肝移植治疗肝脏转移性胃肠道间质瘤(附二例报告)
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摘要
目的初步探讨肝移植对无法切除的肝脏转移性胃肠道间质瘤(gastrointestinal stromal tumors,GIST)的疗效,并结合文献探讨其综合治疗策略。方法回顾性分析中山大学附属第一医院2例GIST术后肝转移病例行肝移植手术的临床资料。结果 1例63岁女性因十二指肠间质瘤行胰十二指肠切除术,另1例46岁女性因小肠间质瘤行小肠部分切除术,分别于13年和5年后出现了无法切除的多灶性肝转移。2例均给予序贯伊马替尼和苏尼替尼治疗,并联合经动脉化疗栓塞治疗,分别经过2年及1年8个月治疗,无缓解,接受了肝移植手术,术后无严重并发症,病理证实为转移性GIST,术后均接受免疫抑制剂和酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的治疗,分别随访31个月和24个月,未发现肿瘤复发或转移。结论肝移植可作为不可切除的肝转移性GIST病人治疗的一种选择,联合TKI靶向治疗在一定程度上可延长生存期,改善预后。
Objective To explore the efficacy of liver transplantation and comprehensive treatment strategies for cases of metastatic gastrointestinal stromal tumors(GISTs) of liver.Methods The clinical data of two patients with metastatic GISTs of liver in the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively.Results One 63-year-old woman who underwent pancreaticoduodenectomy(PD) due to a duodenal GIST 13 years ago and another 46-year-old woman who had partial resection of small bowel due to small intestinal GIST 5 years ago,were both found unresectable multifocal metastases of liver.Two patients were both treated with sequential imatinib mesylate and sunitinib malate,combined with transarterial chemoembolization(TACE) for 2 years and 1 year and 8 months respectively,and no remission was achieved.They both received liver transplantation successfully and recovered uneventfully.Metastatic GISTs were confirmed by postoperative pathological examination.Both cases were treated with immunosuppressive agents and TKI.There was no recurrence or metastasis during the period of 31-and 24-month follow-up respectively.Conclusion Liver transplantation might be an alternative option with a better prognosis for highly selected patients with unresectable metastatic GIST to the liver,and combined targeted therapy of TKI can prolong the survival and improve the prognosis.
Objective To explore the efficacy of liver transplantation and comprehensive treatment strategies for cases of metastatic gastrointestinal stromal tumors(GISTs) of liver.Methods The clinical data of two patients with metastatic GISTs of liver in the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively.Results One 63-year-old woman who underwent pancreaticoduodenectomy(PD) due to a duodenal GIST 13 years ago and another 46-year-old woman who had partial resection of small bowel due to small intestinal GIST 5 years ago,were both found unresectable multifocal metastases of liver.Two patients were both treated with sequential imatinib mesylate and sunitinib malate,combined with transarterial chemoembolization(TACE) for 2 years and 1 year and 8 months respectively,and no remission was achieved.They both received liver transplantation successfully and recovered uneventfully.Metastatic GISTs were confirmed by postoperative pathological examination.Both cases were treated with immunosuppressive agents and TKI.There was no recurrence or metastasis during the period of 31-and 24-month follow-up respectively.Conclusion Liver transplantation might be an alternative option with a better prognosis for highly selected patients with unresectable metastatic GIST to the liver,and combined targeted therapy of TKI can prolong the survival and improve the prognosis.
引文
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[11] Yoon IS,Shin JH,Han K,et al.Ultrasound-Guided Intraoperative Radiofrequency Ablation and Surgical Resection for Liver Metastasis from Malignant Gastrointestinal Stromal Tumors[J].Korean J Radiol,2018,19(1):54-62.DOI:10.3348/kjr.2018.19.1.54.
[12] Cameron S,Ramadori G,Fuzesi L,et al.Successful liver transplantation in two cases of metastatic gastrointestinal stromal tumors[J].Transplantation,2005,80(2):283-284.
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[14] Miettinen M,Lasota J.Gastrointestinal stromal tumors:review on morphology,molecular pathology,prognosis,and differential diagnosis[J].Arch Pathol Lab Med,2006,130(10):1466-1478.DOI:10.1043/1543-2165(2006)130[1466:GSTROM]2.0.CO;2.
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[16] Lim KT.Surgical treatment of gastrointestinal stromal tumors of the stomach:current status and future perspective[J].Transl Gastroenterol Hepatol,2017,2:104.DOI:10.21037/tgh.2017.12.01.
[17] Chen H,Pruitt A,Nicol TL,et al.Complete hepatic resection of metastases from leiomyosarcoma prolongs survival[J].J Gastrointest Surg,1998,2(2):151-155.
[18] DeMatteo RP,Shah A,Fong Y,et al.Results of hepatic resection for sarcoma metastatic to liver[J].Ann Surg,2001,234(4):540-547.
[19] Machairas N,Prodromidou A,Molmenti E,et al.Management of liver metastases from gastrointestinal stromal tumors:where do we stand?[J].J Gastrointest Oncol,2017,8(6):1100-1108.DOI:10.21037/jgo.2017.08.08.
[20] Bompas E,Boillot O,Bringuier PP,et al.Imatinib in patients with metastatic gastrointestinal stromal tumors relapsing after hepatic transplantation[J].Eur J Cancer,2004,40(9):1456-1457.
[21] Frilling A,Malago M,Testa E,et al.Liver transplantation for metastasized extragastrointestinal stromal tumor:A case report and an overview of literature[J].Transplantation Proceedings,2010,42(9):3843-3848.DOI:10.1016/j.transproceed.2010.06.016.
[22] Pararas N,Levi D,Selvaggi G,et al.Mass clamping of the hilum to facilitate difficult hepatectomy during liver transplantation.A single center 10 year experience[J].Ann Surg,2009,250(2):273-276.DOI:10.1097/SLA.0b013e3181b17161.
[23] Joensuu H,Eriksson M,Sundby Hall K,et al,Reichardt P.One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor:a randomized trial[J].JAMA,2012,307(12):1265-1272.DOI:10.1001/jama.2012.347.
[24] Platoff RM,Morano WF,Marconcini L,et al.Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era:Treatment Strategies for an Incurable Disease[J].Case Rep Oncol Med,2017,2017:8349090.DOI:10.1155/2017/8349090.
[25] Heinrich MC,Corless CL,Demetri GD,et al.Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor[J].J Clin Oncol,2003,21(23):4342-4349.DOI:10.1200/JCO.2003.04.190.
[26] Debiec-Rychter M,Sciot R,Le Cesne A,et al.EORTC Soft Tissue and Bone Sarcoma Group;Italian Sarcoma Group;Australasian GastroIntestinal Trials Group.KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors[J].Eur J Cancer,2006,42(8):1093-1103.DOI:10.1016/j.ejca.2006.01.030.
[27] Singer S,Rubin BP,Lux ML,et al.Prognostic value of KIT mutation type,mitotic activity,and histologic subtype in gastrointestinal stromal tumors[J].J Clin Oncol,2002,20(18):3898-3905.DOI:10.1200/JCO.2002.03.095.
[28] Quek R,Farid M,Kanjanapan Y,et al.Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor[J].Asia Pac J Clin Oncol,2017,13(3):115-124.DOI:10.1111/ajco.12603.
[29] George S,Wang Q,Heinrich MC,et al.Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib:a multicenter phase Ⅱ trial[J].J Clin Oncol,2012,30(19):2401-2407.DOI:10.1200/JCO.2011.39.9394.
[2] Mulkerrin G,Hogan NM,Sheehan M,et al.Melena as an unusual presentation of gastrointestinal stromal tumour,a case report[J].Int J Surg Case Rep,2018,44:172-175.DOI:10.1016/j.ijscr.2018.02.037.
[3] Charo LM,Burgoyne AM,Fanta PT,et al.A Novel PRKAR1B-BRAF Fusion in Gastrointestinal Stromal Tumor Guides Adjuvant Treatment Decision-Making During Pregnancy[J].J Natl Compr Canc Netw,2018,16(3):238-242.DOI:10.6004/jnccn.2017.7039.
[4] Wang T,Zhao H,Gao H,et al.Expression and phosphorylation of FOXO1 influences cell proliferation and apoptosis in the gastrointestinal stromal tumor cell line GIST-T1[J].Exp Ther Med,2018,15(4):3197-3202.DOI:10.3892/etm.2018.5853.
[5] Wardelmann E,Thomas N,Merkelbach-Bruse S,et al.Acquired resistance to imatinib in gastrointestinal stromal tumors caused by multiple KIT mutations[J].Lancet Oncol,2005,6(4):249-251.DOI:10.1016/S1470-2045(05)70097-8.
[6] Zhang Y,Wang YJ,Lu CJ,et al.Giant gastrointestinal stromal tumour of the stomach:a case report with surgical treatment[J].Ann R Coll Surg Engl,2018,100(3):e46-e48.DOI:10.1308/ rcsann.2017.0211.
[7] Ye H,Xin H,Zheng Q,et al.Prognostic role of the primary tumour site in patients with operable small intestine and gastrointestinal stromal tumours:a large population-based analysis[J].Oncotarget,2018,9(8):8147-8154.DOI:10.18632/oncotarget.23692.
[8] Rutkowski P,Jagielska B,Andrzejuk J,et al.The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors(GIST)[J].Contemp Oncol(Pozn),2017,21(4):285-289.DOI:10.5114/wo.2017.72393.
[9] Qiu HB,Zhou ZG,Feng XY,et al.Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy[J].Medicine(Baltimore),2018,97(2):e9097.DOI:10.1097/MD.0000000000009097.
[10] Husted TL,Neff G,Thomas MJ,et al.Liver transplantation for primary or metastatic sarcoma to the liver[J].Am J Transplant,2006,6(2):392-397.DOI:10.1111/j.1600-6143.2005.01179.x.
[11] Yoon IS,Shin JH,Han K,et al.Ultrasound-Guided Intraoperative Radiofrequency Ablation and Surgical Resection for Liver Metastasis from Malignant Gastrointestinal Stromal Tumors[J].Korean J Radiol,2018,19(1):54-62.DOI:10.3348/kjr.2018.19.1.54.
[12] Cameron S,Ramadori G,Fuzesi L,et al.Successful liver transplantation in two cases of metastatic gastrointestinal stromal tumors[J].Transplantation,2005,80(2):283-284.
[13] Liu X,Qiu H,Zhang P,et al.China Gastrointestinal Stromal Tumor Study Group(CN-GIST).Prognostic factors of primary gastrointestinal stromal tumors:a cohort study based on high- volume centers[J].Chin J Cancer Res,2018,30(1):61-71.DOI:10.21147/j.issn.1000- 9604.2018.01.07.
[14] Miettinen M,Lasota J.Gastrointestinal stromal tumors:review on morphology,molecular pathology,prognosis,and differential diagnosis[J].Arch Pathol Lab Med,2006,130(10):1466-1478.DOI:10.1043/1543-2165(2006)130[1466:GSTROM]2.0.CO;2.
[15] Tran T,Davila JA,El-Serag HB.The epidemiology of malignant gastrointestinal stromal tumors:an analysis of 1,458 cases from 1992 to 2000[J].Am J Gastroenterol,2005,100(1):162-168.DOI:10.1111/j.1572-0241.2005.40709.x.
[16] Lim KT.Surgical treatment of gastrointestinal stromal tumors of the stomach:current status and future perspective[J].Transl Gastroenterol Hepatol,2017,2:104.DOI:10.21037/tgh.2017.12.01.
[17] Chen H,Pruitt A,Nicol TL,et al.Complete hepatic resection of metastases from leiomyosarcoma prolongs survival[J].J Gastrointest Surg,1998,2(2):151-155.
[18] DeMatteo RP,Shah A,Fong Y,et al.Results of hepatic resection for sarcoma metastatic to liver[J].Ann Surg,2001,234(4):540-547.
[19] Machairas N,Prodromidou A,Molmenti E,et al.Management of liver metastases from gastrointestinal stromal tumors:where do we stand?[J].J Gastrointest Oncol,2017,8(6):1100-1108.DOI:10.21037/jgo.2017.08.08.
[20] Bompas E,Boillot O,Bringuier PP,et al.Imatinib in patients with metastatic gastrointestinal stromal tumors relapsing after hepatic transplantation[J].Eur J Cancer,2004,40(9):1456-1457.
[21] Frilling A,Malago M,Testa E,et al.Liver transplantation for metastasized extragastrointestinal stromal tumor:A case report and an overview of literature[J].Transplantation Proceedings,2010,42(9):3843-3848.DOI:10.1016/j.transproceed.2010.06.016.
[22] Pararas N,Levi D,Selvaggi G,et al.Mass clamping of the hilum to facilitate difficult hepatectomy during liver transplantation.A single center 10 year experience[J].Ann Surg,2009,250(2):273-276.DOI:10.1097/SLA.0b013e3181b17161.
[23] Joensuu H,Eriksson M,Sundby Hall K,et al,Reichardt P.One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor:a randomized trial[J].JAMA,2012,307(12):1265-1272.DOI:10.1001/jama.2012.347.
[24] Platoff RM,Morano WF,Marconcini L,et al.Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era:Treatment Strategies for an Incurable Disease[J].Case Rep Oncol Med,2017,2017:8349090.DOI:10.1155/2017/8349090.
[25] Heinrich MC,Corless CL,Demetri GD,et al.Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor[J].J Clin Oncol,2003,21(23):4342-4349.DOI:10.1200/JCO.2003.04.190.
[26] Debiec-Rychter M,Sciot R,Le Cesne A,et al.EORTC Soft Tissue and Bone Sarcoma Group;Italian Sarcoma Group;Australasian GastroIntestinal Trials Group.KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors[J].Eur J Cancer,2006,42(8):1093-1103.DOI:10.1016/j.ejca.2006.01.030.
[27] Singer S,Rubin BP,Lux ML,et al.Prognostic value of KIT mutation type,mitotic activity,and histologic subtype in gastrointestinal stromal tumors[J].J Clin Oncol,2002,20(18):3898-3905.DOI:10.1200/JCO.2002.03.095.
[28] Quek R,Farid M,Kanjanapan Y,et al.Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor[J].Asia Pac J Clin Oncol,2017,13(3):115-124.DOI:10.1111/ajco.12603.
[29] George S,Wang Q,Heinrich MC,et al.Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib:a multicenter phase Ⅱ trial[J].J Clin Oncol,2012,30(19):2401-2407.DOI:10.1200/JCO.2011.39.9394.