Men

The most common functional islet cell tumor in MEN 1 patients is the gastrinoma,22'27 34 MEN 1 patients account for approximately 30% of all patients with the ZES, and, even without a family history or other symptoms, all "sporadic" ZES patients should be evaluated for the possibility of MEN 1 and at least a serum calcium and prolactin level obtained.

The surgical treatment of ZES in the MEN 1 patient has remained controversial because of a previously high failure rate in curing the disease.28"31'35"39 Furthermore, with the use of omeprazole, symptoms can be controlled or completely alleviated in most patients. As a result, an operation designed to excise the primary tumor has been deferred in many centers until a pancreatic tumor has been imaged by CT or other study.31'34 There are a number of obvious drawbacks to such an approach. The first is that it ignores the potential malignancy of neuroendocrine tumors that arise in the pancreas and the duodenum. It eliminates the possibility of cure and concedes that the patient will require drug therapy for life. It also potentially subjects these patients to the development of enterochromaffin-like neuroendocrine tumors in the body of the stomach.40 It appears that MEN 1 patients, in contrast with those with sporadic gastrinoma, are genetically susceptible to the development of such tumors, and this possibility may be enhanced by the long-term use of omeprazole in the presence of high levels of serum gastrin.

A policy of delay until a tumor is imaged is based on the presumption that MEN 1 patients have such diffuse functional islet cell disease that eugastrinemia cannot be achieved without a total pancreatectomy. The evidence against this concept is that immunohistochemical staining of the MEN 1 pancreas in patients with ZES shows that the diffuse islet cell dysplasia commonly found is not the source of gastrin hypersecretion.41 Discrete tumors secrete gastrin, and most of these are in the pancreatic head and the duodenum. Furthermore, during the last decade, it has been shown that duodenal tumors are present in most MEN 1 patients and that most of these are associated with lymph node but not liver metastases.10'29'30'37'38'42"45 Complete excision of all involved foci of disease can result in eugastrinemia in most patients.14,29'44

Our policy during the past 20 years has been to attempt to cure all MEN 1 patients with ZES who do not have liver metastases at presentation. The multifaceted approach we currently use has evolved during this time and is based on our previous experience and knowledge gained during this time.

Although liver metastases are currently infrequent (<10%) in MEN 1 ZES patients at the time of diagnosis, a CT or magnetic resonance and an octreotide scan is performed to exclude their presence with reasonable certainty. These studies may also demonstrate one or more pancreatic neuroendocrine neoplasms, although it is considered insensitive in detecting small tumors. The only other localization study that we now consider useful is EUS, with attention directed primarily to the head and uncinate process.44 EUS may detect tumors as small as 0.5 cm within the pancreatic parenchyma that might not be detected intraoperatively by palpation. During the past 10 years in which this procedure has been routinely performed, duodenal tumors have also been detected, in some cases during the preliminary endoscopic visualization of the duodenum.6 However, the detection of small submucosal gastrinomas is the exception rather than the rule, and a negative duodenal evaluation in no way rules out the presence of such tumors.46

Our operative procedure is done through an upper abdominal transverse incision midway between the umbilicus and the xiphoid process. After an initial careful bimanual exploration and ultrasonography of the liver for possible occult metastases, the duodenum and pancreas are widely mobilized by extending the Kocher maneuver to the superior mesenteric vein. Small venous branches on the lateral side of the superior mesenteric vein entering the uncinate process are divided between clips so that the entire uncinate may be freed sufficiently that it can be bimanually palpated. Any palpable nodules or those identified on EUS are exposed after incising the pancreatic capsule and spreading the parenchymal tissue with a fine-tip mosquito hemostat until the capsule of the tumor has been identified. Any detectable neoplasms in the head or uncinate are enucleated. When this has been completed, the greater omentum is reflected from the transverse colon by incising and reflecting its fusion fascia, which allows entrance into the lesser omental space. The splenic flexure is mobilized caudally away from the inferior splenic pole. The retroperitoneum, from the superior mesenteric vein to the spleen, is then incised sharply just below the inferior border of the pancreas. The entire distal pancreas is then mobilized by blunt dissection. When feasible, the small pancreatic branches from the splenic vessels are isolated, clipped, and divided, freeing both the splenic artery and vein from the body and tail to preserve the spleen. In most patients, one or more neuroendocrine tumors is readily identified in either the body or tail (Fig. 81-3). In these cases, we include any lymphatics along the splenic vessels and those around the celiac axis as well. The pancreas is mobilized so that the neck can be transected just to the right of the superior mesenteric vein. The neck is then oversewn with mattress sutures after separately ligating the pancreatic duct. We prefer this technique to the use of either a stapler or cross-clamping of the neck because there is no crushed edge of tissue and the pancreatic duct can be seen and securely ligated.

FIGURE 81-3. Multiple endocrine neoplasia type 1 pancreas with islet cell tumors. Multiple neuroendocrine neoplasms are common.

After the pancreatic portions of the operation have been completed, the duodenum is carefully palpated from the pylorus to the superior mesenteric vein. A longitudinal duo-denotomy centered in the second portion of the duodenum allows excision of any palpable tumors in the anterior and medial aspects of the duodenum. However, in many cases, no tumors are palpable until the duodenotomy allows direct exposure of the mucosal surface. Both proximal and distal areas of the duodenum must be everted into the incision and the mucosa palpated circumferentially to rule out neuroendocrine tumors as small as 1 mm in diameter. Tumors that are 0.5 cm or smaller can usually be enucleated from the submucosa after an elliptical mucosal incision around the tumor. Most larger tumors should be excised with a margin of full-thickness duodenal wall. One or more small excision sites will require separate closure unless the tumor is close to the original duodenotomy. Most MEN 1 patients with ZES have one or more tumors in the first three parts of the duodenum. One of our patients who had a previous Billroth II procedure was found to have 29 separate tumors in the remaining stump and second part of the duodenum proximal to the ampulla of Vater. After local excision of the tumors distal to the ampulla of Vater, the proximal duodenum was mobilized from the pancreas and resected to a level just far enough proximal to the ampulla that it could be safely closed at that level. Most of our MEN 1 patients have had more than one duodenal gastrinoma, although they were not always apparent until after a careful search has been made. The standard duodenotomy is closed in two layers in a vertical direction in which it was performed. When one or more duodenal tumors has been found, all parapancreatic lymph nodes on both surfaces of the pancreatic head are excised as are those along the common bile duct, portal vein, and hepatic artery to the celiac axis. On completion of these procedures, a Jackson-Pratt drain is placed near the pancreatic stump and brought out in the midline above the level of the transverse incision (Fig. 81-4).

During the 17-year period from 1978 to 1995, 25 MEN 1 patients with ZES without liver metastases underwent

type 1-Zollinger-Ellison syndrome: (1) distal pancreatectomy;

(2) enucleation of neuroendocrine (NE) tumors (head, uncinate);

(3) duodenotomy, excision of NE tumors; (4) regional lymph node dissection.

type 1-Zollinger-Ellison syndrome: (1) distal pancreatectomy;

(2) enucleation of neuroendocrine (NE) tumors (head, uncinate);

(3) duodenotomy, excision of NE tumors; (4) regional lymph node dissection.

exploration with intent to "cure" their disease. The first 17 patients were reported elsewhere, with a follow-up ranging from 2 to 16 years.44 Sixty-five percent had normal basal gastrin levels, were asymptomatic, and required no drug therapy. The remaining 35% had a decrease in serum gastrin levels, symptoms, and drug requirements. With longer follow-up, the incidence of eugastrinemia has decreased to about 30% with approximately half having been symptom free for 10 years or longer and one for 25 years. Only one of our MEN 1-ZES patients (n = 44) has developed a single liver metastasis. This was recently treated by right liver lobectomy and he is currently eugastrinemic. Several other patients have been re-explored for recurrences in lymph nodes or apparently new duodenal gastrinomas. No patient has developed, as best as we can determine, either a local recurrence in either the pancreatic head or duodenum after an enucleation.

Gastrinomas were found in the duodenum in 76% of patients and in both duodenum and pancreas in 35%. Approximately half of the duodenal gastrinomas were malignant, as proven by excision of peripancreatic metastatic lymph nodes. All patients were found to have at least one microscopic neuroendocrine tumor involving the distal pancreas, two of which were gastrinomas as determined by immunohistochemical staining.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment