In vivo molecular imaging of HER2 expression in a rat model of Barrett's esophagus adenocarcinoma.

Human epidermal growth factor receptor 2 (HER2) is involved in the malignant progression of several human cancers, including esophageal adenocarcinoma (EAC). The purpose of this study was to evaluate HER2 overexpression and to explore the feasibility of confocal laser endomicroscopy for in vivo molecular imaging of HER2 status in an animal model of Barrett's-related EAC. Rats underwent esophagojejunostomy with gastric preservation. At 30 weeks post-surgery, the esophagus of 46 rats was studied; endoscopic and histological findings were correlated with HER2 immunofluorescence on excised biopsies and gross specimens. At this age, 23/46 rats developed Barrett's esophagus (BE), and 6/46 had cancer (four EAC and two squamous cell carcinomas). A significant overexpression of HER2 was observed in esophageal adenocarcinoma compared with normal squamous esophagus (9.4-fold) and BE (6.0-fold). AKT and its phosphorylated form were also overexpressed in cancer areas. Molecular imaging was performed at 80 weeks post-surgery in four rats after tail injection of fluorescent-labeled anti-HER2 antibody. At this age, 3/4 rats developed advance adenocarcinoma and showed in vivo overexpression of HER2 by molecular confocal laser endomicroscopy with heterogeneous distribution within cancer; no HER2 signal was observed in normal or Barrett's tissues. Therefore, HER2 overexpression is a typical feature of the surgical induced model of EAC that can be easily quantified in vivo using an innovative mini-invasive approach including confocal endomicroscopy; this approach may avoid limits of histological evaluation of HER2 status on 'blinded' biopsies.

Parathyroid carcinoma: case report.

The authors present a case of parathyroid carcinoma in a patient with primary hyperparathyroidism. Following a literature review, the clinical and diagnostic profile, treatment and prognosis of this rare disease are discussed.

Liver trauma. Diagnosis and treatment.

The authors summarize the essential steps in liver surgery. Modern imaging techniques are of great help in establishing a circumstantiated diagnosis of post-traumatic lesions of the intra-abdominal parenchymatous organs, and especially the liver. Such diagnosis must always be based on the AAST (American Association for the Surgery of Trauma) classification, essential for a correct approach. Each therapeutic choice must be based on a careful clinical evaluation to establish whether emergency exploration of the abdomen or simple patient monitoring is indicated. Organ injuries and consequent hemoperitoneum must be found and quantified. In any case, diagnosis and treatment must only begin once all measures have been taken to ensure the maintenance of vital functions and the normalization of the main blood chemistry parameters.

Pancreatic pseudocyst: case report and short literature review.

We report a case of pancreatic pseudocyst secondary to acute necrotizing pancreatitis treated with open cystogastrostomy. Following a literature review, we stress the enormous benefits offered by modern diagnostic techniques, and especially imaging techniques, for the diagnosis and monitoring of this disease. Treatment should be delayed for at least six weeks, following which the drainage by open surgery offers the best results and lowest morbidity and mortality, followed by laparoscopy and endoscopy, indicated in particular cases and in patients where open surgery is contraindicated.

Mucocele of the appendix. Two case reports.

The authors present two cases of mucocele of the appendix and discuss them in relation to the literature and the clinical features of this disease. They clarify the definition of mucocele as an intraluminal accumulation of mucus in the appendix, and concentrate on the observable pathological processes, agreeing on the higher frequency of mucinous cystadenoma and the possibility that mucocele can develop into peritoneal pseudomyxoma or degenerate into cystadenocarcinoma. They also note that most diagnoses are made intra-operatively during appendectomy, and that, in cases suspected preoperatively, thorough investigation with imaging techniques is very important in order to plan the best treatment.

[Acute typhlitis associated with taxane-based chemotherapy]. / Tiflite acuta dopo trattamento chemioterapico con taxani.

A rare case of acute typhlitis is reported. The patient had undergone chemotherapy for a breast cancer. Clinical and diagnostic tools as well as general and topical care are examined.

Gastrointestinal telangiectasia: a study by EGD, colonoscopy, and capsule endoscopy in 75 patients.

BACKGROUND: The distribution of lesions in the gastrointestinal tract in patients with sporadic telangiectasia is at present unknown. PATIENTS AND METHODS: 75 patients with sporadic telangiectasia underwent esophagogastroduodenoscopy (EGD), capsule endoscopy, and colonoscopy. Endoscopic diagnosis of telangiectasia and gastrointestinal bleeding were required for enrollment in the study. Hemorrhagic diathesis, co-morbidity, number of blood transfusions, and subsequent management were also noted. RESULTS: 35 of the patients presented with gastroduodenal vascular lesions, 51 with small-bowel lesions, and 28 with colonic lesions. 67 % of patients in whom EGD found telangiectasia also presented small-bowel vascular lesions at capsule endoscopy and 43 % colonic lesions at colonoscopy. 54 % percent of patients with positive colonoscopy also presented gastroduodenal lesions and 48 % small-bowel lesions. Patients with known duodenal lesions were more likely to have small-bowel lesions at capsule endoscopy (odds ratio [OR] 10.19, 95 % CI 2.1 - 49.33, P = 0.003). Patients with associated diseases, such as liver cirrhosis, chronic renal failure, or heart valvulopathy, presented more severe disease requiring blood transfusions (OR 6.37, 95 % CI 1.39 - 29.2, P = 0.015). The number of blood transfusions correlated with the number of sites affected ( R = 0.35, P = 0.002). The detection of new lesions at capsule endoscopy allowed new treatment in 46 % of patients. Mean follow-up was 18 months. CONCLUSIONS: Sporadic telangiectasia is a multifocal disease potentially involving the whole digestive tract. Patients with duodenal telangiectasia show a higher risk of jejunal or ileal lesions. Capsule endoscopy is a useful diagnostic tool for the detection of such small-bowel vascular lesions, indicating a more specific prognosis and treatment strategy.

Interaction between rifaximin and dietary fibre in patients with diverticular disease.

BACKGROUND: Cyclic administration of rifaximin in association with dietary fibre achieves symptomatic relief in uncomplicated diverticular disease (DD) by means of a still undefined mechanism. AIM: To investigate the effects of a combination of rifaximin and fibre on both hydrogen production by intestinal microflora and oro-anal transit time. METHODS: In a controlled, double-blind crossover trial, 64 patients with uncomplicated DD were given bran (20 g/day) and randomly treated with rifaximin (1200 mg/day) or a placebo for 14 days. Evaluation was based on clinical status, breath test, oro-anal transit time and faecal weight. RESULTS: The global symptomatic score was significantly reduced after rifaximin (7.1 +/- 4.1 to 4.1 +/- 3.3; P < 0.005) but not after placebo (6.8 +/- 3.8 to 6.1 +/- 3.5). Hydrogen production significantly increased after placebo from 198 +/- 134 to 267 +/- 161 ppm/min, while Rifaximin reduced it from 222 +/- 187 to 166 +/- 131 ppm/min (P = 0.05). The total oro-anal transit time decreased from 56.1 +/- 28.2 to 51.3 +/- 28.0 h in placebo and from 54.4 +/- 31.9 to 45.1 +/- 32.4 h (P < 0.05) in rifaximin-treated patients. CONCLUSIONS: The administration of rifamixin improves the benefits of dietary fibre in uncomplicated DD by preventing its bacterial degradation.

Wilson disease--a practical approach to diagnosis, treatment and follow-up.

Wilson disease is an inherited, autosomal recessive, copper accumulation and toxicity disorder that affects about 30 individuals per million. This rare disease is caused by mutations in the gene encoding a copper-transporting P-type ATPase, which is important for copper excretion into bile, leading to copper accumulation in the liver. Toxic copper concentrations can also be found in the brain and kidney, and clinical phenotypes include hepatic, haemolytic, neurologic and psychiatric diseases. Diagnosis is based on the combination of clinical features and findings such as increased urinary copper excretion, reduced levels of serum ceruloplasmin, high concentrations of copper in liver tissues and Kayser-Fleischer rings. Genetic studies are also becoming available for clinical use, but the utility of direct mutation analysis is limited. Wilson disease can be treated, and early diagnosis is essential: the goal of therapy is to reduce copper accumulation either by enhancing its urinary excretion or by decreasing its intestinal absorption. Medical therapies include penicillamine, trientine, zinc and tetrathiomolibdate. Liver transplantation is a relatively successful treatment option when medical therapy fails or in case of acute liver failure, even though it is also characterized by short- and long-term complications.

The transjugular route: the key hole to the liver world.

Portal hypertensive complications are major causes of morbidity and mortality in patients with liver cirrhosis. The advent of the transjugular route with its minimal access allows non-surgical management of portal hypertension, therapy of venous complications of liver transplantation, monitoring of therapy for portal hypertension, hepatic venous pressure gradient and is also the major route to treat hepatic venous obstruction syndromes. In addition, the transjugular route is a safe route to perform a liver biopsy (transjugular liver biopsy) and allows retrograde evaluation of the portal vein. All these procedures can be combined in the same session. These hepatic interventional radiological skills should be incorporated into the expertise of the liver team in specialised hepatological centres, particularly in liver transplant centres as they are especially useful in improving outcomes of cirrhotic patients on the liver transplantation waiting list. A limitation in achieving this goal, could be the number of experienced radiologists, but hepatologists can be trained, at least for the most simple procedures (transjugular liver biopsy and hepatic venous pressure gradient). This would allow wider applicability and use of these diagnostic and therapeutic techniques, all through a 2 mm hole in the neck--the key hole to the liver world.

Use of alternative and complementary therapies by inflammatory bowel disease patients in an Italian tertiary referral centre.

BACKGROUND: Alternative and complementary therapies are increasingly used by patients with inflammatory bowel disease, but no data are available on their use in Italy. AIM: To ascertain the prevalence and pattern of the use of alternative and complementary therapies, and demographic and clinical factors associated with their use in a large sample of Italian inflammatory bowel disease patients. METHODS: A structured questionnaire was administered to a cohort of outpatients at a tertiary referral centre. RESULTS: Five hundred and fifty-two patients completed the questionnaire; 156 (28%) reported using alternative and complementary therapies, which mainly involved homeopathy (43.6%), followed by controlled diets or dietary supplements (35.5%), herbs (28.2%), exercise (25.6%) and prayer (14.7%). Alternative and complementary therapies were used to ameliorate intestinal symptoms (52.5%), in the hope of being cured (41%) and to reduce the intake of drugs (39.7%). An improvement in well-being (45.5%) and inflammatory bowel disease symptoms (40.3%) were the most commonly reported benefits. A higher education (p=0.027), a more frequently relapsing disease (p=0.001) and dissatisfaction with the doctor's communication (p=0.001) correlated with alternative and complementary therapy use. Non-compliance with conventional drugs, disease severity and curiosity regarding novel therapies were predictors of alternative and complementary therapy use. CONCLUSIONS: Alternative and complementary therapies are frequently used by Italian inflammatory bowel disease patients. Doctors should improve their empathy and their understanding about possible benefits of alternative and complementary therapies.

[Prevalence of Staphylococcus aureus methicillin-resistant (MRSA) among health care workers]. / Prevalenza di Staphylococcus aureus meticillino-resistente (MRSA) tra gli operatori sanitari.

Methicillin-resistant Staphylococcus Aureus (MRSA) is a type of Staphylococcus that is resistant to certain antibiotics. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin and amoxicillin. Staphylococcus infections, including MRSA, occur most frequently among persons in hospitals and healthcare facilities. The present study was performed to investigate the in vitro activity of oxacillin and other antimicrobial agents against S. aureus strains obtained from nursing personnel. The study included 56 hospital personnel of Universitary Policlinic of Messina. S. aureus strain was isolated in 14 samples (25%); resistent patterns have been studied and results have demonstrated: none methicillin resistant, while 14% oxacillin and tetraciclin resistant. The incidence of methicillin sensitive was 100%, while 86% proved to be sensitive to oxacillin and tetraciclin. In conclusion, the usually hygienic methods (disposable gowns, hygienic hand disinfection after each patients contact, masks use when is a risk of aerosolization of MRSA) are indicate for significantly reducing of these strains. Continuing education programmes can help to increase awareness among hospital staff.

Antibiotic treatment of Crohn's disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin.

BACKGROUND: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients. AIM: To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease. METHODS: We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.). RESULTS: Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05). CONCLUSIONS: Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d.

Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis.

BACKGROUND: Two variants in the organic cation transporter gene cluster have been recently reported to confer susceptibility to Crohn's disease (CD). AIM: To investigate these variants in CD and ulcerative colitis (UC), and their interaction with CARD15 gene and correlation to clinical subphenotypes. METHODS: Case-control association analysis was performed in 899 patients (444 CD and 455 UC) and 611 controls. The organic cation transporter gene cluster single nucleotide polymorphisms G207G-->C and 1672C-->T, the IGR2198a_1 single nucleotide polymorphism in the IBD5 locus, and the R702W, G908R and L1007finsC variants of CARD15 gene were genotyped by ABI-7700, restriction fragment length polymorphic analysis and multiplex pyrosequencing, respectively. RESULTS: The 1672TT and -207CC genotype frequencies were increased in both CD (OR = 1.5, P = 0.011; OR = 1.6, P = 0.002), and UC (OR = 1.5, P = 0.017; OR = 1.4, P = 0.033), respectively. Compared with controls, the TC haplotype frequency was increased in both CD (36% vs. 44%, P < or = 0.01) and UC (36% vs. 45%, P < or = 0.01). The frequency of the TC haplotype was 43% in CARD15-positive and 44% in CARD15-negative CD, respectively. Similar results were found in UC. In CD a significant association of the TC haplotype was found with presence of perianal fistulae (P = 0.007) and steno-fistulizing behaviour (P = 0.037). In UC, the TC haplotype was more frequent in patients with more extensive disease (P = 0.015), and those on immunosuppressives (P = 0.004). CONCLUSIONS: Organic cation transporter gene cluster variants may confer susceptibility to both CD and UC, and the TC haplotype may influence some clinical features of IBD, but does not interact with CARD15 variants.

Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease.

BACKGROUND: Abnormal barrier function may be genetically determined in Crohn's disease. AIM: To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. METHODS: Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. RESULTS: The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01-0.24) vs. 0.01 (0.003-0.19), P=0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P=0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020 insC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Conclusion Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease.

Increased risk of breast cancer in first-degree relatives of Crohn's disease patients. An IG-IBD study.

BACKGROUND: Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. AIM: To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. PATIENTS AND METHODS: A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3,292 first-degree relatives of Crohn's disease patients and in 3,303 first-degree relatives of controls. RESULTS: Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls (p=0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio=2.16; 95% confidence interval=1.14-4.08; p=0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. CONCLUSIONS: These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.

Multidrug resistance 1 gene polymorphisms are not associated with inflammatory bowel disease and response to therapy in Italian patients.

BACKGROUND: Host genetic factors may be important in determining not only disease susceptibility, but also disease behaviour and response to therapy in inflammatory bowel disease. Two polymorphisms (C3435T and G2677T/A) of the multidrug resistance 1 gene have been correlated with the altered P-glycoprotein expression and function in humans, and associated with predisposition to ulcerative colitis and Crohn's disease. AIM: To investigate the contribution of these polymorphisms to disease susceptibility and response to medical therapy. METHODS: A total of 946 inflammatory bowel disease patients (478 Crohn's disease, 272 males, mean age 43 +/- 14 years and 468 ulcerative colitis, 290 males, mean age 48 +/- 15 years) and 450 healthy controls were genotyped for the single nucleotide polymorphisms C3435T and G2677T/A. Patients were also classified on the basis of response to medical therapy (mesalazine, steroids, immunosuppressives and infliximab). RESULTS: Both single nucleotide polymorphisms were in Hardy-Weinberg equilibrium and significant linkage disequilibrium. No significant difference in the allele, genotype, and haplotype frequencies was found in both Crohn's disease and ulcerative colitis patients compared with the controls. No correlation with clinical features was found, except for a reduced frequency of extra-intestinal manifestations in Crohn's disease patients with the G2677T genotype (40%) compared with GG2677 and 2677TT genotypes (54% and 58%, respectively) (P = <0.02). No significant difference was also found after stratifying the patients on the basis of their response to medical therapy. CONCLUSION: The investigated polymorphisms of the multidrug resistance 1 gene have no significant role in disease susceptibility and response to medical therapy in our Italian population of inflammatory bowel disease patients.

Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement.

INTRODUCTION: Despite the explosion of biological therapies, the old immunosuppressants continue to play a pivotal role in the management of inflammatory bowel diseases. AIM: To assess the appropriateness of immunosuppressants-azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and thalidomide-in the treatment of inflammatory bowel disease by using RAND/University of California Appropriateness Method. METHODS: The RAND method consists of a combination of evidence from the literature and experts' opinions. Appropriateness has been defined to mean that the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin. A panel of 10 experts from the Italian Group for Inflammatory Bowel Disease has rated, in two rounds, on a scale from 1 to 9, the appropriateness of each indication selected by the Promoter Centre, on the basis of their own clinical experience. An indication was considered appropriate if the median of the panelists' ratings fell within the area 7-9, inappropriate in the area 1-3 and uncertain in the area 4-6. A total of 2781 indications were grouped into 13 categories (mild to moderate Crohn's disease; severe Crohn's disease; fistulizing Crohn's disease; steroid-dependant and -resistant Crohn's disease; maintenance of remission induced by medical treatment in Crohn's disease; maintenance of remission induced by surgery in Crohn's disease; mild to moderate ulcerative colitis; severe ulcerative colitis; steroid-dependant and -resistant ulcerative colitis; maintenance of remission induced by medical treatment in ulcerative colitis; extra-intestinal manifestations in inflammatory bowel disease; pregnancy and inflammatory bowel disease; azathioprine-resistant or -intolerant inflammatory bowel disease patients). RESULTS: Of the 2781 scenarios, 212 (7.6%) were rated appropriate, 645 (23.2%) uncertain and 1924 (69.2%) inappropriate. The most relevant results were: in steroid-dependant or -resistant Crohn's disease, azathioprine, 6-mercaptopurine and methotrexate were defined as appropriate in 25 (86.2%) and 14 (48.3%) of the 29 scenarios respectively; in Crohn's disease, azathioprine and 6-mercaptopurine were defined as appropriate combined with Infliximab (bridge therapy); in steroid-dependant or -resistant ulcerative colitis, azathioprine and 6-mercaptopurine were defined as appropriate in 45 (77.6%) out of 58 scenarios, while methotrexate was defined appropriate only after previous azathioprine failure; in severe ulcerative colitis, cyclosporine A was defined as appropriate only after previous failure with steroids; in azathioprine-intolerant or -resistant inflammatory bowel disease patients, methotrexate was appropriate in 20 (66.7%) out of 30 scenarios; it is inappropriate to stop azathioprine treatment before conception in the presence of active disease. The use of FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate or uncertain. CONCLUSIONS: Results of this study show that only azathioprine, 6-mercaptopurine and methotrexate are appropriate in the treatment of inflammatory bowel diseases. Cyclosporine A was found to be appropriate only in severe ulcerative colitis after the failure of steroids. FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate but experience with these agents is somewhat limited.

Effects of iron manipulation on trace elements level in a model of colitis in rats.

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 iron-deprived 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.