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In 1996 a consensus workshop on the preoperative diagnosis and surgical treatment of neuroendocrine tumor disease took place in Berlin. Although there was a consensus on the diagnosis and surgical treatment by world experts in neuroendocrine surgery in some areas, it became clear that certain management policies vary among centers. In large part, diverging policies reflect a lack of controlled studies. This paper summarizes the various opinions brought forward during this conference and emphasizes consensus approaches for the diagnosis and therapy of neuroendocrine neoplasms.

Small doses (30 U) of secretin were injected directly into the splenic, gastroduodenal, hepatic, and superior mesenteric arteries of 13 patients with Zollinger-Ellison syndrome who were undergoing angiography to localize gastrin-secreting tumors of the islet cells. Blood samples from the right hepatic vein and a peripheral vein were drawn before and 30, 60, 120, and 210 seconds after each intraarterial secretin (IAS) injection. A 50% rise in gastrin level in the 30-second sample from the hepatic vein localized the gastrinoma to the head, body, or tail of the pancreas, depending on the artery into which secretion was injected. IAS results were positive in seven of 13 patients (54%); selective angiography was positive in five of 13 (38%); and the combined study, selective angiography with IAS injection, was positive in 10 of 13 (77%). Portal venous sampling was positive in six of 13 (46%). Selective IAS injection, combined with angiography, is the most sensitive study for localizing gastrinomas and avoids percutaneous transhepatic catheterization for portal venous sampling.

To determine whether newly described bombesin (BN) receptor antagonists distinguish subtypes of BN receptors, we investigated their abilities to interact with BN receptors on esophageal muscle or pancreatic acinar tissue. For inhibition of binding of 125I-[Tyr4]BN to rat pancreatic tissue, the relative potencies were [D-Phe6]BN-(6-13)ethyl ester (5 nM) greater than Ac-gastrin-releasing peptide (GRP)-(20-26)ethyl ester (17 nM) greater than [D-Phe6,Cpa,14, psi 13-14]BN-(6-14) (40 nM) greater than [Leu14, psi 13-14]BN (0.43 microM) greater than [Tyr4,D-Phe12]BN = [D-Pro4, D-Trp7,9,10]substance P (SP)-4-11 (13 microM) greater than [Leu14, psi 9,10]BN (32 microM) greater than [D-Arg1,D-Trp7,9,Leu11]SP (70 microM). Each antagonist also inhibited binding of 125I-[Tyr4]BN or 125I-Bolton-Hunter-neuromedin B to rat esophageal tissue, and the potency of each antagonist for each tracer was similar. In comparison to rat pancreas, [D-Phe6]BN-(6-13)ethyl ester, Ac-GRP-(20-26)ethyl ester, [D-Phe6,Cpa14, psi 13-14]BN-(6-14), [Leu14, psi 13-14]BN, and [Leu14, psi 9,10]BN had a 10,000-, 2,940-, 1,425-, 122-, and 4-fold, respectively, weaker affinity for BN receptors. In contrast [Tyr4,D-Phe12]BN, [D-Pro4,D-Trp7,9,10]SP-4-11, and [D-Arg1,D-Trp7,9,Leu11]SP had a 4-, 4-, and 9-fold, respectively, higher affinity compared with pancreatic tissue. Comparison of the activity of each peptide at inhibiting the ability of equipotent concentrations of BN or neuromedin B to stimulate contraction of rat esophageal muscle demonstrated that each peptide had the same relative potencies as for inhibiting binding.(ABSTRACT TRUNCATED AT 250 WORDS)

In this prospective study, magnetic resonance (MR) imaging was used to localize gastrinoma in 24 patients with Zollinger-Ellison syndrome. The results were confirmed by means of either surgery or percutaneous liver biopsy and compared with results of computed tomographic (CT) scanning, selective abdominal angiography, and abdominal ultrasound (US). For primary extrahepatic gastrinoma (intra-or extrapancreatic), MR imaging had a sensitivity of 20% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 11%. For metastatic gastrinoma in the liver, MR imaging had a sensitivity of 43% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 81%. The ability of MR imaging to depict extrahepatic gastrinomas was directly related to tumor size; no tumors smaller than 1 cm were detected, and 50% of tumors 3 cm or larger were detected. MR imaging was as effective as abdominal US but less effective than either CT scanning or selective abdominal angiography for the detection of extrahepatic gastrinoma. In seven patients with hepatic gastrinoma, three gastrinomas were detected with MR imaging and with abdominal US, while five were detected with CT scanning and with selective abdominal angiography. These results indicate that, at the present time, MR imaging is generally not useful in the initial attempt to localize gastrinomas.

In the present study we examined the actions of various secretagogues on pepsinogen secretion from freshly dispersed chief cells prepared from guinea pig stomach. Chief cells were obtained by preparing dispersed gastric glands, subjecting the glands to mechanical disruption in the presence of EGTA, and fractionating the resulting mucosal cells on a Percoll density gradient. Chief cells constituted 90% of the final cell suspension and cell viability was 99%. In these cells, pepsinogen secretion was stimulated by agents whose actions are probably mediated by calcium: carbachol, cholecystokinin, and A23187. Pepsinogen secretion was also stimulated by agents whose actions are probably mediated by cAMP: secretin, vasoactive intestinal peptide, and 8-bromo-cAMP. Reducing the incubation temperature from 37 degrees to 4 degrees C or adding carbonyl cyanide m-chlorophenylhydrazone abolished secretagogue-induced pepsinogen secretion. These results indicate that freshly dispersed chief cells from guinea pig stomach are responsive to secretagogues and provide a suitable model for investigating cellular mechanisms of secretagogue-induced pepsinogen secretion.

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