Allogeneic Small Bowel Transplantation

Allogeneic small bowel transplantation (referred to as small bowel transplantation) began to be used in clinical practice in 1964. At that time, it was not well solved in terms of transplantation technology, immune rejection, infection and recovery of intestinal function, which hindered the further transplantation of intestinal transplantation. The application has become a late success in large organ transplantation. In 1990, Grant reported a case of a liver-intestinal joint transplant that survived for more than one year and considered that it can increase immune tolerance after liver and bowel transplantation. Later, the United States Todo compared liver-intestinal transplantation and small bowel transplantation alone, but believed that the latter's technical operation is relatively simple, and postoperative recovery is relatively smooth. Although there have been successful cases reported in the literature, there are still less than a thousand cases (2003), and the progress is very slow. Curing disease: Indication Small bowel transplantation is considered to be a reasonable method for the treatment of irreversible intestinal failure. Intestinal failure refers to the balance of water and electrolytes in the intestines of patients whose anatomical or functional relationship cannot maintain the body's minimum nutritional needs. It includes short bowel syndrome, extensive chronic inflammatory bowel disease, severe mesenteric vascular disease, enteric nerves, muscles, and congenital intestinal malformations. Contraindications Because small bowel transplantation is a complicated operation. Therefore, in addition to general contraindications for major abdominal surgery, it has extensive adhesions to the abdominal cavity; it has not been suitable for the application of immunosuppressive diseases; high malnutrition has damaged vital organs and elderly patients with weak (>50 Years old) should be carefully chosen. Preoperative preparation 1. Preparation for the intestines. The donor can be given an immunosuppressive agent such as cyclosporine A (CsA), FK506 or the like before surgery. The intestines can be prepared by the use of laxatives and antibiotics to remove intestinal contents, and sufficient heparin can be administered to prevent blood clots. However, it is difficult to achieve these preparations when the donor is obtained from a non-brain death donor. 2. The use of immunosuppressive agents. Receptors should be treated with immunosuppressive agents before surgery. CsA and FK506 can be given 1 to 2 days before surgery. The intestines are also prepared for cleaning and bacteriostatic. Malnourished people should first do preoperative nutritional support. On the day of surgery, prophylactic broad-spectrum antibiotics were given at the beginning of the operation. After the start of the operation, a large dose of methylprednisolone 500-1000 mg was given intravenously for continuous instillation; CSA or FK506 was also given at the beginning of the operation. CsA is intravenously administered at 6 mg/(kg·d) (the effect of intravenous injection is 3 times that of oral preparation), and prostaglandin E10.6 g/(kg·min) or ATG (Anti thymoglobulin), OKTs, and the like are also administered. Currently, FK506 or CsA can be used in combination with methylprednisolone, cyproterone, and cyanidin (humanized IL2 receptor blocker). All immunosuppressants should be adjusted according to the blood concentration and the patient's signs, symptoms and liver and kidney function. 3. Prevention of infection. In the case of immunosuppressive applications, the incidence of infection in organ transplant patients is very high, the main point of anti-infection is to prevent infection, all operations are strictly in accordance with aseptic technical requirements, strengthen the disinfection and isolation system, and apply broad-spectrum antibiotics. 4. Promote the recovery of bowel function. The purpose of bowel transplantation is to create a new intestine that maintains the body's nutritional needs and other functions. Undoubtedly, maintaining nutrition is the most important thing. The absorption function of nutrients involves many aspects, the most important of which is the recovery of intestinal mucosal morphology and function. Promoting the recovery of the intestinal mucosa in terms of morphology and function is the core problem of post-transplantation. The intestinal mucosa is a tissue that is resistant to ischemia, especially to warm ischemia. In China, it is not possible to completely avoid thermal ischemia from the corpse. To this end, we must try to restore the mucosa of the intestines to the process of degeneration and regeneration to normal. After a tolerable warm ischemia (<6min) and total ischemic time (<17hr), the absorption function changed, and its absorption function was significantly impaired within 2 weeks after surgery, and it began to recover at 4 weeks. It shows a process from degeneration of inflammation to repair and regeneration to normal, which lasts about 2 months. The longer the ischemic time, the slower or even unable to recover its function. Therefore, it is required during surgery to minimize the time of warm ischemia and recovery of blood circulation. The xylose absorption test is an effective method for detecting intestinal absorption function. Parenteral nutrition is the main nutrient pathway before the intestinal function is restored. After the start of enteral nutrition, the parenteral nutrition can be slowly removed until the enteral nutrition can be fully supplied. In theory, glutamine is an essential tissue nutrient for the intestinal mucosa. It can help the intestinal mucosa to repair. When the intestinal peristalsis is restored, it can be slowly infused from the high jejunostomy. The absorption of early amino acids is better than glucose and fat. Intestinal preparations in which an amino acid is a nitrogen source are suitable. The chyme can stimulate the regeneration of mucosal villi, and it is necessary to give oral diet in time. Intestinal nutrition can promote the proliferation of intestinal mucosal cells, which is beneficial to maintain the intestinal mucosal barrier function. When the intestinal mucosal barrier function is disordered, it is easy to have intestinal bacteria prone to cause systemic inflammatory reaction, sepsis, and induce rejection. happened. Surgical procedure Small bowel transplantation is not a qualitative operation. It can be a single small bowel transplant, or it can be combined with other organs. The most common is liver-intestinal joint transplantation. Due to long-term application of parenteral nutrition, liver damage to failure is reported in the literature. The number of bowel transplants is equal to that of liver and gallbladder joint transplantation. Like other organ transplants, the entire operation can be divided into donor surgery, recipient surgery and perioperative management. Now I will introduce an individual small bowel transplant. 1, donor surgery The ideal donor should be of similar age, similar in body shape, and the same sex, so that the volume, length, and diameter of the transplanted gut are the same as those of the host. It is required to have the same blood type, and it is best to do HLA matching and lymphatic test. However, when a non-brain death donor is used under conditions where the current donor is difficult, it is difficult to do so, but the blood type must be the same. (1) In order to shorten the warm ischemia time and obtain the intestine, the operation group should cooperate closely and move quickly. Firstly, a large amount of iodophor was poured into the abdominal wall of the donor to disinfect the skin, and a large incision of "ten" was made. Immediately after entering the abdominal cavity, a large amount of sterile crushed ice was placed. (2) The upper aorta of the radial artery was separated and the lower abdomen was ligated. Immediately, the catheter was inserted into the catheter at a temperature of 120 cmH2O at a pressure of 120 cmH2O at 4 °C, and then poured into a UW solution (University of Wisconsin solution). (3) The abdominal aorta was blocked by ligation under the arm, and the perfusate was retrogradely injected into the superior mesenteric artery (SMA). Then, the peritoneum was cut along the right colon and the left colon, and the entire intestinal spleen, spleen, pancreas, duodenum, and stomach were picked up. The hepatic and duodenal ligaments were clamped in the hepatic hilum, and the renal vessels were cut off by both jaws. The aorta and inferior vena cava above and below the superior mesenteric artery segment were cut, and the pylorus and duodenum were closed with vascular clamp. And cut off. The entire small intestine, pancreas, spleen, etc. were taken out and immersed in 4 ° CUW solution, and the catheter was reinserted from the aortic segment, and about 1000 ml of UW solution was injected. It was required to complete the lavage of the mesenteric vascular bed in a short period of time, and the small intestine and its small intestine The mesentery should be bloodless, and the entire small intestine and nearby organs should be obtained. It usually takes about 10 minutes. The intestines and the like are transferred to the operating room for further processing. The isolated SMA has a Carrel aortic piece in the opening, and the superior mesenteric vein (SMV) is separated into the portal vein, taking care to prevent vascular skeletalization, but the side branch and surrounding tissue should be cleaned. (4) The cut mesenteric vessels should be properly stopped. The pancreas, duodenum and proximal jejunum were removed, and the distal ileum was 50 cm each, leaving the small intestine 3 to 4 m. Both ends of the intestine were opened, and a solution of kanamycin 2 g of 0, 5% metronidazole 100 ml at 4 ° C was used for intestinal lumen perfusion, and UW solution was perfused. The whole process of dressing the intestine should be immersed in 4 ° CUW liquid, and pay attention to keep the temperature of the liquid at 4 ° C, strictly in accordance with aseptic technique. 2, receptor surgery Depending on the complexity of the patient's intra-abdominal lesions, surgery is initiated several hours before or at the same time as donor consolidation. It is generally required that the recipient's transplant bed should be completed before the donor is properly prepared to shorten the donor's ischemic time. Do not allow the prepared sausage to wait for the preparation of the receptor bed. The incisions were selected as required, and most of the incisions were made with a long incision in the abdomen to facilitate upward, downward, left and right extension. After the abdomen, the intestinal fistula that needs to be removed is first removed. In addition to embolization of MSV, attention should be paid to the preservation and preservation of the residual part of the superior mesenteric vein. Observe the thickness and residual length of the vein, consider whether it can be used for anastomosis, and then consider other steps. In the selection of surgical methods for small bowel transplantation, the main consideration is mesenteric venous return; the length of the intestine; the anastomosis of the intestine and the recipient intestine is the completion of the first phase or the completion of the phase. Return of mesenteric vein: usually only the main blood vessels of the artery and vein are to be anastomosed. The anastomosis of the artery is only suitable for the position of the anastomosis. It is convenient to operate and ensure sufficient blood supply. The anastomosis of the vein should be considered as the portal vein system or the systemic vein system. The latter, such as the common iliac vessels, is convenient to expose and has a shallow position. There is no major difficulty in technical operation, such as kidney ectopic transplantation. However, the main disadvantage is that the mesenteric blood flow directly returns to the body vein system. The nutrients and some factors in the reflux blood cannot directly enter the liver, which is unfavorable to the liver and nutrition. The mesenteric venous blood contains a large amount of ammonia and directly enters the body vein. After the system is easy to cause hyperammonemia. Therefore, most scholars advocate that mesenteric venous blood should be refluxed to the portal system to enter the liver. For this reason, the blood vessels for the mesentery and the blood vessels of the host usually have the following four forms: 1 The superior mesenteric artery and vein are respectively matched with the common iliac artery, the common iliac vein or the abdominal aorta and the inferior vena cava of the host. The venous blood flow returns directly to the systemic venous system. 2 The donor MSV and the host MSV do the opposite end-to-end or side-to-side anastomosis, depending on the host's MSV caliber. The donor MSA and the host renal artery planar lower aorta end-to-side anastomosis, as long as the host's MSV can be used for anastomosis, this procedure is not difficult, and the venous reflux is reasonable, and more is used. 3 Intestinal MSV and the host's portal vein do end-to-side anastomosis, MSA and the host's abdominal aorta do end-to-side anastomosis. This procedure is not suitable for use when the MSV of the host is suitable for anastomosis. The reverse flow of the vein is direct, and the direct access to the portal vein is an advantage. However, the entire pancreas and duodenum should be lifted inward, and the operation range is slightly larger. The MSA should be correspondingly fitted to the higher abdominal aorta plane, which increases the operation. Difficulty. 4 In a few cases, the splenic spleen of the host is excised, and the MSA and MSV of the intestine are matched with the spleen and venous stump. Animal experiments and clinical applications have this type of surgery, the disadvantage is that the spleen artery, vein diameter is small, blood circulation is insufficient, and it is easy to have anastomotic stricture. Especially not for adults. Regardless of the site of the anastomosis, the host vessel anastomosis and the vessel itself should be considered. Is there enough arterial blood supply? Can the vein reverse the blood flow without causing congestion? The donor MSV and MSA should usually be used. The pipe diameter shall prevail. The vascular anastomosis was continuously valgus and anastomosed with 5-0 polymer line. Pay attention to prevent the formation of blood clots during operation, and try to avoid blood leakage and needle filling. When anastomosis, it is generally preferred to first anastomosis of the vein. When the anastomosis is performed, the plasma is infused with 4°C from the artery, and the UW preservation solution in the intestinal blood vessel is excluded from the blood vessel and does not return to the receptor circulatory system. Since the whole intestine can be filled with 1400-1800 ml of blood, the anesthesiologist should be notified before the opening cycle to pre-fill the blood volume to avoid sudden hypovolemia. Whether anticoagulant is applied after surgery should be based on the scope of the surgical field trauma and the degree of oozing, and the patient's coagulation condition. Usually, when the blood volume is sufficient and the anastomotic operation is satisfactory, it is generally unnecessary to apply anticoagulant after surgery. Length of the intestine: It used to be a problem with more discussion. The longer the length, the more lymphoid tissue it contains, and the more likely it is to be different. And sometimes it is provided by the living body, and the length is cut to a certain extent. However, it is worthwhile to consider whether the length of the transplanted intestine can maintain nutrition after surgery, and whether the function of the intestine can be fully recovered is also worth considering. At present, the clinical experience is not enough, and it is still inconclusive as to how long it is appropriate. It has been reported that the living donor is only 60 cm long, and the corpse is mostly a small bowel transplant. In the early reports, small bowel transplantation was the main case, but in patients without colon, diarrhea was often aggravated after surgery. Therefore, patients with no colon can be transplanted with the small intestine together with the ileum, cecum, ascending colon, or more colon, which is conducive to the absorption of fluid to reduce diarrhea, but increases the risk of bacterial translocation and infection. Most authors disapprove of transplanting the colon. Intestinal anastomosis is completed in the first or second phase: in the animal experiment, the second phase is used to complete the transplantation. In the first stage of operation, the anastomosis of the arteries and veins is first provided, and the temporary dislocation of the two ends of the intestine is beneficial for observation and experimental research. Thereafter, after the survival of the intestine is confirmed, the second stage of surgery will complete the transplantation of the intestine and the recipient intestine. Although clinically, there is also a need for feeding and observation. However, if secondary surgery is used, especially after the application of more immunosuppressive agents and adrenocortical hormones, it will have an effect on controlling infection and incision healing. Therefore, it is now more than one phase to complete the anastomosis between the intestine and the host intestine. However, for the intestinal tract, the intubation stoma can be made at the proximal end, and the distal end of the intestine is made to be side-end or side-to-side anastomosis with the host intestine, and then the external stoma is put out as an observation window. The terminal ileostomy can be reset and closed after the prolonged period of acute rejection, and the absorption is improved. Generally, it is performed about 6 months after transplantation. complication Complications after small bowel transplantation include rejection, infection and diarrhea in addition to complications after general abdominal surgery. Rejection (rejeerion) (1) GVHD guest versus host disease: GVHD is a donor-to-host response in organ transplantation, and is more common in bone marrow transplantation and intestinal transplantation. GVHD is more common in mouse model animal experiments. The incidence is lower in clinical cases. Mainly manifested as systemic symptoms, rash. Pathological sections of the rash may show lymphocytic infiltration at the junction of the cortex and the epidermal layer with degeneration of the basal cells. (2) Acute rejection: Due to the presence of more lymphoid tissue in the intestinal wall and mesentery, the incidence of small bowel transplant rejection is higher. The 7th International Small Intestine Transplantation Conference (2001) reported a total of 656 cases of globally registered small bowel transplantation, with a rejection rate of 88%. Todo reported that the incidence of rejection was as high as 93.8% (15/16) in 15 cases and 16 bowel transplants. The incidence rate was 87.5% (14/16) in the first month after surgery and 28.6% in 3 months. (4/14), 36.4% at 6 months, but at 12 months, 3 of 7 patients had acute rejection, manifested as fever, abdominal pain, vomiting and watery diarrhea, and severe intestinal paralysis , intestinal bleeding, septic shock and ARDS-like performance. The diagnosis is mainly based on intestinal mucosal biopsy and pathological section observation. Treatment is a large dose of adrenal cortical hormone shock, increased immunosuppressive CsA or FK506, and given OKTs, anti-lymphocyte globulin, anti-thymocyte globulin and so on. Proper treatment, most patients can recover. (3) Chronic rejection: The main lesions of chronic rejection are thickening of small blood vessel wall, fibrosis of intestinal wall, symptoms of uncontrollable diarrhea, abdominal pain, intermittent sepsis, progressive weight loss and intermittent intestinal bleeding. Colonoscopy showed a pseudomembrane formation in the intestinal mucosa, thickening of the mucosal folds, and a chronic ulcer to the lumen of the intestine. For example, angiography shows a segmental stenosis of the mesenteric vascular arch, suggesting that the transplanted intestine should be removed. 2. Infection After small bowel transplantation, in addition to the infection of immune function, it is easy to have general purulent infections such as pneumonia and venous catheter-related infections. It is easy to have infection, mold infection and cytomegalovirus infection (cytomega lovirus infectien) caused by intestinal bacterial translocation. Bacterial translocation causes infection to be associated with rejection. In the event of rejection, intestinal mucosal barrier function is impaired and bacterial translocation is easy. Mold infections are associated with bacterial translocations, the use of immunosuppressants and high doses of antibiotics. Cytomegalovirus has a high carrying rate in the human population. After organ transplantation, it can be infected by the application of immunosuppressive agents, often showing pneumonia or enteritis. Therefore, some scholars advocate the use of ganiclovir or immunoglobulin prevention after surgery, the diagnosis is mainly dependent on cytomegalovirus antibody test. 3. Diarrhea There are many reasons for diarrhea after intestinal transplantation. In addition to rejection and cytomegalovirus infection, there may be dysbacteriosis and mold infection. It can be caused by nerve severing, lymphatic severing, hormonal imbalance, and incomplete recovery of intestinal mucosal function. Therefore, there are many cases of diarrhea after surgery, and anti-diarrheal agents such as compound phenethylpiperidine, loperamide, kaolin, bismuth subcarbonate, etc. may be used, and sometimes it is difficult to work, and there are also those who apply somatostatin. Some patients have removed the small intestine and the large colon and transplanted only the small intestine. The small intestine compensatory function is slow and the diarrhea can be longer. In these patients, the ileocecal and part of the colon can be transplanted at the same time.