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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_987_Библиотеки_им_академика_М_И_Перельмана.pdf
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D. Hubbs and T. Fahey
Well-Differentiated Neuroendocrine Tumors
• Include pancreatic islet cell tumors and gastrointestinal carcinoid tumors.
• Typically slow-growing, and surgical intervention can often be curative.
Poorly Differentiated Neuroendocrine Tumors
• Have fewer or more poorly dened neuroendocrine features.
• Subclassied as small cell (~40%) and large cell (~60%).
• All PD-NETs are G3 by denition.
• Not associated with functional secretory syndromes.
• Aggressive tumors with early distant spread and a poor prognosis.
• Majority of patients have metastatic disease at diagnosis.
Pancreatic Neuroendocrine Tumors [4–8]
General
• Pancreatic neuroendocrine tumors (pNETs) are rare tumors with an incidence of
<1 case per 100,000 people per year.
• Account for <3% of primary pancreatic neoplasms.
• Genetic predisposition to pancreatic NETs in MEN1 and Von Hippel-Lindau
disease.
• All evaluations should include a thorough history and physical to evaluate for
syndromic ndings.
• Functional pNETs are diagnosed biochemically.
• The majority of pNETs are not associated with pathologic hormonal secretion
and are considered non-functional.
Insulinomas
• Pancreatic beta-cell origin.
• Syndromic Presentation: episodic symptoms of hypoglycemia such as weakness,
sweating, anxiety, confusion, and loss of consciousness.
• Whipple’s Triad: Symptoms of hypoglycemia, hypoglycemia (glucose <50mg/
dL) at the time of symptoms, and symptoms improve with increased glucose.
• Biochemical Evaluation: 72-h fast protocol with labs including glucose, insulin,
proinsulin, C-peptide, and screening for oral hypoglycemic agents.
25 Evaluation andDiagnosis ofPancreatic andGastrointestinal Neuroendocrine Tumors
• Factitious hypoglycemia can be due to exogenous administration of insulin.
These patients will have suppressed proinsulin and C-peptide.
223
Gastrinoma
• Syndromic Presentation (Zollinger-Ellison Syndrome): refractory peptic ulcer
disease and diarrhea.
• Upper endoscopy should be performed to evaluate ulcers and examine for intraluminal tumor.
• Biochemical Evaluation: Stop PPIs, fasting gastrin >1000pg/mL, and gastric pH
<2 is diagnostic. Secretin stimulation test used if indeterminate.
• Genetic testing recommended as 20% of patients have MEN1.
• Screen for MEN1 with serum prolactin, parathyroid hormone, and calcium levels.
• Gastrinomas are the most common pNET in MEN1.
• Majority of tumors are located in the Gastrinoma Triangle:
– Junction of cystic duct and common bile duct.
– Junction second and third portion duodenum.
– Junction of neck and body of pancreas.
Glucagonoma
• Pancreatic alpha-cell origin.
• 4 Ds of glucagonoma syndromic presentation
– Diabetes (Glucose intolerance).
– Dermatitis (Necrolytic migratory erythema).
– Depression (Neuropsychiatric symptoms).
– Deep vein thrombosis or pulmonary embolism.
• Biochemical Evaluation: fasting plasma glucagon (>500pg/mL) with normal or
elevated blood glucose.
Somatostatinoma
• Pancreatic delta-cell origin.
• Syndromic Presentation: Cholelithiasis, steatorrhea, glucose intolerance.
• Biochemical Evaluation: plasma somatostatin 3× the upper limit of normal.
• True syndromic presentation is uncommon, and most are identied after they
become large enough to cause mass effect with pain or obstructive symptoms.
224
D. Hubbs and T. Fahey
VIPoma
• Syndromic Presentation (WDHA Syndrome): Watery diarrhea (>700mL/day),
hypokalemia, and achlorhydria.
• Biochemical Evaluation: VIP (>75pg/mL) and BMP.
Non-functional pNET
• Clinical Presentation: Abdominal pain, nausea, weight loss.
• Tumors are typically identied incidentally when undergoing workup for nonspecic abdominal complaints.
• Biochemical Evaluation: Chromogranin A and pancreatic polypeptide.
• Diagnosis by endoscopic ultrasound with ne needle aspiration.
Distribution ofpNETs [6]
• The most common location of a pNET varies by its subtype (Fig.25.1).
• Gastrinoma—Head.
• Somatostatinoma—Head.
• Non-functional—Head.
• Insulinoma—Equal distribution.
• VIPoma—Body and tail.
• Glucagonoma—Tail.
pNET Localization
• Multiple diagnostic modalities are utilized for pNET localization and staging.
• Localization typically proceeds from least invasive to most invasive modalities.
Fig. 25.1 Letters
representing pNETs
arranged in their most
common pancreatic
distribution
25 Evaluation andDiagnosis ofPancreatic andGastrointestinal Neuroendocrine Tumors
225
• Triphasic contrast-enhanced CT: Arterial enhancement with portal venous washout, initial imaging study of choice (Fig.25.2).
• Contrast-enhanced MRI: More sensitive than CT for detection of liver metastases. Often ordered if CT ndings are indeterminate (Fig.25.2).
• Somatostatin receptor functional imaging: useful for the evaluation of primary
and metastatic NETs. Gallium-68 DOTATATE PET/CT is the functional imaging
study of choice due to its high sensitivity for WD-NETs. PD-NETs are less likely
to express somatostatin receptors and thus less likely to be detected.
• Endoscopic ultrasonography: useful for evaluation of the pancreas when less
invasive methods have failed to localize a tumor; can also provide ne needle
aspiration for pathologic diagnosis.
• Selective arterial calcium stimulation with hepatic venous sampling: used for
tumor localization when all other modalities have failed to localize a suspected
pNET.Also used for determination of insulinoma vs islet-cell hypertrophy.
Gastrointestinal Neuroendocrine Tumors [1, 2, 9, 10]
General
• WD-NETs of the gastrointestinal tract are often referred to as carcinoid tumors
or neuroendocrine neoplasms.
• These tumors have enterochromafn cell origins.
• Typically less aggressive than gastrointestinal adenocarcinoma.
• Most tumors are asymptomatic and found incidentally.
• Mechanical symptoms due to mass effect, obstruction, or invasion.
• Functional symptoms due to increased systemic serotonin and vasoactive
peptides.
ab
Fig. 25.2 CT (A) and MRI (B) demonstrating well-differentiated neuroendocrine tumors in the
body and tail of the pancreas
226
D. Hubbs and T. Fahey
Diagnostic Evaluation
• Gastrointestinal NETs are often identied incidentally on cross-sectional imaging or endoscopy.
• Vague symptoms such as abdominal pain or carcinoid syndrome symptoms may
prompt diagnostic evaluation with imaging and endoscopy.
• Gastrointestinal masses identied on imaging often undergo endoscopic evaluation (EGD, push enteroscopy, colonoscopy) and biopsy.
• Tissue from biopsy used for histologic diagnosis.
Carcinoid Syndrome
• Syndromic presentation: Diarrhea and ushing.
• Typically, symptoms start after liver metastasis from primary tumor in the jejunum, ileum, or proximal colon.
• Symptoms are due to systemic effects of serotonin and other vasoactive tumor
secretions.
• 24h urinary 5-HIAA: Test of choice for carcinoid syndrome.
• CT and MRI are used to evaluate the burden of liver disease and 68 DOTATATE
PET/CT can be used to identify small primary tumors.
• Carcinoid Crisis: hemodynamic instability due to increased tumor secretions;
treated with octreotide.
• Carcinoid heart disease: Build up of brous tissue in the heart and great vessels
leading to right-sided heart failure. Diagnosed with an echocardiogram and managed medically, or surgically with cardiac valve replacement.
Gastric Neuroendocrine Tumors
• Type 1: Most common, associated with chronic atrophic gastritis, multiple
tumors <1cm in size, typically slow-growing and benign.
• Type 2: Associated with concurrent gastrinoma, also usually slow-growing.
• Type 3: Larger, more aggressive tumors, not associated with atrophic gastritis or
concurrent gastrinoma. Frequent metastatic disease at the time of diagnosis.
Intestinal Neuroendocrine Tumors
• Small Intestine: Abdominal pain due to obstruction or intussusception, tumors
are most commonly found in the ileum.
25 Evaluation andDiagnosis ofPancreatic andGastrointestinal Neuroendocrine Tumors
227
• Appendix: WD-NETs are the most common appendiceal tumors, most are identied incidentally on nal pathology after appendectomy.
• Colon: tumors are typically asymptomatic until they are very large, thus usually
identied in older patients.
• Rectum: Now the most common site where gastrointestinal NETs are identied
due to incidental discovery on screening colonoscopies.
References
1. Fernandez CJ, etal. Gastroenteropancreatic neuroendocrine neoplasms: a clinical snapshot.
World J Gastrointest Surg. 2021;13(3):231–55.
2. Rindi G, etal. Overview of the 2022 WHO classication of neuroendocrine neoplasms. Endocr
Pathol. 2022;33(1):115–54.
3. Walter T, et al. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas:
are they really heterogeneous? Insights from the FFCD-GTE national cohort. Eur J Cancer.
2017;79:158–65.
4. Falconi M, etal. ENETS consensus guidelines update for the Management of Patients with
functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine
tumors. Neuroendocrinology. 2016;103(2):153–71.
5. Okabayashi T, et al. Diagnosis and management of insulinoma. World J Gastroenterol.
2013;19(6):829–37.
6. O'Grady HL, Conlon KC. Pancreatic neuroendocrine tumours. Eur J Surg Oncol.
2008;34(3):324–32.
7. Thompson SM, etal. Selective arterial calcium stimulation with hepatic venous sampling differentiates Insulinoma from nesidioblastosis. J Clin Endocrinol Metab. 2015;100(11):4189–97.
8. Halfdanarson TR, etal. The north American neuroendocrine tumor society consensus guidelines for surveillance and medical Management of Pancreatic Neuroendocrine Tumors.
Pancreas. 2020;49(7):863–81.
9. Dakin GF, etal. Presentation, treatment, and outcome of type 1 gastric carcinoid tumors. J
Surg Oncol. 2006;93(5):368–72.
10. Modlin IM, etal. A three-decade analysis of 3,911 small intestinal neuroendocrine tumors: the
rapid pace of no progress. Am J Gastroenterol. 2007;102(7):1464–73.
Chapter 26
Surgery forPancreatic Neuroendocrine
Tumors: Techniques andPotential
Complications
KevinC.McGann andColleenM.Kiernan
Introduction
• Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon tumors
that originate from neuroendocrine cells.
• The pancreas has four basic endocrine cell types which are located in discrete
regions and secrete hormones that lead to characteristic clinical syndromes:
alpha (glucagon), beta (insulin), D cells (D1: somatostatin, D2: VIP), and G cells
(gastrin).
• While ultimately nuanced by the specic tumor type, size, grade, stage, location,
and proximity to critical structures, the mainstay treatment for PNETs is surgery.
Pancreas Anatomy andSurgical Planning
• Five anatomical sections comprise the pancreas. The head and uncinate process
are supplied from the superior and inferior pancreaticoduodenal arteries (via the
gastroduodenal and superior mesenteric arteries, respectively). The neck, body,
and tail are fed by the splenic arterial system. Venous anatomy mirrors the arterial system (Fig.26.1) [1].
• Lymphatic drainage can be simplied into regional quadrants, corresponding to
the left and right superior and inferior pancreas. The left side of the pancreas
drains toward the gastrosplenic omental nodes superiorly and splenic hilum
K. C. McGann · C. M. Kiernan (*)
Department of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical
Center, Nashville, TN, USA
e-mail: kevin.mcgann@vumc.org; colleen.m.kiernan@vumc.org
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_26
229© The Author(s), under exclusive license to Springer Nature
230
Fig. 26.1 Arterial anatomy of the pancreas. (Adapted from www.netterimages.com/Image
ID 4416)
K. C. McGann and C. M. Kiernan
nodes inferiorly. The right side of the pancreas drains toward the gastroduodenal
nodes superiorly and the infrapancreatic nodes inferiorly (Fig.26.2) [1].
• Embryologically, the pancreas originates as dorsal and ventral buds, which nor-
mally fuse to form main and accessory ducts. The main pancreatic and common
bile duct meet at the ampulla of Vater and drain into the duodenum via the major
papilla. The accessory duct drains proximally via a minor papilla. Failed fusion
causes pancreas divisum [1].
• Imaging studies dene the region and extent of disease, and taken in the larger
context of pancreas anatomy, inform discussions on surgical planning and
approach to resection [2].
• When a PNET is suspected, localization of the tumor should rst be performed.
CT and MRI are mainstay imaging modalities, as PNETs are usually hypervascular and well delineated by these studies. Adjunct studies may include endoscopic ultrasound, somatostatin receptor scintigraphy (SRS; except insulinomas,
as most PNETs express somatostatin receptors), and angiography with or without pharmacologic stimulation [3].
• Because of the limited localization data provided by SRS, hybrid single-photon
emission CT/CT imaging (SPEC/CT) is being increasingly used due to its
enhanced ability for anatomic localization [1].
• Preoperative workup also must evaluate for metastatic disease, which most com-
monly occurs in the peripancreatic lymph nodes and liver. A multidisciplinary
26 Surgery for Pancreatic Neuroendocrine Tumors: Techniques and Potential…
Fig. 26.2 Lymphatic drainage of the pancreas. (Adapted from Strasberg SM, Drebin JA, Linehan
D: Radical antegrade modular pancreatosplenectomy. Surgery 133:521–527, 2003)
231
treatment plan for metastatic PNETs to the liver may ultimately include hepatic
resection, liver-directed therapy, and even transplantation.
• While not intended to be comprehensive in nature, the remainder of this chapter
serves to outline a framework for the surgical approach to non-functional PNET
(NF-PNET) >2 cm in size and functional PNETs by individual tumor type.
Treatment of small, nonfunctional PNETs continues to be heavily debated and is
beyond the scope of this text.
Surgical Techniques forPNETs
There are several surgical approaches to PNETs, some of which will be outlined
here. When discussing the operative management of these tumors, consideration of
the malignant potential is paramount and determines whether tumors can be
removed in isolation (e.g., enucleation) or formal surgical resection (distal pancreatectomy, pancreatoduodenectomy) with lymph node removal should be performed
[4]. The basic approaches to common techniques will be outlined below and subsequently applied to an overview discussion of appropriate surgical management by
specic PNET type.
232
K. C. McGann and C. M. Kiernan
Enucleation [1, 4, 5]
Applications
• Laparoscopic or open approach.
• May require intraoperative ultrasound.
• Appropriate for well-dened tumors that are likely benign, small (<2cm), not
adjacent to pancreatic/bile ducts or vasculature, and without evident nodal invasion or metastasis.
Technical Overview
• Intraoperative ultrasound to determine the boundaries of the tumor and no ductal
involvement.
• Parenchymal incision directly over the tumor.
• Dissection right around the tumor capsule is performed using blunt and judicious
electrocautery (often with bipolar forceps).
• Stay or retraction sutures may aid exposure, elevating tumor from the surround-
ing pancreas.
• Careful dissection and attention not to injure the pancreatic ductal system is
paramount.
• Hemostasis is ensured after enucleation using electrocautery and suture as
necessary.
• A gravity drain is left at the resection bed.
Pancreatoduodenectomy (Whipple Procedure) [1, 2]
Applications
• Typically performed open.
• Formal anatomic resection.
• Associated with signicant morbidity and complications, therefore indicated for
larger tumors located in the head, uncinate process, and neck that are not amenable to more conservative treatment approaches.
Technical Overview
• Visual inspection for gross metastatic disease.
• The Kocher maneuver is performed to mobilize the duodenum and head of pan-
creas and expose the infrahepatic IVC to the level of the left renal vein.
Mobilization should extend to the left lateral aspect of the aorta.
• The gastrocolic ligament is divided for entry into the lesser sac. The SMV is dis-
sected, and the pancreatic head is then mobilized.