Effect of graft type on postoperative liver function recovery in living liver donors.

BACKGROUND: Donor safety is the primary focus in living-donor liver transplantation. Although, the procedure carries a significant risk of morbidity and even death, the use of marginal living donors is a current issue of discussion. PATIENTS AND METHODS: Between September 2001 and October 2008, we performed 203 liver transplantation procedures using organs from living donors. Of 203 donors, 115 were men and 88 were women, with a mean (SD; range) age of 34.5 (9; 19-66) years. One hundred fifty donors were first-degree relatives of the recipients, 36 were second-degree relatives, and 17 were spouses. We did not accept grafts with remnant volume less than 40% or from donors with impaired liver function. We performed 96 right-lobe 38 left-lobe, and 69 left-lateral segmentectomies. For the right-lobe grafts, the median hepatic vein was always left in the remnant liver. The mean ratios of remnant to total donor liver volume were 42.0%, 66.8%, and 74.6% for the right-, left-, and left lateral segmentectomies, respectively. Mean hospitalization time was 7.0, 6.2, and 9.7 days, respectively. Mean operative time was 330, 324, and 324 minutes, respectively. Only 15 donors (7.8%) received autologous blood transfusions during surgery. Liver function tests including alanine aminotransferase, aspartate aminotransferase and bilirubin concentrations and prothrombin time were assessed postoperative days 1, 3, and 5 at outpatient follow-up, usually at week 3. RESULTS: There were no deaths; however, 26 complications occurred in 20 of 203 donors (5.2%), most of which were treated with radiologic interventions. CONCLUSION: Larger grafts produce impaired function in the early postoperative period; however, they do not have a negative effect in the long term. The remnant volume should be measured fastidiously, and surgeons must avoid taking large volumes of liver, especially in right-lobe donors.

Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

Role of heparin on TNF-alpha and IL-6 levels in liver regeneration after partial hepatic resection.

OBJECTIVES: The aim of this study was to investigate the effect of heparin on TNF-alpha and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model. MATERIALS AND METHODS: 32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH(50)/ml). On the 5th postoperative day, blood was taken to assess CH(50) activity and the levels of TNF-alpha and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed. RESULTS: Serum CH(50) activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-alpha level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01). CONCLUSION: Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.

Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters.

Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.

Role of donor age and acute rejection episodes on long-term graft survival in cadaveric kidney transplantations.

Cadaveric donors can provide an effective solution to the problem of organ shortage, and many factors that may affect the functioning and survival of cadaveric kidneys have been studied. We aimed to clarify the impact of donor age and acute rejection episodes on long-term graft and patient survival in patients receiving cadaveric renal transplants. We retrospectively evaluated the long-term outcomes of 207 patients who had received cadaveric renal transplants between 1985 and 2004. Mean recipient age, HLA mismatch, mean donor age, delayed graft function (DGF), mean cold ischemia time, acute rejection episodes in the first 6 months after transplantation, and 1-, 3-, and 5-year graft survivals were evaluated. Two study groups were created according to donor age: group 1 (n = 126) was composed of patients receiving kidneys from donors younger than 50 years, and group 2 (n = 81) was composed of patients receiving kidneys from donors 50 years of age or older. Mean recipient age, HLA mismatch, and mean cold ischemia time between groups were not different. The DGF rate in group 1 was 40% (n = 50) and in group 2 was 46% (n = 37) (P > .05). The 1-, 3-, and 5-year survival rates of patients without acute rejection within the first 6 months after transplantation in group 1 (58/126; 46%) versus those in group 2 (46/81; 57%) were 95% versus 90%, 65% versus 60%, and 40% versus 35%, respectively (P > .05). The 1-, 3-, and 5-year graft survival rates of patients with acute rejection within the first 6 months in group 1 (n = 68) versus those in group 2 (n = 35) were 93% versus 89%, 71% versus 55%, and 44% versus 28%, respectively (P = .005). There was no significant difference in 1-, 3-, and 5-year survival rates between patients with DGF in both groups. Acute rejection episodes within the first 6 months after cadaveric transplantation, especially in patients receiving kidneys from donors older than 50 years, were shown to affect 5-year survival of the kidney graft. However, cadaver age alone had no negative effect on 5-year graft survival rates. Cadaveric donors older than 50 years may be a solution to the organ shortage in the treatment of end-stage renal disease.

The effect of graft nephrectomy on long-term graft function and survival in kidney retransplantation.

We retrospectively evaluated the long-term results of 53 (3.5%) recipients who received second allograft among 1486 kidney transplants between November 3, 1975 and June 30, 2004. Two study groups were patients in Group 1 (n = 21) who underwent allograft nephrectomy and those in Group 2 (n = 32) who did not. We assessed demographic features, rejection rates throughout the follow-up period, and serum creatinine levels at 12 months as well as graft and patient survival rates, postoperative complications, time interval between transplantations, and HLA matches. Forty-three patients who underwent retransplantation received kidneys from living-related donors and the remaining 10 from cadaveric donors. Mean serum creatinine levels of Group 1 versus Group 2 were 1.8 mg/dL (range, 0.8 to 6.6 mg/dL) versus 2.1 +/- 1.1 mg/dL (range, 1.1 to 7.1 mg/dL). HLA-AB and HLA-DR mismatches were 1.9 +/- 1.1 versus 1 +/- 0.6, respectively (P = .01). Acute rejection rates were not significantly different between Groups 1 (9/21, 43%) and 2 (12/32, 38%) (P < .05). The average intervals between the first and the second transplantations were 62 +/- 26 months in Group 1 (P = .02) and 32 +/- 11 months in Group 2. One-, 3-, and 5-year graft survival rates in Group 1 versus Group 2 were 83% versus 89% (P > .05); 64% versus 79% (P > .05), and 45% versus 68% (P = .04), respectively. In conclusion, we did not observe any advantage of graft nephrectomy before retransplantation. The length of the interval between the first and the second transplantations may have a negative correlation with second graft survival.

OKT3 treatment for steroid-resistant acute rejection in kidney transplantation.

Orthoclone (OKT3, Ortho Biotech Inc, USA) monoclonal antilymphocyte antibody is a powerful T-cell-specific immunosuppressive agent. OKT3 has been used for induction therapy in kidney and liver transplantation, as well as to treat acute or steroid-resistant acute rejection episodes (ARE). This study was a retrospective analysis of 43 renal transplant recipients who developed steroid-resistant ARE and were treated with OKT3 between September 1994 and June 2004. The recipients were 36 men and 7 women of mean age 32.7 +/- 11.6 years (range, 19 to 48 years). The mean time from transplantation to OKT3 treatment was 7.2 +/- 6.7 months. Thirty-four episodes (79.1%) responded to OKT3 therapy with improved graft function, but the remaining 9 (20.9%) grafts did not respond. Among the 34 OKT3 responders, the mean serum creatinine decreased from 3.96 +/- 2.5 mg/dL to 2.45 +/- 1.77 mg/dL after treatment. Eleven (25.6%) of the 43 patients experienced minor side effects: fever, dyspnea, tachycardia, bradycardia. One patient (2.3%) developed acute pulmonary edema; one (2.3%), cytomegalovirus infection; and eight (18.6%), bacterial infections. The 1-, 3-, and 5-year graft survival rates for the 34 patients who responded to OKT3 therapy were 96%, 93%, and 85%, respectively. All patients are currently alive. The results indicate that OKT3 is a safe, effective treatment choice for steroid-resistant ARE in kidney transplantation.

Effect of routine insertion of a double-J stent after living related renal transplantation.

It is still not clear whether double-J stents (DJS) are of benefit. We sought to determine whether routine prophylactic use of DJS reduced postoperative complications after renal transplantation. We prospectively evaluated 42 living donor renal transplantations performed between September 2001 and September 2003. The patients were randomly assigned to one of two groups: 21 operations (group 1), included a DJS placed during Lich-Gregoir ureterocystotomy and 21 cases (group 2), a Lich-Gregoir ureterostomy without DJS insertion. Among group 1, the DJS were removed within the first month after transplantation. One patient in group 1 (5%) developed a urinary leakage. In group 2, there was one case of delayed graft function (5%) and one patient developed a hematoma (5%) at the operative site. The group rates for urinary tract infection were not significantly different (P > .05). In the early postoperative period, a renal biopsy was performed if a patient's creatinine level was elevated or remained elevated during 3 days after transplantation. Four patients in group 1 and 10 patients in group 2 required a renal biopsy (P = .04). All four of the group 1 biopsies and three of the group 2 specimens revealed acute rejection. The other seven group 2 biopsies showed tubuloepithelial injury. We suggest that ureteral stasis may cause tubuloepithelial injury and slow down the decrease in creatinine levels. In our model, the DJS did not increase urinary tract infections but provided a smooth decline in creatinine levels, which may reduce the question of acute rejection.

Comparison of hemodynamic changes associated with two different polytetraflouroethylene arteriovenous fistulae in hemodialysis patients.

The aim of this prospective study was to identify hemodynamic factors associated with two different types of polytetrafluroethylene (PTFE) AV grafts. The study was conducted on 46 hemodialysis patients over a 3-year period. The subjects were randomly assigned to one of two study groups: Group 1 patients (n = 24) underwent a brachiocephalic loop PTFE fistula; Group 2 patients (n = 22), a brachioaxillary PTFE fistula. Preoperatively, we recorded each individual's subclavian catheter history, hemodialysis frequency, and serum levels of parathormone (PTH), calcium (Ca)-phosphorus (P) product, homocysteine, protein C, and protein S. Doppler ultrasonography was used to evaluate vascular hemodynamic changes in the proximal and distal portions of the AV fistula at 48 hours and 1 week postoperatively. Group 1 showed a significantly greater number of ipsilateral subclavian catheter interventions prior to AV graft surgery than Group 2 (14 versus 7, respectively; P = .05; chi-square). The mean peak systolic velocity in the brachial artery in Group 1 was significantly higher than that in Group 2 at 1-week postoperatively (P = .04, paired t-test). The mean radial artery diameter in Group 1 was greater than that of Group 2 at 1 week postoperatively (P = .05, Student t-test). At 48 hours postoperatively the observed change in cephalic vein diameter in Group 1 was significantly greater than the change in axillary vein diameter in Group 2 (P = .08, paired t-test). Preoperatively, the mean serum protein C and protein S levels in Group 1 were higher than those in Group 2 (P = .03 and P = .04, respectively; Mann-Whitney U test). The total numbers of dialysis sessions per week in each group were significantly different (P = .001, chi-square). Six Group 1 patients exhibited graft thrombosis at 48 hours after AV graft surgery. None of the patients in Group 2 exhibited thrombosis at 48 hours or 1 week postoperatively. The results indicate that patients with brachiocephalic PTFE AV grafts show more significant changes in the cephalic vein and brachial artery than patients with brachioaxillary PTFE AV grafts. The findings also suggest that more ipsilateral subclavian catheter interventions and a higher weekly frequency of hemodialysis prior to AV graft surgery are risk factors for early thrombosis of PTFE AV grafts.

Scintigraphic evaluation of paired renal allografts from the same cadaveric donor.

The aim of this study was to compare the outcome of paired grafts in renal recipients from the same cadaveric donor using quantitative Tc-99m DTPA scintigraphy. Fifty recipients from 25 cadaveric donors were followed for a median period of 3 years. Serial Tc-99m DTPA scintigraphy was performed starting on the third posttransplant day and images evaluated quantitatively. The quantitative parameters included Hilson's perfusion index, time to maximum activity, time to half of maximum activity, the ratio of the graft activity at 20 to 3 minutes, and glomerular filtration rate. In the early postoperative period, 20 of 25 paired kidneys showed similar performances. At the end of the first year 22 of 25 pairs showed a similar evolution. At the end of the third year, the number was 21 of 25. We concluded that if cold ischemia time was prudent, there was no difference in graft outcome between the first and the second recipient of a renal transplant from the same cadaveric donor.

Tacrolimus conversion in kidney transplant recipients: analysis of 107 patients.

Early results of an alteration in immunosuppressive protocol of tacrolimus conversion at a mean follow-up of 16 (range 1 to 36) months are presented with a mean time after transplantation of 34 +/- 1.4 months (range 1 to 158 months). Chronic allograft nephropathy in 16 (17%) patients, nephrotoxicity related to cyclosporine in 27(23%) patients and steroids resistant acute rejection in 64 (58%) represented the indications for tacrolimus conversion. Before starting tacrolimus there were 1 acute rejection episode in 37 patients, 2 in 17 patients, and 3 in 10 patients. After the drug conversion, 1 acute rejection occurred in 18 and 2 acute rejection in 4 patients. Graft loss was seen in 16 (16%) patients after drug conversion. Tacrolimus was withdrawn due to diabetes mellitus (n = 9), epilepsy (n = 4), and severe Nocardia sepsis, lymphoma and Kaposi sarcoma (each in one patient). Decreases in serum creatinine and increases in blood glucose levels were significantly associated with the tacrolimus doses (P = 0.0004 and P = 0.0400, respectively). The increase in creatinine clearance values were closely related to higher tacrolimus levels. The target range with maximum efficacy and minimum toxicity seemed to be 10 to 15 ng/mL. Tacrolimus conversion can be successful in cases of rejection and nephrotoxicity, but dose-dependent blood glucose elevations require close observation in these patients.

Immunosuppressive therapy and Kaposi's sarcoma after kidney transplantation.

Immunosuppressive therapy for organ transplant recipients is complicated by high rates of malignant diseases, one of which is Kaposi's sarcoma (KS). Between November 1975 and March 2003, 1425 patients underwent renal transplantation at our center, including the 1095 most recent procedures. Fifty-two malignancies were observed in 50 patients (4.7%), including 16 cases of KS. The 16 recipients comprised 6 men and 10 women of mean age 39 +/- 9 years (range 10 to 62 years). At the time of KS diagnosis, 14 recipients were receiving cyclosporine, azathioprine, and prednisolone, and the other 2 azathioprine and prednisolone. The mean time from transplantation to diagnosis was 24 +/- 15.2 months (range 8 to 74 months). One recipient showed a lymphoma concomitant with KS. Seven patients had lesions limited to the skin, 5 had the skin and gastrointestinal tract disease, and 4 had disseminated disease. After KS was confirmed, the first-line treatment was cyclosporine and azathioprine withdrawal with tapering of prednisolone. The tumors were managed by appropriate surgical and/or medical therapy. At the time of this presentation, 9 individuals are alive, 4 with normal renal function. Five patients lost their grafts due to chronic rejection. We found that the combination of immunosuppressive drug withdrawal and chemotherapy is effective in patients with limited disease, but the results are poor in cases of generalized disease.