Clinical Features of de Novo Lung Neuroendocrine Tumor after Liver Transplantation for Hepatocellular Carcinoma

• Jianwen Lin

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Jiali Yang

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Jianjun Lu

  Medical Records, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Xiaoyi Hao

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Jiawei Liu

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Huali Yan

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Huayi Li

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Yu Guo

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Yong Gu

  Departments of Private Medical Center, and Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

• Quanyong Cheng

  Departments of Private Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

Objective: To analyze the clinical features of de novo lung neuroendocrine tumor (NET) after liver transplantation (LT) for hepatocellular carcinoma (HCC).

Method: Retrospectively reviewed the clinical data of the 1253 patients who underwent LT from 2013 to 2022 in our institute.

Result: Out of 1253 recipients of LT 7 patients suffered de novo lung carcinoma, of these 2 patients suffered lung NET accounting for 28.6% (2/7) of de novo lung carcinoma both at extensive stage. New on-set lung lesions and hilar and mediastinal lymphadenopathy were found by imaging tests; and were diagnosed as lung NETs in both patients through pathological examination. The interval between LT and diagnosis of lung NET ranged from 5.9 to 44.7 months. Both patients received cisplatin and etoposide as first-line chemotherapy and achieved partial remission. The progression-free survival period ranged from 1.9 to 2.2 months. Survival after diagnosis of lung NET ranged from 7.0 to 10.9 months. One of the patients tried to cease immunosuppressants during chemotherapy and incurred graft rejection.

Conclusion: Lung NET may have a higher proportional incidence of de novo lung carcinoma in LT recipients. Early diagnosis is vital for the treatment of lung NET, while predictive and timely biopsy based on imaging findings is crucial for making an early diagnosis.

Shalaby S, Burra P. De novo and recurrent malignancy. Best Practice & Research Clinical Gastroenterology 2020; 46-47: 101680. https://doi.org/10.1016/j.bpg.2020.101680

Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation 2005; 80(2 Suppl): S254-64. https://doi.org/10.1097/01.tp.0000186382.81130.ba

Chapman JR, Webster AC, Wong G. Cancer in the transplant recipient. Cold Spring Harb Perspect Med 2013; 3(7). https://doi.org/10.1101/cshperspect.a015677

Seree O, et al. Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients. Liver Transpl 2018; 24(10): 1425-1436. https://doi.org/10.1002/lt.25310

Schrem H, et al. Incidence and Long-Term Risk of De Novo Malignancies After Liver Transplantation With Implications for Prevention and Detection. Liver Transplantation 2013; 19: 1252-1261. https://doi.org/10.1002/lt.23722

Choudhary NS, et al. Extrahepatic Malignancies and Liver Transplantation: Current Status. Journal of Clinical and Experimental Hepatology 2021; 11(4): 494-500. https://doi.org/10.1016/j.jceh.2020.10.008

Mehta N, et al. Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant. JAMA Oncol 2017; 3(4): 493-500. https://doi.org/10.1001/jamaoncol.2016.5116

Sapisochin G, et al. Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series. Ann Surg Oncol 2015; 22(7): 2286-94. https://doi.org/10.1245/s10434-014-4273-6

Kornberg A, et al. Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: clinical patterns and outcome variables. Eur J Surg Oncol 2010; 36(3): 275-80. https://doi.org/10.1016/j.ejso.2009.10.001

Sharma P, et al. Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era. Dig Dis Sci 2012; 57(3): 806-12. https://doi.org/10.1007/s10620-011-1910-9

Fernandez-Sevilla E, et al. Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection? Liver Transpl 2017; 23(4): 440-447. https://doi.org/10.1002/lt.24742

Alshahrani AA, et al. Clinical Features and Surveillance of Very Late Hepatocellular Carcinoma Recurrence After Liver Transplantation. Ann Transplant 2018; 23: 659-665. https://doi.org/10.12659/AOT.910598

Roh YN, et al. The prognosis and treatment outcomes of patients with recurrent hepatocellular carcinoma after liver transplantation. Clin Transplant 2014; 28(1): 141-8. https://doi.org/10.1111/ctr.12286

Patel JA, Daoud D, Jain A. Review of Standardized Inci--dence Ratios (SIR) of non-lymphoid de novo malignancies after liver transplantation: Structured analysis of global differences. Transplantation Reviews 2022; 36(1): 100670. https://doi.org/10.1016/j.trre.2021.100670

Chandok N, Watt KD. Burden of de novo malignancy in the liver transplant recipient. Liver Transplantation 2012; 18: 1277-1289. https://doi.org/10.1002/lt.23531

Mukthinuthalapati PK, Gotur R, Ghabril M. Incidence, risk factors and outcomes ofde novo malignancies post liver transplantation. World Journal of Hepatology 2016; 8(12): 533. https://doi.org/10.4254/wjh.v8.i12.533

Miao Y, et al. De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population. Transplantation 2009; 87(9): 1347-59. https://doi.org/10.1097/TP.0b013e3181a238f6

Travis WD. Pathology of lung cancer. Clin Chest Med 2011; 32(4): 669-92. https://doi.org/10.1016/j.ccm.2011.08.005

Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol 2013; 31(8): 992-1001. https://doi.org/10.1200/JCO.2012.46.9270

Kalemkerian GP, et al. Small cell lung cancer. J Natl Compr Canc Netw 2013; 11(1): 78-98. https://doi.org/10.6004/jnccn.2013.0011

Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer 2017; 17(12): 725-737. https://doi.org/10.1038/nrc.2017.87

Kalemkerian GP. Staging and imaging of small cell lung cancer. Cancer Imaging 2012; 11: 253-8. https://doi.org/10.1102/1470-7330.2011.0036

Agarwal PD, Lucey MR. Management of hepatocellular carcinoma recurrence after liver transplantation. Annals of Hepatology 2022; 27(1): 100654. https://doi.org/10.1016/j.aohep.2021.100654

Sapisochin G, Bruix J. Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14(4): 203-217. https://doi.org/10.1038/nrgastro.2016.193

Uka K, et al. Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World Journal of Gastroenterology 2007; 13(3): 414-420. https://doi.org/10.3748/wjg.v13.i3.414

Ost D, Fein AM, Feinsilver SH. Clinical practice. The solitary pulmonary nodule. N Engl J Med 2003; 348(25): 2535-42. https://doi.org/10.1056/NEJMcp012290

Pastorino U, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997; 113(1): 37-49. https://doi.org/10.1016/S0022-5223(97)70397-0

Caparica R, et al. Pulmonary Nodules in Patients With Nonpulmonary Cancer: Not Always Metastases. J Glob Oncol 2016; 2(3): 138-144. https://doi.org/10.1200/JGO.2015.002089

Schneider BJ, Saxena A, Downey RJ. Surgery for Early-Stage Small Cell Lung Cancer. Journal of the National Comprehensive Cancer Network 2011; 9(10): 1132-1139. https://doi.org/10.6004/jnccn.2011.0094

Yang CJ, et al. Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer. Journal of Clinical Oncology 2016; 34(10): 1057-1064. https://doi.org/10.1200/JCO.2015.63.8171

Brock MV, et al. Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has come. The Journal of Thoracic and Cardiovascular Surgery 2005; 129(1): 64-72. https://doi.org/10.1016/j.jtcvs.2004.08.022

Farago AF, Keane FK. Current standards for clinical management of small cell lung cancer. Translational Lung Cancer Research 2018; 7(1): 69-79. https://doi.org/10.21037/tlcr.2018.01.16

Travis WD, et al. The 2015 World Health Organization Classification of Lung Tumors. Journal of Thoracic Oncology 2015; 10(9): 1243-1260. https://doi.org/10.1097/JTO.0000000000000630

Ajithkumar TV, et al. Management of solid tumours in organ-transplant recipients. Lancet Oncol 2007; 8(10): 921-32. https://doi.org/10.1016/S1470-2045(07)70315-7

Mazariegos GV, et al. Weaning of immunosuppression in liver transplant recipients. Transplantation 1997; 63(2): 243-9. https://doi.org/10.1097/00007890-199701270-00012

Shaked A, et al. Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. American Journal of Transplantation 2019; 19(5): 1397-1409. https://doi.org/10.1111/ajt.15205

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