Skip to main content
SpringerLink
Log in
Book cover

Pancreatic Cancer pp 1153–1171Cite as

Modern Japanese Approach to Pancreas Cancer

  • Reference work entry

  • 1863 Accesses

Abstract:

Strong invasiveness, late appearance of clinical symptoms and a lack of efficient screening methods make the prognosis of pancreatic cancer dismal. Principal clues to early diagnosis of pancreatic cancer including pancreatic duct dilatation, diabetes, and intraductal papillary mucinous neoplasms are discussed, referring to many Japanese contributions. The Japan Pancreas Society (JPS) published Clinical Guidelines for Management of Pancreatic Cancer in 2006. The guidelines provide answers to 29 clinical questions with graded evidence-based recommendations. Diagnosis, chemotherapy, radiation therapy, surgical, and adjuvant treatments are addressed using two algorithms for the diagnosis and treatment. Treatment of the clinical stage IVa disease is still controversial, being resectable in some patients but not in others. Patients with no major arterial invasion should undergo resection rather than chemoradiation according to a prospective randomized study from Japan. The survival benefit of combined resection of the portal vein has not been proven yet. With regard to surgical treatments Japanese surgeons pursued cure by means of extended resection with complete dissection of retroperitoneal lymph nodes and neural plexus. However, several prospective randomized trials did not confirm the survival benefit of extended resection compared to standard resection with regional lymph node dissection only. One prospective randomized multi-institutional study from Japan yielded no significant difference in 1-year and 3-year survival rates after extended resection. The survival benefit of extended resection in those with lymph node metastasis demonstrated in one study may still justify D2 lymph node dissection. Current interest is focused on the significance of postoperative adjuvant chemotherapy. The analysis of the JPS Pancreatic Cancer Registry indicates that the 5-year survival rate of patients with resected pancreatic cancer has been significantly improved after the introduction of gemcitabine into Japan. A prospective randomized comparison of resection with and without postoperative administration of gemcitabine for 6 months conducted in Europe showed lengthened disease-free and overall 5-year survival rates. A Japanese group conducted a similar study with gemcitabine adjuvant treatment for 3 months after resection, which produced similarly prolonged disease free survival so far. If 5-year overall survival should not be improved, it may suggest the necessity of a longer period of adjuvant chemotherapy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   649.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Japan Pancreas Society: Pancreatic cancer registry report 2007. Survival rates after resection of ordinary-type pancreatic cancer. Suizou 2007;22:e39–e390. http://www.jstage.jst.go.jp/article/suizo/22/1/e39/_pdf/-char/ja/

    Google Scholar 

  2. Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, Gullerud RE, Donohue JH, Nagorney DM, Farnell MB: Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg 2008;247:456–462.

    Article  PubMed  Google Scholar 

  3. The Japan Pancreas Society: Evidence-based clinical guidelines for the management of pancreatic cancer. Tokyo, Japan: Kanehara, 2006 (in Japanese)

    Google Scholar 

  4. The Japan Pancreas Society: Classification of pancreatic carcinoma. 2nd English version. Tokyo, Japan: Kanehara, 2003.

    Google Scholar 

  5. Inoue K, Ohuchida J, Ohtsuka T, Nabae T, Yokohata K, Ogawa Y, Yamaguchi K, Tanaka M: Severe localized stenosis and marked dilatation of the main pancreatic duct are indicators of pancreatic cancer instead of chronic pancreatitis on endoscopic retrograde balloon pancreatography. Gastrointest Endosc 2003;58:510–515.

    Article  PubMed  Google Scholar 

  6. Tada M, Omata M, Kawai S, Saisho H, Ohto M, Saiki RK, Sninsky JJ: Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res 1993;53:2472–2474.

    CAS  PubMed  Google Scholar 

  7. Suehara N, Mizumoto K, Muta T, Tominaga Y, Shimura H, Kitajima S, Hamasaki N, Tsuneyoshi M, Tanaka M: Telomerase elevation in pancreatic ductal carcinoma compared to nonmalignant pathological states. Clin Cancer Res 1997;3:993–998.

    CAS  PubMed  Google Scholar 

  8. Suehara N, Mizumoto K, Tanaka M, Niiyama H, Yokohata K, Tominaga Y, Shimura H, Muta T, Hamasaki N: Telomerase activity in pancreatic juice differentiates ductal carcinoma from adenoma and pancreatitis. Clin Cancer Res 1997;3:2479–2483.

    CAS  PubMed  Google Scholar 

  9. Tada M, Teratani T, Komatsu Y, Kawabe T, Shiratori Y, Omata M: Quantitative analysis of ras gene mutation in pancreatic juice for diagnosis of pancreatic adenocarcinoma. Dig Dis Sci 1998;43:15–20.

    Article  CAS  PubMed  Google Scholar 

  10. Tateishi K, Tada M, Yamagata M, Isayama H, Komatsu Y, Kawabe T, Shiratori Y, Omata M: High proportion of mutant K-ras gene in pancreatic juice of patients with pancreatic cystic lesions. Gut 1999;45:737–740.

    Article  CAS  PubMed  Google Scholar 

  11. Uehara H, Nakaizumi A, Tatsuta M, Baba M, Takenaka A, Uedo N, Sakai N, Yano H, Iishi H, Ohigashi H, Ishikawa O, Okada S, Kakizoe T: Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations. Am J Gastroenterol 1999;94:2513–2518.

    Article  CAS  PubMed  Google Scholar 

  12. Nakaizumi A, Uehara H, Takenaka A, Uedo N, Sakai N, Yano H, Ohigashi H, Ishikawa O, Ishiguro S, Sugano K, Tatsuta M: Diagnosis of pancreatic cancer by cytology and measurement of oncogene and tumor markers in pure pancreatic juice aspirated by endoscopy. Hepatogastroenterology 1999;46:31–37.

    CAS  PubMed  Google Scholar 

  13. Sato N, Maehara N, Mizumoto K, Nagai E, Yasoshima T, Hirata K, Tanaka M: Telomerase activity correlates with aggressive behavior of human pancreatic cancer cells. Cancer 2000;91:496–504.

    Article  Google Scholar 

  14. Tada M, Tateishi K, Kawabe T, Sasahira N, Isayama H, Komatsu Y, Shiratori Y, Omata M: Quantity of mutant K-ras gene in pancreatic secretions for diagnosis of pancreatic carcinoma with different assays: analysis of 100 patients. Clin Chim Acta 2002;324:105–111.

    Article  CAS  PubMed  Google Scholar 

  15. Ohuchida K, Mizumoto K, Ishikawa N, Sato N, Nagai E, Yamaguchi K, Takaishi H, Ide T, Tanaka M: A highly sensitive and quantitative telomerase activity assay with pancreatic juice is useful for diagnosis of pancreatic carcinoma without problems due to polymerase chain reaction inhibitors. Cancer 2004;101:2309–2317.

    Article  CAS  PubMed  Google Scholar 

  16. Ohuchida K, Mizumoto K, Ogura Y, Ishikawa N, Nagai E, Yamaguchi K, Tanaka M: Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer. Clin Cancer Res 2005;11:2285–2292.

    Article  CAS  PubMed  Google Scholar 

  17. Ohuchida K, Mizumoto K, Fujita H, Yamaguchi H, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M: Sonic hedgehog is an early developmental marker of intraductal papillary mucinous neoplasms: clinical implications of mRNA levels in pancreatic juice. J Pathol 2006;210:42–48.

    Article  CAS  PubMed  Google Scholar 

  18. Ohuchida K, Mizumoto K, Yamada D, Fujii K, Ishikawa N, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M: Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer. Int J Cancer 2006;1182:405–411.

    Article  Google Scholar 

  19. Ohuchida K, Mizumoto K, Ohhashi S, Yamaguchi H, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M: Twist, a novel oncogene, is upregulated in pancreatic cancer: Clinical implication of Twist expression in pancreatic juice. Int J Cancer 2007;120:1634–1640.

    Article  CAS  PubMed  Google Scholar 

  20. Ohuchida K, Mizumoto K, Yu J, Yamaguchi H, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M: S100A6 is increased in a stepwise manner during pancreatic carcinogenesis: clinical value of expression analysis in 98 pancreatic juice samples. Cancer Epidemiol Biomarkers Prev 2007;16:649–654.

    Article  CAS  PubMed  Google Scholar 

  21. Hashimoto Y, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Ohge H, Fukuda E, Sueda T, Hiyama E: Detection of human telomerase reverse transcriptase (hTERT) expression in tissue and pancreatic juice from pancreatic cancer. Surgery 2008;143:113–125.

    Article  PubMed  Google Scholar 

  22. Uehara H, Nakaizumi A, Iishi H, Takenaka A, Eguchi H, Ohigashi H, Ishikawa O: In situ telomerase activity in pancreatic juice may discriminate pancreatic cancer from other pancreatic diseases. Pancreas 2008;36:236–240.

    Article  CAS  PubMed  Google Scholar 

  23. Girelli CM, Reguzzoni G, Limido E, Savastano A, Rocca F: Pancreatic carcinoma: differences between patients with or without diabetes mellitus. Recent Prog Med 1995;86:143–146.

    CAS  Google Scholar 

  24. Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A: Cancer and diabetes--a follow-up study of two population-based cohorts of diabetic patients. J Intern Med 1997;241:471–475.

    Article  CAS  PubMed  Google Scholar 

  25. Ogawa Y, Tanaka M, Inoue K, Yamaguchi K, Chijiiwa K, Mizumoto K, Tsutsu N, Nakamura Y: A prospective pancreatographic study of the prevalence of pancreatic carcinoma in patients with diabetes mellitus. Cancer 2002;94:2344–2349.

    Article  PubMed  Google Scholar 

  26. Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM: Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology 2005;129:504–511.

    PubMed  Google Scholar 

  27. Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K, Matsuno S, International Association of Pancreatology: International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006;6:17–32.

    Article  PubMed  Google Scholar 

  28. Nakaizumi A, Tatsuta M, Uehara H, Takenaka A, Ohigashi H, Ishikawa O, Ishiguro S: Usefulness of simple endoscopic aspiration cytology of pancreatic juice for diagnosis of early pancreatic neoplasm. A prospective study. Dig Dis Sci 1997;42:1796–1803.

    Article  CAS  PubMed  Google Scholar 

  29. Yamaguchi K, Nakamura K, Yokohata K, Shimizu S, Chijiiwa K, Tanaka M: Pancreatic cyst as a sentinel of in situ carcinoma of the pancreas. Report of two cases. Int J Pancreatol 1997;22:227–231.

    CAS  PubMed  Google Scholar 

  30. Yamaguchi K, Ohuchida J, Ohtsuka T, Nakano K, Tanaka M: Intraductal papillary-mucinous tumor of the pancreas concomitant with ductal carcinoma of the pancreas. Pancreatology 2002;2:484–490.

    Article  PubMed  Google Scholar 

  31. Tada M, Kawabe T, Arizumi M, Togawa O, Matsubara S, Yamamoto N, Nakai Y, Sasahira N, Hirano K, Tsujino T, Tateishi K, Isayama H, Toda N, Yoshida H, Omata M: Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study in 197 patients. Clin Gastroenterol Hepatol 2006;4:1265–1270.

    Article  PubMed  Google Scholar 

  32. Tanaka M, Yokohata K, Konomi H, Yamaguchi K, Chijiiwa K, Ohta M: Segmental balloon cytology for preoperative localization of in situ pancreatic cancer. Gastrointest Endosc 1997;46:447–449.

    Article  CAS  PubMed  Google Scholar 

  33. Uehara H, Nakaizumi A, Ishikawa O, Iishi H, Tatsumi K, Takakura R, Ishida T, Takano Y, Tanaka S, Takenaka A: Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas. Gut 2008;57:1561–1565.

    Article  CAS  PubMed  Google Scholar 

  34. Imamura M, Doi R, Imaizumi T, Funakoshi A, Wakasugi H, Sunamura M, Ogata Y, Hishinuma S, Asano T, Aikou T, Hosotani R, Maetani S: A randomized multicenter trial comparing resection and radiochemotherapy for resectable locally invasive pancreatic cancer. Surgery 2004;136:1003–1011.

    Article  PubMed  Google Scholar 

  35. Doi R, Imamura M, Hosotani R, Imaizumi T, Hatori T, Takasaki K, Funakoshi A, Wakasugi H, Asano T, Hishinuma S, Ogata Y, Sunamura M, Yamaguchi K, Tanaka M, Takao S, Aikou T, Hirata K, Maguchi H, Aiura K, Aoki T, Kakita A, Sasaki M, Ozaki M, Matsusue S, Higashide S, Noda H, Ikeda S, Maetani S, Yoshida S: The Japan Pancreatic Cancer Study Group: Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: Final results of a randomized multi-institutional trial. Surg Today 2008;38:1021–1028.

    Article  PubMed  Google Scholar 

  36. Pedrazzoli S, DiCarlo V, Dionigi R, Mosca F, Pedersoli P, Pasquali C, Kleoppel G, Dhaene K, Michelassi F: Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg 1998;228:508–517.

    Article  CAS  PubMed  Google Scholar 

  37. Yeo CJ, Cameron JL, Lillemoe KD, Sohn TA, Campbell KA, Sauter PK, Coleman J, Abrams RA, Hruban RH: Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 2002;236:355–366.

    Article  PubMed  Google Scholar 

  38. Nguyen TC, Sohn TA, Cameron JL, Lillemoe KD, Campbell KA, Coleman J, Sauter PK, Abrams RA, Hruban RH, Yeo CJ: Standard vs. radical pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective, randomized trial evaluating quality of life in pancreaticoduodenectomy survivors. J Gastrointest Surg 2003;7:1–9.

    Article  PubMed  Google Scholar 

  39. Farnell MB, Pearson RK, Sarr MG, DiMagno EP, Burgart LJ, Dahl TR, Foster N, Sargent DJ: Pancreas Cancer Working Group. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery 2005;138:618–630.

    Article  PubMed  Google Scholar 

  40. Nagino M, Yuji N: Does “extended” surgery for pancreatic head adenocarcinoma have survival impact? Nippon Geka Gakkai Zasshi 2006;107:173–176 (Review in Japanese).

    PubMed  Google Scholar 

  41. Boeck S, Ankerst DP, Heinemann V: The role of adjuvant chemotherapy for patients with resected pancreatic cancer: systematic review of randomized controlled trials and meta-analysis. Oncology 2007;72:314–321.

    Article  CAS  PubMed  Google Scholar 

  42. Japan Pancreas Society: Report of the Pancreatic Cancer Registry 2007. Trend of survival of the patients with histologically confirmed unresectable invasive pancreatic cancer of JPS Stage IVa, IVb and unknown Stage. Suizou 2007;22:e45. http://www.jstage.jst.go.jp/article/suizo/22/1/e45/_pdf/-char/ja/

  43. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H: Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267–277.

    Article  CAS  PubMed  Google Scholar 

  44. Neuhaus P, Riess H, Post S, Gellert K, Ridwelski K, Schramm H, Zuelke C, Fahlke J, Langrehr J, Oettle H, Deutsche Krebsgesellschaft (CAO/AIO): CONKO-001: Final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer. Chicago: ASCO, 2008.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masao Tanaka

Authors
  1. Masao Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this entry

Cite this entry

Tanaka, M. (2010). Modern Japanese Approach to Pancreas Cancer. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_49

Download citation

Publish with us

Policies and ethics

Search

Navigation