Pancreatic Cancer: An Exocrine Tumor With Endocrine Characteristics.

IF 7.5 1区 医学 Q1 SURGERY Annals of surgery Pub Date : 2024-12-01 Epub Date: 2023-12-05 DOI:10.1097/SLA.0000000000006168
Xinzhe Zhu, Zhiwen Xiao, He Liu, Pin Zhang, Shengming Deng, Lei Ding, Jingjing Feng, Jianfeng Luo, Quanxing Ni, Guopei Luo, Xianjun Yu
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Abstract

Objective: To examine the characteristics of patients with pancreatic cancer with long-term survival.

Background: Although pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified.

Methods: An indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤37 U/mL) subgroup.

Results: A normal CA19-9 level was an independent variable for overall survival (median survival, 18.1 vs 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose ( P < 0.001) and increased expression of insulin ( P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients.

Conclusions: CA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.

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胰腺癌:具有内分泌特征的外分泌肿瘤。
目的:探讨胰腺癌患者长期生存的特点。背景:虽然胰腺癌是一种高度致命的恶性肿瘤,但少数患者能够长期生存。这些患者的特征在很大程度上仍未确定。方法:采用经验证的胰腺癌生物标志物碳水化合物抗原19-9 (CA19-9)建立无痛亚组。1558例患者中,13.9%属于ca19 -9正常(≤37 U/mL)亚组。结果:正常的A19-9水平是总生存期的自变量(中位生存期,18.1个月vs. 9.7个月,风险比= 0.53,P < 0.001)。IV期ca19 -9正常癌患者的5年生存率高于I-IV期ca19 -9高癌患者(22.4%比6.8%,P = 0.034)。与ca19 -9高亚组相比,ca19 -9正常亚组表现出循环葡萄糖水平降低(P < 0.001)和胰岛素表达增加(P < 0.001)。葡萄糖是通过己糖胺生物合成途径进行CA19-9生物合成的底物。此外,在糖尿病的胰腺癌动物模型中,葡萄糖控制降低了CA19-9水平,提高了总生存率。在一项临床试验(NCT05306028)中,在接受主要抗癌治疗前,90.9%的患者血糖控制降低了CA19-9水平。结论:ca19 -9正常胰腺癌是一个明显的低糖高胰岛素的惰性亚组。血糖控制是一种很有前途的治疗胰腺癌的策略。
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来源期刊
Annals of surgery
Annals of surgery 医学-外科
CiteScore
14.40
自引率
4.40%
发文量
687
审稿时长
4 months
期刊介绍: The Annals of Surgery is a renowned surgery journal, recognized globally for its extensive scholarly references. It serves as a valuable resource for the international medical community by disseminating knowledge regarding important developments in surgical science and practice. Surgeons regularly turn to the Annals of Surgery to stay updated on innovative practices and techniques. The journal also offers special editorial features such as "Advances in Surgical Technique," offering timely coverage of ongoing clinical issues. Additionally, the journal publishes monthly review articles that address the latest concerns in surgical practice.
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