Hiren J. Mehta

The Utility of Nodule Volume in the Context of Malignancy Prediction for Small Pulmonary Nodules

BACKGROUND An estimated 150,000 pulmonary nodules are identified each year, and the number is likely to increase given the results of the National Lung Screening Trial. Decision tools are needed to help with the management of such pulmonary nodules. We examined whether adding any of three novel functions of nodule volume improves the accuracy of an existing malignancy prediction model of CT scan-detected nodules. METHODS Swensens 1997 prediction model was used to estimate the probability of malignancy in CT scan-detected nodules identified from a sample of 221 patients at the Medical University of South Carolina between 2006 and 2010. Three multivariate logistic models that included a novel function of nodule volume were used to investigate the added predictive value. Several measures were used to evaluate model classification performance. RESULTS With use of a 0.5 cutoff associated with predicted probability, the Swensen model correctly classified 67% of nodules. The three novel models suggested that the addition of nodule volume enhances the ability to correctly predict malignancy; 83%, 88%, and 88% of subjects were correctly classified as having malignant or benign nodules, with significant net improved reclassification for each (P<.0001). All three models also performed well based on Nagelkerke R2, discrimination slope, area under the receiver operating characteristic curve, and Hosmer-Lemeshow calibration test. CONCLUSIONS The findings demonstrate that the addition of nodule volume to existing malignancy prediction models increases the proportion of nodules correctly classified. This enhanced tool will help clinicians to risk stratify pulmonary nodules more effectively.

Curcumin and lung cancer—a review

Curcumin (diferuloylmethane) is the most important component of the spice turmeric and is derived from the rhizome of the East Indian plant Curcuma longa. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including antioxidant, analgesic, anti-inflammatory, and antiseptic activities. Recently, curcumin has been widely studied for its anticancer properties via its effects on a variety of biological pathways involved in apoptosis, tumor proliferation, chemo- and radiotherapy sensitization, tumor invasion, and metastases. Curcumin can be an effective adjunct in treating solid organ tumors due to its properties of regulating oncogenes like p53, egr-1, c-myc, bcl-XL, etc.; transcription factors like NF-kB, STAT-3, and AP-1; protein kinases like MAPK; and enzymes like COX and LOX. Lung cancer is the most common malignancy worldwide and a leading cause of cancer-related deaths. Seventy-five percent of lung cancer presents at an advanced stage where the existing treatment is not very effective and may result in tremendous patient morbidity. As a result, there is a significant interest in developing adjunctive chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo studies of curcumin in lung cancer.

Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease

Background: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. Objectives: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. Methods: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. Results: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. Conclusion: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

Lung cancer mimicking as pregnancy with pneumonia

SUMMARY Lung cancer that presents with secretion of beta HCG is rare. We report a case of a young female patient who presented with symptoms of pneumonia and was found to have a positive pregnancy test. With non-resolution of the consolidation and progression of her symptoms she subsequently was found to have large cell lung cancer with ectopic beta HCG secretion. Ectopic production of a variety of hormones such as ADH, parathyroid hormone, ACTH, insulin-like growth factor thus leading to presentation as endocrine syndromes in patients with lung cancer is well known. The presentation of lung cancer mimicking as pregnancy has not been previously reported. This case illustrates the importance of considering the possibility of paraneoplastic secretion of beta HCG in female patients who have a positive pregnancy test in an appropriate clinical setting. This may prevent a delay in the diagnosis and treatment of malignancy in young women.

The American College of Radiology Lung Imaging Reporting and Data System: Potential Drawbacks and Need for Revision

&NA; Lung cancer screening using low‐dose CT scanning reduces lung‐cancer‐specific and overall mortality in high‐risk patients. A significant limitation of lung cancer screening is the false‐positive rate. The American College of Radiology Lung Imaging Reporting and Data System (Lung‐RADS) was designed to standardize reporting of low‐dose lung cancer screening results and to decrease the false‐positive rate without significantly compromising sensitivity. Implementing Lung‐RADS can also improve cost‐effectiveness. However, Lung‐RADS has never been studied in a prospective fashion. It also does not have a specific reporting category for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules. We report four such cases from our lung cancer screening program. We believe that this is a significant limitation of Lung‐RADS and should be revised in its new version.

Restoration of Patency to Central Airways Occluded by Malignant Endobronchial Tumors Using Intratumoral Injection of Cisplatin

RATIONALE Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. OBJECTIVES The objective of this study was to analyze our experience with bronchoscopic endobronchial intratumoral injection of cisplatin for malignant airway obstruction. METHODS We conducted a retrospective analysis of patients with malignant airway obstruction treated with bronchoscopic intratumoral injection of cisplatin. Patient characteristics, histology, degree of airway obstruction, procedural methods, treatment cycles, performance status, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic measurements performed on completion the of final treatment session. Adverse events and overall survival were abstracted. MEASUREMENTS AND MAIN RESULTS Between January 2009 and September 2014, 22 patients (10 men, 12 women; mean age ± SD, 64.4 ± 9.5 yr) were treated with one to four injections of 40 mg of cisplatin mixed in 40 ml of 0.9% NaCl. Treatments were completed 1 week apart. The primary etiologies of airway obstruction included squamous cell carcinoma (n = 11), adenocarcinoma (n = 6), small cell carcinoma (n = 2), large cell undifferentiated carcinoma (n = 1), and metastatic endobronchial cancer (n = 2). Twenty-one of 22 patients were evaluable for response. The majority of patients (15/21, 71.4%) responded to therapy, defined as greater than 50% relative reduction in obstruction from baseline. Treatment response was obtained regardless of tumor histology, concurrent systemic therapy, number of treatment cycles administered, performance status, or use of additional ablative interventions. Responders had significantly improved overall survival as compared with nonresponders, although the difference was small. Severe treatment-related side effects or complications were not observed. CONCLUSIONS Subject to the limitations of a single-center retrospective study and a subjective primary outcome measure, we have demonstrated the feasibility of improving the patency of central airways that are largely or completely occluded by endobronchial malignant tumor using intraluminal injection of cisplatin. Additional longer-term, larger-scale safety and comparative effectiveness studies of this palliative treatment modality are warranted.

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Stomatococcus mucilaginosus is an oral commensal that has been occasionally reported to cause severe infections in immunocompromised patients. There is no information about the pathogenic role of S. mucilaginosus in airway infections. In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized with S. mucilaginosus in their lower airways by culture growth from bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus, we developed a murine model of S. mucilaginosus lung infection. Intratracheal injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx with production of proinflammatory cytokines, chemokines, and lipid mediators, mainly PGE2 with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of TLR2 was necessary for induction of COX-2 and production of PGE2 by S. mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S. mucilaginosus compared with wild-type mice. Administration of PGE2 to TLR2−/− mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role for COX-2–induced PGE2 production in immune response to S. mucilaginosus. Mechanistically, induction of COX-2 in macrophages was dependent on the p38-ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and Pseudomonas aeruginosa showed an increased mortality compared with mice treated with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved survival in mice infected with PA103 and S. mucilaginosus. These data provide novel insights into the bacteriology and personalized microbiome in patients with bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients with bronchiectasis.

Lung RADS: Potential Drawbacks and Need for Revision.

&NA; Lung cancer screening using low‐dose CT scanning reduces lung‐cancer‐specific and overall mortality in high‐risk patients. A significant limitation of lung cancer screening is the false‐positive rate. The American College of Radiology Lung Imaging Reporting and Data System (Lung‐RADS) was designed to standardize reporting of low‐dose lung cancer screening results and to decrease the false‐positive rate without significantly compromising sensitivity. Implementing Lung‐RADS can also improve cost‐effectiveness. However, Lung‐RADS has never been studied in a prospective fashion. It also does not have a specific reporting category for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules. We report four such cases from our lung cancer screening program. We believe that this is a significant limitation of Lung‐RADS and should be revised in its new version.

Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin

PURPOSE A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). METHODS Patients treated between Jan 2009-September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8-12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. RESULTS 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9±8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6-11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. CONCLUSION EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population.

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer

Pembrolizumab was recently approved as a first line agent for metastatic NSCLC in patients with high programmed death‐ligand 1 (PD‐L1) expression.