Yu F, Venzon D J, Serrano J, Goebel S U, Doppman J L, Gibril F, Jensen R T
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1804, USA.
J Clin Oncol. 1999 Feb;17(2):615-30. doi: 10.1200/JCO.1999.17.2.615.
The long-term clinical course of unselected patients with gastrinomas as well as other functional pancreatic endocrine tumors (PETs) in whom the excess-hormone state is controlled is largely unknown. To address this issue, patients with gastrinomas were assessed.
Two hundred twelve patients with Zollinger-Ellison syndrome (ZES) were prospectively studied. All had controlled acid hypersecretion and were assessed yearly, with a mean follow-up period of 13.8+/-0.6 years (range, 0.1 to 31 years). Annual assessments of possible factors that might affect prognosis or treatment approaches were performed, such as those for tumor size and location; the presence, location, and extent of metastases; and the occurrence of ectopic Cushing's syndrome or another PET syndrome. Deaths were categorized as ZES-related or non-ZES-related and classified into different causes.
Thirty-one percent of patients died, all of non-acid-related causes. One half died of a ZES-related cause; they differed from those who died of non-ZES deaths by having a large primary tumor, more frequently a pancreatic tumor; lymph node, liver, or bone metastases; ectopic Cushing's syndrome; or higher gastrin levels. The extent of liver metastases correlated with survival rate. The presence of liver metastases alone only moderately decreased survival time; however, the additional development of bone metastases or ectopic Cushing's syndrome markedly decreased survival rate.
In ZES, gastrinoma growth is now the main single determinant of long-term survival, with one half of patients dying a gastrinoma-related death and none an acid-related death. Large primary tumors that are pancreatic in location, the development of liver metastases, (especially if associated with bone metastases or Cushing's syndrome), and the extent of liver metastases are all important prognostic factors. The identification of these factors allows the recognition of subgroups that can be used to tailor antitumor treatment approaches.
未经过挑选的胃泌素瘤患者以及其他功能性胰腺内分泌肿瘤（PETs）患者，其激素分泌过多状态得到控制后的长期临床病程在很大程度上尚不清楚。为解决这一问题，对胃泌素瘤患者进行了评估。
对212例佐林格-埃利森综合征（ZES）患者进行了前瞻性研究。所有患者胃酸分泌过多均得到控制，每年进行评估，平均随访期为13.8±0.6年（范围为0.1至31年）。对可能影响预后或治疗方法的因素进行年度评估，例如肿瘤大小和位置、转移的存在、位置和范围，以及异位库欣综合征或其他PET综合征的发生情况。死亡分为与ZES相关或与非ZES相关，并分类为不同原因。
31%的患者死亡，均为非酸相关原因。一半患者死于与ZES相关的原因；他们与死于非ZES相关原因的患者不同之处在于有较大的原发肿瘤，更常见的是胰腺肿瘤；有淋巴结、肝脏或骨转移；异位库欣综合征；或胃泌素水平较高。肝转移程度与生存率相关。仅存在肝转移仅适度缩短生存时间；然而，骨转移或异位库欣综合征的额外出现显著降低生存率。
在ZES中，胃泌素瘤的生长现在是长期生存的主要单一决定因素，一半患者死于与胃泌素瘤相关的死亡，无一例死于与酸相关的死亡。位于胰腺的大原发肿瘤、肝转移的发生（特别是如果与骨转移或库欣综合征相关）以及肝转移的程度都是重要的预后因素。识别这些因素有助于识别可用于定制抗肿瘤治疗方法的亚组。
