The status of diagnosis and treatment of borderline resectable pancreatic ductal adenocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GAO Yang , ZHANG Shengning , ZHANG Xibing ,  LI Li , RAN Jianghua

Department of Hepatobiliary, Pancreas, and Vascular Surgery, The First People’s Hospital of Kunming, Kunming 650051, P. R. China;

Corresponding author：

LI Li, Email: ynkmlili62@hotmail.com

Keywords：

borderline resectable pancreatic ductal adenocarcinoma; diagnosis; treatment; review

DOI：

10.7507/1007-9424.201801087

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the diagnosis and treatment progress of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) in recent years. Methods Through the retrieval of relevant literatures, the progress in the diagnosis and treatment of BR-PDAC in recent years were reviewed, to summarize the current status of definition, management, and outcome of BR-PDAC. Results Pancreatic surgery had significantly changed during the past years and resection approaches had been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, BR-PDAC, which had recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), had become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. The key point was preoperative diagnostic accuracy to define the resectability of BR-PDAC and radical tumor resection followed by neoadjuvant treatment. Conclusion Surgery followed by neoadjuvant treatment is the only treatment option for BR-PDAC with the chance of long-term survival.

Citation： GAO Yang, ZHANG Shengning, ZHANG Xibing, LI Li, RAN Jianghua. The status of diagnosis and treatment of borderline resectable pancreatic ductal adenocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(8): 1016-1022. doi: 10.7507/1007-9424.201801087 Copy

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2.	Hackert T, Büchler MW. Pancreatic cancer: advances in treatment, results and limitations. Dig Dis, 2013, 31(1): 51-56.
3.	Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol, 2014, 32(6): 504-512.
4.	Reames BN, Ghaferi AA, Birkmeyer JD, et al. Hospital volume and operative mortality in the modern era. Ann Surg, 2014, 260(2): 244-251.
5.	Nikfarjam M, Sehmbey M, Kimchi ET, et al. Additional organ resection combined with pancreaticoduodenectomy does not increase postoperative morbidity and mortality. J Gastrointest Surg, 2009, 13(5): 915-921.
6.	Beltrame V, Gruppo M, Pedrazzoli S, et al. Mesenteric-Portal Vein Resection during Pancreatectomy for Pancreatic Cancer. Gastroenterol Res Pract, 2015, 2015: 659730.
7.	Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic Adenocarcinoma, version 2.2014: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw, 2014, 12(8): 1083-1093.
8.	Klauss M, Mohr A, von Tengg-Kobligk H, et al. A new invasion score for determining the resectability of pancreatic carcinomas with contrast-enhanced multidetector computed tomography. Pancreatology, 2008, 8(2): 204-210.
9.	Shrikhande SV, Barreto SG, Goel M, et al. Multimodality imaging of pancreatic ductal adenocarcinoma: a review of the literature. HPB (Oxford), 2012, 14(10): 658-668.
10.	Grenacher L, Klauss M. Computed tomography of pancreatic tumors. Radiologe, 2009, 49(2): 107-123.
11.	Bockhorn M, Uzunoglu FG, Adham M, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery, 2014, 155(6): 977-988.
12.	Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol, 2009, 16(7): 1727-1733.
13.	Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol, 2006, 13(8): 1035-1046.
14.	Zhou Y, Zhang Z, Liu Y, et al. Pancreatectomy combined with superior mesenteric vein-portal vein resection for pancreatic cancer: a meta-analysis. World J Surg, 2012, 36(4): 884-891.
15.	Hartwig W, Vollmer CM, Fingerhut A, et al. Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS). Surgery, 2014, 156(1): 1-14.
16.	Fortner JG. Regional resection of cancer of the pancreas: a new surgical approach. Surgery, 1973, 73(2): 307-320.
17.	Del Chiaro M, Segersvärd R, Rangelova E, et al. Cattell-Braasch Maneuver Combined with Artery-First Approach for Superior Mesenteric-Portal Vein Resection During Pancreatectomy. J Gastrointest Surg, 2015, 19(12): 2264-2268.
18.	Giovinazzo F, Turri G, Katz MH, et al. Meta-analysis of benefits of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma. Br J Surg, 2016, 103(3): 179-191.
19.	Murakami Y, Satoi S, Motoi F, et al. Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma. Br J Surg, 2015, 102(7): 837-846.
20.	Hartwig W, Hackert T, Hinz U, et al. Multivisceral resection for pancreatic malignancies: risk-analysis and long-term outcome. Ann Surg, 2009, 250(1): 81-87.
21.	Hackert T, Weitz J, Büchler MW. Splenic artery use for arterial reconstruction in pancreatic surgery. Langenbecks Arch Surg, 2014, 399(5): 667-671.
22.	Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg, 2011, 254(6): 882-893.
23.	Sanjay P, Takaori K, Govil S, et al. ‘Artery-first’ approaches to pancreatoduodenectomy. Br J Surg, 2012, 99(8): 1027-1035.
24.	Inoue Y, Saiura A, Yoshioka R, et al. Pancreatoduodenectomy With Systematic Mesopancreas Dissection Using a Supracolic Anterior Artery-first Approach. Ann Surg, 2015, 262(6): 1092-1101.
25.	Sperti C, Berselli M, Pedrazzoli S. Distal pancreatectomy for body-tail pancreatic cancer: is there a role for celiac axis resection? Pancreatology, 2010, 10(4): 491-498.
26.	Jing W, Zhu G, Hu X, et al. Distal pancreatectomy with en bloc celiac axis resection for the treatment of locally advanced pancreatic body and tail cancer. Hepatogastroenterology, 2013, 60(121): 187-190.
27.	Strasberg SM, Fields R. Left-sided pancreatic cancer: distal pancreatectomy and its variants: radical antegrade modular pancreatosplenectomy and distal pancreatectomy with celiac axis resection. Cancer J, 2012, 18(6): 562-570.
28.	Hirano S, Kondo S, Hara T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg, 2007, 246(1): 46-51.
29.	Wang X, Dong Y, Jin J, et al. Efficacy of modified Appleby surgery: a benefit for elderly patients? J Surg Res, 2015, 194(1): 83-90.
30.	Miura T, Hirano S, Nakamura T, et al. A new preoperative prognostic scoring system to predict prognosis in patients with locally advanced pancreatic body cancer who undergo distal pancreatectomy with en bloc celiac axis resection: a retrospective cohort study. Surgery, 2014, 155(3): 457-467.
31.	Okada K, Kawai M, Tani M, et al. Surgical strategy for patients with pancreatic body/tail carcinoma: who should undergo distal pancreatectomy with en-bloc celiac axis resection? Surgery, 2013, 153(3): 365-372.
32.	Takahashi Y, Kaneoka Y, Maeda A, et al. Distal pancreatectomy with celiac axis resection for carcinoma of the body and tail of the pancreas. World J Surg, 2011, 35(11): 2535-2542.
33.	Hackert T, Stampfl U, Schulz H, et al. Clinical significance of liver ischaemia after pancreatic resection. Br J Surg, 2011, 98(12): 1760-1765.
34.	Bhayani NH, Enomoto LM, James BC, et al. Multivisceral and extended resections during pancreatoduodenectomy increase morbidity and mortality. Surgery, 2014, 155(3): 567-574.
35.	Kulemann B, Hoeppner J, Wittel U, et al. Perioperative and long-term outcome after standard pancreaticoduodenectomy, additional portal vein and multivisceral resection for pancreatic head cancer. J Gastrointest Surg, 2015, 19(3): 438-444.
36.	Burdelski CM, Reeh M, Bogoevski D, et al. Multivisceral resections in pancreatic cancer: identification of risk factors. World J Surg, 2011, 35(12): 2756-2763.
37.	Hartwig W, Gluth A, Hinz U, et al. Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. Br J Surg, 2016, 103(12): 1683-1694.
38.	Gillen S, Schuster T, Meyer Zum Büschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med, 2010, 7(4): e1000267.
39.	Petrelli F, Coinu A, Borgonovo K, et al. FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas, 2015, 44(4): 515-521.
40.	Tang K, Lu W, Qin W, et al. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. Pancreatology, 2016, 16(1): 28-37.
41.	Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol, 2015, 22(4): 1153-1159.
42.	Ajani JA, D’Amico TA, Almhanna K, et al. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw, 2015, 13(2): 194-227.
43.	Schorn S, Demir IE, Reyes CM, et al. The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma - A systematic review and meta-analysis. Cancer Treat Rev, 2017, 55: 96-106.
44.	Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg, 2015, 261(1): 12-17.
45.	Patel BN, Giacomini C, Jeffrey RB, et al. Three-dimensional volume-rendered multidetector CT imaging of the posterior inferior pancreaticoduodenal artery: its anatomy and role in diagnosing extrapancreatic perineural invasion. Cancer Imaging, 2013, 13(4): 580-590.
46.	De Robertis R, Tinazzi Martini P, Demozzi E, et al. Prognostication and response assessment in liver and pancreatic tumors: The new imaging. World J Gastroenterol, 2015, 21(22): 6794-6808.
47.	Mornex F, Girard N, Delpero JR, et al. Radiochemotherapy in the management of pancreatic cancer--part I: neoadjuvant treatment. Semin Radiat Oncol, 2005, 15(4): 226-234.
48.	Strobel O, Berens V, Hinz U, et al. Resection after neoadjuvant therapy for locally advanced, " unresectable” pancreatic cancer. Surgery, 2012, 152(3 Suppl 1): S33-S42.
49.	Nanda RH, El-Rayes B, Maithel SK, et al. Neoadjuvant modified FOLFIRINOX and chemoradiation therapy for locally advanced pancreatic cancer improves resectability. J Surg Oncol, 2015, 111(8): 1028-1034.
50.	Christians KK, Tsai S, Mahmoud A, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist, 2014, 19(3): 266-274.
51.	James ES, Yao X, Cong X, et al. Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC), J Clin Oncol, 2014, 3 (Suppl 1): 32.
52.	Chuong MD, Frakes JM, Figura N, et al. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer. J Gastrointest Oncol, 2016, 7(2): 221-227.
53.	Katz MH, Shi Q, Ahmad SA, et al. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg, 2016, 151(8): e161137.
54.	Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet, 2017, 389(10073): 1011-1024.
55.	Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg, 2008, 206(5): 833-846.
56.	Hartwig W, Strobel O, Hinz U, et al. CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol, 2013, 20(7): 2188-2196.
57.	Aldakkak M, Christians KK, Krepline AN, et al. Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer. HPB (Oxford), 2015, 17(10): 942-952.
58.	Kurahara H, Maemura K, Mataki Y, et al. Prognostication by inflammation-based score in patients with locally advanced pancreatic cancer treated with chemoradiotherapy. Pancreatology, 2015, 15(6): 688-693.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin, 2015, 65(1): 5-29.
2. Hackert T, Büchler MW. Pancreatic cancer: advances in treatment, results and limitations. Dig Dis, 2013, 31(1): 51-56.
3. Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol, 2014, 32(6): 504-512.
4. Reames BN, Ghaferi AA, Birkmeyer JD, et al. Hospital volume and operative mortality in the modern era. Ann Surg, 2014, 260(2): 244-251.
5. Nikfarjam M, Sehmbey M, Kimchi ET, et al. Additional organ resection combined with pancreaticoduodenectomy does not increase postoperative morbidity and mortality. J Gastrointest Surg, 2009, 13(5): 915-921.
6. Beltrame V, Gruppo M, Pedrazzoli S, et al. Mesenteric-Portal Vein Resection during Pancreatectomy for Pancreatic Cancer. Gastroenterol Res Pract, 2015, 2015: 659730.
7. Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic Adenocarcinoma, version 2.2014: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw, 2014, 12(8): 1083-1093.
8. Klauss M, Mohr A, von Tengg-Kobligk H, et al. A new invasion score for determining the resectability of pancreatic carcinomas with contrast-enhanced multidetector computed tomography. Pancreatology, 2008, 8(2): 204-210.
9. Shrikhande SV, Barreto SG, Goel M, et al. Multimodality imaging of pancreatic ductal adenocarcinoma: a review of the literature. HPB (Oxford), 2012, 14(10): 658-668.
10. Grenacher L, Klauss M. Computed tomography of pancreatic tumors. Radiologe, 2009, 49(2): 107-123.
11. Bockhorn M, Uzunoglu FG, Adham M, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery, 2014, 155(6): 977-988.
12. Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol, 2009, 16(7): 1727-1733.
13. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol, 2006, 13(8): 1035-1046.
14. Zhou Y, Zhang Z, Liu Y, et al. Pancreatectomy combined with superior mesenteric vein-portal vein resection for pancreatic cancer: a meta-analysis. World J Surg, 2012, 36(4): 884-891.
15. Hartwig W, Vollmer CM, Fingerhut A, et al. Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS). Surgery, 2014, 156(1): 1-14.
16. Fortner JG. Regional resection of cancer of the pancreas: a new surgical approach. Surgery, 1973, 73(2): 307-320.
17. Del Chiaro M, Segersvärd R, Rangelova E, et al. Cattell-Braasch Maneuver Combined with Artery-First Approach for Superior Mesenteric-Portal Vein Resection During Pancreatectomy. J Gastrointest Surg, 2015, 19(12): 2264-2268.
18. Giovinazzo F, Turri G, Katz MH, et al. Meta-analysis of benefits of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma. Br J Surg, 2016, 103(3): 179-191.
19. Murakami Y, Satoi S, Motoi F, et al. Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma. Br J Surg, 2015, 102(7): 837-846.
20. Hartwig W, Hackert T, Hinz U, et al. Multivisceral resection for pancreatic malignancies: risk-analysis and long-term outcome. Ann Surg, 2009, 250(1): 81-87.
21. Hackert T, Weitz J, Büchler MW. Splenic artery use for arterial reconstruction in pancreatic surgery. Langenbecks Arch Surg, 2014, 399(5): 667-671.
22. Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg, 2011, 254(6): 882-893.
23. Sanjay P, Takaori K, Govil S, et al. ‘Artery-first’ approaches to pancreatoduodenectomy. Br J Surg, 2012, 99(8): 1027-1035.
24. Inoue Y, Saiura A, Yoshioka R, et al. Pancreatoduodenectomy With Systematic Mesopancreas Dissection Using a Supracolic Anterior Artery-first Approach. Ann Surg, 2015, 262(6): 1092-1101.
25. Sperti C, Berselli M, Pedrazzoli S. Distal pancreatectomy for body-tail pancreatic cancer: is there a role for celiac axis resection? Pancreatology, 2010, 10(4): 491-498.
26. Jing W, Zhu G, Hu X, et al. Distal pancreatectomy with en bloc celiac axis resection for the treatment of locally advanced pancreatic body and tail cancer. Hepatogastroenterology, 2013, 60(121): 187-190.
27. Strasberg SM, Fields R. Left-sided pancreatic cancer: distal pancreatectomy and its variants: radical antegrade modular pancreatosplenectomy and distal pancreatectomy with celiac axis resection. Cancer J, 2012, 18(6): 562-570.
28. Hirano S, Kondo S, Hara T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg, 2007, 246(1): 46-51.
29. Wang X, Dong Y, Jin J, et al. Efficacy of modified Appleby surgery: a benefit for elderly patients? J Surg Res, 2015, 194(1): 83-90.
30. Miura T, Hirano S, Nakamura T, et al. A new preoperative prognostic scoring system to predict prognosis in patients with locally advanced pancreatic body cancer who undergo distal pancreatectomy with en bloc celiac axis resection: a retrospective cohort study. Surgery, 2014, 155(3): 457-467.
31. Okada K, Kawai M, Tani M, et al. Surgical strategy for patients with pancreatic body/tail carcinoma: who should undergo distal pancreatectomy with en-bloc celiac axis resection? Surgery, 2013, 153(3): 365-372.
32. Takahashi Y, Kaneoka Y, Maeda A, et al. Distal pancreatectomy with celiac axis resection for carcinoma of the body and tail of the pancreas. World J Surg, 2011, 35(11): 2535-2542.
33. Hackert T, Stampfl U, Schulz H, et al. Clinical significance of liver ischaemia after pancreatic resection. Br J Surg, 2011, 98(12): 1760-1765.
34. Bhayani NH, Enomoto LM, James BC, et al. Multivisceral and extended resections during pancreatoduodenectomy increase morbidity and mortality. Surgery, 2014, 155(3): 567-574.
35. Kulemann B, Hoeppner J, Wittel U, et al. Perioperative and long-term outcome after standard pancreaticoduodenectomy, additional portal vein and multivisceral resection for pancreatic head cancer. J Gastrointest Surg, 2015, 19(3): 438-444.
36. Burdelski CM, Reeh M, Bogoevski D, et al. Multivisceral resections in pancreatic cancer: identification of risk factors. World J Surg, 2011, 35(12): 2756-2763.
37. Hartwig W, Gluth A, Hinz U, et al. Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. Br J Surg, 2016, 103(12): 1683-1694.
38. Gillen S, Schuster T, Meyer Zum Büschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med, 2010, 7(4): e1000267.
39. Petrelli F, Coinu A, Borgonovo K, et al. FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas, 2015, 44(4): 515-521.
40. Tang K, Lu W, Qin W, et al. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. Pancreatology, 2016, 16(1): 28-37.
41. Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol, 2015, 22(4): 1153-1159.
42. Ajani JA, D’Amico TA, Almhanna K, et al. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw, 2015, 13(2): 194-227.
43. Schorn S, Demir IE, Reyes CM, et al. The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma - A systematic review and meta-analysis. Cancer Treat Rev, 2017, 55: 96-106.
44. Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg, 2015, 261(1): 12-17.
45. Patel BN, Giacomini C, Jeffrey RB, et al. Three-dimensional volume-rendered multidetector CT imaging of the posterior inferior pancreaticoduodenal artery: its anatomy and role in diagnosing extrapancreatic perineural invasion. Cancer Imaging, 2013, 13(4): 580-590.
46. De Robertis R, Tinazzi Martini P, Demozzi E, et al. Prognostication and response assessment in liver and pancreatic tumors: The new imaging. World J Gastroenterol, 2015, 21(22): 6794-6808.
47. Mornex F, Girard N, Delpero JR, et al. Radiochemotherapy in the management of pancreatic cancer--part I: neoadjuvant treatment. Semin Radiat Oncol, 2005, 15(4): 226-234.
48. Strobel O, Berens V, Hinz U, et al. Resection after neoadjuvant therapy for locally advanced, " unresectable” pancreatic cancer. Surgery, 2012, 152(3 Suppl 1): S33-S42.
49. Nanda RH, El-Rayes B, Maithel SK, et al. Neoadjuvant modified FOLFIRINOX and chemoradiation therapy for locally advanced pancreatic cancer improves resectability. J Surg Oncol, 2015, 111(8): 1028-1034.
50. Christians KK, Tsai S, Mahmoud A, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist, 2014, 19(3): 266-274.
51. James ES, Yao X, Cong X, et al. Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC), J Clin Oncol, 2014, 3 (Suppl 1): 32.
52. Chuong MD, Frakes JM, Figura N, et al. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer. J Gastrointest Oncol, 2016, 7(2): 221-227.
53. Katz MH, Shi Q, Ahmad SA, et al. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg, 2016, 151(8): e161137.
54. Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet, 2017, 389(10073): 1011-1024.
55. Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg, 2008, 206(5): 833-846.
56. Hartwig W, Strobel O, Hinz U, et al. CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol, 2013, 20(7): 2188-2196.
57. Aldakkak M, Christians KK, Krepline AN, et al. Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer. HPB (Oxford), 2015, 17(10): 942-952.
58. Kurahara H, Maemura K, Mataki Y, et al. Prognostication by inflammation-based score in patients with locally advanced pancreatic cancer treated with chemoradiotherapy. Pancreatology, 2015, 15(6): 688-693.

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The status of diagnosis and treatment of borderline resectable pancreatic ductal adenocarcinoma

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