The association of endoplasmic reticulum aminopeptidase-1 (ERAP-1) with Familial Mediterranean Fever (FMF).

BACKGROUND: The ERAP1 gene cleaves the receptors and reduces their ability to transmit chemical signals to the cell that affect the process of inflammation and, secondly, it cleaves many types of proteins into small peptides that are recognized by the immune system. OBJECTIVE: ERAP-1 gene mutations may create a sensitivity for Familial Mediterranean Fever (FMF). METHOD: We included 15 FMF patients with the M694 (+) mutation in the study in order to exclude patients without pyrin gene mutations and create a homogeneous study group. Fifteen patients with ulcerative colitis formed the control group. RESULTS: There wasn't any case without ERAP-1 gene mutations. At least one mutation at exon 3 or exon 10 was found in all cases in both groups. There were 14 ERAP-1 gene mutations at exon 10 and 11 at exon 3 in patients with FMF. Interestingly, if there were ERAP-1 gene mutations at exon 3, a p.Arg127 Pro (c.380 G>C) mutation always existed for three FMF patients with polymorphic mutations at this exon. There were 11 ERAP-1 gene mutations at exon 10 and 12 gene mutations at exon 3 in patients with ulcerative colitis. Exon 3 mutations were usually single p.Arg127 Pro (c.380 G>C) mutations for 12 patients with ulcerative colitis as seen in the patients with FMF. The single mutation was always p.Ser453 Ser (c.1359T>C) for patients with ulcerative colitis at exon 10. CONCLUSION: There are more ERAP-1 mutations in the FMF group in comparison to the ulcerative colitis group. So, there may be a strong susceptibility to ERAP-1 gene mutations in FMF patients according to our results. However, further studies with larger study and control groups are needed.

The relationship between serum adiponectin and resistin levels, insulin resistance and colorectal adenomas.

BACKGROUND/AIMS: The relationship between adipocytokines and the development of colorectal cancer is well-documented. Our aim was to assess the relationship among serum adiponectin and resistin levels, insulin resistance, and colorectal adenoma to evaluate whether these parameters can be used as biomarkers to predict the development of colorectal adenoma. MATERIALS AND METHODS: This is a cross-sectional case-control study conducted in 32 patients with colorectal adenoma and 30 control subjects. Serum adiponectin and resistin levels, body mass index values, waist and hip circumferences and Homeostasis Model Assessment scores were measured. RESULTS: Resistin levels were slightly higher and adiponectin was slightly lower in patients with colorectal adenoma compared with controls; however, the differences in both parameters failed to reach statistical significance. The body mass index values and waist circumference of the patient group were significantly higher than controls (p=0.003 and p=0.002, respectively). Fasting serum insulin levels and Homeostasis Model Assessment scores of patients with colorectal adenoma were significantly higher than those of controls (p=0.02 and p=0.02, respectively). There was no relation between the number of colorectal adenomas and serum adiponectin or resistin levels. CONCLUSION: Our data indicate that obesity and insulin resistance may contribute to the development of colorectal adenoma and that serum adiponectin levels and insulin resistance may not have a substantial predictive value for colorectal adenoma.

Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer.

BACKGROUND: Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. MATERIALS AND METHODS: Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. RESULTS: At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. CONCLUSIONS: Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk.

Asymptomatic brain lesions on cranial magnetic resonance imaging in inflammatory bowel disease.

BACKGROUND/AIMS: This study aimed to examine the frequency and type of asymptomatic neurological involvement in inflammatory bowel disease (IBD) using cranial magnetic resonance imaging (MRI). METHODS: Fifty-one IBD patients with no known neurological diseases or symptoms and 30 controls with unspecified headaches without neurological origins were included. Patients and controls underwent cranial MRI assessments for white matter lesions, sinusitis, otitis-mastoiditis, and other brain parenchymal findings. RESULTS: The frequencies of white matter lesions, other brainstem parenchymal lesions, and otitis-mastoiditis were similar in IBD patients and controls (p>0.05), whereas sinusitis was significantly more frequent in IBD patients (56.9% vs 33.3%, p=0.041). However, among those subjects with white matter lesions, the number of such lesions was significantly higher in IBD patients compared to controls (12.75±9.78 vs 3.20±2.90, p<0.05). The incidence of examined pathologies did not differ significantly with disease activity (p>0.05 for all). CONCLUSIONS: The incidence of white matter lesions seemed to be similar in IBD patients and normal healthy individuals, and the lesions detected did not pose any clinical significance. However, long-term clinical follow-up of the lesions is warranted.

Efficacy of a modified sequential therapy including bismuth subcitrate as first-line therapy to eradicate Helicobacter pylori in a Turkish population.

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem. OBJECTIVES: The aim of this study was to assess efficacy of a modified sequential therapy with the addition of a bismuth preparation, as first-line treatment in the eradication of H. pylori infection. MATERIALS AND METHODS: One hundred and forty-two H. pylori-positive patients were included in the study. Patients were given a 14-day sequential therapy program consisting of pantoprazole, 40 mg (b.i.d. for 14 days); colloidal bismuth subcitrate, 300 mg 4 (two tablets before breakfast and dinner, for 14 days); amoxicillin, 1 g (b.i.d.for the first 7 days); tetracycline, 500 mg (q.i.d. for the second 7 days); and metronidazole, 500 mg (t.i.d. for the second 7 days). Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. RESULTS: Of the 142 patients included, 131 completed the study. "Per-protocol" and "intention-to-treat" analyses revealed high eradication rates in this group (92.0-95% CI, 87.2-96.8%, and 81.0-95% CI, 74.5-87.4%, respectively). There was no relation to sex and age with this modified sequential therapy. Compliance was satisfactory (11 patients - four women and seven men were unavailable for follow-up), and side effects were minimal (six patients had to stop treatment - metronidazole-related facial swelling and numbness on the face and hands in two patients; tetracycline-related fever and epigastric pain and nausea and vomiting in two patients; and amoxicillin-related diarrhea and vaginal discharge in two patients). These side effects were reversible and resolved after the cessation of the related medication. CONCLUSIONS: This 14-day modified sequential treatment, including bismuth, achieves a significantly high eradication rates in patients with H. pylori infection, with five satisfactory patient compliance and minor side effects.

The size of the esophageal hiatus in gastroesophageal reflux pathophysiology: outcome of intraoperative measurements.

OBJECTIVE: The aim of the study was to investigate the impact of the size of the esophageal hiatus on lower esophageal sphincter pressure (LESP) and acid reflux. METHODS: Patients with gastroesophageal reflux disease who underwent Nissen fundoplication in 2006-2008 were included. All underwent esophageal manometry and 22 had 24-h pH monitoring. The area of the esophageal hiatus was calculated from a photograph shot during surgery. A hiatal index was calculated via division of hiatal area with body mass index (BMI). Correlation and logistic regression analysis were performed. RESULTS: Twenty-eight patients (average age 44, 14 males) were enrolled. The mean BMI, LESP, DeMeester score, hiatal area, and hiatal index were 27 +/- 3.9 kg/m(2), 11.7 +/- 6.6 mmHg, 43 +/- 34, 3.83 +/- 1.24 cm(2), and 0.143 +/- 0.048, respectively. There was a significant negative correlation between hiatal area, hiatal index and LESP (-0.513, p = 0.005, r = -0.439, p = 0.019 respectively). Additionally there was a negative correlation between hiatal area and total LES length (r = -0.508, p = 0.013) and a significant positive correlation between hiatal area, hiatal index, and DeMeester scores (0.452, p = 0.035, 0.537, p = 0.01, respectively). Height and hiatal area were significant factors in multiple linear regression. CONCLUSIONS: The size of the esophageal hiatus significantly affects LESP and acid reflux, and hiatal index is a new value, which appears to reflect the amount of acid reflux. Total LES length is also shortened in patients with a large hiatus.

Chemical colitis due to glutaraldehyde: case series and review of the literature.

Chemical colitis can occur as a result of accidental contamination of endoscopes or by intentional/accidental administration of enemas containing various chemicals.We present three cases of glutaraldehyde induced colitis and review the cases in the literature. Glutaraldehyde induced colitis presents clinically with severe abdominal pain, bloody and mucoid diarrhea, rectal bleeding, and tenesmus 48-72 h after colonoscopy. Endoscopic findings are nonspecific and mimic ischemic colitis, inflammatory bowel disease, and infectious colitis. The timing of symptoms and the knowledge that glutaraldehyde is a chemical irritant to colonic mucosa is important for the diagnosis. The treatment is mainly supportive but sometimes necessitates mesalamine, prednisolone, or metronidazole and the resolution is rapid. In endoscopy units, strict adherence to published disinfection protocols is very important and the cleaning, rinsing and drying protocols also deserve the same attention.

Type 2 diabetes mellitus and CA 19-9 levels.

AIM: To prospectively investigate serum CA 19-9 levels in type 2 diabetic patients in comparison with age- and gender-matched control subjects. METHODS: We recorded duration of diabetes and examined fasting glucose levels, HbA1c levels and serum CA 19-9 levels in 76 type 2 diabetic patients and 76 controls. Abdominal CT was performed in order to eliminate abdominal malignancy in the diabetic and control groups. RESULTS: The average CA 19-9 level was 46.0 +/- 22.4 U/mL for diabetic patients whereas it was 9.97 +/- 7.1 U/mL for the control group (P < 0.001). Regression analysis showed a positive correlation between diabetes and CA 19-9 independent from age, gender, glucose level and HbA1c level (t = 8.8, P < 001). Two of the diabetic patients were excluded from the study because of abdominal malignancy shown by CT at the initial evaluation. For all patients, abdominal CT showed no pancreatic abnormalities. CONCLUSION: CA 19-9 is a tumor-associated antigen, which is elevated in pancreatic, upper gastrointestinal tract, ovarian hepatocellular, and colorectal cancers, as well as in inflammatory conditions of the hepatobiliary system, biliary obstruction and in thyroid diseases. Diabetes has been claimed to be a risk factor for pancreatic cancer, which is increasing its incidence and has one of the lowest survival rates of all cancers. CA 19-9 is used in the diagnosis of pancreatic cancer but is also a marker of pancreatic tissue damage that might be caused by diabetes. We propose that a higher cut-off value of CA 19-9 should be used in diabetics to differentiate benign and malignant pancreatic disease, and subtle elevations of CA 19-9 in diabetics should be considered as the indication of exocrine pancreatic dysfunction.

Dorsal pancreatic agenesis.

CONTEXT: Agenesis of the dorsal pancreas is a rare entity and might present with various symptoms. We report a case which presented with chronic pancreatitis. CASE REPORT: The patient presented with epigastric pain and we found dorsal pancreatic agenesis causing chronic pancreatitis. CONCLUSIONS: Dorsal pancreatic agenesis can be easily diagnosed with new techniques and its association with clinical syndromes can be better understood.

A case of herpes simplex hepatitis with hepatic nodules in an immunocompetent patient.

Herpes simplex hepatitis is a rare cause of acute hepatitis in immunocompetent patients. Herpes hepatitis presents with nonspecific symptoms like fever, loss of appetite, vomiting, nausea and abdominal pain. Elevated transaminase values with leukopenia, relatively low bilirubin level and mucosal herpetic lesions often provide clues to the diagnosis. We describe an immunocompetent woman with herpes simplex hepatitis presenting with multiple hypodense lesions in the liver and mucocutaneous herpetic lesions.

Laparoscopic repair of a gastric volvulus occurring as a long-term complication of left pneumonectomy: report of a case.

Gastric volvulus is an extremely rare late complication of pneumonectomy. We report the case of a 61-year-old man who presented with a 1-year history of progressive intolerance of solids and weight loss 33 years after a left pneumonectomy. Preoperative examinations showed a mesenteroaxial gastric volvulus. We performed a laparoscopic Toupet fundoplication and anterior gastropexy, following which his symptoms disappeared.

Endoscopic scoring of late gastrointestinal mucosal damage after adjuvant radiochemotherapy.

AIM: To evaluate late effects of chemoradiation on gastrointestinal mucosa with an endoscopic scoring system and compare it to a clinical scoring system. METHODS: Twenty-four patients going to receive chemoradiation after gastric surgery underwent endoscopy four wk after surgery and one year after the chemoradiation finished. Upper gastrointestinal findings were recorded according to a system proposed by World Organisation for Digestive Endoscopy (OMED) and clinical scoring was done with RTOG-EORTC radiation morbidity scoring systems. RESULTS: There was no significant endoscopic difference in gastric and intestinal mucosa after chemoradiation (P > 0.05) and there was no association between endoscopic scores and clinical scores. Endoscopic changes were minimal. CONCLUSION: Late effects after chemoradiation in operated patients with gastric cancers can be evaluated with an endoscopic scoring system objectively and this system is superior to clinical scoring systems.

Is adiponectin level a predictor of nonalcoholic fatty liver disease in nondiabetic male patients?

AIM: Adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumor necrosis factor. We studied its levels in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD) and compared with control group. METHODS: Thirty-five patients who had elevated serum aminotransferase levels with bright liver and 34 healthy volunteers without liver disease were evaluated. Age, gender and body mass index (BMI) were recorded. Fasting plasma glucose, insulin, adiponectin, proinsulin and lipid profile were measured. A standard oral glucose tolerance test (OGTT) with insulin response was performed and the index of insulin resistance was calculated according to the homeostasis model assessment (HOMA) method. RESULTS: According to the OGTT results, none of the participants had diabetes. Serum adiponectin levels were statistically significantly lower in patients with NAFLD than in control group (8.14+/-3.4 microg/mL vs 12.4+/-9.4 microg/mL, respectively, P<0.01). A statistically significant correlation was found between adiponectin and BMI (r : -0.33, P<0.01), HOMA (r : -0.26, P<0.05), proinsulin (r : -0.32, P<0.01), AST (r : -0.25, P<0.05), ALT (r : -0.26, P<0.05) or GGT (r : -0.22, P<0.05). In multiple regression analysis models, adiponectin levels were the only predictor of NAFLD in males, whereas in female group it was the BMI. CONCLUSION: Low adiponectin level might be a predictor of NAFLD especially in male nondiabetics.

Encapsulating peritonitis and familial Mediterranean fever.

AIM: To investigate the relationship between encapsulating peritonitis and familial Mediterranean fever (FMF). METHODS: The patient had a history of type 2 diabetes and laparoscopic cholecystectomy was performed one year ago for cholelithiasis. Eleven months after the operation she developed massive ascites. Biochemical evaluation revealed hyperglycemia, mild Fe deficiency anemia, hypoalbuminemia and a CA-125 level of 2 700 IU. Ascitic evaluation showed characteristics of exudation with a cell count of 580/mm(3). Abdominal CT showed omental thickening and massive ascites. At exploratory laparotomy there was generalized thickening of the peritoneum and a laparoscopic clip encapsulated by fibrous tissue was found adherent to the uterus. Biopsies were negative for malignancy and a prophylactic total abdominal hysterectomy and bilateral salpingooophorectomy were performed. RESULTS: The histopathological evaluation was compatible with chronic nonspecific findings and mild mesothelial proliferation and chronic inflammation at the uterine serosa and liver biopsy showed inactive cirrhosis. CONCLUSION: The patient was evaluated as sclerosing encapsulating peritonitis induced by the laparoscopic clip acting as a foreign body. Due to the fact that the patient had FMF the immune response was probably exaggerated.

Association of nonalcoholic fatty liver disease with insulin resistance: is OGTT indicated in nonalcoholic fatty liver disease?

Nonalcoholic fatty liver disease (NAFLD) is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia. We tested the hypothesis that there may be an association between NAFLD and insulin resistance (IR); and its correlation with glucose tolerance status of subjects who aren't known patients with diabetes. One hundred and seventy-six consecutive patients with elevated serum aminotransferase levels and bright liver were evaluated. Sixty-two patients were excluded from the study. Age, gender, height, weight, body mass index, waist circumferences, and family history of diabetes were recorded. Fasting plasma glucose, insulin, lipid profile were measured. A standard oral glucose tolerance test (OGTT) was performed and the index of IR was calculated according to the HOMA method. Patients with a normal glucose tolerance formed group 1 (64 patients) and patients with impaired or diabetic glucose tolerance group 2 (50 patients). Age, female sex, family history of type 2 diabetes, fasting insulin, fasting plasma glucose and HOMA-R index were statistically significantly different between the groups. Although the subjects in the study are not known patients with diabetes, the prevalence of impaired or diabetic glucose tolerance was prominent. In conclusion, performing OGTT in cases with nonalcoholic fatty liver disease may be useful for early screening of diabetes mellitus.