Research progress on pancreatic cancer-associated diseases_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SHEN Jian , PAN Penglin ,  WU Heshui

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, R. P. China;

Corresponding author：

WU Heshui, Email: heshuiwu@hust.edu.cn

Keywords：

pancreatic cancer; pancreatic cancer-associated diseases; pathological mechanism; management; review

DOI：

10.7507/1007-9424.201909053

Video：

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Objective To conclude the current status and research progress on the pathological mechanism, development and management of pancreatic cancer-associated diseases and provide evidence for intervention of such diseases.Method The relevant literatures were reviewed, and the research progress on pancreatic cancer-associated diseases were summarized.Results There are many types of pancreatic cancer-associated diseases, and common diseases included pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, diabetes, and chronic pancreatitis. Although management and following-up about this kind of diseases remain controversial, the basic consensus has been reached.Conclusion Adequate follow-up is required for patients with pancreatic cancer-associated disease, individualized interventions should be taken if necessary.

Citation： SHEN Jian, PAN Penglin, WU Heshui. Research progress on pancreatic cancer-associated diseases. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(6): 768-773. doi: 10.7507/1007-9424.201909053 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Notta F, Hahn SA, Real FX. A genetic roadmap of pancreatic cancer: still evolving. Gut, 2017, 66(12): 2170-2178.
3.	Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
4.	Ying H, Dey P, Yao W, et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev, 2016, 30(4): 355-385.
5.	Elta GH, Enestvedt BK, Sauer BG, et al. ACG clinical guideline: diagnosis and management of pancreatic cysts. Am J Gastroenterol, 2018, 113(4): 464-479.
6.	Pittman ME, Rao R, Hruban RH. Classification, morphology, molecular pathogenesis, and outcome of premalignant lesions of the pancreas. Arch Pathol Lab Med, 2017, 141(12): 1606-1614.
7.	Hijiya N, Tsukamoto Y, Nakada C, et al. Genomic loss of DUSP4 contributes to the progression of intraepithelial neoplasm of pancreas to invasive carcinoma. Cancer Res, 2016, 76(9): 2612-2625.
8.	Nagata N, Kawazoe A, Mishima S, et al. Development of pancreatic cancer, disease-specific mortality, and all-cause mortality in patients with nonresected IPMNs: a long-term cohort study. Radiology, 2016, 278(1): 125-134.
9.	Oyama H, Tada M, Takagi K, et al. Long-term risk of malignancy in branch duct intraductal papillary mucinous neoplasms. Gastroenterology, 2020, 158(1): 226-237. e5.
10.	Lafemina J, Katabi N, Klimstra D, et al. Malignant progression in IPMN: a cohort analysis of patients initially selected for resection or observation. Ann Surg Oncol, 2013, 20(2): 440-447.
11.	Tanaka M, Fernandez-del CC, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology, 2012, 12(3): 183-197.
12.	Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut, 2013, 62(3): 339-347.
13.	Marchegiani G, Andrianello S, Pollini T, et al. "Trivial" cysts redefine the risk of cancer in presumed branch-duct intraductal papillary mucinous neoplasms of the pancreas: a potential target for follow-up discontinuation? Am J Gastroenterol, 2019, 114(10): 1678-1684.
14.	彭承宏, 郝纯毅, 戴梦华, 等. 胰腺囊性疾病诊治指南(2015 版). 中国实用外科杂志, 2015, 35(9): 955-959.
15.	The European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut, 2018, 67(5): 789-804.
16.	Hayakawa H, Fukasawa M, Sato T, et al. Carcinoembryonic antigen level in the pancreatic juice is effective in malignancy diagnosis and prediction of future malignant transformation of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol, 2019, 54(11): 1029-1037.
17.	Hirono S, Shimizu Y, Ohtsuka T, et al. Recurrence patterns after surgical resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas; a multicenter, retrospective study of 1074 IPMN patients by the Japan Pancreas Society. J Gastroenterol, 2019, [Epub ahead of print].
18.	Postlewait LM, Ethun CG, McInnis MR, et al. Association of preoperative risk factors with malignancy in pancreatic mucinous cystic neoplasms: a multicenter study. JAMA Surg, 2017, 152(1): 19-25.
19.	Humpton TJ, Alagesan B, DeNicola GM, et al. Oncogenic KRAS induces NIX-mediated mitophagy to promote pancreatic cancer. Cancer Discov, 2019, 9(9): 1268-1287.
20.	Middlebrooks CD, Stacey ML, Li Q, et al. Analysis of the CDKN2A gene in FAMMM syndrome families reveals early age of onset for additional syndromic cancers. Cancer Res, 2019, 79(11): 2992-3000.
21.	He P, Yang JW, Yang VW, et al. Kruppel-like factor 5, increased in pancreatic ductal adenocarcinoma, promotes proliferation, acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia, and tumor growth in mice. Gastroenterology, 2018, 154(5): 1494-1508.
22.	Basturk O, Hong SM, Wood LD, et al. A revised classification system and recommendations from the baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol, 2015, 39(12): 1730-1741.
23.	Willmann JK, Bonomo L, Testa AC, et al. Ultrasound molecular imaging with BR55 in patients with breast and ovarian lesions: first-in-human results. J Clin Oncol, 2017, 35(19): 2133-2140.
24.	Illes D, Terzin V, Holzinger G, et al. New-onset type 2 diabetes mellitus—A high-risk group suitable for the screening of pancreatic cancer? Pancreatology, 2016, 16(2): 266-271.
25.	Li D, Yeung SC, Hassan MM, et al. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology, 2009, 137(2): 482-488.
26.	Andersen DK, Korc M, Petersen GM, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer. Diabetes, 2017, 66(5): 1103-1110.
27.	Hart PA, Andersen DK, Mather KJ, et al. Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas, 2018, 47(10): 1239-1243.
28.	Li W, Zhang L, Chen X, et al. Hyperglycemia promotes the epithelial-mesenchymal transition of pancreatic cancer via hydrogen peroxide. Oxid Med Cell Longev, 2016, 2016: 5190314.
29.	Duan Q, Li H, Gao C, et al. High glucose promotes pancreatic cancer cells to escape from immune surveillance via AMPK-Bmi1-GATA2-MICA/B pathway. J Exp Clin Cancer Res, 2019, 38(1): 192.
30.	Koo DH, Han KD, Park CY. The incremental risk of pancreatic cancer according to fasting glucose levels: nationwide population-based cohort study. J Clin Endocrinol Metab, 2019, 104(10): 4594-4599.
31.	Lu Y, Garcia RL, Malgerud L, et al. New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer. Br J Cancer, 2015, 113(11): 1607-1614.
32.	Li D, Tang H, Hassan MM, et al. Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. Cancer Causes Control, 2011, 22(2): 189-197.
33.	Augereau C, Collet L, Vargiu P, et al. Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells. Hum Mol Genet, 2016, 25(22): 5017-5026.
34.	Shadhu K, Xi C. Inflammation and pancreatic cancer: An updated review. Saudi J Gastroenterol, 2019, 25(1): 3-13.
35.	Shimosegawa T. A New insight into chronic pancreatitis. Tohoku J Exp Med, 2019, 248(4): 225-238.
36.	Bhanot U, Kohntop R, Hasel C, et al. Evidence of notch pathway activation in the ectatic ducts of chronic pancreatitis. J Pathol, 2008, 214(3): 312-319.
37.	Ren R, Yu J, Zhang Y, et al. Inflammation promotes progression of pancreatic cancer through WNT/beta-catenin pathway-dependent manner. Pancreas, 2019, 48(8): 1003-1014.
38.	Duell EJ, Lucenteforte E, Olson SH, et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol, 2012, 23(11): 2964-2970.
39.	Matsubayashi H, Takaori K, Morizane C, et al. Familial pancreatic cancer: Concept, management and issues. World J Gastroenterol, 2017, 23(6): 935-948.
40.	Rivero-Sanchez L, Arnau-Collell C, Herrero J, et al. White-light Endoscopy is adequate for lynch syndrome surveillance in a randomized and non-inferiority study. Gastroenterology, 2019: pii: S0016-5085(19)41311-5.
41.	Poddar U, Yachha SK, Mathias A, et al. Genetic predisposition and its impact on natural history of idiopathic acute and acute recurrent pancreatitis in children. Dig Liver Dis, 2015, 47(8): 709-714.
42.	Soura E, Eliades PJ, Shannon K, et al. Hereditary melanoma: Update on syndromes and management: genetics of familial atypical multiple mole melanoma syndrome. J Am Acad Dermatol, 2016, 74(3): 395-410.
43.	Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer, 2015, 121(2): 269-275.
44.	Moussata D, Senouci L, Berger F, et al. Familial adenomatous polyposis and pancreatic cancer. Pancreas, 2015, 44(3): 512-513.
45.	Winter JM, Maitra A, Yeo CJ. Genetics and pathology of pancreatic cancer. HPB (Oxford), 2006, 8(5): 324-336.
46.	Owens DK, Davidson KW, Krist AH, et al. Screening for pancreatic cancer: US preventive services task force reaffirmation recommendation statement. JAMA, 2019, 322(5): 438-444.
47.	Tanaka M, Fernandez-Del CC, Kamisawa T, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology, 2017, 17(5): 738-753.
48.	Vege SS, Ziring B, Jain R, et al. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology, 2015, 148(4): 819-e13.
49.	Stark A, Donahue TR, Reber HA, et al. Pancreatic Cyst disease: a review. JAMA, 2016, 315(17): 1882-1893.
50.	Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2017, 15(8): 1028-1061.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Notta F, Hahn SA, Real FX. A genetic roadmap of pancreatic cancer: still evolving. Gut, 2017, 66(12): 2170-2178.
3. Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
4. Ying H, Dey P, Yao W, et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev, 2016, 30(4): 355-385.
5. Elta GH, Enestvedt BK, Sauer BG, et al. ACG clinical guideline: diagnosis and management of pancreatic cysts. Am J Gastroenterol, 2018, 113(4): 464-479.
6. Pittman ME, Rao R, Hruban RH. Classification, morphology, molecular pathogenesis, and outcome of premalignant lesions of the pancreas. Arch Pathol Lab Med, 2017, 141(12): 1606-1614.
7. Hijiya N, Tsukamoto Y, Nakada C, et al. Genomic loss of DUSP4 contributes to the progression of intraepithelial neoplasm of pancreas to invasive carcinoma. Cancer Res, 2016, 76(9): 2612-2625.
8. Nagata N, Kawazoe A, Mishima S, et al. Development of pancreatic cancer, disease-specific mortality, and all-cause mortality in patients with nonresected IPMNs: a long-term cohort study. Radiology, 2016, 278(1): 125-134.
9. Oyama H, Tada M, Takagi K, et al. Long-term risk of malignancy in branch duct intraductal papillary mucinous neoplasms. Gastroenterology, 2020, 158(1): 226-237. e5.
10. Lafemina J, Katabi N, Klimstra D, et al. Malignant progression in IPMN: a cohort analysis of patients initially selected for resection or observation. Ann Surg Oncol, 2013, 20(2): 440-447.
11. Tanaka M, Fernandez-del CC, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology, 2012, 12(3): 183-197.
12. Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut, 2013, 62(3): 339-347.
13. Marchegiani G, Andrianello S, Pollini T, et al. "Trivial" cysts redefine the risk of cancer in presumed branch-duct intraductal papillary mucinous neoplasms of the pancreas: a potential target for follow-up discontinuation? Am J Gastroenterol, 2019, 114(10): 1678-1684.
14. 彭承宏, 郝纯毅, 戴梦华, 等. 胰腺囊性疾病诊治指南(2015 版). 中国实用外科杂志, 2015, 35(9): 955-959.
15. The European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut, 2018, 67(5): 789-804.
16. Hayakawa H, Fukasawa M, Sato T, et al. Carcinoembryonic antigen level in the pancreatic juice is effective in malignancy diagnosis and prediction of future malignant transformation of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol, 2019, 54(11): 1029-1037.
17. Hirono S, Shimizu Y, Ohtsuka T, et al. Recurrence patterns after surgical resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas; a multicenter, retrospective study of 1074 IPMN patients by the Japan Pancreas Society. J Gastroenterol, 2019, [Epub ahead of print].
18. Postlewait LM, Ethun CG, McInnis MR, et al. Association of preoperative risk factors with malignancy in pancreatic mucinous cystic neoplasms: a multicenter study. JAMA Surg, 2017, 152(1): 19-25.
19. Humpton TJ, Alagesan B, DeNicola GM, et al. Oncogenic KRAS induces NIX-mediated mitophagy to promote pancreatic cancer. Cancer Discov, 2019, 9(9): 1268-1287.
20. Middlebrooks CD, Stacey ML, Li Q, et al. Analysis of the CDKN2A gene in FAMMM syndrome families reveals early age of onset for additional syndromic cancers. Cancer Res, 2019, 79(11): 2992-3000.
21. He P, Yang JW, Yang VW, et al. Kruppel-like factor 5, increased in pancreatic ductal adenocarcinoma, promotes proliferation, acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia, and tumor growth in mice. Gastroenterology, 2018, 154(5): 1494-1508.
22. Basturk O, Hong SM, Wood LD, et al. A revised classification system and recommendations from the baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol, 2015, 39(12): 1730-1741.
23. Willmann JK, Bonomo L, Testa AC, et al. Ultrasound molecular imaging with BR55 in patients with breast and ovarian lesions: first-in-human results. J Clin Oncol, 2017, 35(19): 2133-2140.
24. Illes D, Terzin V, Holzinger G, et al. New-onset type 2 diabetes mellitus—A high-risk group suitable for the screening of pancreatic cancer? Pancreatology, 2016, 16(2): 266-271.
25. Li D, Yeung SC, Hassan MM, et al. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology, 2009, 137(2): 482-488.
26. Andersen DK, Korc M, Petersen GM, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer. Diabetes, 2017, 66(5): 1103-1110.
27. Hart PA, Andersen DK, Mather KJ, et al. Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas, 2018, 47(10): 1239-1243.
28. Li W, Zhang L, Chen X, et al. Hyperglycemia promotes the epithelial-mesenchymal transition of pancreatic cancer via hydrogen peroxide. Oxid Med Cell Longev, 2016, 2016: 5190314.
29. Duan Q, Li H, Gao C, et al. High glucose promotes pancreatic cancer cells to escape from immune surveillance via AMPK-Bmi1-GATA2-MICA/B pathway. J Exp Clin Cancer Res, 2019, 38(1): 192.
30. Koo DH, Han KD, Park CY. The incremental risk of pancreatic cancer according to fasting glucose levels: nationwide population-based cohort study. J Clin Endocrinol Metab, 2019, 104(10): 4594-4599.
31. Lu Y, Garcia RL, Malgerud L, et al. New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer. Br J Cancer, 2015, 113(11): 1607-1614.
32. Li D, Tang H, Hassan MM, et al. Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. Cancer Causes Control, 2011, 22(2): 189-197.
33. Augereau C, Collet L, Vargiu P, et al. Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells. Hum Mol Genet, 2016, 25(22): 5017-5026.
34. Shadhu K, Xi C. Inflammation and pancreatic cancer: An updated review. Saudi J Gastroenterol, 2019, 25(1): 3-13.
35. Shimosegawa T. A New insight into chronic pancreatitis. Tohoku J Exp Med, 2019, 248(4): 225-238.
36. Bhanot U, Kohntop R, Hasel C, et al. Evidence of notch pathway activation in the ectatic ducts of chronic pancreatitis. J Pathol, 2008, 214(3): 312-319.
37. Ren R, Yu J, Zhang Y, et al. Inflammation promotes progression of pancreatic cancer through WNT/beta-catenin pathway-dependent manner. Pancreas, 2019, 48(8): 1003-1014.
38. Duell EJ, Lucenteforte E, Olson SH, et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol, 2012, 23(11): 2964-2970.
39. Matsubayashi H, Takaori K, Morizane C, et al. Familial pancreatic cancer: Concept, management and issues. World J Gastroenterol, 2017, 23(6): 935-948.
40. Rivero-Sanchez L, Arnau-Collell C, Herrero J, et al. White-light Endoscopy is adequate for lynch syndrome surveillance in a randomized and non-inferiority study. Gastroenterology, 2019: pii: S0016-5085(19)41311-5.
41. Poddar U, Yachha SK, Mathias A, et al. Genetic predisposition and its impact on natural history of idiopathic acute and acute recurrent pancreatitis in children. Dig Liver Dis, 2015, 47(8): 709-714.
42. Soura E, Eliades PJ, Shannon K, et al. Hereditary melanoma: Update on syndromes and management: genetics of familial atypical multiple mole melanoma syndrome. J Am Acad Dermatol, 2016, 74(3): 395-410.
43. Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer, 2015, 121(2): 269-275.
44. Moussata D, Senouci L, Berger F, et al. Familial adenomatous polyposis and pancreatic cancer. Pancreas, 2015, 44(3): 512-513.
45. Winter JM, Maitra A, Yeo CJ. Genetics and pathology of pancreatic cancer. HPB (Oxford), 2006, 8(5): 324-336.
46. Owens DK, Davidson KW, Krist AH, et al. Screening for pancreatic cancer: US preventive services task force reaffirmation recommendation statement. JAMA, 2019, 322(5): 438-444.
47. Tanaka M, Fernandez-Del CC, Kamisawa T, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology, 2017, 17(5): 738-753.
48. Vege SS, Ziring B, Jain R, et al. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology, 2015, 148(4): 819-e13.
49. Stark A, Donahue TR, Reber HA, et al. Pancreatic Cyst disease: a review. JAMA, 2016, 315(17): 1882-1893.
50. Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2017, 15(8): 1028-1061.

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Research progress on pancreatic cancer-associated diseases

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