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S Todo

Publications and source records attributed to S Todo.

At least 235 records · Page 13Linked to original sources

The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation.

OBJECTIVE: This study analyzed the incidence and timing of biliary tract complications after orthotopic liver transplantation (OLTx) in 1792 consecutive patients. These results were then compared with those of previously reported series. Finally, recommendations were made on appropriate management strategies. SUMMARY BACKGROUND DATA: Technical complications after OLTx have a significant impact on patient and graft survival. One of the principal technical advances has been the standardization of techniques for biliary reconstruction. Nonetheless, biliary complications still occur. A 1983 report from the University of Pittsburgh reported biliary complications in 19% of all transplants, and an update in 1987 reported biliary complications in 13.2% of transplants. METHODS: The medical records of all patients who underwent liver transplantation and were hospitalized between January 1, 1988 and July 31, 1991 were reviewed. The case material consisted of the medical records of 217 patients treated for 245 biliary complications. RESULTS: Primary biliary continuity was established by either choledochocholedochostomy over a T-tube (C-C, n = 129) or a Roux-en-Y choledochojejunostomy with an internal stent (C-RY, n = 85). The overall incidence for biliary complication in this large series was 11.5%. Strictures (n = 93) and bile leak (n = 58) were the most common complications (69.6%). Most biliary complications (n = 143, 66%) occurred within the first 3 months after surgery. In general, leaks occurred early, and strictures developed later. Bile leaks were equally frequent in both C-C and C-RY (27.1% and 25.9%, respectively); strictures were more common after a C-RY type of reconstruction (36.4% and 52.9%, respectively). Twenty-one patients died, an incidence of 9.6%. Fifteen of the 21 biliary-related deaths were among patients treated for rejection before the recognition of biliary tract pathologic findings. CONCLUSIONS: Progress has been made on improving the results of biliary reconstruction after OLTx. Nonetheless, patients continue to experience biliary complications after OLTx, and these complications cause considerable loss of grafts and life. If significant additional improvement in patient and graft survival are to be obtained, the technical performance of OLTx must continue to improve.

Adult↗

Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression.

OBJECTIVE: The efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined. SUMMARY BACKGROUND DATA: After 3 years of preclinical research, a clinical trial of FK 506 for orthotopic liver transplantation was begun in February 1989, first as a rescue therapy for patients with intractable rejection with conventional immunosuppression, then as a primary drug. METHODS: Between August 1989 and December 1993, 1391 recipients (1188 adult and 203 pediatric) of primary liver allografts were treated with FK 506 from the outset. Results from these patients were analyzed and compared with those of 1212 historical control patients (971 adult and 241 pediatric) given cyclosporine-based immunosuppression. RESULTS: Actuarial survival at 4 years was 86.2% with FK 506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and 71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was reduced significantly for FK 506 patients. Four-year graft survival was 77.0% with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p < 0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult recipients (p < 0.0000). Regression analysis revealed that reduction in mortality or graft loss from uncontrollable rejection, sepsis, technical failure, and recurrent original liver disease were responsible for the improved results with FK 506 therapy. CONCLUSIONS: FK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation.

Actuarial Analysis↗

Haemophagocytic lymphohistiocytosis, interferon-gamma-naemia and Epstein-Barr virus involvement.

To clarify the correlation between Epstein-Barr virus (EBV) involvement and hypercytokinaemia in haemophagocytic lymphohistiocytosis (HLH), we analysed serum interferon-gamma levels and EBV-DNA in biological specimens obtained from 25 HLH cases (23 children and two adults). We found that HLH patients showed a wide range of serum IFN-gamma levels from 0.2 to 1300 U/ml, with a median 126 U/ml for EBV-DNA-positive (n = 9) and 4.5 U/ml for EBV-DNA-negative (n = 16) groups. The latter group could be classified further into a group with hyper-IFN-gamma-naemia (> 4.5 U/ml) (n = 8) and a group without hyper-IFN-gamma-naemia (n = 8). The survival of the hyper-IFN-gamma-naemic cases was significantly poorer than non-hyper-IFN-gamma-naemic cases. We conclude that EBV is probably involved in one third of the HLH cases, all of whom show hyper-IFN-gamma-naemia, and in the half of the HLH cases with hyper-IFN-gamma-naemia who have a rapidly fatal outcome.

Adolescent↗

The biological basis of and strategies for clinical xenotransplantation.

Recent discoveries have suggested that the exchange of multiple leukocyte lineages between grafts and host and subsequent long-term chimerism in both is the seminal mechanism of the acceptance of organs transplanted from the same (allografts) or different species (xenografts). This insight suggests new strategies which may allow xenotransplantation, the principal obstacle to which has been humoral rejection. We have defined humoral rejection as a family of complement activation syndromes afflicting allografts and xenografts in which there is a strong (but not invariable) association with performed antigraft antibodies, invariable evidence of complement activation, histopathologic stigmas of vascular endothelial damage, and a concomitant local or systemic coagulopathy. The generic descriptive term hyperacute rejection is a misnomer because a slow-motion version of the same "humoral" process can occur with some allografts and is the rule with the so-called concordant species xenotransplantations. The pathway of experience and discovery leading to this conclusion shows clearly that the distinction frequently made between allograft versus xenograft humoral rejection does not actually exist in principle, but only in details and intensity. Breaking down this barrier to xenotransplantation, whether or not it is associated with antibodies, is unrealistic. However, the possibility of avoiding the barrier has been exposed by showing that animal organs can be humanized, with a mixed donor and recipient cell population similar to the chimerism seen in long surviving allografts or even with complete leukocyte replacement. Pilot experiments in rodents suggest that organs from fully xenogeneic chimeras can be made into xenogeneic targets that are no more provocative of complement activation than allografts when they are transplanted into the donor bone marrow species. Although the validity of this concept of organ xenograft preparation is only at the pilot stage of verification, there is reason to suspect that the complement trigger of humoral rejection can be thereby disarmed. If this can be accomplished, independent evidence suggests that cellular rejection can be controlled with conventional T-cell directed immunosuppression, perhaps even with surprising ease. The potential subtle liability of synthetic products of xenogeneic parenchymal cells is not yet known.

Animals↗

Intestinal transplantation.

Intestinal transplantation is often the only alternative form of treatment for patients dependent on total parenteral nutrition for survival. Although a limited number of intestinal transplantations have been performed, results with FK 506 immunosuppression are comparable to those for other organ transplants. The impact of successful intestinal transplantation on gastroenterology will likely be similar to the impact of kidney and liver transplantation on nephrology and hepatology.

Adolescent↗

Intestinal transplantation at the University of Pittsburgh.

Our experience with clinical intestinal transplantation under FK 506 immunosuppression showed that 50% of the recipients were able to be independent from TPN after transplantation, but 10% require partial TPN with functioning grafts, 10% needed total TPN after graft removal, and 30% of the recipients died postoperatively, mostly from sepsis due to severe graft rejection. For further improvement in patient survival and in the quality of life for patients after intestinal transplantation, it is mandatory to establish a new strategy for treatment and prevention of graft rejection and systemic infection.

Adult↗

Three years clinical experience with intestinal transplantation.

BACKGROUND: After the successful evolution of hepatic transplantation during the last decade, small bowel and multivisceral transplantation remains the sole elusive achievement for the next era of transplant surgeons. Until recently, and for the last thirty years, the results of the sporadic attempts of intestinal transplantation worldwide were discouraging because of unsatisfactory graft and patient survival. The experimental and clinical demonstration of the superior therapeutic efficacy of FK 506, a new immunosuppressive drug, ushered in the current era of small bowel and multivisceral transplantation with initial promising results. STUDY DESIGN: Forty-three consecutive patients with short bowel syndrome, intestinal insufficiency, or malignant tumors with or without associated liver disease, were given intestinal (n = 15), hepatic and intestinal (n = 21), or multivisceral allografts that contained four or more organs (n = 7). Treatment was with FK 506 based immunosuppression. The ascending and right transverse colon were included with the small intestine in 13 of the 43 grafts, almost evenly distributed between the three groups. RESULTS: After six to 39 months, 30 of the 43 patients are alive, 29 bearing grafts. The most rapid convalescence and resumption of diet, as well as the highest three month patient survival (100 percent) and graft survival (88 percent) were with the isolated intestinal procedure. However, this advantage was slowly eroded during the first two postoperative years, in part because the isolated intestine was more prone to rejection. By the end of this time, the best survival rate (86 percent) was with the multivisceral procedure. With all three operations, most of the patients were able to resume diet and discontinue parenteral alimentation, and in the best instances, the quality of life approached normal. However, the surveillance and intensity of care required for these patients for the first year, and in most instances thereafter, was very high, being far more than required for patients having transplants of the liver, kidney or heart. CONCLUSIONS: Although intestinal transplantation has gone through the feasibility phase, strategies will be required to increase its practicality. One possibility is to combine intestinal transplantation with contemporaneous autologous bone marrow transplantation.

Adolescent↗