Negro Silvia, Perissinotto Eleonora, Mammi Isabella, Crivellari Gino, Schiavi Francesca, Cappello Filippo, Spolverato Gaya, Ferrari Davide, Rausa Emanuele, Vitellaro Marco, Fassan Matteo, Cavestro Giulia Martina, Mannucci Alessandro, Lonardi Sara, Bergamo Francesca, Urso Emanuele D L
3rd Surgical Unit, Department of Surgical, Gastroenterological and Oncological Sciences, University of Padua, Padua, Italy.
Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
Tumori. 2025 Jan 30:3008916241310706. doi: 10.1177/03008916241310706.
Lynch syndrome is the most common hereditary cancer predisposition, accounting for 1-5% of colorectal cancer cases, and is driven by germline mutations in DNA mismatch repair genes. Despite established diagnostic criteria, such as the Amsterdam guidelines, Lynch syndrome remains largely underdiagnosed. To address this gap, universal tumour screening has been introduced for all newly diagnosed cases of colorectal cancer and endometrial cancer, significantly improving early detection. The surgical management of colorectal cancer in patients with Lynch syndrome remains controversial. While extended colectomy reduces the risk of metachronous colorectal cancer, surgical strategies must be carefully individualised based on patient-specific factors. Chemoprevention with aspirin has shown promise in reducing the risk of colorectal cancer, with ongoing trials investigating optimal dosing. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionised the treatment of Microsatellite Instability-High/deficient Mismatch Repair colorectal cancer, offering durable responses and significant survival benefits. In addition, the neoadjuvant use of immune checkpoint inhibitors is paving the way for non-surgical interventions, potentially transforming the management of colorectal cancer in patients with Lynch syndrome. A multidisciplinary approach and continued research are essential to optimise cancer prevention, treatment and quality of life for people with Lynch syndrome.
林奇综合征是最常见的遗传性癌症易感性疾病，占结直肠癌病例的1 - 5%，由DNA错配修复基因的种系突变引起。尽管有既定的诊断标准，如阿姆斯特丹指南，但林奇综合征在很大程度上仍未得到充分诊断。为了弥补这一差距，已对所有新诊断的结直肠癌和子宫内膜癌病例进行普遍肿瘤筛查，显著提高了早期检测率。林奇综合征患者结直肠癌的手术治疗仍存在争议。虽然扩大结肠切除术可降低异时性结直肠癌的风险，但手术策略必须根据患者的具体因素进行仔细个体化。阿司匹林化学预防在降低结直肠癌风险方面已显示出前景，目前正在进行试验以研究最佳剂量。免疫疗法，尤其是免疫检查点抑制剂，彻底改变了微卫星高度不稳定/错配修复缺陷型结直肠癌的治疗方式，带来了持久的反应和显著的生存益处。此外，免疫检查点抑制剂的新辅助使用为非手术干预铺平了道路，可能改变林奇综合征患者结直肠癌的治疗方式。多学科方法和持续研究对于优化林奇综合征患者的癌症预防、治疗和生活质量至关重要。
