Ibrahim Hatemi

Screening for Iron Overload in the Turkish Population

Background/Aims: Hereditary hemochromatosis (HH), the most common autosomal recessive disease in the white population, is characterized by excessive gastrointestinal absorption of iron and loading of parenchymal organs. HFE mutations of C282Y and H63D are largely responsible for HH in populations of Celtic ancestry. Although many screening studies related to HH have been done in Northern Europe, the USA and Australia, as yet, no such study has been published on Turkey. In this study we aimed to screen the Turkish population for iron overload. Methods: Random samples were obtained from 4,633 healthy adults (3,827 male, 806 female, mean age ± SD 35 ± 8 years, range 14–76) for the measurement of transferrin saturation (TS). Measurements were repeated after an overnight fast in the subjects whose initial TS was ≧50%. Serum ferritin levels and C282Y and H63D gene mutations were studied in cases when fasting TS was ≧50%. In cases where the serum ferritin level was >200 ng/ml with or without HFE mutations, liver biopsy was performed for histological evaluation and determination of iron content. Results: In 158 subjects, TS was ≧50% in the non-fasting state. A second determination of TS after an overnight fast was performed in 135 subjects. In 26 subjects, the TS was ≧50% in the fasting state. HFE mutation and serum ferritin levels were measured in these 26 subjects. Eleven subject (10 male, 1 female) were heterozygote and 1 male subject was homozygote in reference to H63D. C282Y mutation was not found. Four of these 26 subjects (all males, aged 23, 24, 40, 49) had increased serum ferritin levels and liver biopsy was performed. In 1 male (aged 49) who was heterozygote for H63D genotype with a serum ferritin level of 645 ng/ml, iron overload in liver tissue was shown by histology as well as atomic absorption spectrophotometry. Conclusion: The prevalence of hemochromatosis in the Turkish population is much lower in comparison to populations of Celtic ancestry and C282Y mutation is non-existent.

Bone marrow transplantation for Behçet’s disease: a case report and systematic review of the literature

OBJECTIVES Behçets disease (BD) can be life threatening and may be refractory to corticosteroids and immunosuppressives. There has been some experience with haematopoietic stem cell transplantation (HSCT) in BD either for severe, refractory disease or for a haematological condition. The objectives of this study were to describe a BD patient undergoing HSCT and to evaluate the outcomes of BD patients who underwent HSCT. METHODS We report a BD patient with refractory gastrointestinal (GI) involvement who had HSCT for concomitant myelodysplastic syndrome (MDS). We also performed a systematic literature search regarding HSCT for either refractory disease or concomitant haematological conditions in BD patients. RESULTS A 30-year-old woman with refractory GI BD involvement with trisomy 8 MDS underwent a successful myeloablative allogeneic HSCT resulting in complete resolution of both BD and MDS. Additionally we identified 14 manuscripts providing data on 19 patients with BD who had HSCT. Among these 20 patients, including ours, refractory disease was the indication of transplantation in 9, while 11 patients were transplanted because of accompanying haematological conditions. Transplant indications for the nine patients (four male, five female) with refractory BD were neurological involvement in five, pulmonary artery aneurysm in two, GI disease in one and not reported in one patient. Three patients with neurological disease, both patients with pulmonary artery aneurysm and the patient with intestinal involvement achieved complete remission of their disease. Six patients transplanted for haematological conditions, including the presented case, also had GI involvement of BD. All of these patients achieved complete remission of GI findings after HSCT. CONCLUSION When considering HSCT, the potential adverse events and complications, which can be fatal, need to be kept in mind.

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease.

BACKGROUND/AIMS Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to find the relation between oxidative stress parameters and histopathological findings in NAFLD patients with and without insulin resistance (IR). MATERIALS AND METHODS Thirty-two patients with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied (M/F: 17/15; mean age 46.5±11.4 years). Twenty-one NAFLD patients with IR were compared with 11 patients without IR. The fasting insulin level was measured, and the insulin resistance index was calculated using the homeostasis model assessment (HOMA) method. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were measured in tissue and serum specimens. Glutathione (GH) was measured in tissue homogenates. Nitric oxide (NO), vitamin E and C levels were measured in serum. RESULTS Patients with IR had significantly higher tissue MDA levels (p=0.001) and significantly decreased tissue SOD and GH levels (p=0.001 and 0.002, respectively) than those without IR. The steatosis grade, necroinflammatory grade and stage were significantly higher in patients with IR (p=0.035, 0.003 and 0.001, respectively). HOMA IR significantly correlated with the necroinflammatory grade, stage, tissue MDA, SOD and GH (p=0.013, 0.001, 0.008, 0.001 and 0.001, respectively). Serum MDA (β=1.88, p=0.002), serum SOD (β=0.57, p=0.006), tissue MDA (β=0.22, p=0.006), tissue SOD (β=1.48, p=0.071) and stage (β=2.81, p=0.003) were independently associated with increased HOMA IR. Increased MDA [OR: 1.51; 95% CI: (1.03-2.22); p=0.034] was a risk factor for non-alcoholic steatohepatitis (NASH), and increased SOD activity had a preventive effect against NASH [OR: 0.008; 95% CI: (0.001-0.98); p=0.04]. CONCLUSION This study shows that insulin resistance in NAFLD correlates with enhanced oxidative stress. Histopathological disease severity significantly correlated with oxidative stress parameters. These data show that NAFLD patients with IR may have increased risk for disease progression.

Characteristics, Treatment, and Long-Term Outcome of Gastrointestinal Involvement in Behcet's Syndrome: A Strobe-Compliant Observational Study From a Dedicated Multidisciplinary Center

AbstractGastrointestinal involvement is rare in Behçets syndrome (BS) patients from the Mediterranean basin. We report the demographic and disease characteristics, treatment modalities, and outcome of patients with gastrointestinal involvement in BS (GIBS).We retrospectively reviewed the charts of all BS patients in our BS clinic with a diagnosis of GIBS. Patients were invited to the clinic to assess their outcome.Among 8763 BS patients, we identified 60 with GIBS (M/F: 32/28, mean age at diagnosis: 34 ± 10, mean follow-up: 7.5 ± 4 years), after excluding 22 patients with mimicking symptoms. Six (10%) had juvenile-onset BS. The most common intestinal localization was ileocecal region (36/59, 61%) mainly as big oval ulcer/s. Initial treatment was azathioprine for moderate to severe (n = 37) and 5-ASA for mild cases (n = 16). Anti-TNFs and/or thalidomide provided remission in 12 of 18 (67%) refractory patients. Emergency surgery was required in 22 patients. Nine patients did not receive postoperative immunomodulators and 8 relapsed. Overall, 48 of 60 (80%) patients were in remission (29/48 without treatment) at the time of survey. Three recently treated and 2 refractory patients were still active, 3 had died due to non-GI-related reasons, and 4 were lost to follow-up.Careful evaluation for excluding mimickers is important during the diagnosis of GIBS. Azathioprine seems to be a good choice as first-line treatment with high remission rates and few adverse events. Thalidomide and/or TNF-alpha antagonists may be preferred in resistant cases. Surgery may be required for perforations or massive bleeding, and postoperative immunosuppressive treatment is necessary for preventing postoperative recurrences.

Concordance of Endoscopic Ultrasonography-Guided Fine Needle Aspiration Diagnosis with the Final Diagnosis in Subepithelial Lesions

Background/Aims In this study we aimed to determine the rate of concordance of endoscopic ultrasonography (EUS)-guided fine needle aspiration (FNA) diagnosis with the final diagnosis obtained by surgery or endoscopic resection and follow-up in upper gastrointestinal subepithelial lesions. Methods We retrospectively studied patients with subepithelial lesions who underwent EUS at our center from 2007 to 2011. Results We had a final diagnosis in 67 patients (mean age±SD, 51.23±12.48 years; 23 [34.3%] female, 44 [65.6%] male). EUS-FNA was performed in all of the patients. On-site pathology was not performed. In nine of the patients, the obtained material which was obtained was insufficient. The cytologic examination was benign in 31 and malignant in 27 of the patients. Based on the final diagnosis, the EUS-FNA had a sensitivity of 96%, a specificity of 100%, and a diagnostic yield of 85%. Conclusions The diagnostic yield of EUS-FNA, in the absence of the on-site cytopathologist, is feasible for the diagnosis of subepithelial lesions of the upper gastrointestinal system.

Acute colitis presenting with hematochezia in a patient with chronic myeloid leukemia during dasatinib therapy.

An 18-year-old male patient was diagnosed with a high Sokal risk chronic-phase CML in January 2000. He first received hydroxyurea (HU) for six years, and then he was admitted to our hematology department and imatinib mesylate (IM) 400 mg/daily was initiated in September 2006. He never achieved major molecular and complete cytogenetic responses with IM, and he did not have a donor for allogeneic hematopoietic stem cell transplantation. DAS 100 mg/day was started in September 2007, six weeks after the initiation of DAS, the patient presented with rectal bleeding and diarrhea. He never had such complaints prior to DAS. A colonoscopic examination was performed in November 2007, which revealed exudation, erosions and multiple ulcers with nodular hyperemic lesions in the entire colon. Histopathological examination showed nonspecific colitis. First glucocorticosteroid then oral 5-aminosalicylic acid (5-ASA) was started, and his complaints were diminished but never totally resolved. A BCR-ABL kinase domain mutation analysis was performed which lead to the identification of T315I, and dasatinib was stopped in June 2008. After the interruption of DAS, his rectal bleeding and diarrhea were completely resolved. HU was restarted, but during the follow-up, he was deceased due to myeloid blast crisis in September 2010.

Familial chylomicronemia syndrome related chronic pancreatitis: A single-center study

BACKGROUND Hypertriglyceridemia induces acute recurrent pancreatitis, but its role in the etiology of chronic pancreatitis (CP) is controversial. This study aimed to evaluate the clinical, laboratory and radiological findings of 7 patients with CP due to type 1 hyperlipidemia compared to CP patients with other or undefined etiological factors. METHODS We retrospectively analyzed the clinical, laboratory and radiological findings of 7 CP patients with type 1 hyperlipidemia compared to CP patients without hypertriglyceridemia. These 7 patients had multiple episodes of acute pancreatitis and had features of CP on abdominal CT, endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasonography. RESULTS All CP patients were classified into two groups: a group with type 1 hyperlipidemia (n=7) and a group with other etiologies (n=58). The mean triglyceride level was 2323+/-894 mg/dL in the first group. Age at the diagnosis of CP in the first group was significantly younger than that in the second group (16.5+/-5.9 vs 48.3+/-13.5, P<0.001). The number of episodes of acute pancreatitis in the first group was significantly higher than that in the second group (15.0+/-6.8 vs 4.0+/-4.6, P=0.011). The number of splenic vein thrombosis in the first group was significantly higher than that in the second group (4/7 vs 9/58, P=0.025). Logistic regression analysis found that younger age was an independent predictor of CP due to hypertriglyceridemia (r=0.418, P=0.000). CONCLUSIONS Type 1 hyperlipidemia appears to be an etiological factor even for a minority of patients with CP. It manifests at a younger age, and the course of the disease might be severe.

Behçet’s syndrome: providing integrated care

Behçet’s syndrome (BS) is a multisystem vasculitis that presents with a variety of mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system involvement. Although it occurs worldwide, it is especially prevalent in the Far East and around the Mediterranean Sea. Male gender and younger age at disease onset are associated with a more severe disease course. The management of BS depends on the severity of symptoms. If untreated, morbidity and mortality are considerably high in patients with major organ involvement. Multidisciplinary patient care is essential for the management of BS, as it is for other multisystem diseases. Rheumatologists, dermatologists, ophthalmologists, neurologists, cardiovascular surgeons and gastroenterologists are members of the multidisciplinary team. In this study, we reviewed the epidemiology, etiology, diagnostic criteria sets, clinical findings and treatment of BS and highlighted the importance of the multidisciplinary team in the management of BS.

Systemic vasculitis and the gut.

Purpose of review Gastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed. Recent findings Diagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield. There are conflicting reports on the association of antineutrophilic cytoplasmic antibodies (ANCA) type with the frequency of gastrointestinal involvement in ANCA-associated vasculitis. Pancreatitis is a rare but serious complication of ANCA-associated vasculitis. Terminal ileitis may be observed in immunoglobulin A vasculitis and can be hard to distinguish from Crohns disease. High fecal calprotectin levels can indicate active gastrointestinal involvement in both immunoglobulin A vasculitis and Behçets syndrome. Refractory gastrointestinal involvement in Behçets syndrome can be treated with thalidomide and/or TNF-&agr; antagonists. The outcome of mesenteric vasculitis in systemic lupus erythematosus can be improved with high-dose glucocorticoids and cyclophosphamide or rituximab. Summary Gastrointestinal system can be commonly involved in immunoglobulin A vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, and Behçets syndrome and can be an important cause of morbidity and mortality. Treatment depends on the type of vasculitis and is usually with high-dose corticosteroids and immunosuppressives.

Gastrointestinal Involvement in Behçet Disease

Behçet disease (BD) is a variable vessel vasculitis that can involve several organs and systems. Gastrointestinal (GI) involvement has an acute exacerbating course with ulcers, most commonly in the ileocolonic area. These ulcers can be large and deep, causing perforation and massive bleeding. This article highlights the current knowledge on the epidemiology, clinical findings, diagnosis, and management of GI involvement of BD, with emphasis on recent findings.