Risk prediction algorithms for prolonged postoperative ileus: A systematic review.

AIM: Prolonged postoperative ileus (PPOI) is common and is associated with a significant healthcare burden. Previous studies have attempted to predict PPOI clinically using risk prediction algorithms. The aim of this work was to systematically review and compare risk prediction algorithms for PPOI following colorectal surgery. METHOD: A systematic literature search was conducted using MEDLINE, Embase, Web of Science and CINAHL Plus. Studies that developed and/or validated a risk prediction algorithm for PPOI in adults following colorectal surgery were included. Data were collected on study design, population and operative characteristics, the definition of PPOI used and risk prediction algorithm design and performance. Quality appraisal was assessed using the PROBAST tool. RESULTS: Eleven studies with 87 549 participants were included in our review. Most were retrospective, single-centre analyses (6/11, 55%) and rates of PPOI varied from 10% to 28%. The most commonly used variables were sex (8/11, 73%), age (6/11, 55%) and surgical approach (5/11, 45%). Area under the curve ranged from 0.68-0.78, and only three models were validated. However, there was significant variation in the definition of PPOI used. No study reported sensitivity, specificity or positive/negative predictive values. CONCLUSION: Currently available risk prediction algorithms for PPOI appear to discriminate moderately well, although there is a lack of validation data. Future studies should aim to use a standardized definition of PPOI, comprehensively report model performance and validate their findings using internal and external methodologies.

Causes and costs of delayed closure of ileostomies in rectal cancer patients in Australasian units.

BACKGROUND: Defunctioning loop ileostomies (DLIs) are a frequent adjunct to rectal cancer surgery. Delayed closure of DLIs is common and associated with increased morbidity. The reasons for delayed DLI closure are often unknown. The economic burden of delayed DLI closure is not quantified. The present study aimed to determine the reasons for, and economic burden of, delayed DLI closure. METHODS: Clinical and economic data were audited from a prospective database of patients in two Australasian colorectal cancer centres. Patients treated at each unit with low/ultra-low anterior resection for rectal cancer with formation of DLI between January 2014 and December 2019 were included. Post-operative complication rate, stoma-related complication rate and costs of hospital admissions and stoma care were recorded and analysed. Multivariate linear regression analysis was used to investigate risk factors for delay to closure. RESULTS: 146 patients underwent low/ultra-low anterior resection with DLI; 135 patients (92.5%) underwent reversal. The median duration to reversal was 7 months (IQR 4.5-9.5). Sixty-six percent of patients underwent reversal >6 months after their index surgery. Neoadjuvant and adjuvant chemotherapy were associated with delayed reversal (P < 0.001). Non-English speakers waited longer for DLI closure (P = 0.028). The costs of outpatient stoma care (P < 0.001), post-operative care (P = 0.004), and total cost of treatment (P = 0.014) were significantly higher in the delayed closure group, with a total cost of treatment difference of $3854 NZD per patient. CONCLUSIONS: Causes of delay include systemic factors and demographic factors that can be addressed directly, addressing such causes may alleviate a significant economic burden.

Effect of prucalopride to improve time to gut function recovery following elective colorectal surgery: randomized clinical trial.

BACKGROUND: Delayed return to gut function and prolonged postoperative ileus (PPOI) delay recovery after colorectal surgery. Prucalopride is a selective serotonin-4-receptor agonist that may improve gut motility. METHODS: This was a multicentre, double-blind, parallel, placebo-controlled randomized trial of 2 mg prucalopride versus placebo in patients undergoing elective colorectal resection. Patients with inflammatory bowel disease and planned ileostomy formation were excluded, but colostomy formation was allowed. The study medication was given 2 h before surgery and daily for up to 6 days after operation. The aim was to determine whether prucalopride improved return of gut function and reduced the incidence of PPOI. The primary endpoint was time to passage of stool and tolerance of diet (GI-2). Participants were allocated in a 1 : 1 ratio, in blocks of 10. Randomization was computer-generated. All study personnel, medical staff, and patients were blinded. RESULTS: This study was completed between October 2017 and May 2020 at two tertiary hospitals in New Zealand. A total of 148 patients were randomized, 74 per arm. Demographic data were similar in the two groups. There was no difference in median time to GI-2 between prucalopride and placebo groups: 3.5 (i.q.r. 2-5) versus 4 (3-5) days respectively (P = 0.124). Prucalopride improved the median time to passage of stool (3 versus 4 days; P = 0.027) but not time to tolerance of diet (2 versus 2 days; P = 0.669) or median duration of hospital stay (4 versus 4 days; P = 0.929). In patients who underwent laparoscopic surgery (125, 84.5 per cent), prucalopride improved median time to GI-2: 3 (2-4) days versus 4 (3-5) days for placebo (P = 0.012). The rate of PPOI, complications, and adverse events was similar in the two groups. CONCLUSION: Prucalopride did not improve time to overall recovery of gut function after elective colorectal surgery. Registration number: NCT02947269 (http://www.clinicaltrials.gov).

Evaluation of the inflammatory profile following uncomplicated elective colectomy.

BACKGROUND: Attenuation of the inflammatory response in patients undergoing colectomy with modern perioperative care and laparoscopic surgery has been a focus of research in recent years. Despite reported benefits, significant heterogeneity remains with studies including patients undergoing both rectal and colon surgery and including surgery with postoperative complications. Therefore, the aim of the study was to evaluate the inflammatory response in patients undergoing elective colectomy without complications, specifically comparing open and laparoscopic approaches. METHODS: A multicenter prospective study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were included over a 3-year period. Perioperative blood samples were collected and analysed for the following inflammatory markers: IL-6, IL-1ß, TNFα, IL-10, CRP, leucocyte and neutrophil count. Statistical analysis was performed using SPSS statistical software. RESULTS: A total of 168 colectomy patients without complications were included in the analysis. Patients that underwent laparoscopy had significantly reduced IL-6, neutrophils and CRP on postoperative day (POD) 1 (p < 0.05) compared to an open approach. IL-10 and TNFα were significantly reduced on POD 2 (p < 0.05) in laparoscopic patients. Patients with a Body Mass Index (BMI) greater than 30 kg/m2 had significantly higher levels of CRP regardless of operative approach. Statins altered both preoperative and postoperative inflammatory markers. CONCLUSION: The postoperative inflammatory response is influenced by surgical approach, perioperative medications, and patient factors. These findings have important implications in the utility of biomarkers in the diagnosis of postoperative surgical complications, in particular in the early diagnosis of anastomotic leak.

Detection of Anastomotic Leakage Following Elective Colonic Surgery: Results of the Prospective Biomarkers and Anastomotic Leakage (BALL) Study.

BACKGROUND: Anastomotic leakage (AL) is an infrequent but life-threatening surgical complication following colorectal surgery. Early diagnosis remains clinically difficult but is a necessity to reduce associated morbidity and mortality. Clinical review and radiological modalities for the diagnosis of leakage remain non-specific and often only detect AL once it is well developed. Inflammatory biomarkers however have shown promise in early pre-clinical detection of leakage following colorectal surgery. METHODS: A multi-center, prospective observational study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were initially recruited over a 3-y period. Perioperative blood samples were collected to measure interleukin (IL)-6, IL-1ß, tumor necrosis factor α, IL-10, C-reactive protein (CRP), leukocyte and neutrophil counts. Statistical analysis was performed to compare patients with an uncomplicated recovery with patients with AL. RESULTS: Sixteen patients developed AL (5.7%), diagnosed at a median post-operative (POD) day 7. CRP and IL-6 were consistently elevated in the early post-operative period in patients with AL, and had the best diagnostic accuracy on POD 3 (area under the curve 0.70; P = 0.02) and POD 1 (area under the curve 0.69; P = 0.02), respectively. IL-10, once adjusted for body mass index and surgical approach, was the sole biomarker significantly elevated in patients with AL on POD 4. CONCLUSIONS: Early post-operative elevations of CRP and IL-6 provide utility for early detection of AL after elective colectomy. Application of these inflammatory biomarkers and their combinations in daily practice warrants further investigation.

Post-operative ileus: definitions, mechanisms and controversies.

Post-operative ileus (POI) is a syndrome of impaired gastrointestinal transit which occurs following abdominal surgery. There are few effective targeted therapies for ileus, and research has been limited by inconsistent definitions and an incomplete understanding of the underlying pathophysiology. Despite considerable effort, there remains no widely-adopted definition of ileus, and recent work has identified variation in outcome reporting is a major source of heterogeneity in clinical trials. Outcomes should be clearly-defined, clinically-relevant, and reflective of the underlying biology, impacts on hospital resources and quality of life. Further collaborative efforts will be needed to develop consensus definitions and a core outcome set for postoperative gastrointestinal recovery. Investigation into the pathophysiology of POI has been hindered by use of low-resolution techniques and difficulties linking cellular mechanisms to dysmotility patterns and clinical symptoms. Recent evidence has suggested the common assumption of post-operative GI paralysis is incorrect, and that the distal colon becomes hyperactive following surgery. The post-operative inflammatory response is important in the pathophysiology of ileus, but the time course of this in humans remains unclear, with the majority of evidence coming from animal models. Future work should investigate dysmotility patterns underlying ileus, and identify biomarkers which may be used to diagnose, monitor and stratify patients with ileus.

Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial.

BACKGROUND & AIMS: Antibiotic treatment is the standard care for patients with uncomplicated acute diverticulitis. However, this practice is based on low-level evidence and has been challenged by findings from 2 randomized trials, which did not include a placebo group. We investigated the non-inferiority of placebo vs antibiotic treatment for the management of uncomplicated acute diverticulitis. METHODS: In the selective treatment with antibiotics for non-complicated diverticulitis study, 180 patients hospitalized for uncomplicated acute diverticulitis (determined by computed tomography, Hinchey 1a grade) from New Zealand and Australia were randomly assigned to groups given antibiotics (n = 85) or placebo (n = 95) for 7 days. We collected demographic, clinical, and laboratory data and answers to questionnaires completed every 12 hrs for the first 48 hrs and then daily until hospital discharge. The primary endpoint was length of hospital stay; secondary endpoints included occurrence of adverse events, readmission to the hospital, procedural intervention, change in serum markers of inflammation, and patient-reported pain scores at 12 and 24 hrs. RESULTS: There was no significant difference in median time of hospital stay between the antibiotic group (40.0 hrs; 95% CI, 24.4-57.6 hrs) and the placebo group (45.8 hrs; 95% CI, 26.5-60.2 hrs) (P = .2). There were no significant differences between groups in adverse events (12% for both groups; P = 1.0), readmission to the hospital within 1 week (1% for the placebo group vs 6% for the antibiotic group; P = .1), and readmission to the hospital within 30 days (11% for the placebo group vs 6% for the antibiotic group; P = .3). CONCLUSIONS: Foregoing antibiotic treatment did not prolong length of hospital admission. This result provides strong evidence for omission of antibiotics for selected patients with uncomplicated acute diverticulitis. ACTRN: 12615000249550.

Prolonged Postoperative Ileus Significantly Increases the Cost of Inpatient Stay for Patients Undergoing Elective Colorectal Surgery: Results of a Multivariate Analysis of Prospective Data at a Single Institution.

BACKGROUND: Prolonged postoperative ileus is a common major complication after abdominal surgery. Retrospective data suggest that ileus doubles the cost of inpatient stay. However, current economic impact data are based on retrospective studies that rely on clinical coding to diagnose ileus. OBJECTIVE: The aim of this study was to determine the economic burden of ileus for patients undergoing elective colorectal surgery. DESIGN: Economic data were audited from a prospective database of patients who underwent surgery at Auckland City Hospital between September 2012 and June 2014. SETTINGS: Auckland City Hospital is a large tertiary referral center, using an enhanced recovery after surgery protocol. PATIENTS: Patients were prospectively diagnosed with prolonged postoperative ileus using a standardized definition. MAIN OUTCOME MEASURES: The cost of inpatient stay was analyzed with regard to patient demographics and operative and postoperative factors. A multivariate analysis was performed to determine the cost of ileus when accounting for other significant covariates. RESULTS: Economic data were attained from 325 patients, and 88 patients (27%) developed ileus. The median inpatient cost (New Zealand dollars) for patients with prolonged ileus, including complication rates and length of stay, was $27,981 (interquartile range= $20,198 to $42,174) compared with $16,317 (interquartile range = $10,620 to $23,722) for other patients, a 71% increase in cost (p < 0.005). Ileus increased all associated healthcare costs, including medical/nursing care, radiology, medication, laboratory costs, and allied health (p < 0.05). Multivariate analysis showed that ileus remained a significant financial burden (p < 0.005) when considering rates of major complications and length of stay. LIMITATIONS: This is a single-institution study, which may impact the generalizability of our results. CONCLUSIONS: Prolonged ileus causes a substantial financial burden on the healthcare system, in addition to greater complication rates and length of stay in these patients. This is the first study to assess the financial impact of prolonged ileus, diagnosed prospectively using a standardized definition. See Video Abstract at http://links.lww.com/DCR/A825.

Gastrografin may reduce time to oral diet in prolonged post-operative ileus: a pooled analysis of two randomized trials.

BACKGROUND: Gastrografin has been suggested as a rescue therapy for prolonged post-operative ileus (PPOI) but trial data has been inconclusive. This study aimed to determine the benefit of gastrografin use in patients with PPOI by pooling the results of two recent randomized controlled trials assessing the efficacy of gastrografin compared to placebo given at time of PPOI diagnosis. METHODS: Anonymized, individual patient data from patients undergoing elective bowel resection for any indication were included, stoma closure was excluded. The primary outcome was duration of PPOI. Secondary outcomes were time to tolerate oral diet, passage of flatus/stool, requirement and duration of nasogastric tube, length of post-operative stay and rate of post-operative complications. RESULTS: Individual patient data were pooled for analysis (53 gastrografin, 55 placebo). Gastrografin trended towards a reduction in PPOI duration compared to placebo, respectively, median 96 h (interquartile range, IQR, 78 h) versus median 120 h (IQR, 84 h), however, this result was non-significant (P = 0.11). In addition, no significant difference was detected between the two groups for time to passage of flatus/stool (P = 0.36) and overall length of stay (P = 0.35). Gastrografin conferred a significantly faster time to tolerate an oral diet compared to placebo (median 84 h versus median 107 h, P = 0.04). There was no difference in post-operative complications between the two interventions (P > 0.05). CONCLUSION: Gastrografin did not significantly reduce PPOI duration or length of stay after abdominal surgery, but did reduce time to tolerate a solid diet. Further studies are required to clarify the role of gastrografin in PPOI.

Prospective comparison of return of bowel function after left versus right colectomy.

BACKGROUND: Passage of flatus and stool represents a key milestone in recovery after colonic resections. Colorectal surgeons may hold varied expectations regarding recovery rates after left- versus right-sided colectomies, but there is currently little evidence to inform post-operative care. This study prospectively compared gut function recovery after left- versus right-sided resections. METHODS: Prospective data were analysed from 94 consecutive patients undergoing elective colorectal resections with primary anastomosis at Auckland City Hospital. Patients having ileostomies were excluded. Primary analysis compared time to first bowel motion between left- versus right-sided resections, excluding patients who developed prolonged post-operative ileus, while secondary analyses compared length of stay, rates of prolonged ileus and other complications. RESULTS: Analysis included 42 patients with left-sided and 52 with right-sided resections. No significant differences were observed for complications (P = 0.1), length of stay (P = 0.9) or development of prolonged ileus (P = 0.2). Rate of return of bowel function was faster in patients after left-sided resections (median 2.5 versus 4 days; P = 0.03 by Log-rank (Mantel-Cox) test), when patients with prolonged post-operative ileus were excluded. An association was also identified between length of bowel resected and time to recovery of bowel function for right-sided (P = 0.02) but not left-sided resections (P = 0.9). CONCLUSION: This study shows that for patients who do not progress to prolonged ileus, those with left-sided resections experience faster return of bowel function when compared with those having right-sided resections. The reason for this finding is currently unknown and deserves further attention.

The "rectosigmoid brake": Review of an emerging neuromodulation target for colorectal functional disorders.

The regulation of gastrointestinal motility encompasses several overlapping mechanisms including highly regulated and coordinated neurohormonal circuits. Various feedback mechanisms or "brakes" have been proposed. While duodenal, jejunal, and ileal brakes are well described, a putative distal colonic brake is less well defined. Despite the high prevalence of colonic motility disorders, there is little knowledge of colonic motility owing to difficulties with organ access and technical difficulties in recording detailed motor patterns along its entire length. The motility of the colon is not under voluntary control. A wide range of motor patterns is seen, with long intervals of intestinal quiescence between them. In addition, the use of traditional manometric catheters to record contractile activity of the colon has been limited by the low number of widely spaced sensors, which has resulted in the misinterpretation of colonic motor patterns. The recent advent of high-resolution (HR) manometry is revolutionising the understanding of gastrointestinal motor patterns. It has now been observed that the most common motor patterns in the colon are repetitive two to six cycles per minute (cpm) propagating events in the distal colon. These motor patterns are prominent soon after a meal, originate most frequently in the rectosigmoid region, and travel in the retrograde direction. The distal prominence and the origin of these motor patterns raise the possibility of them serving as a braking mechanism, or the "rectosigmoid brake," to limit rectal filling. This review aims to describe what is known about the "rectosigmoid brake," including its physiological and clinical significance and potential therapeutic applications.

Sacral resection with pelvic exenteration for advanced primary and recurrent pelvic cancer: a single-institution experience of 100 sacrectomies.

BACKGROUND: Recurrent and advanced primary pelvic cancers present a complex clinical issue requiring multidisciplinary care and radical extended surgery. Sacral resection is necessary for tumors that invade posteriorly but is associated with increased morbidity and mortality. OBJECTIVE: This study aimed to analyze the morbidity and survival associated with pelvic exenteration involving sacrectomy for advanced pelvic cancers at a single institution. DESIGN: This study used patient demographics, operative and pathologic reports, and prospective survival data to determine factors affecting patient outcomes. SETTINGS: Data were collected for patients who had operations between July 1998 and April 2012 at Royal Prince Alfred Hospital. PATIENTS: One hundred patients underwent pelvic exenteration with a sacrectomy for advanced pelvic cancers. Sacrectomy was performed for 18 primary and 61 recurrent rectal cancers, 17 anal cancers, and 4 other cancers. MAIN OUTCOME MEASURES: This study looked at postoperative major and minor morbidity rates, as well as disease-free and overall survival rates after sacral resection. It compared the outcomes of high sacrectomy (at or above S2) versus low sacrectomy. RESULTS: Clear margins were achieved in 72 of 100 patients. The overall complication rate was 74% (43% major and 67% minor) with no 30-day or in-hospital mortality. Estimated overall and disease-free survival rates after curative resection were 38% and 30% at 5 years. Involved margins (p = 0.006), lymph node involvement (p = 0.008), and anterior organ invasion (p = 0.008) had a negative impact on patient survival. High sacrectomy increased the incidence of neurologic deficit postoperatively (p = 0.04) but did not alter the rate of R0 resection or patient survival. LIMITATIONS: Retrospective data were required to analyze patient morbidity, as well as operative and pathologic factors. CONCLUSIONS: This series supports sacral resection for curative surgery in advanced pelvic cancers, achieving excellent R0 and long-term survival rates. Cortical bone invasion and high sacrectomy were not contraindications to surgery and had acceptable outcomes.

Assessing the impact of a sacral resection on morbidity and survival after extended radical surgery for locally recurrent rectal cancer.

OBJECTIVES: To describe the experience of sacrectomy with extended radical resection in the treatment of locally recurrent rectal cancer. BACKGROUND: Resections of the bony pelvis, especially the sacrum, are becoming more common as part of extended radical exenterations for patients with recurrent rectal cancer. However, sacrectomy has been shown to carry a significant decrease in survival. Morbidity rates have been associated with the level of the sacrectomy (ie, >S3 junction). METHODS: An analysis was conducted using prospective data from patients with recurrent rectal cancer who underwent pelvic exenteration involving sacrectomy from July 1998 until June 2011. The impact of the proximal level of sacrectomy [low (≤S3) vs high (≥S2-S3 disc)] was compared. RESULTS: Of 240 exenteration patients, 79 underwent sacrectomy, with 49 for recurrent rectal cancer. An R0 margin was achieved in 36 (74%) patients. Achievement of clear operative margins (R0) conferred a large and significant benefit for disease-free survival compared with R1 and R2 resections (median 45 months vs 19 and 8 months, respectively; P = 0.045). Complications were reported in 40 (82%) patients, with major and minor complications in 19 (39%) and 38 (78%) patients, respectively. The proximal level of the sacrectomy (high vs low) did not significantly impair the ability to achieve a clear margin and was not associated with an increase in major or minor complications. CONCLUSIONS: This large, single-center series has demonstrated that extended pelvic exenteration involving sacrectomy has excellent R0 margins and survival rates for recurrent rectal cancer. A high sacrectomy has comparable results with a more distal abdominosacral resection.