International journal of pancreatology : official journal of the International Association of Pancreatology最新文献

Studies with different strains of Syrian hamsters and Syrian golden hamsters have revealed the remarkable potential of islet cells to undergo orthotopic and heterotopic metaplasia. The most common spontaneous change included the development of hepatocytes in aged and malnourished hamsters. Of the many other alterations that occurred during carcinogenesis, most of the metaplastic changes originated within the islet periphery and progressed inside and outside the islets. The development of ductular structures within islets and their progression either to structures identical to human serous cystadenoma or to highly invasive adenocarcinomas were the most common alterations. The remarkably greater invasive potential of cancer cells arising within the islets contrasted sharply with the slow growth of the tumors developing within ducts (intraductal tumors). Studies in human tissue also showed development of malignant cells within islets, and, in some cases, transition of islet cells to malignant cells was suggested. The overall results, along with recent findings in other studies in cultured human and hamster islets, indicate the enormous potential of islet cells to differentiate and undergo malignant transformation. Whether the metaplastic and malignant cells derive from stem cells embedded within islets or from transdifferentiated islet cells remains to be seen.

Background: Steatorrhea following major pancreatic resection can be difficult to control, requiring high doses of pancreatic enzyme supplements. The aim of this study was to demonstrate equivalent efficacy of high-dose and standard-dose pancreatin in treating steatorrhea after pancreatectomy.

Methods: A randomized, double-blind, crossover study was conducted with a 2-wk run-in period for stabilization on a suitable dose of standard-dose pancreatin and two 14-d treatment periods using either high-dose or standard-dose pancreatin at this dosage. Parameters used to demonstrate efficacy of treatment were stool fat excretion, stool volume, and clinical symptoms.

Results: Thirty-nine patients who had undergone total or partial pancreatectomy were randomised; 37 completed all parts of the study. During stabilization, the mean daily capsule intake was 19.4 (range 9-54); even so, 22 (56%) patients had stool fat excretion > 7 g/d. There were significant correlations between stool fat excretion and stool volume (p < 0.0001) and stool frequency (p < 0.01), but not with indices of abdominal pain and global symptoms. Both high-dose and standard-dose pancreatin demonstrated statistically similar efficacy in the treatment period.

Conclusion: The use of high-dose pancreatin for the treatment of pancreatic insufficiency in patients following pancreatectomy should significantly reduce capsule intake with increased convenience and greater compliance rate. Our results, however, indicate that further progress is needed to resolve steatorrhea following pancreatic resection.

Compared to pseudocyst formation after prior pancreatitis, true cysts of the pancreas are rare. Pancreatic cysts with irregular wall components or a mucinous content raise the suspicion for the presence of a cystic neoplasm, and surgical resection is recommended. A case of a patient with a history of prostate cancer is described in whom a cyst of the pancreatic tail was discovered incidentally. Based on the radiographic features, which did not support the presence of a serous cystadenoma, a spleen-preserving distal pancreatectomy was performed. Histologic features were characteristic for a lymphoepithelial cyst (LEC) of the pancreas, lined with thinned squamous epithelium surrounded by benign lymphoid tissue. Since LECs of the parotid gland, which are associated with acquired human immunodeficiency, are frequently related to Epstein-Barr virus (EBV) infection, EBV in situ hybridization was performed and did not reveal evidence for EBV. Twenty-eight instances of pancreatic LECs have been reported, primarily affecting adult males, without evidence of increased numbers of EBV-positive cells. The pathogenesis, differential diagnosis, and clinical implications of lymphoepithelial pancreatic cysts are discussed.

Background: The diagnosis, early assessment, and management of severe acute pancreatitis remain difficult clinical problems. This article presents the consensus obtained at a meeting convened to consider the evidence in these areas. The aim of the article is to provide outcome statements to guide clinical practice, with an assessment of the supporting evidence for each statement.

Method: Working groups considered the published evidence in the areas of diagnosis, assessment of severity, nonoperative treatment, and surgical treatment of severe acute pancreatitis. Outcome statements were defined to summarize the conclusions on each point considered. The findings were discussed and agreed on by all participants. A careful assessment was made of the strength of the available evidence (proven, probable, possible, unproven, or inappropriate).

Findings and conclusions: There is reliable evidence to support much current practice. Clear guidance can be given in most areas examined, and several areas were identified where further investigation would be helpful. Diagnosis using plasma concentrations of pancreatic enzymes is reliable. Rapid advances are taking place in the assessment of severity. Several new therapeutic strategies show real promise for the reduction of morbidity and mortality rates. Surgical debridement is required for infected pancreatic necrosis, but is less often necessary for sterile necrosis.

Background: Tissue-specific ablation of a gene using the Cre-loxP system has been used as an important tool to define its role, in addition to the total ablation, to avoid the embryonic lethality in case of wide expression of the target gene.

Methods: The RIP-Cre genetic construct was generated by standard subcloning techniques and microinjected into one cell embryo to develop the transgenic mouse line. Transgenic mice were screened by polymerase chain reaction (PCR) using DNA isolated from tell digestion. Tissue specificity of RIP was demonstrated by transient transfection of RIP-1acZ construct to NIT-1 cells (mouse insulinoma cell line) in vitro.

Results: The 448 nucleotides of RIP were sufficient for beta-cell specific expression of the reporter gene as evidenced by the presence of blue color in the nucleus of NIT-1 cells. Isolated RIP-Cre transgene was microinjected, and PCR screening identified two independent lines of transgenic mice. Tissue specificity of RIP was demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) using the islet RNA from the transgenic mice.

Conclusion: We have established a tissue-specific transgenic mouse model using Cre recombinase linked to rat insulin promoter (RIP) to drive the expression of the reporter gene specifically in the beta-cells. The RIP-Cre transgenic mice will allow beta-cell specific ablation of target gene(s) to define its role in the regulation of islet physiology.

Endoscopic retrograde cholangiopancreatography (ERCP) is diagnostic. Similarly, secretin stimulated ultrasonography may positively predict the outcome of minor papilla therapy. Computed tomography is only helpful for the detection of complications. Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive diagnostic tool in development. It is accurate and might replace ERCP for diagnosis. Clinically, symptomatic patients with PD may be divided into five groups: group 1, those with minimal symptoms; group 2, those with recurrent acute pancreatitis or upper abdominal pain with no other cause; group 3, those with chronic pancreatitis; group 4, those with chronic pancreatic pain; and group 5, those with other complications. Group 1 should be treated with medical therapy alone. The response to surgical or endoscopic therapy of the minor papilla is good in group 2 (75-90%), moderate in group 3 (40-60%), and poor in group 4 (20-40%). A few patients require other forms of pancreatic surgery, such as Puestow's operation, Beger's operation, or distal pancreatectomy. With careful selection of patient and therapy, good response to the therapy can be achieved. Pancreas divisum (PD) is the most common congenital anomaly of the pancreas, with an incidence of up to 10%. Symptoms or complications developing in individuals with PD are uncommon (5% of individuals with PD). It seems unlikely that PD alone could cause obstructive pancreatitis and the presence of another factor, such as minor papilla insufficiency, is probably required for this relatively common anomaly to develop complications.

Conclusion: Serum increases of aminotransferases, especially alanine aminotransferase (ALT), were suggestive of microlithiasis in idiopathic acute pancreatitis, particularly when assessed early after the onset of abdominal pain.

Background: It has been shown that biochemical laboratory values only are useful parameters in distinguishing gallstone from nongallstone acute pancreatitis. We assessed the diagnostic usefulness of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for identification of occult microlithiasis in idiopathic acute pancreatitis.

Methods: Ninety-one patients with idiopathic acute pancreatitis who underwent microscopic examination of stimulated duodenal bile sediments were retrospectively studied. According to earliness of ALT and AST assay after the onset of abdominal pain, patients were divided into two groups: group A, within the first 24 h (n = 56) and group B, between 24 and 72 h (n = 35).

Results: ALT and AST values expressed as number of elevations of the upper limits of normal were higher in group A patients with positive biliary drainage than in group B. Median (range) ALT and AST values were 2.5 (0.1-18.1) vs 0.4 (0.1-8.6) and 3 (0.3-17.4) vs 0.5 (0.3-11.9), respectively. In the univariate analysis and receiver operating characteristic (ROC) curves, ALT within the first 24 h showed a sensitivity of 73%, specificity of 86%, and positive predictive value of 92% for a cutoff of 1.2 elevations of the upper limit of normal. These values were slightly higher, although without statistically significant differences, than those of AST (73, 80, and 89%, respectively).

Conclusion: Abnormality of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 appears to play a limited role in pancreatic ductal carcinogenesis.

Background: Recently, a human G/T-specific TDG gene was identified. This protein acts in a system correcting G/T mispairs to G/C pairs. TDG was mapped to chromosome bands 12q22-q24.1, one of the regions frequently lost in pancreatic cancer. Therefore, there is the possibility that the TDG gene on 12q is one of the genes responsible for pancreatic ductal carcinogenesis.

Methods: Nucleotide sequences of the entire coding region of the TDG gene were analyzed in 21 human pancreatic cancer cell lines. mRNA expression of the TDG gene was also analyzed by Northern hybridization in several human tissues and 21 human pancreatic cancer cell lines.

Results: Decreased levels of mRNA expression were detected in the pancreatic cancer cell lines, but no somatic mutations were observed.

Conclusion: The results of this study show that routine measurements of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) cannot improve screening for pancreatic cancer despite the frequently present tissue overexpression. Both values fail to reveal this malignancy in a serum test. Patients with chronic pancreatitis exhibit no or very low concentrations of EGF. In cases where preoperative diagnosis is difficult the noninvasive EGF and EGF-R serum measurements may be helpful in discriminating between pancreatic cancer and chronic pancreatitis.

Background: EGF and EGF-R are frequently overexpressed in the tissue of patients suffering from ductal pancreatic cancer and to lesser degree in patients with chronic pancreatitis. The aim of this study was to determine the value of serum measurements in these patients to detect malignant pancreatic disease. In cases of pancreatic cancer, the tissue expression of EGF and EGF-R was evaluated by immunohistochemistry.

Method: Thirty-five patients with chronic pancreatitis and 31 patients with pancreatic cancer were evaluated; 71 patients admitted for routine surgery (hernia repair, cholecystectomy, goiter surgery) served as controls.

Results: EGF and EGF-R values were not significantly different in pancreatic cancer as compared to controls and did not correlate with other tumor markers (CA 19-9, carcinoembryonic antigen [CEA], tumor polypeptide antigen [TPA]) or with the stage of the disease. Fourteen patients (67%) with pancreatic cancer displayed tissue overexpression for EGF and 11 patients for EGF-R (52%). These patients, however, also failed to exhibit any significant pathological changes in serum concentration. In chronic pancreatitis, EGF and EGF-R were significantly decreased as compared to pancreatic cancer and controls. This was an unexpected finding. There was a positive correlation to clinical exocrine insufficiency.