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Biomedical subjects

P McKiernan

Publications and source records attributed to P McKiernan.

At least 19 recordsLinked to original sources
PubMed2004

Management of hepatic epithelioid haemangio-endothelioma in children: what option?

Hepatic epithelioid haemangio-endothelioma (HEHE) is an endothelium-derived tumour of low-to-medium grade malignancy. It is predominantly seen in adults and is unresponsive to chemotherapy. Liver transplantation is an accepted indication when the tumour is unresectable. Hepatic epithelioid haemangio-endothelioma is very rare in children and results after transplantation are not reported. The aim of this study is to review the experience of three European centres in the management of HEHE in children. A retrospective review of all paediatric patients with HEHE managed in three European centres is presented. Five children were identified. Four had unresectable tumours. The first had successful resection followed by chemotherapy and is alive, without disease 3 years after diagnosis. One child died of sepsis and one of tumour recurrence in the graft and lungs 2 and 5 months, respectively, after transplant. Two children who had progressive disease with ifosfamide-based chemotherapy have had a reduction in clinical symptoms and stabilisation of disease up to 18 and 24 months after the use of platinum-based chemotherapy. HEHE seems more aggressive in children than reported in adults and the curative role of transplantation must be questioned. Ifosfamide-based chemotherapy was not effective. Further studies are necessary to confirm if HEHE progression in children may be influenced by platinum-based chemotherapy.

Adolescent↗
PubMed2003

Familial hepatoblastoma and APC gene mutations: renewed call for molecular research.

Recent findings have increased our understanding of the molecular mechanisms involved in the pathogenesis of hepatoblastoma and their relationship to the molecular pathology of familial adenomatous polyposis (FAP). Here, we describe hepatoblastoma in siblings who share a gene mutation for FAP inherited from their father. This observation confirms the link between these diseases and has implications for future molecular research. We also raise the question; should other members of 'at-risk' families be screened following a new diagnosis of either hepatoblastoma or FAP?

Biomedical Research↗
PubMed2003

New perspective for the management of near-total or total intestinal aganglionosis in infants.

BACKGROUND/PURPOSE: Extensive intestinal aganglionosis is rare. The diagnosis and treatment are known to be difficult and it had been considered to be fatal. The aim of this study was to review our experience with children with extensive intestinal aganglionosis. METHODS: Retrospective analysis was conducted in patients referred to the intestinal transplantation unit since 1993. Presentation and outcome were analysed looking at 2 groups who had either undergone previous subtotal intestinal resection (group I) or no or limited resection (group II). RESULTS: Eight children were selected (3 patients in group I and 5 in group II). Group I was remarkable in that patients all were referred early in age with progressing liver failure. Parents of one patient refused to accept transplantation as treatment, and he died one month later. Two noncirrhotic patients were maintained in the parenteral nutrition programme and currently progress well with enteral feedings. The other 5 patients underwent transplant, and 4 of 5 are alive after transplantation with a mean follow-up of 22.2 months (range 0.4 to 63.6). CONCLUSIONS: Subtotal resection of intestine at the time of diagnosis must be avoided. Conservative management with parenteral nutrition may be associated with long-term good outcome. Small bowel transplant may open new perspective in the management of patients with end-stage liver disease.

Female↗
PubMed2003

Progress in treatment and outcome for children with neonatal haemochromatosis.

AIM: To evaluate the role of antioxidant treatment and liver transplantation in the management of neonatal haemochromatosis. METHODS: A retrospective review was performed of eight infants with acute liver failure and raised ferritin levels between 1990 and 1998. From 1994, treatment with an antioxidant cocktail (vitamin E, N-acetylcysteine, selenium, prostaglandin E1, and desferrioxamine) was begun once the diagnosis was suspected. Pathological and other findings were reviewed, and outcome before and after antioxidant treatment was evaluated. RESULTS: Median age at presentation was 4 days with median ferritin levels of 4180 micro g/l (range 1650-40 000 micro g/l; normal range 110-503 micro g/l). Three infants presented before 1994. One infant died before liver transplantation from acute liver failure and one from neurological damage after transplantation. The third patient underwent successful transplantation at day 13 and remains well on follow up 8 years later. From 1994, five patients received antioxidant treatment, of whom two responded: both responders started antioxidants earlier (by day 5) than non-responders and had lower peak ferritin levels (< 4200 micro g/l) and a milder phenotype. Treatment was continued until ferritin levels were < 500 micro g/l. Both children remain well with mean follow up of 42 months, with no recurrence of iron overload. One child showed a partial response to treatment and survived long enough for a liver transplant, but died from graft failure after the transplant. Two children did not respond to antioxidant treatment; both had multiorgan failure and were not listed for transplantation. Only three of the eight patients survived (37.5%) over this time period. CONCLUSION: Neonatal haemochromatosis can be a fatal disease with > 60% mortality. Early treatment with antioxidant cocktail is beneficial and may be curative in those who present with milder phenotype. Liver transplantation should always be considered at an early stage in non-responders and in children with more severe acute liver failure.

Antioxidants↗
PubMed2002

Cross-cultural differences in the management of children and adolescents with diabetes.

Glycaemic control deteriorates frequently in adolescents with diabetes. There is a considerable body of work on the effect of psychological aspects of management in this age group, but few randomized controlled trials of the effect of specific behavioural therapy and lifestyle modification on the improvement of glycaemic control. Of recent interest have been the observations from the Hvidøre Study Group on cross-cultural differences in glycaemic control. The average glycosylated haemoglobin in 22 centres, across 18 countries, varied in young people, with HbA1c levels ranging from 7.6 to 10.2%. No obvious differences in management were identified in this survey that could account for the disparities in glycaemic control. Data from the Scottish Study Group demonstrated similar variation in average glycaemic control in centres across a single culture. Using the qualitative methodology of anthropological research, some specific factors were identified that appear to influence young people's response to diabetes management and strategies employed by health professionals in their advice and care of the diabetes, particularly in relation to intensive insulin regimens. The main cultural factors influencing glycaemic control appear to be communication, reciprocal support between young people and professional heart carers and family structure within an individualistic, as against an egalitarian, society. Shared beliefs about teenage risk behaviour together with the medicalization of adolescence within medical culture also appears to be highly influential. The aim of this educational discussion group was to explore how a variety of health care professionals from distinctive cultures approach diabetes care delivery in this age group. The specific success and difficulties in different cultures in managing the young person with diabetes were investigated. Also discussed was how qualitative research methodology may generate further research in this area.

Adolescent↗
PubMed2001

Successful ribavirin therapy for life-threatening laryngeal papillomatosis post liver transplantation.

A 3-yr-old girl developed severe progressive juvenile laryngeal papillomatosis (JLP) 2 yr after liver transplantation (Tx) for biliary atresia. The papillomata were resistant to withdrawal of immunosuppression, to laser surgery, and to subcutaneous interferon (3 MU/m2, three times weekly), necessitating tracheostomy. Oral ribavirin therapy (25 mg/kg/day) in combination with no immunosuppression effectively prevented the rapid recurrence of JLP over 5 yr. Hence, oral ribavirin is a potentially useful therapy in this life-threatening situation and may also be of benefit in other children with severe JLP.

Antiviral Agents↗
PubMed1999

Outcome of liver retransplantation in children.

Irreversible liver graft failure is a life-threatening complication. We reviewed the first 200 pediatric liver transplantations in Birmingham. Forty-one children developed primary graft failure, 9 of whom developed secondary graft failure. The main indications for graft failure were primary nonfunction (PRNF; 8 patients), vascular complications (VASC; 23 patients), and chronic rejection (CHRE; 19 patients). Thirty-two children underwent retransplantation (ReTx) (21 children received reduced grafts; 11 children, whole hepatic grafts). Patient survival was significantly worse for retransplant recipients compared with children receiving a single graft (63% v 76. 5% actuarial patient survival at 1 year; P <.05). Primary graft 1-year actuarial survival was 74% in first grafts compared with 47% for regrafts (P <.05), but improved with time. The graft 1-year survival rate was 55% for whole grafts and 45% for reduced and/or split grafts in the first 100 grafts compared with 83% and 66% in the second 100 grafts, respectively (P <.01). Emergency ReTx within a month of transplantation was associated with more complications and a worse outcome (1-year survival rate, 37%) compared with patients who underwent ReTx later (1-year survival rate, 72%; P <. 01). The incidence of primary graft failure decreased from 33% in the first 100 grafts to 16% in the second 100 grafts (P <.01), as did the incidence of PRNF, which decreased from 8% to 0% (P <.05). Although the rates of graft failure from VASC decreased from 15% to 8% (P =.2) and CHRE decreased from 11% to 8% (P =.6), neither reached statistical significance. The improved results overall are because of advances in surgical techniques, intensive care management, and graft preservation and refinements in immunosuppression. We conclude that ReTx for a child with primary graft failure is justified.

Adolescent↗
PubMed1999

Indications and outcome of liver transplantation in tyrosinaemia type 1.

UNLABELLED: A retrospective analysis was performed on 17 patients presenting with tyrosinaemia type 1 (TT1) between 1989-1997; 7 pre 1992 prior to the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and 10 post 1992. During this time, eight children (5 males) underwent orthotopic liver transplantation (OLT); six prior to the introduction of NTBC in 1992 and two on NTBC therapy. The primary indications for OLT pre-1992 were risk of hepatocellular carcinoma with evidence of hepatic dysplasia in all, associated with liver failure in two, and rise in alpha-fetoprotein (AFP) in four. Two of the ten treated with NTBC required OLT. The indications were non-response to NTBC in one child and development of hepatic dysplasia associated with poor quality of life in the second patient. Median age for OLT was 64 months (range 5-127 months) with a median weight of 24 kg (range 6-25 kg). The histology of hepatectomy specimens at transplantation showed: cirrhosis in 8, hepatic dysplasia in 6 and hepatocellular carcinoma in 1. Plasma tyrosine and AFP returned to normal in all cases. Urinary succinylacetone reduced but persisted in small amounts (median 7.7 micromol/mmol creatinine). Hypertrophic cardiomyopathy resolved in 3/3 patients. Hypoglycaemia, not responding to dietary therapy or NTBC treatment, resolved post-transplant in one patient. There were two deaths, one from primary non-function and one from chronic rejection. Late complications in survivors (n=6) include post-transplant lymphoproliferative disease of the iris in one child which resolved and renal dysfunction with a fall in glomerular filtration rate in three (50%). Median follow up post OLT is 6.7 years (range 1-7 years). Quality of life post-transplant in survivors is good with unrestricted diet in all. CONCLUSION: Liver transplantation is an effective treatment for TT1 with good quality of life. The current indications of OLT in TT1 are non-response to NTBC, risk of malignancy and poor quality of life related to dietary restriction and frequency of blood sampling.

Adolescent↗
PubMed1999

Liver transplantation in mitochondrial respiratory chain disorders.

UNLABELLED: Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or other extra-hepatic symptoms may pre-exist, or appear in the post-transplant follow up. Pre-transplant evaluation should aim to rule out neurological disease, which may be difficult to differentiate from signs accompanying liver insufficiency. Cerebrospinal fluid lactic acid levels, compared to blood lactate, may be suggestive of central nervous system involvement. Of 11 cases with respiratory chain disorders who had liver transplantation in various centres, 4 are alive and well on follow up, and 6 died, three of them having developed neurological disease post orthotopic liver transplantation. All three patients with initial liver and gastro-intestinal disease died early after transplantation, indicating that these may be poor candidates for this procedure. CONCLUSION: Liver transplantation is feasible in hepatic respiratory chain disorders, but extra-hepatic disease should be ruled out before transplantation. Extra-hepatic manifestations may, however, appear and cause patient death despite successful transplantation.

Electron Transport↗
PubMed1999

Orthotopic liver transplantation for unresectable hepatoblastoma: a single center's experience.

BACKGROUND/PURPOSE: Complete surgical resection after chemotherapy is the definitive treatment for hepatoblastoma. However, orthotopic liver transplantation (OLT) is now accepted as a treatment modality for patients with unresectable tumours. The aim of this study was to review a single center's experience of OLT for unresectable hepatoblastoma. METHODS: A retrospective review of 8 patients with unresectable hepatoblastoma who were referred for liver transplantation was conducted. RESULTS: The patients assessed had an age range of 5 to 105 months at presentation; median, 24 months, (5 boys; 3 girls). Two patients have familial adenomatous polyposis, and one has right hemihypertrophy. All 8 patients had received standard chemotherapy according to SIOP (International Society of Pediatric Oncology) protocols. Extrahepatic metastases were found in 3 patients at diagnosis, but none had detectable metastases at the time of OLT. Four patients continued chemotherapy while awaiting OLT. Three patients received whole grafts, and 5 received reduced grafts. The median follow-up period was 22 months (range, 2 to 78 months). Five patients are alive and well, although 1 patient had a second OLT for biliary cirrhosis secondary to biliary stricture at 6 years. Three patients died: one 26 days post OLT of sepsis and two of disease recurrence at 22 months and 70 months posttransplant. The actuarial survival rate is 88% and 65% at 1 and 5 years, respectively, whereas the overall survival rate is 62.5%. CONCLUSION: OLT for unresectable hepatoblastoma without extra hepatic metastases is highly successful with a low recurrence rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Emergency transjugular intrahepatic portosystemic shunt prior to liver transplantation.

Transjugular intrahepatic portosystemic shunt (TIPSS) is a new development in the management of severe variceal haemorrhage which has been established in adult patients. We have successfully adapted this technique for children and describe our initial experience in the case of a 9-year-old boy who presented with acute and chronic liver failure and uncontrollable life-threatening bleeding from oesophageal and gastric varices, despite intensive medical management including sclerotherapy. A 10-mm TIPSS was successfully placed with immediate reduction in portal pressure and cessation of variceal bleeding. The patient's condition stabilised sufficiently for him to undergo liver transplantation 2 days later, at which time the TIPSS was patent.

Child↗