Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Histopathology. 2020 Dec;77(6):865-876. doi: 10.1111/his.14220. Epub 2020 Sep 20.
Proton pump inhibitors (PPIs) are among the most widely used medications in the United States. Most PPI users have persistent hypergastrinaemia during treatment. However, gastric neuroendocrine tumours diagnosed in long-term PPI users are rarely reported. Their clinicopathological features and prognosis are not characterised. It remains unclear whether or not they can be classified as Type III sporadic tumours.
We retrospectively characterised 66 gastric neuroendocrine tumours from patients without atrophic gastritis and gastrinoma from two tertiary care medical centres, including 38 tumours in patients who had used PPIs for at least 1 year and 28 tumours from patients without long-term PPI use (control group, Type III tumours). Compared to controls, tumours from long-term PPI users tended to be in the pT1-2 category (98% versus 79%, P = 0.09) and less often invaded the serosa (3% versus 18%, P = 0.08) or lymphovascular spaces (11% versus 32%, P = 0.06). Using Kaplan-Meier analysis, long-term PPI users had significantly longer overall survival than controls (P = 0.035). While three control patients developed distant metastasis and seven died, long-term PPI users were without distant metastasis (P = 0.06) or death (P = 0.002) during follow-up. However, five long-term PPI users developed additional gastric neuroendocrine tumour(s), while none of the controls did (P = 0.07).
Our results show that gastric neuroendocrine tumours of long-term PPI users are probably less aggressive compared to Type III sporadic tumours and have an indolent disease course. Our findings support the classification of gastric neuroendocrine tumours in long-term PPI users as a separate subtype.
质子泵抑制剂 (PPI) 是美国使用最广泛的药物之一。大多数 PPI 使用者在治疗期间持续存在高胃泌素血症。然而，长期使用 PPI 的患者中诊断出的胃神经内分泌肿瘤很少报道。它们的临床病理特征和预后尚未确定。目前尚不清楚它们是否可以归类为 III 型散发性肿瘤。
我们回顾性描述了来自两个三级保健医疗中心的无萎缩性胃炎和胃泌素瘤的 66 例胃神经内分泌肿瘤患者的特征，包括至少使用 PPI 1 年的 38 例肿瘤患者和 28 例无长期 PPI 使用的患者（对照组，III 型肿瘤）。与对照组相比，长期使用 PPI 的患者的肿瘤更倾向于处于 pT1-2 期（98%对 79%，P=0.09），且更不易侵犯浆膜（3%对 18%，P=0.08）或淋巴管（11%对 32%，P=0.06）。使用 Kaplan-Meier 分析，长期使用 PPI 的患者总生存期明显长于对照组（P=0.035）。对照组中有 3 例患者发生远处转移，7 例患者死亡，而长期使用 PPI 的患者在随访期间无远处转移（P=0.06）或死亡（P=0.002）。然而，有 5 例长期使用 PPI 的患者发生了额外的胃神经内分泌肿瘤，而对照组没有（P=0.07）。
我们的结果表明，与 III 型散发性肿瘤相比，长期使用 PPI 的患者的胃神经内分泌肿瘤可能侵袭性较低，疾病进程较惰性。我们的发现支持将长期使用 PPI 的患者的胃神经内分泌肿瘤分类为一个单独的亚型。
