PubMed Health⌕ Search

Biomedical subjects

R Fiasse

Publications and source records attributed to R Fiasse.

At least 19 recordsLinked to original sources

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.

Adolescent↗

Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease.

OBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNF have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CD patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease.

Adolescent↗

A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism.

BACKGROUND: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim was to assess the value of C-reactive protein and TNF-alpha serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease. METHODS: Two-hundred-and-twenty-six Crohn disease patients treated in the setting of an expanded access programme to infliximab in Belgium were studied. There were 136 refractory luminal diseases and 90 refractory fistulizing diseases. Luminal diseases were treated with one single infusion; fistulizing diseases with three infusions at weeks 0, 2 and 6. A clinical response to treatment was defined as either a Crohn disease activity index <150 (complete) or a drop of 70 points (partial) at week 4, for luminal disease, and as either complete fistula healing (complete) or a decrease of at least 50% of the number of draining fistulas on two consecutive visits between weeks 0 and 18, for fistulizing disease. CRP and serum TNF-alpha levels were measured at week 0 before treatment and were compared between responders and non-responders. Patients were genotyped for the -308 TNF gene polymorphism, and allelic as well as genotype frequencies were compared between responders and non-responders. RESULTS: There were 73.2% responders (46.4% complete and 26.8% partial) and 26.8% non-responders. Response rates were similar in luminal and fistulizing diseases. CRP level before treatment was significantly higher in responders than in non-responders (16.8 mg/l (5-160) versus 9.6 mg/l (5-143); P = 0.02). Furthermore, response rate was significantly higher in patients with elevated CRP (>5 mg/l) than in patients with a normal CRP value (<5 mg/l) before treatment (76% versus 46%; P=0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype frequencies for -308 TNF gene polymorphism were not significantly different between responders and non-responders--with the exception of a slightly higher TNF2 frequency in non-responders in luminal disease (22.1 % versus 11.6%; P = 0.04). However, this was not associated with a significant difference in genotype frequencies. CONCLUSION: A positive clinical response to infliximab was associated with a higher CRP level before treatment in our population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism. We therefore suggest that CRP level may help to identify better candidates for infliximab treatment.

Adolescent↗

Inflammatory bowel disease in spouses and their offspring.

BACKGROUND & AIMS: The rarity of inflammatory bowel disease (IBD) in both husband and wife is often given as an argument against an infectious origin. We registered conjugal instances of IBD in Northern France and in Belgium between 1989 and 2000. METHODS: Couples were assigned to group A if both partners had symptoms of IBD before cohabitation, to group B if one spouse had IBD before cohabitation and the other experienced first symptoms afterwards, and to group C if both partners got the disease after cohabitation. Risk of IBD was assessed in their offspring. RESULTS: Thirty conjugal instances were registered. Seventeen were concordant for Crohn's disease and 3 for ulcerative colitis; 10 were mixed. Two belonged to group A, 6 to group B, and 22 to group C. In group C, IBD occurred in the first affected spouse an average of 9 years after cohabitation and in the second spouse an average of 8.5 years later. Group C conjugal forms were more frequent than expected by chance (P < 0.02). Fifty-four children were born to 25 couples; among them 9, of whom 4 were siblings, developed Crohn's disease at a median age of 15 years. CONCLUSIONS: The frequency of conjugal forms of IBD suggests an etiologic role for environmental factors. Offspring of 2 affected parents have a high risk of developing IBD.

Adolescent↗

Skeletonizing en bloc esophagectomy for cancer.

OBJECTIVE: To evaluate the long-term outcome of patients with esophageal cancer after resection of the extraesophageal component of the neoplastic process en bloc with the esophageal tube. SUMMARY BACKGROUND DATA: Opinions are conflicting about the addition of extended resection of locoregional lymph nodes and soft tissue to removal of the esophageal tube. METHODS: Esophagectomy performed en bloc with locoregional lymph nodes and resulting in a real skeletonization of the nonresectable anatomical structures adjacent to the esophagus was attempted in 324 patients. The esophagus was removed using a right thoracic (n = 208), transdiaphragmatic (n = 39), or left thoracic (n = 77) approach. Lymphadenectomy was performed in the upper abdomen and lower mediastinum in all patients. It was extended over the upper mediastinum when a right thoracic approach was used and up to the neck in 17 patients. Esophagectomy was carried out flush with the esophageal wall as soon as it became obvious that a macroscopically complete resection was not feasible. Neoplastic processes were classified according to completeness of the resection, depth of wall penetration, and lymph node involvement. RESULTS: Skeletonizing en bloc esophagectomy was feasible in 235 of the 324 patients (73%). The 5-year survival rate, including in-hospital deaths (5%), was 35% (324 patients); it was 64% in the 117 patients with an intramural neoplastic process versus 19% in the 207 patients having neoplastic tissue outside the esophageal wall or surgical margins (P <.0001). The latter 19% represented 12% of the whole series. The 5-year survival rate after skeletonizing en bloc esophagectomy was 49% (235 patients), 49% for squamous cell versus 47% for glandular carcinomas (P =.4599), 64% for patients with an intramural tumor versus 34% for those with extraesophageal neoplastic tissue (P <.0001), and 43% for patients with fewer than five metastatic nodes versus 11% for those with involvement of five or more lymph nodes (P =.0001). CONCLUSIONS: The strategy of attempting skeletonizing en bloc esophagectomy in all patients offers long-term survival to one third of the patients with resectable extraesophageal neoplastic tissues. These patients represent 12% of the patients with esophageal cancer suitable for esophagectomy and 19% of those having neoplastic tissue outside the esophageal wall or surgical margins.

Adenocarcinoma↗

An unusual metastatic motilin-secreting neuroendocrine tumour with a 20-year survival. Pathological, biochemical and motility features.

Motilin-secreting neuroendocrine tumours have been rarely described. Immunohistochemical, biochemical and motility investigations were performed in a 62-year-old man with liver and bone metastases of a motilin-secreting neuroendocrine tumour originating from a rectal polyp removed 14 years previously. Symptoms related to liver metastases were reduced by a right hepatectomy whereas plasma motilin levels were decreased. The patient also underwent two operations for spinal cord decompression and survived 6 more years under medical treatment, mainly octreotide. Immunohistochemistry revealed predominant expression of motilin-containing cells, with rare cells expressing somatostatin and pancreatic polypeptide, and staining for only one panendocrine marker, neurone-specific enolase. A liver tumour extract contained 17.9 microg motilin per gram of tissue, which permitted to isolate and characterize human motilin, which was identical to porcine motilin. Plasma column gel chromatography revealed a main peak corresponding apparently to porcine motilin. The patient had no symptoms of disturbed motility. Gastric emptying and gastroduodenojejunal motility were found within normal limits. The absence of alterations of gut motility was perhaps related to sustained autonomous motilin production. The long evolution of this type of tumour suggests that plasma motilin determination should be added to the investigations for neuroendocrine tumours.

Bone Neoplasms↗

Healing of severe esophagitis improves esophageal peristaltic dysfunction.

Reflux esophagitis is frequently associated with peristaltic dysfunction, which increases with the severity of inflammatory lesions. In order to assess peristaltic dysfunction with more accuracy before and after healing, we used a 24-hr pH and pressure recording method. Nineteen patients (median age: 65, range: 33-77) with stage II and III (Savary-Miller classification) esophagitis and peristaltic dysfunction were treated with 40 mg omeprazole for three to six months until complete endoscopic healing was achieved. Before treatment, median contraction amplitude was significantly lower than median contraction amplitude of a control group of comparable age [31 (21-53) versus 42 (21-77) mm Hg, P < 0.01], as well as median percentage of peristaltic contractions [27 (16-63) versus 44 (11-56), P < 0.01]. At the end of treatment, a statistically significant improvement of esophageal motor functions was observed for both median contraction amplitude [38 (26-55), P = 0.001] and median percentage of peristaltic waves [45 (23-68), P = 0.0001]. The posttreatment values, although still low, were not significantly different from control values. In conclusion, complete healing of grade II and III esophagitis improves peristalsis. Inflammatory processes related to severe esophagitis may be involved in failed peristalsis and low contraction amplitude.

Adult↗

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.

Biopsy↗

Acute lower gastrointestinal bleeding in Crohn's disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group.

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological characteristics and therapeutic options of hemorrhagic forms of Crohn's disease. METHODS: Thirty-four cases of hemorrhagic forms of Crohn's disease were studied retrospectively. Acute lower gastrointestinal hemorrhage was defined as acute rectal bleeding originating in diseased bowel and requiring a transfusion of at least 2 units of red blood cells within 24 h. Upper gastrointestinal tract hemorrhage or anal lesions and postoperative bleeding were excluded. RESULTS: Mean age at time of hemorrhage was 34.2 +/- 14 yr. Mean duration of disease before the hemorrhage was 5.6 +/- 6 yr. The hemorrhage occurred during a flare up of the disease in 35% of cases. The hemorrhage revealed Crohn's disease in 23.5% of cases. The hemorrhage was more frequent in colonic disease (85%) than in isolated small bowel disease (15%) (p < 0.0001). The origin of bleeding was identified in 65% of cases, by colonoscopy (60%), by angiography (3 patients), or at surgery (1 patient). The bleeding lesion was an ulcer in 95% of cases, most often in the left colon. The treatment was surgical in 20.5% (colectomy in 36%), endoscopical (7 patients, including 5 successes), or medical. Hemorrhage recurred in 12 patients (35%) within a mean time of 3 yr (4 days-8 yr), requiring surgery in 3 cases. No death was observed. CONCLUSIONS: This study performed in a series characterized by a nonsurgical recruitment, the largest to date, shows that hemorrhagic forms of Crohn's disease may reveal disease in 23.5%, occurs in quiescent Crohn's disease in two-thirds of cases. Given the potential efficacy of endoscopical or medical treatment, as well as the absence of mortality, a conservative approach may be suggested as first-line therapy in the majority of patients.

Acute Disease↗

Crohn's disease stable remission after human immunodeficiency virus infection.

We retrospectively assessed the clinical course in four patients with long-standing Crohn's disease who became infected with human immunodeficiency virus (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our four patients. They experienced a stable remission of Crohn's disease symptoms after HIV infection. In three patients Crohn's disease was in stable remission for 5, 8, and 8 years after HIV infection and all three died from acquired immunodeficiency syndrome-related disease. One patient was still alive without recurrence of Crohn's disease symptoms 7 years following HIV detection. Our observations of a spontaneous improvement in the clinical course of Crohn's disease after HIV infection, suggests that the integrity of the immune response, especially that of CD4 T cells, plays a major role in the tissue injury mechanism in Crohn's disease.

Adolescent↗

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.

Antineoplastic Agents, Hormonal↗

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.

Amino Acid Sequence↗

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.

Female↗

Occurrence, in Crohn's disease, of antibodies directed against a species-specific recombinant polypeptide of Mycobacterium paratuberculosis.

Sera from patients with Crohn's disease and control were analyzed by an enzyme-linked immunosorbent assay based on the Mycobacterium paratuberculosis-specific recombinant polypeptide a362. Anti-a362 immunoglobulin G (IgG) (P < 0.05) and IgA (P < 0.001) titers were higher in patients with Crohn's disease than in controls. A monomodal Gaussian distribution of anti-a362 IgA levels were found for controls, and a bimodal distribution was found for patients with Crohn's disease. An M. paratuberculosis etiology is suggested for the 36% of patients with Crohn's disease who had an anti-a362 IgA level higher than that of controls.

Antibodies, Bacterial↗

[Anal surgery in Crohn disease].

For twenty years, opinions concerning local surgery of anal lesions in Crohn's disease have changed in practice and in the literature. We have reviewed 209 patients, usually in remission of disease, with at least 6 months' follow-up, who underwent local surgery for various anal lesions from 1974 to 1992. In this study, our indications and results are discussed and compared to the literature. Results of partial haemorrhoidectomy are successful. In anorectal stenosis, with rectal involvement, surgery improves the symptoms and can avoid or delay proctectomy. Results of surgery for simple fistulas appear to be identical in cases with or without Crohn's disease. In complex and suprasphincteric fistulas, seton management improves chronic suppuration, occasionally cures the lesion and reduces the number of tracts. After seton drainage, transanal rectal advancement flaps can be performed, but the results of this procedure have yet to be confirmed.

Anus Diseases↗