H Furukawa

Outcome analysis of 71 clinical intestinal transplantations

ObjectiveThe aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as part of an organ complex. Summary Background DataEven with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. MethodsBetween May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three more recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. ResultsOf the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrlimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2–3 months without evidence of graft-versus-host disease. ConclusionTo improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria.

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

OBJECTIVEnThe efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined.nnnSUMMARY BACKGROUND DATAnAfter 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.nnnMETHODSnBetween 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.nnnRESULTSnActuarial 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.nnnCONCLUSIONSnFK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation.

Incidence and risk factors associated with the development of cytomegalovirus disease after intestinal transplantation

From May 1990 to March 1993, 38 patients (21 adults and 17 children) received 40 allografts that included the small bowel (14 isolated small bowel, 21 small bowel and liver, and 5 multivisceral transplantations). Fifteen patients (39%) had 26 episodes of CMV disease: 7 with one episode, 6 with two, and 1 each with three and four. CMV enteritis accounted for 21 (81%) of the episodes, hepatitis and pneumonitis for 2 each, and a viral syndrome for 1. Coxs proportional hazards univariate and multivariate analyses showed that significant first-episode risk factors were: CMV seropositive donors for negative recipients (relative risk [RR], 3.86; P = 0.02), the average daily plasma trough level of tacrolimus (RR, 2.15; P = 0.04), and total amount of steroid boluses (RR, 2.90; P = 0.02). CMV disease recurrence factors were: CMV seronegative recipients (RR, 8.60; P = 0.02) and total amount of steroid bolus pulses (RR, 12.39; P = 0.004). Because long courses of ganciclovir prophylaxis could not prevent the development of CMV disease, avoidance of CMV seropositive grafts in seronegative recipients and new strategies to prevent heavy immunosuppression without the penalty of rejection will be necessary to ameliorate this problem in intestinal transplant recipients.

Abdominal multivisceral transplantation

Under FK506-based immunosuppression, 13 abdominal multivisceral transplantations were performed in 6 children and 7 adults. Of the 13 recipients, 7 (53.8%) are alive and well with functioning grafts after 9 to 31 months. Six recipients died: three from PTLD, one from rejection, one from sepsis, and one from respiratory failure. In addition to rejection, postoperative complications occurring in more than isolated cases included PTLD (n = 6), abdominal abscess formation (n = 5), pancreatitis (n = 3), and ampullary dysfunction (n = 2). In addition, infection by enteric microorganisms was common during the early postoperative period. Currently, all 7 survivors are on an oral diet and have normal liver function. Two recipients (one insulin-dependent) require antidiabetes treatment, in one case following distal pancreatectomy and in the other after two episodes of pancreatic rejection. Thus, abdominal multivisceral transplantation is a difficult but feasible operation that demands complex and prolonged posttransplantation management. It is not yet ready for application and awaits a better strategy of immune modulation.

Cytomegalovirus infection after intestinal transplantation in children.

Sixteen episodes of cytomegalovirus (CMV) disease occurred in 10 of 41 children undergoing intestinal transplantation from 1990 to 1995. Stratification of CMV disease by donor (D)/recipient (R) serological status was as follows: 3 of 8, D+/R-; 3 of 9, D+/R+; 4 of 9, D-/R+; and 0 of 15, D-/R-. Treatment resulted in resolution of CMV disease in 93.3% of episodes. No deaths attributable to CMV disease occurred in this series. CMV in D+/R- children resulted in more extensive and persistent disease. However, patient and graft survival rates were similar in the different D/R subgroups and between children with and without CMV disease. Cumulative dose of steroid boluses (relative risk [RR], 1.59; 95% confidence interval [CI], 1.14-2.21) and history of steroid recycles (RR, 2.72; 95% CI, 1.21-6.13) were associated with CMV disease. These results suggest that although CMV-associated morbidity in pediatric intestinal transplant recipients was substantial, it was not associated with an increased rate of mortality or graft loss, even among high-risk D+/R- patients.

Acute Invasive Sinusitis Due to Trichoderma longibrachiatum in a Liver and Small Bowel Transplant Recipient

We describe a case of acute invasive sinusitis due to an unusual moniliaceous fungus, Trichoderma longibrachiatum Rifai 1969 (a member of the class Hyphomycetes), in a small bowel and liver transplant recipient treated with tacrolimus (FK-506) and prednisone. The patient was successfully treated with surgical debridements and amphotericin B followed by oral itraconazole.

Cold preservation of the human colon and ileum with University of Wisconsin solution

The inclusion of the colon in the intestinal graft resulted in worsening patient and graft outcome and increased the incidence of infection and rejection. In this study, we examine the role of ischemia on the barrier function of the epithelium during cold ischemia.

Tube choledochoureterostomy: a simple method for bile diversion.

A technique of bile diversion by tube choledochoureterostomy has been devised for the purpose of studying the role of bile in the intestinal absorption of drugs. This method was used in six dogs. No technical difficulties or major complications developed, as are inevitable with alternative methods, including external fistula.

HEAVY WATER CONTAINING ORGAN PRESERVATION SOLUTION, DSOL, AMELIORATES GRAFT SURVIVAL AND FUNCTION OF THE RAT HEARTS AFTER EXTENDED COLD PRESERVATION: 1562

K. Wakayama1, M. Fukai2, K. Yamashita3, D. Fukumori3, S. Shibasaki4, H. Gentaro3, M. Zaitsu4, Y. Tsunetoshi5, M. Sugawara6, M. Taniguchi7, T. Suzuki3, T. Shimamura3, H. Furukawa8, M. Ozaki4, S. Todo3 1Depertment Of General Surgery, Hokkaido University, Sapporo/JAPAN, 2First Department Of Surgery, Hokkaido University, School of Medicine, Sapporo/Hokkaido/JAPAN, 3First Department Of General Surgery, Hokkaido University, Sapporo/JAPAN, 4Department Of General Surgery, Hokkaido University, Sapporo/JAPAN, 5General Surgery, Hokkaido University, Sapporo/JAPAN, 6Department Of Pharmacy, Hokkaido Univ. Hospital, Sapporo/JAPAN, 7Department Of Organ Transplantation And Regeneration, Graduate School of Medicine, Hokkaido University, Sapporo/Hokkaido/JAPAN, 82nd Department Of Surgery, Asahikawa Medical College, Asahikawa/JAPAN