Figure 56-4. Schematic depiction of data from percutaneous transhepatic portal venous sampling (PTPVS) in a patient with an

insulinoma. Insulin levels are given in microunits per milliliter. These data localize the neoplasm to the head of the pancreas.

(Adapted from Norton JA, Sigel B, Baker AR, et al. Localization of an occult insulinoma by intraoperative ultrasonography. Surgery

1985;97:381–384.)

Venous Sampling

Percutaneous transhepatic portal venous sampling (PTPVS) and arterial stimulation with venous

sampling (ASVS) are two techniques that are used exclusively for the diagnosis and localization of PENs.

In a small number of cases, CT, MRI, SRS, and EUS are unsuccessful at localizing a PEN. When

insulinoma or gastrinoma are suspected, PTPVS may help in localizing the occult neoplasm.73–77 The

technique involves placing a catheter percutaneously through the liver into the portal vein and then

sequentially sampling for hormone levels in the splenic vein, superior mesenteric vein, and portal vein,

thereby regionalizing the location of hormone production (Fig. 56-4). The overall accuracy of this test

ranges from 70% to greater than 95% depending on the number of samples obtained, the persistence of

autonomous hormone production by the tumor, and the careful handling and assaying of all samples.

ASVS involves the selective visceral arterial injection of secretin or calcium with concurrent hepatic

venous sampling for either gastrin or insulin.78,79 Gastrinoma cells are known to respond to secretin by

releasing gastrin,80,81 and insulinoma cells are known to respond to calcium by releasing insulin. The

provocative secretogogue is serially injected through an arterial catheter into at least three sites – the

splenic, gastroduodenal, and inferior pancreaticoduodenal arteries. Samples are drawn from a hepatic

vein catheter before and immediately after each injection. The arterial supply to the occult tumor can

then be deduced based on which selective secretogogue injection is followed by a large increase in

hepatic vein hormone concentration (Fig. 56-5). This technique, particularly when combined with

intraoperative ultrasonography, results in a sensitivity of greater than 90%, essentially obviating the

need for blind resection in unlocalized insulinomas.71,82 Additionally, ASVS can differentiate the 5% of

patients with nesidioblastosis from those with insulinoma.83

SURGICAL EXPLORATION

At the time of surgical exploration for PEN, a complete evaluation of the pancreas and peripancreatic

regions is performed. The body and tail of the pancreas are exposed by dividing the gastrocolic ligament

and entering the lesser sac. This portion of the pancreas can be partially elevated out of the

retroperitoneum by dividing the inferior retroperitoneal attachments to the gland. After the second

portion of the duodenum has been elevated out of the retroperitoneum by means of the Kocher

maneuver, the pancreatic head and uncinate process are palpated bimanually. The liver is carefully

assessed for evidence of metastatic disease. Potential extrapancreatic sites of tumor are evaluated in all

cases, with particular attention paid to the duodenum, splenic hilum, small intestine and its mesentery,

peripancreatic lymph nodes, and reproductive tract in women. The goals of surgical therapy for PENs

include controlling the symptoms of hormone excess, safely resecting maximal tumor mass, and

preserving maximal pancreatic parenchyma. Management strategies, including preoperative,

intraoperative, and postoperative considerations, vary for the different types of endocrine neoplasms of

the pancreas.

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Figure 56-5. Graphic depiction of the results of arterial stimulation with venous sampling (ASVS) in a patient with gastrinoma.

The rise in hepatic vein gastrin concentration (gastrin gradient) is plotted on the y-axis, and basal values are plotted on the x-axis:

1, 100% rise; 2, 200% rise; and so forth. A rise in the hepatic vein gastrin concentration observed after the injection of secretin into

the superior mesenteric artery (SMA) and gastroduodenal artery (GDA) localizes the neoplasm to the head of the pancreas or

duodenum. SPL, splenic artery. (Adapted from Thom AK, Norton JA, Doppman JL, et al. Prospective study of the use of intraarterial secretin injection and portal venous sampling to localize duodenal gastrinomas. Surgery 1992;112:1002–1028; discussion

1008–1009.)

INSULINOMA

Insulinoma is the most common functional neoplasm of the endocrine pancreas (Table 56-5). The

insulinoma syndrome is associated with the following features, known as Whipple triad84:

1. Symptoms of hypoglycemia during fasting

2. Documentation of hypoglycemia, with a serum glucose level typically below 50 mg/dL

3. Relief of hypoglycemic symptoms following administration of exogenous glucose

6 Autonomous insulin secretion in insulinomas leads to spontaneous hypoglycemia, with symptoms

that can be classified into two groups (Table 56-5). Neuroglycopenic symptoms include confusion,

seizure, obtundation, personality change, and coma. Hypoglycemia-induced symptoms, related to a

surge in catecholamine levels, include palpitations, trembling, diaphoresis, and tachycardia. In most

cases, patients consume carbohydrate-rich meals and snacks to relieve or prevent these symptoms.

Table 56-5 Insulinoma

Whipple triad is not specific for insulinoma. The differential diagnosis of adult hypoglycemia is

extensive and includes the following: reactive hypoglycemia, functional hypoglycemia associated with

gastrectomy or gastroenterostomy, nonpancreatic tumors, pleural mesothelioma, sarcoma, adrenal

carcinoma, hepatocellular carcinoma, carcinoid, hypopituitarism, chronic adrenal insufficiency,

extensive hepatic insufficiency, and surreptitious self-administration of insulin or ingestion of oral

hypoglycemic agents.

A common error made in evaluating a patient with suspected insulinoma is to begin with an oral

glucose tolerance test. Instead, insulinoma is most reliably diagnosed by means of a monitored fast (via

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