The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment o...The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.展开更多
AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with ...AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα.Each group of mice was matched with a similar group of sham control animals.Macroscopic and histological features were scored blindly.Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage.RESULTS:DSS produced submucosal erosions,ulcers,inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc.The effect was more pronounced in the latter group (vs Zn diet,P < 0.02).Myeloperoxidase activity (vs controls,P < 0.02) and DNA adducts,greatly elevated in the DSS fed colitis group (vs controls,P < 0.05),were significantly reduced in the treated groups,with a more remarkable effect in the group receiving combined therapy (vs standard diet,P < 0.04).CONCLUSION:DSS induces colonic inflammation which is modulated by the administration of anti-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.展开更多
AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS: The series included...AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS: TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1β was higher in cirrhosis patients (P=0.05). A sig- nificant correlation was found between TNF-α and staging (P= 0.05) and between IL-1β levels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype (P= 0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.展开更多
Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G contributed analyti...Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G contributed analytic tools; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C analyzed the data; Diamantis G and Scarpa M wrote the paper; all authors revised and approved the final version of the manuscript.展开更多
Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attrib...Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.展开更多
About 50% of patients with hepatitis C virus(HCV)infection complain of neuropsychiatric symptoms,"brain fog",weakness,fatigue,and exhibit some degree of quality of life impairment,irrespective of the severit...About 50% of patients with hepatitis C virus(HCV)infection complain of neuropsychiatric symptoms,"brain fog",weakness,fatigue,and exhibit some degree of quality of life impairment,irrespective of the severity of liver disease.Since the first observation of HCV-related cognitive deficits,10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment.Unfortunately,these have often included patients with cirrhosis,patients who had acquired the infection through previous intravenous drug misuse,who had a history of relatively recent treatment with interferon,or were on psychoactive medication.In addition,different neuropsychological batteries and tests that explored different cognitive domains were used,which makes the results of the studies difficult to compare.Finally,limited information is available on the pathogenesis of HCV-related cognitive impairment.Cerebral and/or systemic inflammation may be important players but their potential role has not been substantiated by experimental data.The present review outlines the available evidence of the presence of cognitive impairment in patients with HCV infection,with a focus on the potential relationship with cerebral and/or systemic inflammation.展开更多
AIM:To assess B1a cell expression in the rectal mucosa of ulcerative colitis (UC) patients in comparison with healthy controls.METHODS:Rectal mucosa biopsies were collected from 15 UC patients and 17 healthy controls....AIM:To assess B1a cell expression in the rectal mucosa of ulcerative colitis (UC) patients in comparison with healthy controls.METHODS:Rectal mucosa biopsies were collected from 15 UC patients and 17 healthy controls.CD5 + B cells were analysed by three colour flow cytometry from rectal mucosal samples after mechanical disaggregation by Medimachine.Immunohistochemical analysis of B and T lymphocytes was also performed.Correlations between,on the one hand,rectal B1a cell concentrations and,on the other,erythrocyte sedimentation rate and C-reactive protein levels and clinical,endoscopic and histological disease activity indices were evaluated.RESULTS:Rectal B-lymphocyte (CD19 + /CD45 +) rate and concentration were higher in UC patients compared with those in healthy controls (47.85% ± 3.12% vs 26.10% ± 3.40%,P=0.001 and 501 ± 91 cells/mm 2 vs 117 ± 18 cells/mm 2,P < 0.001);Rectal B1a cell density (CD5 + CD19 +) was higher in UC patients than in healthy controls (85 ± 15 cells/mm 2 vs 31 ± 6.7 cells/mm 2,P=0.009).Rectal B1a cell (CD5/CD19 +) rate correlated inversely with endoscopic classification (Rs=-0.637,P < 0.05).CONCLUSION:B1a lymphocytes seem to be involved in the pathogenesis of UC,however,the role they play in its early phases and in disease activity,have yet to be defined.展开更多
AIM:To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for he...AIM:To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified as minimal, mild, moderate or severe. RESULTS: HBV recurred in 7/42 (16.6%) patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients (7.1%), minimal/non-specific changes were observed in 18 (64.2%), and at least 1 biopsy showed CH in the remaining 8 (28.5%). Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg+ or HBsAg- liver diseases.CONCLUSION: Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.展开更多
Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells h...Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastro-enterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immunemediated conditions,further studies are needed to fully understand the biology of stem cellsand carefully assess their put ativeonco- genicproperties.Moreover,there searchonstemcellsarousesferventethical,socialandpoliticaldebate.TheItalianSocietyofGastroenterologysponsoredaworkshoponstemcellsheldinVeronaduringtheⅩⅥCongressoftheFederationofItalianSocietiesofDigestiveDiseases(March 6-9,2010).Here,we report on the issues discussed,including liver and intestinal diseases that may benefit from stemcell therapy,the biology of hepatic and intestinal tissue repair,and stem cell usage inclinical trials.展开更多
AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxi...AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo , S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150 000/μL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFα, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150 000/μL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen. CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.展开更多
Diverticular disease(DD) of the colon is very common in developed countries and is ranked the fifth most important gastrointestinal disease worldwide.The management of acute diverticulitis without perforation and peri...Diverticular disease(DD) of the colon is very common in developed countries and is ranked the fifth most important gastrointestinal disease worldwide.The management of acute diverticulitis without perforation and peritonitis is still debated.Health related quality of life(HRQL),subjectively perceived by patients,is becoming a major issue in the evaluation of any therapeutic intervention,mainly in patients with chronic disease.To date only a few published studies can be found on Medline examining HRQL in patients with DD.The aim of this study was to review the impact of surgery for DD on HRQL.All Medline articles regarding HRQL after surgery for colonic DD,particularly those comparing different surgical approaches,were reviewed.DD has a negative impact on HRQL with lower scores in bowel function and systemic symptoms.Both surgery-related complications and disease activity have a significant impact on patients' HRQL.While no signif icant differences in HRQL between different operations for DD in non-randomized studies were revealed,the only prospective double-blind randomized study that compared laparoscopic and open colectomy found that patients undergoing laparoscopic colectomy had signif icantly reduced major postoperative complication rates and subsequently had better HRQL scores.Formal assessment of HRQL could be a good instrument in the selection of appropriate patients for elective surgery as well as in the assessment of surgical outcome.展开更多
AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to...AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis.METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet,iron-supplemented diet, and sham-treated controls.Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured.RESULTS: Macroscopic damage was reduced in irondeprived groups and increased in iron-supplemented rats.Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats.CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.展开更多
Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cau...Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation (STC) and is also seen after solid organ transplantation. The incidence of veno occlusive disease (VOD) after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient 〉 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic add, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a b-ansjugular intrahepatic portosystemic shunt (TIPS) can be tried, especially to treat VOD after liver transplantation and when multiorgan failure (HOF) is not present. Liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure.展开更多
AIM:To evaluate the data from a survey carried out in Italy regarding the endoscopic approach to acute pancreatitis in order to obtain a picture of what takes place after the release of an educational project on acute...AIM:To evaluate the data from a survey carried out in Italy regarding the endoscopic approach to acute pancreatitis in order to obtain a picture of what takes place after the release of an educational project on acute pancreatitis sponsored by the Italian Association for the Study of the Pancreas.METHODS:Of the 1 173 patients enrolled in our survey,the most frequent etiological category was biliary forms(69.3%) and most patients had mild pancreatitis(85.8%).RESULTS:344/1 173(29.3%) underwent endoscopic retrograde cholangiopancreatography(ERCP).The mean interval between the onset of symptoms and ERCP was 6.7 ± 5.0 d;only 89 examinations(25.9%) were performed within 72 h from the onset of symptoms.The main indications for ERCP were suspicion of common bile duct stones(90.3%),jaundice(44.5%),clini cal worsening of acute pancreatitis(14.2%) and cho langitis(6.1%).Biliary and pancreatic ducts were visua lized in 305 patients(88.7%) and in 93 patients(27.0%) respectively.The success rate in obtaining a cholangio gram was statistically higher(P = 0.003) in patients with mild acute pancreatitis(90.6%) than in patients with severe disease(72.2%).Biliary endoscopic sphinc terotomy was performed in 295 of the 305 patients(96.7%) with no difference between mild and severe disease(P = 0.985).ERCP morbidity was 6.1% and mortality was 1.7%;the mortality was due to the complications of acute pancreatitis and not the endoscopic procedure.CONCLUSION:The results of this survey,as with those carried out in other countries,indicate a lack of compliance with the guidelines for the indications for interventional endoscopy.展开更多
AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent mu...AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.展开更多
AIM: (1) To compare the prevalence of osteoporosis (t-score ≤-2.5 SD) between stage IV PBC patients, and two groups of age- and sex-matched controls: one with hepatitis C virus (HCV)-related cirrhosis, and th...AIM: (1) To compare the prevalence of osteoporosis (t-score ≤-2.5 SD) between stage IV PBC patients, and two groups of age- and sex-matched controls: one with hepatitis C virus (HCV)-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population, (2) to identify the main risk factors for the development of bone loss. METHODS: Thirty-five stage IV PBC patients (mean age 52.5±10 years), 49 females with HCV-related cirrhosis (mean age 52.9±5.8 years) and 33 healthy females (mean age 51.8±2.22 years) were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin (Ca corr.), 25-hydroxy vitamin D (25-OH vit D), parathyroid hormone, osteocaldn. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS: Osteoporosis was present in 5/35 PBC patients (14.2%) and in 7/49 HCV-related drrhotic patients (14.3%), without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI〈23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION: PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.展开更多
Objective. Capsule endoscopy is becoming known as a valid tool for identifying sources of obscure gastrointestinal (GI) bleeding. Fewer data are available about its clinical value for other indications. Material and m...Objective. Capsule endoscopy is becoming known as a valid tool for identifying sources of obscure gastrointestinal (GI) bleeding. Fewer data are available about its clinical value for other indications. Material and methods. Sixty patients (31 F, mean age 47 years, range 14- 80 years) with no signs of overt GI bleeding were investigated by Given M2A video capsule for suspected small- bowel disease. The main clinical features were: iron deficient anemia (20), abdominal pain (12), chronic diarrhea (9), malabsorption and weight loss (7), Crohn’s disease (CD) (5), and familial adenomatous polyposis (3). Three patients underwent wireless endoscopy for suspected GI neoplasm and one for portal thrombosis. Results. Complete vision of the small bowel was achieved in 55 patients. No small- bowel lesions were identified in 17 patients, but 5 of them had gastric abnormalities. Small- bowel abnormality was found in 38 patients. Lesions compatible with CD were found in 14 patients, diffuse or patchy enteropathy in 7 and polyps in 6. Actively bleeding lesions were detected in 6 patients and potential bleeding sources in 5. Capsule endoscopy had an overall diagnostic yield of 62% . In particular, three small- bowel malignancies were detected and 9 patients received a better definition of their already- known pathology. However, further endoscopies were needed in 10 patients to obtain a diagnosis. One patient, diagnosed with ileal CD, underwent surgery, as the capsule remained trapped in a stricture. Conclusions. Wireless endoscopy effectively visualizes small- bowel abnormalities even though more accurate selection of the patients is needed in order to optimize its diagnostic efficacy.展开更多
Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least...Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least 6cm associated with systemic toxicity. Methods: Overall, 15 patients had surgery for TM at our institutions over a 10- year period (1993- 2003). In contrast to other studies that used medical therapy as the first- line treatment for TM, in our experience all patients underwent surgery as soon as possible after diagnosis of TM (early surgery). Results: 14 patients underwent subtotal colect- omy with terminal ileostomy, while for 1 patient the surgical procedure consisted only in a decompressive cecostomy. Two major complications occurred consisting of 2 cases of multiple organ failure leading to death. No other major complications or deaths were reported. The overall mortality rate was therefore 13% (0% in patients < 65 years). Conclusion: This study shows that early surgery has the potential to represent a valid therapeutic strategy for patients with TM resulting in a small number of TM- related complications and deaths. Elderly patients seem to have a high risk of multiple organ dysfunction syndrome and postsurgical death.展开更多
文摘The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.
文摘AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα.Each group of mice was matched with a similar group of sham control animals.Macroscopic and histological features were scored blindly.Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage.RESULTS:DSS produced submucosal erosions,ulcers,inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc.The effect was more pronounced in the latter group (vs Zn diet,P < 0.02).Myeloperoxidase activity (vs controls,P < 0.02) and DNA adducts,greatly elevated in the DSS fed colitis group (vs controls,P < 0.05),were significantly reduced in the treated groups,with a more remarkable effect in the group receiving combined therapy (vs standard diet,P < 0.04).CONCLUSION:DSS induces colonic inflammation which is modulated by the administration of anti-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.
基金Supported by PRIN grants from the Italian Ministry of Science and Technology, No. 2003063143-006
文摘AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS: TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1β was higher in cirrhosis patients (P=0.05). A sig- nificant correlation was found between TNF-α and staging (P= 0.05) and between IL-1β levels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype (P= 0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.
文摘Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G contributed analytic tools; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C analyzed the data; Diamantis G and Scarpa M wrote the paper; all authors revised and approved the final version of the manuscript.
文摘Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.
文摘About 50% of patients with hepatitis C virus(HCV)infection complain of neuropsychiatric symptoms,"brain fog",weakness,fatigue,and exhibit some degree of quality of life impairment,irrespective of the severity of liver disease.Since the first observation of HCV-related cognitive deficits,10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment.Unfortunately,these have often included patients with cirrhosis,patients who had acquired the infection through previous intravenous drug misuse,who had a history of relatively recent treatment with interferon,or were on psychoactive medication.In addition,different neuropsychological batteries and tests that explored different cognitive domains were used,which makes the results of the studies difficult to compare.Finally,limited information is available on the pathogenesis of HCV-related cognitive impairment.Cerebral and/or systemic inflammation may be important players but their potential role has not been substantiated by experimental data.The present review outlines the available evidence of the presence of cognitive impairment in patients with HCV infection,with a focus on the potential relationship with cerebral and/or systemic inflammation.
文摘AIM:To assess B1a cell expression in the rectal mucosa of ulcerative colitis (UC) patients in comparison with healthy controls.METHODS:Rectal mucosa biopsies were collected from 15 UC patients and 17 healthy controls.CD5 + B cells were analysed by three colour flow cytometry from rectal mucosal samples after mechanical disaggregation by Medimachine.Immunohistochemical analysis of B and T lymphocytes was also performed.Correlations between,on the one hand,rectal B1a cell concentrations and,on the other,erythrocyte sedimentation rate and C-reactive protein levels and clinical,endoscopic and histological disease activity indices were evaluated.RESULTS:Rectal B-lymphocyte (CD19 + /CD45 +) rate and concentration were higher in UC patients compared with those in healthy controls (47.85% ± 3.12% vs 26.10% ± 3.40%,P=0.001 and 501 ± 91 cells/mm 2 vs 117 ± 18 cells/mm 2,P < 0.001);Rectal B1a cell density (CD5 + CD19 +) was higher in UC patients than in healthy controls (85 ± 15 cells/mm 2 vs 31 ± 6.7 cells/mm 2,P=0.009).Rectal B1a cell (CD5/CD19 +) rate correlated inversely with endoscopic classification (Rs=-0.637,P < 0.05).CONCLUSION:B1a lymphocytes seem to be involved in the pathogenesis of UC,however,the role they play in its early phases and in disease activity,have yet to be defined.
文摘AIM:To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified as minimal, mild, moderate or severe. RESULTS: HBV recurred in 7/42 (16.6%) patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients (7.1%), minimal/non-specific changes were observed in 18 (64.2%), and at least 1 biopsy showed CH in the remaining 8 (28.5%). Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg+ or HBsAg- liver diseases.CONCLUSION: Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.
文摘Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastro-enterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immunemediated conditions,further studies are needed to fully understand the biology of stem cellsand carefully assess their put ativeonco- genicproperties.Moreover,there searchonstemcellsarousesferventethical,socialandpoliticaldebate.TheItalianSocietyofGastroenterologysponsoredaworkshoponstemcellsheldinVeronaduringtheⅩⅥCongressoftheFederationofItalianSocietiesofDigestiveDiseases(March 6-9,2010).Here,we report on the issues discussed,including liver and intestinal diseases that may benefit from stemcell therapy,the biology of hepatic and intestinal tissue repair,and stem cell usage inclinical trials.
文摘AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo , S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150 000/μL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFα, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150 000/μL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen. CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.
文摘Diverticular disease(DD) of the colon is very common in developed countries and is ranked the fifth most important gastrointestinal disease worldwide.The management of acute diverticulitis without perforation and peritonitis is still debated.Health related quality of life(HRQL),subjectively perceived by patients,is becoming a major issue in the evaluation of any therapeutic intervention,mainly in patients with chronic disease.To date only a few published studies can be found on Medline examining HRQL in patients with DD.The aim of this study was to review the impact of surgery for DD on HRQL.All Medline articles regarding HRQL after surgery for colonic DD,particularly those comparing different surgical approaches,were reviewed.DD has a negative impact on HRQL with lower scores in bowel function and systemic symptoms.Both surgery-related complications and disease activity have a significant impact on patients' HRQL.While no signif icant differences in HRQL between different operations for DD in non-randomized studies were revealed,the only prospective double-blind randomized study that compared laparoscopic and open colectomy found that patients undergoing laparoscopic colectomy had signif icantly reduced major postoperative complication rates and subsequently had better HRQL scores.Formal assessment of HRQL could be a good instrument in the selection of appropriate patients for elective surgery as well as in the assessment of surgical outcome.
文摘AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis.METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet,iron-supplemented diet, and sham-treated controls.Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured.RESULTS: Macroscopic damage was reduced in irondeprived groups and increased in iron-supplemented rats.Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats.CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.
文摘Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation (STC) and is also seen after solid organ transplantation. The incidence of veno occlusive disease (VOD) after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient 〉 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic add, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a b-ansjugular intrahepatic portosystemic shunt (TIPS) can be tried, especially to treat VOD after liver transplantation and when multiorgan failure (HOF) is not present. Liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure.
基金Supported by an Unrestricted Grant from Sanofi-Aventis,Milan,Italy
文摘AIM:To evaluate the data from a survey carried out in Italy regarding the endoscopic approach to acute pancreatitis in order to obtain a picture of what takes place after the release of an educational project on acute pancreatitis sponsored by the Italian Association for the Study of the Pancreas.METHODS:Of the 1 173 patients enrolled in our survey,the most frequent etiological category was biliary forms(69.3%) and most patients had mild pancreatitis(85.8%).RESULTS:344/1 173(29.3%) underwent endoscopic retrograde cholangiopancreatography(ERCP).The mean interval between the onset of symptoms and ERCP was 6.7 ± 5.0 d;only 89 examinations(25.9%) were performed within 72 h from the onset of symptoms.The main indications for ERCP were suspicion of common bile duct stones(90.3%),jaundice(44.5%),clini cal worsening of acute pancreatitis(14.2%) and cho langitis(6.1%).Biliary and pancreatic ducts were visua lized in 305 patients(88.7%) and in 93 patients(27.0%) respectively.The success rate in obtaining a cholangio gram was statistically higher(P = 0.003) in patients with mild acute pancreatitis(90.6%) than in patients with severe disease(72.2%).Biliary endoscopic sphinc terotomy was performed in 295 of the 305 patients(96.7%) with no difference between mild and severe disease(P = 0.985).ERCP morbidity was 6.1% and mortality was 1.7%;the mortality was due to the complications of acute pancreatitis and not the endoscopic procedure.CONCLUSION:The results of this survey,as with those carried out in other countries,indicate a lack of compliance with the guidelines for the indications for interventional endoscopy.
文摘AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.
文摘AIM: (1) To compare the prevalence of osteoporosis (t-score ≤-2.5 SD) between stage IV PBC patients, and two groups of age- and sex-matched controls: one with hepatitis C virus (HCV)-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population, (2) to identify the main risk factors for the development of bone loss. METHODS: Thirty-five stage IV PBC patients (mean age 52.5±10 years), 49 females with HCV-related cirrhosis (mean age 52.9±5.8 years) and 33 healthy females (mean age 51.8±2.22 years) were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin (Ca corr.), 25-hydroxy vitamin D (25-OH vit D), parathyroid hormone, osteocaldn. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS: Osteoporosis was present in 5/35 PBC patients (14.2%) and in 7/49 HCV-related drrhotic patients (14.3%), without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI〈23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION: PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.
文摘Objective. Capsule endoscopy is becoming known as a valid tool for identifying sources of obscure gastrointestinal (GI) bleeding. Fewer data are available about its clinical value for other indications. Material and methods. Sixty patients (31 F, mean age 47 years, range 14- 80 years) with no signs of overt GI bleeding were investigated by Given M2A video capsule for suspected small- bowel disease. The main clinical features were: iron deficient anemia (20), abdominal pain (12), chronic diarrhea (9), malabsorption and weight loss (7), Crohn’s disease (CD) (5), and familial adenomatous polyposis (3). Three patients underwent wireless endoscopy for suspected GI neoplasm and one for portal thrombosis. Results. Complete vision of the small bowel was achieved in 55 patients. No small- bowel lesions were identified in 17 patients, but 5 of them had gastric abnormalities. Small- bowel abnormality was found in 38 patients. Lesions compatible with CD were found in 14 patients, diffuse or patchy enteropathy in 7 and polyps in 6. Actively bleeding lesions were detected in 6 patients and potential bleeding sources in 5. Capsule endoscopy had an overall diagnostic yield of 62% . In particular, three small- bowel malignancies were detected and 9 patients received a better definition of their already- known pathology. However, further endoscopies were needed in 10 patients to obtain a diagnosis. One patient, diagnosed with ileal CD, underwent surgery, as the capsule remained trapped in a stricture. Conclusions. Wireless endoscopy effectively visualizes small- bowel abnormalities even though more accurate selection of the patients is needed in order to optimize its diagnostic efficacy.
文摘Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least 6cm associated with systemic toxicity. Methods: Overall, 15 patients had surgery for TM at our institutions over a 10- year period (1993- 2003). In contrast to other studies that used medical therapy as the first- line treatment for TM, in our experience all patients underwent surgery as soon as possible after diagnosis of TM (early surgery). Results: 14 patients underwent subtotal colect- omy with terminal ileostomy, while for 1 patient the surgical procedure consisted only in a decompressive cecostomy. Two major complications occurred consisting of 2 cases of multiple organ failure leading to death. No other major complications or deaths were reported. The overall mortality rate was therefore 13% (0% in patients < 65 years). Conclusion: This study shows that early surgery has the potential to represent a valid therapeutic strategy for patients with TM resulting in a small number of TM- related complications and deaths. Elderly patients seem to have a high risk of multiple organ dysfunction syndrome and postsurgical death.