Charles E. Morrow

Surgical resection for metastatic neoplasms of the lung: Experience at the university of minnesota hospitals

Pulmonary resection for metastatic disease in 167 patients undergoing 207 thoracotomies resulted in a cumulative survival rate of 29% at five years and 20% at 10 years, with an operative mortality of 0.6%. The most favorable prognosis was associated with testicular and renal cell carcinomas and sarcomas. Less favorable tumors were malignant melanoma, carcinoma of the colon and rectum, and cervix uteri. A significant factor influencing survival was duration of disease‐free interval with a 50% five‐year survival rate in patients whose primary tumor was treated over five years ago. Patients with multiple pulmonary metastases had a five‐year survival rate of 27% vs. 22% of patients with solitary metastases. Of 23 patients with tumor extending to the chest wall, diaphragm, or pleura, only two survived five years. Of 26 patients with mediastinal involvement none survived two years.

Predictive value of thallium stress testing for coronary and cardiovascular events in uremic diabetic patients before renal transplantation

Coronary artery disease and the ability of noninvasive exercise perfusion imaging with thallium-201 to predict future coronary and cardiovascular events was prospectively evaluated in a group of 85 insulin-dependent diabetic renal transplantation candidates. Sixty patients received renal allografts (36 living related donors, 24 cadaver donors) after a thallium stress test; the actuarial 2 year patient survival rate after transplantation was 84 percent. Twenty-five patients remained on dialysis, and the 2 year actuarial survival rate from onset of dialysis was 41 percent, significantly lower than the actuarial survival rate of transplanted patients (p less than 0.01). Thirteen transplanted patients had positive thallium stress test results, and 6 (46 percent) had cardiovascular events (two fatal). In contrast, of 47 transplant patients with negative thallium stress test results, only 13 (28 percent) had cardiovascular events (four fatal). Five patients treated by hemodialysis only had positive test results and three (60 percent) had cardiovascular events (two fatal), whereas of 20 hemodialysis patients with negative test results, 9 (45 percent) suffered cardiovascular events (four fatal). In this study, cardiovascular events included arrhythmia, stroke, and pulmonary embolism. Within the total group, 4 of 18 patients (22 percent) with a positive test result (22 percent) had a fatal myocardial infarction, whereas only 3 of 67 patients (4 percent) with a negative result had a fatal myocardial infarction (p less than 0.05). In comparison, 24 of 85 patients had a history or electrocardiographic evidence of preexisting cardiovascular disease, and 13 (54 percent) had subsequent cardiovascular events (5 of 11 patients with positive test results and 8 of 13 patients with negative results). In summary, renal transplant candidates with positive thallium stress test results appear to be at increased risk compared with those with negative results for the development of fatal myocardial infarction, but thallium stress testing is no more predictive for future coronary and cardiovascular events than is a history or an abnormal electrocardiogram.

Improved patient and primary renal allograft survival in uremic diabetic recipients.

From January 1968 to December 1981, 470 uremic diabetic patients received primary renal allografts at the University of Minnesota. Until 1979, the patient and graft survival rates were less good in diabetic than in nondiabetic recipients. Since 1979, the results in diabetics have been at least equal to those achieved in nondiabetic patients. Two-year actuarial patient and graft survival rates in diabetic renal allograft recipients were, respectively, 71 and 66% from 1968 to 1976 (n = 156), 78 and 64% from 1976 to 1979 (n = 187), and 88 and 82% from 1979 to 1981 (n = 127). Improved survival rates were seen in all donor source and recipient age categories. For comparison, the 2-year patient and graft survival rates in nondiabetic renal allograft recipients who received transplants between 1979 and 1981 (n = 162) were 92 and 79%. Changes associated with improved survival rates included performance of pretransplant splenectomy on all patients except those receiving grafts from HLA-identical siblings, deliberate transfusions of blood from ≥5 random donors at least 1 month before transplantation, intensive insulin therapy for diabetic management post-transplant, and less vigorous treatment of repetitive rejection episodes. The current results show that diabetic recipients are no longer at higher risk than nondiabetics for graft or patient loss, at least during the first 2 years after transplantation.

Cyclosporin A for Immunosuppression: Observations in Rat Heart, Pancreas, and Islet Allograft Models and in Human Renal and Pancreas Transplantation

Cyclosporin A (CsA) is a unique immunosuppressive cyclic polypeptide that is currently being used, either alone or in combination with low-dose prednisone, to treat recipients of renal or pancreas allografts in clinical trials. CsA is very effective in preventing rejection of heart and renal allografts in rodents, but in nontoxic doses does not consistently prevent rejection of pancreas and islet allografts. Therefore, we tested low-dose CsA in various combinations with low-dose prednisone, azathioprine, or total lymphoid irradiation in rat heart, pancreas, and islet allograft models. Several combinations are synergistic and when administered continuously can indefinitely prevent rejection of heart allografts, but only delay rejection of pancreatic allografts, transplanted across a major histocompatibility barrier. CsA by itself prolonged the survival of islet allografts transplanted across a minor, but not a major, histocompatibility barrier. CsA and azathioprine had a synergistic effect in the minor histocompatibility barrler islet transplant model, but, in the nontoxic combinations tested, could not prevent rejection indefinitely. A randomized prospective trial comparing standard immunosuppressive therapy (ALG, prednisone, and azathioprine), with CsA and low-dose prednisone for clinical renal allotransplantation is ongoing at the University of Minnesota. Current actuarial 1-yr graft survival is 93% for CsA-treated patients (N = 48) and 81% for conventionally treated patients (N = 52). Patient survival is 98% for CsA and 100% for conventionally treated patients. A pilot trial of CsA in the clinical pancreas transplant program at the University of Minnesota is also underway. Since 1978, 46 pancreas transplants have been performed in 43 patients. Of 30 technically successful pancreatic allografts, 5 of 12 recipients treated with conventional immunosuppression and 6 of 18 recipients treated with CsA currently have functioning grafts and are insulin independent between 1 and 44 months after transplantation. The results of metabolic studies are similar in conventional and CsA-treated patients with functioning pancreas grafts. Since pancreas grafts may fail for reasons other than rejection, further observations are needed to ascertain the role of CsA in clinical pancreas transplantation.

Lack of donor-specific tolerance in mice with established anti-Ia-treated islet allografts.

Pancreatic islet allografts pretreated in vitro with monoclonal Ia antibody and transplanted beneath the renal capsule result in normoglycemia beyond 100 days in streptozotocin-induced diabetic recipient mice that differ only at H-2 K, H-2 K + I, or H-2 K + I + D from the donors. Mice with established islet allografts are not tolerant of donor-specific skin or islet antigens, but rather reject donor skin grafts in an accelerated fashion. Established anti-Ia antibody pretreated islet allografts continue to express target antigens and remain susceptible to rejection after challenge with donor skin grafts.

Giant duodenal ulcer

Abstract Benign giant duodenal ulcer appears to be a unique type of generalized peptic ulcer disease. Massive hemorrhage, perforation, and obstruction are frequent complications. The disorder is best diagnosed endoscopically and treated with one of the standard acid-reducing procedures.

Cold storage preservation of islet and pancreas grafts as assessed by in vivo function after transplantation to diabetic hosts

Abstract The major goal of hypothermic (4–8 °C) preservation of intact pancreases or isolated islets will be to provide sufficient time for HLA typing, cross matching, selection, and preparation of recipients—logistical efforts requiring 12–72 hr for clinical kidney transplantation, usually in vitro function of islets after cold storage, but the critical test of viability—permanent restoration of normoglycemia after transplantation to diabetic recipients—has been tested in only a few experiments. Reversal of hyperglycemia by syngeneic or autogenic transplants in diabetic animals has been achieved after CS of dispersed pancreatic tissue from neonatal rats in GIB media for ⩽ 146 hr, adult dogs in TCM 199 for ⩽24 hr, and adult DL-ethionine-treated rats in RPMI 1640 for ⩽72 hr. In the neonatal rat donor model, intravenous glucose tolerance test (IVGTT) results were similar in recipients of fresh or stored islets; in the dog model, IVGTT test results were variable, but generally inferior in recipients of stored as compared to fresh islets; in the adult rat donor model, recipients of ⩽24-hr coldstorage islets had insulin and IVGTT K values similar to those of recipients of fresh islets, but the success rate progressively declined for CS times >24 hr. Various agents were added to the media, but the need or the optimal concentrations were not critically determined by using different recipes for different groups of recipients. Cold storage of intact pancreas autografts has been tested in dogs; simple electrolyte solutions are satisfactory for 24 hr, but only a silica gel-filtered plasma-based solution has been reliable for 48 hr. Pulsatile machine perfusion (PMP) of canine pancreas grafts for 24 hr has had a success rate similar to CS in some experiments and lower in others. PMP has been almost totally unreliable for >24 hr. Further refinements are needed if preservation of islets for >24 hr and pancreases for >48 hr are to be consistently successful. If current experimental techniques are effective for human islets or pancreases, however, these times are sufficient to complete the logistical maneuvers required before transplantation.

The effect of mismatching for HLA-DR in recipients of renal allografts sharing one HLA-ABC haplotype with related donors

The effects of mismatching for DR antigens on renal allograft survival rates have largely been restricted to analyses of cadaver transplant results. Analyses of HLA matching in recipients of transplants from related donors have focused on the number of haplotypes shared between the recipients without regard to DR, or on the total number of HLA antigens mismatched, or on the degree of MLC responsiveness of the recipient to the donor. Most related donor-recipient pairs sharing only one HLA haplotype will be mismatched for DR at the other haplotype, but because there are a limited number of DR alleles, sharing of DR antigens on the mismatched haplotypes occurs relatively frequently. To determine the influence of mismatching for DR on the fate of renal allografts from related donors, we analyzed the results of 172 kidney transplants from related donors who shared one HLA-ABC haplotype with the recipient. There were 156 primary grafts and 16 retransplants; 147 donor-recipient pairs were satisfactory typed for DR antigens. Because genotyping was not usually done, we performed two analyses under two different assumptions. The first assumption was that individuals expressing less than or equal to 1 DR antigen had null antigens, or were homozygous for DR; the alternative assumption was that blanks were true antigens and individuals with blanks were heterozygous. The first assumption is more likely to be correct, and is the assumption used in most analyses of the effect of DR antigen mismatches on the results of cadaveric transplantation. Under the first assumption, of the 147 related donor-recipient pairs in whom DR typing was satisfactory, 33% were mismatched for 0, 64% for 1, and 3% for 2 DR antigens. The one-year absolute graft survival rates in recipients of kidneys from donors with 0 mismatches for DR was 92% (n = 49); in those with one mismatch for DR it was 82% (n = 94); and from those with two mismatches it was 50% (n = 4). The one-year graft survival rate in 25 donor-recipient pairs in which one or both members could not be satisfactorily DR typed was 76%. Differences in graft survival rates between the 0 and 1 and the 1 and 2 DR-mismatched groups were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal allograft survival in patients with positive B cell crossmatch to their donor.

B cell crossmatches were performed at cold (4 C) and warm (22 C and 37 C) temperatures on 193 renal allograft recipients with negative T cell crossmatches to their donor; 152 of the patients were also tested for autoantibody to autologous B cells. Fifty-six (29%) had a positive B cell crossmatch (21 cold, 35 warm); 14 were autoantibody positive, 23 autoantibody negative, and 19 were not tested for autoantibody. There were no differences in HLA-A, B, C, or DR antigen disparity between the B cell positive (14, 0 DR mismatch; 25,1 DR mismatch; 9, 0 DR mismatch) and the B cell negative group (40, 0 DR mismatch; 57,1 DR mismatch; 13, 2 DR mismatch). Similarly, age, diabetic status, and number and type of pretransplant blood transfusions were comparable between B cell positive and negative groups. Although there were no hyperacute rejections, 2-year actuarial graft survival was significantly lower in the B cell positive group, regardless of donor source, graft number, or temperature of reaction. Patients with a positive B cell crossmatch, presumably due to demonstrable autoantibody, may have better graft survival rates than patients with a positive B cell crossmatch and no autoantibody.

The postoperative course and quantitative aspects of rat islet and segmental pancreas isografts.

Duct-ligated segmental pancreas transplants with systemic venous drainage were compared to intrahepatic islet grafts for beta-cell mass (proportional to tissue insulin content) and function in diabetic Lewis rats. Rats were serially killed to measure insulin in the segmental pancreas grafts and in the liver of the islet recipients. Segmental pancreas weight was maximum and insulin concentration and content lowest (P less than 0.05) on Day 3 when acute inflammation was present. At 21 days, there was no inflammation, and graft weight had decreased, but not to Day 0 level because of normal growth; insulin concentration was similar on Days 21 and 0. At 3 months, moderate fibrosis of the graft was present, but both total insulin and insulin concentration had increased (P less than 0.05). In the recipients of islet grafts, total insulin in the liver on Day 1 was only 43% of that contained in the original islet preparation, but by 3 months the insulin content in the liver had increased to that transplanted. IVGTT K values were similar in normal rats (-3.5 +/- 0.7%) and in recipients of segmental pancreas (-4.5 +/- 1.6%) and islet (-4.0 +/- 1.5%) grafts at 3 months post transplant. Acute segmental graft pancreatitis resolved, followed by an increase in beta-cell mass. Islet cell damage during transplantation is either reversible or residual viable islets proliferate, and provide metabolic control equivalent to segmental pancreas transplants, even though the final beta-cell mass is less.