Antirejection therapy with Tripterygium woifordii and low-dose cyclosporine in small bowel transplantation in pigs

AIMS Antirejection therapy with tripterygium wolfordii(TW) and low-dose cyclosporine(CsA)was better than treatments with large dosage CsA in small bowel transplantation. METHODS This paper presents the experiment of two step segmental small bowel transplantation with TW,a traditional Chinese medicine and low dose CsA in pigs. RESULTS Rejection was developed in Group I without im- munosuppression as well as in Group Ⅳ treated with low-dose CsA.The mean survival time of grafts was 12.8±2.7days and 12.4±2.6 days respectively.The animals of Group Ⅱ were treated with high-dose CsA for 100 days and then with TW.in which two pigs were killed for severe pneumonia on day 92,97 and two pigs survived more than 348 and 327 days respective- ly.Five animals in Group Ⅲ in which TW and low-dose CsA were administered for 100 days and then TW was the only drug used in living animals,survived 243.2±90.9 days,none of which succumbed to infection. CONCLUSIONS:We are the first to use TW in small bowel transplantation and f Group Ⅰ(n=10):control group,received no immunosuppression.

Fecal microbiota transplantation for irritable bowel syndrome:Current evidence and perspectives

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology.We focus specifically on the mechanisms underlying the effects of fecal microbiota transplantation(FMT)for irritable bowel syndrome(IBS),the factors which affect the outcomes of FMT in IBS patients,and challenges.FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS.The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials,yielding divergent outcomes.The current frontier in this field seeks to elucidate these variations,underscore the existing knowledge gaps that necessitate exploration,and provide a guideline for successful FMT implementation in IBS patients.At the same time,the application of FMT as a treatment for IBS confronts several challenges.

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

Mesenchymal stem cell therapy in patients with small bowel transplantation:Single center experience

AIM: To study the effects of mesenchymal stem cell (MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation.

Diagnosis and treatment of acute rejection in the first case of human living-related small bowel transplantation with a long-term survival in China

AIM： To report the comprehensive diagnosis and treatment of acute rejection in the first case of living-related small bowel transplantation with a long-term survival in China. METHODS： A 18-year-old boy with short gut syndrome underwent living-related small bowel transplantation, with the graft taken from his father （44-year old）. A segment of 150-cm distal small bowel was resected from the donor. The ileo-colic artery and vein from the donor were anastomosed to the infrarenal aorta and vena cava of the recipient respectively. The intestinal continuity was restored with an end-to-end anastomosis between the recipient jejunum and donor ileum, and the distal end was fistulized. FK506, MMF and prednisone were initially used for post-transplant immunosuppression. Endoscopic observation and mucosal biopsies of the graft were carried out through the terminal ileum enterostomy; serum was collected to detect the levels of IL-2R, IL-4, IL-6 and IL-8. The change of the graft secretion and absorption was observed. RESULTS： Acute rejection was diagnosed promptly and cured. The patient was in good health, 5 years after living- related small bowel transplantation. CONCLUSION： The correct diagnosis and treatment of acute rejection are the key to the long-term survival after living-related small bowel transplantation.

Isolated small bowel transplantation outcomes and the impact of immunosuppressants: Experience of a single transplant center

AIM: To investigate patient and graft outcomes in isolated small bowel transplant(SBTx) recipients and immunosuppressant induction agent impact on outcomes.METHODS: A retrospective review of the perioperative data of patients who underwent SBTx transplant during an 8-year period was conducted. The intraoperative data were: patient demographics, etiology of short gut syndrome, hemodynamic parameters, coagulation profiles, intraoperative fluid and blood products transfused, and development of post-reperfusion. The postoperative data were: hospital/intensive care unit stays, duration of mechanical ventilation, postoperative incidence of acute kidney injury, and 1-year patient and graft outcomes. The effects of the three immunosuppressant induction agents(Zenapax, Thymoglobulin, Campath) on patient and graft outcomes were reviewed.RESULTS: During the 8-year period there were 77 patients; 1-year patient and graft survival were 95% and 86% respectively. Sixteen patients received Zenapax, 22 received Thymoglobulin, and 39 received Campath without effects on patient or graft survival(P = 0.90, P = 0.14, respectively). The use of different immune induction agents did not affect the incidence of rejection and infection during the first 90 postoperative days(P = 0.072, P = 0.29, respectively). The Zenapax group received more intraoperative fluid and blood products and were coagulopathic at the end of surgery. Zenapax and Thymoglobulin significantly increased serum creatinine at 48 h(P = 0.023) and 1 wk(P = 0.001) post-transplant, but none developed renal failure or required dialysis at the end of the first year.CONCLUSION: One-year patient and graft survival were 95% and 86%, respectively. The use of different immunosuppressant induction agents may affect the intraoperative course and short-term postoperative morbidities, but not 1-year patient and graft outcomes.

Protective effect of L-arginine preconditioning on ischemia and reperfusion injury associated with rat small bowel transplantation

AIM: To investigate the protective effect and possible mechanism of L-arginine preconditioning on ischemia and reperfusion injury associated with small bowel transplantation (SBT).METHODS: Male inbred Wistar rats weighting between 180 and 250 g were used as donors and recipients in thestudy. Heterotopic rat SBT was performed according to the techniques of Li and Wu. During the experiment, intestinal grafts were preserved in 4 ℃ Ringer's solution for 8 h before being transplanted. Animals were divided into three groups. In group 1, donors received intravenous L-arginine (50 mg/kg, 1 mL) injection 90 min before graft harvesting. However, donors in control group were given normal saline (NS) instead. In group 3, six rats were used as sham-operated control. Specimens were taken from intestinal grafts 15 min after reperfusion. Histological grading, tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed. The graft survival of each group was monitored daily until 14 d after transplantation. RESULTS: Levels of MDA and MPO in intestine of shamoperated rats were 2.0±0.22 mmol/g and 0.66±0.105 U/g. Eight hours of cold preservation followed by 15 min of reperfusion resulted in significant increases in tissue MDA and MPO levels. Pretreatment with L-arginine before graft harvesting resulted in lower enhancement of tissue levels of MDA and MPO and the differences were significant (4.71±1.02 mmol/g vs8.02±3.49 mmol/g, 1.03±0.095 U/g vs 1.53±0.068 U/g, P＜0.05). Besides, animals in L-arginine pretreated group had better histological structures and higher 2-wk graft survival rates comparing with that in NS treated group (3.3±0.52 vs6±0.1, 0/6 vs6/6, P＜0.05or 0.01).CONCLUSION: L-arginine preconditioning attenuates ischemia and reperfusion injury in the rat SBT model,which was due to antioxidant activities partially.

Enzymes activity of intestinal grafts after liver small bowel transplantation in rats

OBJECTIVES: To investigate the activity alterations of enzymes in intestine grafts after liver/small bowel transplantation in rats and the relations of these changes to immune rejection of grafts. METHODS: A model of liver/small bowel transplantation (LSBT) was established in closed colony SD and Wistar rats. The activity of enzymes including triphosphatase (ATPase), alkalinophosphatase (AKP), acytelcholinesterase (AchE), oxidesynthase (NOS) and monoamine oxidase (MAO) in bowel grafts was studied histochemically at regular postoperative intervals. RESULTS: The activity of enzymes in the wall of the grafts disappeared eventually in isolated small bowel transplantation (SBT) rats. In contrast, the activity in LSBT rats remained and recovered postoperatively. CONCLUSIONS: The rejection in grafted intestine could be prevented or delayed in LSBT rats. The changes in the activity of enzymes and neurons might be used to detect the rejection and function of the graft.

Endoscopic monitoring in small bowel transplantation

AIM To investigate the role of endoscopic monitoring in small bowel transplantation. METHODS This study consisted of two parts: the experimental study and clinical study. In the experimental study, white outbred pigs underwent segmental small bowel allotransplantation. The proximal and distal intestine were brought out as stomas (Thiry Vella loop). The grafts, treated with or without immunosuppression, were monitored by endoscopy via stomas. In the clinical study, a female patient with short bowel syndrome received whole small bowel allotransplantation. The graft was monitored by endoscopy via distal stoma. RESULTS The most common endoscopic findings of graft rejection following small bowel allotransplantation were mucosal erythema, erosion and ulceration. Diffuse ulceration with bleeding was seen in late phase of rejection. CONCLUSION Endoscopic monitoring is essential to small bowel transplantation.

Formation of microchimerism in rat small bowel transplantation by spienocyte infusion

AIM： To investigate the effect of donor splenocyte infusion combined with cyclosporine A （CsA） on rejection of rat small bowel transplantation （SBT）. METHODS： Male Sprague-Dawley （SD） rats and female Wistar rats weighing 230-270 g were used as donors and recipients respectively in the study. Heterotopic small bowel transplantation was performed. The rats were divided into three groups： group one receiving allotransplantation （SD→Wistar）, group two receiving allotransplantation （SD→Wistar） ＋ donor splenocyte infusion, group three receiving allotransplantation （SD →Wistar） ＋ donor splenocyte infusion ＋ CsA followed by CsA 10 mg/kg per day after transplantation, in which recipient Wistar rats were injected with 2 ×10^8 SD splenocytes 28 d before transplantation, and treated with CsA after transplantation. Finally, the specific DNA fragment of donor Y chromosome was detected in recipient peripheral blood and skin by PCR. The survival time after small bowel transplantation was observed. Gross and histopathological examinations were performed. RESULTS： The survival time after small bowel transplantation was 7.1 ± 1.2 d in group 1, 18.4 ± 3.6 d in group 2 and 31.5± 3.1 d in group 3. The survival time was significant longer （P 〈 0.01） in group 3 than in groups 1 and 2. The gross and histopathological examination showed that the rejection degree in group 3 was lower than that in groups 1 and 2.CONCLUSION： Donor splenocyte infusion combined with CsA decreases remarkably the rejection and prolongs the survival time after rat small bowel transplantation.

Small bowel obstruction caused by a bezoar following an adult simultaneous liver-kidney transplantation:A case report

BACKGROUND Small bowel obstructions(SBOs)are common following a large intra-abdominal operation;however,SBOs caused by bezoars are unreported in patients following liver-kidney transplantation procedures,particularly in adults.CASE SUMMARY A 65-year-old Caucasian female presented with nausea and nonbilious emesis during her postoperative course following a simultaneous liver-kidney transplantation.She developed worsening nausea and vomiting with significant abdominal distension and obstipation.Computed tomography imaging showed a marked abnormal dilation of multiple small bowel loops with a distinct transition point that was suggestive of a small bowel obstruction.An exploratory laparotomy revealed a foreign body in the intestinal track approximately 30 cm from the ileocecal valve.The foreign body was extracted and identified as a bezoar with hair follicles and old digestive contents.Following the operation,the patient demonstrated rapid clinical improvement with resolution of nausea,emesis,and progress in bowel motility.CONCLUSION SBOs caused by bezoars can occur immediately following a liver-kidney transplantation and should not be discounted as a diagnosis.

Management of intestinal failure in inflammatory bowel disease:Small intestinal transplantation or home parenteral nutrition?

Inflammatory bowel disease and Crohn’s disease in particular, is a common cause of intestinal failure. Current therapeutic options include home parenteral nutrition and intestinal transplantation. For most patients, home intravenous therapy including parenteral nutrition, with a good probability of long-term survival, is the favoured choice. However, in selected patients, with specific features that may shorten survival or complicate home parenteral nutrition, intestinal transplantation presents a viable alternative. We present survival, complications, quality of life and economic considerations that currently influence individualised decision-making between home parenteral nutrition and intestinal transplantation.

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

The intestinal microbiota plays an important role in inflammatory bowel disease(IBD).The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals.However,there are still no definitive microbial pathogens linked to the onset of IBD.The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients.The special alterations of gut microbiota associated with IBD remain to be evaluated.The microbial interactions and hostmicrobe immune interactions are still not clarified.Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy,few available strains and no standardized administration.Fecal microbiota transplantation(FMT)may restore intestinal microbial ho-meostasis,and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection.Additionally,synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD.However,FMT-related barriers,including the mechanism of restoring gut microbiota,standardized donor screening,fecal material preparation and administration,and long-term safety should be resolved.The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germfree/human flora-associated animals and chemostat gut models.

Where are we at with short bowel syndrome and small bowel transplant?

Intestinal failure can be defined as the critical reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements in adults or children.Short bowel syndrome(SBS)is characterized by a state of malabsorption following extensive resection of the small bowel.SBS may occur after resection of more than 50%and is certain after resection of more than 70%of the small intestine,or if less than 100 cm of small bowel is left.Several treatment modalities other than total parenteral nutrition,including hormones(recombinant human growth hormone,glucagon-like peptide-2)and tailoring surgeries(Bianchi procedure,serial transverse enteroplasty),had been proposed,however these were either experimental or inefficient.Small bowel transplant is a rather new approach for SBS.The once feared field of solid organ transplantation is nowadays becoming more and more popular,even in developing countries.This is partially secondary to the developments in immunosuppressive strategy.In this regard,alemtuzumab deserves special attention.There are more complex surgeries,such as multivisceral transplantation,for multi-organ involvement including small bowel.This latter technique is relatively new when compared to small bowel transplant,and is performed in certain centers worldwide.In this review,an attempt is made to give an insight into small bowel syndrome,small bowel transplantation,and related issues.

Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

AIM To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection. METHODS Lewis rat BMMSCs were cultured in vitro. Third-passage BMMSCs were transduced with the CXCR3 / HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to small bowel transplant. Six time points (instant, 1 d, 3 d, 7 d, 10 d, and 14 d) (n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines. RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group (53 d) was significantly longer than that of the HO-1 modified BMMSCs group (39 d), the BMMSCs group (26 d), and the NS group (control group) (16 d) (P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3 / HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased (P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-gamma, and TNF-alpha levels were significantly decreased and the levels of IL-10 and TGF-beta were significantly increased (P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.

Can fecal microbiota transplantation cure irritable bowel syndrome?

To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).METHODSWe searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles.RESULTSA total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration.CONCLUSIONData on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.

Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation

AIM To analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome(SFSS) after living donor liver transplantation(LDLT). METHODS Through-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT(A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range(0-144 m). RESULTS SFSS was diagnosed in 20(11.5%) of our recipients. While extra-small graft [small for size graft(SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis(P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis(P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10(40%) SFSS vs 3/7(42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe(RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10(28.6%) SFSS vs 52/152(34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7-and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7-and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference(P = 0.00). CONCLUSION SFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention(i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).

Artificial intelligence in detection of small bowel lesions and their bleeding risk:A new step forward

The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

Fecal microbiota transplantation against irritable bowel syndrome?Rigorous randomized clinical trials are required

Halkj?r et al searched systematically nine articles including 48 patients, and concluded that fecal microbiota transplantation(FMT) can be an ideal treatment option for irritable bowel syndrome(IBS) subjects. Regardless of the few successes in current traditional therapies(change in diet, herbal medicine and antibiotics) in IBS, a sharp increase in interests in the FMT option has been reported in the current century. However, there is a long list of unclear issues concerning the application of FMT for the treatment of IBS. Route of delivery and optimum dosage are the major concerns to consider before using in clinical practice.

Outcomes of right-lobe and left-lobe living-donor liver transplantations using small-for-size grafts

AIM To analyze the outcomes of living-donor liver transplantation(LDLT) using left-lobe(LL) or right-lobe(RL) small-for-size(SFS) grafts.METHODS Prospectively collected data of adult patients who underwent LDLT at our hospital in the period from January 2003 to December 2013 were reviewed. The patients were divided into the RL-LDLT group and the LL-LDLT group. The two groups were compared in terms of short-and long-term outcomes, including incidence of postoperative complication, graft function, graft survival, and patient survival. A SFS graft was defined as a graft with a ratio of graft weight(GW) to recipient standard liver volume(RSLV)(GW/RSLV) of < 50%. The Urata formula was used to estimate RSLV.RESULTS Totally 218 patients were included for analysis, with 199 patients in the RL-LDLT group and 19 patients in the LL-LDLT group. The two groups were similar in terms of age(median, 53 years in the RL-LDLT group and 52 years in the LL-LDLT group, P = 0.997) but had significantly different ratios of men to women(165:34 in the RL-LDLT group and 8:11 in the LL-LDLT group, P < 0.0001). The two groups were also significantly different in GW(P < 0.0001), GW/RSLV(P < 0.0001), and graft cold ischemic time(P = 0.007). When it comes to postoperative complication, the groups were comparable(P = 0.105). Five patients died in hospital,4(2%) in the RL-LDLT group and 1(5.3%) in the LLLDLT group(P = 0.918). There were 38 graft losses, 33(16.6%) in the RL-LDLT group and 5(26.3%) in the LL-LDLT group(P = 0.452). The 5-year graft survival rate was significantly better in the RL-LDLT group(95.2% vs 89.5%, P = 0.049). The two groups had similar 5-year patient survival rates(RL-LDLT: 86.8%, LL-LDLT: 89.5%, P = 0.476).CONCLUSION The use of SFS graft in LDLT requires careful tailormade surgical planning and meticulous operation. LLLDLT can be a good alternative to RL-LDLT with similar recipient outcomes but a lower donor risk. Further research into different patient conditions is needed in order to validate the use of LL graft.