Association between the heme oxygenase-1 promoter polymorphism and renal transplantation outcome in Greece.

BACKGROUND: Heme oxygenase-1 (HO-1) is the enzyme that catabolizes heme into carbon monoxide, biliverdin, and free iron. The induction of this enzyme is an important cytoprotective mechanism, which occurs as an adaptive and beneficial response to a wide variety of oxidant stimuli. HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. HO-1 inducibility is mainly modulated by a (GT)(n) repeat polymorphism in the promoter region, and has been shown that short repeats (S) are associated with greater upregulation of HO-1, compared with long repeats (L). In the present study we investigated the influence of this HO-1 gene polymorphism on clinical outcome after transplantation and on renal transplant function. METHODS: DNA from 175 donor/recipient pairs who underwent transplantation between October 2002 and June 2007 was genotyped. We divided the HO-1 alleles into 2 subclasses, the S ≤ 27 repeats and L > 27 repeats. RESULTS: There has been significant relevance between the genotype of the donor and the outcome of the graft, as far as recipients with normal graft function and recipients with deteriorated graft function are concerned (P = .021). In patients with normal graft function, grafts from L-homozygotes were found in 24%, whereas in patients with deteriorated function, grafts from L-homozygotes exhibited in higher rate (50%). Neither the donor's nor the recipient's polymorphism influenced the graft survival (log-rank test P = .228 for the donors and log-rank test P = 0.844 for the recipients). There was no evidence of a gene-dose effect on graft survival (P = .469). Recipients of allografts from S-carriers donors had significantly lower serum creatinine levels at 24 months compared with recipients of allografts from L-homozygotes donors (P = .016).

Hepatic focal nodular hyperplasia: when a benign lesion becomes "malignant". Report of a case.

In a 34 year-old woman complaining of right upper quadrant pain and having mildly elevated total bilirubin, the imaging investigation revealed a liver lesion with characteristics of focal nodular hyperplasia, measuring 3.8 cm, at the confluence of the hepatic veins. The mass was obstructing the left and middle hepatic veins and nearly obstructing the right hepatic vein. Dilation of the splenic vein with development of retropancreatic varices, splenomegaly and free abdominal fluid were also present. The patient underwent an uncomplicated left hemihepatectomy. Patients postoperative total bilirubin was normalized. Tomographic imaging three months after the liver resection revealed resolution of all the Budd-Chiari radiographic signs. This is a report of a case where a hepatic focal nodular hyperplasia, despite its benign nature, required extensive and urgent surgical intervention due to its location and potential dangers secondary to the development of portal hypertension.

Tc-99m sestamibi accuracy in detecting parathyroid tissue is increased when combined with preoperative laboratory values: a retrospective study in 453 Greek patients with chronic renal failure who underwent parathyroidectomy.

PURPOSE: Technetium(99m) sestamibi (MIBI) has poor sensitivity and specificity when applied to patients with secondary hyperparathyroidism. We investigated whether the combination of MIBI with preoperative parameters increased its accuracy. PATIENTS AND METHODS: This prospective study of 453 consecutive patients with secondary hyperparathyroidism who underwent parathyroidectomy (bilateral neck exploration) included preoperative MIBI scintigraphy compared with intraoperative and histopathology findings. Four patient groups were comprised according to the results: true positivity (TP), true negativity (TN), false positivity (FP), and false negativity (FN). RESULTS: MIBI scintigraphy sensitivity, specificity, positive predictive value, and negative predictive value were 66.4%, 50%, 76.3%, and 37.9%, respectively. For the TP group, mean age and mean parathormone (PTH) value were 56 years and 754, respectively. The binary logistic regression for the prediction (1) or not (2) of TP was as follows: 0.138 + (-.011) * age + 0.001 * PTH (P = .012). For the TN group, the mean age and mean phosphate value were 49 years and 5.24, respectively. The binary logistic regression for the prediction (1) versus not (2) of the TN was as follows: -1.463 + age * (-.029) + phosphate * 0.233 (P = .012). CONCLUSION: MIBI accuracy in patients with secondary hyperparathyroidism was increased when combined with other preoperative parameters. The sensitivity was increased as patients were older and the PTH levels were lower. The specificity was increased as patients were younger and the phosphate levels were lower.

Use of everolimus in de novo renal recipients: initial experience in the Greek population.

Although everolimus has proven to be as clinically efficacious as mycophenolate mofetil (MMF), there are reports that proliferation signal inhibitors are associated with poor tolerability. This study reported the experience of a Greek transplant center using either everolimus or MMF in de novo renal transplant recipients. In this retrospective study, a cohort of 40 patients who received everolimus after renal transplant was matched for 10 descriptive parameters with a cohort of another 40 patients who received MMF. The primary endpoint was renal function measured by creatinine and its clearance as well as wound dehiscence and opportunistic infections. The mean creatinine clearance at month 3 was 61.03 +/- 16.99 mL/min versus 60.99 +/- 8.03 for living related recipients on everolimus versus MMF, respectively. The mean creatinine clearance at month 3 was 71.24 +/- 12.61 and 62.61 +/- 20.24 mL/min for cadaveric recipients on everolimus versus MMF, respectively. In addition, the incidence of wound dehiscence was 33.34% versus 3.92% and the incidence of cytomegalovirus infection, 8.33% versus 17.64% for the same two groups, respectively.

Impact of double-j ureteric stent in kidney transplantation: single-center experience.

We retrospectively evaluated the use of double-j stent and the incidence of urological complications in 2 groups of patients who received a kidney transplant. From January 2005 to September 2007 we studied 172 patients receiving kidney transplants, 65 and 107 from living and cadaver donors, respectively. From the 172 patients, a total of 34 were excluded due to ureterostomy or Politano-Leadbetter ureterovesical anastomosis. Another 21 patients were excluded from the study due to graft loss due to acute or hyperacute rejection, cytomegalovirus (CMV) infection, or vascular complication. The remaining patients were divided into 2 groups: group A (44 patients) and B (73 patients) with versus without the use of a double-j-stent, respectively. The 2 groups were comparable in terms of donor and recipient gender, ischemia time, and delayed graft function. We failed to observes significant differences between the 2 groups in mean hospital stay (23 +/- 9 and 19 +/- 9), urinary leak (2.3% and 4.1%), and urinary tract infection (20.4% and 19.2%), among groups A and B, respectively. The only difference observed concerned the gravity of the urinary leak; no surgical intervention was needed among the double-j stent group versus 2 patients demanding ureterovesical reconstruction in the nonstent group. In conclusion, our data suggested that the routine use of a double-j stent for ureterovesical anastomosis neither significantly increased urinary tract infection rates, nor decreased the incidence of urinary leaks, but may decrease the gravity of the latter as evidenced by the need for surgical intervention.

The evolution of the role of liver transplantation in treating alcoholic cirrhosis in Greece.

BACKGROUND: Liver transplantation represents the main treatment for alcoholic cirrhosis. The goal of this article is to review the results of liver transplantation for alcoholic cirrhosis in Greece over the last 2 decades. METHODS: Among 247 patients who underwent liver transplantation between 1991 and 2007, 34 (13.7%) experienced alcoholic cirrhosis as the primary diagnosis. We reviewed their demographic data, stage of liver disease, and outcomes regarding survival via a Kaplan-Meier curve. Also we analyzed the causes of death and the postoperative complications. RESULTS: Mean Model for End-Stage Liver Disease (MELD) score was 18.4. Other diagnoses included hepatitis C virus (HCV; 23.5%), hepatitis B virus (HBV; 14.7%), and hepatocellular carcinoma (8.8%). Eleven patients died the most frequent causes being primary graft nonfunction (n = 3), hepatic artery thrombosis (n = 2), sepsis (n = 2), and portal vein thrombosis (n = 2). Complications included rejection (32.4%), infection (26.5%), hepatic graft dysfunction (11.8%), and recurrent HCV, recurrent HBV, and renal failure (8.8% each). Recurrence of alcoholism was observed in 3 patients (8.8%) with mild effects on liver function tests. There has been a significant increase in the number of liver transplantations for alcoholic cirrhosis in the last 6 years, namely 25 patients versus 9 in the previous 10 years. CONCLUSIONS: We observed a significant increase in the frequency of alcoholic cirrhosis leading to liver transplantation in the last several years in Greece.

Outcomes of kidney transplantation in Greek and Albanian patients: a single centre experience.

BACKGROUND AND AIM: It has been reported that racial and ethnic (genetic make up), as well as socioeconomic differences may affect the results of kidney transplantation. Socioeconomic factors are quite difficult to differentiate from genetic factors. It is not surprising that a group with poorer access to health care, less private insurance and less income does less well with serious medical problems. The aim of this study was to compare the outcomes of kidney transplantations in Greek (G) and Albanian (A) patients. PATIENTS AND METHODS: Twenty nine transplanted patients of Albanian ancestry were matched with 29 Greek patients retrospectively. Their mean age was 34 (G) and 31 (A) years, there were 21 men and 8 women in each group (G, A) and they received 26 kidneys from living related donors and 3 kidneys from cadaveric donors respectively. Arterial blood pressure (ABP), body weight (BW), serum creatinine, serum total protein and albumin, total cholesterol, HDL-cholesterol and triglycerides, 24 hour proteinuria were measured on 7th, 15th postoperative day, 1st , 3rd , 6th month and 1st year after transplant. BMI was calculated before and 1 year after transplantation and acute rejection episodes were recorded too. Methylprednizolone (MP), cyclosporine (CsA) dose /kg BW were calculated at baseline, 1, 3, 6, 12 months after transplant. Cumulative patient and graft survival at 1 and 5 years were calculated too. RESULTS: Patient survival at 1 and 5 years was 100% / 93.1% and 100% /93.1% respectively (p: NS). Graft survival at 1 and 5 years was 100% / 93.10% and 93.75% / 86.45% respectively (p: NS). BW (but not BMI) and total cholesterol levels in Greek patients were higher compared to those of Albanian patients during the 1st post transplant year (p: 0.044 and p: 0.021 respectively). MP dose in A patients was higher during the first year (p: 0.05). CONCLUSION: Patients and graft survival do not present difference between G and A patients. There is significant difference on cholesterol profile between G and A patients. A larger number of transplants are possibly needed to allow us to draw firm conclusions.

Cyclosporine enhances liver regeneration: the role of hepatocyte MHC expression and PGE2--a study relevant to graft immunogenicity.

AIM: We have investigated CsA induced liver hyperplasia to explore the potential effects on the immunogenicity of the regenerating liver within the clinical context of rejection after transplantation. MATERIALS AND METHODS: Flow cytometry analysis of hepatocytes, isolated 48 hours after 2/3 partial hepatectomy (PH2/3) or sham operation in rats, was performed to determine the effect of CsA on DNA synthesis and MHC molecule expression. The possible role of PGE2 was evaluated by the administration of SC-19220, an EP1-PGE2 receptor antagonist. RESULTS: CsA augmented liver regeneration and this was partially attenuated by SC-19220. The moderate expression of class I MHC expression, as well as the very low class II MHC expression detected in normal hepatocytes by flow cytometry was augmented after PH2/3 and reduced by CsA. The CsA-mediated decrease of hepatocyte immunogenicity was not SC-19220 dependent. CONCLUSIONS: It is proposed that the enhancing effect of CsA on hepatocyte proliferation is by means of an indirect mechanism that can be attributed to a) reduced immunogenicity of the regenerating liver as a result of inhibition of class I and II MHC hepatocyte expression and b) increased PGE2 synthesis in the liver mediated by its action on EP1 receptor.

Liver transplantation outcomes in patients with cirrhosis and hepatocellular carcinoma: experience of a single center in a viral hepatitis endemic area.

Our center has performed 205 orthotopic liver transplantations (OLT) in 201 patients. Hepatocellular carcinoma (HCC) was discovered in 32 (15%) patients, 5 of whom were diagnosed incidentally in recipient explants. The main underlying diagnosis was viral hepatitis (n = 28; 87.5%). Most patients (17; 53.1%) were diagnosed as having Child class B cirrhosis. Single tumors measuring <3 cm were diagnosed in 29 (90.6%) patients. Downstaging chemoembolization was performed in 7 (21.8%) patients. Preoperative aFP levels were normal in 20 (62.5%) patients. In the rest (n = 12; 37.5%), aFP levels normalized immediately after the OLT. In the latter group, 2 patients had a delayed (2 years) postoperative increase in aFP levels; both patients had tumor recurrence in the graft. All patients with hepatitis B received antiviral treatment with HBIG and lamivudine. There were 9 deaths (28.1%) in the immediate postoperative period (<30 days). One-year survival rate was 62.5% (n = 20). Actuarial 5-year survival rate was 55%, and actuarial 10-year survival rate was 40%. In conclusion, OLT has become the standard treatment for patients diagnosed with HCC in a population that shows cirrhosis most of the time to be secondary to viral hepatitis, provided that recipients are selected according to the size of the neoplasm and that they receive adequate antiviral prophylaxis.

Management of a giant ruptured hepatocellular adenoma. Report of a case.

This report describes a rare case of a young woman with massive intra-abdominal bleeding due to a giant ruptured hepatocellular adenoma. The patient had never used oral contraceptive pills and she was urgently operated for haemorrhage control in another hospital where the left hepatic artery was also ligated. After haemodynamic stabilization in the ICU and because of a complicated postoperative course (signs of intraabdominal sepsis) she was transferred to our hospital and a left lobectomy was performed. We present the case and comment on the preferred treatment modalities of hepatocellular adenomas.

Combined treatment of hypercholesterolemia of renal transplant allograft recipients with fluvastatin and gemfibrozil.

The aim of this study was to investigate the safety and efficacy of combined treatment with fluvastatin (F) and gemfibrozil (G) in hypercholesterolemic renal transplant recipients (RTR). Ten hypercholesterolemic (total cholesterol [TC] > 220 mg/dl) RTR (7 men) with mean age 44 years (range 25-56 years) who remained hypercholesterolemic after 3 months of treatment (period A) with fluvastatin (40 mg/d) continued taking the same dose of F plus G (600 mg/dl) for another 3-month period (B). Serum total cholesterol, high density lipoprotein cholesterol (HDL-C), LDL cholesterol (LDL-C), triglyceride, serum creatinine (creatinine phosphokinase (CPK), serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT) were measured before treatment and at the end of periods A and B. Mean TC levels were 360.30 +/- 62.42 mg/dl, 324.10 +/- 100.53 mg/dl, 270.80 +/- 67.77 mg/dl; mean LDL-C levels were 259.33 +/- 71.43 mg/dl, 219.60 +/- 81.31 mg/dl, 189.70 +/- 65.51 mg/dl; mean HDL-C levels were 37.10 +/- 11.68 mg/dl, 39.80 +/- 13.21 mg/dl, 41.00 +/- 12.94 mg/dl; mean triglyceride levels were 354.60 +/- 183.29 mg/dl, 349.30 +/- 242.94 mg/dl, 207.00 +/- 85.35 mg/dl before treatment and at the end of periods A and B, respectively. There was a statistically significant fall of serum TC (P = 0.002), LDL-C (P = 0.016), and triglyceride (P = 0.029) levels at the end of periods A and B. Kidney and liver function did not change. F and G combined treatment is safe and useful in patients who do not respond satisfactorily to monotherapy with F. Gemfibrozil augments the effect of F on TC, LDL-C, and triglyceride levels.

Prosthetic mesh repair of multiple recurrent and large abdominal hernias in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to find out whether prosthetic mesh repair of recurrent and large abdominal hernias in continuous ambulatory peritoneal dialysis (CAPD) patients is effective in maintaining them on CAPD. DESIGN: Retrospective analysis of case notes over a period of 5 years. SETTING: Single renal unit of a university hospital. PATIENTS: Forty-six of 217 CAPD patients (16%) had their hernias repaired. Among them, 5 women in whom hemodialysis was not possible had multiple or large hernias repaired with polypropylene (PP) mesh. RESULTS: Radical repair was achieved by a modified operation consisting of a conventional hernioplasty complemented by a supporting prostetic overlay mesh, without discontinuation of CAPD. The patients continued CAPD for a mean period of 17.6 months without hernia recurrence. Two patients died in the twelfth and fifteenth post-operative month due to cardiac arrest and hepatic failure, respectively, and the remaining 3 are alive and have been doing well on CAPD for 13, 14, and 21 months. CONCLUSIONS: Prosthetic mesh repair of large recurrent hernias in CAPD patients with vascular access problems seems to be a valuable method to maintain them on this renal replacement therapy.