Segmental living related small bowel transplantation in adults

The advent of small bowel transplantation has provided selected patients with chronic intestinal irreversible failure with a physiologic alternative to total parenteral nutrition. Recently a standardized technique for living related small bowel transplantation (LR-SBTx) has been developed. Three patients with short bowel syndrome underwent LR-SBTx at our institution. All donors were ABO compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm of ileum was harvested and transplanted with its vascular pedicle constituted by the ileocolic artery and vein. The grafts were transplanted with a short cold and warm ischemia time. The immunosuppression regimen consisted of oral FK-506, prednisone, and intravenous induction with atgam. Serial biopsies of the intestinal grafts were performed to evaluate rejection or viral infections. The postoperative course was uneventful for all donors. All of the recipients are currently alive and well. Two of three patients are off total parenteral nutrition and tolerating an oral diet with no limitations on daily activity. In the third patient, the graft was removed 6 weeks after transplantation. At the time of enterectomy, no technical or immunologic complications were documented. Absorption tests for D-xylose and fecal fat studies were performed showing functional adaptation of the segmental graft. All biopsies were negative for acute rejection. A well-matched segmentai ileal graft from a living donor can provide complete rehabilitation for patients with short bowel syndrome. Our initial experience suggests that the risk of acute rejection and infection is greatly reduced compared to cadaveric bowel transplantation. Further clinical application of this procedure is warranted. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

简化的大鼠异位全小肠移植术

目的:建立简化的大鼠异位全小肠移植术技术,以提高手术成功率,为相关研究奠定基础.方法:供、受体均为雄性近交系Wistar大鼠,共180只,配对手术.采用供肠的肠系膜上动脉与受体肾下腹主动脉端侧吻合、门静脉与受体左肾静脉套管法端端吻合重建移植小肠血供,移植小肠远端腹壁造口.结果:手术耗时130min,移植小肠热缺血时间约30min.90只受全大鼠术扣即时存活率为100%,长期存活率(＞7d)为95.6%.结论:简化术式具有操作简便,移植小肠的热缺血时间短,手术成功率高等优点,有利于后续研究工作的开展.     

An experimental technique to assess the immunologic consequences of segmental small bowel transplantation

BACKGROUND: The amount of native small bowel required for adequate nutrition is variable, but lies between 10% and 20% of full length. Currently, for patients requiring small bowel transplantation (SBT), standard practice is to transplant the entire small bowel if space permits. Few experimental studies have addressed the effect of the length of small bowel transplanted on immune responses and in those that have, the amount of mesenteric lymph node (MLN) transplanted has always been a potential confounding factor, as have differences between jejunum and ileum. METHODS: Full-length and segmental heterotopic rat SBT was performed between PVG donor and DA recipients. To transplant reduced length small bowel grafts but to exclude immunologic differences between jejunum and ileum, equal lengths of bowel were resected from proximal and distal ends in the donor. A proportional amount of MLN was carefully dissected using a microvascular technique and then excised. Serial serum samples from the transplant recipients were tested for anti-PVG (rejection) and anti-DA (graft-versus-host) antibodies using a two-color flow cytometric technique, described previously, with the aim of looking for differences in immunologic responses to full and segmental grafts. RESULTS: We have established a model of segmental SBT that includes a proportional amount of MLN and is free from differences between jejunum and ileum. Preliminary data have demonstrated the development of circulating anti-host and anti-graft antibodies with time for both full-length and segmental SBT.     

Simplified techniques in rat heterotopic small bowel transplantation

AIM: Establish a simplified heterotopic small bowel transplantation (SBT) in the rat. METHODS: Ninety pairs of male Wistar rats were used as donors and recipients. The whole small intestine with a vascular pedicle composed of superior mesenteric artery (SMA) and portal vein (PV) was harvested as the graft. Revascularization was accomplished by end-to-side anastomosis between donor SMA and recipient infrarenal aorta and cuffed end-to-end anastomosis between donor PV and left renal vein of recipient. The distal end of graft was exteriorized to form an enterostoma. RESULTS: Average time of an operation was 130 minutes and the mean warm ischemia time of grafts was 30 minutes. The technical success rate of this model was 100% and 7-day survival was 95.6% (86/90). CONCLUSION: This simplified technique was effective and practical to improve the outcome of rat heterotopic SBT.     

大鼠异位节段小肠移植模型建立技术的改进

目的：建立大鼠异位节段小肠移植模型。方法：对40例（80只）Wistar大鼠施行异位小肠移植,供受体术前抗生素灌胃,改变供受体术式,减少受体手术时间、手术损伤及供肠缺血时间;采用腹主动脉-肠系膜上动脉吻合以及左肾静脉-门静脉单套管吻合,血管吻合方法采用单纯间断吻合,重建供肠血管;移植小肠双造口,静脉补液通路采用股静脉。结果：肠缺血时间≤35min,吻合口无狭窄,40例大鼠接受小肠移植,建模成功35例。结论：改进小肠移植技术中的多个细节后,降低了大鼠小肠移植术的难度。     

Cervical small bowel transplantation in the rat: a useful tool

Orthotopic intestinal transplantation in the rat is highly successful, but circumstances may require an extraabdominal graft location. We describe a microsurgical technique for cervical intestinal transplantation in the rat, which has been used to investigate the immune status of hosts already bearing an intraabdominal bowel transplant. A 10 cm segment of donor jejunum is harvested on a pedicle of superior mesenteric artery and superior mesenteric vein. In the recipient, the carotid artery (CA) and external jugular vein (EJV) are isolated. The venous anastomosis is performed end to end to the medial EJV branch, and the arterial anastomosis is completed end to side to the CA. Both anastomoses are performed with interrupted 10-0 nylon. The bowel is placed in a subcutaneous pocket in the neck, with both ends exteriorized. The procedure was performed in 11 donor-recipient pairs planned to elicit rejection, graft-vs.-host disease (GVHD) or graft acceptance. No technical complications were encountered. All rats survived long term, and their grafts were monitored histologically. The expected immune responses were observed, but rejection and GVHD were not fatal to the host with this model. We conclude that this technique is feasible and reliable to monitor the progress of isolated intestinal transplants. The location in the neck does not disrupt normal intestinal function of the recipient and may have multiple applications in the study of intestinal transplant immunology and physiology.     

Influence of the length of the small bowel graft on the severity of graft versus host disease

The influence of the length and origin of a small bowel graft on graft versus host disease (GVHD) was studied in 33 (Lewis x brown Norway) F1 hybrids transplanted with different types of Lewis small bowel grafts. Recipients of an entire small bowel graft (N = 9), a jejunal graft (N = 6), or an ileal graft (N = 6) displayed a similar acute lethal GVHD, with 100% mortality rate and equivalent survival time (15 +/- 0.7, 16.8 +/- 0.9, and 16 +/- 0.6 days, respectively) (P greater than 0.01). On the other hand, 80% of the recipients of a segmental jejunal graft (N = 10) recovered from a transitory form of GVHD and regained weight similarly to the isografted rats (N = 4). It was concluded that the entire small bowel, jejunum, and ileum can provoke an equivalent GVHD after transplantation, whereas a segment of jejunum decreases the intensity of GVHD, probably by reducing the amount of transplanted lymphoid tissue.     

Small bowel transplantation in the rat: The adverse effect of increased pressure during the flushing procedure of the graft

The influence of the pressure during the flushing procedure on the results of the subsequent transplantation was investigated in a model of heterotopic functional small bowel transplantation in the outbred Wistar rat. In this model insufficient small bowel preservation will result in a lethal shock, soon after revascularization. If the size of the small bowel graft was reduced to a 15-cm segment of the proximal jejunum, improper preservation did not lead to lethal shock, but to histological changes of the graft. The influence of high flushing pressure (80 cm), medium flushing pressure (50 cm), low flushing pressure (35 cm), and no flushing procedure at all, was investigated in different groups of rats. Flushing was performed by gravity using chilled Ringer's lactate solution (4°C), buffered with NaHCO₃ at a pH of 7.4. The results were evaluated histologically as well as clinically. Results indicated flushing of the graft to be superior to a nonflushing procedure. A flushing pressure of 80 cm and even 50 cm proved to be harmful to the jejunal graft. Flushing pressure of 35 cm resulted in successful segmental (jejunal) and subtotal (minus 5- to 7-cm distal ileum) small bowel transplantation. However, survival of a total small bowel graft could not be achieved with the optimal flushing procedure indicating that the functional integrity of a small bowel graft also depends on conditions other than the method of short-term preservation.     

Oral absorption of tacrolimus in children with intestinal failure due to short or absent small bowel

We describe two children with intestinal failure due to short or absent small bowel who underwent isolated liver transplantation for liver disease related to parenteral nutrition. Both received reduced-size liver grafts whilst awaiting a suitable small bowel donor. Immunosuppressive therapy was based on oral tacrolimus and intravenous steroids. Therapeutic levels of tacrolimus were achieved at low dosage of 0.14–0.28 mg/kg per day. Median and mean blood tacrolimus levels were 9.9 and 13.7 ng/ml (range 4.9–42.3 ng/ml) in case 1 and 5.8 and 7.2 ng/ml (range 1–30 ng/ml) in case 2 before small bowel transplantation, respectively. Following small bowel transplantation, levels were 17.1 and 20.1 ng/ml (range 9.2– 30 ng/ml), with oral doses of 0.54–1.35 mg/kg per day. Both children died of adenovirus pneumonia, with functioning grafts. Our experience demonstrates that effective levels of immunosuppression can be achieved by oral administration of tacrolimus in children with short or absent small bowel. Received: 10 November 1998 Received after revision: 4 May 1999 Accepted: 19 July 1999     

Small bowel and colon transplantation in rats using porto-portal cuff anastomosis

Portal versus systemic venous drainage and colon grafting are major controversies in the techniques of intestinal transplantation. The rat is the best animal for research in this field. Nevertheless, this model requires complex microvascular anastomoses that are responsible for the high incidence of technical failures. A cuff technique is an easier anastomosis method than a hand-suture. We describe a simplified rat model of small bowel and colon transplantation using a porto-portal cuff anastomosis. DONOR: The entire small bowel, cecum, and ascending colon are harvested on a vascular pedicle, consisting of a long aortomesenteric conduit and portal vein. The right colonic vessels are preserved. The graft is flushed and a cuff device is placed on the end of the portal vein. RECIPIENT: The graft is implanted through an end-to-side aorto-aorta hand-sewn anastomosis. A segment between the first and second jejunal branch is isolated between clamps to insert into the portal cuff. After reperfusion, the recipient's mesentery is divided just below the cuff anastomosis. The recipient jejunum, ileum, and ascending colon are removed en bloc, and the graft is anastomosed in continuity with the remaining naive intestine concluding the operation. This simplified technique surmounts the technical obstacles in rats because it is easily and quickly performed, maintaining the physiological portal drainage, preserving graft ileocecal valve and ascending colon, and reaching acceptable success after a short period of training.     

Living related small bowel transplantation: donor surgical technique

OBJECTIVE: To describe a standardized technique for ileal graft procurement in the setting of living related bowel transplantation. SUMMARY BACKGROUND DATA: Living donor transplantation has been successfully developed for kidney, liver, pancreas, and lung transplantation. More recently, living related small bowel transplantation (LR-SBTx) has been developed with the aim of expanding the pool of intestinal graft donors and reducing the mortality in patients on the waiting list. To date, a total of 25 LR-SBTx worldwide have been reported to the international registry. We herein report the largest single center experience. METHODS: A segment of ileum, 150 to 200 cm, is resected 20 cm proximal to the ileocecal valve (ICV), which is always preserved. The arterial inflow is given by the terminal branch of the superior mesenteric artery and venous outflow by a proximal segment of the superior mesenteric vein. The entire bowel is measured intraoperatively and at least 60% of intestine length is left in the donor. RESULTS: Since 1998, we have performed 9 terminal ileum resections for small bowel donation. None of the donors has experienced persistent alteration of bowel habits or malabsorption; only 1 minor wound complication has occurred. CONCLUSIONS: Terminal ileal resection with preservation of the ICV seems to assure fast functional recovery of the donor and has minimal postoperative complications.     

Chronic rejection in a small bowel transplant with successful revision of the allograft by segmental resection: case report

An 8-year-old girl was admitted for severe electrolyte imbalance and for hyponatremic seizure. In July 2005, at 3 years of age, she underwent isolated small-bowel transplantation of 100 cm ileum from her father. Her own bowel was only 50 cm of proximal jejunum which had been directly connected to the anus due to extended total aganglionosis. The graft was placed into the middle of her remaining bowel, using the splenic artery and vein as feeding vessels with saving of the spleen. Daclizumab induction and tacrolimus monotherapy were applied for immunosuppression. Two acute cellular rejection episodes, E on day 10 and 4 years after transplantation, were successfully treated with OKT-3 and recombinant antithymocyte globulin, respectively. However, because of intermittent bowel dysfunction, she was hospitalized several times for hydration and metabolic care. On admission, her abdomen was moderately distended, and a simple abdominal film showed a fixed dilated loop. Colonoscopy could not pass the narrowed lumen, with stiffness at the anastomosis between the graft and the distal bowel. Endoscopic biopsy at the entrance to the stricture showed a nonspecific inflammatory reaction with fibrosis. Similar findings on a gastrograffin enema suggested chronic rejection (CR). On laparotomy, an irregularly narrowed fibrotic loop was noticed at the distal part of the graft, proximal to the anastomosis. We performed a 20-cm segmental resection with an end-to-end anastomosis. Histopathologic findings showed CR with fibrosis and hyalinization of the entire bowel wall and vessel walls with mild cellular infiltrations. She recovered in 10 days. The graft may have been saved, but intermittent requirement of hydration over the following months suggested progressive graft dysfunction. A case of segmental involvement of CR with subsequent successful graft salvage by partial resection is rare in the literature.     

Immunologic benefits of longer graft in rat allogenic small bowel transplantation

BACKGROUND: The effect of graft length on rejection reaction in small bowel transplantation (SBT), which is poorly understood, is tested using rat allogenic SBT models with a short course of tacrolimus. MATERIALS AND METHODS: Inbred Brown Norway rats (major histocompatibility complex: RT1) and Lewis rats (RT1) were used as donors and recipients, respectively. The intestinal tract of the recipient was partially or totally replaced by segmental (15 cm) or whole (70 cm) donor intestine, using two different SBT models. With tacrolimus treatment (0.64 mg/kg per day, 0-13 postoperative days, intramuscularly), recipients' body weights and their survival were evaluated. To compare the extent of peripheral chimerism, donor passenger leukocytes were followed using flow cytometry with a donor-specific monoclonal antibody, OX-27. For the periodical histologic analysis, heterotopic SBT and protocol biopsies of the graft were also performed with short or long intestinal grafts. RESULTS: In a classical Monchik and Russell orthotopic SBT model, whole SBT recipients survived more than 60 days. However, all of the allogenic segmental SBT recipients died within 14 days without histologic sign of graft rejection. In the modified orthotopic SBT model using a cuff technique without systemic clamping, all recipients with segmental allograft survived longer than 29 days. However, recipients with whole graft tended to survive longer than those with segmental graft. The suffering period, lasting from the onset of rejection to death, was significantly shorter in the segmental group than in the whole group. Flow cytometric analysis showed that recipients with whole intestinal grafts had significantly higher ratio of donor passenger leukocytes in peripheral blood. Histologic studies of the protocol biopsies showed that the shorter graft tended to be more severely rejected than the longer graft. CONCLUSIONS: We have demonstrated experimentally that long intestinal grafts have immunologic advantage over short grafts.     

En block combined reduced-liver and small bowel transplants: from large donors to small children

BACKGROUND: The critical shortage of size-matched donor organs for infants and small children in need of combined liver and intestinal transplantation has lead to long waiting times and a high risk of dying before transplantation. Utilizing grafts from larger donors could alleviate this problem, but using larger composite grafts in small children has been challenging and unsuccessful in the past. METHODS: We conducted a pilot study for evaluating the results of transplanting into small recipients a composite graft (reduced-size liver and whole small bowel, including duodenum and pancreas head) procured from large donors. Liver size reduction was performed ex situ using the extrahilar approach, which leaves the liver hilum untouched. Straightforward implantation of the graft was performed by simple, two-step vascular anastomoses. The preservation of the donor duodenum in continuity with the combined graft avoided the need for biliary reconstruction, thus preserving maximal bowel length for gut continuity restoration in the recipient. RESULTS: Two children, weighing 7.6 and 9.8 kg, respectively, underwent transplantation of a composite graft procured from donors weighing 35 kg. Their waiting time (68 and 97 days, respectively) was shorter compared with our previous experience with conventional techniques. Both are currently alive and well, at home and on full enteral feeds, 15 and 11 months after transplantation, respectively. CONCLUSION: This new technique has extended the range of possible donors for small candidates waiting for combined grafts and was successful in two patients. It should be considered for small recipients in the future.     

Comparison of conventional laparoscopic and hand-assisted oncologic segmental colonic resection

Background Laparoscopically assisted colon resection has evolved to be a viable option for the treatment of colorectal cancer. This study evaluates the efficacy of hand-assisted laparascopic surgery (HALS) as compared with totally laparoscopic surgery (LAP) for segmental oncologic colon resection with regard to lymph node harvest, operative times, intraoperative blood loss, pedicle length, incision length, and length of hospital stay in an attempt to help delineate the role of each in the treatment of colorectal cancer. Methods Patient charts were retrospectively reviewed to acquire data for this evaluation. Between June 2001 and July 2005, 40 patients underwent elective oncologic segmental colon resection (22 HALS and 18 LAP). The main outcome measures included lymph node harvest, operative times, intraoperative blood loss, pedicle length, incision length, and length of hospital stay. Results The two groups were comparable in terms of demographics. The tumor margins were clear in all the patients. The HALS resection resulted in a significantly higher lymph node yield than the LAP resection (HALS: 16 nodes; range, 5–35 nodes vs LAP: 8 nodes; range, 5–22 nodes; p < 0.05) and significantly shorter operative times (HALS: 120 min; range, 78–181 min vs LAP: 156 min; range, 74–300 min; p < 0.05). Both groups were comparable with regard to length of hospital stay, pedicle length, and intraoperative blood loss. However, the LAP group yielded a significantly smaller incision for specimen extraction (LAP: 7 cm; range, 6–8 cm vs HALS: 5.5 cm; range, 5–7 cm; p < 0.05). Conclusion The findings suggest that hand-assisted laparoscopic oncologic segmental colonic resection is associated with shorter operative times, more lymph nodes harvested, and equivalent hospital stays, pedicle lengths, and intraoperative blood losses as compared with the totally laparoscopic approach. The totally laparoscopic technique was completed with a smaller incision. However, this less than 1 cm reduction in incision length has doubtful clinical significance.     

Immunological advantage on small bowel graft induced by simultaneously transplanted liver in porcine auxiliary liver/small bowel transplantation

BACKGROUND: We developed a new porcine model for auxiliary liver/small bowel transplantation (LSBT). The possible immunological advantage on small bowel graft induced by simultaneously transplanted liver in the large animal was assessed. METHODS: Thirty outbreed long-white pigs were randomized into two groups. Group A animals received LSBT without immunosuppressive treatment (n = 10). Group B animals had segmental small bowel allotransplantation without immunosuppressive treatment (n = 10). The postoperative survival time, initial acute rejection time, and pathological rejection scores were analyzed. RESULTS: There was no remarkable difference in survival time between groups A and B (10.33 days vs 12.89 days, P > .05), but the initial time of acute rejection in intestinal grafts in group A was obviously delayed when compared to group B (8.22 days vs 4.33 days, P < .05), and the rejection scores in group A were remarkably lower than those of group B (0 vs 0.44 on postoperative day (POD) 3, P < .05; 0.22 vs 1.78 on POD 5, P < .05; 1.11 vs 2.56 on POD 7, P < .05). CONCLUSIONS: An immunological advantage on intestinal graft can be induced by simultaneously transplanted liver in auxiliary LSBT. Compared to isolated segmental small bowel allotransplantation, the intestinal graft in LSBT has a delayed initial time of acute rejection and lower acute rejection scores. The liver graft may reduce the risk of intestinal rejection and thus protect the bowel graft.     

血缘性活体部分小肠移植术二例

目的 探讨血缘性活性小肠移植治疗短肠综合征的效果。方法 对2例短肠综合征患者切取有血缘关系的供肠行部分小肠移植术,1例18岁,男性,供体为患者的父亲,供肠150cm。另1例15岁,男性供体为患者的母亲,供肠160cm。移植肠动、静脉分别与受者的腹主动脉及下腔静脉行端侧吻合,移植肠一期消化道重建,末端造口,术后给予抗排异、抗感染、抗凝血及营养支持等治疗。结果 第1例患者术后曾出现贫血、急性排异反应,经积极处理得到控制,目前已存活26个月,肠道吸收功能正常,自由经口进食,能参加日常工作,第2例患者术后26d发生排异反应,顷冲击治疗好转,术后80d再次发生重度排异反应,经甲基强的松龙冲击无效,改为单克隆抗淋巴细胞抗体、抗胸腺细胞球蛋白冲击治疗,排异反应虽有好转,但发生不可控制的感染。抢救无效死亡。生存5个月。结论 具有血缘关系的活体部分小肠移植是治疗短肠综合征的一种方法。     

First successful clinical small intestine transplantation. Tactics and surgical technic

A case of successful clinical small bowel transplantation is demonstrated. A segment of 60 cm of jejunum and ileum has been harvested from the sister of the recipient and has been brought in heterotopic position in the first operative step. It was anastomosed to the recipient's GI-tract 6 weeks later. This procedure has the advantage that the graft can recover from ischemic damage in heterotopic position and that an immunological steady state can be achieved. This case of successful clinical small bowel transplantation offers a new causal therapy for patients with short gut syndrome.     

短肠综合征合并高位肠瘘患者施行亲属活体小肠移植一例

目的总结短肠综合征合并高位肠瘘患者施行亲属活体小肠移植的经验和体会。方法为1例因肠系膜上动脉栓塞而切除空肠、大部分回肠及右半结肠的患者施行亲属活体小肠移植,供者为患者之子,移植回肠长度为150 cm,供肠热缺血时间1 min,冷缺血时间65 min。受者切除肠瘘,供肠动、静脉分别与受者的腹主动脉和下腔静脉行端侧吻合,供肠的近端与受者的空肠残端行端端吻合,远端侧壁与结肠残端行侧端吻合,移植小肠末端造口,作为观查窗。术后使用他克莫司、霉酚酸酯和甲泼尼龙预防排斥反应,并给予抗感染、抗凝以及胃肠外为主、肠内营养为辅的支持治疗。结果术后移植小肠功能接近正常,能胜任一般的体力劳动。术后110 d,患者因情绪变化突发心脏意外,抢救无效死亡。结论合并肠瘘的短肠综合征并非小肠移植禁忌证,术前充分准备和术后细致观察及管理是成功的关键。     

Treatment of short gut syndrome with early living related small bowel transplantation

AIM: To investigate the results of treating short bowel syndrome with an early living related small bowel transplantation (SBT). METHODS: A 17-year-old boy with a 20-cm-long residual intestine due to necrotic volvulus received an early living related SBT from his mother. Donor-specific blood transfusion was performed for 8 weeks before transplantation, each time for 50 mL every week. Cytomegalovirus status in both donor and recipient was negative. A 160-cm distal ileal segment was removed from the donor. The graft ilecolic artery and vein were anastomosed to the recipient's infrarenal aorta and caval vein. The proximal end of the graft was anastomosed end-to-end to the residual recipient jejunum; the distal anastomosis, between the distal end of the graft and transverse colon. An ileostomy was also performed. Immunosuppression, infection prophylaxis, and antithrombotic and nutrition support were given postoperatively. RESULTS: The donor had an uneventful recovery. No technical complications were observed. The recipient was alive and well at 31 weeks after the operation. No graft rejection or infection was observed. He was off TPN 8 weeks after the operation and took low-fat food. The D-xylose test in the recipient was almost normal. CONCLUSIONS: Early living related small intestine transplantation is a good treatment for short bowel syndrome.