Isolated intestinal transplantation for intestinal failure

OBJECTIVE: Parenteral nutrition sustains life in patients with intestinal failure. However, some experience life-threatening complications from parenteral nutrition, and in these individuals intestinal transplantation may be lifesaving. METHODS: This is a retrospective review of 28 consecutive isolated small bowel transplants performed in eight adults and 20 children between December 1993 and June 1998 at the University of Nebraska Medical Center. RESULTS: The 1-yr patient and graft survivals were 93% and 71%, respectively. The causes of graft loss were hyperacute rejection (n = 1), acute rejection (n = 5), vascular thrombosis (n = 1), and patient death (n = 1). The median length of time required until full enteral nutrition was 27 days. All 28 patients have experienced acute rejection of their small bowel grafts and rejection led to graft failure in five. Jaundice and/or hepatic fibrosis was present preoperatively in 17 of the 28 recipients and hyperbilirubinemia was completely reversed in all patients with functional grafts within 4 months of transplantation. Three patients developed post-transplant lymphoproliferative disease (11%). Three recipients developed cytomegalovirus enteritis and all were successfully treated. CONCLUSIONS: Patient survival after intestinal transplantation is comparable to parenteral nutrition for patients with intestinal failure. Better immunosuppressive regimens are needed to decrease the risk of graft loss from acute rejection. The incidence of posttransplant lymphoproliferative disorder is higher after intestinal transplantation than after other solid organ transplants and the risk of cytomegalovirus enteritis is low with the use of cytomegalovirus seronegative donors. Liver dysfunction in the absence of established cirrhosis can be reversed.     

Treatment of intestinal failure: intestinal transplantation

Over the past 15 years, intestinal transplantation for the treatment of intestinal failure has changed from a desperate last-ditch effort into a standard therapy for which a good outcome is expected. Patient survival after intestinal transplantation has improved in the past 3-5 years and now approaches that of other solid organ allograft recipients, including liver and kidney, and is similar to survival on permanent therapy with parenteral nutrition. Complications are more common and often more severe during the initial hospitalization period after intestinal transplantation than they are after transplantation of other solid organs. After intestinal transplantation the initial hospitalization period is, therefore, usually 3-8 weeks long. Nearly all patients discharged after intestinal transplantation have good allograft function and have been weaned from total parenteral nutrition. The cost of the initial hospitalization period is one to two times the cost of permanent total parenteral nutrition for 1 year, which means that, in most cases, intestinal transplantation is cost-saving within 2 years of transplantation. In addition, quality of life after intestinal transplantation, as determined by standardized quality of life measures, is good or normal.     

Small intestinal bacterial overgrowth and intestinal permeability

Abstract

Objective. Capsule endoscopy (CE) is the gold standard to diagnose small bowel bleeding. The “suspected blood indicator” (SBI) offers an automated detection of active small bowel bleeding but validity of this technique is unknown. The objective was to analyze specificity and sensitivity of the SBI using the second small bowel capsule generation for the detection of active bleeding. Methods. This is a retrospective analysis of all patients (199) who attended our clinic for CE from June 2008 through March 2013. The second-generation PillCam SB 2 capsule was used for detection of (1) luminal blood content and (2) potentially responsible small bowel lesions. The findings of an independent investigator were correlated to SBI findings and a number of SBI markings were analyzed by a receiver operating characteristic (ROC). Results. In 157/199 cases, no sign of active bleeding or altered blood was detected. One hundred and thirty-seven of these 157 cases provided at least one SBI marking and a mean of 18.4 positive SBI markings per record were found. In 20 cases, neither SBI nor the human investigator detected abnormalities. Thirteen patients showed investigator-detected minor bleeding with mean SBI findings of 36 positive screenshots per record. When major bleeding was diagnosed by the investigator (n = 29), SBI detected a mean of 46.6 SBI-positive markings. SBI turned positive in 179 patients, whereas the investigator detected active bleeding in 42 cases. All patients with active bleeding were detected by SBI (sensitivity 100%, specificity 13%). ROC analysis revealed 51.0 SBI markings being the optimal cutoff for active versus no bleeding (sensitivity 79.1%, specificity 90.4%, misclassification of 15.3%). Conclusion. The new SBI software is a reliable tool to exclude active bleeding and/or major lesions but analysis of the CE video by a trained investigator is still important for the detection of lesions responsible for past bleeding.     

肠缺血再灌注时肠道菌群变化及胃肠多肽的作用

目的探讨肠缺血再灌注(IIR)后猕猴肠道菌群变化的原因。方法将10只健康成年猕猴分为对照组和IIR组,每组各5只。IIR组肠系膜上动脉夹闭60 min,松解再灌注24 h,造成缺血再灌注损伤。对照组行假手术。观察动物肠道大体形态改变,测定胃pH值;细菌培养分析回肠菌群的变化;免疫组化定位测定回肠局部胃肠多肽的分布,并用放射免疫分析法定量测定其水平变化,并在体外将胃肠多肽与肠道细菌共向孵育,观察两者有无相互作用。结果猕猴IIR损伤后,回肠内细菌较正常增加约106倍,以大肠杆菌等需氧菌为优势菌群;小肠明显充血扩张;胃内pH值由2.80±0.84增至7.20±0.84,伴有胆汁反流;全回肠组织中胃肠多肽(生长抑素、血管活性肠肽、P物质)明显增加,而黏膜中生长抑素及血管活性肠肽的浓度却减少;胃肠多肽与肠道细菌共同培养后,胃肠多肽的含量及细菌数量均无明显变化。结论猕猴IIR后,小肠细菌过度生长可能由小肠动力降低直接或间接导致。小肠肌间神经丛中的生长抑素及血管活性肠肽增加可能是此刻小肠动力降低的启动因素。     

Comparative study of intestinal tuberculosis and primary small intestinal lymphoma

AIM:To characterize the clinical,radiological,endoscopic and pathological features of intestinal tuberculosis(ITB)and primary small intestinal lymphoma(PSIL).METHODS:This was a retrospective study from February 2005 to October 2012 of patients with a diagnosis of ITB(n=41)or PSIL(n=37).All patients with ITB or PSIL underwent computed tomography(CT)and pathological examination.Thirty-five patients with ITB and 32 patients with PSIL underwent endoscopy.These patients were followed for a further 18 mo to ascertain that the diagnosis had not changed.Clinical,endoscopic,CT and pathological features were compared between ITB and PSIL patients.RESULTS:Night sweating,fever,pulmonary TB and ascites were discovered significantly more often in ITB than in PSIL patients(P<0.05),however,abdominal mass,hematochezia and intestinal perforation were found significantly more frequently in PSIL than in ITB patients(P<0.05).Ring-like and rodent-like ulcers occurred significantly more often in ITB than in PSIL patients(P<0.05),however,enterorrhagia and raised lesions were significantly more frequent in PSIL than in ITB patients(P<0.05).The rate of granuloma was significantly higher in ITB than in PSIL patients(87.8%vs 13.5%,χ2=43.050,P<0.05),and the incidence of confluent granulomas with caseous necrosis was significantly higher in ITB than in PSIL patients(47.2%vs0.0%,χ2=4.034,P<0.05).Multi-segmental lesions,mural stratification,mural gas sign,and intestinal stricture were more frequent in ITB than in PSIL patients(P<0.05),however,a single-layer thickening of bowel wall,single segmental lesions,and intussusception were more common in PSIL than in ITB patients(P<0.05).Necrotic lymph nodes,comb sign and inflammatory mass were more frequent in ITB than in PSIL patients(P<0.05).The bowel wall enhancement in ITB patients was greater than that in PSIL patients(P<0.05),while the thickening and lymph node enlargement in PSIL patients were higher than those in ITB patients(P<0.05).CONCLUSION:Combined evaluation of clinical,radiological,endoscopic and pathological features is the key to differentiation between ITB and PSIL.     

Chronic pancreatitis： Maldigestion, intestinal ecology and intestinal inflammation

Exocrine pancreatic insufficiency caused by chronic pancreatitis results from various factors which regulate digestion and absorption of nutrients. Pancreatic function has been extensively studied over the last 40 years, even if some aspects of secretion and gastrointestinal adaptation are not completely understood. The main clinical manifestations of exocrine pancreatic insufficiency are fat malabsorption, known as steatorrhea, which consists of fecal excretion of more than 6 g of fat per day, weight loss, abdominal discomfort and abdominal swelling sensation. Fat malabsorption also results in a deficit of fat-soluble vitamins （A, D, E and K） with consequent clinical manifestations. The relationships between pancreatic maldigestion, intestinal ecology and intestinal inflammation have not received particular attention, even if in clinical practice these mechanisms may be responsible for the low efficacy of pancreatic extracts in abolishing steatorrhea in some patients. The best treatments for pancreatic maldigestion should be re-evaluated, taking into account not only the correction of pancreatic insufficiency using pancreatic extracts and the best duodenal pH to permit optimal efficacy of these extracts, but we also need to consider other therapeutic approaches including the decontamination of intestinal lumen, supplementation of bile acids and, probably, the use of probiotics which may attenuate intestinal inflammation in chronic pancreatitis patients.     

Phasic study of intestinal homeostasis disruption in experimental intestinal obstruction

AIM: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction.METHODS: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3⁺, CD4⁺ and CD8⁺ T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay.RESULTS: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer’s patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8⁺ T cells, driven by an increase in CD3⁺ and CD8⁺ T cells and a decrease in CD4⁺ T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction.CONCLUSION: Intestinal obstruction can induce disruption of intestinal homeostasis.     

Radiation-induced intestinal pseudoobstruction

A case of intestinal pseudoobstruction occurring 30 yr after radiation therapy is described. Mechanical causes of obstruction were excluded by laparotomy. Histology of full-thickness sections of the small bowel revealed vascular ectasia and sclerosis, serosal fibrosis, neuronal proliferation within the submucosa, and degeneration of the muscle fibers of the circular layer of the muscularis propria. On the basis of the clinical and histologic findings we conclude that, in this patient, intestinal pseudoobstruction was due to muscular and neuronal injury from abdominal irradiation.     

Chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a syndrome defined by the presence of chronic intestinal dilation and dysmotility in the absence of mechanical obstruction or gross inflammatory disease. Specific diseases may affect any level of the brain-gut axis. For most patients, the diagnosis relies upon a combination of historical, laboratory, manometric and histological features. Recent advances into the autoimmune nature of etiologies such as Chagas' disease and paraneoplastic dysmotility and into the genetic basis of mitochondrial neurogastrointestinal encephalomyopathy, multiple endocrine neoplasia IIB and Hirschsprung's disease have greatly refined our understanding and diagnosis of these disorders. At present, medical therapy of CIPO remains limited. Current and future developments in pharmacologic agents targeting specific enteric neurotransmitters and motility patterns hold much promise for improving the care of the patients afflicted with this complex and often debilitating syndrome.     

Chronic intestinal pseudo-obstruction

Opinion statement For many patients, nutritional support and relief of symptoms remain the primary management goal of pseudo-obstruction. Specific pharmacological agents for this disorder are, in general, lacking. Given that the efficacy of many of the individual available agents is far from excellent, several centers have turned to combination therapy. Though there is at present no evidence from controlled studies to support this strategy, it is, at the very least, theoretically attractive as these agents act through a number of separate mechanisms. The combination of a prokinetic and an emetic may prove especially useful. As the pseudo-obstruction syndromes are, individually, rare, and experience with any given prokinetic agent in these disorders limited, it is difficult to develop strict guidelines for their use in this context. It stands to reason that a response to a prokinetic agent would seem unlikely in a patient with an advanced myopathic process; anecdotal evidence suggests, however, that some patients with severe scleroderma may derive some symptomatic improvement. Where oral therapy is tolerated, cisapride would appear the best choice among available agents. When this fails, subcutaneous octreotide may be added or substituted. In the acute situation, intravenous erythromycin may alleviate gastroparesis, but probably exerts little beneficial effect beyond the pylorus; parenteral metoclopramide may be tried, but, here again, convincing evidence of efficacy is lacking. The roles of endoscopy and surgery are largely confined to facilitating nutrition and providing decompression.     

Vasoactive intestinal peptide

Dose—response characteristics of feline corpus circular muscle were studiedin vitro for three neuropeptides individually and with vasoactive intestinal peptide. Bombesin, substance P, and cholecystokinin-octapeptide each elicited concentration-dependent isometric contractions that were reduced by 10^–8 M or 10^–7 M vasoactive intestinal peptide (P<0.01). The concentration of each neuropeptide producing a half-maximal response was increased more than one logfold to 10^–6 M by vasoactive intestinal peptide. Tetrodotoxin blocked responses to bombesin (P<0.001) and reduced responses to substance P (P<0.05), but had no effect on responses to cholecystokinin-octapeptide (P>0.1). These results demonstrate inhibition of neuropeptide responses of gastric smooth muscle and support vasoactive intestinal peptide as an inhibitory regulator of gastric motor function.     

Chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.