ABSTRACT
The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.
Subject(s)
Humans , Biomarkers , Gastrointestinal Microbiome , Graft Rejection , Allergy and Immunology , Immunity, Mucosal , Intestine, Small , Microbiology , Transplantation , Metagenomics , Transplantation Tolerance , Allergy and ImmunologyABSTRACT
Objective An ideal small bowel transplantation model is the prerequisite and guarantee of small bowel transplan-tation-related researches.The aim of this study is to establish a pig model of orthotopic segmental small bowel transplantation by modifi-cation of blood vessel reconstruction and surgical techniques. Methods Twenty healthy pigs were equally assigned as donors and re-cipients.The superior mesenteric vessels were freed and the distal ileum harvested as grafts.After irrigation and preservation, the small bowel was transplanted by end-to-end anastomosis of the superior mesenteric arteries and veins, and then the small bowel was re-constructed simultaneously to restore intestinal continuity, with the proximal part of the graft brought out as a stoma for the purpose of graft monitoring. Results Transplantation was successfully performed in 9 of the 10 cases, with a success rate of 90%.The donor operations averaged 100 min, recipient operations 172 min, warm ischemia 1.3 min, cold ischemia 96 min, and vascular anastomosis 27.6 min.No postoperative anastomosis fistula occurred in any of the cases. Conclusion The pig model of orthotopic segmental small bowel transplantation is ideal for small bowel transplantation-related researches.
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Objective To investigate the expression of platelet derived growth factor(PDGF) in small bowel transplantation of rats.Methods Isogeneic and allogeneic small bowel transplantation were performed in rats by microsurgical technology.All rats were divided into two groups:isogeneic control group and allogeneic test group.Transplanted tissues were test on 7th,28th and 90th after surgery.Positioning using immunohistochemical method the expression of PDGF.Real time PCR and immunohistochemical staining were also performed to detect the expression of PDGF.Results The unique feature including intestinal graft fibrosis was showed in tissues.Immunohistochemistry results showed PDGF expression was higher in intestinal glands.PDGF mRNA levels in transplanted tissues showed a gradual upward trend,and the top levels is in POD90.Conclusion PDGF expression was significantly higher in the late of intestinal transplantation,which showed an guideline for chronic rejection of intestinal transplantation.
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ObjectiveTo modify the technique of whole small bowel transplantation in rats to improve the survival.MethodsOne hundred and six SD rats served as donors and recipients to establish a homogeneous and orthotopic model of small bowel transplantation without fistula.Anastomosis of aorta and vein was done with three- cuff technique,the vena mesenterica superior of recipient was done under a surgical microscope.End-to-end anastomosis was performed between donor proximal small intestine and receptor jejunum,and also between the remote and receptor ascending colon.Surviving more than 3 days after surgery was defined as the operation was successful.ResultsThe operation was successfully carried out in 48 cases with the survival rate of 90.6％ (48/53).The average warm ischemic time was 0 minute,and the average cold ischemic time was(30 ±2.48)min.The survival rate( ＞7 d) was 97.9％ (47/48).ConclusionsOn the basis of three-cuff technique,the survival of SBT was greatly improved.When the vena mesenterica superior of recipient was done under a surgical microscope,the surgical training time was shortened.
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ObjectiveTo investigate the continuous pathological features of biopsy specimens from five cases of small bowel allotransplantation (SBT) in order to provide more reliable information for the diagnosis and treatment of acute rejection (AR) in SBT.Methods324 biopsy specimens of intestinal mucosa after SBT from 5 patients were collected and studied by histology,histochemistry and electron microscopy.ResultsIn the early stage after operation (0～3 months),AR IND-1 grade was diagnosed for four times on 3 of 5 patients.During 3-6 months,AR IND-1 grade for three times was diagnosed in 2 cases,and AR 2 grade for two times during 7 ～ 12 months. All the patients suffered ischemia reperfusion injury, lymphatic vessel reconstruction and AR.Conclusion The pathological examination of biopsy specimens of intestinal mucosa is still the most reliable detecting method to diagnose AR,and continuous observation may play an important role to monitor the occurrence,development,and treatment response of AR. The final diagnosis of AR depends on structure of intestinal mucosa,crypt epithelium injury and inflammatory cells infiltration. The communication among the pathologist and surgeon is the best way to reduce misdiagnoses.Ultrastructural examination is used to verify the pathogenic microorganism.
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Objective To investigate the clinical presentation, endoscopy and pathological features of subclinical cellular rejection (SCR) of small bowel allotransplantation. Methods Three times of SCR in a patient after isolated small bowel transplantation were studied by endoscopy and microscopy, and the clinical data and literature were reviewed. Results SCR was an unusual type of acute rejection after small bowel transplantation. SCR showed low-grade morphological changes of acute rejection, and may be relived after low-dose steroid or bolus steroid was given. Conclusion The causes of SCR are not clear now. SCR may be the early stage of clinical acute rejections, and may be correlated with unexpected high grade acute rejection, and chronic loss function of graft. The biopsy through ileoscopy is a "golden standard" of diagnosis of SCR in small bowel transplantation.However, the vessel lesions of graft, ileus, and inflammation should be excluded before diagnosis.
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ObjectiveTo investigate the surgical procedures of orthotopic small bowel transplantation (SBT) model in mice to study the function and rejection of SBT.MethodsWe established a mouse SBT allograft model as follows: the donor portal vein was anastomosed end by side with the recipient inferior vena cava; the donor superior mesenteric artery with aorta patch was anastomosed end by side with recipient abdominal aorta.After an appropriate length of the recipient's small bowel was removed,the donor's small bowel and the recipient's small bowel were end-to-end anastomosed discontinuously.The mice were fasted for 4 d after the operation,free access to water and subcutaneously injection of 2 mL of 5％ glucose saline twice daily.Operation success was regarded as survival for more than 5 d.There is no antibiotic and immunosuppressor.ResultsA total of 30 transplantations were done,the 5 d survival rate was 60％ ( 18/30),and 12 died within 5 d.Among the dead recipients,5 died of arterial anastomotic stenosis and anastomotic thrombosis,2 of hemorrhagic shock caused by anastomotic bleeding,and the other 5 of intra-abdominal infection caused by postoperative intestinal fistula.The donors' operative time was (40 ± 4.5 ) min,warm ischemia time was about 0.5 min,donor preparation time was about 3 min,and cold preservation time was (30 ±7.5) min.The recipients' operative time was (95 ±8.0) min,among which,the abdominal aorta and inferior vena cava clamping time was ( 38 ± 3.5 ) min,the venous anastomotic time was (10 ±2.0) min and the arterial anastomotic time was (15 ± 3.0) min.The mean intraoperative blood loss of the surviving recipient mice was about 0.2 mL.ConclusionHigh quality vascular anastomosis,and rehydration of donors and recipients are crucial factors for improving the success rate of SBT.
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Objective To summarize the timing and diagnostic value of endoscopic biopsy of intestinal graft after small bowel transplantation (SBTx).Methods Fifteen cases of SBTx were divided into 3 eras:era Ⅰ (1994-1995)-3 cases of SBTx treated with cyclosporine-based immunosuppression; era Ⅱ (2003-2006)-7 cases of SBTx treated with tacrolimus-based immunosuppression,and era Ⅲ (2007-present) than CVC group 5 cases of SBTx treated with Atemtuzumab induction therapy and maintenance tacrolimus monotherapy.The scheme of endoscopic surveillance was initially used in era Ⅲ, the first endoscopic biopsy was performed on postoperative day 3,2 times weekly during the first month, followed once weekly during months 2-3, once every other week during months 4-6 and once monthly thereafter.When clinical signs and symptoms of rejection were present, and during rejection episodes, the additional endoscopic biopsies were also performed.Results A total of 276 biopsies of these 15 SBTx recipients were obtained.Fifty-one biopsies (18.5%) were diagnosed as acute cellular rejection (ACR), which included IND to mild (n = 32,11.6 %), moderate (n = 9,3.3 %), and severe (n = 1 0, 3.6 %), two biopsies (0.7 %) were diagnosed as cytomegalovirus (CMV) enteritis and other 2 biopsies (0.7 %) bacteria enteritis.The ACR episodes verified by biopsy pathology and undergoing anti-rejection treatment were 20 (11 IND to mild,5 moderate,and 4 severe) ,and 1 episode of CMV enteritis and 1 episode of bacteria enteritis were observed.Conclusion Endoscopic surveillance and biopsy pathology is crucial diagnostic tool for ACR and sepsis.ACR surveillance after SBTx and early diagnosis of ACR could be made with scheming endoscopic biopsies.Endoscopic biopsy can be used to make differential diagnosis when clinical signs and symptoms were present, and to guide the treatment during anti-rejection episode.
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Objective Invasive fungal infection (IFI) after small bowel transplantation (SBTx) is aggressive and associated with high mortality rates. This paper reviewed preliminary experience of treatment of IFI in 15 cases after SBTx. Methods Fifteen cases of SBTx were divided into 3 groups according to the eras. era Ⅰ (1994-1995)-3 cases of SBTx treated with cyclosporine-based immunosuppression, era Ⅱ (2003-2006)-7 cases of SBTx treated with tacrolimus-based immunosuppression, and era Ⅲ (2007-present)-5 cases of SBTx treated with Alemtuzumab induction therapy and maintenance tacrolimus monotherapy. During era Ⅰ and era Ⅱ, Fluconazole Ⅳ was used as prophylaxis and treatment protocol. If the IFI was aggressive, Amphotericin B or Amphotericin B Liposome were also given with initial dose of 1-5 mg/d (or 0.02-0.10 mg·kg~(-1)·d~(-1). During era Ⅲ, 2-weeks Arnphotericin B Liposome was used as prophylaxis therapy after SBTx, and the dose of 6 mg· kg~(-1)·d~(-1) of Amphotericin B Liposome was given to treat IFI after SBTx. The administration manner of Amphotericin B Liposome was also improved during era Ⅲ, and the initial dose achieved 6 mg without gradually increasing process. Closely surveillance of vital sign, liver and renal function, and electrolyte was also carried out, and the doses of Amphotericin B Liposome were titrated according liver and renal function. Results Four of 15 SBTx recipients suffered from IFI with the occurrence rate of 26.7%, 1, 2 and 1 recipient(s) suffered from IFI during different 3 eras, respectively. Three recipients died of severe IFI after SBTx during era Ⅰ and era Ⅱ. One SBTx recipient with IFI during the era Ⅲ totally recovered after 44-days treatment of Amphotericin B Liposome with the totally dose of 9100 mg, and the renal dysfunction was observed and.ameliorated after ceasing of Amphotericin B Liposome. The mortality of these 4 IFI after SBTx was 75%. Conclusion IFI after SBTx is associated with high mortality rate. Amphotericin B Liposome can effectively control IFI after SBTx. With closely surveillance of recipient renal function, high dose of Amphotericin B Liposome can be safely used.
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Fungal infection is an uncommon complication after small bowel transplantation. We present a rare form of mucormycosis found in the small bowel graft and in the skin of a recipient. We reviewed chart data and performed MEDLINE searches and found that this case was the first to report 2 kinds of mucormycosis to be found after organ transplantation. The patient was a 12 month old female baby who underwent small bowel transplantation due to short bowel syndrome. After 12 days she experienced acute cellular rejection which responded to steroid. 6 days later due to sustained fever, poor feeding and abdominal distention endoscopic biopsy was done which revealed mucormycosis. Antifungal treatment with lipo-amphotericin B was initiated, yet there was no improvement of clinical symptoms. On the 23 post operative day a black eschar developed on the incision site of the skin and biopsy was done which revealed cutaneous mucormycosis. Infected skin debridement and graftectomy was done but our patient expired because of septic shock.
Subject(s)
Female , Humans , Biopsy , Debridement , Fever , Mucormycosis , Organ Transplantation , Rejection, Psychology , Shock, Septic , Short Bowel Syndrome , Skin , Tissue Donors , TransplantsABSTRACT
Recently,there was great development in the field of small bowel transplantation,which has been become effective in clinical research.However,similarly with the transplantations of heart,lung,liver and kidney,chronic rejection was becoming an important factor for the long-term survivals of grafts.With the deepening comprehensions towards the mechanism of chronic rejection,more methods and therapies were tried and tested.
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Small bowel transplantation is becoming the treatment of choice for short-gut syndrome. Improvements in surgical techniques, immunosuppressants, and anesthetic management of patients have allowed this procedure to become the standard of treatment for patients who are unable to continue total parenteral nutrition (TPN) therapy due to TPN-associated complications. We experienced small bowel transplantation in a 10-month-old male infant who had small bowel resection for small bowel volvulus and has suffered from complications such as recurrent sepsis, disseminated intravascular coagulation (DIC) due to long-term TPN. We report our experience with a brief review of the relevant literature.
Subject(s)
Humans , Infant , Male , Disseminated Intravascular Coagulation , Immunosuppressive Agents , Intestinal Volvulus , Parenteral Nutrition, Total , SepsisABSTRACT
Small bowel transplantation is the most rapidly evolving area of the solid organ transplantation. Pathophysiologic nature of the intestinal failure leads various surgical options performing intestinal transplantation, e.g. isolated intestine, liver and intestine, and multivisceral transplantation. Because of high dosing of immunogenic tissue from the allograft, prevention and treatment of the acute rejection is still one of the main hurdles to improve clinical outcome after transplantation. With the contribution of refining surgical skills, novel immunosuppressive therapy, and upgraded patient management before and after transplantation, clinical outcome has been improved significantly for last decade. The indication of the intestinal transplantation, however, still remained to use this novel treatment option as a life- saving procedure in intestinal failure patients and not to be justified for pre-emptive intestinal transplantation. Intestinal or multivisceral transplantation has so many unveiled areas, which warrants additional vigorous study.
Subject(s)
Humans , Allografts , Intestines , Liver , Organ Transplantation , TransplantsABSTRACT
@#ObjectiveTo summarize the means of prevention and treatment for early complications (in the first month) of partial live small bowel transplantation.MethodsThrombus of anastomosis blood vessel, bleeding, infection, rejection, dysfunction of transplantated bowel were the main complications in the first month after operation, which should be paied more attention to. ResultsFour patients suffered acute rejection, respiratory tract infection, dysfunction of transplantated bowel in first month after operation. After accurately treating, all the complications were cured. The function of transplantated bowels were well. ConclusionPreventing and treating early complications accurately after partial live small bowel transplantation is important.
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General treatment of short bowel syndrome is long-term total parenteral nutrition (TPN). But long-term TPN therapy produces thrombus, infection and obstruction of central veins and results in the life-threatening complications. Recently we experienced first case of small bowel transplantation in a 57-year old female with only 30 cm jejunum and distal part of colon to the splenic flexure who was suffering short bowel syndrome due to previous wide resection of small bowel. We report successful anesthetic management of small bowel transplantation in the patient with short bowel syndrome who has been suffered from life threatening complications due to long-term TPN therapy.
Subject(s)
Female , Humans , Middle Aged , Colon , Colon, Transverse , Jejunum , Parenteral Nutrition, Total , Short Bowel Syndrome , Thrombosis , VeinsABSTRACT
Objective:To investigate appropriate accommodation of nutrition after living-related small bowel transplantation.Methods: According to the function of allograft and general body state,TPN was used and gradually transferred to PN+EN,finally to TEN.The clinical and laboratory nutrition markers in 4 recipients were observed.Results: 2 recipients survived over 4 years,various kinds of nutrition markers were normal,and the health status was good.One recipient died of acute pulmonary infarction at 19 days.Another recipient died of multiple system organ infection at 5 months.Conclusion: EN cand promote restoration of allograft function.
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Objectives: To investigate the effects of immediate reconstruction of lymphatic drainage of the graft after small bowel transplantation (SBT) and early enteral nutrition (EN) support on plasma level of free fatty acids (FFAs) using a model of lymphatic reconstruction (LR) after SBT. Methods: The level of FFAs in two groups (depend on LR or non LR), including C 14 , C 16 , C 18∶1 , C 18∶2 and C 20∶4 in plasma were measured by gas chromatography before and day 1, 4, 7, 10 and 14 after the operation. Results: The plasma concentrations of FFAs in LR group were higher than in non LR group. Conclusions: Immediate reconstruction of lymphatic drainage of the intestinal graft after SBT and early EN support will not only provide sufficient energy for host, but also correct the lower concentration of FFAs in plasma effectively.