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Background <p>The prognostic significance of carcinoid syndrome (CS) in patients with neuroendocrine tumors (NETs) remains unclear. We aimed to evaluate its significance on surgical and long-term outcomes in a well-defined cohort of patients undergoing cytoreductive hepatectomy for small bowel NET liver metastasis (sbNETLM).</p> Methods <p>Patients undergoing cytoreductive hepatectomy between January 2000 and December 2020 were included (CS, <i>n</i>&#xa0;=&#xa0;154; non-functional, <i>n</i>&#xa0;=&#xa0;133); post-progression analysis extended through December 2023 in 191 patients.Query</p> Results <p>Age (60 vs. 63 years; <i>p</i>&#xa0;=&#xa0;0.059) and sex distribution (47% vs. 54% male; <i>p</i>&#xa0;=&#xa0;0.278) were similar in patients with CS compared with non-functional sbNETLM. CS was associated with more (<i>p</i>&#xa0;&lt;&#xa0;0.001) and larger (<i>p</i>&#xa0;&lt;&#xa0;0.001) hepatic metastases, requiring more frequent major hepatectomies (<i>p</i>&#xa0;&lt;&#xa0;0.001). Postoperative morbidity (22% vs. 21%; <i>p</i>&#xa0;=&#xa0;0.925) and 90&#xa0;day mortality (1% vs. 2%; <i>p</i>&#xa0;=&#xa0;0.666) were similar in major resections. In CS patients, median overall survival (mOS) and median progression-free survival (mPFS) were shorter (mOS: 10.1 vs. 12.5 years, <i>p</i>&#xa0;=&#xa0;0.035; mPFS: 1.6 vs. 2.4 years, <i>p</i>&#xa0;=&#xa0;0.015). In subgroups with extensive tumor burden, CS was linked to shorter mOS (9.2 vs. 15.3 years, <i>p</i>&#xa0;=&#xa0;0.028). Post-progression, 50% of CS patients and 41% of initially non-functional sbNETLM developed secondary CS, increasing the risk of carcinoid heart disease and mortality from cardiac and renal failure. CS was the strongest liver metastasis-specific predictor of mortality in multivariable regression analysis (HR 1.73, <i>p</i>&#xa0;=&#xa0;0.004).</p> Conclusion <p>While surgical risk is not elevated, long-term survival is reduced in CS. Secondary CS can develop after tumor progression, even in initially non-functional sbNETLM, further worsening prognosis. Regular screening and proactive management of CS may improve long-term outcomes.</p>

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Carcinoid Syndrome Impacts Long-Term Outcomes After Hepatectomy for Small Bowel Neuroendocrine Tumor Liver Metastasis

  • 期刊论文

  • 发表日期：

    2025年10月3日

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  • Markus Ammann,
  • Hallbera Gudmundsdottir,
  • Elizabeth B. Habermann,
  • Jonas Santol,
  • Vanja Podrascanin,
  • Yawen Dong,
  • Cornelius A. Thiels,
  • Susanne G. Warner,
  • Mark J. Truty,
  • Michael L. Kendrick,
  • Rory L. Smoot,
  • Heidi M. Connolly,
  • Thorvardur R. Halfdanarson,
  • Sean P. Cleary,
  • David M. Nagorney,
  • Patrick P. Starlinger

摘要

Background

The prognostic significance of carcinoid syndrome (CS) in patients with neuroendocrine tumors (NETs) remains unclear. We aimed to evaluate its significance on surgical and long-term outcomes in a well-defined cohort of patients undergoing cytoreductive hepatectomy for small bowel NET liver metastasis (sbNETLM).

Methods

Patients undergoing cytoreductive hepatectomy between January 2000 and December 2020 were included (CS, n = 154; non-functional, n = 133); post-progression analysis extended through December 2023 in 191 patients.Query

Results

Age (60 vs. 63 years; p = 0.059) and sex distribution (47% vs. 54% male; p = 0.278) were similar in patients with CS compared with non-functional sbNETLM. CS was associated with more (p < 0.001) and larger (p < 0.001) hepatic metastases, requiring more frequent major hepatectomies (p < 0.001). Postoperative morbidity (22% vs. 21%; p = 0.925) and 90 day mortality (1% vs. 2%; p = 0.666) were similar in major resections. In CS patients, median overall survival (mOS) and median progression-free survival (mPFS) were shorter (mOS: 10.1 vs. 12.5 years, p = 0.035; mPFS: 1.6 vs. 2.4 years, p = 0.015). In subgroups with extensive tumor burden, CS was linked to shorter mOS (9.2 vs. 15.3 years, p = 0.028). Post-progression, 50% of CS patients and 41% of initially non-functional sbNETLM developed secondary CS, increasing the risk of carcinoid heart disease and mortality from cardiac and renal failure. CS was the strongest liver metastasis-specific predictor of mortality in multivariable regression analysis (HR 1.73, p = 0.004).

Conclusion

While surgical risk is not elevated, long-term survival is reduced in CS. Secondary CS can develop after tumor progression, even in initially non-functional sbNETLM, further worsening prognosis. Regular screening and proactive management of CS may improve long-term outcomes.