TGF-beta, radiation-induced pulmonary injury and lung cancer

PURPOSE: To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Plasma TGF-beta was investigated in 27 patients with stage III NSCLC, who were treated with 60 Gy (2Gy/day) radiotherapy with or without carboplatin. TGF-beta was measured prior to beginning radiotherapy and weekly during treatment; evaluated as a ratio between TGF-beta levels obtained during treatment and the pretreatment TGF-beta level. The endpoints of the study were development of symptomatic radiation pneumonitis and tumour response. RESULTS: Nine of the 27 patients developed pneumonitis. The patients who developed pneumonitis had high persistent TGF-beta levels throughout the course of treatment (TGF-beta ratio>1), whereas the TGF-beta levels in patients who did not develop pneumonitis were unchanged or declined towards normal (TGF-beta ratio < 1). Patients who responded to treatment had low or normal TGF-beta levels during treatment compared with patients who failed to respond. Other parameters such as pretreatment TGF-beta values, carboplatin treatment or field size did not appear to have a significant effect, which is probably due to the small number of patients entered in the study. CONCLUSION: This pilot study, with a limited number of patients, suggests the hypothesis that elevated TGF-beta levels during radiotherapy may not only indicate patients with a higher risk of developing pulmonary toxicity but also patients with a higher risk of treatment failure. This remains to be tested in a larger clinical study.     

TGF-beta,radiation-induced pulmonary injury and lung cancer

Purpose : To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients. Materials and methods : Plasma TGF-beta was investigated in 27 patients with stage III NSCLC, who were treated with 60 Gy (2Gy/day) radiotherapy with or without carboplatin. TGF-beta was measured prior to beginning radiotherapy and weekly during treatment; evaluated as a ratio between TGF-beta levels obtained during treatment and the pretreatment TGF-beta level. The endpoints of the study were development of symptomatic radiation pneumonitis and tumour response. Results : Nine of the 27 patients developed pneumonitis. The patients who developed pneumonitis had high persistent TGF-beta levels throughout the course of treatment (TGF-beta ratio>1), whereas the TGF-beta levels in patients who did not develop pneumonitis were unchanged or declined towards normal (TGF-beta ratio<1). Patients who responded to treatment had low or normal TGF-beta levels during treatment compared with patients who failed to respond. Other parameters such as pretreatment TGF-beta values, carboplatin treatment or field size did not appear to have a significant effect, which is probably due to the small number of patients entered in the study. Conclusion : This pilot study, with a limited number of patients, suggests the hypothesis that elevated TGF-beta levels during radiotherapy may not only indicate patients with a higher risk of developing pulmonary toxicity but also patients with a higher risk of treatment failure. This remains to be tested in a larger clinical study.     

肺通气血流灌注显像、螺旋CT肺动脉造影及D-二聚体测定对诊断肺栓塞的临床价值

目的探讨放射性核素肺通气血流灌注比值(V/Q)显像和螺旋CT肺动脉造影(SCTPA)以及血浆D-二聚体(dimer)检测对肺栓塞(PE)诊断的临床价值。方法对我院2010年2月—2013年2月可疑肺栓塞的患者,行V/Q显像、SCTPA检查和血浆D-二聚体测定以及相关检查,以最终临床诊断为依据,分别评价V/Q显像、SCTPA和血浆D-二聚体测定对PE的诊断价值。结果 278例高度怀疑PE患者经上述检查确诊PE患者151例,V/Q显像、SCTPA检查和血浆D-二聚体测定诊断PE的灵敏度、特异性、阳性预测值、阴性预测值分别为93.6%(132/141)、96.0%(120/125)、96.4%(132/137)、93.0%(120/129);95.8%(137/143)、96.9%(124/128)、97.2%(137/141)、95.4%(124/130);99.3%(140/141)、43.1%(59/137)、64.2%(140/218)、98.3%(59/60)。结论血浆D-二聚体测定的价值主要用于排除PE。对PE患者的检查应力求全面,V/Q显像、SCTPA检查均有其优点和不足,只有全面掌握各项检查的特点,才能对该项检查对疾病的诊断价值做出正确评价,从而正确运用这一诊断方法更好地服务于临床。     

Challenges, controversies, and hot topics in pulmonary embolism imaging

OBJECTIVE: The purpose of this article is to discuss the diagnostic role of pulmonary CT angiography (CTA) in the workup of pulmonary embolism (PE), including specific populations, and issues such as pulmonary CTA combined with indirect CT venography; radiation dose considerations; the management of isolated subsegmental PE; and new technologic developments, such as dual-source/dual-energy pulmonary CTA. CONCLUSION: The role of pulmonary CTA will continue to grow with the emergence of MDCT and dual-energy CT and their improved capabilities. However, the need for any given CT examination should always be justified on the basis of the individual patient's benefits and risks.     

Relationship between peripheral lung cancer and the surrounding bronchi, pulmonary arteries, pulmonary veins: a multidetector CT observation

Aim

This study aimed to investigate the relationship between peripheral lung cancer and the surrounding pulmonary vessels and bronchi using contrast-enhanced multidetector computed tomography (MDCT) and to analyze associated factors such as pathology types, stage, size, density, and location of peripheral lung cancer.

Materials and Methods

A total of 93 patients with solitary peripheral lung cancers underwent contrast-enhanced MDCT before thoracotomy were enrolled. Multiplanar reconstruction, maximal intensity projection, and volume rendering were used for demonstrating the patterns of the tumor-bronchi (Br), tumor-pulmonary artery (PA) and tumor-pulmonary vein (PV) relationship, respectively. Five subtypes were identified: Type1 (Br1, PA1 and PV1), Br, PA, or PV was erupted at the edge of nodule; Type2 (Br2, PA2, and PV2), erupted at the center of nodule; Type3 (Br3, PA3 and PV3), penetrated through the nodule; Type4, (Br4, PA4 and PV4), contacting the nodule but stretched or encased; Type5 (Br5, PA5, and PV5), contacting the nodule but smoothly compressed.

Results

Both bronchi and PA were interrupted in 70 (Type 1+2); both narrowed in 9 (Type 3+4). The bronchi and PA changes surrounding the lung cancer had positive relations (χ²=12.3918, r=0.7524, P<.01). Br1 and PA1 were more often seen in the group of solid, ≥2.0 cm, and Stage II-IV focal lesions, while Br2 and PA2, more often in the group of part-solid, non-solid, <2.0 cm, and Stage I focal lesions. PV2 was more often seen in the part-solid and non-solid focal lesions group, while PV (4+5), more often in solid focal lesions group.

Conclusion

MDCT can demonstrate and subtype relationships among peripheral lung cancer and the bronchi, pulmonary arteries and pulmonary veins. This can be the basis for further clinical research and differential diagnosis.     

Deep venous thrombosis,pulmonary embolism and long-distance flights

Deep vein thrombosis resulting in lethal pulmonary thromboembolism is not-infrequently encountered in forensic cases. Predisposing factors include immobility, recent surgery, previous deep venous thromboses/pulmonary thromboembolism, indwelling central venous lines, major trauma, the oral contraceptive pill, pregnancy, congenital cardiac disease, sepsis, malignancy, systemic lupus erythematosus, renal failure and certain inherited thrombophilias. Venous thrombosis associated with air travel was reported in the early 1950’s and called the “economy class syndrome”, although it is now recognized that reduced movement on long distance flights is more significant than seating class. Long-distance flights of eight hours or more are associated with a two to fourfold increase in the risk of deep venous thrombosis, but only in those individuals who have underlying risk factors. With increasing numbers of flights of more than 16 h duration forensic pathologists are well placed to monitor the potential impact of extended flying on the incidence of lethal pulmonary thromboembolism.     

Survey on the use of pulmonary scintigraphy, spiral CT and conventional pulmonary angiography for suspected pulmonary embolism in the British Isles

AIM: To determine current clinical practice in the radiological diagnosis of acute pulmonary embolism and assess the use of spiral volumetric computed tomography. METHOD: A survey of 327 acute hospitals including cardiothoracic and orthopaedic tertiary referral centres was undertaken to assess current utilization of lung scintigraphy, spiral computed tomography and pulmonary angiography in the investigation of suspected pulmonary embolism. Responses were received from 215/327 (66%) centres. RESULTS: Lung scintigraphy was provided by 208 hospitals (144 on-site and 64 off-site). Spiral CT services were provided by 111 (52%) hospitals (on- or off-site), 142 (66%) units had access to angiographic facilities. Sixty-three centres out of 215 (29%) offered both on-site lung scintigraphy and spiral CT while only 41/215 (19%) hospitals were able to undertake all three tests on-site. On average, 501 perfusion (Q) or ventilation-perfusion (V/Q) scintigrams were performed per hospital per year with 26 spiral CT studies and just 4.6 pulmonary angiograms. CONCLUSION: These data suggest that lung scintigraphy is frequently the only imaging test in patients other than chest radiography, despite the large number of indeterminate results reported in most series.     

Energy efficiency and pulmonary artery flow after balloon pulmonary angioplasty for inoperable,chronic thromboembolic pulmonary hypertension: Analysis by phase-contrast MRI

PurposeThe aims of this study were to propose a new quantitative method for pulmonary artery (PA) flow energetics using phase-contrast magnetic resonance imaging (PC-MRI), and to investigate how balloon pulmonary angioplasty (BPA) impacts energetics in chronic thromboembolic pulmonary hypertension (CTEPH).Materials and methodsPC-MRI at 3-Teslar and with a flow sensitive gradient echo was used to examine energetics prior to and following BPA for 24 CTEPH patients. Stroke volume (m; ml) and mean velocity (V; mm/s) for the main pulmonary artery (PA), right PA, and left PA were calculated from a time-flow curve derived from PC-MRI. Based on the Bernoulli principle, PA energy was identified as 1/2 mV² (μj/kg), and energy loss was defined as the following equation “energy loss = main PA energy − (rt. PA energy + lt. PA energy)”.ResultsRight PA energy was significantly greater post-BPA than pre-BPA (61 ± 55 vs. 32 ± 40 μj/kg). There was no difference in main PA and left PA energies. Energy loss was significantly decreased post-BPA (18 ± 97 μj/kg) than pre-BPA (79 ± 125 μj/kg). An optimal cutoff of left PA energy of 45 μj/kg pre-BPA can be used to predict patients with mPAP ≥ 30 mmHg after BPA, with an area under the curve of 0.91, 78% sensitivity, and 92% specificity.ConclusionAnalysis of PA energetics using phase-contrast MRI demonstrates that BPA improves energy loss in CTEPH. In addition, BPA responses can be predicted by PA energy status pre-treatment.     

Consistency of response and image recognition,pulmonary nodules

Objective:

To investigate the effect of recognition of a previously encountered radiograph on consistency of response in localized pulmonary nodules.

Methods:

13 radiologists interpreted 40 radiographs each to locate pulmonary nodules. A few days later, they again interpreted 40 radiographs. Half of the images in the second set were new. We asked the radiologists whether each image had been in the first set. We used Fisher''s exact test and Kruskal–Wallis test to evaluate the correlation between recognition of an image and consistency in its interpretation. We evaluated the data using all possible recognition levels—definitely, probably or possibly included vs definitely, probably or possibly not included by collapsing the recognition levels into two and by eliminating the “possibly included” and “possibly not included” scores.

Results:

With all but one of six methods of looking at the data, there was no significant correlation between consistency in interpretation and recognition of the image. When the possibly included and possibly not included scores were eliminated, there was a borderline statistical significance (p = 0.04) with slightly greater consistency in interpretation of recognized than that of non-recognized images.

Conclusion:

We found no convincing evidence that radiologists'' recognition of images in an observer performance study affects their interpretation on a second encounter.

Advances in knowledge:

Conscious recognition of chest radiographs did not result in a greater degree of consistency in the tested interpretation than that in the interpretation of images that were not recognized.In visual observer performance studies, observers'' memory of images can potentially be a source of bias by preventing the observer from interpreting the image on the second or subsequent viewing(s) independently of the interpretation at the preceding viewing(s). To reduce the potential for memory-related bias, most observer performance studies allow some time to elapse between one test involving a set of images and the next. This time delay varies a great deal between studies. In a study involving the identification of rib fractures, Fuhrman et al¹ waited at least 2 years between readings. In a different study comparing detection of pulmonary nodules with varied types of monitors, Graf et al² used an average time delay of 2 days. Metz,³ advising on the design of observer performance studies, suggested that investigators separate readings by as much time as possible.Although there is obvious concern among investigators regarding possible memory-related bias, radiologists'' memory for previously encountered images has seldom been investigated. Four papers do suggest that the radiologists'' ability to recognize previously encountered experimental images may be rather limited.^4–7Ultimately, the importance of memory for previously seen images in terms of design of observer studies lies not in how well radiologists consciously recognize the images that they have previously seen and distinguish them from new images but in how much their familiarity with the image affects their subsequent interpretations. This question has also seldom been addressed. Hardesty et al,⁴ studying radiologists'' interpretation of mammograms that they had previously encountered clinically months earlier, found that when each radiologist''s previously interpreted studies were mixed in with those of their colleagues, only one radiologist correctly recognized a single mammogram that he had previously interpreted, and then he interpreted it differently in the experiment than what he had done originally.Kallergi et al⁸ compared interpretations by two readers of 43 combined positron-emission tomography and CT (PET/CT) studies in patients with thyroid cancer. The readers first interpreted whole-body PET/CT. 2 days later, they interpreted the whole-body images together with dedicated images of the head and neck. At least 1 month later, they again performed the second type of interpretation with both whole-body and dedicated head-and-neck images. There were significant differences between the first and third readings and between the second and third readings but not between the first and second readings, which suggested that lingering memory of the first interpretation had impacted the second interpretation but not the third, which had occurred weeks later.Haygood et al⁹ compared radiologists'' consistency in interpretation of the placement of a central venous access line on repeated interpretation of images that they recognized vs those they did not recognize. There was no statistically significant difference in the likelihood of a similar interpretation on the second reading based on whether the image had been recognized. Indeed, the trend was for less consistency in interpretation for those images that were recognized than for those that were not.⁹Our objective in this study was to examine whether conscious recognition of a chest radiograph viewed in the first half of the experiment affects the interpretation of the presence or absence and location of pulmonary nodules on a second encounter with the same chest radiograph.     

Radiographic, CT, and MRI findings in primary pulmonary angiosarcoma.

We report a rare instance of primary pulmonary angiosarcoma presenting as a large solitary mass in the left upper lobe with mediastinal invasion. In particular, we emphasize the magnetic resonance (MR) imaging features, which included a markedly heterogeneous pattern consisting of hyperintense areas scattered throughout a background of intermediate signal intensity, rendering the lesion a cauliflower-like appearance especially on T2-weighted images. Being unreported so far in primary pulmonary angiosarcomas, these distinct MR imaging findings may be helpful in the differentiation of these neoplasms from lung cancers.     

High altitude pulmonary edema, down syndrome, and obstructive sleep apneas

A 24-year-old adult with a Down syndrome was admitted in December 2006 at the Moutiers hospital in the French Alps for an acute inaugural episode of high altitude pulmonary edema (HAPE) that occurred in the early morning of day 3 after his arrival to La Plagne (2000 m). This patient presented an interventricular septal defect operated on at the age of 7, a hypothyroidism controlled by 50 microg levothyrox, a state of obesity (BMI 37.8 kg/m(2)), and obstructive sleep apneas with a mean of 42 obstructive apneas or hypopneas per hour, treated with continuous positive airway pressure (CPAP). The patient refused to use his CPAP during his stay in La Plagne. At echocardiography, resting parameters were normal, with a left ventricular, ejection fraction of 60%, a normokinetic right ventricle, and an estimated systolic pulmonary artery pressure (sPAP) of 30 mmHg. At exercise, sPAP rose to 45 mmHg and the right ventricle was still normokinetic and not dilated. An exercise hypoxic tolerance test performed at 60 W and at the equivalent altitude of 3300 m revealed a severe drop in arterial oxygen saturation down to 60%, with an abnormal low ventilatory response to hypoxia, suggesting a defect in peripheral chemosensitivity to hypoxia. In conclusion, patients with Down syndrome, including adults with no cardiac dysfunction and regular physical activity, are at risk of HAPE even at moderate altitude when they suffer from obstructive sleep apneas associated with obesity and low chemoresponsiveness. This observation might be of importance since an increasing number of young adults with Down syndrome participate in recreational or sport activities, including skiing and mountaineering.