Joann Sparks

Primary peptic ulcerations of the jejunum associated with islet cell tumors. Twenty-five-year appraisal.

A review of 42 patients with gastrinoma, who either survived five years or longer or who died during this period of evaluation, was carried out to define the surgical principles which might be combined with the recent trend toward cimetidine therapy. Thirty-four (80%) of the patients had total gastrectomy with an operative mortality rate of 2.3%, and eight patients (20%) had less than total gastrectomy. No tumor was found in six patients with hypcrgastrinemia and an abnormal secretin bolus whose five-year survival rate was 100%. Of the thirty-six patients having tissue proof of gastrinoma, twenty-two (61%) had complete resection of all gross tumor resulting in a 76% five-year survival rate. Fourteen patients had un-resectable tumor or partial resection with a five-year survival rate of 21%. Complete gross tumor resection increased mean survival by six years (p < 0.01), but resulted in persistent eugastrinemia in only two patients. Long-term survival was possible with a combination of vagotomy, lesser gastric procedures, tumor resection, and cimetidine, seven of eight patients living more than five years. Surgical management of gastrinoma should be directed toward aggressive tumor resection and vagotomy, with reliance on cimetidine therapy postoperativcly to control the gastric hypcrsecretion. Total gastrectomy should be reserved for cimetidine failures and those who do not wish to take cimetidine for the rest of their lives.

Observations on the postoperative tumor growth behavior of certain islet cell tumors.

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angingram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.

Suppression of Gastrin and Gastric Acid Secretion in the Zollinger-Ellison Syndrome by Long-Acting Somatostatin (SMS 201-995)

(1986). Suppression of Gastrin and Gastric Acid Secretion in the Zollinger-Ellison Syndrome by Long-Acting Somatostatin (SMS 201-995) Scandinavian Journal of Gastroenterology: Vol. 21, No. sup119, pp. 206-211.

Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors?

Effective medical therapy of gastric hypersecretion in Zollinger-Ellison syndrome may delay the diagnosis of gastrinoma. To examine the impact of effective medical therapy on the surgical treatment of gastrinoma we reviewed the records of 108 patients diagnosed between 1948 and 1998 at a single institution. Minimum follow-up was 5 years. The experience was divided into four periods: I, 1955-1965-initial recognition, n = 11; II, 1966-1975-increasing recognition, n = 27; III, 1976-1985-widespread application of gastrin radioimmunoassay, n = 21; and IV, 1986-1998-widespread use of effective medical therapy, n = 49. There was no significant difference in age or sex in the groups. Gastric surgery was less common in period IV (37% compared with 86% to 100% in previous periods) as was total gastrectomy (6% compared with 43% to 78%; P <0.0001). Tumor resection was attempted in a similar percentage of patients in each group (57% to 67%). The incidence of metastatic disease in period III was 19% (P = 0.034 versus period I, 45%, period II, 56%, and period IV, 55%). The 5-year disease-free survival increased in period III to 29% (P = 0.001 versus period I, 0%, period II, 4%, and period IV, 2%). The results support the effectiveness of acid suppressive therapy by H2 antagonists and proton pump inhibitors as evidenced by the decrease in gastric surgery. However, in the era of effective medical therapy, the surgeon sees the patient with more advanced disease and 5-year cure is less likely. Physicians must maintain a high index of suspicion for this disease and not mask a potential malignancy with prolonged control of acid-related symptoms without taking steps to diagnose gastrinoma.

Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995).

Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.

Histoplasmosis: to skin test or not to skin test?

SummaryA single skin test with commercially-available histoplasmin did not stimulate significant antibody response in the sera of 187 persons when measured by the yeast phase complement-fixation, collodion agglutination or histoplasmin latex agglutination tests. Similarly, no effect was noted with the histoplasmin complement-fixation test in the sera of 97 skin-test negative individuals; in contrast 26.7% of skin-test positive persons developed significant titer increases.

Experimental Histoplasmosis in Monkeys.

Summary Severe disease was produced in monkeys by yeast phase H. capsulatum administered intravenously and intratracheally. Monkeys inoculated intranasally exhibited a more mild disease process. No significant clinical signs of illness were seen in monkeys inoculated by the gastric route.

Somatostatin-like peptides alter calcium but not secretin sensitivity of gastrinoma cells☆

The provocation of gastrin release by calcium or secretin is accepted as a method to differentiate the hypergastrinemia of the Zollinger-Ellison syndrome from that of other causes. We have previously shown that calcium and secretin failed to provoke gastrin release from acutely dispersed gastrinoma cells. This disparity between the in vivo and in vitro effects of these two provocative agents suggests that intermediates may be necessary for calcium- or secretin-induced gastrin release. In an acute cell dispersion, serum-free model, two gastrinomas with low levels of endogenous somatostatin (SRIF) and other peptides failed to respond to calcium or secretin provocation. Conversely, a third tumor containing high levels of endogenous SRIF-like peptides and low levels of other gut peptides did respond to calcium, but not to secretin provocation in vitro. We suggest that in vivo, SRIF modulation of gastrin release is a prerequisite for calcium-simulated gastrin secretion.

Gastrin release from dispersed gastrinoma cells: Effects of calcium and calcium lonophore (A23187)

Dispersed single-cell suspensions of human gastrinoma tissue were incubated for 15, 60, and 120 min in a calcium-containing medium, (0.1, 2, 10 mM) in calcium-free medium and in calcium-free medium containing the calcium ionophore A23187 (0.01, 1, and 100 micrograms/ml). Supernatant and pellet (intracellular) gastrin levels were determined by radioimmunoassay. Supernatant gastrin levels remained stable over 120 min in calcium chloride or calcium gluconate containing medium, while intracellular pellet gastrin approximately tripled during the same incubation period. Total gastrin (supernatant plus pellet) approximately doubled during the 2-hr incubation in calcium. However, calcium (0.1, 2, or 10 mM) failed to produce a dose-dependent rise in supernatant, pellet, or total gastrin when compared to calcium-free incubates. Contrary to the expected gastrin response to calcium, supernatant and pellet gastrin levels were higher in incubates in calcium-free medium than in calcium-containing incubates. A23187 (0.01 or 1 mcg/ml) in a calcium-free medium decrease supernatant gastrin while high dose ionophore (100 mcg/ml) increased supernatant gastrin. All doses of ionophore stimulated pellet and total gastrin levels. Thus, it appears that the clinical augmentation of gastrin levels, seen with calcium challenge in vivo may not be solely due to changes in serum calcium.