Clinical follow-up on weight loss, glycemic control, and safety aspects of 24 months of duodenal-jejunal bypass liner implantation.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device designed to induce weight loss and improve glycemic control. The liner is licensed for a maximum implant duration of 12 months. It might be hypothesized that extension of the dwelling time results in added value. The goals of our study were to determine weight change, change in glycemic control, and safety in patients with an intended 24 months of DJBL dwelling time. METHODS: Patients were initially selected for a 12-month implantation period. When no physical complaints or adverse events (AEs) occurred, motivated patients who responded well were selected for extension of dwelling time to 24 months. Patients underwent a control endoscopy 12 months after implantation and visited the out-patient clinic every 3 months up to explantation. Patients agreed to remove the DJBL when complaints or AEs occurred that could not be treated conservatively. RESULTS: Implantation was extended in 44 patients, and 24 (55%) patients completed the full 24 months. Twenty patients required early removal due to AEs. During dwelling time, body weight decreased significantly (15.9 kg; TBWL 14.6%). HbA1c decreased non-significantly (4.9 mmol/mol). The number of insulin users and daily dose of insulin both decreased significantly. At 24 months after removal, glycemic control had worsened, while body weight was still significantly lower compared to baseline. In total, 68% of the patients experienced at least one AE. Two patients developed a hepatic abscess. CONCLUSIONS: DJBL treatment results in significant weight loss and improves glycemic control during implantation. The largest beneficial effects occur during the first 9-12 months after implantation. Extension of dwelling time to 24 months results only in stabilization of body weight and glycemic control. After explantation, weight improvements are maintained, but glycemic control worsens. As the cumulative risk of AEs increases with time, a maximal dwelling time of 12 months is advisable.

High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients.

Naive and central memory T lymphocytes (TN and TCM ) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of TN and TCM lymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively. Biopsy samples of inflamed and normal intestine, respectively, were analysed by immunohistochemistry for lymphocytes (CD3/CD20), blood vessels (CD31) and peripheral lymph node addressin (PNAd) expression (MECA-79). TN and TCM lymphocyte subsets were identified by flow cytometric immunophenotyping. A higher number of HEVs was found in the inflamed colon of patients with ulcerative colitis [median 3·05 HEV/mm2 ; interquartile range (IQR) = 0-6·39] and ileum of Crohn's disease patients (1·40; 0-4·34) compared to healthy controls (both 0; P = 0·033). A high density of colonic HEVs (HEVhigh ) was associated with increased infiltration of TN and TCM in the inflamed gut (median 87%; IQR = 82-93% of T cell population), compared to HEVlow patients (58%; 38-81%; P = 0·003). The number of colonic follicles was higher in HEVhigh patients (median 0·54/mm2 ; IQR 0·28-0·84) compared to HEVlow patients (0·25/mm2 ; 0·08-0·45; P = 0·031) and controls (0·31/mm2 ; 0·23-0·45; P = 0·043). Increased homing of TN and TCM lymphocytes to inflamed gut tissue in IBD patients might be facilitated by ectopic formation of extrafollicular HEVs and TLOs in a subgroup of patients.

[Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial]. / Probioticaprofylaxe bij voorspeld ernstige acute pancreatitis: een gerandomiseerde, dubbelblinde, placebogecontroleerde trial.

OBJECTIVE: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. METHOD: A total of 296 patients with predicted severe acute pancreatitis (APACHE II score > or = 8, Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l) were included and randomised to one of two groups. Within 72 hours after symptom onset, patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days. The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up: infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis or infected ascites. Secondary endpoints were mortality and adverse reactions. The study registration number is ISRCTN38327949. RESULTS: Treatment groups were similar at baseline with regard to patient characteristics and disease severity. Infections occurred in 30% of patients in the probiotics group (46 of 152 patients) and 28% of those in the placebo group (41 of 144 patients; relative risk (RR): 1.1; 95% CI: 0.8-1.5). The mortality rate was 16% in the probiotics group (24 of 152 patients) and 6% (9 of 144 patients) in the placebo group (RR: 2.5; 95% CI: 1.2-5.3). In the probiotics group, 9 patients developed bowel ischaemia (of whom 8 patients died), compared with none in the placebo group (p = 0.004). CONCLUSION: In patients with predicted severe acute pancreatitis, use of this combination of probiotic strains did not reduce the risk of infections. Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients.

Heterozygous alpha-I antitrypsin deficiency as a co-factor in the development of chronic liver disease: a review.

Alpha-I antitrypsin (AIAT) is an acute-phase protein that is produced in liver cells. AIAT deficiency is a hereditary disease which is defined by the hepatic production of an abnormal protein that can not be released into the plasma. This leads to deficiency of plasma AIAT and subsequently to an impaired protection against proteases, resulting in pulmonary disease. Accumulation of the abnormal protein in hepatocytes can lead to liver damage. Serum level measurement, phenotyping and liver biopsy can be used for establishing the diagnosis. Homozygous AIAT deficiency can cause neonatal hepatitis; in adults end-stage liver disease, cirrhosis and hepatocellular carcinoma can develop. There are strong arguments to consider heterozygous AIAT deficiency as an important co-factor in the aetiology of chronic liver disease. Studies have shown that AIAT heterozygosity can be considered a modifier for hepatitis C virus, end-stage liver disease, cirrhosis and hepatocellular carcinoma. The accumulation of AIAT in the hepatocytes occurs more profoundly in a diseased liver, and as a consequence it affects the natural course of the liver disease. Therapeutic options include augmentation therapy (infusion of purified human plasma AIAT) in pulmonary disease; in end-stage liver disease liver transplantation is an option. For the future, other interventions such as gene therapy or strategies to inhibit polymerisation are promising.

[A man with oral ulcers caused by hypereosinophilic syndrome and a good response to the tyrosine-kinase inhibitor imatinib]. / Een man met orale ulcera door hypereosinofiel syndroom en met een goede respons op de tyrosinekinaseremmer imatinib.

For the last 2 years, a 55-year-old man had painful, recurrent oral ulcers. Histological examination showed non-specific inflammation. Eosinophilia in the blood and bone marrow raised the suspicion of hypereosinophilic syndrome. No other specific organ involvement was observed. The diagnosis was confirmed by detection of the fusion gene 'FIP1-like-1-platelet-derived growth factor receptor alpha' (FIP1L1-PDGFRA) in the peripheral blood and bone marrow. Treatment with the tyrosine-kinase inhibitor imatinib resulted in a rapid response that has been maintained for more than 2 years. Hypereosinophilic syndrome is a rare haematological disorder. Until recently diagnosis was made by exclusion, and the course of disease was often fatal. Fusion of the FIP1L1 gene to the PDGFRA gene was identified recently in some patients with hypereosinophilic syndrome. The fusion results in a novel tyrosine kinase that is constitutively activated and may induce proliferation ofhaematopoietic cells. Treatment with imatinib targets this tyrosine kinase. These advances in our understanding of the molecular biology of the disease will lead to a new classification of hypereosinophilic syndrome with specific therapeutic options.

[Heterozygosity for alpha1-antitrypsin deficiency as a cofactor in the development of chronic liver disease]. / Heterozygotie voor alpha1-antitrypsinedeficiëntie als cofactor bij de ontwikkeling van een chronische leveraandoening.

In 3 patients, 2 men aged 51 and 40 years and a 50-year-old woman, with liver-function disorders due to excessive consumption of alcohol, the liver function deteriorated rapidly resulting in the patients' death. All 3 were found to be heterozygous for alpha1-antitrypsin (AT) deficiency. Alpha1-AT deficiency can lead to cirrhosis of the liver and pulmonary emphysema. There are indications that heterozygous alpha1-AT deficiency can contribute to the development of a chronic liver disease, even when the serum level of alpha1-AT is within the normal range, especially in association with other risk factors such as alcohol abuse or chronic viral hepatitis. Persons with this mutation also have an increased risk for the development of cryptogenic cirrhosis and primary liver-cell carcinoma. Determination of the alpha1-AT phenotype should perhaps be recommended for all patients with a chronic liver disease, especially if the liver function deteriorates more rapidly than expected, even in the presence of a normal alpha1-AT serum level. A liver biopsy remains the gold standard for establishing the presence of alpha1-AT deposits in the liver.

Contrast Enhanced Abdominal Ultrasound in the Assessment of Ileal Inflammation in Crohn's Disease: A Comparison with MR Enterography.

BACKGROUND AND AIMS: To prospectively examine the feasibility and accuracy of Contrast Enhanced Ultrasound (CEUS) in the assessment of Crohn's disease (CD) activity in the terminal ileum in comparison to Magnetic Resonance Enterography (MRE), using endoscopy as a reference standard. METHODS: 105 consecutive patients with alleged clinically active CD were assessed by MRE and CEUS. CEUS of the terminal ileum was performed using an intravenous microbubble contrast enhancer. Accuracy values of CEUS and MRE for the presence of active terminal ileitis were evaluated using the Receiver Operating Characteristic method, using endoscopic findings as a reference standard. Sensitivity and specificity values of MRE and CEUS were compared by the McNemar test. RESULTS: CEUS was feasible in 98% of patients, MRE in all. Optimal diagnostic accuracy in CEUS was obtained at a peak intensity value of 10%, showing 100% sensitivity, 92% specificity and an accuracy of 99% in demonstrating ileal mucosal inflammation. For MRE, overall sensitivity, specificity and accuracy were, 87%, 100%, and 88%, respectively. CEUS and MRE were highly correlated in assessing length and wall thickness of the terminal ileum. CEUS identified 11 of 16 MRE-detected strictures, but no fistulae. CONCLUSION: The accuracy of CEUS is comparable to that of MRE in the assessment of active, uncomplicated terminal ileal CD and therefore a valuable bedside alternative to MRE in the follow-up of these patients.

Cyclosporin in the treatment of adults with refractory coeliac disease--an open pilot study.

AIM: To evaluate the effect of cyclosporin treatment on clinical and histological parameters in adult patients with refractory coeliac disease. METHODS: Thirteen patients were treated with oral cyclosporin for 2 months, aiming at serum levels of 100-200 ng/mL. Seven extended medication intake up to a maximum of 12 months. Before and after treatment, clinical parameters were monitored and small intestinal biopsies taken. Ten of 13 patients were typed for HLA-DQA1 and -DQB1 alleles. RESULTS: Eight of 13 patients responded histologically to cyclosporin treatment. Normalization of villi was demonstrated in five patients, three after prolonged treatment. Eight patients reported a clinical response, of whom six had concomitant histological improvement. No serious side-effects of cyclosporin were noticed. Nine of 10 patients who were immunogenetically typed carried the coeliac disease associated serologic DQ2 markers, one carried neither DQ2 nor DQ8 markers. CONCLUSION: In our study group of 13 adult refractory coeliac disease patients, cyclosporin in therapeutic doses induced a histological improvement in eight patients (61%), in five of whom (38%) normalization of villi was demonstrated. Thus, we believe that cyclosporin is a therapeutic option in refractory coeliac disease, although we could not confirm earlier reports of unconditional successful treatment.

Azathioprine and prednisone combination therapy in refractory coeliac disease.

INTRODUCTION: Refractory coeliac disease (RCD) is a rare syndrome with a poor prognosis, defined by malabsorption due to gluten-related enteropathy after initial or subsequent failure of a strict gluten-free diet and after exclusion of any disorder mimicking coeliac disease. PATIENTS AND METHODS: Nineteen patients were included and treated. Based on intraepithelial T-lymphocyte(IEL) phenotyping, patients were recorded as having RCD type I with normal IELs, or RCD type II with phenotypically immature IELs defined by a lack of characteristic T-cell markers. Treatment consisted of azathioprine combined with prednisone for 1 year, which was tapered and, if possible, stopped. RESULTS: Clinical improvement was seen in nearly all patients in both groups. Eight of 10 RCD type I patients responded histologically, and complete normalization of villi was seen in four patients. In RCD type II, 6/8 patients developed enteropathy-associated T-cell lymphoma (EATL) and 7/8 patients died. CONCLUSIONS: For the first time we report a promising therapeutic treatment option for RCD type I. In RCD type II, azathioprine and prednisone therapy (APT) is not effective, therefore we suggest that other (chemo)therapeutic agents are considered. Not all RCD type II patients presented with a monoclonal TCRgamma-gene rearrangement and immunohistological changes as is currently reported in the literature. Therefore, immunophenotyping seems mandatory in the work-up of RCD.

The absorption kinetics of subcutaneously infused U 40 and U 100 insulin in diabetics.

The influence of U 40 and U 100 insulin on the insulin kinetics during continuous subcutaneous insulin infusion (CSII) was investigated in eight insulin-dependent diabetics. CSII was started at t = -1.5 h with a bolus of 2 IU at the individual treatment infusion rate (22-35 IU/24 h), followed at t = 0 h by a premeal dose of 6 IU. Insulin delivery was interrupted for 120 min at t = 4 h and reinitiated with a loading dose of 2 IU for another 2 h. The incremental peak plasma free insulin levels and the time to reach these levels after the premeal insulin dose were not significantly different: 17 +/- 2 vs. 16 +/- 2 mU/l and 144 +/- 22 vs. 129 +/- 9 min for U 40 and U 100 insulin, respectively. During the 2 h interruption of insulin delivery plasma free insulin levels declined by 5.0 +/- 1.6 and 7.2 +/- 1.3 mU/l (NS) for U 40 and U 100 insulin, respectively. The blood glucose profiles were virtually identical throughout the studies for either insulin concentration. These results indicate that varying the insulin concentration in the range between U 40 and U 100 does not affect the insulin kinetics during CSII in insulin-dependent diabetics.

A pilot study of recombinant human interleukin-10 in adults with refractory coeliac disease.

Refractory coeliac disease (RCD) is a rare diagnosis made after the exclusion of any disorder mimicking CD and after initial or subsequent failure of a strict gluten-free diet (GFD) to restore normal intestinal architecture. In the past, treatments such as steroids, cyclosporin and azathioprine have been tried, but literature on this subject consists mainly of case reports. Interleukin-10 (IL-10) may be beneficial in RCD because of its inhibitory effect on T-lymphocyte- and monocyte-driven immune responses. We performed a pilot, non-randomized, open label study to evaluate recombinant human IL-10 in RCD. IL-10 (8 mcg/kg) was administered subcutaneously, three times a week for 3 months in 10 RCD patients. Small bowel biopsies were taken at T = 0, T = 3 months and T = 9 months. The mucosal histopathology at 3 months was the primary end point for evaluation of efficacy. Evaluations of clinical features, malabsorption parameters and safety were made prior to, during and after treatment. Before treatment, all RCD patients had partial to total villous atrophy (Marsh III ABC). Two patients dropped out of the study: one because of headaches, the other because of thrombocytopenia. In the remaining eight patients, after 3 months of IL-10 treatment histology was unchanged in five patients, improved in two patients and deteriorated in one patient. Disappearance of villous atrophy was seen in only one patient. Three patients reported a clinical response, i.e. relief of fatigue, abdominal complaints and diarrhoea. After stopping IL-10 treatment the symptoms recurred. The laboratory parameters remained the same during treatment and in follow-up. In conclusion, in our study group of 10 RCD patients, IL-10 in the given dosage was not overall effective in our study group of RCD patients. Two dropped out because of side effects and in only one patient did we see a normalization of villous architecture.

Refractory coeliac disease: a window between coeliac disease and enteropathy associated T cell lymphoma.

The treatment of coeliac disease (CD) is straightforward and simple: life-long adherence to a gluten-free diet. However, in a small subgroup of patients, the clinical and histological abnormalities persist or recur. This non-responsiveness leaves a poorly understood syndrome known as refractory coeliac disease (RCD). A specific definition of RCD is lacking in the literature. We speculate that RCD may appear in a subgroup of coeliacs with persisting histologic abnormalities. In all patients screened for RCD we look for DQ2 and DQ8. In non-DQ2/DQ8 patients we reconsider the diagnosis of CD and of auto-immune enteropathy. Most of the patients referred to us because of suspicion of RCD are affected by other diseases. Probably the commonest cause of non-responsiveness is continued gluten intake. Exocrine pancreas insufficiency, hyperthyroid disease, collagenous colitis are other common explanations. RCD and enteropathy-associated T cell lymphomas (EATL) can be distinguished by intra-epithelial lymphocyte phenotyping and TCR-gamma gene rearrangements. In RCD, an unexplained sustained stimulation of T cell cytotoxic activity is present. Immunosuppressive treatment might moderate this. Cyclosporine has been reported as a resounding success in case reports; however, our results were disappointing. We suggest azathioprine and steroids in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD with aberrant T-lymphocytes we suggest chemotherapy. As the prognosis of EATLs is extremely poor the early detection of RCD with aberrant T cells is crucial.

Coeliac disease: changing views on gluten-sensitive enteropathy.

BACKGROUND: The continuing flow of scientific development in coeliac disease in the past decade points to the need for the formulation of a new concept of pathophysiology and clinical approach to the coeliac condition. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6; immunological research has led to the concept of a T-cell-driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies; and our understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten-sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs, and it may present with less severe symptoms of malabsorption. Screening studies suggest an overall prevalence of up to 1 in 200-300. METHODS: Update on histopathology concentrating on the work of our research group. RESULTS: We specifically describe the work of our group in Arnhem concerning the identification and validation of the spectrum of intestinal histopathology in gluten-sensitive enteropathy, i.e. lymphocytic enteritis (Marsh I lesion), lymphocytic enteritis with crypt hyperplasia (Marsh II lesion), and villous atrophy, subdivided into partial villous atrophy (Marsh IIIA), subtotal villous atrophy (Marsh IIIB) and total villous atrophy (Marsh IIIC). Special attention is given to a subgroup of 'refractory coeliacs', including the identification of (pre-)malignant aberrant T cells in the intestinal mucosa of these patients. CONCLUSION: New data on immunogenetics, epidemiology, histopathology and patient characteristics point to a significant change of view on coeliac disease.

Routine duodenal biopsy to screen for coeliac disease is not effective.

BACKGROUND: Routine duodenal biopsies during upper gastrointestinal endoscopy (UGE) have been suggested to be useful in detecting coeliac disease (CD). However results from previous studies are not conclusive. The aim of this study is to investigate the diagnostic yield and cost-effectiveness of routine duodenal biopsy during UGE. METHODS: In this retrospective single-centre study, we studied 6442 patients undergoing first-time UGE at the Rijnstate Hospital, Arnhem, the Netherlands, from January 2009 to December 2010. All UGE reports were analysed for indication, duodenal intubation, and endoscopic aspect of duodenal mucosa. Endomysium and tissue transglutaminase antibody titre, when present, were scored as positive or negative. CD was defined as Marsh 3a or higher. Costs of duodenal biopsies and pathology analysis were calculated. Comparisons were done with T-tests for continuous data and Chi-square tests for categorical data. RESULTS: Forty-one patients had newly diagnosed CD; 34 of these 41 patients had definite indications for biopsy prior to UGE, e.g. positive serology or symptoms. Thus, routine duodenal biopsies identified seven patients as having CD, who otherwise would not have been biopsied. The number needed to biopsy was therefore 577, spending more than v 30,000 per case. CONCLUSIONS: We do not recommend routine duodenal biopsy to screen for coeliac disease because of the high number needed to biopsy as well as high costs.

Colonic explosion during endoscopic polypectomy: avoidable complication or bad luck?

We were confronted recently by an intraluminal colonic explosion during a colonic polypectomy procedure using snare loop electrocautery, probably caused by the presence of hydrogen and/or methane in combustible concentrations. Our patient needed immediate surgery, when several lacerations were found in the colon: a right hemicolectomy and a partial sigmoid resection with primary anastomoses were performed. Colonic bacteria, rests of fecal fluids, certain cleansing solutions, and oxygen insufflation are the main factors involved in cases of colonic explosion. We describe this dramatic event in our patient and discuss whether this complication might be avoidable in the future.

Basal and fat-stimulated plasma peptide YY levels in celiac disease.

The distal gut hormone peptide YY (PYY) mediates feedback inhibition of gastric acid secretion, gastrointestinal motility, and pancreatic enzyme output. To investigate the influence of maldigestion on PYY, we determined plasma PYY levels in patients with celiac disease under basal conditions and in response to intraduodenal fat. Basal PYY was increased in untreated celiac patients (N = 13) compared to patients on a gluten free diet (N = 9) [15.6 (11.8-27.0) pM vs 12.2 (10.1-13.1) pM; P < 0.05] and compared to control subjects (N = 15) [9.5 (8.3-10.4) pM; P < 0.001]. Integrated PYY in response to intraduodenally infused predigested fat (1071+/-293 pM 80 min) was significantly (P < 0.05) greater than in response to undigested fat (322+/-223 pM 80 min) in six untreated celiacs. Plasma concentrations of PYY and cholecystokinin were strongly correlated (r = 0.79; P < 0.001). We conclude that basal PYY levels in untreated celiac disease are elevated, that predigestion of fat enhances PYY release in these patients, and that PYY secretion is correlated with CCK release.

Venous versus arterialised venous blood for assessment of blood glucose levels during glucose clamping: comparison in healthy men.

The aim of this study was to investigate the influence of the arteriovenous (A-V) gradient in blood glucose concentrations at low and high insulin levels on the determination of glucose requirements during glucose clamping in 9 healthy, insulin sensitive, male volunteers. In a random order two clamps were performed, once using arterialised venous blood (A Clamp, mean pO2 = 11.5 +/- 0.36 kPa, 86 +/- 2.7 mmHg), and once using venous blood (V clamp, mean pO2 = 7.9 +/- 0.21 kPa, 59 +/- 1.6 mmHg). Insulin levels were maintained at 48 +/- 2.4 mU/l from 0-180 min and at 1054 +/- 114 mU/l from 180-360 min. Elevation of insulin levels caused a significant rise of the A-V gradient: from 0.3 +/- 0.1 to 0.5 +/- 0.1 mmol/l (p < 0.05) and from 0.2 +/- 0.1 to 0.3 +/- 0.1 mmol/l (p < 0.05) during the A and V clamps, respectively. Despite these A-V glucose gradients no significant differences were found for the glucose requirements during the last 30 min of each period of insulin infusion between the A and V clamps: 43.70 +/- 3.4 vs 44.8 +/- 2.8 mumol.kg-1.min-1 during the low insulin level and 77.3 +/- 5.0 vs 76.2 +/- 3.4 mumol.kg-1.min-1 during the high insulin level. We conclude that the A-V glucose gradient, even at high insulin levels, does not influence the assessment of glucose requirements to a measurable extent, allowing the use of the simpler technique of taking venous rather than arterialised venous blood for the measurements of glucose levels during glucose clamping.

Argon plasma coagulation in flexible gastrointestinal endoscopy: pilot experiences.

BACKGROUND AND STUDY AIMS: In argon plasma coagulation (APC), high-frequency energy is transmitted to tissue by ionized gas, thus reducing contact with the tissue to a minimum. Successful endoscopic APC was initially reported in the palliative treatment of gastrointestinal neoplasms. The main objectives in this pilot study were to evaluate the treatment indications, efficacy and safety of the use of APC. PATIENTS AND METHODS: Between September 1994 and January 1996, APC was used to treat 125 patients with various forms of gastrointestinal pathology. RESULTS: For local palliative treatment, APC was successfully used alongside snare loop coagulation, dilation, stenting and/or radiotherapy to treat the following conditions: carcinoma of the esophagus: 15 patients, mean number of treatment sessions (MTS) 3.3; gastric carcinoma: 10 patients, MTS 4.9; rectosigmoid carcinoma: seven patients, MTS 2.7; carcinoma of the papilla of Vater: two patients, MTS 1.5. Repeated treatment was also effective for tubulovillous adenoma of the rectum (20 patients, MTS 2.5), stomach (three patients, MTS 2.0), duodenum (two patients, MTS 1.5) and papilla of Vater (two patients, MTS 3.0). In addition, APC proved helpful in coagulating the remaining tissue and achieving hemostasis after polypectomy in the colon (18 patients, MTS 1.2) and in endoscopic treatment of Zenker's diverticulum, for coagulation of the tissue bridge and hemostasis (31 patients, MTS 2.5). Finally, APC was helpful in coagulation of multiple gastric polyps (one patient, one session), hemostasis in superficial ulceration of the duodenal bulb (one patient, one session), after dilation of benign stenoses of anastomoses in the esophagus (one patient, one session) and colon (one patient, one session) and for vascular malformations in the colon (three patients, MTS 1.3), duodenum (one patient, one session), antrum (one patient, two sessions), and watermelon stomach (six patients, MTS 2.8). We recognized signs of perforation in six patients after treatment of Zenker's diverticulum (n = 3), polypectomy in the colon (n = 2) and coagulation of angiodysplasia in the cecum. Laparotomy was carried out in two patients; in one, a perforation was sutured, and in the other no focus of leakage was seen. All six patients recovered without further complications. No complications were observed in any other patients. CONCLUSIONS: These initial experiences indicate that APC seems to be effective in a number of indications, and relatively safe. Objective evaluation, a longer follow-up period, and comparative trials with other treatment modalities should follow.

Glutathione S-transferases in small intestinal mucosa of patients with coeliac disease.

Patients with villous atrophy due to coeliac disease have an increased risk of developing small intestinal malignancies. Intestinal glutathione (GSH) and glutathione S-transferases (GST) are involved in the protection against carcinogenesis. The aim of this study was to evaluate GSH content and GST enzyme activity in small intestinal mucosa of untreated coeliacs compared to controls. We evaluated GSH content and GST enzyme activity, including the levels of GST classes alpha, mu, pi and theta, in small intestinal biopsies of untreated coeliacs (flat mucosa, Marsh IIIC, n = 12) compared to normal subjects (n = 23). Next, we evaluated GSH and GST's in coeliacs in remission (Marsh 0 - I, n = 11), coeliacs with persisting villous atrophy while on a gluten-free diet (partial villous atrophy, Marsh IIIA (n = 5); subtotal villous atrophy, Marsh IIIB (n = 6)) and patients with infiltrative / crypt-hyperplastic Marsh II lesions (n = 4). Total GST enzyme activity and content of GSTalpha are markedly suppressed in Marsh IIIC lesions compared to controls (resp. 220 +/- 79 vs. 464 +/- 189 nmol / mg protein*min (P < 0.001) and 2.79 +/- 2.46 vs. 6.47 +/- 2.29 mg / mg protein (P < 0.001)). In coeliacs in remission these levels normalized. Total GST enzyme activity and GSTalpha levels are proportionately lowered according to the degree of mucosal pathology in Marsh II, IIIA and IIIB. (Spearman's sigma correlation coefficient for total GST, -0.596, P < 0.001; GSTalpha, -0.620, P < 0.001). GSTmu, pi and theta and GSH levels are not significantly different in the selected study groups of mucosal pathology compared to controls. Total GST enzyme activity and content of GSTalpha in small intestinal mucosa are significantly lower in untreated coeliac disease compared to controls. In Marsh II, IIIA and IIIB, GST enzyme activity and GSTalpha content are proportionally lower according to the degree of mucosal pathology. Normal values are seen in coeliacs in remission. This correlation between coeliac disease and a suppressed GSH / GST detoxification system may explain in part the carcinogenic risk in untreated coeliac disease.

Gluten challenge in borderline gluten-sensitive enteropathy.

OBJECTIVES: In patients with signs and symptoms of malabsorption, suggestive of gluten-sensitive enteropathy, small intestinal biopsies sometimes only reveal infiltration of lymphocytes into the mucosal epithelium. This infiltrative lesion (Marsh I) is not a definite proof for gluten-sensitive enteropathy. However, in the present study, we aimed to show that a subgroup of these patients could ultimately be identified as being gluten sensitive. METHODS: A total of 38 patients with a Marsh I lesion were subjected to a gluten challenge comprising 30 g of gluten added daily to a normal gluten-containing diet for 8 wk. Before and after the challenge, small intestinal biopsies were taken, and symptoms and signs of malabsorption were scored. RESULTS: In 12 patients we demonstrated a significant change in mucosal histopathology, i.e., subtotal villous atrophy (Marsh IIIB, n = 1), partial villous atrophy (Marsh 3A, n = 6) or infiltrative-crypthyperplastic lesions (Marsh II, n = 5). In the other 26 patients, the small intestinal mucosa remained unchanged. After initiation of a gluten-free diet, follow-up small intestinal biopsies in 12 patients who initially had progressive mucosal pathology after gluten challenge showed normalization of mucosal pathology in seven cases, regression to a Marsh I lesion in four, and to a Marsh II lesion in one. Symptom relief was seen in all 12 patients. Ten of 26 patients without histological response to the gluten challenge were motivated to adhere to a gluten-free diet. Follow-up biopsies revealed unchanged Marsh I lesions in eight patients and normalization (Marsh 0) in two patients. Three patients had follow-up biopsies while on a normal diet. All had unchanged Marsh I lesions. CONCLUSIONS: In the present study we demonstrated that a gluten challenge might be useful in identifying patients as being sensitive to gluten if initial small intestinal biopsies reveal only minor abnormalities.