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Consequent to recent advances in surgical techniques and management, survival rate has increased substantially over the last 25 years, particularly in colorectal cancer patients. However, post-operative morbidity and mortality from colorectal cancer vary widely across the country. Therefore, standardised outcome measures are emphasised not only for professional accountability, but also for comparison between treatment units and regions. In a heterogeneous population, the use of crude mortality as an outcome measure for patients undergoing surgery is simply misleading. Meaningful comparisons, however, require accurate risk stratification of patients being analysed before conclusions can be reached regarding the outcomes recorded. Sub-specialised colorectal surgical units usually dedicated to more complex and high-risk operations. The need for accurate risk prediction is necessary in these units as both mortality and morbidity often are tools to justify the practice of high-risk surgery. The Acute Physiology And Chronic Health Evaluation (APACHE) is a system for classifying patients in the intensive care unit. However, APACHE score was considered too complex for general surgical use. The American Society of Anaesthesiologists (ASA) grade has been considered useful as an adjunct to informed consent and for monitoring surgical performance through time. ASA grade is simple but too subjective. The Physiological & Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and its variant Portsmouth POSSUM (P-POSSUM) were devised to predict outcomes in surgical patients in general, taking into account of the variables in the case-mix. POSSUM has two parts, which include assessment of physiological parameters and operative scores. There are 12 physiological parameters and 6 operative measures. The physiological parameters are taken at the time of surgery. Each physiological parameter or operative variable is sub-divided into three or four levels with an exponentially increasing score. However, POSSUM and P-POSSUM over-predict mortality in patients who have had colorectal surgery. Discrepancies in these models have led to the introduction of a specialty-specific POSSUM: the ColoRectal POSSUM (CR-POSSUM). CR-POSSUM only uses six physiological parameters and four operative measures for prediction of mortality. It is much simplified to allow ease of use., (Copyright © 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: The English arm of the UK Bowel Cancer Screening Pilot has recently concluded its third round. The primary aim of this study was to assess the effects of this programme on the emergency and elective cancer workload at University Hospitals Coventry and Warwickshire NHS Trust; the largest trust within the screened region. The secondary aim was to assess its effect upon Dukes staging, mortality and stoma formation for emergency colorectal cancer (CRC) admissions., Design: A retrospective analysis of validated data for CRC admissions over a period of 6 years from 1999 to 2004 was performed. The first year, 1999, represented the pre-screening year (PSY) which was taken as a baseline. Data for the next 5 years, screening years 1-5 (SY1-SY5), were recorded for the mode of admission, occurrence of emergency surgery, 30-day mortality and Dukes staging., Results: In the PSY (1999), 29.4% of CRCs were admitted as an emergency, decreasing to 15.8% by 2004 (p = 0.001). As a consequence, there was a significant decrease in the number of emergency CRC procedures performed over the same period (p<0.05). There was also a significant reduction in the 30-day mortality from 48% in 1999 to 13% in 2004 (p<0.05). Dukes stage C carcinomas, however, remained the predominant stage presenting as emergencies throughout the studied period (SY3, 53%; SY4, 38%; SY5, 50%)., Conclusion: Following commencement of the UK Bowel Cancer Screening Pilot, there has been a significant decline in emergency CRC workload with a marked improvement in 30-day mortality and decreased stoma formation, in Coventry and North Warwickshire. It is postulated that the witnessed and notable positive impact over such a short time period is the result of increased detection of asymptomatic malignancies within the screening programme, increased public awareness of the symptoms of CRC, together with a change in attitudes and referral patterns of general practitioners within Coventry and North Warwickshire.

Background: Postoperative morbidity and mortality from colorectal cancer varies widely across hospitals in the UK. We aimed to assess whether a newly developed score from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) could predict mortality from colorectal cancer surgery as accurately as the Physiology and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM), Portsmouth POSSUM (P-POSSUM), or the ColoRectal POSSUM (CR-POSSUM)., Methods: We analysed prospectively 618 patients with histologically confirmed colorectal cancer who had surgery to remove primary tumours done by colorectal surgeons or non-colorectal surgeons in a 3-year period. We compared observed mortality with those predicted by the ACPGBI, POSSUM, P-POSSUM, and CR-POSSUM scoring systems using the Hosmer-Lemeshow test and Receiver Operating Characteristic (ROC) curve analysis., Findings: Between April 1, 2002, and May 31, 2005, 618 consecutive patients with colorectal cancer had surgery to remove primary tumours. Overall observed 30-day mortality over the 3 years was 10.2% (95% CI 8.0-12.9). Overall predicted mortality (mean score) by use of POSSUM was 12.7% (11.7-13.7), by use of P-POSSUM was 4.4% (3.4-5.4), by use of CR-POSSUM was 9.6% (8.6-10.6), and by use of ACPGBI score was 8.1% (7.3-8.8)., Interpretation: POSSUM overpredicted mortality, whereas P-POSSUM underpredicted mortality from colorectal-cancer surgery. CR-POSSUM was a more-accurate predictor of mortality in most analyses than was POSSUM and P-POSSUM. Although CR-POSSUM gave the closest prediction of overall mortality, analyses of subgroups of patients showed that ACPGBI score predicted overall mortality most accurately.

Background: In the search for occult metastases in lymph nodes or circulating tumour cells, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed to detect tumour-specific splice variants of the transcript of the CD44 gene. The assay was highly sensitive and could detect ten tumour cell per 10(5) leucocytes., Methods: RNA was purified from peripheral blood (n = 24) and regional lymph nodes (n = 14) from patients with colorectal cancer. Complementary DNA was made and amplified using primers specific for the CD44 gene. Southern blotting with exon-specific probes was used to enhance the sensitivity., Results: Tumour cells were detected in peripheral blood samples in four patients and lymph nodes in nine, in one of whom conventional histology had not detected tumour cells., Conclusion: This technique may be useful in the early diagnosis of primary or metastatic tumours, in assessing prognosis and in detecting residual disease after treatment.

Background: The CD44 gene codes for a family of heavily glycosylated cell surface proteins that have been linked with tumour metastasis. The aim of the study was to analyse the expression of CD44 messenger RNA in colorectal cancer., Methods: The expression of CD44 variants 2 and 7 in colorectal tumour samples was compared with that in normal colon and lymphocytes from 59 patients using reverse transcription-polymerase chain reaction followed by blot hybridization with exon-specific probes, and a nested polymerase chain reaction., Results: All samples of tumour and metastatic tissue showed complex overexpression of many alternatively spliced products of the CD44 gene. Normal colon, liver and lymphocytes predominantly expressed the standard form of the CD44 molecule (CD44S) with low levels of two or three variants hybridizing to exons v2 and v7., Conclusion: Deranged CD44 gene activity in colorectal cancer cells is confirmed. The analysis of CD44 gene expression may provide a promising marker for the early detection of colonic tumours.

The presence of free malignant cells in the peritoneal cavity following potentially curative resection of colorectal cancer may be responsible for some cases of local recurrence. Twenty-six patients (age 58-88 years, male:female 12:14) undergoing colorectal cancer surgery were studied to determine frequency of occurrence of tumour cells in the peritoneal cavity using an immuno-magnetic cell separation technique. Peritoneal washings were collected after opening the peritoneal cavity and also prior to closure. A murine monoclonal antibody specific for epithelial cells was added to the peritoneal washings followed by magnetic labelled goat-antimouse antibody. The labelled tumour cells were retrieved by passing through the magnetic activated cell sorter (MACS). Tumour cells were detected in peritoneal washings from 11 patients (preresection only n = 0, post-resection only n = 6, and both n = 5). Five of these 11 patients had potentially curative surgery. This study supports the use of MACS in detecting free malignant cells in the peritoneal cavity.

Significant numbers of infiltrating mononuclear cells are commonly observed in solid tumours, although their role in restricting tumour growth is not clear. Tumour-infiltrating lymphocytes (TIL) from 38 patients with colorectal cancer, in parallel with peripheral blood lymphocytes (PBL), were assayed to determine their ability to proliferate in response to concanavalin A (ConA), interleukin-2 (IL-2), ConA+IL-2, phorbol 12-myristate 13-acetate (PMA)+ionomycin ionomycin (IOM), and staphylococcal enterotoxin B(SEB). These reagents were selected to give a range of weak to strong proliferative responses either via or independent of the T cell receptor. Proliferation of TIL was significantly lower than that of PBL in all cultures: ConA (P < 0.001), IL-2 (P = 0.002), ConA+IL-2 (P < 0.001), PMA+IOM (P < 0.001), SEB (P = 0.002). In addition to the low proliferative capacity of TIL, production of cytokines by TIL may also play a role in control of tumour growth. We have assayed IFN gamma production in the supernatants from 16 paired TIL and PBL cultures, and tumour necrosis factor alpha (TNF alpha) in 6 paired cultures. TNF alpha concentrations were significantly lower in TIL cultures than in PBL cultures stimulated with ConA (P < 0.05), but no different in control or IL-2 stimulated cultures. IFN gamma levels did not significantly differ between PBL and TIL cultures, indicating that despite the restricted proliferative capacity of TIL, these cells remain capable of secreting significant amounts of IFN gamma.