George E. Pierce

Ten-year experience in transplantation of A2 kidneys into B and O recipients

BACKGROUNDnThis article summarizes our 10-year multicenter experience with transplantation of 50 blood group A2 and A2B kidneys into B and O patients.nnnMETHODSnSince 1986, we have transplanted kidneys from 46 cadaver donors and 4 living donors who were blood group A2 (47 donors) or A2B (3 donors) into 19 B and 31 O patients. In 1991, we began allocating these kidneys preferentially to B and O recipients who were selected based on a history of low (< or =4) anti-A IgG isoagglutinin titers. Immunosuppression was no different from that used in ABO-compatible grafts.nnnRESULTSnThe 1-month function rate before thus selecting the patients was 68% (19/28), but is now 94% (17/18). Two-year cadaver-donor graft survival with this selection method is 94%, compared with 88% for 640 concurrent and consecutive ABO-compatible transplants (log-rank, 0.15). All four living-related transplants are still functioning, with a mean follow-up of 71 months. Since we began allocating A2 kidneys preferentially to B and O recipients, the percentage of the B patients who received A2 or A2B kidneys has increased from 29% (8/28) to 55% (10/18).nnnCONCLUSIONSnTransplantation of A2 or A2B kidneys into B and O patients is clinically equivalent to that of ABO-compatible transplantation when recipients are selected by low pretransplant anti-A titer histories. This approach increases access of blood group B recipients to kidneys.

Transhiatal versus transthoracic esophagectomy for adenocarcinoma of the distal esophagus and cardia

BACKGROUNDnTranshiatal esophagectomy is a popular method of resection because of its reported lower morbidity and mortality and similar survival rates compared to transthoracic esophagectomy. A review of recent experience with these two procedures for resection of distal esophageal and cardia adenocarcinoma is reported.nnnMETHODSnFrom 1988 to 1994, 48 patients with adenocarcinoma of the distal esophagus and gastric cardia were resected with intent to cure, 32 by transhiatal esophagectomy (group 1) and 16 by transthoracic esophagectomy (group II). The two groups were comparable in terms of patient demographics, preoperative risk factors, tumor stage, tumor differentiation, and involvement of resection margins (all not significant [NS]).nnnRESULTSnThere was no significant difference in median intensive care unit stay, median hospital stay, incidence of postoperative anastomotic leak, and stricture. Respiratory complications were higher in group I (41% versus 6%, P = 0.01). Hospital mortality was not significantly different for the two groups (group I 3.1% versus group II 0%, NS). Actuarial 5-year survival rates (Kaplan-Meier) were 12% for group I and 39% for group II (NS).nnnCONCLUSIONSnThese results suggest that when compared with transhiatal esophagectomy, the transthoracic approach is at least as safe, has comparable complication and survival rates, and remains an acceptable procedure for resection of adenocarcinomas of the distal esophagus and gastric cardia.

Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching.

BACKGROUNDnCadaveric renal retransplantation is associated with a higher risk of early graft failure than primary grafts. A large proportion of those graft losses is likely attributable to donor-directed HLA class I antibodies, detectable by flow cytometry cross-matching but not by conventional crossmatching techniques.nnnMETHODSnLong-term graft survival in a group of 106 recipients of consecutive cadaveric renal regrafts between 1990 and 1997, in whom a negative flow T-cell IgG crossmatch was required for transplantation, was compared with two other groups of cadaveric transplant recipients. The first group consisted of 174 cadaveric regrafts transplanted between 1985 and 1995 using only a negative anti-human globulin (AHG) T-cell IgG crossmatch. The second group was primary cadaveric transplants done concurrently with the flow group (1990 to 1997) using only the AHG T-cell IgG crossmatch.nnnRESULTSnThe long-term (7 year) graft survival rate of flow crossmatch-selected regraft recipients (68%; n= 106) was significantly improved over that of regraft recipients who were selected for transplantation by only the AHG crossmatch technique (45%; n=174; log-rank=0.001; censored for patients dying with a functioning graft). Graft outcome for the flow cross-matched regraft recipients was not significantly different from that of primary cadaveric patients (72%; n=889; log-rank=0.2; censored for patients dying with a functioning graft). Finally, a positive B-cell IgG flow cytometric crossmatch had no influence on long-term regraft outcome.nnnCONCLUSIONSnThe use of the flow T-cell IgG cross-match as the exclusion criterion for cadaveric renal retransplantation yields an improved long-term graft outcome over that obtained when only the AHG cross-match is used and has improved survival of regraft recipients to the level of our primary cadaveric renal transplant population.

Hemodynamics of the hypogastric arterial circulation

This study was designed to assess the major sources of collateral supply to the hypogastric arterial bed (HGA). Peak systolic HGA and radial arterial pressure were obtained before and after clamping a patent HGA and after additional clamping of the contralateral HGA, the contralateral external iliac artery (EIA), or the ipsilateral EIA both selectively and in combinations. These procedures were performed in 10 patients with aortoiliac (AI) aneurysms or occlusive disease. In seven patients with aneurysms, clamping the contralateral HGA decreased the HGA stump pressure index from 0.57 to 0.49 (p less than 0.05), and clamping only the ipsilateral EIA decreased the stump pressure index to 0.38 (p less than 0.001). In three patients with occlusive disease, clamping the contralateral HGA did not decrease the stump pressure index, clamping both the contralateral HGA and EIA decreased the index from 0.61 to 0.57 (p greater than 0.05), and clamping only the ipsilateral EIA decreased the pressure index to 0.40 (p less than 0.01). These data suggest that branches of the ipsilateral EIA femoral arterial system provide a more significant collateral pathway than the contralateral HGA. These results suggest that it is important to relieve occlusive disease in the ipsilateral EIA femoral arterial system if a patent HGA is ligated or bypassed during AI reconstructions. Conversely, it is especially important to preserve forward perfusion in a patent HGA in a patient with compromised ipsilateral EIA femoral runoff.

Cold ischemia time: An independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft

Background. Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). Methods. We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. Results. By multivariate analysis, a CIT of 15 hr or more (vs.<15 hr) independently increased the risk of the AHG Class I PRA level being ≥20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14;P =0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT<15 hr group (25.9%±33.9; n=24) compared with the CIT≥15 hr group (46.3%±36.5; n=66) (P <0.001). Conclusion. Longer CIT induces a humorally more immunogenic kidney.

Hemodynamics of the inferior mesenteric arterial circulation.

The purpose of this study was to determine the significance of collateral supply from the hypogastric arteries (HGAs) to the inferior mesenteric arterial (IMA) bed. Peak systolic stump IMA and radial arterial pressures were obtained before and after clamping the right HGA, the left HGA, both HGAs, the middle colic artery (MCA) only, or the MCA plus right HGA, MCA plus left HGA, and MCA plus both HGAs in patients with aortoiliac aneurysm or occlusive disease. Six patients (four with aneurysms and two with occlusive disease) had patent IMAs. Five patients (four with aneurysms and one with occlusive disease) had chronically occluded IMAs. In the six patients with patent IMAs, clamping of the HGAs decreased the IMA-stump pressure index (IMA-SPI) from 0.61 +/- 0.20 to 0.56 +/- 0.17, 0.54 +/- 0.17, and 0.54 +/- 0.19, respectively (p greater than 0.05) whereas clamping only the MCA decreased the IMA-SPI from 0.61 +/- 0.20 to 0.32 +/- 0.15 (p less than 0.01). In the five patients with chronically occluded IMAs, clamping of the HGAs decreased the IMA-SPI from 0.60 +/- 0.11 to 0.59 +/- 0.12, 0.58 +/- 0.12, and 0.57 +/- 0.11, respectively (p greater than 0.05), whereas clamping the MCA decreased the IMA-SPI from 0.60 +/- 0.11 to 0.34 +/- 0.04 (p less than 0.01). These data suggest that branches of the superior mesenteric artery provide the major collateral pathway to the IMA bed and that the contribution through branches of the HGAs is insignificant in the acute setting.

Successful transplantation of blood group A2 kidneys into non-A recipients

The ABO subgroup A2 has been reported to be less reactive with the anti-A1 antibody naturally occurring in the serum of group O and B recipients and to occur in approximately 20% of group A individuals. Between March 1986 and February 1987, the Midwest Organ Bank (MOB) in Kansas City, screened all group A renal donors for the A2 subgroup. A total of 190 cadaver-donor kidneys were retrieved during this time, of which 68 were subgroup A1 and 16 were subgroup A2 (incidence of A2 = 19% of As and 8.5% of all donors). Of the subgroup A2 kidneys, 13 were transplanted into 9 group O and 4 group B recipients. One group O recipient received an HLA-identical A2 living-related graft. Recipients were not preselected or modified by splenectomy, plasmapheresis, or other means, and were treated with cyclosporine, steroids—and, in most cases, azathioprine, after transplantation. There was one hyperacute rejection and there were 5 acute cellular rejection episodes, 3 of which were reversed. One additional patient died at 2.5 months with a functioning graft. Including the successful living-related graft, 10 of 14 patients (71%) have functioning grafts, with a follow-up of 5 to 14 months, and a mean creatinine of 1.7 mg/dl. We find that the A2 subgroup represents a small but important minority of A donors, and that transplantation into non-A recipients can generally, but not universally, be safely accomplished. We recommend the screening of A donors for the A2 subgroup in both the cadaver-donor and living-related groups, and suggest that the utilization of A2 donors in non-A patients may contribute to the transplantation of group O and highly sensitized patients—and, in some cases, improve the degree of HLA matching.

The risk of stroke with occlusion of the internal carotid artery

Reports of all cervicocephalic arteriograms (n = 1836) performed at one institution during a 10-year period were reviewed and the patients were classified into three groups according to the indication for arteriography. Group I included all patients with symptoms or findings compatible with occlusive disease of the carotid or vertebral artery (n = 806). Group II included patients with cerebrovascular symptoms unrelated to carotid or vertebral disease (e.g., patients with subarachnoid hemorrhage) (n = 367). Group III consisted of patients with no evidence of cerebrovascular disease (e.g., patients with primary and metastatic brain tumors) (n = 663). One hundred ten atherosclerotic occlusions of the internal carotid artery (ICA) were found in 106 patients in group I. Fifty-one percent of these patients had a history of stroke before arteriography, 24% had transient ischemic attacks (TIAs) or amaurosis fugax (AF), and 12% had nonhemispheric symptoms. Only 13% (1.7% of group I patients) were without symptoms. Ninety-one percent of the strokes and 75% of the TIAs or AF were ipsilateral to the ICA occlusion. Seventy-six percent of patients with stroke and 80% with ipsilateral TIAs or AF vs only 29% of patients without symptoms had contralateral stenosis of 60% diameter reduction or greater (p less than 0.003). No occlusions of the ICA occurred in groups II or III. Three hundred forty-six patients in groups II and III were more than 60 years of age. Assuming either Poisson or binomial distributions, the incidence of silent ICA occlusion in the population at large older than 60 years was estimated at less than 1% (p less than 0.03).

Allogeneic versus semiallogeneic F1 bone marrow transplantation into sublethally irradiated MHC-disparate hosts. Effects on mixed lymphoid chimerism, skin graft tolerance, host survival, and alloreactivity.

In models of tolerance associated with mixed lymphoid chimerism, depletion of Thy 1+ cells from the allogeneic donor inoculum may decrease the level of chimerism achieved and the capacity of donor cells to induce tolerance. To determine whether the apparent role of Thy 1+ cells in the facilitation of bone marrow engraftment and induction of skin graft tolerance is related to alloaggression, the capacity of fully allogeneic C57BL/6J, H-2b BM cells to establish mixed lymphoid chimerism and skin graft tolerance in sublethally irradiated (2.5 Gy x 3) BALB/c, H-2d hosts was compared with that of semi-allogeneic BALB/c x C57BL/6J F1 H-2d/b BM cells which genetically lack the potential for graft-versus-host reactivity against parental recipients. The levels of mixed chimerism observed with allogeneic and semi-allogeneic F1 BM cells were nearly identical: 21.0 +/- 9.7% of spleen cells in H-2b BM-injected and 18.6 +/- 8.8% of spleen cells in H-2d/b BM-injected H-2d hosts were of donor allotype. There was no difference in the fraction of hosts rendered tolerant to C57BL/6J, H-2b skin grafts by H-2b vs. H-2d/b BM at either excess (94% vs. 92% tolerant) or threshold (37% vs. 40% tolerant) numbers of donor cells. Spleen cells from both types of mixed chimeras failed to respond to donor antigens in MLR. Both H-2b and H-2d/b BM-injected H-2d hosts rejected third party C3H/HeJ, H-2k skin grafts and responded to third party stimulators in MLR. Although these nonspecific allo-immune responses were not as strong as the responses of normal animals, they were suppressed to an equivalent degree in both types of chimeras. Graft-versus-host disease, if present in irradiated H-2b BM-injected hosts, did not significantly affect survival compared with survival of irradiated H-2d/b BM-injected animals. These results suggest that the tolerizing capacity of allogeneic BM does not depend upon GVHD and that allogeneic and semi-allogeneic BM establish mixed lymphoid chimerism and induce skin graft tolerance by similar mechanisms across a complete MHC disparity in sublethally irradiated adult hosts.

Influence of the Rh (D) blood group system on graft survival in renal transplantation.

BACKGROUNDnThe Rh (D) blood group system has not traditionally been considered to be a clinically relevant histocompatibility barrier in transplantation since conflicting results of its clinical importance have been reported.nnnMETHODSnWe analyzed 786 consecutive primary cadaveric renal transplants performed by transplant centers in our Organ Procurement Organization (OPO) between 1990 and 1997. We also analyzed United Network for Organ Sharing (UNOS) data on 26,469 kidney transplants done from April 1994 to June 1996.nnnRESULTSnMultivariate analysis revealed that Rh identity between the recipient and donor was significantly related to better graft outcome (risk ratio, 0.43; 95% confidence interval, 0.30 to 0.61; P=0.0001). Multivariate analysis of the UNOS data revealed that the Rh -/- group may have a positive influence on graft survival with a risk ratio of 0.43 (P=0.14).nnnCONCLUSIONnMultivariate analysis of primary cadaveric renal allografts performed within the Midwest Organ Bank OPO indicates that Rh (D) is a clinically relevant histocompatibility barrier that influences 7-year graft survival.