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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 19 recordsLinked to original sources
PubMed2006

The uncertainty of the surgical margin in the treatment of head and neck cancer.

We discuss our surgical philosophy concerning the subtle interplay between the size of the surgical margin taken and the resultant morbidity from ablative oncological procedures, which is ever more evident in the treatment of head and neck malignancy. The extent of tissue resection is determined by the "trade off" between cancer control and the perioperative, functional and aesthetic morbidity and mortality of the surgery. We also discuss our dilemmas concerning recent minimally invasive endoscopic microsurgical techniques for the trans-oral laser removal or co-ablation of aero-digestive tract tumours, which result in a minimal surgical margin of oncological clearance. By a process of inductive argument as to the nature of the surgical margin, we consider whether the risks of taking a lesser margin with adjuvant therapy is justified by the attendant gain in reduced surgical morbidity and the possible costs in tumour control.

Head and Neck Neoplasms↗
PubMed2006

Diversity of TMPRSS2-ERG fusion transcripts in the human prostate.

TMPRSS2-ERG gene fusions have recently been reported to be present in a high proportion of human prostate cancers. In the current study, we show that great diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found in human prostates. Fourteen distinct hybrid transcripts are characterized, each containing different combinations of sequences from the TMPRSS2 and ERG genes. The transcripts include two that are predicted to encode a normal full-length ERG protein, six that encode N-terminal truncated ERG proteins and one that encodes a TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid transcripts were found in samples taken from separate regions of individual cancer-containing prostates, suggesting that TMPRSS2-ERG gene fusions may be arising independently in different regions of a single prostate.

Gene Expression Regulation, Neoplastic↗
PubMed2006

A novel mutation in the XPA gene associated with unusually mild clinical features in a patient who developed a spindle cell melanoma.

BACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)- and chemical-induced DNA damage. The condition is characterized by an increased sensitivity of the skin to UV radiation, with early development of pigmentary changes and premalignant lesions in sun-exposed areas of the skin, signs of photoageing and a greatly increased incidence from a young age of skin tumours including melanoma. Approximately 20% of patients with XP show neurological abnormalities of varying severity due to primary neuronal degeneration. Genetic analysis by somatic cell hybridization has led to the identification in the NER-defective form of XP of seven complementation groups, designated XP-A to XP-G. These complementation groups correspond to different proteins involved in the NER process. XP-A classically includes some of the most severely affected patients. OBJECTIVES: We describe a 61-year-old Punjabi woman with XP. Remarkably she had only mild cutaneous abnormalities, minimal neurological features and unusual longevity, and developed a malignant spindle cell melanoma. There are few previous reports of spindle cell melanoma associated with XP. To gain insight into the aetiology of these unusual features, we sought to analyse the DNA repair properties of the patient and identify the complementation group and the causative mutation in the defective gene. METHODS: Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The complementation group was assigned by fusing the cells of our patient with XP cells of known complementation groups and determining the ability to carry out unscheduled DNA repair. Molecular analysis of the cDNA was carried out by polymerase chain reaction and DNA sequencing. RESULTS: Levels of DNA repair were extremely low and complementation analysis assigned the defect to the XP-A group. Sequencing of the XPA gene revealed a novel homozygous mutation of A-->G at the eighth nucleotide of intron 4 causing aberrant splicing and a nonfunctional truncated XP-A protein. However, a small amount of normally spliced mRNA was detected at <5% the level in normal cells. CONCLUSIONS: The small amount of normally spliced mRNA detected may be sufficient to explain the relatively mild clinical features in our patient.

Afghanistan↗
PubMed2006

The comparative roles of electron microscopy and immunohistochemistry in the diagnosis of soft tissue tumours.

Electron microscopy has contributed to the diagnosis of soft tissue tumours for four decades, and immunohistochemistry for two. Because of its relative ease of use and interpretation, the latter technique has become extensively and routinely applied to identify lines of differentiation in benign soft tissue tumours and in sarcomas. The use of electron microscopy has declined but retains a role because few antibodies are wholly specific or fully sensitive, some tumours are polyphenotypic or divergent in differentiation, and others have no specific antigens. Immunohistochemistry is superior in diagnosis of smooth muscle tumours, small round cell tumours, sarcomas with epithelioid morphology, and most synovial sarcomas. Electron microscopy is of particular value for peripheral nerve sheath tumours, marker-negative synovial sarcomas, pleomorphic sarcomas and mesotheliomas. As with all adjunctive techniques, immunohistochemistry and electron microscopy should be used in a complementary fashion according to the nature of the diagnostic problem.

Diagnosis, Differential↗
PubMed2006

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Humans↗
PubMed2005

Construction of tissue microarrays from prostate needle biopsy specimens.

Needle biopsies are taken as standard diagnostic specimens for many cancers, but no technique exists for the high-throughput analysis of multiple individual immunohistochemical (IHC) markers using these samples. Here we present a simple and highly reliable technique for constructing tissue microarrays (TMAs) from prostatic needle biopsies. Serial sectioning of the TMAs, called 'Checkerboard TMAs', facilitated expression analysis of multiple proteins using IHC markers. In total, 100% of the analysed biopsies within the TMA both preserved their antigenicity and maintained their morphology. Checkerboard TMAs will allow the use of needle biopsies (i) alongside other tissue specimens (trans-urethral resection of prostates and prostatectomies in the case of prostate cancer) in clinical correlation studies when searching for new prognostic markers, and (ii) in a diagnostic context for assessing expression of multiple proteins in cancers from patients prior to treatment.

Biopsy, Needle↗
PubMed2005

Prognostic factors in advanced synovial sarcoma: an analysis of 104 patients treated at the Royal Marsden Hospital.

AIMS: Key prognostic factors at diagnosis of synovial sarcoma are well defined from the literature. There are few data regarding prognostic parameters in the setting of advanced disease. Our aim was to look specifically at a cohort of patients with advanced synovial sarcoma and to identify potential prognostic factors. PATIENTS AND METHODS: One hundred and four patients with advanced synovial sarcoma were identified from the Royal Marsden Hospital's sarcoma database between 1978 and 2003. Patient data were analysed retrospectively. Most patients were aged between 20 and 50 years at diagnosis. Seventy-one patients were deceased at the time of analysis. Ninety-two patients received chemotherapy for management of advanced disease (most commonly doxorubicin + ifosfamide). RESULTS: Median survival following development of advanced disease was 22 months. Predictors of survival with advanced disease were age <35 years (P = 0.03) and response to first-line chemotherapy (P = 0.05). The response rate to doxorubicin plus ifosfamide was 58.6%, and this was superior to either agent when given singly. Metastasectomy was not associated with improved prognosis in this series. CONCLUSIONS: Synovial sarcoma is a chemosensitive soft tissue sarcoma. Compared with historical controls, survival with advanced disease seems to have improved over the years, possibly as a result of better use of chemotherapy. Age <35 years and response to first-line chemotherapy predict for improved survival with advanced disease.

Adult↗
PubMed2005

Surgical management of primary and recurrent retroperitoneal liposarcoma.

BACKGROUND: Surgery plays a dominant role in the initial and subsequent treatment of retroperitoneal liposarcoma (RPLS). This study was a review of outcomes of patients treated at the Royal Marsden Hospital. METHODS: Records of all patients who had surgery for RPLS since 1990 were reviewed, with particular attention to local recurrence and disease-specific survival. Patients with primary RPLS and those with recurrent RPLS, who had palliative surgery after a variable number of operations performed elsewhere, were considered separately. RESULTS: Seventy-two patients had surgery for primary RPLS, over half of whom underwent resection of a contiguous organ to achieve clearance. Follow-up of at least 12 months was available for 58 patients. Thirty-four patients had no evidence of recurrence after median follow-up of 26 (range 12-151) months. Low-grade tumour and macroscopic clearance of tumour were significantly associated with a reduced risk of local recurrence and improved survival. Forty-seven patients had palliative surgery for recurrent RPLS. Median survival from time of last operation to death was 27 (range 0-79) months. Follow-up was to a median of 68 (range 14-261) months. CONCLUSION: Patients with low-grade RPLS that has been completely resected at the initial operation have the most favourable prognosis. Palliative resection is worthwhile to treat troublesome symptoms of recurrence.

Adult↗
PubMed2005

Imaging features of retroperitoneal and pelvic schwannomas.

AIM: To describe the imaging features of retroperitoneal and pelvic schwannomas. MATERIALS AND METHODS: The presenting cross-sectional imaging for 18 sequential patients with retroperitoneal or pelvic schwannomas was reviewed retrospectively. Note was made of tumour diameter, position, homogeneity, margin, shape, calcification and invasion into adjacent structures. Where MRI had been performed, T1 and T2 signal intensity relative to skeletal muscle, and the degree and pattern of enhancement with gadolinium, were also assessed. RESULTS: Imaging from 13 patients was available for review. The mean tumour diameter was 8.7 cm (range 4 to 15 cm); 9 schwannomas were located in the pelvis and 4 in the retroperitoneum; 12 cases showed smooth, regular margins and 1 case irregular, invasive margins. The tumours were homogeneous in 5 cases and heterogeneous with cystic change in 8; in 2 cases there was smooth expansion of a sacral nerve root exit foramen, and in 1 there was bony destruction of the sacrum and extension of tumour into the spinal canal. In 5 cases MRI was performed; on T1-weighted images all tumours were isointense; on T2-weighted images 4 tumours were hyperintense and 1 was isointense to skeletal muscle. In all cases the diagnosis was confirmed by core biopsy. CONCLUSION: Retroperitoneal and pelvic schwannomas typically form large, well-circumscribed masses in the retroperitoneum or presacral area, and frequently undergo cystic degeneration. They can occasionally cause bony changes in the spine, but otherwise do not invade or obstruct adjacent structures. Although they are rare, it is important for the radiologist to recognize the typical appearance of schwannomas because they can be mistaken for malignant tumours.

Adult↗
PubMed2005

Evaluation of perineurial differentiation in epithelioid sarcoma.

AIMS: To investigate the differentiation pattern of epithelioid sarcoma in terms of perineurial and endothelial differentiation, and its relationship to that of meningioma. METHODS AND RESULTS: Nine cases of epithelioid sarcoma and five cases of meningioma were studied in an immunohistochemical analysis of 'perineurial' antigens [GLUT-1, claudin-1, epithelial membrane antigen (EMA) and VE-cadherin] and of 'endothelial' antigens not present on normal perineurium (CD34, CD31, Fli-1). Both epithelioid sarcoma and meningioma showed frequent expression of the perineurial markers GLUT-1, claudin-1 and EMA. VE-cadherin was identified in one of five meningiomas, and in the only case of epithelioid sarcoma in which suitably fixed material was available. CD34 was expressed by all epithelioid sarcomas studied but by none of the meningiomas. Fli-1 was present in a substantial majority of epithelioid sarcomas and by all the meningiomas. CD31 was not detected in any epithelioid sarcoma or meningioma. CONCLUSIONS: The results were evaluated in the context of previous immunohistochemical, ultrastructural and genetic studies and suggest that epithelioid sarcoma may be a form of malignant perineurioma with a range of differentiation (epithelial features) akin to that seen in meningioma, reflecting the close relationship between perineurium and meningothelium.

Antigens, CD↗
PubMed2005

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique.

AIMS: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. CONCLUSIONS: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.

Biomedical Research↗
PubMed2004

Short-term sleep deficits do not adversely affect acquisition of laparoscopic skills in a laboratory setting.

BACKGROUND: Residents often are sleep deprived after being on call. This study evaluated the effects of these sleep deficits on the acquisition of laparoscopic skills in the laboratory setting. METHODS: The amount of sleep on the preceding night was recorded for 40 residents undergoing surgical skills training. The residents underwent a pretest, training, practice, and a posttest using basic (pegboard, cup drop, rope pass) and task-specific (pattern cutting, clip application, loop application) drills. Time to completion, penalty score, and total score were assessed. RESULTS: Significant improvements were seen in the time and total score for all six drills, with a significant decrease in penalty scores noted for the pegboard and rope pass drills. No significant differences in skill acquisition were attributable to amount of sleep. CONCLUSION: Training in the laboratory results in significant improvement of basic laparoscopic skills. Because short-term sleep deficits do not appear to hinder the acquisition of these skills, this model can be effectively applied, even after residents correct have been on call.

Adult↗