Annals of Surgical Oncology

, Volume 24, Issue 4, pp 1127–1133 | Cite as

Pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors is an Independent Poor Prognostic Factor

  • Yoshihide Nanno
  • Ippei Matsumoto
  • Yoh Zen
  • Kyoko Otani
  • Jun Uemura
  • Hirochika Toyama
  • Sadaki Asari
  • Tadahiro Goto
  • Tetsuo Ajiki
  • Keiichi Okano
  • Yasuyuki Suzuki
  • Yoshifumi Takeyama
  • Takumi Fukumoto
  • Yonson Ku
Pancreatic Tumors

Abstract

Background

The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs.

Methods

The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection.

Results

MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P < 0.001), with a 5 years recurrence-free rate of 41%. On multivariate analysis, MPD involvement was significantly associated with nodal metastasis [odds ratio (OR) 16; 95% confidence interval (CI) 3.8–89; P < 0.001] and recurrence (OR 8.0; 95% CI 1.7–46; P = 0.009). The radiology–pathology correlation revealed that stenosis of the MPD was due to periductal and/or intraductal tumor invasion. Cases with MPD involvement had microscopic venous invasion (P = 0.010) and perineural infiltration (P = 0.002) more frequently than did those with no ductal infiltration.

Conclusions

MPD involvement in PNETs may serve as an imaging sign indicating an aggressive clinical course.

References

  1. 1.
    Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRefPubMedGoogle Scholar
  2. 2.
    Postlewait LM, Ethun CG, Baptiste GG, et al. Pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy. J Surg Oncol. 2016;114:440–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Hashim YM, Trinkaus KM, Linehan DC, Strasberg SS, Fields RC, Cao D, Hawkins WG. Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs). Ann Surg. 2014;259:197–203.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Fesinmeyer MD, Austin MA, Li CI, De Roos AJ, Bowen DJ. Differences in survival by histologic type of pancreatic cancer. Cancer Epidemiol Biomark Prev. 2005;14:1766–73.CrossRefGoogle Scholar
  6. 6.
    Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469–92.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Krampitz GW, Norton JA, Poultsides GA, Visser BC, Sun L, Jensen RT. Lymph nodes and survival in pancreatic neuroendocrine tumors. Arch Surg. 2012;147:820–7.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gibril F, Doppman JL, Reynolds JC, et al. Bone metastasis in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their detection, frequency, location, and effect to their detection on management. J Clin Oncol. 1998;16:1040–53.CrossRefPubMedGoogle Scholar
  9. 9.
    Kulke MH, Shah MH, Benson AB 3rd, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Cancer Netw. 2015;13:78–108.Google Scholar
  10. 10.
    Fesinmeyer MD, Austin MA, Li CI, De Roos AJ, Bowen DJ. Differences in survival by histologic type of pancreatic cancer. Cancer Epidemiol Biomark Prev. 2005;14:1766–73.CrossRefGoogle Scholar
  11. 11.
    Tatsumoto S, Kodama Y, Sakurai Y, Shinohara T, Katanuma A, Maguchi H. Pancreatic neuroendocrine neoplasm: correlation between computed tomography enhancement patterns and prognostic factors of surgical and endoscopic ultrasound-guided fine-needle aspiration biopsy specimens. Abdom Imaging. 2013;38:358–66.CrossRefPubMedGoogle Scholar
  12. 12.
    Tsutsumi K, Ohtsuka T, Mori Y, et al. Analysis of lymph node metastasis in pancreatic neuroendocrine tumors (PNETs) based on the tumor size and hormonal production. J Gastroenterol. 2012;47:678–85.CrossRefPubMedGoogle Scholar
  13. 13.
    Shanahan MA, Salem A, Fisher A, Cho CS, Leverson G, Winslow ER, Weber SM. Chromogranin A predicts survival for resected pancreatic neuroendocrine tumors. J Surg Res. 2016;201:38–43.CrossRefPubMedGoogle Scholar
  14. 14.
    Obara T, Shudo R, Fujii T, et al. Pancreatic duct obstruction caused by malignant islet cell tumors of the pancreas. Gastrointest Endosc. 2000;51:604–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Kitami CE, Shimizu T, Sato O, et al. Malignant islet cell tumor projecting into the main pancreatic duct. J Hepatobiliary Pancreat Surg. 2000;7:529–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Akatsu T, Wakabayashi G, Aiura K, et al. Intraductal growth of a nonfunctioning endocrine tumor of the pancreas. J Gastroenterol. 2004;39:584–8.PubMedGoogle Scholar
  17. 17.
    Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol. 2005;19:783–98.CrossRefPubMedGoogle Scholar
  18. 18.
    Bosman FT, Cameiro F, Hruban RH, et al. WHO classification of tumours. No. 3. WHO classification of tumours of the digestive system, 4th edn. Lyon: IARC, 2010.Google Scholar
  19. 19.
    Nanno Y, Toyama H, Otani K, et al. Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence. Pancreatology. 2016;16:882–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Parekh JR, Wang SC, Bergsland EK, Venook AP, Warren RS, Kim GE, Nakakura EK. Lymph node sampling rates and predictors of nodal metastasis in pancreatic neuroendocrine tumor resections: the UCSF experience with 149 patients. Pancreas. 2012;41:840–4.CrossRefPubMedGoogle Scholar
  21. 21.
    Bilimoria KY, Talamonti MS, Tomlinson JS, Stewart AK, Winchester DP, Ko CY, Bentrem DJ. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients. Ann Surg. 2008;247:490–500.CrossRefPubMedGoogle Scholar
  22. 22.
    Jarufe NP, Coldham C, Orug T, Mayer AD, Mirza DF, Buckels JA, Bramhall SR. Neuroendocrine tumours of the pancreas: predictors of survival after surgical treatment. Dig Surg. 2005;22:157–62.CrossRefPubMedGoogle Scholar
  23. 23.
    Nagai E, Yamaguchi K, Hashimoto H, Sakurai T. Carcinoid tumor of the pancreas with obstructive pancreatitis. Am J Gastroenterol. 1992;87:361–4.PubMedGoogle Scholar
  24. 24.
    Ogawa M, Kawaguchi Y, Maruno A, et al. Small serotonin-positive pancreatic endocrine tumors caused obstruction of the main pancreatic duct. World J Gastroenterol. 2012;18:6669–73.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chaudhry A, Funa K, Oberg K. Expression of growth factor peptides and their receptors in neuroendocrine tumors of the digestive system. Acta Oncol. 1993;32:107–14.CrossRefPubMedGoogle Scholar
  26. 26.
    Chaudhry A, Papanicolaou V, Oberg K, Heldin CH, Funa K. Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Cancer Res. 1992;52:1006–12.PubMedGoogle Scholar
  27. 27.
    Curran T, Pockaj BA, Gray RJ, Halfdanarson TR, Wasif N. Importance of lymph node involvement in pancreatic neuroendocrine tumors: impact on survival and implications for surgical resection. J Gastrointest Surg. 2015;19:152–60.CrossRefPubMedGoogle Scholar
  28. 28.
    Kaltenborn A, Matzke S, Kleine M, et al. Prediction of survival and tumor recurrence in patients undergoing surgery for pancreatic neuroendocrine neoplasms. J Surg Oncol. 2016;113:194–202.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Yoshihide Nanno
    • 1
  • Ippei Matsumoto
    • 2
  • Yoh Zen
    • 3
  • Kyoko Otani
    • 3
  • Jun Uemura
    • 4
  • Hirochika Toyama
    • 1
  • Sadaki Asari
    • 1
  • Tadahiro Goto
    • 1
  • Tetsuo Ajiki
    • 1
  • Keiichi Okano
    • 4
  • Yasuyuki Suzuki
    • 4
  • Yoshifumi Takeyama
    • 2
  • Takumi Fukumoto
    • 1
  • Yonson Ku
    • 1
  1. 1.Division of Hepato-Biliary-Pancreatic Surgery, Department of SurgeryKobe University Graduate School of MedicineKobeJapan
  2. 2.Division of Hepato-Biliary-Pancreatic Surgery, Department of SurgeryKindai University Faculty of MedicineOsaka-SayamaJapan
  3. 3.Department of Diagnostic PathologyKobe University Graduate School of MedicineKobeJapan
  4. 4.Department of Gastroenterological SurgeryKagawa University Faculty of MedicineTakamatsuJapan

Personalised recommendations