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BACKGROUND: This endoscopic follow-up study was undertaken to evaluate the risk of gastric cancer (GC) and carcinoids in patients with pernicious anaemia (PA) and to analyse whether early detection of GC could be provided by regular endoscopic follow-up. METHODS: Screening gastroscopy was performed in 71 patients with pernicious anaemia, and thereafter they were followed up with gastroscopies at 3-year intervals for a mean time of 5.8 years. Standardized incidence ratios (SIR) were calculated, the expected number being based on incidence rates in the whole Finnish population. RESULTS: Two GCs were found during the follow-up period; one of these patients was asymptomatic and the other had abdominal symptoms. The SIR was 5.0 (95% confidence interval, 0.6-18). Eight carcinoids were detected, and all but one were removed endoscopically, and no metastases were found. The patients who had carcinoid tumours were younger at the diagnosis of PA than those who did not develop carcinoids (mean, 40 versus 55 years). Additionally, the patients with carcinoids had longer duration of PA (mean, 11 versus 5 years). CONCLUSIONS: During the follow-up period the risk of GC was increased. The risk of gastric carcinoids seems to be very high in patients with pernicious anaemia when compared with a normal population, but they are mostly relatively benign tumours. Regular routine gastroscopic follow-up is not indicated in patients with pernicious anaemia.

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To assess the value of gastroscopic cancer surveillance of patients with pernicious anaemia, 56 patients were re-endoscoped and biopsied after three years. In addition, changes in the density of fundic mucosal endocrine cells were evaluated morphometrically. Two cases (3.6%) of early gastric cancer and two cases of small gastric carcinoid tumours (3.6%) were detected in addition to the five carcinoids that had been found at the initial endoscopic screening. Nodular argyrophil cell hyperplasia and morphometric density of argyrophil cells were not stable phenomena: nodular hyperplasias regressed in five patients, remained similar in six, and progressed to a small carcinoid tumour in one. Serum gastrin concentrations did not correlate well with changes in the endocrine cell density. Regular endoscopic surveillance for gastric cancer may be beneficial and realistic in young patients with pernicious anaemia while the importance of fundic endocrine cell hyperplasia and that of small gastric carcinoids need further study.

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Eight patients with metastatic carcinoid tumor, seven of whom had symptoms of the carcinoid syndrome, were treated with either human leukocyte interferon (seven patients) or recombinant alpha-interferon (IFN alpha-2b) (one patient) at doses of 4.5 to 21 x 10(6) IU weekly for 1 to 21 (mean, 8.5) months. Tumor regression on computed tomography (CT) scan was found in one patient, the CT findings remained unchanged in three, and the tumor progressed in four patients. A clearcut and continuing decrease in urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed in one patient and a transient one in four patients. The symptoms improved in only two of seven patients. Four patients had leukopenia develop, which was circumvented by reducing the dose. The authors conclude that interferon therapy of the carcinoid tumor is not as successful as has been suggested in previous reports.

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The number and density of argyrophil endocrine cells were morphometrically calculated in gastric fundal mucosal biopsy specimens taken from 64 patients with pernicious anaemia (five with gastric carcinoids, 15 with nodular argyrophil cell hyperplasia, 44 with diffuse argyrophil cell hyperplasia) and from 14 healthy controls. Similar calculations were also made on the ileal mucosa away from the tumour of 10 patients with ileal carcinoids and 10 controls. In the stomach, the argyrophil cell counts were twice as high in the patients with pernicious anaemia than in controls and the densities in the whole mucosa or in the epithelial structures were similarly three to five times higher. The cell counts in the patients showed positive correlation with the serum gastrin concentration. The patients with nodular argyrophil cell hyperplasia and gastric carcinoids formed a uniform group with the highest cell counts and serum gastrin concentrations; the difference between the groups was in the longer duration of pernicious anaemia in the patients with carcinoid tumours. On the other hand, no endocrine cell hyperplasia was seen in those with ileal carcinoids. It is concluded that fundal mucosal endocrine cells show an increase in patients with pernicious anaemia that is related to the gastrin concentration. This phenomenon may favour the development of hyperplastic endocrine cell nodules and, eventually, carcinoid tumours.

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Clinical data about 104 patients with gastrointestinal carcinoids emphasized the heterogeneous nature of these tumours in different organs. The sites of the primary tumours were the stomach in 12 (11%), the duodenum in 3 (3%), the small bowel in 48 (45%), the appendix in 28 (26%), the colon in 6 (6%), and the rectum in 6 cases (6%). Gastric carcinoids were multiple in 4 (33%) and small-bowel carcinoids in 11 cases (23%). None of the gastric, duodenal, or rectal carcinoids had generated metastases, as contrasted to 34 (72%) small-bowel carcinoids. Twelve patients had symptoms of the carcinoid syndrome caused by hepatic metastases from ileal (11) or appendiceal (1) primary tumours. At least two patients with duodenal carcinoids had Zollinger-Ellison syndrome produced by the tumours. The cumulative 5-year survival rate was 91-100% for gastric, appendiceal, and rectal carcinoids, 77% for small-bowel carcinoids, and 33% for colonic carcinoids. Resectable mesenteric lymph node metastases did not affect the 5-year survival of patients with small-bowel carcinoids as compared with the tumours confined to the bowel wall. Poor prognosis was associated with hepatic metastases at the time of diagnosis. Small-bowel carcinoids remain a challenge in clinical work because of their distinct metastatic propensity and problematic diagnosis.

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Among 196 patients examined in 1972-1985 because of pernicious anemia (PA), 105 patients under the age of 76 years were invited for gastroscopic screening, and 71 patients (68%) participated. Gastroscopy revealed carcinoid tumor(s) in 5 patients (7%) but no case of carcinoma. In addition, one patient with gastric carcinoid, 5 patients with adenocarcinomas and one with a concomitant carcinoid and carcinoma had already been diagnosed earlier in the overall PA group on the basis of clinical symptoms. Thus, within a follow-up of 0-20 years (mean 7 years) the total frequency of gastric carcinoid tumors was 4% and that of carcinoma 3%. Patients with carcinoid tumors had a long duration of PA and young age of onset; these cases were not necessarily those with the highest serum gastrin levels. Even though most gastric carcinoids are small subclinical tumors of uncertain clinical significance, their unexpectedly high frequency, combined within the risk of carcinoma in PA, might indicate the need for gastroscopic follow-up, at least in cases of juvenile onset PA.

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Fourteen patients with carcinoid syndrome due to metastatic ileal (10), ileo-coecal (3) or appendiceal (1) carcinoid tumours were treated with hepatic dearterialization procedures: 15 surgical interruptions of arterial connections to the liver and 1 angiographic embolization of hepatic arteries. 11 patients had complained of recurrent attacks of flush, diarrhea and/or dyspnea and 3 patients had already progressed to general debility and cardiac failure caused by tumour products. Hepatic dearterialization abolished the carcinoid syndrome symptoms for 3-60 months (mean 19 months). Urinary 5-HIAA decreased for a mean period of 27 months. After relapsing symptoms 2 patients had redearterialization of the liver with a renewed symptomless period and lowered 5-HIAA excretion. Operative mortality was 19%: the deaths occurred when liver dearterialization was performed for end-stage patients or simultaneously with bowel resection, which should be considered as contraindications. Hepatic dearterialization seems to be temporarily effective in relieving carcinoid syndrome symptoms and in reducing hormonally active tumour mass and serotonin formation.

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The clinical and pathologic data from 11 patients with gastric carcinoid tumours were analysed. Histological examination revealed associated atrophic gastritis in corpus in all patients, and 4 patients had pernicious anaemia. Most patients underwent an extensive gastric resection, complicated by one death. Several facts that should have an influence upon the surgical strategy were noticed. The patients were comparatively young; the mean age was 52 years. Ten of the tumours were located in the corpus and fundus area, and only one was antral. The two largest tumours measured 2-3 cm in diameter, the others being less than 1 cm, but at least in four cases multifocal. None of the tumours metastasized, but the largest one recurred locally. Limited surgical procedures and follow-up with repeated gastroscopies might be advisable in small gastric carcinoids which seem to be low grade malignant tumours with slow growth.

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