Tahir Qayyum

The prognostic value of histological tumor necrosis in solid organ malignant disease: a systematic review

BACKGROUND Tumor necrosis has been proposed as a marker of poor prognosis in a variety of solid organ malignant tumor types. Despite this, its assessment has yet to be adopted into routine clinical practice and the mechanisms underpinning the relationships with cancer outcome are undetermined. AIMS To examine the prognostic value of tumor necrosis in solid organ malignant disease and to summarize the known clinical, pathological and inflammatory associations. METHODS A systematic review of data published from 1966-2011 was undertaken by two reviewers according to a predefined protocol. A total of 57 independent studies relating to renal (n = 23), breast (n = 13), lung (n = 7), colorectal (n = 5) and other solid tumors (n = 9) were included in the final review. CONCLUSION There is now a substantial body of evidence confirming the prognostic value of tumor necrosis in solid organ malignant disease. There are consistent associations between necrosis and the presence of other high-risk tumor characteristics but the survival impact appears to be independent of pathological stage. We propose that relationships with the host inflammatory response, both local and systemic, may explain the influence of tumor necrosis on cancer outcome.

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.

A Prospective Study of the Role of Inflammation in Bladder Cancer

Introduction: To examine the role of inflammation in bladder cancer, we assessed the relationship between a systemic inflammation prognostic score (modified Glasgow Prognostic Score, mGPS), the tumor inflammatory cell infiltrate as measured by the Klintrup-Makinen score and tumor necrosis with cancer specific survival in patients with bladder cancer. Materials and Methods: The cohort consisted of 68 bladder cancer patients, 47 with localised disease and 21 with muscle invasive disease. The mGPS response was constructed by measuring C-reactive protein and albumin concentrations and the Klintrup-Makinen score was evaluated histologically for the local inflammatory response. Pathological parameters such as grade, T stage and tumor necrosis were also assessed. Results: Median follow was 47 months and 24 patients died of their disease. On univariate analysis, T stage (p < 0.001), grade (p < 0.001) and mGPS (p = 0.002) were significant predictors of cancer specific survival. On multivariate analysis, T stage (hazard ratio 5.98, 95% confidence interval 3.18–11.24, p < 0.001) and mGPS (hazard ratio 1.78, 95% confidence interval 1.09–2.9, p = 0.02) were significant independent predictors of cancer specific survival. Conclusion: A preoperative systemic inflammatory response is an independent predictor of poor cancer specific survival in patients with bladder cancer.

The Epidemiology and Risk Factors for Renal Cancer

Background: Renal cancer is a frequently occurring malignancy with over 270,000 new cases diagnosed and it being responsible for 110,000 deaths annually on a global basis. Incidence rates have gradually increased whilst mortality rates are starting to plateau. Objective: To review epidemiology and risk factors for renal cancer. Methods: The current data is based on a thorough review of available original and review articles on epidemiology and risk factors for renal cancer with a systemic literature search utilising Medline. Results: The prevalence of associated risk factors such as genetic susceptibility, smoking, hypertension and obesity are changing and could account for the changes in incidence whilst the role of diet and occupational exposure to carcinogens requires further investigation. Conclusion: Despite the evidence of various associated risk factors, further work is required from well designed studies to gain a greater understanding of the etiology of renal cancer.

The Prognostic Use of Inflammation and Tissue Necrosis in Benign Prostatic Hyperplasia

Introduction: Evidence for the role of inflammation in benign prostatic hyperplasia (BPH) is conflicting. Establishing the prognostic significance of local and systemic inflammation and tissue necrosis scoring systems in BPH may elucidate the potential of inflammatory pathways as a target of therapeutic intervention in these patients. Patients and Methods: Consecutive patients with histological BPH diagnosed between 1996 and 2005 were identified. Systemic inflammation was assessed by the modified Glasgow prognostic score (mGPS), local inflammation by the Klintrup-Makinen criteria and tissue necrosis was evaluated by an extent-based classification. Results: In 392 BPH patients, there was a trend for increased local inflammation and tissue necrosis to be associated with shorter time to failure of pre-operative medical treatment of BPH (p = 0.096 and 0.088, respectively). High modified Glasgow prognostic score was associated with older age (p = 0.002) and higher levels of deprivation (measured by the Scottish Index of Multiple Deprivation) (p = 0.021). Conclusions: The prognostic use of established scoring systems of systemic and local inflammation and tissue necrosis in BPH requires further investigation. It remains unclear as to whether targeting inflammation in BPH has therapeutic potential.

Body Mass Index Predicts Failure of Surgical Management in Benign Prostatic Hyperplasia

Introduction: Inflammation is postulated to link obesity and benign prostatic hyperplasia (BPH). The role of inflammation and the prognostic significance of body mass index (BMI) was investigated in BPH patients. Subjects and Methods: Consecutive patients with histological BPH were identified from 1996 to 2005. Systemic inflammation was assessed by modified Glasgow Prognostic Score (mGPS) and local inflammation by Klintrup-Makinen criteria. Results: In 392 patients, BMI was associated with cardiovascular disease (p = 0.033), type 2 diabetes mellitus (p = 4.45 × 10-8), aspirin usage (p = 0.018) and failure of surgical treatment (p = 0.001). mGPS and Klintrup-Makinen scores were not associated with clinical variables or outcome measures. On multivariate analysis BMI was an independent predictor of time to failure of surgical management of BPH, HR 1.56 (95% CI 1.11-2.19), p = 0.010. Conclusions: The mGPS and Klintrup-Makinen scores were not associated with BMI in BPH patients. High BMI is associated with failure of surgical management of BPH. Preoperative weight loss should be strongly encouraged in these patients.

The Prognostic Role of the Non-Canonical Nuclear Factor-Kappa B Pathway in Renal Cell Carcinoma Patients

Background: In the United Kingdom, 8,000 cases of renal cancer are diagnosed each year, with a 5-year survival rate of 50%. Treatment options are limited; a potential therapeutic target is the non-canonical nuclear factor-kappa B (NF-κB) pathway. This pathway plays a role in multiple oncogenic processes in solid tumors. The aim of this study was to investigate the non-canonical nuclear factor pathway in renal cell carcinoma (RCC). Materials and Methods: NIK, IKKα, and RelB were investigated via immunohistochemistry in a cohort of 192 patients with clear cell renal cancer. Results: High cytoplasmic NIK was associated with poorer cancer-specific survival (p = 0.006) and 10-year survival stratified from 85% (low) to 65% (high, p = 0.005). Similarly, high cytoplasmic RelB was associated with poorer cancer-specific survival (p = 0.041) and 10-year survival stratified from 88% (low) to 73% (high, p = 0.030). When clinicopathological characteristics were assessed, cytoplasmic NIK was associated with survival (p = 0.014), whereas cytoplasmic RelB was associated with increased tumor grade (p = 0.020) and decreased inflammation (p = 0.019). Upon multivariate analysis, it was found that cytoplasmic NIK was independently associated with cancer-specific survival (p = 0.009). Conclusions: The non-canonical NF-κB pathway is associated with poorer cancer-specific survival in RCC patients, making it a viable target for therapeutic intervention. Furthermore, cytoplasmic NIK is a potential prognostic biomarker for this disease.

Pathological Correlation between Number of Biopsies and Radical Surgery: Does It Make a Difference to Final Pathology?

Aims: To evaluate whether the number of biopsies performed via transrectal ultrasound (TRUS) accurately predicts pathological parameters such as Gleason sum, prostatic intraepithelial neoplasia and perineural invasion of the final prostatectomy specimen. Materials and Methods: The cohort consisted of 99 patients whom had undergone radical prostatectomy. Comparisons were made between the number of biopsies utilised and the presence of the pathological parameters from tissue at time of diagnosis and tissue from the final prostatectomy. Results: A significant difference was noted between Gleason sum, prostatic intraepithelial neoplasia and perineural invasion from tissue at time of diagnosis irrespective of the number of biopsies utilised and tissue from the radical specimen (p < 0.001, p < 0.001, p < 0.001 respectively). No difference was noted in the mean Gleason sum when 11-14 biopsies were utilised at TRUS and the Gleason sum from the radical specimen. Conclusion: We have demonstrated that the number of biopsies utilised at time of TRUS for diagnosis predicts the accuracy of pathological parameters in the final radical prostatectomy specimen. We believe that 11-14 biopsies should be utilised at time of TRUS as this allows a higher accuracy in the Gleason sum and therefore allows optimum treatment plans to be devised.

The Accuracy of Magnetic Resonance Imaging in Radical Prostatectomy

Aims: The aim of this study was to examine the accuracy of standard magnetic resonance imaging (MRI) in the localised staging of prostate cancer in those who had undergone radical prostatectomy. Patients and Methods: The cohort consisted of 110 patients who had undergone MRI for staging of prostate cancer and subsequently underwent radical prostatectomy. T stage was analysed both on MRI and from the specimen following radical surgery. Results: Of the patients 57% of patients had their disease up-staged following radical surgery from preoperative MRI findings. Of those patients who had their disease up-staged following surgery, nearly 50% of patients had gone from organ confined disease at time of MRI to extra-prostatic involvement from the surgical specimen. Conclusion: We have reported that MRI has a wide range of accuracy. Given developments in MRI technologies further work should be pursued to help in the staging of this disease for which decision to treat is difficult.