Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

The incidence of early onset colorectal cancer in Aotearoa New Zealand: 2000-2020.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC), diagnosed before age 50, has been rising in many countries in the past few decades. This study aims to evaluate this trend in Aotearoa New Zealand and assess its impact on Maori. METHODS: Crude incidence and age-standardized incidence of colorectal cancer (CRC) was analyzed from all new cases from the Aotearoa New Zealand national cancer registry for the period 2000-2020. Trends were estimated by sex, ethnicity, age group and location of cancer and projections made to 2040. RESULTS: Between 2000 and 2020, there were a total of 56,761 cases of CRC diagnosed in Aotearoa New Zealand, 3,702 of these being EOCRC, with age-standardized incidence decreasing significantly (P = 8.2 × 10- 80) from 61.0 to 47.3 cases per 100,000. EOCRC incidence increased on average by 26% per decade (incidence rate ratio (IRR) 1.26, p = < 0.0001) at all sites (proximal colon, distal colon and rectum), while the incidence in those aged 50-79 years decreased on average by 18% per decade (IRR 0.82, p = < 0.0005), again across all sites. There was no significant average change in CRC incidence in those over 80 years. In Maori, there was no significant change in age-standardized incidence. There was however a significant increase in crude incidence rates (IRR 1.28, p = < 0.0005) driven by significant increases in EOCRC (IRR1.36, p = < 0.0005). By 2040, we predict the incidence of EOCRC will have risen from 8.00 to 14.9 per 100,000 (6.33 to 10.00 per 100,000 in Maori). However, due to the aging population an estimated 43.0% of all CRC cases will be diagnosed in those over 80 years of age (45.9% over 70 years of age in Maori). CONCLUSION: The age-standardized incidence of CRC from 2000 to 2020 decreased in Aotearoa New Zealand, but not for Maori. The incidence of EOCRC over the same period continues to rise, and at a faster rate in Maori. However, with the ageing of the population in Aotearoa New Zealand, and for Maori, CRC in the elderly will continue to dominate case numbers.

Use of artificial intelligence for the prediction of lymph node metastases in early-stage colorectal cancer: systematic review.

BACKGROUND: Risk evaluation of lymph node metastasis for early-stage (T1 and T2) colorectal cancers is critical for determining therapeutic strategies. Traditional methods of lymph node metastasis prediction have limited accuracy. This systematic review aimed to review the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers. METHODS: A comprehensive search was performed of papers that evaluated the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers. Studies were appraised using the Joanna Briggs Institute tools. The primary outcome was summarizing artificial intelligence models and their accuracy. Secondary outcomes included influential variables and strategies to address challenges. RESULTS: Of 3190 screened manuscripts, 11 were included, involving 8648 patients from 1996 to 2023. Due to diverse artificial intelligence models and varied metrics, no data synthesis was performed. Models included random forest algorithms, support vector machine, deep learning, artificial neural network, convolutional neural network and least absolute shrinkage and selection operator regression. Artificial intelligence models' area under the curve values ranged from 0.74 to 0.9993 (slide level) and 0.9476 to 0.9956 (single-node level), outperforming traditional clinical guidelines. CONCLUSION: Artificial intelligence models show promise in predicting lymph node metastasis in early-stage colorectal cancers, potentially refining clinical decisions and improving outcomes. PROSPERO REGISTRATION NUMBER: CRD42023409094.

Do treatment patterns differ in those with early-onset colorectal cancer?

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is increasing. International guidelines state that treatment should not differ from that of older patients. Several studies have shown that patients under 50 years are receiving more aggressive treatment, without any survival benefit. We aim to determine if treatment for stages 2 and 3 EOCRC differs from those of late-onset colorectal cancer (LOCRC) patients. METHODS: This was a retrospective, population-based, cohort study of the treatment patterns of patients diagnosed with colorectal cancer in Canterbury, New Zealand, from 2010 to 2021 age <50 years, compared to those aged 60-74 years. RESULTS: A total of 3263 patients were diagnosed with CRC between 2010 and 2021. Following exclusions, we identified 130 EOCRC and 668 LOCRC patients. Stage 2 EOCRC patients are more likely to be offered adjuvant chemotherapy (p = <0.001). Furthermore, EOCRC patients with either stage 2 or 3 disease are more likely to receive multi-agent therapy (p = <0.01), without any associated increase in survival. CONCLUSION: EOCRC patients are given more adjuvant chemotherapy, without a corresponding improvement in outcomes, highlighting a potential for increased treatment-related harms, particularly in stage 2 disease. Clinicians should be mindful of these biases when treating young cancer patients and need to carefully consider treatment-related harms.

Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer.

Objective: Chronic colonic inflammation seen in inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). Colitis-associated cancers (CAC) are molecularly different from sporadic CRC. This study aimed to evaluate spatially defined molecular changes associated with neoplastic progression to identify mechanisms of action and potential biomarkers for prognostication. Design: IBD patients who had undergone colectomy for treatment of their IBD or dysplasia were identified from an institutional database. Formalin-fixed paraffin embedded samples from areas of normal, inflamed, dysplastic and adenocarcinoma tissue were identified for digital spatial profiling using the Nanostring GeoMx™ Cancer Transcriptome Atlas. RNA expression and quantification of 1812 genes was measured and analysed in a spatial context to compare differences in gene expression. Results: Sixteen patients were included, nine patients had CAC, two had dysplasia only and five had colitis only. Significant, step-wise differences in gene expression were seen between tissue types, mainly involving progressive over-expression of collagen genes associated with stromal remodelling. Similarly, MYC over-expression was associated with neoplastic progression. Comparison of normal and inflamed tissue from patients who progressed to those who did not also showed significant differences in immune-related genes, including under-expression of thte chemokines CCL18, CCL25 and IL-R7, as well as CD3, CD6 and lysozyme. The known oncogene CD24 was significantly overexpressed. Conclusion: Both tissue types and patient groups are molecularly distinguishable on the basis of their gene expression patterns. Further prospective work is necessary to confirm these differences and establish their clinical significance and potential utility as biomarkers.

Comparing outcomes and cost in surgery versus watch & wait surveillance of patients with rectal cancer post neoadjuvant long course chemoradiotherapy.

BACKGROUND: Watch and wait (W&W) in complete clinical responders after neoadjuvant chemoradiotherapy has increasingly robust data supporting its oncological safety. Recently, studies have assessed the real-world costs of this strategy compared to surgical resection. Our aim was to compare our oncological safety and costs associated with operative and surveillance strategies to international literature. METHODS: Data were retrospectively collected and analysed via electronic health records from March 2014 to March 2021 in Christchurch, New Zealand. Two cohorts were created based on intention to treat. All hospital events were recorded and costed, as well as oncologic outcomes. Our primary endpoints were the cumulative cost of both strategies, 3-year survival rate, and disease-free survival. RESULTS: Forty-eight patients were identified who had rectal cancers resected (OT) with a yPT0N0 pathology, and 42 who were on the wait-and-watch (W&W) audit after having a clinical complete response. After exclusions, we identified 38 OT and 23 W&W patients; the W&W group were more co-morbid (P = 0.05), had worse functional status (P = 0.008), higher BMI (P = 0.34) and more favourable clinical tumour staging (P = 0.01). The operative treatment (OT) group (n = 38) had more acute admissions (34% versus 13% in W&W, P = 0.08, OR 0.29). There was a 35.7% (n = 8 of 23) local recurrence in W&W and none in the OT group (P ≤ 0.001), with successful salvage in the W&W with local recurrence in 71.5% (n = 5 of 7). Three-year distant metastasis-free rate was 97.3% in the OT group and 90.9% in W&W (p = 0.05). Overall survival was 100% (W&W) and 94.7% (OT); (P = 0.019). Care in the OT group cost more than W&W, accounting for local regrowth management; $NZ70,759.56 versus $NZ47,905.52 (P = 0.014). CONCLUSION: This study found better oncological outcomes in the OT group, whilst the W&W group had reduced morbidity and acute bed days. The cost of wait and watch was approximately two-thirds that of operative treatment, even accounting for salvage procedures for local regrowth.

Management of rectal cancer in the era of total neoadjuvant therapy and watch and wait: A multidisciplinary team discussion at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting 2022.

Rectal cancer is a common malignancy. The management of rectal cancer has recently evolved and has undergone a paradigm shift with the advent of treatment approaches such as total neoadjuvant therapy and the watch-and-wait approach. However, despite the recently available evidence, there is no consensus on the optimal management approach in the setting of locally advanced rectal cancer. To address some of the controversies, a joint multidisciplinary panel discussion was conducted at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in November 2022. Members from different subspecialties formed two panels and discussed three clinical cases in a debate format. Each case represented some of the complex issues faced by clinicians in this setting. The discussion is now presented in this manuscript, which depicts the different available management approaches and reiterates the importance of a multidisciplinary approach.

Circulating Tumour DNA Guided Adjuvant Chemotherapy Decision Making in Stage II Colon Cancer-A Clinical Vignette Study.

Circulating tumour DNA (ctDNA) is a promising biomarker that may better identify stage II colon cancer (CC) patients who will benefit from adjuvant chemotherapy (AC) compared to standard clinicopathological parameters. The DYNAMIC study demonstrated that ctDNA-informed treatment decreased AC utilisation without compromising recurrence free survival, but medical oncologists' willingness to utilise ctDNA results to inform AC decision is unknown. Medical oncologists from Australia, Canada and New Zealand were presented with clinical vignettes for stage II CC comprised of two variables with three levels each (age: ≤50, 52-69, ≥70 years; and clinicopathological risk of recurrence: low, intermediate, high) and were queried about ctDNA testing and treatment recommendations based on results. Sixty-four colorectal oncologists completed at least one vignette (all vignettes, n = 59). The majority of oncologist were Australian (70%; Canada: n = 13; New Zealand: n = 6) and had over 10 years of clinical experience (n = 41; 64%). The proportion of oncologists requesting ctDNA testing exceeded 80% for all vignettes, except for age ≥ 70 and low-risk disease (63%). Following a positive ctDNA result, the proportion of oncologists recommending AC (p < 0.01) and recommending oxaliplatin-based doublet (p < 0.01) increased in all vignettes. Following a negative result, the proportion recommending AC decreased in all intermediate and high-risk vignettes (p < 0.01).

Quality of life in early-onset colorectal cancer patients: systematic review.

BACKGROUND: There is an increasing incidence of early-onset colorectal cancer; however, the psychosocial impacts of this disease on younger adults have been seldom explored. METHODS: A systematic review was conducted according to the PRISMA guidelines. The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, PubMed, and Scopus were searched, and papers were included if published in English within the last 10 years and if they reported results separately by age (including early-onset colorectal cancer, defined as colorectal cancer diagnosed before the age of 50 years). Critical appraisal of all studies was done using the Joanna Briggs Institute tools. The primary outcome of interest was the global quality of life in patients with early-onset colorectal cancer. Secondary outcomes included the effect on sexual function, body image, finances, career, emotional distress, and social and family functioning. RESULTS: The search yielded 168 manuscripts and 15 papers were included in the review after screening. All studies were observational, and included a total of 18 146 patients, of which 5015 were patients with early-onset colorectal cancer. The studies included scored highly using Joanna Briggs Institute critical appraisal tools, indicating good quality and a low risk of bias, but data synthesis was not performed due to the wide range of scoring systems that were used across the studies. Six papers reported significant negative impacts on quality of life in patients with early-onset colorectal cancer. Three of the four studies that compared the quality of life in patients with early-onset colorectal cancer with older patients found that the younger group had worse mean quality-of-life scores (P ≤ 0.05). Secondary outcomes measured in five studies in relation to sexual dysfunction, body image, financial and career impacts, and social and family impacts and in eight studies in relation to emotional distress were found to be more severely impacted in those with early-onset colorectal cancer compared with those with late-onset colorectal cancer. CONCLUSION: Whilst data are limited, the impact of colorectal cancer is different in patients with early-onset colorectal cancer compared with older patients in relation to several aspects of the quality of life. This is particularly prominent in areas of global quality of life, sexual functioning, family concerns, and financial impacts.

Early onset colorectal cancer in Canterbury, New Zealand.

BACKGROUND: The overall incidence of colorectal cancer is decreasing in much of the world, yet the incidence in those under 50 years of age is increasing (early onset colorectal cancer (EOCRC)). The reasons for this are unclear. This study was undertaken to describe the clinical, pathological and familial characteristics of patients with EOCRC and their oncological outcomes and compare this with previously published data on late onset colorectal cancer (LOCRC). METHODS: A retrospective review of all patients diagnosed with EOCRC in Canterbury between 2010 and 2017 was conducted. Data was collected on demographics, family history, treatment, and oncologic outcomes. Kaplan-Meier survival curves were calculated to assess overall survival based on disease stage. RESULTS: During the study period (2010-2017) there were 3340 colorectal cancers diagnosed in Canterbury, of which 201 (6%) were in patients under 50 years (range: 17-49). Of these, 87 (43.3%) were female and 125 (62.2%) were aged between 40 and 49 years. 28 (13.9%) were associated with hereditary conditions. Of the 201 patients, 139 (69.2%) had rectal or left-sided cancers. 142 (70.6%) patients presented with either stage 3 or 4 disease and the 5-year overall survival by stage was 79.1% and 14.4%, respectively. CONCLUSION: EOCRC is increasing and usually presents as distal left sided cancers, and often at an advanced stage. They do not appear to have the common risk factors of family history or inherited pre-disposition for colorectal cancer. Planning by healthcare providers for this epidemiological change is imperative in investigating symptomatic patients under 50 and optimizing early detection and prevention.

Risk of colorectal cancer in patients with appendicitis over the age of 40 years.

AIM: Acute appendicitis in late adulthood is hypothesized to be associated with an increased risk of colorectal cancer (CRC). This study aimed to establish whether patients over the age of 40 years presenting with appendicitis had an increased risk of being diagnosed with CRC over the subsequent 3 years. METHOD: This is a retrospective review of patients aged 40 years and over presenting to Canterbury District Health Board with appendicitis from January 2010 to December 2015. Clinical details were obtained for these patients and cross-referenced with the New Zealand Cancer Registry for the 3 years following diagnosis. The incidence ratio rate (IRR) and standardized incidence ratio (SIR) were calculated by establishing the incidence of CRC in this cohort and comparing it with the Canterbury population data. RESULTS: A total of 1099 patients met the inclusion criteria. The majority (75%) underwent CT as part of their initial work-up. The rate of colonoscopy increased with age from around 10% between 40 and 49 years to 27% for those 70 years and over. Eleven cases of CRC were identified, resulting in an IRR 2.35 (95% CI 1.17-4.21). The SIR for this population was 3.28 (95% CI 1.82-5.92). CONCLUSION: The rate of CRC is significantly increased compared with the background population in this cohort. The results of this study support luminal investigation of adults aged 40 years and over who present with acute appendicitis as CT alone was insufficient to detect the pathology.

Pelvic exenteration: a review of current issues/controversies.

Management of advanced or recurrent pelvic cancer has evolved dramatically over the past few decades. Patients who were previously considered inoperable are now candidates for potentially curative surgery and avoid suffering with intractable symptoms. Up to 10% of primary rectal cancers present with isolated advanced local disease and between 10% and 15% of patients develop localized recurrence following proctectomy. Advances in surgical technique, reconstruction and multidisciplinary involvement have led to a reduction in mortality and morbidity and culminated in higher R0 resection rates with superior longer-term survival outcomes. Recent studies boast over 50% 5-year survival for rectal with an R0 resection. Exenteration has cemented itself as an important treatment option for advanced primary/recurrent pelvic tumours, however, there are still a few controversies. This review will discuss some of these issues, including: limitations of resection and the approach to high/wide tumours; the role of acute exenteration; re-exenteration; exenteration in the setting of metastatic disease and palliation; the role of radiotherapy (including intra-operative and re-irradiation); management of the empty pelvis; and the impact on quality of life and function.

Circulating Bacterial DNA: A New Paradigm for Cancer Diagnostics.

Cell-free DNA applications for screening, diagnosis and treatment monitoring are increasingly being developed for a range of different cancers. While most of these applications investigate circulating tumor DNA (ctDNA) or methylation profiles of ctDNA, circulating bacterial DNA (cbDNA) has also been detected in plasma and serum samples from cancer patients. Recent publications have the detection of cbDNA in studies of breast, gastric, colorectal, hepatocellular and ovarian cancers. In several cases, distinction between patients and healthy controls was possible, based on cbDNA profiles, in addition to potential prognostic value. A large pan-cancer study demonstrated the feasibility of cbDNA to distinguish between four types of cancer and healthy controls, even in patients with early-stage disease. While improvements in, and standardization of laboratory and bioinformatics analyses are needed, and the clinical relevance of cbDNA yet to be ascertained for each cancer type, cbDNA analysis presents an exciting prospect for future liquid biopsy screening and diagnostics in cancer.

Abdominal and perineal hernia rates following vertical rectus abdominis myocutaneous (VRAM) flap reconstruction - a supraregional experience.

BACKGROUND: Vertical rectus abdominis myocutaneous (VRAM) flap has proven to be a robust reconstruction method following radical pelvic surgery. Radical pelvic surgery is associated with high morbidity due to pelvic complications and non-healing perineal wounds, as a result of non-collapsible pelvic dead space and pre-operative adjuvant radiotherapy insult. VRAM flap reconstruction addresses both issues by obliterating the dead space and introducing healthy non-radiated tissue. However, flap reconstruction complications can include donor site hernias (abdominal wall), perineal hernias, and flap-specific complications. This study aimed to evaluate the abdominal and perineal hernia rates as well as radiological evidence of flap vascularity post-operatively. METHODS: We conducted a retrospective analysis of patients who underwent a VRAM flap reconstruction following radical pelvic surgery at Christchurch hospital over a 10-year period. We identified the presence of donor site hernias (abdominal wall hernias), perineal hernias, and flap vascularity on post-operative radiological imaging performed within 48 months. RESULTS: Seventy-seven patients underwent a VRAM flap reconstruction of which 60 patients met the inclusion requirements for the study (mean age was 60.3 years [range 26-89]; 31 were male and 29 were female). Eighteen patients underwent an APR and 42 underwent a partial or a complete pelvic exenteration and the majority of them (75.0%) were for rectal cancers. Available imaging was on average 21.6 months post-operatively (IQR 11.8-31.3 months). The donor site hernia rate was 16.7%, and the perineal hernia rate was 3.3%. VRAM flap appeared to have DIEA flow in 98.3% of the patients. CONCLUSION: VRAM flap reconstruction of complex pelvic defects remains a robust method of choice in complex pelvic reconstruction with little morbidity.

The long-term incidence of dysplasia and colorectal cancer in a Crohn's colitis population-based cohort.

AIM: The risk of developing colorectal cancer (CRC) in Crohn's disease (CD) has been variably reported. Chronic inflammation is associated with an increased risk of neoplasia; variable outcomes in CD possibly reflect the heterogeneous nature of the disease. The aim of this work was to characterize the risk of CRC in a New Zealand population-based cohort of CD patients with colonic inflammation. METHOD: A review of all participants with CD in the population-based Canterbury Inflammatory Bowel Disease Study was conducted. Data on demographics, endoscopic surveillance, presence of dysplasia/neoplasia and oncological outcome were extracted. The age-adjusted standardized incidence ratio (SIR) was used to compare the incidence of CRC in the cohort with the incidence of CRC in the New Zealand population in 2006. RESULTS: Data on 649 patients with CD were collected. Four hundred and thirty-six participants (58% female) with ileocolonic or colonic CD were included for analysis. CRC was diagnosed in 13 patients (62% female). The median age at CRC diagnosis was 58.5 years, and the mean duration of CD prior to diagnosis of CRC was 20.4 years. When compared with the New Zealand population (using census data), the overall age-adjusted SIR was 4.1 (95% CI 2.4-7.1). CONCLUSION: This population-based cohort of patients with colonic CD shows a significantly increased risk of CRC compared with the general population. This is consistent with the colonic location of inflammation increasing the risk of neoplasia. Inclusion of patients with isolated upper gastrointestinal/ileal CD in similar studies may mask the truly increased risk for patients with long-standing colonic inflammation.