Italian journal of gastroenterology and hepatology最新文献

Gastric carcinoid tumours can be divided into subtypes with a different pathogenesis and biological behaviour. Individualized surgical treatment of these tumour types is discussed. Liver metastases imply a major problem in patients with carcinoid tumours. Patients with distant metastases can undergo resection for potential cure, or for symptom palliation, due to the slow growth rate of many carcinoid tumours. In patients with the midgut carcinoid syndrome and bilobar liver metastases, interventional treatment by tumour removal and liver embolization followed by medical therapy (octreotide and/or interferon) seem to prolong survival and reduce hormonal symptoms. Patients with the foregut carcinoid syndrome may present special problems with life-threatening release of histamine during interventional treatment.

With insulinoma, Zollinger-Ellison syndrome is one of the most common functional islet-cell tumour. Since it is a life-threatening condition, needing appropriate management, the diagnosis must be accurately established. This paper reviews the clinical situations leading to suspect the diagnosis and the biological tests, mainly the secretin test, that confirm the diagnosis. The different ways of performing the secretin test and the respective results are presented. This review will also focus on some aspects of the diagnosis of multiple endocrine neoplasia type 1 in these patients.

Most of the neuroendocrine tumours produce and secrete a large number of peptide hormones and amines. Each of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycaemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of: urinary-5-HIAA, serum or plasma gastrin, insulin, glucagon, and VIP, respectively. About 1/3 of neuroendocrine tumours belong to the so-called "non-functioning" tumours. Therefore, general markers such as chromogranin A, pancreatic polypeptide, serum neuronspecific enolase and subunit of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone related syndromes. Among these general tumour markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumours. This is because it may also be increased in many cases of less well differentiated tumours of neuroendocrine origin that do not secrete known hormones. Then chromogranin A is considered the best general neuroendocrine serum or plasma marker available at the moment and is increased in 50-100% of patients with various neuroendocrine tumours. Chromogranin A serum or plasma levels reflect tumour load and may be an independent marker of prognosis in patients with midgut carcinoids.

Aim: To evaluate the prognosis of chronic hepatitis C in relation to interferon therapy response and the persistence of therapeutic benefits.

Patients/methods: We studied the clinical outcome of 191 patients with chronic infection (152 chronic hepatitis C and 39 cirrhosis) treated with recombinant alpha-interferon (3-6 MU on alternate days for 1 year) during a mean period of 47 months (range 22.5-73.8). Control tests were done at 6-month intervals. HCV RNA was determined pre- and post-treatment in all participants, but continued yearly in long-term responders. The appearance of cirrhosis was estimated using a non-invasive method that utilizes a model based on clinical, instrumental and biochemical variables. Ascites, encephalopathy, haemorrhage, hepatocellular carcinoma, and death were considered liver-disease-related events.

Results: A total of 39 patients were long-term responders, 36 relapsers, and 116 non-responders; 92% of long-term responders cleared HCV RNA and remained negative throughout the study period. The 3 HCV-RNA-positive long-term responders continued being so. No biochemical relapse was observed in long-term responders regardless of virological status. New cirrhosis was observed in 3/30 relapsers, in 9/85 non-responders, and in no long-term responders. Overall, 9 episodes of severe events occurred in 20% of cirrhotics and in 0.6% of chronic hepatitis, all non-responders.

Conclusions: Long-term response interrupts the progression to cirrhosis and reduces the incidence of severe complications. Multivariate analysis revealed that "baseline diagnosis of cirrhosis" was the only independent factor predictive of an unfavourable outcome of chronic HCV-related liver disease.

Background: The usefulness of ursodeoxycholic acid after liver transplantation is controversial. Tauroursodeoxycholic acid, the natural taurine-amidate, is a highly hydrophilic and cytoprotective bile salt currently under investigation.

Aims: To investigate the clinical usefulness of tauroursodeoxycholic acid after liver transplantation.

Patients: Thirty-three patients undergoing liver transplantation entered the study.

Methods: Sixteen patients were randomized to receive tauroursodeoxycholic acid (250 b.i.d. for 12 months) and 17 served as controls. Tauroursodeoxycholic acid was given from day 5 after transplantation for one year.

Results: Tauroursodeoxycholic acid treatment was safe and well tolerated. No drop outs occurred. Among the 29 patients undergoing long-term follow-up, five deaths occurred (3 of whom in the tauroursodeoxycholic acid group), none of which was related to treatment. The one-year actuarial survival was 78.6% in patients treated with tauroursodeoxycholic acid and 86.7% in controls (n.s.). No differences were observed with respect to early or late graft function and survival, nor to acute cellular rejection. Tauroursodeoxycholic acid therapy was associated with lower serum cholesterol levels (p < 0.02) during the early postoperative months; with milder cholestasis; with a drop in biliary cholates but no changes in endogenous hydrophobic bile salts.

Conclusions: Long-term treatment with low dose tauroursodeoxycholic acid after liver transplantation is safe but does not affect graft function and survival.

The tight junctions are narrow belts that circumferentially surround the upper part of the lateral surfaces of the adjacent epithelial cells to create fusion points or "kisses". They are involved in maintaining the cellular polarity and in the establishment of compositionally distinct fluid compartments in the body. Tight junctions are formed by many specific proteins and are connected with the cytoskeleton. In contrast to what might be expected, the intestinal tight junctions are highly dynamic areas and their permeability can change in response to both external and intracellular stimuli. In fact, the tight junctions play an important role in the regulation of the passive transepithelial movement of molecules. A number of signalling molecules have been implicated in the regulation of tight junction function, including Ca++, protein kinase C, G proteins, phospholipase A2 and C. In many intestinal and systemic diseases, changes in intestinal permeability are related to alteration of tight junctions as an expression of intestinal barrier damage. Moreover, permeability of the tight junctions can be modified by bacterial toxins, cytokines, hormones and drugs. A better understanding of tight junction structure, biogenesis and regulation mechanisms should throw further light on the intestinal barrier functions and suggest innovative therapeutic strategies.

Maintenance of remission induced by medical therapy and prevention of recurrence after intestinal resection are two of the major goals in Crohn's disease treatment. Two main groups of drugs are employed in prevention of relapse and recurrence: sulfasalazine and 5-aminosalicylic derivatives and the group of azathioprine/6-mercaptopurine. Although most clinical trials on the efficacy of sulfasalazine as maintenance therapy of Crohn's disease have given negative results, it could probably be favourably used in remission maintenance of Crohn's colitis. Controlled studies and two reviews have shown that 5-aminosalicylic derivatives are effective in reducing the risk of relapse. Ileitis and ileocolitis respond better than colitis. These drugs are also able to reduce the severity of lesions and of symptoms after surgery. 6-mercaptopurine and azathioprine can be used in more aggressive forms of the disease. The efficacy of this immuno-suppressive therapy is reported in over 70% of patients and the incidence of associated side effects is acceptable, but 6-mercaptopurine and azathioprine act slowly and the long latency period limits the usefulness of these drugs in some patients.