由于种系基因检测的可用性不断增加，实体瘤癌症预防的降低风险手术是一个紧迫的临床课题。我们研究了降低风险的全胃切除术 (RRTG) 的短期和长期结果，以及其对遗传性弥漫性胃癌综合征患者的健康相关生活质量 (QOL) 的鲜为人知的影响。接受 RRTG 作为一部分的个体对遗传性胃癌的单机构自然史研究进行了检查。评估了临床病理学细节、急性和慢性手术发病率以及健康相关的生活质量。使用经过验证的问卷来确定 QOL 评分和心理社会精神治疗指标。2017 年 10 月至 2021 年 12 月期间，有 126 名患者因致病性或可能致病性种系 CDH1 变异而接受了 RRTG。大多数患者（87.3%；110 /126) 患有 pT1aN0 胃癌，最终病理学具有印戒细胞特征。急性（<30 天）术后主要发病率较低（5.6%；7/126），并且几乎所有患者（98.4%）在全胃切除术后体重减轻。胃切除术后 2 年，94% (64/68) 的患者表现出至少一种慢性并发症（即胆汁反流、吞咽困难和微量营养素缺乏）。职业改变（23.5%）、离婚（3%）和酒精依赖（1.5%）是一些患者因全胃切除术而改变生活的后果。在中位随访时间为 24 个月的患者中，生活质量评分在胃切除术后 1 个月时下降，并在 6-12 个月时恢复到基线。RRTG 与改变生活的不良事件相关，在为 CDH1 变异患者提供咨询时应讨论这些不良事件。胃癌的预防。判断癌症预防手术的风险不仅应该根据如果不治疗则因疾病死亡的可能性来判断，还应该根据器官切除的实际后果来判断。

Risk-reducing surgery for cancer prevention in solid tumors is a pressing clinical topic because of the increasing availability of germline genetic testing. We examined the short- and long-term outcomes of risk-reducing total gastrectomy (RRTG) and its lesser-known impacts on health-related quality of life (QOL) in individuals with hereditary diffuse gastric cancer syndrome.Individuals who underwent RRTG as part of a single-institution natural history study of hereditary gastric cancers were examined. Clinicopathologic details, acute and chronic operative morbidity, and health-related QOL were assessed. Validated questionnaires were used to determine QOL scores and psycho-social-spiritual measures of healing.One hundred twenty-six individuals underwent RRTG because of a pathogenic or likely pathogenic germline CDH1 variant between October 2017 and December 2021. Most patients (87.3%; 110/126) had pT1aN0 gastric carcinoma with signet ring cell features on final pathology. Acute (<30 days) postoperative major morbidity was low (5.6%; 7/126) and nearly all patients (98.4%) lost weight after total gastrectomy. At 2 years after gastrectomy, 94% (64/68) of patients exhibited at least one chronic complication (ie, bile reflux, dysphagia, and micronutrient deficiency). Occupation change (23.5%), divorce (3%), and alcohol dependence (1.5%) were life-altering consequences attributed to total gastrectomy by some patients. In patients with a median follow-up of 24 months, QOL scores decreased at 1 month after gastrectomy and returned to baseline by 6-12 months.RRTG is associated with life-changing adverse events that should be discussed when counseling patients with CDH1 variants about gastric cancer prevention. The risks of cancer-prevention surgery should not only be judged in the context of likelihood of death due to disease if left untreated, but also based on the real consequences of organ removal.