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.

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.

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.

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.

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.

LekCheck: A Prospective Study to Identify Perioperative Modifiable Risk Factors for Anastomotic Leakage in Colorectal Surgery.

OBJECTIVE: To assess potentially modifiable perioperative risk factors for anastomotic leakage in adult patients undergoing colorectal surgery. SUMMARY BACKGROUND DATA: Colorectal anastomotic leakage (CAL) is the single most important denominator of postoperative outcome after colorectal surgery. To lower the risk of CAL, the current research focused on the association of potentially modifiable risk factors, both surgical and anesthesiological. METHODS: A consecutive series of adult patients undergoing colorectal surgery with primary anastomosis was enrolled from January 2016 to December 2018. Fourteen hospitals in Europe and Australia prospectively collected perioperative data by carrying out the LekCheck, a short checklist carried out in the operating theater as a time-out procedure just prior to the creation of the anastomosis to check perioperative values on 1) general condition 2) local perfusion and oxygenation, 3) contamination, and 4) surgery related factors. Univariate and multivariate logistic regression analysis were performed to identify perioperative potentially modifiable risk factors for CAL. RESULTS: There were 1562 patients included in this study. CAL was reported in 132 (8.5%) patients. Low preoperative hemoglobin (OR 5.40, P < 0.001), contamination of the operative field (OR 2.98, P < 0.001), hyperglycemia (OR 2.80, P = 0.003), duration of surgery of more than 3 hours (OR 1.86, P = 0.010), administration of vasopressors (OR 1.80, P = 0.010), inadequate timing of preoperative antibiotic prophylaxis (OR 1.62, P = 0.047), and application of epidural analgesia (OR, 1.81, P = 0. 014) were all associated with CAL. CONCLUSIONS: This study identified 7 perioperative potentially modifiable risk factors for CAL. The results enable the development of a multimodal and multidisciplinary strategy to create an optimal perioperative condition to finally lower CAL rates.

Malignant Features in Pretreatment Metastatic Lateral Lymph Nodes in Locally Advanced Low Rectal Cancer Predict Distant Metastases.

INTRODUCTION: Pretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known of the impact on oncological outcomes when in addition malignant features are present in enlarged LLN. PATIENTS AND METHODS: A multicenter retrospective cohort study was conducted at five tertiary referral centers in the Netherlands and Australia. All patients were diagnosed with locally advanced low rectal cancer with LLN on pretreatment magnetic resonance imaging (MRI) and underwent n(C)RT followed by TME. LLN were considered enlarged with a short axis of ≥ 5 mm. Malignant features were defined as nodes with internal heterogeneity and/or border irregularity. Outcomes of interest were local recurrence-free survival (LRFS), distant metastatic-free survival (DMFS), and overall survival (OS). RESULTS: Out of 115 patients, the majority was male (75%) and the median age was 64 years (range 26-85 years). Median pretreatment LLN short axis was 7 mm (range 5-28 mm), and 60 patients (52%) had malignant features. After a median follow-up of 47 months, patients with larger LLN (7 + mm) had a worse LRFS (p = 0.01) but no difference in DMFS (p = 0.37) and OS (p = 0.54) compared with patients with smaller LLN (5-6 mm). LLN patients with malignant features had no difference in LRFS (p = 0.20) but worse DMFS (p = 0.004) and OS (p = 0.006) compared with patients without malignant features in the LLN. Cox regression analysis identified LLN short axis as an independent factor for LR. Malignant features in LLN were an independent factor for DMFS. CONCLUSION: The current study suggests that pretreatment enlarged LLN that also harbor malignant features are predictive of a worse DMFS. More studies will be required to further explore the role of malignant features in LLN.

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.

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.

Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

Artificial intelligence for pre-operative lymph node staging in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Artificial intelligence (AI) is increasingly being used in medical imaging analysis. We aimed to evaluate the diagnostic accuracy of AI models used for detection of lymph node metastasis on pre-operative staging imaging for colorectal cancer. METHODS: A systematic review was conducted according to PRISMA guidelines using a literature search of PubMed (MEDLINE), EMBASE, IEEE Xplore and the Cochrane Library for studies published from January 2010 to October 2020. Studies reporting on the accuracy of radiomics models and/or deep learning for the detection of lymph node metastasis in colorectal cancer by CT/MRI were included. Conference abstracts and studies reporting accuracy of image segmentation rather than nodal classification were excluded. The quality of the studies was assessed using a modified questionnaire of the QUADAS-2 criteria. Characteristics and diagnostic measures from each study were extracted. Pooling of area under the receiver operating characteristic curve (AUROC) was calculated in a meta-analysis. RESULTS: Seventeen eligible studies were identified for inclusion in the systematic review, of which 12 used radiomics models and five used deep learning models. High risk of bias was found in two studies and there was significant heterogeneity among radiomics papers (73.0%). In rectal cancer, there was a per-patient AUROC of 0.808 (0.739-0.876) and 0.917 (0.882-0.952) for radiomics and deep learning models, respectively. Both models performed better than the radiologists who had an AUROC of 0.688 (0.603 to 0.772). Similarly in colorectal cancer, radiomics models with a per-patient AUROC of 0.727 (0.633-0.821) outperformed the radiologist who had an AUROC of 0.676 (0.627-0.725). CONCLUSION: AI models have the potential to predict lymph node metastasis more accurately in rectal and colorectal cancer, however, radiomics studies are heterogeneous and deep learning studies are scarce. TRIAL REGISTRATION: PROSPERO CRD42020218004 .

Current practice in Australia and New Zealand for defunctioning ileostomy after rectal cancer surgery with anastomosis: Analysis of the Binational Colorectal Cancer Audit.

AIM: This study aimed to investigate the use of defunctioning stomas after rectal cancer surgery in Australia and New Zealand, as current practice is unknown. METHODS: From the Binational Colorectal Cancer Audit database, data on rectal cancer patients who underwent a resection between 2007 and 2019 with the formation of an anastomosis were extracted and analysed. The primary outcome was the rate of defunctioning stoma formation. Secondary outcomes were anastomotic leakage (AL) rates and other postoperative complications, length of hospital stay (LOS), readmissions and 30-day mortality rates between stoma and no-stoma groups. Propensity score matching was performed to correct for differences in baseline characteristics between stoma and no-stoma groups. RESULTS: In total, 2581 (89%) received a defunctioning stoma and 319 (11%) did not. There were more male patients in the stoma group (65.5% vs. 57.7% for the no-stoma group; P = 0.006). The median age was 64 years in both groups. The stoma group underwent more ultra-low anterior resections (79.9% vs. 30.1%; P < 0.0001), included more American Joint Committee on Cancer Stage III patients (53.7% vs. 29.2%; P < 0.0001) and received more neoadjuvant therapy (66.9% vs. 16.3%; P < 0.0001). The AL rate was similar in both groups (5.1% vs. 6.0%; P = 0.52). LOS was longer in the stoma group (8 vs. 6 days; P < 0.0001) with higher 30-day readmission rates (14.9% vs. 8.3%; P = 0.003). After propensity score matching (n = 208 in both groups), AL rates remained similar (2.9% for stoma vs. 5.8% for no-stoma group; P = 0.15), but stoma patients required less reoperations (0% vs. 8%; P = 0.016). The stoma group had higher postoperative ileus rates and an increased LOS. CONCLUSION: In Australia and New Zealand, most patients who underwent rectal cancer resections with the formation of an anastomosis received a defunctioning stoma. A defunctioning stoma does not prevent AL from occurring but is mostly associated with a lower reoperation rate. Patients with a defunctioning stoma experienced a higher postoperative ileus rate and had an increased LOS.

PyRICo-Pilot: pyridostigmine to reduce the duration of postoperative ileus after colorectal surgery - a phase II study.

AIM: Postoperative ileus (POI) is a major problem after colorectal surgery. Acetylcholinesterase inhibitors such as pyridostigmine increase gastrointestinal (GI) motility through a cholinergic anti-inflammatory pathway. The purpose of this phase II pilot study is to determine the safety of oral pyridostigmine after elective colorectal surgery. METHOD: This is a Stage 2b safety study (IDEAL framework). All adult patients undergoing elective colorectal resection or formation or reversal of stoma at the Royal Adelaide Hospital between September 2020 and January 2021 were eligible. The primary outcomes were 30-day postoperative complications, reported adverse events and GI-2 - a validated composite outcome measure of recovery of GI function after surgery, defined as the interval from surgery until first passage of stool and tolerance of a solid intake for 24 h (in whole days) in the absence of vomiting. RESULTS: Fifteen patients were included in the study. The median age was 58 (range 50-82) years and seven (47%) were men. Most participants had an American Society of Anesthesiologists grade ≥2 (53%) and the median body mass index was 27 (24-35) kg/m2 . There were 13 postoperative complications [seven were Clavien-Dindo (CD) 1, five CD 2 and one CD 3]. None appeared directly related to pyridostigmine administration, and none of the patients had any overt symptoms of excessive parasympathetic activity. Median GI-2 was 2 (1-4) days. CONCLUSION: Oral pyridostigmine appears to be safe to use after elective colorectal surgery in a select group of patients. However, considering this is a pilot study with a small sample size, larger controlled studies are needed to confirm this finding and establish efficacy for prevention of POI.

Oncologic Outcomes After Isolated Limb Infusion for Advanced Melanoma: An International Comparison of the Procedure and Outcomes Between the United States and Australia.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS). METHODS: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes. RESULTS: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013). CONCLUSIONS: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients.

BACKGROUND: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

Outcomes of Minimally Invasive Versus Open Proctectomy for Rectal Cancer: A Propensity-Matched Analysis of Bi-National Colorectal Cancer Audit Data.

BACKGROUND: Minimally invasive surgery is commonly used in the treatment of rectal cancer, despite the lack of evidence to support oncological equivalence or improved recovery compared with open surgery. OBJECTIVE: This study aims to analyze prospectively collected data from a large Australasian colorectal cancer database. DESIGN: This is a retrospective cohort study using propensity score matching. SETTING: This study was conducted using data supplied by the Bi-National Colorectal Cancer Audit. PATIENTS: A total of 3451 patients who underwent open (n = 1980), laparoscopic (n = 1269), robotic (n = 117), and transanal total mesorectal excision (n = 85) for rectal cancer were included in this study. MAIN OUTCOME MEASURE: The primary outcome was positive margin rates (circumferential resection margin and/or distal resection margin) in patients treated with curative intent. RESULTS: Propensity score matching yielded 1132 patients in each of the open and minimally invasive surgery groups. Margin positivity rates and lymph node yields did not differ between groups. The open group had a significantly lower total complication rate (27.6% vs 35.8%, p < 0.0001), including a lower rate of postoperative small-bowel obstruction (1.2% vs 2.5%, p = 0.03). The minimally invasive surgery group had significantly lower wound infection rate (2.9% vs 5.0%, p = 0.02) and a shorter length of hospital stay (8 vs 9 days, p < 0.0001). There was no difference in 30-day mortality. LIMITATIONS: Results are limited by the quality of registry data entries. CONCLUSION: In this patient population, minimally invasive proctectomy demonstrated similar margin rates in comparison with open proctectomy, with a reduced length of stay but a higher overall complication rate. See Video Abstract at http://links.lww.com/DCR/B190. RESULTADOS DE LA PROCTECTOMÍA MÍNIMA INVASIVA VERSUS ABIERTA PARA EL CÁNCER DE RECTO: UN ANÁLISIS DE PROPENSIÓN DE LOS DATOS BINACIONALES DE AUDITORÍA DEL CÁNCER COLORRECTAL: La cirugía mínima invasiva, frecuentemente se utiliza en el tratamiento del cáncer rectal, a pesar de la falta de evidencia que respalde la equivalencia oncológica o la mejor recuperación, en comparación con la cirugía abierta.El estudio tiene como objetivo analizar datos prospectivamente obtenidos, de una gran base de datos de cáncer colorrectal de Australia.Estudio de cohorte retrospectivo utilizando el emparejamiento de puntaje de propensión.Este estudio se realizó utilizando datos proporcionados por la Auditoría Binacional del Cáncer Colorrectal.Se incluyeron en este estudio un total de 3451 pacientes que se trataron de manera abierta (n = 1980), laparoscópica (n = 1269), robótica (n = 117) y taTME (n = 85) para cáncer rectal.Los resultados primarios fueron de tasas de margen positivas (margen de resección circunferencial y/o margen de resección distal) en pacientes con intención curativa.La coincidencia de puntaje de propensión arrojó 1132 pacientes en cada uno de los grupos de cirugía abierta y mínima invasiva. Las tasas de positividad del margen y los rendimientos de los ganglios linfáticos no difirieron entre los dos grupos. El grupo abierto tuvo una tasa de complicaciones totales significativamente menor (27.6% vs 35.8%, p <0.0001), incluida una tasa menor de obstrucción postoperatoria del intestino delgado (1.2% vs 2.5%, p = 0.03). El grupo de cirugía mínimamente invasiva tuvo una tasa de infección de la herida significativamente menor (2.9% frente a 5.0%, p = 0,02) y una estancia hospitalaria más corta (8 frente a 9 días, p <0.0001). No hubo diferencias en la mortalidad a los 30 días.Los resultados están limitados por la calidad de la entrada de datos de registro.En esta población de pacientes, la proctectomía mínima invasiva demostró tasas de margen similares en comparación con la proctectomía abierta, con una estadía reducida pero una tasa más alta de complicaciones en general. Consulte Video Resumen en http://links.lww.com/DCR/B190. (Traducción-Dr. Fidel Ruiz Healy).

A global survey of surgeons' preferences and practice with regard to laxative use after elective colorectal surgery.

PURPOSE: The role of laxatives after elective colorectal surgery is unclear, resulting in heterogenous guidelines and variability in clinical practice. This study aimed to gauge surgeons' preferences and practice with regard to laxative use following elective colorectal surgery. METHODS: A short one-minute anonymous web-based questionnaire designed in English and Chinese (Mandarin) using the Research Electronic Data Capture application (REDCap) was distributed to member surgeons of every identifiable international colorectal specialist society via email communication, physical newsletters and social media channels. Frequency of laxative use after elective colorectal surgery, type of laxative used, and, if not used, the reasons for not using laxatives were collected. RESULTS: A total of 852 surgeons, representing 28 surgical societies completed the survey: 80% were colorectal surgeons and 20% were general surgeons with colorectal interest. Twenty-seven percent of the respondents routinely prescribed laxatives after colorectal surgery. There was wide variation in the type of laxatives used, with magnesium-based laxatives (42%), macrogol (Movicol, 36%) and lactulose (Duphalac, 22%) being the most common. Geographical location was correlated with choice of laxative. Those not routinely using laxatives stated the reasons as being no evidence for benefit (48%), potential of adverse events (24%), more than one reason (21%) and other (7%). The majority (93%) non-users would consider using laxatives if better evidence was available. CONCLUSION: Most surgeons do not routinely prescribe laxatives after elective colorectal surgery due to lack of evidence. Amongst those surgeons who do use them, there is wide variability in the type of laxatives used.

Long-Term Oncologic Outcomes After Isolated Limb Infusion for Locoregionally Metastatic Melanoma: An International Multicenter Analysis.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma located on a limb. The current international multicenter study evaluated the perioperative and long-term oncologic outcomes for patients who underwent ILI for stage 3B or 3C melanoma. METHODS: Patients undergoing a first-time ILI for stage 3B or 3C melanoma (American Joint Committee on Cancer [AJCC] 7th ed) between 1992 and 2018 at five Australian and four United States of America (USA) tertiary referral centers were identified. The primary outcome measures included treatment response, in-field (IPFS) and distant progression-free survival (DPFS), and overall survival (OS). RESULTS: A total of 687 first-time ILIs were performed (stage 3B: n = 383, 56%; stage 3C; n = 304, 44%). Significant limb toxicity (Wieberdink grade 4) developed in 27 patients (3.9%). No amputations (grade 5) were performed. The overall response rate was 64.1% (complete response [CR], 28.9%; partial response [PR], 35.2%). Stable disease (SD) occurred in 14.5% and progressive disease (PD) in 19.8% of the patients. The median follow-up period was 47 months, with a median OS of 38.2 months. When stratified by response, the patients with a CR or PR had a significantly longer median IPFS (21.9 vs 3.0 months; p < 0.0001), DPFS (53.6 vs 12.7 months; p < 0.0001), and OS (46.5 vs 24.4 months; p < 0.0001) than the nonresponders (SD + PD). CONCLUSION: This study is the largest to date reporting long-term outcomes of ILI for locoregionally metastatic melanoma. The findings demonstrate that ILI is effective and safe for patients with stage 3B or 3C melanoma confined to a limb. A favorable response to ILI is associated with significantly longer IFPS, DPFS, and OS.

Treatment of Clinically Positive Cervical Lymph Nodes by Limited Local Node Excision and Adjuvant Radiotherapy in Melanoma Patients with Major Comorbidities.

INTRODUCTION: When cervical lymph nodes are clinically positive for metastatic melanoma, surgeons may be hesitant to recommend a therapeutic complete lymph node dissection if the patient is elderly or has major comorbidities. A limited local node excision of the clinically positive nodes only, followed by adjuvant radiotherapy to the entire node field, may be an effective alternative in such patients. METHODS: All patients who had presented with a primary head and neck melanoma or an unknown primary site and had subsequently undergone limited local node excision and adjuvant radiotherapy for macroscopically involved cervical nodes between 1993 and 2010 at a tertiary referral center were selected for study. RESULTS: Twenty-eight patients were identified, with a median age of 78 years and a median of 2 major comorbidities. The 5-year regional control, disease-free survival, and overall survival rates were 69%, 44%, and 50%, respectively. At the time of data analysis, seven patients were alive without evidence of disease. Twenty-one patients had died: 11 of melanoma (4 with neck recurrence) and 10 of other causes (2 with neck recurrence). CONCLUSIONS: Excision of clinically positive metastatic cervical lymph nodes followed by radiotherapy provides satisfactory regional disease control without risking serious morbidity or mortality in melanoma patients whose general condition is considered a contraindication for therapeutic complete lymph node dissection.