Health-related quality of life after prophylactic cranial irradiation for stage III non-small cell lung cancer patients: Results from the NVALT-11/DLCRG-02 phase III study.

BACKGROUND AND PURPOSE: The NVALT-11/DLCRG-02 phase III trial (clinicaltrials.gov identifier: NCT01282437) showed that, after standard curative intent treatment, prophylactic cranial irradiation (PCI) decreased the incidence of symptomatic brain metastases (BM) in stage III non-small cell lung cancer (NSCLC) patients compared to observation. In this study we assessed the impact of PCI on health-related quality of life (HRQoL). In addition, an exploratory analysis was performed to assess the impact of neurocognitive symptoms and symptomatic BM on HRQoL. MATERIALS AND METHODS: Stage III NSCLC patients were randomized between PCI and observation. HRQoL was measured using the EuroQol 5D (EQ-5D-3L), EORTC QLQ-C30 and QLQ-BN20 instruments at completion of standard curative intent treatment and 4 weeks, 3, 6, 12, 24 and 36 months thereafter. Generalized linear mixed effects (GLM) models were used to assess the impact of PCI compared to observation over time on three HRQoL metrics: the EORTC QLQ-C30 global health status and the EQ-5D-3L utility and visual analogue scale (EQ VAS) scores. RESULTS: In total, 86 and 88 patients were included in the PCI and observation arm, with a median follow-up of 48.5 months (95% CI 39-54 months). Baseline mean HRQoL scores were comparable between the PCI and observation arm for the three HRQoL metrics. In the GLM models, none of the HRQoL metrics were clinically relevant or statistically significantly different between the PCI and the observation arm (p-values ranged between 0.641 and 0.914). CONCLUSION: No statistically significant nor a clinically relevant impact of PCI on HRQoL was observed.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease): new insights in pathogenesis, complications, and treatment.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a hereditary disorder leading to easily bleeding telangiectases on skin and mucosal surfaces, and it is associated with the presence of arteriovenous malformations (AVMs) in multiple organ systems. These AVMs may cause serious complications when they are located in the lungs, liver, or brain. The prevalence of AVMs in patients with HHT might be higher than previously estimated. Nowadays, treatment is often possible. In some families, mutations have been shown in the gene encoding for a transforming growth factor receptor, endoglin. Genetic heterogeneity has been demonstrated, suggesting involvement of other transforming growth factor receptors. This might explain the variable clinical expression of the disease. In view of the high prevalence of pulmonary and cerebral AVMs, all patients with HHT should be screened for their presence, and relatives of patients with HHT should be investigated for presence of the disease.

[Pulmonary infection caused by non-tuberculous mycobacteria in two patients with bronchiectasis]. / Infectie met niet-tuberculeuze mycobacteriën bij 2 patiënten met bronchiëctasieën.

Two patients, a woman aged 67 years and a man aged 80 years, had chronic cough among other respiratory symptoms. In the woman, chest radiograph and CT-scan revealed partial atelectasis of the middle lobe and bronchiectasis. In the man, an interstitial pattern was seen on chest radiograph, and CT scan showed diffuse bronchiectasis. In both the man and the woman, non-tuberculous mycobacteria were identified (Mycobacterium avium complex and Mycobacterium abscessus, respectively). Treatment was successful in both patients. Non-tuberculous mycobacteria can cause considerable pulmonary infection in patients with bronchiectasis.

Screening family members of patients with hereditary hemorrhagic telangiectasia.

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder which may give rise to arteriovenous malformations in lungs and brain. When left untreated, these may cause serious complications. We screened family members of HHT patients for presence of the disease and associated pulmonary or cerebral arteriovenous malformations. PATIENTS AND METHODS: We investigated 98 family members of HHT patients on an outpatient basis. A stepped screening protocol was used based on prevalence of different manifestations of HHT. RESULTS: Thirty-six cases of HHT were found in the 98 persons screened. Pulmonary arteriovenous malformations were found in 12 of the 36 patients (33%), and cerebral arteriovenous malformations in 4 (11%). Therapy was recommended in 9 patients with pulmonary arteriovenous malformations and in 2 with cerebral arteriovenous malformations. CONCLUSIONS: Family members of known HHT patients should be encouraged to engage in a screening program, since the prevalence of potentially serious localizations is higher than previously thought.

Unusual complications after embolization of a pulmonary arteriovenous malformation.

A pulmonary arteriovenous malformation was embolized in a patient with hereditary hemorrhagic telangiectasia. Several unusual complications, including early deflation of a detachable balloon, migration of a coil, and development of severe pulmonary hypertension, occurred. Pulmonary hypertension was attributed to a coexistent left-to-right shunt caused by a large hepatic arteriovenous malformation.

Pleural effusion without ascites in a patient with cirrhosis.

The development is described of a massive right pleural effusion in a patient with alcoholic cirrhosis of the liver and alcoholic hepatitis, but without ascites. The literature is reviewed.

Surplus value of eosinophil count and ECP to diagnose and monitor asthmatic patients.

BACKGROUND: Eosinophil cationic protein (ESP) is one of the granule proteins in eosinophilic granulocytes. Release of this protein may reflect the activity state of eosinophilic granulocytes in diseased subjects. The purpose of this study was to evaluate the additional value of serum ECP measurement over the eosinophil count, (specific) IgE concentration and CRP concentration in order to evaluate the effects of treatment in patients started on corticosteroids and to distinguish individual patients with asthma from healthy subjects on the basis of laboratory results. METHODS: In a longitudinal study, serial measurements of serum ECP, eosinophil count and other laboratory parameters have been evaluated and compared with spirometry and tests of bronchial hyperresponsiveness in ten asthmatic subjects. The subjects were investigated before therapy was started and 3, 6 and 9 months after the start of therapy with inhaled corticosteroids. Laboratory parameters in the patient group are compared with results obtained from a reference group of apparently healthy subjects (n=223). RESULTS: Statistically significant correlations are observed between blood eosinophil counts and serum ECP concentrations with the hyperresponsiveness tests PC20 (r=0.44 and r=0.46, respectively) and with a decrease in FEV(1) after exercise (r=0.66 and r=0.60, respectively). A significant difference was detected between serum ECP concentrations from the patients' group and from the reference group. However, a wide range of overlapping results was observed between the reference group and the asthmatic patients. CONCLUSIONS: Asthma is a disease which is now more frequently treated by general practitioners. In general practice there is not always the opportunity to evaluate asthma activity by the application of hyperreactivity tests. When hyperreactivity testing is not available, measuring serum ECP concentration or eosinophil blood count would be an alternative method to monitor the effects of corticosteroid treatment. In this study the additional value of serum ECP in addition to the eosinophil count is evaluated to determine the effects of treatment in patients who started with application of corticosteroids. However, because of the analogous correlation coefficients of laboratory parameters with tests regarding hyperresponsiveness, no additional benefit of serum ECP concentration over eosinophil blood count in monitoring the effect of corticosteroids can be detected. The additional value of serum ECP concentrations and eosinophil counts to detect an asthmatic constitution for individual cases is doubtful.

Adrenal insufficiency secondary to postoperative bilateral adrenal haemorrhage.

Two case reports are presented of adrenal insufficiency due to bilateral adrenal haemorrhage following surgery. This unusual complication with its non-specific manifestations may result in unexpected clinical deterioration of the postoperative patient. Corticosteroid replacement and repletion of sodium and water deficits should be given promptly when adrenal haemorrhage is suspected.

Primary nasal tuberculosis.

We present a case of a patient with primary nasal tuberculosis. Although this is a rare finding, it should be considered when a patient presents with a nasal obstruction. Smears for acid fast bacilli and cultures tend to be negative in nasal tuberculosis. Diagnosis is often based on histo- pathologic findings. Nasal TB is known to respond well to the regular treatment for (pulmonary) tuberculosis.

Epistaxis in hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is characterized by easily bleeding telangiectases of the skin and mucosa. Epistaxis is the most common symptom of HHT. Larger arteriovenous malformations (AVM) occur in the lungs (in up to 33% of the patients), brain (in up to 11% of patients), and liver. These may cause severe complications which can be prevented by early therapy. To gain insight in the characteristics of epistaxis in HHT, 171 persons were investigated, who either had HHT or participated in a screening programme for relatives of HHT patients. Of these, 58 persons had HHT. Epistaxis without signs of HHT was present in 12 persons, whereas 10% of HHT patients did not have epistaxis. Seventeen HHT patients with epistaxis had visited an otorhinolaryngologist before, without a correct diagnosis of HHT being made. Telangiectases were most common on lips, tongue, the nasal septum, and the turbinates. In view of the prevalence of visceral AVM and the associated complications, HHT patients presenting to an otorhinolaryngologist should be encouraged to engage in a screening programme for these AVM.

Extrinsic allergic alveolitis caused by goose feathers in a duvet.

A patient with extrinsic allergic alveolitis had precipitating antibodies to many avian antigens. A duvet containing goose feathers proved to be the source of antigenic material.

Embolisation of pulmonary arteriovenous malformations: results and follow up in 32 patients.

BACKGROUND: Pulmonary arteriovenous malformations may cause a number of complications when left untreated. Embolisation of the feeding vessels is a relatively new approach and information concerning its efficacy and long term results is scarce. METHODS: Pulmonary arteriovenous malformations with feeding arteries of > 3 mm were treated by embolisation. Right to left shunt fraction and arterial oxygen pressure breathing air (PaO2) were measured before and after treatment. Six monthly measurement of shunt fraction was used for follow up. RESULTS: In 32 patients 92 pulmonary arteriovenous malformations were treated by coil embolisation. Mean shunt fraction decreased from 16.6% to 7.4% and PaO2 increased from 9.6 kPa to 11.5 kPa. Treatment was incomplete in two patients, one of whom was subsequently treated surgically. Serious complications occurred in one patient. Recanalisation of embolised vessels occurred in two cases after 22 and 28 months, respectively. Mean period of follow up was 25 months. CONCLUSIONS: Embolisation is a safe and efficacious treatment for most pulmonary arteriovenous malformations. Long term studies are necessary to determine the risk of recanalisation.

Linkage of hereditary haemorrhagic telangiectasia to chromosome 9q34 and evidence for locus heterogeneity.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterised by arteriovenous lesions and recurrent haemorrhage in virtually every organ. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we report confirmation of this localisation in three unrelated families of Dutch origin. A fourth unrelated HHT family, in which considerably fewer pulmonary arteriovenous malformations (PAVM) were present, yielded evidence for non-linkage to this region. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9 linked form of HHT than in patients with the non-linked form.