Successful rechallenge with clozapine after treatment associated eosinophilia.

OBJECTIVE: Eosinophilia has been associated with the use of clozapine. Where clozapine associated eosinophilia develops, and is associated with organ specific damage, clozapine is usually ceased. In cases of treatment associated eosinophilia without evidence of organ specific damage, clozapine would also typically be withdrawn. There are small numbers of reports in the literature describing patients who have had a successful rechallenge of clozapine having previously stopped treatment due to eosinophilia without associated organ specific inflammation. We report the case of a man who underwent a successful retrial of clozapine. METHOD: Case from authors' clinical practice reviewed. RESULTS: We present the case of a young man with treatment resistant schizophrenia who underwent a successful re-challenge of clozapine, having previously ceased treatment due to an eosinophilia associated with treatment. CONCLUSION: We believe that the current report provides further evidence that it may be unnecessary to cease treatment in all patients who develop an eosinophilia without organ dysfunction whilst on clozapine. Furthermore, where clozapine has been ceased due to an eosinophilia without evidence of organ specific inflammation, clozapine rechallenge with increased haematological monitoring should be considered.

Tumoral C-reactive protein and nuclear factor kappa-B expression are associated with clinical outcome in patients with prostate cancer.

Prostate cancer (Pca) is the most common form of cancer affecting men, despite recent advances in PCa treatments, one third of patients diagnosed each year succumb to this disease. The inflammatory response has been implicated in prostate cancer progression. The pro-inflammatory transcription factor, NFκB/p65 has been implicated in PCa progression. Few studies have examined the involvement of NFκB and inflammatory signalling in PCa.Immunohistochemistry was employed to investigate the expression of NFκB/p65, C-reactive protein and Ki67 in 61 clinical samples. Tumours expressing high levels of p65 (p=0.004), CRP (p=0.011) and Ki67 (p=0.0003) had a shorter disease specific survival. Upon combining p65 and CRP status it was observed that those tumours with low expression of both proteins had a median survival of 11 years compared to 3.9 years for those with tumours with high expression of both (p=0.005). CRP expression was significantly higher in the 21 patients who died of their disease and on multivariate analysis CRP expression retained independent significance (p=0.005). This study suggests CRP and NFκB may function collectively to drive prostate cancer progression in a subset of patients. Tumoral CRP is a significant independent predictor of cancer specific survival. The relationship between tumour CRP and signalling pathways warrants further investigation in a larger cohort.

Systemic inflammatory response and survival in patients with localised prostate cancer: 10-year follow-up.

AIM: To examine the prognostic value of circulating C-reactive protein concentrations at diagnosis in patients with organ-confined prostate cancer. PATIENTS AND METHODS: Ninety-eight patients with histologically proven clinically localised prostate cancer were studied. Clinical stage, tumour grade, circulating PSA and C-reactive protein concentrations at diagnosis were recorded. RESULTS: The majority of patients was under the age of 70 years and had low-grade tumours. Approximately half the patients received radical local treatment. During the follow-up period (median 10 years) 38 patients died, of whom 18 died of prostate cancer, 6 of other cancers and 14 of non-cancer causes. On univariate survival analysis, age (p < 0.001), Gleason score (p < 0.05), C-reactive protein (p < 0.05) and treatment (p < 0.05) were significant predictors of overall survival. On univariate survival analysis, age (p < 0.001), Gleason score (p < 0.05) and C-reactive protein (p < 0.05) were significant predictors of prostate cancer-specific survival. On multivariate analysis of these significant variables age (HR 4.88, 95% CI 1.79-13.29, p < 0.01), Gleason score (HR 2.16, 95% CI 1.23-3.78, p < 0.01) and C-reactive protein (HR 1.88, 95% CI 1.01-3.52, p < 0.05) remained significant independent predictors of prostate cancer-specific survival. CONCLUSION: The results of the present study show that the presence of a systemic inflammatory response, at diagnosis, independently predicts poor long-term cancer outcome in patients with localised prostate cancer.

The relationship between the local and systemic inflammatory responses and survival in patients undergoing resection for localized renal cancer.

OBJECTIVE: To examine the relationship between the systemic inflammatory response (C-reactive protein, CRP), tumour interleukin-6 receptor and cyclooxygenase (COX)-2 expression, tumour T-lymphocytic (CD4+, CD8+) infiltration and cancer survival in patients undergoing resection for renal cell carcinoma (RCC), as both the local and systemic inflammatory responses appear to predict the outcome in these patients. PATIENTS AND METHODS: The study included 60 patients undergoing nephrectomy for localized RCC. Pre-operative circulating CRP levels were measured and tumour interleukin-6 receptor and COX-2 expression, tumour CD4+ and CD8+ T lymphocytes were assessed using immunohistochemical analysis. RESULTS: The median follow-up was 78 months, with 14 patients relapsing from their disease and nine cancer-specific deaths. On univariate and multivariate survival analysis, tumour stage and grade and CRP levels were identified as significant factors associated with relapse-free and cancer-specific survival. There was a significant direct relationship between Fuhrman grade and CD4+ T-lymphocytic infiltrate (P < 0.05). An increase in tumour expression of interleukin-6 receptor was weakly associated with an increase in tumour CD8+ T-lymphocytic infiltration (P = 0.057). An increase in tumour CD4+ T-lymphocytic infiltration was associated with an increase in CD8+ T-lymphocytic infiltration (P < 0.01). CONCLUSIONS: The present results suggest that tumour-based factors such as interleukin-6 receptor and COX-2 expression or T-lymphocytic subset infiltration are subordinate to systemic factors such as CRP level in determining survival in patients with localized RCC.

Systemic inflammatory response, prostate-specific antigen and survival in patients with metastatic prostate cancer.

BACKGROUND: It is increasingly recognised that, in cancer patients, disease progression is dependent on a complex interaction of the tumour and the host inflammatory response and that the systemic inflammatory response, as evidenced by an elevated C-reactive protein (CRP) concentration, may be a useful prognostic factor. MATERIALS AND METHODS: The prognostic value of CRP compared with prostate-specific antigen (PSA) was examined in 62 patients with metastatic prostate cancer receiving androgen-deprivation therapy. RESULTS: In all, 41 (66%) of patients died, 38 (61%) of their disease. On univariate survival analysis, PSA (p < 0.05) and CRP (p < 0.05) were significant predictors of cancer-specific survival. On multivariate analysis, both PSA (HR 1.96, 95% CI 1.00-3.83, p = 0.049) and CR (HR 1.97, 95% CI 0.99-3.92, p = 0.052) were independent predictors of cancer-specific survival. PSA concentrations were significantly correlated with those of CRP (r(s) = 0.46, p < 0.001). CONCLUSION: The results of the present study suggest that, in patients with metastatic prostate cancer, the presence of an elevated CRP concentration predicts poor outcome, independent of PSA.

Vitamin antioxidants, lipid peroxidation and the systemic inflammatory response in patients with prostate cancer.

The relationship between lipid soluble antioxidant vitamins, lipid peroxidation, disease stage and the systemic inflammatory response were examined in healthy subjects (n = 14), patients with benign prostate hyperplasia BPH (n = 20), localized (n = 40) and metastatic (n = 38) prostate cancer. Prostate cancer patients had higher concentrations of malondialdehyde (p < 0.05) and lower circulating concentrations of lutein (p < 0.05), lycopene (p < 0.001) and beta-carotene (p < 0.05). Patients with metastatic prostate cancer, when compared with patients having localized disease, had a higher Gleason score (p < 0.01) and had more hormonal treatment, but lower concentrations of PSA (p < 0.05), alpha-tocopherol (p < or = 0.05), retinol (p < 0.01), lutein (p < 0.05) and lycopene (p < 0.01). In the prostate cancer patients, PSA was correlated with the concentrations of the lipid peroxidation product, malondialdehyde (rs= 0.353, p = 0.002). C-reactive protein was not correlated with the vitamin antioxidants nor malondialdehyde. In contrast, there was a negative correlation between malondialdehyde concentrations and both lutein (rs= -0.263, p = 0.020) and lycopene (rs= -0.269, p = 0.017). These results indicate that lower concentrations of carotenoids, in particular, lycopene reflect disease progression rather than the systemic inflammatory response in patients with prostate cancer.