胃神经内分泌肿瘤的研究进展
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摘要
胃神经内分泌肿瘤是临床较少见的一类肿瘤性病变,由于病例报道少,临床诊断率较低,在国内外尚无统一的诊疗方法。得益于内镜技术的发展以及临床上广泛应用的质子泵抑制剂,胃神经内分泌肿瘤的发病率和诊断率呈现上升的趋势。通过研究其发病机制,学者发现其发生与各种原因引起的高胃泌素血症密切相关。根据疾病的进展状态和临床表现,学者对胃神经内分泌肿瘤进行了分型和病理分级。临床上运用的诊断方法有胃镜、影像学、核医学、胃泌素、Cg A等检查。根据临床分型的不同,治疗手段也存在差异,如果疾病进展迅速且分级较高,则应积极行外科手术切除病灶加术后辅助化学药物治疗。其他更好的治疗方法还在不断探索中。
Gastric neuroendocrine tumors are rarely seen in the gastric tumors, because there are few case reports and the clinical diagnosis rate is low. There is no consensus treatment method in the world. However, with the benefit of esophagogastrodenoscopy and widespread use of proton pump inhibitors, the diagnostic rate of gastric neuroendocrine tumors is on the increase, which gives us an updated understanding for the pathogenesis and pathophysiology of the disease. By studying its pathogenesis, scholars have found that hypergastrinemia caused by various causes is closely related to its occurrence. Gastric neuroendocrine tumors are classifi ed into different types or pathological grades depending on the state of progression of the disease and the unique clinical manifestations. Clinically used diagnostic methods include gastroscopy, medical imageology, nuclear medicine, gastrin, CgA, etc. There are also differences in treatments depending on the clinical classifi cation. If the disease progresses rapidly and the grade is high, surgical resection of the lesion plus postoperative adjuvant chemotherapy should be actively performed. Other bett er treatments are still being explored.
Gastric neuroendocrine tumors are rarely seen in the gastric tumors, because there are few case reports and the clinical diagnosis rate is low. There is no consensus treatment method in the world. However, with the benefit of esophagogastrodenoscopy and widespread use of proton pump inhibitors, the diagnostic rate of gastric neuroendocrine tumors is on the increase, which gives us an updated understanding for the pathogenesis and pathophysiology of the disease. By studying its pathogenesis, scholars have found that hypergastrinemia caused by various causes is closely related to its occurrence. Gastric neuroendocrine tumors are classifi ed into different types or pathological grades depending on the state of progression of the disease and the unique clinical manifestations. Clinically used diagnostic methods include gastroscopy, medical imageology, nuclear medicine, gastrin, CgA, etc. There are also differences in treatments depending on the clinical classifi cation. If the disease progresses rapidly and the grade is high, surgical resection of the lesion plus postoperative adjuvant chemotherapy should be actively performed. Other bett er treatments are still being explored.
引文
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[16]Nandy N,Hanson JA,Strickland RG,et al.Solitary gastric carcinoid tumor associated with long-term Use of omeprazole:A case report and review of the literature[J].Diges Dis Sci,2016,61(3):708-712.
[17]Mulkeen A,Cha C.Gastric carcinoid[J].Curr Opin Oncol,2005,17(1):1-6.
[18]Basuroy R,Haji A,R amage JK,et al.The investigation and management of rectal neuroendocrine tumours[J].Aliment Pharmacol Ther,2016,39(10):1071-1084.
[19]Delle Fave G,Kwekkeboom DJ,Van Cutsem E,et al.ENETSconsensus guidelines for the management of patients w ith gastroduodenal neoplasms[J].Neuroendocrinology,2012,95(2):74-87.
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[22]Borch K,Stridsberg M,Burman P,et al.Basal chromogranin a and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-a gastritis[J].Scand J Gastroenterol,1997,32(3):198-202.
[23]Fendrich V,Bartsch DK.Surgical treatment of gastrointestinal neuroendocrine tumors[J].Langenbecks Arch Surg,2011,396(3):299-311.
[24]Hirschowitz BI.Clinical aspects of ECL-cell abnormalities[J].Yale JBiol Med,1998,71(3/4):303-310.
[25]Strosberg JR,Coppola D,Klimstra DS,et al.The NANETS consensus guidelines for the diagnosis and management of poorly differentiated(high-grade)extrapulmonary neuroendocrine carcinomas[J].Pancreas,2010,39(6):799-800.
[26]Hadoux J,Malka D,Planchard D,et al.Post-first-line FOLFOXchemotherapy for grade 3 neuroendocrine carcinoma[J].Endoc Relat Cancer,2015,22(3):289-298.
[27]Hentic O,Hammel P,Couvelard A,et al.FOLFIRI regimen:an effective second-line chemotherapy after failure of etoposideplatinum combination in patients with neuroendocrine carcinomas grade 3[J].Endoc Relat Cancer,2012,19(6):751-757.
[28]Pericleous M,Toumpanakis C,Lumgair H,et al.Gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation:case report and review of the literature[J].Case Rep Oncol,2012,5(2):313-319.
[29]Somnay YR,Dull BZ,Eide J,et al.Chrysin suppresses achaetescute complex-like 1 and alters the neuroendocrine phenotype of carcinoids[J].Cancer Gene Ther,2015,22(10):496-505.
[30]Merola E,Sbrozzi-Vanni A,Panzuto F,et al.Type I gastric carcinoids:A prospective study on endoscopic management and recurrence rate[J].Neuroendocrinology,2012,95(3):207-213.
[31]Grozinsky-Glasberg S,Thomas D,Strosberg JR,et al.Metastatic type 1 gastric carcinoid:a real threat or just a myth?[J].World JGastroenterol,2013,19(46):8687-8695.
[32]Rappel S,Altendorfhofmann A,Stolte M.Prognosis of gastric carcinoid tumours[J].Digestion,1995,56(6):455-462.
[33]Hosokawa O,Kaizaki Y,Hattori M,et al.Long-term follow up of patients with multiple gastric carcinoids associated with type Agastritis[J].Gast Cancer,2005,8(1):42-46.
[34]Kim BS,Park YS,Yook JH,et al.Differing clinical courses and prognoses in patients with gastric neuroendocrine tumors based on the 2010-WHO classification scheme[J].Medicine,2015,94(44):e1748.
[35]La Rosa S,Inzani F,Vanoli A,et al.Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms[J].Hum Pathol,2011,42(10):1373-1384.
[36]Thomas D,Tsolakis AV,Grozinsky-Glasberg S,et al.Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors:data from a multicenter study[J].Europ J Endocrinol,2013,168(2):185-193.
[37]Jenny HE,Ogando PA,Fujitani K,et al.Laparoscopic antrectomy:a safe and definitive treatment in managing ty pe 1 gastric carcinoids[J].Am J Surg,2016,211(4):778-782.
[38]Tan H.Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms[J].Transl Gastroenterol Hepatol,2016,1:87.
[39]Postlewait L M,Bapti ste G G,Ethun CG,et al.A 15-year experience with gastric neuroendocrine tumors:Does type make a difference?[J].J Surg Oncol,2016,114(5):576-580.
[40]Chen WC,Warner RR,Ward SC,et al.Management and disease outcome of type I gastric neuroendocrine tumors:the Mount Sinai experience[J].Digest Dis Sci,2015,60(4):996-1003.
[2]Niederle B.Gastroenteropancreatic neuroendocrine tumours:the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification:an analysis based on prospectively collected parameters[J].Endocr Relat Cancer,2010,17(4):909-918.
[3]Cho MY,Kim JM,Sohn JH,et al.Current trends of the incidence and pathological diagnosis of gastroenteropancreatic neuroendocrine tumors(GEP-NETs)in Korea 2000-2009:Multicenter Study[J].Cancer Res Treat,2012,44(3):157-165.
[4]O’Connor JM,Marmissolle F,Bestani C,et al.Observational study of patients with gastroenteropancreatic and bronchial neuroendocrine tumors in Argentina:Results from the large database of a multidisciplinary group clinical multicenter study[J].Molec Clin Oncol,2014,2(5):673-684.
[5]Modlin IM,Lye KD,Kidd M.A 5-decade analysis of 13,715 carcinoid tumors[J].Cancer,2010,97(4):934-959.
[6]Modlin IM,Kidd M,Lye KD.Biology and management of gastric carcinoid tumours:A review[J].Eur J Surg,2002,168(12):669-683.
[7]Nikou GC,Angelopoulos TP.Current concepts on gastric carcinoid tumors[J].Gastroenterol Res Pract,2012,2012:287825.
[8]Ant H.WHO classification of tumours of the digestive system,fourth edition[J].Ann Pathol,2011,31(5 Suppl):S27-31.
[9]Massironi S,Zilli A,Conte D.Somatostatin analogs for gastric carcinoids:For many,but not all[J].World J Gastroenterol,2015,21(22):6785-6793.
[10]2013年中国胃肠胰神经内分泌肿瘤病理诊断共识专家组.中国胃肠胰神经内分泌肿瘤病理诊断共识(2013版)[J].中华病理学杂志,2013,42(10):691-694.Chinese Expert Team on Pathological Diagnosis of Gastrointestinal Pancreatic Neuroendocrine Tumors.Consensus on pathological diagnosis of gastrointestinal pancreatic neuroendocrine tumors in China(2013 edition)[J].Chinese Journal of Pathology,2013,42(10):691-694.
[11]Rindi G,Kloppel G,Alhman H,et al.TNM staging of foregut(neuro)endocrine tumors:a consensus proposal including a grading system[J].Virchows Archiv,2006,449(4):395-401.
[12]Cancer AJCO.AJCC Cancer staging atlas[M].New York,Springer:2012.
[13]Gilligan CJ,Lawton GP,Tang LH,et al.Gastric carcinoid tumors:the biology and therapy of an enigmatic and controversial lesion[J].Am J Gastroenterol,1995,90(3):338-352.
[14]Ruszniewski P,Delle Fave G,Cadiot G,et al.Well-differentiated gastric tumors/carcinomas[J].Neuroendocrinology,2006,84(3):158-164.
[15]Burkitt MD,Pritchard DM.Pathogenesis and management of gastric carcinoid tumours[J].Aliment Pharmacol Ther,2006,24(9):1305-1320.
[16]Nandy N,Hanson JA,Strickland RG,et al.Solitary gastric carcinoid tumor associated with long-term Use of omeprazole:A case report and review of the literature[J].Diges Dis Sci,2016,61(3):708-712.
[17]Mulkeen A,Cha C.Gastric carcinoid[J].Curr Opin Oncol,2005,17(1):1-6.
[18]Basuroy R,Haji A,R amage JK,et al.The investigation and management of rectal neuroendocrine tumours[J].Aliment Pharmacol Ther,2016,39(10):1071-1084.
[19]Delle Fave G,Kwekkeboom DJ,Van Cutsem E,et al.ENETSconsensus guidelines for the management of patients w ith gastroduodenal neoplasms[J].Neuroendocrinology,2012,95(2):74-87.
[20]Verbeek WHM,Korse CM,Tesselaar ME.GEP-NETs Update:Secreting gastro-enteropancreatic neuroendocrine tumours and biomarkers[J].Eur J Endocrinol,2016,174(1):R1.
[21]Warner R.Review of the pathogenesis,diagnosis,and management of type I gastric carcinoid tumor[J].World J Surg,2011,35(8):1879-1886.
[22]Borch K,Stridsberg M,Burman P,et al.Basal chromogranin a and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-a gastritis[J].Scand J Gastroenterol,1997,32(3):198-202.
[23]Fendrich V,Bartsch DK.Surgical treatment of gastrointestinal neuroendocrine tumors[J].Langenbecks Arch Surg,2011,396(3):299-311.
[24]Hirschowitz BI.Clinical aspects of ECL-cell abnormalities[J].Yale JBiol Med,1998,71(3/4):303-310.
[25]Strosberg JR,Coppola D,Klimstra DS,et al.The NANETS consensus guidelines for the diagnosis and management of poorly differentiated(high-grade)extrapulmonary neuroendocrine carcinomas[J].Pancreas,2010,39(6):799-800.
[26]Hadoux J,Malka D,Planchard D,et al.Post-first-line FOLFOXchemotherapy for grade 3 neuroendocrine carcinoma[J].Endoc Relat Cancer,2015,22(3):289-298.
[27]Hentic O,Hammel P,Couvelard A,et al.FOLFIRI regimen:an effective second-line chemotherapy after failure of etoposideplatinum combination in patients with neuroendocrine carcinomas grade 3[J].Endoc Relat Cancer,2012,19(6):751-757.
[28]Pericleous M,Toumpanakis C,Lumgair H,et al.Gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation:case report and review of the literature[J].Case Rep Oncol,2012,5(2):313-319.
[29]Somnay YR,Dull BZ,Eide J,et al.Chrysin suppresses achaetescute complex-like 1 and alters the neuroendocrine phenotype of carcinoids[J].Cancer Gene Ther,2015,22(10):496-505.
[30]Merola E,Sbrozzi-Vanni A,Panzuto F,et al.Type I gastric carcinoids:A prospective study on endoscopic management and recurrence rate[J].Neuroendocrinology,2012,95(3):207-213.
[31]Grozinsky-Glasberg S,Thomas D,Strosberg JR,et al.Metastatic type 1 gastric carcinoid:a real threat or just a myth?[J].World JGastroenterol,2013,19(46):8687-8695.
[32]Rappel S,Altendorfhofmann A,Stolte M.Prognosis of gastric carcinoid tumours[J].Digestion,1995,56(6):455-462.
[33]Hosokawa O,Kaizaki Y,Hattori M,et al.Long-term follow up of patients with multiple gastric carcinoids associated with type Agastritis[J].Gast Cancer,2005,8(1):42-46.
[34]Kim BS,Park YS,Yook JH,et al.Differing clinical courses and prognoses in patients with gastric neuroendocrine tumors based on the 2010-WHO classification scheme[J].Medicine,2015,94(44):e1748.
[35]La Rosa S,Inzani F,Vanoli A,et al.Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms[J].Hum Pathol,2011,42(10):1373-1384.
[36]Thomas D,Tsolakis AV,Grozinsky-Glasberg S,et al.Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors:data from a multicenter study[J].Europ J Endocrinol,2013,168(2):185-193.
[37]Jenny HE,Ogando PA,Fujitani K,et al.Laparoscopic antrectomy:a safe and definitive treatment in managing ty pe 1 gastric carcinoids[J].Am J Surg,2016,211(4):778-782.
[38]Tan H.Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms[J].Transl Gastroenterol Hepatol,2016,1:87.
[39]Postlewait L M,Bapti ste G G,Ethun CG,et al.A 15-year experience with gastric neuroendocrine tumors:Does type make a difference?[J].J Surg Oncol,2016,114(5):576-580.
[40]Chen WC,Warner RR,Ward SC,et al.Management and disease outcome of type I gastric neuroendocrine tumors:the Mount Sinai experience[J].Digest Dis Sci,2015,60(4):996-1003.