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Aim The study aimed to describe genetical and clinical features of attenuated familial adenomatous polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance. Method A questionnaire study was carried out of polyposis registries with data on patients with presumed AFAP, defined as having ≤100 colorectal adenomas at age ≥25. Results One hundred and ninety-six patients were included. The median number of adenomas was 25 (0-100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty-two patients had a colectomy and an ileorectal anastomosis and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5′ end, exon 9 and 3′ end). Conclusions A subset of FAP patients with a milder phenotype does exist and treatment and surveillance had to be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following clinical diagnostic criteria for AFAP: a dominant mode of inheritance of colorectal adenomatosis and <100 colorectal adenomas at age 25 or older. Colonoscopy had to be preferred to sigmoidoscopy and surveillance had to be life-long. In the majority of patients, prophylactic colectomy and ileorectal anastomosis are recommended at the age of 20-25 years. [ABSTRACT FROM AUTHOR]

Background:Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer.Methods:In a case–control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved – Fluorescence Immuno Assays (TR-FIA's).Results:All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other non-malignant findings; uPAR(I) P=0.0006, suPAR(I–III) P<0.0001 and suPAR(I–III)+(II–III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI:1.86–6.37). CRC patients had a mean elevated level of 20.9% (95% CI:10.2–32.6) for suPAR(I–III) and 18.5% (95% CI:9.0–28.8) for suPAR(I–III)+(II–III) compared with subjects with non-malignant findings.Conclusions:The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of the measured uPAR forms were cancer specific, our findings suggest that uPAR expression could be useful in the early detection of CRC when combined with other markers and clinical variables. [ABSTRACT FROM AUTHOR]

The article examines the risk factors for death within 30 days after colonic cancer surgery. The researchers calculated the thirty-day mortality of some 2,157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 using logistic regression analysis. Based on the results, the researchers concluded that emergency surgery for colonic cancer is still associated with an increased risk of death.

Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are central components of the MBL pathway of complement activation, and may have potential as clinical biomarkers in colorectal cancer (CRC). Prior to clinical usage, knowledge of the biological variations of the molecules is needed. We here investigate variations of MBL and MASP-2 in healthy persons over time and in relation to gender, age and physical activity. MBL and MASP-2 concentrations were determined in serum from healthy adults over a 3-week period and this was repeated 6 months later ( n = 32); during a 24-h period ( n = 16); and in relation to physical exercise ( n = 14). Concentrations in serum and plasma were compared ( n = 198). No significant variation over 6 months and no circadian variation was found for MBL ( P = 0.39 and P = 0.34 respectively) or MASP-2 ( P = 0.54 and P = 0.55). Physical exercise did not affect the levels ( P > 0.8). Serum and plasma levels were only marginally different, and were independent of age and gender. Circulating levels of MBL and MASP-2 are stable over time in healthy individuals, which is advantageous for their potential application as biomarkers. [ABSTRACT FROM AUTHOR]

Objective Pre- and post-operative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements. Patients and methods Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all samples by a validated ELISA method. Results Geometric mean preoperative TIMP-1 level was 142 ng/ml (range 54–559 ng/ml) among CC patients compared with 106 ng/ml (range 64–167 ng/ml) among patients with nonmalignant diseases ( P < 0.0001). TIMP-1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant ( P < 0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP-1 levels at each time point. Conclusions Major surgery has considerable impact on plasma TIMP-1 levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP-1 levels within 30 days postoperatively. [ABSTRACT FROM AUTHOR]

Background: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection in certain patient groups. It is hypothesized that a deficient MBL pathway might be more frequent among patients with CRC than in healthy individuals. The MBL pathway was therefore evaluated in serum obtained preoperatively from 193 patients with primary CRC and in serum from 150 healthy volunteers. Methods: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. Results: Serum MBL levels were significantly ( P < 0.0002) increased in patients with colorectal cancer (1384 (400-2188) ng/mL) (median, inter-quartile range) compared with levels in healthy blood donors (924 (230-1476) ng/mL). Similarly, the MBL/MASP activity was significantly ( P < 0.0002) increased in patients (584 (202-914) mU/mL) compared with in blood donors (319 (0-684) mU/mL). This was independent of age, gender, tumour location in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference ( P = 0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). Conclusions: Overall, the MBL complement activation pathway is significantly increased in patients with colorectal cancer compared with healthy persons. However, similar frequencies of MBL pathway deficiency are observed in patients and healthy persons. [ABSTRACT FROM AUTHOR]

Background: Results from short-term studies of histamine type 2 (H[SUB2]) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H[SUB2]-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. Methods: Patients seheduled for elective resection of primary tumours were consecutively included in a randomized double-blind placebo-controlled clinical study designed to evaluate the effect of ranitidine on survival. Before skin incision ranitidine 100 mg or placebo was given intravenously twice daily followed by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the protocol. The patient cohort has been followed continuously without loss of any patient, and a final statistical analysis was performed on an intention-to-treat basis after more than 5 years; this included a subgroup analysis of perioperative blood transfusion and postoperative infectious complications. Results: The median observation period of the 740 patients included was 6.8 (range 5.4-7.9) years. A univariate analysis of all 740 patients and of the subgroup of 560 who underwent curative resection showed no significant effect of ranitidine on survival. Furthermore, ranitidine had no survival benefit in curatively resected patients who received a perioperative blood transfusion (n = 358), but it improved the survival of non-transfused patients (n = 202; hazard ratio (HR) 0.6 (95 per cent confidence interval (c.i.) 0.4 to 0.9), P = 0.02) and of non-transfused patients who did not develop postoperative infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including... [ABSTRACT FROM AUTHOR]

Summary Background The frequency of postoperative infectious complications is significantly increased in patients with colorectal cancer receiving perioperative blood transfusion. It is still debated, however, whether perioperative blood transfusion alters the incidence of disease recurrence or otherwise affects the prognosis. Methods Patient risk variables, variables related to operation technique, blood transfusion and the development of infectious complications were recorded prospectively in 740 patients undergoing elective resection for primary colorectal cancer. Endpoints were overall survival (n = 740) and time to diagnosis of recurrent disease in the subgroup of patients operated on with curative intention (n = 532). The patients were analysed in four groups divided with respect to administration or not of perioperative blood transfusion and development or non-development of postoperative infectious complications. Results Overall, 19 per cent of 288 non-transfused and 31 per cent of 452 transfused patients developed postoperative infectious complications (P < 0·001). The median observation period was 6·8 (range 5·4–7·9) years. In a multivariate analysis, risk of death was significantly increased among patients developing infection after transfusion (n = 142) compared with patients receiving neither blood transfusion nor developing infection (n = 234): hazard ratio 1·38 (95 per cent confidence interval (c.i.) 1·05–1·81). Overall survival of patients receiving blood transfusion without subsequent infection (n = 310) and patients developing infection without preceding transfusion (n = 54) was not significantly decreased. In an analysis of disease recurrence the combination of blood transfusion and subsequent development of infection (hazard ratio 1·79 (95 per cent c.i. 1·13–2·82)), localization of cancer in the rectum and Dukes classification were independent risk factors. Conclusion Blood transfusion per se may not be a risk factor for poor prognosis after colorectal cancer surgery. However, the combination of perioperative blood transfusion and subsequent development of postoperative infectious complications may be associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1-1.8,P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor of the 'British Journal of Cancer,' describing the phenomenon of a consistent shift in preoperative plasma and serum vascular endothelial growth factor (VEGF) determinations between two different enzyme-linked immunosorbent assay batch numbers in patients with primary colorectal carcinoma. Doubts about accuracy of serum VEGF cutoff levels.