BACKGROUND & AIMS:Lynch syndrome is the most common inherited cause of colorectal cancer (CRC). Contemporary and mutation-specific estimates of CRC-risk in patients undergoing colonoscopy would optimize surveillance strategies. We performed a prospective national cohort study, using data from New Zealand, to assess overall and mutation-specific risk of CRC in patients with Lynch syndrome undergoing surveillance.METHODS:We performed a prospective study of 381 persons with Lynch syndrome in New Zealand (98 with Lynch-syndrome associated variants in MLH1, 159 in MSH2, 103 in MSH6, and 21 in PMS2). Participants were offered annual colonoscopy starting at age 25 y, and those who underwent 2 or more colonoscopies before December 31, 2017 were included in the final analysis. Patients with previous colonic resection, history of CRC or diagnosis of CRC at index colonoscopy were excluded.RESULTS:Study participants underwent 2061 colonoscopies during 2296 person-y; the median observation-period was 4.43 y and mean-age at enrollment was 43 y. Eighteen patients developed CRC (8 with variants in MLH1, 8 in MSH2, and 2 in MSH6) after a median follow-up period of 6.5 y (range 1-16 y). Eighty-three percent of patients had a surveillance colonoscopy in preceding 24 months before diagnosis of CRC; 94% were diagnosed with stage 0-II CRC and there was no CRC-related mortality. The overall-risk of developing CRC in the 5 y after first surveillance colonoscopy was 2.49% (95% CI, 1.18-5.23); cumulative risks for CRC in patients with Lynch syndrome-associated variants in MLH1, MSH2, or MSH6 by age 70 y were 17.7%, 17.8%, and 8.5%, respectively. Age-adjusted CRC-risk in patients with variants in MSH6 was lower than in MLH1 (hazard ratio, 0.2; 95% CI, 0.04-0.94; P = .02). Of patients with CRC, 33% had an adenomatous polyp resected from same segment in which a colorectal tumor later developed.CONCLUSIONS:The risk of CRC in patients with Lynch syndrome-associated mutations in MSH6 or PMS2 was significantly lower than in patients with mutations in MLH1. Incomplete adenomatous polyp resection might be responsible for one third of surveillance-detected CRCs.

AIMTo investigate differences in survival after diagnosis with colorectal cancer (CRC) by rurality, ethnicity and deprivation.METHODSIn this retrospective cohort study, clinical records and National Collections data were merged for all patients diagnosed with CRC in New Zealand in 2007-2008. Prioritised ethnicity was classified using New Zealand Cancer Registry data; meshblock of residence at diagnosis was used to determine rurality and socioeconomic deprivation.RESULTSOf the 4,950 patients included, 1,938 had died of CRC by May 2014. The five-year risks of death from CRC were: Māori 47%; Pacific 59%; non-Māori-non-Pacific (nMnP) 38%. After adjustment for demographic characteristics, comorbidity and disease stage at diagnosis, compared to nMnP the relative risk (RR) for Māori was 1.1 (95%CI: 0.8-1.3) and for Pacific 1.8 (95% CI: 1.4-2.5). We found no differences in risk of death from CRC by rurality, but some differences by deprivation.CONCLUSIONSDisparity in outcome following diagnosis with CRC exists in New Zealand. Much of this disparity can be explained by stage of disease at diagnosis for Māori, but for Pacific peoples and those in deprived areas other factors may influence outcome. Further analyses of the PIPER data will explore the impact of any differences in management.

509 Background: A Cochrane meta-analysis of randomised trials using histamine-type 2 receptor antagonists with surgery for colorectal cancer (CRC) demonstrated a hazard ratio of 0.53 for mortality if patients used cimetidine. The benefit is likely to be specific to patients whose tumours express the antigens that allow circulating cells to bind to endothelial selectin (E-selectin), the expression of which is induced by inflammatory cytokines perioperatively and inhibited by cimetidine. This trial sought to evaluate several key issues critical to informing the conduct of a phase 3 trial. Methods: Patients with non-metastatic CRC planned for curative-intent surgery were randomised to receive cimetidine 800mg BID or placebo orally for 5 weeks, starting 2-7 days preoperatively. A subset of patients had serial blood sampling for inflammatory cytokines. In addition to DFS and OS, endpoints assessed include treatment compliance and toxicity, recruitment issues, post-operative stay and complications, and tumour characteristics including expression of sialyl Lewis antigens and COX-2. Results: 123 patients (36% female) have been recruited in 4 centres over 3.5 years; another 4 are required to complete the planned 120 treated patients. The primary tumour was rectal in 45% and pathological postoperative tumour stage was 0-I, II, III, and IV in 29%, 33%, 35%, and 2% respectively. About 50% of CRC patients were eligible and fewer than half of those were recruited. Patient compliance was excellent with 89% of patients taking their medication orally in the first 2 days postoperatively. Inflammatory cytokines were commonly elevated postoperatively for up to 2 weeks but normalised by 4 weeks. Immunostaining for tumour antigens is in progress and will be presented. DFS and OS data are immature. Conclusions: Oral administration of cimetidine for 5 weeks is well-tolerated and feasible over the perioperative period, and covers the duration of elevated inflammatory cytokines. Correlative immunostaining studies will be presented. Clinical trial information: 12609000769280.

Aims Mitochondrial Tu translation elongation factor (TUFM) is a nuclear encoded protein that participates in mitochondrial polypeptide translation. TUFM has been reported to be overexpressed in many tumour types including colorectal carcinoma (CRC) by proteomics. The present study aims to examine the prognostic implication of TUFM in CRC. Methods Immunohistochemical staining was performed in tissue microarrays composed of 123 cases of CRC using a polyclonal anti-TUFM antibody. Immunoreactivity was quantified using Image-Pro plus software, and analysed in association with patients' clinicopathological parameters and survival time. Results The immunoreactivity of TUFM was negative in 25%, weak in 50% and strong in 25% of CRC cases. TUFM immunoreactivity had no significant association with the clinicopathological parameters examined including TNM stage and grade. However, strong TUFM expression significantly correlated with a higher 5-year recurrence rate (p=0.024). Kaplan-Meieranalysis revealed that patients with strong TUFM expression had significantly shorter cancer-specific survival than patients with negative TUFM (log-rank test, p = 0.038). In multivariate analysis, strong TUFM expression remained a stage-independent unfavourable prognostic indicator (p=0.024). Conclusions Increased expression of TUFM is a promising new prognostic indicator for CRC. Selective inhibition of TUFM in tumour cells may present a new avenue for the targeted therapy of this cancer.

Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease. Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy. We have identified that cathepsin D expression was significantly greater in cells from invasive front (IF) area and liver metastasis (LM) than those from main tumour body (MTB). Cathepsin D expression was subsequently examined by immunohistochemistry in tissue microarrays from 119 patients with CRC. Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival. However, cathepsin D expression in cells from the MTB was highly elevated in late stage CRC and showed significant correlation with subsequent distant metastasis and shorter cancer-specific survival. We also found that macrophages surrounding tumour cells stained strongly for cathepsin D but there was no significant correlation found between cathepsin D in macrophages at IF and MTB of CRC patient with the clinic-pathological parameters examined.

Self-diagnosis has been around for many years. In today's society with free access to information, particularly through the Internet, it is more prominent than ever. With new information sources available to patients, doctors may have their diagnostic process influenced. This is the case of a gentleman who self-diagnosed, and subsequently influenced his doctor's diagnostic process, with results detrimental to his outcome. It illustrates the importance of awareness of the risks of self diagnosis, and management of patients who present with information and preconceived ideas regarding their condition.

AIM The high incidence rates of colorectal cancer (CRC) in New Zealand (NZ) are well publicised. Minimal information is available comparing national extent of this disease at time of diagnosis with other countries, especially countries now performing screening for CRC. Just how late do our cancers present? What is the difference compared with other countries now performing screening? METHOD Data were retrieved and analysed from the World Health Organization and Cancer Registries in New Zealand and five other countries from 2001-2004. Extent of disease was classified as localised, regional, distant and unknown. RESULTS NZ has the lowest percentage of surgically curable localised disease (28%) when compared with Australia (New South Wales) (34%), United Kingdom (42%), American (SEER-9) (40%) and Hong Kong (35%) data. 20% of disease at diagnosis in NZ is metastatic. CONCLUSION By international standards, NZ has a marked and previously undefined low rate of early stage diagnosis of CRC. Extent of disease is more advanced in New Zealand patients than in other countries with recently commenced screening programmes (e.g. Australia and the UK). In 2001, NZ also had the highest age-specific incidence of colorectal cancer in the 50-70 years age group, when compared with Australia, USA, UK and Japan. Colorectal cancer will continue to be a significant health issue for the NZ population, with predicted increasing total numbers of people affected, and increasing costs of chemotherapy for advanced cancer. The concerning international comparisons shown in this article further emphasize the need for more immediate strategies to improve rates of early stage colorectal cancers at time of diagnosis.

Introduction The surgical and oncological treatment of colorectal cancer has undergone steady evolution over the last 20 years, however nationally derived survival figures have been disappointingly slow to improve. This study is an analysis of prospectively collected data (taken over a 6-year period) on the outcome of colorectal cancer management from a single university surgical unit in New Zealand.Methods A comprehensive dataset was prospectively collected on all patients seen with colorectal cancer by a single surgical team, and complete follow-up was obtained. Details of surgical and oncology treatment of the primary lesion and of any subsequent disease and treatment were recorded. Survival was analysed by clinical and pathological variables.Results Over 6 years, 244 new patients with a total of 263 primary colorectal cancers were seen.; 97% of these patients had an operation and 95% had the primary tumour resected. The mortality after elective operation was 0.5% (1/197) and 8% (3/39) after urgent or emergency surgery. After a median follow-up of 32 months, recurrence in the pelvis was apparent in 1 of 72 patients after curative resection of rectal cancer and 4 of 18 after palliative resection, thus giving a total pelvic recurrence rate of 6% at 30 months. The 5-year survival rate of all new patients seen with a rectal cancer was 58% and 56.5 % for patients with a colon cancer.Conclusions A combination of low operative mortality rates, low local recurrence rates in rectal cancer, the increasing use of adjuvant therapies, and careful follow up to detect (and where possible resect) metastatic disease at an early stage is associated with good cancer-specific survival figures. However further improvement in survival will need a shift to earlier stage at diagnosis and more effective chemotherapy (both in the adjuvant setting and for advanced disease) if significant gains in survival are to be made.

AIM:To determine whether the outcome of patients admitted to hospital with lower gastrointestinal bleeding (LGB) is affected by their use of aspirin (ASA) or non-aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs).METHODS:A retrospective review of all patients admitted to Wellington Hospital over a four-and-a-half-year period from January 1998 with a coded discharge diagnosis that included LGB. Data were collected on requirement for blood transfusion (BT), number of units transfused, drug use, requirement for surgery, and in-hospital mortality.RESULTS:There were 168 admissions to hospital with LGB over the study period of which, after exclusions, 146 formed the basis of this study. The mean age of patients was 69 years, with an equal gender distribution. Fifty three per cent of patients were taking medication known to interfere with platelet function (42% ASA, 18% NANSAIDs, and 7% both). Diverticular disease was the most common diagnosis. Eight patients required surgery for bleeding and there were two in-hospital deaths (1.4%). Forty three per cent of admitted patients required BT. Patients taking ASA or NANSAIDs (drug group) were more likely to receive a BT (relative risk 2.7, p <0.00001) than patients in the non-drug group. The median number of units received in transfused patients and requirement for surgery, although higher in the drug group, were not statistically different between the drug the non-drug group.CONCLUSIONS:Patients admitted to hospital with LGB while taking ASA or NANSAIDs are significantly more likely to need BT but use of these agents does not result in a more frequent requirement for surgery.

AIM:To audit the quality and completeness of histopathology reports of rectal cancer resections submitted to the National Cancer Registry in 2000.METHODS:All 388 mid- and low-rectal-cancer specimen reports submitted to the Registry were reviewed. Reports were scored according to a pre-defined 'proforma' as to the completeness of the pathological examination and the submitted report.RESULTS:Scores from teaching hospitals, public non-teaching hospitals and private laboratories did not differ significantly. Multiple staging systems were used in 40% of reports and no stage was allocated in 31% of reports. Circumferential margin involvement was recorded in 63% of reports.CONCLUSIONS:No significant differences exist in the quality of pathology reporting of rectal cancer between different laboratory types, either public or private. There is a lack of uniform reporting of rectal cancer stage, with multiple staging systems in use. Circumferential margin involvement is frequently omitted in spite of its documented value as an indicator of quality of rectal cancer surgery, as an important predictor of local recurrence, and its more-recently established value as a marker for distant metastasis and survival.

AIM:Colorectal cancer (CRC) is a major cause of cancer death in New Zealand. Incidence and mortality rates are regularly reported but more detailed information concerning the epidemiology of the disease is not readily available. The aim of this study is to describe the epidemiology of colorectal cancer, with particular reference to gender; subsite distribution; stage at diagnosis; tumour grade; the contribution of recognisable aetiological factors; and the resection rate and type of surgery performed for rectal cancer.METHODS:All 2272 pathology reports of colorectal cancer submitted to the National Cancer Registry for the year 2000 were reviewed and restaged according to the classical Dukes system. Age, gender, stage, subsite distribution, differentiation, tumour type, associated pathology and type of rectal cancer specimen were recorded.RESULTS:The gender ratio for all cases was equal. One third of resected cancers were in the rectum, one third in the left colon and one third were proximal to the splenic flexure. Men had more rectal cancer (M:F 1.6:1) and women more colon cancer (0.9:1). Right-sided cancers were of significantly higher grade than left-sided cancers. The proportion of right-sided cancers increased with advancing age in both men and women. Three per cent of patients had synchronous tumours and 0.2% of patients had phenotypic features of familial adenomatous polyposis (FAP). Fourteen per cent of patients were Dukes stage A at diagnosis, 43% stage B and 43% stage C. Rectal cancers were more likely to be stage A than colon cancers (odds ratio 1.6). Stage and grade of CRC were significantly associated. Ninety one per cent of cancers were resected; 29% of patients with rectal cancer had an abdominoperineal resection and 6% a local excision.CONCLUSIONS:The current stage distribution of CRC is in keeping with a predominantly unscreened population. The subsite distribution of cancer and its relationship to age and gender are similar to other high-risk countries; however, its relationship to grade of tumour has not previously been reported. An abdominoperineal resection rate of 29% reflects the mix of specialised colorectal and general surgical units treating rectal cancer in New Zealand and is in line with or better than recent overseas data that reflect national or regional practice.