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Biomedical subjects

A M Lessells

Publications and source records attributed to A M Lessells.

At least 19 recordsLinked to original sources
PubMed1999

Primary non-Hodgkins lymphoma of muscle.

A retrospective analysis was made of all patients with primary muscle non-Hodgkin's lymphomas registered with the Scotland and Newcastle Lymphoma Group over a 15-year period. Only eight patients were identified. The median age was 69 years (range 27-93). Five patients were male and six lymphomas were of high grade histology. The glutei and upper arm muscles were the main sites of origin, with the additional involvement of adjacent bone in four patients; only three had lymph node involvement at presentation. Most patients (6/8) received both chemotherapy and radiotherapy. The median survival was 33 months. The conclusion is that this is a small group of patients whose outlook is not as poor as has been suggested in previous reports.

Adult↗
PubMed1998

Nitric oxide and gall-bladder motor function.

BACKGROUND: The L-arginine: nitric oxide (NO) pathway has been shown to be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission. AIM: To determine the role of the L-arginine: NO pathway in gall-bladder motor function. METHODS: Strips of fresh bovine and human gall-bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb's solution upon CCK-stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L-NG-monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gall-bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall-bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L-NMMA. RESULTS: In the in vitro study, GTN and SNP significantly reduced the tension of CCK-stimulated muscle contraction whilst Kreb's solution had no effect. L-NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall-bladders. In the in vivo study, both GTN and SNP caused significant impairment of gall-bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L-NMMA. CONCLUSION: Pharmacological doses of NO donors impair postprandial gall-bladder emptying in vivo and relax gall-bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.

Adult↗
PubMed1997

Observer variability in the histopathological reporting of needle biopsy specimens of the prostate.

The Scottish Pathology Consistency Group has in previous studies examined the consistency of histopathological reporting of biopsies from the cervix, bladder, bronchus, and rectum. In the current study, consisting of 100 needle biopsy specimens of the prostate, a single hematoxylin-eosin (H&E) slide from each case was circulated in batches of 10 to the 12 pathologists, who filled in a simple proforma. This had two sections: a diagnostic category (benign; suspicious or malignant) along with a standard Gleason score for those regarded as malignant. The majority diagnosis of the 100 cases was benign, 53; suspicious, 1; and malignant, 46. The Kappa value for benign cases versus others was 0.86 and for malignant cases versus others was 0.91. Analysis of the data on Gleason scores showed a value of 0.54 when cases were divided into two categories (2 to 6 v 7 to 10) and 0.41 when three categories were used (2 to 4; 5 to 6; 7 to 10). Although not initially part of the design of the study, the majority diagnosis was compared with the original reported diagnosis. In a small subset, examination of further levels, basal cell antibody staining, along with further clinical information, was obtained. With this added information, it appears that there were probably 52 benign and 48 malignant cases. Of the 48 malignant cases, the group majority diagnosis was malignant, 46; suspicious, 1; and benign, 1. The original reported diagnosis was 56 benign, 1 suspicious, and 43 malignant. The group therefore appeared to perform better than the original reporting pathologists. When compared with the results of our previous studies, this study has shown that the diagnosis of carcinoma of the prostate on a needle biopsy is robust.

Biopsy, Needle↗
PubMed1997

CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Adult↗
PubMed1996

Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours.

The extracellular matrix protein tenascin (TN) is overexpressed in a number of solid tumours. Thi however, is the first study to examine TN expression in ovarian tumours. TN protein was examined in froze sections of 50 human ovarian tumours by immunohistochemistry. Malignant and borderline tumours showed significantly greater incidence and intensity of stromal staining than benign tumours (P < 0.0001 and P = 0.038 respectively). Seven omental metastases were also examined and showed a strikingly similar protein distribution to their primary tumour counterparts. The expression pattern of different RNA isoforms, created by alternative splicing of the primary transcript, was identified using reverse transcription-polymerase chain reactions (RT-PCR). The smallest TN RNA splice variant (284 bp) was found in all tumours examined, while the appearance of larger molecular weight transcripts (approximately 490 and 556 bp), as major forms, was predominantly limited to malignant tumours, with 9/12 malignant tumours showing this pattern compared with 1/6 benign tumours. These data suggest that malignant ovarian tumours have increased expression of TN compared with benign tumours and this may be associated with induction of specific isoforms.

Female↗
PubMed1996

The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer.

The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-alpha showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P = 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-alpha nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer.

Base Sequence↗
PubMed1996

Ductal (endometrioid) adenocarcinoma of the prostate: a clinicopathological study of 16 cases.

Sixteen cases of ductal (endometrioid) carcinoma of the prostate are presented. The tumour presents in elderly men (age range 65-87 years) with haematuria or obstructive symptoms. Serum prostate specific antigen may be normal or raised. On cytoscopy, there is often an exophytic lesion in the region of the verumontanum. Histologically, two variants are recognized: papillary and cribriform, of which there were eight cases each. Eight cases consisted of pure ductal carcinoma and seven were mixed, containing a variable proportion of micro-acinar carcinoma. The associated micro-acinar carcinoma had a Gleason score of at least 5. One case of carcinosarcoma with a ductal epithelial component was also included. All cases displayed positive immunohistochemical staining for prostate specific antigen and prostatic acid phosphatase and but were negative for the basal cell marker MA903. The tumour responds well to orthodox micro-acinar carcinoma therapy and appears notably sensitive to hormonal manipulation. Follow-up of the mixed group is restricted to a maximum of 3 years. Of the eight pure cases, five patients are still alive with survival periods of 11, 8, 7, 3 and 1 years. Three patients died of intercurrent disease of which one patient survived 12 years, having received no treatment. This tumour, therefore, can be regarded as having a good prognosis.

Acid Phosphatase↗
PubMed1996

Observer variability in histopathological reporting of non-small cell lung carcinoma on bronchial biopsy specimens.

AIMS: To evaluate the ability of histopathologists to sub-classify non-small cell lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. METHODS: Twelve histopathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing non-small cell lung carcinoma. For each case, two sections were circulated, one stained by haematoxylin and eosin and the other by a standard method for mucin (alcian blue/periodic acid Schiff). The participants were allowed to indicate their degree of confidence in their classification of each case. A standard proforma was completed and the results were analysed using kappa statistics. RESULTS: Where the participants were confident in their classification, they were actually quite good at sub-classifying the non-small cell carcinoma sections (kappa = 0.71, standard error = 0.058). Overall, however, the results were only fair (kappa = 0.39, standard error = 0.034). CONCLUSIONS: The majority of non-small cell lung carcinomas can be correctly categorised on adequate bronchial biopsy material. Where a confident diagnosis was made, both squamous carcinoma (kappa = 0.73) and adenocarcinoma (kappa = 0.83) were well recognised.

Adenocarcinoma↗
PubMed1995

c-erbB growth-factor-receptor proteins in ovarian tumours.

Immunohistochemical expression of EGF-R, c-erbB-2 and c-erbB-3, members of the type-1 family of receptor tyrosine kinases, were investigated in 67 primary ovarian-tumour samples (46 malignant, 8 borderline and 13 benign), and related to tumour clinicopathological features. The incidence of all 3 receptor proteins was highest in overtly malignant tumours. No significant correlations were observed between either EGF-R or c-erbB-3 and clinical parameters such as tumour stage, differentiation or extent of debulking surgery, but c-erbB-2 was significantly associated with several indicators of prognosis, including early stage and good/moderate differentiation in optimally debulked tumours. Multiple expression of c-erbB receptor proteins was also significantly higher in malignant tumours compared with borderline and benign tumours. Early-stage tumours were also more likely to express multiple c-erbB-receptor proteins than were late-stage tumours. Co-expression of EGF-R with c-erbB-2, and c-erbB-2 with c-erbB-3 was significantly greater in malignant tumours than in borderline or benign tumours, and within the malignant tumour group, positive associations were observed between EGF-R and c-erbB-3, also between c-erbB-2 and c-erbB-3. Because of the evidence of increased expression of individual c-erbB proteins as well as multiple expression of this family of growth-factor receptors in malignant ovarian tumours, we hypothesize that stimulation by the appropriate ligands may confer a selective advantage to cells expressing more than one receptor. Increased expression of c-erbB growth-factor receptors in malignancy may mediate increased propensity for tumour development.

Adult↗
PubMed1995

Presentation of endometriosis to general surgeons: a 10-year experience.

The presentation and management of 24 patients with endometriosis (median age 34 (range 21-68)years) presenting to general surgeons over a period of 10 years (1985-1994) was reviewed. Patients presented with an abdominal wall swelling related to a previous Pfannenstiel incision (seven patients), umbilical swelling (four), inguinal canal swelling (two), incidentally following appendicectomy (five), terminal ileal obstruction (two), rectal bleeding (two) and urinary symptoms (two). Endometriosis was not suspected in most patients but was confirmed by surgical excision or resection with minimal morbidity. No recurrence occurred during a median follow-up of 53 (range 9-113) months. Endometriosis is a disease rarely seen by general surgeons and is often diagnosed incidentally or on histological examination. Cyclical symptoms associated with menstruation are present in 50 per cent of patients and should suggest the diagnosis in those presenting with scar-related and/or subcutaneous swellings. Simple excision or resection of the presenting lesion provides adequate treatment but, since pelvic endometriosis may be present, referral to a gynaecologist is recommended in every case.

Abdominal Muscles↗
PubMed1995

c-erbB-3 protein expression in ovarian tumours.

In this study the expression of c-erbB-3 protein was investigated in a range of human ovarian tumours using a monoclonal antibody (RTJ1) raised to a synthetic peptide from the cytoplasmic domain of the human c-erbB-3 protein. A total of 73 samples from 71 patients were graded as negative, weak, moderate or strong according to the intensity of immunohistochemical staining observed, and this was related to tumour characteristics and other clinical parameters. In terms of positivity vs negativity, of the 73 samples examined, 62 (85%) showed positive immunohistochemical staining for c-erbB-3. The majority of all ovarian tumours studied were positive for c-erbB-3 regardless of whether they were malignant (89%), borderline (100%) or benign (61%), however the incidence of positivity was significantly less in the benign group than in overtly malignant tumours (P = 0.03). c-erbB-3 positivity was not significantly associated with either age at diagnosis, tumour stage, differentiation, ploidy, percentage in S-phase or post-operative tumour bulk in malignant tumours. In terms of intensity of staining no significant difference was observed either within the common epithelial group or between this group and tumours of a benign nature. A significantly more intense pattern of c-erbB-3 staining was observed in tumours of borderline malignancy when compared with their overtly malignant counterparts (P = 0.002). Patients presenting with early-stage malignant tumours (I/II) were more likely to display intense tumour staining than those with late-stage disease (III/IV) (P = 0.04). These investigations suggest that c-erbB-3 protein is frequently expressed in both benign and malignant ovarian tumours, and that overexpression is more common in borderline and early invasive lesions.

Age Factors↗
PubMed1994

Observer variability in the histopathological reporting of abnormal rectal biopsy specimens.

AIMS: To study the consistency of reporting of abnormal rectal biopsy specimens, especially in the differentiation of inflammatory bowel disease from other causes of abnormality. METHODS: Sixty rectal biopsy specimens were identified from patients presenting with bloody diarrhoea. These were then circulated to the 11 consultant pathologists in the study who filled in a proforma with a list of 12 diagnostic categories and 22 features. RESULTS: Forty one of the 60 cases were examples of inflammatory bowel disease. In 33 of these cases nine or more pathologists had made the diagnosis. Further categorisation into ulcerative colitis and Crohn's disease showed better recognition of ulcerative colitis. In the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous colitis and solitary rectal ulcer syndrome was good, but the results were poorer in the case of infective colitis. CONCLUSION: The findings suggest that a group of consultant pathologists can differentiate between inflammatory bowel disease and other causes of an abnormal rectal biopsy specimen and can also recognise pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.

Biopsy↗
PubMed1994

Observer variability in histopathological reporting of malignant bronchial biopsy specimens.

AIMS: To evaluate the ability of histopathologists to classify lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. METHODS: Eleven histopathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing lung carcinoma. A single haematoxylin and eosin stained section from each case was circulated and a standard proforma completed. These were analysed using kappa statistics. RESULTS: The histopathologists were excellent at distinguishing between small cell and non-small-cell carcinoma kappa = 0.86), but not so good at subclassifying the non-small cell carcinoma group kappa = 0.25). CONCLUSIONS: The clinically important distinction between small cell and non-small cell carcinoma of the lung is reliably made by competent histopathologists even on limited material.

Biopsy↗
PubMed1992

External quality assurance in histopathology: experience of the east of Scotland scheme.

AIMS: To examine the overall organisation of a voluntary external quality assurance scheme in histopathology, selection of case material and marking systems; and to assess the scheme in relation to contemporary histopathological practice. METHODS: Case material was derived from all participating departments and a positive marking system was used throughout the scheme. RESULTS: The mean response rate by those agreeing to participate was 66% and remains stable. The mean score of each set (n = 8) was high (63-80%) but scores about the mean varied widely in each set. The positive marking system was satisfactory and provided information equivalent to negative and weighted marking systems. The use of local coordinators providing the link between the central organiser and individuals has spread the administrative load and facilitated the introduction of small biopsy specimens. The selection of suitable case material has proved difficult at times. CONCLUSIONS: The scheme has an important role in histopathology quality assurance. It has been operative for four years and is widely accepted in the east of Scotland; it can be adapted to suit local circumstances.

Adult↗
PubMed1991

Surgery following chemotherapy for metastatic testicular teratoma.

Twenty patients with metastatic testicular teratoma underwent surgery for residual disease after chemotherapy. Twelve patients in whom complete excision of all residual masses was possible are alive with no evidence of disease. Four patients have died of malignant teratoma, 2 have active malignant disease and 2 have inoperable residual cystic disease. Patients with malignant teratoma intermediate (MTI) primary testis tumours, and those with bulky abdominal disease at presentation, are more likely to have residual masses requiring excision. Completeness of excision appears to be the most important predictor of disease-free survival.

Adolescent↗