Background Br Aims: Long-term survival of patients with Zollinger-Ellison syndrome (ZES) is largely determined by the presence or absence of liver metastases, However, because of the lack of precision of these criteria, development of further indicators is still required. Recent evidence showing that autoantibodies directed against the p53 protein could predict poor survival for some types of cancers prompted us to investigate the presence of such antibodies in sera from patients with ZES and their potential value as survival indicator, Methods: Anti-p53 antibodies were detected in the sera of 44 consecutive patients with ZES using both an enzyme-linked immunosorbent assay (ELISA) and Western blotting. The mean follow-up of these patients was 92 months, Results: Anti-p53 antibodies were detected in 7 of the patients with ZES (16%) by both ELISA and Western blotting. Univariate and multivariate analyses showed that the presence of anti-p53 antibodies (P = 0.0009 and P = 0.017, respectively) and liver metastases (P = 0.0009 and P = 0.012, respectively) was independently associated with shorter survival, Conclusions: These results suggest that anti-p53 antibodies are an indicator of survival and could be used in combination with staging to determine which patients with ZES have poor prognoses and therefore require reinforced therapy.

Dans un article de 1894, Letulle (M.) invoque l'ulcere simple du duodenum en en donnant une description histologique particuliere: il s'agissait de cas autopsiques. Le diagnostic de cette lesion anatomique a-t-il evolue?

Annals of the New York Academy of SciencesVolume 697, Issue 1 p. 229-232 “Restraint Ulcer” as a Model of Stress-Induced Gastric Lesion A Historical Note SERGE BONFILS, SERGE BONFILS INSERM U. 10, Hǒpital Bichat F-75877 Paris Cedex 18, FranceSearch for more papers by this author SERGE BONFILS, SERGE BONFILS INSERM U. 10, Hǒpital Bichat F-75877 Paris Cedex 18, FranceSearch for more papers by this author First published: October 1993 https://doi.org/10.1111/j.1749-6632.1993.tb49935.xCitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume697, Issue1Corticotropin‐Releasing Factor and Cytokines: Role in the Stress Response–Proceedings of the Hans Selye Symposium on Neuroendocrinology and StressOctober 1993Pages 229-232 RelatedInformation

Dans un article de Therese (L.) datant de 1893, les details fournis sur la secretion gastrique sont d'une extreme precision et devraient pouvoir constituer un guide d'execution pour ceux qui desireraient se lancer dans une telle etude

Evolution of gastrinoma tumoral mass, fasting serum gastrin concentrations, and gastric endocrine cells has been analyzed in 21 patients with the Zollinger-Ellison syndrome committed to long-term omeprazole treatment (up to 7.75 years, median 37 months). Gastrinoma growth was seen in eight patients. Significant increase in serum gastrin was only observed in the group of patients with gastrinoma growth. Fundic argyrophil cell densities were correlated with serum gastrin (r′=0.68,P=0.002). Argyrophil and antral gastrin cell densities significantly increased during the survey, but increases were greater in the group with gastrinoma growth (respectively, +136% and +131%) than in the other group (respectively, +34% and +43%). Progression in the degree of argyrophil cell hyperplasia, noted qualitatively, was observed in 11 patients. Fundic carcinoids developed in three of these 11 patients, all three having multiple endocrine neoplasia type 1 (MEN 1). Positive linear individual correlations (r≥0.85) between argyrophil cell densities and corresponding durations of omeprazole treatment were found in nine of the 10 patients studied at least three times and who had a clear-cut increase in those cell densities. Thus, increase in serum gastrin and fundic argyrophil cell densities appeared closely associated with gastrinoma growth; however, duration of drug-induced hypochlorhydria may also affect cell proliferation.

The difficult and controversial diagnostic and therapeutic management of patients having gastrinoma or insulinoma with multiple endocrine neoplasia type I (MEN-I) has been discussed by reference to the literature and a personal series of 45 gastrinoma/MEN-I patients followed consecutively at Bichat Hospital. In both gastrinoma/ and insulinoma/MEN-I patients, anatomic distribution and morphology of tumoral process(es) are usually multiple, diffuse, of small size, and associated with endocrine cell hyperplasia and even nesidioblastosis. These features enhance the difficulty of tumor localization and eradication. Despite the dramatic development of modern medical imagery and surgical experience, the real possibility, on a long-term basis, of curing the patients from their disease remains limited, especially in the gastrinoma/MEN-I patients. In the latter group, according to our experience, persistence or recurrence of the disease after surgery is usual, and metachronous hepatic metastasis development is frequently observed when the follow-up is long enough. Patients with liver metastases, however, seem to undergo a more indolent course than sporadic gastrinoma cases. In insulinoma/MEN-I patients, removal of the functionally dominant islet cell area(s) is essential. Various preoperative and intraoperative localization techniques allow efficacious selective pancreatic surgery in many cases. The latter refinements and the promises of long-acting somatostatin analogs, if confirmed, might restrict to exceptional circumstances the indication of near-total or total pancreatectomy.

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.

This study reports the effects of 4 and 5-year treatment with octreotide (200 micrograms sc bid) in the Zollinger-Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h-1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pretreatment BAO value: 115 mmol h-1), BAO progressively decreased to 42 mmol h-1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30-68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35-89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin-cell density was in the normal range. No long-term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients.

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80 000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2 700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1 994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.

Decreases in biologic activity have been reported following repeated administration of various drugs, presumable because long-term administration of a drug that blocks a specific receptor results in regulation at the receptor level. Administration of nizatidine 300 mg or ranitidine 300 mg at night to healthy volunteers showed that, although ranitidine was more effective than nizatidine in suppressing gastric acid secretion (measured by 24-hour intragastric pH monitoring) during the night after administration of the first dose, tolerance to ranitidine developed during the 28-day period of drug administration. Conversely, nizatidine displayed stable antisecretory efficacy during this period. The changes in efficacy of the two drugs from day 1 to day 28 were statistically significant in favor of nizatidine (P < 0.05). Tolerance to ranitidine was also observed throughout the 24-hour period. This study has confirmed earlier studies.

The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia, age, and sex on gastric endocrine cell densities were studied in 48 patients with the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women (p < 0.05). It showed no appreciable difference between young and old women but it declined with age in men. The mean argyrophil cell density, when adjusted for sex, was higher (+48.5%, p = 0.06) in patients with Zollinger-Ellison syndrome associated with MEN 1 than in those with sporadic type disease. This measurement was not significantly different between the two groups of patients when antisecretory treatments were considered. In patients with sporadic type disease, fundic argyrophil cells showed a normal pattern (16%) or diffuse (71%) or linear (13%) hyperplasia. In patients with MEN 1 diffuse and linear hyperplasia were of the same order (53% and 47%). Furthermore, fundic argyrophil endocrine tumours developed in five of 17-that is, 29.5% of patients with associated MEN 1 while none was seen in patients with sporadic type disease. These tumours showed an exclusive or prominent enterochromaffin like cell population. Antral gastrin and somatostatin cell densities and fasting serum gastrin concentrations were similar in the two groups of patients with Zollinger-Ellison syndrome. Whatever the underlying mechanism for carcinoidosis, the risk of developing fundic enterochromaffin like cell tumours in Zollinger-Ellison syndrome patients who present with MEN 1 is probably higher than was initially estimated and suggests that regular follow up of these patients is necessary.

Endoscopic information was obtained for 52 patients with ulcerative proctitis (23 F, 29 H) seen during a ten-year period. The median follow-up was 68 +/- 8 months. During the first referral period (38 patients experienced a first attack), endoscopic particularities were available: inflammation involved the anal mucosa above the dental line (n = 16), the whole circumference of rectal mucosa (n = 19) or the anterior wall exclusively (n = 33). The upper limit was 12.2 +/- 0.6 cm from the anal verge. Inflammatory lesions were higher in circumferencial conditions, when patients were older (late onset disease) but sex and ethnic state did not influence results of endoscopic presentation. Exulcerations or superficial ulcers were visualized in 16 and spontaneous bleeding in 43. Forty-five patients achieved clinical accuracy after 9.4 +/- 1 ms, but 32 only a complete endoscopic remission. Mean number of relapses was 3.6 +/- 0.4; 13 patients experienced a single attack. During relapses, inflammation was stable in 11 of 38 patients. Extension to the rectum in rectosigmoid junction, and sigmoid and above by 6, 14, and 7 patients respectively. After 5 years follow-up, the cumulative risk of further extension was 37 percent and 13 percent, respectively. Low abdominal pain, an family history of ulcerative colitis, and high inflammatory lesions at referral were significantly associated with a higher risk of extension. Cancer did not occur and not surgery was necessary during the follow-up. Idiopathic proctitis is perhaps at the "benign end" of the spectrum of ulcerative colitis. Nevertheless, its endoscopic particularities should be noticed.(ABSTRACT TRUNCATED AT 250 WORDS)