BACKGROUND: Currently no consensus exists regarding what pre-reversal investigations are required to assess integrity of the rectal anastomosis. The objective of this study was to compare pre-reversal assessments of anastomotic integrity and to evaluate trends that might have influenced timings for reversal. METHODS: From a prospectively maintained database, patients with colorectal cancer resections between March 2012 and October 2019 were identified. Patient characteristics, pre-reversal contrast enema and flexible sigmoidoscopy findings were recorded, and management of complications were recorded. Time-to-ileostomy reversal and time series for trends were analysed. RESULTS: There were 154 patients included. Pre-reversal contrast enema or sigmoidoscopy detected a possible stricture or leak at the rectal anastomotic site in 11% (15/132) and 15% (18/112), respectively. When both modalities were used there was concordance of 86.1% and a positive likelihood ratio of 5.73. Of 125 (81.2%) ileostomies reversed, the median time-to-reversal was 11.99 months; time series analysis over the 7-year period showed no significant trend for average patient-days from booking to reversal (P = 0.60). Cox regression modelling did not identify any influential risk factors for the times taken to reversal. CONCLUSION: This study supports the use of both contrast enema and flexible sigmoidoscopy in the assessment of rectal anastomosis integrity. Most patients with complications can have their ileostomies reversed. Patients who have adjuvant chemotherapy have a prolonged time to reversal.

AIM: Colorectal cancer surveillance is an essential part of care and should include clinical review and follow-up investigations. There is limited information regarding postoperative surveillance and survivorship care in the Australian context. This study investigated patterns of colorectal cancer surveillance at a large tertiary institution. METHODS: A retrospective review of hospital records was conducted for all patients treated with curative surgery between January 2012 and June 2017. Provision of clinical surveillance, colonoscopy, computed tomography (CT), and carcinoembryonic antigen (CEA) within 24 months postoperatively were recorded. Kaplan-Meier estimates were used to evaluate time-to-surveillance review and associated investigations. RESULTS: A total of 675 patients were included in the study. Median time to first postoperative clinical review was 20 days (95% confidence interval (CI), 18-21) with only 31% of patients having their first postoperative clinic review within 2 weeks. Median time to first CEA was 100 days (95% CI, 92-109), with 47% of patients having their CEA checked within the first 3 months, increasing to 68% at 6 months. Median time to first follow-up CT scan was 262 days (95% CI, 242-278) and for colonoscopy, 560 days (95% CI, 477-625). Poor uptake of surveillance testing was more prevalent in patients from older age groups, those with multiple comorbidities, and higher stage cancers. CONCLUSION: Colorectal cancer surveillance is multi-disciplinary and involves several parallel processes, many of which lead to inconsistent follow-up. Further prospective work is required to identify the reasons for variation in care and which aspects are most important to cancer patients.

Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined analysis of data across completed studies could further our understanding of circulating tumor DNA (ctDNA) as a prognostic marker and inform future trial design. We combined individual patient data from three independent cohort studies of nonmetastatic colorectal cancer (CRC). Plasma samples were collected 4 to 10 weeks after surgery. Mutations in ctDNA were assayed using a massively parallel sequencing technique called SafeSeqS. We analyzed 485 CRC patients (230 Stage II colon, 96 Stage III colon, and 159 locally advanced rectum). ctDNA was detected after surgery in 59 (12%) patients overall (11.0%, 12.5% and 13.8% for samples taken at 4-6, 6-8 and 8-10 weeks; P = .740). ctDNA detection was associated with poorer 5-year recurrence-free (38.6% vs 85.5%; P < .001) and overall survival (64.6% vs 89.4%; P < .001). The predictive accuracy of postsurgery ctDNA for recurrence was higher than that of individual clinicopathologic risk features. Recurrence risk increased exponentially with increasing ctDNA mutant allele frequency (MAF) (hazard ratio, 1.2, 2.5 and 5.8 for MAF of 0.1%, 0.5% and 1%). Postsurgery ctDNA was detected in 3 of 20 (15%) patients with locoregional and 27 of 60 (45%) with distant recurrence (P = .018). This analysis demonstrates a consistent long-term impact of ctDNA as a prognostic marker across nonmetastatic CRC, where ctDNA outperforms other clinicopathologic risk factors and MAF further stratifies recurrence risk. ctDNA is a better predictor of distant vs locoregional recurrence.

BACKGROUND: The association between smoking, diabetes and obesity and oncological outcomes in patients with stage III colon cancer treated with surgery and adjuvant chemotherapy is unclear. AIM: To evaluate whether smoking, obesity and diabetes are associated with the disease-free survival and overall survival rates of patients with stage III colon cancer who have received adjuvant chemotherapy. METHODS: Patients were selected from the prospectively maintained Australian Cancer Outcomes and Research Database (ACCORD). All stage III colon cancer patients who received adjuvant chemotherapy between January 2003 to December 2015 were retrospectively analyzed. The three primary exposures of interest were smoking status, body mass index (BMI) and diabetic (DM) status. The primary outcomes of interest were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 785 patients between 2003 and 2015 were included for analysis. Using Kaplan-Meier survivorship curves, there was no association between OS and smoking (P = .71), BMI (P = .3) or DM (P = .72). Similarly, DFS did not reveal an association with smoking (P = .34), BMI (P = .2) and DM (P = .34). Controlling for other covariates the results did not reach statistical significance in adjusted multiple regression models. CONCLUSION: Smoking, obesity and DM were not shown to influence DFS or OS for patients with stage III colon cancer who have received adjuvant chemotherapy.

INTRODUCTION: Nutritional intervention and prevention of malnutrition is significantly important for patients with upper gastrointestinal oesophageal, pancreatic and gastric cancer. However, there is limited information regarding nutritional status, and perioperative nutritional interventions that patients receive when undergoing curative surgery. METHODS AND ANALYSIS: Patients diagnosed with upper gastrointestinal cancer, planned for curative intent resection across 27 Australian hospitals will be eligible to participate in this point prevalence study. The primary aim is to determine the prevalence of malnutrition in patients with upper gastrointestinal cancer at the time of surgery using subjective global assessment. Secondary aims are to determine the type and frequency of perioperative nutritional intervention received, the prevalence of clinically important weight loss and low muscle strength, and to investigate associations between the use of an evidence-based nutrition care pathway or protocol for the nutritional management of upper gastrointestinal surgical oncology patients and malnutrition prevalence. Data collection will be completed using a purpose-built data collection tool. ETHICS AND DISSEMINATION: Ethical approval was granted in May 2019 (LNR/51107/PMCC-2019). The design and reporting of this study comply with the Strengthening the Reporting of Observational Studies in Epidemiology checklist for reporting of observational cohort studies. Findings will be published in peer-reviewed scholarly journals and presented at relevant conferences. Results will assist in defining priority areas for research to improve patient outcomes.

Malnutrition is highly prevalent in people with head and neck cancer (HCN) and is associated with poorer outcomes. However, variation in malnutrition diagnostic criteria has made translation of the most effective interventions into practice challenging. This study aimed to determine the prevalence of malnutrition in a HNC population according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and assess inter-rater reliability and predictive validity. A secondary analysis of data available for 188 patients with HNC extracted from two cancer malnutrition point prevalence studies was conducted. A GLIM diagnosis of malnutrition was assigned when one phenotypic and one etiologic criterion were present. Phenotypic criteria were ≥5% unintentional loss of body weight, body mass index (BMI), and subjective evidence of muscle loss. Etiologic criteria were reduced food intake, and presence of metastatic disease as a proxy for inflammation. The prevalence of malnutrition was 22.6% (8.0% moderately malnourished; 13.3% severely malnourished). Inter-rater reliability was classified as excellent for the GLIM criteria overall, as well as for each individual criterion. A GLIM diagnosis of malnutrition was found to be significantly associated with BMI but was not predictive of 30 day hospital readmission. Further large, prospective cohort studies are required in this patient population to further validate the GLIM criteria.

Biallelic protein-truncating mutations in the adenomatous polyposis coli (APC) gene are prevalent in sporadic colorectal cancer (CRC). Mutations may not be fully inactivating, instead producing WNT/β-catenin signalling levels 'just-right' for tumourigenesis. However, the spectrum of optimal APC genotypes accounting for both hits, and the influence of clinicopathological features on genotype selection remain undefined. We analysed 630 sporadic CRCs for APC mutations and loss of heterozygosity (LOH) using sequencing and single-nucleotide polymorphism microarrays, respectively. Truncating APC mutations and/or LOH were detected in 75% of CRCs. Most truncating mutations occurred within a mutation cluster region (MCR; codons 1282-1581) leaving 1-3 intact 20 amino-acid repeats (20AARs) and abolishing all Ser-Ala-Met-Pro (SAMP) repeats. Cancers commonly had one MCR mutation plus either LOH or another mutation 5' to the MCR. LOH was associated with mutations leaving 1 intact 20AAR. MCR mutations leaving 1 vs 2-3 intact 20AARs were associated with 5' mutations disrupting or leaving intact the armadillo-repeat domain, respectively. Cancers with three hits had an over-representation of mutations upstream of codon 184, in the alternatively spliced region of exon 9, and 3' to the MCR. Microsatellite unstable cancers showed hyper-mutation at MCR mono- and di-nucleotide repeats, leaving 2-3 intact 20AARs. Proximal and distal cancers exhibited different preferred APC genotypes, leaving a total of 2 or 3 and 0 to 2 intact 20AARs, respectively. In conclusion, APC genotypes in sporadic CRCs demonstrate 'fine-tuned' interdependence of hits by type and location, consistent with selection for particular residual levels of WNT/β-catenin signalling, with different 'optimal' thresholds for proximal and distal cancers.

Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A population-based series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5-101.2). The diabetes patients (21.6%, n = 241) were older than nondiabetes patients (median 74.0 versus 69.6, p = 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%, p = 0.002) but were equally likely to complete treatment (69.7 versus 67.7%, p = 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71-1.63) or overall survival (HR = 1.23, 95% CI 0.88-1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer.

BACKGROUND: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. METHODS: APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. RESULTS: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.

BACKGROUND: The aims of the study were to determine the radiological leak rate in those patients who had undergone a resection for left-sided colorectal cancer and to see if the presence of a leak can be related with the postoperative clinical period. We also aimed to identify any common factors between patients with leak. METHODS: A retrospective analysis of prospectively collected data of all patients who underwent a left-sided colorectal cancer resection with formation of a defunctioning ileostomy was undertaken. Between 2005 and 2010, 418 such patients were identified. RESULTS: A water-soluble contrast enema was performed in 339 patients (81.1 %). Of these, 24 (7.1 %) were reported to show an anastomotic leak. Data for these 24 patients is presented in this study. Twenty-three (95.8 %) of the leaks occurred in patients who had undergone an anterior resection; 95.8 % of the patients with a leak were male. Fifteen (62.5 %) patients underwent neo-adjuvant radiation. The mean length of stay in those patients shown to have a subsequent radiological leak was 18.8 days (median), compared with the overall unit figures of 12 days. Only 29.2 % of the patients who had a leak identified had an uncomplicated postoperative period. Overall 87.5 % of the patients had a reversal of the ileostomy. CONCLUSIONS: Radiological leakage is not uncommon. The majority of patients, who were shown to have a radiological leak in this study, were male, had undergone an anterior resection, had received neo-adjuvant radiation, had a longer initial length of stay and had postoperative complications. Water-soluble contrast enemas could be selectively used in patients with these characteristics.