Complications of short bowel syndrome

Short bowel syndrome is the commonest reversible cause of intestinal failure. Most of the children are started on parenteral nutrition (PN) after surgery to enable growth and allow time for intestinal adaptation i.e. a process whereby the shorter length of bowel is able to achieve complete function as if the entire length of bowel is present. With advances in management a majority of children with short bowel syndrome are able to discontinue PN and establish on full enteral feeds. This article mainly focuses on the complications of short bowel syndrome that need to be avoided in order for intestinal adaptation to progress and the child to be established on enteral feeds/oral diet.     

Pediatric intestinal transplantation: historical notes,principles and controversies

The development in technique and immunosuppressive management of the last 12 yr have made intestinal transplantation an effective treatment for children with intestinal failure. The information provided in this review support such a conclusion, but was more clearly validated by the March 2001 Medicare Report which provided a national coverage decision of the Social Security Act for intestinal transplantation. As of May 2001, there were 55 centers world-wide which have performed 696 intestinal transplants in 656 patients. (Intestinal Transplant Registry, http://www.lhsc.on.ca/itr) the majority of recipients have been children, and there has been a greater need for liver replacement in conjunction with the allograft intestine because of a higher incidence of TPN-induced cholestatic liver disease in children. Though overall long-term survival is approximately 50%, similar advances in surgical, clinical and immunosuppressive management since 1995 have improved patient survival to more than 70% in most experienced programs. Over 80% of survivors are enjoying nutrition-supporting intestinal function. The major causes of graft loss and patient demise continues to be rejection and infection. Tacrolimus remains the mainstay of immunosuppressive therapy. Further experience other induction protocols utilizing rapamycin and daclizumab, as well graft pretreatment protocols may further enhance results in the future.     

Intestinal transplantation in children

Intestinal transplant is now considered a viable option for children with irreversible intestinal failure suffering life limiting complications of parenteral nutrition. Identifying the possible candidates and referring them early to the transplant centre allows consideration of transplantation before the clinical situation deteriorates, and ensures the establishment of communication pathways between the family, transplant centre and the patient's local team. This encourages optimal care both before and after transplantation, and has been shown to improve long-term outcome.There are different types of intestinal transplants that may be performed according to the indication. With improvements in surgical techniques, immunosuppression, early identification of rejection and good communication between professionals and families, outcomes for patients undergoing these procedures continue to improve.     

Blood flow in experimental short bowel syndrome

Mechanisms of intestinal adaptation after major loss of small bowel have been studied extensively but little attention has been paid to related changes in blood flow. In 1972, Touloukian and Spencer were the first to study intestinal blood flow after 50% midintestinal resection in rats [16]. In the present study an 80% midintestinal resection was performed in rats (n = 54). Blood flows to the jejunal and ileal remnants, the anastomosis, and the cecum and colon were measured with the radioactive microsphere method on days 1, 2, 3, 5, and 28 after surgery. Results were compared with blood flow estimates after jejunal or ileal tranection (n = 48) and with normal controls (n = 9). The results showed that the operative stress of intestinal transection is followed by a brief increase in intestinal blood flow. After 80% small-bowel resection, intestinal blood flow remains more significantly elevated for at least 3 days. Blood flow to the ileal remnant remains elevated for at least 4 weeks after surgery. The mechanisms responsible for the increase in blood flow remain to be defined. Offprint requests to: M. E. Höllwarth     

Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia

The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15‐yr‐old male from pre‐B‐cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre‐B‐cell acute lymphoblastic leukemia. He is currently alive 31 months post‐transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed.     

Endogenous ethanol fermentation in a child with short bowel syndrome

The term "auto-brewery syndrome" has been frequently used to describe patients who show features of alcohol intoxication because of abnormal yeast proliferation after ingesting carbohydrate-rich meals. We present a case of a 3-y-old girl with short bowel syndrome (SBS) who demonstrated signs of alcohol intoxication on repeated occasions. A blood test indicated an ethanol concentration of 15 mmol/l, and cultures from gastric fluid and faeces showed the presence of Candida kefyr. An association was found between the introduction of a carbohydrate-rich fruit drink and the occurrence of symptoms. CONCLUSION: The possibility of endogenous ethanol fermentation should be considered in patients with SBS and the diagnosis of auto-brewery syndrome added to the differential diagnosis list for D-lactic acidosis. Management includes both antifungal treatment and special diet modification.     

Current status of small bowel transplantation in children

Small bowel transplantation is gradually changing from an experimental procedure to a very desirable and viable treatment option in children with irreversible intestinal failure due to either short bowel syndrome or functional impairment. Long term total parenteral nutrition and home parenteral nutrition would be necessary to manage these children in the absence of a small bowel transplant programme. Parenteral nutrition is also associated with complications which can result in chronic liver disease. In India, there is no infrastructure for this treatment option and even if it was there the cost of this method of treatment is likely to be more than the cost of post-operative immunosuppression. Small bowel can be transplanted as an isolated graft, in combination with the liver or as part of a multiviscera! transplant. The operative techniques have been standardised. Major post-operative complications result from sepsis and lymphoproliferative diseases. The best results have been obtained with a combined liver and small bowel transplant.     

Management of short bowel syndrome in infancy

Short bowel syndrome (SBS) is a reduction in functioning bowel length which is most often a result of surgical resection. Risk factors in the neonatal period include necrotising enterocolitis, small bowel atresia and gastroschisis. With increasing survival of preterm infants there is an increase in incidence. Management is dependent on the use of parenteral nutrition to maintain fluid and electrolyte homeostasis and promote growth and development with the longer term aim being to promote intestinal adaptation to achieve partial or complete enteral autonomy. In this review we discuss the incidence, aetiology, pathophysiology, medical and surgical treatments and outcome.     

Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long-term total parenteral nutrition

It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long-term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter-related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood-identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non-palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.     

Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.     

Non-Hodgkin's lymphoma after liver transplantation: Response to chemotherapy

An increased incidence of lymphoproliferative disorders immunosuppressed organ transplant recipients has long been recognised. Lymphoproliferative disorders occur in 2% of orthotopic liver transplant patients. Different therapies have been used, but the optimal treatment remains unknown. Relatively little information is available on experience with cytotoxic chemotherapy. Three children who developed Burkett-like, non-Hodgkin's lymphomas after liver transplantation are described. The disease failed to regress after initial management, which included a reduction in immunosuppression. With cytotoxic chemotherapy all three achieved complete remission, which continued 36+, 35+, and 16+ months after diagnosis. Results suggest that in selected cases chemotherapy can be safe in late-onset lymphomas appearing after solid organ transplantation. © 1996 Wiley-Liss, Inc.     

Living donor small bowel transplantation: Literature review 2003–2006

The experience with living donors for intestinal transplantation is limited. However, Intestinal Registry data suggest that the outcomes of the procedure are comparable with those obtained with intestinal transplant from deceased donors. In selected cases, this strategy may have a role in the treatment of patients with irreversible intestinal failure suffering life-threatening complications from total parenteral nutrition. The present review covers most of the published data on this topic between 2003 and 2006, with special reference to living donor intestinal transplantation of pediatric recipients.     

Surgical therapy for short bowel syndrome

Patients with short bowel syndrome (SBS) suffer tremendous morbidity secondary to prolonged hospitalization and chronic parenteral nutrition (TPN). Overall, the majority of infants will adapt and ultimately become independent of TPN, but this process may require many months or years. Reasons for continued TPN dependency include bowel dysmotility, bacterial overgrowth, insufficient adaptation, or very short bowel length. It is this subpopulation of patients who may benefit from surgical procedures that optimize intestinal adaptation and increase the mucosal absorptive surface area. The goal of this review article is to summarize the process of intestinal adaptation and then to outline the surgical principles and techniques available to surgeons who treat this complicated group of patients.     

Frequent IgE sensitization to latex, cow's milk, and egg in children with short bowel syndrome

Children with short bowel syndrome (SBS) undergo frequent operations, so they are at risk for sensitizing to latex. There have been isolated reports of sensitization to food in these children. In a cross-sectional study, we assessed sensitization to latex, cow's milk, and egg with skin prick tests (SPT) and serum-specific immunoglobulin E (IgE) in 14 children with SBS. Data were collected about the number of operations with latex devices, serum total IgE, and history of feeding with milk formula. Ten children were sensitized to latex (specific IgE median: 6.7 kU/l, range: 0.5–33). Compared with those non-sensitized, sensitized children had significantly (p < 0.05) higher levels of serum total IgE in z-units (mean rank 3.25 vs. 9.2, respectively), and more operations with latex devices (mean rank 3.75 vs. 9). Eight children were sensitized to cow's milk, one with only positive SPT, the other seven with serum-specific IgE (median: 3.5, range: 0.5–21.1 kU/l), and five to egg (specific IgE median: 0.68, range: 0.58–2.17 kU/l). Except for some isolated days with cow's milk formula, the children had been initially fed with a diet without intact cow's milk proteins. Sensitization to latex, cow's milk, and egg is very frequent in children with SBS. They should be treated in a latex-free environment since the very early stages of the disease, and should be routinely studied regarding food sensitization, as this might contribute as an added factor in the chronic diarrhea of these patients.     

Long-term nutritional assessment in children with short bowel syndrome

目的 比较不同剩余小肠长度的短肠综合征患儿长期随访营养状况.方法 对我院已脱离肠外营养2年以上的短肠综合征的14例患儿进行随访.随访内容包括人体测量(身高、体重)和血液生化指标测定(血常规;肝功能;血铜、锌、铁、钙、磷、镁;维生素A、维生素E、β-胡萝卜素、维生素B12),并根据剩余小肠长度≤60 cm和＞60 cm分两组进行比较.结果 1例患儿存在轻度营养不良,1例患儿存在重度营养不良,1例患儿超重.≤60 cm和＞60 cm组比较,年龄别身高百分比29.65±19.22、53.31±36.15和Z-评分-0.73±0.90、0.48±2.00、年龄别体重百分比44.39±31.41、47.43±29.42和Z-评分-0.57±1.90、-0.30±0.63以及BMI百分比49.20±39.82、43.71±19.43和Z-评分-0.22±2.11、-0.20±0.57均无统计学意义.剩余小肠≤60 cm组患儿的维生素A、维生素E水平为(46.87±20.07) μg/dl和(4.89±4.57)王g/L均低于剩余小肠＞60 cm组的(152.27±75.98) μg/dl和(11.68±5.97)μg/L,两组比较差异有统计学意义.Hb、MCV、MCH、MCHC、前白蛋白、白蛋白、血铜、锌、铁、钙、磷、镁、β-胡萝卜素、维生素B12水平无差异.结论 短肠综合征患儿脱离肠外营养大于2年的远期营养状况基本正常,剩余小肠长度不同对脱离肠外营养2年后患儿的体格发育情况无明显影响,但是剩余小肠过短脂溶性维生素A、E吸收仍存在问题,需坚持全面随访.     

短肠综合征儿童导管相关性血流感染的单中心回顾性研究

目的评估儿童短肠综合征(SBS)导管相关血流感染(CRBSI)的发生率和危险因素。方法回顾性分析2015年8月至2019年12月收治的19例SBS患儿的临床资料,评估CRBSI的发生率和相关危险因素。结果在19例SBS患儿中,共置管57次,总置管日为1 907天,其中6例患儿共发生11次CRBSI,发生率为5.8次/1000导管日。SBS患儿CRBSI的常见表现为发热(6/11,54.5%)、嗜睡(5/11,45.4%)、体质量不增(7/11,63.6%)和肠造瘘量增加(7/11,63.6%)。与未发生CRBSI组相比,CRBSI组SBS患儿的回盲瓣缺失以及肠外营养持续时间≥120天的比例更高,差异均有统计学意义(P0.05)。SBS患儿发生CRBSI时的血培养共获得11次阳性结果,最常见的病原微生物为肺炎克雷伯杆菌(6/11,54.55%)。结论 CRBSI发生可能与回盲瓣缺失和肠外营养持续时间长有关。     

Recent advances and future prospects in intestinal and multi-visceral transplantation

From an experimental procedure, intestinal transplantation (ITx) has evolved over the last 10 yr into a treatment option for patients suffering from short bowel syndrome and who develop life-threatening complications from total parenteral nutrition (TPN) (e.g. liver dysfunction, line sepsis, shortage of venous access, etc.). One-year survival rates are approximately 70% and thus similar to lung Tx. However, the intestine remains the most challenging abdominal organ to transplant. This is because of the severe immune response (mostly rejection) that is produced, and therefore the need for profound immunosuppression with its attendant complications (sepsis, lymphoma, direct drug toxicity). Unlike other organs, graft loss as a result of acute rejection can occur late after transplantation (more than 1 yr post-transplant). With regard to the actual immunosuppressive regimens, considerable experience in patient management is required to optimize outcome of those complex transplants, which are permanently at risk of rejection and infection. ITx remains an unfinished product, and the application of ITx to patients doing well on TPN warrants further research in the understanding of the rejection process, in the development of less toxic and more efficient immunosuppressive protocols, and in the development of immunomodulatory strategies, to better control rejection and thereby reduce the need for immunosuppression.     

Fatal deterioration of neurological disease after orthotopic liver transplantation for valproic acid-induced liver damage

We describe a 12-year-old girl with an early onset neurologic disease of slow progressiveness and electro-encephalography showing epileptic activity. The girl developed fulminant liver failure 5 months after the start of valproic acid treatment. Repeated mitochondrial assays failed to prove a mitochondrial disorder, but muscle biopsies were slightly pathological. Liver histology indicated acute-on-chronic liver disease. Six weeks after a successful orthotopic liver transplantation her neurological condition deteriorated rapidly, soon leading to generalized cortical disease and death. Post-mortem brain examination showed advanced central nervous destruction. We suggest that this is a late-onset Huttenlocher variant of Alpers' syndrome, where fulminant liver failure can be triggered by valproic acid, and orthotopic liver transplantation can subsequently trigger a fatal neurologic deterioration. Our case illustrates that when a referral center receives a previously unknown patient with hepatocellular insufficiency, it might be impossible to differentiate between fulminant vs. acute-on-chronic liver failure, and the decision whether to perform a liver transplantation or not would become difficult.     

Prevention of parenteral nutrition-associated liver disease in children

Liver injury is associated with parenteral nutrition therapy. Severity of injury varies from minimal and transient increases in liver-related blood tests to biliary cirrhosis and liver failure. Severe parenteral nutrition-related liver disease is usually confined to patients who have undergone massive intestinal resection. In these patients, early sepsis appears to cause initial liver injury, and recurring sepsis and inflammation, local or systemic, may result in its perpetuation and progression. Liver disease associated with parenteral nutrition is not necessarily related either to duration of parenteral nutrition or to delayed intestinal feeding. However, treatment includes enteral nutrition to promote enterohepatic circulation of bile acids and management of inflammation and sepsis, including control of intestinal bacterial overgrowth. Restriction of intravenous lipid emulsions may be important. The clinical picture of advanced liver failure related to short bowel syndrome differs from liver failure with an anatomically normal gastrointestinal tract. In the former, hyperbilirubinemia, hepatosplenomegaly, and functional hypersplenism dominate the clinical picture, and severe ascites and esophageal variceal hemorrhage are unusual. Early referral of these patients for intestinal and/or liver transplantation may provide the best chance for long-term survival.