André Dong Won Lee

Study of morbidity in orthotopic small intestine transplantation with Wistar rats: experimental study

BACKGROUND Transplantation of the small intestine is a surgical procedure currently under investigation for its possible application in the treatment of patients with short bowel syndrome, aiming at the reintroduction of an oral diet. AIM To define the morbidity and mortality of intestinal transplantation in small animals using microsurgery. Intra and postoperative morbidity and mortality were studied in Wistar rats submitted to orthotopic intestinal allotransplantation. MATERIAL AND METHOD The animals were divided into three groups: group A (37 donor animals), group B (37 recipient animals), and group C (10 control animals). Group B was divided into three subgroups according to survival time. Subgroup TI consisted of animals that died during surgery or due to causes directly related to surgical intervention, subgroup T2 consisted of animals that died between the 4th and 29th postoperative day, and subgroup T3 consisted of animals that survived after 30 days. Transplanted animals were evaluated in terms of surgical technique used (vascular and intestinal anastomosis), graft quality, surgical time, and clinical parameters. The animals that died by the 29th postoperative day were submitted to autopsy and the remaining ones were sacrificed after 30 days. RESULT There was a high rate of complication of a surgical nature. Early mortality rate, i.e., mortality up to the third postoperative day, was 54% with vascular anastomosis being the major cause of death. Surgical time was evaluated in a restricted and homogeneous group and showed a strong prognostic value in terms of successful transplantation. Clinical parameters such as weight loss, reduction of ingestion, reduction of motor activity and diarrhea were directly correlated with acute rejection. CONCLUSION The experimented intestinal transplant is a procedure companied by considerable morbidity and mortality due to surgical complications in postoperative period, vascular anastomosis and total surgical time.

Home Parenteral Nutrition Program and Referral of Potential Candidates for Intestinal and Multivisceral Transplantation in a Single Brazilian Center

Intestinal failure is a multifaceted condition that may require high-complexity treatment and a multidisciplinary program, including home parenteral nutrition therapy (HPNT) and intestinal transplantation. In this article, we profile a Brazilian single-center experience with 128 cases of HTPN followed for the last 30 years and appraise the referral for potential intestinal and multivisceral transplantation.

Transplante de intestino delgado

BACKGROUND Small bowel transplantation evolution, because of its complexity, was slower than other solid organs. Several advances have enabled its clinical application. AIM To review intestinal transplantation evolution and its current status. METHOD Search in MEDLINE and ScIELO literature. The terms used as descriptors were: intestinal failure, intestinal transplantation, small bowel transplantation, multivisceral transplantation. Were analyzed data on historical evolution, centers experience, indications, types of grafts, selection and organ procurement, postoperative management, complications and results. CONCLUSION Despite a slower evolution, intestinal transplantation is currently the standard therapy for patients with intestinal failure and life-threatening parenteral nutrition complications. It involves some modalities: small bowel transplantation, liver-intestinal transplantation, multivisceral transplantation and modified multivisceral transplantation. Currently, survival rate is similar to other solid organs. Most of the patients become free of parenteral nutrition.

Multivisceral transplantation in pigs: a model for research and training.

OBJECTIVE To present a model for research and training in multivisceral transplantation in pigs. METHODS Eight Large White pigs (four donors and four recipients) were operated. The multivisceral transplant with stomach, duodenum, pancreas, liver and intestine was performed similarly to transplantation in humans with a few differences, described below. Anastomoses were performed as follows: end-to-end from the supra-hepatic vena cava of the graft to the recipient juxta diaphragmatic vena cava; end-to-end from the infra-hepatic vena cava of the graft to the inferior (suprarenal) vena cava of the recipient; and end-to-side patch of the aorta of the graft to the infrarenal aorta of the recipient plus digestive reconstruction. RESULTS The performance of the multivisceral transplantion was possible in all four animals. Reperfusions of the multivisceral graft led to a severe ischemia-reperfusion syndrome, despite flushing of the graft. The animals presented with hypotension and the need for high doses of vasoactive drugs, and all of them were sacrificed after discontinuing these drugs. CONCLUSION Some alternatives to minimize the ischemia-reperfusion syndrome, such as the use of another vasoactive drug, use of a third pig merely for blood transfusion, presence of an anesthesia team in the operating room, and reduction of the graft, will be the next steps to enable experimental studies.

REFERRAL FOR INTESTINAL TRANSPLANTATION IN ADULTS AT A SINGLE CENTER.: 2866

Introduction Since 1991, the Short Bowel Syndrome (SBS) Group from Clinic Hospital of University of São Paulo Medical School provides gratuity clinical treatment and nutritional support for patients with SBS. Nowadays, we follow 120 patients in our group. From these patients, 28 patients were preferred to receive HTPN. In this report we evaluated 28 adults patients dependent of HTPN. Material and method We selected 28 patients for the training program. Patients that did not achieve understanding joined the day hospital program and were excluded of this survey. We evaluated their age, gender, main disease, remnant bowel, complications from SBS, number of catheter infection, incidence and cause of death and referral for intestinal transplantation. All central line catheters (Hickman) were inserted by vascular surgeon in the operating room. Line positioning was confirmed by fluoroscopy. Radiographic barium contrast were performed to evaluate the length of intestine. The patients we distributed in four subgroups: A: more than 50% jejunum-ileal tract (JIT) resection with ileoceal valve (ICV), B: more than 50% JIT resection without ICV; C: less than 50% JIT resection with ICV; D: less then 50% JIT resection without ICV. Central line infection was detected via paired blood cultures and a culture of the central line tip. Indications for intestinal transplant include: SBS with end stage of liver disease (characterized by bilirubin above 3mg/dL, coagulopathy, liver fibrosis, thrombocytopenia and esophageal varices), thrombosis in two or more central veins, incidence of two or more central catheter infection per year, frequent hydroelectrolyte disturbances and non metastic desmoid tumor. Results After 6 months, 14 patients (50%) continued exclusively in HTPN and 50% recovered per oral nutrition. All of HTPN dependent became potential referrals for intestinal transplantation. Their mean age was 39.79 ± 14.94 years. 60% was male and 40% was female. The main disease were: intestinal pseudobstruction (20%), mesenteric thrombosis (16%), trauma (16%), intestinal malrotation (10%), lymphoma non Hodgkin (10%), colon cancer + mesenteric thrombosis (6%), Appendicitis + peritonitis (10%), Crohn (3%), Gardner syndrome (3%), peritoneal dialysis + peritonitis – 3%, provoked abortion – 3%. According to bowel length, 15,60% patients were in Subgroup A, 6,40% in B, 28% in C and 50% in D. Complications of HTPN include: infection of catheter (85%), thrombosis of subclavian/julgular vein (65,60%), liver steatosis (38%), cholelithiasis (16%), cholestasis (13%), nephrolothiasis (10%), electrolytes disturbance (22%). The mean of central line infections was 2.00 ± 1,62. According to the patients follow up we observed that 47 % were alive. 53% died due HTPN complication, 47% by sepsis and central line infections, 3% by heart infarction and 3% by electrolyte disturbance. Conclusion HTPN may improve the survival in SBS if the patient is assisted by a qualified multidisciplinary group. However; the incidence of morbidity-mortality in these patients is high. Intestinal transplantation is the best therapeutic option that can improve the quality of life of these patients, mainly in environments with lack of institutions specialist in HTPN. Early referral for intestinal transplantation, before patient’s condition worsening, may improve the results of this procedure.

Estudo das alterações das citocinas inflamatórias na rejeição aguda do transplante intestinal em ratos

BACKGROUND: Intestinal transplantation is a possible treatment for patients with short bowel syndrome, aiming the reintroduction of oral diet. However, the major obstacle in this procedure is the strong rejection. Delay in rejection diagnosis may be irreversible and lethal. AIM: To define method for early diagnosis of rejection based on the presence of interleucin-6 (IL-6) e interferon- g (IFN-g) from intestinal allograft. MATERIAL AND METHODS: Isogenic rats Brown-Norway (BN) and Lewis (LEW) were submitted to intestinal heterotopic allotransplantation and divided in two groups: LEW donor to LEW recipient isograft group (C) and BN donor to LEW recipient allograft group (Tx). According to the day of sacrifice, Tx group were subdivided in three subgroups with eight animals each as follow: Tx3- sacrificed at third postoperative day (POD), Tx5 - sacrificed at fifth POD and Tx7 - sacrificed at seventh POD. Eight animals from control group were subdivided in three moments according to the time of biopsy from the graft as follow: C3 - biopsy at third POD; C5 - biopsy at fifth POD and C7 - biopsy at seventh POD. All animals from control group were sacrificed at seventh POD. Rejection parameters were compared between the control groups (C3 vs C5, C3 vs C7 and C5 vs C7, and allograft group (Tx3 vs Tx5, Tx3 vs Tx7 and Tx5 vs Tx7). The same parameters were analyzed between the control group and allograft groups ( C3 vs Tx3, C5 vs Tx5 and C7 vs Tx7). RESULTS: In C group no statistical significant difference regarding the immunoexpression of the cytokines, while in Tx group, immunoexpression of IL-6 and IFN-g were remarkable since the fifth postoperative day.

Participação da apoptose na rejeição aguda do transplante intestinal em ratos

BACKGROUND Intestinal transplantation is a possible treatment for patients with short bowel syndrome, aiming the reintroduction of oral diet. However, the major obstacle in this procedure is the strong rejection. Delay in rejection diagnosis may be irreversible and lethal. AIM To define method for early diagnosis of rejection based on the apoptosis from intestinal allograft. MATERIAL AND METHODS Isogenic rats Brown-Norway (BN) and Lewis (LEW) were submitted to intestinal heterotopic allotransplantation and divided in two groups: LEW donor to LEW recipient isograft group C and BN donor to LEW recipient allograft group (Tx). According to the day of sacrifice, Tx group were subdivided in three subgroups with eight animals each as follow: Tx3-- sacrificed at third postoperative day (POD), Tx5 -- sacrificed at fifth POD and Tx7 -- sacrificed at seventh POD. Eight animals from control group were subdivided in three moments according to the time of biopsy from the graft as follow: C3 -- biopsy at third POD; C5 -- biopsy at fifth POD and C7 -- biopsy at seventh POD. All animals from control group were sacrificed at seventh POD. Rejection parameters were compared between the control groups (C3 vs C5, C3 vs C7 and C5 vs C7, and allograft group (Tx3 vs Tx5, Tx3 vs Tx7 and Tx5 vs Tx7). The same parameters were analyzed between the control group and allograft groups ( C3 vs Tx3, C5 vs Tx5 and C7 vs Tx7). In C group no statistical significant difference regarding the expression of the apoptotic cells were detected, while in Tx group, the presence of apoptotic cells were remarkable since the third postoperative day.