Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Surgery, Kyoto City Hospital, Kyoto, Japan.
J Hepatobiliary Pancreat Sci. 2024 Jul;31(7):455-467. doi: 10.1002/jhbp.12002. Epub 2024 Jun 6.
De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living-donor liver transplantation (LDLT) remain unclear.
We retrospectively reviewed 1781 primary LDLT recipients (1990-2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age-adjusted Japanese general population.
After 21 845 person-years follow-up, 153 DNM lesions (8.6%) were identified in 131 patients (7.4%). The incidence was 0.007 person-years. DNMs included 81 post-transplant lymphoproliferative disorders (PTLDs), 14 colorectal, 12 lung, and 12 gastric cancers, and so on. Comorbid DNMs significantly worsened recipient survival than those without (p < .001). The 5- and 10-year recipient survival after DNM diagnosis were 65% and 58%, respectively. Notably, SIR: 8.12 (95% CI: 3.71-15.4, p < .001) and SIR: 3.11 (1.34-6.12, p = .01) were significantly high, but had decreased time-dependently to SIR: 1.31 (0.68-2.29, p = .42) and SIR: 1.34 (0.75-2.20, p = .33), indicating no longer significant difference in DNMs development. Currently, however, SIR: 2.27 (1.54-3.22, p < .001) and SIR: 2.07 (1.40-2.96, p < .001) have become significantly higher again, reflecting recent aging of recipients (>50 years) and resultant increases in non-PTLD DNMs. Furthermore, characteristically in LDLT, the fewer the donor-recipient HLA-mismatches, the less the post-transplant DNMs development.
DNM development after LDLT was significantly higher than in the general population due to higher PTLD incidence (1993-1998), but once became equivalent (2005-2013), then significantly increased again (2014-2019) due to recent recipient aging and resultant increase in solid cancers.
实体器官移植后新发恶性肿瘤（DNM）是主要的不良事件；然而，活体供肝移植（LDLT）后 DNM 的特征和近期趋势仍不清楚。
我们回顾性分析了 1781 例原发性 LDLT 受者（1990-2020 年），并按年龄调整后计算了与日本普通人群相比 DNM 的标准化发病比（SIR）。
在 21845 人年的随访中，131 例患者（7.4%）中发现了 153 例 DNM 病变（8.6%）。发病率为 0.007 人年。DNM 包括 81 例移植后淋巴增殖性疾病（PTLD）、14 例结直肠癌、12 例肺癌和 12 例胃癌等。合并 DNM 显著降低了受者的生存（p<0.001）。DNM 诊断后 5 年和 10 年的受者生存率分别为 65%和 58%。值得注意的是，SIR：8.12（95%CI：3.71-15.4，p<0.001）和 SIR：3.11（1.34-6.12，p=0.01）显著升高，但随着时间的推移，SIR 逐渐降低至 1.31（0.68-2.29，p=0.42）和 SIR：1.34（0.75-2.20，p=0.33），表明 DNM 的发展不再有显著差异。然而，目前 SIR：2.27（1.54-3.22，p<0.001）和 SIR：2.07（1.40-2.96，p<0.001）再次显著升高，反映了受者（>50 岁）的近期老龄化和非-PTLD DNM 的增加。此外，在 LDLT 中，供体与受者 HLA 错配越少，移植后 DNM 的发展就越少。
由于 PTLD 发病率较高（1993-1998 年），LDLT 后 DNM 的发展明显高于普通人群，但一旦在 2005-2013 年变得相当，随后由于受者的近期老龄化和由此导致的实体癌增加，再次显著增加（2014-2019 年）。
