Underdiagnosis, false diagnosis and treatment of COPD in a selected population in Northern Greece.

BACKGROUND: In the primary care setting, diagnosis and treatment of COPD is not always consistent with GOLD guidelines. OBJECTIVES: To calculate the prevalence of COPD underdiagnosis, false diagnosis and treatment in the general population of northern Greece. METHODS: Observational study in the context of an early COPD detection and smoking cessation project. Inclusion criteria: >40-year-old, current and former smokers (>10 pack-years) in five primary care centres of northern Greece from 2012 to 2019. Participation was achieved via a campaign (posters and advertisements in the mass media). RESULTS: We examined 5,226 subjects (mean age: 58.2 ± 12.7 years, 61.5% males, current smokers: 56.2%) of whom 564 (10.8%) had symptoms and spirometrically confirmed COPD. There were 5 groups of 'interest:' a) 117/264 (44.3%) with a previous correct diagnosis COPD and correct treatment; b) 139/264 (52.7%) previous correct diagnosis COPD but overtreatment; c) 8/264 (3%) previous correct diagnosis COPD but undertreatment; d) 461 subjects (63.6% of those with previous COPD diagnosis) had previous false diagnosis of COPD (= also overtreatment); e) 300/564 (53.2%) previously not diagnosed COPD (=underdiagnosis and also undertreatment). We found that 322/461 (69.8%) of those with a previous false diagnosis have been prescribed long-acting bronchodilators plus ICS. CONCLUSION: Among the general population subjects in northern Greece, more than 50% of patients with COPD were underdiagnosed, more than 50% of correctly diagnosed COPD patients were overtreated and most patients taking inhaled drugs were those with a false diagnosis of COPD (possibly GOLD stage 0).

Comparison of Three Screening Questionnaires for Chronic Obstructive Pulmonary Disease in the Primary Care.

BACKGROUND: Even though the diagnosis of chronic obstructive pulmonary disease (COPD) is easy and based mainly on spirometry and symptoms, the prevalence of underdiagnosis is extremely high. The use of simple screening tools (e.g., questionnaires, hand-held spirometers) has been proved to be a simple method for case finding of COPD. Nevertheless the most appropriate target group of the general population has not been specified yet. OBJECTIVES: The aim of the present study was to compare 3 screening questionnaires among smokers aged >40 years in the primary care setting. METHODS: We excluded all subjects with a previous medical diagnosis of bronchial asthma or chronic pulmonary disease other than COPD. All participants were in a stable clinical condition, filled in the International Primary Care Airways Group (IPAG) questionnaire, the COPD Population Screener (COPD-PS) questionnaire, and the Lung Function Questionnaire (LFQ) and underwent spirometry. Medical diagnosis of COPD was established by an experienced pulmonologist. RESULTS: We studied 3,234 subjects during a 3.5-year period. COPD prevalence was 10.9% (52.1% underdiagnosis). All 3 questionnaires showed extremely high negative predictive values (94-96%), so in this case the diagnosis of COPD could be safely excluded. The area under the curve was similar across the 3 questionnaires (AUCROC: 0.794-0.809). The COPD-PS questionnaire demonstrated the highest positive predictive value (41%) compared to the other 2. On the other hand, the IPAG questionnaire and LFQ demonstrated higher sensitivities than COPD-PS resulting in lower percentages of missed cases. CONCLUSIONS: Three validated screening questionnaires for COPD demonstrated different diagnostic characteristics.

Estimating the extent and economic impact of under and overdiagnosis of chronic obstructive pulmonary disease in primary care.

The aim of the present study was to estimate the frequency of under- and over-diagnosis as well as overtreatment and their impact on the financial burden of inhaled drugs for stable chronic obstructive pulmonary disease (COPD). We examined 3200 subjects (65.5% males) of the general population (>40 year old, current or former smokers, and asthma patients were excluded) during a 3-year period. All participants gave detailed medical history, underwent spirometry, and their current and past inhaled medications were registered through the national electronic prescription system. We diagnosed 342 subjects (10.7%) with COPD of whom 180 (52.6%) had no prior medical diagnosis. Overdiagnosis was the case for 306 subjects (9.6%) of whom 35.1% were treated with inhaled drugs during the last year. We calculated that 55.4% of the current cost for inhaled drugs is wasted to overtreatment and overdiagnosis. If there was adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines both for the diagnosis and treatment it would be a net profit of 36,059€ annually, which would be increased to 116,017€ if we had excluded underdiagnosed patients. Under- and over-diagnosis of COPD as well as non-adherence to GOLD guidelines for treatment are common problems in the primary care setting that increase significantly the economic burden of inhaled medications.

Evaluation of a Decision Support System for Obstructive Sleep Apnea with Nonlinear Analysis of Respiratory Signals.

INTRODUCTION: Obstructive Sleep Apnea (OSA) is a common sleep disorder requiring the time/money consuming polysomnography for diagnosis. Alternative methods for initial evaluation are sought. Our aim was the prediction of Apnea-Hypopnea Index (AHI) in patients potentially suffering from OSA based on nonlinear analysis of respiratory biosignals during sleep, a method that is related to the pathophysiology of the disorder. MATERIALS AND METHODS: Patients referred to a Sleep Unit (135) underwent full polysomnography. Three nonlinear indices (Largest Lyapunov Exponent, Detrended Fluctuation Analysis and Approximate Entropy) extracted from two biosignals (airflow from a nasal cannula, thoracic movement) and one linear derived from Oxygen saturation provided input to a data mining application with contemporary classification algorithms for the creation of predictive models for AHI. RESULTS: A linear regression model presented a correlation coefficient of 0.77 in predicting AHI. With a cutoff value of AHI = 8, the sensitivity and specificity were 93% and 71.4% in discrimination between patients and normal subjects. The decision tree for the discrimination between patients and normal had sensitivity and specificity of 91% and 60%, respectively. Certain obtained nonlinear values correlated significantly with commonly accepted physiological parameters of people suffering from OSA. DISCUSSION: We developed a predictive model for the presence/severity of OSA using a simple linear equation and additional decision trees with nonlinear features extracted from 3 respiratory recordings. The accuracy of the methodology is high and the findings provide insight to the underlying pathophysiology of the syndrome. CONCLUSIONS: Reliable predictions of OSA are possible using linear and nonlinear indices from only 3 respiratory signals during sleep. The proposed models could lead to a better study of the pathophysiology of OSA and facilitate initial evaluation/follow up of suspected patients OSA utilizing a practical low cost methodology. TRIAL REGISTRATION: ClinicalTrials.gov NCT01161381.

Umeclidinium bromide/vilanterol combination in the treatment of chronic obstructive pulmonary disease: a review.

Chronic obstructive pulmonary disease (COPD) is a common disease among the elderly that could be prevented by smoking cessation. As it is characterized by airflow limitation that is not fully reversible, bronchodilator therapy is the first choice of treatment. Symptomatic COPD patients with or without risk for future exacerbations have a strong indication for the permanent use of long- and ultralong-acting ß2-agonists and/or long-acting muscarinic antagonists. Combining bronchodilators is an effective approach, as they demonstrate synergic action at a cellular level and have additive clinical benefits and fewer adverse events compared with increased doses of the monocomponents. Novel fixed-dose combinations of long-acting ß2-agonists/long-acting muscarinic antagonists in one inhaler have been approved for clinical use by the US Food and Drug Administration and the European Medicines Agency. This review focuses on published clinical trials about the fixed-dose combination of umeclidinium/vilanterol trifenatate in patients with COPD. Results from six studies (five of them of 12 weeks' duration and one that lasted 1 year, including more than 6,000 patients in total) showed that umeclidinium/vilanterol trifenatate improved lung function, dyspnea, and health-related quality of life and decreased the exacerbation rate with no serious adverse events. More longstanding trials are needed to evaluate the effect of the drug on disease progression and compare it directly with other fixed-dose combinations.

Reference Equations for Static Lung Volumes and TLCO from a Population Sample in Northern Greece.

Background: The most commonly used reference equations for the measurement of static lung volumes/capacities and transfer factor of the lung for CO (TLCO) are based on studies around 30-40 years old with significant limitations. Objectives: Our aim was to (1) develop reference equations for static lung volumes and TLCO using the current American Thoracic Society/European Respiratory Society guidelines, and (2) compare the equations derived with those most commonly used. Methods: Healthy Caucasian subjects (234 males and 233 females) aged 18-91 years were recruited. All of them were healthy never smokers with a normal chest X-ray. Static lung volumes and TLCO were measured with a single-breath technique according to the latest guidelines. Results: Curvilinear regression prediction equations derived from the present study were compared with those that are most commonly used. Our reference equations in accordance with the latest studies show lower values for all static lung volume parameters and TLCO as well as a different way of deviation of those parameters (i.e. declining with age total lung capacity, TLCO age decline in both sex and functional residual capacity age rise in males). Conclusions: We suggest that old reference values of static lung volumes and TLCO should be updated, and our perception of deviation of some spirometric parameters should be revised. Our new reference curvilinear equations derived according to the latest guidelines could contribute to the updating by respiratory societies of old existing reference values and result in a better estimation of the lung function of contemporary populations with similar Caucasian characteristics. © 2015 S. Karger AG, Basel.

Effects of particulate air pollution on nasal and lung function development among Greek children: a 19-year cohort study.

The aim was to investigate respiratory symptoms, lung function and nasal airflow development among a cohort of children who were exposed to particulate air pollution. We used questionnaires, spirometry and rhinomanometry, while central-monitored PM10 concentrations were used for exposure assessment. We initially examined 1046 children (10-12 year old) in the heavily polluted town of Ptolemaida, Greece, and 379 children in the cleaner town of Grevena (control group). We re-evaluated 312 of the former and 119 of the latter after 19 years. PM10 concentrations were above permissible levels in Ptolemaida during all study period. At both visits, nasal flow was significantly lower in the study sample. At the follow-up visit, 34.3% had severe nasal obstruction (< 500 ml/s) and 38.5% reported chronic nasal symptoms. Spirometric parameters did not differ compared to the control group. Particulate air pollution had significant and negative effects on nasal but not on lung function development.

Exposure to PM10 as a risk factor for the development of nasal obstruction and chronic obstructive pulmonary disease.

OBJECTIVES: To investigate whether air pollution is a potential risk factor for airways obstruction. METHODS: A prospective cohort study (11.3 +/- 2.9 years) that took place in two areas (Eordea where concentration of PM10 was high and Grevena, Greece). We used the MRC questionnaire, spirometry, and anterior rhinomanometry at both visits. RESULTS: Initially we examined 3046 subjects. After excluding chronic obstructive pulmonary disease (COPD) patients, we re-examined 872 subjects and 168 of them had developed COPD (Grevena: 24.3%, Eordea: 18.5%). Multivariable logistic regression analysis showed that the area of residence and thus exposure to air pollution was not a risk factor for the development of COPD (OR: 0.51, 95% CI: 0.18-1.46, P = 0.21). On the other hand, residence in Eordea was strongly related to the development of severe nasal obstruction (OR: 11.47, 95% CI: 6.15-21.40, P < 0.001). Similar results were found after excluding patients with COPD stage I as well as in the subgroup of never smokers. CONCLUSION: Air pollution was associated with severe nasal obstruction but not with COPD development.

COPD assessment test: a simple tool to evaluate disease severity and response to treatment.

The COPD assessment test (CAT) is a short questionnaire designed to assess the impairment in health status of COPD patients. We aimed to determine the change of the CAT in COPD patients after 1 year of treatment and test the association between the score and clinical and lung function variables. Methods A cohort of 111 newly diagnosed COPD patients in primary care was evaluated at baseline and one year after the implementation of the recommended treatment according to the Global Initiative for the management of COPD (GOLD). Results Most of the patients (82%) were diagnosed with mild to moderate airflow limitation (mean FEV1 72 ± 21.5% predicted) and the CAT score increased in proportion with the GOLD stage of severity. The CAT significantly correlated with the number of exacerbations, visits to general practitioners and days of hospitalization both at the beginning and at 1 year follow-up. A strong negative correlation between the CAT score and FEV1 predicted was also observed. The CAT was responsive to the application of treatment with a significant improvement in the mean score (95% confidence interval) following 12 months of treatment by -2.4 (-2.9, -1.9) despite the small decline in lung function indices. The number of exacerbations in the preceding year and FEV1 were independent predictors of the CAT score in the general linear model. Conclusion The CAT questionnaire may serve as a simple, measurable tool complementary to spirometry in the assessment of severity and of response to treatment in unselected COPD patients in primary care.

Smoking among adolescents in Northern Greece: a large cross-sectional study about risk and preventive factors.

BACKGROUND: The aim of the present study was to investigate epidemiological data about cigarette smoking in relation with risk and preventive factors among Greek adolescents. METHODS: We randomly selected 10% of the whole number of schools in Northern Greece (133 schools, 18,904 participants were included). Two anonymous questionnaires (smoker's and non-smoker's) were both distributed to all students so they selected and filled in only one. A parental signed informed consent was obtained using an informative leaflet about adolescent smoking. RESULTS: The main findings of the study were: a) 14.2% of the adolescents (mean age+/-SD: 15.3+/-1.7 years) reported regular smoking (24.1% in the age group 16-18 years), b) 84.2% of the current smokers reported daily use, c) students who live in urban and semirural areas smoke more frequently than those in rural areas, d) students in technically oriented schools smoke twice as frequent compared to those in general education, e) risk factors for smoking: male gender, low educational level of parents, friends who smoke (OR: 10.01, 95%CI: 8.53-11.74, p<0.001), frequent visits to internet cafes (OR:1.53, 95%CI: 1.35-1.74, p<0.001), parents, siblings (OR:2.24, 95%CI: 1.99-2.51, p<0.001) and favorite artist (OR:1.18, 95%CI: 1.04-1.33, p=0.009) who smoke, f) protective factors against smoking: participation in sports (OR:0.59, 95%CI: 0.53-0.67, p<0.001), watching television (OR:0.74, 95%CI 0.66-0.84, p<0.001) and influence by health warning messages on cigarette packets (OR:0.42, 95%CI: 0.37, 0.48, p<0.001). CONCLUSIONS: Even though prevalence of cigarette smoking is not too high among Greek adolescents, frequency of everyday cigarette use is alarming. We identified many social and lifestyle risk and preventive factors that should be incorporated in a national smoking prevention program among Greek adolescents.

Chest imaging and lung function impairment after long-term occupational exposure to low concentrations of chrysotile.

The aim of the present study was the investigation of radiographic findings in relation to lung function after occupational exposure to permissible levels of relatively pure chrysotile (0.5-3% amphiboles). We studied 266 out of the total 317 employees who have worked in an asbestos cement factory during the period 1968-2004 with chest x-ray, high-resolution computed tomography (HRCT) and lung function tests. Sensitivity of chest x-ray was 43% compared to HRCT. Abnormal HRCT findings were found in 75 subjects (67%) and were related to age, occupational exposure duration, and spirometric data. The presence of parenchymal or visceral pleural lesions (exclusively or as the predominant abnormality) was being accompanied by lower total lung capacity and diffusion capacity. HRCT was much more sensitive than chest x-ray for occupational chrysotile exposure. Lung function impairment was related with parenchymal but not with pleural HRCT abnormalities.

Pulmonary rehabilitation in non-small cell lung cancer patients after completion of treatment.

OBJECTIVES: The functional status of patients with non-small cell lung cancer (NSCLC) is often limited not only by cancer itself, but also by the different types of treatment and by comorbidities [eg, chronic obstructive pulmonary disease (COPD), congestive heart failure]. The aim of this study was to investigate the utility of an inpatient multidisciplinary pulmonary rehabilitation (PR) program on pulmonary function and exercise capacity of patients with NSCLC after completion of their treatment. METHODS: Forty-seven patients with NSCLC underwent a PR program after completing cancer treatment. Pulmonary function tests, arterial blood gases, 6-minute walk test, and dyspnea severity before and after PR were retrospectively analyzed. RESULTS: After undergoing PR, patients exhibited significantly higher forced expiratory volume in the first second (mean increase, 110 ± 240 mL; P=0.007), forced vital capacity (mean increase, 130 ± 290 mL; P=0.001), and 6-minute walk test distance (mean increase, 41 m; P<0.001). A statistically significant improvement in the severity of dyspnea (mean decrease in the Modified Medical Research Council dyspnea scale: 0.26 ± 0.61; P=0.007) was observed. We observed that improvement in pulmonary function and exercise capacity was similar among patients with and without COPD and among patients who underwent thoracic surgery or not. CONCLUSIONS: Patients with NSCLC who could accomplish PR program, after multidisciplinary treatment for the main disease, seem to benefit in terms of exercise capacity and pulmonary function. These benefits are independent of concurrent COPD and surgical treatment for lung cancer.

A combination of the IPAG questionnaire and PiKo-6® flow meter is a valuable screening tool for COPD in the primary care setting.

AIMS: To investigate the validity of the International Primary Care Airways Guidelines (IPAG) questionnaire and PiKo-6® (Ferraris Respiratory Europe Ltd.) flow meter as screening tools for diagnosing chronic obstructive pulmonary disease (COPD) in the primary care setting. METHODS: The first 50 patients in 25 general practice offices completed the IPAG questionnaire and underwent spirometry with the handheld PiKo-6® flow meter. The results were compared with official spirometry parameters after bronchodilation. All participants had no previous medical diagnosis of respiratory diseases. RESULTS: Data from 1,078 out of 1,250 subjects (462 males, mean age 65.3 ± 11.4 years) were analysed. The percentage of smokers was 48.4% (38 ± 29 pack-years). COPD was diagnosed in 111 (10.3%) patients. In the subgroup of smokers the sensitivity and specificity for COPD diagnosis were 91% and 49%, respectively, for the IPAG questionnaire; 80% and 95% respectively for the PiKo-6® spirometer; and 72% and 97% for their combination. The negative predictive value of the questionnaire was 97%, whereas the positive predictive value of the questionnaire/ PiKo-6® combination was 82%. Using a cut-off score of 19 points for the IPAG questionnaire, we calculated the best combination of sensitivity (75%) and specificity (72%). CONCLUSIONS: The IPAG questionnaire and the hand-held PiKo-6® spirometer can be used in combination to increase the possibility of an early and accurate diagnosis of COPD in the primary care setting.

Anemia of chronic disease in chronic obstructive pulmonary disease: a case-control study of cardiopulmonary exercise responses.

BACKGROUND: Anemia may be present in patients with chronic obstructive pulmonary disease (COPD) and further impair their functional capacity. OBJECTIVES: This study investigated the prevalence of anemia of chronic disease (ACD) in COPD patients and its impact on dyspnea and exercise capacity, utilizing cardiopulmonary exercise testing (CPET). METHODS: ACD prevalence was assessed in 283 consecutive patients with stable COPD (263 males, 60 females; age 60.31 ± 5.34 years; percent forced expiratory volume in 1 s 46.94 ± 6.12). ACD diagnosis was based on a combination of clinical and laboratory parameters [hemoglobin (Hb) <13 g/dl for males, <12 g/dl for females; ferritin >30 ng/ml; total iron-binding capacity <250 µg/dl, and transferrin saturation rate between 15 and 50%]. Twenty-seven patients who were identified with ACD (cases) and 27 matched nonanemic patients (controls) completed maximal CPET, and data were compared between the groups. RESULTS: ACD was diagnosed in 29 patients, which represents a prevalence of 10.24%; the severity of anemia was generally mild (mean Hb: 12.19 ± 0.66 g/dl). Patients with ACD had a higher Medical Research Council dyspnea score compared to controls (2.78 ± 0.44 vs. 2.07 ± 0.55; p <0.001) and lower peak O(2) uptake (VO(2)) (59.54 ± 17.17 vs. 71.26 ± 11.85% predicted; p <0.05), peak work rate (54.94 ± 21.42 vs. 68.72 ± 20.81% predicted; p <0.05) and peak VO(2)/heart rate (69.07 ± 17.26 vs. 82.04 ± 18.22% predicted; p <0.05). There was also a trend for a lower anaerobic threshold (48.48 ± 15.16 vs. 55.42 ± 9.99% predicted; p = 0.062). No exercise parameter indicative of respiratory limitation differed between the groups. CONCLUSIONS: ACD occurs in approximately 10% of stable COPD patients and has a negative impact on dyspnea and circulatory efficiency during exercise.

Iliopsoas tuberculous abscess associated with cervical and axillary tuberculous lymphadenopathy.

The authors report a case of iliopsoas tuberculous abscess without obvious spinal column involvement. Cervical and axillary tuberculous lymphadenopathy were also presented. Despite appropriate antituberculous treatment, patient required percutaneous drainage with CT-guided catheter insertion.

An unusual cause of spontaneous pneumothorax.

Bronchopulmonary sequestration is a congenital pulmonary malformation consisting of a non-functioning region of lung parenchyma that receives systemic arterial blood supply. The authors present the case of a 31-year-old male who presented with spontaneous pneumothorax as the initial clinical manifestation of an intralobar bronchopulmonary sequestration. There was a persistent air leak through the chest tube which remained in the pleural cavity for 12 days. CT revealed an area of increased opacity, with focal calcifications and a small eccentric cavity in the posterior basal region of the left lower lobe. Aortography established the final diagnosis.

Assessment of respiratory mechanics by impulse oscillometry in orthopneic patients with acute left ventricular failure.

BACKGROUND: This study investigated the respiratory function and mechanics of patients with orthopnea caused by acute left ventricular failure (ALVF). METHODS: The study comprised 40 patients with ALVF and 15 control subjects. All patients underwent lung function tests and impulse oscillometry in both sitting and supine positions. In a subgroup of 22 patients, isosorbide dinitrate was administered and impulse oscillometry was performed 15 minutes later in the supine position. RESULTS: No patient reported dyspnea while seated, and the orthopnea score was 2.9 ± 1.4. Left ventricular ejection fraction was 43% ± 10%. Patients demonstrated restrictive spirometric pattern in the sitting position, whereas functional residual capacity was comparable to that of the control group. In the supine position, all pulmonary volumes decreased, except inspiratory capacity which increased. Respiratory reactance (Xrs5) was higher in patients in both sitting (421.8 ± 630.6%pred vs 147.2 ± 72.8%pred, P = .01) and supine (699.8 ± 699.9%pred vs 251.2 ± 151.6%pred, P ≤ .001) positions. Respiratory resistance (Rrs5) (10.6% ± 17.8% mean decrease) and Xrs5 (17.2% ± 39.4% mean decrease) improved after nitrates administration. Orthopnea was better correlated with Xrs5%pred in the supine position (r = .42, P = .007). Ejection fraction was positively correlated with inspiratory capacity %pred (r = .42, P = .007) in the sitting position. CONCLUSION: Patients with ALVF demonstrated increased respiratory reactance that correlated with orthopnea severity and improved after nitrates administration.

Screening of patients with Obstructive Sleep Apnea Syndrome using C4.5 algorithm based on non linear analysis of respiratory signals during sleep.

AIM: To classify patients with possible diagnosis of Obstructive Sleep Apnea Syndrome (OSAS) into groups according to the severity of the disease using a decision tree producing algorithm based on nonlinear analysis of 3 respiratory signals instead of the use of full polysomnography. PATIENTS-METHODS: Eighty-six consecutive patients referred to the Sleep Unit of a Pulmonology Department underwent full polysomnography and their tests were manually scored. Three nonlinear indices (Largest Lyapunov Exponent-LLE, Detrended Fluctuation Analysis-DFA and Approximate Entropy-APEN) were extracted from two respiratory signals (nasal cannula flow-F and thoracic belt-T). The oxygen saturation signal (SpO(2)) was also selected. The above measurements provided data to the C4.5 algorithm using a data mining application. RESULTS: Two decision trees were produced using linear and nonlinear data from 3 respiratory signals. The discrimination between normal subjects and sufferers from OSAS presented an accuracy of 84.9% and a recall of 90.3% using the variables age, sex, DFA from F and Time with SpO(2)<90% (T90). The classification of patients into severity groups had an accuracy of 74.2% and a recall of 81.1% using the variables APEN from F, DFA from F and T90. CONCLUSION: It is possible to have reliable predictions of the severity of OSAS using linear and nonlinear indices from only two respiratory signals during sleep instead of performing full polysomnography. The proposed algorithm could be used for screening patients suspected to suffer from OSAS.

Ameloblastoma of the mandible with pulmonary metastases 45 years after initial diagnosis.

Ameloblastoma of the mandible is a rare odontogenic tumour that rarely metastasizes. We report a patient with a slowly progressing ameloblastoma of the mandible diagnosed at the age of seven and resected multiple times due to tumour recurrence. Multiple pulmonary metastatic nodules were resected at thoracotomy 27 years after the initial diagnosis; however, further pulmonary disease was discovered. The patient was admitted with chest pain due to pulmonary metastases 45 years after the initial diagnosis. The metastases were intraluminal and could be attributed to tumour cell aspiration during the surgical procedures on the mandible. The patient also suffered from hypercalcaemia which was attributed to a parathormone-like substance secreted by the tumour.