Maintenance treatment with infliximab for ulcerative ileitis after intestinal transplantation: A case report

BACKGROUND Evidence has been published on the successful applications of the anti-tumor necrosis factor alpha antibody infliximab,such as induction therapy,salvage treatment for acute cellular rejection,and treatment for chronic ulcerative inflammation,in intestinal transplant recipients.However,the optimal protocol for the effective use of infliximab remains largely undetermined due to scarcity of available clinical data.We report a continuative application of infliximab as maintenance therapy for recurrent chronic ulcerative ileitis in a recipient of isolated intestinal transplantation(ITx).CASE SUMMARY The patient was a 11-year-old boy with intestinal motility disorder classified as a hypogenic type of intestinal dysganglionosis.The patient underwent living-donor related intestinal transplant.His immunosuppression regimen consisted of daclizumab,tacrolimus,and steroids.Although he did not show rejection while on tacrolimus monotherapy,routine screening endoscopy showed several ulcerative lesions in the distal end of the graft 2 years after the intestinal transplant.Endoscopic work up to evaluate the progression of anemia revealed stenosis with ulcerative inflammatory changes and multiple longitudinal ulcers in the graft.Since the endoscopic findings suggested ulcerative lesions in Crohn’s disease,infliximab treatment was considered.Treatment with infliximab and a small dose of oral prednisolone afforded successful withdrawal of total parenteral nutrition and maintenance of a well-functioning graft without infectious complications for 5 years since the administration of the first dose of infliximab.CONCLUSION Infliximab is effective as maintenance therapy for recurrent chronic ulcerative ileitis in an isolated ITx patient.

Follow-up and surveillance of immunosuppressive treatment in intestinal transplantation

Objective To evaluate the efficiency of monitoring parameters and methods of immunosuppresive treatment in intestinal transplantation and to provide scientific evidence for establishment of Intestinal Transplant Registry.

Non-composite combined liver and intestinal allotransplantation

BACKGROUND: Patients with short bowel syndrome may require combined liver and intestinal transplantation due to total parenteral nutrition(TPN)-related liver damage. We report combined liver and intestinal allotransplantation as a non-composite technique in a patient in China. METHODS: During the operation, a 380 cm long intestine was transplanted with systemic drainage and aortic inflow, while the liver graft was placed in a piggyback fashion. Warm ischemic time of the donor graft was 2 minutes and 30 seconds, and cold ischemic time for intestinal and the liver graft was 6 hours and 40 minutes and 8 hours and 7 minutes, respectively. Immunosuppressants used after operation included tacrolimus, methylprednisolone, mycophenolate mofetil and Zenapax. RESULTS: The recipient recovered with no evidence of rejection and was kept well on tube feeding. Eventually, he died of massive hemorrhage of the thoracic cavity on day 210 after transplantation. CONCLUSION: The non-composite combined liver and intestinal allotransplantation is superior to composite technique in adult patients, particularly those who have had abdominal infection or repeated abdominal operations.

Semi-mature MyD88-silenced bone marrow dendritic cells prolong the allograft survival in a rat model of intestinal transplantation

Background Semi-mature dendritic cells （DCs） may induce tolerance rather than immunity.However,little is known about the regulatory mechanism by which these DCs induce transplant tolerance.Myeloid differentiation factor 88 （MyD88） is a key adaptor of Toil-like receptor signaling,which plays a critical role in DC maturation.Activation of MyD88-silenced immature DCs results in the generation of semi-mature DCs.We explored the possibility of using these DCs to induce intestinal transplant tolerance in rats.Methods MyD88 expression was silenced in bone marrow DCs （F344 rats） using small interfering RNAs for 24 hours,at which point,lipopolysaccharide （LPS） was added to the culture for another 48 hours.These cells were analyzed for their in vitro and in vivo tolerizing capacities.Results Semi-mature DCs expressing moderate levels of MHC class Ⅱ and low levels of co-stimulatory molecules were found to produce interleukin （IL）-10,while IL-12 production was decreased.In vitro co-culture with completely allogeneic T cells from Wistar rats led to a significant decrease in alloreactive T-cell responses.In vivo,the transfer of semi-mature DCs （1×106 ceils） followed by the transplantation of fully mismatched intestinal grafts （F344 rats） led to significantly prolonged survival compared to rats receiving immature and mature DCs.Serum from semi-mature DC-treated rats contained lower concentrations of the pro-inflammatory cytokines IL-2 and interferon-Y 5 days after transplantation.Conclusion Semi-mature DCs may promote inducible allograft tolerance and this study suggests a new strategy by which to facilitate the induction of transplant tolerance.

Latest developments in chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction(CIPO)is a type of intestinal dysfunction presenting as symptoms of intestinal obstruction but without actual mechanical obstruction.An extremely low incidence,non-specific clinical symptoms,strong heterogeneity,and no definitive cause in some patients make CIPO very difficult to diagnose correctly.Imaging and gastrointestinal manometry are commonly used.Most patients have progressive worsening of their symptoms and require intervention,and nutritional assessment and treatment are very important to determine the prognosis.With improvements in surgical techniques,small bowel transplantation is a feasible treatment option for patients with advanced CIPO;however,the long-term prognosis for CIPO patients remains unsatisfactory.Generally,the disease is rare and difficult to diagnose,which leads to clinicians’lack of understanding of the disease and results in a high rate of misdiagnosis.This review describes the characteristics of CIPO and the latest developments in diagnosis and treatment,in detail.The goal of our review is to improve clinicians'understanding of CIPO so that the disease is identified quickly and accurately,and treated as early as possible to improve patients’quality of life.

Potential importance of early treatment of SARS-CoV-2 infection in intestinal transplant patient: A case report

BACKGROUND Predispositions for severe coronavirus disease 2019(COVID-19)are age,immunosuppression,and co-morbidity.High levels of maintenance immunosuppression render intestinal transplant(ITx)patients vulnerable for severe COVID-19.COVID-19 also provokes several gastroenterological pathologies which have not been discussed in ITx,so far.CASE SUMMARY During the second European COVID-19 wave in November 2020,an ITx recipient was admitted to the hospital because of electrolyte disturbances due to dehydration.Immunosuppression consisted of tacrolimus,azathioprine,and low-dose corticosteroids.During hospitalization,she tested positive on screening COVID-19 nasopharyngeal polymerase chain reaction swab,while her initial test was negative.She was initially asymptomatic and had normal inflammatory markers.Tacrolimus levels were slightly raised,as Azathioprine was temporarily halted.Due to elevated Ddimers at that time,prophylactic low-molecular weight heparin was started.Seven days after the positive test,dyspnea,anosmia,and C-reactive protein increase(25 mg/L)were noted.Remdesivir was administered during 5 d in total.High stomal output was noted in two consecutive days and several days thereafter.To exclude infection or rejection,an ileoscopy and biopsy were performed and excluded these.Four weeks later,she was discharged from the hospital and remains in good health since then.CONCLUSION Early eradication of severe acute respiratory syndrome coronavirus 2 in ITx recipients may be warranted to prevent acute rejection provocation by it.

Endoscopic monitoring in small bowel transplantation

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From portal to splanchnic venous thrombosis:What surgeons should bear in mind

The present study aims to review the evolution of surgical management of portal(PVT) and splanch-nic venous thrombosis(SVT) in the context of liver transplantation over the last 5 decades. PVT is more commonly managed by endovenous thrombectomy, while SVT requires more complex technical expedients. Several surgical techniques have been proposed, such as extensive eversion thrombectomy, anastomosis to collateral veins, reno-portal anastomosis, cavo-portal hemi-transposition, portal arterialization and combined liver-intestinal transplantation. In order to achieve satisfactory outcomes, careful planning of the surgical strategy is mandatory. The excellent results that are ob-tained nowadays confirm that, even extended, splanch-nic thrombosis is no longer an absolute contraindication for liver transplantation. Patients with advanced portal thrombosis may preferentially be referred to specialized centres, in which complex vascular approaches and even multivisceral transplantation are performed.

Concise review on short bowel syndrome: Etiology, pathophysiology, and management

Adults have approximately 20 feet of small intestine,which is the primary site for absorbing essential nutrients and water.Resection of the intestine for any medical reason may result in short bowel syndrome(SBS),leading to loss of major absorptive surface area and resulting in various malabsorption and motility disorders.The mainstay of treatment is personalized close dietary management.Here we present SBS with its pathophysiology and different nutritional management options available.The central perspective of this paper is to provide a concise review of SBS and the treatment options available,along with how proper nutrition can solve major dietary issues in SBS and help patients recover faster.

Auto-intestine transplantation for pancreatic tumors with mesenteric root involvement:a systematic review and survival-based analysis

To analyze a long-term survival outcome of an auto-intestine transplantation(aINTx)for the patients with locally advanced pancreatic tumor and identify the potential prognostic factors,databases were carefully searched for the studies reporting the patients with a locally advanced pancreatic tumor which typically underwent aINTx.We performed a database search using PubMed,the Cochrane Library,EMBASE,and MEDLINE to identify multiple case series of the patients who had pancreatic tumors with mesenteric root involvement and underwent aINTx,to evaluate the treatment outcomes,and calculated the patient survival using the Kaplan–Meier method and Cox proportional hazard regression analysis to properly identify an independent predictor of the survival.A total of 9 retrospective studies with a total of 29 patients were included in our study.The calculated 1-,2-,and 3-year survival rates for the patients with pancreatic cancer and benign or low grade pancreatic tumors were 49.64%,22.06%,and 0%versus 100%,100%,and 80%,respectively.The corresponding median survival time was 13.4months and 84months,respectively.Moreover,when stratifying the pancreatic cancer patients undergoing aINTx on the basis of neoadjuvant chemotherapy(aINTx+neoadjuvant vs aINTx-neoadjuvant)there was a significant difference in the survival(P=0.01).The 1-and 2-year survival rates were 75%and 75%versus 34.1%and 0%,respectively.Corresponding median survival times were 24months and 10months,respectively.Our analysis shows the long-term survival benefit with acceptable morbidity and mortality of pancreatoduodenectomy and aINTx for the pancreatic tumors with the mesenteric root involvement that are otherwise unresectable by the conventional surgical techniques.However,from an oncological point of view,a larger study with the control group is required to determine its safety compared to less aggressive surgical treatment.