胰腺恶性神经内分泌肿瘤的影像学特性及外科治疗
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摘要
目的：探讨胰腺恶性神经内分泌肿瘤的影像学检查方法及其手术方式的选择。
方法：回顾性总结北京协和医院2003.1-2009.12收治的胰腺恶性神经内分泌肿瘤病例32份,所有病人均行B超、CT检查,根据需要进一步行超声内镜、PET、生长抑素受体显像等检查。根据病人肿瘤的分布及疾病特点选择手术方式。收集所有病例的一般资料、术后病理结果以及预后情况,评估它的影像学检查方法及手术方式的选择。
结果：胰腺原发灶的单独切除后功能性神经内分泌肿瘤病人内分泌诱导的临床综合症状全部获得了缓解或部分缓解,非功能性神经内分泌肿瘤病人的临床症状获得缓解；功能性胰腺神经内分泌肿瘤肝转移灶行减瘤术可减轻其内分泌诱导的临床综合症状。
结论：胰腺恶性神经内分泌肿瘤应积极行手术治疗。肝转移灶手术切除结合介入栓塞、射频消融等综合治疗可以缓解临床症状,使病人获得临床受益。
Imaging features and surgical treatment of malignant pancreatic neuroendocrine tumor
Objective:To investigate the imaging methods and surgical options for the malignant pancreatic neuroendocrine tumor.
Methods:We retrospectively summarized the clinic data of 32 patients with malignant pancreatic neuroendocrine tumors who admitted in PeKing Union Medical College Hospital between 2003.1 and 2009.12. All patients underwent BUS, CT examination, or further endoscopic ultrasound, PET, somatostatin receptor imaging, etc. The surgical methods were selected according to locatin of tumors and disease characteristics. The general information, postoperative pathology results, prognosis, imaging methods and surgical options were also collected.
Results:The functional neuroendocrine tumors induced clinical endocrine syndrome of all patients and the clinical symptoms of non-functional neuroendocrine tumors were eased or partial remissioned after pancreatic resection. The endocrine-induced clinical syndrome of functional pancreatic neuroendocrine tumors metastasised in liver can be reduced by cytoreductive surgery.
Conclusion:Malignant pancreatic neuroendocrine tumors should be actively treated surgically. Liver metastases resection combined with embolization or radiofrequency ablation can relieve clinic symptoms, so that patients can get clinical benefit.
方法：回顾性总结北京协和医院2003.1-2009.12收治的胰腺恶性神经内分泌肿瘤病例32份,所有病人均行B超、CT检查,根据需要进一步行超声内镜、PET、生长抑素受体显像等检查。根据病人肿瘤的分布及疾病特点选择手术方式。收集所有病例的一般资料、术后病理结果以及预后情况,评估它的影像学检查方法及手术方式的选择。
结果：胰腺原发灶的单独切除后功能性神经内分泌肿瘤病人内分泌诱导的临床综合症状全部获得了缓解或部分缓解,非功能性神经内分泌肿瘤病人的临床症状获得缓解；功能性胰腺神经内分泌肿瘤肝转移灶行减瘤术可减轻其内分泌诱导的临床综合症状。
结论：胰腺恶性神经内分泌肿瘤应积极行手术治疗。肝转移灶手术切除结合介入栓塞、射频消融等综合治疗可以缓解临床症状,使病人获得临床受益。
Imaging features and surgical treatment of malignant pancreatic neuroendocrine tumor
Objective:To investigate the imaging methods and surgical options for the malignant pancreatic neuroendocrine tumor.
Methods:We retrospectively summarized the clinic data of 32 patients with malignant pancreatic neuroendocrine tumors who admitted in PeKing Union Medical College Hospital between 2003.1 and 2009.12. All patients underwent BUS, CT examination, or further endoscopic ultrasound, PET, somatostatin receptor imaging, etc. The surgical methods were selected according to locatin of tumors and disease characteristics. The general information, postoperative pathology results, prognosis, imaging methods and surgical options were also collected.
Results:The functional neuroendocrine tumors induced clinical endocrine syndrome of all patients and the clinical symptoms of non-functional neuroendocrine tumors were eased or partial remissioned after pancreatic resection. The endocrine-induced clinical syndrome of functional pancreatic neuroendocrine tumors metastasised in liver can be reduced by cytoreductive surgery.
Conclusion:Malignant pancreatic neuroendocrine tumors should be actively treated surgically. Liver metastases resection combined with embolization or radiofrequency ablation can relieve clinic symptoms, so that patients can get clinical benefit.
引文
1.Oberg K,Eriksson B.Endocrine tumours of the pancreas[J]. Best Pract Res Clin Gastroenterol.2005;19(5):753-781
2.Grant CS:Surgical management of malignant islet cell tumors[J].World J Surg 1993;17:498-503.
3.Mantke R, Manger T, Schulz HU, et al.odal treatment of euroendocrine tumors of the pancreas and the ampulla of vater[J].Dig Surg 1999; 16:145-151.
4.Heitz PU, Komminoth P, Perrin A et al. Pancreatic endocrine tumors:Introduction.In: DeLellis DA, Lloyd RV, Heitz PU et al., eds. Pathology and Genetics of Tumours of Endocrine Organs. WHO Classification of Tumours.Lyon, France:IARC Press, 2004:177-182.
5.Fitzgerald TL,Hickner ZJ,Schmitz M,et al.Changing incidence of pancreatic neoplasms: a 16-year review of statewide tumor registry [J].Pancreas 2008;37(2):134-138.
6.Panzuto F,Severi C,Cannizzaro R,et al. Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.[J]. Endocrinol Invest 2004; 27:6-11.
7.Nguyen SQ,Angel LP,Divino CM,et al.Surgery in malignant pancreatic neuroendocrine tumors[J]. Surg Oncol 2007;96(5):397-403.
8.Rockall AG,Reznek RH,Imaging of neuroendocrine tumours (CT/MR/US)[J]. Best Pract Res Clin Endocrinol Metab 2007; 21:43-68
9.Gibril F,Jensen RT.Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumours[J]. Dig Liver Dis 2004; 36 (suppl 1):S106-20.
10.Koukouraki S,Strauss LG,Georgoulias V,et al. Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy [J]. Eur J Nucl Med Mol Imaging 2006; 33:460-66.
11.Dralle H, Krohn SL, Karges W, et al. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors[J].World J Surg 2004; 28:1248-60.
12.Fendrich V, Langer P, Celik I,et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors[J]. Ann Surg 2006; 244:845-51.
13.Hausman MS.Thompson NW.Gauger PGet al. The surgicalmanagement of MEN-1 pancreatoduodenal neuroendocrine disease[J].Surgery.2004;136:1205-1211.
14.Rossella Bettini, Letizia Boninsegna, Stefano Crippa,et al, Surgical Strategy in the Treatment of Pancreatic Neuroendocrine Tumors [J].JOP. J Pancreas (Online) 2006; 7(1):150-156.
15.Park BJ,Alexander HR, Libutti SK, et al. Operative managementof islet-cell tumors arising in the head of the pancreas. Surgery[J].1998; 124:1056-61.
16.Glenn K,Dhanwant Gomezl,Sakwhat H,et al.Results Following Surgical Resection for Malignant Pancreatic Neuroendocrine Tumours. A Single Institutional Experience[J].JOP. J Pancreas (Online) 2008; 9(1):19-25.
17.Paulus G, Schurr MD,Tim Strate MD,et al. Aggressive Surgery Improves Long-term Survival in Neuroendocrine Pancreatic Tumors。An Institutional Experience[J].Ann Surg.2007 Feb;245(2):273-281
18.Norton JA.Endocrine tumours of the gastrointestinal tract:surgical treatment of neuroendocrine metastases [J]. Best Pract Res Clin Gastroenterol.2005;19(4):577-583.
19.Rossella Bettini, Letizia Boninsegna, Stefano Crippa,et al, Surgical Strategy in the Treatment of Pancreatic Neuroendocrine Tumors [J].JOP. J Pancreas (Online) 2006; 7(1):150-156.
20.Hung JS, Chang MC, Lee PH, et al. Is surgery indicated for patients with symptomatic nonfunctioning pancreatic neuroendocrine tumor and unresectable hepatic metastases? [J].World J Surg.2007;31(12):2392-2397.
21.Bartsch DK, Schilling T, Ramaswamy A, et al. Management of nonfunctioning islet cell carcinomas[J]. World J Surg 2000; 24:1418-24. [PMID 11038216]
22.Evans DB, Skibber JM, Lee JE, et al. Nonfunctioning islet cell carcinoma of the pancreas[J]. Surgery 1993; 114:1175-1181.
23.Speer AG, Cotton PB, Russell RC, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice[J].Lancet 1987; 2:57-62.
24.House MG, Cameron JL, Lillemoe KD, et al. Differences in survival for patients with resectable versus unresectable metastases from pancreatic islet cell cancer[J].Gastrointest Surg.2006;10(1):138-145.
25.Sarmiento JM, Que FG, Grant CS, et al. Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases:outcomes of an aggressive approach[J].Surgery.2002;132(6):976-982; discussion 982-983.
26.Bonney GK, Gomez D, Rahman SH, et al. Results following surgical resection for malignant pancreatic neuroendocrine tumours:a single institutional experience[J]. JOP. 2008;9(1):19-25.
27.Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases:does intervention alter outcomes? [J]. Am Coll Surg.2000;190(4):432-445.
28.Hellman P, Ladjevardi S, Skogseid B, et al. Radiofrequency tissue ablation using cooled tip for metastases of endocrine tumors[J].World J Surg.2002;26:1052-1056. Epub 2002 May 21.
29.Sarmiento JM, Que FG, Grant CS, et al. Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases:outcomes of an aggressive approach[J].Surgery.2002;132:976-983.
30.Trendle MC, Moertel CG, Kvols LK, et al. Incidence and morbidity of cholelithiasis in patients receiving chronic octreotide for metastatic carcinoid and malignant islet cell tumors[J]. Cancer 1997; 79:830-4.[PMID 9024721]
31.Rosenau J,Bahr MJ, Wasielewski R,et al.Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors[J].Transplantation.2002 Feb 15;73(3):386-94.
32.Olausson M,Friman S,Herlenius G,et al.Orthotopic liver or multivisceral transplantation as treatment of metastatic neuroendocrine tumors[J].Liver Transpl.2007 Mar;13(3):327-33.
33.Sabaretnam M,Chand G,Mishra A,et al.Pancreatic Insulinoma:A Surgical Experience[J].World J Surg.2009 Dec 30.
34.Rothmund M, Angelini L, Brunt M,et al. Surgery for benign insulinoma:an international review,[J]. World J Surg, 1990; 14:393-398.
35.Fendrich.A,Langer.P,Minimally invasive urgery for pancreatic endocrine tumours,[J]. Br. J.Surg.94,1187-1188 (2007).
36.Fernandez-Cruz L, Blanco L, Cosa R,et al. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? [J]. World J Surg.2008 May;32(5):904-917
37.Kulke MH, Stuart K, Enzinger PC, et al. Phase Ⅱ study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors[J].Clin Oncol. 2006;24(3):401-406.
38.Strosberg JR, Choi J, Gardner N, et al. First-line treatment of metastatic pancreatic endocrine carcinomas with capecitabine and temozolomide.[J].Clin Oncol.2008;26(May 20 suppl). Abstract 4612.
39.S(?)rbye H, Westre B, Horn A,et al.Curative surgery after neoadjuvant chemotherapy in metastatic poorly differentiated neuroendocrine carcinoma[J].Eur J Surg Oncol. 2007;33(10):1209-1210. Epub 2007 Mar 12.
40.Bilimoria KY, Talamonti MS, Tomlinson JS,et al.Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors:analysis of 3851 patients[J].Ann Surg.2008;247(3):490-500.
41.Bloomston M, Muscarella P, Shah MH,et al.Cytoreduction results in high perioperative mortality and decreased survival in patients undergoing pancreatectomy for neuroendocrine tumors of the pancreas [J].Gastrointest Surg.2006;10(10):1361-1370.
42.Chung JC, Choi DW, Jo SH, et al. Malignant nonfunctioning endocrine tumors etreatment[J].World J Surg.2007;31(3):579-585.
43.Pamela J, Hodul MD, Jonathan R,et al.Aggressive Surgical Resection in the Management of Pancreatic Neuroendocrine Tumors:When Is It Indicated?[J].Cancer Control.2008 Oct;15(4):314-21.
[1]Xiong HQ,Rosenberg A,LoBuglio A, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer:A multicenter phase Ⅱ trial [J]. Clin Oncol,2004,22(3): 2610-2616.
[2]Philip PA,Benedetti J, Fenoglio-Preiser C, et al., Phase Ⅲ study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma:SWOG S0205 study [J. Clin Oncol ASCO Ann Meeting Proc Part 1,2007,25(18):4509-4509.
[3]Graeven U, Kremer B, Sudhoff T, et al. Phase Ⅰ study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer [J]. Br J Cancer,2006,94:1293-1299.
[4]Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:a phase Ⅲ trial of the National Cancer Institute of Canada Clinical Trials Group [J]. Clin Oncol,2007,25(15), 1960-1966.
[5]Al Zaid Siddiquee K, Turkson J. STAT3 as a target for inducing apoptosis in solid and hematological tumors [J].Cell Res 2008;18(2):254-267
[6]Kindler HL, Friberg G, Singh DA, et al. Phase Ⅱ trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer [J].Clin Oncol,2005, 23(31):8033-8040.
[7]Kindler HL,Niedzwiecki D. Hollis D, et al. A double-blind, placebo-controlled, randomized phase Ⅲ trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo in patients with advanced pancreatic cancer:a preliminary analysis of Cancer and Leukemia Group B (CALGB80303) [J].Clin Oncol,ASCO Ann Meeting Proc Part I, 2007,25:4508-4508.
[8]Iqbal S, Lenz HJ, Yang D, et al. A randomized phase Ⅱ study of BAY 43-9006 in combination with gemcitabine in metastatic pancreatic carcinoma:A California Cancer Consortium study (CCC-P) [J]. Clin Oncol (Meeting Abstracts).2008,26:11082-11082.
[9]Spano JP, Chodkiewicz C, Maurel J, et al. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer:an open-label randomised phase Ⅱ study [J]. Lancet,2008,371 (9630):2101-2108.
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[18]Song D, Chaerkady R, Tan AC, et al. Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer [J]. Mol Cancer Ther,2008,7(10):3275-3284
2.Grant CS:Surgical management of malignant islet cell tumors[J].World J Surg 1993;17:498-503.
3.Mantke R, Manger T, Schulz HU, et al.odal treatment of euroendocrine tumors of the pancreas and the ampulla of vater[J].Dig Surg 1999; 16:145-151.
4.Heitz PU, Komminoth P, Perrin A et al. Pancreatic endocrine tumors:Introduction.In: DeLellis DA, Lloyd RV, Heitz PU et al., eds. Pathology and Genetics of Tumours of Endocrine Organs. WHO Classification of Tumours.Lyon, France:IARC Press, 2004:177-182.
5.Fitzgerald TL,Hickner ZJ,Schmitz M,et al.Changing incidence of pancreatic neoplasms: a 16-year review of statewide tumor registry [J].Pancreas 2008;37(2):134-138.
6.Panzuto F,Severi C,Cannizzaro R,et al. Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.[J]. Endocrinol Invest 2004; 27:6-11.
7.Nguyen SQ,Angel LP,Divino CM,et al.Surgery in malignant pancreatic neuroendocrine tumors[J]. Surg Oncol 2007;96(5):397-403.
8.Rockall AG,Reznek RH,Imaging of neuroendocrine tumours (CT/MR/US)[J]. Best Pract Res Clin Endocrinol Metab 2007; 21:43-68
9.Gibril F,Jensen RT.Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumours[J]. Dig Liver Dis 2004; 36 (suppl 1):S106-20.
10.Koukouraki S,Strauss LG,Georgoulias V,et al. Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy [J]. Eur J Nucl Med Mol Imaging 2006; 33:460-66.
11.Dralle H, Krohn SL, Karges W, et al. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors[J].World J Surg 2004; 28:1248-60.
12.Fendrich V, Langer P, Celik I,et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors[J]. Ann Surg 2006; 244:845-51.
13.Hausman MS.Thompson NW.Gauger PGet al. The surgicalmanagement of MEN-1 pancreatoduodenal neuroendocrine disease[J].Surgery.2004;136:1205-1211.
14.Rossella Bettini, Letizia Boninsegna, Stefano Crippa,et al, Surgical Strategy in the Treatment of Pancreatic Neuroendocrine Tumors [J].JOP. J Pancreas (Online) 2006; 7(1):150-156.
15.Park BJ,Alexander HR, Libutti SK, et al. Operative managementof islet-cell tumors arising in the head of the pancreas. Surgery[J].1998; 124:1056-61.
16.Glenn K,Dhanwant Gomezl,Sakwhat H,et al.Results Following Surgical Resection for Malignant Pancreatic Neuroendocrine Tumours. A Single Institutional Experience[J].JOP. J Pancreas (Online) 2008; 9(1):19-25.
17.Paulus G, Schurr MD,Tim Strate MD,et al. Aggressive Surgery Improves Long-term Survival in Neuroendocrine Pancreatic Tumors。An Institutional Experience[J].Ann Surg.2007 Feb;245(2):273-281
18.Norton JA.Endocrine tumours of the gastrointestinal tract:surgical treatment of neuroendocrine metastases [J]. Best Pract Res Clin Gastroenterol.2005;19(4):577-583.
19.Rossella Bettini, Letizia Boninsegna, Stefano Crippa,et al, Surgical Strategy in the Treatment of Pancreatic Neuroendocrine Tumors [J].JOP. J Pancreas (Online) 2006; 7(1):150-156.
20.Hung JS, Chang MC, Lee PH, et al. Is surgery indicated for patients with symptomatic nonfunctioning pancreatic neuroendocrine tumor and unresectable hepatic metastases? [J].World J Surg.2007;31(12):2392-2397.
21.Bartsch DK, Schilling T, Ramaswamy A, et al. Management of nonfunctioning islet cell carcinomas[J]. World J Surg 2000; 24:1418-24. [PMID 11038216]
22.Evans DB, Skibber JM, Lee JE, et al. Nonfunctioning islet cell carcinoma of the pancreas[J]. Surgery 1993; 114:1175-1181.
23.Speer AG, Cotton PB, Russell RC, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice[J].Lancet 1987; 2:57-62.
24.House MG, Cameron JL, Lillemoe KD, et al. Differences in survival for patients with resectable versus unresectable metastases from pancreatic islet cell cancer[J].Gastrointest Surg.2006;10(1):138-145.
25.Sarmiento JM, Que FG, Grant CS, et al. Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases:outcomes of an aggressive approach[J].Surgery.2002;132(6):976-982; discussion 982-983.
26.Bonney GK, Gomez D, Rahman SH, et al. Results following surgical resection for malignant pancreatic neuroendocrine tumours:a single institutional experience[J]. JOP. 2008;9(1):19-25.
27.Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases:does intervention alter outcomes? [J]. Am Coll Surg.2000;190(4):432-445.
28.Hellman P, Ladjevardi S, Skogseid B, et al. Radiofrequency tissue ablation using cooled tip for metastases of endocrine tumors[J].World J Surg.2002;26:1052-1056. Epub 2002 May 21.
29.Sarmiento JM, Que FG, Grant CS, et al. Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases:outcomes of an aggressive approach[J].Surgery.2002;132:976-983.
30.Trendle MC, Moertel CG, Kvols LK, et al. Incidence and morbidity of cholelithiasis in patients receiving chronic octreotide for metastatic carcinoid and malignant islet cell tumors[J]. Cancer 1997; 79:830-4.[PMID 9024721]
31.Rosenau J,Bahr MJ, Wasielewski R,et al.Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors[J].Transplantation.2002 Feb 15;73(3):386-94.
32.Olausson M,Friman S,Herlenius G,et al.Orthotopic liver or multivisceral transplantation as treatment of metastatic neuroendocrine tumors[J].Liver Transpl.2007 Mar;13(3):327-33.
33.Sabaretnam M,Chand G,Mishra A,et al.Pancreatic Insulinoma:A Surgical Experience[J].World J Surg.2009 Dec 30.
34.Rothmund M, Angelini L, Brunt M,et al. Surgery for benign insulinoma:an international review,[J]. World J Surg, 1990; 14:393-398.
35.Fendrich.A,Langer.P,Minimally invasive urgery for pancreatic endocrine tumours,[J]. Br. J.Surg.94,1187-1188 (2007).
36.Fernandez-Cruz L, Blanco L, Cosa R,et al. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? [J]. World J Surg.2008 May;32(5):904-917
37.Kulke MH, Stuart K, Enzinger PC, et al. Phase Ⅱ study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors[J].Clin Oncol. 2006;24(3):401-406.
38.Strosberg JR, Choi J, Gardner N, et al. First-line treatment of metastatic pancreatic endocrine carcinomas with capecitabine and temozolomide.[J].Clin Oncol.2008;26(May 20 suppl). Abstract 4612.
39.S(?)rbye H, Westre B, Horn A,et al.Curative surgery after neoadjuvant chemotherapy in metastatic poorly differentiated neuroendocrine carcinoma[J].Eur J Surg Oncol. 2007;33(10):1209-1210. Epub 2007 Mar 12.
40.Bilimoria KY, Talamonti MS, Tomlinson JS,et al.Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors:analysis of 3851 patients[J].Ann Surg.2008;247(3):490-500.
41.Bloomston M, Muscarella P, Shah MH,et al.Cytoreduction results in high perioperative mortality and decreased survival in patients undergoing pancreatectomy for neuroendocrine tumors of the pancreas [J].Gastrointest Surg.2006;10(10):1361-1370.
42.Chung JC, Choi DW, Jo SH, et al. Malignant nonfunctioning endocrine tumors etreatment[J].World J Surg.2007;31(3):579-585.
43.Pamela J, Hodul MD, Jonathan R,et al.Aggressive Surgical Resection in the Management of Pancreatic Neuroendocrine Tumors:When Is It Indicated?[J].Cancer Control.2008 Oct;15(4):314-21.
[1]Xiong HQ,Rosenberg A,LoBuglio A, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer:A multicenter phase Ⅱ trial [J]. Clin Oncol,2004,22(3): 2610-2616.
[2]Philip PA,Benedetti J, Fenoglio-Preiser C, et al., Phase Ⅲ study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma:SWOG S0205 study [J. Clin Oncol ASCO Ann Meeting Proc Part 1,2007,25(18):4509-4509.
[3]Graeven U, Kremer B, Sudhoff T, et al. Phase Ⅰ study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer [J]. Br J Cancer,2006,94:1293-1299.
[4]Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:a phase Ⅲ trial of the National Cancer Institute of Canada Clinical Trials Group [J]. Clin Oncol,2007,25(15), 1960-1966.
[5]Al Zaid Siddiquee K, Turkson J. STAT3 as a target for inducing apoptosis in solid and hematological tumors [J].Cell Res 2008;18(2):254-267
[6]Kindler HL, Friberg G, Singh DA, et al. Phase Ⅱ trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer [J].Clin Oncol,2005, 23(31):8033-8040.
[7]Kindler HL,Niedzwiecki D. Hollis D, et al. A double-blind, placebo-controlled, randomized phase Ⅲ trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo in patients with advanced pancreatic cancer:a preliminary analysis of Cancer and Leukemia Group B (CALGB80303) [J].Clin Oncol,ASCO Ann Meeting Proc Part I, 2007,25:4508-4508.
[8]Iqbal S, Lenz HJ, Yang D, et al. A randomized phase Ⅱ study of BAY 43-9006 in combination with gemcitabine in metastatic pancreatic carcinoma:A California Cancer Consortium study (CCC-P) [J]. Clin Oncol (Meeting Abstracts).2008,26:11082-11082.
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