Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1610 2023-08-15 14:27:36 |
2 update references and layout Meta information modification 1610 2023-08-16 04:24:45 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Elkelany, O.O.; Karaisz, F.G.; Davies, B.; Krishna, S.G. Pancreatic Neuroendocrine Tumors and Management. Encyclopedia. Available online: https://encyclopedia.pub/entry/48088 (accessed on 21 June 2024).
Elkelany OO, Karaisz FG, Davies B, Krishna SG. Pancreatic Neuroendocrine Tumors and Management. Encyclopedia. Available at: https://encyclopedia.pub/entry/48088. Accessed June 21, 2024.
Elkelany, Osama O., Fred G. Karaisz, Benjamin Davies, Somashekar G. Krishna. "Pancreatic Neuroendocrine Tumors and Management" Encyclopedia, https://encyclopedia.pub/entry/48088 (accessed June 21, 2024).
Elkelany, O.O., Karaisz, F.G., Davies, B., & Krishna, S.G. (2023, August 15). Pancreatic Neuroendocrine Tumors and Management. In Encyclopedia. https://encyclopedia.pub/entry/48088
Elkelany, Osama O., et al. "Pancreatic Neuroendocrine Tumors and Management." Encyclopedia. Web. 15 August, 2023.
Pancreatic Neuroendocrine Tumors and Management
Edit

The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology.

pancreatic neuroendocrine tumor (PanNET) endoscopic-ultrasound-guided ethanol ablation (EUS-EA) endoscopic-ultrasound-guided radiofrequency ablation (EUS-RFA)

1. Introduction

Pancreatic neuroendocrine neoplasms (PanNENs) include pancreatic neuroendocrine tumors (PanNETs) and pancreatic neuroendocrine carcinomas (PanNECs) [1][2]. PanNETs are well-differentiated neoplasms of the pancreas with a diverse pathophysiology underscoring the complex mechanisms of the gastrointestinal hormones that are often involved. PanNETs, constituting 1–2% of pancreatic cancers, exhibit an incidence of approximately 5 in 100,000 individuals. The growing incidence can be attributed in part to the heightened rate of incidental detection [3][4][5]. These neoplasms can develop sporadically or as a manifestation of a familial syndrome [6][7][8].
From a clinical standpoint, PanNETs are broadly classified into two groups: functional and nonfunctional. Functional PanNETs, which comprise 34.5% of all PanNETs [9], exhibit the excessive secretion of various biologically active peptides, such as insulin or glucagon, leading to the manifestation of diverse syndromes. On the other hand, nonfunctional PanNETs lack the oversecretion of such peptides but share similar histological and pathological characteristics with functional PanNETs [6]. The treatment goals for functional PanNETs involve eliminating neuroendocrine tumor cells to halt hormonal hypersecretion and prevent malignant spread [10]. In contrast, the management of nonfunctional PanNETs is more complex, focusing on predicting and impeding tumor growth and progression [11]. Innovative endoscopic approaches like EUS-guided radiofrequency ablation (RFA) and EUS-guided fine needle injection (FNI) of a chemoablative agent hold promise as effective alternatives to surgical pancreatectomies [12]. With the expanding role of endoscopists in the diagnosis and management of PanNETs, it is imperative to possess a comprehensive understanding of the available tools and approaches to effectively address these conditions.

2. Diagnosis of Functional PanNETs

2.1. Insulinomas

Insulinomas are the most common functional PanNETs, accounting for 20.9% of cases [9]. Typically, insulinomas are benign and well-differentiated NETs; however, approximately 5.8% of insulinomas are malignant [13][14]. While insulinomas are usually sporadic, around 4–5% of patients with insulinomas have multiple endocrine neoplasia type 1 (MEN1) [15]. The gold standard for diagnosing insulinomas is measuring insulin levels after a 72 h fasting test, which demonstrates close to 100% sensitivity and specificity [16]. Once organic hyperinsulinism is confirmed in symptomatic patients (as outlined in Table 1), imaging is necessary to locate the tumor for surgical management. Various imaging modalities can be employed, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) with fine needle aspiration (FNA), arteriography, intra-arterial stimulation with venous sampling (ASVS), and somatostatin receptor scintigraphy [17]. 68Ga-DOTATATE positron emission tomography (PET/CT) and Fluorine-18-L-dihydroxyphenylalanine (18-F-DOPA) PET, which take advantage of PanNET’s propensity for decarboxylate amine precursors, have been found to be more sensitive than CT or MRI in identifying insulinomas or beta cell hyperplasia and are used when conventional imaging modalities yield inconclusive results [15][18]. Regarding the additional benefits of using EUS, a meta-analysis conducted by James et al. revealed that the implementation of EUS was associated with a higher detection rate of PanNETs even after the utilization of CT and MRI imaging. This contributed to an overall increase in PNET detection of more than 25% [19]. In a retrospective study conducted by Pais et al., the sensitivity of EUS-FNA in diagnosing PanNETs was found to be 87%. Notably, this sensitivity remained consistent in both functional and nonfunctional PanNETs. These findings further demonstrate that EUS can be a valuable tool to aid in the diagnosis of PanNETs [20].
Table 1. Characteristics of PanNETs.

2.2. Gastrinomas

The second most common functional PanNETs are gastrinomas (8.2%) [9]. Gastrinomas secrete gastrin and cause Zollinger–Ellison syndrome (ZES) [21]. This syndrome is characterized by hypersecretion of gastric acid leading to peptic ulcer disease and gastroesophageal reflux disease. It is estimated that 25% of gastrinomas occur in patients with MEN1 [22]. A more than one-thousand-fold increase in gastrin levels can be diagnostic [23]. If gastrin levels are only moderately elevated, a secretin test is required, during which gastrin levels are measured after intravenous administration of a secretin bolus [24]. However, gastrin levels can be elevated in patients with atrophic gastritis or in patients receiving proton pump inhibitor therapy [25]. As a result, the diagnostic criteria for ZES are not commonly fulfilled, and greater emphasis is placed on imaging modalities to detect the presence of an intra-abdominal tumor [26].
In a prospective study involving 80 patients with gastrinomas, somatostatin receptor scintigraphy (Octreotide scan) alone yielded a gastrinoma detection rate of 58%, while conventional imaging modalities such as ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and angiography had a detection rate ranging from 9% to 31% [27]. This scintigraphy test utilizes an indium-111 radiolabel that binds to somatostatin receptors, providing an overall sensitivity of 75–100% for detecting PanNETs [28][29]. To enhance its sensitivity, this technique can be combined with single-positron emission computed tomography (SPECT) [30]. More recently, somatostatin receptor PET imaging using three FDA-approved radiotracers, namely gallium-68-dodecanetetraacetic acid, tyrosine-3-octreotate (68-Ga-DOTATATE), 68-Ga-DOTATOC, and 64-Cu-DOTATAT, has emerged as superior to the traditional octreotide scan. These radiotracers have demonstrated high sensitivity, shorter imaging duration, and lower radiation doses. In PanNETs with lower somatostatin receptor expression, imaging with (18)F-FDG PET is preferred [31].
While EUS demonstrates excellent sensitivity and specificity for detecting gastrinomas in the pancreas, its sensitivity may decrease when gastrinomas are localized in the duodenum. However, the high sensitivity of EUS in detecting small PanNETs (less than 2 cm) has led some experts to propose an annual EUS screening for asymptomatic patients with MEN1 [32].

2.3. Glucagonomas, VIPomas, and Somatostatinomas

For the diagnosis of glucagonomas, glucagon levels above 500 pg/mL are commonly observed [33]. However, it is important to note that elevated glucagon levels can also be seen in other conditions such as cirrhosis and diabetes. Therefore, the interpretation of elevated glucagon levels should be combined with the presence of typical glucagonoma syndrome symptoms, including weight loss, necrotic migratory erythema, and hypoalbuminemia [34].
In a study investigating a cohort of 1000 patients with various causes of diarrhea, elevated vasoactive intestinal peptide (VIP) levels were found to be 100% specific in diagnosing VIPomas [35]. This finding is particularly relevant as VIPomas typically present with symptoms such as watery diarrhea, hypokalemia, and achlorhydria. The study demonstrated the high specificity of VIP levels in aiding the diagnosis of VIPomas. It is worth noting that other peptides, including gastrin and insulinoma, can also be elevated in patients with VIPomas [36].
Somatostatinomas can produce a “stomatostatinoma syndrome”, which is characterized by anemia, diabetes, diarrhea, and gallbladder disease [6]. Fasting plasma somatostatin level greater than 14 mol/L and CT of the abdomen are often diagnostic, as these tumors, like glucagonomas, are often large upon presentation [37].

3. Diagnosis of Nonfunctional PanNETs

Nonfunctional PanNETs typically do not cause symptoms until they reach a significant tumor burden or when complications arise from mass effect or metastatic disease. Despite their indolent nature, over 11% of nonfunctional PanNETs are diagnosed as distant metastases. The diagnosis of nonfunctional PanNETs involves a combination of biochemical, radiographic, and histologic evaluations [6][37][38][39].

Neuroendocrine Biomarkers

Neuroendocrine biomarkers play a role in diagnosing and surveilling and are applicable to both functional and nonfunctional PanNETs [40]. One of the most ubiquitously measured biomarkers is a glycoprotein produced by neuroendocrine cells known as chromogranin A (CgA). It has been shown that CgA can affect several elements in the tumor microenvironment, including endothelial cells and fibroblasts. These findings have also suggested that its abnormal secretion could play a role in tumor progression [41]. In the diagnosis of functional and nonfunctional PanNETs, CgA has been found to have a sensitivity of 66% and specificity of 95% [42]. CgA can also be false-positively elevated in several clinical conditions including inflammatory bowel disease, renal failure, liver failure, or pancreatitis. In addition, proton pump inhibitor (PPI) therapy as well steroids have also been shown to increase CgA levels [43][44], and this effect by PPIs can last up to 2 weeks [45]. While these circumstances may limit CgA’s use as a diagnostic biomarker, evidence is favorable for its use as a prognostic factor for progression-free survival (PFS) and overall survival (OS) [42][44].
Neuron-specific enolase (NSE), a glycolytic enzyme expressed in neuroendocrine cells, is another biomarker that has demonstrated prognostic value in progression-free survival and overall survival. The expression of NSE occurs as a late event in the neural cell differentiation process [46]. Its utility as a biomarker is based on its expression in neural maturation and tumor proliferation. While NSE has a diagnostic sensitivity of 31% in comparison to CgA in PanNETs, elevated baseline NSE values similarly showed prognostication on progression-free survival and overall survival [47][48]. Furthermore, early decreases in CgA and NSE levels after treatment can serve as a prognostic marker in patients with advanced PanNETs. The combined use of CgA and NSE has been shown to be more accurate in predicting and prognosticating disease [49].
One of the more novel biomarkers involves measuring circulating neuroendocrine tumor transcripts (NETest). This test uses PCR to measure 51 different transcripts related to neuroendocrine tumors or associated with neoplastic behavior and was found to have a sensitivity of 80% and specificity of 94% for PanNETs in a study that investigated 206 patients with neuroendocrine tumors [50]. The genes tested include KRAS, RAF1, and APLP2, among others. NETest is also associated with disease progression and can potentially be a better predictor of disease than CgA [50][51].

References

  1. Rindi, G.; Klimstra, D.S.; Abedi-Ardekani, B.; Asa, S.L.; Bosman, F.T.; Brambilla, E.; Busam, K.J.; de Krijger, R.R.; Dietel, M.; El-Naggar, A.K.; et al. A common classification framework for neuroendocrine neoplasms: An International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod. Pathol. 2018, 31, 1770–1786.
  2. Klöppel, G. Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications. Visc. Med. 2017, 33, 324–330.
  3. Hallet, J.; Law, C.H.; Cukier, M.; Saskin, R.; Liu, N.; Singh, S. Exploring the rising incidence of neuroendocrine tumors: A population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer 2015, 121, 589–597.
  4. Oberg, K.; Eriksson, B. Endocrine tumours of the pancreas. Best Pract. Res. Clin. Gastroenterol. 2005, 19, 753–781.
  5. Stensbol, A.B.; Krogh, J.; Holmager, P.; Klose, M.; Oturai, P.; Kjaer, A.; Hansen, C.P.; Federspiel, B.; Langer, S.W.; Knigge, U.; et al. Incidence, Clinical Presentation and Trends in Indication for Diagnostic Work-Up of Small Intestinal and Pancreatic Neuroendocrine Tumors. Diagnostics 2021, 11, 2030.
  6. Metz, D.C.; Jensen, R.T. Gastrointestinal neuroendocrine tumors: Pancreatic endocrine tumors. Gastroenterology 2008, 135, 1469–1492.
  7. Alexakis, N.; Connor, S.; Ghaneh, P.; Lombard, M.; Smart, H.L.; Evans, J.; Hughes, M.; Garvey, C.J.; Vora, J.; Vinjamuri, S.; et al. Hereditary pancreatic endocrine tumours. Pancreatology 2004, 4, 417–433; discussion 434–415.
  8. Jensen, R.T.; Berna, M.J.; Bingham, D.B.; Norton, J.A. Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 2008, 113, 1807–1843.
  9. Ito, T.; Igarashi, H.; Nakamura, K.; Sasano, H.; Okusaka, T.; Takano, K.; Komoto, I.; Tanaka, M.; Imamura, M.; Jensen, R.T.; et al. Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: A nationwide survey analysis. J. Gastroenterol. 2015, 50, 58–64.
  10. Ito, T.; Igarashi, H.; Jensen, R.T. Pancreatic neuroendocrine tumors: Clinical features, diagnosis and medical treatment: Advances. Best Pract. Res. Clin. Gastroenterol. 2012, 26, 737–753.
  11. Larghi, A.; Rizzatti, G.; Rimbaş, M.; Crino, S.F.; Gasbarrini, A.; Costamagna, G. EUS-guided radiofrequency ablation as an alternative to surgery for pancreatic neuroendocrine neoplasms: Who should we treat? Endosc. Ultrasound 2019, 8, 220–226.
  12. So, H.; Ko, S.W.; Shin, S.H.; Kim, E.H.; Son, J.; Ha, S.; Song, K.B.; Kim, H.J.; Kim, M.H.; Park, D.H. Comparison of EUS-guided ablation and surgical resection for non-functioning small pancreatic neuroendocrine tumors: A propensity score matching study. Gastrointest. Endosc. 2022, 97, 741–751.e1.
  13. Peltola, E.; Hannula, P.; Huhtala, H.; Metso, S.; Sand, J.; Laukkarinen, J.; Tiikkainen, M.; Sirén, J.; Soinio, M.; Nuutila, P.; et al. Long-term morbidity and mortality in patients diagnosed with an insulinoma. Eur. J. Endocrinol. 2021, 185, 577–586.
  14. Service, F.J.; McMahon, M.M.; O’Brien, P.C.; Ballard, D.J. Functioning insulinoma—incidence, recurrence, and long-term survival of patients: A 60-year study. Mayo Clin. Proc. 1991, 66, 711–719.
  15. Falconi, M.; Eriksson, B.; Kaltsas, G.; Bartsch, D.K.; Capdevila, J.; Caplin, M.; Kos-Kudla, B.; Kwekkeboom, D.; Rindi, G.; Klöppel, G.; et al. ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. Neuroendocrinology 2016, 103, 153–171.
  16. Dizon, A.M.; Kowalyk, S.; Hoogwerf, B.J. Neuroglycopenic and other symptoms in patients with insulinomas. Am. J. Med. 1999, 106, 307–310.
  17. Chatziioannou, A.; Kehagias, D.; Mourikis, D.; Antoniou, A.; Limouris, G.; Kaponis, A.; Kavatzas, N.; Tseleni, S.; Vlachos, L. Imaging and localization of pancreatic insulinomas. Clin. Imaging 2001, 25, 275–283.
  18. Kauhanen, S.; Seppanen, M.; Minn, H.; Gullichsen, R.; Salonen, A.; Alanen, K.; Parkkola, R.; Solin, O.; Bergman, J.; Sane, T.; et al. Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or beta-cell hyperplasia in adult patients. J. Clin. Endocrinol. Metab. 2007, 92, 1237–1244.
  19. James, P.D.; Tsolakis, A.V.; Zhang, M.; Belletrutti, P.J.; Mohamed, R.; Roberts, D.J.; Heitman, S.J. Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: A meta-analysis. Gastrointest. Endosc. 2015, 81, 848–856.e841.
  20. Pais, S.A.; Al-Haddad, M.; Mohamadnejad, M.; Leblanc, J.K.; Sherman, S.; McHenry, L.; DeWitt, J.M. EUS for pancreatic neuroendocrine tumors: A single-center, 11-year experience. Gastrointest. Endosc. 2010, 71, 1185–1193.
  21. Jensen, R.T.; Cadiot, G.; Brandi, M.L.; de Herder, W.W.; Kaltsas, G.; Komminoth, P.; Scoazec, J.Y.; Salazar, R.; Sauvanet, A.; Kianmanesh, R. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: Functional pancreatic endocrine tumor syndromes. Neuroendocrinology 2012, 95, 98–119.
  22. Thakker, R.V.; Newey, P.J.; Walls, G.V.; Bilezikian, J.; Dralle, H.; Ebeling, P.R.; Melmed, S.; Sakurai, A.; Tonelli, F.; Brandi, M.L. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J. Clin. Endocrinol. Metab. 2012, 97, 2990–3011.
  23. Berna, M.J.; Hoffmann, K.M.; Serrano, J.; Gibril, F.; Jensen, R.T. Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature. Medicine 2006, 85, 295–330.
  24. Berna, M.J.; Hoffmann, K.M.; Long, S.H.; Serrano, J.; Gibril, F.; Jensen, R.T. Serum gastrin in Zollinger-Ellison syndrome: II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features. Medicine 2006, 85, 331–364.
  25. Ito, T.; Cadiot, G.; Jensen, R.T. Diagnosis of Zollinger-Ellison syndrome: Increasingly difficult. World J. Gastroenterol. 2012, 18, 5495–5503.
  26. Metz, D.C.; Cadiot, G.; Poitras, P.; Ito, T.; Jensen, R.T. Diagnosis of Zollinger-Ellison syndrome in the era of PPIs, faulty gastrin assays, sensitive imaging and limited access to acid secretory testing. Int. J. Endocr. Oncol. 2017, 4, 167–185.
  27. Gibril, F.; Jensen, R.T. Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors. Yale J. Biol. Med. 1997, 70, 509–522.
  28. Kwekkeboom, D.J.; Krenning, E.P. Somatostatin receptor imaging. Semin. Nucl. Med. 2002, 32, 84–91.
  29. Kapoor, M.; Kasi, A. Octreotide Scan; StatPearls: Treasure Island, FL, USA, 2022.
  30. Modlin, I.M.; Tang, L.H. Approaches to the diagnosis of gut neuroendocrine tumors: The last word (today). Gastroenterology 1997, 112, 583–590.
  31. Hope, T.A.; Allen-Auerbach, M.; Bodei, L.; Calais, J.; Dahlbom, M.; Dunnwald, L.K.; Graham, M.M.; Jacene, H.A.; Heath, C.L.; Mittra, E.S.; et al. SNMMI Procedure Standard/EANM Practice Guideline for SSTR PET: Imaging Neuroendocrine Tumors. J. Nucl. Med. 2023, 64, 204–210.
  32. Rossi, R.E.; Elvevi, A.; Citterio, D.; Coppa, J.; Invernizzi, P.; Mazzaferro, V.; Massironi, S. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J. Gastroenterol. 2021, 27, 5890–5907.
  33. Appetecchia, M.; Lauretta, R.; Rota, F.; Carlini, M. Neuroendocrine tumors biomarkers. In Abdominal Neuroendocrine Tumors; Springer: Berlin/Heidelberg, Germany, 2018; pp. 65–78.
  34. Ma, Z.Y.; Gong, Y.F.; Zhuang, H.K.; Zhou, Z.X.; Huang, S.Z.; Zou, Y.P.; Huang, B.W.; Sun, Z.H.; Zhang, C.Z.; Tang, Y.Q.; et al. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J. Gastroenterol. 2020, 26, 2305–2322.
  35. Bloom, S.R. Vasoactive intestinal peptide, the major mediator of the WDHA (pancreatic cholera) syndrome: Value of measurement in diagnosis and treatment. Am. J. Dig. Dis. 1978, 23, 373–376.
  36. Farina, D.A.; Krogh, K.M.; Boike, J.R. Chronic Diarrhea Secondary to Newly Diagnosed VIPoma. Case Rep. Gastroenterol. 2019, 13, 225–229.
  37. Mansour, J.C.; Chen, H. Pancreatic endocrine tumors. J. Surg. Res. 2004, 120, 139–161.
  38. Gratian, L.; Pura, J.; Dinan, M.; Roman, S.; Reed, S.; Sosa, J.A. Impact of extent of surgery on survival in patients with small nonfunctional pancreatic neuroendocrine tumors in the United States. Ann. Surg. Oncol. 2014, 21, 3515–3521.
  39. Johnston, M.E., 2nd; Carter, M.M.; Wilson, G.C.; Ahmad, S.A.; Patel, S.H. Surgical management of primary pancreatic neuroendocrine tumors. J. Gastrointest. Oncol. 2020, 11, 578–589.
  40. Cloyd, J.M.; Poultsides, G.A. Non-functional neuroendocrine tumors of the pancreas: Advances in diagnosis and management. World J. Gastroenterol. 2015, 21, 9512–9525.
  41. Corti, A. Chromogranin A and the tumor microenvironment. Cell Mol. Neurobiol. 2010, 30, 1163–1170.
  42. Pulvirenti, A.; Rao, D.; McIntyre, C.A.; Gonen, M.; Tang, L.H.; Klimstra, D.S.; Fleisher, M.; Ramanathan, L.V.; Reidy-Lagunes, D.; Allen, P.J. Limited role of Chromogranin A as clinical biomarker for pancreatic neuroendocrine tumors. HPB 2019, 21, 612–618.
  43. Massironi, S.; Conte, D.; Sciola, V.; Spampatti, M.P.; Ciafardini, C.; Valenti, L.; Rossi, R.E.; Peracchi, M. Plasma chromogranin A response to octreotide test: Prognostic value for clinical outcome in endocrine digestive tumors. Am. J. Gastroenterol. 2010, 105, 2072–2078.
  44. Giusti, M.; Sidoti, M.; Augeri, C.; Rabitti, C.; Minuto, F. Effect of short-term treatment with low dosages of the proton-pump inhibitor omeprazole on serum chromogranin A levels in man. Eur. J. Endocrinol. 2004, 150, 299–303.
  45. Mosli, H.H.; Dennis, A.; Kocha, W.; Asher, L.J.; Van Uum, S.H. Effect of short-term proton pump inhibitor treatment and its discontinuation on chromogranin A in healthy subjects. J. Clin. Endocrinol. Metab. 2012, 97, E1731–E1735.
  46. Isgrò, M.A.; Bottoni, P.; Scatena, R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv. Exp. Med. Biol. 2015, 867, 125–143.
  47. Nobels, F.R.; Kwekkeboom, D.J.; Coopmans, W.; Schoenmakers, C.H.; Lindemans, J.; De Herder, W.W.; Krenning, E.P.; Bouillon, R.; Lamberts, S.W. Chromogranin A as serum marker for neuroendocrine neoplasia: Comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J. Clin. Endocrinol. Metab. 1997, 82, 2622–2628.
  48. Yao, J.C.; Pavel, M.; Phan, A.T.; Kulke, M.H.; Hoosen, S.; St Peter, J.; Cherfi, A.; Öberg, K.E. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J. Clin. Endocrinol. Metab. 2011, 96, 3741–3749.
  49. Lv, Y.; Han, X.; Zhang, C.; Fang, Y.; Pu, N.; Ji, Y.; Wang, D.; Xuefeng, X.; Lou, W. Combined test of serum CgA and NSE improved the power of prognosis prediction of NF-pNETs. Endocr. Connect. 2018, 7, 169–178.
  50. Pavel, M.; Jann, H.; Prasad, V.; Drozdov, I.; Modlin, I.M.; Kidd, M. NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive. Neuroendocrinology 2017, 104, 170–182.
  51. Ćwikła, J.B.; Bodei, L.; Kolasinska-Ćwikła, A.; Sankowski, A.; Modlin, I.M.; Kidd, M. Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy. J. Clin. Endocrinol. Metab. 2015, 100, E1437–E1445.
More
Information
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , ,
View Times: 196
Revisions: 2 times (View History)
Update Date: 16 Aug 2023
1000/1000
Video Production Service