Does Ileus Represent the Forgotten End Organ Failure in Critical Illness?

PURPOSE OF REVIEW: This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome. RECENT FINDINGS: Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN).

Safety of hospital discharge before return of bowel function after elective colorectal surgery.

BACKGROUND: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. METHODS: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system. RESULTS: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P < 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). CONCLUSION: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients.

ANTECEDENTES: El íleo es frecuente tras la cirugía colorrectal y se asocia con un aumento del riesgo de las complicaciones postoperatorias. Identificar las características de una recuperación normal del tránsito y la idoneidad para el alta hospitalaria es una tarea difícil. Este estudio examinó la seguridad del alta hospitalaria antes del restablecimiento de la función intestinal. MÉTODOS: Se llevó a cabo un estudio de cohortes prospectivo y multicéntrico a través de una red de colaboración internacional. Se incluyeron pacientes adultos sometidos a resección electiva colorrectal entre enero y abril 2018. El objetivo principal fue el reingreso hospitalario durante los 30 primeros días tras la intervención. Se utilizó un análisis de regresión multivariable para evaluar el impacto del momento del alta en función del restablecimiento de la función intestinal. El objetivo secundario fue las complicaciones postoperatorias en los primeros 30 días después de la cirugía, valoradas mediante el sistema de clasificación de Clavien-Dindo. RESULTADOS: Se incluyeron en el análisis 3.288 pacientes, de los cuales 301 (9,2%) fueron dados de alta antes del restablecimiento de la función intestinal. La mediana de la estancia hospitalaria de los pacientes dados de alta antes y después del restablecimiento de la función intestinal fue 5 (rango intercuartílico: 4-7) y 7 (6-8) días, respectivamente (P < 0,001). No hubo diferencias significativas en las tasas de reingreso entre estos grupos (6,6% versus 8,0%; P = 0,499), y este resultado se mantuvo en el análisis multivariable tras el ajuste por diferencias basales (razón de opotunidades, odds ratio, OR 0,90; i.c. del 95% 0,55-1,46, P = 0,659). Las tasas de complicaciones postoperarorias fueron similares en aquellos dados de alta antes o después del restablecimiento de la función intestinal (complicaciones menores: 34,7% versus 39,5%; complicaciones mayores 3,3% versus 3,4%; P = 0,110). CONCLUSIÓN: Dar de alta antes del restablecimiento de la función intestinal tras cirugía colorrectal electiva parece ser seguro en pacientes debidamente seleccionados.

Small Bowel Dysmotility, Pseudoobstruction, and Functional Correlation with Histopathology: Lessons Learned.

PURPOSE OF REVIEW: Small bowel dysmotility is a broad heterogeneous term that encompasses a wide range of gastrointestinal disorders resulting from abnormal gut motility. Chronic intestinal pseudo-obstruction (CIPO) is a severe, rare, and complex small bowel motility disorder at the extreme end of this spectrum. It is characterized by failure of the intestinal tract to propel contents, which results in signs and symptoms of bowel obstruction albeit in the absence of any obstructive lesion(s). In this article, we discuss up-to-date diagnostic techniques, management options, and histopathological findings in CIPO. RECENT FINDINGS: We will emphasize the latest diagnostic methodologies and therapeutic options as well as enteric histopathologic abnormalities in patients with CIPO. CIPO continues to be a clinical challenge. Several novel pharmacological agents hold promise including gastrointestinal hormone agonists and prokinetics. Furthermore, histopathologic findings may help guide therapy and provide further prognostic significance. At present, nutritional support, symptom management, and avoidance of long-term complications are the mainstay of treatment in CIPO.

Validity of the I-FEED score for postoperative gastrointestinal function in patients undergoing colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is common after gastrointestinal surgery and is associated with significant morbidity and costs. However, POI is poorly defined. The I-FEED score is a novel outcome measure for POI, developed by expert consensus. It contains five elements (intake, response to nausea treatment, emesis, exam, and duration, each scored with 0, 1, or 3 points) and classifies patients into normal, postoperative gastrointestinal intolerance (POGI), and postoperative gastrointestinal dysfunction (POGD). However, it has not yet been validated in a clinical context. The objective was to provide validity evidence for the I-FEED score to measure the construct of POI in patients undergoing colorectal surgery. METHODS: Data previously collected from a clinical trial investigating the impact of different perioperative fluid management strategies on primary POI in patients undergoing elective laparoscopic colectomy (2013-2015) were analyzed. Patients were managed by a longstanding Enhanced Recovery program (expected length of stay (LOS): 3 days). Daily I-FEED scores were generated (normal 0-2, POGI 3-5, POGD 6+ points) up to hospital discharge or postoperative day 7. Validity was assessed by testing the hypotheses that I-FEED score was higher (1) in patients with longer time to GI3 (tolerating diet + flatus/bowel movement), (2) with longer LOS (> 3 days vs shorter), (3) in patients with complications vs without, (4) in patients with poorer recovery (measured by Quality of Recovery-9 questionnaire). RESULTS: A total of 128 patients were included for analysis (mean age 61.7 years (SD 15.2), 57% male, 71% malignancy, and 39.1% rectal resection). Median LOS was 4 days [IQR3-5], and 32% experienced postoperative in-hospital morbidity. Overall, 48% of patients were categorized as normal, 22% POGI, and 30% POGD. The data supported all 4 hypotheses. CONCLUSIONS: This study contributes preliminary validity evidence for the I-FEED score as a measure for POI after colorectal surgery.

Chyme Reinfusion Is Associated with Lower Rate of Postoperative Ileus in Crohn's Disease Patients After Stoma Closure.

BACKGROUND: The rate of postoperative ileus following stoma closure is high in patients with Crohn's disease and temporary enterostomy. AIMS: To evaluate the effect of chyme reinfusion on postoperative outcomes including ileus in these patients. METHODS: Patients were screened from January 2012 to December 2017 and divided into chyme reinfusion group (n = 33) and non-chyme reinfusion group (n = 84). The following 30-day postoperative outcomes were evaluated. Univariate and multivariate analyses and propensity score matching were performed to identify risk factors for these postoperative outcomes. RESULTS: The incidence of postoperative ileus was significantly lower in the chyme reinfusion than in non-chyme reinfusion group, which had been confirmed by the results after matching (3/26 vs 11/26, p = 0.012). The rate of postoperative diarrhea was significantly lower in the chyme reinfusion group compared with non-chyme reinfusion group, whereas the difference was not significant after matching (2/26 vs 6/26, p = 0.191). Additionally, the postoperative length of stay was significantly shorter in the chyme reinfusion than in non-chyme reinfusion group before and after propensity score matching. In the multivariate analysis, chyme reinfusion was an independent protective factor for postoperative ileus (odds ratio 0.218; 95% confidence interval 0.05-0.95; p = 0.042) and for postoperative length of stay (coefficient - 0.191; 95% confidence interval - 0.350 to - 0.032, p = 0.019). CONCLUSIONS: Chyme reinfusion was associated with lower rate of postoperative ileus and shorter length of stay following stoma closure in Crohn's patients with temporary ileostomy. Further randomized clinical trial between patients with or without chyme reinfusion was needed to confirm these conclusions.

Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes.

BACKGROUND: Guillain-Barré syndrome (GBS), when severe, involves the autonomic nervous system; our objective was to assess the spectrum and predictors of dysautonomia, and how it may impact functional outcomes. METHODS: A retrospective review of patients admitted to the Mayo Clinic in Rochester, MN between January 1, 2000, and December 31, 2017, with GBS and dysautonomia was performed. Demographics, comorbidities, parameters of dysautonomia, clinical course, GBS disability score, and Erasmus GBS Outcome Score (EGOS) at discharge were recorded. RESULTS: One hundred eighty seven patients were included with 71 (38%) noted to have at least one manifestation of dysautonomia. There are 72% of patients with a demyelinating form of GBS and 36% of patients with demyelination had dysautonomia. Ileus (42%), hypertension (39%), hypotension (37%), fever (29%), tachycardia or bradycardia (27%), and urinary retention (24%) were the most common features. Quadriparesis, bulbar and neck flexor weakness, and mechanical ventilation were associated with autonomic dysfunction. Patients with dysautonomia more commonly had cardiogenic complications, syndrome of inappropriate antidiuretic hormone, posterior reversible encephalopathy syndrome, and higher GBS disability score and EGOS. Mortality was 6% in patients with dysautonomia versus 2% in the entire cohort (P = 0.02). CONCLUSIONS: Dysautonomia in GBS is a manifestation of more severe involvement of the peripheral nervous system. Accordingly, mortality and functional outcomes are worse. There is a need to investigate if more aggressive treatment is warranted in this category of GBS.

Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons.

OBJECTIVES: Vagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positive muscularis macrophages (mMφ) and dampening surgery-induced intestinal inflammation. Here, we evaluated if 5-HT4 receptor (5-HT4R) agonist prucalopride can mimic this effect in mice and human. DESIGN: Using Ca2+ imaging, the effect of electrical field stimulation (EFS) and prucalopride was evaluated in situ on mMφ activation evoked by ATP in jejunal muscularis tissue. Next, preoperative and postoperative administration of prucalopride (1-5 mg/kg) was compared with that of preoperative VNS in a model of POI in wild-type and α7nAChR knockout mice. Finally, in a pilot study, patients undergoing a Whipple procedure were preoperatively treated with prucalopride (n=10), abdominal VNS (n=10) or sham/placebo (n=10) to evaluate the effect on intestinal inflammation and clinical recovery of POI. RESULTS: EFS reduced the ATP-induced Ca2+ response of mMφ, an effect that was dampened by neurotoxins tetrodotoxin and ω-conotoxin and mimicked by prucalopride. In vivo, prucalopride administered before, but not after abdominal surgery reduced intestinal inflammation and prevented POI in wild-type, but not in α7nAChR knockout mice. In humans, preoperative administration of prucalopride, but not of VNS, decreased Il6 and Il8 expression in the muscularis externa and improved clinical recovery. CONCLUSION: Enteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI. TRIAL REGISTRATION NUMBER: NCT02425774.

Isoperistaltic versus antiperistaltic ileocolic anastomosis. Does it really matter? Results from a randomised clinical trial (ISOVANTI).

BACKGROUND: Right hemicolectomy is a very common surgery. Many studies compare different options for laparoscopic ileocolic anastomoses: intra- or extracorporeal; handsewn or stapled; side-to-side or end-to-side. However, there are no studies about the influence that peristalsis could have on this anastomosis. The aim of this study is to compare safety and feasibility of isoperistaltic and antiperistaltic anastomosis in terms of postoperative morbidity and mortality between both groups. The secondary endpoint is to compare long-term functional outcomes (chronic diarrhoea) and quality of life (GIQLI questionnaire) after a 1-year follow-up period. METHODS: A double-blind, randomised, prospective trial in patients undergoing scheduled surgery for right colon cancer with laparoscopic right hemicolectomy and isoperistaltic (ISO) or antiperistaltic (ANTI) ileocolic anastomoses. RESULTS: Hundred and eight patients were included in the study. Patients were randomised either to isoperistaltic or antiperistaltic configuration (54 ISO/ANTI). No significant differences in baseline variables were found. No differences in surgical time (130 [120-150] min ISO vs. 140 [127-160] ANTI, p = 0.481), nor in anastomotic time (19 [17-22] vs. 20 [16-25], p = 0.207) and nor in postoperative complications: 37.0% ISO versus 40.7% ANTI, (p = 0.693) were found. There were no differences in postoperative ileus (p = 0.112) nor in anastomotic leakage (3.7% vs. 5.56%, p = 1.00). Differences in "time to first flatus" and "time to first deposition" were found in favour of the antiperistaltic group (p = 0.004 and p = 0.017). Anastomotic configuration did not influence hospital stay (3 days [2-6] isoperistaltic vs. 3 [2-4] antiperistaltic, p = 0.236). During follow-up, there were no differences between the two groups at 1, 6 and 12 months (p = 0.154, p = 0.498 and p = 0.683), nor in chronic diarrhoea rates in GIQLI scores (24% ISO vs. 31.4% ANTI, p = 0.541). CONCLUSIONS: The isoperistaltic and antiperistaltic ileocolic anastomosis present similar results in terms of performance, safety and functionality. However, further studies must be carried out in order to assess relationship between postoperative ileus and anastomosis configuration. TRIAL REGISTRATION: Randomised Clinical trial (Identifier: NCT02309931).

Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip.

A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1ß, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.

Neuroimmune interaction and the regulation of intestinal immune homeostasis.

Many essential gastrointestinal functions, including motility, secretion, and blood flow, are regulated by the autonomic nervous system (ANS), both through intrinsic enteric neurons and extrinsic (sympathetic and parasympathetic) innervation. Recently identified neuroimmune mechanisms, in particular the interplay between enteric neurons and muscularis macrophages, are now considered to be essential for fine-tuning peristalsis. These findings shed new light on how intestinal immune cells can support enteric nervous function. In addition, both intrinsic and extrinsic neural mechanisms control intestinal immune homeostasis in different layers of the intestine, mainly by affecting macrophage activation through neurotransmitter release. In this mini-review, we discuss recent insights on immunomodulation by intrinsic enteric neurons and extrinsic innervation, with a particular focus on intestinal macrophages. In addition, we discuss the relevance of these novel mechanisms for intestinal immune homeostasis in physiological and pathological conditions, mainly focusing on motility disorders (gastroparesis and postoperative ileus) and inflammatory disorders (colitis).

Postoperative ileus following major colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is characterized by delayed gastrointestinal recovery following surgery. Current knowledge of pathophysiology, clinical interventions and methodological challenges was reviewed to inform modern practice and future research. METHODS: A systematic search of MEDLINE and Embase databases was performed using search terms related to ileus and colorectal surgery. All RCTs involving an intervention to prevent or reduce POI published between 1990 and 2016 were identified. Grey literature, non-full-text manuscripts, and reanalyses of previous RCTs were excluded. Eligible articles were assessed using the Cochrane tool for assessing risk of bias. RESULTS: Of 5614 studies screened, 86 eligible articles describing 88 RCTs were identified. Current knowledge of pathophysiology acknowledges neurogenic, inflammatory and pharmacological mechanisms, but much of the evidence arises from animal studies. The most common interventions tested were chewing gum (11 trials) and early enteral feeding (11), which are safe but of unclear benefit for actively reducing POI. Others, including thoracic epidural analgesia (8), systemic lidocaine (8) and peripheral µ antagonists (5), show benefit but require further investigation for safety and cost-effectiveness. CONCLUSION: POI is a common condition with no established definition, aetiology or treatment. According to current literature, minimally invasive surgery, protocol-driven recovery (including early feeding and opioid avoidance strategies) and measures to avoid major inflammatory events (such as anastomotic leak) offer the best chances of reducing POI.

Impact of enhanced recovery after surgery (ERAS) protocol on gastrointestinal function in gynecologic oncology patients undergoing laparotomy.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) on postoperative gastrointestinal function in gynecologic oncology patients. METHODS: This retrospective cohort study compared gynecology oncology patients undergoing non-emergent laparotomy from 10/2016 to 6/2017 managed on an ERAS protocol to a control cohort from the year prior to ERAS implementation. Major changes to postoperative care after ERAS implementation included multimodal analgesia, early feeding, goal-directed fluid resuscitation, and early ambulation. The primary outcome was rate of postoperative ileus, defined as nausea and vomiting requiring nothing-per-mouth status or nasogastric tube (NGT) placement. Secondary outcomes included length of stay (LOS) and 30-day readmission. RESULTS: 376 patients met inclusion criteria; 197 in the control group and 179 in the ERAS group. Patient demographics were similar between groups. Ileus rate was significantly lower in the ERAS group (2.8% vs. 15.7%; p < 0.001), and fewer patients in the ERAS group required NGT placement (2.2% vs. 7.1%; p = 0.06). ERAS remained independently associated with decreased ileus rates when controlling for other patient and surgical factors (OR 0.2; p = 0.01). Epidural use was correlated with a significant increase in ileus risk (OR 2.6; p = 0.03), as was increased Charlson Comorbidity Index (OR 1.2; p < 0.01). LOS was significantly decreased in the ERAS group (2.9 vs. 4.0 days; p = 0.04), while 30-day readmission rates were similar (10.1% vs. 10.7%; p = 0.62). CONCLUSIONS: Implementation of an ERAS protocol significantly decreases the risk of postoperative ileus in gynecologic oncology patients undergoing laparotomy. ERAS also reduced LOS compared to pre-ERAS controls.

Multicentre observational study of gastrointestinal recovery after elective colorectal surgery.

AIM: Postoperative ileus (POI) is characterised by delayed gastrointestinal recovery and is common after colorectal surgery. Numerous strategies to optimise POI have been proposed but its management remains an unmet clinical need. This study aimed to characterise the duration and management of gastrointestinal recovery in patients undergoing elective colorectal surgery. METHOD: A snapshot, prospective, observational study was undertaken between November 2016 and January 2017 at 10 regional hospitals in the United Kingdom. Adult patients undergoing elective colorectal surgery with resection of bowel or reversal of stoma were included. Outcomes included time until return of gastrointestinal function, timing of nasogastric tube (NGT) insertion, uptake of targeted interventions and clinical outcomes. Data were validated for accuracy by independent investigators. RESULTS: 204 patients met the eligibility criteria. The median time for gastrointestinal recovery was 3 days (IQR 2-4); right-sided resections were associated with longer gastrointestinal recovery than left sided (4 days (2.75-5.25) vs 3 days (2-4); P = 0.002). The rate of NGT insertion was 22.5% at a median time of 4 (4-4.75) days. NGT insertion after vomiting was associated with a higher incidence of bronchopneumonia compared to early placement (13.3% vs 29.0%). Targeted interventions, such as chewing gum (4.4%), selective mu-receptor antagonists (1.0%) and pro-kinetic agents (13.7%) were infrequently used. CONCLUSION: The average time to gastrointestinal recovery after elective colorectal surgery was three days. Late NGT insertion was associated with an increased incidence of bronchopneumonia. The clinical uptake of targeted interventions to improve gastrointestinal recovery was poor.

Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery.

BACKGROUND: Postoperative ileus (POI) is observed in 20-30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI. The objectives were to compare the expression of arachidonic acid metabolism (AAM) enzymes (1) between patients who underwent colorectal cancer surgery and followed an ERP or not (NERP), (2) and between ERP patients who experimented POI or not and (3) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle. METHODS: This was a translational study. Main outcome measures were gastrointestinal motility recovery data, mRNA expressions of key enzymes involved in AAM (RT-qPCR) and ex vivo motility values of the circular colon muscle. Twenty-eight prospectively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery. RESULTS: ERP reduced colonic mucosal COX-2, microsomal prostaglandin E synthase (mPGES1) and hematopoietic prostaglandin D synthase (HPGDS) mRNA expression. mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance (respectively, r2 = 0.25, p = 0.002 and r2 = 0.6, p < 0.001). In muscularis propria, HPGDS mRNA expression was correlated with GI motility recovery (p = 0.002). The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle (p = 0.03). CONCLUSION: The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1, HPGDS and COX-2. Furthermore, mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients.

Clinical and radiological diagnosis of gallstone ileus: a mini review.

Gallstone ileus is a rare cause of bowel obstruction, which mainly affects the elderly population. The associated mortality is estimated to be up to 30%. The presentation of gallstone ileus is notoriously non-specific, and this often contributes to the delay in diagnosis. The diagnosis of gallstone ileus relies on a radiological approach, and herein we discuss the benefits and drawbacks of the use of different modalities of radiological imaging: plain abdominal films, computed tomography, magnetic resonance imaging, and ultrasound scanning. Based on our case experience and review of the literature, the authors conclude that although an effective first-line tool, plain abdominal films are not adequate for diagnosing gallstone ileus. In fact, the gold standard in an acutely unwell patient is computed tomography.

Irf4-dependent CD103+CD11b+ dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus.

OBJECTIVE: Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. DESIGN: POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball. The impact of the microbiota on intestinal peristalsis was evaluated after oral antibiotic treatment. RESULTS: We found that Cd11c-Cre+ Irf4flox/flox mice lack CD103+CD11b+ DCs, a DC subset unique to the intestine whose function is poorly understood. Their absence in the intestinal muscularis reduced pathogenic inducible nitric oxide synthase (iNOS) production by monocytes and macrophages and ameliorated POI. Pathogenic iNOS was produced in the jejunum by resident Ly6C- macrophages and infiltrating chemokine receptor 2-dependent Ly6C+ monocytes, but in the colon only by the latter demonstrating differential tolerance mechanisms along the intestinal tract. Consistently, depletion of both cell subsets reduced small intestinal POI, whereas the depletion of Ly6C+ monocytes alone was sufficient to prevent large intestinal POI. The differential role of monocytes and macrophages in small and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI. CONCLUSIONS: Our findings reveal that CD103+CD11b+ DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes and macrophages and for dysregulating intestinal motility in POI.

Nicotine chewing gum for the prevention of postoperative ileus after colorectal surgery: a multicenter, double-blind, randomised, controlled pilot study.

PURPOSE: When postoperative ileus is not resolved after 5 days or recurs after resolution, prolonged POI (PPOI) is diagnosed. PPOI increases discomfort, morbidity and hospitalisation length, and is mainly caused by an inflammatory response following intestinal manipulation. This response can be weakened by targeting the cholinergic anti-inflammatory pathway, with nicotine as essential regulator. Chewing gum, already known to stimulate gastrointestinal motility itself, combined with nicotine is hypothesised to improve gastrointestinal recovery and prevent PPOI. This pilot study is the first to assess efficacy and safety of nicotine gum in colorectal surgery. METHODS: Patients undergoing elective oncological colorectal surgery were enrolled in this double-blind, parallel-group, controlled trial and randomly assigned to a treatment protocol with normal or nicotine gum (2 mg). Patient reported outcomes (PROMS), clinical characteristics and blood samples were collected. Primary endpoint was defined as time to first passage of faeces and toleration of solid food for at least 24 h. RESULTS: In total, 40 patients were enrolled (20 vs. 20). In both groups, six patients developed PPOI. Time to primary endpoint (4.50 [3.00-7.25] vs. 3.50 days [3.00-4.25], p = 0.398) and length of stay (5.50 [4.00-8.50] vs. 4.50 days [4.00-6.00], p = 0.738) did not differ significantly between normal and nicotine gum. There were no differences in PROMS, inflammatory parameters and postoperative complications. CONCLUSIONS: We proved nicotine gum to be safe but ineffective in improving gastrointestinal recovery and prevention of PPOI after colorectal surgery. Other dosages and administration routes of nicotine should be tested in future research.

Postoperative Ileus: Pathophysiology, Current Therapeutic Approaches.

Postoperative ileus, which develops after each abdominal surgical procedure, is an iatrogenic disorder characterized by a transient inhibition of gastrointestinal motility. Its pathophysiology is complex involving pharmacological (opioids, anesthetics), neural, and immune-mediated mechanisms. The early neural phase, triggered by activation of afferent nerves during the surgical procedure, is short lasting compared to the later inflammatory phase. The latter starts after 3-6 h and lasts several days, making it a more interesting target for treatment. Insight into the triggers and immune cells involved is of great importance for the development of new therapeutic strategies. In this chapter, the pathogenesis and the current therapeutic approaches to treat postoperative ileus are discussed.

Gallstone ileus: An overview of the literature. / El íleo biliar: una revisión de la literatura médica.

INTRODUCTION: Gallstone ileus represents 4% of the causes of bowel obstruction in the general population, but increases to 25% in patients above the age of 65 years. Gallstone ileus does not present with unique symptoms, making diagnosis difficult. Its management is surgical, but there is no consensus as to which of the different surgical techniques is the procedure of choice. At present, there is no recent review of this pathology. AIM: To conduct an up-to-date review of this disease. MATERIALS AND METHODS: Articles published within the time frame of 2000 to 2014 were found utilizing the PUBMED, EMBASE, and Cochrane Library search engines with the terms "gallstone ileus" plus "review" and the following filters: "review", "full text", and "humans". RESULTS: The results of this review showed that gallstone ileus etiology was due to intestinal obstruction from a gallstone that migrated into the intestinal lumen through a bilioenteric fistula. The presence of 2 of the 3 Rigler's triad signs was considered diagnostic. Abdominal tomography was the imaging study of choice for gallstone ileus diagnosis and the surgical procedures for management were enterolithotomy, one-stage surgery, and two-stage surgery. Enterolithotomy had lower morbidity and mortality than the other 2 procedures. CONCLUSIONS: The aim of gallstone ileus treatment is to release the obstruction, which is done through enterolithotomy. It is the recommended technique for gallstone ileus management because of its lower morbidity and mortality, compared with the other techniques.

Recovery of gastric ileus following laparoscopic ventral rectopexy within an enhanced recovery protocol.

PURPOSE: The enhanced recovery after surgery (ERAS) protocol has had limited adoption in laparoscopic ventral rectopexy (LVR), and the extent of gastric ileus shortly after LVR remains unknown. This study was designed to assess the degree of gastric emptying shortly after LVR within an ERAS protocol. METHODS: From August 2012 to June 2014, 40 patients diagnosed with external or internal rectal prolapse were recruited. All patients underwent LVR within an ERAS protocol. Carbohydrate solution (CS) was administered before and 5 h after surgery on the same day. The pyloric area (PA) was measured using ultrasonography before and after each CS intake. RESULTS: The PA was measured in 34 patients. The PA measured prior to CS intake, before surgery, was not significantly different from that after surgery. The rate of increase in the PA, which was calculated by the PA measured 1 h after CS intake divided by the PA measured prior to CS intake before surgery, was not significantly different from that after surgery. The postoperative hospital stay was 1 (1-2) day, and 36 patients (90 %) were discharged on the first postoperative afternoon. CONCLUSION: Postoperative gastric ileus was resolved in most cases within 5 h after LVR under an ERAS protocol.