Wigle, Dennis A.

BackgroundThere is no accurate method distinguishing different types of pulmonary nodules.PurposeTo investigate whether multiparametric 3T MRI biomarkers can distinguish malignant from benign pulmonary nodules, differentiate different types of neoplasms, and compare MRI‐derived measurements with values from commonly used noninvasive imaging modalities.Study TypeProspective.SubjectsSixty‐eight adults with pulmonary nodules undergoing resection.SequencesRespiratory triggered diffusion‐weighted imaging (DWI), periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) fat saturated T2‐weighted imaging, T1‐weighted 3D volumetric interpolated breath‐hold examination (VIBE) using CAIPIRINHA (controlled aliasing in parallel imaging results in a higher acceleration).Assessment/StatisticsApparent diffusion coefficient (ADC), T1, T2, T1 and T2 normalized to muscle (T1/M and T2/M), and dynamic contrast enhancement (DCE) values were compared with histology to determine whether they could distinguish malignant from benign nodules and discern primary from secondary malignancies using logistic regression. Predictability of primary neoplasm types was assessed using two‐sample t‐tests. MRI values were compared with positron emission tomography / computed tomography (PET/CT) to examine if they correlated with standardized uptake value (SUV) or CT Hounsfield unit (HU). Intra‐ and interreader agreements were assessed using intraclass correlations.ResultsForty‐nine of 74 nodules were malignant. There was a significant association between ADC and malignancy (odds ratio 4.47, P < 0.05). ADC ≥1.3 μm2/ms predicted malignancy. ADC, T1, and T2 together predicted malignancy (P = 0.003). No MRI parameter distinguished primary from metastatic neoplasms. T2 predicted PET positivity (P = 0.016). T2 and T1/M correlated with SUV (P < 0.05). Of 18 PET‐negative malignant nodules, 12 (67%) had an ADC ≥1.3 μm2/ms. With the exception of T2, all noncontrast MRI parameters distinguished adenocarcinomas from carcinoid tumors (P < 0.05). T1, T2, T1/M, and T2/M correlated with HU and therefore can predict nodule density. Combined with ADC, washout enhancement, arrival time (AT), peak enhancement intensity (PEI), Ktrans, Kep, Ve collectively were predictive of malignancy (P = 0.012). Combined washin, washout, time to peak (TTP), AT, and PEI values predicted malignancy (P = 0.043). There was good observer agreement for most noncontrast MRI biomarkers.Data ConclusionMRI can contribute to pulmonary nodule analysis. Multiparametric MRI might be better than individual MRI biomarkers in pulmonary nodule risk stratification.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018.

Abstract Background Pneumatosis intestinalis has long been a marker of advanced bowel ischemia and prompts urgent laparotomy. In post-operative settings, the presence of pneumatosis represents a significant management dilemma. We share a case-series of post-esophagectomy patients with pneumatosis intestinalis and no corollary intra-abdominal pathologic findings on re-exploration. Methods January 2000 to December 2017, 1760 patients underwent Ivor-Lewis esophagectomy or gastrectomy with jejunostomy-tube placement. Charts were reviewed retrospectively to identify patients with pneumatosis intestinalis discovered in the post-operative period. Demographic data, operative details and postoperative course were reviewed including incidence and details of re-exploration. Results Eleven patients met inclusion criteria. Nine were male (81.8%) and mean age was 69 years. All patients had radiographic confirmation of pneumatosis intestinalis and in many cases portal venous gas (Figure 1). Clinical course was variable without discernable trends in vitals or laboratory values. Development of significant postoperative ileus along with delivery of enteral tube feeds through a jejunostomy tube preceded development of the pneumatosis in all patients. Nine patients were re-explored and none had evidence of bowel ischemia. Conclusion The finding of pneumatosis intestinalis in the post-operative setting can be alarming and pose a management dilemma. With the advent of improved and readily available imaging, there has been an increase in findings that have no corollary physical symptomatology. In this series of patients, despite dramatic radiographic findings, none had ischemic bowel. Pneumatosis intestinalis alone in patients who have undergone esophagectomy should not be considered an indication for emergency re-exploration. Disclosure All authors have declared no conflicts of interest.

Abstract Background The purpose of this study was to evaluate the survival difference in clinical T2N0 esophageal cancer patients receiving neoadjuvant chemoradiotherapy (CRT) vs. upfront surgery. Methods Between 1/1/1995 to 12/31/2012, a prospectively maintained database was used to identify patients with cT2N0 esophageal adeno- and squamous cell carcinoma. Exclusion criteria included: lack of endoscopic esophageal ultrasonographic (EUS) staging, incomplete resection, and prior treatment with endoscopic mucosal or submucosal resection. Cox-proportional hazard ratios were used to compare the primary outcomes of overall (OS) and disease-free survival (DFS). Secondary outcomes included: rate of postoperative complications, rate of pathologic upstaging/response, and induction/adjuvant treatment completion rate. Pre-hoc subgroup analysis compared pathologically upstaged patients receiving upfront surgery followed by adjuvant chemotherapy to those treated with neoadjuvant CRT. Results A total of 161 cT2N0 esophageal cancer patients were identified based on EUS staging. Upfront surgery was offered to 134 patients (83%), with 27 patients (17%) receiving induction CRT. Univariate analysis did not demonstrate any significant baseline differences between the two groups. In the upfront surgery group, 53 (39.6%), 28 (20.9%) and 53 (39.6%) patients were pathologically down-staged, accurately staged and upstaged respectively. Upstaging was higher in the upfront surgery group (53/134, 39.6% vs. 4/27, 14.8%; P = 0.02), while 11/27 (40.7%) patients receiving neoadjuvant CRT demonstrated complete pathologic response. Of those eligible for adjuvant chemotherapy, only 21/55 (38.2%) received treatment. In the neoadjuvant CRT group, 51.9% completed all planned therapy, compared to 23.6% of patients treated with upfront surgery followed by adjuvant chemotherapy (P = 0.01). Cox proportional hazard ratio did not demonstrate an advantage to induction CRT in terms of OS (HR = 1.64, P = 0.43) or DFS (HR = 1.36, P = 0.69). In general, patients with pathologic upstaging had worse OS (HR = 2.73, P = 0.001) and DFS (HR = 4.18, P = 0.003). Conclusion EUS was only accurate in staging T2N0 patients in 20.9% of cases. While neoadjuvant CRT did not confer a survival advantage, these results likely reflect the low number of patients being referred for induction therapy. Neoadjuvant CRT was however associated with lower rates of pathologic upstaging and higher rates of treatment completion. Further research should evaluate the survival outcomes in pathologically upstaged cT2N0 patients not receiving neoadjuvant therapy. Disclosure All authors have declared no conflicts of interest.

Abstract Background The objective of this study was to analyze the induction therapy regimens employed since publication of CROSS Trial in patients treated with locally advanced EGJ cancer in terms of toxicity, complications, survival and recurrence. Methods Retrospective chart review all patients in single institution prospective database who had neoadjuvant CRT→Surgery 2012–2015. Complications during CRT and after surgery graded using National Cancer Institute CTCAE. Cox-proportion hazard ratios were used to compare the primary outcomes of overall survival (OS) and disease-free survival (DFS). Results 288 patients, 237 men and 51 women were identified. 246 were adenocarcinoma, 38 squamous cell carcinoma, and 4 had other histologic types. 4 distinct neoadjuvant regimens were observed: 50.4 Gy radiation with 5-fluorouracil and cisplatin (N = 22), CROSS regimen (41.4 Gy with carboplatin & paclitaxel) (N = 44), 50.4 Gy with carboplatin and paclitaxel (N = 152), and ‘Other’ which include 27 distinct regimens (N = 70). There were no differences in treatment related complications or postoperative complications between regimens. There was no difference in pathologic complete response rate, OS, or DFS between regimens. Conclusion Since the publication of the CROSS Trial, there is a significant heterogenity in the neoadjuvant chemoradiation treatment regimen employed for patients with locally advanced EGJ tumors. Does not appear to be any differences in treatment related complications or postoperative complications between regimens. There was also no difference in pCR, overall survival or disease-free survival. Disclosure All authors have declared no conflicts of interest.

Abstract Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors. Experimental Design: We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Results: Analysis of sequencing data found recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1, RAD51C, TAF1L, EPHB2, POLR3B, and AGFG1. The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were TMEM41B, DEFB127, WDYHV1, and TBPL1. Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-κB and MAPK/ERK pathways. The mutation signature was predominantly C&gt;T and T&gt;C transitions with a minor contribution of T&gt;G transversions. Conclusions: This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. Clin Cancer Res; 24(7); 1691–704. ©2018 AACR.