Gulen Dogusoy

Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid-induced ulcerative colitis in rats.

BACKGROUND Increased free radical production, decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Vitamin E is a powerful antioxidant and a scavenger of hydroxyl radicals, and it has been shown to have anti-inflammatory activities in tissues. We investigated the effects of vitamin E on inflammatory activities using an acetic acid (AA)-induced ulcerative colitis model in rats. METHODS Wistar rats were divided into 4 groups. Acetic acid was given to 2 groups of animals to induce colitis while the other 2 groups received saline intrarectally. One AA-induced colitis group and 1 control group received vitamin E (30 U/kg/d) intraperitoneally and the pair groups received saline. After 4 days, we evaluated colonic changes biochemically by measuring proinflammatory cytokine levels in tissue homogenates and by histopathologic examination. RESULTS Acetic acid caused colonic mucosal injury, whereas vitamin E administration suppressed these changes in the AA-induced colitis group (p < 0.001). Administration of AA resulted in increased levels of tumour necrosis factor-α, interleukin-1β, interleukin-6, myeloperoxidase and malondialdehyde, and decreased levels of glutathione and superoxide dismutase; vitamin E reversed these effects (all p < 0.001). CONCLUSION Our study proposes that vitamin E is an effective anti-inflammatory and antioxidant and may be a promising therapeutic option for ulcerative colitis.

Thoracoscopic enucleation of a giant submucosal tumor of the esophagus.

Since the introduction of thoracoscopy in the surgical field, many thoracic interventions have been considered feasible via thoracoscopic route. The authors reported a case of thoracoscopic enucleation of a giant esophageal submucosal tumor (8.5 cm in diameter) situated along the left side of the midesophagus. Histopathologic evaluation revealed a gastrointestinal stromal tumor (GIST). Postoperative period was uneventful and the patient was discharged on the eighth postoperative day. Given the well-known advantages of minimally invasive surgery, we assume that the removal of esophageal submucosal tumors can first be attempted by thoracoscopic approach, even if the tumor is of a big size. In cases of histopathologically unknown tumors preoperatively, definitive examination of the complete specimen provides the basis for further therapeutic decisions.

AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma.

BACKGROUND In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. METHODS In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. RESULTS One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5+/-6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4+/-22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence.The 5-year estimated overall survival rate was 62.2% in all patients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. CONCLUSIONS For proper patient selection in liver transplantation for HCC, prognostic criteria related to tumor biology (especially AFP level and histological differentiation) should be considered. Poor differentiation and higher AFP levels are indicators of poor prognosis after liver transplantation.

Secondary amyloidosis in Castleman's disease: review of the literature and report of a case

Abstract. It is quite rare to diagnose secondary amyloidosis during the course of Castlemans disease (CD). A 51-year-old female who complained of fatigue, weight loss, and fever was diagnosed with CD – plasma cell type – in our hospital in 1993. One year after diagnosis, she developed nephrotic syndrome, the etiology of which was found to be secondary amyloidosis based on renal biopsy. As the patient rejected therapy, she was discharged after only symptomatic treatment. At her last follow-up in March 2001, she had no complaints; physical examination, blood chemistries, and urinalysis were normal. Abdominopelvic tomography revealed no lymphadenopathy in the abdomen, which had been previously present. We could identify 17 other cases of CD with secondary amyloidosis in the literature. Ours is the 18th such case and the 2nd case of multicentric CD leading to amyloidosis. This case also shows that CD might sometimes run a relatively benign course being cured with no therapy, whereas it might have a rapidly fatal downhill course – even with therapy – in others. Still, effective treatment strategies need to be developed.

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. Objectives The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. Patients and Methods Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. Results No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). Conclusions c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior. These markers were found to be correlated with certain clinicopathologic features, therapy modalities, and survival rates in the current study. These findings may help in planning new, targeted treatment strategies .

Characterization of frequency-dependent material properties of human liver and its pathologies using an impact hammer

The current methods for characterization of frequency-dependent material properties of human liver are very limited. In fact, there is almost no data available in the literature showing the variation in dynamic elastic modulus of healthy or diseased human liver as a function of excitation frequency. We show that frequency-dependent dynamic material properties of a whole human liver can be easily and efficiently characterized by an impact hammer. The procedure only involves a light impact force applied to the tested liver by a hand-held hammer. The results of our experiments conducted with 15 human livers harvested from the patients having some form of liver disease show that the proposed approach can successfully differentiate the level of fibrosis in human liver. We found that the storage moduli of the livers having no fibrosis (F0) and that of the cirrhotic livers (F4) varied from 10 to 20 kPa and 20 to 50 kPa for the frequency range of 0-80 Hz, respectively.

Nitric Oxide and Antioxidant Defense in Patients with Gastric Cancer

In the present study, total nitrate and nitrite level (as end product of nitric oxide), superoxide dismutase activity, and glutathione peroxidase activity in leukocytes were determined in patients with gastric cancer, and the relationship between measured parameters and tumor grade were evaluated. Leukocyte nitrate and nitrite level was found to be increased and superoxide dismutase activity was found to be decreased in patients compared to controls. When the patient group was categorized, nitrate and nitrite level was found to be higher in patients with a high-grade tumor than in patients with a grade I tumor. We concluded that an increased level of leukocyte nitrate and nitrite is related to tumor grade in patients with gastric cancer; antioxidant activity is also impaired in these patients but it does not seem to be related to grade of tumor.

Effect of Simultaneous Splenectomy on the Survival of Patients Undergoing Curative Gastrectomy for Proximal Gastric Carcinoma

Abstract.Purpose: Splenectomy is sometimes performed simultaneously with curative gastrectomy for gastric carcinoma, especially when the tumor originates in the proximal one-third of the stomach or corpus, or when it invades the entire stomach, in an effort to remove metastatic lymph nodes at the splenic hilus and improve survival. However, splenectomy is not an innocent procedure and may cause increased morbidity and even mortality. Moreover, the long-term effect of splenectomy on survival is still controversial. The purpose of this study was to investigate the effect of simultaneous splenectomy on survival in patients with proximal tumors undergoing curative gastrectomy for gastric cancer. Methods: The effect of splenectomy on the 5-year survival of 61 patients with proximal gastric cancer (located in the cardia or the corpus) who underwent curative gastrectomy in our hospital between 1989 and 1993 was investigated retrospectively. Of these 61 patients, 38 (62.3%) underwent splenectomy and 23 (37.7%) did not. The relationship between the clinicohistopathological parameters and 5-year survival was retrospectively analyzed. Results: No significant differences were found in bivariate analysis between the survival of patients who underwent curative gastrectomy with and those who underwent curative gastrectomy without splenectomy (P = 0.984). Multivariate regression analysis indicated that only histological grade (P < 0.003) and lymph node metastasis (P < 0.001) were independent prognostic factors with or without splenectomy. Splenectomy itself was not an independent prognostic factor (P = 0.528). Conclusion: The findings of this retrospective study showed that simultaneous splenectomy had no effect on the survival of patients who underwent curative gastrectomy for gastric carcinoma. Thus, splenectomy may only be appropriate for patients with direct invasion of the spleen.

CASE REPORT: Cytomegalovirus Infection of Gastrointestinal Tract with Multiple Ulcers and Strictures, Causing Obstruction in a Patient with Common Variable Immunodeficiency Syndrome

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by panhypogammaglobulinemia (especially decreased production of IgG but frequently also IgA and IgM, recurrent bacterial infections, and different gastrointestinal appearances), especially inflammatory bowel disease and granulomatous enteropathy, and increased incidence of malignant and autoimmune disease. A small subpopulation of these patients has reduced numbers of circulating B lymphocytes, suggesting a central failure of the development of this cell line (1–3). In 80–90% of the patients there are normal numbers of B lymphocytes, with immature phenotype, because these cells fail to differentiate into immunoglobulin-secreting plasma cells (4). Most patients with this disorder appear to have an intrinsic B-cell defect. Consistent with the evidence that B lymphocytes are able to recognize the antigens and proliferate but fail to differentiate to plasma cells is the fairly common finding of lymphoid hyperplasia, including splenomegaly and nodular hyperplasia of the gut. In some patients, an increase in T-suppressor activity, quantitative deficiency of helper T cells, and production of abnormal immunoglobulins, which are degraded in cytoplasm, have been observed. Two thirds of patients with common variable immunodeficiency have a normal CD4/CD8 ratio, one third has increased relative and absolute numbers of CD3 and CD8 peripheral blood lymphocytes, resulting in a decreased CD4/CD8 ratio. Less than 10% of the patients with normal ratios and 40% with a decreased ratio are anergic, and 30% of the patients with normal ratios and 70% with decreased ratios have splenomegaly (5). Most of the CD8 T cells expressed the CD57 antigen and activation antigens (HLA-DR) (6). Cytomegalovirus (CMV) is a member of the herpesvirus group and causes a wide spectrum of disorders, ranging from an asymptomatic, subclinical infection to a mononucleosis syndrome in healthy individuals to disseminated disease in the immunocompromised host (7). CMV contains doublestranded DNA, a protein capsid, and a lipoprotein envelope and replicates in the cell nucleus. Virus replication is associated with the production of large intranuclear inclusions and smaller cytoplasmic inclusions. Once infected, an individual probably carries the virus for life. Most commonly these infections remain latent. However, with compromise of Tlymphocyte-mediated immunity, CMV reactivation syndromes frequently develop (8). These cells in vivo Manuscript received April 10, 1999; accepted January 31, 2000. From the Internal Medicine Department, Gastroenterology Department, General Surgery Department, Department of Pathology, and Infectious Diseases Department, Cerrahpasa Medical Faculty, University of Istanbul; and Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Pittsburgh, Pennsylvania. Address for reprint requests: Dr. Veysel Tahan, Cerrahpasa Medical Faculty, Internal Medicine Department, 34303 Aksaray, Istanbul, Turkey. Digestive Diseases and Sciences, Vol. 45, No. 9 (September 2000), pp. 1781–1785

Should we suppress the antigenic stimulus in IPSID for lifelong

jects in each study group. At histology, all subjects had mild-to-moderate chronic active superficial gastritis and mild-to-moderateH. pylori density with no major differences between groups. The 40 H. pylori strains tested for antimicrobial susceptibility were all sensitive to amoxicillin (minimal inhibitory concentration [MIC] , 4 mg/ml) and to tetracycline (MIC, 2 mg/ml). Nine (22.5%) strains were resistant to metronidazole (MIC. 8 mg/ml), five (12.5%) strains were resistant to clarithromycin (MIC . 2 mg/ml), and two (5%) strains were resistant to both metronidazole and clarithromycin. One patient in each group did not complete the study because of side effects. Susceptibility testing was associated with a higher eradication rate than nonsusceptibility testing (97.4%vs 79.5% and 95%vs 77.5%, in the PP and ITT analyses, respectively). Moreover, in the PP analysis, 1/39 (2.5%) subject in the susceptibility testing group and 8/39 (20.5%) sub jects in the nonsusceptibility testing group, failed to eradicate the infection ( p , 0.05 by Fisher exact test) (Table 1). In conclusion, pretreatment antimicrobial-susceptibility testing was associated with a higher eradication rate and a significantly lower rate of treatment failure in H. pyloriinfected dyspeptic patients. We postulate that because antimicrobial-resistantH. pylori strains are becoming increasingly prevalent (5), therapeutic regimens based on susceptibility testing may decrease the need for retreatment and prevent the emergence of secondary resistance and might, therefore, prove to be cost-effective.