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Biomedical subjects

D Birt

Publications and source records attributed to D Birt.

At least 19 recordsLinked to original sources

Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery.

PURPOSE: The use of radical radiotherapy and surgery for salvage (RRSS) in locally advanced squamous cell carcinoma (SCC) of the larynx is controversial. In the absence of randomized studies, it is unclear if RRSS can match the rates of locoregional control and survival reported for primary surgery in this setting. The aim of this study was to compare treatment outcomes of radiotherapy and surgery in comparable patients with CS III-IV SCC of the larynx. METHODS AND MATERIALS: Eighty-two patients with untreated T2N+M0 or T3T4NM0 SCC of the larynx were treated with a policy RRSS at the Toronto-Sunnybrook Regional Cancer Centre between June 1980 and December 1990. The medical records at presentation were reviewed independently by a panel of three surgical oncologists blinded as to treatment outcome to determine patient suitability for laryngectomy and neck dissection using eligibility criteria adopted by recent clinical trials. Treatment outcomes for surgery-eligible patients were compared to results of comparably staged patients in the surgical literature since 1980. RESULTS: Sixty-three patients (77%) were eligible for study. With a median follow-up of 3 years, radiotherapy controlled the primary in 8/20 evaluable glottic primaries and 21/41 evaluable supraglottic primaries. Forty-five percent of patients surviving 5 years retained a functional larynx. Sixteen of 29 relapsing patients were salvaged with surgery. Disease above the clavicles was controlled in 65% of T3T4N0N+ glottic primaries (compared to a published range of 53% to 79%) and 82% of T3N0 glottic primaries (compared to a published range of 69% to 84%). The 5-year overall survival of patients with T3T4 glottic cancer was 54% compared to a published range of 50% to 63%. The cause-specific survival (CSS) of patients with T3N0 glottic primaries (86% at 1 year and 73% at 2 years) was identical to the only published report of CSS in the surgical literature. CONCLUSION: A policy of RRSS offers a good chance of laryngeal conservation without compromising ultimate locoregional control or survival when compared to primary laryngectomy and neck dissection in patients with locally advanced carcinoma of the larynx meeting the surgical eligibility of clinical trials.

Aged↗

The role of panendoscopy in the management of mucosal head and neck malignancy-a prospective evaluation.

BACKGROUND: It is common practice for a panendoscopy to be included in the evaluation of patients with mucosal head and neck malignancies. Whether this intervention is efficient or cost-effective has not been established in our patient population. METHODS: Two hundred twenty-four patients with squamous cell carcinoma involving the oral cavity, pharynx, larynx, or neck were evaluated prospectively with panendoscopy and chest x-ray with or without barium swallow. One hundred fifty-four patients had newly diagnosed tumors and 70 were previously diagnosed and currently undergoing symptom-directed investigations. RESULTS: The incidence of synchronous primary tumors was 2.6% (4 of 154); pulmonary, 1.3%; head and neck mucosa, 1.3%; and esophageal, 0%. There was no associated morbidity. CONCLUSIONS: Although there was no associated morbidity, our head and neck oncology group is of the opinion that routine panendoscopy is not warranted. Specific indications for this investigation are discussed.

Barium Sulfate↗

Biomarkers as early predictors of long-term health status and human immune function.

A central issue that must be addressed by phytonutrient research is how to assess the effects of phytonutrients on long-term health. Proper assessment of these effects requires the measurement of biomarkers of long-term health in people consuming any particular phytonutrient. This is a brief review of what is known about biomarkers of cancer risk, immune function, and aging. Relatively few biomarkers of long-term health have been even partially validated in experimental animals or people.

Aging↗

The prognostic significance of tracheostomy in carcinoma of the larynx treated with radiotherapy and surgery for salvage.

PURPOSE: To determine retrospectively the prognostic significance of airway compromise necessitating tracheostomy in carcinoma of the larynx managed with radical radiotherapy and surgery for salvage (RRSS). METHODS AND MATERIALS: The charts of 270 patients managed with RRSS at the Toronto-Sunnybrook Regional Cancer Centre between June 1980 and December 1990 were reviewed. Airway compromise necessitating tracheostomy was documented in 26 patients prior to radiotherapy and 3 patients during radiotherapy. Of 29, 27 had T3T4 primaries. Patients have been followed for a median of 5 years. RESULTS: Patients managed without tracheostomy had a 2-year disease-free survival of 74% compared to 41% for those managed with tracheostomy. The adverse impact of airway compromise was more marked in patients with glottic primaries (78% vs. 32%, p = 0.0001) than those with supraglottic primaries (64% vs. 47%, p = 0.18). Tracheostomy was identified in univariate analysis, but not in multivariate analysis, as having a statistically significant impact on local control and local-regional control. Radiotherapy controlled disease above the clavicles in 185 of 267 (69%) evaluable patients. 83% of isolated local-regional failures underwent salvage surgery. Among those managed without tracheostomy, ultimate local-regional control (LRC) was achieved in 161 (94%) of 172 glottic primaries and 54 (81%) of 67 supraglottic primaries. Among those managed with tracheostomy, ultimate LRC was achieved in 9 (69%) of 13 glottic primaries and 12 (80%) of 15 supraglottic primaries. In a subset analysis of 76 patients with T3T4 primaries, there was no statistically significant difference in larynx preservation, disease-free survival, or cause-specific survival between those managed with and without tracheostomy. CONCLUSION: Airway compromise necessitating tracheostomy is an adverse prognostic factor in patients with carcinoma of the larynx. However, larynx preservation is possible in over 40% of those undergoing tracheostomy and radiotherapy with no compromise of cause-specific survival. The need for pretreatment tracheostomy should not rule out the possibility of RRSS.

Adult↗

Immunologic effects of levamisole in mice and humans: evidence for augmented antibody response without modulation of cellular cytotoxicity.

Selected immunomodulatory effects of levamisole were studied in patients with asymptomatic metastatic colon cancer and in a preclinical model (CF1 female mice treated with methyl-azoxymethanol acetate) for colon tumors. In the patient population studied, there was no augmentation of cellular cytotoxicity or alteration in lymphocyte subpopulations that participate in these functions. An increase in Fc receptor binding on circulating monocytes was apparent at the 4-week timepoint; however, a corresponding increase in antibody-dependent cellular cytotoxicity was observed in only one of the six patients studied. In most patients, cellular cytotoxicity diminished with time. No significant effects on cellular immunity or carcinogenesis were observed in our murine studies. However, treatment with levamisole did increase circulating immunoglobulin levels and IgM response in mice immunized with the T-dependent antigen keyhole limpet hemocyanin. This parameter was not tested in the human trial. Failure to demonstrate antitumor effects on cellular immunity by levamisole in both human and murine studies suggests that these effects, if they do exist, may involve immunological parameters that were not tested using our methods or that may not be apparent in patients with more advanced malignancy.

Adenocarcinoma↗

Changes in the activity of units of the cat motor cortex with rapid conditioning and extinction of a compound eye blink movement.

Patterns of spike activity were measured in the pericruciate cortex of conscious cats before and after development of a Pavlovian conditioned eye blink response. Unit activity was tested with presentations of a click conditioned stimulus (CS) and a hiss discriminative stimulus (DS) of similar intensity to the click. Unit discharge in response to the CS increased after conditioning, but not after backward conditioning when conditioned reflexes (CRs) were not performed. Rates of spontaneous, baseline discharge were not increased after conditioning with respect to rates of discharge measured in the naive state. It appeared that an increase in the ratio of CS-elicited discharge to background activity, together with an increase in the number of units responding to the CS after conditioning, supported discrimination of the CS from the DS and performance of the conditioned blink response. This is the first detailed characterization of patterns of a rapidly conditioned Pavlovian response. Activation of units by the CS preceded the onset of the CR, supporting the hypothesis that the activity played a role in initiating the conditioned eye blink movement. Extinction with retention of performance of the CR was associated with perseverance of the increased unit discharge in response to the CS. Extinction with substantially reduced performance of the CR was associated with diminution of the unit response to the CS below levels found with conditioning. Averages of patterns of spike activity elicited by the CS after conditioning showed components of discharge with onsets of 8-40 msec (alpha 1), 40-72 msec (alpha 2), 72-112 msec (beta), and greater than 112 msec (gamma), corresponding to each of four separate excitatory EMG components of the compound blink CR. Each component increased in magnitude after conditioning, relative to levels found in the naive state. The finding that long- as well as short-latency components of unit activation increased after conditioning supported the hypothesis that generation of both long- and short-latency blink CRs in normal animals may depend significantly on neural circuitry and mechanisms within the motor cortex.

Animals↗

Increases in excitability of neurons of the motor cortex of cats after rapid acquisition of eye blink conditioning.

Measurements were made of resting potentials, input resistance, and excitability to intracellularly applied, depolarizing current pulses in neurons of the pericruciate cortex of conscious cats before and after acquisition of a rapidly conditioned eye blink reflex (CR). Neuronal excitability increased after conditioning, and an increased input resistance was found to be correlated with the increased level of excitability. No associated changes were found in resting potentials as a consequence of conditioning. When cells were divided into groups according to the latency of spike activity elicited by a click conditioned stimulus (CS) in relation to four separate excitatory EMG components of the compound blink CR, excitability increases were found in cells with increased spike activity at alpha 1 (8-40 msec), alpha 2 (40-72 msec), beta (72-112 msec), and gamma (112-160 msec) latencies after delivery of the CS. Also, the proportion of cells with high excitability (less than 0.7 nA required for spike elicitation) was increased at each latency period after conditioning. Increases in later components of spike discharge could also be found in the cells with increases in earlier components of discharge and increased excitability. The findings suggested that excitability increases facilitated a responsiveness to the CS that supported production of long- as well as short-latency components of the blink CR. Many of the changes in neuronal properties found after rapid eye blink conditioning, such as the increases in excitability and resistance and in the proportion of CS-excitable cells, resembled changes found earlier after acquisition of a slowly developing Pavlovian blink CR, using the same click CS and tap unconditioned stimulus without addition of a hypothalamic stimulus. The possibility should be considered that the (10-100 times) more rapidly acquired form of eye blink conditioning does not represent a different form of conditioning, but instead a change in the rate of conditioning supported by the more rapid production of increases in neural excitability.

Animals↗

Changes in membrane currents during Pavlovian conditioning of single cortical neurons.

Single electrode voltage clamp recordings were made during Pavlovian conditioning of single units of the motor cortex of cats. Units that developed a conditioned spike discharge in response to a click conditioned stimulus (CS) after pairing the click with glabella tap and local ionophoretic application of glutamate showed increases in input resistance and reductions of an early outward current induced by depolarizing commands and by return to holding potentials after hyperpolarizing commands. Changes in later currents were also found in some cells. Units that failed to develop a conditioned response did not show these changes. The decreases in membrane currents could contribute to an increased spike discharge in response to the CS as could the increased input resistance observed after conditioning. Conductance changes of this type may serve as engrams by which some forms of memory and learning are expressed across both vertebrate and invertebrate species.

Acoustic Stimulation↗

MRI and neck metastases: a clinical, radiological, pathological correlative study.

In a previous report CT was shown to have no advantage over physical examination in the detection of metastatic neck disease. Therefore, a study was undertaken to evaluate whether MRI would show superiority to the CT in the diagnosis of neck nodes. A series of 35 patients with various head and neck tumors were evaluated clinically, radiographically and pathologically. Eight patients were excluded from the study because of various problems involving the MRI. Therefore, 27 patients with 30 neck dissections were analyzed. There was little advantage of MRI over clinical examination in the detection of metastatic neck disease. The present size criterion for the diagnosis of occult malignant nodes is not reliable. The soft tissue contrast resolution reported by MRI is inadequate to detect minimal morphological changes in lymph nodes involved by metastases, and MRI is difficult in patients who have airway or foodway obstruction.

Head and Neck Neoplasms↗

Mandibulotomy in the irradiated patient.

Though the "mandibular swing," as an approach to certain upper aerodigestive tract malignancies, has been gaining popularity in recent years, there has been little reported as to the feasibility of this procedure in subjects who have received radical preoperative radiotherapy. We have recently reported the results of 23 such patients, and we now present an update. The results presented are of a retrospective analysis of 44 patients, 50% of whom received radical preoperative radiotherapy to fields including the osteotomy site. As in the previous study, there were no statistically significant differences between the complication rates in the irradiated and nonirradiated patient populations. All the patients were orally rehabilitated.

Adult↗

AO/ASIF plate for mandibular reconstruction in tumor surgery: results in 20 cases.

Between May, 1983, and February, 1987, the authors performed mandibular reconstruction using an AO/ASIF plate in 20 patients. Apart from accurate modelling of the resected segment using a template, the key features of the technique include firm fixation and wrapping the plate with pectoralis major muscle. In 19 cases the plate was inserted at the same operation as the resection of a malignant neoplasm. In 10 cases the anterior mandibular osteotomy was placed on the far side of the midline, while in five the mandible was disarticulated through the temporomandibular joint. Eleven patients are alive (average survival 22 months) and nine have died (average survival 10 months). Two AO/ASIF plates have required removal because of exposure, while in three patients limited plate exposure was corrected with a minor surgical procedure. Seven patients had soft tissue complications that were managed conservatively. Nine of the patients had been irradiated previously. Five patients were fitted with dentures successfully. The authors believe that this technique provides a safe, rapid, functional and esthetically satisfactory method of mandibular reconstruction in the patient undergoing surgery for malignant disease.

Adult↗

Mandibulotomy and radical radiotherapy: compatible or not?

The mandibular swing, as an approach to upper aerodigestive tract malignancies, has been gaining popularity in recent years. Little has been reported in the literature as to the feasibility of this procedure in subjects having received radical preoperative radiotherapy. The preliminary results of a retrospective analysis of 23 subjects, 70% of whom received radical preoperative radiotherapy, is presented. There was no statistically significant difference between the complication rates in the irradiated and nonirradiated subject populations. All subjects, ultimately, were orally rehabilitated.

Adult↗

Pavlovian conditioning of discriminatively elicited eyeblink responses with short onset latency attributable to lengthened interstimulus intervals.

Conditioned eyeblink responses were obtained in cats by pairing click (CS) with glabella tap (US) and electrical stimulation of the hypothalamus (HS). Hiss was used as a discriminative stimulus (DS). Onset latencies of conditioned responses (CRs) of 20-56 ms were obtained by using an interstimulus interval (ISI) of 570-10 ms between CS and US-HS. Longer latency (90-320 ms) blink CRs were obtained with ISIs of 340-240 and 340-10 ms. The timing of associatively learned movements has been thought to increase with lengthening of the intervals between CS and US presentation. The production of shorter latency CRs of this type by lengthening the ISI is a novel result and one unexpected from widely held beliefs.

Acoustic Stimulation↗

Observations on the size of the saccule in laryngectomy specimens.

Over 300 instances of the association of laryngocele with laryngeal carcinoma have been reported in Europe, but only seven in North America. In the present study, 353 serially sectioned total laryngectomy specimens were examined and the saccule measured with a steel ruler. Saccules extending superior or posterior to the thyroid cartilage were considered as large. Larynges were classified as "cancer" or "normal", the latter being uninvaded organs from patients with adjacent disease. Among the 242 cancer larynges, there were 43 specimens where the saccule exceeded thyroid cartilage dimensions, a laryngocele rate of 17.8%. Mean saccule height was significantly greater in cancer than in normal specimens in coronal sections (P = 0.04), and mean saccule length was significantly greater in cancer than in normal specimens in horizontal sections (P = 0.001). The incidence of large saccules showed a difference between cancer and normal larynges which was highly significant (P = 0.0002).

Adult↗

An individualized approach to orbital decompression in Graves' orbitopathy.

With better understanding of the various techniques available for orbital decompression, the indications for surgical decompression in Graves' orbitopathy are now less rigid. Decompressions may be performed for (1) prolonged orbital congestion and pain, (2) orbital problems resistant to steroid treatment, (3) orbital problems where there have been steroid complications, (4) severe corneal exposure that cannot be treated with lid-lengthening surgery, and (5) the standard indication--Graves' optic neuropathy. Assessment of muscle size by computed tomographic scanning and ultrasound, as well as the measurement of orbital pressure, are important advances in the assessment of these patients. The lateral approach produces less strabismus and allows for exophthalmos reduction, especially if fascia temporalis is incised and if part of that muscle is removed. The inferomedial approach is advisable in patients with severe posterior optic neuropathy caused by apical crowding of the enlarged muscles, particularly the medial rectus. The two approaches may be combined in severe cases.

Female↗

Laryngocele: a case report and review.

A 60 year old man had a symptomless mass in the neck for two years. Over two weeks he developed hoarseness and dysphagia and successfully underwent excision of a combined internal and external laryngocele. There is some disagreement in the literature as to when an enlarged saccule is a laryngocele and also as to whether laryngoceles result from chronic straining such as playing a wind instrument. Laryngeal carcinoma occasionally occurs in association with a clinical laryngocele. When sought for in laryngectomy specimens the incidence of laryngocele in patients with laryngeal carcinoma has been recorded at 18%.

Deglutition Disorders↗

Profile of malignant disease in the mouth clinic.

Between 1973 and 1981, 2,056 new patients were seen in the Mouth Clinic at Sunnybrook Hospital. Of these 109 proved to have malignant disease, with squamous cell carcinoma being the commonest type. Lower lip and floor of mouth were the most frequent sites. There was a high proportion of small tumors and local surgical excision was the most widely employed primary method of treatment. Radiation and combined treatment were used in larger lesions. Twenty-four patients have so far died of mouth cancer and the presence of enlarged lymph nodes at presentation was an ominous sign. Although containing the usual high proportion of heavy smokers and drinkers this group of patients at present exhibits a lower incidence of second primary malignancies than in some published series. It is concluded that surgery and radiotherapy have equivalent effectiveness in treating small primary lesions, where a policy of observation of the clinically negative neck appeared justified. The best treatment for large lesions and the most appropriate management of the clinically negative neck in intermediate size lesions has not been determined.

Adult↗