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Mohamed Rela

Publications and source records attributed to Mohamed Rela.

At least 19 recordsLinked to original sources
PubMed2006

Staged resection for a ruptured hepatoblastoma: a 6-year follow-up.

Hepatoblastoma (HB) is a rare germ cell tumour of childhood usually presenting with progressive abdominal distention. However, presentation as acute abdomen is a rare occurrence and is secondary to spontaneous rupture. This presentation carries high mortality. To our knowledge, six cases of ruptured hepatoblastoma have previously been reported, although the long-term outcome has not been clear. We report a case of ruptured HB who was managed by initial control of haemorrhage by laparotomy followed by chemotherapy with high-risk hepatoblastoma protocol as per SIOPEL 2 (cisplatin, carboplatin and doxorubicin) and a staged hepatectomy 5 months later. Patient is currently disease free at 6-year follow-up. Staged hepatectomy after initial control of haemorrhage does not preclude a curative resection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Ischemic preconditioning of cadaver donor livers protects allografts following transplantation.

BACKGROUND: Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts. METHODS: Cadaveric donor livers were subjected to IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by reperfusion. Biopsies were obtained from the preconditioned (n=9) and control nonpreconditioned (n=14) liver transplants prior to and 2 hr following reperfusion. Cryosections were stained with antibodies against neutrophils and platelets. RESULTS: IP livers were associated with significantly lower serum levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016) and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following transplantation. Furthermore, recipients of IP livers spent a significantly shorter time in the intensive care unit following transplantation compared to those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008). Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none of the IP allografts showed any change in the levels of platelets or neutrophil infiltration following transplantation. CONCLUSION: IP is an effective method of protecting cadaver donor allografts from cold ischemia and subsequent reperfusion injury. IP is also associated with a reduction in the nonspecific inflammatory response.

Adult↗
PubMed2006

Isolation of hepatocytes from livers from non-heart-beating donors for cell transplantation.

One of the limitations to hepatocyte transplantation is the restricted availability of donor liver tissue. The aim of this study was to evaluate livers from non-heart-beating donors (NHBDs) as a source of hepatocytes for cell transplantation. A total of 20 livers/segments obtained from NHBD were perfused under good manufacturing practices using a standard collagenase digestion method. The donor liver median warm ischemia time was 15 minutes (range, 11-40 minutes), and cold ischemia time was 13 hours (range, 6-30 hours) prior to cell isolation. The cell viability of the hepatocytes obtained was 52% (1-81%), with a yield of 2.2 x 10(6)(0.2-29.7 x 10(6)) cells per gram of tissue. There was a significant negative correlation between hepatocyte viability and length of both warm ischemia (r = -0.544, P = 0.013) and cold ischemia (r = -0.510, P = 0.022). Preliminary experiments were performed on the viability testing of NHBD livers based on digestion of needle biopsies with collagenase and assessment of the hepatocytes produced. Two of the NHBD cell preparations, which had been cryopreserved, were used as part of a series of cell infusions for hepatocyte transplantation. A 3.5-yr-old girl with Crigler-Najjar syndrome type I received 9.7 x 10(8) NHBD hepatocytes (viability on thawing, 65%), and a 4-month-old boy with inherited clotting factor VII deficiency received 5.0 x 10(8) hepatocytes (viability, 57%). In conclusion, hepatocytes suitable for cell transplantation can be obtained from NHBD livers. Higher viability values may be obtained if both warm and cold ischemia times of donor liver can be reduced prior to processing.

Adolescent↗
PubMed2006

Primary pancreatic lymphoma: diagnostic and therapeutic dilemma.

OBJECTIVES: Non-Hodgkin lymphoma predominantly involving the pancreas is a rare tumor and accounts for less than 0.7% of all pancreatic malignancies and 1% of extranodal lymphomas. Diagnosis of primary pancreatic lymphoma can be difficult because it may mimic carcinoma. The principal aims of this review were to highlight the difficulties encountered in making a diagnosis and to identify the role of surgery. METHODS: A PubMed search was conducted using the following terms: primary pancreatic lymphoma and non-Hodgkin lymphoma of the pancreas. Additional references were sourced from key articles. RESULTS: A total of 89 reported cases of pancreatic lymphoma between 1951 and 2005 were reviewed. An accurate preoperative diagnosis of primary pancreatic lymphoma is not always possible. A complete response rate of 100% and a long-term survival rate of 94% have been reported with surgery and adjuvant chemotherapy when compared with a 5-year survival rate of less than 50% and an overall 3-year disease-free survival rate of 44% with current chemotherapy, radiotherapy, or combined methods. CONCLUSION: Pancreaticoduodenectomy may have a therapeutic role in association with chemotherapy.

Antineoplastic Agents↗
PubMed2005

Functional status of patients before liver transplantation as a predictor of posttransplant mortality.

BACKGROUND: Risk models for mortality after liver transplantation have poor predictive ability. We examined whether the performance of these risk models can be improved by including information about patients' functional status (i.e., their ability to carry out activities of daily living) in addition to conventional clinical risk factors. METHODS: The UK and Ireland Liver Transplant Audit has data on all liver transplantations carried out in both countries since 1994. We examined the association of functional status measures taken immediately before transplantation on a 5-point scale (modified version of the Eastern Cooperative Oncology Group performance status) and mortality 90 days after transplantation. Logistic regression was used to adjust for other risk factors. RESULTS: Posttransplant mortality increased from 5.3% in patients able to carry out normal activity without restriction (functional status 1) to 24.8% in patients completely reliant on nursing and medical care (functional status 5; P for trend 0.003). This association remained after adjustment for conventional risk factors (adjusted P for trend 0.003). Adjusted odds ratios with functional status 3 (the most frequent functional status) as baseline category were 0.60 (95% confidence interval 0.29-1.25) for functional status 1, 0.70 (0.50-0.97) for functional status 2, 1.00 (0.71-1.41) for functional status 4, and 1.85 (1.07-3.19) for functional status 5. CONCLUSIONS: Considering a patient's functional status or more general measures of a patient's health status before transplantation in addition to conventional clinical factors may help to improve our ability to predict posttransplant survival.

Activities of Daily Living↗
PubMed2005

Detection and clinical significance of bone marrow micrometastases in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Existing methods of selecting patients with hepatocellular carcinoma (HCC) for liver transplantation rely on computed tomography and magnetic resonance imaging, which fail to detect vascular invasion or micrometastases. Vascular invasion cannot be assessed pretransplant because of the risks of tumor biopsy. Pretransplant detection of micrometastases in bone marrow is an alternative method that may identify patients at risk of recurrence and permit better organ allocation. The authors' aim was to develop an accurate method of detecting hepatocellular carcinoma micrometastases that may have a clinical role in pretransplant assessment. METHODS: Iliac crest bone marrow was sampled from 18 patients with HCC (before liver transplantation) and 14 controls (cirrhosis, 9; hematologic disorders, 5). Mononuclear bone marrow fractions were evaluated for the presence of micrometastases by immunocytochemistry (ICC) using Hep Par-1 (HPICC) and Glypican-3 (GPICC), and by reverse-transcriptase (RT) polymerase chain reaction using two primer pairs targeting albumin (Alb1RT and Alb2RT) and one pair targeting alpha-fetoprotein (AFPRT). Each marker was compared in terms of (1) specificity and (2) positive and negative predictive values for tumor recurrence. RESULTS: The specificity of each marker for detecting HCC micrometastases were as follows: HPICC, 93%; GPICC, 92%; Alb1RT, 33%; Alb2RT, 59%; and AFPRT, 0%. The positive (negative) predictive values for HPICC, GPICC, and Alb2RT for posttransplant tumor recurrence were 42% (100%), 40% (73%), and 0% (43%), respectively. HPICC-positive micrometastases were identified in all patients with postoperative tumor recurrence (n=5) and in 75% of patients with microscopic vascular invasion. CONCLUSIONS: Detection of HCC micrometastases in bone marrow of potential liver transplant candidates is a potentially useful technique that may provide important prognostic information without the need for preoperative tumor biopsy. The authors' preliminary data indicate that HPICC is a promising immunocytochemical marker for HCC micrometastases, and larger studies are needed to confirm its clinical role.

Actins↗
PubMed2005

Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation.

Renal dysfunction of variable severity is being increasingly recognized as a major complication of calcineurin inhibitors (CI), in some patients even necessitating renal transplantation. Close and effective monitoring of the renal function is indicated. Current methods for this monitoring are calculation of the glomerular filtration rate (GFR) based on creatinine or exogenous substances like 51Cr-EDTA. The first method is unreliable in children and the second is expensive and cumbersome. Cystatin C has been shown to be an accurate marker of glomerular filtration but has not been evaluated in a large cohort of pediatric patients before and after liver transplantation (LT). We evaluated the accuracy of cystatin C in 62 children (30 male) with LT, who had their 51Cr-EDTA measured on 40 occasions prior to LT and on 47 occasions after LT. The reciprocal of cystatin C correlated better with 51Cr-EDTA GFR (r = .78) than the reciprocal of creatinine (r = .40). Diagnostic accuracy in the identification of reduced GFR was assessed by ROC analysis. Cystatin C yielded the highest area under the ROC curve (AUC) in all groups assessed. From these data a cutoff level of cystatin C predicting 51Cr-EDTA GFR < 80 ml/min/1.73 m2 was calculated. A level of 1.06 mg/L was found to have a sensitivity of 91% and a specificity of 81%. Applying this cutoff level in our patient group would have avoided 51Cr-EDTA GFR estimation in 43 of the 87 estimations. In conclusion, the use of this simple test could be recommended as screening of renal dysfunction in children with liver disease and after LT.

Biomarkers↗
PubMed2005

Neonatal hemochromatosis--medical treatment vs. transplantation: the king's experience.

The aim of our study was to compare the outcome of medical treatment vs. liver transplantation in infants with neonatal hemochromatosis (NH) referred to King's College Hospital from 1990-2002. We conducted a retrospective review of 19 children from 14 families. Fifteen children presented at birth and 4 during the first week of life. One child was diagnosed by cordocentesis at 30 weeks of gestation. NH recurred in 7 of 9 families with further children. In one family, 2 children from different fathers were affected. All patients had elevated ferritin levels, hypoalbuminemia, and coagulopathy. Liver histology showed parenchymal collapse, diffuse fibrosis, and moderate to severe hepatocyte hemosiderin deposition. Extrahepatic siderosis was demonstrated by magnetic resonance in 2 patients, lip biopsy in 3, and autopsy in 10. Ten patients received a chelation-antioxidant cocktail: 1 survived, 4 died, and 5 required liver transplantation, of whom 2 died. One of the 9 infants who did not receive the cocktail survived with medical support, 3 died, and 5 required transplantation, of whom 3 died. Seven children are alive, 5 after transplantation, at a median follow-up of 5.6 years, with excellent quality of life and no recurrence of the disease. In conclusion, chelation-antioxidant treatment does not appear to modify the prognosis of NH, at least in severe cases. Liver transplantation, with 50% long-term survival, remains the treatment of choice and should be promptly offered to those infants who do not improve with supportive medical treatment.

Antioxidants↗
PubMed2005

Isolation, purification and flow cytometric analysis of human intrahepatic lymphocytes using an improved technique.

Intrahepatic lymphocytes (IHL) with their diverse and distinctive subsets emphasise the importance of the liver as a site of immunological activity, but special care is required for their isolation and characterisation. Protocols for IHL isolation, purification and FACS analysis were devised and compared with published extraction protocols. We have reduced the time that IHL are exposed to potentially damaging enzymes during extraction and purified specific subsets using monoclonal antibody (mAb)-coated magnetic microbeads. This has yielded IHL populations with higher viability than previously described protocols (92-95%, compared with 39-86%). Flow cytometric characterisation of IHL subset immunophenotypes was optimised by combining CD45 staining (fluorescence gating) with traditional light scatter properties. Using a panel of mAb and liver biopsies obtained from 23 cadaveric liver transplant donors, we show that the normal liver contains a heterogeneous IHL population with distinctive phenotypes. CD8+ IHL was the predominant population with a mean CD4/CD8 ratio of 1:1.7. Up to 40% of IHL expressed gammadeltaTCR and a third expressed CD56 NK marker; indicating a site of intense immunological activity. The techniques described will allow these cell types to be isolated, fully characterised and their physiological functions to be determined. The histologically normal liver contains heterogeneous and diverse IHL with large numbers of CD8+, NK, NKT and gammadelta+ cells.

Adolescent↗
PubMed2005

Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts.

BACKGROUND: To increase the number of livers available for transplantation a non-heartbeating donor (NHBD) liver transplant program was started after obtaining hospital ethical committee approval. METHODS: Controlled donors with a warm ischemia of <30 minutes were considered. A 5-minute stand-off period was observed from asystole to skin incision. A super-rapid technique was used for the retrieval. Methods used to assess the suitability for transplantation included liver function tests, morphologic and histologic assessment, and hepatocyte viability testing. RESULTS: Sixty livers were retrieved from NHBDs. Of these, 33 were judged suitable for transplantation. Of these one was exported and transplanted, and one could not be matched to a suitable recipient. A further 27 were not used because of liver appearance in 21, prolonged hypoxia and hypotension in 4, poor perfusion in 1, and donor malignancy in 1. Mean donor age was 39.4 years (range, 0.75-67 years). Causes of death were head trauma in 10 donors, intracranial bleed in 24, and anoxic/ischemic brain injury in 26. Mean warm ischemia time was 14.7 minutes (range, 7-40 minutes). Thirty-two patients were transplanted (one split liver), and the mean age of the recipients was 38.4 years (range, 0.7-72 years). All grafts had good early function except one right lobe split. There were 4 deaths resulting from ischemic brain injury, chronic rejection, biliary sepsis, and multiorgan failure following retransplantation for primary nonfunction. Overall patient and graft survival is 87% and 84%, respectively, at a median follow-up of 15 months. CONCLUSIONS: Early results suggest that controlled NHBDs are a significant new source of grafts, but careful donor selection and short cold ischemia are mandatory.

Academic Medical Centers↗
PubMed2005

The effects of cryopreservation on human hepatocytes obtained from different sources of liver tissue.

Successful cryopreservation of human hepatocytes is important to establish hepatocyte banks for clinical use or in vitro research. The availability of donor tissue from unused liver segments/lobes and non-heart-beating donors (NHBD) has provided newer sources of hepatocytes. The quality of hepatocytes at the time of cryopreservation is important as cells isolated from liver tissue of borderline quality may not withstand the stresses associated with cryopreservation and subsequent thawing. Human hepatocytes were cryopreserved after isolation from mainly donor tissues (n = 40). In vitro assessment of the viability and function of the fresh and thawed cryopreserved hepatocytes was performed. Viability, attachment efficiency, enzyme activity, and albumin production of hepatocytes were all significantly decreased, and LDH leakage significantly increased, on thawing after cryopreservation. The viability of cryopreserved hepatocytes isolated from tissue rejected for orthotopic liver transplantation (36 +/- 15%) was significantly lower than those isolated from tissue where part was used for liver transplantation (47 +/- 14%, p = 0.002), but there were no significant differences in functional parameters. The viability of cryopreserved hepatocytes isolated from NHBD tissue (29 +/- 9%, p = 0.001) and from steatotic donor tissue (35 +/- 11%, p = 0.019) was significantly lower than those isolated from normal donor tissue (49 +/- 14%). There was no difference in functional parameters, except for albumin production of hepatocytes from NHBD tissue (2.9 +/- 1.0 microg/h/mg protein) being significantly lower than those from normal donor tissue (4.8 +/- 2.8 microg/h/mg protein, p = 0.03). The viability and attachment efficiency of cryopreserved hepatocytes isolated from liver tissue from resections for tumors was significantly higher, and the LDH leakage significantly lower, than those isolated from all donor tissue. Hepatocytes isolated from NHBD and steatotic tissue were more vulnerable to the effects of cryopreservation. Further research is required to improve hepatocyte isolation and cryopreservation protocols for different types of liver tissue.

Adolescent↗
PubMed2004

Hepatocyte transplantation for inherited factor VII deficiency.

Hepatocyte transplantation has been investigated in patients with liver-based metabolic disorders and acute liver failure. We report the first use of hepatocyte transplantation in two brothers with severe inherited coagulation factor VII deficiency. Patient 1 received a total of 1.09x10(9) cryopreserved hepatocytes, and patient received 2.18x10(9) fresh and cryopreserved hepatocytes through a Hickman line inserted in the inferior mesenteric vein. Infusion of isolated human hepatocytes improved the coagulation defect and markedly decreased the requirement for exogenous recombinant factor VII (rFVIIa) to approximately 20% of that before cell transplantation. In both patients, episodes of line sepsis were associated with an increase in rFVIIa requirement. Six months posthepatocyte transplantation, higher rFVIIa doses were required, suggesting loss of transplanted hepatocyte function. Because of increasing problems with venous access and long-term uncertainty of the efficacy of hepatocyte transplantation, orthotopic liver transplantation was performed successfully in both cases.

Adolescent↗
PubMed2004

Bile acids analysis: a tool to assess graft function in human liver transplantation.

The expanding use of "sub-optimal" grafts due to donor organ shortage increases the importance of accurate graft assessment before liver transplantation. Bile secretion is an early sign of recovering hepatic function post-transplant. The role of bile acid analysis in assessing graft function before and immediately after liver transplantation has been investigated. Two hundred and sixteen samples of hepatic bile were collected from 35 donors and 13 recipients. Clinical data, bile flow, total bile acid concentration, apparent choleretic activity and bile acid composition were assessed. Sub-optimal donor livers showed a low apparent choleretic activity and a different bile acid composition when compared to normal grafts. In recipients, the pattern of recovery of bile secretion immediately after reperfusion was a useful predictor of graft function. This study characterises bile acid secretion of liver grafts and remarks the potential value of bile acid analysis to assess donor liver quality and early post-transplant graft function.

Adolescent↗
PubMed2004

One liver, three recipients: segment IV from split-liver procedures as a source of hepatocytes for cell transplantation.

Hepatocyte transplantation is emerging as a possible treatment for patients with acute liver failure and liver-based metabolic disorders. With the limited availability of donor tissue, it is important to find new sources of liver tissue for isolation of high-quality hepatocytes. Segment IV with or without the caudate lobe was removed during three split-liver procedures. Hepatocytes were isolated from the tissues using a collagenase perfusion technique under strict sterile conditions. The mean number of hepatocytes that were isolated was 5.14 x 10(8) cells with a mean cell viability of 89%. Two of the hepatocyte preparations were used for cell transplantation in a 1-day-old boy with an antenatal diagnosis of a severe urea cycle defect caused by ornithine transcarbamylase deficiency. The six recipients of split-liver grafts demonstrated no complications related to the removal of segment IV. Segment IV with or without the caudate lobe obtained from split-liver procedures is potentially a good source of high-quality hepatocytes for cell transplantation.

Adolescent↗
PubMed2004

Hepatitis B virus genotype A and D and clinical outcomes of liver transplantation for HBV-related disease.

Hepatitis B virus (HBV) genotypes have been associated with specific patterns of disease and response to antiviral therapy. We investigated the effect of HBV genotype on HBV recurrence and mortality after liver transplantation (LT). Pretransplant sera of 45 hepatitis B surface antigen (HBsAg) positive adults were submitted for HBV genotyping by a reverse-phase hybridization line probe assay with genotype-specific probes. Data were correlated with clinical outcomes after transplantation. Genotype A (n =15), D (n = 13) and A/D (n = 12) accounted for 89% of all genotypes. Coinfection with two HBV genotypes was encountered in 14 (31.1%) patients. Eighteen patients (40 %) developed HBV recurrence at a median of 10 months posttransplant (range, 1-53) and 10 patients (22 %) died at a median of 24 months (range, 3-63). Genotype D patients were more likely to develop HBV recurrence or die compared with genotype A patients, although this did not reach statistical significance. Dual infection with genotype A/D resulted in mortality similar to that of genotype A but recurrence similar to that of genotype D. Active viral replication at time of transplantation was the only independent factor (P = 0.03) that predicted HBV recurrence. In conclusion, HBV genotype A and D did not have a significant impact on clinical outcomes of LT for HBV-related liver disease in patients of European origin. These data do not support routine HBV genotyping in liver transplantation.

Adolescent↗
PubMed2004

Monitoring mycophenolate in liver transplant recipients: toward a therapeutic range.

Predose plasma mycophenolic acid (MPA) concentrations measured with a semi-automated enzyme-multiplied immunoassay were related to adverse events (e.g., rejection, leukopenia, infection), drug dose, and clinical status in 147 adult and 63 pediatric liver allograft recipients receiving adjunctive immunosuppression with mycophenolate mofetil (MMF). In 12 of 13 acute rejection episodes, predose MPA levels were below the 1 mg/L cut-off defined using receiver operating characteristic (ROC) curve analysis. The relative risk of developing infection or leukopenia increased more than 3-fold above predose MPA levels of 3 to 4 mg/L. Plasma MPA levels correlated weakly (r2 = 0.081) with MMF dose and the dose / level relationship was variably influenced by age, the indication for MMF, concentrations of serum albumin and creatinine, and comedication with tacrolimus or cyclosporine. The median mycophenolate dose required per unit mycophenolate level was 50% lower in children than in adults. Comparable drug requirements were also decreased by renal dysfunction (by 40 and 43% in adults and children, respectively), and in patients prescribed MMF alone rather than with tacrolimus or cyclosporine. However, in patients with serum albumin less than 35 g/L, MMF dose requirements were higher than in those with normal albumin levels (by 2.1- and 2.6-fold in adults and children, respectively). In adults, 44.7% achieved clinically acceptable therapeutic MPA concentrations at a dose less than 1 g MMF twice daily and only 6.3% required 1.5 g twice daily as suggested by the manufacturer. The immunoassay was a rapid, reliable, and acceptably precise technique in which only 10.8% of measurements were unproductive. In conclusion, our data suggests that MPA predose level monitoring is both clinically- and cost-effective and that a therapeutic range of 1 to 3.5mg/L (by immunoassay) is applicable in liver allograft recipients given adjunctive MMF.

Adolescent↗
PubMed2004

Bile duct strictures after adult liver transplantation: a role for biliary reconstructive surgery?

There is no accurate method to determine the functional significance of bile duct strictures after liver transplantation, and although biliary reconstructive surgery (Roux-en-Y hepaticojejunostomy, HJ) is the second-line treatment in patients with persistent allograft dysfunction following failed endoscopic therapy, there is no evidence to support this approach. Liver transplant recipients with allograft dysfunction and demonstrable bile duct strictures who had undergone hepaticojejunostomy were identified from a prospective database. Preoperative and follow-up clinical, biochemical, and radiological data were collected. Perioperative liver biopsies were evaluated prospectively by two histopathologists blinded to clinical information. The biopsies were scored according to presence and severity of biliary features, fibrosis, and coexisting diseases. The effects of preoperative factors on postoperative allograft function were analyzed using SPSS statistical software. After hepatico-jejunostomy, graft function returned to normal in 8/44 patients (18%), improved in 16/44 (36%), but remained abnormal in 20/44 (45%), including 4 patients who subsequently underwent retransplantation. Hepaticojejunostomy was more likely to yield a favorable outcome (improved or normal graft function) when performed within 2 years of transplantation. Prolonged duration of biliary obstruction was associated with development of advanced graft fibrosis at the time of surgery, but neither factor significantly influenced postoperative graft function. In conclusion, biliary reconstruction successfully restores graft function in the majority of patients who present with anastomotic strictures within the first 2 years after liver transplantation. In patients presenting with bile duct strictures late after transplantation, surgery should be reserved for selected patients without histological evidence of graft fibrosis (moderate-severe) or significant nonbiliary pathology.

Anastomosis, Surgical↗