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Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours ( n =23) was compared with historic controls ( n =48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.

A key task for health policymakers is to optimise the outcome of health care interventions. The pricing of a new generation of cancer drugs, in combination with limited health care resources, has highlighted the need for improved methodology to estimate outcomes of different treatment options. Here we introduce new general methodology, which for the first time employs continuous hazard functions for analysis of survival data. Access to continuous hazard functions allows more precise estimations of survival outcomes for different treatment options. We illustrate the methodology by calculating outcomes for adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate, which selectively inhibits the activity of a cancer-causing enzyme and is a hallmark representative for the new generation of cancer drugs. The calculations reveal that optimal drug pricing can generate all win situations that improve drug availability to patients, make the most of public expenditure on drugs and increase pharmaceutical company gross profits. The use of continuous hazard functions for analysis of survival data may reduce uncertainty in health care resource allocation, and the methodology can be used for drug price negotiations and to investigate health care intervention thresholds. Health policy makers, pharmaceutical industry, reimbursement authorities and insurance companies, as well as clinicians and patient organisations, should find the methodology useful.

Introduction Improvements are needed in the management of cancer-induced bone pain (CIBP). The objective of this study was to assess the efficacy and safety of pregabalin compared with placebo in the adjunctive treatment of patients with moderate to severe CIBP who were receiving opioids. Methods In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, 152 adults diagnosed with a malignant, solid tumor with metastases to bone were randomized to flexible-dose pregabalin (100, 150, 300, or 600 mg/day) or placebo, as add-on to stable opioid analgesic therapy, which was optimized prior to the start of the study. The primary efficacy endpoint was the duration-adjusted average change (DAAC) from baseline in the daily worst pain at the reference site (measured by 11-point numeric rating scale [NRS]) during the fixed-dosage phase. The study was terminated early following an interim analysis that indicated an increase in sample size would be needed to satisfy statistical assumptions for the primary endpoint. Given the early termination of the study, only descriptive analyses were performed. Results The mean (standard deviation) DAAC from baseline in NRS score for the primary endpoint favored pregabalin treatment: −1.53 (1.81) in the pregabalin group and −1.23 (1.74) in the placebo group. Mean DAAC for average pain and sleep interference (NRS) also favored pregabalin. More patients treated with pregabalin reported improvement (“very much improved,” “much improved,” or “minimally improved”) based on Patient Global Impression of Change: 81.4% compared with 70.0% in the placebo group. Conclusion Data from this study indicate that pregabalin use may reduce metastatic bone pain. Due to the incomplete analysis, further study of pregabalin in the management of CIBP is required.

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group.

Using immunohistochemical techniques we studied duodenal biopsies from 18 patients with coeliac disease and 24 patients with normal duodenal morphology. We had access to antisera against the following gastrointestinal peptides: cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin-17, glucagon-enteroglucagon, motilin, neurotensin, pancreatic peptide (PP), secretin, somatostatin, substance P and vasoactive intestinal peptide (VIP). The somatostatin, GIP, CCK, and glucagon cells were increased in number in coeliac disease. The number of motilin cells was slightly increased, while secretin cells were reduced. Cells storing gastrin-17, substance P, or neurotensin were rare in all patients regardless of diagnosis. No PP immunoreactive cells were found and VIP was localised to neurons only. In biopsies from patients having a mucosa with ridging of villi the number of the various endocrine cell types did not differ from that in the control group.

In obese patients, jejunoileal bypass (JIB) has been used to induce weight reduction. Changes in the neuroendocrine system may be affected by the JIB-operation, because the proximal small intestinal mucosa has a rich supply of endocrine cells and peptidergic nerves. In 37 obese patients operated with JIB 1-30 years ago, small intestinal biopsies were taken at the duodeno-jejunal flexure, proximal to the anastomosis and from 5 unoperated obese persons and 20 normal weight patients. The tissue specimens were processed for immunocytochemical demonstration of cells/nerves containing: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), motilin, somatostatin, serotonin, glicentine, peptide YY (PYY), neurotensin, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and galanin. The number of different endocrine cell-types were counted per unit length of mucosa, and the density of the peptidergic nerves was assessed semiquantitatively according to a schematic scale. JIB-patients had an increased density of CCK and somatostatin cells in the duodenal mucosa. The CCK cells displayed a changed reaction pattern, with a greater cell number reacting with an antiserum directed towards a non-amidated mid-sequence of procholecystokinin compared with the other groups. In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups. JIB induces an up-regulation of somatostatin and CCK precursor-containing cells in the duodenal mucosa. The time duration after the JIB did not seem to influence the results.

Twenty-nine adult patients with coeliac disease and 39 patients with a normal duodenal morphology were studied with respect to the 5-ht containing enterochromaffin cells. Their number in duodenal biopsies was assessed by fluorescence histochemistry and they were examined by immunohistochemistry for peptides known or believed to occur in enterochromaffin cells. Antisera used were raised against substance P, motilin, and leu-enkephalin. In addition, the concentration of 5-HT was determined chemically. In adult coeliac disease there was a significant increase in the number of duodenal enterochromaffin cells compared with the control group. The concentration of 5-HT in the duodenal mucosa was also greatly increased. Substance P was found in a minority population of enterochromaffin cells. These cells were very few and did not increase in number in coeliac disease. Motilin cells were distinct from enterochromaffin cells. No enkephalin immunoreactive cells were found in the biopsies.

Two patients with specific pancreatic amylase deficiency are described. The greatly reduced pancreatic amylase activity was not due to an enzymatically inactive amylase molecule but to an almost complete absence of the molecule itself. The findings are of diagnostic importance as they show that low pancreatic amylase activity in serum or duodenal aspirates, or both, does not necessarily represent chronic exocrine pancreatic disease such as chronic pancreatitis, carcinoma of the pancreas, or cystic fibrosis but may be an isolated finding. In one of our patients a familial occurrence was shown, indicating a congenital deficiency.

The need for partial gastrectomy has decreased as a result of reduced incidence and improved endoscopic and medical treatment of peptic ulcer disease. Nonetheless, several patients with resected stomach remain in the population, and it is well known that important pathological changes can occur in the gastric remnant. We evaluated the morphological and functional status of the gastric stump by use of modified endoscopic Congo red test (MCRT). For this purpose, 87 partially gastrectomized (Billroth I and II) patients referred for elective gastroscopy were consecutively enrolled. We found a high prevalence of severe chronic atrophic fundal gastritis (CAFG) (67%) in the gastric remnant. We also observed, however, that one‐third of the patients had almost unaffected gastric acid production even as long as 26 years after partial gastrectomy. Moreover, the accuracy, sensitivity, and specificity of routine gastroscopy in diagnosing CAFG in the gastric stump were found to be 55%, 50%, and 84%, respectively. The presence of bile reflux correlated well with the degree of CAFG. Importantly, we observed that more than 71% of the patients receiving acid‐suppressing therapy had no or very little capacity to produce gastric acid. Taken together, our study has demonstrated that MCRT is a simple and well‐tolerated method providing important morphological and functional information about the mucosa of the resected stomach. Furthermore, MCRT was superior to routine gastroscopy in diagnosing CAFG in the gastric stump. Outcome studies should define the clinical benefit of MCRT in the management of patients with resected stomach.