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Biomedical subjects

Chris E Freise

Publications and source records attributed to Chris E Freise.

27 records · Page 2Linked to original sources

Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have historically been excluded from consideration for transplantation out of concern for the effects of immunosuppression on the progression of HIV disease. Improvements in HIV-related morbidity and mortality with the use of highly active antiretroviral therapy (HAART) have prompted a reevaluation of transplantation as a treatment option for HIV-infected patients with end-stage kidney and liver disease. METHODS: Eligible patients met standard transplant criteria. They had undetectable plasma HIV-1 RNA levels (viral load) for 3 months (kidney) or were predicted to achieve viral load suppression posttransplantation if unable to tolerate HAART (liver); a CD4+ T-cell count of more than 200 cells/microL (kidney) or more than 100 cells/microL (liver) for 6 months; and no history of opportunistic infections and neoplasm. Standard immunosuppression included prednisone, mycophenolate mofetil (CellCept, Roche Pharmaceuticals, Basel, Switzerland), and cyclosporine (Neoral, Novartis, East Hanover, NJ). RESULTS: Fourteen patients received transplants (10 kidney transplants, mean follow-up 480 days; four liver transplants, mean follow-up 380 days). All of the kidney transplant recipients (100%) are alive and with functioning grafts, and three of four liver transplant patients (75%) are alive and well with functioning grafts (all liver transplant patients with normal liver function tests). The one death occurred 445 days posttransplantation in a liver recipient coinfected with hepatitis C virus, who died as the result of its rapid reoccurrence. Rejection occurred in 5 of 10 kidney transplant recipients but did not occur in any of the four liver transplant recipients. HIV viral loads have remained undetectable in all patients maintained with HAART. CD4 counts have remained stable in patients not treated for rejection. Patients receiving protease inhibitors require 25% of the dose of cyclosporine compared with patients receiving nonnucleoside reverse transcriptase inhibitors. CONCLUSIONS: There has been no evidence of significant HIV progression and no adverse effect of HIV on allograft function. Rejection is a concern in kidney transplant recipients, as is the possible poor outcome in hepatitis C virus-coinfected liver transplant recipients. Preliminary data are encouraging and indicate that transplantation should be a treatment option for individuals with well-controlled HIV disease.

Adult↗

Excellent short-term results with steroid-free maintenance immunosuppression in low-risk simultaneous pancreas-kidney transplantation.

HYPOTHESIS: Steroid avoidance is possible in simultaneous pancreas-kidney transplantation with the use of newer immunosuppressive agents and induction therapy. DESIGN: A retrospective consecutive case review. SETTING: A university tertiary referral center. PATIENTS: Medical records of 40 consecutive patients who underwent pancreas-kidney transplantation from November 2000 to July 2002 were reviewed. INTERVENTION: The immunosuppression protocol used in this series of patients consisted of Thymoglobulin induction combined with mycophenolate mofetil, tacrolimus, and sirolimus for maintenance immunosuppression. Steroids were used as pretreatment only, given with Thymoglobulin, and were typically discontinued by postoperative week 1. MAIN OUTCOME MEASURES: Graft and patient survival rates, rejection rates of the kidney or pancreas, infection rates, and surgical complication rates. RESULTS: Patient, kidney, and pancreas survival rates were 95.0%, 92.5%, and 87.5%, respectively. Biopsy-proven pancreas rejection rates at 1 and 3 months' posttransplantation were 2.5%. Kidney rejection rates at 1 and 3 months were 2.5%. Steroids were given only to patients with documented transplant rejection. Surgical and medical complications were no different from earlier protocols. CONCLUSIONS: Immunosuppression protocols that do not include maintenance steroids have shown minimal rejection in the first 3 months and equivalent patient and graft survival rates compared with protocols that use steroids. The potential beneficial long-term impact of steroid avoidance will require further study.

Adult↗

Techniques to optimize vascular control during laparoscopic donor nephrectomy.

OBJECTIVES: To review our experience with laparoscopic donor nephrectomy for kidney transplantation and describe our technique of vessel ligation. METHODS: We retrospectively analyzed the method of renal artery and vein control during the 97 laparoscopic donor nephrectomies performed at the University of California, San Francisco, since November 1999. In addition, we examined both donor and recipient outcomes after nephrectomy and transplantation in this cohort. RESULTS: Currently, we ligate the renal artery and renal vein using a single Hem-o-lok polymer clip and a single Endo-TA stapler, respectively, and divide the vessels using scissors without securing the graft-side vessels. In contrast to using the Endo-GIA stapler, there is no need to trim staples (approximately 5 mm) from the vessels before anastomosis. Excellent vessel length was achieved in all cases without donor complications, and 99% of recipients had long-term graft function. The only major complications (blood transfusion, conversion to open surgery) occurred early in the series when we used the Endo-GIA stapler to control the vessels. CONCLUSIONS: Although adequate vessel length is typically obtained during left donor nephrectomy, additional length can be achieved using our modification. This may facilitate right donor nephrectomy and help reduce complications, potentially increasing the recovery of right kidneys for transplantation. In addition, performing vessel ligation and division in separate steps is simple, does not change ischemic time, and appears to increase safety.

Anastomosis, Surgical↗

Laparoscopic radical nephrectomy for suspected renal cell carcinoma in dialysis-dependent patients.

OBJECTIVES: To characterize the treatment and outcomes of laparoscopic nephrectomy for suspected renal cancer in patients with dialysis-dependent renal failure. Laparoscopic nephrectomy is currently an accepted modality in the treatment of renal cell carcinoma in many patients. However, the indications for the minimally invasive approach in patients with renal dysfunction are unclear. End-stage renal disease has multiple manifestations associated with increased operative morbidity that are potentially amplified during laparoscopy. METHODS: We reviewed our single-center experience for performing laparoscopic nephrectomy in patients with renal failure. Of patients receiving dialysis and having a kidney removed laparoscopically, 7 underwent the operation for suspected renal carcinoma because of a solid mass on imaging. The preoperative, intraoperative, and postoperative considerations were reviewed. RESULTS: Of the 7 patients, 5 (71%) underwent successful removal of the kidney by laparoscopy. The amount of blood loss (120 mL) and the median time to discharge after surgery (3 days) were comparable to published data and our experience in patients with normal renal function; however, the operative time (mean 294 minutes) was longer. No recurrences had been detected at the last follow-up examination (median 21 months, range 18 to 51). Despite meticulous attention to perioperative and anesthetic considerations, two complications were observed-ileus and necrotizing fasciitis of the flank. CONCLUSIONS: Pure laparoscopic nephrectomy for renal malignancy is feasible in patients with end-stage renal failure. However, this population is at increased risk of complications, despite maintaining the advantages of reduced blood loss and shorter hospitalization. The decision to proceed with laparoscopy and the selection of the specific surgical approach (transperitoneal or retroperitoneal) should be based on both surgeon experience and patient factors. In addition, careful preoperative preparation and intraoperative anesthetic management are crucial.

Adult↗

Expanded experience with laparoscopic nephrectomy and autotransplantation for severe ureteral injury.

PURPOSE: Complex injuries of the upper ureter with significant loss of length are difficult to manage. Traditional options include nephrectomy, bowel interposition and autotransplantation. The advent of laparoscopic donor nephrectomy has created a new option when preservation of functioning renal parenchyma is desirable. We update our experience with severe iatrogenic ureteral injuries requiring laparoscopic nephrectomy and autotransplantation. MATERIALS AND METHODS: Seven patients with severe ureteral injuries were referred for definitive management. In all cases preoperative evaluation demonstrated comparable split renal function and anatomy not amenable to routine reconstruction. Transperitoneal laparoscopic nephrectomy and autotransplantation to the ipsilateral pelvis were attempted. RESULTS: Of the patients 5 had a history of nephrolithiasis with intervention resulting in the ureteral injury and 5 underwent prior endoscopic or open management of the defects. All cases were associated with dense perinephric and perihilar fibrosis. Operative and warm ischemic times averaged 508 and 5 minutes, respectively. After ex vivo graft preparation, ureteral and vessel length and quality were adequate for transplantation in 6 cases. In the other patient the renal pelvis was not amenable for reconstruction. Urinary drainage consisted of ureteroneocystostomy in 2 cases and ipsilateral ureteroureterostomy in 4. There were no intraoperative complications and all grafts functioned immediately. Hospitalization averaged 6.4 days. At a mean followup of 17 months imaging studies demonstrated functioning renal autographs with a mean decrease in serum creatinine of 5%. CONCLUSIONS: Laparoscopic nephrectomy in conjunction with autotransplantation is a viable option for severe proximal ureteral loss. Acceptable perioperative morbidity and excellent graft function were obtained in all cases when the kidney was transplanted. Close cooperation with a transplant team is crucial to coordinate graft harvest, ensure appropriate organ preparation and select the optimal urinary anastomosis.

Adult↗

Management of lymphoceles after renal transplantation: laparoscopic versus open drainage.

PURPOSE: Laparoscopic surgery has become widely accepted for the treatment of lymphoceles following kidney transplantation. In this single center study we retrospectively reviewed our results of the surgical management of post-transplant lymphoceles, assessing indication and outcome of laparoscopic versus open drainage. MATERIALS AND METHODS: The records of 60 patients who underwent surgical treatment for a symptomatic lymphocele following kidney transplantation or combined kidney/pancreas transplantation were retrospectively reviewed. RESULTS: Between 1995 and 2002, 1,836 patients received a kidney transplant at the University of California San Francisco. In 60 patients (3.3%) a symptomatic lymphocele developed and either laparoscopic (20) or open drainage (40) was completed. The conversion rate from laparoscopic to open drainage was 16.5%. The most common indications for open lymphocele drainage were noninfectious wound complications (13 patients) and a high risk of vessel or ureter injury (8) due to proximity of the lymphocele to hilar structures. Additional surgery on the graft was required in 5 patients. Intraoperative blood loss was significantly lower in the laparoscopy group. Median hospital stay was 1 day in the laparoscopy group versus 4 days in the open drainage group. No perioperative complications were observed in either group. After a median followup of 38 months, 2 patients in each treatment group had a symptomatic recurrence. CONCLUSIONS: Although both surgical approaches are safe and effective, laparoscopic drainage should remain the method of choice for the treatment of post-transplant lymphocele. However, open drainage should be performed in patients with wound complications and in those with a small lymphocele adjacent to vital renal structures.

Adult↗

Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice.

BACKGROUND: Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L-/- mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L-/-) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart transplantation. To overcome CD40L-independent immune responses, we used anti-lymphocyte function-associated antigen monoclonal antibody (LFA)-1, which has previously been shown to inhibit CD8+ immune responses. METHODS: We conducted mixed lymphocyte reactions, cytotoxicity assays, skin transplantation, and vascularized heterotopic heart transplantation in wild-type B6 and CD40L-deficient mice in the presence and absence of anti-LFA-1 to study the effects of anti-LFA-1 in the absence of CD40L signaling. RESULTS: Anti-LFA-1 inhibited proliferation of naïve CD40L-/- mixed leukocyte reactions and the lysis of donor targets by CD40L-/- cytotoxic T lymphocytes. Anti-LFA-1-treated CD40L-/- mice that received fully MHC-mismatched skin grafts showed significant prolongation of graft survival, with a median survival time of 55 days (mean 66 days) compared with 13 and 21 days in wild-type and CD40L-/- controls, respectively. CD40L-/- mice that received fully MHC-mismatched vascularized heart transplants treated with four doses of 200 microg of anti-LFA-1 at the time of transplantation did not develop any signs of chronic vasculopathy 150 days after transplantation. CONCLUSION: These results indicate that anti-LFA-1 can complement CD40L inhibition in the prevention of undesirable immune responses.

Animals↗

Successful long-term outcomes using pediatric en bloc kidneys for transplantation.

GOAL: The objective of our study was to determine whether acceptable long-term graft survival and function can be achieved using pediatric en bloc renal transplants by employing specific immunologic and selection strategies. MATERIALS AND METHODS: A retrospective analysis of pediatric en bloc kidney transplants at a single institution was performed. A Kaplan-Meier analysis was used to evaluate graft survival. FINDINGS: Fifty-seven adult recipients with at least a 1-year follow-up period were successfully transplanted using pediatric en bloc kidneys between 1993 and 1998. Complete data regarding immunosuppression were available for 53 patients. All patients had a cyclosporine (CsA)- or tacrolimus (TAC)-based regimen with either azathioprine (Aza) or mycophenolate mofetil (MMF) and corticosteroids. All but two received induction with OKT3. One-, 3-, 4-, 5- and 7-year graft survival was calculated to be 88%, 86%, 83%, 68% and 68%, respectively. The mean serum creatinine value at 3 years was 1.0+/-0.4 mg/dL. Thirteen patients (23%) had biopsy-proven rejection. Ten of 19 (53%) patients treated with CsA/Aza had rejection, whereas 2/15 (13%) on CsA/MMF and 1/19 (5%) of patients on TAC/MMF had rejection. Nine patients (16%) had surgical complications. CONCLUSION: Excellent long-term results can be achieved in pediatric en bloc kidney transplantation using OKT3, TAC and MMF in carefully selected adult recipients.

Age Factors↗