛門管がん、肛門直腸部がんの新規症例数は8590名、死亡数は1350名と報告されている[5]。ここ30年で罹患数は増加し、特に女性、HPV感染、性交渉の生涯人数、陰部疣贅、喫煙、アナルセックスの受け入れ、ヒト免疫不全ウイルス(human immunodeficiency virus、HIV)でリスクが上がる。肛門癌は、他の消化器癌よりも、陰部悪性腫瘍とより似ている。また、男性同士でのアナルセックスによる罹患率の上昇が懸念されている[6][7]
  1. 肛門癌は手術により摘出可能なことが多いが、部位、大きさ、リンパ節転移が予後因子である。専門家へのコンサルトが必要であり、化学療法、放射線療法なども考慮する[1]
 
  1. 肛門上皮内高分化癌から、肛門癌へ移行するのは、子宮頚癌モデルと類似している。(参考文献:[8][9]
  1. 特にHIV陽性で、HPVウイルスに罹患している患者の肛門癌は、上皮内高分化癌から進展する。
  1. 癌化リスクが高い患者群では、肛門癌を積極的に疑うべきである。
問診・診察のポイント  
 
  1. 肛門括約筋や、その直上の腫瘤からの出血は、痔核と誤って認識され、診断が遅れることになる。

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文献 

Matthew V Fargo, Kelly M Latimer
Evaluation and management of common anorectal conditions.
Am Fam Physician. 2012 Mar 15;85(6):624-30.
Abstract/Text The prevalence of benign anorectal conditions in the primary care setting is high, although evidence of effective therapy is often lacking. In addition to recognizing common benign anorectal disorders, physicians must maintain a high index of suspicion for inflammatory and malignant disorders. Patients with red flags such as increased age, family history, persistent anorectal bleeding despite treatment, weight loss, or iron deficiency anemia should undergo colonoscopy. Pruritus ani, or perianal itching, is managed by treating the underlying cause, ensuring proper hygiene, and providing symptomatic relief with oral antihistamines, topical steroids, or topical capsaicin. Effective treatments for anal fissures include onabotulinumtoxinA, topical nitroglycerin, and topical calcium channel blockers. Symptomatic external hemorrhoids are managed with dietary modifications, topical steroids, and analgesics. Thrombosed hemorrhoids are best treated with hemorrhoidectomy if symptoms are present for less than 72 hours. Grades I through III internal hemorrhoids can be managed with rubber band ligation. For the treatment of grade III internal hemorrhoids, surgical hemorrhoidectomy has higher remission rates but increased pain and complication rates compared with rubber band ligation. Anorectal condylomas, or anogenital warts, are treated based on size and location, with office treatment consisting of topical trichloroacetic acid or podophyllin, cryotherapy, or laser treatment. Simple anorectal fistulas can be treated conservatively with sitz baths and analgesics, whereas complex or nonhealing fistulas may require surgery. Fecal impaction may be treated with polyethylene glycol, enemas, or manual disimpaction. Fecal incontinence is generally treated with loperamide and biofeedback. Surgical intervention is reserved for anal sphincter injury.

PMID 22534276
Abstract/Text As summarized in the last issue of the EJM, human papillomaviruses induce a great variety of neoplastic lesions of mucosal epithelia and the skin. Particular types of these viruses are associated with specific human cancers, most notably anogenital carcinomas. These tumours account for about fifteen percent of the whole worldwide cancer burden. However, recent epidemiological studies revealed that papillomavirus infections including those with the cancer-related papillomavirus types are very widespread even among asymptomatic healthy individuals. Here, the current understanding of the molecular events leading to papillomavirus-induced tumours will be reviewed. It is assumed that these tumours arise as a consequence of several molecular modifications of persistently papillomavirus-infected epithelial cells. Experimental studies revealed that the virus types associated with anogenital cancers harbour two potential oncogenes referred to as E6 and E7. These viral genes are consistently expressed in HPV-associated anogenital carcinoma cells. HPV-associated cervical carcinoma cells loose their neoplastic growth properties if the expression of the E6 and E7 genes is inhibited. The proteins encoded by these viral genes thus appear to be ideal targets for a specific pharmacological approach to treat papillomavirus associated cancers or their respective precursor lesions. Recent studies in animals furthermore suggest that active vaccination with the viral oncoprotein E7 prevents growth of papillomavirus associated tumours. Hence, the possibility arises that also in man, vaccination with the viral transforming proteins might prevent the development of papillomavirus associated cancers.

PMID 1341208
J R Daling, N S Weiss, L L Klopfenstein, L E Cochran, W H Chow, R Daifuku
Correlates of homosexual behavior and the incidence of anal cancer.
JAMA. 1982 Apr 9;247(14):1988-90.
Abstract/Text To determine whether characteristics that are correlated with male homosexual behavior are associated with the incidence of cancer, the names of persons with a diagnosis of cancer in western Washington during 1974 to 1979 were linked to those in the state syphlis registry. Eight of 47 men with anal cancer were found to have had a reactive FTA test result; the expected number, based on the proportion of reactive cases among men with other sites of cancer, was only 0.40. Among men with anal cancer identified through ten population-based cancer-reporting systems in the United States, 24.4% had never been married, compared with 7.8% of men with colon and rectal cancer. Neither of these relationships was observed for women with anal cancer. Because in men, but not in women, having had syphilis and being single are associated with the practice of anal intercourse, our data suggest that anal intercourse may be a risk factor for anal cancer.

PMID 7062503
J M Palefsky, E A Holly, M L Ralston, S P Arthur, N Jay, J M Berry, M M DaCosta, R Botts, T M Darragh
Anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual and bisexual men: prevalence and risk factors.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Apr 1;17(4):320-6.
Abstract/Text Anal cancer is more commonly found in homosexual and bisexual men than cervical cancer is in women. Invasive anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), and treatment of ASIL may prevent the development of anal cancer. We characterized the prevalence and risk factors for ASIL in 346 HIV-positive and 262 HIV-negative homosexual men. Anal cytology, biopsy of visible anal lesions, and human papillomavirus (HPV) tests were performed, and data on HIV serostatus, CD4 count, and medical and lifestyle history were collected. ASIL was diagnosed in 36% of HIV-positive men and 7% of HIV-negative men (relative risk [RR] = 5.7; 95% confidence interval [CI], 3.6-8.9). Among HIV-positive men, the RR for ASIL increased with lower CD4 levels but was elevated even in men with CD4 levels >500/mm3 (RR = 3.8; 95% CI, 2.1-6.7) when compared with HIV-negative men. High-level HPV infection, as measured by detection of both hybrid capture (HC) group A and group B types, was another significant risk factor for ASIL in both HIV-positive men (RR = 8.8; 95% CI, 2.3-35) and HIV-negative men (RR = 20; 95% CI, 5.5-71) when compared with HC-negative men. HIV-negative men with anal HPV infection and HIV-positive men, regardless of CD4 level, are at high risk for ASIL.

PMID 9525432
M Melbye, P Sprøgel
Aetiological parallel between anal cancer and cervical cancer.
Lancet. 1991 Sep 14;338(8768):657-9.
Abstract/Text It has been postulated that an infectious agent and/or specific sexual behaviour is involved in the aetiology of anal cancer, in analogy with the aetiology established for cancer of the cervix. A case-control study of 29,648 women with cancers registered in the Danish Cancer Registry during 1968-87 tested the hypothesis that anal cancer patients were more likely than patients with colon, stomach, or vulva cancer to have had a previous diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cervical cancer. The odds ratio of CIN, adjusted for age and year of diagnosis, for anal vs colon cancer was 5.2 (95% confidence interval [CI] 3.3-8.3), that for anal vs stomach cancer 3.6 (2.1-6.0), and that for anal vs vulva cancer 1.6 (0.9-2.9). The median time from diagnosis of CIN to diagnosis of the registered cancer was 151 months for anal, 112 months for vulva, 114 months for colon, and 126 months for stomach cancer. The association with previous invasive cervical cancer was also investigated; no patient with cervical cancer in this second analysis had been included in the CIN analysis. The odds ratios were similar. In addition, anal cancer patients were significantly more likely to have had cervical cancer than were patients with vulva cancer (odds ratio 1.8 [1.0-3.9]). The strong association between anal cancer and CIN/invasive cervical cancer suggests that these cancers share common risk factors. The association is at least as strong as that between cervical and vulva cancer.

PMID 1679474
A B Moscicki, N K Hills, S Shiboski, T M Darragh, N Jay, K Powell, E Hanson, S B Miller, S Farhat, J Palefsky
Risk factors for abnormal anal cytology in young heterosexual women.
Cancer Epidemiol Biomarkers Prev. 1999 Feb;8(2):173-8.
Abstract/Text Although anal cancers are up to four times more common in women than men, little is known about the natural history of anal human papillomavirus (HPV) infections and HPV-related anal lesions in women. This study reports on the prevalence of and risks for anal cytological abnormalities over a 1-year period in a cohort of young women participating in a study of the natural history of cervical HPV infection. In addition to their regularly scheduled sexual behavior interviews and cervical testing, consenting women received anal HPV DNA and cytological testing. Anal cytology smears were obtained from 410 women whose mean age was 22.5 +/- 2.5 years at the onset of the study. Sixteen women (3.9%) were found to have abnormal anal cytology: 4 women had low-grade squamous intraepithelial lesions (SILs) or condyloma; and 12 women had atypical cells of undetermined significance. Factors found to be significantly associated with abnormal anal cytology were a history of anal sex [odds ratio (OR), 6.90; 95% confidence interval (CI), 1.7-47.2], a history of cervical SILs (OR, 4.13; 95% CI, 1.3-14.9), and a current anal HPV infection (OR, 12.28; 95% CI, 3.9-43.5). The strong association between anal intercourse and the development of HPV-induced SILs supports the role of sexual transmission of HPV in anal SILs. Young women who had engaged in anal intercourse or had a history of cervical SILs were found to be at highest risk.

PMID 10067816
J M Palefsky, E A Holly, M L Ralston, S P Arthur, C J Hogeboom, T M Darragh
Anal cytological abnormalities and anal HPV infection in men with Centers for Disease Control group IV HIV disease.
Genitourin Med. 1997 Jun;73(3):174-80.
Abstract/Text OBJECTIVE: To characterise risk factors for abnormal and cytology and anal human papilloma virus (HPV) infection in homosexual/bisexual men with advanced HIV related immunosuppression.
DESIGN: Cross sectional study of men with Centers for Disease Control group IV HIV disease.
SETTING: The University of California San Francisco, AIDS Clinic.
PATIENTS: 129 homosexual or bisexual men with group IV HIV disease.
METHODS: A questionnaire was administered detailing tobacco, alcohol and recreational drug use, medical history, and sexual practices. Anal swabs for cytology and HPV studies were obtained, as was blood for CD4 levels.
MAIN OUTCOME MEASURES: Abnormal anal cytology and anal HPV infection.
RESULTS: Abnormal anal cytology was detected in 39% of subjects and anal HPV infection in 93% as measured by polymerase chain reaction (PCR). Risk factors for abnormal cytology in multivariate analysis included HPV 16/18 infection (measured by PCR, RR = 2.1, 95% CI = 1.2-3.5) and intravenous drug use (RR = 1.8, 95% CI = 1.2-2.7). Infection with HPV 6/11 also had significantly elevated RRs in a separate model. Cigarette smoking, alcohol use, recreational drug use, and low CD4 level were associated with abnormal anal cytology in univariate analysis, as was infection with multiple HPV types and high levels of hybrid capture group B viral DNA.
CONCLUSIONS: Anal cytological abnormalities and HPV infection are common among homosexual/bisexual men with group IV HIV disease. In this study population, the main risk factors for abnormal cytology were HPV infection and intravenous drug use.

PMID 9306896
O A Ogunbiyi, J H Scholefield, A T Raftery, J H Smith, S Duffy, F Sharp, K Rogers
Prevalence of anal human papillomavirus infection and intraepithelial neoplasia in renal allograft recipients.
Br J Surg. 1994 Mar;81(3):365-7.
Abstract/Text A study was performed to test the hypothesis that renal allograft recipients are at high risk of developing anal human papillomavirus (HPV) infection and anal intraepithelial neoplasia (AIN). A total of 133 renal allograft recipients and 145 control patients underwent anoscopy and biopsy. A polymerase chain reaction was used to detect HPV16 DNA in biopsy samples. A histological diagnosis of anal HPV infection or AIN was made in 32 allograft recipients (HPV infection, five; AIN I, 20; AIN II, three; AIN III, three; AIN III and anal cancer, one). One subject with AIN was detected in the control group. HPV16 DNA was detected in 47 and 12.4 per cent of anal biopsies in the allograft and control groups respectively. Renal allograft recipients are at high risk of developing anal HPV infection and neoplasia (P < 0.05). Further studies are required to determine whether screening anal examination is required in organ allograft recipients.

PMID 8173899

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