Use of Acetylcholinesterase Inhibitors in Reducing Time to Gastrointestinal Function Recovery following Abdominal Surgery: A Systematic Review.

INTRODUCTION: Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is one of the major pathways involved in developing POI, but current recommendations to prevent POI do not target this. This review aims to summarise evidence for the use of acetylcholinesterase inhibitors, neostigmine and pyridostigmine, to reduce the time to return of gastrointestinal function (GI) following abdominal surgery. METHODS: A systematic search of various databases was performed from 1946 to May 2023. Randomised controlled trials (RCTs) on acetylcholinesterase inhibitors in intra-abdominal surgery were included. Data on time to flatus and/or stool and side effects were extracted. RESULTS: Among 776 screened manuscripts, 8 RCTs (703 patients) investigating acetylcholinesterase inhibitors in intra-abdominal surgery were analysed. Five studies showed a significant reduction in time to flatus and/or stool by 17-47.6 h. Methodological variations, differing procedure types, and potential bias were observed. Limited studies reported side effects or length of stay. CONCLUSION: Acetylcholinesterase inhibitors may reduce the time for GI to return. However, current evidence is limited and biased. Further studies incorporating acetylcholinesterase inhibitors in an enhanced recovery protocol are required to address this question, especially for patients undergoing colorectal surgery.

Clinical predictors of rectal cancer response after neo-adjuvant (Chemo)Radiotherapy in Australia and New Zealand: Analysis of the Bi-National Colorectal Cancer Audit (BCCA).

Pathological complete response (pCR) is observed in 11-26% of locally advanced rectal cancers undergoing neoadjuvant chemoradiotherapy (nCRT). This study aims to determine pCR rates and clinicopathological predictors in the Australian and New Zealand (ANZ) cohort. The Bi-National Colorectal Cancer Audit (BCCA) was interrogated for all rectal cancer patients who underwent nCRT prior to surgical resection between 2007 and 2020. Patients were divided in two groups: pCR (AJCC tumour regression grade 0) and partial/no response (pPR, regression grade 1,2 or 3). In total, 3230 patients were included. Rates of pCR and pPR were 704 (21.8%) and 2526 (78.2%), respectively. Long-course nCRT (p < 0.0001), lower clinical tumour stage (cT; p < 0.0001), and nodal stage (cN; p = 0.003) were associated with pCR on univariate analysis. On multivariable analysis, cN0 stage and long-course nCRT remained independent factors for a pCR. Awareness of these predictors provides valuable information when counseling patients regarding prognosis and treatment options.

Global cost of postoperative ileus following abdominal surgery: meta-analysis.

BACKGROUND: Following abdominal surgery, postoperative ileus is a common complication significantly increasing patient morbidity and cost of hospital admission. This is the first systematic review aimed at determining the average global hospital cost per patient associated with postoperative ileus. METHODS: A systematic search of electronic databases was performed from January 2000 to March 2023. Studies included compared patients undergoing abdominal surgery who developed postoperative ileus to those who did not, focusing on costing data. The primary outcome was the total cost of inpatient stay. Risk of bias was assessed using the Newcastle-Ottawa assessment tool. Summary meta-analysis was performed. RESULTS: Of the 2071 studies identified, 88 papers were assessed for full eligibility. The systematic review included nine studies (2005-2022), investigating 1 860 889 patients undergoing general, colorectal, gynaecological and urological surgery. These studies showed significant variations in the definition of postoperative ileus. Six studies were eligible for meta-analysis showing an increase of €8233 (95 per cent c.i. (5176 to 11 290), P < 0.0001, I2 = 95.5 per cent) per patient with postoperative ileus resulting in a 66.3 per cent increase in total hospital costs (95 per cent c.i. (34.8 to 97.9), P < 0.0001, I2 = 98.4 per cent). However, there was significant bias between studies. Five colorectal-surgery-specific studies showed an increase of €7242 (95 per cent c.i. (4502 to 9983), P < 0.0001, I2 = 86.0 per cent) per patient with postoperative ileus resulting in a 57.3 per cent increase in total hospital costs (95 per cent c.i. (36.3 to 78.3), P < 0.0001, I2 = 85.7 per cent). CONCLUSION: The global financial burden of postoperative ileus following abdominal surgery is significant. While further multicentre data using a uniform postoperative ileus definition would be useful, reducing the incidence and impact of postoperative ileus are a priority to mitigate healthcare-related costs, and improve patient outcomes.

Evaluation of the EQ-5D-5L, EQ-VAS stand-alone component and Oxford knee score in the Australian knee arthroplasty population utilising minimally important difference, concurrent validity, predictive validity and responsiveness.

PURPOSE: To evaluate the Oxford Knee Score (OKS), EQ-5D-5L utility index and EQ-5D visual analogue scale (EQ-VAS) for health-related quality of life outcome measurement in patients undergoing elective total knee arthroplasty (TKA) surgery. METHODS: In this prospective multi-centre study, the OKS and EQ-5D-5L index scores were collected preoperatively, six weeks (6w) and six months (6 m) following TKA. The OKS, EQ-VAS and EQ-5D-5L index were evaluated for minimally important difference (MID), concurrent validity, predictive validity (Spearman's Rho of predicted and observed values from a generalised linear regression model (GLM)), responsiveness (effect size (ES) and standard response mean (SRM)). The MID for the individual patient was determined utilising two approaches; distribution-based and anchor-based. RESULTS: 533 patients were analysed. The EQ-5D-5L utility index showed good concurrent validity with the OKS (r = 0.72 preoperatively, 0.65 at 6w and 0.69 at 6 m). Predictive validity for the EQ-5D-5L index was lower than OKS when regressed. Responsiveness was large for all fields at 6w for the EQ-5D-5L and OKS (EQ-5D-5L ES 0.87, SRM 0.84; OKS ES 1.35, SRM 1.05) and 6 m (EQ-5D-5L index ES 1.31, SRM 0.95; OKS ES 1.69, SRM 1.59). The EQ-VAS returned poorer results, at 6w an ES of 0.37 (small) and SRM of 0.36 (small). At 6 m, the EQ-VAS had an ES of 0.59 (moderate) and SRM of 0.47 (small). It, however, had similar predictive validity to the OKS, and better than the EQ-5D-5L index. MID determined using anchor approach, was shown that for OKS at 6 weeks it was 8.84 ± 9.28 and at 6 months 13.37 ± 9.89. For the EQ-5D-5L index at 6 weeks MID was 0.23 ± 0.39, and at 6 months 0.26 ± 0.36. CONCLUSIONS: The EQ-5D-5L index score and the OKS demonstrate good concurrent validity. The EQ-5D-5L index demonstrated lower predictive validity at 6w, and 6 m than the OKS, and both PROMs had adequate responsiveness. The EQ-VAS had poorer responsiveness but better predictive validity than the EQ-5D-5L index. This article includes MID estimates for the Australian knee arthroplasty population.

A multi-disciplinary program for opioid sparse arthroplasty results in reduced long-term opioid consumption: a four year prospective study.

INTRODUCTION: The current opioid epidemic poses patient safety and economic burdens to healthcare systems worldwide. Postoperative prescriptions of opioids contribute, with reported opioid prescription rates following arthroplasty as high as 89%. In this multi-centre prospective study, an opioid sparing protocol was implemented for patients undergoing knee or hip arthroplasty. The primary outcome is to report our patient outcomes in the context of this protocol, and to examine the rate of opioid prescription on discharge from our hospitals following joint arthroplasty surgery. This is possibly associated with the efficacy of the newly implemented Arthroplasty Patient Care Protocol. METHODS: Over three years, patients underwent perioperative education with the expectation to be opioid-free after surgery. Intraoperative regional analgesia, early postoperative mobilisation and multimodal analgesia were mandatory. Long-term opioid medication use was monitored and PROMs (Oxford Knee/Hip Score (OKS/OHS), EQ-5D-5 L) were evaluated pre-operatively, and at 6 weeks, 6 months and 1 year postoperatively. Primary and secondary outcomes were opiate use and PROMs at different time points. RESULTS: A total of 1,444 patients participated. Two (0.2%) knee patients used opioids to one year. Zero hip patients used opioids postoperatively at any time point after six weeks (p < 0.0001). The OKS and EQ-5D-5 L both improved for knee patients from 16 (12-22) pre-operatively to 35 (27-43) at 1 year postoperatively, and 70 (60-80) preoperatively to 80 (70-90) at 1 year postoperatively (p < 0.0001). The OHS and EQ-5D-5 L both improved for hip patients from 12 (8-19) preoperatively to 44 (36-47) at 1 year postoperatively, and 65 (50-75) preoperatively to 85 (75-90) at 1 year postoperatively (p < 0.0001). Satisfaction improved between all pre- and postoperative time points for both knee and hip patients (p < 0.0001). CONCLUSIONS: Knee and hip arthroplasty patients receiving a peri-operative education program can effectively and satisfactorily be managed without long-term opioids when coupled with multimodal perioperative management, making this a valuable approach to reduce chronic opioid use.

Short-term difference only in reported outcomes (PROMs) after anterior or posterior approach to total hip arthroplasty: a 4-year prospective multi-centre observational study.

BACKGROUND: The direct anterior approach (DAA) in total hip arthroplasty (THA) may demonstrate better functional recovery compared to the posterior approach (PA). METHODS: In this prospective multi-centre study, patient-related outcome measures (PROMs) and length of stay (LOS) were compared between DAA and PA THA patients. The Oxford Hip Score (OHS), EQ-5D-5L, pain and satisfaction scores were collected at four perioperative stages. RESULTS: 337 DAA and 187 PA THAs were included. The OHS PROM was significantly better in the DAA group at 6 weeks post-operatively (OHS: 33 vs. 30, p = 0.02, EQ-5D-5L: 80 vs. 75, p = 0.03), but there were no differences at 6 months and at 1 year. EQ-5D-5L scores were similar between both groups at all time points. LOS as inpatient was significantly different, in favour of DAA [median 2 days (IQR 2-3) vs. PA 3 (IQR 2-4), p ≤ 0.0001]. CONCLUSIONS: Patients undergoing DAA THA have shorter LOS and report better short-term Oxford Hip Score PROMs at 6 weeks, but DAA did not convey long-term benefits over PA THA.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

A prospective study of diagnostic accuracy of multidisciplinary team and radiology reporting of preoperative colorectal cancer local staging.

INTRODUCTION: The aim of this study was to correlate and assess diagnostic accuracy of preoperative staging at multidisciplinary team meeting (MDT) against the original radiology reports and pathological staging in colorectal cancer patients. METHODS: A prospective observational study was conducted at two institutions. Patients with histologically proven colorectal cancer and available preoperative imaging were included. Preoperative tumor and nodal staging (cT and cN) as determined by the MDT and the radiology report (computed tomography [CT] and/or magnetic resonance imaging [MRI]) were recorded. Kappa statistics were used to assess agreement between MDT and the radiology report for cN staging in colon cancer, cT and cN in rectal cancer, and tumor regression grade (TRG) in patients with rectal cancer who received neoadjuvant therapy. Pathological report after surgery served as the reference standard for local staging, and AUROC curves were constructed to compare diagnostic accuracy of the MDT and radiology report. RESULTS: A total of 481 patients were included. Agreement between MDT and radiology report for cN stage was good in colon cancer (k = .756, Confidence Interval (CI) 95% .686-.826). Agreement for cT and cN and in rectal cancer was very good (kw = .825, CI 95% .758-.892) and good (kw = .792, CI 95% .709-.875), respectively. In the rectal cancer group that received neoadjuvant therapy, agreement on TRG was very good (kw = .919, CI 95% .846-.993). AUROC curves using pathological staging indicated no difference in diagnostic accuracy between MDT and radiology reports for either colon or rectal cancer. CONCLUSION: Preoperative colorectal cancer local staging was consistent between specialist MDT review and original radiology reports, with no significant differences in diagnostic accuracy identified.

Safety and efficacy of short-course intravenous antibiotics after complicated appendicitis in selected patients.

BACKGROUND: After surgery for complicated appendicitis (CA), common practice is to treat all patients with a standardised long-course of intravenous antibiotics (IVAB) to reduce the risk of postoperative surgical infections (PSI). The aim of the current study was to evaluate the safety and efficacy of a short-course IVAB after CA in selected patients. METHODS: The Department's prospectively collected database identified CA patients treated between2015 and 2019. Baseline and treatment characteristics and postoperative outcomes were analysed. The cut-off between short- and long-course IVAB was 2 days. Outcomes of interest were PSI and 30-day unplanned readmission. RESULTS: In total, 226 patients had CA: Ninety-nine CA (43.8%) received short-course IVAB and 127 (56.2%) received long-course. PSI occurred in 6% and 10% of the short-course and long-course patients, respectively (p = 0.34). Length of IVAB after a PSI was comparable to that of patients without PSI (median 3 and 2 days of IVAB respectively; p = 0.28). 30-day unplanned readmission rates were 7% and 6%, respectively (p = 0.99). Length of IVAB for readmitted patients was similar to those who were not readmitted (median 3 days of IVAB in both; p = 0.91). Multivariable analysis showed that the intraoperative findings of the appendix (p = 0.04) was a prognostic predictor for PSI. ASA score (p = 0.02) and surgical approach (p = 0.05) were prognostic predictors for 30-day unplanned readmission. CONCLUSIONS: This study shows that when patients respond well, a short-course IVAB can safely be applied after CA without increasing risk of PSI or 30-day unplanned readmission.

Outcomes of open vs laparoscopic vs robotic vs transanal total mesorectal excision (TME) for rectal cancer: a network meta-analysis.

BACKGROUND: Total mesorectal excision (TME) for rectal cancer can be achieved using open (OpTME), laparoscopic (LapTME), robotic (RoTME), or transanal techniques (TaTME). However, the optimal approach for access remains controversial. The aim of this network meta-analysis was to assess operative and oncological outcomes of all four surgical techniques. METHODS: Ovid MEDLINE, EMBASE, and PubMed databases were searched systematically from inception to September 2020, for randomised controlled trials (RCTs) comparing any two TME surgical techniques. A network meta-analysis using a Bayesian random-effects framework and mixed treatment comparison was performed. Primary outcomes were the rate of clear circumferential resection margin (CRM), defined as > 1 mm from the closest tumour to the cut edge of the tissue, and completeness of mesorectal excision. Secondary outcomes included radial and distal resection margin distance, postoperative complications, locoregional recurrence, disease-free survival, and overall survival. Surface under cumulative ranking (SUCRA) was used to rank the relative effectiveness of each intervention for each outcome. The higher the SUCRA value, the higher the likelihood that the intervention is in the top rank or one of the top ranks. RESULTS: Thirty-two RCTs with a total of 6151 patients were included. Compared with OpTME, there was no difference in the rates of clear CRM: LapTME RR = 0.99 (95% (Credible interval) CrI 0.97-1.0); RoTME RR = 1.0 (95% CrI 0.96-1.1); TaTME RR = 1.0 (95% CrI 0.96-1.1). There was no difference in the rates of complete mesorectal excision: LapTME RR = 0.98 (95% CrI 0.98-1.1); RoTME RR = 1.1 (95% CrI 0.98-1.4); TaTME RR = 1.0 (95% CrI 0.91-1.2). RoTME was associated with improved distal resection margin distance compared to other techniques (SUCRA 99%). LapTME had a higher rate of conversion to open surgery when compared with RoTME: RoTME RR = 0.23 (95% CrI 0.034-0.70). Length of stay was shortest in RoTME compared to other surgical approaches: OpTME mean difference in days (MD) 3.3 (95% CrI 0.12-6.0); LapTME MD 1.7 (95% CrI - 1.1-4.4); TaTME MD 1.3 (95% CrI - 5.2-7.4). There were no differences in 5-year overall survival (LapTME HR 1.1, 95% CrI 0.74, 1.4; TaTME HR 1.7, 95% CrI 0.79, 3.4), disease-free survival rates (LapTME HR 1.1, 95% CrI 0.76, 1.4; TaTME HR 1.1, 95% CrI 0.52, 2.4), or anastomotic leakage (LapTME RR = 0.92 (95% CrI 0.63, 1.1); RoTME RR = 1.0 (95% CrI 0.48, 1.8); TaTME RR = 0.53 (95% CrI 0.19, 1.2). The overall quality of evidence as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments across all outcomes including primary and secondary outcomes was deemed low. CONCLUSIONS: In selected patients eligible for a RCT, RoTME achieved improved distal resection margin distance and a shorter length of hospital stay. No other differences were observed in oncological or recovery parameters between (OpTME), laparoscopic (LapTME), robotic (RoTME), or trans-anal TME (TaTME). However, the overall quality of evidence across all outcomes was deemed low.

Association of anesthesia and analgesia with long-term mortality after hip fracture surgery: an analysis of the Australian and New Zealand hip fracture registry.

INTRODUCTION: Hip fractures are a common frailty injury affecting a vulnerable geriatric population. It is debated if anesthetic and analgesic techniques are associated with altered risk for outcomes in hip fracture patients. This study aimed to determine the association of anesthesia and regional analgesia with all cause 12-month mortality and even longer-term mortality after hip fracture surgery in Australia and New Zealand. METHODS: Data from the Australian and New Zealand Hip Fracture Registry collected from 2016 to 2018, with a minimum follow-up of 12 months, were reviewed. Anesthesia type and use of regional nerve blocks were investigated. The primary outcome was all cause 12-month mortality. RESULTS: 12-month mortality was 30.6% (n=5410) in a total of 17,635 patients. There was no difference in 12-month mortality between patients who received spinal or general anesthesia (p=0.238). The administration of a combination of general and spinal anesthesia for surgery to repair the fracture was an independent predictor of higher 12-month mortality (unadjusted complete case HR=1.17 (95% CI 1.04 to 1.31); p<0.001). Nerve blocks performed in both the emergency department (ED) and the operating theater (OT) were associated with reduced long-term mortality (median follow-up 21 months) with an unimputed unadjusted HR=0.86 (95% CI 0.77 to 0.96; p=0.043). CONCLUSION: There was no difference in the association of 12-month mortality between general and spinal anesthesia in patients undergoing hip fracture surgery. However, there was an association with a higher risk of 12-month mortality in patients who received both general and spinal anesthesia for the same surgery. Patients who received a regional nerve block in both the ED and the OT had a lower association of 12-month and longer-term mortality risk. The reasons for these findings remain unknown and should be the subject of further research investigation.

The Pericapsular Nerve Group (PENG) block combined with Local Infiltration Analgesia (LIA) compared to placebo and LIA in hip arthroplasty surgery: a multi-center double-blinded randomized-controlled trial.

BACKGROUND: The PEricapsular Nerve Group (PENG) block is a novel regional analgesia technique that provides improved analgesia in patients undergoing hip surgery while preserving motor function. In this study the PENG block was investigated for analgesia in elective total hip arthroplasty (THA). METHODS: In this multi-centre double-blinded randomized-controlled trial, in addition to spinal anesthesia and local infiltration analgesia (LIA), THA patients received either a PENG block or a sham block. The primary outcome was pain score (numeric rating scale 0-10) 3 h postoperatively (Day 0). Secondary outcomes were postoperative quadriceps muscle strength, postoperative Day 1 pain scores, opiate use, complications, length of hospital stay, and patient-reported outcome measures. RESULTS: Sixty patients were randomized and equally allocated between groups. Baseline demographics were similar. Postoperative Day 0, the PENG group experienced less pain compared to the sham group (PENG: 14 (47%) patients no pain, 14 (47%) mild pain, 2 (6%) moderate/severe pain versus sham: 6 (20%) no pain, 14 (47%) mild pain, 10 (33%) moderate/severe pain; p = 0.03). There was no difference in quadriceps muscle strength between groups on Day 0 (PENG: 23 (77%) intact versus sham: 24 (80%) intact; p = 0.24) and there were no differences in other secondary outcomes. CONCLUSIONS: Patients receiving a PENG block for analgesia in elective THA experience less postoperative pain on Day 0 with preservation of quadriceps muscle strength. Despite these short-term benefits, no quality of recovery or longer lasting postoperative effects were detected.

Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

PURPOSE: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. METHODS: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. RESULTS: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. CONCLUSION: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

Cost of postoperative ileus following colorectal surgery: A cost analysis in the Australian public hospital setting.

AIM: Postoperative ileus (POI) following surgery results in significant morbidity, drastically increasing hospital costs. As there are no specific Australian data, this study aimed to measure the cost of POI after colorectal surgery in an Australian public hospital. METHODS: A cost analysis was performed, for major elective colorectal surgical cases between 2018 and 2021 at the Royal Adelaide Hospital. POI was defined as not achieving GI-2, the validated composite measure, by postoperative day 4. Demographics, length of stay and 30-day complications were recorded retrospectively. Costings in Australian dollars were collected from comprehensive hospital billing data. Univariate and multivariate analyses were performed. RESULTS: Of the 415 patients included, 34.9% (n = 145) developed POI. POI was more prevalent in males, smokers, previous intra-abdominal surgery, and converted laparoscopic surgery (p < 0.05). POI was associated with increased length of stay (8 vs. 5 days, p < 0.001) and with higher rates of complications such as pneumonia (15.2% vs. 8.1%, p = 0.027). Total cost of inpatient care was 26.4% higher after POI (AU$37,690 vs. AU$29,822, p < 0.001). POI was associated with increased staffing costs, as well as diagnostics, pharmacy, and hospital services. On multivariate analysis POI, elderly patients, stoma formation, large bowel surgery, prolonged theatre time, complications and length of stay were predictive of increased costs (p < 0.05). CONCLUSION: In Australia, POI is significantly associated with increased complications and higher costs due to prolonged hospital stay and increased healthcare resource utilisation. Efforts to reduce POI rates could diminish its morbidity and associated expenses, decreasing the burden on the healthcare system.

A longitudinal validation of the EQ-5D-5L and EQ-VAS stand-alone component utilising the Oxford Hip Score in the Australian hip arthroplasty population.

PURPOSE: To evaluate the measurement properties of the Oxford Hip Score (OHS), EQ-5D-5L utility index and EQ-5D-5L visual analogue scale (EQ-VAS) in patients undergoing elective total hip arthroplasty in Australia. METHODS: In this prospective multi-centre study, the OHS and EQ-5D-5L were collected preoperatively, six weeks (6w) and six months (6m) postoperatively. The OHS, EQ-VAS and EQ-5D-5L index were evaluated for concurrent validity, predictive validity (Spearman's Rho of predicted and observed values from a generalised linear regression model (GLM)), and responsiveness (effect size (ES) and standard response mean (SRM)). RESULTS: 362 patients were included in this analysis for 6w and 269 for 6m. The EQ-5D-5L index showed good concurrent validity with the OHS (r = 0.71 preoperatively, 0.61 at 6w and 0.59 at 6m). Predictive validity for EQ-5D-5L index was similar to OHS when regressed (GLM). Responsiveness was good at 6w (EQ-5D-5L index ES 1.53, SRM 1.40; OHS ES 2.16, SRM 1.51) and 6m (EQ-5D-5L index ES 1.88, SRM 1.70; OHS ES 3.12, SRM 2.24). The EQ-VAS returned poorer results, at 6w an ES of 0.75 (moderate) and SRM 0.8. At 6m the EQ-VAS had an ES of 0.92 and SRM of 1.00. It, however, had greater predictive validity. CONCLUSIONS: The EQ-5D-5L index and the OHS demonstrate strong concurrent validity. The EQ-5D-5L index demonstrated similar predictive validity at 6w and 6m, and both PROMs had adequate responsiveness. The EQ-VAS should be used routinely together with the EQ-5D-5L index. The EQ-5D-5L is suitable to quantify health-related quality of life in Australian hip arthroplasty patients.

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs. METHODS: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed. RESULTS: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3-15%) compared to LLND- (11-27%; RR = 0.40, 95%CI [0.25-0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61-78% vs. 46-79% for LLND-; RR = 0.72, 95%CI [0.51-1.02], p = 0.143), and neither was five-year OS (range 69-91% vs. 72-80%; RR = 0.72, 95%CI [0.45-1.14], p = 0.163). CONCLUSION: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.

Regional variance in treatment and outcomes of locally invasive (T4) rectal cancer in Australia and New Zealand: analysis of the Bi-National Colorectal Cancer Audit.

BACKGROUNDS: Locally invasive T4 rectal cancer often requires neoadjuvant treatment followed by multi-visceral surgery to achieve a radical resection (R0), and referral to a specialized exenteration quaternary centre is typically recommended. The aim of this study was to explore regional variance in treatment and outcomes of patients with locally advanced rectal cancer in Australia and New Zealand (ANZ). METHODS: Data were collected from the Bi-National Colorectal Cancer Audit (BCCA) database. Rectal cancer patients treated between 2007 and 2019 were divided into six groups based on region (state/country) using patient postcode. A subset analysis of patients with T4 cancer was performed. Primary outcomes were positive circumferential resection margin (CRM+), and positive circumferential and/or distal resection margin (CRM/DRM+). RESULTS: A total of 9385 patients with rectal cancer were identified, with an overall CRM+ rate of 6.4% and CRM/DRM+ rate of 8.6%. There were 1350 patients with T4 rectal cancer (14.4%). For these patients, CRM+ rate was 18.5%, and CRM/DRM+ rate was 24.1%. Significant regional variation in CRM+ (range 13.4-26.0%; p = 0.025) and CRM/DRM+ rates (range 16.1-29.3%; p = 0.005) was identified. In addition, regions with higher CRM+ and CRM/DRM+ rates reported lower rates of multi-visceral resections: range 24.3-26.8%, versus 32.6-37.3% for regions with lower CRM+ and CRM/DRM+ rates (p < 0.0001). CONCLUSION: Positive resection margins and rates of multi-visceral resection vary between the different regions of ANZ. A small subset of patients with T4 rectal cancer are particularly at risk, further supporting the concept of referral to specialized exenteration centres for potentially curative multi-visceral resection.

A snapshot of intraoperative conditions to predict prolonged postoperative ileus after colorectal surgery.

BACKGROUND: The cause of prolonged postoperative ileus (PPOI) is multifactorial. The influence of preoperative factors on PPOI has been well documented, but little is known about the impact of intraoperative conditions. The aim of this study was to investigate the influence of intraoperative factors on PPOI in patients undergoing colorectal surgery. METHODS: The LekCheck study database of the Colorectal Unit at the Royal Adelaide Hospital was analysed. Per patient, over 60 data points were prospectively collected between March 2018 and July 2020. Intraoperative data were collected in theatre during a one-off snapshot measure. Univariate and multivariable logistic regression analyses were performed. RESULTS: Data of 336 patients were included. The median age was 66 years and 58.3% were male. Ninety-three patients (27.7%) developed PPOI. Univariate analysis identified the following intraoperative variables as risk-factors of PPOI: greater volumes of intraoperative IV fluid administration (464 versus 415 mL/h for those without PPOI; p = 0.04), side-to-side anastomosis orientation (53.8 versus 41.2%; p = 0.04) and increased perioperative opioid use (6.73 versus 4.11 mg/kg morphine equivalents for patients with and without PPOI, respectively; p = 0.02). Upon multivariable analysis, increased perioperative opioid use remained significant (p = 0.05), as well as the preoperative factors anticoagulation use (p = 0.04) and higher levels of serum total protein (p = 0.02). CONCLUSION: This study suggests that intraoperative factors may also contribute to the development of PPOI, but this could not be confirmed in the multivariate analysis. Further studies including larger patient numbers will be required to determine the impact of intraoperative conditions on the development of PPOI.