Biomedical subjects

D C McMillan

Publications and source records attributed to D C McMillan.

At least 19 recordsLinked to original sources

PubMed2006

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration and COX-2 expression and survival in patients with transitional cell carcinoma of the urinary bladder.

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration, and COX-2 expression and survival was examined in patients with transitional cell carcinoma of the urinary bladder (n=103). Sixty-one patients had superficial disease and 42 patients had invasive disease. Cancer-specific survival was shorter in those patients with invasive compared with superficial bladder cancer (P<0.001). On univariate analysis, stratified by stage, increased Ki-67 labelling index (P<0.05), increased COX-2 expression (P<0.05), C-reactive protein (P<0.05) and adjuvant therapy (P<0.01) were associated with poorer cancer-specific survival. On multivariate analysis of these significant factors, stratified by stage, only C-reactive protein (HR 2.89, 95% CI 1.42-5.91, P=0.004) and adjuvant therapy (HR 0.29, 95% CI 0.14-0.62, P=0.001) were independently associated with poorer cancer-specific survival. These results would suggest that tumour-based factors such as grade, COX-2 expression or T-lymphocytic infiltration are subordinate to systemic factors such as C-reactive protein in determining survival in patients with transitional cell carcinoma of the urinary bladder.

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PubMed2006

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer.

The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stage-independent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (P< or =0.01) were higher and a greater proportion were elevated (P<0.05) in malignant compared with benign disease. The renal cancer patients were grouped according to whether they had evidence of a systemic inflammatory response. In the inflammatory group T stage was higher (P<0.01), both interleukin-6 and interleukin-10 concentrations were higher (P<0.001) and elevated (P<0.10) compared with the non-inflammatory group. Tumour volume was weakly correlated with C-reactive protein (r(2)=0.20, P=0.002), interleukin-6 (r(2)=0.20, P=0.002) and interleukin-10 (r(2)=0.24, P=0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer.

Analysis of Variance↗

PubMed2006

An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of tumours. The aim of the present study was to examine the relationship between clinico-pathological status, preoperative C-reactive protein concentration and cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. One hundred and twenty patients attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow, who were selected for potentially curative surgery, were included in the study. Laboratory measurements of haemoglobin, white cell, lymphocyte and platelet counts, albumin and C-reactive protein were carried out at the time of diagnosis. All patients underwent en-bloc resection with lymphadenectomy and survived at least 30 days following surgery. On multivariate analysis, only the positive to total lymph node ratio (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.44-2.84, P<0.001) and preoperative C-reactive protein concentration (HR 3.53, 95% CI 1.88-6.64, P<0.001) were independent predictors of cancer-specific survival. The patient group with no evidence of a preoperative systemic inflammatory response (C-reactive protein < or =10 mg l(-1)) had a median survival of 79 months compared with 19 months in the elevated systemic inflammatory response group (P<0.001). The results of the present study indicate that in patients selected to undergo potentially curative resection for gastro-oesophageal cancer, the presence of an elevated preoperative C-reactive protein concentration is an independent predictor of poor cancer-specific survival.

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PubMed2006

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.

Adenocarcinoma↗

PubMed2006

The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer.

BACKGROUND: The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score formed from standard thresholds of C reactive protein (CRP) and albumin, has prognostic value in patients with advanced cancer. Little is known about the general biochemical disturbance associated with the systemic inflammatory response in cancer. AIM: To examine the relationship between the GPS and blood biochemistry in patients with advanced lung and gastrointestinal cancer. METHODS: The GPS (albumin <35 g/l = 1 and CRP >10 mg/l = 1 combined to form a prognostic score of 0 (normal) and 1 or 2 (abnormal)) and a variety of biochemical variables were examined in patients (n = 50) with advanced lung or gastrointestinal cancer and in a healthy control group (n = 13). RESULTS: The GPS was normal in all the controls, but abnormal in 78% of the cancer group. Serum levels of sodium, chloride, creatine kinase, zinc and vitamin D were lower in the cancer group (all p<0.01), whereas levels of calcium, copper (both p<0.05), alkaline phosphatase, gamma-glutamyl transferase (both p<0.001) and lactate dehydrogenase (p<0.10) were raised. In the patient group, with increasing GPS, there was a median reduction in Karnofsky Performance Status (25%), haemoglobin (22%), sodium (3%), zinc (15%) and survival (93%, all p<0.05) and a median increase in white cell count (129%), alkaline phosphatase (217%), gamma-glutamyl transferase (371%) and lactate dehydrogenase (130%, all p<0.05). CRP levels were strongly and similarly correlated with alkaline phosphatase and gamma-glutamyl transferase, accounting for more than 25% of the variation in their activities. CONCLUSION: Several correlations were seen between biochemical variables and increasing GPS. In particular, chronic activation of the systemic inflammatory response in cancer was associated with increase in gamma-glutamyl transferase and alkaline phosphatase activity in patients with advanced lung and gastrointestinal cancer.

Adult↗

PubMed2006

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.

C-Reactive Protein↗

PubMed2006

Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied (n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. On multivariate survival analysis, age (hazard ratio (HR) 1.22, 95% CI 1.02-1.46, P<0.05), stage (HR 1.55, 95% CI 1.30-1.83, P<0.001), the GPS (HR 1.51, 95% CI 1.22-1.86, P<0.001) and treatment (HR 2.53, 95% CI 1.80-3.56, P<0.001) were significant independent predictors of cancer survival. A 12-month cancer-specific survival in patients with stage I/II disease receiving active treatment was 67 and 60% for a GPS of 0 and 1, respectively. For stage III/IV disease, 12 months cancer-specific survival was 57, 25 and 12% for a GPS of 0, 1 and 2, respectively. In the present study, the GPS predicted cancer-specific survival, independent of stage and treatment received, in patients with inoperable gastro-oesophageal cancer. Moreover, the GPS may be used in combination with conventional staging techniques to improve the prediction of survival in patients with inoperable gastro-oesophageal cancer.

Aged↗

PubMed2006

Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer.

Prediction of outcome in patients with metastatic breast cancer remains problematical. The present study evaluated the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with metastatic breast cancer. The GPS was constructed as follows: patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. In total, 96 patients were studied. During follow-up 51 patients died of their cancer. On multivariate analysis of the GPS and treatment received, only the GPS (HR 2.26, 95% CI 1.45-3.52, P<0.001) remained significantly associated with cancer-specific survival. The presence of a systemic inflammatory response (the GPS) appears to be a useful indicator of poor outcome independent of treatment in patients with metastatic breast cancer.

Breast Neoplasms↗

PubMed2006

The impact of blood loss, obstruction and perforation on survival in patients undergoing curative resection for colon cancer.

BACKGROUND: Previous studies have drawn attention to the high postoperative mortality and poor survival of patients who present as an emergency with colon cancer. However, these patients are a heterogeneous group. The aim of the present study was to establish, having adjusted for case mix, the size of the differences in postoperative mortality and 5-year survival between patients presenting as an emergency with evidence of blood loss, obstruction and perforation. METHODS: The study included 2068 patients who presented with colon cancer between 1991 and 1994 in Scotland. Five-year survival rates and the adjusted hazard ratios were calculated. RESULTS: Thirty-day postoperative mortality following potentially curative resection was consistently higher in patients who presented with evidence of blood loss, obstruction or perforation (all P < 0.005) than in elective patients. Following potentially curative surgery, cancer-specific survival at 5 years was 74.6 per cent compared with 60.9, 51.6 and 46.5 per cent in those who presented with blood loss, obstruction and perforation respectively (all P < 0.001). The corresponding adjusted hazard ratios (95 per cent confidence interval) for cancer-specific survival, relative to elective patients, were 1.62 (1.22 to 2.15), 2.22 (1.78 to 2.75) and 2.93 (1.82 to 4.70) for patients presenting with evidence of blood loss, obstruction or perforation (all P < 0.001). CONCLUSION: Compared with patients who undergo elective surgery for colon cancer, those who present as an emergency with evidence of blood loss, obstruction or perforation have higher postoperative mortality rates and poorer cancer-specific survival.

Adult↗

PubMed2006

Postoperative serum urea is associated with 30-day mortality in patients undergoing emergency abdominal surgery.

BACKGROUND: Emergency abdominal surgery carries considerable postoperative morbidity and mortality. Hypovolaemia is considered to be a cause of renal hypoperfusion, which is associated with a decreased clearance of serum urea and creatinine. This study examines whether the perioperative serum urea and creatinine concentrations are predictors of mortality in patients undergoing emergency abdominal surgery. METHODS: Consecutive patients (n=300) who underwent emergency abdominal surgery were studied. Age- and sex-specific reference intervals were used for the data analysis. Patients with incomplete biochemical (n=51) or mortality data (n=31) or with pre-existing renal failure (n=9) were excluded from the analysis. RESULTS: 209 patients were analysed, of whom 162 (78%) remained alive and 47 (22%) died following surgery. The non-survivors were older (P<0.05), had undergone more extensive surgery (P<0.001) and were more likely to have been admitted to the intensive care unit (P<0.001). The serum urea concentration was higher preoperatively (P<0.05) and on day one postoperatively (P<0.001) in the non-survivors. On multivariate logistic regression analysis, age (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.43-7.47, P<0.005), severity of surgery (OR 2.21, 95% CI 1.14-4.29, P<0.019), admission to intensive care (OR 0.54, 95% CI 0.11-0.54, P<0.001), seniority of anaesthetist (OR 0.50, 95% CI 0.27-0.90, P<0.022) and day one urea (OR 3.33, 95% CI 1.39-7.99, P<0.007) were independently associated with 30-day mortality. CONCLUSIONS: These results indicate that an increased serum urea concentration, but not serum creatinine concentration, in the postoperative period is associated with an increase in 30-day mortality in patients undergoing emergency abdominal surgery.

Abdomen↗

PubMed2005

An evaluation of the impact of a multidisciplinary team, in a single centre, on treatment and survival in patients with inoperable non-small-cell lung cancer.

Treatment and survival of patients with inoperable Non-small-cell lung cancer in 1997 (n=117) and 2001 (n=126), before and after the introduction of a multidisciplinary team, was examined in a single centre. There were no differences in age, sex and extent of deprivation between the two years. However, in 2001, 23% of patients received chemotherapy treatment compared with 7% in 1997 (P<0.001). Median survival in 2001 was 6.6 months compared with 3.2 months in 1997 (P<0.001).

Age Distribution↗

PubMed2005

A prospective longitudinal study of performance status, an inflammation-based score (GPS) and survival in patients with inoperable non-small-cell lung cancer.

The value of an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was compared with performance status (ECOG-ps) in a longitudinal study of patients (n=101) with inoperable non-small-cell lung cancer (NSCLC). At diagnosis, stratified for treatment, only the GPS (HR 2.32, 95% CI 1.52-3.54, P<0.001) was a significant predictor of survival. In contrast, neither the GPS nor ECOG-ps measured at 3-6 months follow-up were significant predictors of residual survival. This study confirms the prognostic value of the GPS, at diagnosis, in patients with inoperable NSCLC. However, the role of the GPS and ECOG-ps during follow-up has not been established.

Aged↗

PubMed2005

The relationship between the systemic inflammatory response and survival in patients with transitional cell carcinoma of the urinary bladder.

The relationship between tumour stage, grade, elevated C-reactive protein concentration (<10/>10 mg l(-1)), adjuvant therapy and survival was examined in patients with biopsy proven bladder cancer (n=105). On multivariate analysis stage (HR 3.37, 95% CI 1.37-8.29, P=0.008), grade (HR 2.01, 95% CI 1.14-3.57, P=0.017) and preoperative C-reactive protein (HR 3.31, 95% CI 1.09-10.09, P=0.035) were independently associated with cancer-specific survival.

Aged↗

PubMed2005

The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer.

There is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. The aim of the present study was to examine the relationship between tumour T-lymphocyte subset infiltration, the systemic inflammatory response and cancer-specific survival in patients with colorectal cancer. In all, 147 patients undergoing potentially curative resection for colorectal cancer were studied. Circulating concentrations of C-reactive protein were measured prior to surgery. CD4+ and CD8+ T-lymphocyte infiltration of the tumour was assessed using immunohistochemistry and a point counting technique. When patients were grouped according to the percentage tumour volume of CD4+ T-lymphocytes, there was no difference in terms of age, sex, tumour site, stage and tumour characteristics. However, there was an inverse relationship between percentage tumour CD4+ T-lymphocytes and C-reactive protein (P<0.01). On univariate analysis, both C-reactive protein concentrations (P<0.001) and percentage tumour volume of CD4+ (P<0.05) T-lymphocytes were associated with cancer-specific survival. The results of the present study show that low tumour CD4+ T-lymphocyte infiltration is associated with elevated C-reactive protein concentrations and both predict poor cancer-specific survival.

Aged↗

PubMed2005

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 < or = 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.

Aged↗

PubMed2005

Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer.

BACKGROUND: The impact of anastomotic leakage on immediate postoperative mortality in patients undergoing potentially curative resection for colorectal cancer is well recognized. Its impact on long-term survival is less clear. The aim of the present study was to evaluate the relationship between anastomotic leakage and long-term survival in patients undergoing potentially curative resection for colorectal cancer. METHODS: A total of 2235 patients who underwent potentially curative resection for colorectal cancer between 1991 and 1994 in Scotland were included in the study. Five-year survival rates and adjusted hazard ratios were calculated. RESULTS: Fourteen (16 per cent) of the 86 patients with an anastomotic leak died within 30 days of surgery compared with 83 (3.9 per cent) of 2149 without a leak. The 5-year cancer-specific survival rate, including postoperative deaths, was 42 per cent in patients with an anastomotic leak compared with 66.9 per cent in those with no leak (P < 0.001). Excluding postoperative deaths, respective values were 50 and 68.0 per cent (P < 0.001). The adjusted relative hazard ratios, for patients with an anastomotic leak compared with those without a leak, and excluding 30-day mortality, were 1.61 (95 per cent confidence interval (c.i.) 1.19 to 2.16; P = 0.002) for overall survival and 1.99 (95 per cent c.i. 1.42 to 2.79; P < 0.001) for cancer-specific survival. CONCLUSION: Development of an anastomotic leak is associated with worse long-term survival after potentially curative resection for colorectal cancer.

Adult↗

PubMed2004

The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer.

The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL-8)) of this acute phase protein were examined in healthy subjects (n=11) and patients with non-small-cell lung cancer (n=50). Leukaemia inhibitory factor and CNTF were below detection limits in all controls and patients. C-reactive protein, interleukin-6, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and IL-8 concentrations were significantly elevated in cancer patients (P< or =0.001). Cancer patients with elevated C-reactive protein concentrations had greater concentrations of interleukin-6 (P<0.01) and interleukin-1 receptor antagonist (P<0.05). On regression analysis only interleukin-6 was independently associated with C-reactive protein (r=0.616, P<0.001). Interleukin-6 is an important independent mediator of elevated C-reactive protein concentrations in patients with non-small-cell lung cancer.

Adult↗

PubMed2004

The relationship between interleukin-6 and C-reactive protein in patients with benign and malignant prostate disease.

The relationship between interleukin-6 and C-reactive protein was evaluated in patients with benign (n=59) and malignant (n=86) prostate disease. The correlation coefficients for patients with benign prostatic disease and prostate cancer were rs=0.632, P<0.001 and rs=0.663, P<0.001, respectively. These results indicate that the relationship between interleukin-6 and C-reactive protein is similar in patients with benign and malignant prostate disease.

Aged↗