Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss

The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4–6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P < 0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P < 0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted. © 1999 Cancer Research Campaig

The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer

The relationship between the magnitude of systemic inflammatory response and the nutritional/functional parameters in patients with inoperable non-small cell lung cancer were studied. The extent of weight loss, albumin, C-reactive protein, performance status and quality of life was measured in 106 patients with inoperable non-small cell lung cancer (stages III and IV). Survival analysis was performed using the Cox proportional hazard model. The majority of patients were male and almost 80% had elevated circulating C-reactive protein concentrations (>10 mg l−1). On multivariate analysis, age (P=0.012), tumour type (0.002), weight loss (P=0.056), C-reactive protein (P=0.047), Karnofsky performance status (P=0.002) and fatigue (P=0.046) were independent predictors of survival. The patients were grouped according to the magnitude of the C-reactive protein concentrations (⩽10, 11–100 and >100 mg l−1). An increase in the magnitude of the systemic inflammatory response was associated with increased weight loss (P=0.004), reduced albumin concentrations (P=0.001), reduced performance status (P=0.060), increased fatigue (P=0.011) and reduced survival (HR 1.936 95%CI 1.414–2.650, P<0.001). These results indicate that the majority of patients with inoperable non-small cell lung cancer have evidence of a systemic inflammatory response. Furthermore, an increase in the magnitude of the systemic inflammatory response resulted in greater weight loss, poorer performance status, more fatigue and poorer survival

The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin

&lt;b&gt;Aim&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was &#60;10%.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt;&lt;p&gt;&lt;/p&gt; In the large cohort, plasma 25 (OH) D was significantly associated with CRP (rs = −0.113, p&#60;0.001) and albumin (rs = 0.192, p&#60;0.001). 3711 patients had CRP concentrations ≤10 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p&#60;0.001). This decrease was significant when albumin concentrations were reduced between 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 1271 patients had CRP concentrations between 11–80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p&#60;0.001). This decrease was significant when albumin concentration were 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 345 patients had CRP concentrations &#62;80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.&lt;p&gt;&lt;/p&gt

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

The presence of a systemic inflammatory response predicts poorer survival in patients receiving adjuvant 5-FU chemotherapy following potentially curative resection for colorectal cancer

There is increasing evidence that the presence of a systemic inflammatory response plays an important role in survival following curative resection for colorectal cancer. The present study evaluated the relationship between C-reactive protein concentrations and survival in a cohort of patients receiving adjuvant 5-fluorouracil (5-FU) chemotherapy following potentially curative resection for colorectal cancer. In all, 222 patients undergoing potentially curative resection for colorectal cancer were studied. Of these, 50 patients received adjuvant 5-FU-based chemotherapy. Circulating concentrations of C-reactive protein were measured prior to surgery. The minimum follow-up was 15 months; the median follow-up of the survivors was 38 months. During this period 61 patients died, 32 patients of their cancer and 29 of intercurrent disease. In those patients who did not receive adjuvant chemotherapy, age (P<0.001), Dukes stage (P<0.05) and an elevated C-reactive protein (P<0.01) were significantly associated with survival. In those patients who did receive adjuvant chemotherapy, an elevated C-reactive protein concentration (P<0.01) was significantly associated with survival. The presence of a systemic inflammatory response is an independent predictor of poor outcome in patients receiving adjuvant 5-FU-based chemotherapy following potentially curative resection for colorectal cancer

Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas

The aim of the present study was to examine the relationship between the clinicopathological status, the pre- and postoperative systemic inflammatory response and survival in patients undergoing potentially curative resection for ductal adenocarcinoma of the head of the pancreas. Patients (n=65) who underwent resection of ductal adenocarcinoma of the head of pancreas between 1993 and 2001, and had pre- and postoperative measurements of C-reactive protein, were included in the study. The majority of patients had stage III disease (International Union Against Cancer Criteria, IUCC), positive circumferential margin involvement (R1), tumour size greater than 25 mm with perineural and lymph node invasion and died within the follow-up period. On multivariate analysis, tumour size (hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.20–3.68, P=0.009), vascular invasion (HR 2.58, 95% CI 1.48–4.50, P<0.001) and postoperative C-reactive protein (HR 2.00, 95% CI 1.14–3.52, P=0.015) retained independent significance. Those patients with a postoperative C-reactive protein ⩽10 mg l−1 had a median survival of 21.5 months compared with 8.4 months in those patients with a C-reactive protein >10 mg l−1 (P<0.001). The results of the present study indicate that, in patients who have undergone potentially curative resection for ductal adenocarcinoma of the head of pancreas, the presence of a systemic inflammatory response predicts poor outcome

The relationship between the preoperative systemic inflammatory response and cancer-specific survival in patients undergoing potentially curative resection for renal clear cell cancer

The relationship between tumour stage, grade (Fuhrman), performance status (ECOG), a combined score (UCLA Integrated Staging System, UISS), systemic inflammatory response (elevated C-reactive protein concentration), and cancer-specific survival was examined in patients undergoing potentially curative resection for renal clear cell cancer (n=100). On univariate survival analysis, sex (P=0.050), tumour stage (P=0.001), Fuhrman grade (P<0.001), UISS (P<0.001), C-reactive protein (P=0.002) were significant predictors of survival. On multivariate analysis with sex, UISS and C-reactive protein entered as covariates, only UISS (HR 2.70, 95% CI 1.00–7.30, P=0.050) and C-reactive protein (HR 4.00, 95% CI 1.21–13.31, P=0.024) were significant independent predictors of survival. The presence of a preoperative systemic inflammatory response predicts poor cancer-specific survival in patients who have undergone potentially curative resection for renal clear cell cancer

The physiological cost index of walking with a powered knee ankle foot orthosis in subjects with poliomyelitis : A pilot study

Background: A powered knee ankle foot orthosis (KAFO) was developed to provide restriction of knee flexion during stance phase and active flexion and extension of the knee during swing phase of gait. Objectives: The purpose of this study was to determine its effect on the physiological cost index (PCI), walking speed and the distance walked in people with poliomyelitis compared to when walking with a KAFO with drop lock knee joints. Methods: Seven subjects with poliomyelitis volunteered for the study, and undertook gait analysis with both types of KAFO. Results: Walking with the powered KAFO significantly reduced walking speed (p=0.015) and the distance walked (p=0.004), and also it did not improve PCI values (p =0.009) compared to walking with the locked KAFO. Conclusion: Using a powered KAFO did not significantly improve any of the primary outcome measures during walking for poliomyelitis subjects

Star Clusters

This review concentrates almost entirely on globular star clusters. It emphasises the increasing realisation that few of the traditional problems of star cluster astronomy can be studied in isolation: the influence of the Galaxy affects dynamical evolution deep in the core, and the spectrum of stellar masses; in turn the evolution of the core determines the highest stellar densities, and the rate of encounters. In this way external tidal effects indirectly influence the formation and evolution of blue stragglers, binary pulsars, X-ray sources, etc. More controversially, the stellar density appears to influence the relative distribution of normal stars. In the opposite sense, the evolution of individual stars governs much of the early dynamics of a globular cluster, and the existence of large numbers of primordial binary stars has changed important details of our picture of the dynamical evolution. New computational tools which will become available in the next few years will help dynamical theorists to address these questions.Comment: 10 pages, 3 figures, Te