ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

This year has witnessed substantial advances in receptor biology and signal transduction that are relevant to the function and regulation of the healthy pancreas and to the pathogenesis and potential therapy of pancreatitis and pancreatic carcinoma. There has been an expansion in the cast of pancreatic regulatory molecules, now including protease-activated receptors, chemokines, and chemokine receptors. There have been new insights into the cellular distribution and signaling initiated at the classic pancreatic receptors. There have also been dramatic advances in insights into the structure of G protein-coupled receptors, with the first solution of a crystal structure of a member of this superfamily, and into the molecular basis of ligand binding and activation of these important molecules. This will clearly improve the opportunities for the rational design and refinement of receptor-active drugs. In addition to these fundamental advances, there has been renewed attention to the expression, function, and regulation of receptors and signaling pathways in pancreatic cells present in the setting of pancreatitis and pancreatic carcinoma. It is hoped that this will contribute toward earlier diagnosis, more successful therapy, and new chemopreventive strategies for these illnesses.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The exocrine pancreas is regulated by various hormonal factors derived from the gut through hormone-hormonal and neurohormonal interactions. Physiologic stimuli entering the upper small intestine elicit the release of intestinal hormones and activate sensory reflex mechanisms from the intestinal mucosa to stimulate or inhibit exocrine pancreatic secretion. In addition, the endocrine pancreas, intrapancreatic nerves, and some extrapancreatic neural pathways, with or without mediation by the vagus nerve, are known to participate in regulation of exocrine pancreatic secretion. It has been established that two key intestinal hormones, secretin and cholecystokinin (CCK), in physiologic doses, act through the vagal afferent pathway and interact with each other as well as with other gut hormones. The releases of these two hormones are mediated through the corresponding releasing peptides. In the past few years, the roles of secretin-and CCK-releasing peptides have become more clearly defined. The participation of several neurotransmitters and regulatory peptides in the regulation of exocrine pancreatic secretion has also been established. In addition, neurotransmitters and neuropeptides released from the central nervous system may participate in the regulation of pancreatic secretion. It is conceivable that a few neurotransmitters and neuropeptides are involved in each neural regulatory pathway. However, their roles and sites of action in each pathway remain to be determined.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The pathophysiologic concept of acute pancreatitis focuses on early events inside acinar cells such as activation of trypsin. Despite significant progress in the understanding of molecular events in experimental pancreatitis, knowledge of these mechanisms has not yet been translated into therapeutic strategies useful in humans. A single morphologic or laboratory marker reliably predicting the individual course of acute pancreatitis still awaits discovery. The clinical outcome of acute pancreatitis is dependent on the presence of necrosis and systemic complications. The extent of the systemic inflammatory response to local pancreatitis seems to be the rate-limiting step. Several mechanisms shed light on the interconnectivity between intra-acinar protease activation and immunoregulatory processes. Deciphering these cell biologic connections has already had an impact on the clinical management of patients and the identification of prognostic markers in human disease. However, further investigations of pancreatic pathophysiology are needed to initiate novel therapeutic strategies.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

An increasing number of novel mutations are associated with chronic pancreatitis. Some cause a high-penetrance, autosomal dominant type of clinical picture (eg,mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others have a low penetrance or are frequent in the general population (eg,mutations in Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen gene) and act as disease modifiers. The results of recent studies indicate that smoking adversely affects the course and complications of chronic pancreatitis (more frequent and faster rate of calcification and higher risk of development of pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients with this condition should not smoke. Using current diagnostic criteria, the accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is not good. For example, 39% of dyspeptic persons without any other evidence of chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not prevented or increased by pancreatic surgery. Islet cell autotransplantation holds promise for the prevention of diabetes in patients requiring total pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein occlusion is present in 7% of patients undergoing surgery for chronic pancreatitis, but fewer than one fifth of these patients have variceal bleeding before or after surgery.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Transforming growth factor-&bgr; (TGF&bgr;) plays a critical role in pancreatic development and cell proliferation. Binding of TGF&bgr; to its membrane receptor kinases activates the Smad signaling proteins, allowing them to translocate to the nucleus and participate in the transcriptional control of TGF&bgr; target genes. In addition, there is an increasing number of cellular mechanisms affecting the final response of a cell to TGF&bgr;. This includes crosstalk with other signaling pathways and the induction of TGF&bgr; early response genes, such as the TGF&bgr;-inducible early response gene (TIEG) family of transcription factors. Like the Smads, TIEGs behave as downstream effector proteins in TGF&bgr;-mediated pancreatic growth control. The discovery of the Smads and TIEGs has provided new insights into TGF&bgr;-regulated functions. Their significance in pancreatic development and cancer is discussed in this review.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Recent advances have been made in both laparoscopic and endoscopic techniques for diagnosing and treating pancreatic neoplasms. These advances are reviewed. In addition to the traditional methods of pancreatic resection (eg, standard Whipple and pylorus-preserving Whipple), several other techniques have been described and are discussed (eg, median pancreatectomy and extended pancreatectomy). The morbidity and mortality rates of pancreatic operations have diminished, but significant complications still occur (eg, delayed gastric emptying, pancreatic fistula, and biliary strictures). These are discussed. In managing acute and chronic pancreatitis, less invasive and more conservative approaches are being advocated.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Advances in cellular and molecular biology of extrahepatic cholangiocarcinoma and gallbladder adenocarcinoma are providing innovative means for the diagnosis and treatment of biliary tract cancer. Similarly, refinements in noninvasive studies—including helical computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography—are enabling more accurate diagnosis, staging, and treatment planning for these tumors. Complete resection remains the only means for cure, and recent reports from major hepatobiliary centers support aggressive wide resection for bile duct and gallbladder cancer. Palliation of malignant strictures has improved with advanced endoscopic techniques, newer polyurethane-covered stents, endoscopic microwave coagulation therapy, and radiofrequency intraluminal endohyperthermia. The preliminary data on such minimally invasive techniques suggest an improvement in quality of life and survival for selected patients.

ISSN:0267-1379    

出版商:OVID    

年代:2001

数据来源: OVID