Neck dissection for advanced lymph node metastasis before definitive radiotherapy for primary carcinoma of the head and neck.

OBJECTIVE: To evaluate the outcome of neck dissection for advanced metastasis and subsequent planned radiotherapy to the neck and primary tumor. STUDY DESIGN: Single-center, retrospective case series. METHODS: From 1988 to 1998, 37 previously untreated patients were included into the study protocol. Two had a single tumor-positive neck node and the remaining 35 had multiple tumor-positive neck nodes (mean number, 6.0). Extranodal spread was reported in 35 cases (95%); mean nodal size was 5.7 cm (SD, 2.4 cm). Five patients (14%) were not irradiated or were irradiated with palliative intention. Of the remaining patients, 30 received irradiation of 60 Gy or more to the neck and the primary tumor (mean dose, 66.9 Gy; SD, 4.2 Gy). Cumulative survival distributions were estimated by the Kaplan-Meier method, and differences between groups were analyzed with the log-rank test. RESULTS: Treatment-related mortality was observed in three patients (8%). Disease-specific survival was 49% at 2 years and the overall locoregional control rate was 43% at 2 years. Patients with T1 to T2 primary lesions were compared with those with advanced primary disease, and the 2-year local control rates were 76% and 47%, respectively (P = .056). The following prognostic factors were identified for distant metastasis: three or more positive nodes (P = .037), positive surgical margins in the neck dissection specimen (P = .004), and time from diagnosis until neck dissection of 23 days or more (P = .043). The influence of distant metastasis on disease-specific survival was evident (P = .0003). CONCLUSION: Patients with low-T-stage tumors have a better local control rate with this regimen and survival depends on the status of the neck.

Coexistence of widespread clones and large radial clones in early embryonic ferret cortex.

Cell lineage analysis in rodents has shown that the cerebral cortex is formed from both widespread and large radial clustered clones representing partly distinct lineages and producing differing cell types. Since previous cell lineage analysis of the ferret cortex using retroviral libraries showed that most neurons labeled at E33-E35 formed widespread clones, we determined whether clones labeled earlier in neurogenesis showed a greater tendency to form coherent radial clones. Clones labeled at E27-E29 occasionally consisted of widespread multineuron clones (13% of PCR-defined clones), but commonly consisted of small clusters of two to four neurons (65%). Moreover, 6/21 hemispheres contained a single, much larger (6-150 cells) radial cluster. Although large clusters were observed in 28% of experiments, they contained many neurons, accounting for 38% of retrovirally labeled cells. The large clusters showed at most few widely scattered sibling cells, either by histological analysis or by PCR analysis, suggesting that radial and widespread clones coexist but are lineally separate at early stages of corticogenesis. Coexistence of large radial and widespread neuronal clones appears to be an evolutionarily conserved mechanism for cortical neurogenesis.

A comparison of bleomycin-induced damage in lymphocytes and primary oral fibroblasts and keratinocytes in 30 subjects.

The number of chromatid breaks in peripheral blood lymphocytes (PBL) after exposure to bleomycin in the S/G2 phase of the cell cycle (in the literature referred to as 'mutagen sensitivity') is associated with an increased risk of environmentally related cancers, including oral cancer. The aim of this study was to elucidate whether mutagen sensitivity measured in lymphocytes actually reflects chromosomal instability of normal cells in the areas in which tumors develop. Therefore, bleomycin-induced chromosomal damage in and growth inhibition of cultured oral fibroblasts and oral keratinocytes from 30 persons were compared with the standard mutagen sensitivity score in PBL. A correlation was found for the percentage of aberrant metaphases between PBL and oral fibroblasts but not for the number of breaks per cell. These data do not allow a conclusion to be drawn on the use of fibroblasts to study cancer risk. Within the fibroblasts it was found that a high number of breaks per cell was associated with less growth inhibition, indicative of damage-resistant growth. Oral keratinocytes were extremely sensitive to bleomycin, as indicated by a strong cell cycle block which resulted in a mitotic index too low to determine chromosomal breaks. Moreover, in the cell proliferation assay keratinocytes were found to be 100 times more sensitive as compared with fibroblasts. There was no correlation between bleomycin sensitivity of keratinocytes compared with fibroblasts from a single patient as measured by growth inhibition. This may be due to the strong influence of alcohol consumption by the subjects, which was found to increase the sensitivity of keratinocytes but not of PBL and fibroblasts. In conclusion, oral fibroblasts but not keratinocytes can be used to measure sensitivity for chromatid breaks. The apparent influence of environmental factors on keratinocytes makes them a useful source to study exposure characteristics but limits their application for the determination of genetic factors.

Clonal mixing, clonal restriction, and specification of cell types in the developing rat olfactory bulb.

To understand the clonal relationship of various olfactory bulb (OB) cell types, OB progenitor cells were infected at embryonic day (E) 14, E15, and E17 with retroviral libraries encoding alkaline phosphatase or beta-galactosidase. After survival to postnatal day 10-15, sibling relationships were identified by polymerase chain reaction DNA amplification of distinct sequences in the retroviral constructs. Within the OB, clonal progeny dispersed widely in all directions. In sharp contrast, however, clonal dispersion between the OB and neocortex was not observed, although occasional clonal dispersion between the OB and pyriform and hippocampal regions could not be excluded. Most clones (84%) contained a single cell type, especially after E17 injections, suggesting the existence of either restricted precursors, or multipotential progenitors instructed by a restricted cellular environment. Mixed OB clones (16%) contained multiple cell types in the OB, or occasionally glial or neuronal cells outside the OB, demonstrating the existence of multipotential OB progenitors, likely at a stage before formation of the olfactory rostral migratory stream. Surprisingly, OB glial cells were not labeled, suggesting distinct lineages or perhaps distinct migratory paths for glia and neurons into the OB. A hierarchical cell lineage is proposed that involves a multipotential progenitor that gives rise to potentially more limited progenitors.

Biologic implications of genetic changes in head and neck squamous cell carcinogenesis.

Cytogenetic techniques for the analysis of genetic changes common in head and neck squamous cell carcinogenesis show complex patterns of chromosomal deletions, translocations, and amplifications. Powerful molecular biologic techniques have recently made possible the investigation of these abnormalities at the DNA level. Tumour suppressor gene loss and oncogene activation can now be recognized in tumours. Multiple genetic loci are implicated in the carcinogenesis process, while much evidence points to the existence of yet to be recognized tumour suppressor genes. An overview of the genetic changes commonly seen in head and neck squamous cell carcinogenesis and the possible implications of these are presented.

A simple and reliable technique for culturing of human oral keratinocytes and fibroblasts.

Cultures of non-malignant oral cells are needed for many applications in the field of oral biology. We describe an efficient and rapid method for the culture of both keratinocytes and fibroblasts isolated from oral tissue, uvulas from patients undergoing reconstructive surgery and non-cancerous tissue from oral cancer patients. High cell yields with a high purity could be obtained. The technique is described in detail with respect to isolation of the cell types, the best way to propagate for over 5 passages and to measure cell proliferation in a colorimetric assay. Culture was successful in over 80% of cases for keratinocytes and over 63% for fibroblasts. Problems encountered were the risk of microbiological infection, the size of the specimen and the type of culture medium used. The potential applications of these primary cell cultures are mentioned.

Clonal dispersion and evidence for asymmetric cell division in ferret cortex.

Cell lineage analysis with retroviral libraries suggests that clonal progeny disperse widely in rodent cortex. To determine whether widespread dispersion is a general mammalian plan and to investigate phylogenetic differences in cortical development, we analyzed cell lineage in the ferret, a carnivore and near relative of the cat. The ferret possesses a highly developed, folded cerebral cortex, characteristic of higher mammalian species. Progenitor cells of the ferret cerebral cortex were tagged with an amphotropic retroviral library encoding alkaline phosphatase, and sibling relationships were determined using the polymerase chain reaction. Neuronal clones were single neurons (52%) or large clones (48%; average, 7 neurons) containing neurons and glia in widespread cortical locations. Neuronal clones in the ferret labeled at middle to late neurogenesis (embryonic day 33-35) contained large numbers of neurons and showed little tendency to cluster. The large proportion of single neuron clones, contrasted with the large size of multicell clones, suggests that some progenitors divide asymmetrically, producing a postmitotic neuron and regenerating a multipotential cell.

The outcome of vestibular nerve section for intractable vertigo: the patient's point of view.

To document the outcome of vestibular nerve section from the patient's point of view we reviewed 102 patients who had undergone vestibular nerve section 1 to 10 years after operation. Only 3 patients had experienced further vertigo attacks: 2 of these were cured by a further, this time translabyrinthine vestibular nerve section; 1 patient developed multiple sclerosis. In contrast, about 50% of patients developed some subjective problem with balance while standing or walking; in 15% it was present all the time and of moderate severity. Despite this, over 85% of patients reported that they felt much better or back to normal after the operation and were satisfied with the outcome. The development and application of objective preoperative measures of vestibular and, in particular, vestibulospinal function might improve patient selection for vestibular nerve section and thus reduce the number of dissatisfied patients.

Systematic widespread clonal organization in cerebral cortex.

Cell lineage analysis in the cortex has revealed two clonal patterns, clustered and widespread clones. To determine the relationship of these patterns, progenitor cells were infected with a retroviral library encoding alkaline phosphatase, and cortical sibling cells were identified using PCR. Clones labeled at E15 consisted of single cells or small cells clusters (52%) or of widespread cells (48%). However, widespread clones consisted of multiple neuronal or glial cell types, spaced systematically at 2-3 mm intervals. The data suggest that migratory multipotential progenitors divide asymmetrically at intervals defined by cell cycle length, producing single cells or clusters of cells in different cortical regions. Transition from multipotentiality to more restricted potential may correspond to changes in migratory behavior.

Low-grade myxoid chondrosarcoma of the temporal bone: differential diagnosis and report of two cases.

Skull base chondrosarcoma and chordoma are rare tumors that generally have a poor prognosis. In 1973, Heffelfinger et al described a chondroid variant of chordoma, called chondroid chordoma that was found to have a significantly better prognosis than classic chordoma. However, recent evidence suggests that many of the tumors diagnosed as chondroid chordoma may, in fact, be low-grade myxoid chondrosarcomas. This report presents the diagnosis and treatment of two cases of skull base tumor that were diagnosed preoperatively as schwannoma because they were thought initially to be centred on the jugular foramen. Initial histologic evaluation suggested chondroid chordoma, but immunohistologic techniques and a review of the literature led to a diagnosis of low-grade myxoid chondrosarcoma.

HIV risk factors and seroprevalence in surgical patients.

OBJECTIVE: To determine the prevalence of risk factors for human immunodeficiency virus (HIV) infection, and HIV-1 seroprevalence, in surgical patients. DESIGN: Prospective study in which consenting patients completed a questionnaire on factors potentially related to a higher risk of HIV infection, and underwent an HIV-1 antibody test. PATIENTS AND SETTING: Both elective and emergency surgical admissions between July and November 1990 at St Vincent's Hospital, Sydney. RESULTS: Of 1292 patients who were approached to participate, 27 had been previously diagnosed with HIV-1 infection and, of the remaining 1265, eight (0.63%) refused to answer the questionnaire and undergo a blood test, and 12 (0.95%) refused the blood test only. HIV-1 antibody testing was completed for 1171 study subjects. Twenty-six of the 807 men who answered the questionnaire had been previously diagnosed with HIV-1 infection. Of the remaining 781 male patients, 133 (17%) reported a history of homosexual contact, injecting drug use or blood transfusion, 132 (17%) had had a prior HIV-1 antibody test and three were newly diagnosed with HIV-1 infection as a result of the survey. Of 476 women who completed the questionnaire, one had been previously diagnosed with HIV-1 infection, and of the remaining 475, 59 (12.4%) reported injecting drug use or a blood transfusion and 72 (15%) had had a prior HIV-1 antibody test. No women were newly diagnosed with HIV-1 infection. Of patients reporting specific factors, the proportion who had had a prior HIV-1 antibody test varied from 62% for men reporting homosexual contact to 34% for recipients of a blood transfusion between 1980 and 1985. CONCLUSION: Although an appreciable proportion of surgical patients admitted to St Vincent's Hospital reported factors associated with a higher risk of HIV infection, the prevalence of undiagnosed HIV-1 infection is very low, particularly among patients reporting no such factors.

Thoracoabdominal aortic aneurysm reconstruction.

Thoracoabdominal aortic reconstruction distal to the left subclavian artery was carried out on 19 patients between 1974 and 1990. Screening procedures to detect cardiac, respiratory or renal impairment were undertaken in all patients. Reconstruction was in the upper third of the descending aorta in 6 patients, middle third in 6 patients, and lower third in 7 patients. The Crawford inclusion technique was used in all cases. There were six deaths, four of which were from the high reconstruction group, and one each from the middle and lower group. Paraparesis occurred in 4 patients, 2 of whom survived with some impairment. Temporary renal failure was seen in 2 patients, liver failure in 2, respiratory failure in 2, sepsis in 1, myocardial infarction in 1, and severe coagulopathy in 3. The perioperative mortality rate was 32% for the group as a whole and 15% for reconstructions which started at the middle or lower thoracic level. We conclude that the mortality rate for the middle and lower reconstructions is acceptable but that alternative techniques for the high aneurysms should be sought.

Cerebellopontine angle lipomatous hamartoma of nerve: case report.

Cerebellopontine angle lipoma has been previously described in 21 patients and is frequently unresectable. An intracanalicular lipomatous hamartoma in a 60-year-old male is presented. MRI enabled a correct preoperative diagnosis to be made. Complete surgical excision, without major neurologic deficit was achieved. A review of the literature reveals that the tumor is frequently infiltrative, especially when vascular elements are prominent. The histologic characteristics and the hamartomatous nature of the lesion are discussed.

Initial experience of intra-operative red cell salvage.

The use of red cell saving machines is described in 16 cases of aortic reconstruction. There were 3 deaths in the series, all unrelated to use of the technique. Salvaged autologous blood accounted for 45% of red cell requirements. Biochemical and haematologic parameters were monitored before, during and after operation. When large volumes of blood are salvaged, the system becomes cost effective and the risks of homologous transfusion are reduced.