Abnormal circadian blood pressure regulation in liver transplanted children.

HT is a frequent cardiovascular risk factor in liver transplant recipients. However, there are only few studies in the literature regarding the risk of HT in liver transplanted children. The aim of this study was to assess the 24 h BP profiles of liver transplanted patients and to compare the results with healthy children. ABPM was performed on 20 liver transplanted patients and 27 healthy children aged 7.1 ± 4.8 and 8.5 ± 2.9 yr, respectively. HT was defined as SDS > 1.64 (i.e., >95th percentile) adjusted for gender and height. The mean duration of post-transplant follow-up was 32 ± 19 months. Six (30%) patients were found to be hypertensive. The physiological nocturnal BP fall was attenuated significantly in the study group for diastolic BP (11.5 ± 6.1 mmHg vs. 17.7 ± 7.1 mmHg, p = 0.006). Specifically, the number of patients with high nighttime systolic and diastolic BP SDS (p = 0.02 and p = 0.004, respectively) as well as elevated nighttime systolic (p = 0.03) and diastolic (p = 0.003) BPLs was found to be significantly higher than those in the controls. Alteration of the "normal" circadian rhythm is very frequent in liver transplant recipients. Thus, it is recommended to perform ABPM on all liver transplanted children not to underdiagnose HT.

Micronucleus frequencies in peripheral blood lymphocytes of children with chronic kidney disease.

One of the crucial adverse effects of chronic kidney disease (CKD) and its treatment is an elevated cancer risk. There are no data on cytogenetic effects in children with CKD or children undergoing dialysis or those who have received a transplant. In this study, cytogenetic effects in children with CKD in pre-dialysis (PreD) stage, on regular haemodialysis (HD) and transplanted (Tx) compared with a control group of healthy children has been investigated using the cytokinesis-blocked micronucleus (CBMN) assay and fluorescence in situ hybridisation (FISH) combined with CBMN (CBMN-FISH) in peripheral blood lymphocytes. The results revealed a significant increase (P < 0.001) in micronucleus (MN) frequencies [mean ± SD (n)] in the PreD, HD and Tx groups versus the control group [CBMN assay; 9.19 ± 2.61 (16), 9.07 ± 4.86 (15), 6.12 ± 5.33 (17) versus 1.60 ± 0.99 (20), respectively]. Moreover, centromere negative micronucleus (C- MN) and centromere positive micronucleus (C+ MN) frequencies were significantly higher in each subgroup children (PreD, HD and Tx) than in the control group (P < 0.01) although children in Tx group had lower C- MN frequencies than PreD and lower C+ MN frequencies than PreD and HD groups (P < 0.05). Additionally, MN frequencies in mononuclear cells, nucleoplasmic bridges and nuclear buds in binucleated cells were increased in children with CKD (P < 0.001, P < 0.001, P > 0.05, respectively). The nuclear division index significantly decreased in Tx group relative to the control, PreD and HD groups (P < 0.001). Associations between cytogenetic parameters and creatinine or blood urea nitrogen were found (P < 0.05). To provide longer and better life expectancy of children with CKD and treatment modes, further research is needed to better understand and avoid these effects.

Protective role of simvastatin on lung damage caused by burn and cotton smoke inhalation in rats.

BACKGROUND: Smoke inhalation injury is a major comorbid factor in patients with thermal injury and occurs in about 30% of patients with major burns. In addition, inhalation injury reportedly accounts for 20%-84% of the mortality in burned individuals and is associated with higher mortality rates for every age and burn size category. The aim of the present study was to investigate the effects of simvastatin on lung damage with burn and cotton smoke inhalation. METHODS: Wistar rats were randomly assigned to three groups: saline treated control group, via an orogastric route (group 1, n = 6), burn (30%) and cotton smoke inhalated group (group 2, n = 6), and simvastatin treated (25 mg/kg/d, via an orogastric route) burn (30%) and cotton smoke inhalated group (group 3, n = 6). Rats were sacrificed at 48 h of the treatments and the trachea and lungs were removed completely. Tissue samples were taken for histopathologic, immunohistopathologic, and biochemical analyses. Univariate analysis of variance coupled with Duncan's post-hoc test was performed for statistical evaluation. RESULTS: Lung parenchymal and tracheoepithelial damage was confirmed in group 2 by histopathologic examination. Lung malonedialdehyde (MDA) levels were significantly decreased (P < 0.001), while glutathione (GSH) concentration did not alter in group 2 compared with group 1. Also, immunopathologic data revealed that epithelial iNOS level was elevated, while no modulation was detected in the level of myeloperoxidase (MPO). Simvastatin administration resulted in decreasing the lung parenchymal and tracheoepithelial damage. Tissue MDA levels were decreased significantly (P < 0.001), whereas GSH concentrations were elevated in group 3 compared with group 1 and group 2 (P < 0.001). Simvastatin treatment caused a decrease in epithelial iNOS levels, while MPO levels were not modulated. In addition, simvastatin significantly reduced pulmonary apoptosis in lung injury. CONCLUSIONS: Our results have indicated that simvastatin administration seems to play beneficial role in lung injury of rats promoted by combined burn and smoke inhalation. Thus, simvastatin may represent a potential approach to prevent smoke inhalation-associated lung dysfunction. However, the significant decrease in basal oxidant production may cause impairment in cellular signalling processes.

Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay.

One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean ± SD) (5.22 ± 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 ± 1.23), (4.91 ± 1.35), and (5.79 ± 1.94), respectively, vs the healthy children (2.74 ± 2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy.

An extremely uncommon variation of left hepatic artery around the esophagus: a case report.

An extremely rare case of a replaced left hepatic artery (LHA) around the esophagus in a deceased multi-organ donor is reported. The liver could not be harvested unless either of the LHA or the esophagus was transected. This is the second report of a LHA off the left gastric artery with such a peculiar course around the esophagus. Whether to cut the artery or the hollow viscus in such a situation is controversial; nevertheless, a surgeon must precisely identify all the extrahepatic arteries during liver harvest, to prevent injuries that might result in compromised complete arterialization of the graft.

Rituximab for post-transplant recurrences of FSGS.

A 14-yr-old boy whose primary kidney disease was FSGS developed severe recurrence of proteinuria immediately after a second living-related kidney transplant. Despite pre- and post-operative PP and immunosuppressive treatment consisting of steroids, CycA, daclizumab, and MMF, daily protein excretion and serum creatinine increased. We therefore administered rituximab on the fourth day of transplantation. He received four weekly doses of rituximab (375 mg/m(2)/dose), which resulted in a rapid clearing of circulating CD19-positive B cells, and remission of proteinuria was achieved six wk after the first rituximab treatment. Graft function was excellent six months after transplantation with proteinuria of 8 mg/m(2)/h. We conclude that rituximab may be an effective treatment for post-transplant recurrence of FSGS.

Effect of different intra-abdominal pressure levels on QT dispersion in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Hemodynamic changes caused by carbon dioxide (CO(2)) insufflation occur frequently in patients who undergo laparoscopic surgery. One indicator of these changes is corrected QT dispersion (QTcd), an index of myocardial function. Prolongation of QTcd has been associated with cardiovascular morbidity and mortality. We compared the effects of high-pressure (15 mmHg) and low-pressure (7 mmHg) CO(2) pneumoperitoneums on the QT interval, the rate-corrected QT interval (QTc), the QT dispersion (QTd), and the corrected QT dispersion (QTcd) during laparoscopic cholecystectomy. METHODS: Twenty consecutive patients were in a low-pressure pneumoperitoneum group and 32 were in a high-pressure pneumoperitoneum group. A 12-lead electrocardiogram was used to monitor cardiac variables. In all patients, serial electrocardiograms were recorded before anesthesia induction (baseline), immediately after the pneumoperitoneum had been created, every 15 minutes during CO(2) insufflation, and 5 minutes after deflation. Two observers measured the QT intervals independently, and the QTcd was calculated using Bazett's formula. RESULTS: The QT interval and the QTc interval did not change significantly during the study in either group. The QTd and QTcd in the high-pressure pneumoperitoneum group increased significantly during CO(2) insufflation and were significantly higher in the high-pressure pneumoperitoneum group compared with the low-pressure pneumoperitoneum group. Changes caused by CO(2) insufflation were reversible. CONCLUSIONS: Statistically significant increases of QTd and QTcd, which are associated with an increased risk of arrhythmias and cardiac events, occur during CO(2) insufflation in both high-pressure and low-pressure pneumoperitoneums. QTd and QTcd were significantly higher in the high-pressure pneumoperitoneum group than they were in the low-pressure pneumoperitoneum group. QT interval changes were not related to anesthetic agents, surgical stress, hypercapnia, or duration of CO(2) insufflation. Increased intra-abdominal pressure may have caused these changes.

Treatment approaches for spontaneous retroperitoneal bleeding.

In this study, we investigated critical issues in the diagnosis and treatment of spontaneous retroperitoneal bleeding. The medical records of 16 patients who were admitted to the emergency department and were diagnosed as having spontaneous retroperitoneal bleeding were reviewed retrospectively. Retroperitoneal bleeding was diagnosed by intravenous contrast-enhanced computed tomography in 8 men and 8 women (median age, 70.5 years; mean hemoglobin level, 7.4 +/- 1.3 mg/dl). Thirteen patients (81%) received conservative treatment. Bleeding was controlled by therapeutic angiographic intervention in two patients (12%) and by surgery in one patient (6%). Two patients (12%) died. Clinicians should suspect retroperitoneal bleeding in anemic patients who are admitted to an emergency department. If active bleeding is detected, interventional radiologic methods should be used as the initial treatment, and surgery can be performed if conservative and interventional radiologic methods fail.

Male breast cancer: thirteen years experience of a single center.

BACKGROUND: This retrospective study analysed the epidemiological, clinical, and therapeutic profiles of breast cancer in males. METHODS: We report our experience at the Hospital of the University of Baskent, where 20 cases of male breast cancer were observed and treated between 1995-2008. RESULTS: Median age at presentation was 66,7 +/- 10,9 years. Average follow-up was 63 +/- 18,5 months. The main presenting symptom was a mass in 65% of cases (13 patients). Ynvasive ductal carcinoma was the most frequent pathologic type (70% of cases). CONCLUSION: Male breast cancer patients have an incidence of prostate cancer higher than would be predicted in the general population. Cause of men have a higher rate of ER positivity the responses with hormonal agents are good.

Value of an individual liver biopsy in the preoperative evaluation of apparently healthy potential liver donors.

Living donor liver transplantation has acquired widespread acceptance. A thorough workup of the potential living donor is guided by 2 objectives: the first is ensuring the safety of the surgical procedure for the donor, and the second is identifying donor grafts that pose potential risks for the recipient. Of 305 living-related liver donors, liver biopsy was performed in 201. The results of those patients' liver function tests and serologic tests were within normal limits. Forty-one of the 201 patients had steatosis on abdominal ultrasonography or tomography. Of 201 liver biopsies, 94 (46.8%) demonstrated normal findings, whereas 107 (53.2%) showed abnormal findings on pathology. Of 107 patients with abnormal pathological findings, 32 (29.9%) had fatty changes, 4 (3.7%) had steatohepatitis, and 71 (66.4%) had nonsteatotic histologic findings including fibrosis, hepatitis, and granulomatous reactions. In conclusion, our data show that half of the living-related liver donors, appearing absolutely healthy, had biopsies with abnormal pathology results. As it is well known that increasing percentages of steatosis may reduce the functional mass of the graft and occult liver diseases may not be detected without liver biopsy, we recommend that liver biopsies be part of the routine evaluation protocol for living-related liver donors in all transplantation institutions.

MR cholangiopancreatography with T2-weighted prospective acquisition correction turbo spin-echo sequence of the biliary anatomy of potential living liver transplant donors.

OBJECTIVE: The objective of our study was to evaluate the ability of a respiratory navigator-triggered T2-weighted turbo spin-echo (TSE) sequence with a prospective acquisition correction (PACE) technique for MR cholangiopancreatography (MRCP) to depict the biliary anatomy of living donor liver transplantation (LDLT) donors. SUBJECTS AND METHODS: Forty potential LDLT donors who ranged in age from 19 to 54 years were prospectively evaluated with preoperative MRCP. MRCP was performed with a 1.5-T magnetic field using T2-weighted PACE TSE sequence. MRCP source data sets were processed with maximum-intensity-projection (MIP) and shaded surface display (SSD) algorithms. Findings were compared with intraoperative cholangiography. Biliary anatomy was classified according to the classification proposed by Huang and colleagues. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRCP for the detection of aberrant biliary anatomy were calculated. RESULTS: Intraoperative cholangiography and biliary exploration revealed that 27 donor candidates (67.5%) had conventional and 13 (32.5%) had aberrant biliary anatomy. Two donors (5%) had type B biliary anatomy; eight donors (20%), type C; two donors (5%), type D; and one donor (2.5%), unclassified. The sensitivity of MRCP source data sets in differentiating aberrant biliary anatomies from nonaberrant ones was 100%, the specificity was 88.9%, and the accuracy was 92.5%. PPV and NPV were 81.3% and 100%, respectively. The sensitivity of MIP images in differentiating aberrant biliary anatomies was 100%, the specificity was 88.9%, and the accuracy was 92.5%. PPV and NPV were 81.3% and 100%, respectively. The sensitivity, specificity, accuracy, PPV, and NPV of the SSD images in detecting aberrant biliary anatomies were 100%, 77.8%, 85%, 68.4%, and 100%, respectively. CONCLUSION: Preoperative MRCP using a respiratory navigator-triggered T2-weighted TSE sequence with a PACE technique accurately depicts the biliary anatomy in LDLT donors and may guide intraoperative management of the biliary tract.

Long-term survival in a patient after heterotopic segmental auxiliary liver transplantation.

Auxiliary liver transplantation has been used mostly for patients with acute liver failure, but between 1980 and 2000, it has gained wider application for patients with both acute and chronic liver diseases. It is particularly applicable in patients in whom there is specific indication for removing the native liver. However, to date, very few patients have survived auxiliary liver transplantation in the long term. In this report, we describe a patient with normal liver function following heterotopic segmental auxiliary liver transplantation whom we followed for nine yr.

Outcome of pediatric liver transplant in grafts with multiple arteries.

Young age, small diameter of the hepatic artery, presence of multiple arteries, and the selected technique are risk factors for hepatic arterial complications. We report the outcomes of pediatric liver transplant (LT) patients who had received a liver graft with multiple arteries. Since April 2001, 89 pediatric LTs have been performed at our center. Twenty-six liver grafts (29.2%) that had multiple hepatic arteries were analyzed retrospectively. Twenty-five grafts had 2, and 1 graft had 3, hepatic arteries. In 17 grafts with double arteries, and in 1 graft with 3 arteries, the adjacent edges of the hepatic arteries were sutured together at the back table to create a single opening, and the recipient's common hepatic artery was then anastomosed to that orifice. In 8 grafts with double arteries, 2 separate anastomoses were performed between the graft hepatic arteries and the recipient's hepatic artery branches. The mean age of the recipients was 7.9 +/- 5.4 years (range, 0.6-17 years). During the early postoperative period, hepatic arterial thromboses occurred in 3 recipients. Two of these 3 recipients were treated with transcatheter arterial thrombolysis using streptokinase or recombinant plasminogen and intraluminal stent placement, and the remaining recipient was treated with a re-anastomosis using a polytetrafluoroethylene graft. Three recipients died during follow-up, which ranged from 1 to 71 months. In conclusion, multiple graft arteries did not increase the incidence of hepatic arterial complications in our series.

Long term follow-up of glomerular and tubular functions in liver transplanted patients with Wilson's disease.

The aim of this study was to determine the long term outcome of renal glomerular and tubular functions in children receiving an LT for WD. Renal functions were examined in nine children with WD before and long after LT and compared with those of nine liver transplanted children with hepatic diseases other than WD. The duration of follow-up was at least two yr for both groups. GFR, fractional TRP and tubular maximum rate of phosphate reabsorption in relation to GFR (TP/GFR) as well as daily protein and Ca excretion were studied in both groups before and after LT. Pretransplant mean GFR, TRP and TP/GFR were significantly lower in the study group than the controls. A significant increase in the post-transplant TRP and TP/GFR was observed in the study group and the difference between the groups disappeared during the long term follow-up. Urinary protein excretion decreased in both groups after LT. Tubular dysfunction is frequent in patients with WD. LT for hepatic failure secondary to WD is a lifesaving procedure correcting the underlying hepatic defect as well as renal defects.

Liver transplant in an infant with bilateral cystic neuroblastoma complicated by hepatic metastases and life-threatening consumption coagulopathy.

Here we report a patient with stage-4 bilateral cystic adrenal neuroblastomas with disseminated liver metastases and consumption coagulopathy who underwent liver transplant. Our patient was initially diagnosed with infantile hepatic hemangioendothelioma and bleeding into the adrenal glands secondary to consumption coagulopathy (Kasabach-Merritt syndrome). Liver transplant was performed as a life-saving procedure under this diagnosis. We discuss this unique patient because of the diagnostic pitfalls of this rare disease and the successful clinical outcome after LT and subsequent chemotherapy for neuroblastoma.

Interventional radiology in liver transplant.

An increased number of transplant centers now actively perform deceased-donor as well as living-related liver transplants. Although postoperative vascular and nonvascular complications after liver transplant have been well documented, early diagnosis and intervention are important to increase graft and recipient survival. With improvements in interventional radiologic techniques and a multidisciplinary approach to liver transplant, management of complications by percutaneous and endovascular techniques is possible with less morbidity and mortality. This article outlines the recent developments in, and applications of, interventional radiologic techniques in liver transplant patients.

Pulmonary complications and mortality after liver transplant.

OBJECTIVES: Pulmonary complications after liver transplant significantly affect mortality and morbidity; however, their relation has not been clearly established. We sought to determine pulmonary complications during the early and late term after liver transplant and identify risk factors for mortality. MATERIALS AND METHODS: At our institution, 130 liver transplant patients (mean age, 40.1 -/+ 14.6 years; 71.1% male) were retrospectively evaluated, and 114 adult orthotopic liver transplant patients were included. Cause of liver disease, pulmonary function test results, arterial blood gas analyses, surgery duration, length of stay in the intensive care unit and the hospital, pulmonary complications, and mortality causes were noted. RESULTS: Pulmonary complications were detected in 48 patients (42.1%), pneumonia in 24 patients (21.1%), and pleural effusion in 21 patients (18.4%). Development of pulmonary complications was found to be significantly related to survival (P = .001). Fifty-two patients (45.6%) were smokers, a significant predictor of pulmonary complications (P = .03). There was no relation between pulmonary function test results and orthodeoxia and pulmonary complications and mortality. Early and late survival rates were significantly lower in patients in whom a microorganism was isolated on deep tracheal aspirate culture, while early survival was significantly reduced in the presence of a pleural effusion (P < .005). CONCLUSIONS: Pulmonary complications after liver transplant are common. Care must be taken to determine preoperative risk factors, and patients should be observed closely for development of respiratory complications after liver transplant.

Pediatric liver transplant: results of a single center.

OBJECTIVES: Liver transplant in the pediatric population has become an accepted treatment modality for children with end-stage liver disease. In this study, we analyze our experiences with pediatric liver transplant at our center. MATERIALS AND METHODS: Since September 2001, 8 deceased-donor and 96 living-donor liver transplants have been done in 101 children (mean age, 6.7 +/- 5.5 years; range, 2 months to 17 years). The children's charts were reviewed retrospectively. RESULTS: Indications for liver transplant were cholestatic liver disease (n=17), biliary atresia (n=24), Wilson's disease (n=16), fulminant liver failure (n=18), hepatic tumor (n=13), and other (n=13). The median pediatric end-stage liver disease score was 23.1 +/- 11.1 (range, -8 to 48). The median follow-up was 24.2 +/- 19.4 months (range, 1-77 months). Three children underwent retransplant. The main complications were infections (25.9%) and surgical complications (39.5%) (including biliary complications and vascular problems). The incidence of acute cellular rejection was 42.3%. Sixteen children died during follow-up, and, at the time of this writing, the remaining 85 children (85%) were alive with good graft functioning, showing patient survival rates of 90%, 85%, and 83% at 6, 12, and 36 months, respectively. CONCLUSIONS: In conclusion, the overall outcomes of pediatric liver transplantation at our center are quite promising.

Expanded criteria for hepatocellular carcinoma and liver transplantation.

In this study, we evaluated our early results of liver transplantation for hepatocellular carcinoma. Between January 2003 and June 2006, 26 patients (4 women and 22 men; age, 1.1-65 years) with preoperatively diagnosed or incidental hepatocellular carcinoma (HCC) underwent liver transplantation at our center. Inclusion criteria (independent of tumor size and number of tumor nodules) were no invasion of major vascular structure and no evidence of extrahepatic disease. In 13 of the patients, tumors were beyond the Milan criteria. At this writing, with a mean follow-up of 16.5 months (range, 1-31 months), all patients are doing well with excellent graft function. The longest survival is 2.5 years, and our patient survival rate is 100%. There has been only one tumor recurrence that was 4 months after liver transplantation. Liver transplantation provides long patient and disease-free survival, even in patients with HCC that exceeds the Milan criteria.

Perioperative anesthetic management for recipients of orthotopic liver transplant undergoing nontransplant surgery.

OBJECTIVES: The number of organ transplant recipients who present for nontransplant surgery has increased annually. The aim of this study was to evaluate the perioperative anesthetic management of recipients of an orthotopic liver transplant who have undergone nontransplant surgery at Baskent University Hospital. PATIENTS AND METHODS: The medical records of 22 recipients of an orthotopic liver transplant who had undergone a total of 32 nontransplant elective surgeries between December 1988 and February 2006 were retrospectively reviewed. Demographic information, including the anesthetic management and the results of perioperative liver and renal function tests, was recorded. RESULTS: The mean age of the patients at the time of transplant was 20.2 +/- 17.9 years. The mean interval from liver transplant to the first surgery was 739.1 +/- 502.2 days. The most frequent type of surgery was abdominal (28.1%). The types of anesthetic techniques used were general (75%), regional (9.4%), local (9.4%), and sedoanalgesia (6.3%). General anesthesia was induced with thiopental, propofol, or ketamine, and was maintained with isoflurane and nitrous oxide. Endotracheal intubation was performed in 43.8% of the patients. Spinal anesthesia was induced in 3 patients, and peripheral neural blockage was used in 2 patients. Prothrombin time, activated partial thromboplastin time, international normalized ratio, and levels of serum alanine transaminase, aspartate transaminase, total bilirubin, blood urea nitrogen, and creatinine were similar preoperatively and on the first day after surgery (P > .05). CONCLUSIONS: In this study, neither regional nor general anesthesia was associated with a deterioration of liver function. We suggest that recipients of orthotopic liver transplant can undergo nontransplant surgery without postoperative graft dysfunction if hepatic perfusion is maintained with appropriate anesthetic management.