TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats.

PURPOSE: To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. METHODS: Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. RESULTS: Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). CONCLUSIONS: Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.

TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats

Abstract Purpose To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. Methods Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. Results Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). Conclusions Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.

Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast.

BACKGROUND: In this retrospective analysis, the clinicopathological features and pattern of metastatic spread of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed ductal/lobular carcinoma (MDLC), together with the type and outcome of surgical intervention, were comparatively evaluated. METHODS: A total of 633 breast cancer patients with histopathological subtype IDC, ILC or MDLC were included in the study. The mean age was 52.6 ± 12.7 years. Follow-up period ranged between 0 and 33 (median 6.0) years. The groups were compared with respect to age, tumor size, nodal involvement, stage, hormonal therapy, multicentricity, multifocality, bilaterality, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, p53, and Ki67 expression, disease-free survival (DFS) and overall survival (OS) rates, and surgical approach. RESULTS: The distribution of patients was as follows: IDC 508 (80.3 %), ILC 78 (12.3 %), MDLC 47 (7.4 %). Among the parameters evaluated, statistically significant differences were observed in mean tumor size (IDC 2.5 ± 1.98 cm, ILC 3.0 ± 1.8 cm, MDLC 3.2 ± 2.4 cm), advanced T stage (T3 + T4) at diagnosis (IDC 14.7 %, ILC 21.4 %, MDLC 25.6 %), N stage (N0 was dominant in IDC and ILC; N3 was dominant in MDLC), tumor-node-metastasis (TNM) stage (stage II was dominant in IDC and ILC; stage III was dominant in MDLC), HER2/neu expression (IDC 23.8 %, ILC 11.8 %, MDLC 21.4 %), and frequency of bone metastasis (IDC 14.3 %, ILC 17.9 %, MDLC 25.5 %). CONCLUSIONS: MDLC-type tumors have different histopathological characteristics and are often diagnosed at advanced stage. However, their survival outcomes do not vary significantly from ILC and IDC.

Breast Carcinosarcomas.

OBJECTIVE: Carcinosarcomas of the breast are rare and aggressive breast tumors. The optimal treatment strategies and the classification of these difficult to diagnose tumors are not clear in the literature due to their very low incidence. In this study, we aimed to evaluate patients who were operated on for breast carcinosarcoma and discuss the current literature. MATERIALS AND METHODS: Ten patients who were treated with a diagnosis of breast carcinosarcoma between January 2000 - March 2013 at the Izmir Bozyaka Teaching and Training Hospital General Surgery Clinics were retrospectively analyzed. RESULTS: The mean age of the patients was 59.7 (±13.4) years. Eight patients underwent modified radical mastectomy, one patient lumpectomy and one patient breast conserving surgery + sentinel lymph node biopsy procedures. The TNM stage of patients were identified as stage 1 in 2 patients, stage 2 in 6 patients, and stage 3 in 2 patients. 60-month disease-free survival rate was 52.5% (±18.6). The overall survival rate was 53.3% (±20.5). Four patients died during follow-up. CONCLUSION: It is reported that the prognosis of carcinosarcomas are as poor as triple negative epithelial tumors. In contrast to the literature, in our study the disease-free and overall survival rates according to stage were not different from epithelial tumors. In this regard, prospective studies including more patients are required.

Impact of histopathology on the outcome of D1/D2 gastrectomies with R0 resection.

AIMS: The primary objective of this study was to clarify the influence of histotype on the outcome of D1/D2 gastrectomized patients with pathologically proven R0 resection. The secondary objective was to demonstrate overall survival (OS), disease-free survival (DFS), and locoregional recurrence rates following standard curative surgery. PATIENTS AND METHODS: All patients had either pure signet-ring cell carcinoma (SRCC)/poorly differentiated adenocarcinoma (PDC) or moderately differentiated adenocarcinoma (MDC) of the stomach, preoperative radiologic evidence of locoregional disease, and no history of neoadjuvant therapy. Standards of surgical treatment were essentially based on the guidelines of the Japanese Research Society for the Study of Gastric Cancer. RESULTS: Between October 2003 and August 2010, seventy-eight patients were enrolled. Twenty-three patients underwent D1 dissection and 55 underwent D2 dissection. The OS and DFS rates were 33.2 ± 5.9 months versus 31.5 ± 4.3 months (p = 0.81) and 28.9 ± 5.6 months vs. 29.3 ± 4.4 months (p = 0.96) in the MDC and SRCC/PDC groups, respectively. Neither the extent of the operation (D1 vs. D2, p = 0.79) nor the histopathologic subtype of the primary tumor (MDC vs. SRCC/PDC, p = 0.91) influenced the OS and DFS. Multivariate logistic regression analysis disclosed pathologic stage (pTNM) as the only significant prognostic determinant of OS (p = 0.007) and DFS (p = 0.0003). CONCLUSION: Properly performed D1 and D2 dissection in our series resulted in a notable (6.4%) locoregional failure rate. In spite of the satisfactory locoregional control achieved by D1 and D2, there was no improvement in the survival figures of stage IIIA-B and IV gastric cancer patients. The histopathologic subtype of the primary tumor disclosed merely a statistical trend on the outcome measures of gastric cancer after curative surgery.

Case report: blastic Mantle Cell Leukemia.

The patient, who was being followed up for Mantle Cell Lymphoma, was diagnosed with Mast Cell Leukemia 2 years after receiving R-CHOP treatment. The results of flow cytometry, which was performed upon determining leucocytosis and detecting blasts in the peripheral smear following the patient's presentation due to his poor general condition, was consistent with Mantle Cell Leukemia. This case is being presented since there are a very limited number of previously published cases on this topic.