Non Fonksiyonel Nöroendokrin Tümörler
Özet
Gelişen görüntüleme yöntemleri sayesinde günümüzde daha sık tanı alan Non Fonksiyonel Pankreatik Nöroendokrin Neoplaziler (NF-PanNEN), tüm pankreas tümörlerinin %2'sini oluşturan nadir ve genellikle sporadik lezyonlardır. Hastalar çoğunlukla asemptomatik olup, tanı kontrastlı bilgisayarlı tomografi, MRG, fonksiyonel Gallium-68 PET ve endoskopik ultrasonografi (EUSP) gibi ileri tetkiklerle konulmaktadır. Tanı ve takipte en yaygın kullanılan biyobelirteç Kromogranin A'dır. Dünya Sağlık Örgütü (WHO) bu tümörleri Ki-67 indeksi ve mitotik sayıya göre üç dereceye (G1, G2, G3) ayırırken; evreleme için ENETS ve AJCC sistemleri kullanılmaktadır. Tedavi yaklaşımı tümörün boyutuna, derecesine ve metastaz durumuna göre bireyselleştirilir. 2 cm'den küçük, G1 evresindeki ve uzak metastazı bulunmayan tümörlerde enükleasyon veya santral pankreatektomi gibi parankim koruyucu cerrahiler ya da aktif sürveyans uygun birer seçenek olarak öne çıkmaktadır. Ancak bu parankim koruyucu yöntemlerde bile lenf nodu metastazı riski bulunabildiğinden intraoperatif donmuş (frozen) inceleme ve örnekleme önerilir. Tümör boyutu 2 cm'den büyük olduğunda veya lenf nodu tutulumu varlığında, tam bir lenfadenektomi sağlamak amacıyla majör pankreas rezeksiyonları (pankreatikoduodenektomi veya distal pankreatektomi) tercih edilmelidir. Karaciğer metastazı gelişen vakalarda ise tümörün yaygınlığına göre cerrahi rezeksiyon, sistemik tedaviler veya karaciğer nakli değerlendirilmektedir.
Non-Functioning Pancreatic Neuroendocrine Neoplasms (NF-PanNEN) represent rare lesions accounting for 2% of all pancreatic tumors, currently showing increased detection rates due to advanced imaging modalities. Most patients remain asymptomatic, and diagnosis relies on high-resolution contrast-enhanced CT, MRI, Functional 68Ga-PET, and endoscopic ultrasonography (EUSP), with Chromogranin A serving as the primary biomarker for monitoring. The World Health Organization (WHO) classifies these tumors into three grades (G1, G2, G3) based on the Ki-67 index and mitotic count, while AJCC and ENETS systems guide staging. Therapeutic strategies must be individualized considering tumor size, grading, and metastatic status. For G1 tumors smaller than 2 cm without distant metastasis, parenchyma-preserving surgeries, active surveillance, or EUS-guided radiofrequency ablation represent feasible management pathways. However, due to potential lymph node metastasis even in small tumors, intraoperative sampling and frozen section evaluation are highly recommended during parenchyma-preserving approaches. Conversely, for tumors exceeding 2 cm or displaying nodal involvement, standard major resections like pancreatoduodenectomy or distal pancreatectomy accompanied by thorough lymphadenectomy are required to achieve potential cure. In cases involving liver metastases, treatment approaches span surgical resection, systemic therapies, or liver transplantation depending on the specific distribution pattern.
Referanslar
Patel N, Barbieri A, Gibson J (2019) Neuroendocrine tumors of the gastrointestinal tract and pancreas. Surg Pathol Clin 12:1021–1044.
Partelli S, Andreasi V, Muffatti F, et al. Circulating Neuroendocrine Gene Transcripts (NETest): a postoperative strategy for early identification of the efficacy of radical surgery for pancreatic neuroendocrine tumors. Ann Surg Oncol. 2020;27(10):3928–36.
Sundin A, Arnold R, Baudin E, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: radiological, nuclear medicine and hybrid imaging. Neuroendocrinology. 2017;105(3):212–44.
Francesca M, Stefano P, Roberto C et al. Combined 68Ga-DOTA-peptides and 18F-FDG PET in the diagnostic work-up of neuroendocrine neoplasms (NEN). Clin Transl Imaging. 2019; 7:181–87.
Lawrence B, Gustafsson BI, Kidd M et al. The clinical relevance of chromogranin A as a biomarker for gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin N Am. 2011;40(1):111–34.
Oberg K, Couvelard A, Delle Fave G et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: biochemical markers. Neuroendocrinology. 2017;105(3):201–11.
Nobels FRE, Kwekkeboom DJ, Coopmans W et al. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the α-subunit of glycoprotein hormones. J Clin Endocrinol Metab. 1997;82(8):2622–8.
Lloyd RV, Osamura YR, Kloppel G, et al. WHO classification of tumours of endocrine organs: WHO Press; 2017.
Klöppel G, Rindi G, Perren A, et al. The ENETS and UICC TNM classification of neuroendocrine tumors of the gastrointestinal tract and the pancreas: comment.Pathologe. 2010;31(5):353–4.
Brierley JD, Gospodarowicz MK. Wittekind C. TNM classification of malignant tumours – 8th edition. Union for International. Cancer Control. 2017
Partelli S, Javed AA, Andreasi V, et al. The number of positive nodes accurately predicts recurrence after pancreaticoduodenectomy for nonfunctioning neuroendocrine neoplasms. Eur J Surg Oncol. 2018;44(6):778–83.
Parekh JR, Wang SC, Bergsland EK, et al. Lymph node sampling rates and predictors of nodal metastasis in pancreatic neuroendocrine tumor resections: the UCSF experience with 149 patients. Pancreas. 2012;41(6):840–4.
Partelli S, Cirocchi R, Rancoita PMV, et al. A systematic review and meta-analysis on the role of palliative primary resection for pancreatic neuroendocrine neoplasm with liver metastases. HPB. 2018;20(3):197–203.
Hüttner FJ, Koessler-Ebs J, Hackert T, et al. Meta-analysis of surgical outcome after enucleation versus standard resection for pancreatic neoplasms. Br J Surg. 2015;102(9):1026–36.
Chua TC, Yang TX, Gill AJ, et al. Systematic review and meta-analysis of enucleation versus standardized resection for small pancreatic lesions. Ann Surg Oncol. 2016;23(2):592–9.
Heeger K, Falconi M, Partelli S, et al. Increased rate of clinically relevant pancreatic fistula after deep enucleation of small pancreatic tumors. Langenbeck’s Arch Surg. 2014;399(3):315–21.
Partelli S, Bartsch DK, Capdevila J, et al. ENETS consensus guidelines for standard of care in neuroendocrine tumours: surgery for small intestinal and pancreatic neuroendocrine tumours. Neuroendocrinology. 2017;105(3):255–65.
Tanaka M, Heckler M, Mihaljevic AL et al. Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors. Ann Surg Oncol. 2021 Mar;28(3):1614-1624.
Tsuchikawa, T., Tanaka, K., Nakanishi, Y., Asano, T., Noji, T., Nakamura, T. Et al. Clinical Impact of Organ-Preserving Surgery for Pancreatic Neuroendocrine Neoplasms: A Single-Center Experience. Pancreas,2021; 50(2), 196-200.
Partelli S, Mazza M, Andreasi V, et al. Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: Limitations to apply guidelines into real life. Surgery. 2019 Aug;166(2):157-163.
Barthet M, Giovannini M, Gasmi M et al. Long-term outcome after EUS-guided radiofrequency ablation: Prospective results in pancreatic neuroendocrine tumors and pancreatic cystic neoplasms. Endosc Int Open. 2021 Aug;9(8): E1178-E1185. doi: 10.1055/a-1479-2199. Epub 2021 Jul 16. PMID: 34447860; PMCID: PMC8383082.
American neuroendocrine tumor society consensus paper on the surgical management of pancreatic neuroendocrine tumors. Pancreas. 2020;49(1):1–33.
Ausania F, Senra Del Rio P. Lymphadenectomy in pancreatic neuroendocrine neoplasms: Why are we still debating? Pancreatology. 2018; 18:855–61.
Bertani E, Fazio N, Radice D, et al. Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation. Eur J Surg Oncol. 2017;43(2):372–79.
Frilling A, Li J, Malamutmann E, et al. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease. Br J Surg. 2009;96(2):175–84.
Bertani E, Fazio N, Radice D, et al. Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation.Eur J Surg Oncol. 2017;43(2):372–79.
Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I, et al. Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review. Surgery. 2017 Sep;162(3):525-536.
