肾移植术后直肠及肛门恶性肿瘤的诊治

Diagnosis and treatment of rectal or anal carcinoma after renal transplantation

目的:报道肾移植术后直肠及肛门恶性肿瘤患者资料并复习相关文献,为肾移植术后直肠及肛门肿瘤的早期发现与治疗总结经验.方法:收集肾移植术后2年肛门鳞状细胞原位癌1例及肾移植术后14年直肠低分化腺癌及黏液腺癌1例.手术切除标本均中性福尔马林固定,石蜡包埋,4m切片并HE染色,行常规病理检查.应用EBER原位杂交检测EB病毒(Epstein-Barr virus,EBV)感染;导流原位杂交检测人类乳头瘤病毒(human papillomavirus,HPV)感染.在直肠腺癌中应用DNA直接测序检测K-ras、BRAF有无突变.结果:病例1,患者女性,54岁,肾移植术后应用吗替麦考酚酯胶囊、他克莫司胶囊及强的松进行免疫抑制治疗,既往患混合痔30余年.肾移植术后6mo出现间断性无痛性便后出血,保守治疗1年余,逐渐加重1mo,行手术治疗.病理检查示鳞状细胞原位癌.HPV、EBER检查均阴性.随访36mo未见复发及转移.病例2,患者男性39岁,肾移植术后应用吗替麦考酚酯胶囊及强的松进行免疫抑制治疗12年,因移植肾功能丧失停用免疫抑制剂1年后出现便血,消化内镜检查见直肠占位,行手术治疗.病理检查示直肠低分化腺癌,部分为黏液腺癌,脉管内见大量癌栓,癌组织浸润肠壁全层,肠周淋巴结见癌转移.测序发现K-ras与BRAF基因均为野生型.EBER原位杂交阴性,术后18mo见腹腔内复发及肝脏转移.结论:便血可以是肾移植后直肠与肛周恶性肿瘤患者的首发症状,免疫抑制剂的应用可能是肿瘤发生重要的促进因素;对免疫抑制治疗敏感或长期应用免疫抑制剂的患者特别是存在可能促进肿瘤发生的基础疾病的患者尤其应警惕肿瘤的发生.及早建立对肾移植术后患者直肠及肛周肿瘤的筛查制度及方法有利于肿瘤的早诊早治.

AIM： To report a case of rectal adenocarcinoma and a case of anal squamous cell carcinoma in situ after renal transplantation, and review the relevant literature. METHODS： A case of squamous cell carcinoma in situ arising in a patient 2 years after renal transplantation and a case of rectal adenocar- cinoma arising in a patient 14 years after renal transplantation were collected. The resected spec- imens were fixed in buffered formalin, paraffin- embedded, 4 pm-sectioned, and reviewed by two pathologists. Human papillary virus （HPV） and Epstein-Barr virus in the ad K-ras and BRAF genes （EBV） were detected both and squamous carcinoma. were sequenced in rectal adenocarcinoma to identify mutationsRESULTS： The patient suffering from squa- mous cell carcinoma in situ was a 54-year-old female, with a history of mixed hemorrhoid for 30 years without obvious bleeding. The regimen of mycophenolate mofetil （MMF）, prednisone （Pred） and tacrolimus was used to control rejec- tion reactions. Six months after transplantation, the patients complained of intermittent painless hemorrhage. The diagnosis of mixed hemor- rhoid was made by colonoscopy and conserva- tive treatment was performed consequently for the next year. Since the hemorrhage became worse in the last month, hemorrhoid resection was performed. Squamous carcinoma in situ was diagnosed. There was no HPV or EBV in- fection. No adverse events occurred in the next 36-mo follow-up period. The patient suffering from rectal adenocarcinoma was a 39-year old male who complained of bloody stools for one year and aggravation for I mo. Colonoscopy re- vealed a space-occupying lesion localized in the rectum. He was diagnosed with renal failure 15 years ago and accepted renal allograft 14 years ago. MMF and Pred were used as the immu- nosuppressant for 12 years and stopped as the allograft lost its function 2 years ago. Anterior resection was performed and pathologic exami- nation revealed poorly differentiated adenocar- cinoma mixed with mucinous adenocarcinoma accompanied with numerous cancerous emboli and lymph node metastasis （pT3N2aM0）. After 18 mo of follow-up, he suffered from abdominal relapse and hepatic metastasis. The lymphocytes infiltrating into the carcinoma were negative for EBER. Wild-type K-ras and BRAF were detected. CONCLUSION： Bloody stools can be the fist sign of anal or rectal carcinoma. Immunosup- pressive drugs may act as a pivotal enhancer during the pathogenesis of carcinoma. The pa- tients sensitive to immunosuppression therapy and/or undergoing long-term immunosuppres- sion therapy should be cautious of carcinoma.