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26 Surgery for Pancreatic Neuroendocrine Tumors: Techniques and Potential…
• Cholecystectomy with common hepatic duct dissection is performed.
• Duodenal or gastric transection (pylorus-preserving procedure: 2–3cm distal to
pylorus; classic Whipple: antrectomy).
• Pancreatic division (after ligation of pancreaticoduodenal arteries) and jejunal
transection (should be performed at least 10 cm distal to the ligament of
Treitz).
• En bloc removal of the tumor-containing specimen.
• Complex anatomic reconstruction (pancreatic reconstruction with two-layer
pancreatojejunostomy, biliary reconstruction with hepaticojejunostomy, enteric
continuity with gastrojejunostomy).
233
Distal Pancreatectomy [1, 2]
Applications
• Laparoscopic or open approach, anterograde, and retrograde approaches are
described.
• As with pancreatoduodenectomy, distal pancreatectomy is performed for larger
tumors with highly malignant potential.
• Appropriate for tumors in the body and tail.
Technical Overview
• Visual inspection for gross metastatic disease.
• Division of the gastrocolic ligament and entry into the lesser sac.
• Control of the short gastric vessels is obtained. The gastrosplenic ligament is
ligated and divided.
• The stomach is gently retracted toward the patient’s head. Dissection and mobi-
lization of the pancreatic body/tail is then performed.
• The splenic vessels are ligated and divided.
• The pancreas is transected with a vascular stapler, with or without an omental ap.
• The specimen (with or without the spleen) is removed. A drain is left at the sur-
geon’s discretion.
PNET Specics andManagement
Insulinomas [1, 4]
Characteristic Features
• Most common functional PNET.
• >90% are benign tumors
234
K. C. McGann and C. M. Kiernan
• “Whipple Triad”: fasting hypoglycemia, neuroglycopenic symptoms (e.g.,
altered mental status), and improvement of symptoms with glucose
administration.
Localization
• CT, MRI.
• EUS.
• Not SRS (low receptor expression).
Surgical Technique
• Enucleation (most commonly laparoscopic).
• Given the benign nature of insulinomas, enucleation is considered appropriate in
effort to preserve pancreatic tissue.
• The tumor is removed, ideally with the surrounding pancreatic tissue undisrupted.
Considerations
• Formal anatomic resection (distal pancreatectomy, pancreatoduodenectomy)
may be indicated if there is concern for malignancy, large tumor, or tumor within
2mm of the duct on intraoperative ultrasound.
• Perioperative use of glucose infusions and diazoxide (lowers insulin release) is
done in effort to prevent profound hypoglycemia.
Gastrinomas [1, 4]
Characteristic Features
• Second most common functional PNET, 60–90% malignant, often metastatic
disease.
• Mostly located in the “Gastrinoma Triangle,” which is bounded by the cystic
duct, second and third portions of the duodenum, and the junction of the neck
and body of the pancreas.
Localization
• CT, MRI.
• SRS (near uniform receptor expression).
26 Surgery for Pancreatic Neuroendocrine Tumors: Techniques and Potential…
235
• EUS.
• Angiography +/− stimulation (e.g., calcium).
• In a minority of cases, gastrinomas are unable to be localized preoperatively.
Open surgical exploration with intraoperative ultrasound, endoscopy, and duodenotomy may be needed.
Surgical Technique
• Anatomic resection, lymphadenectomy.
• Tumors in the duodenum or head of the pancreas are typically managed with
pancreaticoduodenectomy (Whipple).
• Tumors in the body and tail are managed with a distal pancreatectomy.
• Central pancreatectomy is also described.
• Regional lymph node dissection due to high rates of lymphatic spread and
recurrence.
• The “Thompson Procedure” has been described for MEN-1-associated gastrino-
mas. This involves a distal pancreatic resection in addition to enucleation of
tumors in the pancreatic head, and thereby spares the need for total
pancreatectomy.
Considerations
• Roughly half of gastrinomas are metastatic at diagnosis.
• Treatment for unresectable disease focuses on managing symptoms with medi-
cations such as high-dose PPIs and somatostatin analogs.
VIPomas [1, 4]
Characteristic Features
• Majority are malignant, >70% metastatic.
• “WDHA Syndrome:” watery diarrhea, hypokalemia, and achlorhydria
Localization
• CT, MRI.
• SRS.
• EUS.
• Angiography +/− stimulation.
236
K. C. McGann and C. M. Kiernan
Surgical Technique
• Anatomic resection, lymphadenectomy.
• As with gastrinomas, given the malignant nature, formal anatomic resection with
distal pancreatectomy or pancreaticoduodenectomy with negative margins and
regional lymphadenectomy is indicated.
• Cholecystectomy is also performed due to the need for long-term somatostatin
therapy.
Considerations
• WDHA syndrome necessitates preoperative uid resuscitation and electrolyte
correction.
• Somatostatin analogs can be used to curb diarrhea and decrease resultant
dehydration.
Glucagonomas [1, 4]
Characteristic Features
• Majority are malignant and metastatic.
• “Glucagonoma Syndrome (4Ds)”: diabetes, dermatitis, DVT, and depression
• The pathognomonic skin nding, necrolytic migrating erythema, may signal
disease.
Localization
• CT/MRI (these tumors are easily localized).
Surgical Technique
• Anatomic resection, lymphadenectomy.
• As with gastrinomas and VIPomas, formal resection and regional lymphadenec-
tomy (usually distal pancreatectomy) are done due to highly malignant nature of
these tumors.
• Cholecystectomy is also performed due to the need for long-term somatostatin
therapy.
26 Surgery for Pancreatic Neuroendocrine Tumors: Techniques and Potential…
Considerations
• Glucagonoma syndrome is treated with preoperative nutritional supplementa-
tion, octreotide, and early DVT prophylaxis.
237
Somatostatinomas [1, 4]
Characteristic Features
• 90% are malignant, frequently are metastatic
• Very rare, often found in the head of pancreas.
• Presentation is nonspecic, owing to the broad gastro-inhibitory effect of
somatostatin.
• Clinical ndings may include diabetes, cholecystitis, steatorrhea, and
malabsorption.
Localization
• CT/MRI.
• SRS.
• EUS.
• Angiography +/− stimulation.
Surgical Technique
• Anatomic resection, lymphadenectomy.
• Again, formal resection and regional lymphadenectomy are performed due to the
highly malignant nature of these tumors.
• Cholecystectomy is also performed.
Considerations
• Can be associated with clinical syndromes such as von Recklinghausen disease,
and can also occur with synchronous pheochromocytomas.
Complications after Surgery forPNETs [6–10]
• Surgical resection of PNETs is technically feasible in experienced hands and
decreases disease-specic mortality but is associated with potential postoperative morbidity.
238
K. C. McGann and C. M. Kiernan
• In addition to more generic surgical complications such as infection, there are
several notable complications of PNET surgery that should be highlighted.
– Pancreatic leak is one of the more common complications after surgery for
PNETs, particularly after enucleation procedures. Pancreatic stulas may
occur as a result. Management of pancreatic leaks often requires drainage via
endoscopic or percutaneous techniques in addition to nonoperative medical
management with antibiotics.
– Bleeding may occur from the residual gastroduodenal artery (GDA) stump
postoperatively. This is most commonly managed by angioembolization performed by Interventional Radiology.
– Exocrine insufciency may occur after PNET resection, and as expected, is
directly related to the proportion of pancreatic mass that is surgically removed.
Symptomatic exocrine insufciency is managed with pancreatic enzyme
replacement therapy.
– New onset diabetes may occur in as many as 20–50% of patients
postoperatively.
References
1. Arrington AK, Riall TS.Endocrine pancreas. In: Townsend CM, Beauchamp RD, Evers BM,
Mattox KL, editors. Sabiston textbook of surgery: the biological basis of modern surgical
practice. 21st ed. St. Louis: Elsevier; 2022. p.941–63.
2. American College of Surgeons. Alliance for clinical trials in oncology. Pancreatic surgery, Pancreatoduodenectomy, distal pancreatectomy. In: Hunt KK, Veeramachaneni NK,
Posner MC, Katz MHG, Halverson A, Chang GJ, Blair S, editors. Operative standards
for cancer surgery—breast, lung, pancreas, colon, vol. 1. Philadelphia: Wolters Kluwer
Health; 2015.
3. Dream S, Chen H. Pancreatic neoplasms—endocrine. In: SCORE: the surgical council on
resident education; 2021. https://www.surgicalcore.org/modulecontent.aspx?id=144977.
Accessed 15 Dec 2022.
4. Jensen RT, Cadiot G, Brandi ML, De Herder WW, Kaltsas G, Komminoth P, Scoazec JY,
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(2):98–119.
5. Crippa S, Bassi C, Salvia R, Falconi M, Butturini G, Pederzoli P.Enucleation of pancreatic
neoplasms. J Br Surg. 2007;94(10):1254–9.
6. Beger HG, Poch B, Vasilescu C.Benign cystic neoplasm and endocrine tumours of the pancreas–when and how to operate–an overview. Int J Surg. 2014;12(6):606–14.
7. Jilesen AP, van Eijck CH, Van Dieren S, Gouma D, Van Dijkum EJ.Postoperative complications, in-hospital mortality and 5-year survival after surgical resection for patients with a pancreatic neuroendocrine tumor: a systematic review. World J Surg. 2016;40(3):729–48.
8. Smith JK, Ng SC, Hill JS, Simons JP, Arous EJ, Shah SA, Tseng JF, McDade
TP.Complications after pancreatectomy for neuroendocrine tumors: a national study. J Surg
Res. 2010;163(1):63–8.
26 Surgery for Pancreatic Neuroendocrine Tumors: Techniques and Potential…
9. Haugvik SP, Marangos IP, Røsok BI, Pomianowska E, Gladhaug IP, Mathisen Ø, Edwin
B.Long-term outcome of laparoscopic surgery for pancreatic neuroendocrine tumors. World
J Surg. 2013;37(3):582–90.
10. Lu WJ, Cai HL, Ye MD, Wu YL, Xu B.Enucleation of non-invasive tumors in the proximal
pancreas: indications and outcomes compared with standard resections. J Zhejiang Univ Sci
B. 2017;18(10):906–16.
239
Chapter 27
Surgery forNeuroendocrine Tumors
oftheStomach, Small Intestine, Large
Intestine, andRectum: Techniques
andPotential Complications
HeatherC.Stuart andJaniceL.Pasieka
Gastric Neuroendocrine Tumors
• The incidence of gastric neuroendocrine tumors (G-NETs) has increased 15-fold
over the last decades due to increased utilization of upper endoscopy [1].
• Gastric NETs arise from enterochromafn-like cells (ECL) and are classied
into three types. G-NETs make up approximately 7% of GI-NETs [1, 2]
(Table27.1).
• Hypergastrinemia leads to ECL hyperplasia and promotes the formation of Type
1 and 2G-NETs, while Type 3G-NETS have normal gastrin levels.
• Elevated gastrin can occur for many reasons so thoughtful consideration of the
differential diagnosis is recommended (Table27.2).
• Type 1G-NETs are small and multifocal with high fasting serum gastrin levels
(> 150pg/ml) and high gastric pH (> 2). They develop in the setting of autoimmune atrophic gastritis which causes a decrease in the number of hydrochloric
acid (HCL) producing parietal cells in the gastric body. When pH in the stomach
rises because of lack of HCL, this stimulates normal G-cells in the antrum to
produce gastrin (Fig.27.1). In response to high levels of gastrin enterochromafn cells (ECLs) become hyperplastic and evolve into neuroendocrine tumors.
• Most type 1 NETs, especially <2cm, can be resected endoscopically with sur-
gery reserved for larger tumors. In refractory cases, antrectomy can be considered to remove gastrin-producing G-cells (Table27.1).
H. C. Stuart
Department of Surgery, University of British Columbia, Vancouver, BC, Canada
e-mail: Heather.stuart@vch.ca
J. L. Pasieka (
Department of Surgery, Cumming School of Medicine, University of Calgary,
Calgary, AB, Canada
e-mail: Janice.pasieka@ahs.ca
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_27
*)
241© The Author(s), under exclusive license to Springer Nature
242
H. C. Stuart and J. L. Pasieka
Table 27.1
Prevalence 70–80% 5–10% 10–15%
Gender Female > male Female=male Male > female
Associated
diseases
Serum gastrin Very high High Normal
Gastric pH High >4 Low <2 Normal
Tumor size <1cm/multiple < 1cm/multiple > 1cm/singular
Grade G1 G1/G2 G3
Risk of
metastasis
Treatment Endoscopic
ZES Zollinger-Ellison Syndrome, MEN 1 multiple endocrine neoplasia type 1, PPI proton-pump
inhibitors, SSA somatostatin analogs, TAE transarterial embolization, R FA radiofrequency ablation
Table 27.2
Increased gastrin causing elevated
gastric acid secretion
Gastrinoma Pernicious anemia
G cell hyperplasia Chronic atrophic gastritis
H.Pylori infection Vagotomy
Retained gastric antrum Acid suppression medications
Gastric outlet obstruction Renal impairment
Short bowel syndrome
Gastric neuroendocrine tumors
Type 1 Type 2 Type 3
Atrophic gastritis
+ anti-parietal cell
antibodies
<2% size dependent 10–20% >50%
submucosal
dissection
Surgery if >2cm
Antrectomy for
refractory tumors
Differential diagnosis of hypergastrinemia
MEN1/ZES
MEN 1 gene mutation
Chromosome 11q13
Treat ZES with PPI, SSA
Consider resection of
duodenal gastrinoma(s)
Hypochlorhydria resulting in an increase in gastrin by
the normal G-cells
None
Surgical en bloc resection
+/− chemotherapy
Lu DOTATATE PET/CT
TAE, RFA
• Unlike Type 1, Type 2 G-NETs occur in the setting of normal gastric mucosa
where they autonomously produce gastrin from a duodenal gastrinoma(s), which
stimulates the parietal cells to release HCL. This results in hyperchlorhydria
(pH<2) and the clinical presentation of Zollinger-Ellison syndrome (ZES).
• Type 2G-NETS are almost always associated with multiple endocrine neoplasia
syndrome type 1 (MEN 1). The duodenal gastrinoma(s) associated with MEN1/
ZES cause hypergastrinemia that results in gastric ECL cell hyperplasia and dysplasia, while the parietal cells respond appropriately by producing HCL lowering
gastric pH, causing ZES.However, it is the defect in the Menin protein due to the
mutation in the MEN 1 gene on chromosome 11q13, that leads to the further
development of Type 2G-NETs.
• It is hypothesized that it is the defective Menin protein in MEN 1 that allows for
this neoplastic transformation, as Type 2G-NETs are rarely seen with sporadic
gastrinomas (<1%) while found in 13–43% of MEN1/ZES patients [2–4].
27 Surgery for Neuroendocrine Tumors of the Stomach, Small Intestine, Large…
Gastrin-induced
hyperplasia
Parietal
cell
+/K+
H
AT Pasc
Acid
Histamine
ECL
cell
-ve
CCK-2R
G cell
Gastrin
243
H
R
2
Fig. 27.1 Gastrin production in the stomach. Autoimmune gastritis causes destruction of parietal
cells in the fundus and body of the stomach. The loss of parietal cells leads to hypochlorhydria
which stimulates gastrin production from G cells in the antrum. Hypergastrinemia stimulates
hyperplasia in ECL cells and over time the development of type 1 gastric NETs. (Permission
granted for use by Elsevier for reproduction)
• Patients with Type 2G-NETs should have cross-sectional imaging +/− endo-
scopic ultrasound as lymph node metastases can occur in up to 10–20% of
patients. Resection of the primary tumor is guided by the size and location.
Endoscopic resection can be appropriate for small tumors, but surgical resection
with regional lymphadenectomy should be considered for large or higher
risk tumors.
• Control of ZES and gastrin reduction can usually be achieved with proton-pump
inhibitors (PPIs) and somatostatin analogs (SSA) and are important for symptom
control and prevention of gastrointestinal bleeding. Consideration of resection of
the duodenal gastrinoma is sometimes indicated in medical refractory cases
[1–3, 5] (Table27.1).
• Type 3G-NETs have normal gastrin and normal gastric pH.Patients, often male,
present asymptomatically or with weight loss and abdominal pain. These tumors
have an aggressive tumor biology and over 50% of patients present with nodal
and/or liver metastases [6]. Patients should undergo full staging investigations
with cross-sectional and functional imaging.