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Screening programmes for colorectal cancer (CRC) are being implemented in various countries worldwide including Denmark. The majority of programmes rely on faecal occult blood testing with subsequent colonoscopy. This approach is challenged by limited compliance, which reduces the efficiency of the screening programme. Current research into improve-ments of screening of CRC includes biological markers identified in blood. Combining blood-based biological markers with clinical and demographical parameters have shown promising results, which may improve the present approach to screening.

In Denmark approximately 3,600 patients are diagnosed with colorectal cancer (CRC) every year. 75-80% of patients may undergo intended curative resection, but the disease recurs in about 40% within five years and the prognosis is poor. Hence, there is a need for biological markers that could be used for detection, evaluation of prognosis, therapy selection and monitoring. The serum proteins of the innate immune system mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are novel biomarkers under validation in CRC. Low preoperative MBL levels are predictive of pneumonia which subsequently is associated with poor survival. High MASP-2 levels predict recurrence and poor survival.

In Denmark, approximately 3,600 persons are diagnosed with colorectal cancer every year. Of these patients, 75-80% may undergo intended curative resection, but within a few years the disease recurs in about half of the curatively resected patients. Less than half of the total number of patients will survive the subsequent five years. Radiotherapy and adjuvant systemic chemotherapy have a limited effect on overall survival. It is therefore imperative to optimise the overall treatment of patients with colorectal cancer. One substantial option might be the development, validation and implementation of biological markers that could be used for early detection/screening, prognosis evaluation, surveillance, selection of patients for adjuvant therapy independent of stage of the disease, and monitoring of the given treatment.

Pregnancy involves the coordinated formation of new vessels, a process known as angiogenesis. Several growth factors and specific receptors, e.g. vascular endothelial growth factor (VEGF), PlGF (placenta growth factor) and the soluble VEGF-1 receptor (VEGFR-1) play essential roles in the process. Pregnancy-related pathological conditions (preeclampsia and intrauterine growth restriction (IUGR)) are associated with aberrant expressions of these molecules, which can be measured in blood fractions from pregnant women. Using these as markers before a clinical diagnosis is evident, seems feasible. Pathological conditions, such as inflammation and cancer, also induce angiogenesis. Measurements of other endothelium-derived molecules may add to the specificity and sensitivity of angiogenic proteins as markers.

The prognosis of patients with carcinomas is determined by whether there is dissemination of the primary tumour at the time of diagnosis. A substantial number of patients develop recurrent carcinoma, even though there were no clinical signs of dissemination at the time of primary surgery. Standard methods of tumor staging fail to identify those patients, who are at risk of recurrent disease. Recently several studies have demonstrated that the presence of occult metastatic carcinoma cells in the bone marrow increases the risk of recurrence. This risk is independent of traditional tumour staging, although the findings do not necessarily indicate later development of solid metastases. This review outlines the range of current applications of immunological and molecular methods for detecting disseminated carcinoma cells in blood and bone marrow aspirations, and discusses the applicability and significance of the findings.

To study the effect of preoperative treatment with a single high-dose of glucocorticoid on the systemic and immunological response, wound healing, and convalescence after colonic surgery, thirty patients were double-blind randomized to receive either methylprednisolone 30 mg/kg intravenously 90 minutes prior to induction of anaesthesia (group 1, n = 12), or to receive placebo (group 2, n = 12). Six patients were excluded from the study. Assessments of pain, pulmonary function, convalescence, various injury and wound-healing factors were done until 10 days after surgery. Conventional reduction in pulmonary function and mobilization was improved in group 1. Interleukin-6 and C-reactive protein levels increased significantly less in group 1, as delayed-type hypersensitivity was abolished in group 1. Plasma cascade system activation was significantly less pronounced in group 1. Reduction of collagen turnover was observed in group 1, but without detrimental effect on collagen accumulation. It is concluded that treatment with a single high dose of glucocorticoid before colonic surgery may improve postoperative pulmonary function and mobilization and reduce plasma cascade system activations, the inflammatory response, and immunofunction, but without detrimental effects on wound healing.

The majority of patients diagnosed as having colorectal cancer do not survive five years, although 70%-80% undergo curative surgery. Only a minority of the patients receive additional adjuvant chemo-, radio- and/or immunotherapy, which has proven its efficiency in a minor part of patients with Dukes C disease. Therefore, adjuvant therapy has only an insignificant impact on overall survival improvement. The present treatment of patients with colorectal cancer is far from sufficient, and this has led to considerations of how to optimize both surgical and adjuvant medical treatment strategy. Current biotechnological research in tumour biology has led to the development of several new treatment modalities, and within few years some of these will be tested clinically. It cannot be expected that all modalities may prove equally efficient in all patients. Furthermore, half the operated patients are cured by surgery alone, and these should not receive additional adjuvant treatment. Therefore, considerations are required of how to implement new modalities, and of selection of patients who are expected to benefit from a specific modality or a combination of modalities. It is suggested, that new biological markers of development, growth and dissemination of colorectal cancer can be used to predict prognosis either alone or in various combinations, and as selection markers to discriminate between patients who only need surgery and patients who may need adjuvant treatment.

The objective of the study was to investigate certain immune parameters in patients undergoing elective colorectal surgery and receiving either whole blood transfusion or leucocyte-filtrated blood. Sixty consecutive patients were randomly allocated to receive either whole blood transfusion or leucocyte-filtrated blood leucocyte when transfusion was indicated. The immune parameters were investigated on the day of surgery and on day 3, 7 and 30 postoperatively. Transfusion with whole blood was followed by a significant decrease in lymphocyte proliferation and CD4+/CD8+ ratio (p < 0.01) as well as a significant increase in soluble interleukin-2 receptor and interleukin-6 (p < 0.01). Furthermore transfusion with whole blood was accompanied by a significant increase in postoperative infectious complications (p < 0.01). Patients transfused with leucocyte-filtrated blood had only minor and passing changes in the immune parameters and developed no infectious complications, indicating that effective leucocyte filtration abolishes transfusion-associated immunosuppression.

We report the results of an open, prospective study of 20 patients with moderate to severe psoriasis (median PASI score: 15.7) treated with oral ranitidine 300 mg twice daily for six months. No other medication was allowed during the study period. The median PASI score was reduced to 14.5, 9.1 and 5.7 after one, three and six months of treatment, respectively (p < 0.00001). A mild to moderate worsening was observed in 15 patients within the first month of treatment, but this was not followed by exclusion from the study, and long-term treatment improved disease status in most patients. Eight patients continued therapy with ranitidine 300 mg twice daily after the study was completed. None of these patients relapsed during a follow-up period of 12-18 months. The results of the present study suggest that ranitidine may be beneficial in the treatment of some patients with psoriasis.

The histamine H-2-receptor antagonist ranitidine hydrochloride has been shown to alleviate trauma-, blood transfusion- and sepsis-induced immunosuppression. We evaluated the effect of ranitidine on the postoperative impairment of monocyte and neutrophil function in 24 patients undergoing major elective abdominal surgery. The patients were randomized to receive postoperative adjuvant treatment with ranitidine hydrochloride (100 mg) administered intravenously twice daily for four days, followed by oral ranitidine hydrochloride (150 mg) administered twice daily for five days (n = 11), or no adjuvant treatment (n = 13). Blood monocyte and neutrophil chemotaxis and chemiluminescence were analyzed before the operation and on post-operative days one, three and nine. Monocyte chemotaxis to C5a in the 13 control patients was significantly decreased on day one compared to day 0. Chemotaxis in the 11 ranitidine-treated patients increased significantly from day 0 to day one (p < .01 between groups). Neutrophil chemiluminescence to zymosan and N-f-methionyl-leucylphenylalanine was significantly increased in control patients on day one compared to day 0 (p < .05), while ranitidine reduced chemiluminescence to zymosan insignificantly on day one (p < .07 between groups). Five of the 13 control patients developed postoperative infectious complications, which were related to decreased monocyte chemotaxis to C5a and increased neutrophil chemiluminescence to zymosan when compared to noninfected patients. A significant difference (P < .05) in chemiluminescence to zymosan between infected and noninfected control patients was observed on day three, before clinical signs of infectious disease could be detected. There were no infectious complications in ranitidine-treated patients. These results support previous studies on the effect of ranitidine in reducing postoperative immunosuppression.

Retrospective studies suggest increased postoperative morbidity among alcohol misusers. We have prospectively studied the risk associated with alcohol intake among patients undergoing surgery. We investigated 15 persons who required colorectal surgery and who were drinking at least five Danish drinks per day. These patients were matched for sex, nutrition, age, weight, cardio-pulmonary disease, diagnosis anesthesia, and surgery to 15 control persons who were consuming no more than two drinks daily. None of the patients showed signs of liver disease. The alcohol group developed more postoperative complications than controls (67 vs 20%, p < 0.05) and hospital stay was prolonged (20 vs 12 days, p < 0.05). Preoperatively, alcohol misusers had reduced left ventricular ejection fraction (54 vs 68%, p < 0.01). Delayed-type hypersensitivity responses were reduced in the alcohol group before (53 mm2 vs 78, p < 0.05) and after (18 mm2 vs 55, p < 0.01) surgery. Alcohol misusers had significantly longer bleeding times. Surgical stress responses, as assessed by changes in plasma cortisol and catecholamines, were higher among alcohol misusers (p < 0.05). Postoperative morbidity was increased in alcohol misusers without signs of liver damage. The mechanisms may include subclinical cardiac insufficiency, immunosuppression, and decreased haemostatic function. Preoperative alcohol consumption may be a more important risk factor for postoperative morbidity than previously thought.

On the basis of the literature and the authors own investigations, the present article provides a brief schematic review of the fraction of the physiological immune response which has hitherto been investigated in connection with surgical trauma. Surgery, anaesthesia and blood transfusion induce temporarily acquired immune suppression and thus a potentially increased risk for postoperative infectious complications and recurrence after cancer surgery. The pathological physiological alterations in immune function which develop as a result of anaesthesia, surgery and perioperative blood transfusion are reviewed. The clinical sequelae of preoperative and postoperative immune suppression are increased morbidity and mortality rates. Future research in this field must, therefore, be focussed on detailed investigation of the mechanisms which lead to postoperative immune suppression and development of methods to prevent these.