Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann's reversals.

BACKGROUND: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann's reversal procedure in the prediction of short-term postoperative complications. METHODS: A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. RESULTS: Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. CONCLUSION: Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann's reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.

Is increasing nodal count associated with improved recurrence-free and overall survival following standard right hemicolectomy for colon cancer?

BACKGROUND AND OBJECTIVES: Increasing lymph node harvest for right-sided colon cancer is associated with improved overall survival (OS), but most relevant studies failed to report the extent of resection. We examined the association between increasing lymph node count with standard right hemicolectomy according to nodal status and prognostic outcomes in right-sided tumors. METHODS: Retrospective analysis of prospectively collected clinical data from patients with proximal colonic adenocarcinomas (n = 1390) following right hemicolectomy. Associations between lymph node counts (0-12 vs. 13-15, 16-20, and >20) and recurrence-free survival (RFS) and OS were examined using multivariate Cox modeling adjusted for confounders. RESULTS: We found no association between increasing nodal count and RFS, regardless of nodal status. In the absence of nodal metastases, increasing nodal count (16-20 and >20 vs. 0-12 nodes) was associated with 57% (95% confidence interval [CI]: 0.21-0.89) and 52% (95% CI: 0.24-0.95) improved OS, respectively. In the presence of nodal metastases, increasing nodal count was not associated with OS. Adjuvant chemotherapy did not modify this effect. CONCLUSION: Increasing nodal count (>15 nodes) with right hemicolectomy was not associated with improved RFS. Improved OS was only found for node-negative tumors, casting some doubt on the benefits of resecting more lymph nodes in the presence of nodal metastases.

Stage dependent recurrence patterns and post-recurrence outcomes in non-metastatic colon cancer.

BACKGROUND: Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage. METHODS: Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival. We also explored changes over time. RESULTS: Of 4257 new colon cancers diagnosed 2001 through 2016, 789 (21.1%) had stage I, 1584 (42.4%) had stage II, and 1360 (36.4%) had stage III colon cancer. For consecutive 5-year periods (2001-2005, 2006-2010, 2011-2016), recurrence rates have declined (23.4 vs. 17.1 vs. 13.6%, p < 0.001), however, the resection rates of metastatic disease (29.3 vs. 38.6 vs. 35.0%, p = 0.21) and post-resection 5-year survival (52.0 vs. 51.8 vs. 64.2%, p = 0.12) have remained steady. Primary tumor stage impacted recurrence rate (3.8 vs. 12 vs. 28%, p < 0.0001 for stage 1, 2, and 3), patterns of recurrence, resection of metastatic disease, (50 vs. 42 vs. 30%, p < 0.0001) and post-resection 5-year survival (92 vs. 64 vs. 44%, p < 0.001). CONCLUSION: In this community cohort we defined significant differences in recurrence patterns and post-resection survival by tumor stage, with a diminishing rate of recurrence over time. While recurrence rates were lower with stage I and II disease, the high rate of metastatic disease resection and excellent post-resection outcomes help to justify routine surveillance in these patients.

Validation of Australian and Victorian guidelines for colonoscopy triage.

BACKGROUND: Managing the growing demand for colonoscopies is challenging. AIMS: To assess the diagnostic performance of National and Victorian colonoscopy triage guidelines and potential redistribution of triage categories. METHODS: This is a diagnostic validation study comparing colonoscopy triage guidelines against a reference colonoscopy dataset. Participants were a reference dataset of 2378 colonoscopies from 1 October 2014 to 30 June 2016. Comparison with triage categorisation determined using National Cancer Council Australia guidelines; Victorian triage guidelines; Optimal Cancer Care Pathways recommendations. Main outcome measures were as follows: (i) proportion of colonoscopies assigned to each triage category; (ii) detection rate (proportion of cancers assigned to triage Category 1); and (iii) conversion rate (proportion of triage Category 1 colonoscopies that diagnose a cancer). RESULTS: After adjusting for data absent in referrals, the National and Victorian guidelines reduced the proportion of Category 1 colonoscopies compared with the reference triage (National 76.3% vs 58.6%; 95% CI for difference 15.0-20.3%, P < 0.0001. Victorian 76.3% vs 66.3%; 95% CI for difference 7.4-12.6%, P < 0.0001). Victorian guidelines were associated with the highest detection rate (91.4%) and a conversion rate of 5.4% although the number of cancers limited the power to detect significant differences on these metrics. There was a higher proportion of unclassifiable colonoscopies using the National guidelines than the Victorian ones due to their focus on symptomatic indications. CONCLUSIONS: The Victorian guidelines could reduce the proportion of Category 1 colonoscopies by 10% without reducing conversion or detection rates. This would require improvements in the quality of referrals and ordering faecal occult blood tests in 6% of symptomatic patients.

Real-world outcomes for neoadjuvant capecitabine versus infusional 5-fluorouracil in the treatment of locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation therapy is standard-of-care treatment for locally advanced rectal cancer (LARC). A pathological complete response (pCR) following chemoradiation therapy is an early indicator of treatment benefit and associated with excellent survival outcomes, with capecitabine largely replacing infusional 5-fluorouracil as the choice in routine care of LARC. AIMS: To analyse the uptake of capecitabine usage over time, and on the back of clinical trial data demonstrating equivalence between fluoropyrimidines, confirm that efficacy is maintained in the real-world setting. METHODS: We analysed data from a prospectively maintained colorectal cancer database at three Australian hospitals including patients diagnosed from January 2009 to December 2018. Pathological response was determined as either complete or incomplete and compared for patients receiving 5-FU or capecitabine. RESULTS: A total of 657 patients was analysed, 498 receiving infusional 5-FU and 159 capecitabine. Capecitabine use has markedly increased from approval in 2014 in Australia, now being used in more than 80% of patients. Patient characteristics were similar by treatment, including age, tumour location and pre-treatment stage. pCR was reported in 22/159 (13.8%) of capecitabine-treated patients and 118/380 (23.7%) that received 5-FU (P ≤ 0.01). More capecitabine-treated patients received post-operative oxaliplatin (44.2% vs 6.3%, P < 0.01). Two-year progression-free survival was similar (84.9% vs 88.0%, P = 0.34). CONCLUSIONS: Capecitabine is now the dominantly used neoadjuvant chemotherapy in LARC. Capecitabine use was associated with a lower rate of pCR versus infusional 5-FU, a difference not explained by examined patient or tumour characteristics. Poor treatment compliance with oral therapy in the real-world setting is one possible explanation.

Overexpression of TP53 protein is associated with the lack of adjuvant chemotherapy benefit in patients with stage III colorectal cancer.

TP53 mutations drive colorectal cancer development, with missense mutations frequently leading to accumulation of abnormal TP53 protein. TP53 alterations have been associated with poor prognosis and chemotherapy resistance, but data remain controversial. Here, we examined the predictive utility of TP53 overexpression in the context of current adjuvant treatment practice for patients with stage III colorectal cancer. A prospective cohort of 264 stage III patients was tested for association of TP53 expression with 5-year disease-free survival, grouped by adjuvant treatment. Findings were validated in an independent retrospective cohort of 274 stage III patients. Overexpression of TP53 protein (TP53+) was found in 53% and 52% of cases from the prospective and retrospective cohorts, respectively. Among patients receiving adjuvant chemotherapy, TP53+ status was associated with shorter disease-free survival (p ≤ 0.026 for both cohorts), while no difference in outcomes between TP53+ and TP53- cases was observed for patients treated with surgery alone. Considering patients with TP53- tumors, those receiving adjuvant treatment had better outcomes compared with those treated with surgery alone (p ≤ 0.018 for both cohorts), while no treatment benefit was apparent for patients with TP53+ tumors. Combined cohort-stratified analysis adjusted for clinicopathological variables and DNA mismatch repair status confirmed a significant interaction between TP53 expression and adjuvant treatment for disease-free survival (pinteraction = 0.030). For the combined cohort, the multivariate hazard ratio for TP53 overexpression among patients receiving adjuvant chemotherapy was 2.03 (95% confidence interval 1.41-2.95, p < 0.001), while the hazard ratio for adjuvant treatment among patients with TP53- tumors was 0.42 (95% confidence interval 0.24-0.71, p = 0.001). Findings were maintained irrespective of tumor location or when restricted to mismatch repair-proficient tumors. Our data suggest that adjuvant chemotherapy benefit in stage III colorectal cancer is restricted to cases with low-level TP53 protein expression. Identifying TP53+ tumors could highlight patients that may benefit from more aggressive treatment or follow-up.

Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes.

OBJECTIVE: Tumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear. DESIGN: A prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF/KRAS mutations. Consensus molecular subtype (CMS) status was determined for 142 cases. Associations with 5-year disease-free survival (DFS) were evaluated and validated in an independent cohort of 602 patients. RESULTS: Tumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; Pmultivariate<0.001) and TIL-low/pMMR tumours (HR=2.67; 95% CI=1.47 to 4.84; Pmultivariate=0.001) showed poor DFS. Outcomes of patients with TIL-low/dMMR and TIL-low/pMMR tumours were similar. TIL-high/pMMR tumours showed intermediate survival rates. These findings were validated in an independent cohort. TIL/MMR status was a more significant predictor of prognosis than National Comprehensive Cancer Network high-risk features and was a superior predictor of prognosis compared with genomic (dMMR, pMMR/BRAFwt /KRASwt , pMMR/BRAFmut /KRASwt , pMMR/BRAFwt /KRASmut ) and transcriptomic (CMS 1-4) subtypes. CONCLUSION: TIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.

Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study.

OBJECTIVE: For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC. DESIGN: We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery. Somatic mutations in individual patient's tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results. RESULTS: We analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001). CONCLUSION: Postoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

Understanding patient-reported outcome measures in colorectal cancer.

Quality of life has become increasingly regarded as a key outcome measurement for cancer patients. Patient-reported outcome measures (PROMs) represent the tools used to ascertain self-reported quality of life. This review provides a summary of the literature regarding the use of PROMs in colorectal cancer and evaluates the advantages and limitations of generic and disease specific questionnaires that can be utilized in clinical practice. Factors that influence PROMs are outlined, including cancer characteristics, patient factors and treatment methods. Finally, future directions for the use of PROMs in colorectal cancer to inform healthcare delivery at an individual- and systems-based level are discussed.

Impact of Surgical Complications Following Resection of Locally Advanced Rectal Adenocarcinoma on Adjuvant Chemotherapy Delivery and Survival Outcomes.

BACKGROUND: Surgical complications after resection for locally advanced rectal cancer may influence adjuvant treatment outcomes and survival. Few studies have examined this effect. OBJECTIVE: This study aimed to examine the impact of surgical complications on adjuvant therapy delivery and survival in patients with locally advanced rectal cancer treated with long-course chemoradiation followed by surgery. DESIGN: This is a retrospective analysis of a prospectively collected multicenter colorectal cancer database. SETTINGS: Data were collected from the Australian Comprehensive Cancer Outcomes and Research Database. PATIENTS: All patients who completed neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer between January 2003 and December 2014 were selected. MAIN OUTCOME MEASURES: We examined the types and frequency of surgical complications and their impact on the delivery of adjuvant chemotherapy and survival. RESULTS: Data were available for 517 patients, of whom 147 (28%) had a surgical complication. Patients with a surgical complication were less likely to commence adjuvant chemotherapy (33% vs 66%; p = 0.0005) and more likely to have adjuvant treatment commencing more than 8 weeks from surgery (71.8% vs 21.2%; p = 0.004). Wound-related complications (p = 0.001), return to operating theater (p = 0.004), and readmission within 30 days (p = 0.02) had the most significant negative impact on the delivery of adjuvant chemotherapy. Surgical complications were significantly more likely in males (31.6% vs 20.8%, p = 0.003) and laparoscopic converted cases (47.8% vs 21.8%, p = 0.03). For the entire patient population, adjuvant chemotherapy compared with surveillance was not associated with an improved recurrence-free survival (HR, 1.06; p = 0.83) but was associated with an improved overall survival (HR, 0.53; p = 0.04). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Surgical complications in patients having surgery following neoadjuvant chemoradiotherapy for locally advanced rectal cancer were associated with significantly reduced uptake and delays to receiving adjuvant therapy. Surgical complications, however, were not associated with either significantly reduced recurrence-free or overall survival. Adjuvant chemotherapy delivery was associated with improved overall survival.

Improving Quality of Life for People with Incurable Large-Bowel Obstruction: Randomized Control Trial of Colonic Stent Insertion.

BACKGROUND: Surgery remains the dominant treatment for large-bowel obstruction, with emerging data on self-expanding metallic stents. OBJECTIVE: The aim of this study was to assess whether stent insertion improves quality of life and survival in comparison with surgical decompression. DESIGN: This study reports on a randomized control trial (registry number ACTRN012606000199516). SETTING: This study was conducted at Royal Prince Alfred Hospital, Sydney, and Western Hospital, Melbourne. PATIENTS AND INTERVENTION: Patients with malignant incurable large-bowel obstruction were randomly assigned to surgical decompression or stent insertion. MAIN OUTCOME MEASURES: The primary end point was differences in EuroQOL EQ-5D quality of life. Secondary end points included overall survival, 30-day mortality, stoma rates, postoperative recovery, complications, and readmissions. RESULTS: Fifty-two patients of 58 needed to reach the calculated sample size were evaluated. Stent insertion was successful in 19 of 26 (73%) patients. The remaining 7 patients required a stoma compared with 24 of 26 (92%) surgery group patients (p < 0.001). There were no stent-related perforations or deaths. The surgery group had significantly reduced quality of life compared with the stent group from baseline to 1 and 2 weeks (p = 0.001 and p = 0.012), and from baseline to 12 months (p = 0.01) in favor of the stent group, whereas both reported reduced quality of life. The stent group had an 8% 30-day mortality compared with 15% for the surgery group (p = 0.668). Median survival was 5.2 and 5.5 months for the groups (p = 0.613). The stent group had significantly reduced procedure time (p = 0.014), postprocedure stay (p = 0.027), days nothing by mouth (p = 0.002), and days before free access to solids (p = 0.022). LIMITATIONS: This study was limited by the lack of an EQ-5D Australian-based population set. CONCLUSIONS: Stent use in patients with incurable large-bowel obstruction has a number of advantages with faster return to diet, decreased stoma rates, reduced postprocedure stay, and some quality-of-life benefits.

Impact of regular aspirin use on overall and cancer-specific survival in patients with colorectal cancer harboring a PIK3CA mutation.

BACKGROUND: Recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer (CRC) patients harboring PIK3CA mutations. However, the number of PIK3CA-mutated CRC patients examined in these studies was modest. Our collaborative study aims to validate the association between regular aspirin use and survival in patients with PIK3CA-mutated CRC. PATIENTS AND METHODS: Patients with PIK3CA-mutated CRC were identified at Moffitt Cancer Center (MCC) in the United States and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data and survival data were available. At MCC, PIK3CA mutations were identified by targeted exome sequencing using the Illumina GAIIx Next Generation Sequencing platform. At RMH, Sanger sequencing was utilized. Multivariate survival analyses were conducted using Cox logistic regression. RESULTS: From a cohort of 1487 CRC patients, 185 patients harbored a PIK3CA mutation. Median age of patients with PIK3CA-mutated tumors was 72 years (range: 34-92) and median follow up was 54 months. Forty-nine (26%) patients used aspirin regularly. Regular aspirin use was not associated with improved overall survival (multivariate HR 0.96, p = 0.86). There was a trend towards improved cancer-specific survival (multivariate HR 0.60, p = 0.14), but this was not significant. CONCLUSIONS: Despite examining a large number of patients, we did not confirm that regular aspirin use was associated with statistically significant improvements in survival in PIK3CA-mutated CRC patients. Prospective evaluation of this relationship is warranted.

Colorectal cancer treatment outcomes during the pandemic: Our experience of COVID-19 at a tertiary referral center.

BACKGROUNDS: The coronavirus disease 2019 (COVID-19) has led to major shifts in the management of colorectal cancer (CRC). This study aims to identify the impact and early outcomes of COVID-19 following CRC management at a tertiary referral center in Victoria, Australia. METHODS: This was a retrospective study, utilizing the Australian Comprehensive Cancer Outcomes and Research Database and inpatient records. Patients presenting for CRC management at our institution were identified coinciding with the first Victorian outbreak of COVID-19 (March 26 to September 26, 2020) (COVID). Management decisions including chemoradiotherapy utilization and surgical outcomes were analyzed within 6 months and compared with the corresponding period in 2019 (pre-COVID). RESULTS: A total of 276 patients were included in this study (147 pre-COVID period, 129 COVID period). During the COVID period, more patients (47.6% vs. 60.5%; p = 0.033) presented symptomatically and less for surveillance (10.9% vs. 2.3%; p < 0.01). Eighty-four pre-COVID and 69 COVID period patients proceeded to surgery. The average time from diagnosis date to surgery was 15.6 days less during the COVID period. There were no significant differences in postoperative utilization of higher care (p = 0.74), complications (p = 0.93), median hospital length of stay (p = 0.67), 30-day readmission (p = 0.50), or 30-day reoperation (p = 0.74). In 1.6% of cases, pandemic impacts resulted in a change in management. CONCLUSION: Presentation of patients with CRC varied, with a significant increase in symptomatic presentations and decreased numbers for surveillance. Through flexibility and change in practice, our institution helped improve access to surgical intervention and oncological therapies. Further prospective work is required to identify long-term outcomes and characterize the effects of ongoing disruptions.

Artificial intelligence measured 3D body composition to predict pathological response in rectal cancer patients.

BACKGROUND: The treatment of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Of particular interest are predictors of pathological complete response (pCR) that can guide personalized treatment. There are currently no clinical biomarkers which can accurately predict neoadjuvant therapy (NAT) response but body composition (BC) measures present as an emerging contender. The primary aim of the study was to determine if artificial intelligence (AI) derived body composition variables can predict pCR in patients with LARC. METHODS: LARC patients who underwent NAT followed by surgery from 2012 to 2023 were identified from the Australian Comprehensive Cancer Outcomes and Research Database registry (ACCORD). A validated in-house pre-trained 3D AI model was used to measure body composition via computed tomography images of the entire Lumbar-3 vertebral level to produce a volumetric measurement of visceral fat (VF), subcutaneous fat (SCF) and skeletal muscle (SM). Multivariate analysis between patient body composition and histological outcomes was performed. RESULTS: Of 214 LARC patients treated with NAT, 22.4% of patients achieved pCR. SM volume (P = 0.015) and age (P = 0.03) were positively associated with pCR in both male and female patients. SCF volume was associated with decreased likelihood of pCR (P = 0.059). CONCLUSION: This is the first study in the literature utilizing AI-measured 3D Body composition in LARC patients to assess their impact on pathological response. SM volume and age were positive predictors of pCR disease in both male and female patients following NAT for LARC. Future studies investigating the impact of body composition on clinical outcomes and patients on other neoadjuvant regimens such as TNT are potential avenues for further research.

Recalibration and validation of a preoperative risk prediction model for mortality in major colorectal surgery.

BACKGROUND: In 2009, Barwon Health designed a risk stratification model for mortality in major colorectal surgery with the use of only preoperative risk factors. The Barwon Health 2009 model was shown to predict mortality reliably, and it was comparable to other models, such as the original, POSSUM. However, the Barwon Health 2009 model was never validated with data other than those used to develop the model. OBJECTIVE: The aim of this study was to perform temporal and external validation of the Barwon Health 2009 model and to compare it with other published models. DESIGN: : The temporal validation was a prospective observational study, whereas the external validation was a retrospective observational study. The discrimination and calibration of the models were assessed by using the area under receiver operator characteristic and χ test of Hosmer-Lemeshow goodness-of-fi technique. SETTINGS: This is a multi-institutional study. Data were collected from 2008 to 2010. RESULTS: There were 474 major colorectal cases at Geelong Hospital (temporal validation) and 389 cases at Western Hospital (external validation). The overall mortality rate was 5.10% and 1.03%. In the comparison of the 2 demographics, Geelong Hospital had a higher proportion of patients who were older and had higher ASA scores and comorbidity counts, whereas Western Hospital surgeons were operating on a higher number of urgent cases. Despite the differences, the Barwon Health 2009 model was able to discriminate mortality reliably (area under receiver operator characteristic = 0.753) but had poor model calibration (p < 0.001) on temporal validation. Hence, the model was recalibrated to predict mortality accurately(area under receiver operator characteristic = 0.772; p = 0.83), and this was successfully validated at Western Hospital (area under receiver operator characteristic = 0.788; p = 0.24). CONCLUSIONS: We have developed a model that can accurately predict mortality after major colorectal surgery by using only data that are available preoperatively. After recalibration, the model was successfully validated in a second hospital.

Time to readiness for discharge is a valid and reliable measure of short-term recovery after colorectal surgery.

BACKGROUND: Short-term recovery after colorectal surgery has been traditionally investigated through length of stay (LOS). However, this measure is influenced by several confounding factors. This study aimed to investigate the construct validity and reliability of assessing the time to achieve standardized discharge criteria (time to readiness for discharge, or TRD) as a measure of short-term recovery. In a secondary analysis, we compared sample size requirements for randomized controlled trials (RCTs) using TRD or LOS as outcome measures. METHODS: Seventy patients participated in the construct validity study and 21 patients participated in the reliability study. TRD was defined as the number of days to achieve discharge criteria previously defined by consensus. Construct validity was investigated by testing six hypothesis based on the assumption that TRD measures short-term recovery. Reliability was calculated by comparing measures of TRD by two independent assessors. Variability estimates (standard deviations) of LOS and TRD were used for sample size calculations. RESULTS: Five of the six hypotheses were supported by the data (p < 0.05). Interobserver reliability was excellent (ICC2.1 = 0.99). Sample size estimations showed that RCTs using TRD as an outcome measure require approximately 23 % less participants compared to RCTs using LOS. CONCLUSIONS: The results of this research support the construct-validity and reliability of TRD as a measure of short-term recovery. Using TRD as an alternative to LOS may reduce sample size requirements in future RCTs.

Reversal of Hartmann's procedure: timelines, preoperative investigations and early outcomes. A single Australian institution's ten-year experience.

BACKGROUND: Real-world data on outcomes following Hartmann's reversal is necessary to help optimize the patient experience. We have explored the timing between the index operation and its reversal; what investigations were carried out prior to this, and the associated short-term outcomes. METHODS: A retrospective study of all patients who underwent Hartmann's reversal from 2010 to 2020 within a tertiary referral centre in Melbourne, Australia. One hundred from a total of 406 (25%) who underwent an emergency Hartmann's procedure had a subsequent reversal. Complete patient data was available for 83 of these patients. RESULTS: The average patient age was 60 years, and the median time for reversal was 14.0 (IQR 10-23) months. Seventy-nine of 83 (95%) reversals had a preoperative endoscopic evaluation of both their rectal stump and a complete colonoscopy. Stoma stenosis (n = 2), patient refusal (n = 1) and emergency reversal (n = 1) were cited reasons for not undergoing preoperative endoscopic evaluation. A third (n = 28, 34%) had a computed tomography prior to reversal; the majority was due to their underlying cancer surveillance (n = 21, 75%). Reversal was associated with a morbidity rate of 47% (n = 39). Surgical site infections (SSIs) (n = 21, 25%) were the most common type of complications encountered, with the majority being superficial (n = 15, 71%). SSIs were associated with steroid use (5/21 versus 4/62, p = 0.03) and greater hospital length of stay (6 versus 10 days, p = 0.03). CONCLUSION: Only a quarter of emergency Hartmann's procedures within our institution were reversed. A significant proportion developed postoperative complications. Surgical site infection was the most common morbidity.

Are health outcomes in the older colorectal cancer patients treated by curative intent surgery any different to the younger patients?

BACKGROUND: Colorectal cancer poses a major burden. Its incidence increases with age and older patients with comorbidities have a higher likelihood of major complications. This study investigated the impact of age on health outcomes in colorectal cancer patients treated by surgery. METHODS: A prospective database of all patients undergoing colorectal cancer surgery with curative intent between 2012 and 2017 was used to identify patients. A retrospective review of existing medical records investigating health-related outcomes in colorectal cancer patients undergoing surgery was performed. Primary outcomes measured were overall survival (OS) and disease-free survival (DFS). Difference in restricted mean survival times (RMST) up to a pre-specified time point of 24 months was used to compare four age groups. RESULTS: Six-hundred and fifty-one patients were divided into four age group categories: ≤65-years (n = 244), 66 to 75-years (n = 213), 76 to 85-years (n = 162) and >85-years (n = 32). Older patients were found to have a higher rate of post-operative medical complications (including confusion) (P = 0.001) and a longer length of stay (LOS) (P = 0.01). There was no difference between the 76 to 85-year age group and >85-year age group in OS and DFS. However, there was a reduced OS in older patients (>65) compared to their younger cohorts (<65) (P = 0.04). CONCLUSION: Older patients who undergo curative surgery have reduced OS, increased LOS and higher complication rates. Complex older patients may benefit from geriatric assessment and management in the peri-operative period.

Can sarcopenia predict survival in locally advanced rectal cancer patients?

BACKGROUND: There is mounting evidence that suggests sarcopenia can be used to predict survival outcomes in patients with colon cancer. However, the effect on locally advanced rectal cancer (LARC) is less clear. We sought to determine the association between sarcopenia on Overall Survival and Recurrence-free Survival (OS and RFS) in patients with LARC undergoing multimodal treatment. METHODS: A retrospective study was undertaken of all pre-treatment stage 2-3 rectal cancer patients who underwent neo-adjuvant treatment and surgery with curative intent between January 2010 and September 2016 at Western Health. Sarcopenia was measured on pre-treatment staging scans at the third lumbar vertebrae and defined using cohort-derived, sex-specific thresholds. Primary outcomes were OS and RFS. RESULTS: A total of 132 patients with LARC were analysed. Sarcopenia: Hazard ratio (HR) 3.71; 95% CI, 1.28-10.75, P = 0.016 was independently associated with worse Overall Survival following multivariate analysis. There was no significant relationship between sarcopenia and RFS: Time ratio (TR) 1.67; 95% CI 0.52-5.34, P = 0.386. CONCLUSION: Sarcopenia was found to be an independent risk factor for worse overall survival, but not recurrence free survival, in patients with locally advanced rectal cancer undergoing neo-adjuvant chemo-radiotherapy and surgery with curative intent.

Criteria to determine readiness for hospital discharge following colorectal surgery: an international consensus using the Delphi technique.

BACKGROUND: Standardized discharge criteria are considered valuable to reduce the risk of premature discharge and avoid unnecessary hospital stays. The most appropriate criteria to indicate readiness for discharge after colorectal surgery are unknown. OBJECTIVE: The aim of this study is to achieve an international consensus on hospital discharge criteria for patients undergoing colorectal surgery. DESIGN: Fifteen experts from different countries participated in a 3-round Delphi process. In round 1, experts determined which criteria best indicate readiness for discharge and described specific end points for each criterion. In rounds 2 and 3, experts rated their agreement with the use of a 5-point Likert scale. MAIN OUTCOME MEASURES: Consensus was defined when criteria and end points were rated as agree or strongly agree by at least 75% of the experts in round 3. RESULTS: Experts reached consensus that patients should be considered ready for hospital discharge when there is tolerance of oral intake, recovery of lower gastrointestinal function, adequate pain control with oral analgesia, ability to mobilize and self-care, and no evidence of complications or untreated medical problems. Specific end points were defined for each of the criteria. Experts also agreed that after these criteria are achieved, discharge may take place as soon as the patient has adequate postdischarge support and is willing to leave the hospital. If a stoma was constructed, the patient or the patient's family should have received training on stoma care or had outpatient training arranged. LIMITATIONS: The panel comprised mostly experts from developed countries. This may restrict the applicability of these discharge criteria in countries where there are dissimilar health care resources. CONCLUSION: This Delphi study has provided substantial consensus on discharge criteria for patients undergoing colorectal surgery. We recommend that these criteria be used in clinical practice to guide decisions regarding patient discharge and applied in future research to increase the comparability of study results.