Adjuvant radiotherapy and chemotherapy in breast cancer: 30 year follow-up of survival.

BACKGROUND: The long term outcome (more than 15 years) of adjuvant treatment in patients with primary operable breast cancer has rarely been examined. METHODS: A randomised clinical trial of radiotherapy, chemotherapy (28 day cycles of cyclophosphamide, methotrexate and 5-fluorouracil) or both on women with primary operable breast cancer (n = 322) was followed-up for a median of 27 years. RESULTS: 260 (81%) patients died, 204 (78%) from breast cancer. Cancer specific survival (SE) at 10 years, 20 years and 30 years was 41 (3)%, 34 (3)% and 33 (3)% respectively. Presence of more than 3 involved lymph nodes increased cancer-specific mortality (HR 1.88, 95% CI 1.34-2.63) after adjustment for age, socio-economic deprivation and adjuvant treatment. Both age (HR 1.63, 95% CI 1.19-2.22) and involved lymph nodes (HR 1.59, 95% CI 1.17-2.14) were significant predictors of all-cause mortality after adjustment for other factors. There was no significant difference in all-cause or cancer-specific survival between patients in each of the 3 treatment arms. CONCLUSIONS: The present study highlights the long term impact of node positive disease but does not indicate that any regimen was associated with significantly better long-term survival.

Tumor size is associated with the systemic inflammatory response but not survival in patients with primary operable colorectal cancer.

AIM: To examine the relationship between tumor diameter, C-reactive protein concentrations and survival in patients undergoing surgery for colorectal cancer. METHOD: Tumor diameter and pathological characteristics of the resected specimen were assessed in 227 patients. Circulating concentrations of C-reactive protein were measured prior to surgery. RESULTS: Ninety-six patients had an elevated C-reactive protein concentration (>10 mg/L) prior to surgery. Tumor size was associated with an elevated C-reactive protein concentration (P < 0.001). C-reactive protein concentrations (P < 0.001) were associated with poorer cancer-specific survival. CONCLUSION: Prior to surgery, the maximal tumor diameter is associated with an elevated preoperative C-reactive protein concentration but not survival in patients with primary operable colorectal cancer.

Epidemiology of colorectal liver metastases.

In summary, the natural history of patients presenting with synchronous liver metastases has been well documented. However, the epidemiology and natural history of patients presenting with metachronous disease is scant. It is clear, therefore, that the accurate detection of occult liver metastases at the time of presentation underpins further improvements in the selection of appropriate treatment for patients presenting with colorectal cancer. This will facilitate early referral for investigation and treatment of their liver metastases.

Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer.

BACKGROUND/AIMS: The aim of the study was to examine the value of the combination of an elevated C-reactive protein and hypoalbuminaemia (GPS) in predicting cancer-specific survival after resection for colon and rectal cancer. MATERIALS AND METHODS: The GPS was constructed as follows: Patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) 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. RESULTS: A GPS of 1 (n = 109) was mainly due to an elevated C-reactive protein concentration and the remainder due to hypoalbuminaemia. In those patients with a GPS of 1 due to hypoalbuminaemia (n = 16), the 3-year overall survival rate was 94% compared with 62% in those patients with a GPS of 1 due to an elevated C-reactive protein concentration (n = 93, p = 0.0094). Therefore, the GPS was modified such that patients with hypoalbuminaemia were assigned a score of 0 in the absence of an elevated C-reactive protein. On univariate analysis of those patients with colon and rectal cancer, the modified GPS (p < 0.0001) was significantly associated with overall and cancer specific survival. On univariate survival analysis of those patients with Dukes B colon and rectal cancer, the modified GPS (p < 0.01) was significantly associated with overall and cancer specific survival. CONCLUSION: The results of the present study indicate that the GPS, before surgery, predicts overall and cancer-specific survival after resection of colon and rectal cancer.

The effect of gender on postoperative mortality after emergency abdominal surgery.

BACKGROUND: The factors contributing to the high mortality after emergency abdominal surgery are unclear. Recent studies have revealed gender differences in immune function after trauma and in the presence of sepsis. OBJECTIVE: This study tested the hypothesis that factors determining survival after emergency abdominal surgery differ in males and females. METHODS: Consecutive patients, aged > or =50 years, who underwent emergency abdominal surgery between July 1998 and June 2000 at the Royal and Western Infirmaries in Glasgow, Scotland, were identified for study. Data collected retrospectively included sex, age, severity of surgery, seniority of surgeon and anesthetist, extent of deprivation, and 30-day postoperative mortality. RESULTS: A total of 633 patients were identified for study; 49 (8%) were excluded from analysis because 30-day mortality or surgery details were unavailable. Of the remaining 584 patients, 256 were male and 328 were female. The overall 30-day mortality was 26%, with 74 (29%) males and 79 (24%) females dying within this period. The mortality rates were 25% in males and 10% in females (P = 0.043) after minor surgery, 26% in males and 23% in females (P = NS) after intermediate surgery, and 44% in males and 39% in females (P = NS) after major surgery. On univariate logistic regression analysis in males, increasing age (P < 0.001), severity of surgery (P = 0.04), and seniority of anesthetist (P < 0.001) were associated with mortality. In females, severity of surgery (P < 0.001) was associated with mortality. CONCLUSIONS: These results show that in females, 30-day mortality was determined by severity of surgery, whereas in males increasing age and seniority of anesthetist also influenced 30-day mortality.

The systemic inflammatory response predicts overall and cancer specific survival in patients with malignant lymphoma.

BACKGROUND: The value of C-reactive protein concentrations in the assessment of prognosis in patients with advanced lymphoma has not been clearly defined. MATERIAL/METHODS: Patients with a diagnosis of non-Hodgkin's lymphoma (n = 108) and Hodgkin's lymphoma, (n = 39) and who had measurements of C-reactive protein were studied retrospectively and the data was reviewed over 8 years. RESULTS: Median survival, from the time of sampling, was 7.4 months. On univariate analysis there was a significant relationship between the duration of cancer specific survival and tumour type (p < 0.05), circulating concentrations of albumin (p < 0.001) and C-reactive protein (p < 0.001). In contrast, only C-reactive protein concentration was a predictor of death from intercurrent disease (p < 0.05). On multivariate analysis, C-reactive protein concentration remained a strong independent predictor of both death from cancer and intercurrent disease (p < 0.001). The hazard ratio associated with a unit increase in stratified C-reactive protein concentration was 8.18 (95% CI 4.80 - 13.95) for cancer specific death and 2.11 (95% CI 1.22 - 3.64) for intercurrent death. CONCLUSIONS: The results of the present study demonstrate that patients with advanced lymphoma have evidence of a systemic inflammatory response and the magnitude of the C-reactive protein response predicts the duration of overall and cancer specific survival.

Score based on hypoalbuminemia and elevated C-reactive protein predicts survival in patients with advanced gastrointestinal cancer.

The presence of a systemic inflammatory response (as evidenced by elevated C-reactive protein concentrations) has been shown to be associated with loss of lean body mass and poor survival in cancer patients. The aim of this study is to assess the value of the combination of hypoalbuminemia and an elevated circulating concentration of C-reactive protein as a prognostic score in patients with advanced gastrointestinal cancer. Patients with advanced colorectal (n = 99) and gastric (n = 66) cancer and who had measurements of albumin and C-reactive protein were identified. Hypoalbuminemia (< 35 g/l/ > or = 35 g/l) and an elevated C-reactive protein (< or = 10 mg/l/ > 10 mg/l) were combined to form a prognostic score (0, 1, and 2). In patients with colorectal cancer, median survival was 12.1, 6.1, and 1.7 m (P < 0.001) for scores of 0, 1, and 2, respectively. In patients with gastric cancer the corresponding median survival was 6.1, 3.1, and 1.6 m, respectively (P < 0.01). The results of the present study suggest that, in patients with advanced gastrointestinal cancer, a cumulative score based on hypoalbuminemia and an elevated C-reactive protein may be useful. It has the advantage that it is based on routinely available well-standardized measurements and is simple to use.

A prospective study of the impact of weight loss and the systemic inflammatory response on quality of life in patients with inoperable non-small cell lung cancer.

The relationship between weight loss, the systemic inflammatory response and quality of life in patients with inoperable non-small cell lung cancer (NSCLC) was studied. The extent of weight loss, the systemic inflammatory response (C-reactive protein) and quality of life (EORTC-QLQ-C30) was measured in 106 patients with inoperable NSCLC (stage III and IV). Approximately 40% had more than 5% weight loss and almost 80% had elevated circulating C-reactive protein concentrations (>10 mg/l). The functional scale scores of the EORTC-QLQ-C30 were poor (50 or less) and the fatigue symptom score was also poor (50 or more). When patients were grouped according to whether or not they had experienced more than 5% weight loss, Karnofsky performance status and global quality of life were lower (P<0.05) and symptom scores fatigue (P<0.05) and pain (P<0.01) were greater in the weight-losing group. When the weight-stable cancer patients were grouped according to whether or not they had evidence of a systemic inflammatory response, the symptom fatigue was higher in the inflammatory group (P<0.05). In the weight-stable cancer patients C-reactive protein concentration was correlated with fatigue r=0.31 (P<0.05). The results of the present study indicate that both weight loss and the systemic inflammatory response impact on different aspects of quality of life. In particular, fatigue is associated with the presence of a systemic inflammatory response independent of weight loss.

Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial.

BACKGROUND: The liver is the most frequent site for metastases of colorectal cancer, which is the second largest contributor to cancer deaths in Europe. We did a randomised trial to compare an intrahepatic arterial (IHA) fluorouracil and folinic acid regimen with the standard intravenous de Gramont fluorouracil and folinic acid regimen for patients with adenocarcinoma of the colon or rectum, with metastases confined to the liver. METHODS: We randomly allocated 290 patients from 16 centres to receive either intravenous chemotherapy (folinic acid 200 mg/m2, fluorouracil bolus 400 mg2 and 22-h infusion 600 mg/m2, day 1 and 2, repeated every 14 days), or IHA chemotherapy designed to be equitoxic (folinic acid 200 mg/m2, fluorouracil 400 mg/m2 over 15 mins and 22-h infusion 1600 mg/m2, day 1 and 2, repeated every 14 days). The primary endpoint was overall survival, and analysis was by intention to treat. FINDINGS: 50 (37%) patients allocated to IHA did not start their treatment, and another 39 (29%) had to stop before receiving six cycles of treatment because of catheter failure. The IHA group received a median of two cycles (0-6), compared with 8.5 (6-12) for the intravenous group. 45 (51%) IHA patients who did not start or did not receive six cycles switched to intravenous treatment. In both groups, grade 3 or 4 toxicity was uncommon. Median overall survival was 14.7 months for the IHA group and 14.8 months for the intravenous group (hazard ratio 1.04 [95% CI 0.80-1.33], log-rank test p=0.79). Similarly, there was no significant difference in progression-free survival. INTERPRETATION: Our results showed no evidence of an advantage in progression-free survival or overall survival for the IHA group; thus continued use of this regimen cannot be recommended outside of a clinical trial.

Performance status of male and female advanced cancer patients is independently predicted by mid-upper arm circumference measurement.

In the advanced cancer patient, performance status has considerable prognostic power. Karnofsky performance status, together with variables reported to influence its score, was measured in advanced gastrointestinal cancer patients (n = 148). For male and female patients, age, body mass index, weight loss, triceps skinfold thickness, mid-upper arm circumference, albumin, C-reactive protein, and tumor type and stage were regressed against Karnofsky performance status. On multiple regression analysis, only mid-upper arm circumference and log10 C-reactive protein in men (r2 = 0.462, P < 0.0001) and only mid-upper arm circumference and weight loss in women (r2 = 0.485, P < 0.01) were independent predictors of Karnofsky performance status. There was a significant partial correlation, with gender as a covariable, between log10 C-reactive protein and albumin (r = -0.530, P < 0.0001) and mid-upper arm circumference (r = -0.269, P = 0.035) and weight loss (r = 0.286, P = 0.024). The results of the present study indicate that mid-upper arm circumference is a major factor that influences performance status in male and female patients with advanced gastrointestinal cancer.

Surgery for colorectal cancer.

Colorectal cancer remains the second commonest cause of cancer death in North America and Western Europe. Surgery remains the mainstay of treatment. The aim of surgery should be to achieve cure and to avoid locoregional recurrence. The fixity of the primary tumour determines resectability, and the extent of spread determines ultimate survival. Patients with rectal cancer present a particular problem. There is good evidence that lower local recurrence rates may be achieved both by improvements in surgical technique and the use of adjuvant radiotherapy. The importance of adequate treatment of the circumferential tumour margin cannot be over-emphasised; meticulous attention is required to ensure an adequate circumferential excision. The lowest incidences of locoregional recurrence are reported by surgeons who perform total mesorectal excision. Anorectal function, sexual and urinary dysfunction may occur after rectal excision. Both postoperative and pre-operative radiotherapy can reduce the incidence of local recurrence. However, in view of the low recurrence rates obtained with TME alone, the role of adjuvant radiotherapy requires further evaluation. Several aspects of the surgical management of colorectal cancer, for example, the role of transanal local excision of selected rectal cancers and laparoscopic surgery, the management of obstructed cases and the role of follow-up remain to be defined clearly.

Outcome following surgery for colorectal cancer.

There is evidence to suggest that survival following surgery for colorectal cancer is improving. Audits undertaken in a single institution between 1974-1979 and 1991-1994 provide the opportunity to evaluate the extent to which earlier diagnosis and better surgery contribute to the improvement in survival. There was little evidence that patients were presenting at an earlier stage during the latter period. In contrast, more patients had a potentially curative resection. This analysis confirmed that, over this period, there has been a substantial improvement in survival following surgery for colorectal cancer; this improvement was largely due to better surgery rather than earlier presentation.

Contrast-enhanced Doppler perfusion index: clinical and experimental evaluation.

OBJECTIVE: To assess the potential of the power Doppler signal intensity rate of enhancement due to contrast agent wash-in for assessment of hepatic hemodynamics. METHODS: With the use of standardized settings, power Doppler sonography was performed before and after administration of a contrast agent. Video-recorded examinations were digitized for offline analysis on a personal computer. The temporal changes of the power Doppler signal intensity were quantified to provide contrast agent wash-in curves. The contrast-enhanced Doppler perfusion index was defined by the ratio of the wash-in gradient of the hepatic artery and portal vein as contrast-enhanced Doppler perfusion index = hepatic artery gradient/(hepatic artery gradient + portal vein gradient). The contrast-enhanced Doppler perfusion index was evaluated at 4 contrast agent doses in each of 14 patients with liver metastases and 3 patients with hemangiomas. An in vitro flow model was used to determine the relationships between the power Doppler rate of enhancement and flow in vessels of 4, 8, and 12 mm in diameter. RESULTS: In vivo, there was a significantly higher (P < .0001) mean contrast enhanced Doppler perfusion index in patients with liver metastases (mean, 0.59; 95% confidence interval, 0.54-0.63), compared with patients with hemangiomas (mean, 0.33; 95% confidence interval, 0.24-0.41). The corresponding coefficients of variations were 25% for patients with liver metastases and 31% for patients with hemangiomas. In vitro, the power Doppler rate of enhancement was proportional to flow speed and independent of vessel diameter. CONCLUSIONS: Measurement of the contrast-enhanced Doppler perfusion index may have potential in assessment of hepatic hemodynamics and focal liver disease.

Circulating concentrations of "free" leptin in relation to fat mass and appetite in gastrointestinal cancer patients.

Recent studies have suggested that circulating concentrations of leptin might play a role in cancer cachexia. In the first part of the study, we compared circulating concentrations of free and total leptin, percent fat mass, and the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), together with appetite score, in age- and gender-matched healthy controls (n = 11) and advanced gastrointestinal cancer patients (n = 26). In the second part of the study, the same measurements were repeated before and after megestrol acetate treatment of weight-losing gastrointestinal cancer patients (n = 10). Body mass index and percent fat mass were significantly lower (P < 0.05) and IL-6 and CRP were significantly higher (P < 0.05) in cancer patients than in controls. There was no difference in the percentage of leptin bound in the circulation between controls and cancer patients. Circulating "free" leptin concentrations correlated with percent fat mass in controls (r = 0.745, P = 0.008) and cancer patients (r = 0.600, P = 0.001). In cancer patients, circulating leptin concentrations, either free or total, were not correlated with IL-6 or CRP concentrations. When adjusted for fat mass, the circulating concentrations of free and total leptin were significantly lower in the cancer patients (P < 0.01). Megestrol acetate treatment significantly increased circulating free and total leptin concentrations in the cancer patients (P < 0.05). There was a significant positive correlation between the change in circulating concentrations of free and total leptin and the change in percent fat mass (r = 0.685, P < 0.05 and r = 0.661, P < 0.05, respectively). The results of the present study indicate that the proportions of free and bound leptin in the circulation do not differ between normal subjects and patients with gastrointestinal cancer and in both groups are related to fat mass. Furthermore, the increase in circulating leptin concentrations after megestrol acetate treatment is not associated with any alteration in leptin binding.