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T R Helliwell

Publications and source records attributed to T R Helliwell.

At least 19 recordsLinked to original sources

Hibernoma--correlation of histopathology and magnetic-resonance-imaging features in 10 cases.

UNLABELLED: OBJECTIVE, DESIGN AND PATIENTS: Hibernoma is an uncommon, slow-growing, benign soft-tissue tumour resembling brown adipose tissue. The histological appearances are well-documented, but there are relatively few descriptions of the magnetic resonance (MR) imaging features. We report a retrospective comparison of the histological and MR appearances of ten hibernomas of the extremities, classified histologically into lipoma-like [<70% multivacuolated adipocytes (MVAs)] and non-lipoma-like hibernomas (>70% MVAs). RESULTS: The lipoma-like hibernomas measured 4-27 cm in maximum size. All were well-defined on MR imaging and histology except for one subcutaneous lesion that blended in with surrounding fat histologically. All lesions were isointense with subcutaneous fat on T1- and T2-weighting apart from one lesion that was predominantly slightly hypointense on T1-weighting and predominantly slightly hyperintense on T2-weighting and STIR. Two slightly inhomogeneous lesions contained thin (<5 mm thickness) tortuous vessels. One patient received intravenous contrast, but the lesion did not enhance. The six non-lipoma-like hibernomas measured 2.5-15.5 cm in maximum size and all were unencapsulated. Three were well-defined and three partly ill-defined on MR imaging. There were no significant differences in the MR characteristics of the non-lipoma-like variants. On T1-weighting, the non-lipoma-like hibernomas that contained >90% MVAs were predominantly slightly hypointense to subcutaneous fat. One lesion was isointense with subcutaneous fat, but this lesion only contained from 80-90% MVAs. All non-lipoma-like lesions were slightly hyperintense on STIR but so too were two of the four lipoma-like lesions. Four of the six non-lipoma-like lesions showed marked or moderate inhomogeneity due to thick septa and prominent vessels. Of the two cases that received intravenous contrast, both showed enhancement corresponding to regions of >90% MVAs or prominent vessels within fibrous septa. CONCLUSIONS: MR imaging has shown some distinguishing features between lipoma-like and non-lipoma-like hibernomas. Lipoma-like hibernomas are usually isointense with subcutaneous fat on T1-weighting, are either homogeneous or slightly inhomogeneous and may contain thin tortuous vascular structures. Non-lipoma-like hibernomas are pre-dominantly slightly hypointense to subcutaneous fat on T1-weighting, often display marked or moderate inhomogeneity with prominent septa and vessels and enhancement is typical. The appearances of non-lipoma-like hibernomas are not diagnostic and may be mimicked by lipoma variants and by well-differentiated liposarcoma or atypical lipoma.

Adult↗

Marsh stars in Liverpool.

INTRODUCTION/METHODS: After the recognition of contaminating algae on histopathological sections stained by periodic acid Schiff (PAS) and Grocott methods, a detailed audit was undertaken to assess the extent of contamination and its possible source. RESULTS: The contaminating organism was a member of the staurastrum genus of Chlorophyta, star shaped organisms commonly found in fresh water marshes. The organisms were seen on sections stained by the diastase-PAS, PAS, or Grocott methods and on cytological preparations between July 2003 and May 2004. It is unlikely that contamination of water baths or concentrated staining solutions was to blame, and a more general contamination of the laboratory water supply is the most likely source. CONCLUSIONS: Contaminating organisms may appear on histological and cytological material and their nature and source should be investigated. Although in this instance, confusion with pathologically important organisms was minimal, algae may occasionally cause significant disease.

Artifacts↗

acp Best Practice No 169. Evidence based pathology: squamous carcinoma of the hypopharynx.

This best practice article reviews the published evidence on the pathology and patterns of spread of carcinomas of the hypopharynx, and the relevance of pathological features to prognosis. Medline (1966-2001) was searched using a combination of head and neck neoplasms and prognosis, focusing on hypopharynx and pathology. Other relevant publications were identified from the bibliographies of these papers, and from those obtained opportunistically. There is relatively little pathological literature devoted specifically to squamous carcinomas of the hypopharynx and most information comes from large series of patients with head and neck cancers at a range at sites. Lack of consistency in reporting and shifts in terminology make comparisons between series difficult. The most important features determining prognosis are size and extent of local spread of the primary carcinoma and extent of involvement of regional lymph nodes. There is evidence to support the use of the minimum dataset criteria for head and neck carcinomas at this site. Within the hypopharynx, subsite related differences in aetiology and biology may become important.

Aged↗

Molecular markers of metastasis in squamous carcinomas.

The prognosis for patients with squamous carcinomas of the head and neck region is strongly influenced by the presence or absence of cervical lymph node metastases. Biological markers that indicated a high risk of metastasis would have a major role in determining the optimal therapeutic strategy for these patients. This editorial discusses recent studies of molecular and genetic markers of squamous carcinomas in relation to metastatic potential and highlights some of the issues that limit current progress in this field of study.

Carcinoma, Squamous Cell↗

Bizarre parosteal osteochondromatous proliferation with cortical invasion.

A 15-year-old male presented with an 18-month history of increasing swelling on the radial aspect of his left forearm. Radiographs and MR images showed a partly calcified mass on the lateral border of the radius with erosion of the underlying cortex. Following a CT-guided needle biopsy, the mass was excised by segmental resection of the radial shaft with replacement by a vascularised fibular graft. Histological examination of the resected specimen showed many features typical of a bizarre parosteal osteochondromatous proliferation (BPOP) but with destruction of the underlying cortical bone by cellular spindle cell tissue. Although there were no cytological signs of malignancy, we believe that this unusual disease should be regarded as a particularly aggressive form of BPOP and treated by wide excision. Clinical follow-up of our patient at 2 years shows no sign of local recurrence or metastasis.

Adolescent↗

The management of retroperitoneal soft tissue sarcoma: a single institution experience with a review of the literature.

AIM: Ten percent of soft tissue sarcomas (STS) arise in the retroperitoneal tissues. The prognosis for patients with retroperitoneal sarcoma is poor with a 5-year survival rate between 12% and 70%. Stage at presentation, high histological grade, unresectable primary tumour and incomplete resection are associated with a less favourable outcome. METHODS: Complete follow-up data were available on 22 patients who underwent surgery for retroperitoneal STS in our institution between 1990 and 2000. Patient, tumour and treatment variables were analysed including use of adjuvant therapy and survival status. RESULTS: Eighteen patients underwent surgery for primary disease, four patients were treated for recurrent disease or metastases. Ten patients presented with pain, seven with an abdominal mass, other presentation included weight loss and haematuria. Thirteen patients presented with tumours larger than 10 cm. The tumours were seven liposarcomas, six leiomyosarcomas, three malignant fibrous histiocytomas, two rhabdomyosarcomas, two malignant schwannomas and two undifferentiated sarcomas. Six primary tumours were completely excised, five patients received radiotherapy and five received chemotherapy. Local recurrence rate was 45% and recurrence-free interval for 10 patients with recurrence was 11 months. Five patients received radiotherapy and five received chemotherapy. The median survival for patients with primary tumours was 36 months, and 5-year survival was 44%. Adjuvant therapy was not associated with higher survival rates. CONCLUSION: This study re-emphasizes the poor outcome of patients with retroperitoneal STS. Adjuvant radiotherapy and chemotherapy do not appear to be any proven benefit and the single most important prognostic factor is aggressive successful en bloc resection of the primary tumour. Our resection rate and 5-year survival rates are comparable with previous reported UK series although lower than large reports from North American centres. This might partly be explained by difficulty in data collection in a retrospective analysis, but may reflect inadequate subspecialization in UK centres.

Adult↗

Dermatomyositis and Whipple's disease.

A 14-year-old boy presented with a 3-year history of a skin rash typical of juvenile dermatomyositis, and a 2-month history of mild proximal weakness, myalgia, and weight loss. A quadriceps biopsy showed perifascicular fibre atrophy, focal necrosis and regeneration, immunohistochemical labelling for HLA-1 on the surface of the fibres, and focal C5-9 deposition in capillaries. Macrophages with diastase-resistant, PAS-positive cytoplasm were present. Ultrastructural studies showed electron dense and membranous debris. The patient's symptoms responded to intravenous immunoglobulin and oral prednisolone. Four months after discontinuing prednisolone, the patient developed cardiac failure, ventricular tachycardia, and a recurrence of his rash. The 16S ribosomal RNA specific for Tropheryma whippelii was identified by polymerase chain reaction (PCR) analysis in skeletal and cardiac muscle. The myalgia and skin rash responded to prednisolone and oral co-trimoxazole, and the tachycardia is controlled by oral verapamil. This patient appears to have a novel association of juvenile dermatomyositis and Whipple's disease.

Actinobacteria↗

Basic fibroblast growth factor and angiogenesis in squamous carcinoma of the tongue.

The relationship between basic fibroblast growth factor (bFGF), receptors for bFGF and neoangiogenesis was investigated in 51 patients with squamous cell carcinoma of the tongue, 26 of whom had metastatic disease in cervical lymph nodes. Vessels were demonstrated by immunocytochemical labelling for CD34 and expressed as raw counts and volume-weighted counts. bFGF protein and its receptors FGFR1(flg) and FGFR2(bek), were demonstrated using immunocytochemical labelling. In situ hybridisation for bFGF mRNA was performed using a 250-bp digoxigenin-labelled RNA probe. In normal epithelium, the expression of bFGF protein and mRNA was more intense in the basal layer, while receptors for bFGF were expressed more strongly in the superficial parts. In carcinomas, expression of bFGF was greater in the more poorly-differentiated cells, but showed no relation to the overall tumour differentiation. There was strong bFGF expression in tumour-infiltrating lymphocytes. The expression of bFGF receptors was variable, with FGFR2 being particularly high in areas of keratinisation. There were no consistent changes in bFGF or receptor expression between primary carcinomas and their lymph node metastases, and there was no correlation with measures of vascularity or tumour growth pattern. bFGF is synthesised by all squamous carcinomas and has the potential to modulate angiogenesis. However, these data suggest that changes in the expression of bFGF and its receptors are not related to the intensity of neoangiogenesis in lingual carcinomas or their nodal metastases.

Carcinoma, Squamous Cell↗

Neoangiogenesis and squamous cell carcinoma of the tongue.

The relationship between neoangiogenesis and prognosis was investigated in 51 patients with surgically resected squamous carcinomas of the tongue. Twenty-six patients had lymph node metastases treated by radical neck dissection. Potential methodological sources of variation in vascular counts were examined. Vessels were immunolabeled for CD34, and the vessel counts (VC)--as well as the vessel counts adjusted for tumor area (VV)--were obtained in the most vascular parts of the carcinomas. Vascular hot spots were distributed throughout the carcinomas. The VC per hot spot increased with increasing size of carcinoma, and was higher in the resected carcinoma than in the diagnostic biopsy in four of eight cases. VC was not related to the growth pattern of the carcinoma or to metastasis, but patients with nodal metastases tended to have a lower VV than those with no metastases (p = 0.049). The tumor-specific survival of the whole group was 59%, and patients with nodal metastases had a shorter survival than those without metastases (p = 0.008). Cox's proportional hazards model demonstrated that carcinomas with a low VC tended to have a good prognosis (p = 0.023). The results from this relatively small series of cases support the hypothesis that some measures of neoangiogenesis are independent predictors of the spread and prognosis of lingual carcinomas. The variations in methodology among different studies currently preclude an accurate assessment of the prognostic significance of neoangiogenesis.

Aged↗

Microvascular endothelial activation in the skeletal muscles of patients with multiple organ failure.

The relationship between microvascular damage and the presence of muscle fibre atrophy and necrosis has been investigated in skeletal muscle biopsies taken from 57 patients with multiple organ failure. Immunohistochemical studies showed no loss of capillaries and no luminal thrombosis, while neutrophil leucocytes were more prevalent in the patients' biopsies than in controls. Deposition of the complement membrane attack complex (C5-9MAC) in capillaries was observed in 41% of cases. Endothelial activation was suggested by an increased intensity of expression of ICAM-1, and by an increased proportion of capillaries expressing P selectin and E selectin, although this was not directly associated with neutrophil accumulation. Endothelial swelling was present in many biopsies with 38% of the biopsies having larger capillary profiles on immunohistochemical labelling for von Willebrand factor (vWF), thrombomodulin and CD34, and on Ulex europaeus agglutinin 1 binding. Endothelial swelling was confirmed by image analysis and morphometric evaluation of capillary ultrastructure, however, the capillary luminal area was not reduced as the capillaries were dilated. Increased vWF labelling was associated with C5-9MAC deposition and with fibre necrosis, but the vascular changes were not related to fibre atrophy nor to clinical indices of the severity of the patients' illness. The results suggest that microvascular damage and ischaemia may not be major factors in the pathogenesis of muscle fibre damage in multiple organ failure, but that endothelial activation is a common occurrence. The variability in the patterns of markers of endothelial activation, and the small proportion of capillaries affected, may reflect the complexity of the endothelial response to circulating or locally produced cytokines.

Adult↗

p53 expression and p53 gene mutation in oral cancer and dysplasia.

BACKGROUND: The aim of the current study was to examine the possible association of the p53 tumor suppressor gene with the development of oral cancer. We examined biopsy material from patients with oral squamous cell carcinoma for p53 protein expression and p53 mutations. METHODS: Eighteen samples were analyzed. These comprised oral squamous cell carcinoma biopsy samples and oral dysplastic biopsy material taken from nine patients. An immunohistochemical technique was used to determine p53 protein expression. A direct sequencing technique was used to detect mutations in the p53 gene itself. RESULTS: Overall seven of nine (77%) oral squamous cell carcinomas and seven of nine (77%) oral dysplastic lesions analyzed showed evidence of p53 protein over-expression. Mutations in exons 5 and 6 of the p53 gene were detected in five of nine (55%) oral squamous cell carcinomas and four of nine (44%) dysplastic lesions analyzed. CONCLUSIONS: Both p53 protein over-expression and p53 mutations were noted in dysplastic oral lesions. Over-expression of the p53 protein and p53 gene mutations were not always coexistent, however, suggesting that gene mutation may be only one of the mechanisms responsible for stabilization of the p53 protein.

Carcinoma, Squamous Cell↗

Myotubular myopathy: morphological, immunohistochemical and clinical variation.

Myotubular myopathy frequently presents in male infants with severe generalised muscular hypotonia and weakness associated with ventilatory insufficiency, and is diagnosed on biopsy by the presence of many fibres with central nuclei and mitochondrial aggregation. In a 6-year period, we have investigated five unrelated patients with clinical and pathological features suggesting an X-linked myotubular myopathy, including one female patient. In one male infant, a biopsy of vastus lateralis showed less than 2% centrally-nucleated fibres, while biceps brachii showed up to 15% centrally-nucleated fibres. Immunohistochemical expression of the neural cell adhesion molecule (CD56) was more intense in the biceps muscle than in vastus lateralis, while expression of desmin and vimentin was similar. Morphometric evaluation of tissue from each of the patients revealed a wide spread of values for the number of centrally-nucleated fibres per microscopic field, and variation in the extent of immunohistochemical expression of NCAM, utrophin, laminin alpha 5 chain, vimentin and HLA1 antigen. These variations in the manifestations of myotubular myopathy have not been previously described, and will need to be correlated with the increasing knowledge of the mutations in the MTM1 gene coding for myotubularin.

Adolescent↗

p53 protein expression in tumours from head and neck subsites, larynx and hypopharynx, and differences in relationship to survival.

The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.

Biomarkers, Tumor↗

Tumours of the minor salivary glands.

One hundred and forty-five patients were identified with minor salivary gland tumours. General information and tumour-specific information on stage, grade of tumour, resection margins, recurrence and survival were collected. Data was analysed by both univariate and multivariate methods. Indices predicting tumour recurrence and survival were analysed. Forty-two benign lesions, mostly pleomorphic adenomas were identified, one recurred, all survived. One hundred and three malignant lesions were identified, mostly adenoid cystic carcinomas (70%) or mucoepidermoid carcinomas (19%). Late stage disease and the presence of neck node metastases predicted both early recurrence and high eventual mortality. Survival was favoured by the histological type (mucoepidermoid > adenoid cystic), site of primary (oral cavity and oropharynx > nose, sinuses and larynx) and good general condition. Many tumours recurred after 5 years of disease-free survival and late mortality was a feature (80% survival at 5 years, 20% at 20 years). Many patients survive some time with either local recurrence or distant metastases. Long-term follow-up is advocated as local or distant recurrence may be treatable. The value of super radical treatment of the primary is questionable given the likelihood of recurrence at distant sites.

Adenocarcinoma↗

Mucosal melanoma of the head and neck.

Two hundred and fifty-nine patients with mucosal melanoma of the head and neck were reviewed. The data of these patients were obtained from the records of the Department of Head and Neck Oncology at the University of Liverpool and from the Merseyside and Cheshire Cancer Registry. Survival curves were constructed using the life table method and differences were investigated by the Log Rank Test. Prognostic factors were further analysed by Cox's proportional hazards model. Melanomas of the nasal cavities and sinuses accounted for 69%; 22% occurred in the oral cavity and 9% in the pharynx, larynx and upper oesophagus. In 49% treatment was by wide local resection and in 8% by irradiation. Thirty-six per cent had combined modalities of treatment. Primary site recurrence occurred in 52% and 36% developed nodal recurrence. The tumour specific survival at 5 years was 45% at 10 years 28%, at 20 years 17% and closely resembled the observed survival. Young male patients tended to have a favourable prognosis as did those treated surgically. Radiotherapy on its own was ineffective. Amelanotic melanoma had a particularly poor survival. Whereas site had no effect on survival. The study confirms the poor prognosis of mucosal melanoma of the head and neck. Young patients should be offered radical surgical treatment combined with radical radiotherapy if feasible as this offers the best chance of cure.

Adult↗

Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin.

Muscle wasting and weakness are common features of patients with critical illnesses, and may impair their recovery. This study examines whether cytoskeletal and contractile proteins are damaged, and which proteolytic mechanisms might be involved, in the muscle fibre atrophy or necrosis associated with the acute myopathy of critically ill patients. Ninety-eight muscle biopsies were obtained by the conchotome method from 57 critically ill patients and examined morphometrically and by immunohistochemical labelling. Sequential biopsies showed a mean reduction in fibre cross-sectional areas of 3-4% per day. More intense immunolabelling for desmin was seen in the smaller fibres of 52% of the biopsies, while immunolabelling for dystrophin, actin and myosin heavy chains was maintained. Myosin ATPase activity was weak in the smaller fibres in some biopsies, and electron microscopy showed the loss of myosin filaments in atrophic fibres. These changes suggest that loss of the filamentous structure of myosin, without degradation of the immunolabelled epitopes, leads to the collapse of the intermyofibrillar desmin network. Fibres with abnormal desmin labelling showed increased cathepsin B, lysozyme and ubiquitin immunolabelling. Nine cases showed increased immunolabelling for heat shock protein 72. The changes in desmin immunolabelling were more prevalent in patients with higher APACHE II scores on admission, but were not related to other clinical features. The results indicate that fibre atrophy is associated with myosin filament depolymerization and the presence of several proteolytic enzymes. In our study, these changes occurred in patients who were critically ill but who did not receive large doses of steroids or neuromuscular blocking agents.

Adult↗