Outcomes of concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer and significant comorbidity.

BACKGROUND: published trials of concurrent chemoradiotherapy (CCRT) in stage III non-small-cell lung cancer (NSCLC) generally excluded patients with significant comorbidity. We evaluated outcomes in patients who were selected by using radiation planning parameters and were considered, despite comorbidity, fit enough to receive cisplatin-based chemotherapy. PATIENTS AND METHODS: from 2003 to 2008, 89 patients with stage III NSCLC fit to receive cisplatin-based chemotherapy and a V(20) <42% underwent CCRT at one center outside clinical trials. Most received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrent with involved-field thoracic radiotherapy between 46 and 66 Gy. RESULTS: median age was 64 years; performance status (PS) of zero, one or two in 20/64/5 patients; one or more comorbidities in 41.6%; 14% were treated previously for NSCLC. Median V(20) was 26.6% (range 4%-39.4%). Grade III esophagitis and pneumonitis occurred in 28.1% and 7.9% of patients, respectively, while 4.5% died during treatment. Median overall survival was 18.2 months [95% confidence interval (CI) 13.1-23.3 months]. Independent prognostic factors for overall survival were PS (0 versus ≥ 1, P = 0.041) and planning target volume (P = 0.022). CONCLUSIONS: patients with significant comorbidity who are fit to undergo cisplatin-based CCRT achieve median survivals similar to that reported in phase III trials and with relatively few late toxic effects.

Rapid oral desensitisation procedure in clopidogrel hypersensitivity.

We describe a patient who developed generalised pruritus with oedema and rash two weeks after she had started taking clopidogrel following coronary stent implantation. In the absence of other likely causative agents, clopidogrel hypersensitivity was probable. She was treated with a rapid oral desensitisation procedure, after which a daily dose of 75 mg clopidogrel was well tolerated. No major adverse events occurred during a follow-up period of eight months. Oral desensitisation in clopidogrel hypersensitivity seems to be a safe method to reduce the risk of coronary stent thrombosis. (Neth Heart J 2008;16:21-3.).

Nephrotic proteinuria has No net effect on total body protein synthesis: measurements with (13)C valine.

In nephrotic syndrome, significant amounts of plasma proteins, mostly of hepatic origin, are lost in urine. Total hepatic protein synthesis increases, suggesting that other protein pools must be conserved to maintain steady state. This can be accomplished either by decreased amino acid oxidation or decreased protein synthesis in other organs to replace lost liver-derived proteins. To determine the effect of nephrotic syndrome on total-body protein metabolism, we compared whole-body valine use in seven nephrotic patients and five controls using a primed continuous infusion of [1-(13)C]-valine, with additional priming of NaH(13)CO(3). Plasma [(13)C]-valine, (13)C alpha ketoisovaleric acid, and the expired (13)CO(2) enrichments were used to assess whole-body valine flux, valine oxidation, and nonoxidative valine disposal (NOVD). The valine flux into the blood compartment (97.7 +/- 3.0 versus 95.3 +/- 3.3 micromol/kg/h), oxidation of valine (19.4 +/- 1.9 versus 21.2 +/- 2. 8 micromol/kg/h), and NOVD (78.3 +/- 2.5 versus 74.2 +/- 2.7 micromol/kg/h) were not statistically different in patients compared with controls. Valine oxidation correlated positively with urinary urea excretion (r = 0.70; P = 0.01) in all subjects. Compared with control subjects who have similar urinary urea excretion, nephrotic subjects do not compensate for urinary loss of protein by decreased amino acid oxidation or decreased nonoxidative valine disposal. Previous studies have shown that synthesis of several hepatic proteins increases when subjects are fed the same dietary regime, whereas the present study shows that total-body protein synthesis does not increase. This would imply reduced synthesis of nonhepatic protein pools.

Bleeding varices due to portal hypertension in sarcoidosis. Favorable effect of propranolol and prednisone.

A 58-year-old white man had bleeding varices in the gastric fundus due to portal hypertension attributable to histologically proven hepatic sarcoid involvement with a giant splenomegaly and with an angiographically demonstrated significant flow toward the liver. Treatment with corticosteroids and beta-blockade (30 mg propranolol daily) resulted in no rebleeding for over one year follow-up.

Prescription and usage of long-term oxygen therapy in patients with chronic obstructive pulmonary disease in The Netherlands.

Long-term oxygen therapy (LTOT) has been shown to improve survival in hypoxaemic patients with chronic obstructive pulmonary disease (COPD). This has resulted in recommending the prescription of oxygen for at least 15 h day-1 in most European countries. In order to examine the prescription and usage of LTOT and to assess the adherence to international recommendations for its prescription, a survey was set up in a random sample of clients of the largest oxygen company in the Netherlands. After patients had been visited for an interview, additional postal surveys were sent to the physician who had prescribed LTOT and to the oxygen company. For 175 COPD patients the mean oxygen prescription and mean oxygen usage were 15.6 +/- 5.8 and 14.1 +/- 6.8 h day-1, respectively. In 62 patients (35%) oxygen was prescribed < 15 h day-1, more often by non-chest physicians than by chest physicians (P < 0.0001), and 91 patients (52%) used oxygen < 15 h day-1. Of 113 patients with a prescription > or = 15 h day-1, 39 (35%) used oxygen < 15 h day-1 and 74 for > or = 15 h day-1. The latter were prescribed oxygen for more h day-1, had been longer on LTOT, had a higher resting flow rate, were prescribed a concentrator, employed portable cylinders and used oxygen in public significantly more often than the former. We conclude that in a selected group of LTOT patients with COPD both oxygen prescription and usage were often inadequate, particularly if LTOT was prescribed by non-chest physicians.

Characteristics and complaints of patients prescribed long-term oxygen therapy in The Netherlands.

In patients prescribed long-term oxygen therapy (LTOT), compliance is often poor. Both patient- and treatment-related factors seem to be involved. As a base for improvements in LTOT, the characteristics and complaints of LTOT patients were investigated. A survey was set up in a random sample of clients of the largest oxygen company in the Netherlands. Patients were selected if they were > or = 18 years old, had a phone and if they had had oxygen equipment for > or = 6 months. All patients were visited at home by a medical student. Data are presented for a total of 528 patients (response rate 62%). The typical LTOT patient was a 70-year-old male with chronic obstructive pulmonary disease (COPD), who had had oxygen equipment for 3.5 years and who used oxygen cylinders and nasal cannulae for 13 h day-1. Twenty percent of the patients still smoked. Although LTOT was prescribed in 80% of the patients by a chest physician, prescription was often inadequate. Only 33% of the patients were informed adequately about the therapy. Twenty percent of the patients used oxygen for fewer hours per day than prescribed. Non-compliant patients were mainly men (P = 0.006) and more often ashamed of their therapy (P = 0.023) than compliant patients. The blood oxygen level was monitored regularly in 73% of the patients. Most complaints concerned the oxygen equipment, especially the concentrator. The single most important complaint had to do with restricted autonomy. Only 19% of the patients had no complaints at all. It is concluded that LTOT should be improved with regard to the education, motivation and monitoring of patients. The prescribing physician needs to be included in an education programme. Given the numerous problems these patients experience, LTOT should be improved in particular with regard to equipment convenience.

Infection with Dengue virus.

We report a male Caucasian, with a Dengue virus infection imported from Thailand to The Netherlands. General characteristics of the disease are presented and the supposed pathogenetic mechanisms of the disease are discussed.

Normal perfusion scintigraphy in pulmonary embolism. Causes and diagnostic alternatives.

Diagnosing pulmonary embolism (PE) is a challenge for many physicians as it is a frequently occurring disease with nonspecific symptoms and signs. Ventilation-perfusion (V/Q) scintigraphy is widely used as the first step in diagnosing PE since it is non-invasive and highly sensitive. With a normal perfusion scan, clinically relevant pulmonary thrombo-emboli are considered to be absent. In an ongoing study assessing the value of spiral CT in the diagnosis of PE, we encountered a patient who had a normal perfusion scan while a large partially occluding thrombus in the right lower lobe artery and its branches was depicted by spiral CT and pulmonary angiography. In this article, we discuss the significance of normal findings in perfusion scintigraphy, the causes of false-negative perfusion scans and the role of alternative techniques such as spiral CT and pulmonary angiography.

[The probability of survival of patients with bronchial carcinoma]. / De overlevingskansen van patiënten met bronchuscarcinoom.

A study was made of the effect of the discontinuation of population screening for tuberculosis, on January 1, 1982, on the referral pattern and therapeutic results in patients with bronchial carcinoma. In 1981 only a few patients were referred because of lesions detected at the screening. Accordingly, discontinuing the screening had no demonstrable effect. Also, there was no difference between patients referred because of a fortuitous finding and those who consulted because of symptoms. Nevertheless the results, especially the 5-year survival rates, were far better for those whose tumours had favourable TNM classifications. This applied in particular if resection of parts of the lung was feasible and operation revealed no metastases in mediastinal lymph nodes and no infiltrating growth. For this group of patients the 5-year survival rate amounted to 59.4%. With only symptomatic treatment the rate was 16.7% and for patients with small-cell anaplastic carcinomas given chemotherapy, it was 5.6%.

[Coma due to an overdose of valnoctamide]. / Coma door overdosering van valnoctamide.

We report a 27-year-old man, who became comatose after autopoisoning with a high dose of valnoctamide. He was mechanically ventilated for 12 hours and survived without serious side effects. Valnoctamide blood levels were monitored in order to study the pharmacokinetics of oral overdosing of this drug. Serum half-time levels appeared to be approximately 15 hours.

Rigid external resistances cause effort dependent maximal expiratory and inspiratory flows.

A fixed orifice or a fixed upper airway obstruction (UAO) causes an expiratory and inspiratory plateau-shaped limitation on maximal flow-volume (MEFV, MIFV) curves and, according to the classic concept, a MEF50/MIF50 ratio of 0.9-1.1. However, since maximal expiratory static transrespiratory pressures (PEmax,stat) are clearly greater than the inspiratory ones (PImax,stat), the pressures applied during forced expiration also must be expected to be greater than inspiratory pressures; therefore, the MEF should be larger than the MIF because orifice flow is effort-dependent. We investigated this hypothesis in seven healthy, nonsmoking male volunteers (mean age +/- 1 SD: 34 +/- 10 yr, FVC: 5.9 +/- 1.0 L, PEmax,stat: 168 +/- 16 cm H2O, PImax,stat: 107 +/- 33 cm H2O). They performed MEFV curves and MIFV curves through four different added resistances placed in between the pneumotachograph and the mouth (the orifice diameters ranged between 7.8 mm and 2.8 mm). During these maneuvers dynamic mouth pressures were also measured (PE and PI). We found that the MEF50/MIF50 ratios were significantly increased (p < 0.05) from a control value of 1.1 +/- 0.4 up to 1.5 +/- 0.3 with the resistances. For each added resistance the PE/MEF ratios and (-)PI/MIF ratios were situated on a single line corresponding with the pressure-flow (P/V) characteristics of the resistance. We concluded that external resistances cause a MEF50/MIF50 ratio of clearly more than 1 and that this is determined by the PE/(-)PI ratio, which in healthy subjects is markedly larger than 1.

Relationship between external resistances, lung function changes and maximal exercise capacity.

In upper airway obstruction (UAO) the relationship between the degree of obstruction, exercise limitation and lung function indices is not well established. Therefore, we investigated in nine healthy subjects (age 36+/-9 yrs) the effects of two added resistances at the mouth (R1 = added resistance with 7.8 mm diameter; R2 = 5.7 mm) on forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), airway resistance (Raw) and maximal breathing capacity (measured during 15 s = measured maximum breathing capacity (MBCm); calculated as FEV1x37.5 = calculated maximum breathing capacity (MBCc)) on the one hand, and maximum exercise capacity (W'max), minute ventilation (V'E) and CO2 elimination (V'CO2) on the other. We found that R1 had almost no influence on FEV1 but decreased PEF by approximately 35% and increased Raw by almost 300%; it decreased W'max by merely approximately 10% while maximal exercise ventilation (V'Emax) was only 65% of control and only reached approximately 40% MBCc and approximately 70% MBCm; yet V'E and V'CO2 were significantly reduced at high exercise levels indicating hypoventilation. With R2, FEV1 was reduced by 25% and PEF by 55%, and Raw was increased by 600%; W'max was approximately 60% of control, V'Emax was only 35% of control and reached approximately 30% MBCc and approximately 60% MBCm, V'E was already reduced at moderate exercise levels. We conclude that: 1) an upper airway obstruction of 6 mm diameter (but not of 8 mm) had a marked influence on maximum exercise capacity due to hypoventilation; 2) calculated maximum breathing capacity markedly overestimated measured maximum breathing capacity because the forced expiratory volume in one second is an insensitive index of upper airway obstruction and because it does not take inspiratory flow limitation into account; and 3) a 10% decrease in maximum exercise capacity was linearly related with a 7% decrease in the forced expiratory volume in one second and a 150% increase in airway resistance. A 10% decrease in maximal exercise ventilation was related to a 8.5% decrease in peak expiratory flow and 9% decrease in measured maximum breathing capacity.

Lung function, CT-scan and X-ray in upper airway obstruction due to thyroid goitre.

The purpose of this study was to assess the clinical reliability and to compare routine lung function tests (maximal flows and resistance) and radiological images (computed tomography (CT)-scan and X-ray) in upper airway obstruction. We, therefore, performed these examinations prospectively in 28 female patients (aged 68 +/- 13 yrs) with a goitre and without pulmonary disorders. Lung function measurements consisted of maximum expiratory and inspiratory flow-volume curves and of airway resistance. CT-scans and X-rays were performed during apnoea at functional residual capacity (FRC). Peak expiratory flow was 3.6 +/- 1.3 l.s-1 (i.e. 62 +/- 21% predicted); airway resistance was 0.38 +/- 0.14 kPa (i.e. 149 +/- 58% pred); and specific conductance was 1.0 +/- 0.3 kPa (i.e. 70 +/- 24% pred). Almost all lung function tests were significantly correlated with each other. On CT-scan the tracheal cross-sectional area at the zone of tracheal narrowing could be evaluated in 26 patients and was 58 +/- 17% (CT1/2) of the control area 2 cm above the carina (CT2). On X-ray the sagittal and coronal tracheal diameters at the zone of narrowing could only be measured in 16 subjects and were 60 +/- 17% (X-dia1/2) of the diameter at the control level. CT1/2 and X-dia1/2 were significantly correlated to each other. No correlation was found between the lung function tests and the radiological indices except airway resistance and CT2. Routine lung function and CT-scan do not provide comparable information on the degree of airway obstruction due to a goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosing acute pulmonary embolism: effect of chronic obstructive pulmonary disease on the performance of D-dimer testing, ventilation/perfusion scintigraphy, spiral computed tomographic angiography, and conventional angiography. ANTELOPE Study Group. Advances in New Technologies Evaluating the Localization of Pulmonary Embolism.

In patients with chronic obstructive pulmonary disease (COPD), differentiating a pulmonary embolism (PE) from an exacerbation of COPD can be difficult, since clinical signs and symptoms of the two conditions overlap. Development of reliable noninvasive or minimally invasive techniques for the diagnosis of PE is, especially in these patients, necessary. In this study we assessed the effect of COPD on the accuracy of the clinical probability estimate (CPE), spiral computed tomographic angiography (SCTA), D-dimer analysis, ventilation perfusion (V/Q) scintigraphy, and pulmonary angiography for the diagnosis of PE. From May 1997 through March 1998, 627 consecutive patients with suspected PE were investigated in six teaching hospitals. In these patients, D-dimer testing, CPE, V/Q scintigraphy, and SCTA and/or pulmonary angiography were performed according to a strict diagnostic protocol. The patients were also independently categorized as having COPD or not. A diagnosis of COPD was established in 91 patients (15%). The prevalence of PE was similar in patients with and without COPD (29% and 31%, respectively), notwithstanding the larger proportion of nondiagnostic V/Q scan results in patients with COPD (46% versus 21%, p < 0.001). The distribution of CPEs, diagnostic value of the D-dimer assay and SCTA, and reproducibility of pulmonary angiography were comparable among patients with and without COPD. The presence of COPD does not affect the diagnostic performance of CPE, D-dimer testing, SCTA, or pulmonary angiography. Furthermore, although more nondiagnostic V/Q scan results can be expected in the presence of COPD, V/Q scintigraphy remains a valuable screening test in patients with COPD.

Transtracheal oxygen therapy: an effective and safe alternative to nasal oxygen administration.

Transtracheal oxygen therapy (TTOT) improves the efficiency of oxygen delivery and overcomes the discomfort associated with nasal oxygen delivery in patients on long-term oxygen therapy (LTOT). In addition, TTOT improves compliance and quality of life, and may reduce morbidity. Experience with TTOT in Europe is, however, scarce and the safety of TTOT has not yet been completely determined. These were reasons for testing the acceptance, efficacy and safety of TTOT. Patients were selected on the basis of the accepted indications and contraindications for TTOT. In 75 patients (48 males and 27 females) the mean follow-up time was 16 (range 0.5-51.5) months. Compared to nasal cannulae, TTOT caused a reduction in the oxygen flow rate of 47 (33-60)% at rest and a significant increase in the number of hours that oxygen was used. All patients on TTOT used oxygen for at least 20 h x day(-1). Most patients saw the procedure as a minor intervention. It was usually performed on an out-patient basis. In 34 patients, 51 mainly minor complications were seen, and most of these occurred in the first 10 patients. After precautions had been taken, complications occurred less frequently. No patient needed to be hospitalized because of a complication. TTOT had to be stopped in two patients; nevertheless, all patients preferred TTOT to the nasal cannulae. We conclude that transtracheal oxygen therapy is an effective and safe alternative to nasal oxygen administration, provided that it is restricted to a well-defined group of patients and applied by a motivated and experienced group of physicians.

Accuracy of oxygen delivery by liquid oxygen canisters.

The oxygen flow rate delivered by liquid oxygen canisters may be less than intended, owing to inaccuracies of the set flow rates and/or as a result of the outflow resistance caused by the humidifier, oxygen tubing, delivery or conserving device. The aim of this study was to investigate the accuracy of oxygen delivery by liquid oxygen canisters at different flow rates and levels of outflow resistance. Four stationary and 18 portable liquid oxygen canisters from three manufacturers were tested. All flows were measured using a Timemeter RT 200 Calibration Analyser. An adjustable obstruction was used to calculate the effect of the outflow resistance on the delivered flow rate. The measured and set flow rates of both stationary and portable canisters were strongly correlated. Expressed as a percentage of the set flow rate, the measured flow rate of the canisters varied from 36-128%, with the lowest values at flow rates <1 L x min(-1). Sixty-two (26%) of the measured flow rates differed > or =10% from the set flow rate. A difference of 0.5-1.0 L x min(-1) occurred in 16 (7%) of the measurements, but only at set flow rates >2 L x min(-1). Irrespective of the set flow rate, the measured flow rate was hardly affected by the outflow resistance. We conclude that the accuracy of oxygen delivery by liquid oxygen canisters depends on the inaccuracy of the set flow rates rather than on the outflow resistance, even at high flow rates. Although the differences between the measured and set flow rates were mostly small, they may have clinical significance, particularly in patients with chronic obstructive pulmonary disease. To prevent inaccuracy, monthly checks of the canisters by the oxygen provider at the patient's home are more important than yearly maintenance.