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Orthotopic liver transplantation has become an accepted form of therapy for advanced liver disease. Over a 44-month period, we performed 27 liver transplants in 25 pediatric recipients, including 14 infants (mean age, 7.2 months; mean weight, 5.9 kg) and 11 children (mean age, 9.0 years; mean weight, 34.8 kg). Indications for transplantation were biliary atresia (16), tyrosinemia (3), chronic hepatitis with cirrhosis (2), fulminant hepatic failure (2), and one patient each with Wilson's disease and primary hepatoma. Eighteen patients (72%) had undergone a previous laparotomy, including 19 Kasai procedures in 13 patients with biliary atresia. The average time on the waiting list was 26.8 days (range, 1 to 60), and no patients died while awaiting transplantation. Mean preservation time was 6.9 hours (range, 2 to 13.5), employing cold storage with Collin's solution (16), or more recently, UW solution (11). Urgent liver transplantation was performed in seven cases (25.9%), although at present, we perform liver transplantation as a scheduled semielective procedure with extended preservation times in stable patients. The recipient hepatectomy and orthotopic liver transplantation were performed by standard techniques, with venous bypass used in three cases. Biliary reconstruction was performed with a Roux limb in 16 and via choledochocholedochostomy in ten cases, while arterial reconstruction was end-to-end hepatic artery in 21, and aorto-aortic anastomosis in the remaining six. Two hepatic artery thromboses (7.4%) and two biliary complications (7.4%) occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperbaric oxygen (95%, O2, 25 psi, 48-hr culture) resulted in prolonged thyroid allograft (B10.A) survival in both primary and sensitized recipients (B10.AQR). Recipients receiving noncultured thyroid allografts uniformly rejected the graft by 35 days, while 100% of cultured grafts survived. Noncultured thyroid grafts transplanted to skin-graft-primed recipients were rejected by 21 days. In contrast, 86% of cultured grafts transplanted to primed recipients were still functioning at 35 days. Donor spleen cells or peritoneal exudate cells transferred at the time of thyroid transplant were unable to stimulate cultured allograft rejection. Allografts histologically examined 35 days after transplant revealed, in some grafts, focal cellular infiltrates adjacent to normal, uninfiltrated tissue. To determine if tissue modification was the mechanism of prolonged allograft survival, hyperbaric-oxygen-cultured thyroids were examined for MHC class I expression. Immunoperoxidase staining with monoclonal antibody to MHC class I molecules showed that cultured thyroids were unstained in contrast to fresh thyroids that were uniformly stained. Cytotoxic T lymphocytes specific for H-2Kk administered 10 days following thyroid transplant were unable to eliminate cultured grafts (80% survival) but completely destroyed noncultured grafts. These results indicate that hyperbaric oxygen culture altered MHC class I expression such that it was no longer detectable by monoclonal antibody or cytotoxic T lymphocytes. Thus, the mechanism, explaining graft prolongation after hyperbaric culture in addition to passenger cell depletion, may be alteration of graft antigenicity such that the graft is no longer perceived as foreign.

To obtain sufficient quantities of human fetal pancreatic tissue (HFP) for transplantation, long-term storage of the tissue must be achieved. The functional viability of HFP after cryopreservation by stepwise addition of dimethyl sulfoxide was determined. Human fetal pancreas explants (1-2 mm3; gestational age 16-21 wk) were prepared and slowly cooled (0.25 degrees C/min) to -40 degrees C before placement in liquid nitrogen. After rapid thaw (37 degrees C) and overnight culture, insulin release in response to high glucose and theophylline challenge determined in vitro functional viability. No difference was found between the responses of fresh and cryopreserved tissue (fresh 29.2 +/- 3.0 ng/mg tissue, cryopreserved 29.9 +/- 3.3 ng/mg tissue; P greater than .1). Diabetic BALB/c nu/nu mice transplanted with cryopreserved HFP returned to normoglycemia in 11 +/- 2 wk (range 8-15 wk). Oral glucose tolerance tests indicated in vivo serum glucose control equivalent to or better than that of nondiabetic control mice (peak serum glucose of nondiabetic mice 164 +/- 66 mg/dl, of cryopreserved grafted mice 180 +/- 67 mg/dl; P greater than .8). In vitro insulin release of cryopreserved grafted tissue demonstrated that the tissue had differentiated and matured and was now capable of responding to high-glucose challenge (39.3 +/- 11.5 ng insulin released/mg tissue). The results described herein are the first demonstration that cryopreserved HFP maintains the in vivo capacity to differentiate and mature and the capacity to reverse diabetes in an animal system.

The data presented in this chapter demonstrate that acceptable short-term results can now be achieved for patients receiving a pancreas transplant. We feel that urinary drainage and the use of a whole pancreas with a duodenal segment currently represent the most optimal technical approach. Immunosuppressive therapy using the quadruple induction protocol will prevent early rejection episodes in the majority of patients. Once rejection is diagnosed, one should not hesitate to institute immediate antirejection treatment with OKT3 monoclonal antibody. In our most recent series of 24 combined kidney and pancreas transplants an extremely encouraging outcome can be reported. Of the 24 patients who received a combined cadaver kidney and pancreatic allograft within the last 2 years, 23 are alive and well. Twenty-three also have good-functioning kidneys, of which 21 have a functioning kidney and pancreatic allograft. Based on these results, which will undoubtedly be duplicated in the very near future by a number of other centers, we believe that pancreas transplantation has now emerged into a therapeutic and effective procedure.

Recent advances in the understanding of mechanisms of graft rejection and in the prevention and treatment of rejection are discussed. The clinical success of kidney, liver, heart, and pancreas transplants is analyzed.

Recent reports demonstrate that culture of thyroid allografts before transplantation results in prolonged and sometimes indefinite survival. The loss of passenger leukocytes during organ culture was discussed as a possible reason for these findings. Recent data from a genetically defined system in the mouse demonstrated that passenger leukocytes play an important role in providing a helper stimulus which potentiates the generation of cytotoxic T cells to serologically defined determinants. To ascertain whether this mechanism also is involved in a xenogeneic system, cultured Wistar thyroids were transplanted to DBA/2 mice. The experimental system used was described first by Lafferty and co-workers. Thyroid function was determined by 125-iodine uptake of the graft and by histology. Fresh Wistar thyroids were rejected after a short period of good function on the sixth day after transplantation. Culturing for 10 days resulted in a prolonged graft function up to the fifteenth day. However, if the thyroids were kept in culture for 27 days, no functional signs of rejection could be detected on the twenty-fifth day after transplantation by iodine uptake. The iodine uptake ratio was 47.1 (control group on day 6 was 2.4). Injection of 10(5) fresh donor cells at the time of transplantation reversed the effect of long-term organ culture.

Tolerance was induced against cytotoxic target determinants coded for by genes of the I region. Neonatal recipients were immunized with high doses of cells from an I region incompatible donor. Nonreactivity in adult life did not reflect extensive donor cell chimerism, since the great majority of cells in spleens of animals rendered tolerant were of host phenotype. Although specific nonresponsiveness in CML could be induced by these protocols, the MLC proliferative response was in most cases still present alghough very much decreased. In only a very occasional animal was complete nonreactivity in MLC seen. The nonresponse in CML was paralleled by acceptance of thyroid allografts as measured by radioactive iodine incorporation and morphological studies.

Since February 1986, 23 patients have received Orthoclone OKT3 treatment at our transplant center for renal allograft rejection resistant to steroids and antilymphocyte globulin (ALG). They have been followed for at least 4 months as of this study time (range: 4-15 months). We report here our experience with OKT3, including five late responders--as late as 116 days after OKT3 treatment. Overall rejection was reversed in 19/23 (83%). Rejection was controlled in 95% of primary and 50% of nonprimary transplants; 89% of the male and 80% of the female patients were treated successfully; 94% of the cadaver-donor and 80% of the living-donor transplants responded successfully. The one-year rerejection rate after OKT3 was 50%, and 38% of rerejection episodes were treated successfully. Time (days) required to reverse the episodes of acute graft rejection after the start of OKT3 is plotted, and it shows a distinctive bimodal distribution: first, early responders with a mean +/- SD of 12 +/- 5 days (range: 4-20 days) and second, late responders with a mean +/- SD of 58 +/- 31 days (range: 30-116 days). We conclude that OKT3 is very effective in treating steroid- and ALG-resistant acute rejection episodes, and also that it is important to be aware of the potential late response to OKT3 antirejection therapy and recommend delaying transplant nephrectomy or immunosuppressive withdrawal for as long as possible (probably up to 4 months) for patients who have received OKT3 treatment.

The data presented demonstrate that combined kidney-pancreas grafting can be performed with excellent patient and graft survival. Current long-term studies at our center investigating the effect of pancreas transplantation on diabetic retinopathy and comprehensive quality of life assessment will address the question of whether pancreas transplantation can be considered an effective and therapeutic procedure.

1. Quadruple immunosuppression yields excellent early renal allograft survival in primary renal transplant recipients when compared with non-primary renal transplant recipients. Although significant, the difference between primary and nonprimary recipients at 5 years has narrowed considerably (8%). 2. No beneficial effect of HLA or DR matching was noted in this study in primary transplant recipients. However, a trend toward improved graft survival was noted when patients with greater than or equal to 3 antigens matched or less than 3 antigens mismatched were compared to their counterparts. Further analysis of variables related to graft loss is required before statements regarding this trend can be made. 3. Significantly better results in nonprimary renal transplantation continues to be seen in DR matched recipients. Additionally, the use of OKT3 rather than ALG in DR matched recipients has resulted in a 92.3% 3-year allograft survival despite over half of these patients being highly sensitized. 4. Further follow-up of 2 high-risk groups of patients (diabetics and elderly patients) revealed significant decreases in patient survival at 5 years. This difference was not apparent in our earlier results (3-year follow-up) published in Clinical Transplants 1987. Despite this difference, we believe renal transplantation should continue to be offered to diabetic and elderly patients without other contraindications to transplantation. 5. The availability of the monoclonal antibody OKT3 during the CsA era has resulted in a trend toward improved patient and graft survival when compared with patients in the CsA pre-OKT3 era. This trend toward improved survival is also seen in the high-risk diabetic recipients.

There is much controversy as to whether the analysis of cyclosporine (CsA) should be performed by radioimmunoassay (RIA) or high-performance liquid chromatography (HPLC), and whether the specimen should be serum or whole blood. Whole-blood specimens present specific advantages, but the presence of hemoglobin (Hgb) and other endogenous compounds can produce major errors in the RIA by "quenching" the analytical signal or by interfering with the antigen-antibody binding in the assay. We have developed a simple pretreatment step to remove the Hgb and other proteins responsible for this error. Red cells in whole blood are hemolyzed with a mixture of acetonitrile and water, the protein precipitated with acetonitrile, and the supernatant assayed by RIA. In a controlled study in which CsA concentration was kept constant and the Hgb concentration varied, the errors in measurement were directly proportional (r = 0.999) to the Hgb concentration. CsA values were spuriously deflated or inflated by 22.7 micrograms/L for each gram per 100 milliliters that the Hgb deviated from the 9.2 g/100 ml Hgb in the CsA calibration standards. In a similar study in which patient samples (n = 57) were assayed with and without pretreatment, the fractional error induced by Hgb was compounded in some patients by additional interferences that also appear to be removed by sample pretreatment. Without the pretreatment, CsA values could be in error by 33% when the Hgb varied 4 g/100 ml, thus providing potentially misleading results to the clinician. An I-125-labeled CsA tracer (purported not to be affected by the "quenching" interference of Hgb) produced consistently higher results when it was substituted for the tritiated CsA tracer contained in the Sandoz kit. In summary, sample pretreatment appears to be the simplest method of effectively removing endogenous interferences and minimizing erroneous results from whole blood submitted to the Sandoz RIA for CsA analysis.

Advanced age has been a relative contraindication to kidney transplantation because of the likelihood of increased morbidity and mortality in the geriatric population. However, the introduction of cyclosporine has improved renal allograft survival rates dramatically, and higher-risk patients are now being successfully transplanted. With the introduction of cyclosporine in 1983, we have performed 36 cadaveric renal transplants in 34 recipients 60 years of age or older, including 34 primary and 2 retransplants. Most of the patients (88%) were on dialysis prior to transplantation and 29% had ASCVD. Three-year actuarial patient and allograft survival are 91% and 74%, respectively. Surgical complications were infrequent, and postoperative rejection episodes were less frequent than in younger patients but were more likely to lead to graft loss. Medical complications, especially infection, were common after transplantation but easily managed. Cadaveric renal transplantation with cyclosporine immunosuppression is a safe and effective therapeutic modality that is no longer contraindicated in elderly patients.

In many transplantation systems, the strength of the allograft response correlates with the magnitude of the in vitro mixed lymphocyte culture (MLC) reaction. Because this reaction requires 5 days, it has not been applicable to the prospective matching of cadaver renal allograft donors to the best available potential recipient. The pool primed lymphocyte test (pPLT) is a modification of the standard MLC assay; it measures primed lymphocyte responses after 24 to 30 hr of culture and these results correlate with data obtained after 5 days in the MLC. In this report, we analyze pPLT data from 69 recipients of cadaver renal transplants. No correlation between pPLT response and graft survival was found. Multiple factors were identified that influenced the magnitude of the pPLT response for these patients. Many uremic patients were unable to give any pPLT response, and some cadaver spleen cells were nonstimulatory. Nevertheless, the strength of pPLT responses by control individuals who did respond showed a positive correlation with their MLC responses. Thus, we feel the concept of using pPLT for prospective matching is sound; however, a number of technical variables make it impractical at present for routine transplant matching.

A major dilemma in pancreas transplantation is the lack of reliable methods for the early detection of allograft rejection. Over a 26-mo period, 70 rejection episodes occurred in 36 patients (13 isolated-pancreas, 23 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 300 radionuclide pancreas examinations were performed (mean 8.3/patient) utilizing 99mTc-labeled DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft (technetium index, TI). Rejection episodes were defined as isolated pancreas, isolated kidney, or combined pancreas-kidney. Mean urinary amylase (UA) levels and TI during normal allograft function were 30,256 U/L and 0.57%, respectively, whereas levels heralding rejection were 6873 U/L and 0.39% (P less than .05). The treatment of rejection based on kidney dysfunction or combined pancreas-kidney dysfunction resulted in significantly higher graft salvage and a lower incidence of hyperglycemia compared with isolated-pancreas-allograft rejection. After therapy, a TI greater than 0.3% was associated with 95.9% graft survival, whereas levels less than 0.3% resulted in a 72.7% rate of graft loss (P less than .001). Similarly, pancreas allografts with a UA greater than 10,000 U/L had 92.2% functional survival, whereas levels less than 10,000 U/L resulted in a 53.3% rate of graft loss (P less than 0.001). Overall, reversal of rejection occurred in 80% of cases, with 10 pancreas and 2 kidney allografts lost due to rejection. Monitoring pancreas-allograft function by UA, TI, and renal function in simultaneous transplants allows for the timely diagnosis and successful treatment of pancreas-allograft rejection.

A patient (HLA-A2,3; B35,60) with end-stage renal disease and a high level of pretransfusion (t0) anti-HLA cytotoxic antibodies (60% positive to a random panel), but lacking cytotoxic antibodies against her HLA haploidentical sister (HLA-A2,3; B35,44), received 3 donor-specific transfusions (DST) from the latter: 200 cc fresh whole blood at biweekly intervals, while being treated with azathioprine (AZA, 1 mg/kg/day). Her serum remained negative for antidonor antibodies both by standard cytotoxicity assay and by immunofluorescence flow cytometry after DST + AZA treatment, and she experienced no acute rejection episodes following donor kidney transplantation. Microcytotoxicity inhibition tests were performed using standard HLA-typing sera as a source of Ab-1, and pre- and posttransfusion sera were added to serial dilutions of Ab-1 to test for the presence of Ab-2 (antiidiotype) to donor HLA class I specificities. Although both pre- and posttransfusion sera inhibited cytotoxicity toward HLA-A2 antigens expressed on recipient target cells, only posttransfusion serum was found to inhibit cytotoxicity against the HLA-A2 antigens expressed on donor target cells. Absorption of soluble HLA class I antigens present in pre- or posttransfusion sera removed the inhibition of cytotoxicity toward recipient HLA-A2 but did not affect the inhibition of cytotoxicity toward donor HLA-A2 by posttransfusion sera. The F(ab')2 fragment of the IgG fraction of posttransfusion sera contained the inhibitory activity, suggesting induction of Ab-2 toward idiotypes specific for donor HLA-A2 antigens encoded on the unshared haplotype.

With advances in clinical immunosuppression, results in organ transplantation continue to improve. During a 52-month period, 507 cadaver renal transplants were performed, including 435 primary and 72 nonprimary transplants. All patients were managed with quadruple immunosuppression (prednisone, azathioprine, sequential MALG and cyclosporine). Our experience is divided into pre-OKT3 (n = 228) and OKT3 (n = 279) eras. All kidneys were harvested locally and preserved with pulsatile machine perfusion. The mean duration of preservation was 30.1 hours, with an organ utilization rate of 98.1%. The preservation-related dialysis rate was 13.6%, and primary nonfunction occurred in 8 kidneys (1.6%). Actuarial patient survival in primary and secondary transplant recipients was 90% at 3 years. Overall primary graft survival was 81.6% and nonprimary graft survival, 61.1%. However, the current OKT3 era is characterized by improved patient survival (98% vs 90%, p = 0.001) and primary graft survival (91% vs 80%, p = 0.002) at 1 year when compared with the previous era. Forty-nine patients have received OKT3 therapy, with 31 grafts (63.3%) successfully rescued. Cadaveric renal transplantation with machine preservation, quadruple therapy, and OKT3 rescue is associated with excellent early graft function, reduced acute rejection, and improved patient and allograft survival, even in high-risk recipients.

With refinements in technical aspects of whole organ pancreas transplantation, allograft rejection is currently the major cause of graft failure. The monoclonal antibody OKT3 has emerged as a highly effective antirejection therapy in renal and hepatic allograft recipients, but its efficacy in pancreas transplantation remains to be determined. During a 12-month period, 28 vascularized whole organ pancreas transplants were performed with pancreatico-cystostomy. Sixteen episodes of allograft rejection were treated with monoclonal antibody OKT3. Indications for OKT3 use included steroid- or antilymphocyte globulin (ALG)-resistant allograft rejection in isolated pancreas (n = 8) or simultaneous kidney-pancreas (n = 8) transplants. A total of 34 rejection episodes occurred in the 16 patients (mean, 2.1; range, one to five). The diagnosis of rejection was based on clinical criteria, a reduction in urinary amylase clearance, radionuclide scanning, hyperglycemia, or associated renal allograft dysfunction in combined engraftments. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and prophylactic ALG. OKT3 was administered for a full 14-day course concomitant with low-dose steroids, azathioprine, and cyclosporine. The mean age of the patient population was 32.1 years (range 24 to 39) with a mean duration of insulin-dependent diabetes mellitus (IDDM) of 20.9 years. Monoclonal antibody therapy was instituted in two clinical settings: early rejection (within 3 months of transplant, n = 10); and late rejection (after 3 months, n = 6). OKT3 successfully reversed allograft rejection in ten (62.5%) cases, including six early (60%) and four late (66.7%) episodes. In isolated pancreas transplants, OKT3 therapy reversed pancreas allograft rejection in only two patients (25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Graft availability remains the major limitation to organ transplantation. Belzer-UW solution has been used for multiple organ procurement in 20 consecutive donors. Belzer-UW solution was used for both aortic in situ flush and ex vivo cold storage. From 20 donors, a total of 20 pancreatic grafts, 20 livers, 39 kidneys, and 10 hearts were procured. Mean preservation time was 14.2 hours for the pancreas, 16 hours for the kidney transplanted with the pancreas, 13.8 hours for the liver, and 29.9 hours for the isolated kidneys, which were machine perfused. Graft survival of the organs transplanted at the University of Wisconsin was 100% for kidney and pancreas, 93.3% for the isolated kidney, and 78.5% for the liver. When the organs referred to other centers were included, 84 of 89 procured organs were functioning at 1 month. It is concluded that multiorgan procurement with Belzer-UW solution yields excellent graft function for all abdominal organs.

The present data show that biological and synthetic inducers of interferon are able to reduce the growth of a transplantable malignant melanoma in the Syrian hamster. The advantage of the biological inducer H-MP are that it is not toxic for humans and that a high titer of interferon can be maintained over a long period of time.

It is possible to register the rejection time of allografts quantitatively by the method of thermography. Results are congruent with a micromorphological state, but only partially with the macroscopic pictures.

Organ culture of xenogeneic thyroids leads to a prolonged survival time. This effect can be reversed when donor-specific cells are injected at the time of transplantation. The results of this experiment disprove the assumption that target antigens are modulated or masked by organ culture.

The present data show that SPN have a striking influence on thymus dependent T cells. The enhancing effect of gvh reactions on antibody formation against thymus dependent antigens give a good explanation for the antitumor effects of this substance.

The essence of the clonal deletion model of the donor-specific transfusion (DST) effect is synergy between DST-priming and post-transplant immunosuppression. Using a sensitive kinetics assay of the mixed lymphocyte culture (MLC) response to donor and third-party stimulators, we compared the responses of controls (non-transfused healthy individuals) with those of patients who either had no rejection episodes in the first week posttransplant (group 1) or who had DST-type (greater than 3d onset) rejection episodes (group 2). We found that group 2 patients had normal or above-normal MLC responses after DST plus azathioprine (AZA) pretransplant treatment, but had a reduced/delayed posttransplant anti-donor MLC following reversal of early rejections (P = .05 compared with controls). Group 1 patients had a nonspecifically reduced MLC after DST + AZA treatment (P less than .02 compared with controls), while posttransplant MLC responses showed a return to normal (pretransfusion) levels. These data suggest a synergy of DST with immunosuppressive drug that induced MLC hyporesponsiveness, but only in patients who received anti-lymphoblast globulin or a sustained high dose immunosuppression in the early posttransplant period.

Our purpose was to identify humoral factors induced by donor-specific transfusion (DST) plus azathioprine (AZA) that correlate with improved renal allograft survival (92% at 3-34 months posttransplantation) in a group of 24 DST patients. Plasma was obtained from patients prior to AZA and DST (to), 2-6 weeks after the final transfusion but immediately prior to transplant (tt), and 6-12 weeks after renal transplantation and initiation of standard posttransplant immunosuppressive therapy (tx). Plasma was screened for inhibitory or stimulatory activity in a 6-day primary MLC, with either patient to PBL or unrelated control PBL used as responders. Patient tx plasma was uniformly inhibitory of MLC responses to donor and to pooled third-party stimulators, regardless of the source of responding cells. The tx plasma inhibition was mediated by a nondialysable factor, ruling out a direct drug effect. In contrast, the effect of tt plasma was less pronounced but more specific. In some patients, we observed a strong reproducible inhibition of antidonor MLC by tt plasma. However, other patients did not show this inhibitory effect; thus the inhibition was not statistically significant (1 greater than P greater than .05 by the Wilcoxon t test) when all patients were analyzed. Overall, patient tt plasma affected neither control antidonor MLC nor patient MLC responses to pooled allogenic stimulating cells. In two patients showing strong tt plasma inhibition of antidonor MLC, the inhibition appeared to be Ig-mediated. The results are discussed in relation to current theories of DST mechanisms.

Colon complications are a potential source of serious morbidity to the immunosuppressed patient. Because of multiple predisposing factors, renal transplant patients are a high-risk group for the development of acute colonic pseudo-obstruction. During a recent 18-month period, 290 renal transplants (79 living, 211 cadaveric donors) were performed and prospectively analyzed for colonic dysmotility. A total of 34 episodes of acute colonic ileus (30 primary, 4 recurrent) occurred in 30 (10.3%) renal transplant recipients. Acute colonic ileus was more frequent after living-donor transplantation (19.0% vs. 7.1%, p = 0.006). Analysis of multiple variables revealed that the incidence of acute colonic ileus was directly related to mean cumulative prednisone dosage (p less than 0.05). Medical therapy (rapid steroid reduction, bowel rest) resulted in a 76.7% response, whereas 8 patients underwent colonoscopy because of progression to acute pseudo-obstruction. The success rate for colonoscopic decompression was 87.5%; in 1 patient cecal perforation developed after unsuccessful decompression. Overall, 33 of 34 (97.1%) episodes of acute colonic ileus were successfully treated. Steroid-induced ileus (pseudo-obstruction) is a potentially malignant early form of colonic dysmotility infrequently reported in transplant recipients. Successful management requires early clinical recognition, reduction in steroid dosage, bowel rest, and urgent colonoscopic decompression in select cases.