Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2017

01-04-2017 | Pancreatic Tumors

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

Authors: Yoshihide Nanno, MD, Ippei Matsumoto, MD, PhD, Yoh Zen, MD, PhD, FRCPath, Kyoko Otani, MD, Jun Uemura, MD, Hirochika Toyama, MD, PhD, Sadaki Asari, MD, PhD, Tadahiro Goto, MD, PhD, Tetsuo Ajiki, MD, PhD, Keiichi Okano, MD, PhD, Yasuyuki Suzuki, MD, PhD, Yoshifumi Takeyama, MD, PhD, Takumi Fukumoto, MD, PhD, Yonson Ku, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2017

Login to get access

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.
Literature
1.
go back to reference Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRefPubMed Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
5.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference Kulke MH, Shah MH, Benson AB 3rd, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Cancer Netw. 2015;13:78–108. Kulke MH, Shah MH, Benson AB 3rd, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Cancer Netw. 2015;13:78–108.
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference Akatsu T, Wakabayashi G, Aiura K, et al. Intraductal growth of a nonfunctioning endocrine tumor of the pancreas. J Gastroenterol. 2004;39:584–8.PubMed Akatsu T, Wakabayashi G, Aiura K, et al. Intraductal growth of a nonfunctioning endocrine tumor of the pancreas. J Gastroenterol. 2004;39:584–8.PubMed
18.
go back to reference 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. 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.
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference Nagai E, Yamaguchi K, Hashimoto H, Sakurai T. Carcinoid tumor of the pancreas with obstructive pancreatitis. Am J Gastroenterol. 1992;87:361–4.PubMed Nagai E, Yamaguchi K, Hashimoto H, Sakurai T. Carcinoid tumor of the pancreas with obstructive pancreatitis. Am J Gastroenterol. 1992;87:361–4.PubMed
24.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.PubMed 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.PubMed
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors is an Independent Poor Prognostic Factor
Authors
Yoshihide Nanno, MD
Ippei Matsumoto, MD, PhD
Yoh Zen, MD, PhD, FRCPath
Kyoko Otani, MD
Jun Uemura, MD
Hirochika Toyama, MD, PhD
Sadaki Asari, MD, PhD
Tadahiro Goto, MD, PhD
Tetsuo Ajiki, MD, PhD
Keiichi Okano, MD, PhD
Yasuyuki Suzuki, MD, PhD
Yoshifumi Takeyama, MD, PhD
Takumi Fukumoto, MD, PhD
Yonson Ku, MD, PhD
Publication date
01-04-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5663-8

Other articles of this Issue 4/2017

Annals of Surgical Oncology 4/2017 Go to the issue