A 73 year old female presented with painless fresh rectal bleeding and anaemia. At colonoscopy, a large mass arising from the right colon was visualised and biopsied. Histological evaluation established a diagnosis of melanoma. Thorough clinical examination confirmed the presence of primary localised melanoma which was amenable to resection. At laparotomy, right hemicolectomy and lymphadenectomy were performed. Two years after her surgery, our patient is well without any evidence of disease recurrence. Primary melanoma of the colon is a very rare clinical entity and limited data are available regarding its pathogenesis, treatment and outcome. Primary surgical resection in localised disease appears to be the mainstay of treatment, although the role of adjuvant therapy is still to be established.
Alcohol usage poses serious social and economical challenges.Its overuse is responsible for loss of billions of dollars due to fatal accidents and causes multiple diseases.Chronic alcoholism leads to liver disorders, including steatosis, hepatitis, fibrosis and cirrhosis.Both binge and chronic alcohol drinking result in blood pressure elevation and hypertension.As a significant mechanism, changes in the levels of angiotensinogen-released peptides play an important role in advanced alcohol liver disease.This review summarizes some of the studies that have demonstrated their role in liver fibrosis, cirrhosis and hypertension.Further, the individual variants and polymorphic sites may play a role in alcoholmediated regulation of angiotensinogen.Possible role of human angiotensinogen on alcohol hepatotoxicity is also discussed.
Eosinophilic gastroenteritis (EGE) is a rare disease of the gastrointestinal tract characterized by eosinophilic in- filtration of the bowel wall and variable gastrointestinal manifestation. The signs and symptoms of EGE are related to the extent of bowel involved with eosinophilic infiltration whether mucosa; muscle; and / or subserosa. Peripheral eosino- philia may or may not be present. Diagnosis requires a high index of suspicion and exclusion of other causes of peripheral eosinophilia. We report a case of a young woman who presented with recurrent abdominal pain and ascites. Diagnosis of EGE was made based on clinical, laboratory, radiological and histological criteria. The patient demonstrated overlap be- tween different subtypes of EGE and had an excellent response to steroid treatment.
Background: Fructose malabsorption has been associated with irritable bowel syndrome (IBS), but its impact on infections of the respiratory and urogenital tracts, inflammation of the skin, as well as dyspepsia and heartburn, has not been studied. Methods: Fructose absorptions of 62 outpatients with clinical signs of IBS were monitored by a fructose-H 2 - breath test. Additionally, the urinary fructose concentration was monitored during a 2-hour test period. Patients were asked to answer a questionnaire to evaluate their discomfort and to diagnose multiple chronic or recurrent diseases. Patients with manifested fructose malabsorption were put on a reduced fructose diet for up to 3 years. At the end of follow-up, patients were called in again for evaluatation of their dietary compliance and possible development of persistent complaints. Results: Patients with fructose malabsorption had higher urinary fructose concentrations during the fructose tolerance tests than did normal fructose absorbers (46.7 ± 36.4 mg/dl vs. 18.7 ± 10.1 mg/dl; p<0.01). Chronic or recurrent infections of respiratory and the urogenital tracts, inflammation of the skin, as well as dyspepsia and heartburn were more than twice as high in fructose malabsorbers than in normal absorbers (78.1% vs. 36.7%). The risk of chronic and recurrent illnesses was higher in the group of fructose malabsorption (p=0.002). A fructose-restricted diet significantly reduced the vulnerability to various forms of chronic or recurrent diseases. Conclusions: Chronic and recurrent infections of respiratory and urogenital tracts, inflammation of the skin, dyspepsia and heartburn correlate with fructose malabsorption. A dietary fructose reduction was effective in reducing these illnesses.
Objective: This study was designed to evaluate the efficacy of the Biodesign ® Anal Fistula Plug (AFP) for the closure of Crohn's anorectal fistula. Patients & Methods: This study was a prospective analysis of patients with Crohn's disease who received the AFP for the treatment of anorectal fistulas of Crohn's origin. Under general anesthesia and in the lithotomy or prone jackknife posi- tion, patients underwent irrigation of the fistula tract by saline or hydrogen peroxide. The AFP was then inserted into the fistula tract until it was snug. The internal end of the plug was securely sutured with 2-0 Vicryl ® and covered with a small mucosal advancement flap, while the external opening was left open to allow for drainage. Results: Twenty-one patients with a combined 28 fistula tracts were prospectively enrolled. Three single tract fistula pa- tients were lost to follow up and were excluded from the analysis. At the final follow-up of 12 months, all fistula tracts were successfully closed in 10 of 18 patients, for an overall success rate of 56%; total fistula tracts were closed in 17 of 25 tracts, for an overall success rate of 68%. None of the tracts that were closed recurred during the study period. Conclusions: Closure of Crohn's anorectal fistulas using the anal fistula plug is safe and successful in 56% of patients and 68% of fistula tracts. Given the relatively low morbidity associated with the procedure, the AFP should be considered as a viable treatment option for patients with Crohn's-associated anorectal fistulas.
The alcoholic liver disease (ALD) continues to be a major health problem worldwide with respect to both mor- bidity and mortality. It is usually an outcome of excessive alcohol consumptions but can be worse by poor diet and genetic factors. This review aims to update the recent conditions of the epidemiology, pathogenesis, immune response and thera- pies to ALD. The new insights into the pathogenesis of ALD include the key roles of the excess production of cytokines, reactive oxygen species (ROS) and the shortage of protective mediators, including adiponectin. As the liver injury pro- gresses, the immune system fails to counteract proinflammatory cytokines and ROS which further cause oxidative liver injury. By inducing mitochondrial alterations, oxidative stress promotes hepatocyte necrosis, release of pro-fibrotic cyto- kines and activation of collagen gene expression in hepatic stellate cells contributing to alcohol induced sensitization of hepatocyte to pro-apoptotic action of TNF-α. ALD can progress to cirrhosis, hepatocellular carcinoma, and liver failure. Regulation of perioxisome proliferator activated receptor (PPAR) and sterol regulatory element binding protein (SREBP) accompanied with lifestyle modifications are currently in practice for alleviating ALD.
Background: Transforming growth factor beta 1 (TGF-1) has been implicated in the stimulation of extracellular matrix synthesis in acute and chronic liver disease.Endoglin (CD-105) is a membrane glycoprotein that binds TGF-1 with high affinity.Endoglin is overexpressed in several model of fibrosis.The goal of the present study was to evaluate the effect of bile duct ligation (BDL) on endoglin expression and the effect of endoglin overexpression on liver fibrosis in rats.Methods: Rat livers were transfected with a vector containing full length human endoglin (h-end) or an empty vector (mock) and 48 hours after were subjected to either BDL or sham operation (SO).Eighteen days after, a blood sample was obtained and bilirubin and serum enzyme activities were measured to assess liver damage.Liver fibrosis was quantified by a computer-assisted image analysis of Sirius red stained livers and by liver hydroxyproline content.Endoglin expression in the liver tissue was assessed by Western blot and immunohystochemistry.Results: Both immunohistochemistry and Western blot reveals endoglin upregulation after BDL in rats.In addition, these techniques also reveal effective human endoglin transfection in the rat's liver.After BDL, liver fibrosis and plasma levels of enzymes were similar in h-end transfected and mock-transfected rats.Western blots showed higher endoglin expression after BDL in h-end transfected and mock-transfected rats. Conclusions:The present study provides clear evidence that endoglin is upregulated in the liver of rats with BDL.h-end overexpression did not improve liver fibrosis after BDL in rats.
Objective: The purpose of our study was to examine the discussion prior to open access colonoscopy (OAC) to assess for areas of improvement. Methods: An anonymous questionnaire was administered to consecutive patients undergoing OAC. Results: 426 subjects completed the questionnaire. Male subjects reported a mean 9.7 +4.3 minutes of discussion about CRCS, colonoscopy procedure and preparation compared to female subjects at 7.6 +4.3 min. 52% of participants felt that they were adequately informed prior to OAC. Women were less likely to have discussed other forms of CRCS (OR 0.36, p<0.001), risks of colonoscopy (OR 0.45, p=0.005) medications to avoid (OR 0.51, p=0.012) and were half as likely to feel adequately informed by their practitioner (OR 0.40, p<0.001). Of all PCPs, women felt that GYNs best informed them about their procedure (OR 12.5, p=0.005). Subjects with a relationship for 10 years or greater with their doctor were 43% more likely to be adequately informed (OR 1.43, p=0.00). Conclusion: Despite the time devoted by PCPs patients, particularly women, are least likely to feel informed about the CRCS process. With the increasing efforts to improve CRCS compliance, strategies must be developed to prompt PCPs to discuss the CRCS process with their patients.
Background: Recent data suggest that red blood cell distribution width (RDW) could be a reliable marker in differentiating Crohn's disease (CD) from ulcerative colitis (UC). Aim: Our study was to determine the sensitivity and specificity of RDW and serological markers for inflammatory bowel diseases (IBD), the risk for the diseases in case of abnormal RDW value and positive serological markers separately and conjointly and to evaluate the efficacy of RDW in the differential diagnosis between IBD and irritable bowel syndrome (IBS). We also examined the influence of the drug treatments on the alteration of RDW values. Patients and methods: The clinical records of 98 CD, 81 UC, 26 IBS patients and 84 healthy controls were reviewed. Sensitivity, specificity and relative risk of RDW and ASCA IgA, ASCA IgG and anti-OmpC antibodies for CD and UC were assessed. RDW values of IBS patients and IBD patients were also statistically compared. Results: RDW was significantly elevated in IBD patients compared to IBS patients. 92% specificity cutpoint at a RDW level of 13.4% was detected in both CD and UC independently of the disease activity. Significantly higher risk for CD was observed in case of combined assessment of abnormal RDW and positive ASCA IgA vs. the other serological markers or to separate determination of RDW.
The aim of the present study is to examine the effect of neuropeptide Y and estrogen on type IIb sodium- coupled phosphate co-transporter (NaPi-IIb) gene expression and activity. Uptake studies with human intestinal cell line, Caco-2 cells, showed that treatment with neuropeptide Y and estrogen concentration-dependently increased sodium- dependent phosphate absorption. Reverse transcriptase-polymerase chain reaction analysis indicated that expression of NaPi-IIb mRNA was also increased after Y treatment with neuropeptide and estrogen. These studies show for the first time that neuropeptide Y increased intestinal sodium-dependent phosphate absorption. This increase is associated with the increase of the expression of NaPi-IIb mRNA.
Background: Though several modalities are available for colorectal cancer screening, only about half of adults are being screened.Barriers to compliance include fear of diagnosis, lack of motivation and logistical difficulties, including taking time off work.The aim of the study was to evaluate whether offering a paid day off from work would motivate more patients to undergo screening.Methods: A questionnaire was administered to employees at the the Bronx-Lebanon Hospital Center in 2007.Results: Of the 916 surveys returned, we focused on the 438 responders who needed a screening test due to age greater than 50, or less than 50 but with a family history of colon cancer.Of the 438, fifty responders were not sure or not willing to undergo screening.The remainder were willing or had been screened and were excluded from the analysis.Among the fifty, 17 (34%) were more willing to undergo screening when they were offered a paid day off from work.Six out of ten men (60%) changed their mind based on this incentive while only 11 out of 40 women (27%) did so (p= 0.05).Conclusions: A paid day off from work may increase screening compliance.This effect was more pronounced in men.
Functional dyspepsia is a very common gastrointestinal disorder observed in the general population, in general outpatient clinic and clinical specialty.It is associated with several treatments, hospitalization, prescription and use of several drugs.Moreover, it is related to self medication, absenteeism and also loss of productivity.The objective of this review is to summarize the pathophysiological mechanisms and the treatment of functional dyspepsia.
Objective: The study was designed to describe a cohort of patients with ischemic colitis (I.C.) that required admission and the factors related to severity and mortality.Also, we tried to define the risk of relapse after discharge and the variables associated.Methods: Descriptive and retrospective study of patients with I.C. diagnosed between January 1996 and March 2003.Qualitative variables were analyzed using Fisher exact test and parametric variables were analyzed using Student´s t-test.Those variables statistically significant were included in a Cox regression model.Results: During the study period, 169 patients with I.C. were admitted into hospital.Ten patients required surgery, 8 patients died and 13 were considered severe.The variables independently associated to severity were: cerebrovascular disease (OR: 6.63, 95% CI: 1.59-27.61,p: 0.009), absence of hematochezia (OR: 4.43, 95% CI: 1.12-17.47,p: 0.033), abdominal distention (OR 6.39, 95% CI: 1.65-24.70,p: 0.007) and ileus (OR 8.76, 95% CI: 2.12-36.06,p: 0.003).Only diffuse peritonism was associated to mortality (OR: 26.07, 95% CI: 5.67-119.93,p<0.001).After discharge, seven (4.5%) patients had a relapse (mean time: 5.31t3.67months), with a stricture in 6 of them.A second episode of I.C. (OR: 13.21, 95% CI: 2.52-69.28,p: 0.002), treatment with aspirin (OR 6.41, 95% CI: 1.12-36.64,p: 0.037) and with antihypertensive drugs (OR 0.089, 95% CI: 0.01-0.754,p: 0.027) were independently associated to relapse. Conclusions:We identified several predictive factors that can be used to stratify patients on admission.We found a relation between treatment with aspirin, antihypertensive drugs and relapse that should be confirmed in prospective studies.
Solid-pseudopapillary neoplasm of the pancreas (SPNP), as a distinct tumor, often occurred in young female patients with both exocrine and endocrine differentiation.Our aim was to define the SPNP histogenesis and investigate the relationships between its histological origin and the sexual hormone receptors.20 tumor samples were subjected to the analysis of immunohistologic staining patterns and presence of sex hormone receptors and other markers of SPNP.Immunohistological results indicated that the tumors were positive for alpha-1-antitrypsin (17 cases), vimentin (14 cases), synaptophysin (10 cases), chromaffin granule A (5 cases), cytokeratin and insulin (2 cases), glucagon and S-100 (1 case), progesterone-receptor protein (14 cases), estrogen receptor protein (1 case), pS2 (6 cases), but negative for carcinoembryonic antigen, gastrin and androgen-receptor protein.SPNP is closely associated with the sex hormone receptor.
The hydroxy-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors generally have a good safety profile and are one of the most prescribed drugs in Europe.Nevertheless, differences in physicochemical and pharmacokinetic properties statins may translate into relevant differences in long term safety.In clinical trials, all lipid-lowering agents have been associated with mild asymptomatic elevation of aminotransferase enzymes.Studies that evaluate the risk of hepatotoxicity from statins in hyperlipidemic subjects with elevated baseline serum transaminases are lacking and furthermore, statins are considered contraindicated in patients with chronic liver disease.However, clinical and biochemical monitoring is routinely recommended or required, often to make up for the lack of information on the true risk of clinically significant liver toxicity of these agents in individuals both with and without underlying liver disease although there is no evidence that monitoring reduces the rate of hepatotoxicity.This article will review what is and what is not known about hepatic disease and hepatotoxicity risk due to the statins and offers recommendations for the safe and rational use of this group of drugs in the setting of specials situations.
Background: The aim of this study, conducted over a period of two weeks in summer 2006, was to collect rep- resentative data about reflux in Germany. Methods: 1,892 persons in five German cities and the Federal city-state of Berlin were questioned about the frequency and severity of their reflux symptoms, and what treatments they had opted for. Moreover, this study collected data about so- ciodemographic and socioeconomic status of the respondents. So the relationship between this status and the prevalence of reflux symptoms and individual treatment decisions could be analyzed. Results: Approximately 50% of the interviewees had personally experienced typical reflux symptoms. Approximately 21% of the sample had suffered from these symptoms during the 4 weeks prior to the survey. Typical sociodemographic factors such as gender and socioeconomic factors such as social status explain neither the appearance nor the severity of reflux symptoms; age alone exerts a small positive influence on both variables. Approximately 80% of the interviewees with acute reflux treated their symptoms; dominant choices in this context are dieting, self-medication with OTC drugs, and the consultation of medical experts. Conclusions: Comparing results of this survey with earlier data, reflux prevalence in Germany is rising. Mostly, acutely ill patients treat their symptoms. Surprisingly, socioeconomic status plays no role in explaining treatment decisions of pa- tients.
Enteric neuropathy is emerging as a central theme in a range of digestive tract pathologies.Aberrant nitric oxide (NO) signaling by cellular components of the enteric nervous system or by inappropriate processing of dietary nitrite represents potential disease factors in delayed gastric emptying, diabetic gastroparesis, hypertrophic pyloric stenosis, and in inflammatory barrier dysfunction of the gut.Exploiting the neuronal nitric oxide synthase (nNOS) system to generate NO as a form of treatment is considered an option in these clinical disorders.Here we review the transcriptional regulation of nNOS activity and its pathophysiological role in the digestive tract.We also highlight potentially novel therapeutic strategies that exploit nNOS-derived S-nitrosothiols (SNO) and advanced glycation end products (AGEs).
The Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) is associated with active inflammatory bowel disease; however MAdCAM-1 expression in the pancreas has not been previously documented. This study investi- gated MAdCAM-1 expression during cerulein-induced pancreatitis, and examined MAdCAM-1 expression, regulation and function in cytokine-treated pancreatic endothelial cells. Acute pancreatitis was induced by serial injections of ce- rulein over 10h, at which point tissue samples were collected. Pancreas endothelial cells (PMEC) were prepared from H- 2Kb-tsA58 (Immortomouse) mice. MAdCAM-1 expression was examined by immunoblotting after cytokine (TNF-� , IL-� or IFN-� ) stimulation. 2 nd messages regulating MAdCAM-1 were studied by adding pharmacological blockers prior to cy- tokines. MAdCAM-1 dependent lymphocyte adhesion was monitored using � 4� 7-integrin expressing lymphocytes. In ce- rulein-pancreatitis, MAdCAM-1 was upregulated by 10h, and closely correlated with histopathology. In PMEC, only TNF-� induced MAdCAM-1 dose (0-20ng/ml) and time (>12h-48h) dependently. MAdCAM-1 expression was PKC, ty- rosine kinase, p38 MAPK, and NF-� B-PARP dependent. PMEC-lymphocyte adhesion was increased by TNF-� , and sig- nificantly reduced by MAdCAM-1 antibody. MAdCAM-1 is induced in the inflamed pancreas, and in TNF-� stimulated PMEC, and may represent a novel determinant of pancreatic-lymphocyte recruitment in inflammation. PMEC cells might provide a useful system to study mechanisms related to both acute and chronic pancreatitis.
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rapidly developing hepatic disease that leads to early childhood cirrhosis and liver failure.We present a diagnostically challenging case of a 20-year-old male with 8 years history of recurrent icteric episodes and constantly normal serum levels of GGT.Genetic study disclosed two novel mutations in gene ABCB11 and liver histopathology provided evidence of intrahepatic cholestasis with slowly progressing fibrosis.Concurrent diseases were cholelithiasis and chronic calcifying pancreatitis.
Background: The IBD5 (MIM# 606348) chromosomal region on 5q31 contains the genes for organic cation transporters, OCTN1 and OCTN2, and has been associated with susceptibility to adult onset CD.While several studies argue that OCTN1 and OCTN2 are the causal genes, others fail to replicate these results.Methods: From the Canterbury Inflammatory Bowel Disease Project, 388 CD, 405 UC, and 27 indeterminate colitis (IC) participants were genotyped for functional SNPs in OCTN1, OCTN2, and IL4 genes, in comparison with 370 controls.TaqMan® technologies were used to genotype IL4 rs2243250, OCTN1 rs1050152, and OCTN2 rs2631367 according to standard methodologies.The frequencies of variant SNPs in the control population were compared with frequencies in cases, where phenotype data for IBD was classed according to the Montreal classification.Results: For those individuals carrying only the variant allele in IL4 or OCTN1, despite trends towards increased risk of developing IBD, there were not statistically significant differences.There were no other specific effects of this allele in the location of CD, behaviour of UC or CD, or any other differences between controls and patient subgroups in this population group.However, carrying the variant OCTN2 rs2631367 allele significantly increased the risk of ileocolonic CD (OR=1.42,95% CI=1.02-1.97,p<0.05).Conclusions: Despite earlier reports suggesting that OCTN1 and OCTN2 variants might provide important risk factors for IBD in New Zealand, this larger population-based study failed to confirm the earlier data.SNPs in the IL4 gene did not affect the analysis.We suggest the possibility that strong effects for these variants in these genes seen in some studies could imply gene-environment interactions.
