Understanding short bowel syndrome: Current status and future perspectives

Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other causes are vascular diseases, neoplasms or inflammatory bowel disease. The spectrum of the disease is widely variable from single micronutrient malabsorption to complete intestinal failure, depending on the remaining length of the small intestine, the anatomical portion of intestine and the function of the remnant bowel. Over the last years, the management of affected patients has remarkably improved with the increase in patients’ quality of life and survival, mainly thanks to advances in home-based parenteral nutrition (PN). In the last ten years new treatment strategies have become available together with increasing experience and the encouraging results with new drugs, such as teduglutide, have added a new dimension to the management of SBS.This review aims to summarize the knowledge available in the current literature on SBS epidemiology, pathophysiology, and its surgical (including intestinal lengthening procedures and intestinal transplantation) and medical management with emphasis on the recent advances.Moreover, this review attempts to provide the new understanding and recent approaches to SBS complications such as sepsis, catheter thrombosis, and intestinal failure-associated liver disease.     

Definitions of intestinal failure and the short bowel syndrome

The European Society for Clinical Nutrition and Metabolism defined intestinal failure (IF) as “the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth”. IF is classified as type 1-acute, type 2-prolonged acute and type 3-chronic IF. A short bowel syndrome (SBS) due to the intestinal malabsorption associated with a functional small intestine length of less than 200 cm is the most frequent mechanism of IF. SBS is a difficult and multifaced disease. Complications due to SBS itself and to treatments, such as long term home parenteral nutrition, can adversely affect the patient outcome. The care of SBS requires complex technologies and multidisciplinary and multiprofessional activity and expertise. Patient outcome is strongly dependent on care and support from an expert specialist team. This paper focuses on the aspects of the pathophysiology and on the complications of SBS, which are most relevant in the clinical practice, such as intestinal failure associated liver disease, renal failure, biliary and renal stones, dehydration and electrolyte depletion, magnesium deficiency and d-lactic acidosis.     

How do patients with Crohn's disease fare on home parenteral nutrition?

The United Kingdom and Ireland Register of Home Parenteral Nutrition (HPN) contains details on 237 cases treated between 1977 and 1987. One hundred courses of HPN were given to 89 patients for complications of Crohn's disease. Six registering centers provided 87 percent of the courses of treatment. The short-bowel syndrome was a factor in 60 patients, fistulas in 29 patients, and exacerbation of the disease in 41 patients. Thirty patients had more than one complication. The age distribution of patients with Crohn's disease was the same as for all HPN patients. Nine patients have died and eight have ceased HPN because of complications from the treatment. Fifty two percent of the patients had no complications. Patients with Crohn's disease on HPN had a significantly better lifestyle than the group as a whole (P<.05) and had lower sepsis and complication rates (P<.01 and 0.001, respectively). The 60 Crohn's patients with short-bowel syndrome spent a significantly longer time on HPN than Crohn's patients overall (P<.05). Only 15 of these have been able to cease treatment and resume enteral feeding, compared with 23 of the other 40 patients who were able to resume enteral nutrition after a median of three months. Analysis of the authors' group of 35 patients included in the 100 showed that the only nutritional parameters of use in monitoring the patients' well-being were weight and serum albumin. Eighty percent of the patients with Crohn's disease who were treated by HPN have either successfully resumed enteral feeding or are successfully managing their own HPN. HPN is a safe and effective treatment for patients with acute or chronic intestinal failure from Crohn's disease. Authors writing on behalf of the HPN Register of the United Kingdom and Ireland.     

Survival rate and prognostic factors in patients with intestinal failure

BACKGROUND: Intestinal failure impairs nutritional status and survival expectance. Though intestinal adaptation and enteral independence may be achieved, artificial nutrition is needed in about half of the patients. AIMS: This study is aimed at assessing the causes of death, survival rate, enteral independence in time, and factors affecting the clinical outcome in a group of patients with intestinal insufficiency. PATIENTS: Sixty-eight patients with intestinal insufficiency, due to major intestinal resection in 60 cases (short bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23 cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8 cases, were enrolled and followed-up for (median) 36 months (25th and 75th percentile in 12 and 60 months, respectively). In 60 short bowel syndrome patients, the main conditions that led to intestinal failure were ischemic bowel (28), major surgery complications or severe adhesions (17), radiation enteritis (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma (others). METHODS: Seventeen variables age, underlying disorders, length of remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and home) and its variations in time, causes of death, survival rate and time were considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards regression model. RESULTS: At the time of admission to the hospital, none of the patients had nutritional independence, 54 (79.4%) were on parenteral nutrition and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%) patients showed enteral independence, 39 were on home parenteral nutrition, 3 on enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral supplementation with hydroelectrolyte solutions only. After a median value of 36 months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation with hydroelectrolyte solutions, and 26 cases reached enteral independence. A significant relationship was detected between the length of remnant bowel and types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r = 0.48; P = 0.001), parenteral nutrition being more frequent in patients with very short bowel. Twenty-two patients (32.4%) died (4 from newly occurring malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up. Eleven of 22 patients died from conditions related to intestinal failure (8 cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36, 48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%, respectively, but it was significantly lower for patients with <50 cm of remnant bowel than those with longer residual intestine (P < 0.05), and in patients who started home parenteral nutrition above the age of 45 years (P < 0.02). Survival rate was higher in patients with enteral independence than those with enteral dependence (P < 0.05). Better survival rates were registered in patients with chronic obstructive intestinal pseudo-obstruction and major surgery complications, whereas ischemic bowel and even more radiation enteritis were associated with a lower survival expectance. CONCLUSIONS: Actuarial survival rate of patients with intestinal failure quotes 88 and 78% at 3 and 5 years, respectively. It is influenced by the length of remnant intestine, age at the start of home parenteral nutrition, enteral independence and, to some extent at least, by the primary disorder. Enteral independence can be achieved in time by about 40% of the patients with intestinal insufficiency, but for home parenteral nutrition-dependent cases, intravenous feeding can be stopped in less than one out of five patients during a median 3-year period.     

Role of Serial Transverse Enteroplasty in the Management of Adult-Type Short Bowel Syndrome: Experience from a Single Tertiary Referral Hospital in Turkey

Background: There is little knowledge with regard to the management of intestinal failure in countries where home care services and dedicated intestinal rehabilitation centers are limited. This study presents a single-center experience of treating adult-type short bowel syndrome (SBS) with serial transverse enteroplasty (STEP).Methods: Medical records were retrospectively reviewed from November 2009 to April 2018 on patients with adult-type SBS. All patients underwent STEP, and a representative quota sample of control patients treated with conventional measures were included. Clinico-demographic characteristics including baseline and post-treatment information about the orientation of bowel alignment and nutritional status were evaluated.Results: The mean patient age was 51.1 ± 16.2 in the STEP group and 57.6 ± 12.7 in the control group (P = .304). The median small bowel length was 60 cm (interquartile range (IQR): 40-90) in the STEP group (before the lengthening) and 90 cm (IQR: 70-100) in the control (at the initiation of intestinal rehabilitation) (P = .035). Durations of median follow-up were 18 months (IQR: 14-58) and 10 months (IQR: 3-14), respectively (P = .019). In the STEP group, the mean increase in bowel length after STEP was 37.3 ± 11.6 cm, and at their follow-up 7 patients (64%) had successfully progressed to enteral autonomy. In the control group, only 3 patients (27%) were successful. Mean time to wean parenteral nutrition was 45 ± 54 days, and the mean increase in enteral calorie intake was 1.79 ± 1.60-fold after lengthening in the STEP group.Conclusions: STEP is an easy-to-perform procedure in the surgical rehabilitation of adult-type SBS. When performed simultaneously with reconnection surgery, it may offer a cost-effective and comprehensive solution to the treatment strategy in middle income settings.     

The carina is approximately 1-2 cm above the pericardial reflection among Chinese patients

Background

Central venous catheters (CVCs) and central venous pressure (CVP) monitor is essential in fluid resuscitation and management for critically ill patients. Accuracy of the CVP is mainly dependent on the proper position of the catheter tip. Although the X-ray visible carina was generally recommended as the alternative of pericardial reflection (PR) to guide the placement of CVCs, few data was available with respect to the distance between the carina and PR among Chinese patients. The purpose of this study was to explore the topographic relationship between the trachea carina and PR among Chinese patients by using computed tomography (CT) images.

Methods

CT images of 172 patients who underwent CT pulmonary angiogram or CT angiogram for aorta from January 1, 2013 to November 30, 2013 were retrospectively reviewed. Distances between upper margin of the right clavicular notch, trachea carina, PR and atriocaval junction (ACJ) were calculated using the table positions on axial images.

Results

The mean length of extrapericardial superior vena cava (SVC) was 2.5 cm. For all patients, the PR was lower than the carina by average 1.6 cm.

Conclusions

Given the PR was average 1.6 cm lower than the carina among Chinese patients, placing the CVCs tip approximate 1.6 cm lower the carina among Chinese patients would be more likely to result in a satisfactory placement.     

Clinical outcome of long-term home parenteral nutrition in non-oncological patients: a report from two specialised centres

Objective and methods Forty-one (20 m, 21 f) non-oncological home parenteral nutrition (HPN) patients (52.0±16.6 years, BMI 20.2±4.0 kg/m²), enrolled from 1995 to 2005, underwent a clinical and biochemical follow-up at 3 months, 1 and 3 years. Results At admittance the Karnofsky Index ranged between 40 and 50 in 13 (31.7%) and 60 and 80 in 28 (68.3%) patients; the most frequent underlying disease was mesenteric infarction (11 patients, 27%). All had a central venous access. Mean catheterization days were 864±992, while mean HPN days were 630±668. At the 3-month follow-up, all patients were on HPN, at 1 year 24 (58.5%) and at 3 years 11 (27%). At 3 months, 1 and 3 years there was a significant increase in BMI (p=0.001), body weight (p=0.001) and Karnofsky Index (p=0.001), as well as an improvement of several biochemical parameters. Survival rate of HPN patients was 90.2% at 1 years, 87.8% at 3 years and 82.9% at 5 years. As to HPN-related complications, there was a central venous catheter (CVC) obstruction in 8 patients (19.5%) and 47 CVC infections in 24 (58.5%) patients. The infection rate was 1.32/₀₀ days of catheterization (1.8/₀₀ from 1995 to 1998 and 1.0/₀₀ from 1999 to 2005). Hospitalisation was necessary in over 50% of patients, and death occurred in 8, always as a consequence of the primary disease. Conclusions The experience of the nutritional team and careful patient and caregiver training reduce CVC infection rate and the overall risk of complications possibly due to HPN.     

Parenteral therapy and complications in patients with intestinal failure in a regional unit

Objective: To describe a cohort of patients with intestinal failure (IF) and tunnelled catheters in a regional IF unit, treatment and catheter-related complication rates, and to compare the quality of care with previously published results from specialised IF centres in Denmark.

Methods: A retrospective chart review of an adult IF patient cohort receiving parenteral therapy through tunnelled catheters in a regional IF unit from 2005 to 2014. Demographics, indication, type and frequency of parenteral therapy, dwell time, cause of removal and complications were recorded.

Results: Parenteral therapy was provided to 78 patients with a median age of 64 (25–86) years. Numbers increased from seven patients in 2005 to 40 in 2014. The cause of IF was surgical complications (33%), cancer (28%), inflammatory bowel disease (IBD, 15%) and other causes (24%). The median duration of parenteral therapy was 453 days (range: 16–3651 days). One hundred and forty-two tunnelled catheters were inserted. The incidence of catheter-related blood stream infection (CRBSI) was 1.51/1000 days (95% CI: 1.20–1.90) and the incidence of thrombosis was 0.10/1000 days (0.04–0.25). Seventy-two episodes of CRBSI occurred with 89 microorganisms cultured, the most common being coagulase-negative Staphylococcus (n?=?25, 28%).

Conclusion: The rate of CRBSI did not differ from larger centres in Denmark but the rate of thrombotic events was higher than expected. Parenteral therapy can safely and effectively be offered to patients with IF in smaller centres.     

Glucagon-like Peptide-2 Induces a Specific Pattern of Adaptation in Remnant Jejunum

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 μg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2’s effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2’s effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.     

Short Bowel Syndrome: A Review of Management Options

Extensive resection of the intestinal tract frequently results in inadequate digestion and/or absorption of nutrients, a condition known as short bowel syndrome (SBS). This challenging condition demands a dedicated multidisciplinary team effort to overcome the morbidity and mortality in these patients. With advances in critical care management, more and more patients survive the immediate morbidity of massive intestinal resection to present with SBS. Several therapies, including parenteral nutrition (PN), bowel rehabilitation and surgical procedures to reconstruct bowel have been used in these patients. Novel dietary approaches, pharmacotherapy and timely surgical interventions have all added to the improved outcome in these patients. However, these treatments only partially correct the underlying problem of reduced bowel function and have limited success resulting in 30% to 50% mortality rates. However, increasing experience and encouraging results of intestinal transplantation has added a new dimension to the management of SBS. Literature available on SBS is exhaustive but inconclusive. We conducted a review of scientific literature and electronic media with search terms ''short bowel syndrome, advances in SBS and SBS’ and attempted to give a comprehensive account on this topic with emphasis on the recent advances in its management.     

Short bowel syndrome in children and adults: from rehabilitation to transplantation

Introduction: Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved.

Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results.

Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.     

Restoring gut physiology in short bowel patients: from bench to clinical application of autologous intestinal reconstructive procedures

ABSTRACT

Introduction: Short bowel syndrome represents the leading etiology that causes intestinal failure both in children and adults. Total parenteral nutrition support has dramatically improved the prognosis for these patients but, if related irreversible complications occur, the alternative is represented by surgery and/or transplantation.

Areas covered: Autologous gastrointestinal reconstructive procedures are a feasible, alternative approach with good long-term outcome data inexperienced surgical centers.

Expert opinion: Ongoing innovative efforts have driven the surgical options for successful autologous reconstructive surgery: bowel elongation/tapering techniques (LILT, STEP, and the new SILT) together with the ‘reversed bowel segment’ procedure are now recognized procedures and all must be tailored to the individual patient needs to obtain the optimal result in terms of enteral autonomy. Background laboratory experimentation with new procedures e.g. options for bowel dilation techniques and distraction-induced enterogenesis, may provide additional management and treatment modalities.     

Emerging treatments for short bowel syndrome in adult patients

Introduction: Short bowel syndrome (SBS) is the major cause of chronic intestinal failure (IF), defined as ‘the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth’.

Areas covered: Spontaneous intestinal adaptation, including increased hormonal secretion, development of hyperphagia and gut microbiota dysbiosis, occurs 2 years after resection, improving intestinal absorption and decreasing PN dependency. Hormonal treatments, promoting intestinal hyperadaptation, have been proposed in patients with SBS with chronic IF. Clinical studies showed teduglutide to increase urine production and reduce the need for parenteral support volume in these patients. According to the latest ESPEN Guidelines, if a growth factor treatment is considered, the GPL2 analog, teduglutide, should be the first-choice treatment.

Expert opinion: These therapies underline the importance of patient monitoring at home and the complexity for HPN adaptation. A multidisciplinary approach should be a gold standard.