Tumour angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas.

BACKGROUND: Tumour angiogenesis is essential for the growth, invasion and metastasis of solid tumours. There are several lines of evidence that the mast cells play an important role in tumour angiogenesis. AIMS: The study focused to determine the correlation between the microvessel and mast cell densities, and to evaluate whether tumour angiogenesis and mast cell density could predict recurrence following curative surgery in patients with colorectal carcinomas. PATIENTS: Microvessel and mast cell densities were investigated in tumour specimens from 60 patients with colorectal carcinoma. METHODS: Microvessels were stained by immunohistochemical method using a monoclonal antibody anti-CD34. The routine Giemsa blue staining method was used to assess the mast cells. Microvessels and mast cells were counted in a x400 field. RESULTS: The mean microvessel and mast cell counts were higher in patients with recurrence compared with those patients who were disease-free for at least 24 months (p<0.001). The Spearman's correlation coefficient revealed a significant correlation between mast cell and microvessel counts in colorectal carcinomas (r=0.684; p<0.001). Kaplan-Meier plots of survival showed that the high microvessel (>28) and mast cell (>6) counts correlated with a shorter disease-free survival (p=0.0003 and p=0.0013, respectively). Multivariate analysis showed that the depth of penetration (T4 versus T2) (p=0.004), liver metastasis (p=0.04) and microvessel density (p=0.003) were independent predictors of recurrence. In multivariate analysis, mast cell density did not reach significance. CONCLUSIONS: Our results suggest that the microvessel density of the primary tumour may be an important independent predictor of tumour recurrence and time to recurrence in colorectal carcinomas. The significant correlation between mast cell and microvessel counts suggest that the mast cells may have a role in tumour progression via promoting angiogenesis.

Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience.

OBJECTIVE: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. MATERIALS AND METHODS: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. RESULTS: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. CONCLUSION: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

Cyclosporine nephrotoxicity in the ischemic kidney and the protective effect of pentoxifylline--a study in the rat.

In order to prevent cyclosporine nephrotoxicity in the ischemic kidney, pentoxifylline was used in a rat model. Seventy-two rats were divided into six groups according to treatment after right nephrectomy: Group I was the control, group II was treated with 25 mg/kg cyclosporine, group III underwent renal ischemia for 45 min, group IV was given 25 mg/kg cyclosporine and subjected to renal ischemia, and group V was subjected to renal ischemia and given 45 mg/kg pentoxifylline (repeated at 12, 36, and 48 hr), group VI underwent renal ischemia and was then given both cyclosporine and pentoxifylline. BUN, creatinine, and potassium levels were significantly elevated 24 hr after cyclosporine (group II), ischemia (group III), and cyclosporine and ischemia (group IV). Sodium levels remained unaffected. BUN levels normalized in all but groups III and IV after 48 hr. Creatinine levels normalized in all but group IV after 48 hr. Creatinine clearance fell in all groups and remained low even after 48 hr. Pentoxifylline prevented dramatic rises in BUN and creatinine and levels nearly normalized after 48 hr. It also histologically prevented extensive tissue damage seen after ischemia. In conclusion, pentoxifylline has a protective effect upon the kidney when subjected to cyclosporine in the presence of ischemia.

Diagnostic value of interleukin-6 and C-reactive protein in acute appendicitis.

The aim of this study is prospectively to evaluate the serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels in detection of acute appendicitis in patients with right iliac fossa pain. Data were collected in prospective manner on 102 consecutive patients with right iliac fossa pain. Laparotomy was performed for suspected acute appendicitis for 55 of the 102 patients, of whom 49 patients had appendicitis, 6 patients non-appendicitis (NA), and the other 47 patients had nonspecific abdominal pain (NSAP) and they did not undergo operation. Among those with appendicitis 31 had acute appendix (AA), 8 had gangrenous appendix (GA), and 10 had perforated appendix (PA). The WBC and CRP the mean (SEM) values were significantly different in AA, GA, and PA groups compared with NSAP and NA groups (P < 0.05). Although the mean IL-6 levels were significantly different only in PA group than the others groups (P < 0.05). The sensitivity and specificity of serum CRP measurements were calculated as 96% and 87%, respectively whereas these were 33% and 83% for IL-6 levels for the diagnosis of the acute appendicitis. As a result, measurement of the CRP levels and WBC have an additional diagnostic value on the diagnosis of the acute appendicitis but determination of IL-6 levels which added to the test combination of WBC and CRP, the sensitivity for the diagnosis of the acute appendicitis was not changed whereas the specificity was decreased to 66%.

The effect of Ginkgo biloba on the activity of catalase and lipid peroxidation in experimental strangulation ileus.

This study was designed to assess the therapeutic effect of Ginkgo biloba extract (EGb 761) in experimental strangulation ileus. Rats were divided into control (n = 7), placebo (n = 11), and EGb-treated (n = 11) groups. No surgical procedure was carried out on the control group. Strangulation ileus was produced in the placebo and EGb groups for 2.5 h. At the end of this period, 100 mg/kg EGb in 1 ml of saline was injected intraperitoneally to the EGb-treated group. In the placebo group, animals received an equivalent amount of saline intraperitoneally; 24 h later, repeat laparotomies were performed to take blood and intestinal tissue samples. The EGb treatment decreased tissue malondialdehyde levels and increased catalase activities compared with the placebo group (P < 0.05 for both). Serum creatine kinase and phosphorus levels were also determined in all groups. In the placebo group these were significantly higher than in the control group (P < 0.01 and P < 0.05, respectively). In the EGb group these were not different from controls and the increase in creatine kinase activity in the EGb group was not as high as in the placebo group (P < 0.05). Our results suggest that EGb could be preventive against the effects of strangulation ileus in a rat model.

Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients).

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.