Edward Passaro

The gastrinoma triangle: operative implications

Operative experience with 45 gastrinoma patients has led to the identification of an anatomic area where occult tumors can be discovered and where excision of these tumors had led to apparent cure. Of 36 patients with histologically confirmed gastrinomas, 27 patients (75 percent) had obvious and 9 patients (25 percent) had occult tumors. All nine occult lesions were found within an anatomic triangle defined by the junction of the cystic and common bile ducts superiorly, the junction of the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially. Although occult tumors from three patients (in the lymph nodes in two patients and in the duodenum in one patient) were removed primarily for histologic diagnosis, postoperative serum gastrin levels have remained within the normal range (follow-up of 86 to 99 months). Two patients had excision of the tumor with intent to cure. One patient with a solitary duodenal tumor was apparently cured but committed suicide 3 months postoperatively. The other patient had both obvious primary and occult metastatic tumors within the triangle and was eugastrinemic 9 months after excision. In all patients in whom tumor was found, it was locally excised, and no patient was subjected to radical pancreatic resection. There were no postoperative complications related to tumor removal. An aggressive approach towards curative tumor excision is now advocated for all gastrinoma patients who are suitable operative risks and have no evidence preoperatively of liver metastases or the multiple endocrine neoplasm-type I syndrome.

Rapid appearance of intraventricularly administered neuropeptides in the peripheral circulation

125I-Labeled cholecystokinin octapeptide ([125I]CCK-OP) diffuses rapidly by a non-carrier-mediated mechanism into the peripheral blood following injection into the lateral ventricle of a rabbit. In contrast, no [125I]CCK-OP was observed in the CSF following intravenous injection. This unidirectional free transport mechanism from CSF to blood may apply to other neuropeptides as well.

Human islet isolation in 104 consecutive cases : factors affecting isolation success

One of the major steps toward successful islet transplantation for the treatment of type diabetes is to obtain islets of sufficient number and viability. Using a standardized method of isolating islets, the goal of this study was to analyze the factors influencing the outcome of islet isolation. A total of 104 cadaveric human pancreata were processed for islets by the same team. Data from the islet-processing charts were reviewed retrospectively. The two endpoints were the recovery of islets, viable after 2 days of culture (group V = viable, group NV = nonviable) and the islet yield. Viable islets were recovered in 61% of cases (n = 63). Minimal blood glucose recorded during hospitalization was very significantly lower in group V (124 +/- 5 vs. 148 +/- 9, P = 0.01). Lack of significant medical history in the donor was associated with better viability as compared with various donor predispositions (chi-2 4.21, P = 0.04). Cold ischemia time (8.1 +/- 0.5 hr in group V vs. 9.8 +/- 0.9 hr in group NV, P = 0.07) and collagenase lot (5 lots tested, chi-2 13.1, P = 0.01) also affected the recovery of viable islets. Hospital time was shorter in group V (65.3 +/- 6.8 vs. 80.9 +/- 17.9 hr, P = 0.35). Multivariate logistic regression analyses of viable islet recovery identified minimal blood glucose (P = 0.03) and collagenase lot (P = 0.06) as the most significant risk factors. However, the best multivariate predictive model--which includes blood glucose, collagenase lot, donor age and surgical procurement team--correctly predicted 66.2% of cases only. Multivariate analysis of final islet yield designed hospitalization length, cardiorespiratory arrest, surgical procurement team, and collagenase lot as the best predictors. These data obtained in a large series of pancreata emphasized several donor and technical factors that should target the attention of islet transplant researchers in order to improve islet yield and viability.

Failure of histamine H2-receptor antagonist therapy in Zollinger-Ellison syndrome

Review of a 5 year clinical experience with the histamine H2-receptor antagonists metiamide, cimetidine, and ranitidine in 20 patients with Zollinger-Ellison syndrome disclosed a treatment failure rate of 50 percent. The criterion for failure was hemorrhage in four patients, obstruction followed by hemorrhage in one patient, perforation in one, and intractable pain in four. Nine of the 10 patients in whom treatment failed required total gastrectomy for control of complications; the 10th patient refused operation. Retrospective analysis identified hepatic metastases, the multiple endocrine adenomatosis-type I syndrome, refractory diarrhea, and breaks in the medication schedule as being more common in the treatment failure group, but these trends were not statistically significant in our small series of patients. Nonhealing or recurrent ulcers were found in 90 percent of the patients in whom drug therapy failed and in only 10 percent of those patients in whom therapy was successful (p less than 0.01). There were no differences related to age, sex, duration of symptoms, previous gastric operation, ulcer location, presence of diarrhea, or amount of drug prescribed. Basal and peak acid outputs, basal serum gastrin levels, and response to secretin challenge were also nondiscriminatory. The degree of acid inhibition in response to cimetidine was highly variable from one patient to another and on repeat testing in individual patients, and there was no correlation between acid secretory inhibition and clinical course. When severe complications occurred, reinstituting H2-receptor antagonist therapy or increasing the dose did not avert the need for total gastrectomy. Patients refractory to drug treatment who have persistent or recurrent ulcers should be managed with prompt total gastrectomy to prevent life-threatening complications.

The amylase profile: a discriminant in biliary and pancreatic disease.

Serial serum amylase determinations were made in 85 consecutive patients who presented with an initially elevated value. In 35 patients (Group A), the clinical findings were consistent with biliary tract disease. All underwent cholecystectomy for documented cholelithiasis within a week of diagnosis, and 23 percent had choledocholithiasis as well. Fifty patients (Group B) presented with a first episode of acute alcoholic pancreatitis. An amylase profile, consisting of initial and final values and the daily rate of change, was significantly different between the two groups. The initial serum amylase value was higher in Group A patients and decreased more rapidly to a lower value than in Group B patients. We conclude that both the initial value and pattern of serum amylase decay distinguish the hyperamylasemia of biliary tract disease from that of alcoholic pancreatitis.

Biologic behavior of sporadic gastrinoma located to the right and left of the superior mesenteric artery

Among a series of 107 closely followed patients with gastrinoma, 60 patients with sporadic type tumors were identified and evaluated. There were 44 patients (73%) with tumors to the right of the superior mesenteric artery (SMA). Of these, 16 (36%) had extrapancreatic tumors, 28 (64%) had tumor within lymph nodes, and 9 (20%) had multiple tumors. In this group of patients, there were 19 (43%) cures, and only 9 (20%) patients had hepatic metastases. In contrast, in 16 patients (27%) with tumors to the left of the SMA, there were no extrapancreatic tumors, only 3 patients (19%) had tumor within lymph nodes, and 7 (44%) had multiple tumors. In this group, there was only one cure (6%), and nine (56%) patients had hepatic metastases. These findings suggest two distinct populations of sporadic gastrinoma, one to the right (gastrinoma triangle) and the other to the left (outside triangle) of the SMA, which appear to have different biologic behaviors. These differences may reflect divergent etiologies for these two groups of tumors.

Diagnostic and prognostic molecular markersin cancer

A healthy 28-year-old white woman presented forprenatal care at 25 weeks gestation. Abdominal ultrasound examination showed dilated loops of fetal bowel and increased echogenicity throughout the fetal abdomen, with intra-abdominal calcifications. These findings were interpreted as showing the presence of a small bowel obstruction and were consistent with cystic fibrosis. Samples of both parents blood were sent for genetic analysis, and each revealed deletions of three base pairs on chromosome 7q31. Chorionic villus biopsy was performed, and the fetal DNA exhibited the same mutation. The diagnosis of cystic fibrosis was confirmed prenatally.

Influence of cisternal pressure on passage of neuropeptides from the cerebrospinal fluid into the peripheral circulation

Passage of neuropeptides from the cerebrospinal fluid to circulation depends upon cisternal pressure. When cisternal collecting pressure was kept at -20 cm, plasma levels of gastrin-17 and somatostatin-14 remained at basal values despite perfusion of high doses of the peptides into the cerebro-ventricular system. Progressive reduction of this pressure above -15 cm results in a progressive rise of the peripheral concentration of the peptides. Discrimination between central and peripheral action of centrally administered neuropeptides is, therefore, possible.

Technetium 99m-DTPA microcapsules: A new preparation for gastric emptying studies

Technetium 99m-DTPA microcapsules have been developed to measure gastric emptying. Such capsules not only provide high labeling efficiency in vitro, but demonstrate limited dissociation in vivo, resulting in decreased error during measurement. In normal control subjects, the half-life ranged from 40 to 80 minutes under the aforementioned conditions.

Molecular biology: An overview

An overview of molecular biology is presented for the practicing surgeon. Definitions of the constructs and activity of DNA, RNA, and protein synthesis are defined. These principles are illustrated in their use in recombinant DNA technologies. A glossary is provided for the terms utilized.