Primary Erlotinib Resistance in a Patient with Non-Small Cell Lung Cancer Carrying Simultaneous Compound EGFR L718A, Q849H, and L858R Mutations.

Nowadays, mutations in the epidermal growth factor receptor (EGFR) kinase domain are studied in targeted therapy of non-small cell lung cancer (NSCLC) with EGFR tyrosine kinase inhibitors including gefitinib and erlotinib. The present study reports a rare case of a patient harboring three simultaneous EGFR mutations (L718A, Q849H, and L858R). The development of erlotinib resistance was detected in the subsequent treatment. Using a computational approach, the current study investigated the conformational changes of wild-type and mutant EGFR's kinase domains in the interaction with erlotinib. Their binding modes with erlotinib were elucidated during molecular dynamics simulation, where higher fluctuations were detected in the mutated forms of the EGFR tyrosine kinase domain. Prediction of stability and functional effect of mutations revealed that amino acidic substitutions have decreased the protein stability as well as the binding affinity to erlotinib. These results may be useful for a recommendation of EGFR mutational analysis for patients with NSCLC carcinoma.

Pulmonary artery stenosis shortly after lung transplantation: successful balloon dilation and stent insertion in one case.

BACKGROUND: Pulmonary artery stenosis after lung transplantation is a rare complication. It usually requires surgical correction but even after that the outcome is not favorable.
CASE REPORT: The patient was a 53-years-old woman who was candidate for lung transplantation surgery due to pulmonary fibrosis. After 7 months on waiting list, with severe limitations in daily living activities, she received a single lung transplant in 2007. The surgery was performed without any complication. One day after surgery and after extubation, the patient needed oxygen supplementation through mask with reservoir bag. In bronchoscopy, black-and-white exudate and black membrane that blocked the main bronchus in the transplanted lung was observed. By bronchial lavage the membrane and exudate were successfully removed and patient received antibiotics for documented Aspergillus infection and methylprednisolone pulse therapy for evidences of graft rejection. Despite success in treatments of the mentioned complications, the condition of the patient deteriorated and she became totally dependent to supplemental oxygen. Oxygen consumption level had increase and pulmonary artery pressure was increasing gradually. With suspicion to pulmonary artery stenosis, bronchial CT-Scan with contrast was performed 13 days after transplantation surgery which showed a 50% stenosis. Trans-esophageal echocardiography also showed a stenosis with 40 mmHg gradient. 18 days after transplantation surgery, percutaneous balloon angioplasty was performed which was initially successful but re-stenosis occurred. Seven days later, another balloon angioplasty with stent insertion was performed. After the procedure, the gradient has been removed. Patient was discharged 30 days after transplantation. Follow-up after 10 months revealed no stenosis and the stent was working properly.
CONCLUSIONS: Stent angioplasty can be performed with no problem or complication if pulmonary artery stenosis is seen after lung transplantation.

A proposed grading system for post-intubation tracheal stenosis.

BACKGROUND: Tracheal stenosis is still a serious consequence of endotracheal intubation. Previous classification systems are commonly descriptive and are not intended to deal with management approach. The aim of this study was to present a classification system for post intubation tracheal stenosis and evaluate its efficacy in distinguishing critically ill patients who need surgical intervention. MATERIALS AND METHODS: This classification system was developed based on size and type of stenosis and associated clinical signs and symptoms. Stenosis was graded based on the results of clinical examination and rigid bronchoscopy. All patients received surgical or conservative treatment based on the judgment of a surgeon experienced in management of post-intubation tracheal stenosis without considering their score. ROC curve analysis was done and cut-off point was established based on the greatest Youden index. RESULTS: Sixty patients were studied. Resection and anastomosis were done for 49 patients. The mean score for all samples was 9.18 (range 8.77-9.45). Chosen cutoff point was 8.5 and calculated sensitivity and specificity were 89% and 42%, respectively. Positive and negative predictive values were 83.7% and 54.5%, respectively. A reasonable agreement between the estimated score and surgeon's clinical judgment (kappa = 0.78) was observed. A statistically significant relationship was observed between scores greater than 8.5 and need for surgical intervention (P= 0.007). CONCLUSION: We presented a scoring system for post-intubation and tracheostomy tracheal stenosis using main factors influencing diagnosis and treatment and its efficacy was evaluated prospectively. It seems that this system would be capable of assimilating the treatment interventions and comparing them.

Postlung transplant rehospitalization: a study of causes, health care burden, and outcomes.

OBJECTIVES: Rehospitalization is a significant burden for transplant systems, which use data on hospitalization to monitor practice outcomes. In this study, all rehospitalizations after successful lung transplant performed in our medical center during an 8-year period were assessed for cause, health care resource use, cost, and outcome. MATERIALS AND METHODS: We performed a retrospective chart review of all rehospitalizations of lung transplant recipients in Masih Daneshvari Hospital in Darabad, Tehran, between 2000 and 2008. Baseline data (each patient's age at transplant and rehospitalization, sex, primary lung disease, medications used), cause of rehospitalization (infection, graft rejection, surgical complications, type of infection), health care resources use (length of hospital stay, intensive care unit stay, physician visits, imaging), rehospitalization costs (accommodations, personnel, drugs, paraclinical [ie, laboratory] tests, supplies, procedures) and outcome (death, survival) were noted. RESULTS: In 69% of patients who were rehospitalized after having received a lung transplant, the cause was infection. Other causes were acute rejection in 31% and surgical complications in 6.9%. In 10.3% of those patients, the primary cause for rehospitalization could not be specified. The mean (SD) duration of rehospitalization was 12.8 -/+ 10.4 days. Treatment in the intensive care unit was necessary for 93.1% of the study subjects. The mean (SD) number of physician visits was 27.8 -/+ 27.7, and the fatality rate in the patients studied was 13.8%. CONCLUSIONS: These data may guide the monitoring of the causes, burden, and outcomes of lung transplants performed in our medical center in Iran and in other medical centers.