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Biomedical subjects

C J O'Brien

Publications and source records attributed to C J O'Brien.

At least 91 records · Page 5Linked to original sources

Radical neck dissections for squamous carcinomas: pathological findings and their clinical implications with particular reference to transcapsular spread.

Two hundred fifty radical neck dissections, undertaken for mucosal squamous carcinomas of the head and neck, were reviewed with reference to pathological findings and their clinical implications. No major differences in descriptive surgical pathology were established between irradiated and non-irradiated resections. In general, irradiated dissections had lower total node counts and somewhat fewer nodal metastases involving a smaller number of different nodal groups. The topography of nodal deposits was similar in irradiated and non-irradiated resections. Palpable keratin granulomas (without intact tumor) were almost confined to irradiated patients. Transcapsular spread of tumor from involved lymph nodes was common: it was demonstrated in 160/188 'positive' dissections (85%) and was subclassified as 'macroscopic' in 90 and 'microscopic' in 70. The incidence and extent of transcapsular spread was similar in irradiated and nonirradiated resections. It was more frequently observed in association with large nodal masses but it was also regularly found with small nodal deposits less than 3 cm in diameter. Statistical analyses showed strong associations (p less than 0.0005) between the presence and/or extent of transcapsular spread and subsequent recurrence in the operated neck and overall survival. The predictive value of other clinical and pathological features vis-a-vis local neck recurrence such as numbers of involved nodal groups was weaker. Macroscopic transcapsulr spread emerges as the major prognostic factor for recurrent disease in the neck (p less than 0.0001). Attention is drawn to the advantages of accurate descriptive categories ('macroscopic', 'microscopic') for this critical prognostic feature.

Carcinoma, Squamous Cell↗

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in high-grade non-Hodgkin's lymphoma.

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.

Adolescent↗

Paraplegia due to massive asbestos-related pleural and mediastinal fibrosis.

A case of massive pleural and mediastinal fibrosis related to occupational exposure to asbestos is presented. The terminal illness was marked by the acute onset of paraplegia. Autopsy revealed occlusive lesions of upper intercostal arteries within sheets of dense fibrous tissue and an ischaemic myelopathy. The presence of vascular lesions suggests a relationship with idiopathic mediastinal fibrosis.

Arterial Occlusive Diseases↗

Current status of neck dissection in the management of squamous carcinoma of the head and neck.

Classical radical neck dissection (RND) remains the primary treatment for clinically positive lymph nodes among patients with squamous carcinoma of the upper aerodigestive tract. Recurrence rates following RND range from 20 to 70% depending on the number of nodes involved and the extent of extracapsular spread. Modified radical neck dissection (MRND) is associated with less cosmetic and functional morbidity than RND but, used alone, MRND is only appropriate when clinical neck disease is absent or minimal. Both RND and MRND should be combined with adjuvant postoperative radiotherapy when more than one node is positive or extracapsular spread is present. This approach will significantly decrease regional failure, but may not improve survival because of an increased incidence of distant metastases. MRND is especially useful as an elective procedure to stage the clinically negative neck. A survival benefit from elective neck dissection, however, remains to be demonstrated.

Carcinoma, Squamous Cell↗

Neurological sequelae in patients recovered from fulminant hepatic failure.

Two teenage patients with fulminant hepatic failure progressing to grade 4 encephalopathy with clinical signs of cerebral oedema are described, in whom permanent neurological injury (involving the brain stem in one and the cerebral cortex in the other) was the sequel to an otherwise full recovery. The present day management of cerebral oedema may, as in these two cases, ensure the survival of patients with fulminant hepatic failure who would previously have been likely to die from the effects of raised intracranial pressure. As a result it is now possible more recovered cases will be seen with residual neurological deficits, a previously very rarely recorded event.

Adolescent↗

Downgrading of non-Hodgkin's lymphoma following chemotherapy.

A case of high-grade non-Hodgkin's lymphoma (malignant lymphoma centroblastic) is presented which, following chemotherapy, manifested low-grade histology. The importance of repeated biopsies in cases of persistent or recurrent disease following therapy for lymphoma is emphasized.

Aged↗

Cellular immunity to nucleocapsid and pre-S determinants in asymptomatic carriers of hepatitis B virus.

Previous studies of cellular immunity in asymptomatic HBV carriers have been limited to evaluation of responses to plasma-derived HBsAg preparations. We have explored the specificity of cellular immune responses to HBV antigens in these subjects using an indirect T-lymphocyte migration inhibitory factor assay and three antigen preparations (recombinant nucleocapsid antigen (HBcAg), plasma-derived HBsAg with or without pre-S2, and Saccharomyces cerevisiae-synthesized HBsAg without pre-S2 region). T cells from 10 asymptomatic chronic HBV carriers with normal liver function tests were responsive to nucleocapside determinants (mean migration index = 0.55 +/- SD 0.07) and to pre-S2-positive plasma-derived HBsAg (MI = 0.62 +/- 0.05). However, none responded to HBsAg devoid of pre-S2 sequences (MI = 0.98 +/- 0.04). In further experiments, T cells from three HBV carriers, cultured with six different HBsAg preparations, exhibited responsiveness only to those preparations containing significant pre-S2 activities. Our results show that T-cell immunity to nucleocapsid determinants of the virus and HBsAg in present in asymptomatic HBV carriers; the latter is restricted to antigenic preparations containing significant pre-S2 activities. Hence, T-cell immunity to pre-S determinants may not always be associated with HBV clearance.

Adolescent↗

Influence of aetiology, clinical and histological features on survival in chronic active hepatitis: an analysis of 204 patients.

To determine which clinical and laboratory features may influence survival in patients with chronic active hepatitis, we undertook a retrospective study of 204 patients seen on this unit over a 15-year period and applied logistic regression analysis. One hundred and six patients had autoimmune chronic active hepatitis, 69 'cryptogenic' chronic active hepatitis (no autoimmune markers or other aetiological factors identified), and 29 were HBsAg-seropositive. Variceal haemorrhage, encephalopathy and ascites were common presenting features in the cryptogenic group while the presence of jaundice and other immunopathic diseases did not differ between the groups. Cirrhosis was more common at presentation in the cryptogenic group. Remission was induced with corticosteroids and azathioprine in 82 per cent of patients with autoimmune chronic active hepatis and in 77 per cent of patients with cryptogenic chronic active hepatitis and the annual relapse rate was similar in the autoimmune and cryptogenic groups. Five-year survival was 87 per cent in the autoimmune group, 65 per cent in the cryptogenic group, and 80 per cent in those with HBsAg-positive disease, and on logistic regression analysis, the presence of cirrhosis at presentation was the only independent factor which adversely affected survival. Overall survival in the cirrhotic patients at five and 12 years was 63 and 48 per cent respectively compared with 95 and 92 per cent in those without cirrhosis.

Adolescent↗

Cell-mediated immunity and suppressor-T-cell defects to liver-derived antigens in families of patients with autoimmune chronic active hepatitis.

By means of an indirect T-lymphocyte migration inhibitory factor assay, T-cell sensitisation to the asialoglycoprotein receptor, a liver-specific protein on the surface of hepatocytes, was found in patients with autoimmune chronic active hepatitis (CAH) but not in healthy relatives or spouses. Cellular immunity to a liver-derived lipoprotein complex (LSP) which also contains the asialoglycoprotein receptor, and to which immune reactions have been previously demonstrated in patients with CAH, was also examined. In contrast to the findings with the purified asialoglycoprotein receptor, cell-mediated sensitisation to LSP was detected in all the patients and also in 24% of first-degree relatives and 27% of spouses, suggesting an environmental influence. There was a functional defect in suppressor T lymphocytes specific for liver-derived antigens in 50% of first-degree relatives and 43% of second-degree relatives, but in only 9% of spouses. This abnormality of immunoregulation may be genetically determined and crucial to the development of the disease.

Adult↗

Neck dissection with and without radiotherapy: prognostic factors, patterns of recurrence, and survival.

A group of 179 patients who had 205 neck dissections between 1979 and 1984 has been reviewed to assess the influence of adjuvant radiotherapy on survival. Lymph nodes were histologically involved in 91 of 107 radical neck dissections (85 percent) and 55 of 98 modified neck dissections (56 percent). Eighty-two patients received adjuvant radiotherapy of 5,000 rads or more. Patients with involved nodes had significantly lower survival rates than those with uninvolved nodes. Among patients with involved nodes, survival was significantly lower when two or more nodes were involved, when there was nodal involvement at multiple levels, or when extracapsular spread was present. Adjuvant radiotherapy was associated with a reduced recurrence rate in the ipsilateral neck but the incidence of distant metastases was higher. When patients with involved nodes were subgrouped according to prognostic factors, the survival of irradiated patients was improved only in the highest risk group, but this was not statistically significant. When radiotherapy is added to neck dissection for treatment of cervical metastases it can be expected to reduced ipsilateral neck recurrence and prevent relapse in the contralateral neck. Improved survival may depend on an ability to detect and treat occult distant metastases.

Adult↗

Evaluation of a clinically useful length of 1 mm diameter PTFE as a microvascular graft.

Previous studies of 1 mm internal diameter polytetrafluoroethylene (PTFE) have investigated short graft lengths. The aim of this experiment was to assess a longer, clinically useful graft. Femoro-femoral crossover grafts 6 cm long were implanted into 20 rats and, after an initial observation period of 1 hour, were followed up for four weeks. Ten grafts failed within the first hour post-operatively, one was occluded at 2 weeks and nine were patent at 4 weeks (45% patency). Technical errors causing stasis within the prosthesis led to the early failures. When stasis was avoided patency was good and did not appear to be dependent upon development of a cellular lining within the graft.

Animals↗

T-lymphocyte sensitization to hepatocyte antigens in autoimmune chronic active hepatitis and primary biliary cirrhosis. Evidence for different underlying mechanisms and different antigenic determinants as targets.

Cultured with a liver-derived lipoprotein complex, T lymphocytes from 42 of 45 patients with autoimmune chronic active hepatitis generated migration inhibitory factor compared with 16 of 33 patients with primary biliary cirrhosis. Unlike T lymphocytes from patients with primary biliary cirrhosis, the T-cell reactivity of patients with chronic active hepatitis was always suppressed by T cells from normal subjects and, with two exceptions, by T cells from patients with primary biliary cirrhosis, even when these latter cells exhibited sensitization to this same antigen complex. Using a component of the whole complex, the asialoglycoprotein receptor as antigen, migration inhibitory factor was invariably released by T cells from patients with autoimmune chronic active hepatitis, but from only 2 of 8 patients with primary biliary cirrhosis sensitized to the whole complex. Thus, in autoimmune chronic active hepatitis, but not in primary biliary cirrhosis, the asialoglycoprotein receptor is invariably a target for cellular immune reactions and is associated with a suppressor T-cell defect for hepatocyte antigens.

Adolescent↗

Uncommon malignant tumours of the larynx. A 35 year review.

Sixty-five primary malignant laryngeal tumours, other than simple squamous cell carcinomas, treated at the Royal Marsden Hospital between 1949 and 1984 are presented. Of the 11 histological types pseudosarcomas (24 cases), verrucous carcinomas (9 cases) and lymphoreticular tumours (9 cases) predominated. Determinate three-year follow-up data were available in 50 cases. Sixteen patients (32 per cent) died of their neoplasms but survival was strongly related to histology. Only one death occurred among 24 determinate cases of pseudosarcoma and verrucous carcinoma. Radiotherapy was effective treatment for these two tumour types and for reticuloendothelial tumours. However, combined therapy yielded poor results with the other histological types.

Combined Modality Therapy↗

DNA content and prognosis of non-Hodgkin's lymphoma.

Ninety cases of non-Hodgkin's lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.

Adolescent↗

Reconstruction of the mandible with autogenous bone following treatment for squamous carcinoma.

In a series of 24 patients treated for squamous carcinoma of the oral cavity and oropharynx, 26 mandibular reconstructions using 27 grafts or flaps were performed. Reconstruction was immediate in 23 cases and delayed in three. There were five 'simple' bone grafts, 10 pedicled compound myocutaneous flaps, and 12 vascularized free compound flaps. Operative mortality was 12% and complication rate 65%, but 70% of the grafts survived till death or follow-up of the patients. Three 'simple' bone grafts failed and were removed. Three of five compound pectoralis major flaps failed along with one of five pedicled compound latissimus dorsi flaps. Only one vascularized free compound flap was lost. The major cause of graft failure was intra-oral suture line dehiscence exposing the bone to saliva. Under these circumstances, bone graft necrosis occurred when blood supply to the bone was poor--viz. 'simple' grafts and compound pectoralis major flaps. The vascularized free compound flaps were most reliable but the need for jaw preservation where possible and better patient selection are recognized.

Adult↗