Methyl tertiary-Butyl Ether: Studies for Potential Human Health Hazards

When methyl tertiary-butyl ether (MTBE) in gasoline was first introduced to reduce vehicle exhaust emissions and comply with the Clean Air Act, in the United States, a pattern of complaints emerged characterised by seven “key symptoms.” Later, carefully controlled volunteer studies did not confirm the existence of the specific key symptoms, although one study of self-reported sensitive (SRS) people did suggest that a threshold at about 11–15% MTBE in gasoline may exist for SRSs in total symptom scores. Neurobehavioral and psychophysiological studies on volunteers, including SRSs, found no adverse responses associated with MTBE at likely exposure levels. MTBE is well and rapidly absorbed following oral and inhalation exposures. C_max values for MTBE are achieved almost immediately after oral dosing and within 2 h of continuous inhalation. It is rapidly eliminated, either by exhalation as unchanged MTBE or by urinary excretion of its less volatile metabolites. Metabolism is more rapid humans than in rats, for both MTBE and tert-butyl alcohol (TBA), its more persistent primary metabolite. The other primary metabolite, formaldehyde, is detoxified at a rate very much greater than its formation from MTBE. MTBE has no specific effects on reproduction or development, or on genetic material. Neurological effects were observed only at very high concentrations. In carcinogenicity studies of MTBE, TBA, and methanol (included as an endogenous precursor of formaldehyde, without the presence of TBA), some increases in tumor incidence have been observed, but consistency of outcome was lacking and even some degree of replication was observed in only three cases, none of which had human relevance: α_{2 u}-globulin nephropathy-related renal tubule cell adenoma in male rats; Leydig-cell adenoma in male rats, but not in mice, which provide the better model of the human disease; and B-cell-derived lymphoma/leukemia of doubtful pathogenesis that arose mainly in lungs of orally dosed female rats. In addition, hepatocellular adenomas were significantly higher in female CD-1 mice and thyroid follicular-cell adenomas were increased in female B6C3F1 mice treated with TBA, but these results lack any independent confirmation, which would have been possible from a number of other studies.     

Temperature data and specific absorption rates in pelvic tumours: predictive factors and correlations

The system BSD 2000 has been in clinical use for regional hyperthermia for more than 10 years. Several technical details of this hyperthermia system, as well as the results of clinical studies employing this system have been investigated. The intention of this paper is to investigate the correlation between technical efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power densities and temperatures depending upon parameters such as tumour histology, tumour location, patient age, patient sex, and patient cross section. The possible conclusions of predictive factors derived from the above correlations were closely scrutinized. Data acquired from 772 treatment sessions of 190 patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum, cervix, prostate and anus, have been evaluated. For every session, index temperatures T ₉₀ (temperature attained at 90% of tumour related measurement points), cumulative minutes for T₉₀ > T_ref, tumour related power density (SAR: specific absorption rate, in W/kg) and the effective perfusion W_eff (inml/100gmin) were calculated. Temperatures were measured either invasively or endoluminally. The statistics software SPSS was employed subsequently for univariate, as well as multivariate analyses. The results exhibit that index temperatures mainly depend on the power density SAR and the hyperthermia induced effective perfusion. The total power P (in 100W) and, complementarily, the relative power density ||SAR|| (= SAR/P) seem to have lesser influence. Clear differences between the tumour entities were established regarding their index temperatures and temperature distributions. SAR, W_eff and P were correlated with several anatomical, biological and clinical factors. Sessions rendering low index temperatures and SAR values also revealed decreased individual tolerance to the treatment. This clearly displays that powerinduced side effects define the limits of the efficiency of regional hyperthermia. Equivalent relationships and correlations are derived from intratumoural and endoluminal thermometry. Individual limitations of regional hyperthermia caused by anatomical, biological and clinical factors are liable to be difficult to overcome with the rather restricted potentials of the BSD 2000 system to control the SAR distribution.     

Epidemiology of paediatric central nervous system tumours in Queensland,Australia

Within Australia, there is little epidemiologic information regarding paediatric central nervous system (CNS) tumours. This study examined the epidemiology of childhood CNS tumours at Queensland Children’s Hospital (QCH), the major paediatric referral centre for Queensland and northern New South Wales. We assessed the data from 221 newly diagnosed childhood CNS tumours across a five-year period from 2015 to 2019. Recurrent tumours were excluded. Data was collected on patient age, gender, histopathological diagnosis, tumour grade, anatomical site, and residential geographical location. The incidence within this period ranged from 2.65 to 3.85 cases per 100,000 children. The median symptom interval was 30 days (IQR 14–122) with presenting features similar to previous studies. The symptom interval was shorter for children zero to three years compared to children four years or older. The most frequent tumour was pilocytic astrocytoma, followed by medulloblastoma and Langerhans cell histiocytosis. The posterior fossa was the most frequent anatomical location for tumours. Our study demonstrated a shorter symptom interval in comparison to previous literature. The study was able to determine the incidence and presenting features within an Australian population.     

Invited Review: For the clinical application of thermochemotherapy given at mild temperatures

It has been demonstrated in vitro and in vivo that hyperthermia can enhance the cytotoxicity of some chemotherapeutic agents. This paper summarizes the authors' own laboratory studies on the effect of chemotherapeutic agents given at elevated temperatures, experimental results obtained using animal tumour systems in other laboratories, and clinical trials of thermochemotherapy reported in literature. The in vivo studies have demonstrated that the thermal enhancement of cytotoxicity of many chemotherapeutic agents is maximized at mild temperatures such as at 40.5-43oC. Comparison of in vitro and in vivo results using five agents show that the in vivo thermal enhancement increases with an increase in the activation energy obtained in the temperature range between 40.5 and 43.0oC. A summary of experimental results obtained by various investigators indicates a potentially wide variation in the thermal enhancement of a given agent among the different types of tumours and suggests potential agents useful at moderately elevated temperatures. In vivo studies on nine different agents indicate that the drug(s) of choice at physiological temperatures may not be the drug(s) of choice at elevated temperatures. It is also shown that drug concentration in the target must be high for sufficient thermal enhancement. Clinical trials of thermochemotherapy have employed various heating methods, including local heating, hyerthermic perfusion and whole body hyperthermia. Extensive trials have been made in the treatment of melanoma and soft tissue sarcoma in the extremity. Hyperthermic isolated perfusion with chemotherapeutic(s) provides much higher drug concentration than a systemic drug administration in the target(s), resulting in a high tumour response rate and an increased survival of the patients. It is of interest that the most successful agent used in the treatment of both melanomas and sarcomas is melphalan and is the drug of choice at moderately elevated temperatures among the nine agents tested in the in vivo studies. Current results using the tumour necrosis factor with melphalan are impressive. In several institutes, techniques have been developed to uniformly heat the localized tumour, but studies are needed to find an agent effective at elevated temperatures to each type of tumours and to establish the methods for obtaining a sufficient drug concentration in the target tissue.     

Pre-clinical evaluation of a two-channel microwave hyperthermia system with adaptive phase control in a large animal

A pre-clinical assessment of the heating capabilities of a two-channel 915MHz Microfocus-1000 hyperthermia system, with adaptive phase control, was carried out in a series of experiments using a large animal model. The results of the experimental measurements of specific absorption rate (SAR) and tissue temperature show that when muscle tissue of the hind legs of pigs was compressed to 6.5-7cm, then a pair of parallel opposed, coherently driven, transverse electromagnetic wave applicators could elevate the temperature in deep tissue to therapeutic levels without overheating superficial tissues when the phase difference between applicators was determined by the adaptive phase control algorithm.     

Parapharyngeal space tumours a radiological and surgical correlation

The parapharyngeal space is a deeply situated space on either side of head. Clinical assessment of lesions in this space in very difficult. 28 patients with parapharyngeal space masses diagnosed and managed in the department of Otorhinolaryngology and Head & Neck Surgery of Postgraduate Institute of Medical Education and Research. Chandigarh were studied. 8 patients were excluded as the tumour could not be removed en-bloc in these. 20 were analysed further.     

Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity

Abstract Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature.     

Disección fría y coagulación bipolar versus disección con bisturí armónico en la cirugía de los tumores benignos de la glándula parótida

IntroductionSurgical techniques for extirpation of tumours of the parotid gland have evolved significantly in recent years. Previous data suggest the use of Harmonic Scalpel reduced operative time, intraoperative blood loss, postoperative drain production, and incidence of facial nerve injury, in comparison to cold scalpel dissectionMaterial and methodsretrospective analysis of 2 group of patients operated using harmonic scalpel versus cold knife dissection and bipolar diathermy and compare operative time and post-surgical complication rate:, facial nerve injury, sialocele or salivary fístula formation, after parotidectomy for benign parotid tumours.Results108 patients were included. Regarding surgical time, the mean time to using Harmonic Scalpel was 114 ± 39 (Min: 60/Max: 240), and the mean time using bipolar diathermy was 135 ± 38 (Min: 90/Max: 285) and this was the only significant difference between the 2 techniques (p = .049).ConclusionsHarmonic scalpel is a safe and effective tool to perform parotid surgery in benign tumours. However, a shorter surgical time was the only advantage found over the traditional cold dissection and bipolar dissection method.     

Testicular juvenile granulosa cell and Sertoli cell tumours: A clinicopathological study of 29 cases from the Kiel Paediatric Tumour Registry

Testicular Sertoli cell tumours (SCT) and juvenile granulosa cell tumours (JGCT) are rare in childhood. This study was designed to investigate the clinical picture, morphology and disease course in a comparatively large series of cases (total number = 29). Of 198 cases of childhood testicular tumour documented in the Kiel Paediatric Tumour Registry 18 were cases of infantile SCT (9.1%) and 11 of JGCT (5.6%). The average age at the time of diagnosis was 4.2 months for infantile SCT and 0.4 months for JGCT. SCT and JGCT often showed infiltrative growth into adjacent testicular tissue, dense cellularity and considerable proliferation activity. Immunohistochemically all cases expressed vimentin intermediate filaments in both tumour types. Next in frequency of expression were cytokeratins (SCT: 7/16; JGCT: 7/10) and smooth-muscle actin (SCT: 9/15; JGCT: 4/10). Follow-up studies (24/29) showed that in cases of tumour manifestation in infancy and after complete tumour removal (usually orchiectomy) no local recurrences and no metastases occurred. The most important conclusion for diagnosis and therapy is that despite infiltrative growth, incomplete differentiation, dense cellularity and considerable proliferation activity, after surgical excision infantile SCT and JGCT have a good prognosis. Adjuvant chemotherapy or more extensive operations with lymphadenectomy are thus not indicated.