Surgical Treatment of Sporadic Pancreatic Neuroendocrine Tumors: A State of the Art Review

Haugvik, Sven-Petter; Labori, Knut Jørgen; Edwin, Bjørn; Mathisen, Øystein; Gladhaug, Ivar Prydz

doi:https://doi.org/10.1100/2012/357475

The Scientific World Journal

On this page

Abstract Conclusions References Copyright Related Articles

Review Article | Open Access

Volume 2012 | Article ID 357475 | https://doi.org/10.1100/2012/357475

Surgical Treatment of Sporadic Pancreatic Neuroendocrine Tumors: A State of the Art Review

Sven-Petter Haugvik,^1,2Knut Jørgen Labori,¹Bjørn Edwin,^1,2,3Øystein Mathisen,¹and Ivar Prydz Gladhaug^1,2

Academic Editor: P. Zezos, Y. Motoo

Received12 Oct 2012

Accepted25 Nov 2012

Published10 Dec 2012

Abstract

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms. They are clinically diverse and divided into functioning and nonfunctioning disease, depending on their ability to produce symptoms due to hormone production. Surgical resection is the only curative treatment and remains the cornerstone therapy for this patient group, even in patients with advanced disease. Over the last decade there has been a noticeable trend towards more aggressive surgery as well as more minimally invasive surgery in patients with PNETs. This has resulted in improved long-term survival in patients with locally advanced and metastatic disease treated aggressively, as well as shorter hospital stays and comparable long-term outcomes in patients with limited disease treated minimally invasively. There are still controversies related to issues of surgical treatment of PNETs, such as to what extent enucleation, lymph node sampling, and vascular reconstruction are beneficial for the oncologic outcome. Histopathologic tumor classification is of high clinical importance for treatment planning and prognostic evaluation of patients with PNETs. A constant challenge, which relates to the treatment of PNETs, is the lack of an internationally accepted histopathological classification system. This paper reviews current issues on the surgical treatment of sporadic PNETs with specific focus on surgical approaches and tumor classification.

1. Epidemiology

Pancreatic neuroendocrine tumors (PNETs) are rare and account for about 1-2% of all pancreatic neoplasms [1, 2]. The incidence has increased during the last decades to 4-5 per 100,000 in the general population [3–5]. Autopsy studies have shown that PNETs can be identified in as many as 10% of the population, suggesting that many carry asymptomatic disease [6]. Ten to 15% of all PNETs are part of familial syndromes such as multiple endocrine neoplasia type 1, von Hippel-Lindau, neurofibromatosis and tuberous sclerosis [3], which will not be reviewed further in this paper. The tumorigenesis and molecular pathogenesis of PNETs remain poorly understood.

2. Clinical Presentation

PNETs are clinically diverse and divided into functioning and nonfunctioning disease, dependent on their ability to produce symptoms due to hormone production [7]. The distinction between nonfunctioning and functioning PNETs is based on immunohistochemistry of tumor tissue in addition to clinical symptoms. Thirty to 50% of all PNETs are nonfunctioning [8, 9]. Since nonfunctioning tumors do not cause hormone-dependent symptoms, they are often detected incidentally or through symptoms related to mass effect resulting from local or distant tumor progression [10]. Common symptoms of nonfunctioning PNETs are abdominal pain, nausea and/or vomiting, fatigue, obstructive jaundice, and abdominal mass [11, 12]. Patients with functioning PNETs, such as insulinoma and gastrinoma, often present with characteristic symptoms dependent on the hormones produced. However, the clinical relevance of the distinction between functioning and nonfunctioning PNETs has recently been questioned as the treatment of these tumors follow the same general principles [13].

3. Classification

Classification systems enable patient risk stratifications and directly impact clinical decision making [16]. PNETs are generally classified according to their tumor-node-metastasis (TNM) pattern, defined by TNM staging systems, and grading, defined by the WHO 2010 classification [4, 17]. The latter is based on the tumor antigen and cell proliferation marker Ki-67. A Ki-67 of below 2% corresponds to a neuroendocrine tumor (NET) G1, a Ki-67 of 2–20% corresponds to a NET G2, whereas a Ki-67 above 20% corresponds to a neuroendocrine carcinoma (NEC) G3 [17]. Beside the generally accepted grading system, there are currently two TNM staging systems that are applied for staging of PNET. One system was proposed by the International Union for Cancer Control, American Joint Cancer Committee and the World Health Organization (UICC/AJCC/WHO), and is widely used in the North American region, while the other system was proposed by the European Neuroendocrine Tumor Society (ENETS) and is predominant in the European region [14, 15, 18]. Several studies have demonstrated the usefulness of the ENETS TNM staging system [14, 19–22] and in a recent study, Rindi et al. found that the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system in terms of prognostic stratification for patients with PNETs [14]. The ENETS TNM staging system is shown in Table 1. The final classification of PNETs is based on histopathological examination. The histology report should include a minimum set of criteria, including (1) a macroscopic description of the surgical specimen with exact anatomical site, margins distance, and size of the lesion, (2) a microscopic description with supporting immunohistochemistry, mitotic count, Ki-67 index, node-, and margin status, and (3) diagnosis with distinction between NET and NEC, grade, and TNM stage (Table 2).

4. Surgery

Surgical resection is the only curative treatment for patients with PNETs and remains the cornerstone therapy [11, 23–26], even in patients with advanced disease. The goals for surgical resection are cure, relief from functioning tumors [27], or relief from nonfunctioning tumors causing symptoms related to mass effect (biliary obstruction, gastric outlet obstruction, abdominal pain, gastrointestinal hemorrhage). Resectability rates up to 65% have been reported [28]. However, a substantial portion of patients with PNETs initially present with advanced disease, which cannot be radically resected.

4.1. Surgical Approaches

4.1.1. Functioning Disease

Functioning PNETs primarily include insulinomas and gastrinomas, with an incidence of 70–80% and 20–25% of all PNETs, and an incidence of malignancy of <10% and 50–60%, respectively [9].

Insulinomas are generally solitary, benign, and curable with surgery [9, 28, 29]. Recurrence after resection occurs in about 3% [30, 31]. The procedures of choice are enucleation for small and isolated insulinomas and partial pancreatectomy for large and potentially malignant insulinomas [32, 33]. Beside enucleation, middle pancreatectomy is an alternative parenchyma-sparing technique for this tumor entity [34]. Also, laparoscopic management of insulinoma in the body and tail of the pancreas, with distal pancreatectomy or enucleation, is feasible and safe [35]. In the case of occult insulinoma, blind distal pancreatectomy should be avoided [36]. However, explorative surgery with intraoperative ultrasound may be indicated in cases where preoperative diagnostics could not reveal any pancreatic lesions, as this is an excellent method for identifying occult insulinoma [37].

Gastrinoma is associated with gastric ulcerations due to overproduction of gastrin [38]. The clinical presentation of gastrinoma is referred to as Zollinger-Ellison syndrome. With the introduction of proton pump inhibitors, which prevent ulcer formation, surgery changed from being symptomatic to curative treatment in patients with Zollinger-Ellison syndrome [28]. All patients with Zollinger-Ellison syndrome without multiple neuroendocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure [39]. Routine use of duodenotomy in cases of pancreatic gastrinoma increases short- and long-term cure rates due to a higher detection rate of duodenal gastrinomas, as multiple gastrinomas are relatively common [40].

The incidences of other functioning PNETs, such as vasoactive intestinal peptide-producing tumors (VIPoma), glucagonoma, and somatostatinoma, are very low. These patients should undergo tumor resection to correct the severe hormonally caused metabolic derangements [28].

4.1.2. Nonfunctioning Disease

Nonfunctioning PNETs represent 30–50% of all PNETs and malignancy occurs in 60–90% [8, 9, 41]. Even though curative surgery is rare in patients with nonfunctioning PNETs, long-term survival can be achieved in many patients [12]. There is a strict correlation between tumor size and malignancy in these tumors [42]. Tumors larger than 2 cm have an increased risk of malignancy [43]. Solitary benign nonfunctioning PNETs can be removed by enucleation or spleen- or duodenum-preserving techniques in most cases [8].

4.1.3. Neuroendocrine Carcinoma

Neuroendocrine carcinomas (NECs) are defined as neuroendocrine tumors with a Ki-67 index above 20%, according to the WHO 2010 classification [17]. Such tumors are highly malignant and typically invade adjacent structures or metastasize before the diagnosis is made [44]. NECs of the pancreas are very rare and account for only about 2-3% of all PNETs [45–47]. The outcome is generally poor and most patients die within five years after diagnosis [44, 48]. However, curative resections have been reported in single cases [45]. Therefore, radical surgery should be attempted in localized disease [49, 50], while surgery in metastatic disease is not recommended [48].

4.1.4. Locally Advanced Disease

Locally advanced disease extends beyond the limits of the pancreas directly into surrounding organs or tissue, involves regional lymph nodes, or fulfills both of these criteria [5]. As many PNETs are nonfunctioning and slow-growing, a large proportion of these present with locally advanced disease. Resection for locally advanced PNETs is in general technically feasible and can result in favorable disease-free and overall survival in selected patients [51]. However, most patients will develop recurrence [52]. When not operated, patients with locally advanced PNETs may suffer from complications related to local mass effect and infiltrative growth, including gastrointestinal bleeding, vascular/intestinal/biliary obstruction, and occlusion of the superior mesenteric (SMV) or portal vein (PV) [53]. Hill et al. found that resection of the primary tumor in patients with PNETs is associated with improved survival across all stages of disease [54]. Based on this, surgery of locally advanced PNET without metastasis should be attempted. Interestingly, R1 resections of PNET are not associated with a worse overall survival compared to R0 resections [21, 55].

4.1.5. Metastatic Disease

PNETs commonly metastasize to the liver. This is especially true for nonfunctioning tumors as these are generally diagnosed at a late stage. In selected patients, resection of the primary PNET in the setting of unresectable but limited hepatic metastases may be indicated [56–58] as this may prolong survival [59–61]. As mentioned earlier, it has been shown that resection of the primary tumor in patients with PNETs is associated with improved survival across all stages of disease [54]. However, there is currently no clear answer to when and whether resection of the primary tumor should be performed in metastatic disease [62].

Surgical resection with curative intent or palliative debulking of more than 90% of liver metastases from nonfunctioning PNETs provides favorable oncologic outcomes, despite a high recurrence rate [63–65]. Patients with metastatic disease in the liver may profit from liver resection with long-term palliation and possibly cure in one-third of the patients [66]. Number, size, and localization of tumor sites seem less important than performing a complete resection of metastatic tissue from PNETs [67]. Patients with hormonally active liver metastases without prior extrahepatic or synchronous disease have the greatest survival benefit from surgery [63].

Two-stage procedures for synchronous bilobar liver metastases from NET, including portal vein embolization, enables complete resection and good long-term outcome in selected patients [68]. Debulking extends survival although recurrence is expected [69–71]. Surgical treatment of metastatic PNET should be performed in specialized centers and managed with a multidisciplinary approach [57, 72].

4.2. Technical Aspects

4.2.1. Resection versus Enucleation

Standard surgical approaches to PNETs include pancreaticoduodenectomy and distal or subtotal pancreatectomy. Middle segment pancreatectomy is an alternative in the management of PNETs located in the neck or body of the pancreas [73]. A general risk of major pancreatic resections is functional impairment of the organ due to loss of parenchyma, resulting in exocrine and/or endocrine insufficiency. Thus, parenchyma-sparing surgical techniques should be attempted when possible. Enucleation is a feasible procedure for the radical treatment of benign and borderline pancreatic neoplasms [74] and is associated with long-term survival, despite a relatively high risk of pancreatic fistula formation [75, 76]. Before enucleating a PNET, it is important to consider where the tumor is located in relation to the main pancreatic duct, as enucleations of tumors located very close to this may result in damage to the pancreatic duct and subsequent pancreatic leakage. Decisions regarding enucleations are highly individual compared to standard resections, underlining the importance of treatment in experienced high-volume institutions. Tumor enucleation is associated with shorter operative time, less intraoperative blood loss, and shorter hospital stay compared to pancreaticoduodenectomy and distal pancreatectomy [74].

4.2.2. Open versus Laparoscopic Surgery

Over the last decade there has been a trend towards more parenchyma-sparing and minimally invasive techniques in the management of PNETs. This shift has not increased morbidity or compromised survival [77]. Laparoscopic surgery for small and solitary PNETs is feasible and safe [78–81]. Advantages of the minimally invasive approach are less intraoperative bleeding [82], faster postoperative recovery [83], shorter hospital stay [84, 85], and improved cosmesis, compared to the open approach.

Laparoscopic distal pancreatectomy (LDP) is today an established procedure at several institutions worldwide [86–94]. The procedure provides similar short- and long-term oncologic outcomes as open distal pancreatectomy [85] and a selective use of it also seems to be a cost-efficient alternative to open distal pancreatectomy [82]. LDP with preservation of the spleen is feasible with a moderate risk of postoperative splenic infarction [95]. However, the significance of spleen preservation on oncologic outcome in patients with PNET remains unclear. Beside LDP of PNET in the pancreatic body and tail, laparoscopic enucleation of nonfunctioning PNETs in the pancreatic head [96] and laparoscopic pylorus-preserving pancreatoduodenectomy are feasible procedures that can be considered in selected cases [97]. When performing laparoscopic pancreatic surgery for PNET, intraoperative laparoscopic ultrasound should always be applied, as this allows safe tumor dissection and excision [80]. If the tumor cannot be identified precisely by laparoscopic ultrasound, conversion to open surgery should be considered [98]. Laparoscopic pancreatic surgery demands a high level of surgical skills in minimally invasive surgery and should be performed in specialized centers [99].

4.2.3. Lymph Node Sampling

From studies performed on pancreatic ductal adenocarcinoma, it is known that lymph node status is an important prognostic factor in resectable disease [100–102]. This has also been demonstrated in studies on PNET, where lymph node ratio is a significant predictor of recurrence after curative resection for malignant PNETs [103], and lymph node metastases in PNETs are related to better survival [104]. In many surgical specimens of PNETs, lymph nodes are not evaluated by the pathologist [105]. This may result in understaging of patients with potentially inadequate resection. It is of great importance to know to what extent parenchyma-sparing and minimally invasive pancreatic surgery can provide sufficient lymph node sampling for optimal oncologic outcome. When compared to open surgery, there are studies concluding with a clear limitation of LDP [84] as well as studies concluding with a comparable lymph node sampling after LDP [63]. Enucleations are associated with a low lymph node sampling rate compared with standard resections [105]. Lymph node sampling should be performed routinely when performing parenchyma-preserving or minimally invasive removal for small PNETs, to avoid understaging [34, 43]. Moreover, frozen-section examination should be performed, and when malignancy is confirmed, oncologically appropriate lymph node dissection is recommended [43].

4.2.4. Vascular Reconstruction

Surgery for locally advanced PNETs with vascular involvement is controversial. Vascular reconstruction has already been established in the treatment of locally advanced pancreatic adenocarcinoma [106]. Several case reports [107–109] suggest that a similar approach is feasible and beneficial in selected patients with PNETs. Norton et al. have recently examined this issue systematically [110]. In their study, only 9 of 42 patients with major vascular abutment undergoing resections of PNETs required vascular reconstruction. This shows that in most cases, even if the radiological evaluation suggests vascular involvement and at surgery the PNET is found to partially encase or involve the vessel, the tumor can be removed with careful dissection without requiring vascular reconstruction. Conventional contraindications to surgical resection of pancreatic malignancy, such as superior mesenteric vein invasion, should be reconsidered in patients with locally advanced PNETs [52, 110].

5. Prognosis and Follow-up

The five- and 10-year survival rates for all PNETs are about 65% and 45%, respectively, [19, 111]. The five-year survival rate for functioning PNETs is about 80% [111], while the five- and 10-year survival rates for nonfunctioning PNETs are about 55% and 30%, respectively, [11, 111]. Definitive surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of the liver metastases are predictive factors of long-term survival in patients with PNETs [112].

Long-term follow-up of patients having undergone surgical treatment for nonfunctioning PNETs is essential as there is a risk of late recurrence [34]. There have recently been published several international consensus guidelines on the management of patients with PNETs [113–116], which also include guidelines on follow-up of patients with functioning PNETs [113], nonfunctioning PNETs [114] and NECs [48]. The follow-up of patients with PNETs should be managed by specialized centers with a multidisciplinary approach [16, 57, 72, 117, 118].

6. Conclusions

In conclusion, this paper shows how sporadic PNETs represent a rare and clinically diverse group of pancreatic neoplasms, which requires special attention from hepatopancreatobiliary surgeons. Even though sporadic PNETs are associated with a high malignant potential, they are generally slow-growing. This explains why conventional contraindications to surgical resection of pancreatic malignancy should be reconsidered in patients with locally advanced or even metastatic disease. There is still a need for an internationally accepted histopathological classification system for PNETs. Recent studies suggest that the ENETS TNM staging system is a reliable system in terms of prognostic stratification. Other key points related to surgical treatment of sporadic PNETs with specific focus on surgical approaches and tumor classification are shown in Table 3.

Conflict of Interests

There is no conflict of interests.

References

T. R. Halfdanarson, K. G. Rabe, J. Rubin, and G. M. Petersen, “Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival,” Annals of Oncology, vol. 19, no. 10, pp. 1727–1733, 2008.
View at: Publisher Site | Google Scholar
S. A. Milan and C. J. Yeo, “Neuroendocrine tumors of the pancreas,” Current Opinion in Oncology, vol. 24, no. 1, pp. 46–55, 2012.
View at: Google Scholar
K. Öberg, “Pancreatic endocrine tumors,” Seminars in Oncology, vol. 37, no. 6, pp. 594–618, 2010.
View at: Publisher Site | Google Scholar
G. Rindi and B. Wiedenmann, “Neuroendocrine neoplasms of the gut and pancreas: new insights,” Nature Reviews Endocrinology, vol. 8, pp. 54–64, 2012.
View at: Publisher Site | Google Scholar
J. C. Yao, M. Hassan, A. Phan et al., “One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States,” Journal of Clinical Oncology, vol. 26, no. 18, pp. 3063–3072, 2008.
View at: Publisher Site | Google Scholar
W. Kimura, A. Kuroda, and Y. Morioka, “Clinical pathology of endocrine tumors of the pancreas. Analysis of autopsy cases,” Digestive Diseases and Sciences, vol. 36, no. 7, pp. 933–942, 1991.
View at: Google Scholar
M. H. Kulke, J. Bendell, L. Kvols, J. Picus, R. Pommier, and J. Yao, “Evolving diagnostic and treatment strategies for pancreatic neuroendocrine tumors,” Journal of Hematology and Oncology, vol. 4, article no. 29, 2011.
View at: Publisher Site | Google Scholar
H. Dralle, S. L. Krohn, W. Karges, B. O. Boehm, M. Brauckhoff, and O. Gimm, “Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors,” World Journal of Surgery, vol. 28, no. 12, pp. 1248–1260, 2004.
View at: Publisher Site | Google Scholar
V. Fendrich, J. Waldmann, D. K. Bartsch, and P. Langer, “Surgical management of pancreatic endocrine tumors,” Nature Reviews Clinical Oncology, vol. 6, no. 7, pp. 419–428, 2009.
View at: Publisher Site | Google Scholar
D. B. Evans, J. M. Skibber, J. E. Lee et al., “Nonfunctioning islet cell carcinoma of the pancreas,” Surgery, vol. 114, no. 6, pp. 1175–1182, 1993.
View at: Google Scholar
H. Liang, P. Wang, X. N. Wang, J. C. Wang, and X. S. Hao, “Management of nonfunctioning islet cell tumors,” World Journal of Gastroenterology, vol. 10, no. 12, pp. 1806–1809, 2004.
View at: Google Scholar
D. K. Bartsch, T. Schilling, A. Ramaswamy et al., “Management of nonfunctioning islet cell carcinomas,” World Journal of Surgery, vol. 24, no. 11, pp. 1418–1424, 2000.
View at: Publisher Site | Google Scholar
I. M. Modlin, S. F. Moss, B. I. Gustafsson, B. Lawrence, S. Schimmack, and M. Kidd, “The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant,” Langenbeck's Archives of Surgery, vol. 396, pp. 1145–1156, 2011.
View at: Publisher Site | Google Scholar
G. Rindi, M. Falconi, C. Klersy et al., “TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study,” Journal of the National Cancer Institute, vol. 104, no. 10, pp. 764–777, 2012.
View at: Publisher Site | Google Scholar
G. Rindi, G. Klöppel, and H. Alhman, “TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system,” Virchows Archiv, vol. 449, no. 4, pp. 395–401, 2006.
View at: Publisher Site | Google Scholar
F. Ehehalt, H. D. Saeger, C. M. Schmidt, and R. Grützmann, “Neuroendocrine tumors of the pancreas,” Oncologist, vol. 14, no. 5, pp. 456–467, 2009.
View at: Publisher Site | Google Scholar
F. T. Bosman, F. Carneiro, and R. H. Hruban, WHO Classification of Tumours of the Digestive System, International Agency for Research on Cancer (IARC), Lyon, France, 2010.
G. Rindi, “The ENETS guidelines: the new TNM classification system,” Tumori, vol. 96, no. 5, pp. 806–809, 2010.
View at: Google Scholar
S. Ekeblad, B. Skogseid, K. Dunder, K. Oberg, and B. Eriksson, “Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution,” Clinical Cancer Research, vol. 14, no. 23, pp. 7798–7803, 2008.
View at: Publisher Site | Google Scholar
H. Ito, M. Abramson, K. Ito et al., “Surgery and staging of pancreatic neuroendocrine tumors: a 14-year experience,” Journal of Gastrointestinal Surgery, vol. 14, no. 5, pp. 891–898, 2010.
View at: Publisher Site | Google Scholar
E. Pomianowska, I. P. Gladhaug, K. Grzyb et al., “Survival following resection of pancreatic endocrine tumors: importance of R-status and the WHO and TNM classification systems,” Scandinavian Journal of Gastroenterology, vol. 45, no. 7-8, pp. 971–979, 2010.
View at: Publisher Site | Google Scholar
A. Scarpa, W. Mantovani, P. Capelli et al., “Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients,” Modern Pathology, vol. 23, no. 6, pp. 824–833, 2010.
View at: Publisher Site | Google Scholar
F. Gomez-Rivera, A. E. Stewart, J. P. Arnoletti, S. Vickers, K. I. Bland, and M. J. Heslin, “Surgical treatment of pancreatic endocrine neoplasms,” American Journal of Surgery, vol. 193, no. 4, pp. 460–465, 2007.
View at: Publisher Site | Google Scholar
A. Legaspi, M. F. Brennan, R. A. Prinz et al., “Management of islet cell carcinoma,” Surgery, vol. 104, no. 6, pp. 1018–1023, 1988.
View at: Google Scholar
K. K. Kazanjian, H. A. Reber, and O. J. Hines, “Resection of pancreatic neuroendocrine tumors: results of 70 cases,” Archives of Surgery, vol. 141, no. 8, pp. 765–769, 2006.
View at: Publisher Site | Google Scholar
A. Zerbi, V. Capitanio, L. Boninsegna et al., “Surgical treatment of pancreatic endocrine tumours in Italy: results of a prospective multicentre study of 262 cases,” Langenbeck's Archives of Surgery, vol. 396, no. 3, pp. 313–321, 2011.
View at: Publisher Site | Google Scholar
B. D. Matthews, T. I. Smith, K. W. Kercher, W. D. Holder, and B. T. Heniford, “Surgical experience with functioning pancreatic neuroendocrine tumors,” American Surgeon, vol. 68, no. 8, pp. 660–665, 2002.
View at: Google Scholar
C. S. Grant, “Surgical management of malignant islet cell tumors,” World Journal of Surgery, vol. 17, no. 4, pp. 498–503, 1993.
View at: Google Scholar
D. Grama, B. Eriksson, H. Martensson et al., “Clinical characteristics, treatment and survival in patients with pancreatic tumors causing hormonal syndromes,” World Journal of Surgery, vol. 16, no. 4, pp. 632–639, 1992.
View at: Google Scholar
S. Crippa, A. Zerbi, L. Boninsegna et al., “Surgical management of insulinomas: short- and long-term outcomes after enucleations and pancreatic resections,” Archives of Surgery, vol. 147, no. 3, pp. 261–266, 2012.
View at: Publisher Site | Google Scholar
M. Rothmund, L. Angelini, L. M. Brunt et al., “Surgery for benign insulinoma: an international review,” World Journal of Surgery, vol. 14, no. 3, pp. 393–399, 1990.
View at: Publisher Site | Google Scholar
D. Vaidakis, J. Karoubalis, T. Pappa, G. Piaditis, and G. N. Zografos, “Pancreatic insulinoma: current issues and trends,” Hepatobiliary and Pancreatic Diseases International, vol. 9, no. 3, pp. 234–241, 2010.
View at: Google Scholar
A. Sa Cunha, A. Rault, C. Beau, D. Collet, and B. Masson, “Laparoscopic central pancreatectomy: single institution experience of 6 patients,” Surgery, vol. 142, no. 3, pp. 405–409, 2007.
View at: Publisher Site | Google Scholar
M. Falconi, A. Zerbi, S. Crippa et al., “Parenchyma-Preserving resections for small nonfunctioning pancreatic endocrine tumors,” Annals of Surgical Oncology, vol. 17, no. 6, pp. 1621–1627, 2010.
View at: Publisher Site | Google Scholar
Y. P. Zhao, H. X. Zhan, T. P. Zhang et al., “Surgical management of patients with insulinomas: result of 292 cases in a single institution,” Journal of Surgical Oncology, vol. 103, no. 2, pp. 169–174, 2011.
View at: Publisher Site | Google Scholar
B. Hirshberg, S. K. Libutti, H. R. Alexander et al., “Blind distal pancreatectomy for occult insulinoma, an inadvisable procedure,” Journal of the American College of Surgeons, vol. 194, no. 6, pp. 761–764, 2002.
View at: Publisher Site | Google Scholar
J. A. Norton, T. H. Shawker, J. L. Doppman et al., “Localization and surgical treatment of occult insulinomas,” Annals of Surgery, vol. 212, no. 5, pp. 615–620, 1990.
View at: Google Scholar
E. C. Ellison, J. Sparks, J. S. Verducci et al., “50-year appraisal of gastrinoma: recommendations for staging and treatment,” Journal of the American College of Surgeons, vol. 202, no. 6, pp. 897–905, 2006.
View at: Publisher Site | Google Scholar
J. A. Norton, D. L. Fraker, H. R. Alexander et al., “Surgery to cure the Zollinger-Ellison syndrome,” The New England Journal of Medicine, vol. 341, no. 9, pp. 635–644, 1999.
View at: Publisher Site | Google Scholar
J. A. Norton, H. R. Alexander, D. L. Fraker et al., “Does the use of routine duodenotomy (DUODX) affect rate of cure, development of liver metastases, or survival in patients with Zollinger-Ellison syndrome?” Annals of Surgery, vol. 239, no. 5, pp. 617–626, 2004.
View at: Publisher Site | Google Scholar
F. E. Eckhauser, P. S. Cheung, and A. I. Vinik, “Nonfunctioning malignant neuroendocrine tumors of the pancreas,” Surgery, vol. 100, no. 6, pp. 978–988, 1986.
View at: Google Scholar
R. Bettini, S. Partelli, L. Boninsegna et al., “Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor,” Surgery, vol. 150, no. 1, pp. 75–82, 2011.
View at: Publisher Site | Google Scholar
L. Fernández-Cruz, V. Molina, R. Vallejos, E. Jiménez Chavarria, M.-A. Lõpez-Boado, and J. Ferrer, “Outcome after laparoscopic enucleation for non-functional neuroendocrine pancreatic tumours,” HPB, vol. 14, no. 3, pp. 171–176, 2012.
View at: Publisher Site | Google Scholar
F. Panzuto, L. Boninsegna, N. Fazio et al., “Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression,” Journal of Clinical Oncology, vol. 29, no. 17, pp. 2372–2377, 2011.
View at: Publisher Site | Google Scholar
K. Kinoshita, T. Minami, Y. Ohmori, S. Kanayama, K. Yoshikawa, and T. Tsujimura, “Curative resection of a small cell carcinoma of the pancreas: report of a case of long survival without chemotherapy,” Journal of Gastroenterology and Hepatology, vol. 19, no. 9, pp. 1087–1091, 2004.
View at: Publisher Site | Google Scholar
T. P. O'Connor, T. P. Wade, Y. C. Sunwoo et al., “Small cell undifferentiated carcinoma of the pancreas: report of a patient with tumor marker studies,” Cancer, vol. 70, no. 6, pp. 1514–1519, 1992.
View at: Google Scholar
C. V. Reyes and T. Wang, “Undifferentiated small cell carcinoma of the pancreas: a report of five cases,” Cancer, vol. 47, no. 10, pp. 2500–2502, 1981.
View at: Google Scholar
O. Nilsson, E. Van Cutsem, G. Delle Fave et al., “Poorly differentiated carcinomas of the foregut (gastric, duodenal and pancreatic),” Neuroendocrinology, vol. 84, no. 3, pp. 212–215, 2007.
View at: Publisher Site | Google Scholar
L. Kölby, O. Nilsson, and H. Ahlman, “Gastroduodenal endocrine tumours,” Scandinavian Journal of Surgery, vol. 93, no. 4, pp. 317–323, 2004.
View at: Google Scholar
G. Åkerström, “Management of carcinoid tumors of the stomach, duodenum, and pancreas,” World Journal of Surgery, vol. 20, no. 2, pp. 173–182, 1996.
View at: Publisher Site | Google Scholar
M. Abu Hilal, M. J. W. McPhail, B. A. Zeidan, C. E. Jones, C. D. Johnson, and N. W. Pearce, “Aggressive multi-visceral pancreatic resections for locally advanced neuroendocrine tumours. Is it worth it?” Journal of the Pancreas, vol. 10, no. 3, pp. 276–279, 2009.
View at: Google Scholar
J. A. Norton, M. Kivlen, M. Li et al., “Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors,” Archives of Surgery, vol. 138, no. 8, pp. 859–866, 2003.
View at: Publisher Site | Google Scholar
P. Hellman, M. Andersson, J. Rastad et al., “Surgical strategy for large or malignant endocrine pancreatic tumors,” World Journal of Surgery, vol. 24, no. 11, pp. 1353–1360, 2000.
View at: Publisher Site | Google Scholar
J. S. Hill, J. T. McPhee, T. P. McDade et al., “Pancreatic neuroendocrine tumors,” Cancer, vol. 115, no. 4, pp. 741–751, 2009.
View at: Publisher Site | Google Scholar
E. S. Glazer, J. F. Tseng, W. Al-Refaie et al., “Long-term survival after surgical management of neuroendocrine hepatic metastases,” HPB, vol. 12, no. 6, pp. 427–433, 2010.
View at: Publisher Site | Google Scholar
M. Bruzoni, P. Parikh, R. Celis et al., “Management of the primary tumor in patients with metastatic pancreatic neuroendocrine tumor: a contemporary single-institution review,” American Journal of Surgery, vol. 197, no. 3, pp. 376–381, 2009.
View at: Publisher Site | Google Scholar
R. S. Chamberlain, D. Canes, K. T. Brown et al., “Hepatic neuroendocrine metastases: does intervention alter outcomes?” Journal of the American College of Surgeons, vol. 190, no. 4, pp. 432–445, 2000.
View at: Publisher Site | Google Scholar
C. S. Cho, D. M. Labow, L. Tang et al., “Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms,” Cancer, vol. 113, no. 1, pp. 126–134, 2008.
View at: Publisher Site | Google Scholar
H. Chen, J. M. Hardacre, A. Uzar, J. L. Cameron, and M. A. Choti, “Isolated liver metastases from neuroendocrine tumors: does resection prolong survival?” Journal of the American College of Surgeons, vol. 187, no. 1, pp. 88–92, 1998.
View at: Publisher Site | Google Scholar
S. Musunuru, H. Chen, S. Rajpal et al., “Metastatic neuroendocrine hepatic tumors: resection improves survival,” Archives of Surgery, vol. 141, no. 10, pp. 1000–1004, 2006.
View at: Publisher Site | Google Scholar
F. G. Que, D. M. Nagorney, K. P. Batts, L. J. Linz, and L. K. Kvols, “Hepatic resection for metastatic neuroendocrine carcinomas,” American Journal of Surgery, vol. 169, no. 1, pp. 36–43, 1995.
View at: Publisher Site | Google Scholar
G. Capurso, R. Bettini, M. Rinzivillo, L. Boninsegna, G. D. Fave, and M. Falconi, “Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review,” Neuroendocrinology, vol. 93, no. 4, pp. 223–229, 2011.
View at: Publisher Site | Google Scholar
S. C. Mayo, M. C. De Jong, C. Pulitano et al., “Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis,” Annals of Surgical Oncology, vol. 17, no. 12, pp. 3129–3136, 2010.
View at: Publisher Site | Google Scholar
S. Scigliano, R. Lebtahi, F. Maire et al., “Clinical and imaging follow-up after exhaustive liver resection of endocrine metastases: a 15-year monocentric experience,” Endocrine-Related Cancer, vol. 16, no. 3, pp. 977–990, 2009.
View at: Publisher Site | Google Scholar
D. Cusati, L. Zhang, W. S. Harmsen et al., “Metastatic nonfunctioning pancreatic neuroendocrine carcinoma to liver: surgical treatment and outcomes,” Journal of the American College of Surgeons, vol. 215, no. 1, pp. 117–124, 2012.
View at: Publisher Site | Google Scholar
B. Dousset, O. Saint-Marc, J. Pitre, O. Soubrane, D. Houssin, and Y. Chapuis, “Metastatic endocrine tumors: medical treatment, surgical resection, or liver transplantation,” World Journal of Surgery, vol. 20, no. 7, pp. 908–915, 1996.
View at: Publisher Site | Google Scholar
D. Elias, P. Lasser, M. Ducreux et al., “Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study,” Surgery, vol. 133, no. 4, pp. 375–382, 2003.
View at: Publisher Site | Google Scholar
R. Kianmanesh, A. Sauvanet, O. Hentic et al., “Two-step surgery for synchronous bilobar liver metastases from digestive endocrine tumors: a safe approach for radical resection,” Annals of Surgery, vol. 247, no. 4, pp. 659–665, 2008.
View at: Publisher Site | Google Scholar
J. M. Sarmiento, G. Heywood, J. Rubin, D. M. Ilstrup, D. M. Nagorney, and F. G. Que, “Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival,” Journal of the American College of Surgeons, vol. 197, no. 1, pp. 29–37, 2003.
View at: Publisher Site | Google Scholar
J. M. Sarmiento and F. G. Que, “Hepatic surgery for metastases from neuroendocrine tumors,” Surgical Oncology Clinics of North America, vol. 12, no. 1, pp. 231–242, 2003.
View at: Publisher Site | Google Scholar
G. B. Thompson, J. A. Van Heerden, C. S. Grant, J. A. Carney, and D. M. Ilstrup, “Islet cell carcinomas of the pancreas: a twenty-year experience,” Surgery, vol. 104, no. 6, pp. 1011–1017, 1988.
View at: Google Scholar
G. L. Grazi, M. Cescon, F. Pierangeli et al., “Highly aggressive policy of hepatic resections for neuroendocrine liver metastases,” Hepato-Gastroenterology, vol. 47, no. 32, pp. 481–486, 2000.
View at: Google Scholar
C. Bassi, “Middle segment pancreatectomy: a useful tool in the management of pancreatic neoplasms,” Journal of Gastrointestinal Surgery, vol. 11, no. 4, pp. 421–424, 2007.
View at: Publisher Site | Google Scholar
T. Hackert, U. Hinz, S. Fritz et al., “Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections,” Langenbeck's Archives of Surgery, vol. 396, pp. 1197–1203, 2011.
View at: Publisher Site | Google Scholar
S. Crippa, C. Bassi, R. Salvia, M. Falconi, G. Butturini, and P. Pederzoli, “Enucleation of pancreatic neoplasms,” British Journal of Surgery, vol. 94, no. 10, pp. 1254–1259, 2007.
View at: Publisher Site | Google Scholar
A. Dedieu, A. Rault, D. Collet, B. Masson, and A. Sa Cunha, “Laparoscopic enucleation of pancreatic neoplasm,” Surgical Endoscopy and Other Interventional Techniques, vol. 25, no. 2, pp. 575–576, 2011.
View at: Publisher Site | Google Scholar
J. DiNorcia, M. K. Lee, P. L. Reavey et al., “One hundred thirty resections for pancreatic neuroendocrine tumor: evaluating the impact of minimally invasive and parenchyma-sparing techniques,” Journal of Gastrointestinal Surgery, vol. 14, no. 10, pp. 1536–1546, 2010.
View at: Publisher Site | Google Scholar
A. Assalia and M. Gagner, “Laparoscopic pancreatic surgery for islet cell tumors of the pancreas,” World Journal of Surgery, vol. 28, no. 12, pp. 1239–1247, 2004.
View at: Publisher Site | Google Scholar
B. Edwin, T. Mala, O. Mathisen et al., “Laparoscopic resection of the pancreas: a feasibility study of the short-term outcome,” Surgical Endoscopy and Other Interventional Techniques, vol. 18, no. 3, pp. 407–411, 2004.
View at: Publisher Site | Google Scholar
L. Fernández-Cruz, M. Herrera, A. Sáenz, J. P. Pantoja, E. Astudillo, and M. Sierra, “Laparoscopic pancreatic surgery in patients with neuroendocrine tumours: indications and limits,” Best Practice and Research, vol. 15, no. 2, pp. 161–175, 2001.
View at: Publisher Site | Google Scholar
M. Gagner, A. Pomp, M. F. Herrera et al., “Early experience with laparoscopic resections of islet cell tumors,” Surgery, vol. 120, no. 6, pp. 1051–1054, 1996.
View at: Google Scholar
P. Limongelli, A. Belli, G. Russo et al., “Laparoscopic and open surgical treatment of left-sided pancreatic lesions: clinical outcomes and cost-effectiveness analysis,” Surgical Endoscopy and Other Interventional Techniques, vol. 26, no. 7, pp. 1830–1836, 2012.
View at: Publisher Site | Google Scholar
S. C. Kim, K. T. Park, J. W. Hwang et al., “Comparative analysis of clinical outcomes for laparoscopic distal pancreatic resection and open distal pancreatic resection at a single institution,” Surgical Endoscopy and Other Interventional Techniques, vol. 22, no. 10, pp. 2261–2268, 2008.
View at: Publisher Site | Google Scholar
M. S. Baker, D. J. Bentrem, M. B. Ujiki, S. Stocker, and M. S. Talamonti, “A prospective single institution comparison of peri-operative outcomes for laparoscopic and open distal pancreatectomy,” Surgery, vol. 146, no. 4, pp. 635–645, 2009.
View at: Publisher Site | Google Scholar
D. A. Kooby, W. G. Hawkins, C. M. Schmidt et al., “Curative laparoscopic resection for pancreatic neoplasms: a critical analysis from a single institution,” Journal of the American College of Surgeons, vol. 210, no. 5, pp. 779–785, 2010.
View at: Publisher Site | Google Scholar
L. Fernández-Cruz, R. Cosa, L. Blanco, S. Levi, M. A. López-Boado, and S. Navarro, “Curative laparoscopic resection for pancreatic neoplasms: a critical analysis from a single institution,” Journal of Gastrointestinal Surgery, vol. 11, no. 12, pp. 1607–1622, 2007.
View at: Publisher Site | Google Scholar
J. Y. Mabrut, L. Fernandez-Cruz, J. S. Azagra et al., “Laparoscopic pancreatic resection: results of a multicenter European study of 127 patients,” Surgery, vol. 137, no. 6, pp. 597–605, 2005.
View at: Publisher Site | Google Scholar
B. W. Eom, J. Y. Jang, S. E. Lee, H. S. Han, Y. S. Yoon, and S. W. Kim, “Clinical outcomes compared between laparoscopic and open distal pancreatectomy,” Surgical Endoscopy and Other Interventional Techniques, vol. 22, no. 5, pp. 1334–1338, 2008.
View at: Publisher Site | Google Scholar
M. A. Hilal, M. Hamdan, F. Di Fabio, N. W. Pearce, and C. D. Johnson, “Laparoscopic versus open distal pancreatectomy: a clinical and cost-effectiveness study,” Surgical Endoscopy and Other Interventional Techniques, vol. 26, no. 6, pp. 1670–1674, 2012.
View at: Publisher Site | Google Scholar
D. A. Kooby, T. Gillespie, D. Bentrem et al., “Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches,” Annals of Surgery, vol. 248, no. 3, pp. 438–443, 2008.
View at: Publisher Site | Google Scholar
B. I. Røsok, I. P. Marangos, A. M. Kazaiyan et al., “Single-centre experience of laparoscopic pancreatic surgery,” British Journal of Surgery, vol. 97, no. 6, pp. 902–909, 2010.
View at: Publisher Site | Google Scholar
P. J. Kneuertz, S. H. Patel, C. K. Chu et al., “Laparoscopic distal pancreatectomy: trends and lessons learned through an 11-year experience,” Journal of the American College of Surgeons, vol. 215, no. 2, pp. 167–176, 2012.
View at: Publisher Site | Google Scholar
A. M. Fox, K. Pitzul, F. Bhojani et al., “Comparison of outcomes and costs between laparoscopic distal pancreatectomy and open resection at a single center,” Surgical Endoscopy and Other Interventional Techniques, vol. 26, no. 5, pp. 1220–1230, 2012.
View at: Publisher Site | Google Scholar
G. Butturini, S. Partelli, S. Crippa et al., “Perioperative and long-term results after left pancreatectomy: a single-institution, non-randomized, comparative study between open and laparoscopic approach,” Surgical Endoscopy, vol. 25, pp. 2871–2878, 2011.
View at: Publisher Site | Google Scholar
G. Butturini, M. Inama, G. Malleo et al., “Perioperative and long-term results of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessels conservation: a retrospective analysis,” Journal of Surgical Oncology, vol. 105, no. 4, pp. 387–392, 2012.
View at: Publisher Site | Google Scholar
N. Singh, C. Y. Lo, and W. F. Chan, “Laparoscopic enucleation of a nonfunctioning neuroendocrine tumor at the head of the pancreas,” JSLS, vol. 10, no. 2, pp. 259–262, 2006.
View at: Google Scholar
S. C. Kim, K. B. Song, Y. S. Jung et al., “Short-term clinical outcomes for 100 consecutive cases of laparoscopic pylorus-preserving pancreatoduodenectomy: improvement with surgical experience,” Surgical Endoscopy. In press.
View at: Google Scholar
L. Fernández-Cruz and G. Cesar-Borges, “Laparoscopic strategies for resection of insulinomas,” Journal of Gastrointestinal Surgery, vol. 10, no. 5, pp. 752–760, 2006.
View at: Publisher Site | Google Scholar
A. Toniato, F. Meduri, M. Foletto, A. Avogaro, and M. Pelizzo, “Laparoscopic treatment of benign insulinomas localized in the body and tail of the pancreas: a single-center experience,” World Journal of Surgery, vol. 30, no. 10, pp. 1916–1919, 2006.
View at: Publisher Site | Google Scholar
Y. Murakami, K. Uemura, T. Sudo et al., “Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma,” Journal of the American College of Surgeons, vol. 211, no. 2, pp. 196–204, 2010.
View at: Publisher Site | Google Scholar
T. T. Sahin, T. Fujii, M. Kanda et al., “Prognostic implications of lymph node metastases in carcinoma of the body and tail of the pancreas,” Pancreas, vol. 40, pp. 1029–1033, 2011.
View at: Publisher Site | Google Scholar
E. Pomianowska, A. Westgaard, O. Mathisen et al., “Prognostic relevance of number and ratio of metastatic lymph nodes in resected pancreatic, ampullary, and distal bile duct carcinomas,” Annals of Surgical Oncology. In press.
View at: Google Scholar
L. Boninsegna, F. Panzuto, S. Partelli et al., “Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections,” European Journal of Cancer, vol. 48, no. 11, pp. 1608–1615, 2012.
View at: Google Scholar
P. Tomassetti, D. Campana, L. Piscitelli et al., “Endocrine pancreatic tumors: factors correlated with survival,” Annals of Oncology, vol. 16, no. 11, pp. 1806–1810, 2005.
View at: Publisher Site | Google Scholar
J. R. Parekh, S. C. Wang, E. K. Bergsland et al., “Lymph node sampling rates and predictors of nodal metastasis in pancreatic neuroendocrine tumor resections: the ucsf experience with 149 patients,” Pancreas, vol. 41, no. 6, pp. 840–844, 2012.
View at: Publisher Site | Google Scholar
M. Ouaissi, C. Hubert, R. Verhelst et al., “Vascular reconstruction during pancreatoduodenectomy for ductal adenocarcinoma of the pancreas improves resectability but does not achieve cure,” World Journal of Surgery, vol. 34, no. 11, pp. 2648–2661, 2010.
View at: Google Scholar
T. Akatsu, K. Aiura, M. Shimazu et al., “Successful pancreatectomy with En-bloc resection of the celiac artery and portal vein for pancreatic endocrine carcinoma,” Hepato-Gastroenterology, vol. 54, no. 76, pp. 1269–1271, 2007.
View at: Google Scholar
A. Bedirli, T. E. Patiroglu, O. Sakrak, and Y. Aritas, “Portal vein resection for a portal vein thrombus caused by nonfunctioning islet cell carcinoma: report of a case,” Surgery Today, vol. 34, no. 9, pp. 802–804, 2004.
View at: Publisher Site | Google Scholar
E. Sakamoto, H. Hasegawa, S. Ogiso et al., “Curative resection for a pancreatic endocrine carcinoma involving the portal vein,” Hepato-Gastroenterology, vol. 51, no. 60, pp. 1849–1851, 2004.
View at: Google Scholar
J. A. Norton, E. J. Harris, Y. Chen et al., “Pancreatic endocrine tumors with major vascular abutment, involvement, or encasement and indication for resection,” Archives of Surgery, vol. 146, no. 6, pp. 724–732, 2011.
View at: Publisher Site | Google Scholar
G. Q. Phan, C. J. Yeo, R. H. Hruban, K. D. Lillemoe, H. A. Pitt, and J. L. Cameron, “Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients,” Journal of Gastrointestinal Surgery, vol. 2, no. 5, pp. 473–482, 1998.
View at: Google Scholar
Q. D. Chu, H. C. Hill, H. O. Douglass et al., “Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas,” Annals of Surgical Oncology, vol. 9, no. 9, pp. 855–862, 2002.
View at: Google Scholar
R. T. Jensen, G. Cadiot, M. L. Brandi et al., “ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes,” Neuroendocrinology, vol. 95, no. 2, pp. 98–119, 2012.
View at: Publisher Site | Google Scholar
M. Falconi, D. K. Bartsch, B. Eriksson et al., “ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors,” Neuroendocrinology, vol. 95, no. 2, pp. 120–134, 2012.
View at: Publisher Site | Google Scholar
E. T. Janson, H. Sørbye, S. Welin et al., “Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours,” Acta Oncologica, vol. 49, no. 6, pp. 740–756, 2010.
View at: Publisher Site | Google Scholar
M. H. Kulke, L. B. Anthony, D. L. Bushnell et al., “NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas,” Pancreas, vol. 39, no. 6, pp. 735–752, 2010.
View at: Publisher Site | Google Scholar
M. A. Kouvaraki, C. C. Solorzano, S. E. Shapiro et al., “Surgical treatment of non-functioning pancreatic islet cell tumors,” Journal of Surgical Oncology, vol. 89, no. 3, pp. 170–185, 2005.
View at: Publisher Site | Google Scholar
S. L. Ong, G. Garcea, C. A. Pollard et al., “A fuller understanding of pancreatic neuroendocrine tumours combined with aggressive management improves outcome,” Pancreatology, vol. 9, no. 5, pp. 583–600, 2009.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2012 Sven-Petter Haugvik et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

6734

Downloads

1975

Citations