Long-term follow-up of patients with endoscopic treatment of sporadic adenomas of the papilla of vater.

BACKGROUND AND STUDY AIMS: Knowledge about the long-term outcome of patients after endoscopic treatment of ampullary adenomas remains poor, although surgical series have suggested that the initial endoscopic evaluation of these diseases might overlook cancer foci developed in adenomas. The aim of this study was to evaluate retrospectively the long-term outcome in patients with ampullary adenomas treated endoscopically, with a focus on the possible development of cancer. PATIENTS AND METHODS: The study included 24 patients (median age 59 years, range 34 - 84) with macroscopically benign adenomas of the papilla of Vater treated using mainly laser photodestruction between 1983 and 1996. Medical, endoscopic, surgical, and histological reports were reviewed. Patients and general practitioners were contacted to determine patient outcome when endoscopic follow-up had been discontinued. RESULTS: Endoscopic remission (macroscopic and histological) was achieved in 16 patients (66.6 %) with one recurrence (6.2 %) during a mean endoscopic follow-up of 66 months (4-168 months). Endoscopic treatment was discontinued in five (20.8 %) patients (with minimal residual adenoma and advanced age and/or severe unrelated disease), and failed in three patients (12.5 %) (failure of Nd:YAG laser in one case, severe pancreatitis and pancreatic duct ingrowth in one case each). After a mean clinical follow-up of 81 months (8-172 months), two patients (8.3 %) had undergone pancreaticoduodenectomy; eight (33.3 %) had died from unrelated diseases; and 14 (58.3 %) were alive and asymptomatic without any evidence of ampullary cancer. CONCLUSIONS: Long-term follow-up revealed no case of advanced ampullary cancer and suggested that endoscopic treatment was satisfactory for the large majority of patients with ampullary adenomas.

Long-term survival after photodynamic therapy for esophageal cancer.

BACKGROUND/AIMS: Photodynamic therapy (PDT) has been adapted to the endoscopic treatment of digestive cancer, but its indications and efficacy remain uncertain. The aim of this study was to assess its feasibility in the curative treatment of small esophageal tumors. METHODS: From 1983 to 1991, PDT was used to treat 123 patients with esophageal cancer who were recommended for nonsurgical treatment of squamous cell carcinoma (n = 104) and adenocarcinoma (n = 19). Endoscopic ultrasonography (EUS) was performed in 88 patients; 61 were staged uT1 and 27 were staged uT2. A hematoporphyrin derivative was injected 72 hours before laser irradiation with a 630-nm dye laser. PDT was applied alone in 56 patients and as part of a multimodal protocol in the 67 others. RESULTS: The complete response rate at 6 months was 87%. The 5-year survival rate was 25% +/- 6%, and the 5-year disease-specific survival rate was 74% +/- 5%. The complete response rate and survival rate were not different (1) between the PDT alone and the PDT multimodal treatment groups, (2) between the adenocarcinoma and squamous cell carcinoma groups, and (3) between the uT1 and uT2 EUS groups. PDT-related complications were esophageal stenosis (n = 43) and cutaneous photosensitization (n = 16). CONCLUSIONS: In patients with small esophageal tumors who pose high surgical risk, photodynamic therapy is an effective treatment.

Endoscopic ultrasonography in the preoperative staging of esophageal cancer.

Endoscopic ultrasonography is the best available method for the locoregional staging of esophageal carcinoma. Its main limitations are represented by a) tumor stenosis, b) distinguishing between malignant and benign lymph nodes, and c) distinguishing between mucosal and submucosal cancer. In untreated esophageal carcinoma, three main groups can be distinguished, based on clinical and morphological evaluation (endoscopy, abdominal ultrasound and CT). EUS is not useful when palliative treatment aiming to relieve dysphagia is the only treatment. In tumors with a superficial pattern at endoscopy, EUS is necessary to distinguish T1 from more invasive tumors, but endoscopic treatment (photodynamic therapy, strip biopsy) is indicated only in nonsurgical patients. In the last, and largest, group of tumors with no clear surgical contraindication, EUS is necessary when surgery is not the only treatment considered. EUS staging then improves patient management (surgery alone, surgery with preoperative treatment, or nonsurgical treatment; type of surgery). Moreover, it provides a good evaluation of the prognosis, and allows better follow-up after nonsurgical treatment.

Esophageal squamous cell carcinoma associated with gastric adenocarcinoma.

Adenocarcinoma of the stomach occurred in six of 425 consecutive patients with esophageal squamous cell cancer. In two cases, the gastric cancer, which was recognized at 17 and 29 months, respectively, after the nonsurgical treatment of the esophageal tumor, was treated by surgical resection. In three cases, the tumors which were diagnosed simultaneously, were treated by surgery (one case) resection of the gastric tumor and nonsurgical therapy for the esophageal tumor (one case), and nonsurgical therapy for both tumors (one case). In one case, a gastric cancer was resected 6 years before diagnosis of an esophageal tumor and a second cancer in the gastric stump. A nonsurgical protocol was then adopted for both tumors. The association of these two cancers raises questions concerning their epidemiology, diagnosis, prognosis, and management. There is room for nonsurgical multimodality protocols and, in association with surgery, survival was prolonged for more than 1 year in five of six patients.

Ontogeny of vasoactive intestinal peptide in the human fetal digestive tract.

Immunocytochemistry and radioimmunoassay were used to assess the appearance time and tissue distribution of vasoactive intestinal peptide (VIP) in the digestive tract of the human fetus. By radioimmunoassay, VIP was measurable from 10 weeks of gestation. The peptide was abundantly distributed in the jejuno-ileum and colon, where the tissue peptide concentration rose from 9-14 weeks of gestation (18.4 +/- 4.4 and 22.0 +/- 5.0 pmol/g wet weight, respectively) to 15-21 weeks (83.0 +/- 21.1 and 98.6 +/- 36.4 pmol/g, respectively). Lower concentrations were recorded in pancreas from 9-14 weeks of gestation (4.3 +/- 0.8 pmol/g) to 15-21 weeks (13.9 +/- 3.7 pmol/g). The peptide concentration was 15.6 +/- 1.9 pmol/g in fundus and 25.5 +/- 3.2 pmol/g in antrum from 15 to 21 weeks of gestation. The highest concentration was recorded in duodenum from 15 to 21 weeks of gestation (118.4 +/- 40.8 pmol/g wet weight). Tissue VIP concentration and age were positively correlated in the jejuno-ileum. By immunofluorescence, immunoreactive VIP was localized in nervous fibers in the muscularis externa, in the submucosa and in the lamina propria. Scarce cell bodies were also found in the myenteric plexus. No immunofluorescent endocrine cells were observed. These results suggest: (1) the early appearance of immunoreactive VIP in gut, as early as 10 weeks of gestation; (2) the peptide, localized in nervous structures only, follows the same distribution pattern as that in adults; (3) the development of VIPergic structures is a continuous process, initiated during the 3rd month of pregnancy.

Plasma somatostatin concentration in the preterm neonate.

Plasma somatostatin concentration was measured by radioimmunoassay in 26 preterm neonates (mean gestational age 34 weeks). None were seriously ill and they were all fed with breast-milk 12 h after birth. In a longitudinal study the concentrations were (mean +/- SEM): 21 +/- 2 pmol/l (n = 8) at 2-8 h of age, 24 +/- 2 pmol/l (n = 11) at the age of 2 days and 25 +/- 2 pmol/l (n = 15) at the age of 8 days. These levels were significantly higher than in 30 healthy control adults: 11 +/- 1 pmol/l (P less than 0.01). Gavage with breast milk on the 2nd day induced a significant decrease from 21 +/- 4 to 15-2 pmol/l in 60 min (P less than 0.05). This data shows that the high plasma levels in neonates correspond to the high density of somatostatin in the neonatal pancreas and digestive tract. It also indicates that somatostatin is regulated by feeding in the neonate.

Effects of somatostatin-14 and somatostatin-28 on bombesin-stimulated release of gastrin, insulin, and glucagon in the dog.

The effects of somatostatin-14 (S14) and somatostatin-28 (S28), a novel intestinal peptide containing somatostatin tetradecapeptide in its C-terminal position, on the bombesin-stimulated release of gastrin, insulin, and glucagon were tested. On iv infusion of bombesin, the increase in the level of glucagon was seen to be twice that of gastrin, and the insulin increase was 8 times that of gastrin. Plasma concentrations of somatostatin were not modified. S14 and S28 inhibited the release of gastrin, insulin, and glucagon; insulin release was inhibited most effectively, with glucagon release next, and gastrin release least inhibited. Based on the exogenous dose needed to produce equal effects, S28 was more potent than S14 on a molar basis, but based on the plasma concentrations needed to produce equal effects, S14 and S28 were equipotent.

Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man.

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.

Calcitonin-producing pancreatic somatostatinoma.

A pancreatic somatostatinoma metastatized to the liver was detected in a 70-yr-old woman presenting with chronic diarrhea, steatorrhea, pancreatic insufficiency, diabetes mellitus, and achlorhydria. At immunocytochemistry, most tumor cells stored both somatostatin and calcitoninlike substances. Chromatography of acid extracts of the tumor on G50 Sephadex gave two distinct peaks coeluting with cyclic ovine somatostatin and human calcitonin, respectively, thus ruling out the hypothesis of a single cross-reacting molecule synthetized by the neoplastic cells. When the tumor was extracted at neutral pH, larger molecular forms of the above components were found, which accounted for less than 20% of the total immunoreactivity. Gel permeation of plasma showed that the circulating calcitonin- and somatostatinlike components consisted of three and four different forms, respectively, including components of molecular weights similar to those of the reference peptides. Inhibition curves and immunoadsorption experiments indicated that the large forms were immunologically similar, if not identical, to the corresponding standard preparations. The present case illustrates the occasional ability of neoplastic somatostatin cells of pancreas to synthetize simultaneously components immunologically related to somatostatin and calcitonin. These two inappropriate secretions could account for the symptoms displayed by this patient.

Ontogeny of somatostatin in the human gastro-intestinal tract, endocrine pancreas and hypothalamus.

The appearance, time and distribution of somatostatin in the pancreas, gastro-intestinal tract and hypothalamus were studied comparatively in human foetuses aged 6--32 weeks, by immuno-cytochemistry and radioimmunoassay. Somatostatin was detected by both methods in all segments including the colon. The first cells were observed, and somatostatin was present in measurable amounts at 8 weeks in pancreas, duodenum and intestine, while the peptide was detected at 12 weeks in antrum and colon, at 14 weeks in fundus, and at 16 weeks in hypothalamus. Subsequently, the largest cell population was located in the pancreas, where peptide concentration and age were positively correlated (P less than 0.01, r = 64). From 15 to 21 weeks of age, the mean somatostatin concentration in pancreas (12.4 +/- 1.84 ng/mg) was clearly higher than in hypothalamus (0.05 +/- 0.02 ng/mg) or in any segment of the gut, where values ranged from 0.36 +/- 0.06 (fundus) to 4.74 +/- 0.83 ng/mg (duodenum). The early appearance time of somatostatin, and its specific distribution with preferential location in the pancreas, suggest that the peptide may play a major role for the development of the foetal digestive tract, and that it may be involved in the regulation of other endocrine secretions, especially in the pancreas.

Somatostatin in mucosa of stomach and duodenum in gastroduodenal disease.

In order to study the distribution of somatostatin in the upper digestive tract in man, biopsies were taken through endoscopy or at surgery from the fundus, antrum, and duodenal bulb in 15 subjects with no gastroduodenal lesion, 12 patients with severe antral and/or fundic atrophy in the sampling area, 28 patients with an active duodenal ulcer, and 14 patients with a nonmalignant gastric ulcer. The specimens were extracted in 2 N acetic acid and tested for somatostatin content with a specific radioimmunoassay. In the control subjects, the somatostatin concentration (nanograms per milligram of wet weight) was 0.60 +/- 0.12 in the fundus, 1.68 +/- 0.33 in the antrum, and 1.35 +/- 0.30 in the duodenal bulb. Atrophy of the gastric mucosa was associated with a reduction of the somatostatin concentration in the fundus and the antrum. No significant variation was observed in the present series of patients with gastric ulcer. Duodenal ulcer was associated with a reduction of the somatostatin concentration in the antrum (P less than 0.02). These results indicate that somatostatin is widely distributed from fundus to duodenal bulb in adult human subjects, and that lower antral concentrations are observed in patients with duodenal ulcer.

Gastric clearance of serum albumin in patients with alcoholic liver cirrhosis.

Gastric albumin clearance studies were carried out in 26 patients with alcoholic cirrhosis and in 10 control subjects. The mean clearance was significantly higher in patients than in control subjects. An increased protein gastric loss in cirrhotic patients was observed only in presence of gastritis. The presence or absence of distended esophageal varices did not influence the protein loss.

[Purification of human gastric glycoprotein and a study of its carbohydrate components (author's transl)]. / Purification d'une glycoprotéine gastrique humaine et étude de ses composants glucidiques.

Mucus was extracted from human gastric mucosa by homogenization in distilled water. The crude extract was purified from plasma, salivary and tissue contaminants by different steps involving chromatography on Sepharose 6B, Sepharose 2B and immunosorbents. The native glycoprotein so prepared was found to be immunologically pure; it migrated as a single band in acrylamide agarose gel electrophoresis at pH 8.6 and 3.5. The molecule exhibits blood group acitivity, contains 0.71 per cent sialic acid but no sulphate. The carbohydrate moiety contains glucosamine, galactosamine, fucose, galatose and mannose in the molar proportions 3: 1.95: 2.92:4.53:0.05.