Faculty Bibliography

OBJECTIVES: Sublobar resection is advocated for patients with NSCLC and compromised cardiopulmonary reserve, and for selected patients with early stage disease. Anatomic segmentectomy (AS) has traditionally been considered superior to wedge resection (WR), but well-balanced comparative studies are lacking. We hypothesize that WR and AS are associated with comparable oncologic outcomes for patients with cT1N0 NSCLC. METHODS: A retrospective review of a prospective database was performed (2000-2014) for cT1N0 patients, excluding patients with multiple primary tumors, carcinoid tumors, adenocarcinoma in situ, and minimally invasive adenocarcinoma. Demographic, clinical, and pathological data were reviewed. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Multivariable analysis (MVA) of factors affecting DFS was performed by Cox regression analysis. For further comparison of the effect of resection type on survival, propensity score matching (i.e., by age, sex, Charlson comorbidity index, percent forced expiratory volume in 1 second (FEV1%), clinical tumor size, and tumor maximum standardized uptake value) was performed to obtain balanced cohorts of patients undergoing WR and AS (n = 76 per group). RESULTS: Two hundred eighty-nine patients met our selection criteria, including WR in 160 and AS in 129. Poor performance status and limited cardiopulmonary reserve were the primary indications for sublobar resection in 76% of WR patients and in 62% of AS patients (p = 0.011). Thirteen patients (4.5%) had pN1/2 disease. Patients undergoing AS were more likely to have nodal sampling/dissection [123 (95%) versus 112 (70%); p < 0.001], more stations sampled (3 versus 2; p < 0.001), and more total nodes resected (7 versus 4; p = 0.001). However, there was no difference between patients undergoing WR versus AS in local recurrence [15 versus 14; p = 0.68] or 5-year DFS (51% versus 53%; p = 0.7; median follow-up 34 months). Univariate analysis showed no effect of extent of resection on DFS [hazard ratio 1.07 (95% confidence interval 0.74-1.56); p = 0.696]. MVA showed that only tumor maximum standardized uptake value was associated with worse DFS [hazard ratio 1.07 (95% confidence interval 1.01-1.13); p = 0.016]. In the propensity-matched analysis of balanced subgroups, there was also no difference (p = 0.950) in 3- or 5-year DFS in cT1N0 patients undergoing WR (65% and 49%) or AS (68% and 49%). CONCLUSIONS: Our data show that WR and AS are comparable oncologic procedures for carefully staged cT1N0 NSCLC patients. Although AS is associated with a more thorough lymph node dissection, this did not translate to a survival benefit in this patient population with a low rate of nodal metastases.

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers, but its role in primary and metastatic non-small cell lung carcinoma (NSCLC) remains to be determined. Here, we investigate the clinical relevance of RHAMM expression in NSCLC. RHAMM protein expression correlates with histological differentiation stages and extent of the primary tumor (T stages) in 156 patients with primary NSCLC. Importantly, while focal RHAMM staining pattern is present in 57% of primary NSCLC, intense RHAMM protein expression is present in 96% of metastatic NSCLC cases. In a publicly available database, The Cancer Genome Atlas (TCGA), RHAMM mRNA expression is 12- and 10-fold higher in lung adenocarcinoma and squamous lung carcinoma than in matched normal lung tissues, respectively. RHAMM mRNA expression correlates with stages of differentiation and inferior survival in more than 400 cases of lung adenocarcinoma in the Director's Challenge cohort. Of 4 RHAMM splice variants, RHAMMv3 (also known as RHAMMB) is the dominant variant in NSCLC. Moreover, shRNA-mediated knockdown of RHAMM reduced the migratory ability of two lung adenocarcinoma cell lines, H1975 and H3255. Taken together, RHAMM, most likely RHAMMv3 (RHAMMB), can serve as a prognostic factor for lung adenocarcinomas and a potential therapeutic target in NSCLC to inhibit tumor migration.

Cardiac amyloidosis is an infiltrative disorder of the myocardium. It is the result of one of 4 types of amyloidosis: primary systemic (immunoglobulin light chain), secondary, familial (hereditary), or senile. Cardiac amyloidosis ultimately causes congestive heart failure due to irreversible restrictive cardiomyopathy. Because of the rapid progression of the disease, early recognition and determination of underlying etiology are important for tailored therapy. Current interventions range from conservative heart failure management to autologous stem cell and heart transplantation. We present a case of cardiac amyloidosis accompanying undiagnosed multiple myeloma to illustrate the rapid progression of the disease and the complexities of diagnosing and treating this disorder.

Lymphangiomatosis (eg, generalized lymphatic anomaly) is an abnormal proliferation of lymphatic endothelial cells. It is often a childhood disease, but it may present in adulthood by infiltrating organs and cause obstruction, bleeding, or disruption of lymphatic flow. Pulmonary involvement may be mild or cause diffuse interstitial lung disease, airway obstruction, hemoptysis, chylothorax, chylopericardium, and culminate in respiratory failure. Treatment has been limited to surgical resection or drainage procedures because there is no accepted effective systemic therapy. This report presents a patient with lymphangiomatosis and life-threatening hemoptysis in whom positive immunostaining forc-KITsuggested upregulation of tyrosine kinase and whose disease was controlled with imatinib.

BACKGROUND:Bronchial carcinoids are characterized by neuroendocrine differentiation and have distinct biological behavior, recurrence patterns, and prognosis compared with adenocarcinomas or squamous cell carcinomas. Because of their often indolent nature, it has been suggested that routine postoperative imaging surveillance may not be warranted in the majority of patients. This study aims to define the factors that predict disease-free survival (DFS) and recurrence after resection of these tumors, with the goal of identifying high-risk patients for whom image surveillance may be warranted. METHODS:We conducted a retrospective review of a prospective database to identify patients with completely resected bronchial carcinoid tumors. Surgical procedure, histology, pathological stage, follow-up, tumor recurrence, and survival were assessed. RESULTS:One hundred and forty-two patients were identified. Median age was 62 years and the majority was women (106). Surgical procedures included 20 wedge resections, 10 segmentectomies, 99 lobectomies, 3 bilobectomies, 2 pneumonectomies, 6 sleeve resections, and 2 bronchectomies. Pathologic stages included I (81%), II (10%), III (8%), and IV (1%). With a median follow-up of 31 months, there were seven recurrences. The 5- and 10-year overall survival rates were 92% and 75% and DFS rates were 88% and 72%, respectively. There were 34 patients with atypical carcinoids, and 6 (18%) developed recurrence, compared with 1 recurrence (1%) in the group of 108 patients with typical carcinoids (p = 0.0008). For atypical carcinoid tumors, the 5- and 10-year DFS rates were 72% and 32% versus 92% and 85% in typical carcinoid tumors (p = 0.001). Patients with more advanced tumor stage pT2-4 and pathologic N1/N2 nodal metastases had a significantly decreased 5- and 10-year DFS compared with those with early pT1 stage (p = 0.029) or those without nodal disease (p = 0.043). Multivariate Cox regression analyses showed advancing age (p = 0.001), atypical histology (p = 0.021), and advanced tumor stage (p = 0.047) were significant negative predictors for DFS. CONCLUSION/CONCLUSIONS:Long-term survival after resection of bronchial carcinoids is common, especially for patients with typical carcinoid tumors. DFS can be negatively influenced by atypical histology, advanced tumor, and nodal statuses. Efforts at postoperative image surveillance should target those patients with such high-risk factors.