The "Fonds Georges Brohée": a longstanding Belgian national initiative to stimulate research in hepatogastroenterology.

The Fonds Brohée/Brohée fund was created in 1964 at the initiative of 16 Belgian physicians, in the memory of Georges Brohée, the founder of the Belgian Society of Gastroenterology in 1928 and of its Journal in 1933, first published under the name "Le Journal Belge de Gastro-entérologie", then until today as "Acta Gastro-Enterologica Belgica". The goal of the Fonds is to stimulate research in the field of gastroenterology in Belgium, by awarding a young researcher (< 40 years) for an outstanding work in the clinical, translational or fundamental setting. Since 1966, 26 remarkable works have been awarded in various areas of interest in gastrointestinal diseases, whether in IBD, functional disorders, digestive oncology and, last but not least, hepatology. Since the recognition of their work, many of the awardees have become recognized for their expertise well beyond Belgium. Hopefully, the Foundation will continue to thrive and flourish after 55 years, as the members of its board and its healthy finances will allow to continue to promote and encourage high-quality research by young hepato-gastroenterologists in Belgium.

[Chronic inflammatory bowel disease: Crohn's disease and ulcerative colitis]. / Les maladies inflammatoires chroniques de l'intestin: maladie de Crohn et rectocolite ulcero - hemorragique.

Inflammatory bowel diseases comprise Crohn's disease, ulcerative colitis and indeterminate colitis, generally beginning in young subjects and increasing in frequency in Western countries. Despite their still unknown aetiologies, some pathogenic mechanisms have been elucidated after the recent discovery of numerous susceptibility genes and rare environmental factors. These diseases have a course consisting of episodes of flare-up alternating with periods of remission. Medical treatment for induction of a remission comprises besides aminosalicylates, corticosteroids including budesonide and immunosuppressive drugs, anti-TNF-alpha drugs (infliximab, adalimumab) indicated in case of failure of previous therapies. Surgery is indicated for complications and failure of medical treatment.With current therapy, most of the patients are able to fulfil their familial, social and professional projects.

The history of Acta Gastro-Enterologica Belgica.

The history of Acta Gastro-Enterologica Belgica is long, rich… and cloudy. There is no centralised archive available. However, all currently active gastroenterologists in Belgium have been trained with the journal, have published abstracts or manuscripts in it, or at least know of its existence. Whereas it started as a national society's journal in 1933, it has grown to a competitive international journal with Impact Factor. We felt the need to reconstruct the journal's long history, since this was never done before. This review tried to highlight some of the important milestones, without claiming to be complete. Looking back helps to better foresee and anticipate the future.

Immunisation after hepatitis B polyvalent vaccination among children in South Kivu Province, Democratic Republic of the Congo.

BACKGROUND: The World Health Organization recommends the integration of vaccination against hepatitis B virus (HBV) into the national immunisation programmes of all highly endemic countries. Protective efficacy, defined as a hepatitis B surface antibody (HBsAb) level ≥10 mIU/mL, is ideally obtained in >90 - 95% of immunised children. The Democratic Republic of the Congo (DRC) implemented this recommendation in 2007 by introducing administration of hepatitis B vaccine in a combined formulation. OBJECTIVES: To assess the rate of seroprotection in children who received hepatitis B vaccine in the DRC context. METHODS: This descriptive cross-sectional study was conducted during routine postnatal consultations at the General Hospital of Bukavu in South Kivu Province, DRC. A total of 200 infants aged 6 - 12 months and their mothers were consecutively enrolled. All the infants received the three-dose regimen of hepatitis B vaccine 6, 10 and 14 weeks after birth. The mothers were tested for hepatitis B surface antigen and HIV, while HBsAb levels were measured in the infants to determine immune response. RESULTS: Seroprotection was achieved in 84.5% of the infants. No maternal (age, parity, duration of pregnancy, HIV and HBV status) or infant (sex, weight at birth) factors were found to be associated with absence of immunological response. CONCLUSIONS: The study demonstrated that the rate of seroprotection in the current vaccination programme against HBV in DRC was lower than desirable but comparable to rates reported in some other African countries. Further studies are needed to assess this finding and to evaluate ways to optimise the seroprotection rate.

Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms.

PURPOSE: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL). PATIENTS AND METHODS: Eligible patients had the following substantial daily symptoms: for patients with carcinoid tumors, three or more stools and/or 1.5 or more flushing episodes; for patients with gastrinoma, greater than 50% elevated basic acid output; and for patients with vasoactive intestinal peptide-secreting tumors (VIPomas), four or more stools and/or a stool volume of >/= 800 mL, a measurable tumor, and an elevated biochemical tumor marker (>/= two times the upper limit of the normal reference range). Lanreotide PR was administered intramuscularly every 14 days at 30 mg for 6 months. We measured efficacy by studying symptoms, tumor markers, tumor size, and QOL. Side effects were scored according to the National Cancer Institute's toxicity grading system and ultrasound examination of the gallbladder. RESULTS: Fifty-five patients were included in the study (48 patients with carcinoid tumors, six patients with gastrinoma, and one patient with VIPoma). Symptomatic improvement (> 50% reduction) occurred in 38% of the assessable patients with carcinoid tumors, in 67% of the gastrinoma patients, and in the VIPoma patient. Tumor markers normalized in two of 45 assessable patients, 19 patients exhibited a reduction (> 50%), 19 patients exhibited no change, and tumor markers rose by more than 50% in five patients. Tumor size was reduced in two of 31 assessable patients and remained stable in 25 patients; four patients experienced progression. QOL assessments after 1 month showed improvements in emotional and cognitive function, and diminished fatigue, sleeping disorders, and diarrhea. Eight of 30 assessable patients developed gallstones. CONCLUSION: Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.

Motilin-producing liver and bone metastases evidenced 14 years after resection of a rectal polyp.

A 62-year-old man with a history of a resected rectal polyp was diagnosed 14 years later with right liver and multiple bone metastases. The liver biopsy showed a malignant epithelial tumor that was positive for neuron-specific enolase immunostaining and negative for chromogranin. Electron microscopy was characteristic of that for an endocrine tumor. Most circulating hormonal peptide levels were within normal ranges and only motilin level was elevated. On the right hepatectomy, the three large metastases had a histologic picture suggestive of an endocrine tumor. Immunohistochemistry revealed in some areas numerous tumor cells expressing motilin, and a few cells were strongly positive for pancreatic polypeptide and somatostatin. The retrospective analysis of the rectal polyp showed a similar histology and immunohistochemical profile, indicating that this lesion was the primary tumor. Motilin-positive cells from one of the hepatic lesions were identified on semithin sections and further processed for electron microscopy. Neurosecretory granules were numerous in all cells. Immunoelectron localization enabled us to characterize the motilin-containing neurosecretory granules, which had a mean diameter of 168.3x38.1 nm. Although not all tumor cells were motilin-positive, a diagnosis of motilinoma for the rectal polyp and its hepatic and bone metastases was proposed.

Somatostatin receptor imaging with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors: safety, efficacy and impact on patient management.

UNLABELLED: Indium-111-pentetreotide, a radiolabeled somatostatin analog, has been proposed for imaging tumors bearing somatostatin receptors. This study evaluates the safety, efficacy and impact on patient management of this scintigraphic agent in patients with gastroenteropancreatic (GEP) neuroendocrine tumors. METHODS: We studied 47 consecutive patients with a proven or clinically suspected GEP neuroendocrine tumor who were imaged 4 and 24 hr after injection of 111In-pentetreotide. The patients were monitored for adverse reactions and changes in vital signs or clinical chemistry over 24 hr. The scintigraphic findings were compared with results from conventional imaging methods. The patients were followed over a minimal 6-mo period during which further localization procedures were performed to confirm or refute the additional tumor sites found at scintigraphy. RESULTS: No adverse reactions or clinically relevant changes in clinical chemistry were noted after injection of the radiopharmaceutical. The final diagnosis of a GEP neuroendocrine tumor was retained in 38 patients. Somatostatin receptor-positive lesions were found in 33 of these patients, whereas conventional methods were positive in 31 patients. Of the 54 sites seen by conventional procedures, 50 sites were also detected scintigraphically. CONCLUSION: Indium-111-pentetreotide is a safe, sensitive imaging agent in the detection of GEP neuroendocrine tumor sites. Indium-111-pentetreotide also provides information on the somatostatin receptor status of the tumor and may therefore aid in therapeutic decisions.

Indium-111-pentetreotide uptake in endocrine tumors and lymphoma.

UNLABELLED: The biodistribution of 111In-pentetreotide was assessed in patients with gastroenteropancreatic (GEP) neuroendocrine tumors or lymphoma and in control patients and analyzed as a function of scanning time, presence or absence of tumor uptake, tumor type and previous octreotide treatment. METHODS: Patients underwent imaging 4 and 24 hr after injection of approximately 200 MBq 111In-pentetreotide. The frequency of organ visualization was assessed on planar views. Total organ and tumor uptake (% injected dose [ID]) was determined using the geometric mean method and regional tissue uptake (% ID/100 ml) by semiquantitative SPECT. RESULTS: Liver, spleen, kidneys and urinary bladder were visualized in all patients. Thyroid, bowel and pituitary were more often visualized at 24 hr than at 4 hr. Activity in the gallbladder, breast, ureters and ascites was only occasionally observed. Total liver, spleen and thyroid uptake was stable over time, whereas kidney activity decreased slightly. At 24 hr, regional uptake was threefold lower in the liver than in the spleen or kidneys and was similar in the three groups. In patients with long-term octreotide therapy, a positive correlation was found between the duration of octreotide therapy and liver or spleen uptake. Total and regional tumor uptake showed high intraindividual and interindividual variations. Total tumor activity was stable over 24 hr in patients with GEP and decreased in those with lymphoma. The mean regional tumor uptake was 10-fold lower in patients with lymphoma than in those with GEP. Cold octreotide injected 24 hr after tracer administration did not result in any displacement of organ and tumor activity. CONCLUSION: Organ uptake seems not to be influenced by the presence of 111In-pentetreotide-positive lesions or by tumor type. Tumor uptake is highly variable among patients and clearly lower in patients with lymphoma than in those with GEP. The widespread of uptake values in tumors indicates that radiotherapy using radiolabeled somatostatin analogs may not be applicable to all patients with 111In-pentetreotide-positive tumors.

Rapid improvement of bone metabolism after infliximab treatment in Crohn's disease.

BACKGROUND: Crohn's disease is associated with low bone mineral density and altered bone metabolism. AIM: To assess the evolution of bone metabolism in Crohn's disease patients treated with infliximab. METHODS: We studied 71 Crohn's disease patients treated for the first time with infliximab for refractory Crohn's disease. Biochemical markers of bone formation (type-I procollagen N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin) and of bone resorption (C-telopeptide of type-I collagen) were measured in the serum before and 8 weeks after infliximab therapy and compared with values in a matched healthy control group. RESULTS: Eight weeks after treatment with infliximab, a normalization of bone markers was observed with a median increase in formation markers of 14-51% according to marker and a lower but significant decrease in resorption marker (median 11%). A clinically relevant increase in bone formation markers was present in 30-61% of patients according to the marker. A clinically relevant decrease in C-telopeptide of type-I collagen was present in 38% of patients. No association was found with any tested demographic or clinical parameter. CONCLUSION: Infliximab therapy in Crohn's disease may rapidly influence bone metabolism by acting either on bone formation or bone resorption. This improvement seems to be independent of clinical response to infliximab.

Effect of a 2 g cimetidine infusion on twenty-four-hour intragastric pH in critically ill patients.

We evaluated the effect of a cimetidine continuous infusion (2 g in 24 h) on the intragastric pH of 16 critically ill patients (11 men, 5 women, mean age 45 years). During the 24 h pre-trial period and the subsequent 24 h cimetidine infusion, an intragastric combined electrode was placed in the fundus and the pH recorded with a portable pH module and data collection unit. In each patient, the cimetidine infusion induced a prolonged rise of intragastric pH. For all patients the mean percentage of readings above pH 4.0 was 11% pre-trial and 75% during the cimetidine 24 h infusion (p less than 0.001). The percentages of readings above 5.0, 6.0, 7.0 were also significantly higher during infusion than pre-trial in the 16 patients. After starting the cimetidine infusion, there was a concomitant rise of median plasma cimetidine and median intragastric pH in the 7 patients studied. After 6 h, median plasma cimetidine remained above 1 mcg/ml. These results and recent data from the literature suggest that in critically ill patients a continuous infusion of cimetidine might prevent stress ulcerations better than bolus injections by maintaining intragastric pH above 4.0 during longer time intervals.

Purification and amino acid sequence of human motilin isolated from a motilin containing liver metastasis.

The acid extract of a liver metastasis from a patient with elevated plasma motilin levels contained large quantities of motilin (3.37 micrograms/ml). The extract was concentrated on a C18-column and motilin was isolated by gel chromatography (Sephadex G-50) followed by cation ion exchange chromatography (HR5/5 Mono-S) and three successive steps of reverse phase chromatography (Nucleosil 300-5 C18). The pure peptide was sequenced and the identity of porcine and human motilin was confirmed. This is the first report of a tumor containing large amounts of motilin.

Intrathoracic Nissen fundoplication: long-term clinical and pH-monitoring evaluation.

From 1976 until April 1989, 31 intrathoracic total fundoplications were performed for reflux esophagitis and irreducible hiatus hernia. In the first 16 patients (group 1) the operation was complicated with acute perforation of the wrap in 4 cases, bronchogastric fistula in 1, and herniation of the wrap higher in the chest in 1. Technical modifications were applied to 15 more recent patients (group 2). These are enlargement of the hiatus, looseness of the wrap and its appropriate anchorage, avoidance of forceps when handling the stomach, care with the vagi, and efficient gastric decompression in the postoperative period. The postoperative course was always uneventful in group 2. Twenty-six patients, who still have their initial wrap, were considered for clinical evaluation: 11 from group 1 (mean follow-up, 81.5 months) and 15 from group 2 (mean follow-up, 32.8 months). All are free from any symptom of reflux; gas-bloat syndrome is infrequent and dysphagia is relieved. Twenty-four-hour pH monitoring, performed in 14 patients (3 from group 1 and 11 from group 2) (mean follow-up, 42 months), was normal in 13; a pathological upright reflux (time pH less than 4, 8.4%) was demonstrated in one symptom-free woman in whom endoscopy was unremarkable. Mechanisms of complications experienced in group 1 are analyzed in the light of the technical evolution of the procedure, and the place of the intrathoracic total fundoplication in the management of short esophagus is defined, considering the other available surgical techniques.

Feasibility and effectiveness of en bloc resection of the esophagus for esophageal cancer. Results of a prospective study.

En bloc resection of the esophagus was attempted by right thoracotomy, laparotomy, and left cervicotomy in 82 patients suffering from an esophageal cancer. Tumors were classified by the depth of wall penetration and node involvement: 21 tumors penetrated at the most into but not through the muscle (W1), and 61 invaded the full thickness of the wall (W2). Twenty-five were associated with normal lymph nodes (N0), 26 with metastatic thoracic nodes only (N1), and 31 with metastatic extrathoracic nodes (N2). Digestive continuity was restored by gastric pull-up in all cases except one in which the transverse colon was used. Thirty day and hospital mortality were 0 and 2.4% (2/82) respectively. Posterior mediastinectomy was feasible in 65 patients but in seven of them an unsuspected metastatic spread was detected during the second step of the operation. It was not feasible in 17 patients owing to the involvement of adjacent mediastinal organs. It was feasible in all W1 tumors and in 72% of W2. Feasibility did not significantly depend on the tumor location or length. Of the 24 palliative operations, 17 were carried out for N2 tumors. After potentially curative mediastinectomy (N = 58), three year survival was 38% and after palliative operation (N = 24), 18 months survival was 11% only. After mediastinectomy, survival dropped as the node involvement and the depth of wall penetration increased (W1: 66%, W2: 28%, N0: 58%, N1: 32% at three years and N2: 17% at 2 years). Overall survival in group N2 was not significantly different from that achieved in palliative cases and no patient classified W2 N2 was alive at 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, radiological and functional results of remedial antireflux operations.

Fifty-five patients were reoperated on for an unsatisfactory outcome after antireflux surgery. Presenting symptoms were heartburn alone (27), heartburn and dysphagia (10), dysphagia alone (9), chest pain (4), left shoulder pain (1), left shoulder pain and fever (1), and signs of anemia (3). The symptom of dysphagia was usually of immediate onset whereas heartburn reoccurred after a symptom-free period (p = 0.014). The most common failed antireflux procedure was a Nissen fundoplication (37). The incompleteness of the residual wrap, its location around the stomach and the irreducibility of the gastro-oesophageal junction below the diaphragm were accurately predicted by barium swallow study in 70, 83 and 92% of the patients, respectively. Abnormal oesophageal body motility was related to oesophagitis, herniation of the residual repair into the chest or both (16/20), and it normalized in 6 of the 11 patients evaluated at follow-up. Oesophageal acid exposure and prevalence of oesophagitis were higher in patients with heartburn than in those with other symptoms (p < 0.02). Intraoperative findings were breakdown of the repair, its location around the stomach, its herniation into the chest, its too excessive tightness, a gastric fistula, or any combination. Remedial surgery consisted of a new antireflux procedure (42), a new antireflux procedure combined with closure of a gastric fistula (3), a closure of a gastric fistula alone (1), a closure of the crura (4), an oesophageal resection (3), a total gastrectomy (1), and a duodenal diversion (1).(ABSTRACT TRUNCATED AT 250 WORDS)

[Anal surgery in Crohn's disease. Clinical and functional results]. / Chirurgie anale dans la maladie de Crohn. Résultats cliniques et fonctionnels.

The aim of this study was to evaluate the results of anal surgery performed in 105 patients for perianal symptomatic complications of Crohn's disease. The patients were divided into 3 groups: group I: 45 patients with simple fistulae; group II: 53 patients with complex fistulae; group III: 7 patients with other symptomatic perianal lesions. All patients underwent a resection of their perianal lesions. Complete wound healing was obtained in 95 patients after a mean interval of 11 weeks. Satisfactory results persisted during a mean follow-up of 5 years. The functional results were clinically evaluated in 100 patients: 90 patients were asymptomatic, 6 patients complained of soiling and 4 patients noticed occasional incontinence for flatus and liquid stools. Anorectal function was studied by manometry in the last 31 patients who underwent surgery. Before surgery, the resting anal pressure and the maximal voluntary squeezing pressure were significantly lower than in control subjects. After surgery, there was no statistical difference between the pre- and postoperative results for both parameters. In conclusion, anal surgery in Crohn's disease is hazardous because of the complexity of lesions and preoperative anorectal dysfunction. However, the clinical and functional results obtained in our patients were satisfactory.

Single dose ranitidine: influence of the time of administration on gastric acidity in normal subjects and in patients with duodenal ulcer.

Using ambulatory 24 hour pH monitoring, intragastric acidity was measured in 6 healthy volunteers and 8 patients with duodenal ulcer. According to a latin square design each patient was randomly assigned to receive placebo, 300 mg ranitidine at 19.00 h or 300 mg ranitidine at 22.00 h, on three separate occasions. Validation of the method was achieved by comparing the values indicated by the intragastric electrode and the pH of simultaneously aspirated gastric juice (y = 0.87x + 0.66, r = 0.93). Comparing the area under the curve of intragastric hydrogen ion activity, as well as the percent of time less than pH 5, we found a better inhibition of nocturnal acidity (20.00 h-08.00 h) with 19.00 h ranitidine than with ranitidine administered at 22.00 h (p less than 0.01). By contrast, there was no significant difference in diurnal acidity between both ranitidine regimens and placebo.

[Ileo-anal anastomosis in hemorrhagic-ulcerative rectocolitis and familial adenomatous polyposis: is it mandatory to perform resection of the endo-anal mucosa?]. / L'anastomose iléo-anale dans la rectocolite ulcéro-hémorragique et la polypose adénomateuse familiale: faut-il faire une mucosectomie endo-anale de principe?

The aim of this study was to assess the clinical outcome after ileal pouch-anal anastomosis with mucosectomy for ulcerative colitis and for familial adenomatous polyposis, and to characterize the histology of the stripped endoanal mucosa with particular reference to the ulcerative colitis activity, adenomatous polyps and dysplasia. Twenty-eight patients were operated, 16 for ulcerative colitis (group I) and 12 for familial adenomatous polyposis (group II). In group I, there were no intraoperative complications, but mucosectomy was tedious in 10 patients (62%) and the anastomosis was performed under some degree of tension in 10 patients (62%). In group II, there was a direct injury of the internal sphincter by a posterior tear during the mucosal stripping in one case. Mucosectomy was easy to perform in 8 patients (67%) and 10 anastomoses (84%) were performed under tension. In both groups, there were no postoperative complications related to the mucosectomy or to the anastomosis itself. Functional results were good, with a normal continence in 80% of ulcerative colitis patients and 92% of familial adenomatous polyposis patients. Review of histological sections of the stripped anal mucosa in group I showed chronic active ulcerative colitis in 8 patients (50%), chronic non-active ulcerative colitis in 4 (25%) and quiescent ulcerative colitis in 4 (25%). There was only one case of moderate dysplasia in a patient with a Dukes A carcinoma. In group II, anal mucosa showed micropolyps in all cases with mild dysplasia in 3 cases (25%) and moderate dysplasia in 9 (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Physiopathology and diagnostic methods in esophagitis due to reflux]. / Physiopathologie et méthodes d'exploration de l'oesophagite par reflux.

Several sensitive and specific methods are now available for the investigation of gastro-oesophageal reflux and oesophagitis. Nevertheless, judicious medical or surgical management requires a good understanding of the pathophysiological aspects of these conditions and of the significance of the investigation results.

[Digestive fistulas in Crohn's disease]. / Fistules digestives dans la maladie de Crohn.

From 1977 up to 1983, 29 patients were operated upon for Crohn's disease with digestive fistula (dead fistulae, ileocecal and contiguous ileoileal fistulae being excluded). The majority of the fistulae arose from the distal ileum (n = 22). After an average duration of the disease of 7 1/2 years, the patients were admitted for surgical treatment, either electively (group I, n = 19), or in urgency (group II, n = 10). Eleven patients exhibited some signs of malnutrition, 13 needed a total parenteral nutrition for an average of 10 days; one patient had to be operated upon in emergency (hemorrhage and sepsis); the others had a normal bowel preparation. The resection of the diseased bowel at the origin of the fistulae included right ileocolic resections (n = 25), left (n = 1) or total (n = 3) colectomies, with primary anastomosis in all but two cases. The "target bowel" was treated as conservatively as possible: limited small bowel resection, single suture of the gastric, duodenal or sigmoidal walls, and bladder drainage. A segmental resection of the sigmoid colon was realized in 5 cases where a single closure of the wall defect was impossible. There was no postoperative death, no septic complications, and no signs of anastomotic dehiscence. Fistula recurrence "in situ" occurred only once. A spectacular health improvement, with a significant weight gain, was observed in 85% of the cases. Further outcome of the disease remains out of control.

[Superselective vagotomy. Preliminary results]. / La vagotomie supersélective. Résultats préliminaires

Twelve patients suffering from an intractable duodenal ulcer are included in this review. Eleven were treated by superselective vagotomy without drainage, one had a selective vagotomy with pyloroplasty. A peroperative control of the gastric acidity after pentagastrin stimulation was used in all cases and permitted section of forgotten nerve fibers. Short-term results are satisfactory: after 2-6 months the clinical state of the patients is excellent (Visick I and II), basal acidity is decreased by 58 to 66% of preoperative value, the Hollander tests are negative except two. After more than 6 months, the few available results are satisfactory except one case of recurrent ulcer. The one case with a 1 year follow-up is excellent, clinically and as to acid secretion.