Skip to main content
SpringerLink
Log in

Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging.

Methods

Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery.

Results

From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent.

Conclusions

Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fitzgerald TL, Dennis SO, Kachare SD, Vohra NA, Zervos EE (2015) Increasing incidence of duodenal neuroendocrine tumors: incidental discovery of indolent disease? Surgery 158:466–471

    Article  PubMed  Google Scholar 

  2. Lipinski M, Rydzewska G, Foltyn W, Andrysiak-Mamos E, Bałdys-Waligórska A, Bednarczuk T, Blicharz-Dorniak J, Bolanowski M, Boratyn-Nowicka A, Borowska M, Cichocki A, Ćwikła JB, Falconi M, Handkiewicz-Junak D, Hubalewska-Dydejczyk A, Jarząb B, Junik R, Kajdaniuk D, Kamiński G, Kolasińska-Ćwikła A, Kowalska A, Król R, Królicki L, Kunikowska J, Kuśnierz K, Lampe P, Lange D, Lewczuk-Myślicka A, Lewiński A, Londzin-Olesik M, Marek B, Nasierowska-Guttmejer A, Nowakowska-Duława E, Pilch-Kowalczyk J, Poczkaj K, Rosiek V, Ruchała M, Siemińska L, Sowa-Staszczak A, Starzyńska T, Steinhof-Radwańska K, Strzelczyk J, Sworczak K, Syrenicz A, Szawłowski A, Szczepkowski M, Wachuła E, Zajęcki W, Zemczak A, Zgliczyński W, Kos-Kudła B (2017) Gastroduodenal neuroendocrine neoplasms, including gastrinoma—management guidelines (recommended by the polish network of neuroendocrine tumours). Endokrynol Pol 68:138–153

    Article  CAS  PubMed  Google Scholar 

  3. Jensen RT, Rindi G, Arnold R, Lopes JM, Brandi ML, Bechstein WO, Christ E, Taal BG, Knigge U, Ahlman H, Kwekkeboom DJ, O’Toole D, Frascati Consensus Conference; European Neuroendocrine Tumor Society (2006) Well differentiated duodenal tumor/carcinoma (excluding gastrinomas). Neuroendocrinology 84:165–172

    Article  CAS  PubMed  Google Scholar 

  4. Vanoli A, La Rosa S, Klersy C, Grillo F, Albarello L, Inzani F, Maragliano R, Manca R, Luinetti O, Milione M, Doglioni C, Rindi G, Capella C, Solcia E (2017) Four neuroendocrine tumor types and neuroendocrine carcinoma of the duodenum: analysis of 203 cases. Neuroendocrinology 104:112–125

    Article  CAS  PubMed  Google Scholar 

  5. Kloppel G, Perren A, Heitz PU (2004) The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci 1014:13–27

    Article  PubMed  Google Scholar 

  6. Hoffmann KM, Furukawa M, Jensen RT (2005) Duodenal neuroendocrine tumors: classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 19:675–697

    Article  CAS  PubMed  Google Scholar 

  7. Modlin IM, Champaneria MC, Chan AK, Kidd M (2007) A three-decade analysis of 3911 small intestinal neuroendocrine tumors: the rapid pace of no progress. Am J Gastroenterol 102:1464–1473

    Article  PubMed  Google Scholar 

  8. Massironi S, Campana D, Partelli S, Panzuto F, Rossi RE, Faggiano A, Brighi N, Falconi M, Rinzivillo M, Delle Fave G, Colao AM, Conte D (2018) Heterogeneity of duodenal neuroendocrine tumors: an Italian Multi-center Experience. Ann Surg Oncol 25:3200–3206

    Article  PubMed  Google Scholar 

  9. Delle Fave G, O’Toole D, Sundin A, Taal B, Ferolla P, Ramage JK, Ferone D, Ito T, Weber W, Zheng-Pei Z, De Herder WW, Pascher A, Ruszniewski P, Vienna consensus conference participants (2016) ENETS consensus guidelines update for gastroduodenal neuroendocrine neoplasms. Neuroendocrinology 103:119–124

    Article  CAS  PubMed  Google Scholar 

  10. Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT (2016) ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 103:153–171

    Article  CAS  PubMed  Google Scholar 

  11. Rossi RE, Rausa E, Cavalcoli F, Conte D, Massironi S (2018) Duodenal neuroendocrine neoplasms: a still poorly recognized clinical entity. Scand J Gastroenterol 53:835–842

    Article  PubMed  Google Scholar 

  12. Basford P, Bhandari P (2016) Endoscopic resection of sporadic duodenal neuroendocrine tumors: why is this not so easy? Endoscopy 48:965–966

    Article  PubMed  Google Scholar 

  13. Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, Washington KM, Carneiro F, Cree IA (2020) The 2019 WHO classification of tumours of the digestive system. Histopathology 76:182–188

    Article  PubMed  Google Scholar 

  14. Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B, all other Frascati Consensus Conference participants; European Neuroendocrine Tumor Society (ENETS); European Neuroendocrine Tumor Society (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449:395–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hatzitheoklitos E, Büchler MW, Friess H, Poch B, Ebert M, Mohr W, Imaizumi T, Beger HG (1994) Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features. Cancer 73:1580–1588

    Article  CAS  PubMed  Google Scholar 

  16. Milanetto AC, Pasquali C, Da Broi M, Brambilla T, Capretti G, Zerbi A (2018) Ampullary neuroendocrine neoplasms: surgical experience of a rare and challenging entity. Langenbecks Arch Surg 403:581–589

    Article  CAS  PubMed  Google Scholar 

  17. Kim GH, Kim JI, Jeon SW, Moon JS, Chung IK, Jee SR, Kim HU, Seo GS, Baik GH, Lee YC, Korean College of Helicobacter and Upper Gastrointestinal Research (2014) Endoscopic resection for duodenal carcinoid tumors: a multicenter, retrospective study. J Gastroenterol Hepatol 29:318–324

    Article  PubMed  Google Scholar 

  18. Fukasawa H, Tounou S, Nabetani M, Michida T (2017) Endoscopic resection of ampullary neuroendocrine tumor. Intern Med 56:499–503

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yokoyama S, Takifuji K, Tani M, Kawai M, Naka T, Uchiyama K, Yamaue H (2011) Endoscopic resection of duodenal bulb neuroendocrine tumor larger than 10 mm in diameter. BMC Gastroenterol 11:67

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gilani N, Ramirez FC (2007) Endoscopic resection of an ampullary carcinoid presenting with upper gastrointestinal bleeding: a case report and review of the literature. World J Gastroenterol 13:1268–1270

    Article  PubMed  PubMed Central  Google Scholar 

  21. Fukatsu H, Kawamoto H, Fujii M, Tsutsumi K, Kato H, Hirao K, Kurihara N, Okamoto Y, Ogawa T, Ishida E, Okada H, Sakaguchi K (2007) Periampullary carcinoid tumor. Endoscopy Suppl 1:E49-50

    Article  Google Scholar 

  22. Yi H, Wu C, Mou Y, Liu W, Li J, Zhang Q, Luo R, Tang MCC, Hu B (2012) Successful en bloc resection of papillary neuroendocrine tumors by duodenoscope using endoscopic submucosal dissection method. Clin Res Hepatol Gastroenterol 36:e100–e103

    Article  PubMed  Google Scholar 

  23. Odabasi M, Yildiz KM, Cengiz E, Hasan AH, Gunay E, Ozkan E, Aktekin A, Kaya B, Muftuoglu TM (2013) Treatment of ampullary neuroendocrine tumor by endoscopic snare papillectomy. Am J Case Rep 14:439–443

    Article  PubMed  PubMed Central  Google Scholar 

  24. Panzuto F, Massironi S, Partelli CD, Rinzivillo M, Invernizzi P, Andreasi V, Lamberti G, Falconi M (2020) Gastro-entero-pancreatic neuroendocrine neoplasia: the rules for non-operative management. Surg Oncol 35:141–148

    Article  PubMed  Google Scholar 

  25. Dogeas E, Cameron JL, Wolfgang CL, Hirose K, Hruban RH, Makary MA, Pawlik TA, Choti MA (2017) Duodenal and ampullary carcinoid tumors: size predicts necessity for lymphadenectomy. J Gastrointest Surg 21:1262–1269

    Article  PubMed  Google Scholar 

  26. Soga J (2003) Endocrinocarcinomas (carcinoids and their variants) of the duodenum. An evaluation of 927 cases. J Exp Clin Cancer Res 22:349–363

    CAS  PubMed  Google Scholar 

  27. Hatta W, Koike T, Iijima K, Asanuma K, Asano N, Musha H, Inomata Y, Sano T, Endo H, Ikehata A, Horii T, Ohyauchi M, Yokosawa S, Kasajima A, Fujishima F, Sasano H, Nakaya N, Nakamura T, Shimosegawa T (2017) The risk factors for metastasis in nonampullary duodenal neuroendocrine tumors measuring 20 mm or less in diameter. Digestion 95:201–209

    Article  PubMed  Google Scholar 

  28. Untch BR, Bonner KP, Roggin KK, Reidy-Lagunes D, Klimstra DS, Schattner MA, Fong Y, Allen PJ, D’Angelica MI, DeMatteo RP, Jarnagin WR, Kingham PT, Tang LH (2014) Pathologic grade and tumor size are associated with recurrence-free survival in patients with duodenal neuroendocrine tumors. J Gastrointest Surg 18:457–462

    Article  PubMed  Google Scholar 

  29. Gamboa AC, Liu Y, Lee RM, Zaidi MY, Staley CA, Kooby DA, Winer JH, Shah MM, Russell MC, Cardona K, Maithel SK (2019) Duodenal neuroendocrine tumors: somewhere between the pancreas and small bowel? J Surg Oncol 120:1293–1301

    Article  PubMed  PubMed Central  Google Scholar 

  30. Park SG, Lee BE, Kim GH, Park JW, Lee MW, Kim SJ, Choi CW, Lee S, Park DY (2019) Risk factors for lymph nodemetastasis in duodenalneuroendocrine tumors: a retrospective, single-center study. Medicine (Baltimore) 98:e15885

    Article  Google Scholar 

  31. Cannon ME, Carpenter SL, Elta GH, Nostrant TT, Kochman ML, Ginsberg GG, Stotland B, Rosato EF, Morris JB, Eckhauser F, Scheiman JM (1999) EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms. Gastrointest Endosc 50:27–33

    Article  CAS  PubMed  Google Scholar 

  32. Albores-Saavedra J, Hart A, Chable-Montero F, Henson DE (2010) Carcinoid and high-grade neuroendocrine carcinoma of the ampulla of Vater: a comparative analysis of 139 cases from surveillance, epidemiology, and end results program—a population based study. Arch Pathol Lab Med 134:1692–1696

    Article  PubMed  Google Scholar 

  33. Zilli A, Arcidiacono PG, Conte D, Massironi S (2018) Clinical impact of endoscopic ultrasonography on the management of neuroendocrine tumors: lights and shadows. Dig Liver Dis 50:6–14

    Article  PubMed  Google Scholar 

  34. Jencks DS, Adam JD, Borum ML, Koh JM, Stephen S, Doman DB (2018) Overview of current concepts in gastric intestinal metaplasia and gastric cancer. Gastroenterol Hepatol (N Y) 14:92–101

    Google Scholar 

  35. Barrio M, Czernin J, Fanti S, Ambrosini V, Binse I, Du L, Eiber M, Herrmann K, Fendler WP (2017) The impact of somatostatin receptor-directed PET/CT on the management of patients with neuroendocrine tumor: a systematic review and meta-analysis. J Nucl Med 58:756–761

    Article  PubMed  Google Scholar 

  36. Zimmer T, Stolzel U, Bader M, Koppenhagen K, Hamm B, Buhr H, Riecken EO, Wiedenmann B (1996) Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localization of insulinomas and gastrinomas. Gut 39:562–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Khan RN, Bansal VK, Kumar S, Jindal V, Misra MC, Bhatia V (2009) Duodenal gastrinoma: a diagnostic dilemma. Am J Surg 197:e48–e50

    Article  PubMed  Google Scholar 

  38. Acs G, McGrath CM, Gupta PK (2000) Duodenal carcinoid tumor: report of a case diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy with immuno-cytochemical correlation. Diagn Cytopathol 23:183–186

    Article  CAS  PubMed  Google Scholar 

  39. Soga J (2005) Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer 103:1587–1595

    Article  PubMed  Google Scholar 

  40. Dalenback J, Havel G (2004) Local endoscopic removal of duodenal carcinoid tumors. Endoscopy 36:651–655

    Article  CAS  PubMed  Google Scholar 

  41. Ichikawa J, Tanabe S, Koizumi W, Kida Y, Imaizumi H, Kida M, Saigenji K, Mitomi H (2003) Endoscopic mucosal resection in the management of gastric carcinoid tumors. Endoscopy 35:203–206

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

    R. E. Rossi

  2. Pancreatic and Endocrine Digestive Surgical Unit, Department of Surgery, Oncology and Gastroenterology, Università degli Studi di Padova, Padua, Italy

    A. C. Milanetto, A. David & C. Pasquali

  3. Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, San Raffaele Scientific Institute, “Vita-Salute” University, Milan, Italy

    V. Andreasi, S. Partelli & M. Falconi

  4. Department of Experimental, Diagnostic and Specialty Medicine, ENETS Center of Excellence, Bologna University, St. Orsola-Malpighi University Hospital, Bologna, Italy

    D. Campana & G. Lamberti

  5. HBP Surgery, Hepatology and Liver Transplantation Unit, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan, Italy

    R. E. Rossi, J. Coppa & V. Mazzaferro

  6. Pancreatic Surgery, Humanitas Clinical, and Research Center-IRCCS, ENETS Center of Excellence, Humanitas University, Milan, Rozzano, Italy

    G. Nappo & A. Zerbi

  7. Digestive Disease Unit, ENETS Center of Excellence, Sant’Andrea University Hospital, Rome, Italy

    M. Rinzivillo & F. Panzuto

  8. Division of Gastroenterology, San Gerardo Hospital, Bicocca School of Medicine, University of Milano, Monza, Italy

    P. Invernizzi & S. Massironi

  9. Division of Endocrinology, Department of Clinical Medicine and Surgery, ENETS Center of Excellence, University “Federico II” of Naples, Naples, Italy

    R. Modica

  10. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    V. Mazzaferro

Authors
  1. R. E. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. C. Milanetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Andreasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Campana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Coppa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Nappo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Rinzivillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. Invernizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R. Modica
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. David
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S. Partelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. G. Lamberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. V. Mazzaferro
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A. Zerbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. F. Panzuto
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. C. Pasquali
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. M. Falconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. S. Massironi
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

ItaNet (Italian Association for Neuroendocrine Tumours) study group

Corresponding author

Correspondence to R. E. Rossi.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Due to the retrospective nature of the study informed consent was not necessary. All the data were anonymized.

Availability of data and material (data transparency)

Data and material are available and anonymized.

Code availability (software application or custom code)

SAS/STAT® release 9.2 software (SAS Institute Inc., Cary, NC, USA), Graph Pad Prism version 6.00 (GraphPad Software, San Diego, CA, USA) and MedCalc version 17.9.5 (MedCalc Software bvba, Ostend, Belgium).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rossi, R.E., Milanetto, A.C., Andreasi, V. et al. Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy. J Endocrinol Invest 44, 2227–2234 (2021). https://doi.org/10.1007/s40618-021-01528-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-021-01528-1

Keywords

Search

Navigation