Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis.

OBJECTIVE: This study was designed to identify the effect of rivaroxaban, a direct factor Xa inhibitor, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Twenty-four female Wistar rats were divided into 4 groups of 6 each. Group 1 received TNBS + rivaroxaban, group 2 received TNBS + methylprednisolone, group 3 received TNBS and group 4 received a saline enema. Colitis was induced in the rats by the intracolonic administration of TNBS. Rivaroxaban and methylprednisolone were given by oral gavage daily for 7 days. The rats were killed 7 days after the induction of colitis. RESULTS: Rivaroxaban and methylprednisolone significantly reduced gross damage and histopathological scores. Rivaroxaban was more effective than methylprednisolone in terms of microscopic mucosal healing. Rivaroxaban attenuated the accumulation of malonyldialdehyde (MDA) and transforming growth-factor ß1 (TGF-ß1) and the activities of myeloperoxidase (MPO), matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Methylprednisolone reduced only the activity of MPO and the accumulation of MDA and TGF-ß1. Superoxide dismutase activity showed a restoration to normal levels after rivaroxaban and methylprednisolone administration. CONCLUSIONS: Rivaroxaban showed a therapeutic effect in the TNBS model of experimental colitis, and it seemed to be at least as effective as methylprednisolone. This effect may be brought about by the inhibition of oxidative stress and metalloproteinase activity associated with tissue injury and remodeling.

Folate deficiency in Crohn's disease.

There are several causes for folate deficiency in Crohn's disease: malnutrition, malabsorption, excess folate utilization and medications. A combination of these factors may be responsible for the deficiency of this vitamin in some cases.

Circulating CD4+CD25+ regulatory T cells in the pathobiology of ulcerative colitis and concurrent primary sclerosing cholangitis.

BACKGROUND: Immunopathogenetic features of primary sclerosing cholangitis (PSC) in ulcerative colitis (UC) still remains unclear. Peripheral blood CD4+CD25+ regulatory T cells have a key role in the induction and maintenance of peripheral self-tolerance and inhibit several organ-specific autoimmune diseases. Therefore, CD4+CD25+ T cells are believed to play an essential role in autoimmune diseases. The aim of the present study is to analyze the role of CD4+CD25+ T cells in the pathogenesis of UC-associated PSC. METHODS: This study evaluated the levels of CD4+CD25+ T cells in peripheral blood mononuclear cells (PBMC) of 27 UC patients with PSC and 20 UC patients as controls. CD4+CD25+ T cells were isolated from PBMC with a direct immunofluorescence technique, using mice monoclonal antibodies namely FITC-labeled anti-CD4 and PE-labeled anti-CD25. In each patient, CD4+CD25+ T cells percentage in PBMC were studied by flow cytometry, and then the number of CD4+CD25+ T cells were calculated. RESULTS: Twenty-seven UC patients with PSC and 20 UC patients without PSC as controls were enrolled in the present study. The percentage of CD4+CD25+ regulatory T cells among PBMC were significantly elevated in UC + PSC patients compared with UC patients without PSC (p = 0.04). CONCLUSIONS: CD4+CD25+ T cells were found to be elevated in UC patients with PSC suggesting a partial role of activated T cell response in the disease pathophysiology. Our findings imply that CD4+CD25+ regulatory T cells may play a key role in the immunopathogenesis of UC-associated PSC and may affect the therapeutic management of these diseases.

Can red cell distribution width help to discriminate benign from malignant biliary obstruction? A retrospective single center analysis.

BACKGROUND/AIMS: Differentiation of benign obstructive jaundice from malignant obstructive jaundice still remains difficult, despite improvements in diagnostic modalities. The aim of this study is to evaluate the usefulness of red cell distribution width (RDW) in differentiating benign and malignant causes of obstructive jaundice. METHODOLOGY: One hundred and ninety four consecutive patients (101 malignant, 93 benign) with a history of obstructive jaundice were reviewed in the period between January 2008 and August 2009. Definition of biliary strictures was suggested by cholangiographic features and supported by brush cytology, fine needle aspiration (FNA) and the presence of mass or metastases by imaging and/or clinical followup. Patients were divided into two groups, benign and malignant, based on the discharge diagnosis. RESULTS: The receiver operating characteristic analysis showed that a RDW of 14.8% was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 72% and a specificity of 69% (AUC=0.755, 95% CI=0.649-0.810). RDW was increased (>14.8%) in 31.6% of benign cases and 68.4% of malignancies. Depressed RDW levels (<14.8%) were found in 72.9% of benign cases and 27.1% of malignancies, which was statistically significant (p<0.001). CONCLUSIONS: Our results show that RDW is useful in the differentiation of benign from malignant causes of biliary obstruction when using an optimized cut-off value. In patients in whom biliary obstruction is suspected, an elevated RDW value may be a reliable additional predictor for differentiating the underlying etiology of biliary obstruction.

The role of mean platelet volume in the diagnosis of hepatocellular carcinoma in patients with chronic liver disease.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has poor long-term prognosis so we need new diagnostic techniques and markers to detect HCC in the early phases. The aim of this study was to analyze the levels of serum mean platelet volume in HCC. METHODOLOGY: The clinical data of 230 subjects with normal, chronic hepatitis, cirrhosis and HCC were retrospectively analyzed at our hospital between January 2009 and December 2009. The levels of MPV were determined in patients with liver disease and compared between patient groups and with healthy persons. RESULTS: Serum MPV levels were significantly increased compared to the patients with chronic hepatitis, cirrhosis, and the control group (p<0.01). The cut-off value for MPV for the detection of HCC in cirrhotic patients was calculated as ≥9.2fl using ROC analysis [Sensitivity: 68.3%, specificity: 62.1%, AUC: 0.676 (0.580-0.773), p<0.001]. Additionally, serum MPV levels show higher sensitivity for diagnosis of HCC than AFP. An AFP of more than 7.4IU/mL and an MPV of ≥9.2fl, both put together, had a specificity of 95.2%, while when used separately, they have a sensitivity of 87.5%. CONCLUSIONS: MPV may be a potential or adjunctive marker of HCC in patients with chronic liver disease.

Endoscopic and pathological aspects of gastric polyps: a Turkish referral center study.

BACKGROUND/AIMS: The aim of the present study was to retrospectively analyze all the polyps of patients undergoing endoscopic polypectomy or forceps biopsy according to their types, frequency, localization, number and gender distribution. METHODOLOGY: Data from patients who underwent upper endoscopy in the Türkiye Yüksek Ihtisas Postgraduate Research Hospital between March 2007 and November 2009 were analyzed retrospectively. Forceps biopsy or polypectomy were performed for all polypoid lesions that were identified during the endoscopy. RESULTS: In the study period, 14,935 patients underwent 18,522 upper endoscopies. After excluding cirrhotic patients, and patients with a history of prior gastrectomy, chronic gastritis and edema or congestion, the remaining 124 (0.83%) patients with gastric polyps were included in the study. Histopathologically, the most frequently diagnosed polyps were hyperplastic polyps (55.6%). Fundic gland polyps (9.7%), foveolar hyperplasia (8.1%) and inflammatory polyps (7.3%) were also frequent. Adenocarcinoma was more frequently seen in males, whereas hyperplastic polyps and carcinoid tumors were found more often in females, and this difference was statistically significant (p<0.009). CONCLUSIONS: Results of the present study indicate that hyperplastic polyps make up the largest group. Although there is widespread PPI use, no increases in the frequency of fundic gland polyps were observed. However, increases in the ratio of carcinoid tumors suggest a suspicion of tumor development with PPI use.

Double balloon enteroscopy: a 3-year experience at a tertiary care center.

BACKGROUND/AIMS: To evaluate the indications, diagnostic yield, therapeutic interventions, complications and safety of double balloon enteroscopy (DBE) in clinical practice. METHODOLOGY: The medical records of the patients who underwent DBE at the Turkiye Yuksek Ihtisas Hospital between October 2007 and January 2010 were examined to note the demographic data, indications for the examination, results of previous non-invasive small bowel imaging and endoscopic procedures and the results of DBE including findings, endoscopic interventions, complications and pathological reports. RESULTS: A total of 139 procedures were performed in 118 patients. DBE was performed 81 times through mouth and 26 times through anus and additionally both approaches were used 16 times in the same patients. Panenteroscopy was successfully performed in 13 of 16 patients (87.5%) in whom it was attempted. The most common indication was obscure gastrointestinal bleeding (28.8%). DBE had an overall diagnostic and/or therapeutic contribution in 63 (53.4%) patients. The main pathologies detected on DBE were polyps (12.7%), infammation (10.7%) and vascular lesions (3.4%). Complications were recognized in four cases (3.4%) but no major complication occured. CONCLUSIONS: Our retrospective analysis showed that DBE is a useful, safe and well-tolerated method with a diagnostic and therapeutic impact for the management of small bowel diseases.

ERCP experience in patients with choledochoduodenostomy: diagnostic findings and therapeutic management.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP), besides reducing the need for surgery in a wide spectrum of biliary disease, is increasingly be used for the treatment of biliary complications of surgery. In this paper, we review our experience with postoperative ERCPs required after biliary surgery with a special focus on side-to-side choledochoduodenostomy (CD). METHODS: The records of 70 patients with a history of CD who underwent ERCP from May 2000 to February 2006 were analyzed. RESULTS: There were 70 patients, 32 (45.7%) women and 38 (35.6%) men, with a mean age of 56 (range, 21-80) years. Indications for ERCP were cholangitis in 46 (65.7%), abnormal liver function tests with abdominal pain and abnormal USG in 22 (31.4%), and abnormal liver function tests and abnormal USG in 2 (2.9%). Overall 133 ERCP were performed. Anastomotic stenosis was found in 14 (20%), benign biliary stricture above the anastomosis in 13 (18.6%), sump syndrome in 11 (15.7%), common bile duct stone in 8 (11.4%), malignancy in 4 (5.7%), hepatolithiasis in 1 (1.4%), and secondary sclerosing cholangitis in 1 (1.4%). ERCP was normal in 18 (25.8%). Patients were managed by stone extraction in 8 (11%), stent insertion in 22 (36%), balloon dilatation in 15 (21%), nasobiliary drainage in 11 (16%), and bougie dilatation in 2 (3%) patients. CONCLUSIONS: We have reported one of the largest groups of patients with CD in the literature and showed that ERCP is a very important diagnostic and therapeutic tool for the management of biliary problems after CD.

Elevated levels of circulating angiotensin converting enzyme in patients with hepatoportal sclerosis.

BACKGROUND AND AIMS: Hepatoportal sclerosis (HPS) is a clinicopathologic condition that is clinically characterized by portal hypertension (varices and portosystemic collateral vessels), splenomegaly and pancytopenia, in the absence of cirrhosis. Although the etiology is obscure, a number of theories such as immunologic and vascular endothelial cellular abnormalities have been put forward to explain the underlying pathophysiology. Angiotensin-converting enzyme (ACE), an important molecule of the renin-angiotensin system (RAS), is also known as a regulatory molecule in systemic and portal circulation in distinct disorders. The aim of the present study was to investigate the possible role of the ACE in the context of RAS in HPS pathogenesis. MATERIALS AND METHODS: The study was conducted on 30 HPS patients (16 men, 14 women; median age 36 years, range 18-63) and 20 healthy controls. The clinical features of HPS patients including demographics, laboratory, and ultrasonography findings were summarized. Serum ACE levels were measured by using commercially available kits. RESULTS: Serum median ACE levels were 36 (8-174) U/l and 16 (8-43) U/l for the HPS patients and controls, respectively. Serum ACE levels were significantly higher in patients with HPS compared to the control group (P < 0.05). CONCLUSION: ACE in the context of RAS may be associated with pathological endothelial occlusive events in the microenvironment of the portal circulation in HPS. Revealing the interactions between circulating and local RAS within the hepatic microenvironment would enlighten the biologic basis and clinical management of liver diseases.

Does interleukin-18 play a role in the pathogenesis of hepatic encephalopathy?

BACKGROUND/AIMS: It has been suggested that the presence of inflammation may accentuate the neuropsychologic alterations in hepatic encephalopathy (HE). The aim of the study was to investigate any association between alterations in plasma levels of the pro-inflammatory cytokine IL-18 and HE. METHODOLOGY: The study population included 63 patients with cirrhosis and 20 healthy controls. Laboratory data included international normalized ratio, plasma albumin, bilirubin, urea, creatinine, hsCRP and IL-18 (pg/mL). HE was assessed using West Haven criteria and critical flicker frequency (CFF) measurement. RESULTS: Forty-two of the 63 cirrhotic patients had HE (4, 16, 21 and 1 patients in grade 0, 1, 2, 3, respectively). hsCRP and IL-18 were significantly increased in patients with HE compared with the control group (1.6 +/- 4.8 vs 0.5 +/- 0.8, p<0.001 and 121.4 (13.6-2043.6) vs 56.3 (13.0-174.0), p=0.006, respectively). The levels of hsCRP and IL-18 were significantly higher in the all cirrhotic patients than in the control subjects (p=0.002 and p=0.008 respectively). hsCRP was significantly higher in patients with HE (2.2 +/- 6) than in patients without HE (0.7 +/- 1.2) (p=0.013). The levels of IL-18 were found higher in patients with HE than in patients without HE [121.4 (13.6-2043.6) vs 103.8 (13.0-828.0)] but the difference was not significant (p=0.215). IL-18 was higher in patients with elevated hsCRP [124.6 (13.6-2043.6)] compared with those who had normal hsCRP [75.6 (13.0-753.2)] (p=0.029). CONCLUSION: There is an inflammatory response in the presence of cirrhosis and HE; and IL-18 may play a role in the perpetuation of chronic inflammation.

What are the clinical implications of nodular gastritis? Clues from histopathology.

There is no widely accepted histopathological definition for nodular gastritis. In this study we aim to uncover the pathologic entity responsible for the nodular appearance and to find clues about the clinical implications of nodular gastritis. Antral biopsy specimens of 160 patients with nodular gastritis and 133 patients without nodular gastritis were examined by an experienced pathologist for dysplasia, foveolar hyperplasia, inflammatory activity, intraepithelial lymphocytosis, intestinal metaplasia, and lymphoid follicle/aggregate formation, and comparative analysis was performed between the two groups of patients. The presence of intraepithelial lymphocytosis was more frequent in patients with nodular gastritis (P < 0.05). There was no difference between the two groups regarding the other pathological features such as presence of dysplasia, inflammatory activity, intestinal metaplasia, lymphoid hyperplasia, and Helicobacter pylori (H. pylori) infection. Increase of intraepithelial lymphocytes may contribute to formation of macroscopical nodules in this peculiar type of gastritis. Nodular gastritis would not indicate a new therapeutic approach in addition to the current measures for Helicobacter pylori infection.

A case of patent ductus venosus complicated with tumor-like lesions of the liver.

Patent ductus venosus (PDV) is a very rare congenital vascular anomaly of the liver. We report a 17-year-old male patient presenting with elevated liver enzymes and multiple liver masses. Physical examination was normal except for pectus excavatum deformity. Ultrasonography revealed multiple tumor-like lesions of the liver and a dilated portal vein with mild splenomegaly. Liver biopsy obtained from liver parenchyma revealed minimal hepatocellular damage. PDV was diagnosed by CT (computed tomography) portography. The radiologic findings of chronic liver disease and multiple liver masses were attributed to presence of PDV. Although it is very rare, PDV might be a diagnostic possibility in patients with mass lesions in the liver.

Research for bleeding tendency in patients presenting with significant epistaxis.

To evaluate the association of inherited coagulopathies and acquired conditions (e.g. hypertension, aspirin use) with emergency department admission due to epistaxis. Patients admitted to the emergency department with epistaxis were included. A questionnaire for personal and family history of any bleeding disorder was used. Physical examination including ear, nose and throat examination was performed. Platelet counts, International Normalized Ratio, activated partial thromboplastin time, factors VIII, IX and XI, von Willebrand factor and ristocetin cofactor activity levels were determined. Nineteen patients were included in the study. Personal history of mucocutaneous bleeding was present in four cases and family history in two cases. Only one case (5%) had a decreased von Willebrand factor level (45%), and also had a personal and family history of bleeding tendency. Ten patients (53%) had a history of aspirin use. Thirteen (68%) patients had hypertensive values on admission. Aspirin use and hypertension were the leading causes of emergency service admission in adults due to epistaxis in this study, although the number of the patients was relatively low. Regarding the low prevalence of inherited coagulopathies, detailed coagulation tests should be reserved for adult patients with positive personal and/or family history of bleeding.

Pentoxifylline attenuates mucosal damage in an experimental model of rat colitis by modulating tissue biomarkers of inflammation, oxidative stress, and fibrosis.

BACKGROUND/AIM: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days. RESULTS: IP and IR pentoxifylline similarly and significantly reduced damage and histopathological scores. Pentoxifylline attenuated the accumulation of malonyldialdehyde and transforming growth factor ß1 and the activities of myeloperoxidase, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1, and it also restored superoxide dismutase activity. The IP route was more effective than the IR route in this regard. Administration of IP pentoxifylline before or after induction did not influence all parameters. Conclusions: Pentoxifylline showed a therapeutic effect in this experimental colitis model. IP administration seemed to be better. This effect may occur as a result of inhibition of oxidative stress and metalloproteinase activity.

Hemorrhage into a thyroid nodule as a cause of thyrotoxicosis.

OBJECTIVE: To describe a case of thyrotoxicosis after nontraumatic hemorrhage into the thyroid gland during anticoagulant therapy. METHODS: We report the details of the initial presentation, subsequent course, and outcome in a patient with a nontraumatic thyroid hematoma and thyrotoxicosis. RESULTS: In a 63-year-old woman, an acute painful neck mass developed during follow-up while she was receiving low-molecular-weight heparin therapy for deep vein thrombosis. Ultrasound study and magnetic resonance imaging revealed a massive intrathyroidal hematoma. This finding was followed by an increase in serum free thyroxine and free triiodothyronine levels and a decrease in the level of serum thyroid-stimulating hormone (thyrotropin). Anticoagulant therapy was discontinued. The clinical course of the thyrotoxicosis was self-limited, and no antithyroid therapy was necessary. The serum thyroid hormone levels decreased into normal ranges as the hematoma underwent subtotal shrinkage. CONCLUSION: Endocrine glands are highly vascularized tissues, but nontraumatic hematomas into these organs are extremely rare conditions. Nevertheless, physicians should be aware of the potential occurrence of such a situation, as emphasized in the current case report.

Paradoxical deterioration during the course of antituberculous treatment.

Paradoxical deterioration during antituberculous therapy is defined as the clinical or radiological worsening of pre-existing tuberculous lesions or the development of new lesions in a patient who initially improves. Although it has frequently been reported for patients infected with human immunodeficiency virus (HIV), it can also be seen in HIV-negative patients. Here, we present a case of miliary tuberculosis in a patient who clinically deteriorates after antituberculous treatment, and discuss this confusing entity under the light of the pertinent literature.

Cauda equina syndrome as a rare manifestation of leukemia relapse during postallograft period.

Here we report a 41-year-old woman with the diagnosis of acute myeloid leukemia. While being followed on remission after allogeneic peripheral blood stem cell transplantation, she developed systemic and central nervous system (CNS) relapse. CNS involvement presented first with meningeal irritation signs and then with cauda equina syndrome (CES). We define an interesting presentation of CES as abdominal pain and discuss the rare coexistence of the syndrome and leukemia under the light of the pertinent literature.