Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease.

BACKGROUND: Neuropeptides, such as substance P (SP), are mediators of neurogenic inflammation and play an important role in inflammatory disorders. To further investigate the role of the SP pathway in inflammatory bowel disease (IBD), we analyzed the following in normal intestinal tissue specimens and in tissue specimens from patients with Crohn's disease (CD) and ulcerative colitis (UC): neurokinin receptor-1 (NK-1R); its isoforms (NK-1R-L and NK-1R-S); its ligand SP, encoded by preprotachykinin-A (PPT-A); and the SP-degradation enzyme, neutral endopeptidase (NEP). METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was used to simultaneously determine the expression of NK-1R-L, NK-1R-S, and PPT-A. Protein levels of NK-1R and NEP were determined by immunoblot analysis. RESULTS: In noninflamed small-bowel tissue samples of CD patients, PPT-A mRNA expression was significantly increased, whereas there was no difference between inflamed or noninflamed UC and normal intestinal tissue samples. Examining subgroups of diverse intestinal segments from CD and UC samples with various levels of inflammation revealed no differences in NK-1R-L and NK-1R-S mRNA expression, whereas there was a tendency toward overall lower NK-1R-S mRNA copy numbers. Immunoblot analysis showed upregulation of NK-1R protein levels in cases of IBD, with more pronounced enhancement in cases of CD than in UC. For NEP, there were no differences in protein levels in normal, CD, and UC intestinal tissues. COMMENTS: These observations suggest a contribution of SP and its receptor, NK-1R, in the local inflammatory reaction in IBD and particularly in ileal CD. Moreover, significant upregulation of PPT-A mRNA in the noninflamed ileum of these patients suggests an influence of inflamed intestines on their healthy counterparts.

Contrast-enhanced computed tomography in acute pancreatitis: does contrast medium worsen its course due to impaired microcirculation?

BACKGROUND: An early and accurate diagnosis of severe acute (necrotizing) pancreatitis is important to allow timely institution of therapy to limit the extra-pancreatic sequelae of this necrotizing process and to minimize the incidence of super-infection of the necrosis (i.e., progression to infected necrosis). Contrast-enhanced computed tomography (CECT) has become the cornerstone of diagnosis by confirming the clinical diagnosis of severe acute pancreatitis based on the various clinical scoring criteria. Moreover, CECT serves as an anatomic roadmap for guiding radiological and surgical interventions. However, still-controversial experimental studies in animals in the mid-1990s suggested that the use of intravenous radiographic contrast media early in the course of the disease might exacerbate the necrotizing process by further impairing the already compromised pancreatic microcirculation. A series of experimental and clinical studies followed that have both refuted and supported this claim; unfortunately, none is conclusive, and the topic remains, as yet, unresolved. AIMS: Our objective was to review objectively the available literature found by a Medline search on this subject. METHODS: Meta-analysis and review. RESULTS AND CONCLUSION: Our conclusion, after analysis of these studies, is that there are no well-substantiated data that could resolve the controversy. However, several caveats will be offered.

Detection of circulating tumor cells by cytokeratin 20 and prostate stem cell antigen RT-PCR in blood of patients with gastrointestinal cancers.

BACKGROUND: Detection of circulating tumor cells in blood may be an important diagnostic and prognostic factor in the management of tumor patients. The present study aimed to examine whether cytokeratin 20 (CK-20) and prostate stem cell antigen (PSCA) are useful markers for the detection of disseminated cancer cells in the blood of tumor patients. MATERIALS AND METHODS: A nested RT-PCR assay was used to detect CK-20 and PSCA mRNA in blood samples from 18 healthy donors, 15 patients with non-malignant disease, 9 patients with benign tumors and 47 patients with malignant tumors (11 pancreatic carcinoma, 8 gastric cancer, 15 colorectal carcinoma and 13 miscellaneous tumors). RESULTS: CK-20 expression was observed in the peripheral blood of 19 out of 47 (40.4%) patients with malignant tumors, 2 out of 9 (22.2%) patients with benign tumors and 3 out of 15 (20%) patients with non-tumor diseases. PSCA expression was present in the blood of 22 out of 47 (46.8%) patients with malignant tumors and particularly in 7 out of 11 (63.6%) patients with pancreatic cancer. CK-20 and PSCA expression was not observed in blood samples from healthy donors. There was a relationship between PSCA expression and tumor stage. CONCLUSION: The present results demonstrate that it is possible to apply a simple and reliable method for the detection of circulating tumor cells based on CK-20 and PSCA RT-PCR assays.

Influence of contrast-enhanced computed tomography on course and outcome in patients with acute pancreatitis.

INTRODUCTION: Many of the complications in severe acute pancreatitis result from the amplifying effects of microcirculatory disruption. Contrast medium may cause significant additional reductions of capillary flow, which has been shown to aggravate acute pancreatitis in experimental studies. AIM: To investigate the role of serial contrast-enhanced computed tomography (CECT) in patients with acute pancreatitis. METHODOLOGY: A retrospective analysis evaluated 302 patients with moderate to severe acute pancreatitis. Among these patients, 264 underwent CECT within 96 hours of the onset of symptoms and again during the course, but in 38 patients no serial CECT was performed. Outcome measurement was analyzed by comparison of hospital stay and mortality rate between the two patient groups. Influences of contrast medium on severity of disease were detected by monitoring complications during the course of treatment, C-reactive protein, and APACHE II score. RESULTS: The 1-month mortality rate was less in patients with CECT (6.4% versus 15.8%, p <0.05). There were no significant differences considering the incidence of additional complications, and hospital stay was not significantly longer (29 +/- 36 versus 19 +/- 13 days). C-reactive protein and APACHE II score had similar time courses. CONCLUSION: Contrast-enhanced computed tomography remains crucial in identifying patients with acute pancreatitis at high risk to develop necrosis of the pancreas and systemic complications. Contrast medium has been found to aggravate acute pancreatitis in animal models. As compared with the patient group without being exposed to contrast medium, however, this study did not show a deterioration of acute pancreatitis by administration of contrast medium in men.