原发性硬化性胆管炎肝移植术后新发癌症（不包括非黑色素瘤皮肤癌）的危险因素及预后
Risk Factors and Outcomes of De Novo Cancers (Excluding Nonmelanoma Skin Cancer) After Liver Transplantation for Primary Sclerosing Cholangitis.
作者信息
Mouchli Mohamad A, Singh Siddharth, Loftus Edward V, Boardman Lisa, Talwalkar Jayant, Rosen Charles B, Heimbach Julie K, Wiesner Russell H, Hasan Bashar, Poterucha John J, Kymberly Watt D
机构信息
1 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. 2 Division of Gastroenterology, Department of Internal Medicine, University of California San Diego, La Jolla, CA. 3 William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN.
出版信息
Transplantation. 2017 Aug;101(8):1859-1866. doi: 10.1097/TP.0000000000001725.
BACKGROUND
Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT.
METHODS
All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT.
RESULTS
Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy.
CONCLUSION
The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.
背景
与其他肝移植受者相比，原发性硬化性胆管炎（PSC）患者肝移植（LT）后发生恶性肿瘤的风险可能更高。我们旨在确定PSC患者LT后长期癌症相关死亡率的累积发生率和危险因素。
方法
1984年至2012年期间，所有因PSC接受LT且无胆管癌的成年患者均接受随访，随访至2015年6月。我们估计了LT后新发恶性肿瘤的累积发生率、危险因素和死亡率。
结果
共纳入293例患者（平均[标准差]年龄47[12]岁；63.3%为男性；LT时2.4%吸烟）。中位随访11.5年（范围6.4 - 18.6年），64例患者（21.8%）发生73例非皮肤癌，包括46例实体器官癌（肾癌11例；结直肠癌11例；前列腺癌7例；乳腺癌5例；胰腺癌5例；卵巢/子宫内膜/外阴癌3例；新发胆管癌4例）。22例患者发生血液系统恶性肿瘤（移植后淋巴细胞增殖性疾病18例；霍奇金病2例；骨髓增生异常综合征2例）。5例患者发生黑色素瘤。癌症的1年、5年、10年和20年累积发生率分别为2.1%、8.6%、18.7%和27%。发生癌症的PSC患者的死亡率高于未发生癌症的PSC患者（风险比，2.2；P < 0.01）。多因素分析显示，受者年龄和LT前国际标准化比值升高与新发（非皮肤）恶性肿瘤风险增加相关。
结论
晚期PSC患者LT后10年癌症累积风险为18.7%，移植后淋巴细胞增殖性疾病、结直肠癌和肾细胞癌最为常见。LT后新发非皮肤癌降低了总体移植后生存率。仅受者年龄和LT时国际标准化比值升高与非皮肤癌风险增加相关。
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