Effects of selective Cox-2 inhibitor, rofecoxib, alone or combination with furosemide on renal functions and renal Cox-2 expression in rats.

BACKGROUND: Nonsteroidal anti-inflammatory drugs act by inhibiting the rate-limiting enzymes cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2), which are important in prostanoid formation. The aim of this experimental study was to examine the effects of selective Cox-2 inhibitor, rofecoxib, with or without furosemide, on urine and serum electrolytes, creatinine clearance, plasma renin activity (PRA), and Cox-2 expression in the renal cortex. METHODS: Forty male Wistar albino rats were randomized into four groups, group 1, group 2, group 3, and group 4, and were treated with placebo, furosemide (20 mg/kg), rofecoxib (10 mg/kg) plus furosemide (12 mg/kg), and rofecoxib (10 mg/kg), respectively, and followed for 7 days. Body weights were measured daily. Urine osmolality and volume, and serum and urinary creatinine, sodium (Na(+)), and potassium (K(+)) were measured. Renal cortical Cox-2 protein expression was examined by immunohistochemical method. RESULTS: Compared with groups 1 and 3, body weights were significantly reduced in groups 2 and 4 (16.2 and 19.8 g, respectively; P < 0.05 for all). Urine volume in group 2 increased significantly compared with groups 1, 3, and 4 (P < 0.001, P < 0.008, and P < 0.004, respectively). Urine osmolality in group 2 decreased significantly compared with groups 1 and 3 (P < 0.05 for all). Blood urea nitrogen, serum creatinine and sodium, creatinine clearance, and 24-h urine Na(+) and K(+) levels were similar in all groups. Serum K(+) level was lowest in group 2, and there was a statistically significant difference between groups 2 and 4 (P < 0.05). Plasma renin activity was similar in all groups (P > 0.05). Renal cortical Cox-2 protein expression was lowest in group 1 and was significantly different from the other groups (P < 0.01 for all). The relationship between Cox-2 expression and plasma renin activity was not significant in any group (P > 0.05, r(2):0.05). CONCLUSIONS: Rofecoxib neutralized the diuretic effect of furosemide in rats treated with a combination of furosemide and rofecoxib. Renal cortical Cox-2 protein expressions due to furosemide and rofecoxib with or without furosemide were similar and significantly increased compared with controls. Renal failure due to rofecoxib did not developed in any rat, but selective Cox-2 inhibitor, rofecoxib, might have similar renal effects as nonselective nonsteroidal drugs for blunting the diuretic effect of furosemide.

Targeted treatment with pazopanib in metastatic soft tissue sarcoma: Nearly complete response in two cases.

Soft tissue sarcomas (STS) are a group of rare mesenchymal cancers that include approximately 50 histological types and account for 1% of all adult cancers. The standard curative treatment option for localized disease is surgical resection and, if a surgically removed tumor exhibits high-risk characteristics, adjuvant chemotherapy and radiotherapy may be administered. Sarcoma presenting at an advanced stage has a dismal prognosis and survival has not markedly improved over the last 20 years. The standard first-line treatment for advanced STS, other than gastrointestinal stromal tumors, is cytotoxic chemotherapy. Therapies targeting pro-angiogenic factors have been a focus of drug development for STS over the last few years. Pazopanib, a multitargeted tyrosine kinase inhibitor, is a novel treatment option for patients with metastatic STS in the second-line setting. This is a presentation of 2 case reports of patients with metastatic STS who responded well to treatment with pazopanib.

Primary extranodal non-Hodgkin's lymphoma: clinicopathological features, survival and treatment outcome in two cancer centers of southern Turkey.

BACKGROUND: The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. MATERIALS AND METHODS: Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. RESULTS: pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5- 1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. CONCLUSIONS: Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.

Secondary malignancy after imatinib therapy: eight cases and review of the literature.

Chronic myeloid leukemia (CML) is a clonal stem cell disorder, and imatinib is a small molecule inhibitor of Bcr-Abl tyrosine kinase (TK) used in cases with CML. Immediate and short-term side effects of this tyrosine kinase inhibitor (TKI) are well known, but the long-term side effects have not yet been clearly identified. Although an increased risk of secondary cancer in cases treated by imatinib was not found in two large series, secondary malignancies have been reported in some cases using TKIs, and this issue is important in daily clinical practice for clinicians. Here we report eight cases with neoplasias that developed during imatinib therapy and review secondary malignant disorders occurring during/after imatinib treatment.

Prevalence of thyroid dysfunction in untreated cancer patients: a cross-sectional study.

The relationship between thyroid disease and cancer (and cancer therapies) has been under investigation for years. Factors that increase the risk for thyroid disease include iodine deficiency, autoimmune disorders, old age, and pregnancy. The screening policy for thyroid disease in the healthy population is not precisely defined, and the frequency of thyroid dysfunction in untreated cancer patients has not been investigated in any great detail. This study was designed to compare the prevalence of thyroid dysfunction in 457 untreated cancer patients at the time of initial diagnosis to that of 373 age- and sex-matched subjects who were healthy and cancer-free (control group). Thyroid dysfunction was found in 29.5 % (135/457) of the cancer patients, while only 15.4 % (56/373) of the control group had thyroid dysfunction (p = 0.0001). The most prevalent abnormality was euthyroid sick syndrome (14.0 %, 64/457). Overt and subclinical hyperthyroidism and overt hypothyroidism were observed more frequently in cancer patients than the control group, and these differences were all statistically significant. Thyroid dysfunction was more frequent in patients with poor performance scores and those over the age of 50 years. These data indicate that alterations in thyroid hormone metabolism are twice as common in patients with untreated cancer than in control subjects. Those alterations may lead to delayed diagnosis, suboptimal treatment, and a poorer prognosis. In all, this study suggests that screening with thyroid function tests is strongly recommended in all newly diagnosed cancer patients.

Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience.

PURPOSE: Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting. MATERIAL AND METHODS: Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed. For statistical analysis demographic and clinical characteristics of patients, primary biliary drainage method, metal stent occlusion rate, time to stent occlusion, and overall survival rates were recorded. RESULTS: A total of 34 eligible patients were analyzed. 27 patients had metal stent placement. These 27 patients formed the basis of this study. Median overall survival (OS) was 6.0 months. After metal stent deployment bilurubin levels were normalized within a mean of 10 days. During the follow-up period, 13 patients were experienced metal stent occlusion. Median TtSO was 10 weeks. Cytotoxic chemotherapy was administered to 14 (52%) patients. Patients without stent dysfunction had significantly higher rate of chemotherapy exposure rate (p=0.021). Statistical analysis, however, failed to exhibit significant effect of stent dysfunction on OS. CONCLUSION: In advanced cholangiocarcinoma, relief of bile duct obstruction is an important part of the initial patient management. This study therefore described the clinical value of percutaneous metal stent in cholangiocarcinoma patients and raises the question about patency of metal stent in cholangiocarcinoma whether we can expect success similar to the success achieved in pancreas carcinoma.

Weekly cisplatin versus standard three-weekly cisplatin in concurrent chemoradiotherapy of head and neck cancer: the Baskent University experience.

BACKGROUND: The majority of patients with head and neck cancer are treated with concurrent chemoradiotherapy. However, toxicity is substantial so that alternate schedules of cisplatin have been tried to overcome this problem. No formal comparison, however, has been reported between alternate schedules and reference regimen. PATIENTS AND METHODS: Fifty-five eligible patients treated with concurrent chemoradiotherapy were retrospectively analyzed. The patients treated with weekly cisplatin were defined as group A, while the patients treated with standard regimen were defined as group B. Basic demographics and clinical characteristics', overall survival rate, locoregional or systemic relapse rates, and time to local/systemic relapse were recorded. RESULTS: One, two, and three-year probability of survival in groups A and B were 75% to 65% after one year, 63% to 56%after two, and 63% to 52% after three, respectively. Although time to local and systemic relapse was higher in group B as compared to group A, a statistical analysis was failed to show any significant difference. Furthermore, there was no significant difference between groups with respect to major toxicity. CONCLUSION: In patients with head and neck cancer, concurrent chemoradiotherapy with weekly cisplatin might be as effective as concurrent chemoradiotherapy with bolus cisplatin.

The effects of the nonsteroidal anti-inflammatory drug diclofenac sodium on the rat kidney, and alteration by furosemide.

INTRODUCTION: Renal physiology is a partially cyclooxygenase (COX)-dependent system. Kidneys express both COX-1 and COX-2 enzymes. In this study, we tried to investigate the effects of diclofenac sodium (D), with or without furosemide (F), on plasma renin activity (PRA), serum and urine electrolytes, creatinine clearance, and COX-1 and COX-2 expression in the renal cortex. METHOD: Forty-two Wistar-albino rats were divided into four groups (G). G1, G2, G3, and G4 were treated with placebo, F (20 mg/kg), F (20 mg/kg) plus D (2.5 mg/kg), and D (2.5 mg/kg), respectively, and followed for seven days. Urinary osmolality and volume, and levels of serum and urinary creatinine, sodium, and potassium were measured. Renal COX-1 and COX-2 expression were examined by the immunohistochemical method. RESULTS: Compared with G1, body weights were significantly reduced in G3 and G4 (P < 0.05 for all). Serum sodium in G2 decreased significantly compared with G1, G3, and G4. Serum potassium in G2 decreased significantly compared with G1 and G3. Urine volume in G2 increased significantly compared with G1, G3, and G4. Urine osmolality in G2 and G4 decreased significantly compared with G1 and G3. Urine Na in G2 increased significantly compared with G4. Although urine K was lowest in G4, there were no statistically significant differences between the groups. Creatinine clearance decreased in G4 compared with the other groups. PRA was similar in all groups. Renal cortical COX-2 expression was lowest in G1. COX-1 expression in cortical collecting tubules was significantly reduced in G3 and G4 compared with G1 and G2 (P < 0.05 for all). Although creatinine clearance in G4 was significantly lower than in G3, COX-1 and COX-2 expression were no different in G3 and G4. DISCUSSION: Acute renal failure was caused by D. F prevented development of renal failure in rats treated with a combination of D and F. The diuretic effect of F was neutralized by D. Whereas COX-1 expression was reduced by D and by the combination of D and F in G3 and G4, renal COX-2 immunoreactivity was increased by F and D and the combination of both. Although creatinine clearance was lower in rats that were given D alone compared with the combination of F and D, COX-1 and COX-2 expression were similar in these groups.