Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation? : A planning study.

BACKGROUND: After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. MATERIALS AND METHODS: In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a "selective" PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an "elective" PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a "selective" pleural irradiation plan (SPI plan) and an "elective" pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). RESULTS: In the SPI plans, the average median dose to the S­PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S­PTV to >58 Gy. In the EPI plans, the average median doses to the E­PTV and to the S­PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. CONCLUSION: The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema.

Clinical studies suggest that bronchial obstruction and emphysema increase susceptibility to lung cancer. We assessed the possibility of a common genetic origin and investigated whether the lung cancer susceptibility locus on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema. Three variants in the 5p15.33 locus encompassing the TERT and CLPTM1L genes were genotyped in 777 heavy smokers and 212 lung cancer patients. Participants underwent pulmonary function tests and computed tomography of the chest, and completed questionnaires assessing smoking behaviour. The rs31489 C-allele correlated with reduced forced expiratory volume in 1 s (p=0.006). Homozygous carriers of the rs31489 C-allele exhibited increased susceptibility to bronchial obstruction (OR 1.82, 95% CI 1.24-2.69; p=0.002). A similar association was observed for diffusing capacity of the lung for carbon monoxide (p=0.004). Consistent with this, CC-carriers had an increased risk of emphysema (OR 2.04, 95% CI 1.41-2.94; p=1.73 × 10(-4)) and displayed greater alveolar destruction. Finally, CC-carriers also had an increased risk for lung cancer (OR 1.90, 95% CI 1.21-2.99; p=0.005), and were more susceptible to developing both lung cancer and bronchial obstruction than lung cancer alone (OR 2.11, 95% CI 1.04-4.26; p=0.038). The rs31489 variant on 5p15.33 is associated with bronchial obstruction, presence and severity of emphysema, and lung cancer.

Permanent pacemakers in pregnancy.

Advances in cardiology and cardiovascular surgery have increased the use of permanent pacemakers in young adults such that there are more women with pacemakers becoming pregnant. This case report describes the pregnancy and delivery of a young woman with a demand pacemaker and reviews the principles of management of cardiac pacemakers in pregnancy. As part of the multidisciplinary team including cardiology, anesthesia, nursing and caring for these patients, it is important that obstetricians be informed and follow the principles of management of cardiac pacemakers in pregnancy to continue to achieve successful pregnancy outcomes.

Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit.

We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections. We investigated whether whole-genome sequencing (WGS) of MSSA surveillance would provide additional evidence for transmission. MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to WGS and bioinformatic analysis for identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. By measuring the genetic diversity in background surveillance, we defined transmission-level relatedness and identified isolates that had been unjustly assigned to clusters based on MLVA, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates provided evidence that HCWs were involved in multiple outbreaks, yet it alleviated concerns about one particular HCW. The improved resolution and accuracy of genomic outbreak analyses substantially altered the view on outbreaks, along with apposite measures. Therefore, inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference.

Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects and clinical integration.

Lung cancer is a common disease and is a leading cause of death in many countries. The management of lung cancer is directed by an optimal staging of the tumour. Integrated positron emission tomography (PET)/computed tomography (CT) is an anatomo-metabolic imaging modality that has recently been introduced to clinical practice and combines two different techniques: CT, which provides very detailed anatomic information; and PET, which provides metabolic information. One of the advantages of PET/CT is the improved image interpretation. This improvement can result in the detection of lesions initially not seen on CT or PET, a more precise location of lesions, a better characterisation of the lesion as benign or malignant and a better differentiation between tumour and surrounding structures. Initial studies demonstrate better results for PET/CT in the staging of lung cancer in comparison with PET alone, CT alone or visual correlation of PET and CT. The purpose of the present article is to discuss technical aspects of integrated PET/CT and to attempt to outline how to introduce integrated PET/CT in clinical and daily practice.

Maternal respiratory distress and successful reversal with sugammadex during intrauterine transfusion with fetal paralysis.

A 70 kg, 34-year-old woman at 29 weeks-of-gestation required intrauterine transfusion for Rh (D) alloimmunization. In the ambulatory treatment clinic, 19 mg of rocuronium was administered intramuscularly in split doses into the fetal buttock. The fetus moved and inadvertent maternal neuromuscular blockade occurred, leading to respiratory distress. The patient was transferred to the operating room where she had poor muscle tone, dyspnea and dysphonia. Sugammadex 100 mg was administered intravenously and complete resolution of neuromuscular blockade was demonstrated using a Neuromuscular Transmission™ monitor. When neuromuscular blocking agents are administered in ambulatory settings, management protocols, reversal agents, and skilled assistance should be immediately available for managing potentially life-threatening complications.

The effects of stress on alcohol consumption: mild acute and sub-chronic stressors differentially affect apomorphine susceptible and unsusceptible rats.

The aim of this study was to investigate the effects of mild acute and mild sub-chronic challenges on alcohol intake and preference in the genetically selected ratlines of apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) animals. Animals from both lines were subjected to the 24 hr continuous alcohol vs. water paradigm under baseline conditions, after a single stressor and after multiple stressors. The intake of alcohol in ml was measured and converted to two values, namely intake in g/kg/24 hour of, and preference for, alcohol. This study shows that under baseline conditions the APO-UNSUS animals consume/prefer more alcohol than the APO-SUS animals. After an acute challenge the APO-SUS animals show a large increase in consumption, whereas the APO-UNSUS animals display only a small increase. Furthermore, sub-chronic challenges can further increase the consumption of the APO-UNSUS rat, but not that of the APO-SUS rat. The APO-SUS/ APO-UNSUS rats represent a good model to study the interaction between genetic factors and stress on directing alcohol consumption.

The inner and outer of our thorax: silicone breast implants and pulmonary alveolar proteinosis.

Pulmonary alveolar (phospholipo)proteinosis (PAP) is a rare lung disease, predominantly autoimmune in nature. This case report describes a patient with insidious dyspnoea since 5 years and a milky appearance of her bronchoalveolar fluid, leading to the diagnosis of PAP. The onset of symptoms coincided with an exchange of her silicone breast implants. Giant cell reaction in axillary adenopathies pointed towards silicone leakage. Adjuvants, such as silicone, might boost pre-existing antigen reactions of the immune system, potentially leading to autoimmune phenomena.

The striato-nigro-collicular pathway and explosive running behaviour: functional interaction between neostriatal dopamine and collicular GABA.

The nature of the functional interaction between neostriatal dopamine activity and collicular GABA activity was studied. To this end we analyzed the ability of apomorphine injections into the neostriatum (50-500 ng/0.5 microliters per side) to reinitiate explosive running behaviour in rats pretreated with a subthreshold dose of picrotoxin into the colliculus superior (30-80 ng/0.5 microliters per side). Apomorphine was found to reinitiate the former behaviour dose dependently and its effect could be antagonized by a very low dose of neostriatally applied haloperidol (250 ng/0.5 microliters per side). It was possible to delineate the most critical region within the structures studied. Evidence is presented in favour of the previously reported hypothesis that increasing dopaminergic neostriatal activity within the terminal region of the nitrostriatal pathway results in a decreasing GABAergic activity within the terminal region of the GABAergic striato-nigro-collicular pathway.

Radiological aspects of Zenker's diverticulum.

In a retrospective study of 143 patients with Zenker's diverticulum followed for a period of 20 years, we classified the diverticula into 4 categories (A, B, C and D) using Brombart's scheme as a basis; the difference between the first two categories, however, was made on the basis of a morphological-dynamic criterion rather than a purely morphological one. Furthermore, a quantitative index was introduced to define the size of the diverticulum. In two cases we noted a substantial increase in volume with the transition from category C to D after more than 3 years, but we were unable to demonstrate an evolution from category A to B, nor from B to C. Our study confirms, on a large scale, the presence of three possible pathogenetic mechanisms, as proposed earlier in the literature: decreased relaxation of the upper esophageal sphincter as the most frequent factor in all categories except category A, and delayed opening or early closing of this sphincter as less frequent factors. The good relaxation of the upper esophageal sphincter in our category A, the different sex ratio and the absence of evolution in this category suggest that category A does not necessarily evolve further.

[Possible substitution between intramural and extramural care. An exploration from a needs approach]. / Mogelijke substitutie tussen intramurale en extramurale zorg. Een verkenning vanuit een behoeftenbenadering.

This article concerns the possibility of substitution within the health and welfare system for the aged, in particular the possibility of shifting from institutional care (homes for the aged) towards community care (home care programmes). Based on an analysis of the need for support among elderly persons requesting admission into residential homes, it was concluded that such a shift will be possible. Attention was then paid to the planned introduction of more restricted admission-norms as part of old-age-policy in the Netherlands. Of some importance is whether this more strict admission-policy will lead to a decline in the percentage of elderly in residential homes below the existing norm of 7%. This seems unlikely, mainly because most of the aged requesting admission into residential homes already have such a need for support that they will meet the requirements of a more restricted admission policy.

[Control of allocation through decision making on requests for care. Study of indications for nursing homes]. / Beheersing van een voorziening via het beslissen over hulpvragen. Onderzoek naar de indicatiestelling voor het verzorgingstehuis.

The allocation of social services is the central theme in this article. More in particular attention is drawn to the admission-decisions for residential homes. The Dutch government has created specific regulatory forms to control the admission policy of private institutions in this field. Two interrelated goals are associated with this regulation: first that of selectivity (admission restricted to those 'in need'), and second that of objectivity (equal treatment and equal opportunities with regard to admission). This article gives the results of an empirical investigation into the problem of goal-attainment. It is concluded, that both selectivity and objectivity are only partially achieved. These findings will be relevant for intended changes in admission-policy. Current proposals present the choice between more or less centrally guided admission norms, favoring the latter. However, from the theory of rationing this can be seen as a shift towards a more hidden system of rationing, which is less predictable in outcome contrary to the aforementioned goals of selectivity and objectivity.

Invasive staging of the mediastinum.

Staging of patients with lung cancer provides accurate information on the extent of disease and guides the choice of treatment. Non-invasive imaging techniques are safe, however these imaging techniques have limited accuracy in detection of mediastinal lymph node metastases. The American College of Chest Physicians guidelines for lung cancer staging recommend that patients with abnormal lymph nodes on CT or PET, or centrally located tumors without mediastinal LNs, should undergo invasive staging. Mediastinal nodal sampling has traditionally been performed by cervical mediastinoscopy. However, with the development of endoscopic needle aspiration techniques such as endobronchial ultrasound (EBUS) to guide transbronchial needle aspiration (TBNA) and endoscopic ultrasound (EUS), the diagnostic algorithm for lung cancer is changing.

Staging of lung cancer. Do we need a diagnostic CT of the brain after an integrated PET/CT for the detection of brain metastases?

Brain CT has been recommended in staging of patients with lung cancer because of its usefulness in the detection of metastases. Purpose of this study is to examine if a diagnostic brain CT (CT,) can be obviated when an integrated PET/CT (PET/CT) is available. 87 consecutive patients underwent a diagnostic brain CT and a whole-body PET/CT within a period of 3 weeks to stage a known primary tumour. CT examinations were evaluated by two experienced neuroradiologists on the detection of brain lesions (benign and malignant). The results of PET/CT and CT reading were compared and both readings were compared with the clinical results. Statistical analysis was done by measuring sensitivity, specificity, PPV, NPV and accuracy. The relative accuracies were compared by a McNemar (exact) test for correlated proportions. Considering the CT, as standard of reference, sensitivity, specificity, PPV, NPV and accuracy for the brain CT of PET/CT (CT2) and PET/CT were respectively 83%, 96%, 77%, 97%, 94% and 69%, 98%, 90%, 95%, 94%. Considering the clinical diagnosis as standard of reference these figures were for CT1, CT2 and PET/CT respectively 80%, 100%, 100%, 96%, 96% and 66%, 95%, 77%, 93%, 90% and 66%, 97%, 83%, 93%, 91%. There was no statistical difference between CT1 and CT2. The comparison of the additional CT in PET/CT with a diagnostic CT of the brain did not yield a statistical difference in the detection of brain lesions despite the inferior quality of the CT component of PET/CT. A diagnostic brain CT can be obviated when a PET/CT is available.

Integrated PET/CT and cancer imaging.

Integrated Positron Emission Tomography/Computed Tomography (PET/CT) is an imaging technique that was introduced in clinical practice in 1998. PET/CT is the combination of two different examination techniques in one machine: Computed Tomography (CT) giving anatomic information and Positron Emission Tomography (PET) giving metabolic information. PET/CT has two major advantages: CT can be used for attenuation correction and PET/CT improves diagnostic accuracy when compared to CT and PET alone.The quality of PET/CT images depends on different parameters such as CT dose, patient respiration, and the use of intravenous (i.v.) and per oral (PO) contrast. A rapidly expanding amount of literature demonstrates the additional value of PET/CT in the diagnosis, staging, prognosis, treatment planning, assessment of treatment response and diagnosis of recurrence of many tumor types. CT increases the sensitivity of the PET/CT examination, but the most beneficial effect of having the CT data is the increase of the specificity of the PET data. PET data also helps to specify CT information.The utility of PET/CT for tumor staging, which is one of the major imaging study indication, seems to be very high, and therefore PET/CT may become the scanner of the future. Till this moment there are no many published studies about the cost-effectiveness of PET/CT. The integration of PET/CT in clinical practice will result in higher equipment running costs, but these costs are likely not to be prohibitive to the diffusion of this combined technology.