Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical trial.

BACKGROUND: Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery. METHODS: This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis. RESULTS: Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects. CONCLUSION: Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au).

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.

Does Sarcopenia Predict Local Response Rates After Chemoradiotherapy for Locally Advanced Rectal Cancer?

BACKGROUND: The predictive value of sarcopenia for tumor response to neoadjuvant chemoradiotherapy is unclear. OBJECTIVE: This study aimed to investigate the association between sarcopenia and pathological tumor regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. DESIGN: Retrospective cohort study from a prospectively collected database. Univariate logistic regression was performed to assess the association between sarcopenia and tumor response. SETTINGS: This study was conducted at 2 tertiary care centers. PATIENTS: Participants were patients undergoing neoadjuvant chemoradiotherapy for locally advanced rectal cancer (T3/4, N0/+) between 2007 and 2018. INTERVENTION: Sarcopenia was diagnosed using sex-specific cutoffs of lean muscle mass. Using the initial staging CT, lean muscle mass was estimated using the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra, normalized for patient height. MAIN OUTCOME MEASURES: The primary end point was pathological tumor regression grade, defined as good (tumor regression grade 0/1) vs poor (tumor regression grade 2/3). RESULTS: The study included 167 patients with locally advanced rectal cancer with a median age of 60 (20-91) years, with 132 in the nonsarcopenia group and 35 in the sarcopenia group. Eighty-nine percent of patients had stage 3 cancer. Nine patients (5.4%) had a complete clinical response, 1 patient did not respond to treatment and opted for nonoperative management, and the remaining 157 patients (94.0%) proceeded to surgery. Pathological data revealed no significant difference between good tumor regression grade patients in the sarcopenia group compared with the nonsarcopenia group. Univariate analysis revealed BMI ≥25 kg/m 2 to be a risk factor for good tumor regression grade ( p = 0.002). LIMITATIONS: This study was limited by its retrospective design and small sample size. CONCLUSIONS: Sarcopenia is not a predictor of poor neoadjuvant chemoradiotherapy response in patients with locally advanced rectal cancer. Increasing BMI was associated with good tumor regression grade. Future multicentered studies are warranted to validate this finding. See Video Abstract at http://links.lww.com/DCR/C78 . LA SARCOPENIA PREDICE LAS TASAS DE RESPUESTA LOCAL DESPUS DE LA QUIMIORRADIOTERAPIA PARA EL CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El valor predictivo de la sarcopenia para la respuesta tumoral a la quimiorradioterapia neoadyuvante no está claro.OBJETIVO:Este estudio investiga la asociación entre la sarcopenia y el grado de regresión tumoral patológica después de la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo a partir de una base de datos recolectada prospectivamente. Se realizó una regresión logística univariante para evaluar la asociación entre la sarcopenia y la respuesta tumoral.ENTORNO CLINICO:Este estudio se realizó en dos centros de atención terciaria.PACIENTES:Pacientes sometidos a quimiorradioterapia neoadyuvante por cáncer de recto localmente avanzado (T3/4, N0/+) entre 2007-2018.INTERVENCIÓNES:La sarcopenia se diagnosticó utilizando puntos de corte de masa muscular magra específicos por género. Utilizando la tomografía computarizada de estadificación inicial, se estimó la masa muscular magra utilizando el área transversal del músculo psoas a nivel de la tercera vértebra lumbar, normalizada para la altura del paciente.PRINCIPALES MEDIDAS DE VALORACIÓN:El criterio principal de valoración fue el grado de regresión tumoral patológica, definido como bueno (grado de regresión tumoral 0/1) frente a malo (grado de regresión tumoral 2/3).RESULTADOS:El estudio incluyó a 167 pacientes con cáncer de recto localmente avanzado con una mediana de edad de 60 años (20-91), 132 en el grupo sin sarcopenia y 35 en el grupo con sarcopenia. Ochenta y nueve por ciento estaban en etapa III. Seis pacientes (5,4%) tuvieron respuesta clínica completa sostenida, un paciente no respondió al tratamiento y optó por manejo conservador, los 157 restantes (94,0%) procedieron a cirugía. Los datos patológicos no revelaron diferencias significativas entre los pacientes con buen grado de regresión tumoral en el grupo de sarcopenia en comparación con el grupo sin sarcopenia. El análisis univariado reveló que un IMC ≥25 kg/m2 era un factor de riesgo para un buen grado de regresión tumoral (p = 0,002).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo y tamaño de muestra pequeño.CONCLUSIÓNES:La sarcopenia no es un predictor de mala respuesta a la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado. El aumento del IMC se asoció con un buen grado de regresión tumoral. Se justifican futuros estudios multicéntricos para validar este hallazgo. Consulte Video Resumen en http://links.lww.com/DCR/C78 . (Traducción-Dr. Ingrid Melo ).

Can sarcopenia predict complete response after total neoadjuvant therapy in advanced rectal cancer? A multicentre observational cohort study.

BACKGROUND: The association between sarcopenia and response to neoadjuvant treatment remains unclear. This study investigates sarcopenia as a predictor of overall complete response (oCR) after Total Neoadjuvant Therapy (TNT) for advanced rectal cancer. METHOD: A prospective observational study was performed of patients with rectal cancer undergoing TNT at three South Australian hospitals between 2019 and 2022. Sarcopenia was diagnosed by pretreatment computed tomography measurement of psoas muscle cross-sectional area at the third lumbar vertebra level, normalised for patient height. The primary endpoint was oCR rate defined as the proportion of patients who achieved either clinical complete response (cCR) or pathological complete response. RESULTS: This study included 118 rectal cancer patients with an average age of 59.5 years, 83 (70.3%) of whom formed the non-sarcopenic group (NSG) and 35 (29.7%) the sarcopenic group (SG). The oCR rate was significantly higher in NSG compared with the SG (p < 0.001). cCR rate was significantly greater in NSG compared with the SG (p = 0.001). Multivariate analysis revealed sarcopenia (p = 0.029) and hypoalbuminemia (p = 0.040) were risk factors for cCR and sarcopenia was an independent risk factor for oCR (p = 0.020). CONCLUSION: Sarcopenia and hypoalbuminemia were negatively associated with tumour response following TNT in advanced rectal cancer patients.

Incidence and associated morbidity of sarcopenia in non-malignant small and large bowel anastomosis: propensity score-matched analysis.

PURPOSE: Sarcopenia is a prognostic factor for poor outcomes in colorectal cancer, but data are scarce in colorectal surgery for benign conditions where patients could benefit from a deferral of surgery to enter a prehabilitation programme. We assessed the incidence of sarcopenia and complications in patients with benign colorectal disease. METHODS: Patients who underwent elective non-malignant colorectal surgery during 2018-2022 were retrospectively identified. The cross-sectional psoas area was calculated using computed tomography (CT) imaging mid-3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome was complications measured by the comprehensive complication index (CCI). RESULTS: Of 188 patients identified, 39 (20.7%) were sarcopenic. Patients diagnosed with sarcopenia were older (63 vs. 58 years, p = 0.047) and had a reduced BMI (24.7 vs. 27.38 kg/m2, p = 0.001). Sarcopenic patients had more complications (82.1 vs. 64.4%, p = 0.036), and CCI was statistically but not clinically higher (20.9 vs. 20.9, p = 0.047). On univariate linear regression analysis, age ≥ 65 years old, ASA grade ≥ 3, active smokers, sarcopenia, and preoperative anaemia were predictive of CCI. Propensity score-matched analysis was performed, matching 78 cases to remove selection bias, which demonstrated sarcopenia had no impact on postoperative complications. On multivariate analysis, age (p = 0.022), smoking (p = 0.005), and preoperative anaemia (p = 0.008) remained predictive of CCI. CONCLUSION: Sarcopenia is prevalent in one-fifth of patients undergoing benign colorectal surgery. Taking advantage of the longer preoperative waiting periods, sarcopenia could be explored as a target for prehabilitation programmes to improve outcomes.

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.

Examining the effect of Libet clock stimulus parameters on temporal binding.

Temporal binding refers to the subjective temporal compression between actions and their outcomes. It is widely used as an implicit measure of sense of agency, that is, the experience of controlling our actions and their consequences. One of the most common measures of temporal binding is the paradigm developed by Haggard, Clark and Kalogeras (2002) based on the Libet clock stimulus. Although widely used, it is not clear how sensitive the temporal binding effect is to the parameters of the clock stimulus. Here, we present five experiments examining the effects of clock speed, number of clock markings and length of the clock hand on binding. Our results show that the magnitude of temporal binding increases with faster clock speeds, whereas clock markings and clock hand length do not significantly influence temporal binding. We discuss the implications of these results.

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 .

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.

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.

Synchronous stimulation in the rubber hand illusion task boosts the subsequent sense of ownership on the vicarious agency task.

The relationship between sense of agency and sense of ownership remains unclear. Here we investigated this relationship by manipulating ownership using the rubber hand illusion and assessing the resulting impact on self-experiences during the vicarious agency illusion. We tested whether modulating ownership towards another limb using the rubber hand illusion would subsequently influence the illusory experience of ownership and agency towards a similar-looking limb in the vicarious agency task. Crucially, the vicarious agency task measures both sense of agency and sense of ownership at the same time, while removing the confounding influence of motor signals. Our results replicated the well-established effects of both paradigms. We also found that manipulating the sense of ownership with the rubber hand illusion influenced the subsequent vicarious experience of ownership but not the vicarious experience of agency. This supports the idea that sense of agency and sense of ownership are, at least partially, independent experiences.

Intraperitoneal Local Anesthetic Instillation and Postoperative Infusion Improves Functional Recovery Following Colectomy: A Randomized Controlled Trial.

BACKGROUND: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy. OBJECTIVE: This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care. DESIGN: This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). SETTINGS: This study was conducted at 3 hospital sites in South Australia. PATIENTS: Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. INTERVENTIONS: Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. MAIN OUTCOME MEASURES: Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded. RESULTS: The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent. LIMITATIONS: This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control. CONCLUSIONS: We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A698.

The interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival outcomes after adjuvant 5FU based chemotherapy in stage III colon cancer.

PURPOSE: The predictive role of biomarkers in colon cancer is still being defined. The aim of this study is to determine the interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival benefit after adjuvant 5-FU based chemotherapy in stage III colon cancer. METHODS: We performed a retrospective cohort study including all curatively resected stage III colon cancer cases over a 33-year period. A clinicopathological database was collated (adjuvant chemotherapy, age, gender, obstruction, perforation, tumor location, grade, mucin, nodal stage, extramural vascular, and perineural invasion). BRAF (V600E) mutation testing was performed and MSI status established by immunohistochemistry for mismatch repair proteins and molecular testing for National Cancer Institute panel markers. Patients were categorized into four groups for comparison: MSS and BRAF-ve (termed " traditional"), MSI and BRAF-ve (termed " presumed Lynch"), MSI and BRAF+ve (termed " sporadic MSI"), and MSS and BRAF+ve (termed " other BRAF"). The primary endpoint was cancer specific survival. Interaction testing was conducted to determine whether there were different responses to chemotherapy between groups. RESULTS: A total of 686 unselected cases met inclusion criteria and had tissue available, of which 15.7% had BRAF mutation (BRAF+ve) and 13.8% had MSI. Thirty-nine percent received chemotherapy. Overall, adjuvant chemotherapy produced a cancer specific survival benefit (HR 0.66, 95% CI, 0.49-0.88, P < 0.01). On adjusted analysis, neither BRAF nor MSI status were individually predictive of survival benefit. On adjusted analysis specifically of the chemotherapy effect in each subgroup, only patients in the presumed Lynch (HR 0.260, 95% CI, 0.09-0.80, P < 0.01) and other BRAF groups (HR 0.45, 95% CI, 0.23-0.87, P < 0.01) had a significant survival benefit from chemotherapy. On interaction testing of subgroups, adjusting for all the clinicopathological parameters, only patients in the presumed Lynch group (HR 0.277, 95% CI, 0.10-0.75, P < 0.01) gained a differentially greater benefit from chemotherapy than other groups. CONCLUSIONS: In this historical cohort, MSI testing is predictive of response to adjuvant chemotherapy in stage III colon cancer, but only when results are interpreted in combination with BRAF. This supports the role of routine testing for these biomarkers.

Extended venous thromboembolism prophylaxis after colorectal cancer surgery: the current state of the evidence.

There is level one evidence to support combined mechanical and chemical thromboprophylaxis for 7-10 days after colorectal cancer surgery, but there remains a paucity of data to support extended prophylaxis after discharge. The aim of this clinical review is to summarise the currently available evidence for extended venous thromboprophylaxis after elective colorectal cancer surgery. Clinical review of the major clinical guidelines and published clinical data evaluating extended venous thromboprophylaxis after elective colorectal cancer surgery. Five major guideline recommendations are outlined, and the results of the five published randomised controlled trials are summarised and reviewed with a specific focus on the efficacy and cost-effectiveness of extended heparin prophylaxis to prevent clinically relevant post-operative venous thromboembolism (VTE) after colorectal cancer surgery. Extended VTE prophylaxis after colorectal cancer surgery reduces the incidence of asymptomatic screen detected deep venous thrombosis (DVT) only, with no demonstrable reduction in symptomatic DVT, symptomatic PE, or VTE related death. Evidence for cost-effectiveness is limited. As the incidence of clinical VTE is very low in this patient subgroup overall, future research should be focused on higher risk patient subgroups in whom a reduction in VTE may be both more demonstrable and clinically relevant.

The medial frontal-prefrontal network for altered awareness and control of action in corticobasal syndrome.

The volitional impairments of alien limb and apraxia are a defining feature of the corticobasal syndrome, but a limited understanding of their neurocognitive aetiology has hampered progress towards effective treatments. Here we combined several key methods to investigate the mechanism of impairments in voluntary action in corticobasal syndrome. We used a quantitative measure of awareness of action that is based on well-defined processes of motor control; structural and functional anatomical information; and evaluation against the clinical volitional disorders of corticobasal syndrome. In patients and healthy adults we measured 'intentional binding', the perceived temporal attraction between voluntary actions and their sensory effects. Patients showed increased binding of the perceived time of actions towards their effects. This increase correlated with the severity of alien limb and apraxia, which we suggest share a core deficit in motor control processes, through reduced precision in voluntary action signals. Structural neuroimaging analyses showed the behavioural variability in patients was related to changes in grey matter volume in pre-supplementary motor area, and changes in its underlying white matter tracts to prefrontal cortex. Moreover, changes in functional connectivity at rest between the pre-supplementary motor area and prefrontal cortex were proportional to changes in binding. These behavioural, structural and functional results converge to reveal the frontal network for altered awareness and control of voluntary action in corticobasal syndrome, and provide candidate markers to evaluate new therapies.

Machine learning prediction model for postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) continues to be a major cause of morbidity following colorectal surgery. Despite best efforts, the incidence of POI in colorectal surgery remains high (~30%). This study aimed to investigate machine learning techniques to identify risk factors for POI in colorectal surgery patients, to help guide further preventative strategies. METHODS: A TRIPOD-guideline-compliant retrospective study was conducted for major colorectal surgery patients at a single tertial care centre (2018-2022). The primary outcome was the occurrence of POI, defined as not achieving GI-2 (outcome measure of time to first stool and tolerance of oral diet) by day four. Multivariate logistic regression, decision trees, radial basis function and multilayer perceptron (MLP) models were trained using a random allocation of patients to training/testing data sets (80/20). The area under the receiver operating characteristic (AUROC) curves were used to evaluate model performance. RESULTS: Of 504 colorectal surgery patients, 183 (36%) experienced POI. Multivariate logistic regression, decision trees, radial basis function and MLP models returned an AUROC of 0.722, 0.706, 0.712 and 0.800, respectively. The MLP model had the highest sensitivity and specificity values. In addition to well-known risk factors for POI, such as postoperative hypokalaemia, surgical approach, and opioid use, the MLP model identified sarcopenia (ranked 4/30) as a potentially modifiable risk factor for POI. CONCLUSION: MLP outperformed other models in predicting POI. Machine learning can provide valuable insights into the importance and ranking of specific predictive variables for POI. Further research into the predictive value of preoperative sarcopenia for POI is required.

Sense of agency in joint action: a critical review of we-agency.

The sense of agency refers to the experience of control over voluntary actions and their effects. There is growing interest in the notion of we-agency, whereby individual sense of agency is supplanted by a collective agentic experience. The existence of this unique agentic state would have profound implications for human responsibility, and, as such, warrants further scrutiny. In this paper, we review the concept of we-agency and examine whether evidence supports it. We argue that this concept entails multiplying hypothetical agentic states associated with joint action, thus ending up with an entangled phenomenology that appears somewhat speculative when weighted against the available evidence. In light of this, we suggest that the concept of we-agency should be abandoned in favor of a more parsimonious framework for the sense of agency in joint action.

Deep learning to predict lymph node status on pre-operative staging CT in patients with colon cancer.

INTRODUCTION: Lymph node (LN) metastases are an important determinant of survival in patients with colon cancer, but remain difficult to accurately diagnose on preoperative imaging. This study aimed to develop and evaluate a deep learning model to predict LN status on preoperative staging CT. METHODS: In this ambispective diagnostic study, a deep learning model using a ResNet-50 framework was developed to predict LN status based on preoperative staging CT. Patients with a preoperative staging abdominopelvic CT who underwent surgical resection for colon cancer were enrolled. Data were retrospectively collected from February 2007 to October 2019 and randomly separated into training, validation, and testing cohort 1. To prospectively test the deep learning model, data for testing cohort 2 was collected from October 2019 to July 2021. Diagnostic performance measures were assessed by the AUROC. RESULTS: A total of 1,201 patients (median [range] age, 72 [28-98 years]; 653 [54.4%] male) fulfilled the eligibility criteria and were included in the training (n = 401), validation (n = 100), testing cohort 1 (n = 500) and testing cohort 2 (n = 200). The deep learning model achieved an AUROC of 0.619 (95% CI 0.507-0.731) in the validation cohort. In testing cohort 1 and testing cohort 2, the AUROC was 0.542 (95% CI 0.489-0.595) and 0.486 (95% CI 0.403-0.568), respectively. CONCLUSION: A deep learning model based on a ResNet-50 framework does not predict LN status on preoperative staging CT in patients with colon cancer.

Action-effect binding is decreased in motor conversion disorder: implications for sense of agency.

The abnormal movements seen in motor conversion disorder are affected by distraction and entrainment, similar to voluntary movement. Unlike voluntary movement, however, patients lack a sense of control for the abnormal movements, a failure of "self-agency." The action-effect binding paradigm has been used to quantify the sense of self-agency, because subjective contraction of time between an action and its effect only occurs if the patient feels that they are the agent responsible for the action. We used this paradigm, coupled with emotional stimuli, to investigate the sense of agency with voluntary movements in patients with motor conversion disorder. Twenty patients with motor conversion disorder and 20 age-matched and sex-matched healthy volunteers used a rotating clock to judge the time of their own voluntary key presses (action) and a subsequent auditory tone (effect) after they completed conditioning blocks in which high, medium, and low tones were coupled to images of happy, fearful, and neutral faces. The results replicated those produced previously: it was reported that an effect after a voluntary action occurred earlier, and the preceding action occurred later, compared with trials that used only key presses or tones. Patients had reduced overall binding scores relative to healthy volunteers, suggesting a reduced sense of agency. There was no effect of the emotional stimuli (faces) or other interaction effects. Healthy volunteers with subclinical depressive symptoms had higher overall binding scores. We demonstrate that patients with motor conversion disorder have decreased action-effect binding for normal voluntary movements compared with healthy volunteers, consistent with the greater experience of lack of control.