Gastric electrical stimulation results in improved metabolic control in diabetic patients suffering from gastroparesis.

AIMS/HYPOTHESIS: Symptoms of gastroparesis possess a heavy impact on the quality of life; delayed gastric emptying may result in poor metabolic control in diabetics. Gastric electrical stimulation (GES) has recently been introduced as a treatment option in patients with drug refractory gastroparesis to increase the quality of life by alleviating nausea and vomiting frequencies. However, the effect of GES on metabolic control has not been assessed yet. METHODS: We performed a prospective single center study on the long-term effect (12 months) of continuous high-frequency/low-energy GES on symptoms, gastric emptying (measured scintigraphically), and metabolic control (HbA1c) in insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis for more than one year. RESULTS: Seventeen (12 female, 5 male) patients entered the study; all were available for analysis at all time points. No therapy-associated adverse events occurred. Weekly vomiting and nausea frequencies decreased significantly at 6 and 12 months. Gastric retention rates improved significantly from 83 % (2 h) and 38 % (4 h) to 35 % (2 h)/14 % (4 h) and 25 % (2 h)/17 % (4 h) at 6 and 12 months, respectively. HbA1c values were lowered in all 17 subjects; initially, all HbA1c values were above 7.5 %; at 6 and 12 months, mean values had significantly decreased from 8.6 % to 6.2 % and 6.5 %, respectively. CONCLUSIONS/INTERPRETATION: Gastric electrical stimulation offers symptom control in diabetics with drug-refractory gastroparesis and decreases gastric retention. This study, for the first time, documents a positive effect of this therapy on metabolic control as indicated by HbA1c, a surrogate marker of the risk of diabetic complications.     

Virtual colonography: identification and differentiation of colorectal lesions using multi-detector computed tomography

OBJECTIVE: Early detection of precancerous or malignant lesions may be decisive for prognosis of patients with colorectal cancer. In this prospective feasibility study, multi-detector spiral computed tomography (CT) colonography was compared with conventional colonoscopy for the detection of colorectal polyps. MATERIAL AND METHODS: Seventy-eight patients underwent CT colonography (standard colonoscopy preparation, distension with room air, prone and supine position) immediately before colonoscopy. Sixty-five (83%) were asymptomatic screening subjects, while the rest had symptoms suggestive of colorectal disease. Presence, location, and size of lesions were prospectively assessed. Sensitivity, specificity, and positive and negative predictive values of CT colonography were calculated using conventional colonoscopy as the reference standard. RESULTS: Conventional colonoscopy was normal in 52 patients. In 26 patients a total of 49 polyps and 3 carcinomas were identified. All three carcinomas and 39 polyps (80%) were identified by CT colonography. Seven of 7 polyps > or = 10 mm (100%), 13 of 16 polyps of 6 to 9 mm (81%), and 19 of 26 polyps < or = 5 mm (73%) in diameter were identified. Fourteen false-positive findings (10 of which were < or = 5 mm in diameter) were related to 8 patients (specificity at the patient level was 86%). In 10 patients, a total of 10 polyps were missed by CT colonography, 7 of which were < or = 5 mm in diameter. CONCLUSIONS: In this feasibility study, multi-detector spiral CT colonography allows accurate detection of polyps > 5 mm in diameter, but at the expense of low specificity in the small size range.     

Arterioportal fistula: a rare cause of portal hypertension and abdominal pain.

Esophageal varices are commonly caused by portal hypertension secondary to cirrhosis. We report the case of a 71-year-old woman who presented with esophageal variceal bleeding due to portal hypertension caused by an arteriovenous fistula. The fistula, which was probably brought about by a liver biopsy performed 18 years previously, was complicated by bleeding. Since this event, the patient has reported right upper quadrant pain. Embolization resulted in elimination of the varices as well as abdominal discomfort.     

Effects of secretin antibody on gastric acid inhibition and pancreatic bicarbonate stimulation by acidified liver extract meal in dogs

Duodenal acidification is known to inhibit gastric H+ secretion while stimulating pancreatic HCO-3 secretion, but the mechanisms of these effects have not been fully explained. This study was designed to determine the role of endogenous and exogenous secretin in gastric inhibition and pancreatic stimulation by an acidified liver extract (LE) meal in conscious dogs prepared with chronic gastric and pancreatic fistulas pretreated with normal serum (control) or anti-secretin serum. In control tests, plasma gastrin and gastric H+ secretion showed a marked rise with LE meals at pH ranging from 7.0 to 4.0, but significantly declined at pH 3.0 and 2.0. Plasma secretin and pancreatic secretion started to rise with LE meals at pHs below 4.5, and both reached peaks at pH 2.0. Exogenous secretin infused at graded doses suppressed plasma gastrin and gastric H+ responses to LE meals at doses of 1.0 and 2.0 U/kg-h, but increased, dose-dependently, plasma secretin and pancreatic HCO-3 starting with a dose of 0.03 U/kg-h. Following the administration of anti-secretin serum, the effects of exogenous secretin on plasma gastrin and secretin levels as well as on gastric and pancreatic secretion were almost completely abolished. The increase in plasma secretin and pancreatic HCO-3 responses to LE meals at pH below 4.5 were also abolished by anti-secretin serum, but the suppression of plasma gastrin level and the inhibition of gastric H+ responses to LE meals at lower pH (3.0 and 2.0) remained virtually unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bicarbonate and cyclic AMP content of pure human pancreatic juice in response to graded doses of synthetic secretin.

In seven healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the papilla of Vater. Synthetic secretin was intravenously infused in doses doubled every 20 min. The volume of pancreatic juice was proportional to the log of the secretin dose. A significant rise (P less than 0.05) in pancreatic juice flow was elicited at a dose as low as 8.05 ng per kg per hr. Maximum flow rate approximating 250 mul per 5 min per kg of body weight was attained during infusion of 129 ng per kg per hr. At the same dose maximal bicarbonate outputs averaging 383 muEq per hr per kg of body weight were obtained, whereas bicarbonate ion concentration approached peak values (135 +/- 9 muEq per ml) at 32.2 ng per kg per hr. Bicarbonate concentrations showed a tendency to fall at supramaximal doses. The effect of increasing secretin doses on bicarbonate and cyclic AMP concentrations was remarkably similar (rs = 0.635, P less than 0.001) suggesting the participation of cyclic AMP in human pancreatic bicarbonate secretion.     

Extent of Primary Breast Cancer Surgery: Standards and Individualized Concepts

Surgery is still a main therapeutic option in breast cancer treatment. Nowadays, methods of resection and reconstruction vary according to different tumors and patients. This review presents and discusses standards of care and arising questions on how radical primary breast cancer surgery should be according to different clinical situations. In most early breast cancer patients, breast conservation is the method of choice. The discussion on resection margins is still controversial as different studies show conflicting results. Modified radical mastectomy is the standard in locally advanced breast cancer patients, although there are different promising approaches to spare skin or even the nipple-areola complex. A sentinel node biopsy is the standard of care in clinically node-negative invasive breast cancer patients, whereas the significance of axillary lymphonodectomy seems to be questioned through a number of different findings. Although there are interesting findings to modify surgical approaches in very young or elderly breast cancer patients, it will always be an individualized approach if we do not adhere to current guidelines. Up to date, there are no special surgical procedures in BRCA mutation carriers or patients of high-risk families.     

13-norleucine motilin versus pentagastrin: contrasting and competitive effects on gastrointestinal myoelectrical activity in the conscious dog.

In conscious fasted dogs, with chronically-implanted electrodes in stomach and small intestine, typical aborally-propagated interdigestive myoelectric complexes were induced by the infusion of 13-nor-leucine motilin (13-Nle-M); whereas when the normal interdigestive activity was abolished by the infusion of pentagastrin, the resulting 'postprandial' pattern of activity was not significantly modified by the administration of 13-Nle-M. Results from this study provide further evidence that Motilin as well as Gastrin may be involved in the control of gastrointestinal motility in dogs.     

IL-10 Synergizes with IL-4 and IL-13 in Inhibiting Lysosomal Enzyme Secretion by Human Monocytes and Lamina Propria Mononuclear Cells from Patients with Inflammatory Bowel Disease

Tissue injury and inflammation in inflammatorybowel disease (IBD) are associated with enhancedmonocytic lysosomal enzyme release. In this study,peripheral monocytes and lamina propria mononuclearcells (LPMNC) were isolated from IBD patients andnormal controls. Cells were stimulated withlipopolysaccharide after treatment with IL-13, IL-4, andIL-10, and enzyme secretion was assessed by using thecorresponding p-nitrophenyl glycosides as substrates.Molecular forms of cathepsin D were examined to describethe mode of enzyme release. IL-10 and IL-4 stronglydown-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness tothe inhibitory effect of IL-13. Impaired monocyteresponse was not found with combinations of IL-13 andIL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretioncompared with LPMNC from noninvolved IBD mucosa butresponded inefficiently to either IL-4, IL-13, or IL-10alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressedenzyme release by these cells. Both the precursor andmature forms of cathepsin D were elevated in IBDpatients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both theprecursor and mature form of cathepsin D. Our resultsfavor the potent clinical utility of combined treatment,thus improving chances of developing effective treatments for human IBD.