Browsing by Author "Moore, S. W."

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Chasing the ubiquitous RET proto-oncogene in South African MEN2 families - Implications for the surgeon
    (2010) Moore, S. W.; Zaahl, M. G.
    The RET proto-oncogene (REarranged during Transfection; RET) plays an important role in the causation of many thyroid tumours. Germline RET proto-oncogene missense mutations have been clearly linked to medullary thyroid carcinoma (MTC) and the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2A, MEN2B). Methods. We investigated a cohort of MEN2-related patients referred to Tygerberg Hospital, W Cape (2003 2009). The study cohort was divided into three groups based on pathology (viz. MEN/MTC, phaeochromocytoma, and a miscellaneous group of MEN pathologies). Families with identified high-risk factors were recalled. Serum calcitonin levels were monitored where indicated. DNA was extracted from whole blood by standard techniques and polymerase chain reaction (PCR) products screened for RET gene variations by heteroduplex singlestrand duplication techniques (heteroduplex single-strand conformation polymorphism analysis) being validated with automated sequencing techniques showing conformational variants in acrylamide gel. Results. We screened 40 persons, male/female ratio 1:1.5. Three ethnic groups were represented (white (12), black (11) and mixed race (17)). Nine were index MTC cases, 5 phaeochromocytoma, 3 Hirschsprung's diseaseMEN associations and 2 miscellaneous (1 neuroblastoma, 1 intestinal neuronal dysplasia), while 1 fell into the MEN2B category. The remaining 19 were unaffected relatives screened for carrier status, among whom a familial recurrence was observed in 7. On genetic testing, an RET point mutation at the highrisk 634 cysteine allele was identified in 11 cases. A further cysteine radical mutation at the 620 position was related to MEN2 in 3 families plus 1 other family referred from elsewhere. Other less-recognised gene variations were detected throughout the RET gene in 70% of cases and included the 691 position on codon 11 (11 cases); the 432 position (4 cases, 1 homozygous) intronic mutations on exon 4 (1 case); and an IVS19-37G/C and a D1017N variation in exon 19 in 2 MEN families. Fifteen MTC patients have had thyroidectomies, of which 2 were prophylactic (C-cell hyperplasia; early occult MTC). A further 3 are awaiting prophylactic surgery. Conclusion. RET gene mutation carries a risk of MEN2 and MTC in all ethnic groups in South Africa. Prophylactic surgery may prevent MTC, so genetic screening is important to identify and treat high-risk patients.
  • Thumbnail Image
    Item
    Lessons from the hepatoblastoma- familial polyposis connection
    (Health and Medical Publishing Group (HMPG), 2012-11) Moore, S. W.; Tshifularo, N.; Grobbelaar, J. J.
    Background. Approximately one-third of hepatoblastoma (HB) patients have associated congenital abnormalities, but familial recurrence is rare, except in association with familial adenomatous polyposis (FAP). This correlation may be missed if not actively sought, with implications for long-term outcome and management. Methods. We retrospectively investigated 3 families with an HB-familial polyposis connection, from a cohort of 113 FAP families (1989 - 2010). Data were analysed to assess clinical problem, treatment, complications and management. Long-term morbidity and functional outcome were analysed to identify management difficulties. Results. Three FAP families (2.65%) had an HB association. In one case, undiagnosed FAP at the time of HB diagnosis was only detected 5 years later, when the mother presented with advanced colorectal carcinoma. A chromosome 5 APC gene mutation (exon 15 codon 793 C→T) was then identified. In a second case, a nonrelated boy presented with a stage 4 multifocal HB with lung metastases. Genetic studies identified an APC gene mutation (exon 6 codon 232 C→T). Further family investigation showed >20 related FAP patients. A third HB-FAP association was identified in a known FAP family early in the study, prior to the availability of genetic testing. Conclusion. Although a rare association, a family history of FAP in HB patients is an important ‘hidden connection’. Germline variation may be outside the usual FAP gene site. Identifying families with unknown HB/FAP is important due to long-term management implications and follow-up.
  • Thumbnail Image
    Item
    Obstructive jaundice and hydatid cysts mimicking choledochal cyst
    (Health and Medical Publishing Group (HMPG), 2007-09) Saczek, K.; Moore, S. W.; De Villiers, R.; Blaszczyk, M.
    Hydatid disease remains a common problem in endemic regions throughout the world. Endemic areas include Australasia, Africa, the Americas, the Middle East, Greece, Spain and Eastern Europe. Hydatid cysts (HCs) typically occur in the liver and lungs, but can occur at multiple other sites throughout the body
  • Thumbnail Image
    Item
    Paediatric blunt abdominal trauma : are we doing too many computed tomography scans?
    (Medpharm Publications, 2013-02) Arnold, M.; Moore, S. W.
    Blunt abdominal trauma in childhood contributes significantly to both morbidity and mortality. Selective non-operative management of blunt abdominal trauma in children depends on both diagnostic and clinical factors. Computed tomography (CT) scanning is widely used to facilitate better management. Increased availability of CT may, however, result in its overuse in the management of blunt abdominal trauma in children, which carries significant radiation exposure risks. Aim. To evaluate the use and value of CT scanning in the overall management and outcome of blunt abdominal trauma in children in the Tygerberg Academic Hospital trauma unit, Parow, Cape Town, South Africa, before and after improved access to CT as a result of installation of a new rapid CT scanner in the trauma management area (previously the scanner had been 4 floors away). Methods. Patients aged 0 - 13 years who were referred with blunt abdominal trauma due to vehicle-related accidents before the introduction of the new CT scanner (group 1, n=66, November 2003 - March 2009) were compared with those seen in the 1-year period after the scanner was installed (group 2, n=37, April 2009 - April 2010). Details of clinical presentation, imaging results and their influence on management were retrospectively reviewed. A follow-up group was evaluated after stricter criteria for abdominal CT scanning (viz. prior evaluation by paediatric surgical personnel) were introduced (group 3, n=14, November 2011 - May 2012) to evaluate the impact of this clinical screening on the rate of negative scans. Results. There were 66 patients in group 1 and 37 in group 2. An apparent increase in CT use with increased availability was accompanied by a marked increase in negative CT scans (38.9% compared with 6.2%; p<0.006). Despite a slightly higher prevalence of associated injuries in group 2, as well as a slightly longer length of hospital stay, there was a similar prevalence of intra-abdominal injuries detected in positive scans in the two groups. In addition, rates of small-bowel perforation in the two groups were similar. The rate of negative scans in group 3 was 46.2% (6/13), but all except one of these patients had a severe brain injury preventing adequate clinical evaluation of intra-abdominal injury. Conclusion. CT scanning for blunt abdominal trauma in children is essential in the presence of appropriate clinical indications. Ease of access probably increases availability, but the rate of negative scans may increase. Management guidelines should be in place to direct CT scanning to cases in which clinical examination and/or other modalities indicate a likelihood of intra-abdominal injury. The principle of ‘as low (radiation) dose as reasonably achievable’ (ALARA) should be adhered to because of the increased radiation exposure risks in children.
  • Thumbnail Image
    Item
    Paediatric surgery : birth of a new specialty or a coming of age?
    (Health and Medical Publishing Group (HMPG), 2008-04) Moore, S. W.; Sidler, D.; Rode, H.
  • Thumbnail Image
    Item
    Problems related to cytomegalovirus infection and biliary atresia
    (Health and Medical Publishing Group (HMPG), 2012-11) Zabiegaj-Zwick, C.; Nel, E. D.; Moore, S. W.
    Background. Human cytomegalovirus (CMV) infection is related to biliary disease, being cholestatic in its own right. It has also been associated with intrahepatic bile duct destruction and duct paucity, indicating a possible role in the pathogenesis and progression of extrahepatic biliary atresia (BA). BA patients who are CMV-IgM-positive appear to have greater liver damage than uninfected patients, consequently affecting outcome. Methods. We reviewed the medical records of 74 patients diagnosed with hepatobiliary disease between 2000 and 2011, assessing clinical outcome and potential risk factors. Patients, categorised into those with and those without BA, were compared in terms of CMV infection. Results. The 74 patients included 39 (52%) BA and 35 non-BA patients; following the exclusion of patients due to insufficient data, 27 (69%) BA and 31 non-BA patients were reviewed. Twenty-one (78%) BA patients were CMV-positive (IgM/IgG), including 20 IgM-positive patients versus 8 in the non-BA group (p<0.01). Two (7.5%) CMV-IgM-positive BA infants were HIV-exposed versus 7 (35%) in the non-BA group (p<0.01). Long-term outcomes included 3 deaths in the non-HIV CMV-positive group and a higher rate of severe early liver damage, suggesting a poorer outcome in CMV affected patients. Conclusions. Our results suggest a correlation between CMV exposure/infection and BA which affects clinical outcome. HIV positivity does not preclude BA and should be investigated further.