Lee Colin Y C, Olivier Adriaan, Honing Judith, Lydon Anne-Marie, Richardson Susan, O'Donovan Maria, Tischkowitz Marc, Fitzgerald Rebecca C, di Pietro Massimiliano
School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Early Cancer Institute, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Lancet Oncol. 2023 Jan;24(1):107-116. doi: 10.1016/S1470-2045(22)00700-8. Epub 2022 Dec 9.
Hereditary diffuse gastric cancer, generally caused by germline pathogenic variants in CDH1, presents with early-onset signet ring cell carcinoma. Prophylactic total gastrectomy is the definitive treatment. Endoscopic surveillance can inform the timing of prophylactic total gastrectomy through detection of microscopic signet ring cell carcinoma foci. However, evidence is scarce about the optimal endoscopic sampling technique and characterisation of signet ring cell carcinoma foci in hereditary diffuse gastric cancer. We aimed to formally assess the diagnostic yield of different sampling strategies and to identify criteria for the characterisation of endoscopic lesions.
For this prospective longitudinal cohort study, we included individuals aged 18 years or older at the Cambridge University Hospitals National Health Service (NHS) Foundation Trust who fulfilled testing criteria for hereditary diffuse gastric cancer between June 1, 2005, and July 31, 2021. The primary outcome was detection of intramucosal signet ring cell carcinoma foci. We assessed the detection rate and anatomical location of signet ring cell carcinoma in random biopsy samples taken according to a systematic protocol compared with biopsies targeted to endoscopic findings. Endoscopic lesions were examined with white-light and narrow band imaging with magnification to assess the likelihood of cancerous foci.
145 individuals were included, of whom 68 (47%) were male and 92 (63%) carried the CDH1 pathogenic variant. 58 (40%) patients were diagnosed with invasive signet ring cell carcinoma over a median follow-up time of 51 months (IQR 18-80). The first diagnosis of signet ring cell carcinoma was most commonly made from random biopsies (29 [50%] of 58 patients), rather than targeted biopsies (15 [26%] patients). The anatomical distribution of signet ring cell carcinoma foci detected by random biopsies more accurately reflected those identified in prophylactic total gastrectomy specimens than did targeted biopsies. Omitting random biopsies in our cohort would have led to an under-diagnosis rate of 42%. Using a novel panel of endoscopic criteria, gastric lesions containing signet ring cell carcinoma were predicted with a sensitivity of 67·3% and a specificity of 90·2%.
Random biopsies enhance the early detection of signet ring cell carcinoma and are complementary to targeted biopsies in surveillance of hereditary diffuse gastric cancer. This sampling method should be the standard of care when performing all surveillance endoscopies for individuals with hereditary diffuse gastric cancer.
UK Medical Research Council.
遗传性弥漫性胃癌通常由CDH1基因种系致病性变异引起，表现为早发性印戒细胞癌。预防性全胃切除术是确定性治疗方法。内镜监测可通过检测微小印戒细胞癌病灶来确定预防性全胃切除术的时机。然而，关于遗传性弥漫性胃癌中最佳内镜采样技术及印戒细胞癌病灶特征的证据较少。我们旨在正式评估不同采样策略的诊断率，并确定内镜病变特征的标准。
在这项前瞻性纵向队列研究中，我们纳入了2005年6月1日至2021年7月31日期间在剑桥大学医院国民保健服务（NHS）基金会信托机构符合遗传性弥漫性胃癌检测标准、年龄在18岁及以上的个体。主要结局是检测黏膜内印戒细胞癌病灶。我们评估了根据系统方案采集的随机活检样本中印戒细胞癌的检出率和解剖位置，并与针对内镜检查结果的活检进行比较。通过白光和窄带成像放大检查内镜病变，以评估癌灶的可能性。
共纳入145名个体，其中68名（47%）为男性，92名（63%）携带CDH1致病性变异。在中位随访时间51个月（四分位间距18 - 80）期间，58名（40%）患者被诊断为浸润性印戒细胞癌。印戒细胞癌的首次诊断最常见于随机活检（58名患者中的29名[50%]），而非靶向活检（15名[26%]患者）。与靶向活检相比，随机活检检测到的印戒细胞癌病灶的解剖分布更准确地反映了预防性全胃切除标本中发现的情况。在我们的队列中省略随机活检会导致42%的漏诊率。使用一组新的内镜标准，预测含有印戒细胞癌的胃病变的敏感性为67.3%，特异性为90.2%。
随机活检可提高印戒细胞癌的早期检测率，在遗传性弥漫性胃癌监测中是对靶向活检的补充。在对遗传性弥漫性胃癌个体进行所有监测性内镜检查时，这种采样方法应成为标准治疗手段。
英国医学研究理事会。
