Making enhanced recovery the norm not the exception.

BACKGROUND: Enhanced Recovery After Surgery ("STAAR" in our system) is multimodal care focused on the reduction of physiological and psychological stress. While enhanced recovery is well established in colorectal surgery, and there is evidence for effectiveness in other surgical disciplines, to date widespread use is limited. METHOD: We implemented a Lean process that, within 12 months, expanded STAAR to 13 surgical services lines involving >130 surgeons, and impacting the care of >6000 surgical patients/year. RESULTS: Implementation involved educational and administrative meetings (279 in the first 6 months) and rounding. Use of STAAR was defined as >60% compliance. LOS was reduced up to 40%, mortality index and transfusion decreased 67% and 23% respectively. Case mix index increased 17%. Readmission rates, infections, ER visits were not increased. CONCLUSION: Using a Lean process focused on value, STAAR protocols became the standard rather than the exception. Time investment by senior surgical leadership was extensive.

Cytomegalovirus disease in African-American kidney transplant patients.

BACKGROUND: Cytomegalovirus (CMV) disease is a serious infection after kidney transplantation. The risk factors and the impact of CMV disease in African-American (AA) kidney transplant patients have not been well characterized. METHODS: We performed a retrospective analysis on 448 AA patients transplanted between 1996 and 2005. A 3-month universal chemoprophylaxis with ganciclovir or valganciclovir was administered to CMV donor-positive/recipient-negative (D+/R-) patients and to those treated with anti-thymocyte globulin for rejection, but not routinely to those with other D/R serostatus. RESULTS: A total of 31 AA patients (7%) developed clinical CMV disease. Compared with other D/R serostatus groups, the D+/R- group had the highest 3-year cumulative incidence of CMV disease (16.9% vs. 6.3% in D+/R+, 4.9% in D-/R+, and 2.4% in D-/R-). The D+/R- group also had the worst 3-year death-censored allograft survival (75% vs. 92% in D+/R+, 94% in D-/R+, and 96% in D-/R-, log-rank P = 0.01). Multivariate analysis found that D+/R- serostatus (odds ratio [OR] 5.4, 95% confidence interval [CI] 0.6-48.2, P = 0.003) and donor age > 60 years (OR 9.1, 95% CI 1.3-65, P = 0.03) were independent risk factors for CMV disease. CONCLUSION: The D+/R- group has the highest incidence of CMV disease and the worst 3-year renal allograft survival despite 3-month universal prophylaxis. Prolonged chemoprophylaxis may be needed to prevent the late development of CMV disease and to improve allograft survival in the high-risk group of AA kidney transplant recipients.

The contribution of donor quality to differential graft survival in African American and Caucasian renal transplant recipients.

Although a number of factors contributing to the disparity in graft survival between African American (AA) and Caucasian kidney transplant recipients have been described, the role of donor quality is less well understood. This study was undertaken to determine the impact of donor quality differences on this disparity, based on review of UNOS (United Network for Organ Sharing) data on deceased donor renal transplantation from 2000 to 2010. Donor quality was determined by the kidney donor risk index (DRI), and was compared between AA and Caucasian recipients. There were 33,405 Caucasians and 22,577 African Americans in the study, with mean DRI of 1.17 versus 1.27 (p < 0.001), respectively. In analysis 2,446 recipients of each race matched by propensity scoring (based on medical, socioeconomic and immunologic covariates), mean DRI was 1.25 for Caucasians and 1.28 (p = 0.02) for AA. The hazard ratio (HR) for graft failure associated with AA race was 1.8 (p < 0.001) on unadjusted analysis, and decreased to 1.6 (p < 0.001) after matching for DRI. These results indicate a significant disparity in quality of kidneys received by African Americans, which propensity analysis indicates is partially explained by differences in medical, immunologic and socioeconomic factors. Furthermore, this difference in donor quality partially accounts for poorer graft survival in African Americans.

Deceased donor management and demographic factors related to kidney allograft rejection and graft survival.

BACKGROUND: There is agreement that the number of organ donors and the number of organs recovered per donor are not maximized despite promotion of awareness and new guidelines for transplant teams. A single standard for donor management does not exist, in part because there is no consensus with respect to donor factors and management effect on transplant outcomes. METHODS: This retrospective study analyzed the long-term outcomes of 402 deceased donor kidney transplant recipients with respect to donor factors. This study differed from previous studies in that all recipients were treated with the same selection and immunosuppressive protocols. RESULTS: Factors associated with improved graft survival included cause of death, more organs donated, and lower peak sodium (P < .01). Delayed graft function (DGF) decreased if more organs were donated, but increased when the donor was given dopamine. Recipients of donor kidneys with higher final creatinine values were more likely to show DGF (P < .01). A decrease in acute rejection episodes was observed among patients whose donors had received dopamine, donated more organs, and had a shorter time between incision and cross clamp (P < .05). Kidneys from donors with a higher final creatinine displayed fewer rejection episodes; those with a higher peak creatinine experienced more rejection episodes (P < .05). CONCLUSION: The effect of donor variables on kidney transplant outcomes is important and may not be consistent with traditional expectations. Additional data collection and assessment of both short- and long-term transplant outcomes are critical to improve our understanding of the impact of deceased donor factors and management.

A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation.

Leukocyte function associated antigen-1 (LFA-1) has a multifaceted role in the immune response, including adhesion and trafficking of leukocytes, stabilizing the immune synapse of the MHC-TCR complex and providing costimulation signals. Monoclonal antibodies to the CD11a chain of LFA-1 have been seen to result in effective immunosuppression in experimental models. Efalizumab, a humanized IgG1 anti-CD11a, is approved for use in psoriasis and may provide effective immunosuppression in organ transplantation. Thirty-eight patients undergoing their first living donor or deceased renal transplant were randomized to receive efalizumab 0.5 or 2 mg/kg weekly subcutaneously for 12 weeks. Patients were maintained on full dose cyclosporine, mycophenolate mofetil and steroids or half dose cyclosporine, sirolimus and prednisone. At 6 months following transplant patient survival was 97% and graft survival was 95%. Clinical biopsy-proven acute rejection in the first 6 months after transplantation was confirmed in 4 of 38 patients (11%). Three patients (8%) developed post transplant lymphoproliferative disease, all treated with the higher dose efalizumab and full dose cyclosporine. The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation.

Disability following kidney transplantation: the link to medication coverage.

There is no uniformity regarding patient disability following kidney transplantation. Given improved results of patient and graft survival, and the link between insurance, medication coverage and disability, efforts must be made to define disability after a successful transplant. We conducted an individual questioner study of kidney transplant patients to determine factors relating to patient-perceived disability. Seventy patients participated in the study. Patient perception of disability did not correlate with education or ethnicity. Most patients believed they were disabled on dialysis and this did not change following transplantation. While 42 (60%) of the patients felt that they could work, either full-time or part-time, only 20 (28%) were actually working or in school. Most patients believe that working will eliminate disability status and, therefore, insurance and medication coverage. Patients considered disability more related to their status as a kidney transplant patient than any specific physical limitations. The link, whether real or perceived, between 'disability' and immunosuppressive medication coverage is a significant barrier for many patients. The transplant community must reach some degree of consensus regarding post-transplant activity restrictions. The transplant community needs to find a way to take an active role in post-transplant education and employment.

Giant biliary cystadenoma: case report and literature review.

Biliary cystadenoma is a very rare cystic neoplasm of the liver. This tumor is insidiously progressive and usually presents in white females in their fifth decade. It has a characteristic appearance on ultrasound, computed tomography, and angiography. The exact etiology of these tumors is unknown, but several theories have been proposed. Historically these cystic tumors have been treated by a variety of techniques including aspiration, fenestration, internal drainage, and resection. Previously reported series have confirmed a >90 percent recurrence rate with anything less than complete excision. In addition biliary cystadenoma is a premalignant lesion and only surgical excision can differentiate it from its malignant counterpart, biliary cystadenocarcinoma.

Extrapancreatic pseudoaneurysm after pancreas transplantation.

Pseudoaneurysms after pancreatic transplantation are an infrequent event. Repair usually involves removal of the transplant. We describe a patient with a pseudoaneurysm associated with pancreatic transplantation. The pseudoaneurysm originated from the external iliac artery distal to the donor Y-graft anastomosis. Diagnosis was made by duplex ultrasound. Surgical repair was effected through a retroperitoneal incision enabling vascular control. The patient has done well postoperatively, and with 1-year follow-up, continues to have normal renal and pancreatic allograft function.

Budd-Chiari syndrome: current management options.

OBJECTIVE: To assess the outcomes of current treatment strategies for Budd-Chiari syndrome. SUMMARY BACKGROUND DATA: Budd-Chiari syndrome, occlusion or obstruction of hepatic venous outflow, is a disease traditionally managed by portal or mesenteric-systemic shunting. The development of other treatment options, such as catheter-directed thrombolysis, transjugular portosystemic shunting (TIPS), and liver transplantation, has expanded the therapeutic algorithm. METHODS: The authors reviewed the medical records of all patients diagnosed with Budd-Chiari syndrome at the Johns Hopkins Hospital during the past 20 years. RESULTS: A total of 54 patients were identified: 13 (24%) male patients and 41 (76%) female patients, ranging in age from 2 to 76 years (median 33 years). Twenty-one (39%) had polycythemia vera, 3 (5.6%) used estrogens, 11 (20%) had a myeloproliferative or coagulation disorder, and in 7 (13%) the cause remained unknown. Forty-three patients were treated with surgical shunting, 24 mesocaval and 19 mesoatrial. Actuarial survival rates at 1, 3, and 5 years after shunting were 83%, 78%, and 75%, respectively. Of 33 patients surviving more than 4 years, 28 (85%) had relief of clinical symptoms. Five patients required shunt revision and eight had radiologic procedures to maintain shunt patency. Primary and secondary shunt patency rates were 46% and 69% respectively for mesoatrial shunts and 70% and 85% respectively for mesocaval shunts. Clot lysis was successful as primary treatment in seven patients. TIPS was performed in three patients, one after a failed mesocaval shunt. During an average of 4 years of follow-up, these patients required multiple procedures to maintain TIPS patency. Six patients underwent liver transplantation. Of these, three had previous shunt procedures. Five of the transplant recipients are alive with follow-up of 2 to 9 years (median 6). CONCLUSIONS: Both shunting and transplantation can result in a 5-year survival rate of at least 75%, and other treatment modalities may be appropriate for highly selected patients. Optimal management requires that treatment be directed by the predominant clinical symptom (liver failure or portal hypertension) and anatomical considerations and be tempered by careful assessment of surgical risk.

Treatment of antibody-mediated accelerated rejection using plasmapheresis.

Accelerated antibody-mediated rejection is believed to be due to an anamnestic response of an allograft recipient to donor antigens. Few reports have demonstrated successful reversal of this type of rejection, and no consensus exists for either diagnosis or treatment. Accelerated antibody-mediated rejection was suspected on the basis of clinical findings and confirmed by cytotoxic and flow crossmatches, and leukocyte antibody screens. Serial crossmatches and antibody screens were performed through post-transplant day 112. Plasmapheresis was performed on post-transplant days 1, 2, 4, 6, 12, 14, 20, and 28. The duration of treatment was determined by the cytotoxic crossmatch results. We present a case of successfully treated accelerated antibody-mediated rejection using plasmapheresis and aggressive immunosuppression. Serial crossmatch and leukocyte antibody screen results are presented that confirm the production of anti-donor antibody and demonstrate the effectiveness of the treatment protocol in eliminating detectable levels of the anti-donor antibody. At 6 months post-transplant, the patient has a serum creatinine of 1.1 and has not had any additional rejection episodes or infectious complications. The protocol suggested in this paper allows for rapid diagnosis, institution of treatment, and monitoring the efficacy of treatment, providing the basis for follow-up clinical trials.

Laparoscopic living donor nephrectomy: advantages of the hand-assisted method.

INTRODUCTION: The laparoscopic technique for living donor nephrectomy is a technically difficult procedure that has not yet gained widespread acceptance in the transplant community. The procedure may be more acceptable if alterations to the technique made it easier to perform and decreased operative times. METHODS: In August 1998, we altered the laparoscopic procedure to include the use of a device allowing hand assistance. Subsequently, all living donor nephrectomies have been done using the hand-assisted method. In this article, the results of 10 cases performed using the original laparoscopic technique are compared with the results of 12 cases using the hand-assisted technique, and a brief description of modifications to the original technique is given. RESULTS: No patients where turned down as living donors, and no contraindications to the pure or hand-assisted laparoscopic techniques where found. The hand-assisted technique significantly reduced the operative time (2.02+/-0.44 vs. 3.12+/-0.36 hr, P<0.05) and the warm ischemic time (1.23+/-0.54 vs. 3.91+/-0.53 min, P<0.05). The length of stay and recovery time to normal activities were not different between the pure laparoscopic and hand-assisted groups. CONCLUSION: The advantages of the hand-assisted technique include the ability to use tactile sense to facilitate dissection, retraction, and exposure. In addition, the final stages of vascular stapling and kidney removal are more sure and rapid. The modifications of the laparoscopic technique presented here provide measurable and subjective improvements to laparoscopic living donor nephrectomy. The hand-assisted method of laparoscopic nephrectomy may make the operation available to more transplant centers.

Utility of CT angiography for evaluation of living kidney donors.

We reviewed our initial experience with helical computed tomography (CT) angiography in the evaluation of living kidney donors which, until now, has necessitated arteriography. Nineteen donors (12 women, 7 men) have had their renal anatomy evaluated solely by CT angiography preoperatively. All scans demonstrated normal collecting systems and single ureters. Five donors (26%) had supernumerary renal arteries. Fourteen donors had single, 4 donors had two, and 1 donor had three renal arteries. Helical CT demonstrated small polar vessels in several donors. Two donors (10%) had supernumerary renal veins. Accuracy of vascular anatomy defined on CT was 90% when confirmed at operation. Anatomically all CT findings were consistent with operative findings except in 1 donor who was found to have a 0.8 cm lesion near the renal hilum. At our institution, the total charges for selective renal arteriography are $3845 and for helical CT with three-dimensional (3-D) reconstruction are $1546. The amount of contrast dye (approximately 100 mL) is equivalent. Patients uniformly reported that the CT scan was a convenient and painless procedure. The accuracy of helical CT angiography is equivalent to arteriography in assessing renal vascular anatomy (with the additional benefit of imaging venous and parenchymal anatomy). Charges for helical CT are 59% less. There is greater patient acceptance and potentially less morbidity associated with the non-invasive nature of helical CT. We believe that CT angiography is the radiologic procedure of choice for the assessment of renal anatomy in potential living kidney donors.

Management of severe pancreatitis in renal transplant recipients.

OBJECTIVE: The authors determine if any aspects of the treatment of renal transplant patients with pancreatitis were of particular benefit with regard to graft and patient survival. BACKGROUND: The incidence of pancreatitis in renal transplant patients is low (1%-2%), but the mortality of the disease approaches 100%. Although several descriptive reports have been published, there is no consensus-regarding management. METHODS: The authors conduct a retrospective chart review. RESULTS: Twenty-one patients were identified with posttransplant pancreatitis (1.3% incidence). The cause of pancreatitis was presumed to be maintenance immunosuppression in all cases. Patients were classified by dynamic computed tomography (CT) scans having 1) mild/edematous disease (4 patients), 2) localized abscess or pseudocyst (6 patients), or 3) severe disease (11 patients). Patients with mild/edematous pancreatitis did well with medical management. The six patients with localized abscess or pseudocyst were successfully treated with standard operative intervention. Of the 11 patients with severe disease, 6 had several days of intensive medical management before operation, and all died. The other five patients underwent early operative intervention based principally on CT scan findings, and all survived. The latter group had multiple operations and four of five had functioning renal allografts at discharge. CONCLUSION: The severity of pancreatitis in the posttranplant patients may be difficult to assess by clinical criteria. Dynamic CT scanning is, therefore, essential in defining the extent of disease. Early, and perhaps repeated, operations may be lifesaving in those patients having CT scan findings of severe pancreatitis.

Traumatic hypothermia is related to hypotension, not resuscitation.

STUDY OBJECTIVE: To determine whether posttraumatic hypothermia is associated with hemorrhage or with resuscitation. METHODS: We used a sequential hemorrhage-resuscitation rat model. Rats were subjected to hemorrhage (30 mL/kg), then 1 hour of shock, followed by 2:1 crystalloid/blood resuscitation (60 mL/kg) at ambient temperature. A control group underwent neither hemorrhage nor resuscitation. RESULTS: We recorded core temperature and blood pressure every 10 minutes. Temperature drop averaged 3.4 degrees C and was fastest during hypotensive shock. Rate of temperature change correlated with blood pressure (beta = .0102, P < .001), shock phase (beta = .4504, P = .041), and blood pressure during shock phase (beta = .0116, P < .001), but not with resuscitation phase or with duration of shock or resuscitation. Three of 14 rats died during shock, none during resuscitation. An increase in temperature was noted in 1 of 14 rats during shock and in 7 of 11 rats during resuscitation. CONCLUSION: Hemorrhage-associated hypothermia occurs during hypotensive shock, not during fluid resuscitation.

Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats.

Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes .OH production, we examined whether administration of a novel, long-acting iron chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of HES-DFO further significantly decreased the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy.

The effectors of cell death in allograft rejection are poorly understood. Oxygen derived free radicals (ODFR) may participate in graft destruction. We examined the impact of the antioxidants ascorbic acid (AA) and alpha-tocopherol (AT) with low dose CsA on rat cardiac allograft survival. Lewis rats that had undergone heterotopic abdominal cardiac transplantation with Wistar-Furth allografts (day 0) were divided into 6 groups. Group 1 was the control group; groups 2 and 3 received AA (1200 mg/kg), and groups 4 and 5 received AT (800 IU/kg) by gavage daily until rejection. Groups 3, 5, and 6 were given CsA (2.5 mg/kg i.m.) days 1-15. Allograft rejection times (in days) were 7.7 +/- 1, 10.3 +/- 1.5 (P < 0.01 vs. group 1), 37.1 +/- 6.4 (P < 0.01 vs. group 1, P = 0.0004 vs. group 6), 9.0 +/- 1.4, 26.5 +/- 3.6 (P < 0.01 vs. group 1, P < 0.03 vs. group 6), and 20 +/- 4.9 (P < 0.01 vs. group 1) for groups 1, 2, 3, 4, 5, and 6. To assess the impact of AA on ODFR production, chemiluminescence was performed on zymosan-activated Lewis whole blood from control rats and rats administered AA. AA significantly decreased peak chemiluminescence (P < 0.05) as compared with nontreated rats indicating effective ODFR scavenging. To determine whether AA and AT inhibit lymphocyte stimulation, mixed lymphocyte response testing was performed with irradiated Wistar-Furth lymphocytes as stimulator cells for Lew responder cells from rats treated as groups 3, 5, and 6. CsA significantly suppressed (P < .05) proliferation as compared with untreated controls. Neither AA nor AT enhance CsA's immunosuppressive effect by mixed lymphocyte response testing. In summary, prolongation of allograft survival with antioxidants AA and AT does not result from abrogation of lymphocyte responsiveness or alteration in CsA bioavailability. Rather, these data suggest that ODFR are involved in allograft destruction and support a role for effective antioxidant therapy in the treatment of allograft rejection.

A prospective randomized comparison of quadruple versus triple therapy for first cadaver transplants with immediate function.

In January 1988, we initiated a prospective, randomized comparison of prophylactic antilymphoblast globulin (ALG; quadruple therapy) versus no prophylactic ALG (triple therapy) in the setting of immediate graft function (defined by a brisk diuresis and a 20% decline in serum creatinine within 24 hr). Recipients were stratified according to presence of diabetes and age greater or less than 50 years. Recipients on quadruple therapy (n = 61) received 7 days of prophylactic Minnesota ALG (5 mg/kg on day 1, 10 mg/kg on day 2, 20 mg/kg on days 3-7). CsA, 10 mg/kg/day, began on day 6. AZA began at 2.5 mg/kg/day and was adjusted according to white blood cell count. Recipients on triple therapy (n = 60) began immediate CsA, 10 mg/kg/day orally and AZA, 5 mg/kg/day, tapering to 2.5 mg/kg/day by day 8. Both groups received identical prednisone tapers beginning at 1 mg/kg/day, decreasing to 0.5 mg/kg/day by 2 weeks and to 0.15 mg/kg/day by 6 months. Demographic characteristics between groups were not different with respect to diabetes, age, sex, race, per cent panel-reactive antibodies (PRA), or HLA matching. Follow-up ranged from 2 to 4.5 years. Patient survival was 93% for the quadruple therapy group and 90% for triple therapy. Actuarial graft survival was 79% in the quadruple group and 72% in the triple group (P = 0.18). Graft loss due to rejection occurred in 6/61 receiving ALG versus 7/60 in the immediate CsA group. Three of 4 high PRA recipients in the immediate CsA group lost their grafts within 30 days compared with none in the ALG group. The mean time to graft loss was significantly longer for the quadruple therapy group (17 +/- 8 months) compared with the triple therapy group (4 +/- 5 months), P = 0.006. The total number of rejection episodes was similar for both groups (29/61 vs. 31/60), as was the number who were rejection free (51% vs. 47%). The use of OKT3 was also similar between groups (28% vs. 30%). The quadruple therapy group had a higher incidence of CMV infection: 20% vs. 7% (P < 0.05), but no grafts or patients were lost as a result. Serum Cr was not different at 1 and 12 months (1.5 and 1.6 vs. 1.6 and 1.7, respectively), nor were Cr clearances (63 and 68 vs. 60 and 63). Conclusion. Early initiation of oral CsA in the setting of immediate graft function is not associated with significant nephrotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)