Differential expression of connective tissue growth factor in inflammatory bowel disease

Inflammatory bowel disease consists of Crohn's disease (CD) and ulcerative colitis (UC). A major clinical problem in some patients is to differentiate clearly between these entities, which is important when planning appropriate medical and surgical treatment. Connective tissue growth factor (CTGF), a novel peptide involved in fibrotic disorders, was analyzed in the present study in CD and UC patients to evaluate its possible role in these two disorders. Twenty-five normal human intestinal tissue samples were obtained through an organ donor program. CD tissues were obtained from 28 individuals undergoing partial intestinal resection (17 small bowel; 11 large bowel) due to complications of the disease. UC tissue samples were obtained from 16 patients undergoing colectomy due to complications of the disease. Expression of CTGF was studied by Northern blot analysis. In situ hybridization was used to localize mRNA moieties in the tissue samples. Northern blot analysis revealed an average 5-fold increase in CTGF mRNA expression in 89% (25/28) of CD tissue samples by comparison with normal controls (p < 0.0001). In contrast, in UC samples CTGF mRNA levels were comparable to those of normal controls. However, UC tissue samples exhibited enhanced TGF-beta1 mRNA levels (4-fold; p < 0.05). In situ hybridization in CD samples showed CTGF mRNA localized especially in fibroblasts within the submucosal layer, around lymph follicles and in some areas of intense damage in the proximity of the luminal surface, whereas inflammatory cells were devoid of any CTGF mRNA signal. The present data indicate that CTGF plays a different role in IBD and might be useful, especially in those cases with unusual disease presentation, to better differentiate UC and CD. In addition, our data indicate a crucial role for CTGF in CD, where fibrosis and stenosis are frequent complications that require surgery.     

Detection of oncogenes in chronic pancreatitis

BACKGROUND: The pathogenesis of chronic pancreatitis (CP) remains poorly understood. Recently, molecular biology has identified the genetic background for many patients with hereditary CP. In addition, a number of studies have focused on the detection of proto-oncogenes and tumour suppressor gene mutations in the pathogenesis of CP. So far, the use of these mutations (with the exception of mutations causing hereditary CP), as diagnostic and prognostic markers is still controversial. DISCUSSION: It is well known that the risk of pancreatic cancer in patients with CP, especially the hereditary form, is high. At present, there is insufficient evidence to show a clear relationship between the development of pancreatic cancer and certain mutations. New biotechnological methods, such as DNA array expression analysis, expand our knowledge of the molecular pathogenesis of this disease and may help to develop specific diagnostic, prognostic and therapeutic tools. However, until long-term studies examine the safety and efficacy of certain genetic markers, long-term follow-up of patients with CP who harbour mutations is needed.     

联合应用激光微切和实时定量RT-PCR检测单个胰岛的基因表达

在显微镜下用紫外激光微切机将单个胰岛从胰腺切片中切下，提取RNA后逆转录成cDNA并在实时定量RY—PCR中得到有效的扩增，其表达量与细胞数量成正比。     

The diagnostic value of the amino acid absorption test in detection of a disorder of exocrine pancreatic function]

The amino acid consumption test (AACT) during exogenous stimulation with secretin and CCK was proposed as a sensitive and highly specific test for detection of exocrine pancreatic insufficiency. To further investigate the diagnostic value of this test we measured the AACT in comparison with the pancreolauryl serum test (PLT) in patients with chronic pancreatitis and in patients with gastrointestinal diseases but without pancreatic disease. A total of 48 patients, 23 patients with chronic pancreatitis (CP) and 25 patients with gastrointestinal diseases, were included in the study. Diagnosis of chronic pancreatitis was established by standardized morphological criteria in ultrasound, ERCP, CT, and was confirmed by surgery in 11 cases. The PLT was abnormal in 83% of patients with chronic pancreatitis and normal in 92% of the control subjects (diagnostic accuracy 88%). Basal amino acid concentration was comparable in patients with chronic pancreatitis and in control subjects (300 +/- 12 [symbol: see text] 325 +/- 16 mumol/l). The peak decrease of amino acids occurred after 30 min during combined stimulation with secretin and ceruletide and was not different between the two groups (CP: 11.2 +/- 1.7%, controls: 13.9 +/- 1.9% below basal values). With a 12% decrease of amino acids as cutoff, sensitivity was 74% and specificity 52% (diagnostic accuracy 63%). Integrated amino acid decrease did not show any significant differences between CP and controls (CP: 228 +/- 63% min, controls: 397 +/- 80% min). Determination of the individual amino acids serine, valine, histidine, and isoleucine could also not discriminate between patients with chronic pancreatitis and other gastrointestinal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surveillance of pre-malignant disease of the pancreatico-biliary system

Technical advancements in ultrasonography, contrast-enhanced computed tomography and magnetic resonance imaging, as well as the wider availability of these ultramodern imaging techniques, have resulted in the early detection and a better classification of various asymptomatic and symptomatic pancreatico-biliary lesions. Pre-malignant biliary and pancreatic lesions are rare disorders, and no clear data are available to define their malignant potential. Because of the lack of controlled epidemiological data, the time span for malignant transformation and its frequency cannot be defined in the majority of these lesions. Adenomyomatosis of the gallbladder and gallbladder polyps larger than 10 mm should be treated by cholecystectomy even in asymptomatic patients because of an increased risk of malignant transformation. Chronic cholangitis, primary sclerosing cholangitis and choledochal cysts are also pre-malignant conditions. The timing of surgery, once it is advised for a pre-malignant condition that is still benign, should, however, be individualized to the particular patient situation. In patients with chronic pancreatitis, surgery may be indicated for disease-related complications. In as much as chronic pancreatitis predisposes to a higher risk of pancreatic cancer, any suspicion of malignancy should warrant a surgical exploration. Intraductal papillary tumours and mucin-producing pancreatic tumours are other pre-malignant pancreatic lesions whose malignant potential cannot be precisely determined pre-operatively. They should be resected in situations where there is a high degree of suspicion even without a clear objective diagnosis. In conclusion, pre-malignant hepato-biliary and pancreatic lesions of uncertain pathology should undergo early resection in view of treatment limitations and the dismal prognosis of established cancers. While hepato-biliary and pancreatic surgery is nowadays performed in specialized centres, with a low post-operative morbidity and mortality, it is equally important to understand that observation alone with regular computed tomography or magnetic resonance imaging control can no longer be recommended in the management of these lesions.     

Real-time quantitative PCR of telomerase mRNA is useful for the differentiation of benign and malignant pancreatic disorders

The presence of telomerase activity has been proposed as a specific and sensitive marker for malignant tissue, and positivity rates of up to 95% have been reported in pancreatic cancer. In the present study telomerase activity analysis was reevaluated in 29 pancreatic cancer tissues compared with 36 chronic pancreatitis tissues and 21 normal controls, and a study was made of whether malignant and benign pancreatic disorders can be better differentiated using a novel technique real-time quantitative PCR analysis-analyzing telomerase mRNA expression. Telomerase activity was present in 35% (10 of 29) of pancreatic cancer samples, 3% (one of 36) of chronic pancreatitis samples, and none of the normal pancreatic tissue samples in the TRAP assay. Real-time quantitative PCR analysis revealed the presence of telomerase mRNA expression in 50% (10 of 20) of normal, 86% (31 of 36) of chronic pancreatitis, and 90% (26 of 29) of pancreatic cancer samples. However, quantification of the expression data revealed that the relative increase above normal was 5.5 (range, 3.5-8.6) for chronic pancreatitis and 23.9 (range, 18.6-30.7) for pancreatic cancer samples (p < 0.01). No relationship was found between telomerase activity and the fold increase of telomerase mRNA above normal and gender, patient age, tumor stage, or tumor grade. These data indicate that detection of telomerase activity using the TRAP assay has limitations in differentiating benign and malignant pancreatic disorders. However, telomerase mRNA analysis by real-time quantitative PCR analysis allows a highly sensitive detection and differentiation of pancreatic cancer from normal pancreas and chronic pancreatitis and thereby may serve as a new reliable, easy, and effective diagnostic tool for cancer diagnosis.     

Spätkomplikationen nach Pankreaseingriffen

Background

Benign and malignant pathologies of the pancreas can result in a relevant chronic disease burden. This is aggravated by morbidities resulting from surgical resections as well as from progression of the underlying condition.

Objective

The aim was to summarize the current evidence regarding epidemiology, pathophysiology, diagnosis and treatment of endocrine and exocrine pancreatic insufficiency, as well as of pancreatic pseudocysts.

Material and methods

A selective literature search was performed and a summary of the currently available data on the surgical sequelae after pancreatic resection is given.

Results

Reduction of healthy pancreatic parenchyma down to 10–15?% leads to exocrine insufficiency with malabsorption and gastrointestinal complaints. Orally substituted pancreatic enzymes are the therapy of choice. Loss of pancreatic islets and/or islet function leads to endocrine insufficiency and pancreoprivic diabetes mellitus. Inflammatory, traumatic and iatrogenic injuries of the pancreas can lead to pancreatic pseudocysts, which require endoscopic, interventional or surgical drainage if symptomatic. Finally, pancreatic surgery harbors the long-term risk of gastrointestinal anastomotic ulcers, bile duct stenosis, portal vein thrombosis and chronic pain syndrome.

Conclusion

As the evidence is limited, an interdisciplinary and individually tailored approach for delayed pancreatic morbidity is recommended.