Bhaskar Bhardwaj

Pulmonary adenocarcinoma: implications of the recent advances in molecular biology, treatment and the IASLC/ATS/ERS classification.

A decade ago, lung cancer could conveniently be classified into two broad categories-either the small cell lung carcinoma (SCLC), or the non-small cell lung carcinoma (NSCLC), mainly to assist in further treatment related decision making. However, the understanding regarding the eligibility of adenocarcinoma histology for treatments with agents such as pemetrexed and bevacizumab made it a necessity for NSCLC to be classified into more specific sub-groups. Then, the availability of molecular targeted therapy with oral tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib not only further emphasized the need for accurate sub-classification of lung cancer, but also heralded the important role of molecular profiling of lung adenocarcinomas. Given the remarkable advances in molecular biology, oncology and radiology, a need for felt for a revised classification for lung adenocarcinoma, since the existing World Health Organization (WHO) classification of lung cancer, published in the year 2004 was mainly a pathological system of classification. Thus, there was a combined effort by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS) and the European Respiratory Society (ERS) with an effort to inculcate newly established perspectives from clinical, molecular and radiological aspects in evolving a modern classification for lung adenocarcinomas. This review provides a summary of the recent advances in molecular biology and molecular targeted therapy with respect to lung adenocarcinoma. Also, a brief summation of the salient recommendations provided in the IASLC/ATS/ERS classification of lung adenocarcinomas is provided. Lastly, a discussion regarding the future prospects with lung adenocarcinoma is included.

Revisiting opioid overdose induced acute respiratory distress syndrome.

Sir, Opioids are commonly used analgesic drug class with morphine like activity. Although respiratory system is the most affected organ system in opioid overdose; acute lung injury and acute respiratory distress syndrome (ARDS) are infrequently reported. A 25-year-old male presented after ingesting unknown amounts of hydrocodone. Patient was found to be unresponsive, with agonal respiration. Initial vital signs showed blood pressure 100/60 mmHg, pulse 110 beats/min, respiratory rate 8 breaths/min and oxygen saturation (SpO2) of 70%. Chest examination revealed decreased air entry bilaterally with bibasal crackles. Initial arterial blood gas (ABG) analysis showed respiratory acidosis with pH 7.22, partial pressure of carbon dioxide (PaCO2) at 70 mmHg, partial pressure of oxygen (PaO2) at 42 mmHg and SpO2 of 72%. An emergent orotracheal intubation was performed due to severe hypoxemia and to maintain a patent airway. Pink frothy secretions were seen in the endotracheal tube immediately after intubation and a chest radiograph showed diffuse bilateral infiltrates [Figure 1]. Mechanical ventilation was started at assist control mode with initial tidal volume of 500 ml, fraction of inspired oxygen (FiO2) at 100% and positive end expiratory pressure (PEEP) at 5 cm H2 O. Patient remained hypoxemic and repeat ABG analysis showed partial pressure of PaO2 42 mm Hg and SpO2 80% prompting increase in the PEEP up to 10 cm H2O, which improved PaO2 to 85 mm Hg. Based on initial PaO2/FiO2 ratio of 52 and characteristic radiographic bilateral opacities, severe ARDS was diagnosed. An echocardiogram showed normal left ventricular function and serum levels of brain natriuretic peptide (BNP) was normal at 88 pg/ml. Lung protective ventilation to achieve adequate oxygenation was continued. Furosemide was given to maintain a negative fluid balance. Patient could be successfully extubated on the 2nd day. Chest radiograph on day 3 showed complete resolution of ARDS [Figure 2]. Figure 1 An antero-posterior chest radiograph demonstrating diffuse pulmonary edema in the intubated patient Figure 2 A postero-anterior chest radiograph in the same patient 48 h later demonstrates complete resolution of the pulmonary edema Opioid overdose has been implicated as a cause of ARDS.[1] Sporer and Dorn described 27 patients of non-cardiogenic pulmonary edema (NCPE) secondary to heroin overdose.[2] Overall, clinical presentation of opioid-induced ARDS is generally indistinguishable from other causes of ARDS. Presence of frothy, sometimes blood tinged pulmonary secretions and bilateral diffuse infiltrates on chest radiograph are characteristic. Occasionally, it may be necessary to demonstrate normal cardiac pump function through measurements of serum BNP levels, echocardiogram and rarely right heart catheterization. The mechanisms behind opioid induced NCPE and ARDS remain largely unknown. The role of increased pulmonary capillary permeability due to hypoxemia, potent histamine release and respiratory acidosis caused by depression of medullary respiratory centers have been implicated.[3,4] Interestingly, the use of reversal agents like naloxone itself has also been described as the primary cause of pulmonary edema.[5] Patients with opioid-induced NCPE and ARDS can have severe hypoxemia frequently needing invasive mechanical ventilation. An early orotracheal intubation should be considered in obtunded or severely hypoxemic patients. Following intubation, general management strategies used in any form of ARDS comprising of lung protective strategies of ventilation, appropriate PEEP and diuretics are used. Overall prognosis remains good with most patients recovering within 24 h. In summary, our case demonstrates an infrequently seen respiratory complication in opioid overdose. Timely management decisions about adequate use of reversal agents and considering early mechanical ventilation in severely hypoxemic patients can be lifesaving.

Molecular targeted therapy to improve radiotherapeutic outcomes for non-small cell lung carcinoma

Effective treatments for non-small cell lung carcinoma (NSCLC) remain elusive. The use of concurrent chemotherapy with radiotherapy (RT) has improved outcomes, but a significant proportion of NSCLC patients are too frail to be able to tolerate an intense course of concurrent chemoradiotherapy. The development of targeted therapies ignited new hope in enhancing radiotherapeutic outcomes. The use of targeted therapies against the epidermal growth factor receptor (EGFR) has offered slight but significant benefits in concurrent use with RT for certain patients in certain situations. However, despite theoretical promise, the use of anti-angiogenics, such as bevacizumab and endostatin, has not proven clinically safe or useful in combination with RT. However, many new targeted agents against new targets are being experimented for combined use with RT. It is hoped that these agents may provide a significant breakthrough in the radiotherapeutic management of NSCLC. The current review provides a brief discussion about the targets, the targeted therapies, the rationale for the use of targeted therapies in combination with RT, and a brief review of the existing data on the subject.

A case of spontaneous pneumothorax following radiation therapy for non-small cell lung cancer.

Spontaneous pneumothorax (SPTX) is a potentially devastating rare complication of the thoracic radiation therapy. Most of the cases in the medical literature, have been described in lymphoma patients receiving radiation therapy. The pathogenesis of this adverse event remains undefined although different mechanisms have been proposed. We present a case of post-radiation therapy SPTX in a non-small cell lung cancer (NSCLC), following intensity modulated radiation therapy (IMRT), which to our knowledge is the first such reported case related to this newer mode of radiation therapy. This report highlights the importance of keeping a close eye for this complication as timely treatment with chest tube insertion and drainage of the pneumothorax can be a lifesaving in these patients.

Pulmonary Adenocarcinoma in a Young Patient of Pulmonary Langerhans Cell Histiocytosis (PLCH)

tonic-clonic seizure. Magnetic resonance imaging of the brain showed a partially cystic and partially solid left frontal lobe mass lesion (Fig. 1). The patient underwent a surgical resec- tion of the lesion, and pathological examination of the lesion was consistent with adenocarcinoma (AC) of unknown ori- gin. We ordered a positron emission tomography-computed tomography scan to look for the primary site of the AC, which showed a hypermetabolic left upper lobe lung mass with hypermetabolic activity in the left hilar region (Fig. 2). A computed tomography scan of the thorax was done subse- quently, which showed the left upper lobe lung mass (2.7 cm × 2.1 cm) with hilar lymphadenopathy (Fig. 2) and innumerable bizarre shaped, disorganized cystic lung lesions consistent with the diagnoses of pulmonary Langerhans cell histiocyto- sis (PLCH) (Fig.3). A computed tomography-guided biopsy of the left upper lobe lung lesion was done, which was consis- tent with diffusely infiltrating AC of the lung (Fig. 4). Biopsy specimen was tested for two most common types of somatic epidermal growth factor receptor mutations, exon 19 dele- tion and exon 21 L858R point mutation, both of which were absent. Fluorescence in situ hybridization analysis of tumor specimen showed absent anaplastic lymphoma kinase (ALK) rearrangement on chromosome 2p23 but interestingly showed amplification of ALK signal in 58.5% of the analyzed cells. The patient was started on cisplatin and pemetrexed for the treatment of primary metastatic lung AC.

Pulmonary apical fibrosis in a patient treated earlier for breast cancer

A 46-year-old woman who completed 10 years of follow-up after successful treatment for right-sided breast cancer presented in peak winter with discomforts of cough and accompanying chest-wall musculoskeletal pain persisting for 4 days. She had earlier received multimodality therapy with surgery (modified radical mastectomy), radiotherapy (to the ipsilateral postmastectomy chest wall, axilla and the supraclavicular area), chemotherapy and hormonal therapy. A chest radiograph demonstrated right pulmonary apical fibrosis (figure 1). A CT scan demonstrated a band which showed no contrast enhancement (figure 2). There were no cavitations or calcifications. The rest of the lungs and the mediastinum were unremarkable. A workup on the lines of tuberculosis was …

A painful sneeze: spontaneous thoracic lung herniation induced by vigorous sneeze.

Lung herniation, defined as the protrusion of lung tissue outside the normal boundaries of thoracic cage, is an unusual event. This most commonly occurs as a consequence of thoracic trauma. Spontaneous subtypes of lung herniation are rare with only a few cases reported in medical literature. We present a 63-year-old male who presented with spontaneously herniated lung after an episode of vigorous sneezing. The possible underlying mechanisms, important physical examination and diagnostic imaging findings, and aspects of management considerations are briefly discussed.

Differentiating pulmonary lymphangioleiomyomatosis from pulmonary langerhans cell histiocytosis and Birt-Hogg-Dube syndrome.

Lung India • Vol 30 • Issue 4 • Oct ‐ Dec 2013 Chest radiograph did not show any abnormal findings. We obtained a high resolution computed tomography (CT) scan of the chest which revealed multiple bizarre shaped lung parenchymal cysts mostly involving the upper lobes of the lungs and sparing the bases [Figure 1, Panel A and B]. Based on these characteristic findings a diagnosis of PLCH was made and patient was strongly advised against smoking and was prescribed some over-the-counter cough suppressants for symptomatic relief. Patient successfully quit smoking and over next 1 year her symptom improved greatly.

Radiographic illusion of cardiomegaly resulting from a pulmonary blastoma in a patient imaged for evaluation of chronic bronchitis

Cardiomegaly is conveniently defined by a simple and time-tested method, using a posteroanterior chest radiograph obtained in mid-inspiration, as a ‘cardiothoracic ratio greater than 0.5’. The cardiothoracic ratio is in turn calculated by measuring the distance from the midline to the most lateral aspect of the left and right cardiac silhouette borders, and dividing the sum by the maximum horizontal measurement of the thorax, from the left to right pleural surface at the level of the diaphragmatic apices.1 The accompanying images belong to a man who presented with symptoms of …