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.     

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.     

Human gut hormone profiles in patients with short bowel syndrome

We have studied gut hormone profiles in a small number of patients on treatment with home parenteral nutrition following near-total enterectomy who had no evidence of Inflammatory bowel disease and who were otherwise healthy. These and age- and sex-matched controls had gut hormone profiles measured after an overnight fast and a standard test meal. Circulating pancreatic glucagon concentrations and profiles were the same in both groups as were the Neurotensin and VIP. Peptide YY (PYY) concentrations and profiles were markedly raised in the short bowel group. It is suggested that the normal glucagon responses reflect the integrity of the remaining duodenum and pancreas. Circulating neurotensin and VIP originate largely from outside the bowel and so the removal of the gut source does not significantly affect their profiles. Enteroglucagon and PYY are secreted from terminal ileum and colon in response to unabsorbed food residues. The elevated circulating levels and profiles are consistent with those observed by others in patients with jejunoileal bypass or major resections in whom unabsorbed nutrients reach the colon.     

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.     

短肠综合征1例报道

短肠综合征对人体危害极大,死亡率高,早期发现、诊断,以减少坏死小肠面积及各种炎性因子的释放,减轻全身炎性反应尤为重要。     

胰高血糖素样肽-2对短肠大鼠残留小肠吸收功能基因表达的影响

目的研究胰高血糖素样肽-2(GLP-2)对短肠大鼠残留小肠钠葡萄糖共同转运体(SGLT1)和二肽转运体(PEPT1)的mRNA表达影响。方法将75%小肠切除大鼠分为空白对照组(空白组)、生长激素对照组(GH组)和胰高血糖素样肽2组(GLP-2组),另设一组正常进食大鼠作空白组的对照组(正常组)。术后1d起进食标准大鼠饲料。术后6d取末端回肠黏膜,用逆转录多聚酶链反应方法半定量检测其SGLT1和PEPT1的mRNA表达情况。结果残留回肠SGLT1和PEPT1的mRNA表达,空白组显著高于正常组(P<0.05),空白组和GH组及GLP2组之间差异均无统计学意义(P>0.05)。结论GLP-2术后短期应用对短肠大鼠残留回肠SGLT1和PEPT1的mRNA表达可能无显著影响。     

Post-infectious irritable bowel syndrome in patients with Shigella infection

BACKGROUND AND AIMS: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI-IBS) have been documented. The aims of this study were to verify the role of bacterial gastroenteritis in the development of IBS and the risk factors for the development of PI-IBS. The clinical course of PI-IBS was also investigated. METHODS: We recruited 143 patients with shigellosis during its outbreak and 113 controls. Both groups were followed up for 12 months. Bowel symptoms were evaluated by use of questionnaires at 3, 6 and 12 months after the initial recruitment. RESULTS: Complete data were obtained from 101 patients (70.6%) and 102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS (adjusted OR; 2.9, 95% CI; 1.1-7.9). Of the 15 patients, five had IBS symptoms consistently for 12 months, three did not have IBS symptoms initially and seven had fluctuating bowel symptoms. The duration of diarrhea was an independent risk factor of PI-IBS. CONCLUSIONS: Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.     

肠易激综合征病人肠道气体定量分析

目的　通过X线腹部平片对肠道气体进行定量测试 ,分析肠道气体容量与肠易激综合征(IBS)的关系。方法　 4 8例根据罗马Ⅱ标准诊断的IBS病人和 2 5例正常对照的X线腹部平片经数字化转换后输入电脑 ,肠道气体量在电脑显示为象素值 ,经体格标准化后 ,以气体容量积分 (GVS)表达。以对照GVS的 x± 2s为正常值 ,分析GVS与IBS型别的关系。结果　正常对照GVS为 0 .0 5 5±0 .0 12 ,离散系数为 2 1.8% ;便秘型IBS均值 (0 .0 76± 0 .0 2 7,t =3.5 99,P <0 .0 1)与正常人比较显著增高 ,4 4 .4 %的个体GVS大于正常值 ,余在正常范围 ;腹泻型IBS均值 (0 .0 4 8± 0 .0 32 ,t =1.4 76 ,P >0 .0 5 )与正常人比较差异无显著性 ,但离散系数高达 6 6 .7% ,4 2 .9%的病人GVS降低 ,14 .3%增高。结论　IBS病人肠道气体容量存在明显改变 ,并与型别有关 ;便秘型以增多为主 ,腹泻型以减少为主。     

简短炎症性肠病生活质量问卷的信效度评价

背景简短炎症性肠病问卷(the short inflammatory bowel disease questionnaire,SIBDQ)广泛用于评估炎症性肠病(inflammatory bowel disease,IBD)患者的健康相关生活质量.目的引进SIBDQ量表并评估其信效度.方法根据Brislin模型的翻译-回译流程得到中文版SIBDQ(SIBDQ-C).对2020-06/2021-06就诊于广州中医药大学第一附属医院、中山大学第一附属医院IBD患者进行测评;使用克朗巴赫系数、分半信度和重测信度检验量表的信度,使用验证性因子分析评价其结构效度.结果共发放问卷113份,最终回收112份.SIBDQ-C的Cronbach’sα为0.90,折半系数为0.86;量表四个维度间的Spearman相关系数在0.61到0.77之间;验证性因子分析的近似误差方根、非范拟合指数、比较拟合指数、拟合优度指数分别为0.08、0.93、0.97、0.92;不同粪便形态患者的SIBDQ-C总分及各维度得分均有统计学差异(P<0.05).结论SIBDQ-C具有良好的信度及效度,可以用于临床测量我国IBD患者的生活质量.     

Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure

Short bowel syndrome (SBS) with intestinal failure (IF) is a rare but severe complication of Crohn’s disease (CD), which is the most frequent benign condition that leads to SBS after repeated surgical resections, even in the era of biologics and small molecules. Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF. These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBS-IF patients on parenteral support or nutrition. Teduglutide has been approved for the treatment of SBS-IF, and apraglutide is currently in clinical development. The use of these drugs was examined with a focus on their use in CD patients.     

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.     

Sandostatin impairs postresection intestinal adaptation in a rat model of short bowel syndrome

Because of its antisecretory properties, sandostatin has been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of sandostatin on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of SBS. Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-sandostatin rats underwent bowel resection and were treated with sandostatin (SBS-SND). Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-SND animals demonstrated lower (vs SBS rats) duodenal and jejunal bowel weights, jejunal and ileal mucosal weight, jejunal and ileal mucosal DNA and protein, jejunal and ileal villus height, cell proliferation index in the ileum, and enterocyte apoptosis in jejunum and ileum. We conclude that in a rat model of SBS sandostatin decreases cell proliferation and inhibits structural intestinal adaptation.     

Follow-up of patients with functional bowel symptoms treated with a low FODMAP diet

AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease.METHODS: Consecutive patients with irritable bowel syndrome(IBS) or inflammatory bowel disease(IBD) and co-existing IBS fulfilling the ROME Ⅲ criteria, who previously attended an outpatient clinic for low FODMAP diet(LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietarytreatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent.RESULTS: One hundred and eighty patients were included, 131(73%) IBS and 49(27%) IBD patients. Median age was 43 years(range: 18-85) and 147(82%) were females. Median follow-up time was 16 mo(range: 2-80). Eighty-six percent reported either partial(54%) or full(32%) efficacy with greatest improvement of bloating(82%) and abdominal pain(71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group(42% vs 29%, P = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group(25%, P 0.001) and IBD group(23%, P = 0.002) along with a significant increase in patients with a mild indolent disease course of 37%(P 0.001) and 23%(P = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group(P 0.001) and 66% in the IBD group(P 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course(P 0.001). Satisfaction with dietary management was seen in 83(70%) IBS patients and 24(55%) IBD patients. Eightyfour percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients.CONCLUSION: These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients.     

Elevated plasma glucagon-like peptide 1 and 2 concentrations in ileum resected short bowel patients with a preserved colon

BACKGROUND: The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially from L cells located mainly in the ileum. Both hormones prolong intestinal transit and GLP-2 is intestinotrophic in rodents. Patients with a jejunostomy have poor adaptation, rapid gastric and intestinal transit, and impaired postprandial GLP-2 secretion. Ileum resected short bowel patients with a preserved colon show evidence of functional adaptation and have normal gastric emptying. AIM: To investigate if GLP-1 and GLP-2 contribute to the positive effects of a preserved colon in short bowel patients by measuring circulating levels of GLP-1 and GLP-2 in seven ileum resected short bowel patients with a preserved colon and seven age and sex matched controls. METHODS: GLP-1 and GLP-2 immunoreactivity was measured by specific radioimmunoassays in plasma collected at fasting and at regular intervals 180 minutes after a test meal. RESULTS: Median (25-75%) fasting GLP-2 values were 72 (69-105) pmol/l versus 23 (19-27) pmol/l (p=0.001) and meal stimulated area under the curve was 21 078 (14 811-26 610) min x pmol/l versus 11 150 (7151-12 801) min x pmol/l (p=0.01) in short bowel patients with a preserved colon compared with control subjects. Fasting GLP-1 values were 10 (6-12) pmol/l versus 5 (3-5) pmol/l (p=0.01) and meal stimulated area under the curve was 3418 (2966-6850) min x pmol/l versus 2478 (1929-3199) min x pmol/l (p=0.04), respectively. CONCLUSION: Ileum resected short bowel patients with a preserved colon had elevated fasting plasma concentrations of GLP-1 and GLP-2 and significantly larger meal stimulated areas under the curve compared with age and sex matched controls. Elevated GLP-1 and GLP-2 concentrations may contribute to the positive effects of a preserved colon on intestinal motility and functional adaptation in ileum resected short bowel patients.     

What do patients with irritable bowel syndrome dream about? A comparison with inflammatory bowel disease

BACKGROUND: It is a common experience for people to dream of events about which they are either anxious or concerned. We therefore hypothesised that the dreams of patients with irritable bowel syndrome may reflect their worries about their problem especially as hospital out-patients with this disorder tend to exhibit some anxiety. In addition, dreaming about, for instance bowels, in patients with irritable bowel syndrome in excess of that observed in other gastrointestinal disorders may be of importance. AIM: To establish whether patients with irritable bowel syndrome dream about bowel-related issues more than controls or patients with inflammatory bowel disease. PATIENTS AND METHODS: A total of 57 patients with irritable bowel syndrome and 57 patients with inflammatory bowel disease were compared with 60 healthy controls. All subjects completed a structured questionnaire concerning sleeping habits and dream characteristics as well as an assessment of anxiety and depression. RESULTS: There were no differences in the sleeping habits between any of the groups. However, significantly more patients with irritable bowel syndrome and inflammatory bowel disease dreamt about their bowels (22% inflammatory bowel disease patients, 18% irritable bowel syndrome patients vs 3% of controls, p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) and soiling themselves (16% of inflammatory bowel disease patients, 14% of irritable bowel syndrome patients vs 2% of controls; p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) than controls. CONCLUSION: Chronic gastrointestinal disorders, of both a functional and organic nature, may influence the nature of dreams. In those patients who dream about their symptoms, it would be interesting to know whether this affects the course of their disease, either positively or negatively, in any way.     

Severe short bowel syndrome with a surgically reversed small bowel segment

Summary We report a case of short bowel syndrome (60 cm of jejunum anastomosed to the left colon) with reversal of the distal 15 cm of jejunum in a 21-year-old man. The nutritional absorptive capacity and digestive motility was studied for 18 months postoperatively. His absorptive capacity reached subnormal values allowing him oral nutritive autonomy and normal social life. The results of the manometric study suggested that the reversed segment delayed intestinal transit time. The prolonged contact of the chyme with the intestinal absorptive mucosa possibly increased its absorptive capacity.Our data and the literature reports suggest that reversal of a bowel loop could help wean patients from their dependence on parenteral nutrition.     

Impaired meal stimulated glucagon-like peptide 2 response in ileal resected short bowel patients with intestinal failure

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a growth factor for the intestinal epithelium in rodents and may affect intestinal transit. AIMS: To study the GLP-2 response to nutrient ingestion in seven short bowel patients with intestinal failure and seven controls. METHODS: The patients and controls were admitted twice for two test meals after a night of fasting. Meal A was liquid (300 ml, 1.88 MJ); meal B was a regular breakfast (755 g, 3.92 MJ). Plasma samples were collected for 180 minutes; GLP-2 immunoreactivity was measured with an NH(2) terminal specific radioimmunoassay. RESULTS: Both meals elicited significant increases in plasma GLP-2 in controls. The magnitude and duration of the responses were dependent on the meal size: the maximum median (25-75%) increases after meal A and B were 24 (3-28) and 48 (33-56) pmol/l. Plasma GLP-2 returned to basal concentrations 180 minutes after meal A, but remained at 50% of peak values after meal B. In the patients neither meal significantly changed the GLP-2 concentration; the maximum median elevation after meal B was 5 (2-8) pmol/l. There were significant differences between patients and controls with respect to the GLP-2 responses to meals A and B. CONCLUSION: Identification of GLP-2 as a tissue specific intestinal growth factor and demonstration of an impaired meal stimulated GLP-2 response in short bowel patients raises the possibility that GLP-2 administration may constitute a new therapeutic strategy, enhancing jejunal adaptation in ileum resected short bowel patients with intestinal failure.     

Implementation of a multidisciplinary team approach and fish oil emulsion administration in the management of infants with short bowel syndrome and parenteral nutrition-associated liver disease

OBJECTIVE:

To describe the authors’ experience with the implementation of a multidisciplinary approach and use of fish oil emulsion (FOE) in the management of infants with short bowel syndrome (SBS) and parenteral nutrition-associated liver disease (PNALD).

METHODS:

Between August 2006 and June 2009, four cases of SBS and severe PNALD were managed by the team using specifically developed protocols. The FOE was initiated if serum direct bilirubin levels were ≥100 μmol/L. To quantify the degree of exposure to high serum direct bilirubin levels over time, the area under the curve (AUC) for each patient was calculated before and after initiation of FOE. Linear regression analyses were performed to evaluate correlations between the AUC, duration of cholestasis and initiation of FOE.

RESULTS:

All patients survived and no complications were observed during the study period. After the first patient, FOE was initiated progressively earlier, but poor correlation between the AUC before and after its introduction was observed (r²=0.41924). However, there was strong correlation between the duration of PNALD before FOE initiation and time to resolution (r²=0.72133): the earlier the FOE was initiated, the shorter the time to resolution.

CONCLUSION:

The authors report a positive experience with the implementation of a multidisciplinary approach and the use of FOE in infants with SBS and severe PNALD. The earlier the FOE was initiated during the cholestatic process, the shorter the time to resolution. The present study is a hypothesis generator, raising the question of whether an earlier introduction of this particular therapy can effectively shorten the cholestasis process in these patients.     

Surgical management and autologous intestinal reconstruction in short bowel syndrome

Short bowel syndrome (SBS) is a serious condition with considerable morbidity and mortality. When treatment with parenteral nutrition fails and life-threatening complications occur, autologous intestinal reconstruction (AIR) should be considered before intestinal transplantation (ITx). Single or combined ITx should be reserved for patients with severe liver disease and as last resort in the treatment of SBS. Longitudinal intestinal lengthening and tailoring (LILT) has proven its value in AIR, but its availability depends on the expertise of the surgeons. Serial transverse enteroplasty (STEP) has similar success rates as LILT and fewer patients progress to ITx. STEP is also applicable at small bowel dilatation in ultra-short bowel syndrome. The scope may be widened when duodenal dilatation can be treated as well. Spiral intestinal lengthening and tailoring (SILT) is a promising alternative. More research is needed to confirm these findings. Therefore we suggest an international data registry for all intestinal lengthening procedures.