Mucins, trefoil factors and pancreatic duodenal homeobox 1 expression in spasmolytic polypeptide expressing metaplasia and intestinal metaplasia adjacent to gastric carcinomas.

INTRODUCTION: Gastric cancers are the second cause of cancer related deaths all around the world but gastric carcinogenesis remains a mystery. Intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) are the two types of preneoplastic metaplasias. In this study, we aimed to investigate expression of Pancreatic duodenal homeobox 1 (PDX1), mucins (MUCs), trefoil factors (TFFs) in SPEM and IM surrounding gastric carcinomas. MATERIAL AND METHODS: Tissue samples of tumor adjacent gastric mucosa including IM (n = 61) and SPEM (n = 36) from 70 gastrectomy specimens were used for immunohistochemical analysis of PDX1, mucins (MUC5AC, MUC6) and trefoil factors (TFF2, TFF3). RESULTS: Nuclear expression of PDX1 was present in both SPEM (32/36) and IM (60/61) and there was no significant difference in expression of PDX1 between the two types of metaplasias. While TFF3 and MUC5AC were abundant in IM, SPEM showed 100% expression of TFF2 and MUC6 and also lower positivity with TFF3 and MUC5AC. PDX1 positivity was related to expression of MUC5AC (60/61, p < 0.001) and TFF3 (60/61, p < 0.001) in IM and also associated with expression of MUC5AC (14/32, p < 0.05), MUC6 (32/32, p < 0.001), TFF2 (32/32, p < 0.001) and TFF3 (9/32, p < 0.05) in SPEM. Coexpression of TFF3 and TFF2 was present in 10 of 36 (27.7%) samples of SPEM and also 29 of 61 (47.5%) samples of IM exhibited dual expression of trefoil peptides. CONCLUSIONS: PDX1 may affect the development of SPEM and IM. Expression patterns of TFFs and MUCs may indicate that IM evolves from SPEM.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats.

AIM: To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats. METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method. RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 +/- 1.2, 33.8 +/- 2.9, 36.7 +/- 0.5 mug collagen/mg protein, respectively) compared to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% +/- 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05). CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

The correlation between TTF-1 immunoreactivity and the occurrence of lymph node metastases in patients with lung cancer.

AIMS AND BACKGROUND: Thyroid transcription factor (TTF-1) is a tissue-specific transcription factor expressed in the epithelial cells of thyroid and lung. The aim of this study was to evaluate the relationship between the expression of TTF-1 and clinico-pathological parameters in pulmonary adenocarcinoma and adenosquamous carcinoma. METHODS: Resection material of pneumonectomies and lobectomies of 39 patients was retrospectively examined. Twenty-eight patients were diagnosed with adenocarcinoma and 11 with adenosquamous carcinoma. Tumors were classified into 3 groups: a strongly positive group (++) with double dagger 50% tumor cells positive for TTF-1; a weakly positive group (+) with 1-49% positive tumor cells; and a negative group (-) with less than 1% or no positive tumor cells. Analysis was performed with Kaplan-Meier estimates and log-rank tests. RESULTS: Staining for TTF-1 was negative in 10 cases. There was focal staining in 9 cases, while there was diffuse staining in 20 (51%) cases out of 39, and 15 (75%) of these were adenocarcinomas. There was a statistically significant association between TTF-1 and lymph node metastases (P = 0.029). No relationship was found between TTF-1 positivity and disease-free and overall survival. CONCLUSIONS: TTF-1 expression may be a predictor of lymph node metastases. Additional work in a larger group of patients is needed to better assess the utility of this marker.

Expression of Bcl-2 and Ki-67 in tamoxifen-associated endometrial polyps: comparison with postmenopausal polyps.

BACKGROUND: The aim of this study was to evaluate the expression of Bcl-2 and Ki-67 in tamoxifen (TAM)-associated endometrial polyps and postmenopausal polyps. MATERIAL AND METHODS: For this purpose, a retrospective analysis of paraffin-embedded specimens was carried out. Polyps of 20 postmenopausal and 14 TAM-treated patients, 11 simple endometrial hyperplasia, 10 atypical complex endometrial hyperplasia and 8 endometrial adenocarcinoma specimens were included in the study. Hematoxylin/eosin-stained sections were evaluated. Immunohistochemical staining was performed to investigate the expression of Bcl-2 protein and the Ki-67 proliferation index. RESULTS: There was no statistically significant difference between the 5 groups with regard to Bcl- 2 staining (p > 0.05). However, Bcl-2 expression in TAM-associated polyps was higher (86%) than in the postmenopausal control group (80%). Positive Ki-67 was highest in the endometrial adenocarcinoma specimens, followed by the atypical complex endometrial hyperplasia group (p < 0.0001). Compared to these 2 groups, Ki- 67 expression was lower in TAM-associated polyps, but Ki-67 indexes were significantly higher in the TAM-associated group than in the control group (p < 0.0001). CONCLUSION: Since TAM-associated polyps tend to have higher proliferation indexes and Ki-67 ratios than control groups, we suggest that they are likely to have a higher malignant potential.

Placenta percreta diagnosed after first-trimester pregnancy termination: a case report.

BACKGROUND: Placenta percreta in early pregnancy has been documented in only a few cases. This is the first report of placenta percreta diagnosed after an extended period from pregnancy termination. CASE: A woman with a history of a previous cesarean section presented with heavy and irregular vaginal bleeding beginning immediately after pregnancy termination at 7 weeks' gestation. Failed response to hormonal treatment and curettage necessitated hysterectomy. Histologic examination revealed a placenta percreta. CONCLUSION: Although placenta percreta is an uncommon occurrence, clinicians should consider it in patients who have a uterotomy scar and complain of long-term metrorrhagia following pregnancy termination.

Multifocal mesenchymal hamartoma of the chest wall.

Chest wall hamartomas are extremely rare. Frequently mesenchymal hamartomas are presented as a single mass and contain some primitive mesenchymal elements such as chondroid and trabecular bone structures. A 60-year-old man presented to hospital with chest pain. Thirteen years earlier, his CXR and thoracic CT showed three masses on the right and two masses on the left, but he had not received any treatment thereafter. His CT showed the same masses present 13 years earlier, but they were bigger and right thoracotomy was undertaken. At thoracotomy, two sections of the mass in the right posterior mediastinum and one section of the mass in the right apex were excised. They had an occasional bloody appearance and contained small cystic areas, and some areas were extremely hard. Microscopic examination showed that the lesions consisted of mature adipose tissue, a large number of veins of different diameters and collagen tissue. Besides, primitive mesenchymal elements, lymphoid cell accumulations and trabecular bone structures were seen focally. Bilateral chest wall hamartomas are extremely rare and may be confused with malignancy.

Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats.

BACKGROUND: Oxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated. OBJECTIVE: The aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease. METHODS: This 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing ∼200 g were randomly assigned to 1 of 6 groups: (1) liquid diet+ethanol+vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet+ethanol+vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet+ethanol+vitamin E 15 mg/kg+vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet+ethanol (LDet); (5) liquid diet+isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis. RESULTS: Seventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P<0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P<0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P<0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] µg collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] µg collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P<0.01, P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P<0.01, P<0.05, and P<0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P<0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P<0.05). CONCLUSIONS: The results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study. (Curr Ther Res Clin Exp. 2006;67:118-137) Copyright © 2006 Excerpta Medica, Inc.

Effect of pentoxifylline and indomethacin on rabbits with endotoxin induced disseminated intravascular coagulation (DIC) and comparison with heparin.

We evaluated the effects of pentoxifylline and indomethacin and heparin in a rabbit model of disseminated intravascular coagulation (DIC) induced by infusion of 100 µg/kg/hour of Escherichia coli endotoxin lipoplysaccharide (LPS) for 6 hour. Heparin, indomethacin, pentoxifylline or saline were administered simultaneously with LPS. In addition, a control group was formed which was administered only saline. Hemostatic markers at 0, 1/2, 2, and 6 hour as well as histopathologic changes in the organs and the mortality at 24 hour were determined. The infusion of LPS caused a severe impairment in hemostasis and fibrin accumulation in the pulmonary vasculature. Heparin significantly improved hemostatic impairment and reduced the fibrin accumulation in the pulmonary vasculature. Pentoxifylline and indomethacin had no significant effect on DIC, except that pentoxifylline prevented the decrement in platelet count slightly (p< 0.05). None of the drugs, including heparin, had any effect on mortality. As a result, the prevention of the synthesis of only one cytokine or autocoid is not considered enough to control the results of endotoxemia.

Lymphoepithelioma-like carcinoma of the urinary bladder: a case report and discussion of differential diagnosis.

Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is very rare. It is mandatory to make differential diagnosis among lymphoma, chronic cystitis and LELC because of different therapeutic approach. A bladder tumor was found in a 90-year-old patient suffering from hematuria. After transurethral resection, undifferentiated tumor with prominent lymphoid infiltration was seen on light microscopy. Immunohistochemical examination demonstrated positive staining of tumor cells with cytokeratin (CK), epithelial membrane antigen and CK-20. We presented the case because of its rarity and related literature was reviewed.

The potential cardioprotective effects of amifostine in irradiated rats.

PURPOSE: The aim of this study is to determine the cardioprotective efficacy of amifostine. The study consists of researching the relationship between plasma brain natriuretic peptide levels and the electrical and morphologic changes in irradiated rats with or without amifostine. METHODS AND MATERIALS: Sixty Wistar albino rats were divided into 4 groups, and their hearts were given 15 Gy/fraction with (60)Co. In Groups I and II, the rats were killed after 24 hours to detect early effects; in Groups III and IV, the rats were killed 100 days after irradiation to detect late effects. Before irradiation, Groups I and III received 0.9% saline solution, whereas Groups II and IV received amifostine (200 mg/kg). Twenty rats were used as a control group. RESULTS: On the 100th day, mild myocardial degeneration was detected in 5 rats (33%) from Group III (no amifostine). This percentage was statistically different from that of Group IV (treated with amifostine) and the controls (p = 0.042). There was no statistically significant difference between the mean plasma brain natriuretic peptide values of the groups (p > 0.05). There was no significant difference in electrocardiographies between the groups. There was no correlation between continuous variables. CONCLUSION: In the amifostine group (IV) on the 100th day, there was no myocardial degeneration, suggesting that amifostine has a cardioprotective effect.

Epithelial-myoepithelial carcinoma of the lung. A case report and review of the literature.

Primary lung tumors mimicking the salivary gland-type neoplasms are extremely rare. These types of tumors originate from submucosal bronchial glands. Epithelial-myoepithelial carcinoma is an uncommon tumor in this group, and only 7 cases have been reported. It is considered to be a low-grade malignant neoplasm. We report a case of epithelial-myoepithelial carcinoma of bronchial gland origin in a 73-year-old man who presented with coughing and dyspnea. The bronchus of the left lower lobe contained a tumor mass that had a polypoid growth pattern. The tumor also extended into the pulmonary parenchyma, forming a well-circumscribed mass with a pushing margin. The tumor consisted of epithelial and myoepithelial cells. The epithelial cells were positive for cytokeratins and epithelial membrane antigen, while the myoepithelial cells were positive for S100 protein and muscle-specific actin. According to these findings, we diagnosed epithelial-myoepithelial carcinoma. After undergoing pneumonectomy, the patient has been disease free for 34 months.

Expression of the cyclin-dependent kinase inhibitor p27 in transitional cell bladder cancers: is it a good predictor for tumor behavior?

OBJECTIVES: Progression of the cell cycle is regulated by the interactions of cyclins, cyclin dependent kinases (CDKs) and CDK inhibitors (CDKIs). p27 is a member of the universal cyclin-dependent kinase inhibitor family. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid and endocrine tissues. It has been suggested that p27 is an independent prognostic factor in various human cancers. The prognostic value of p27 protein expression is not completely understood in bladder cancer yet. AIMS: To investigate the immunohistochemical expression of p27 in transitional cell bladder cancers and its relationship with clinicopathological data, proliferating cell nuclear antigen (PCNA) and p53 oncoprotein immunoreactivity. METHODS: The expression of p27 protein was immunohistochemically analyzed in paraffin-embedded specimens of 75 patients with transitional cell carcinoma of the bladder. p27 expression was compared with tumor grade, stage, growth pattern, disease-free survival, progression, PCNA and p53 immunoreactivity. RESULTS: Expression of p27 was not significantly related to clinicopathologic parameters, disease-free survival, progression, PCNA and p53 immunoreactivity. CONCLUSION: The results indicate that p27 is not a good predictor for outcome of transitional cell carcinoma of the bladder.