Gut Liver 2012; 6(4): 405-410 https://doi.org/10.5009/gnl.2012.6.4.405 Endoscopic Ultrasound in Gastroenteropancreatic Neuroendocrine Tumors
Author Information
Michelle Kang Kim*

Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.



Correspondence to: Michelle Kang Kim. Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1069, New York, NY 10029, USA. Tel: +1-212-241-7535, Fax: +1-212-241-2276, michelle.kim@mssm.edu
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Keywords: Endoscopic ultrasound, Neuroendocrine tumor, Carcinoid, Pancreas, Stomach
Keywords: Endoscopic ultrasound, Neuroendocrine tumor, Carcinoid, Pancreas, Stomach
INTRODUCTION

Neuroendocrine tumors (NETs) are rare, but increasingly recognized entities. Endoscopic ultrasound (EUS) is an invaluable technique in the diagnosis and management of these tumors. In this review, we will describe the current status of EUS in the staging, localization, and diagnosis of these tumors. We will also address potential future applications of EUS in the treatment of NETs.

BACKGROUND

Gastroenteropancreatic (GEP)-NETs represent a group of neoplasms with neuroendocrine phenotype which are frequently dispersed throughout the gastrointestinal tract and have diverse biologic behavior. With an incidence of approximately 0.5% of all neoplasms, NETs are generally considered to be rare.1 In recent years, however, the incidence has risen, generally thought to be due to improved detection, with the widespread availability and accessibility of endoscopy and cross sectional imaging modalities, rather than an actual increase in frequency.2-4

Recently, various organizations have made efforts to classify and to standardize the nomenclature of these tumors. In 2010, the World Health Organization created a standard classification for these tumors, clarifying terminology and creating a uniform grading system that could be used worldwide (Table 1).5 This has clarified both clinical care and research investigation.

NETs are a heterogeneous group of tumors that may present with quite variable symptoms and also may or may not be associated with an overproduction of a group of hormones (Table 2). Tumors may be functional, with the often dramatic symptoms of a gastrinoma or insulinoma, or nonfunctional, which is frequently detected incidentally or with symptoms related to mass effect of the tumor or its metastases.

Endoscopy has typically successfully localized and enabled confirmation of the disease in gastroenteropancreatic (GE-NETs). Standard cross-sectional imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are also frequently used to diagnose and localize NETs, particularly pancreatic (P)-NETs (Table 3). Because NETS frequently express somatostatin receptors on their surface, somatostatin receptor scintigraphy (SRS) has particular avidity for NETS and may frequently elucidate the location of these lesions.

There are limitations to these imaging modalities, however (Table 4). For examples, as insulinomas infrequently express somatostatin receptors, SRS is frequently negative with these particular tumors.6 The current sensitivities and specificities for NETs with CT and MRI range from 64% to 82% and 74% to 100%, respectively.7 EUS, with its unique combination of endoscopy and ultrasound, is able to address these limitations. EUS can provide additional information to the endoscopist regarding GE-NETs. In addition, it allows access to P-NETS. In this way, EUS is now able to localize, stage, and confirm and treat disease.

STAGING EUS FOR GE-NETS

With increased access to endoscopy, GE-NETs in the stomach, duodenum, and rectum are increasingly frequently incidentally detected on upper endoscopy and colonoscopy.8-10 Patients are frequently asymptomatic without any symptoms referable to the GE-NET. Management of these tumors frequently involves endoscopic resection for appropriate patients. Before proceeding with endoscopic resection, however, endoscopists frequently perform a staging EUS to confirm the appropriateness of an endoscopic resection, usually endoscopic mucosal resection (EMR).

Multiple studies have assessed the utility of EUS prior to endoscopic resection of GE-NETs. The most extensive literature has been conducted with rectal NETs. The largest study by Kobayashi et al.11 studied 66 rectal tumors. Fifty-seven rectal NETs were smaller than 10 mm and were limited lesions without muscularis propria infiltration. These were all able to be removed endoscopically. In those 9 rectal NETs measuring greater than 11 mm, 5 demonstrated muscularis propria involvement and 4 demonstrated metastatic disease.

Similarly, gastric NETs that are smaller than 1 cm in size without evidence of deep invasion on EUS may be managed endoscopically by polypectomy or EMR.12 Larger lesions, measuring between 1 and 2 cm, may be removed endoscopically or surgically.8,12-16 The exception here is that type 3 gastric NETs, which are sporadic and not associated with hypergastrinemia, are typically treated surgically because of their more aggressive nature.8,17,18

A similar approach applies to duodenal NETs. EUS is particularly useful for assessment of depth of lesion involvement, again prior to consideration of an endoscopic procedure such as EMR.

Overall, in a recent study reviewing 18 patients with 23 GE-NETs, EUS was performed before endoscopic resection to confirm the limited nature of the lesion and the appropriate candidacy of the lesion for endoscopic resection.19 EUS sensitivity was 94% in detection of appropriate candidates for endoscopic resection. Complete resection was achieved in 90.5% of lesions.

Endoscopic submucosal dissection (ESD), initially evaluated in the endoscopic treatment of early gastric cancer, has also been evaluated as a mode of endoscopic resection for GE-NETs.20 In a study looking at 22 rectal NETs, all 22 tumors were located in the submucosal layer.20 EUS was 100% accurate in assessing the depth of the lesion. ESD was able to be performed in all cases, with postprocedure bleeding in 9% of cases and without any perforations. No postprocedure recurrence was noted during the mean follow up period of 30 months. Although ESD is more technically difficult to perform than EMR and may offer a more complete resection of rectal NETs, the added utility of this procedure still needs to be evaluated in further studies.

DIAGNOSTIC EUS FOR LOCALIZATION OF P-NETS

The important ability of EUS to localize P-NETs was first described in the paper authored by Rosch et al.21 In this study, 50 patients with clinical suspicion of NET whose tumors were undetected by radiologic imaging underwent EUS with successful localization of NETs in 82% of patients. EUS was particularly successful in identification of P-NETs with 82% sensitivity and 92% specificity.

With the unique proximity of the echoendoscope to the pancreas, EUS is particularly well suited to identification of small pancreatic lesions, able to detect lesions as small as 2 to 5 mm (Fig. 1).21 EUS is particularly able to localize gastrinomas and insulinomas. Nearly all insulinomas are located in the pancreas. The average size of insulinomas at initial diagnosis is under 1 cm, with 90% under 2 cm.22 Reported detection rates have ranged from 79% to 94%, with higher sensitivity in the head and lower sensitivity in the tail.23

EUS is also well suited to identification of gastrinomas. Fifty percentage are located in the pancreas, while the other 50% are located in the duodenum. Pancreatic gastrinomas are generally localized in 75% to 94% of cases, while extrapancreatic (duodenal) gastrinomas are less frequently visualized, thought to be a result of their generally smaller sizes. EUS is also helpful for detection of adjacent metastatic lymph nodes within the so-called gastrinoma triangle.24

EUS has also been used to survey patients at increased risk of developing pancreatic NETs. For example, patients with multiple endocrine neoplasia (MEN) typically have P-NETs in 36% to 81% of patients. In one study describing a surveillance program of 51 MEN1 patients, EUS identified a median of 3 tumors per patient, with median size 6 mm.25 Over 5 years, 37.5% developed additional or enlarging tumors. Less than 10% of these lesions were detected by other imaging modalities including CT, MR, or SRS.

Recently, there has been the development of adjunctive techniques with EUS to further increase potential detection of small lesions. In one study from Japan, contrast enhanced harmonic EUS detected hypervascular enhancement in P-NETs.26 Contrast enhanced EUS was also found to be superior to multidetector CT in diagnosing small pancreatic cancers less than 2 cm.

EUS FOR P-NETS

P-NETs typically appear as a hypoechoic, well-demaracated, round, homogeneous lesion.27 While the majority of P-NETs are solid lesions, P-NETs may less commonly also appear cystic; this is particularly important in light of the increased detection of pancreatic cystic lesions.28 A peripancreatic lymph node may also mimic a P-NET. Potential pitfalls include an isoechoic appearance, small size, multiplicity, and pedunculated lesions at the pancreatic tail.29 In addition, because patients may present with multiple NETs, it is important to examine the entire pancreas to exclude a synchronous lesion. In one study evaluating risk factors for a negative EUS, female gender, low body mass index, and young age were found to be associated with a negative study. The authors hypothesized that this may be due to weak contrast of the tumor to healthy pancreatic tissue; the pancreas of a slim young woman may be more hypoechoic than in others due to low fat content.30

EUS-GUIDED TISSUE ACQUISITION OF P-NETS

There are multiple techniques used to obtain tissue confirmation of NETs. The most commonly used is EUS-guided fine needle aspiration (EUS-FNA). With this technique, the endosonographer gently inserts a 22 gauge or 25 gauge needle into the target lesion. The FNA may be performed with or without suction. The aspirate is then examined by a cytopathologist, ideally on site. The diagnosis, however, is generally confirmed with immunohistochemical studies from the cell block. Commonly performed stains include chromogranin and synatophysin; other stains may include neuron specific enolase, CDX, and CD56 (Table 5).31,32 As with other pancreatic tumors, the ideal number of passes to perform is 5 to 7 for a pancreatic tumor, 2 to 3 for a liver metastasis, and 2 to 5 for lymph nodes.33,34

Another method that has been used to obtain tissue is the Trucut core biopsy. This method offers the benefit of a more substantive specimen, providing cellular architecture for pathologic analysis. These core biopsies may provide microscopic information such as degree of atypia, presence or absence of necrosis, mitotic index, and Ki-67 (proliferative index). This information is particularly important as it may provide prognostic information and aid in the grading of P-NETs.35 However, the use of the Trucut needle has been limited by the technical difficulties of using this device. Studies are currently in process of evaluating biopsy needles that might be easier to use; in particular new needles will need to address current challenges such as maneuvering in the duodenum.

INTERVENTIONAL EUS

Recently, there has been an increased trend toward not only diagnostic EUS and FNA to acquire tissue, but also EUS delivery of therapeutic agents. This technique, termed EUS-guided fine needle injection (EUS-FNI) has been used in multiple contexts. It was first described in NETs in 2002, when a P-NET was tattooed with India ink to allow for more readily identifiable tumor in the operating room.36 A similar study described a patient who underwent tattoo of a P-NET after a previous laparotomy without identification of the tumor. The tattoo enabled a successful resection of the pancreatic tumor in the operating room.37

Using the same reasoning that EUS is a sensitive tool in evaluating the pancreas in real time, able to simultaneously visualize normal structures, pathologic lesions, and especially to avoid vascular structures, endoscopists have also used EUS to deliver therapeutic agents (Table 6).38 There have been multiple reports of ablation of insulinomas, leading to dramatic improvement of refractory hypoglycemic symptoms.39 Although EUS-FNI is still considered investigational, this technique may ultimately allow for a way to treat symptoms in a minimally invasive way in patients who are poor surgical candidates.

EUS-FNI has also been tried most often in pancreatic adenocarcinoma. Multiple antitumor agents have been used to selectively target pancreatic tumors. These include allogenic mixed lymphocyte culture (cytoimplant),40 an adenovirus which preferentially kills malignant tumor cells (ONYX-015),41 and an adenovector containing the human tumor necrosis factor gene (TNFerade).42,43

Immunotherapy has also been used in an attempt to stimulate the body's immune system against tumor cells. In one study by Hirooka et al.,44 five patients received intravenous gemcitabine was combined with EUS-administered OK432-pulsed dendritic cells. One patient demonstrated partial remission, while 2 others had stable disease for more than 6 months.

Other ablative techniques have also been delivered via EUS. These include modalities such as radiofrequency ablation,45 photodynamic therapy,46 and brachytherapy.47,48 While the first two techniques have mostly been evaluated in animal models, brachytherapy has been reported in pilot studies in human patients.45,46 In these studies, radioactive seeds of iodine-125 were injected under EUS guidance into advanced pancreatic tumors. Their results demonstrated partial response or stable disease in 30% of patients.

CONCLUSIONS

EUS is an invaluable tool in the evaluation and management of NETs. EUS can effectively stage patients with localized GE-NETs, often enabling identification of those patients who could safely undergo endoscopic resection of GE-NETs. EUS also adds significant ability to identify previously unlocalized tumors, particularly in the case of insulinomas, gastrinomas, and MEN patients. The addition of FNA to EUS has enabled tissue confirmation. Finally, recent developments in EUS-FNI offer hope that EUS may contribute not only to diagnostic purposes, but also therapeutic ones. Future studies will identify the utility of EUS-FNI in the management of patients with NETs.

Figures
Fig. 1. (A) Endoscopic image of a gastric neuroendocrine tumor (NET). (B) Endosonographic image of a small pancreatic NET, measuring 6×7 mm.
Tables

World Health Organization (WHO) Classification of Gastroenteropancreatic Neuroendocrine Tumors

HPF, high-power field.


HPF, high-power field.

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) and Their Syndromes

HIAA, hydroxyindoleacetic acid; VIP, vasoactive intestinal peptide.


HPF, high-power field.

Imaging Methods


HPF, high-power field.

Accuracy of CT, MRI, and EUS in the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

CT, computed tomography; MRI, magnetic resonance imaging; EUS, endoscopic ultrasound; P-NET, pancreatic neuroendocrine tumor.


HPF, high-power field.

Immunohistochemistry (IHC) Performed in Gastroenteropancreatic Neuroendocrine Tumors


HPF, high-power field.

Potential Therapeutic Approaches for Gastroenteropancreatic Neuroendocrine Tumors

EUS, endoscopic ultrasound; TNFerade, tumor necrosis factor gene.


HPF, high-power field.
References
  1. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97;934-959.
    Pubmed
  2. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9;61-72.
    Pubmed
  3. Kulke MH, Scher?bl H. Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2009;3;S62-S66.
    Pubmed
  4. Vagefi PA, Razo O, Deshpande V, et al. Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005. Arch Surg. 2007;142;347-354.
    Pubmed
  5. Bosman FT , Carneiro F , Hruban RH , Theise ND. WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer; .
  6. Cutler S, Ghassemian M, Bonetta D, Cooney S, McCourt P. A protein farnesyl transferase involved in abscisic acid signal transduction in Arabidopsis. Science. 1996;273;1239-1241.
    Pubmed
  7. Tamm EP, Kim EE, Ng CS. Imaging of neuroendocrine tumors. Hematol Oncol Clin North Am. 2007;21;409-432.
    Pubmed
  8. Borch K, Ahr?n B, Ahlman H, Falkmer S, Gran?rus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242;64-73.
    Pubmed
  9. Modlin IM, Sandor A. An analysis of 8,305 cases of carcinoid tumors. Cancer. 1997;79;813-829.
    Pubmed
  10. Jetmore AB, Ray JE, Gathright JB, McMullen KM, Hicks TC, Timmcke AE. Rectal carcinoids: the most frequent carcinoid tumor. Dis Colon Rectum. 1992;35;717-725.
    Pubmed
  11. Kobayashi K, Katsumata T, Yoshizawa S, et al. Indications of endoscopic polypectomy for rectal carcinoid tumors and clinical usefulness of endoscopic ultrasonography. Dis Colon Rectum. 2005;48;285-291.
    Pubmed
  12. Ruszniewski P, Delle Fave G, Cadiot G, et al. Well-differentiated gastric tumors/carcinomas. Neuroendocrinology. 2006;84;158-164.
    Pubmed
  13. Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1,914 reported cases. Cancer. 2005;103;1587-1595.
    Pubmed
  14. Hosokawa O, Kaizaki Y, Hattori M, et al. Long-term follow up of patients with multiple gastric carcinoids associated with type A gastritis. Gastric Cancer. 2005;8;42-46.
    Pubmed
  15. Dakin GF, Warner RR, Pomp A, Salky B, Inabnet WB. Presentation, treatment, and outcome of type 1 gastric carcinoid tumors. J Surg Oncol. 2006;93;368-372.
    Pubmed
  16. Wangberg B, Grimelius L, Gran?rus G, Conradi N, Jansson S, Ahlman H. The role of gastric resection in the management of multicentric argyrophil gastric carcinoids. Surgery. 1990;108;851-857.
    Pubmed
  17. Burkitt MD, Pritchard DM. Review article: pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther. 2006;24;1305-1320.
    Pubmed
  18. Hou W, Schubert ML. Treatment of gastric carcinoids. Curr Treat Options Gastroenterol. 2007;10;123-133.
    Pubmed
  19. Varas MJ, Gornals JB, Pons C, et al. Usefulness of endoscopic ultrasonography (EUS) for selecting carcinoid tumors as candidates to endoscopic resection. Rev Esp Enferm Dig. 2010;102;577-582.
    Pubmed
  20. Ishii N, Horiki N, Itoh T, et al. Endoscopic submucosal dissection and preoperative assessment with endoscopic ultrasonography for the treatment of rectal carcinoid tumors. Surg Endosc. 2010;24;1413-1419.
    Pubmed
  21. Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. 1992;326;1721-1726.
    Pubmed
  22. Akerstr?m G, Hellman P. Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21;87-109.
    Pubmed
  23. Sotoudehmanesh R, Hedayat A, Shirazian N, et al. Endoscopic ultrasonography (EUS) in the localization of insulinoma. Endocrine. 2007;31;238-241.
    Pubmed
  24. Kann PH. The value of endoscopic ultrasound in localizing gastrinoma. Wien Klin Wochenschr. 2007;119;585-587.
    Pubmed
  25. Thomas-Marques L, Murat A, Delemer B, et al. Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol. 2006;101;266-273.
    Pubmed
  26. Kitano M, Kudo M, Yamao K, et al. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol. 2012;107;303-310.
    Pubmed
  27. Figueiredo FA, Giovannini M, Monges G, et al. Pancreatic endocrine tumors: a large single-center experience. Pancreas. 2009;38;936-940.
    Pubmed
  28. Kongkam P, Al-Haddad M, Attasaranya S, et al. EUS and clinical characteristics of cystic pancreatic neuroendocrine tumors. Endoscopy. 2008;40;602-605.
    Pubmed
  29. Kann PH, Wirkus B, Keth A, Goitom K. Pitfalls in endosonographic imaging of suspected insulinomas: pancreatic nodules of unknown dignity. Eur J Endocrinol. 2003;148;531-534.
    Pubmed
  30. Kann PH, Ivan D, Pf?tzner A, Forst T, Langer P, Schaefer S. Preoperative diagnosis of insulinoma: low body mass index, young age, and female gender are associated with negative imaging by endoscopic ultrasound. Eur J Endocrinol. 2007;157;209-213.
    Pubmed
  31. Chang F, Chandra A, Culora G, Mahadeva U, Meenan J, Herbert A. Cytologic diagnosis of pancreatic endocrine tumors by endoscopic ultrasound-guided fine-needle aspiration: a review. Diagn Cytopathol. 2006;34;649-658.
    Pubmed
  32. Chang F, Vu C, Chandra A, Meenan J, Herbert A. Endoscopic ultrasound-guided fine needle aspiration cytology of pancreatic neuroendocrine tumours: cytomorphological and immunocytochemical evaluation. Cytopathology. 2006;17;10-17.
    Pubmed
  33. Erickson RA, Sayage-Rabie L, Beissner RS. Factors predicting the number of EUS-guided fine-needle passes for diagnosis of pancreatic malignancies. Gastrointest Endosc. 2000;51;184-190.
    Pubmed
  34. LeBlanc JK, Ciaccia D, Al-Assi MT, et al. Optimal number of EUS-guided fine needle passes needed to obtain a correct diagnosis. Gastrointest Endosc. 2004;59;475-481.
    Pubmed
  35. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39;707-712.
    Pubmed
  36. Gress FG, Barawi M, Kim D, Grendell JH. Preoperative localization of a neuroendocrine tumor of the pancreas with EUS-guided fine needle tattooing. Gastrointest Endosc. 2002;55;594-597.
    Pubmed
  37. Zografos GN, Stathopoulou A, Mitropapas G, et al. Preoperative imaging and localization of small sized insulinoma with EUS-guided fine needle tattoing: a case report. Hormones (Athens). 2005;4;111-116.
    Pubmed
  38. Seo DW. EUS-guided antitumor therapy for pancreatic tumors. Gut Liver. 2010;4;S76-S81.
    Pubmed
  39. Jurgensen C, Schuppan D, Neser F, Ernstberger J, Junghans U, St?lzel U. EUS-guided alcohol ablation of an insulinoma. Gastrointest Endosc. 2006;63;1059-1062.
    Pubmed
  40. Chang KJ, Nguyen PT, Thompson JA, et al. Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma. Cancer. 2000;88;1325-1335.
    Pubmed
  41. Hecht JR, Bedford R, Abbruzzese JL, et al. A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin Cancer Res. 2003;9;555-561.
    Pubmed
  42. Chang KJ, Irisawa A. EUS 2008 Working Group document: evaluation of EUS-guided injection therapy for tumors. Gastrointest Endosc. 2009;69;S54-S58.
    Pubmed
  43. Chang KJ, Lee JG, Holcombe RF, Kuo J, Muthusamy R, Wu ML. Endoscopic ultrasound delivery of an antitumor agent to treat a case of pancreatic cancer. Nat Clin Pract Gastroenterol Hepatol. 2008;5;107-111.
    Pubmed
  44. Hirooka Y, Itoh A, Kawashima H, et al. A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. Pancreas. 2009;38;e69-e74.
    Pubmed
  45. Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999;50;392-401.
    Pubmed
  46. Yusuf TE, Matthes K, Brugge WR. EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model (with video). Gastrointest Endosc. 2008;67;957-961.
    Pubmed
  47. Jin Z, Du Y, Li Z, Jiang Y, Chen J, Liu Y. Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study. Endoscopy. 2008;40;314-320.
    Pubmed
  48. Sun S, Xu H, Xin J, Liu J, Guo Q, Li S. Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial. Endoscopy. 2006;38;399-403.
    Pubmed
Tables

World Health Organization (WHO) Classification of Gastroenteropancreatic Neuroendocrine Tumors

HPF, high-power field.


HPF, high-power field.

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) and Their Syndromes

HIAA, hydroxyindoleacetic acid; VIP, vasoactive intestinal peptide.


HPF, high-power field.

Imaging Methods


HPF, high-power field.

Accuracy of CT, MRI, and EUS in the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

CT, computed tomography; MRI, magnetic resonance imaging; EUS, endoscopic ultrasound; P-NET, pancreatic neuroendocrine tumor.


HPF, high-power field.

Immunohistochemistry (IHC) Performed in Gastroenteropancreatic Neuroendocrine Tumors


HPF, high-power field.

Potential Therapeutic Approaches for Gastroenteropancreatic Neuroendocrine Tumors

EUS, endoscopic ultrasound; TNFerade, tumor necrosis factor gene.


HPF, high-power field.
Figures
Fig. 1. (A) Endoscopic image of a gastric neuroendocrine tumor (NET). (B) Endosonographic image of a small pancreatic NET, measuring 6×7 mm.
Search for
Article
Archives