Efficacy of different surgical treatments for management of anal fistula: a network meta-analysis.

PURPOSE: Currently, the anal fistula treatment which optimises healing and preserves bowel continence remains unclear. The aim of our study was to compare the relative efficacy of different surgical treatments for AF through a network meta-analysis. METHODS: Systematic searches of MEDLINE, EMBASE and CENTRAL databases up to October 2022 identified randomised controlled trials (RCTs) comparing surgical treatments for anal fistulae. Fistulae were classified as simple (inter-sphincteric or low trans-sphincteric fistulae crossing less than 30% of the external anal sphincter (EAS)) and complex (high trans-sphincteric fistulae involving more than 30% of the EAS). Treatments evaluated in only one trial were excluded from the primary analyses to minimise bias. The primary outcomes were rates of success in achieving AF healing and bowel incontinence. RESULTS: Fifty-two RCTs were included. Of the 14 treatments considered, there were no significant differences regarding short-term (6 months or less postoperatively) and long-term (more than 6 months postoperatively) success rates between any of the treatments in patients with both simple and complex anal fistula. Ligation of the inter-sphincteric fistula tract (LIFT) ranked best for minimising bowel incontinence in simple (99.1% of comparisons; 3 trials, n = 70 patients) and complex anal fistula (86.2% of comparisons; 3 trials, n = 102 patients). CONCLUSIONS: There is insufficient evidence in existing RCTs to recommend one treatment over another regarding their short and long-term efficacy in successfully facilitating healing of both simple and complex anal fistulae. However, LIFT appears to be associated with the least impairment of bowel continence, irrespective of AF classification.

The impact of transanal tube design for preventing anastomotic leak in anterior resection: a systematic review and meta-analysis.

BACKGROUND: Placement of a transanal tube (TAT) into the rectum is a strategy used to attempt to prevent anastomotic leak (AL) in anterior resection surgery. There is a wide variation in materials and tube design in devices used as TATs and previous meta-analyses have not considered TAT design in their analyses. This study reviews the impact that design of TAT has on AL rates. METHODS: A systematic review of the literature was performed with the aim of identifying studies evaluating the use of TATs for preventing AL and then defining the design of TATs. Studies were then compared in groups based on TAT design in a meta-analysis to evaluate whether design is an important variable in outcomes. RESULTS: Thirty-three studies were included. There was a wide variety of tubes used as TATs. On meta-analysis, catheter-type TATs were associated with a substantially lower rate of AL (OR: 0.46; 95% CI 0.30, 0.68). By contrast, stent-type TATs were not associated with any reduction in the incidence of AL (OR: 1.06, 95% CI 0.50, 2.22). Catheter-type TATs were also associated with substantial reductions in the rate of reoperation (OR: 0.32; 95% CI 0.20, 0.50), whereas stent-type TATs showed no benefit in the rate of reoperation (OR: 0.79; 95% CI 0.37, 1.65). CONCLUSIONS: Off-the-shelf catheter-type transanal tubes appeared effective in preventing AL, whereas custom-designed stent-type TATs were not demonstrated to be effective; although high quality evidence is limited. TAT design should be an important consideration in further research of the use of TATs in anterior resection surgery.

Network meta-analysis of local and regional analgesia following colorectal resection.

BACKGROUND: Postoperative pain management after colorectal surgery remains challenging. Systemic opiates delivered on demand or via a patient-controlled pump have traditionally been the mainstay of treatment. Opiate analgesia is associated with slower gastrointestinal recovery and unpleasant side-effects; many regional and local analgesic techniques have been developed as alternatives. METHODS: MEDLINE, Embase and CENTRAL databases were searched systematically for RCTs comparing analgesic techniques after major colorectal resection. A network meta-analysis was performed using a Bayesian random-effects framework with a non-informative prior. Primary outcomes included pain at rest and cumulative opiate consumption 24 h after surgery. Secondary outcomes included pain at rest and cumulative opiate consumption at 48 h, pain on movement and cough at 24 and 48 h, time to first stool, time to tolerance of oral diet, duration of hospital stay, nausea and vomiting, and postoperative complications. RESULTS: Seventy-four RCTs, including 5101 patients and 11 different techniques, were included. Some inconsistency and heterogeneity was found. SUCRA scores showed that spinal analgesia was the best intervention for postoperative pain and opiate reduction at 24 h. Transversus abdominus plane blocks were effective in reducing pain and opiate consumption 24 h after surgery. Subgroup analysis showed similar results for open versus minimally invasive surgical approaches, and enhanced recovery after surgery programmes. CONCLUSION: Spinal analgesia and transversus abdominus plane blocks best balanced pain control and opiate minimization in the immediate postoperative phase following colorectal resection. Multimodal analgesia reduces pain, minimizes systemic opiate use and optimizes postoperative recovery.

ANTECEDENTES: El tratamiento del dolor postoperatorio después de cirugía colorrectal sigue siendo difícil. Los opiáceos sistémicos administrados a demanda o mediante una bomba controlada por el paciente ha sido tradicionalmente el principal tratamiento. Sin embargo, la analgesia con opiáceos se asocia con una recuperación gastrointestinal más lenta y con efectos secundarios desagradables, lo que dado lugar al desarrollo de numerosas técnicas analgésicas regionales y locales como modalidades alternativas. MÉTODOS: Se realizaron búsquedas sistemáticas en las bases de datos Medline, Embase y CENTRAL para identificar ensayos controlados aleatorizados (randomized controlled trials, RCTs) que compararan técnicas analgésicas después de una resección colorrectal mayor. Se realizó un metaanálisis en red utilizando un marco bayesiano de efectos aleatorios con una distribución a priori no informativa. Los criterios de valoración primarios incluyeron dolor en reposo y el consumo de opiáceos a las 24 horas después de la operación. Los criterios de valoración secundarios incluyeron dolor en reposo y el consumo de opiáceos a las 48 horas, dolor con el movimiento y al toser (a las 24 y 48 horas), tiempo hasta la primera deposición, tiempo hasta tolerar la dieta oral, duración de la estancia hospitalaria, náuseas y vómitos, y complicaciones postoperatorias. RESULTADOS: Se incluyeron 74 RCTs, con un total de 5.101 pacientes y 11 técnicas diferentes. Se encontró cierta inconsistencia y heterogeneidad. Las puntuaciones de dolor en reposo más bajas y la menor ingesta de opiáceos postoperatorios a las 24 horas correspondieron a la analgesia espinal. Los bloqueos del plano transverso del abdomen fueron efectivos para reducir el dolor y el consumo de opiáceos a las 24 horas después de la cirugía. El análisis de subgrupos mostró resultados similares para los abordajes quirúrgicos abiertos versus mínimamente invasivos y para los programas de recuperación intensificada después de la cirugía (Enhanced Recovery After Surgery, ERAS). CONCLUSIÓN: La analgesia espinal y el bloqueo del plano transverso del abdomen consiguieron un mejor control del dolor y una disminución de los opiáceos en el postoperatorio inmediato tras la cirugía colorrectal. La analgesia multimodal reduce el dolor, minimiza el uso de opiáceos sistémicos y optimiza la recuperación postoperatoria.

Establishing core outcome sets for gastrointestinal recovery in studies of postoperative ileus and small bowel obstruction: protocol for a nested methodological study.

INTRODUCTION: Gastrointestinal recovery describes the restoration of normal bowel function in patients with bowel disease. This may be prolonged in two common clinical settings: postoperative ileus and small bowel obstruction. Improving gastrointestinal recovery is a research priority but researchers are limited by variation in outcome reporting across clinical studies. This protocol describes the development of core outcome sets for gastrointestinal recovery in the contexts of postoperative ileus and small bowel obstruction. METHOD: An international Steering Group consisting of patient and clinician representatives has been established. As overlap between clinical contexts is anticipated, both outcome sets will be co-developed and may be combined to form a common output with disease-specific domains. The development process will comprise three phases, including definition of outcomes relevant to postoperative ileus and small bowel obstruction from systematic literature reviews and nominal-group stakeholder discussions; online-facilitated Delphi surveys via international networks; and a consensus meeting to ratify the final output. A nested study will explore if the development of overlapping outcome sets can be rationalized. DISSEMINATION AND IMPLEMENTATION: The final output will be registered with the Core Outcome Measures in Effectiveness Trials initiative. A multi-faceted, quality improvement campaign for the reporting of gastrointestinal recovery in clinical studies will be launched, targeting international professional and patient groups, charitable organizations and editorial committees. Success will be explored via an updated systematic review of outcomes 5 years after registration of the core outcome set.

In depth analysis of kinase cross screening data to identify chemical starting points for inhibition of the Nek family of kinases.

Potent, selective, and cell active small molecule kinase inhibitors are useful tools to help unravel the complexities of kinase signaling. As the biological functions of individual kinases become better understood, they can become targets of drug discovery efforts. The small molecules used to shed light on function can also then serve as chemical starting points in these drug discovery efforts. The Nek family of kinases has received very little attention, as judged by number of citations in PubMed, yet they appear to play many key roles and have been implicated in disease. Here we present our work to identify high quality chemical starting points that have emerged due to the increased incidence of broad kinome screening. We anticipate that this analysis will allow the community to progress towards the generation of chemical probes and eventually drugs that target members of the Nek family.

Hyperactive cyclic motor activity in the distal colon after colonic surgery as defined by high-resolution colonic manometry.

BACKGROUND: Recovery after colonic surgery is invariably delayed by disturbed gut motility. It is commonly assumed that colonic motility becomes quiescent after surgery, but this hypothesis has not been evaluated rigorously. This study quantified colonic motility through the early postoperative period using high-resolution colonic manometry. METHODS: Fibre-optic colonic manometry was performed continuously before, during and after surgery in the left colon and rectum of patients undergoing right hemicolectomy, and in healthy controls. Motor events were characterized by pattern, frequency, direction, velocity, amplitude and distance propagated. RESULTS: Eight patients undergoing hemicolectomy and nine healthy controls were included in the study. Colonic motility became markedly hyperactive in all operated patients, consistently dominated by cyclic motor patterns. Onset of cyclic motor patterns began to a minor extent before operation, occurring with increasing intensity nearer the time of surgery; the mean(s.d.) active duration was 12(7) per cent over 3 h before operation and 43(17) per cent within 1 h before surgery (P = 0.024); in fasted controls it was 2(4) per cent (P < 0·001). After surgery, cyclic motor patterns increased markedly in extent and intensity, becoming nearly continuous (active duration 94(13) per cent; P < 0·001), with peak frequency 2-4 cycles per min in the sigmoid colon. This postoperative cyclic pattern was substantially more prominent than in non-operative controls, including in the fed state (active duration 27(20) per cent; P < 0·001), and also showed higher antegrade velocity (P < 0·001). CONCLUSION: Distal gut motility becomes markedly hyperactive with colonic surgery, dominated by cyclic motor patterns. This hyperactivity likely represents a novel pathophysiological aspect of the surgical stress response. Hyperactive motility may contribute to gut dysfunction after surgery, potentially offering a new therapeutic target to enhance recovery.

Association Between Circular Stapler Diameter and Stricture Rates Following Gastrointestinal Anastomosis: Systematic Review and Meta-analysis.

BACKGROUND: Stricture is a common complication of gastrointestinal (GI) anastomoses, associated with impaired quality of life, risk of malnutrition, and further interventions. This systematic review and meta-analysis aimed to determine the association between circular stapler diameter and anastomotic stricture rates throughout the GI tract. METHODS: A systematic literature search of EMBASE, MEDLINE and Cochrane Library was performed. The primary outcome was the rate of radiologically or endoscopically confirmed anastomotic stricture. Pooled odds ratios (OR) were calculated using random-effects models to determine the effect of circular stapler diameter on stricture rates in different regions of the GI tract. RESULTS: Twenty-one studies were identified: seven oesophageal, twelve gastric, and three lower GI. Smaller stapler sizes were strongly associated with higher anastomotic stricture rates throughout the GI tract. The oesophageal anastomosis studies showed; 21 versus 25 mm circular stapler: OR 4.39 ([95% CI 2.12, 9.07]; P < 0.0001); 25 versus 28/29 mm circular stapler: OR 1.71 ([95% CI 1.15, 2.53]; P < 0.008). Gastric studies showed; 21 versus 25 mm circular stapler: OR 3.12 ([95% CI 2.23, 4.36]; P < 0.00001); 25 versus 28/29 mm circular stapler: OR 7.67 ([95% CI 1.86, 31.57]; P < 0.005). Few lower GI studies were identified, though a similar trend was found: 25 versus 28/29 mm circular stapler: pooled OR 2.61 ([95% CI 0.82, 8.29]; P = 0.100). CONCLUSIONS: The use of larger circular stapler sizes is strongly associated with reduced risk of anastomotic stricture in the upper GI tract, though data from lower GI joins are limited.