'Idiopathic' intestinal failure--the importance of identifying and treating primary psychopathology.

BACKGROUND: Gastrointestinal neuromuscular disorders (GINMD) are an important cause of intestinal failure (IF). We present six cases of IF in whom a diagnosis of GINMD was initially suspected, but in whom psychopathology was discovered to be the primary etiology. METHODS: (i) Six consecutive cases referred to our unit with IF, initially presumed to be due to GINMD, were selected. Informed consent was obtained from all patients. Case notes were reviewed for salient clinical information. (ii) A literature search was performed to ascertain the epidemiology of psychopathology in IF and the current evidence for the management of severe functional GI disorders with a multidisciplinary psychiatric approach. KEY RESULTS: (i)All six cases required multidisciplinary psychiatric management in a specialized psychiatric unit that included the use of antidepressants, antipsychotics, mood stabilizers, and Electroconvulsive therapy in addition to nutritional support via enteral or parenteral routes. (ii) The evidence base for the treatment of severe FGIDs is sparse. CONCLUSIONS & INFERENCES: There is a need for additional reporting of such cases and further research. Our experience would suggest that a delay in the involvement of a specialist liaison psychiatrist has the potential to be life threatening in such cases. This may be more likely with greater severity, where the apparent predominance of 'physical' symptoms generates reluctance in both patient and physician to consider a psychiatric etiology and also appears to occur due to a lengthier investigative process than existed previously. We therefore propose that the provision of a specialist psychiatric assessment for all patients presenting with IF is indicated at the point of initial clinical contact, based upon the substantial clinical benefit it has the potential to confer upon a significant minority. This process need not delay investigation, which can continue as indicated in parallel, but can be life-saving.

The evolving role of post-ligament of Trietz nasojejunal feeding in enteral nutrition and the need for improved feeding tube design and placement methods.

Nutrition support is an important link in the chain of therapy for intensive care unit patients. The early institution of nutrition support significantly reduces the incidence of septic complications, reduces mortality, and shortens hospital stay. Unfortunately, impaired gastrointestinal function, particularly gastric atony, restricts the use of nasogastric enteral tube feeding, and the use of this route of administration in these patients can lead to regurgitation, aspiration, and the development of pneumonia. Postpyloric enteral feeding was heralded as a means of overcoming many of these problems. Overall, the results of controlled studies do not support a role of postpyloric duodenal feeding in reducing the incidence of aspiration pneumonia. As a consequence, post-ligament of Treitz nasojejunal enteral feeding is proposed as the technique of choice in these patients. Feeding tube design must incorporate a gastric aspiration port to overcome problems of gastroesophageal acid reflux, duodenogastric bile reflux, and increased gastric acid secretion, problems that occur during "downstream" jejunal feeding. Tube placement technique will need to be refined and patients will need to receive a predigested enteral diet. In postoperative surgical patients in the intensive care unit, there is also a need for a newly designed dual-purpose nasogastric tube capable initially of providing a means of undertaking gastric aspiration and decompression and subsequently a means of initiating nasogastric enteral feeding.

Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome.

BACKGROUND: Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). AIM: To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. METHODS: In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. RESULTS: The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). CONCLUSION: The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.

Formulation of enteral diets for use in jejunal enteral feeding.

Nasogastric enteral feeding is not tolerated in patients with gastric atony and in many critically-ill patients in whom gastric emptying may be delayed and in whom gastro-oesophageal regurgitation may lead to pulmonary aspiration of enteral feed and the development of pneumonia. Initial attempts to overcome these problems led to the development of post pyloric enteral feeding techniques with the infusion port of the tubes positioned in the duodenum. In many centres this technique is still the most practised post-pyloric enteral feeding technique. Nasoduodenal feeding tubes often retroperistalse into the stomach. The technique of choice, therefore, in these difficult patients is to position the infusion port of the feeding tube well distal to the ligament of trietz (post ligament of trietz nasojejunal enteral tube feeding). While nasogastric and nasoduodenal enteral feeding techniques have been shown to elicit a stimulatory exocrine pancreatic response, distal jejunal enteral feeding does not. During this mode of feeding the ileal brake is activated and pancreatic exocrine pancreatic secretion inhibited by the action of the released peptide YY and glucagon-like peptide-1 hormones, in turn the inhibition of pancreatic secretion being the result of inhibition of trypsin secretion. In the light of the findings showing the absence of a stimulatory pancreatic exocrine response to nasojejunal enteral feeding these patients should receive a predigested rather than a polymeric enteral diet.

Systematic review and meta-analysis: the clinical and physiological effects of fibre-containing enteral formulae.

BACKGROUND: Enteral nutrition can be associated with gastrointestinal side effects and fibre supplementation has been proposed as a means to normalize bowel function. AIM: To evaluate systematically the effects of fibre supplementation of enteral feeds in healthy volunteers and patients both in the hospital and community settings. METHODS: Electronic and manual bibliographic searches were conducted. Controlled studies in adults or children, comparing fibre-supplemented vs. fibre-free formulae given as the sole source of nutrition for at least 3 days, were included. RESULTS: Fifty-one studies (including 43 randomized-controlled trials), enrolling 1762 subjects (1591 patients and 171 healthy volunteers) met the inclusion criteria. Fibre supplementation was generally well tolerated. In the hospital setting, the incidence of diarrhoea was reduced as a result of fibre administration (OR 0.68, 95% CI: 0.48-0.96; 13 randomized-controlled trials). Meta-regression showed a more pronounced effect when the baseline incidence of diarrhoea was high. In both patients and healthy subjects, fibre significantly reduced bowel frequency when baseline frequency was high and increased it when it was low, revealing a significant moderating effect of fibre. CONCLUSIONS: The review indicates that the fibre-supplemented enteral formulae have important physiological effects and clinical benefits. There is a need to use a consistent approach to undertake more studies on this issue in the community setting.

Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo-obstruction: a controlled multinational case series.

BACKGROUND AND AIMS: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a severe motility disorder associated with significant morbidity. Several histopathological (neuropathic and myopathic) phenotypes have been described but only a single adult with jejunal smooth (circular) muscle alpha-actin deficiency. We present a prospective multinational case series investigating smooth muscle alpha-actin deficiency as a biomarker of this disease. METHODS: A total of 115 fully clinically and physiologically (including prolonged (24 hour) ambulatory jejunal manometry) characterised CIIP patients from three European centres were studied. Immunohistochemical localisation of actins and other cytoskeletal proteins were performed on laparoscopic full thickness jejunal biopsies and compared with adult controls. Distribution of alpha-actin was also characterised in other gut regions and in the developing human alimentary tract. RESULTS: Twenty eight of 115 (24%) CIIP patient biopsies had absent (n = 22) or partial (n = 6) jejunal smooth muscle alpha-actin immunostaining in the circular muscle layer. In contrast, smooth muscle alpha-actin staining was preserved in the longitudinal muscle and in adult jejunal controls (n = 20). Comparative study of other adult alimentary tract regions and fetal small intestine, suggested significant spatial and temporal variations in smooth muscle alpha-actin expression. CONCLUSIONS: The ability to modulate alpha-smooth muscle actin expression, evident in development, is maintained in adult life and may be influenced by disease, rendering it a valuable biomarker even in the absence of other structural abnormalities.

Pseudo-pseudo-obstruction: lessons in diagnosis and management.

Chronic intestinal pseudo-obstruction (CIP) has been defined as a rare and severe, disabling disorder, which is characterised by recurring episodes or continuous symptoms and signs of bowel obstruction, including radiological features of obstruction. It is suggested that the diagnosis should be broadened to include patients with severe gastrointestinal symptoms who do not have radiological features of obstruction but who have manometric features of CIP and/or have demonstrable end organ list of pathological features described in CIP. A case of pseudo-pseudo-obstruction is described in this issue of the Journal. Originally the patient was thought to have CIP, and a mechanical cause of obstruction was suspected based on small intestine manometric features, suggesting a distal mechanical obstruction and a worsening of symptoms when treated with a prokinetic agent. As patients with CIP can develop mechanical obstruction and episodes of mechanical obstruction can mimic CIP, small intestine manometry and trials of prokinetic therapy should be undertaken in all difficult cases of obstruction and particularly in patients with documented CIP.

Chronic idiopathic intestinal pseudo-obstruction: the need for a multidisciplinary approach to management.

At the outset of the research programme into irritable bowel syndrome (IBS) it was perceived that there was a need to develop a symptom-based classification for the patients. Four groups of patients were identified, those with spastic colon syndrome, diarrhoea-predominant spastic colon syndrome, functional diarrhoea and midgut dysmotility. While working with outpatients with IBS it was noted how some of them had suffered symptoms for many years; specifically, a group of patients satisfying the criteria for midgut dysmotility had also suffered from particularly severe and intractable intestinal symptoms. These patients underwent 24 h ambulatory studies of small intestinal motility and the majority were found to have manometric features of chronic idiopathic intestinal pseudo-obstruction (CIIP). To characterise the cause, laparoscopic full-thickness small intestine and colonic biopsies have been obtained in forty-five of the latter group of patients. Of these patients 58% have been found to have complete or partial deficiency of alpha-actin epitope staining in the inner circular layer of small intestinal smooth muscle. This deficiency is believed to represent an important biomarker rather than the cause of CIIP, since alpha-actin epitope deficiency has been observed in association with enteric neuropathy and myopathies. In relation to the management of CIIP patients, a multidisciplinary model is proposed incorporating management of co-morbid psychological and psychiatric pathology, abdominal and musculoskeletal pain, fatigue, urological symptoms and nutrition. A six-stage nutritional management plan for these patients is presented.

Review article: The rationale for antidepressant therapy in functional gastrointestinal disorders.

The rationale for antidepressants in the treatment of functional gastrointestinal disorders (FGDs) has been the subject of much interest. However, because of our incomplete understanding of FGDs, this rationale remains unclear. A key point is whether the high degree of psychiatric co-morbidity associated with FGDs (40-90%) represents a shared pathophysiology or the ascertainment bias of tertiary referral patients. Our aims were four-fold: (i) to review the current rationale for antidepressant therapy in FGDs; (ii) to review the studies comparing the characteristics of FGDs with both organic gastrointestinal disease and psychiatric disorders; (iii) to propose a model of FGDs which explains the high psychiatric co-morbidity; (iv) to compare the treatment regimes and effectiveness of antidepressants in FGDs and psychiatric illnesses. The review highlights two important observations. Firstly, the characteristics of FGDs are similar to those of affective disorders and dissimilar to those of organic disease. Secondly, although antidepressants benefit FGD sufferers, their benefits in psychiatric illnesses are greater. We conclude that, in view of the degree of similarity between FGDs and affective disorders, FGDs could be considered as affective disorders in their own right and, if the prescription of antidepressants conformed to their use in affective disorders, FGD morbidity would be reduced.

Clinically significant benign pneumoperitoneum as a complication of percutaneous endoscopic gastrostomy.

Benign pneumoperitoneum is a complication of percutaneous endoscopic gastrostomy (PEG) feeding tube placement. The rate of occurrence is reported as up to 25%. It is usually an incidental finding that arises immediately following the procedure. We report a case of pneumoperitoneum that developed a significant time after the initial procedure. The patient developed intractable vomiting and had to be fed parenterally. The pneumoperitoneum resolved and the gastrostomy tube feed was re-started.

Distal colonic motor activity in four subgroups of patients with irritable bowel syndrome.

With the aim of improving end organ treatment, we describe a new system of classifying irritable bowel syndrome (IBS) according to clinical features into four groups, spastic colon syndrome (SCS), functional diarrhea (FD), diarrhea-predominant spastic colon syndrome (DPSCS), and midgut dysmotility (MGD). The aim of the study was to investigate fasting and postprandial distal colonic motility in the four groups of patients and to compare the results with normal controls. Distal colonic motility studies were performed in the unprepared colon. 2.5-hr recordings were made from four channels with a standard meal administered at 0.5 hr. The intubated colon was treated as a study segment and data analyzed for study segment activity index (SSAI) and number and mean amplitude of pressure peaks over 30-min epochs. Patients with SCS had significantly higher (P < 0.05) mean amplitude of pressure peaks (60 min, 120 min) and SSAI (120 min) than controls and patients with FD, DPSCS, and MGD. In contrast, patients with FD and DPSCS had significantly (P < 0.05) lower postprandial SSAI than controls and patients with SCS (60 min, 120 min). With the exception of raised postprandial mean amplitude of pressure peaks (120 min), MGD patients had normal distal colonic motility. Division of IBS patients into subgroups has highlighted significant differences in distal colonic motility that provide insights into etiopathogenesis and should assist targeting of current and newly developed therapies, particularly receptor active agents.