[The variations of transplant anastomosis to the pharynx or esophagus during partial or total esophagoplasty].

Different modifications of colic and gastric transplants connection to the gullet or esophagus in the neck have been described. The most functional and cosmetic types of anastomoses have been specified. The utility of single-stage subtotal or total esophagoplasty with the use of colon segment regardless of the transplant length has been proved. The short- and long-term follow up of different modifications of anastomoses has been given.

[The nearest and long-term results of surgical treatment of patients with scarry strictures of the esophagus after chemical burn].

Results of esophagoplasty (small intestine--5, stomach--35, colon--40) were studied in 80 patients with scarry stricture of the esophagus. The development of cancer in the burned esophagus was established in 3 out of 5 patients in 35-45 years after operation. Good and satisfactory results were obtained in 97.8% of the patients within the period from 5 to 17 years after gastro- and coloesophagoplasty. Unsatisfactory results were found in 3.2%. Total lethality after esophagoplasty was 12.5%.

Contemporaneous chronic rejection of multiple allografts with principal pancreatic involvement in modified multivisceral transplantation.

The patient was a 10 yr-old-male with short gut syndrome secondary to Hirschsprung's disease, who underwent a modified (no liver) multivisceral transplant (stomach, pancreas, small and large intestine). The patient experienced malabsorption early in the post-operative course and had been dependent on a combination of enteral and intravenous nutrition. He developed symptoms of bowel obstruction and was suspected to have chronic rejection by an exploratory laparotomy four yr after transplant. Re-transplantation of a multivisceral transplant (stomach, pancreas, liver, small and large intestine) was performed. Microscopic examinations of the explanted allograft organ block revealed varying degrees of chronic rejection in many of the organs but with the pancreatic allograft being affected most severely. The malabsorption symptom following the first transplant may have been caused by the early onset of chronic pancreatic allograft dysfunction. Our case indicates varying severity of chronic rejection among multiple allografts where the pancreatic allograft appeared most susceptible to chronic rejection.

[Esophagoplasty in patients with the "waning" stomach or without the stomach]. / Ezofagoplastika pri "ushcherbnom" zheludke ili ego otsutstvii.

An experience with 48 intrathoracic esophagoplasties in patients with "waning" stomach or its absence is generalized. The results obtained show that scarry-ulcerous damages of the pyloroduodenal and cardioesophageal portions, local surgical procedures, gastrostomy included, are not considered as deterrent factors for using the stomach as the plasty material for esophagoplasty. For the resected stomach or its absence the small intestine should be preferred in the formation of the anastomosis within the limits of the thoracic cavity and large intestine--when putting anastomosis on the neck. A complete clinical effect was obtained in 45 patients. Three patients died (6.25%).

Combined cuff and suture technique for orthotopic whole intestinal transplantation in rats.

For the purpose of immunological study on small intestinal transplantation (SIT), rat SIT models using direct suture technique widely have been used, which requires at least several months of training for microsurgery. Alternatively, a simple cuff technique for SIT has been mainly used by us, which reduces warm-ischemic time and the training period, but the entire intestinal grafts usually obtain a limited blood supply. This report describes a modification of a combined cuff and suture technique for rat SIT to aid beginning microsurgical transplantation researchers. The advantages are 1) use of only arterial suturing, making it easier for beginners, with the cuff technique applied to the more difficult vein anastomosis; 2) achievement of better arterial inflow and graft survival than when the arterial cuff technique is used; and 3) doing only partial clamping of the aorta, which improves animal survival and success of the procedure. A very high successful rate in orthotopic whole SIT was achieved even by beginners.

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.

[A comparative evaluation of different methods of esophagoplasty]. / Sravnitel'naia otsenka razlichnykh sposobov ézofagoplastiki.

Intraoperative comparative oxyhemo- and thermometry of fragments of the gastrointestinal tract used for creation of the artificial esophagus were performed in 41 patients. The relationship of the degree of ischemic alterations in the transplant tissues and the development of postoperative complications was determined.

Comparison of rejection rate and functional outcome of small bowel transplantation alone or in conjunction with the ileocecal valve versus combined small and large bowel transplantation.

Preservation of the ileocecal valve improves absorptive function and decreases the amount of small bowel needed for survival in patients with short gut syndrome. We compared the results of small and large bowel transplant (SLBTx), small bowel transplant only (SBTx), and SBTx with the ileocecal valve (ICVTx) in a porcine model. Total enterectomy was performed on 18 Yorkshire-Landrace pigs followed by orthotopic SBLTx (n = 6), SBTx (n = 6), and ICVTx (n = 6). A jejunostomy and an ileostomy were constructed for biopsies. Overall mean survival was 17 d with no statistically significant difference between groups. Rejection was seen in 6/6 SLBTx, 4/6 SBTx, and 4/6 ICVTx recipients. Acute rejection was seen in 84.3% of SLBTx, 52.3% of SBTx, and 42.5% of the ICVTx mucosal biopsy samples. Two cases of intra-abdominal infection were in the ICVTx group only. Weight loss was 147 g/d in the SLBTx group, 643 g/d in the SBTx group, and 393 g/d in the ICVTx group. While the functional outcome after SLBTx and ICVTx was noticeably better than the SBTx group, the increased rejection and intra-abdominal infection rates make transplanting the large bowel or the ileocecal valve a less attractive clinical option.

[Can intestinal transplantation constitute treatment for intestinal failure?]. / La transplantation intestinale peut-elle être la thérapeutique de l'insuffisance intestinale?

The management of patients with intestinal failure has benefited from progress in parenteral nutrition (PN), especially home-based parental nutrition. Intestinal transplantation is now possible and in some conditions, constitutes the logical treatment option. Since 1985, more than 300 small-bowel grafts have been performed, involving the isolated small bowel with or without the colon (45%), the liver + small bowel (40%) or several organs (15%). 2/3 of recipients were under 20 years of age, and indications were short-bowel syndrome (64%), severe intractable diarrhea (13%), abdominal cancer (13%), or chronic intestinal pseudo-obstruction syndrome (8%). 51% of patients survived > 2 years after the graft. Patient and graft survival depends on the type of immunosuppression, i.e. Cyclosporine or FK 506. The results must be interpreted carefully as they represent the first experience in numerous centers using different immuno-suppressive protocols, without any randomization. The results from the largest of these centers more closely reflect the current situation and may exceed a 70% 2-year survival rate. Functional grafts lead to gastrointestinal autonomy (weaning of PN) while maintaining satisfactory nutritional status and normal growth in childhood. Intestinal transplantation is theoretically indicated for all patients permanently or persistently dependent on PN. However, as PN is generally well tolerated, even for long periods, each indication for transplantation must be carefully weighed up in terms of the iatrogenic risk and quality of life. When PN has reached its limits, especially those associated with vascular, infectious, hepatic or metabolic complications, intestinal transplantation must be undertaken. Transplantation of the small bowel alone remains the first option, as combined liver-small bowel grafting is only indicated in case of life-threatening progressive cirrhogenic liver disease.

[Comparative assessment of contractility of different sections of the intestine (an experimental study)]. / Sravnitel'naia otsenka sokratitel'noi sposobnosti raznykh otdelov kishechnika (eksperimental'noe issledovanie).

Contractility of different portions of the intestine used for partial or complete replacement of the bladder was studied on the circular fragments of non-inbred rats' intestine. The contractility was studied at rest, in response to electric stimulation, addition to the solution of growing concentrations of cholinomimetic or adrenomimetic drugs, to depolarization of smooth cell membrane with hypersodium solution. It was established that contractility of the large intestine contrary to that of the small intestine is characterized by diminished amplitude of spontaneous contractions. In addition of cholino- and adrenomimetics, amplitude of the phasic and tonic reactions in the large intestine fragments compared to those of the small one was decreased. The conclusion was made that the large intestine is preferable for taking transplants partially replacing urinary bladder to correct its reservoir function whereas small intestinal grafts are more suitable for total replacement of the detrusor.

Analyses of extrathymic T cell differentiation in nu/nu mice by grafting embryonal organs.

Fetal (days 15 to 17) organs such as the small intestine, stomach and pancreas were engrafted under the renal capsules of athymic nude (nu/nu) mice to examine the capacity of these organs to induce the differentiation of T cells. Eight weeks after engraftment, the engrafted organs had differentiated into adult-type organs histologically. In the lamina propria of the engrafted small intestine, large intestine, and stomach, there were clusters of lymphocytes or lymphoid follicles, which included Thy1.2+ or CD4+ T cells. Flow cytometric analyses revealed that the lymphocytes from the lymph nodes of sham-, esophagus-, or pancreas-engrafted mice included very few T cells (1.20%), whereas those from the lymph nodes of the fetal small intestine-, large intestine-, or stomach-engrafted mice included significant numbers of T cells (8.36%) 8 weeks after engraftment, although there were not as many as in the fetal thymus-engrafted mice (17.97%). The peripheral T cells in the small intestine-, large intestine-, or stomach-engrafted mice were of bone marrow origin, and consisted of Thy1.2+, CD3+, and CD4+8-, or CD4-8+ with T cell receptor (TcR) alpha beta cells. Taken together, these findings indicate that not only the murine small intestine and large intestine but also the stomach have the capacity to induce the differentiation of T cells.

[Reconstructive plastic surgery of the esophagus in children]. / Rekonstruktivno-plasticheskaia khirurgiia pishchevoda u detei.

The article presents the authors' experiences with reconstructive-plastic operations of the esophagus in children. The esophagoplasty was performed in 60 patients with congenital and acquired diseases. Among the congenital diseases are esophageal atresia, short esophagus and Barrett's esophagus, the acquired diseases include postburn scarry injuries. The optimum method of creation of the artificial esophagus are described. Of great significance are thought to be angiosurgical and microsurgical methods of cutting out the intestinal transplants. Cases of free autotransplantation of the intestinal segments for the substitution of the injured esophagus are described. Positive results were obtained in most cases.

[Flexibility of the surgical model of intestinal transplantation in swine]. / Flessibilità del modello chirurgico di trapianto intestinale sperimentale nel suino.

AIM: To verify the feasibility to introduce variations in the technique of intestinal transplantation, we developed three different intestinal transplant models in pigs. EXPERIMENTAL DESIGN: Feasibility and comparative study. ENVIRONMENT: Pre-clinical organ transplant surgery. MATERIALS AND METHODS: Sixty outbread piglets (mean weight 27.1 +/- 4.4 kg) received a total orthotopic intestinal allograft from equivalent donors perfused through the aorta with UW solution at 4 degrees C. Intraluminal flushing of the graft was always avoided. The animals were divided in 3 groups according to the transplantation procedure adopted. Group 1 (n = 9): excision of small and large bowel and replacement with small bowel only; group 2 (n = 39): excision of small bowel and its replacement; group 3 (n = 12): excision of small and large bowel and their "en-bloc" replacement. The superior mesenteric artery and vein were anastomosed end-to-end in all groups. RESULTS: The lowest perioperative mortality occurred in group 2 (28%), followed by group 3 (58%) and group 1 (78%). However, in group 1 the incidence of perioperative deaths was influenced by our learning curve in surgical and anesthesiologic management. No significant differences were noted in terms of cold and warm ischaemia time of the grafts, length of operative time, histopathologic analysis of preservation injury. The addition of the colon in the transplanted graft resulted in a more critical hemodynamic profile at reperfusion. CONCLUSION: Three different experimental models of intestinal transplantation are feasible in pigs. The choice can be made based on the type of study needed.

Combined transplantation of small and large bowel. FK506 versus cyclosporine A in a porcine model.

Clinically, FK506 is superior to CsA after solitary small bowel transplantation (SBTx). Development of diarrhea after SBTx has been the rationale for adding the colon to small bowel grafts. However, the additional lymphoid and bacterial content transferred with total small plus large bowel transplants (TBTx) might aggravate the alloimmune response-rejection and graft-versus-host disease (GVHD)-and increase the risk of infection. We studied the incidence of rejection, GVHD, and infection after TBTx and the impact of CsA versus FK506. We performed orthotopic TBTx with portal drainage after total enterectomy in outbred Yorkshire Landrace pigs, divided into 3 groups: control pigs (n=6) received no immunosuppression; CsA pigs (n= 14) received CsA (5 mg/kg), antilymphocyte globulin (10 mg/kg for 10 days), prednisone (2 mg/kg), and AZA (2.5 mgtkg); and FK506 pigs (n=9) received FK506 (0.2 mg/kg) and prednisone (2 mg/kg). Trough CsA whole blood levels were >400 ng/ml for the first 7 days and >200 ng/ml thereafter. FK506 levels were > 15 ng/ml. We excluded from further analysis 5 early deaths (<3 days) due to anesthesiologic (n=2) or technical reasons (n=3). Median survival of control pigs was 9.5 days (range, 4-13). Cyclosporine did not extend survival: median, 9 days (range, 5-31) (P=0.6). FK506 prolonged survival: median, 37 days (range, 21-49) (P<0.001 vs. control and CsA pigs). Of FK506 pigs, 60% gained weight (+75 g/day), whereas 100% of controls and 75% of CsA pigs lost weight (-550 g/day and -300 g/day, respectively). All control pigs died of rejection within 2 weeks versus none of the FK506 pigs. However, 36% of CsA pigs died of rejection. Groupwise comparison showed less rejection in FK506 versus control pigs (P<0.001) and in FK506 versus CsA pigs (P<0.03), but no difference between CsA and control pigs. None of the control pigs died of GVHD versus 18% of CsA pigs (by day 31) and 37% of FK506 pigs (by day 49). Groupwise comparison showed increased GVHD in FK506 versus control pigs (P<0.001) and a tendency toward increased GVHD in FK506 versus CsA pigs (P=0.08). None of the control pigs died of infection alone versus 22% of CsA pigs (by day 31) and 67% of FK506 pigs (by day 49). Groupwise comparison showed increased infection in FK506 versus control pigs (P<0.001). We detected significant endotoxemia early and late postoperatively. But we saw no specific correlation between endotoxemia, rejection, GVHD, or infection. Based on this study, we have drawn several conclusions: (1) In untreated pigs, TBTx provokes a severe rejection response, but no lethal GVHD. (2) Cyclosporine and particularly FK506 pigs have a high incidence of infection and lethal GVHD, a complication that we had not seen after solitary SBTx. (3) FK506 is superior to CsA in controlling rejection and in prolonging graft and recipient survival; FK506, however, does not reduce GVHD, but rather tends to augment it. (4) TBTx causes endotoxemia. As with solitary SBTx, FK506 is superior to CsA after TBTx. However, longterm survival is difficult to achieve on FK506 recipients because of the development of GVHD and infection.

Conventional patterns of human intestinal proliferation in a severe-combined immunodeficient xenograft model.

The present work describes the pattern of human intestinal proliferation in an immunodeficient murine xenograft model, which we have shown to closely mimic cell division in normal paediatric gut. Cellular proliferation was measured using a double-label technique combining MIB-1 immunohistochemistry and [3H]thymidine autoradiography, to critically compare values for the tissue growth fraction (G1, G2, S- and M-phase cells) and DNA synthesizing (S-phase) cells in xenograft epithelium, lamina propria, muscularis externa and intraepithelial lymphocytes. The MIB-1 monoclonal antibody (which recognises the cell-cycle dependent nuclear antigen Ki-67) specifically labelled proliferating human cells within the xenografts and did not cross-react with dividing murine cells. This was confirmed using ultrastructural in situ hybridisation with human- and mouse-specific DNA probes to identify the genetic origin of proliferating cells. In general, we found a good tissue correlation between MIB-1 and [3H]thymidine labelling, the only exception being an apparent dysregulation of Ki-67 antigen expression in regenerating xenograft epithelium. In developed xenograft intestine, the highest levels of proliferation were consistently recorded within the crypt epithelium, where 15.7%-26.7% of cells were actively cycling and S-phase occupied approximately half of the cell cycle. The frequency distribution of proliferating epithelial cells within small and large intestinal xenograft crypts was clearly tissue-specific, showing typical patterns of cell division. Therefore, the presence of functional pluripotent epithelial stem cells and conventional spatio-temporal patterns in cellular proliferation, migration, de-cycling, lineage commitment and cytodifferentiation now makes this an attractive experimental model with which to study human intestinal crypt responses to various types of tissue manipulation, e.g. cytotoxic, radiotherapeutic, dietary, endocrine and gene-targeting therapy.

Intestinal de-epithelialization and augmentation cystoplasty: an animal model.

OBJECTIVES: An animal model of augmentation cystoplasty was developed in New Zealand rabbits to study the effects of intestinal de-epithelialization on subsequent re-epithelialization by bladder urothelium. METHODS: Twenty-four rabbits underwent augmentation cystoplasty using intestinal segments that were either treated with protamine sulfate and urea solution or else anastomosed with an intact epithelium. Half of the rabbits receiving the de-epithelialized intestinal segments were subjected to glycosaminoglycan replacement therapy by administration of intravesical heparin. Experimental and control rabbits were sacrificed at 1-, 2-, and 3-month intervals. RESULTS: Histologic examination of the augmented sections showed small areas of urothelium growing over the intestinal epithelium (approximately 15%). The heparin-treated group demonstrated the greatest amount of re-epithelialization. There was no obvious histologic difference in the amount of collagen present in the augmented tissues in any of the experimental groups. CONCLUSIONS: In a preliminary study, New Zealand rabbits appear to be satisfactory as an experimental animal for studying the augmentation cystoplasty procedure and for the development of therapeutic interventions for enhancing epithelial growth. Protamine and urea will de-epithelialize the bowel and heparin may promote epithelialization of augmented intestinal segment by transitional epithelium.