Modifications in combined liver-small bowel transplantation in pigs

AIM: To inlToduce combined liver-small bowel transplantation in pigs.METHODS: Eighteen transplantations in 36 large white pigs were performed. Three modifications in combined liver-small bowel transplantation model were applied: Veno-venous bypass was not used. Preservation of the donor duodenum and head of pancreas in continuity with the combined graft to avoid biliary reconstruction. The splenic vein of donor was anastomosed end-to-end with the portal vein of recipients by the formation of a “cuff”.RESULTS: Without immunosuppressive therapy, 72-hour survival rate of the transplanted animals was 72 % (13/18).Five of 18 pigs operated died of respiratory failure (3 cases) and bleeding during hepatectomy (2 cases). The longest survival time of animals was 6 days.CONCLUSION: Our surgical modifications are feasible and reliable, which have made the transplantation in pigs simpler and less aggressive, and thus these can be used for preclinical study.     

Auxiliary en-bloc liver-small bowel transplantation with partial pancreas preservation in pigs

AIM: The aim of this study was to describe an auxiliary combined liver-small bowel transplantation model with the preservation of duodenum, head of pancreas and hepatic biliary system in pigs. The technique, feasibility, security and immunosuppression were commented. METHODS: Forty outbred long-white pigs were randomized into two groups, and the auxiliary composite liver/small bowel allotransplantations were undertaken in 10 long-white pigs in each group with the recipient liver preserved. Group A was not treated with immunosuppressive drugs while group B was treated with cyclosporine A and methylprednisolone after operation. The hemodynamic changes and amylase of body fluid (including blood, urine and abdominal drain) were analyzed. RESULTS: The average survival time of the animals was 10+/-1.929 d (6 to 25 d) in group A while more than 30 d in group B. The pigs could tolerate the hemodynamic fluctuation during operation and the hemodynamic parameters recovered to normal 2 h after blood reperfusion. The transient high amylase level was decreased to normal one week after operation and autopsy showed no pancreatitis. CONCLUSION: Auxiliary en-bloc liver-small bowel transplantation with partial pancreas preservation is a feasible and safe model with simplified surgical techniques for composite liver/small bowel transplantation. This model may be used as a preclinical training model for clinical transplantation method, clinical liver-small bowel transplantation related complication research, basic research including immunosuppressive treatment, organ preservation, acute rejection, chronic rejection, immuno-tolerance and xenotransplantation.     

Donor immune reconstitution after liver-small bowel transplantation for multiple intestinal atresia with immunodeficiency

The syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3(+) lymphocytes and 50% of his CD19(+) lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3(+)CD4(-)CD8(-) with T-cell receptor gammadelta heterodimers and CD3(+)CD4(-)CD8(+) with CD8alphaalpha homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs.     

小鼠小肠移植血管吻合技术的改进

目的　改进血管吻合技术,提高小鼠小肠移植血管吻合的成功率。方法　BAL B/ c小鼠小肠移植模型6 0例,每组2 0例,分别采用改良连续缝合方法(A组)、间断缝合方法(B组)及每针均收紧的连续缝合方法(C组) ,将小鼠供体腹主动脉和门静脉分别与受体腹主动脉和下腔静脉行端侧吻合。结果　三组总手术时间:A组(15 2±4 6 )分钟,B组(190±5 1)分钟,C组(183±38)分钟,A组与B、C两组相比,P <0 .0 5 ,差异有显著性。血管并发症:A组5例(2 5 % ) ,B组13例(6 5 % ) ,C组12例(6 0 % ) ,A组与B、C两组相比,P <0 .0 5 ,差异有显著性。总手术成功2 6例(43.3% ) ,其中A组13例(6 5 % ) ,B组6例(30 % ) ,C组7例(35 % ) ,A组与B、C两组相比,P<0 .0 5 ,差异有显著性。结论　改良连续血管吻合方法手术时间短,血管并发症少,手术成功率高。     

Anti-rejection therapy with tripterygium woifordii and low-dose cyclosporine for small bowel transplantation in pigs

AIM: To determine whether anti-rejection therapy with tripterygium wolfordii (TW) and low-dose cyclosporine (CsA) is better than treatments with large-dose CsA for small bowel transplantation. METHODS: Two-step segmental small bowel transplantation was performed in pigs and followed by treatment with either no, low-dose or high-dose CsA, which was followed by TW, a traditional Chinese medicine, or not. RESULTS: The transplanted pigs receiving no CsA developed organ rejection, as did the pigs who received the low-dose CsA treatment alone; the mean survival time of the grafts was 12 ± 8.2 ± 7 d and 12 ± 4.2 ± 6 d respectively. Of the 4 transplanted pigs receiving the high-dose CsA for 100 d and then the TW treatment, 2 required euthanasia for severe pneumonia that developed on day 92 and 97 respectively, and the other 2 survived more than 348 and 327 d respectively. Of the 5 transplanted pigs receiving low-dose CsA for 100 d and then the TW treatment, all survived for 243 ± 2.90 ± 9 d and none succumbed to infection. CONCLUSION: We are the first to use TW in small bowel transplantation and to show that TW can be a powerful and effective anti-rejection agent when applied in conjunction with the standard immunosuppressant CsA.     

大鼠肝肠联合移植后肝对小肠的免疫保护作用

目的：建立大鼠肝肠联合整体移植模型,研究移植肝是否对移植小肠具有免疫保护作用．方法：选用封闭群SD大鼠和近交系Wistar大鼠．实验分5组：同基因小肠移植组、同基因肝移植组、异基因小肠移植组、异基因肝移植组、肝肠联合移植组．同基因移植供受体均为Wistar大鼠,异基因小肠移植、肝移植和肝肠联合移植供受体分别选用SD和Wistar大鼠．肝肠联合移植在切取移植物后,利用供体胸段下腔静脉在门静脉侧壁建立一袖套,并安置套管．受体手术时,将此门静脉侧壁袖套与受体门静脉残端套管法吻合．供体肠系膜上动脉与受体右肾动脉吻合．免疫保护作用通过术后5,7,14 d从各组随机取出4只大鼠的移植物普通病理检查及细胞凋亡检测评估．结果：肝肠联合移植模型建立手术成功率73．3%(22/30)．同基因移植组术后仅表现为缺血-再灌注损伤所致的轻度组织损伤及炎症反应,移植物细胞凋亡数逐渐减少．异基因移植术后均出现急性排斥、移植物细胞凋亡数递增,并且较同基因移植多,差别有显著性．小肠移植术后5,7,14 d分别表现为轻度、中度和重度排斥．而肝肠联合移植的小肠移植物术后5,7,14 d分别表现为轻度、轻度和中度排斥,且14 d时小肠细胞凋亡数较异基因小肠移植组少,差别具有显著性(16．9±4．3 vs 20．5±6．3,P＜0．05)．术后各时间点异基因肝移植和肝肠联合移植的移植肝排斥反应严重程度相同,细胞凋亡数比较无显著差异．结论：此法建立大鼠肝肠联合移植模型可行．肝肠联合移植时肝对小肠具有免役保护作用．     

雷公藤联合小剂量环孢素A抑制猪小肠移植排斥反应

目的雷公藤联合小剂量环孢素抑制小肠移植排斥反应优于大剂量环孢素治疗。方法以猪为动物模型,采用节段小肠二步移植法作同种异体移植,给予传统中药雷公藤和小剂量环孢素。结果无免疫抑制组(Ⅰ组)和单独小剂量环孢素组(Ⅳ组)发生排斥反应,移植物平均存活分别为12.8±2.7d 和12.4±2.6d。大剂量环孢素组(Ⅱ组)和雷公藤加小剂量环孢素组(Ⅲ组)均未出现排斥反应,但Ⅱ组中有2只猪因严重感染分别丁第92、97d死亡。Ⅱ、Ⅲ组存活100d以上的猪为Ⅴ组,仅给予雷公藤,均获得满意的长期存活,未发生感染。结论首先将雷公藤应用于小肠移植,并且发现雷公藤是有效的抗排斥药物。雷公藤可部分取代环孢素防治小肠移植后早期的急性排斥,在移植后期,单独应用雷公藤可抑制慢性排斥。     

Inflammatory bowel disease induced by combined bacterial immunization and oral carrageenan in guinea pigs

A model of experimentally induced inflammatory bowel disease (IBD) featuring colitis, originally devised by Onderdonk and co-workers in guinea pigs, was modified to establish the optimal conditions for ulcer development. Upon varying the time of subcutaneous immunization with Bacteroides vulgatus and concomitant oral administration of acid-degraded iota-carrageenan and viable B. vulgatus, it was found that the optimal times of administering these agents were one to two weeks and five to six days, respectively. Light microscopy of the colon and cecum of the guinea pigs given the optimized treatment for ulcer induction revealed pronounced edema, inflammation, and lesions of the mucosa. Transmission electron microscopy of the mucosa from these animals showed the presence of large numbers of leukocytes in the subepithelial region, the majority being polymorphonuclear neutrophils which possessed large electron-dense granules or rods. Oral administration of 300 mg/kg/day sulfasalazine (salicylazosulfapyridine) for 14 days to guinea pigs given the optimized treatment for ulcer induction failed to reduce the numbers of ulcers or the histopathology gradings and fine structural changes of the mucosal inflammatory changes, but did reduce the symptoms of diarrhea.     

Small bowel transplantation

Until very recently, outcomes from small bowel transplantation (SBTx) lagged behind those in liver, heart, and kidney transplantation because of the magnitude of the immunologic burden; the strong expression of histocompatibility antigens; and the contamination in grafts by bacterial organisms. With novel techniques of immune-induction therapies, such as recipient "preconditioning" with lymphocyte reduction, followed by the more subtle use of immunosuppression-based singleagent tacrolimus, graft and host 1-year survival is now over 90% in the most active US centers, a finding that parallels the outcomes in liver and kidney transplantation. In contrast to the alternative therapy for permanent intestinal failure, home total parenteral nutrition (TPN), SBTx improves quality of life and restores digestive and absorptive function, making patients nutritionally autonomous. With survival beyond 1 to 3 years, the procedure is cost-effective. Current results support expansion of the indications for SBTx from use as salvage therapy for patients with TPN failure to preemptive therapy for patients at risk of developing TPN failure.     

Small bowel transplantation

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N=6) or tacrolimus (N=10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7;P<0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.     

Abdominal multivisceral transplantation in pigs

We investigated the technical aspects of porcine abdominal multivisceral transplantation, in terms of pathophysiological features in animals given no immunosuppresant. The splanchnic organs of the donor animal were flushed in situ with University of Wisconsin solution via the abdominal aorta, using a pump. After a relatively short period of cold storage in saline, multivisceral grafts, including the liver, pancreas, and gastrointestinal tract, were transplanted orthotopically. Of the 18 recipient pigs that underwent the operation, 9 (50%) died within 24 h, mainly because of respiratory insufficiency (n = 5) and circulatory shock (n = 3). Three animals (17%) were lost to acute renal failure between the second and fifth postoperative days. Six pigs (33%) survived for more than 1 week, and the causes of death in these animals were bowel obstruction (n = 1), pneumonia (n = 2), rejection of the intestinal graft (n = 2), and deterioration (n = 1). Although the results of this study were not satisfactory, abdominal multivisceral transplantation using pigs is practical and may lead to the possible resolution of various problems, in regard to the immunologic aspects and the interrelationship of transplanted complex organs.     

Modified laparoscopic splenectomy: a beneficial technique for ABO-incompatible living donor renal transplantation candidates on hemodialysis

Advances in laparoscopy have enabled minimally invasive surgical treatment of splenic diseases. Even with these advances, laparoscopic splenectomy in patients on dialysis can be difficult because of tissue fragility due to the underlying renal disease. We report a safe surgical technique for laparoscopic splenectomy in patients on maintenance dialysis that is suitable for use before ABO-incompatible living donor renal transplantation (LDRTx). Between June 1972 and December 2006, a total of 800 patients underwent LDRTx in our department, including 82 patients who underwent ABO-incompatible LDRTx. Between April 2001 and December 2006 we performed laparoscopic splenectomy in 48 hemodialysis patients as a pretreatment before ABO-incompatible LDRTx. Under general anesthesia the operation was performed using a new technique, referred to as the "splenic hilum lump method." We evaluated the surgical outcomes, such as the operative time, amount of blood loss, efficacy, and complications. The mean operative time was 131.6 +/- 38.4 min and mean blood loss was 126 +/- 395 mL. Blood transfusion was required in three patients. All cases had satisfactory kidney function after LDRTx and none developed kidney graft failure due to acute rejection. Almost all patients could walk the day after laparoscopic splenectomy and were satisfied with the cosmetic appearance of the scar after wound healing. The surgical technique we report here can be safely performed on patients with renal failure who require caution because of tissue fragility. Laparoscopic splenectomy is a safe, effective and less invasive operative procedure as a pretreatment for ABO-incompatible LDRTx.     

Capsule enteroscopy in small bowel transplantation

BACKGROUND: Enteroscopy plays a key role in the post-operative monitoring of patients with small bowel transplantation for the early detection of post-transplant complications and for the assessment of the graft's integrity. Routine surveillance enteroscopies (trans-stomal terminal ileoscopy or jejunoscopy) are invasive, may be unsafe in frail patients, and only allow incomplete exploration of the transplanted graft, which may be unsatisfactory. since the distribution of the lesions is often patchy or segmental. AIMS. To evaluate the potential of capsule enteroscopy, a new, minimally invasive technique which allows complete exploration of the small bowel. in small bowel transplant recipients. METHODS: Five small bowel transplanted patients underwent capsule enteroscopy with the GIVEN endoscopy system. The results of capsule enteroscopy were compared with those of trans-stomal ileoscopy. RESULTS: Capsule enteroscopy was better tolerated than ileoscopy and good quality images of the small bowel were obtained in four patients. The terminal ileum was normal both on ileoscopy and capsule enteroscopy. Mucosal changes in segments not reached by ileoscopy were detected by capsule enteroscopy in three of four patients. CONCLUSIONS: Capsule enteroscopy is better tolerated than ileoscopy, allows complete exploration of the transplanted graft and can detect mucosal changes in segments not reached by ileoscopy.     

大鼠小肠移植的外科技术

目的总结大鼠异位全小肠移植的外科手术．方法整块切取的供肠的范围包括全小肠、门静脉及带肠系膜上动脉的腹主动脉段端，在术中进行供肠原位灌注和肠腔灌洗．动脉吻合采用供体的带肠系膜上动脉的腹主动脉段端侧吻合于受体的腹主动脉，静脉吻合利用Ｃｕｆ套管技术将供体的门静脉与受体的左肾静脉端端吻合．移植肠两端腹壁双造口．供、受体术中均补液６ｍＬ～８ｍＬ．结果共进行１８９次移植手术，其中正式实验３３次，手术成功率为８４８％．供体手术时间８０ｍｉｎ±１０ｍｉｎ；供肠修理时间１０ｍｉｎ±３ｍｉｎ；受体手术时间９５ｍｉｎ±１５ｍｉｎ，其中动脉吻合时间１８ｍｉｎ±５ｍｉｎ，静脉吻合时间１ｍｉｎ；移植肠温缺血时间２２ｍｉｎ±５ｍｉｎ，冷缺血时间控制在６０ｍｉｎ以内．整个手术过程为一人操作，手术时间约３ｈ．结论移植肠的获取、血管吻合技术、术中血容量的维持是外科技术的关键，移植肠术中的处理及保温、感染问题也应重视     

Endoscopic monitoring in small bowel transplantation

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Fecal microbiota transplantation for managing irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder affecting 11.2% of the world adult population. The intestinal microbiome is thought to play a pivotal role in the pathophysiology of IBS. The composition of the fecal microbiome in IBS patients differs from that in healthy individuals, but the exact bacteria species involved in the development of IBS remain to be determined. There is also an imbalance between useful and harmful bacteria (dysbiosis) in the intestinal microbiome in patients with IBS. Consuming prebiotics, probiotics, or synbiotics has a limited effect on IBS symptoms. In contrast, fecal microbiome transplantation (FMT) in IBS patients reverses the dysbiosis to normobiosis and reduces the IBS symptoms in about 70% of patients, and is not associated with any serious adverse events.

Area covered: The available data on the microbiome and FMT in IBS regarding the efficacy of FMT in managing IBS were found using a PubMed search of these topics.

Expert commentary: FMT is a promising tool for managing irritable syndrome. It appears to be effective, easy, and inexpensive procedure. However, more controlled studies involving larger cohorts of IBS are needed before FMT can be used as a routine procedure in the clinic.