Exploration of the Gastrinoma Triangle
Jeffrey A. Norton
Introduction
Gastrin-secreting neoplasms were first described by Zollinger and Ellison in 1955.
These unusual neoplasms can be either benign or malignant. The diagnosis of the Zollinger-Ellison syndrome depends on an increased fasting serum gastrin concentra- tion (>100pg/ml), increased basal acid output (>10mEq/l), and an abnormal secretin test (increase of >200pg/ml in serum gastrin concentration after 2U/kg of intravenous secretin). While originally believed to be primarily neoplasms of the pancreas, today we know that most “curable” gastrinomas arise in the wall of the proximal duodenum.
Gastrinomas can occur as sporadic (non-familial) neoplasms or as one of the manifesta- tions of multiple endocrine neoplasia-1 syndrome (MEN-1); MEN-1 includes neoplasms of the pituitary and parathyroids, neuroendocrine neoplasms of the duodenum and pancreas, and carcinoid neoplasms of the foregut and midgut.
Indications and Contraindications
Indications
■Zollinger-Ellison syndrome without evidence of unresectable metastatic disease
Contraindications
■“Falsely” increased serum gastrin concentration secondary to:
– Pernicious anemia
– Medications that inhibit acid production, e.g., H
2receptor inhibitors, proton pump inhibitors
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G-cell hyperplasia
Preoperative Investigations and Preparation for the Procedure
History: – Peptic ulcer disease (PUD), watery diarrhea, gastroesophageal reflux disease (GERD) and possibly a family history of the associated endocrinopathies, primary hyperparathyroidism, prolactinoma, insulinoma, Cushing’s syndrome, carcinoid tumors or carcinoid syndrome.
Clinical evaluation: – Upper gastrointestinal endoscopy with/without endoscopic ultrasonography.
Laboratory tests: – Fasting serum concentration of gastrin, basal acid output off all acid secretory inhibitors for at least 3–7days, secretin test.
– When indicated, serum concentrations of intact PTH, total or ionized calcium, prolactin, fasting glucose, pancreatic poly- peptide, chromogranin A, and serotonin, 24-h urine excretion of free cortisol, and if indicated 5-hydroxyindole acetic acid (HIAA).
Medical – Appropriately high doses of proton pump inhibitor to stop acid management: hypersecretion and control PUD, GERD, and diarrhea. Often up to 80–120mg pantoprazole two or three times a day or 20–40mg of omeprazole. Pantoprazole can be given at the same dose either intravenously or orally and is indicated in the perioperative period.
Radiologic – CT or MR to image pancreas, duodenum, and liver, and to localization studies: exclude liver metastases.
– Somatostatin receptor scintigraphy, the so-called Octreo-Scan, is the best imaging study which images 90% of gastrinomas;
although it will detect distant metastases, it frequently misses the small duodenal gastrinomas.
– Endoscopic ultrasonography can detect small tumors within
the pancreas, but may miss duodenal gastrinomas.
Procedure: Exploration of the Gastrinoma Triangle
STEP 1 Exposure of the pancreas
The gastrinoma triangle is defined as the region that includes the head of the pancreas and the duodenum in which over 85% of gastrinomas arise.
Most gastrinomas arise in the proximal duodenum, especially the occult neoplasms, but gastrinomas also occur in the pancreatic head, especially in association with the multiple endocrine neoplasia (MEN) syndrome.
Several “primary” lymph node gastrinomas have been reported to occur within the gastrinoma triangle with long-term cure after lymphadenectomy alone.
Sporadic gastrinomas are usually solitary and often (~50%) metastatic to lymph nodes.
In the familial MEN-1 setting, gastrinomas are usually multiple within the duodenum and pancreas and can metastasize as well. In all instances, the duodenal gastrinomas are most frequently missed, and thus opening the duodenum for transmural palpation is critical for their operative detection.
Access is best obtained via a bilateral subcostal division of the falciform ligament, and installation of a mechanical retractor (we prefer the Thompson retractor).
Next, the surgeon opens the lesser sac widely by dividing the gastrocolic ligament
from the hepatic flexure to the splenic flexure, thereby exposing the entire neck, body,
and tail of the pancreas. The tissue along the inferior border of the pancreas is opened
to allow the surgeon to palpate tumors within the pancreas between the thumb and fore-
fingers.
STEP 2 Extended Kocher maneuver
The next maneuver involves an extended Kocher maneuver by mobilizing the entire right colon and the proximal as well as the distal duodenum; this allows palpation of the head of the pancreas and, equally important, the wall of the duodenum.
Intraoperative ultrasonography is performed in a systematic fashion with a near- field, high-resolution transducer. Small neoplasms within the pancreas are identified by their sonolucent nature compared to the more echo-dense pancreas. Although intra- operative ultrasonography of the duodenum is also performed, duodenal gastrinomas, if small, are often missed by this procedure.
Finally, the liver is also evaluated for metastases.
STEP 3 Lymphadenectomy of gastrinoma triangle
All lymph nodes within the gastrinoma triangle are excised in a systematic fashion for pathologic analysis starting with a lymphadenectomy of the hepatoduodenal ligament.
Lymph nodes from the porta hepatis to the duodenum are excised, labeled, and sent for pathologic analysis, as are nodes from both the anterior and posterior border of the head of the pancreas.
Neuroendocrine neoplasms identified within the head of the pancreas are enucleated
with palpation or via ultrasonographic control. When a tumor is enucleated from the
head of the pancreas, 5ml of fibrin glue is applied to the site of enucleation, and a closed
suction drain is placed nearby.
STEP 4 Opening the duodenum to identify and remove duodenal gastrinomas (A, B)
If the location of the tumor is not known, a duodenotomy is essential, because duodenal gastrinomas often may only become detectable by this method. The surgeon can palpate the tumor within the wall of the duodenum between the index finger within the
duodenal lumen and the thumb on the serosal side.
If the duodenal tumor has been identified, the duodenal incision used to remove the duodenal gastrinoma can be used to explore the remainder of the duodenum.
Because the neoplasm arises from the submucosa and can invade the mucosa, the gastrinoma should be excised via a full thickness specimen with a rim of normal duodenal wall around the tumor. In patients with MEN-1, multiple duodenal neoplasms may be present, and the surgeon must carefully palpate and inspect the remainder of the inner surface of the duodenum after it is open to exclude the presence of other
neoplasms. Do not confuse the ampulla of Vater or the entrace of the minor pancreatic
duct with a gastrinoma. After excising a duodenal gastrinoma, the duodenum is closed
with a single-layer, full-thickness, monofilament absorbable suture in a transverse direc-
tion so as not to narrow the lumen. If a long duodenotomy is necessary, a longitudinal
closure is performed. A periduodenal or peripancreatic closed suction drain is left.
Postoperative Tests
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The patient is kept on the same dose of proton pump inhibitor postoperatively for 1–3months as the preoperative dose; parietal cell hypertrophy as occurs with Zollinger-Ellison syndrome may take approximately 3–6months to involute.
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A postoperative fasting serum gastrin measurement should be compared to the preoperative level. For selected patients, fasting serum gastrin, basal acid output, and secretin stimulated gastrin are not done 3–6months postoperatively.
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On occasion, we often obtain a CT with oral contrast on postoperative day 5 to rule out a duodenal leak and a peripancreatic fluid collection.
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The drain is removed when the patient is eating a regular diet, drainage fluid is low in amylase activity, and the volume is less than 20ml/day for 2 consecutive days.
We may discharge the patient with a drain in place to be removed later.
Local Postoperative Complications
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Short term:
– Duodenal leak
– Pancreatic leak and/or abscess – Pancreatic fistula
– Intra-abdominal bleeding – Pancreatitis
– Duodenal ulcer bleeding
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Long term:
– Duodenal stricture
– Recurrent hypergastrinemia
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Other manifestations of MEN-1 (hypothalamic, parathyroid, carcinoid)
Tricks of the Senior Surgeon
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Do not cut corners; do the same operation every time regardless of the preopera- tive localization studies.
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Develop a dedicated team approach; an ultrasonographer willing to take the time and effort to find the gastrinoma is crucial.
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Beware of the ampulla and the pancreatic duct on the medial wall of the duodenum as these can feel like nodules and have been mistaken for a duodenal gastrinoma. I remove the gallbladder and pass a catheter through the cystic duct into the duodenum if there is any question about the location of ampulla. On occasion, I have given secretin intraoperatively to stimulate pancreatic secretion if there is a question that I may be identifying the pancreatic duct orifice.
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Exclude MEN-1 preoperatively by screening for other endocrinopathies and questioning family history.
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Remember that patients with both Zollinger-Ellison syndrome and MEN-1 generally have multiple pancreatic and duodenal neuroendocrine neoplasms, and thus cure-rate is very low. If a patient also has primary hyperparathyroidism, do the parathyroid operation first as this may ameliorate the manifestations of Zollinger-Ellison syndrome.
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