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1.  Therapeutic approach to "downhill" esophageal varices bleeding due to superior vena cava syndrome in Behcet's disease: a case report 
BMC Gastroenterology  2006;6:43.
Background
One of the rare presentations of superior vena cava syndrome is bleeding of "downhill" esophageal varices (DEV) and different approaches have been used to control it. This is a case report whose DEV was eradicated by band ligation for the first time.
Case presentation
We report a 42-year-old man who is a known case of Behcet's disease. The patient's first presentation was superior vena cava syndrome due to thrombosis followed by bipolar ulcers and arthralgia. He received warfarin, prednisolone and azathioprine. The clinical course of the patient was complicated by one episode of hematemesis without abdominal pain when the patient's PT was in therapeutic range. After resuscitation and correction of PT with fresh frozen plasma transfusion, upper gastrointestinal endoscopy was done. Prominent varices were seen in the upper third of the esophagus, tapering to the middle part without acute bleeding. Stomach and duodenum were normal. Color ultrasonography evaluation of the portal, hepatic and splenic veins was negative for thrombosis. Band ligation was done and the patient's bleeding did not recur.
Conclusion
Band ligation is a safe and effective method for controlling DEV bleeding in patients with uncorrectable underlying disorders.
doi:10.1186/1471-230X-6-43
PMCID: PMC1769384  PMID: 17192182
2.  Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis 
BMC Gastroenterology  2006;6:42.
Background
The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant.
Methods
We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects.
Results
We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients.
Conclusion
We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes.
doi:10.1186/1471-230X-6-42
PMCID: PMC1762011  PMID: 17163998
3.  Time trends in socioeconomic differences in incidence rates of cancers of gastro-intestinal tract in Finland 
BMC Gastroenterology  2006;6:41.
Background
The magnitude of socioeconomic differences in health varies between societies, and over time within a given society. We studied the association between social class and incidence of cancers of the gastro-intestinal tract over time in a large cohort in Finland.
Methods
We studied social class variation among 45–69 year-old Finns during 1971–95 in incidence of cancers of the gastro-intestinal tract by means of a computerized record linkage of the Finnish Cancer Registry and the 1970 Population Census, which included social class data.
Results
There were 2.3 million individuals in the cohort under follow-up, with 1622 cases of cancer of the esophagus, 8069 stomach (non-cardia), 1116 cardia, 408 small intestine, 6361 colon, 5274 rectum, 1616 liver, 1756 gallbladder, and 5084 pancreas during 1971–1995. Cancers of the esophagus, stomach, cardia, gallbladder and pancreas were most common among persons belonging to a low social class. Cancers of the small intestine in males only, colon in both genders, and rectum in females were most common in the higher social classes. Incidence of stomach cancer decreased and incidence of colon cancer increased over time in both genders in all social classes, and the large differences between social classes remained unchanged over time. Incidence rates of cardia cancer did not change substantially over time.
Conclusion
There is a large variation in incidence of cancer of the gastrointestinal tract by social class in Finland. Although much of the observed social class differences probably could be explained by known etiological factors such as diet, physical exercise, alcohol consumption, smoking and exogenous hormone use, part of the variation is apparently attributable to largely unknown factors.
doi:10.1186/1471-230X-6-41
PMCID: PMC1769383  PMID: 17144908
4.  The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis 
BMC Gastroenterology  2006;6:39.
Background
Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment.
Aim
To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis.
Methods
Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients.
Results
Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p < 0.001 in Gr I as compared to 10.6% ± 4.6 to 13.5% ± 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 ± 37 meq/l) VS 100 ± 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 ± 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 ± 26), and measured CCT of 87 ± 30 cc/min (P < 0.001).
Conclusion
A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.
doi:10.1186/1471-230X-6-39
PMCID: PMC1702545  PMID: 17134488
5.  Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor 
BMC Gastroenterology  2006;6:40.
Background
The urokinase-type (uPA) and tissue-type (tPA) plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen (Plg) to the active protease plasmin. Based on the efficient activation of plasminogen when uPA is bound to its receptor (uPAR) and on the role of uPA in plasmin-mediated liver repair, we hypothesized that uPA requires uPAR for efficient liver repair.
Methods
To test this hypothesis, we administered one dose of carbon tetrachloride (CCl4) to mice with single or combined deficiencies of uPA, uPAR and tPA, and examined hepatic morphology, cellular proliferation, fibrin clearance, and hepatic proteolysis 2–14 days later.
Results
Absence of uPAR alone or the combined absence of uPAR and tPA had no impact on the resolution of centrilobular injury, but the loss of receptor-free uPA significantly impaired the clearance of necrotic hepatocytes up to 14 days after CCl4. In response to the injury, hepatocyte proliferation was normal in mice of all genotypes, except for uPAR-deficient (uPAR°) mice, which had a reproducible but mild decrease by 33% at day 2, with an appropriate restoration of liver mass by 7 days similar to experimental controls. Immunostaining and zymographic analysis demonstrated that uPA alone promoted fibrin clearance from centrilobular regions and efficiently activated plasminogen.
Conclusion
uPA activates plasminogen and promotes liver matrix proteolysis during repair via a process that neither requires its receptor uPAR nor requires a contribution from its functional counterpart tPA.
doi:10.1186/1471-230X-6-40
PMCID: PMC1697812  PMID: 17134505
6.  Post traumatic intra thoracic spleen presenting with upper GI bleed! – a case report 
BMC Gastroenterology  2006;6:38.
Background
Isolated splenic vein thrombosis with left sided portal hypertension is a rare cause of upper gastrointestinal bleed. Diagnosis is difficult and requires a high index of suspicion, especially in patients presenting with gastrointestinal bleed in the presence of splenomegaly and normal liver function tests.
Case presentation
A 64 year old male presented with haematemesis and melaena. An upper gastrointestinal endoscopy revealed the presence of antral erosions in the stomach and fundal varices. A computerised tomography scan of abdomen confirmed the presence of a diaphragmatic tear and the spleen to be lying in the left hemi thorax. The appearances of the splenic vein on the scan were consistent with thrombosis.
Conclusion
Left sided portal hypertension as a result of isolated splenic vein thrombosis secondary to trauma is rare. The unusual presentation of our case, splenic herniation into the left hemithorax, causing fundal varices leading to upper gastrointestinal bleed 28 years after the penetrating injury, makes this case most interesting. We believe that this has not been reported in literature before.
doi:10.1186/1471-230X-6-38
PMCID: PMC1687187  PMID: 17132174
7.  Acceptability and outcomes of the Percutaneous Endoscopic Gastrostomy (PEG) tube placement- patients' and care givers' perspectives 
BMC Gastroenterology  2006;6:37.
Background
Percutaneous endoscopic gastrostomy tube has now become a preferred option for the long-term nutritional support device for patients with dysphagia. There is a considerable debate about the health issues related to the quality of life of these patients. Our aim of the study was to assess the outcome and perspectives of patients/care givers, about the acceptability of percutaneous endoscopic gastrostomy tube placement.
Methods
This descriptive analytic study conducted in patients, who have undergone percutaneous endoscopic gastrostomy tube placement during January 1998 till December 2004. Medical records of these patients were evaluated for their demographic characteristics, underlying diagnosis, indications and complications. Telephonic interviews were conducted till March 2005, on a pre-tested questionnaire to address psychological, social and physical performance status, of the health related quality of life issues.
Results
A total of 191 patients' medical records were reviewed, 120 (63%) were males, and mean age was 63 years. Early complication was infection at PEG tube site in 6 (3%) patients. In follow up over 365 ± 149 days, late complications (occurring 72 hours later) were infection at PEG tube site in 29 (15 %) patient and dislodgment/blockage of the tube in 26 (13.6%). Interviews were possible with 126 patients/caretakers. Karnofsky Performance Score of 0, 1, 2, 3 and 4 was found in 13(10%), 18(14%), 21(17%), 29(23%) and 45(36%) with p-value < 0.001. Regarding the social and psychological aspects; 76(60%) would like to have the PEG tube again if required, 105(83 %) felt ease in feeding, and 76(60%) felt that PEG-tube helped in prolonging the survival. Regarding negative opinions; 49(39 %) felt that the feeding was too frequent, 45(36 %) felt apprehensive about dependency for feeding and 62(49%) were concerned about an increase in the cost of care.
Conclusion
PEG-tube placement was found to be relatively free from serious immediate and long- term complications. Majority of caregivers and patient felt that PEG-tube helped in feeding and prolonging the survival. Studies are needed to assess the real benefit in terms of actual nutritional gain and quality of life in such patients.
doi:10.1186/1471-230X-6-37
PMCID: PMC1676010  PMID: 17125502
8.  Predictors of gallstone composition in 1025 symptomatic gallstones from Northern Germany 
BMC Gastroenterology  2006;6:36.
Background
Gallstones represent a prevalent and costly health problem. The changing epidemiology and the emerging non-surgical interventions for gallstone disease necessitate the definition of target populations for future therapies. This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany.
Methods
One thousand and seventy-four post-cholecystectomy gallstone specimens were obtained. Demographic and clinical information was provided by questionnaire (N = 1025 independent individuals with complete information). Two samples from each gallstone were analyzed using Fourier transformed infrared spectrometry.
Results
The most prevalent substance was cholesterol, which was detected in 95.0% of gallstone specimens. Bilirubin and bilirubinate were present in 30.0% and calcium was detected in 10.0% of the spectra. Ninety-two percent of measurements from the same stone yielded the same "main" substances, indicating a homogenous stone composition in most cases. Female sex and higher body mass index (BMI) were associated with the presence of cholesterol as a main substance in the gallstones (p < 0.001).
Conclusion
The changing epidemiology of gallstone disease is reflected by a marked shift in stone composition: Only two percent of stones in this study were pigment stones as compared to 91% percent of stones containing cholesterol as a main substance. Obese individuals from Germany with a BMI > 30 kg/m2 have in 95% cholesterol-dominant gallstones and represent a potential target population for non-surgical interventions for the prevention or treatment of cholesterol stones.
doi:10.1186/1471-230X-6-36
PMCID: PMC1664574  PMID: 17121681
9.  Effect of resveratrol on alcohol-induced mortality and liver lesions in mice 
BMC Gastroenterology  2006;6:35.
Background
Resveratrol is a polyphenol with important antiinflammatory and antioxidant properties. We investigated the effect of resveratrol on alcohol-induced mortality and liver lesions in mice.
Methods
Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol). Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. The animals had free access to standard diet. Blood levels were determined for transaminases, IL-1 and TNF-α. A histological evaluation was made of liver damage, and survival among the animals was recorded.
Results
Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p < 0.05). IL-1 levels were significantly reduced in the alcohol plus resveratrol group compared with the alcohol group (p < 0.05). TNF-α was not detected in any group. Histologically, the liver lesions were more severe in the alcohol group, though no significant differences between groups were observed. Mortality in the alcohol group was 78% in the seventh week, versus 22% in the alcohol plus resveratrol group (p < 0.001). All mice in the alcohol group died before the ninth week.
Conclusion
The results obtained suggest that resveratrol reduces mortality and liver damage in mice.
doi:10.1186/1471-230X-6-35
PMCID: PMC1657014  PMID: 17105669
10.  Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease 
BMC Gastroenterology  2006;6:34.
Background
Liver biopsy is considered the gold standard for assessing histologic lesions of non-alcoholic fatty liver disease (NAFLD). The aim was to develop and validate a new biomarker of non alcoholic steato hepatitis (NASH) the NashTest (NT) in patients with NAFLD.
Methods
160 patients with NAFLD were prospectively included in a training group, 97 were included in a multicenter validation group and 383 controls. Histological diagnoses used Kleiner et al's scoring system, with 3 classes for NASH: "Not NASH", "Borderline", "NASH"). The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV, NPV) were assessed.
Results
NT was developed using patented algorithms combining 13 parameters: age, sex, height, weight, and serum levels of triglycerides, cholesterol, alpha2macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase, transaminases ALT, AST, and total bilirubin. AUROCs of NT for the diagnosis of NASH in the training and validation groups were, respectively, 0.79 (95%CI 0.69–0.86) and 0.79 (95%CI 0.67–0.87; P = 0.94); for the diagnosis of borderline NASH they were: 0.69 (95%CI 0.60–0.77) and 0.69 (95%CI 0.57–0.78; P = 0.98) and for the diagnosis of no NASH, 0.77 (95%CI 0.68–0.84) and 0.83 (95%CI 0.67–0.90; P = 0.34). When the two groups were pooled together the NashTest Sp for NASH = 94% (PPV = 66%), and Se = 33% (NPV = 81%); for borderline NASH or NASH Sp = 50% (PPV = 74%) and Se = 88% (NPV = 72%).
Conclusion
In patients with non-alcoholic fatty liver disease, NashTest, a simple and non-invasive biomarker reliably predicts the presence or absence of NASH.
doi:10.1186/1471-230X-6-34
PMCID: PMC1657015  PMID: 17096854
11.  The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population 
BMC Gastroenterology  2006;6:33.
Background
Fatty liver (FL) is the most frequent liver disease in Western countries. We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL in the general population.
Methods
216 subjects with and 280 without suspected liver disease were studied. FL was diagnosed by ultrasonography and alcohol intake was assessed using a 7-day diary. Bootstrapped stepwise logistic regression was used to identify potential predictors of FL among 13 variables of interest [gender, age, ethanol intake, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), body mass index (BMI), waist circumference, sum of 4 skinfolds, glucose, insulin, triglycerides, and cholesterol]. Potential predictors were entered into stepwise logistic regression models with the aim of obtaining the most simple and accurate algorithm for the prediction of FL.
Results
An algorithm based on BMI, waist circumference, triglycerides and GGT had an accuracy of 0.84 (95%CI 0.81–0.87) in detecting FL. We used this algorithm to develop the "fatty liver index" (FLI), which varies between 0 and 100. A FLI < 30 (negative likelihood ratio = 0.2) rules out and a FLI ≥ 60 (positive likelihood ratio = 4.3) rules in fatty liver.
Conclusion
FLI is simple to obtain and may help physicians select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. Validation of FLI in external populations is needed before it can be employed for these purposes.
doi:10.1186/1471-230X-6-33
PMCID: PMC1636651  PMID: 17081293
12.  Ruptured appendiceal cystadenoma presenting as right inguinal hernia in a patient with left colon cancer: A case report and review of literature 
BMC Gastroenterology  2006;6:32.
Background
Mucoceles resulting from cystadenomas of the appendix are uncommon. Although rare, rupture of the mucoceles can occur with or without causing any abdominal complaint. There are several reports associating colonic malignancy with cystadenomas of the appendix. Herein, we report an unusual and interesting case of right inguinal hernia associated with left colon cancer.
Case presentation
A case of ruptured mucocele resulting from cystadenoma of the appendix was presented as right inguinal hernia in a 70-year-old male. The patient underwent colonoscopy, x-ray, ultrasound and computed tomography. Localized pseudomyxoma peritonei associated with adenocarcinoma of the descending colon was diagnosed. The patient underwent segmental resection of the colon, appendectomy, debridement of pseudomyxoma and closure of the internal ring of right inguinal canal. He is free of symptoms in one year follow-up.
Conclusion
Synchronous colon cancer may occur in patients with appendiceal mucoceles. In such patients, the colon should be investigated and colonoscopy can be performed meticulously in cases of ruptured mucoceles and localized pseudomyxoma peritonei. Surgical intervention is the current choice of management.
doi:10.1186/1471-230X-6-32
PMCID: PMC1634861  PMID: 17074081
13.  Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI) attenuate inflammation in DSS-induced colitis in rats 
BMC Gastroenterology  2006;6:31.
Background
Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit.
Methods
Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1β, TNF-α, IL-10 and TGF-β) and malondialdehyde (MDA).
Results
OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups.
Conclusion
Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations.
doi:10.1186/1471-230X-6-31
PMCID: PMC1634862  PMID: 17069659
14.  Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen 
BMC Gastroenterology  2006;6:30.
Background
The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis.
Methods
Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the DNA, in pancreatic mRNA and in zymogen granule lysates. Serum levels of amylase, lipase and cytokines (MCP-1, IL-6) were monitored and the histological appearance of the tissue was investigated. Pancreatitis was induced by 7 hourly injections of 50 μg/kg cerulein. The procedure was repeated twice weekly for 10 consecutive weeks. The animals were sacrificed 24 (n = 8) and 48 hours (n = 8) after the first injection and at the end of the whole treatment (n = 7).
Results
The transgene was detected at the genomic level and in pancreatic mRNA. The corresponding protein was found in low amounts in zymogen granule lysates. R122H mice showed elevated pancreatic lipase, but there was no spontaneous development of pancreatitis within 18 months. After induction of pancreatitis, levels of lipase (after 24 hours) and amylase (after 48 hours) were higher in R122H mice compared to controls. Repeated treatment with cerulein resulted in a slightly more severe pancreatitis in R122H animals. Amylase, lipase, and the cytokine levels were similar to controls.
Conclusion
The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. The rather small difference in comparison to controls could be due to the low expression of the transgene in the mouse pancreas.
doi:10.1186/1471-230X-6-30
PMCID: PMC1637108  PMID: 17069643
15.  Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs) of the small intestine: before the era of imatinib mesylate 
BMC Gastroenterology  2006;6:29.
Background
Gastrointestinal stromal tumors (GISTs), the most common type of mesenchymal tumors of the gastrointestinal (GI) tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS) and overall survival (OS) to clarify the difference between high- and low-risk patients.
Methods
The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model.
Results
The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8%) developed disease recurrence (liver metastasis was the most common form of recurrence). The follow-up period ranged from 5 to 202 months (median: 33.2 months). The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count < 5/50 high power field, and tumor with low cellularity were predictors of long-term favorable OS.
Conclusion
Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection.
doi:10.1186/1471-230X-6-29
PMCID: PMC1633731  PMID: 17062131
16.  A case report on a patient suffering from recurrent vomiting episodes, whose condition improved markedly during pregnancy and breast feeding 
BMC Gastroenterology  2006;6:28.
Background
The normal physiology of the gastrointestinal tract has been only cursorily examined. Consequently, the pathophysiology of disturbances of the gastrointestinal functions is poorly known. Recurrent vomiting is one of many functional conditions for which it is difficult to find an explanation and to treat. In the following a case is described of a patient presenting with recurrent vomiting episodes, whose condition improved spontaneously during pregnancy and breast feeding.
Case presentation
A woman with recurrent vomiting episodes over several years was examined by esophagogastroduodenoscopy. This showed a non-peristaltic ventricle. Treatment with the procinetic drug cisapride (Prepulsid®) improved the peristalsis and reduced the symptoms. During pregnancy and breast feeding, she was free of symptoms, in spite of having discontinued her medication with cisapride (Prepulsid®).
Conclusion
The fact that the patient improved during pregnancy and breast feeding, would seem to indicate the involvement of factors in the physiology of pregnancy and breast feeding that are of importance for gastric motility. This deserves further investigation.
doi:10.1186/1471-230X-6-28
PMCID: PMC1624839  PMID: 17054800
17.  Helicobacter pylori genotypes identified in gastric biopsy specimens from Jordanian patients 
BMC Gastroenterology  2006;6:27.
Background
The genetic diversity of Helicobacter pylori can be analyzed at two different levels: the genomic variation between strains originating from different individuals, and the variation in bacterial populations within an individual host. We reported for the first time the H. pylori genotypes in Jordanian patients with gastrointestinal diseases.
Methods
Upper endoscopy was performed on 250 patients with symptoms of gastrointestinal diseases. Multiple gastric biopsy specimens were taken from the antrum. All the biopsies were tested by PCR for the H. pylori virulence genes vacA, cagA, and iceA, and 151 were tested by histology.
Results
The biopsies positive for H. pylori by PCR were 110/250 (44%), and by histology 117/151 (77.5%), and these results were highly associated (P < 0.02). Analyses of virulence genes revealed that iceA2 (73.6%) was the predominant genotype, the vacAs2 allele was more frequently identified than the vacAs1 allele, while the cagA genotype was low (26.4%). The presence of certain genotypes might be associated with each other, but the presence of certain genotypes was not significantly associated with the age, or gender of the patient.
Conclusion
The results illustrate the geographic nature of the genetic diversity of H. pylori, as the identified genotypes are similar to those reported in neighboring countries. This study provides a baseline data of H. pylori genotypes identified in gastric biopsy specimens from Jordan, serving as a powerful epidemiological tool for prospective investigations to better understand the genetic diversity of this pathogen.
doi:10.1186/1471-230X-6-27
PMCID: PMC1599735  PMID: 17018159
18.  Migraine, fibromyalgia, and depression among people with IBS: a prevalence study 
BMC Gastroenterology  2006;6:26.
Background
Case descriptions suggest IBS patients are more likely to have other disorders, including migraine, fibromyalgia, and depression. We sought to examine the prevalence of these conditions in cohorts of people with and without IBS.
Methods
The source of data was a large U.S. health plan from January 1, 1996 though June 30, 2002. We identified all people with a medical claim associated with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with an ICD-9 code for routine medical care. In the cohorts, we identified all claims for migraine, depression, and fibromyalgia. We estimated the prevalence odds ratios (PORs) of each of the three conditions using the Mantel-Haenszel method. We conducted quantitative sensitivity analyses to quantify the impact of residual confounding and in differential outcome identification.
Results
We identified 97,593 people in the IBS cohort, and a random sample of 27,402 people to compose the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in the IBS cohort of having any one of the three disorders relative to the comparison cohort (POR 1.6, 95% CI 1.5 – 1.7). There was a 40% higher odds of depression in the IBS cohort (POR 1.4, 95% CI 1.3 – 1.4). The PORs for fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 – 1.9; POR for migraine 1.6, 95% CI 1.4 – 1.7). Differential prevalence of an unmeasured confounder, or imperfect sensitivity or specificity of outcome detection would have impacted the observed results.
Conclusion
People in the IBS cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and depression.
doi:10.1186/1471-230X-6-26
PMCID: PMC1592499  PMID: 17007634
19.  Reactive Lymphoid Hyperplasia of the liver in a patient with colon cancer: report of two cases 
BMC Gastroenterology  2006;6:25.
Background
Reactive lymphoid hyperplasia (RLH) of the liver is very rarely reported, and we encountered two cases of RLH of the liver in a patient with colon cancer.
Case presentation
In the first case, a 77-year-old woman was admitted for the surgical removal of a ascending colon cancer. A hepatic tumor in the left lobe was concurrently revealed by computed tomography (CT), and magnetic resonance imaging (MRI). The appearance suggested liver metastasis. Right hemicolectomy and partial hepatectomy were performed. On histopathological examination, lymphoid follicles with germinal centers were seen in the tumor-like lesion, and remarkable lymphoid infiltration with germinal centers was seen in the portal area around the nodule. Immunohistochemical studies revealed polyclonality of infiltrating lymphocyte. Consequently, this nodular lesion was diagnosed as RLH of the liver. In the second case, a 64-year-old woman who had a radical right hemicolectomy for stage II ascending colon cancer 10 years ago was admitted with dysuria. A hepatic tumor in the left lobe was concurrently revealed by CT and MRI, suggesting hepatocellular carcinoma. A left lateral segmentectomy was performed. Microscopically, this lesion revealed the almost same findings as the first case, so this nodular lesion was diagnosed as RLH of the liver.
Conclusion
Our two cases were the first report of RLH of the liver accompanying colon cancer. Because there are a very few cases, so it is not clear whether the malignancies were involved in the onset of RLH. But we believe that new factors involved in the onset mechanism of RLH may be identified by carefully monitoring the clinical course of our two patients.
doi:10.1186/1471-230X-6-25
PMCID: PMC1579220  PMID: 16965640
20.  Rhinosinusitis derived Staphylococcal enterotoxin B plays a possible role in pathogenesis of food allergy 
BMC Gastroenterology  2006;6:24.
Background
Staphylococcal enterotoxin B (SEB) is a potent immunomodulator and implicated with pathogenesis of inflammatory diseases mediated by Th1 or Th2 dominant immune responses. The objective of this study is to determine a possible association between rhinosinusitis derived SEB and pathogenesis of food allergy (FA).
Methods
The study included chronic rhinosinusitis (CRS) patients with FA (N = 46) or without FA (N = 33). Controls included FA patients without CRS (N = 26) and healthy volunteers (N = 25). In CRS patients, we assessed the parameters associated with FA including prick skin test (PST) reactivity to food allergens, serum levels of allergen-specific IgE and cytokines (IL-4, IL-13, IFN-Î3), and the number/reactivity of food-allergen specific Th1/Th2 cells in the peripheral blood before and 2 months after sinus surgery. Changes of these parameters were evaluated in comparison with changes in SEB concentration in the sinus lavage and stool samples and also in vitro reactivity to SEB. In CRS patients with FA, we also assessed changes in reactivity to oral challenge of offending food before and after sinus surgery.
Results
Two months following sinus surgery, we observed statistically significant reduction in PST and oral challenge reactivity in CRS patients with FA in parallel to decrease in serum levels of Th2 cytokines (IL-4 and IL-13) and allergen specific IgE. Improvement of reactivity to food allergens was positively associated with decline in SEB concentrations in the sinus lavage and stool samples. In vitro study results also indicated a role of SEB in aggravation of Th2 skewed responses to food allergens. Such changes were not observed in CRS-non FA patients or control FA patients.
Conclusion
The rhinosinusitis derived SEB plays a certain role in the pathogenesis of FA by augmenting and/or maintaining polarized Th2 responses. Removal of SEB-producing pathogens from the rhinosinuses may be beneficial for attenuating the FA symptoms in patients with CRS-FA.
doi:10.1186/1471-230X-6-24
PMCID: PMC1559701  PMID: 16919166
22.  Integrative roles of transforming growth factor-α in the cytoprotection mechanisms of gastric mucosal injury 
BMC Gastroenterology  2006;6:22.
Background
Transforming growth factor α (TGFα) protects against gastric mucosal injury and facilitates wound healing. However, its overexpression is known to induce hypertrophic gastropathy resembling Menetrier's disease in transgenic (TG) mice on an FVB background, as one of the authors reported previously. We studied another TGFα-expressing mouse line on a CD1 background, whose gastric mucosa appears normal. Since this TG mouse had a strong resistance to ethanol-induced gastric injury, we considered the long-term effect of TGFα on several gastric protection mechanisms.
Methods
TGFα-expressing transgenic (TG) mouse lines bearing human TGFα cDNA under the control of the mouse metallothionein gene I promoter were generated on a CD1 mouse background, and analyzed their ethanol injury-resistant phenotypes produced by TGFα.
Results
In the TG mucosa, blood flow was well maintained after ethanol injury. Further, neural and inducible types of NO synthases were consistently and widely expressed in the TG mucosa, compared with the limited distribution of neural type NO synthase in the luminal pit region of the wild-type (WT) mucosa. COX-2 and its upstream transcription factor NfkB were constitutively elevated in the TG mucosa even before ethanol administration, whereas they were induced in the same region of the WT mucosa only after ethanol injury. Two anti-apoptotic proteins, HSP70 and Bcl-2, were upregulated in the TG mucosa even before ethanol administration, while they were not expressed in the WT mucosa before the injury. Furthermore, pro-caspase 3 activation was inhibited in the TG mucosa, while it was converted to the active form in the WT mucosa following ethanol administration.
Conclusion
We conclude that TGFα maintains the gastric mucosal defense against gastric injury by integrating other cytoprotective mechanisms.
doi:10.1186/1471-230X-6-22
PMCID: PMC1552080  PMID: 16879752
23.  Factors associated with disease evolution in Greek patients with inflammatory bowel disease 
BMC Gastroenterology  2006;6:21.
Background
The majority of Crohn's disease patients with B1 phenotype at diagnosis (i.e. non-stricturing non-penetrating disease) will develop over time a stricturing or a penetrating pattern. Conflicting data exist on the rate of proximal disease extension in ulcerative colitis patients with proctitis or left-sided colitis at diagnosis. We aimed to study disease evolution in Crohn's disease B1 patients and ulcerative colitis patients with proctitis and left-sided colitis at diagnosis.
Methods
116 Crohn's disease and 256 ulcerative colitis patients were followed-up for at least 5 years after diagnosis. Crohn's disease patients were classified according to the Vienna criteria. Data were analysed actuarially.
Results
B1 phenotype accounted for 68.9% of Crohn's disease patients at diagnosis. The cumulative probability of change in disease behaviour in B1 patients was 43.6% at 10 years after diagnosis. Active smoking (Hazard Ratio: 3.01) and non-colonic disease (non-L2) (Hazard Ratio: 3.01) were associated with behavioural change in B1 patients. Proctitis and left-sided colitis accounted for 24.2%, and 48.4% of ulcerative colitis patients at diagnosis. The 10 year cumulative probability of proximal disease extension in patients with proctitis and left-sided colitis was 36.8%, and 17.1%, respectively (p: 0.003). Among proctitis patients, proximal extension was more common in non-smokers (Hazard Ratio: 4.39).
Conclusion
Classification of Crohn's disease patients in B1 phenotype should be considered as temporary. Smoking and non-colonic disease are risk factors for behavioural change in B1 Crohn's disease patients. Proximal extension is more common in ulcerative colitis patients with proctitis than in those with left-sided colitis. Among proctitis patients, proximal extension is more common in non-smokers.
doi:10.1186/1471-230X-6-21
PMCID: PMC1557858  PMID: 16869971
24.  Genetic variability in the precore and core promoter regions of hepatitis B virus strains in Karachi 
BMC Gastroenterology  2006;6:20.
Background
Hepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi.
Methods
A total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays.
Results
Of the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of clinical cirrhosis in patients with HBeAg positive or negative strains with or without PC and BCP mutations. Of the 38 HBeAg positive patients, 9 (24%) had PC and BCP mutations. In the HBeAg negative patient group, mutations were detected in 44 (62%) of the strains investigated. More than one mutation was common, seen in 26 (37%) patients with HBeAg negative disease and 6 (16%) patients with HBeAg positive disease. Twelve (17%) HBeAg negative patients had dual T1762 and A1764 mutations. None of the HBeAg positive patients had T1762 mutation. Mutations were undetectable in 27 (38%) of patients with HBeAg negative disease.
Conclusion
Our study shows that type D is the main HBV genotype in Karachi, Pakistan. Significant numbers of patients infected with this genotype have PC and BCP variants. Mutations at more than one site are common. Patients harboring these mutants do not differ significantly in their clinical presentation from patients having wild type infection.
doi:10.1186/1471-230X-6-20
PMCID: PMC1544342  PMID: 16863587
25.  Gastrointestinal failure in intensive care: a retrospective clinical study in three different intensive care units in Germany and Estonia 
BMC Gastroenterology  2006;6:19.
Background
While gastrointestinal problems are common in ICU patients with multiple organ failure, gastrointestinal failure has not been given the consideration other organ systems receive. The aim of this study was to evaluate the incidence of gastrointestinal failure (GIF), to identify its risk factors, and to determine its association with ICU mortality.
Methods
A retrospective analysis of adult patients (n = 2588) admitted to three different ICUs (two ICUs at the university hospital Charité-Universitätsmedizin Berlin, Germany and one at Tartu University Clinics, Estonia) during the year 2002 was performed.
Data recorded in a computerized database were used in Berlin. In Tartu, the data documented in the patients' charts was retrospectively transferred into a similar database. GIF was defined as documented gastrointestinal problems (food intolerance, gastrointestinal haemorrhage, and/or ileus) in the patient data at any period of their ICU stay. ICU mortality, length of stay, and duration of mechanical ventilation were assessed as outcome parameters.
Results
GIF was identified in 252 patients (9.7% of all patients). Only 20% of GIF patients were identifiable at admission. GIF was related to significantly higher mortality (43.7% vs. 5.3% in patients without GIF), as well as prolonged length of ICU stay (10 vs. 2 days) and mechanical ventilation (8 vs. 1 day), p < 0.001, respectively. Patients' profile (emergency surgical or medical), APACHE II and SOFA scores and the use of catecholamines at admission were identified as independent risk factors for the development of GIF. Development of GIF during ICU stay was an independent predictor for death.
Conclusion
Gastrointestinal failure represents a relevant clinical problem accompanied by an increased mortality, longer ICU stay and mechanical ventilation.
doi:10.1186/1471-230X-6-19
PMCID: PMC1513588  PMID: 16792799

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