Dysplasia and cancer in inflammatory bowel disease 10 years after diagnosis: results of a population-based European collaborative follow-up study.

OBJECTIVE: To determine dysplasia and cancer in the 1991-2004 European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS AND METHODS: A patient questionnaire and a physician per patient form were completed for each of the 1,141 inflammatory bowel disease patients (776 ulcerative colitis/365 Crohn's disease) from 9 centers (7 countries) derived from the EC-IBD cohort. Rates of detection of intestinal cancer and dysplasia as well as extra-intestinal neoplasms were computed. RESULTS: Patient follow-up time was 10.3 +/- 0.8 (range 9.4-11) years. The mean age of the whole group of IBD patients was 37.8 +/- 11.3 (range 16-76) years. Thirty-eight patients (3.3%; 26 with ulcerative colitis/12 with Crohn's disease, 21 males/17 females, aged 61.3 +/- 13.4, range 33-77 years), were diagnosed with 42 cancers. Cancers occurred 5.4 +/- 3.3 (range 0-11) years after inflammatory bowel disease diagnosis. Colorectal cancer was diagnosed in 8 (1 Crohn's disease and 7 ulcerative colitis patients--0.3 and 0.9% of the Crohn's disease and ulcerative colitis cohort, respectively) of 38 patients and 30 cancers were extra-intestinal. Four of 38 patients (10.5%) were diagnosed as having 2 cancers and they were younger compared to patients with one cancer (p = 0.0008). There was a trend for a higher prevalence of intestinal cancer in the northern centers (0.9%) compared to southern centers (0.3%, p = NS). Southern centers had more cases of extra-intestinal cancer compared to northern centers (2 vs. 3.8%, p = 0.08). Ten patients (0.9%; 8 with ulcerative colitis/2 with Crohn's disease, 8 males, aged 62.3 +/- 14.1 years) had colorectal dysplasia. CONCLUSIONS: In the first decade of the EC-IBD Study Group cohort follow-up study, the prevalence of cancer was as expected with most patients having a single neoplasm and an extra-intestinal neoplasm. In northern centers there was a trend for more intestinal cancers, while in southern centers there was a trend for more extra-intestinal cancers compared to northern centers.

Close relation between cirrhosis and gallstones: cross-sectional and longitudinal survey.

BACKGROUND: Increased gallstone prevalence and incidence in cirrhosis have already been reported in different series, including a limited number of patients with cirrhosis. OBJECTIVE: To evaluate the frequency of gallstones and related risk factors in a large series of patients with cirrhosis. PATIENTS AND METHODS: The cross-sectional study involved 1010 patients with cirrhosis related to alcohol abuse, chronic viral infection, or miscellaneous causes (42%, 48%, and 10%, respectively) in Child class A, B, or C (48%, 36%, and 16%, respectively). In the longitudinal study gallstone development was monitored ultrasonographically in 618 patients free of gallstones at enrollment. RESULTS: The overall prevalence of gallstone(s) was 29.5% and increased significantly with age without differences according to sex or cause of cirrhosis. Multiple logistic regression analysis showed that only Child classes B and C were significantly related to a higher risk of gallstone (odds ratio, 1.63 for class C vs class A and 1.91 for class B vs class A; P = .001). During a mean+/-SD follow-up of 50 months+/-9 months, 141 (22.8%) of 618 patients developed gallstone(s), with an estimated cumulative probability of 6.5%, 18.6%, 28.2%, and 40.9% at 2, 4, 6, and 8 years, respectively. Multivariate analysis showed that Child class (hazard ratio, 2.8 for class C vs class A and 1.8 for class B vs class A; P = .002 and P = .001, respectively) and high-body mass index (hazard ratio, 1.31; P = .04) carried a significantly greater risk of gallstone formation. CONCLUSION: Cirrhosis per se represents a major risk factor for gallstones whose prevalence and incidence were far higher than those reported in a general population from the same area.

Epidemiological aspects of inflammatory bowel disease in a north Italian population: a 4-year prospective study.

OBJECTIVE: To determine the incidence and clinical characteristics at presentation of inflammatory bowel disease (IBD) in a defined area of north Italy. DESIGN: A 4-year prospective population-based epidemiological study. SETTING: An area in Lombardia defined by the National Health Service scheme with about 294,000 inhabitants, two referral hospitals and 259 general practitioners (GPs). PATIENTS: Subjects presenting to a GP with symptoms compatible with IBD underwent a diagnostic work-up at one of the referral hospitals. Those with ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis diagnosed according to a defined protocol were included, as were residents of the area with IBD diagnosed elsewhere. Rigid case ascertainment methods were used. Patients were followed for one year; 125 patients were identified. RESULTS: The patient ascertainment rate was constant over the 4 years; UC was diagnosed in 82 patients, CD in 40, and indeterminate colitis in three. The mean annual incidence of IBD for the whole period was 10.6/10(5) inhabitants (95% confidence limits, 7.2-15.1), 7.0/10(5) for UC (4.3-10.7) and 3.4/10(5) (1.6-6.3) for CD. The mean interval between onset of symptoms and diagnosis was under 6 months. The clinical characteristics of our patients were similar to those of north European and American series. CONCLUSION: The incidence of IBD was higher than previously observed in Italy but was still lower than in some north European countries and in the USA. Our data could be used as a basis for future longitudinal studies and in international comparative investigations.

[Prevalence of infections of the ascitic fluid in 81 consecutive cirrhotic patients]. / Prevalenza di infezione del liquido ascitico in 81 cirrotici consecutivamente osservati.

During a period of 30 months the ascites of 81 patients with liver cirrhosis (65 males and 16 females; 25 in Child B class and 56 in Child C class) consecutively admitted to an Internal Medicine Department have been examined. The number of polymorphonuclear leukocytes (PMNs) and the protein content of ascites were evaluated, and cultures for aerobic and anaerobic bacteria were performed. In 46 patients ascites were sterile (SA); bacteriascites (BA) was observed in 3 patients; neutrocytic ascites (NA) in 18 patients; spontaneous bacterial peritonitis (SBP) in the remaining 14 patients. The number of PMNs and total protein content turned out to be significantly higher and lower respectively in SBP compared to the other groups (p < 0.02). In 10 out of the 17 patients with BA and SBP bacteria of enteric origin were isolated. Total mortality was 23.5% (4 cases).

Metastasis in the chest wall and in the right ventricle from hepatocellular carcinoma. Description of a clinical case.

The ante mortem diagnosis of right ventricular metastasis from hepatocellular carcinoma (HCC) is quite rare. Also the metastatic invasion of the chest wall following a liver biopsy is seldom reported. We describe a 67 year old patient that, 30 months after a liver biopsy showing HCC, developed an isolated metastasis of the chest in the site of the biopsy which was treated by radiotherapy. The same patient, after 8 months, complained of dyspnea on effort and ECG showed signs of ischemia: echocardiogram, CT scan and MRI revealed the presence of a metastatic mass in the right ventricular cavity. Post mortem examination confirmed the diagnosis.

[Spontaneous bacterial peritonitis (SBP): prevalence and characteristics in a population of 314 cirrhotic patients evaluated at hospital admission]. / La peritonite batterica spontanea (PBS): prevalenza e caratteristiche in una popolazione di 314 pazienti cirrotici valutati all'ingresso in ospedale.

BACKGROUND: The aim of this study was to evaluate the incidence and the characteristics of the infections of ascitic fluid in cirrhotic patients at the moment of hospital admission. METHODS: A total of 314 patients consecutively submitted to ascitic fluid tap within 3 days of hospital admission were studied. Each patient was classified according to Child-Plugh classes. Neoplastic ascites were excluded. The ascitic fluid was analyzed for PMN count, protein and albumin content, cultural and cytological examinations. The patients with ascitic fluid PMN > 250/ml were immediately treated with antibiotics. RESULTS: Out of 314 patients 11% had SBP (94% in class C patients according to Child-Plugh classification), 17% CNNA and 3% MNNB. 15% of SBP patients were asymptomatic. Total protein content in ascitic fluid was significantly lower in SBP and MNNB compared to CNNA and sterile ascites. 56% of the isolated bacteria was Gram-negative, and the most frequently found were Streptococcus, Escherichia coli and Staphylococcus. 80% of the patients with ascites infection underwent third generation cephalosporin treatment. SBP mortality (29%) was significantly higher than CNNA (9%), MNNB (10%) and sterile ascites (11%), also taking into account the subgroup without ascites infection and class C group (14%). CONCLUSIONS: In view of the high incidence (even in the absence of invasive procedures), of the possibility of symptom free patients and of the high mortality of SBP, it is advisable to carry out routine tap in all cirrhotics with ascites at hospital admission.

[Intrahepatic cholestasis: clinical and nosological classification. Critical survey of personal experience]. / Colestasi intraepatica: inquadramento nosografico e clinico. Revisione critica di casistica personale.

We reviewed 20 patients (16 females and 4 males) with intrahepatic cholestasis and recognised the following miscellaneous disorders: 12 primary biliary cirrhosis (PBC), 3 primary sclerosing cholangitis (PSC), 1 immune cholangiopathy (IC), 3 liver sarcoidosis and 1 cholestasis with Horton's arteritis. The aim of the study was to identify potentially differetiating clinical and biochemical findings in intrahepatic cholestasis. Sixty females were affected with changes reflecting a cholestatic pattern including an elevated alkaline phosphatasis and gammaglutamyltransferase level. Pruritus was found in 50 percent of PBC patients; fever addressed often, in liver sarcoidosis and Horton's arteritis. A striking increase of unesterified cholesterol was a common feature of PBC. An elevated polyclonal serum IgM in PBC such as in PSC. A circulating IgM antimitochondrial antibody and antinuclear antibodies were found in 90 percent of PBC patients; isolated antinuclear antibodies were detected in immune colangiopathy patients (IC). Liver biopsy was necessary to establish the diagnosis of intrahepatic cholestasis. Overlapping histopathologic features made diagnosis hard in cholestatic disorders, all but in liver sarcoidosis. Treatment with UDCA or TUDCA+/-colchicin, reduced cholestatic enzymes in 85 percent of PBC cohort, while it was unsuccessful in PSC-group. Steroid treatment was successful in sarcoidosis, Horton's arteritis and immune colangiopathy. Cy A did not improve clinical and biochemical features in PBC.

[Comparison between torasemide and furosemide in the treatment of ascites in cirrhotic patients]. / Confronto tra torasemide e furosemide nella terapia dell'ascite in pazienti cirrotici.

Twenty patients with cirrhosis and ascites were randomly divided in two groups to receive 20 mg/die of the new-loop-diuretic torasemide (T), and 50 mg/die of furosemide (F). All patients also received 200 mg/die of potassium canrenoate. Natriuretic and diuretic effects and consequent loss of weight were significantly better in the torasemide-group (T-group). Otherwise, loss of potassium and sodium/potassium ratio in urine were not significantly higher for T-group. Ammonium lowered with T and remained unchanged with F, but the difference was not statistically significant. No change was observed in blood-pressure, pulse-frequency, electrolyte plasmatic levels, azotemia, creatininemia and serum albumin. A significant increase of diuresis was obtained from the fourth day of treatment onwards by replacing F with T in the F-group. The T-group maintained T for eight days just to evaluate its efficacy and tolerability in the middle term: diuresis kept efficient and no side-effects occurred. This trial showed that T was a good and handy drug for cirrhosis with ascites whether as an alternative to F, or as a sequential treatment.

[The neuroleptic malignant syndrome (NMS). A report of a clinical case with a protracted and recurrent course. A review of the literature]. / Sindrome maligna da neurolettici (SMN). Descrizione di un caso clinico a decorso protratto e recidivante. Rassegna della letteratura.

Neuroleptic malignant syndrome (NMS), characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction, can suddenly arise in patients treated with neuroleptic agents and carries a high mortality rate even today. A case of NMS due to i.m. therapy with haloperidol decanoate is reported in this paper, characterized by sustained course and a severe relapse due to a different therapy with another neuroleptic agent. The patient however, after a prolonged remission from the relapse, was able to resume long term therapy with neuroleptic drugs. The importance of monitoring blood levels of CPK during the follow-up and the effectiveness of therapy with bromocriptine and dantrolene in confirmed. Although the patient presented a good clinical response, she developed permanent cerebral and muscular damage. A wide review of the literature on NMS is reported to throw light on this syndrome, whose recognition and prompt diagnosis are necessary to reduce mortality.

[Therapy of chronic hepatitis C with alpha-interferon in 182 patients. Evaluation of results, response predictive factors and side effects]. / Terapia delle epatiti croniche da virus C con alpha-interferone in 182 pazienti. Valutazione di risultati, fattori predittivi la risposta ed effetti collaterali.

BACKGROUND: The aim of this study was to assess the results, predictors of response and side effects of therapy with alpha-interferon (IFN) in chronic C virus (HCV) infection. METHODS: A group of 182 patients (150 chronic hepatitis and 32 cirrhosis) was treated with alpha-interferon--recombinant IFN in 120 cases (66%), and lymphoblastoid IFN in 62 cases (34%)--at a dosage of 3 MU three times weekly for 12 months. All our patients were prospectively followed for at least 6 months, and 133 patients for more than 2 years. RESULTS: A short-term positive response was achieved in 65% of our patients, a sustained response in 34%, and a long-term response in 35%, the responses being similar both for hepatitis and cirrhosis. Liver histology, after 2 years, improved in 73% of long-term responders, whereas it improved only in 34% of relapsers. The predictors of response were: age, duration of disease, baseline levels of gamma-glutamyltranspeptidase (GGT) and serum ferritin. Both types of IFN proved to have the same efficacy. Side effects were observed in 52% of our patients, which were correlated with age and female sex. CONCLUSIONS: Interferon therapy yields good results, if administered for 12 months, in young patients with disease of short duration and low baseline levels of GGT and serum ferritin, even in the presence of cirrhosis, if at early-stage. Patients with normal alanine aminotransferase (ALT) levels after 3 years may be considered fully recovered. The dosage employed was well tolerated.

Communication of information to patients with inflammatory bowel disease: A European Collaborative Study in a multinational prospective inception cohort.

BACKGROUND AND AIMS: Communication to patients of information about their disease has become increasingly important in modern medicine, and particularly with chronic nonfatal disorders like inflammatory bowel disease (IBD), but the subject is not adequately researched or understood. METHODS: We studied the media and preferences for communication of information in a multi-national community-based inception cohort of European and Israeli patients with IBD and 10 years follow-up, using structured questionnaires categorizing demographics, disease status, current and preferred sources of information, use of electronic media, role of patients' associations, and satisfaction level. RESULTS: The 917 patients completing the questionnaire were derived from northern (60%) and southern (40%) countries. The mean age was 48.3 years (62% under 50 years); 51% were males; 67% had ulcerative colitis, 33% Crohn's disease. Sixty-six percent of patients designated the specialist as their primary source of information, 77% indicated satisfaction with their current information, and 65% reported not receiving information about medical treatment in the past year. Patient concerns were about new research into their illness (64%), medical treatments (58%), risks and complications (51%) and genetics (42%). Preferred sources of information were paper bulletin (76%), electronic media (30%) and international organization (79%). Diagnosis (ulcerative colitis or Crohn's disease), gender, education level and country impacted significantly on patients' choices. CONCLUSIONS: In providing health care information to patients with IBD their individual attitudes and preferences must be considered. There should be greater roles for IBD patients' associations and international IBD-research organizations, and an increasing use of electronic media.

Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort.

BACKGROUND: No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. METHODS: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. RESULTS: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30-2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10-3.14)) and males (SMR 1.79 (95% CI 1.11-2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32-3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80-2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. CONCLUSIONS: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Non-alcoholic steatohepatitis. Report of five cases and review of the literature.

We describe three men and two women, aged 18-50, with an occasional finding of increased aspartate and alanine aminotransferase and gamma-glutamyl transpeptidase levels in the absence of any drug treatment and past or current alcohol abuse. Two patients were overweight (body mass index 29 and 32, respectively) and physical examination was normal in all but one case. Tests for hepatitis A, B and C, Epstein-Barr virus, cytomegalovirus, toxoplasma and autoimmune hepatitis were negative and metabolic diseases (Wilson's disease, haemochromatosis, alpha-l-antitrypsin deficiency) were excluded by specific tests. Ultrasound liver scan revealed massive steatosis in all patients. Liver histology showed diffuse steatosis and parenchymal inflammation in all cases, with concomitant fibrosis and Mallory bodies in three of them. Findings were consistent with non-alcoholic steatohepatitis, a rare condition with potential progression to cirrhosis in a minority of cases. This disease, for which no treatment is currently available, must be considered in all subjects with elevated aminotransferases, in the absence of known causes of liver damage.

Lipid composition in ganglia of Mollusca.

The aim of the present study is to ascertain lipid composition in the ganglia of Mollusca. Nervous ganglia in the periesophageal ring dissected from Helix pomatia, Lymnaea stagnalis, Murex trunculus and Murex brandaris were studied by biochemical and histochemical procedures. Glycosphyngolipids are present mainly as sulpholipid; sialic acid and gangliosides are not present as revealed by Svennerholm's reaction and TLC separation. The phospholipid/cholesterol ratios are: 0.47 (Helix), 0.42 (Lymnaea), 0.86 (Murex brandaris) and 1.01 (Murex trunculus).

Cholelithiasis in cirrhosis: analysis of 500 cases.

The prevalence of cholelithiasis (gallstones or previous cholecystectomy) was evaluated in a series of 500 cirrhotic patients from Northern Italy (329 males and 171 females, mean age 58 +/- 11 (SD) yr and 61 +/- 10 yr, respectively). Cirrhosis was related to chronic alcohol abuse in 180 cases, non-A non-B (NANB) hepatitis in 160, hepatitis B virus (HBV) in 94 (including 38 with concomitant alcohol abuse), idiopathic hemochromatosis in 44, and miscellaneous causes in the remaining 22 (including 15 with primary biliary cirrhosis). One hundred and sixteen patients (23.2%) had gallstones, and 31 others (6.2%) had previously undergone cholecystectomy, with an overall prevalence of cholelithiasis of 29.4%. The frequency was similar in both sexes (91/329 males, 27.7% vs. 56/171 females, 32.7%; p = NS), showed a slight increase with age, and differed significantly according to etiology (p less than 0.05), with the highest prevalence in the miscellaneous group and the alcoholics (36.4% and 33.3%, respectively). No significant difference was found in the prevalence of cholelithiasis according to Child's A, B, or C class.

Prevalence of cholelithiasis in alcoholic and genetic haemochromatotic cirrhosis.

The prevalence of cholelithiasis and possible related factors was evaluated in 350 consecutive patients with alcoholic cirrhosis (218 cases, 174 male and 44 female, mean age 58 +/- 9 years) or genetic haemochromatotic cirrhosis (132 cases, 115 male and 17 female, mean age 53 +/- 10 years). At enrollment patients with alcoholic cirrhosis were significantly older than those with genetic haemochromatotic cirrhosis (P < 0.01), and their clinical status was more severe (Child's class B/C in 99 alcoholic cirrhosis cases versus 27 genetic haemochromatotic cirrhosis cases, P < 0.01). The overall frequency of cholelithiasis was 31% (67 cases) in the alcoholic cirrhosis group and 30% (40 cases) in the genetic haemochromatotic cirrhosis group, without differences according to gender, classes of age (< or = 49, 50-59, > or = 60 years), or HBsAg positivity in either group. In addition, in the genetic haemochromatotic cirrhosis group the presence of diabetes (45 cases), alcohol misuse (38 cases) and beta-thalassemia trait (13 cases) did not influence the prevalence of cholelithiasis. Body mass index, serum cholesterol and triglycerides, and the severity of the underlying liver disease (Child's class) did not distinguish patients with or without cholelithiasis. In conclusion, the frequency of cholelithiasis was high in both alcoholic cirrhosis and genetic haemochromatotic cirrhosis, and was three times higher than that reported in controls from the general population of the same area.

Clinical significance of gastric dysplasia: a multicenter follow-up study. Gastrointestinal Endoscopic Pathology Study Group.

The evolution of gastric moderate and severe dysplasia was examined in a prospective multicenter study. One-hundred-and-nine of 141 patients with the endoscopic-bioptic diagnosis of moderate or severe dysplasia had an adequate follow-up and were included into the study. After revision of the initial slides by a gastrointestinal pathologist, 57 patients whose lesions did not meet the histological criteria for dysplasia were excluded, being reclassified as hyperplastic or metaplastic lesions (group 2). The 52 patients with confirmed moderate or severe dysplasia (group 1) were followed up for at least six months or underwent surgery for confirmed dysplasia or cancer. Thirty-two cancers were found in group 1 (33% in patients with moderate and 81% in patients with severe dysplasia). Among them, about half (n = 17) were early gastric cancers. Neither severe dysplasia nor cancer were found during the follow-up in group 2. Mean follow-up time was 13 months in group 1 and 16 months in group 2. Our results indicate that: 1) Confirmed moderate dysplasia shows a high risk of cancer development and requires strict bioptic follow-up; 2) Surgery is indicated in confirmed severe gastric dysplasia seen in the early detection of gastric cancer.