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
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.
Transplantation. 2017 Aug;101(8):1859-1866. doi: 10.1097/TP.0000000000001725.
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.
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.
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.
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.
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。
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。
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。
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。