Can quantitative 99mTc-MDP bone scans be used to predict longitudinal growth of epiphyseal plate allografts after microvascular transplantation? An experimental study

Allograft and autograft microvascular proximal tibial epiphyseal plate transplants were performed in female New Zealand White (NZW) rabbits to quantify the growth rate and total growth potential of immunosuppressed and nonimmunosup-pressed rabbits. The purpose of this experiment is to examine whether the ^99mTc-MDP radionuclide uptake of the transplanted epiphyseal plate at 1 week postoperatively, done to assess anastomotic patency of the transplant, could also serve as a predictor of eventual longitudinal growth of the transplant or replant. All transplants and replants demonstrating positive ^99mTc-MDP uptake in the proximal tibial epiphyseal plate at 1 week showed continued longitudinal growth. The precise amount of ^99mTc-MDP uptake, however, did not correlate with the amount of growth at 3 and 5 weeks follow-up. © 1995 Wiley-Liss, Inc.     

Prolongation of long-term kidney graft survival by a simultaneous liver transplant: the liver does it,and the heart does it too

BACKGROUND: Whereas some authors reported that kidney transplants were protected from rejection by simultaneous liver grafts, other authors failed to obtain evidence for a kidney graft-protective role for the liver. METHODS: The survival rate of 383 kidney grafts in recipients of combined kidney-liver transplants performed between 1985 and 2000 and reported to the international Collaborative Transplant Study (CTS) was analyzed and compared retrospectively with that of a matched group of control patients who were transplanted with kidneys only. In addition, 105 combined kidney-heart transplants performed during the same time period were analyzed. RESULTS: At 1 year, the survival rate of kidney grafts in recipients of kidney-liver transplants was significantly lower than that in kidney only recipients (P<0.0001). Subsequently, however, kidneys in kidney-liver recipients fared much better so that the success rates were virtually identical after 8 years of follow-up (62.1+/-3.5% vs. 61.9+/-2.3%, P=ns). Half-life times after the first posttransplant year were 27.6 and 14.5 years for combined or single kidney grafts, respectively, and the projected 20-year graft survival rates were 46% and 35%, respectively. The 8-year survival rate of kidney grafts in recipients of combined kidney-heart recipients was 63.5+/-6.2%, the associated half-life time 31.6 years, and the projected 20-year graft survival rate 49%. CONCLUSIONS: The long-term kidney graft survival rate is higher in recipients of combined kidney-liver transplants than in recipients of kidney grafts only. Because the success rate is equally high in recipients of combined kidney-heart transplants, it is necessary to reexamine the hypothesis that the liver possesses a unique capacity of protecting a simultaneous kidney graft from rejection.     

A Review of Arterial Grafts Used for Microvascular Arterial Reconstruction

Arterial grafts are sometimes used in microvascular reconstruction and their clinical benefit over standard venous grafts is unknown. To determine arterial graft utilization in clinical microvascular arterial reconstruction, a review of the literature was done. PubMed search resulted with 4,352 finds, and after screening for relevance, 11 articles reporting on 55 arterial grafts were analyzed. All reports were retrospective studies, case reports, and case series, with no randomized controlled trials. Two retrospective series reported better patency of arterial versus venous grafts in upper-limb revascularization for chronic occlusion, but the findings were highly biased. Better patency of arterial grafts did not lead to higher rate of clinical improvement. Antiplatelet and lipid-lowering agents seem to be underused in venous graft recipients and use of no-touch venous grafting has not been reported. Based on the available data, routine use of arterial grafts cannot be recommended. Studies that show better patency of arterial grafts in hand revascularization for chronic vascular insufficiency are retrospective and biased, so a randomized controlled trial is needed.     

Allogenic transplants of bone revascularized by microvascular anastomoses: a preliminary study

An area of experimental bone grafting that needs further study is the use of free vascularized allografts of bone. In 35 outbred mongrel dogs, the viability of vascularized bone allografts with and without azathioprine immunosuppression was compared to vascularized autogenous bone grafts. Viability was assessed by histologic techniques, fluorochrome bone labeling, and electron microscopy. Autogenous vascularized bone grafts remained viable, and it was concluded that microvascular technique was not the limiting factor in attaining survival of the grafts. The behavior of autogenous vascularized bone grafts with and without the influence of azathioprine was similar. Allogenic vascularized bone transplants uniformly failed at a period between 2 and 3 weeks. Immunosuppression with azathioprine did not appreciably affect survival of the osteocytes. However, the host response to the foreign tissue was slightly modified. The clinical ramifications of bone transplantations in humans are not analogous to the clinical situation of transplantation of other organs. If vascularized bone transplants are performed in humans, a relatively safe form of immunosuppression is necessary. This study suggests that azathioprine alone does not offer sufficient immunosuppression to insure viability of the vascularized transplant.     

Allogenic transplants of bone revascularized by microvascular anastomoses: A preliminary study

An area of experimental bone grafting that needs further study is the use of free vascularized allografts of bone. In 35 outbred mongrel dogs, the viability of vascularized bone allografts with and without azathioprine immunosuppression was compared to vascularized autogenous bone grafts. Viability was assessed by histologic techniques, fluorochrome bone labeling, and electron microscopy. Autogenous vascularized bone grafts remained viable, and it was concluded that microvascular technique was not the limiting factor in attaining survival of the grafts. The behavior of autogenous vascularized bone grafts with and without the influence of azathioprine was similar. Allogenic vascularized bone transplants uniformly failed at a period between 2 and 3 weeks. Immunosuppression with azathioprine did not appreciably affect survival of the osteocytes. However, the host response to the foreign tissue was slightly modified. The clinical ramifications of bone transplantations in humans are not analogous to the clinical situation of transplantation of other organs. If vascularized bone transplants are performed in humans, a relatively safe form of immunosuppression is necessary. This study suggests that azathioprine alone does not offer sufficient immunosuppression to insure viability of the vascularized transplant.     

Significance of HLA matching in renal transplantation. A prospective one-center study of 485 transplants matched or mismatched for HLA-A, B, C, D, and DR antigens.

Matching for HLA haplotypes as well as for HLA-A and B antigens improved graft survival in 112 living related first transplants. In cadaveric first transplants, matching for HLA-A and B antigens had a beneficial effect on the fate of 373 grafts, while matching for HLA-C antigens had no predictive value. One hundred seventeen cadaveric transplants and their recipients were prospectively typed for the HLA-DR antigens. Compatibility for HLA-DR was found to be prognostically beneficial irrespective of matching for HLA-A and B antigens, and with no difference between transfused and nontransfused patients. Matching both for HLA-A , B and D/DR was thus found to influence the outcome of renal transplantation.     

Best results in living donor transplantation using an aggressive policy in microsurgical bench reconstruction of nonoptimal arterial supply

The increasing of number of patients awaiting kidney transplantation have forced surgeons to use nonoptimal organs, such as kidneys with multiple/diseased arteries as well as those coming from living donors (LDs). Two hundred and sixty six LD transplants performed in cyclosporine era included 44 coming from a LD over 60 years of age. They were categorized into three groups according to the number of renal arteries and the surgical techniques employed for the arterial anastomosis: group I (n = 213) had a single "normal" renal artery. Group II (n = 11) were grafts with two (n = 10) or three (n = 1) arteries, which were directly reconstructed by intracorporeal conventional separate anastomoses. Group III of 42 recipients had grafts with either one artery affected by intrinsic renovascular disease (n = 18) or multiple arteries (n = 24) that were reconstructed at the bench. Recipient survival at 1 year was comparable, namely, 98%, 100%, and 100% rates in groups I, II, and III, respectively. Graft survivals not censored for death were 87%, 85%, 100% at 3 years for groups I, II, and III, respectively. The use of microvascular reconstructions ex vivo can widen the criteria for acceptance of LDs who display multiple or diseased renal arteries.     

Superior results with combined kidney-pancreas transplants.

From February of 1987 to February of 1991 the authors performed 23 pancreas transplants for Type I diabetes mellitus. Eight of the pancreas transplants were in patients who had a previous kidney transplant, 14 were simultaneous kidney and pancreas transplants, and 1 was in a pre-uremic diabetic. Two patients have been retransplanted after losing first grafts. All pancreata were retrieved from heart-beating cadaver donors. Pancreata were transplanted into the iliac fossa of the recipient using the iliac artery and vein as arterial inflow and venous outflow, respectively. Drainage of the pancreatic ductal system was accomplished by anastomosing either a patch or segment of duodenum surrounding the ampulla of Vater to the urinary bladder. All pancreata functioned initially with no patient requiring insulin 6 hours after surgery. Two grafts were lost early due to thrombosis of the venous drainage of the transplant; 4 grafts were lost to acute rejection; 3 were lost to chronic rejection; and 1 patient died with a functioning pancreas. One-year graft survival for all pancreatic grafts is 62 per cent. One-year patient survival is 96 per cent. One-year pancreatic graft and patient survival for the 14 combined kidney-pancreas transplants is 88 per cent and 100 per cent, respectively. Two kidneys transplanted with pancreata also were lost to acute rejection. Pancreas transplantation has proven to be a viable treatment alternative for selected patients with Type I diabetes mellitus. Long-term results are best when pancreas transplantation is done in combination with renal transplantation.     

Immunoarchitecture and specific functions of splenic autotransplants at different implantation sites.

The present study deals with the morphological and functional development of intraomentally and subcutaneously implanted splenic tissue. Spleens and splenic transplants from 138 Lewis rats were investigated with immunohistological, immunological and molecular biological methods at different times after operation (up to 200 days postoperatively). The analysis of the development revealed a nonsignificant reduction concerning the weight of subcutaneous replants and a nonsignificant decrease of the weight of female transplants of both groups at different phases after operation. The cell composition of cell suspensions from spleen and both transplant types showed a deficiency of T, B, MHC-I+ cells and a certain macrophage subset (ED-3+ cells) in transplants. In a quantitative immunohistological analysis of compartments (red pulp, periarteriolar lymphoid sheaths, marginal zone and follicles) the T cell reduction was related to the Tsupp/cyt cells and T cell receptor bearing cells in the periarteriolar lymphoid sheaths, whereas the density of T helper cells was normal. In addition, a different homing of kappa-light chain positive and leukocyte common antigen (B cell type)-positive B cells in follicles and marginal zone was detected. The amount of two macrophage subsets (ED-1+ and ED-2+ cells) was increased in the red pulp. Only minor differences in the immunoarchitecture of transplants at different implantation sites were measured. A functional analysis of spleen compared to both transplant groups elicited a B cell defect after LPS stimulation in subcutaneous transplants and a reduced allogeneic response of both transplant types but a normal proliferation of T cells after ConA stimulation and a correct IgM antibody response against sheep red blood cells. The in vivo mRNA expression and the expression kinetics of interferon-gamma and granulocyte-macrophage colony-stimulating factor after antigen stimulation differed in both transplant groups with a remarkable permanent expression of both mediators in subcutaneous transplants. It can be summarized that the results clearly indicate a development of spleen-like immunoarchitecture of intraomental replants with subtle cellular, functional and molecular alterations. In contrast, despite a comparable development, some severe functional defects occurred in subcutaneous implants pointing out the important role of interactions between the regenerating splenic tissue and the target tissue on a functional and molecular level.     

Autologe und homologe Kreuzbandtransplantate—feingeweblicher Einbau,klinische Ergebnisse

A successful integration of cruciate ligament grafts is dependent upon the structure of connective tissue transplants, the conservation in case of homologous grafts, the functional load, the fixation of the graft, and the bed for the transplant. As shown by our own experimentations on animals, the integration of connective tissue transplants depends above all on the connective tissue type (native, conserved), the functional stimulus, and the bed for the transplant. Nevertheless, the communications in literature indicate identical clinical results for different types of autologous transplants, which gives occasion, to mention the specific cruciate ligament stability tests, i.e. the Lachman test and the Pivot-Shift sign. The authors discuss their own results achieved by using one third of a patellar tendon or pes anserinus tendons as cruciate ligament substitutes.     

Microsurgical management of complex fingertip injuries: comparison to conventional skin grafting

In selected cases of severe fingertip injuries, an aggressive approach using microvascular and microneural techniques can yield functional results equal or superior to conventional methods of treatment in less severe injuries. A series of 20 patients were treated microsurgically from 1983 to 1986 for severe acute distal finger injuries or their early sequelae--five distal replantations, eight neurovascular free tissue transfers, and nine distal neurorrhaphies/nerve grafts with or without vascular conduit. Concurrently, 33 simpler tip avulsions were treated with full-thickness skin grafts for comparison. In the microsurgical series, one replant and the distal 1 cm of a free toe flap necrosed. Replants averaged two-point discrimination of 9.8 mm and pulp pinch 65 percent of normal; free toe transfers, two-point of 6 mm, pulp pinch 58 percent; distal nerve reconstruction, two-point 6 mm. Operating time per digit averaged 5.0 hours for replants, 4.3 hours for toe flaps, and 1.5 hours for nerve repair/grafts. All patients returned to full pre-injury employment within six months. None required revisional surgery for dysesthetic fingertips. In the conventional skin graft series, greater than six months follow-up is available in 17 patients. Average two-point was 7 mm (range: 3 to greater than 15 mm) and pulp pinch 83 percent of normal. There were seven poor results with cold intolerance, numbness, and paresthesias, three of which required revisional surgery. The data suggest that microsurgical management of fingertip injuries achieves results comparable to skin grafts, despite the greater complexity of the initial injury. This approach has resulted in fewer secondary tip revisions. Operative times are acceptable. Parameters of sensory return are similar, although pulp pinch is slightly less. Disability times are comparable to the average in major pulp losses. Of importance, final permanent partial factors of disability are diminished in rating, due to retained digital length, improved esthetic appearance, and less dysesthesia/cold intolerance.     

Renal transplantation: a twenty-five year experience.

Boston has played a significant role in the development of renal transplantation. In Boston was performed the first successful isograft between identical twins (1954) the first successful allograft between fraternal twins (1959) and the first successful allograft from a cadaveric donor (1962). An immunosuppressive drug was also described in Boston by hematologists Schwartz and Dameschek (1959) and modified for renal transplantation in dogs (1961) and used for the first time in a human recipient in March 1962. By 1965 renal transplantation had become a clinical reality. Three hundred and ninety-eight of 589 recipients (68%) since 1950 are still alive, a remarkable figure considering that it includes all the earliest experimental transplants. One hundred and ninety-five of 295 (68%) with living-related donor transplants still have functioning allografts; 104/265 (39%) with cadaveric donor transplants have functioning grafts currently. Since 1968 transplants from living-related donors have an 80% one year survival whereas cadaveric donor transplants have approximately a 50% one year survival. Seventy-nine per cent of all one year survivors have had excellent psycho-social rehabilitation.     

Combined transplantation of skin and cartilage as composite graft: Surgical technique and results

Summary Transplantation of composite grafts is a proven technique, especially in reconstructive surgery of the face. For good results, careful planning, gentle handling and perfect technique are necessary. The authors present their method and show the results of 64 transplants done between 1983 and 1986.     

Serial Ten-Year Follow-Up of HLA and MICA Antibody Production Prior to Kidney Graft Failure

The role of HLA antibodies in chronic allograft rejection was examined utilizing a unique resource of sera collected annually and stored over a 12-year period from patients with rejected or retained grafts. In patients selected for not having preformed HLA antibodies, 679 postoperative serial serum samples from 39 patients who rejected their grafts and 26 with functioning grafts were tested for HLA Class I and Class II antibodies by flow cytometry and for MICA antibodies by cytotoxicity on recombinant cell lines. HLA antibodies were found in 72% of patients who rejected grafts, compared to 46% with functioning transplants (p<0.05). In addition, the incidence of IgG HLA plus MICA antibodies was higher (77%) among those with failed transplants than those with functioning transplants (42%) (p<0.01). Finally, if patients with IgM anti-HLA antibodies were included, 95% of the 39 patients who rejected their grafts had HLA or MICA antibodies, compared to 58% with functioning grafts (p<0.01). Patients who rejected transplants had HLA and MICA antibodies more frequently than those with functioning grafts. These antibodies found in the peripheral circulation, were not necessarily donor-specific, but their association with failure is consistent with a causality hypothesis.     

Evaluation of patency of synthetic and autogenous venous and arterial micrografts in rats

Long-term patency rates of synthetic and autogenous venous and arterial microvascular grafts in rats were compared. The grafts were interposed between the carotid arteries. The geometry of the anastomoses was designed in a manner intended to be comparable to the situation commonly encountered in cerebral revascularization procedures in man. Patency rates were 37.5% for synthetic grafts, 90% for venous grafts, and 60% for arterial grafts. Venous grafts are the best currently available microvascular prostheses.     

Vascularized bone autografts. Experience with 41 cases

Forty-one autogenous vascularized bone grafts have been performed by the authors since 1976. Twenty-two free vascularized fibular grafts were performed in a lower extremity and ten in an upper extremity. Ten of these patients were treated for locally aggressive, benign, or low-grade malignant bone tumors, while the remainder of the patients were treated for massive trauma-derived, segmental bone defects. The average length of the bone defect was 14.9 cm for tumor cases and 16.2 cm for trauma cases. In four patients (12.5%), the operation was unsuccessful, resulting in amputation. Nine patients were treated by osteocutaneous groin flaps, with one failure, resulting in amputation. Vascularized autogenous bone grafts transferred by microvascular anastomoses have been found an effective method of treatment for massive segmental bone defects.     

Five-year results of renal transplantation in highly sensitized recipients

Abstract  A special program for the priority allocation of cadaver donor kidneys to highly sensitized patients was initiated 10 years ago. During the period from 1985 to 1994, 329 transplants were performed at 35 transplant centers. Five-year graft survival rates were: 59 ± 4 % for 156 first grafts, 52 ± 5 % for 133 second grafts, and 18 ± 7 % for 40 third or fourth grafts. The success rates of first and second grafts were comparable with the corresponding success rates of first and second cadaver transplants in non-sensitized recipients reported to the Collaborative Transplant Study. There was a highly significant impact of HLA matching on graft survival. Among first and second grafts, 35 transplants with no mismatches for HLA-B+DR had a 76 ± 8 % success rate at 5 years, compared with a 55 ± 4 % rate for 208 grafts with one or two mismatches and a 37 ± 8 % rate for 46 grafts with three or four mismatches (weighted regression P < 0.001).     

Role of splenectomy in renal transplantation

One hundred sixteen renal transplants in 99 patients were reviewed. Patients were divided into four groups: 53 live donor recipients with pretransplant splenectomy, 13 nonsplenectomized live donor recipients, 20 cadaver recipients with splenectomy, and 30 nonsplenectomized cadaver recipients. Nonsplenectomized live donor recipients had fewer rejection episodes per month of graft function (p < 0.005). Serum creatinine in functioning grafts showed no differences between splenectomized and nonsplenectomized patients. In 73 splenectomized patients there were 14 related septic and/or thromboembolic complications, 6 fatal. Mean daily azathioprine dosage was greater in splenectomized patients (p < 0.005). There were no hyperacute rejections of second transplants in splenectomized patients, while 2 occurred in 8 nonsplenectomized patients. Splenectomy prior to renal transplantation did not decrease the number of rejection episodes per month of graft function and was associated with a higher rate of septic and thromboembolic complications.     

The use of jejunal transplants to treat a genetic enzyme deficiency.

INTRODUCTION: The Gunn rat is an excellent animal model of Crigler-Najjar syndrome, type 1. The liver and small intestine synthesize no functional bilirubin uridine diphosphoglucuronosyl transferase and, consequently, the animals cannot conjugate bilirubin. In prior studies, the authors have shown that 15- to 20-cm jejunal transplants from normal Wistar rats lowered but did not normalize serum bilirubin levels. Phenobarbital has been used to increase enzyme conjugation of bilirubin. HYPOTHESIS: Phenobarbital treatment of Gunn recipients of jejunal transplants from Wistar rats normalizes serum bilirubin levels. METHODS: Forty-three Gunn recipients of jejunal transplants from Wistar rats were divided into four groups: 1) heterotopically placed grafts (Thiry-Vella loops), saline-treated, n = 14; 2) heterotopically placed grafts, phenobarbital-treated (80 mg/kg/day), n = 17; 3) orthotopically placed (in intestinal continuity) grafts, saline-treated, n = 5; and 4) orthotopically placed grafts, phenobarbital-treated, n = 7. Serum was collected before operation and weekly for 8 weeks for measurement of serum total, indirect, and direct bilirubin levels. Animals received cyclosporine, 5 micrograms/kg, daily intramuscularly. RESULTS: Phenobarbital significantly augmented the bilirubin-lowering effect of heterotopic jejunal transplants (group 2). Mean total serum bilirubin fell from 9.14 +/- 0.01 to a nadir of 1.63 +/- 0.11 mg/dL at 6 weeks, after which time, levels began to rise toward baseline (as noted previously). Serum indirect bilirubin levels behaved in a similar fashion. Phenobarbital treatment "normalized" serum bilirubin levels in recipients of orthotopic Wistar jejunal grafts (group 4). Mean total serum bilirubin plummeted from 8.41 +/- 0.20 to 0.76 +/- 0.15 mg/dL at 1 week, and levels remained within the normal range for the entire 8-week study period. Identical changes were observed for serum indirect bilirubin levels. CONCLUSIONS: The combination of phenobarbital treatment and orthotopic small bowel transplantation may be an appropriate therapeutic alternative to liver transplantation in the management of Crigler-Najjar syndrome, type 1.     

Immediate skin grafting on microvascular free tissue transfers

Clinical reports of pedicled muscle flaps and microvascular tissue transfers include two distinctly different strategies for skin grafting. Some authors describe immediate grafting, whereas others recommend a three- to 5-day interval between flap transfer and grafting. No systematic analysis of either strategy has been reported. We reviewed 51 consecutive successful free tissue transfers that involved immediate skin grafting. Ninety-six percent of the grafts survived without complication. Bot muscle and fascial flaps supported skin grafts. Skin grafts survived infected recipient sites, pedicle revisions, partial flap necrosis, and secondary operation. We conclude that immediate skin grafting on free tissue transfers is reliable.