Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options with very low response rate. Lung cancer is the most common cause of cancer death worldwide. Therapies that target driver gene mutations (e.g. EGFR, ALK, ROS1) and checkpoint inhibitors such anti-PD-1 and PD-L1 immunotherapies are being used to treat lung cancer patients. Identification of correlations between driver mutations and PD-L1 expression will allow for the best management of patient treatment. 851 cases of non-small cell lung cancer cases were profiled for the presence of biomarkers EGFR, KRAS, BRAF, and PIK3CA mutations by SNaPshot/sizing genotyping. Immunohistochemistry was used to identify the protein expression of ALK and PD-L1. Total PD-L1 mRNA expression (from unsorted tumor samples) was quantified by RT-qPCR in a sub-group of the cohort to assess its correlation with PD-L1 protein level in tumor cells. Statistical analysis revealed correlations between the presence of the mutations, PD-L1 expression, and the pathological data. Specifically, increased PD-L1 expression was associated with wildtype EGFR and vascular invasion, and total PD-L1 mRNA levels correlated weakly with protein expression on tumor cells. These data provide insights into driver gene mutations and immune checkpoint status in relation to lung cancer subtypes and suggest that RT-qPCR is useful for assessing PD-L1 levels.

Lung cancer is generally treated with conventional therapies, including chemotherapy and radiation. These methods, however, are not specific to cancer cells and instead attack every cell present, including normal cells. Personalized therapies provide more efficient treatment options as they target the individual's genetic makeup. The goal of this study was to identify the frequency of causal genetic mutations across a variety of lung cancer subtypes in the earlier stages. 833 samples of non-small cell lung cancer from 799 patients who received resection of their lung cancer, were selected for molecular analysis of six known mutations, including EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK. A SNaPshot assay was used for point mutations and fragment analysis searched for insertions and deletions. ALK was evaluated by IHC +/- FISH. Statistical analysis was performed to determine correlations between molecular and clinical/pathological patient data. None of the tested variants were identified in most (66.15%) of cases. The observed frequencies among the total samples vs. only the adenocarcinoma cases were notable different, with the highest frequency being the KRAS mutation (24.49% vs. 35.55%), followed by EGFR (6.96% vs. 10.23%), PIK3CA (1.20% vs. 0.9%), BRAF (1.08% vs. 1.62%), ALK (0.12% vs. 0.18%), while the lowest was the HER2 mutation (0% for both). The statistical analysis yielded correlations between presence of a mutation with gender, cancer type, vascular invasion and smoking history. The outcome of this study will provide data that helps stratify patient prognosis and supports development of more precise treatments, resulting in improved outcomes for future lung cancer patients.

Background. Digital chest drainage devices objectively measure airflow to guide chest tube management. There are contradictory results regarding their utility in reducing length of stay and chest tube duration. The objective of this study was to compare digital and analog devices in patients undergoing anatomic lung resection. Methods. A single-institution randomized trial was conducted. Patients undergoing anatomic lung resection between November 2013 and July 2016 were randomized to digital or analog devices. Chest tubes were managed using a standardized protocol. Hospital length of stay and chest tube duration were primary outcomes. Chest tube clamping, number of chest roentgenograms, and chest tube reinsertion were secondary outcomes. Results. The study randomized 215 patients, with 107 in the digital group and 108 in the analog group. There was no significant difference in outcomes for length of stay (p = 1), chest tube duration (p = 0.71), number of chest roentgenograms performed (p = 0.78) or need for chest tube reinsertion (p = 0.21). The only significant finding was a higher number of patients who had their chest tubes clamped before removal, with 47% in the analog group and 19% in the digital group (p < 0.0001). Conclusions. Digital devices did not result in reduced chest tube duration or hospital length of stay. Approximately one half of the patients in the analog group had their chest tubes clamped before removal because of uncertainty in air leak assessment. Digital devices provided objective quantification of air leaks that decreased chest tube clamping. (C) 2018 by The Society of Thoracic Surgeons

Air leaks are the most common complication after pulmonary resection. Enhanced recovery after surgery (ERAS) programs must be designed to manage parenchymal air leaks. ERAS programs should consider two components when creating protocols for air leaks: assessment and management. Accurate assessment of air leaks using traditional analogues devices, newer digital drainage systems, portable devices and chest X-rays (CXR) are reviewed. Published data suggests that digital drainage systems result in a more confident assessment of air leaks. The literature regarding the management of postoperative air leaks, including the number of chest tubes, the role of applied external suction, invasive maneuvers and discharge with a portable device is reviewed. The key findings are that a single chest drain is adequate in the majority of cases to manage an air leak, the use of applied external suction is unlikely to prevent or prolong an air leak, autologous blood patch pleurodesis may potentially shorten postoperative air leaks and there is sufficient data to support that patients can safely be discharged with a portable drainage system. There is also literature to support the design of protocols for management of postoperative air leaks. Standardization of postoperative care through ERAS programs will allow for the design of larger RCTs to better understand some of the controversies around the management of postoperative air leaks.

Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options to chemotherapies that have very low response rate. New therapies that target driver gene mutations (e.g., EGFR, ALK, ROS1, BRAF) are being used to treat patients who have tumors with these mutations. In addition, a type of immunotherapy called immune checkpoint inhibitor is being used to treat lung cancer patients. For instance, patients with tumors that express PD-L1 are responsive to anti-PD-1/PD-L1 therapy. Thus, being able to identify the presence of driver mutations and PD-L1 will help patients to benefit from different therapies. A total of 844 cases of non-small cell lung cancer samples have been profiled for the presence of EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations by SNaPshot/sizing genotyping. Immunohistochemistry (IHC) was used to identify the protein expression of ALK and PD-L1. Histologic examination was performed to determine the pathologic type, grade, and lymphatic/vascular invasion. Statistical analysis revealed a number of correlations between the presence of the mutations, PD-L1 expression and the patient pathologic data. Specifically, it was determined that women had lung tumors with a significantly greater number of EGFR mutations than men (p value = 0.001). Examining the presence of ALK, EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations against the presence of pleural invasions yielded a p-value of 0.071, which implies evidence that different mutations are not associated with pleural invasion. However, EGFR mutations were associated with the absence of vascular and lymphatic invasions in lung cancer patients (p value = 0.001, 0.002 respectively). In addition, while the expression of PD-L1 does not associate with the patients who express KRAS mutation, it is associated with lung cancer patients who express EGFR mutation (p value = 0.002). Knowing the mutational and PD-L1 status in lung cancer patients will help patients benefit from targeted therapies and/or checkpoint inhibitors. Citation Format: Akram Alwithenani, Marika Forsythe, Mathieu Castonguay, Wenda Greer, Gorden Flowerdew, Drew Bethune, Harry Henteleff, Madelaine Plourde, Aneil Mujoomdar, Daniel French, Micheal Johnston, Paola Marcato, Zhaolin Xu. Investigating targeted driver mutations and PD-L1 expression for improved therapy of non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B21.

Achalasia is a chronic disease affecting the myenteric plexus of the esophagus and lower esophageal sphincter. Treatment is aimed at palliating symptoms to improve quality of life. Treatment options for symptom relapse after esophagomyotomy include botox injection, repeat myotomy, per-oral endoscopic myotomy, or pneumatic balloon dilation (PBD). Data demonstrating the safety and efficacy of PBD for recurrence are scarce. With a lack of published data, guidelines have suggested avoiding PBD for recurrent achalasia because of concern for a high risk of perforation.

# 01: Iron deficiency in bariatric surgery patients — a single-centre experience over 5 years {#article-title-2} As the prevalence and severity of obesity have increased in Canada, so too has the demand for bariatric surgery. The objective of this study was to determine the incidence of

Esophagectomy has been the standard of care for patients with intramucosal adenocarcinoma (IMC) in the setting of Barrett’s esophagus. It is, however, associated with significant post-operative morbidity and mortality. Endoscopic mucosal resection (EMR) offers a minimally invasive approach with lesser morbidity. This study investigates the transition from esophagectomy to EMR for IMC with respect to eradication rates, post-operative morbidity, and long-term survival.

BACKGROUND:Endoscopic mucosal resection (EMR) is increasingly being used as a first-line treatment for Barrett esophagus (BE) with high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC). We reviewed our experience with endoscopic treatment of BE with HGD and IMC at our institution with respect to eradication rates, complications and long-term recurrence.METHODS:We performed a single-centre retrospective review of all patients referred between October 2010 and August 2014 for EMR with dysplastic BE or IMC. We performed EMR using a cap-fitted endoscope, and the procedure was repeated every 3 months until eradication or progression of disease.RESULTS:A total of 28 patients were identified: 16 with dysplastic BE (14 HGD, 1 low-grade dysplasia, 1 intermediate dysplasia) and 12 with IMC. Complete eradication of HGD was achieved in 11 of 14 (79%) patients. Three of 12 (25%) patients initially referred with suspected IMC were found to have invasive adenocarcinoma on EMR. Eradication was successful in 8 of 9 (89%) patients with true IMC, with 1 patient progressing to salvage esophagectomy. Complications occurred in 2 of 28 (7%) patients; both had esophageal strictures managed with dilatation. Median duration of follow-up was 371 days.CONCLUSION:Our experience supports the safety of EMR as a first-line treatment for patients with BE with dysplasia and IMC in early short-term follow-up.

Objective To determine if a combination of CT and demographic features can predict EGFR mutation status in bronchogenic carcinoma. Methods We reviewed demographic and CT features for patients with molecular profiling for resected non-small cell lung carcinoma. Using multivariate logistic regression, we identified features predictive of EGFR mutation. Prognostic factors identified from the logistic regression model were then used to build a more practical scoring system. Results A scoring system awarding 5 points for no or minimal smoking history, 3 points for tumours with ground glass component, 3 points for airbronchograms, 2 points for absence of preoperative evidence of nodal enlargement or metastases and 1 point for doubling time of more than a year, resulted in an AUROC of 0.861. A total score of at least 8 yielded a specificity of 95 %. On multivariate analysis sex was not found to be predictor of EGFR status. Conclusions A weighted scoring system combining imaging and demographic data holds promise as a predictor of EGFR status. Further studies are necessary to determine reproducibility in other patient groups. A predictive score may help determine which patients would benefit from molecular profiling and may help inform treatment decisions when molecular profiling is not possible. Key points • EGFR mutation - targeted chemotherapy for bronchogenic carcinoma has a high success rate . • Mutation testing is not possible in all patients . • EGFR associations include subsolid density , slow tumour growth and minimal / no smoking history . • Demographic or imaging features alone are weak predictors of EGFR status . • A scoring system , using imaging and demographic features , is more predictive .

ALK gene rearrangements are identified in 2–5 % of all non-small cell lung cancer and are more common in lifetime non-smokers with adenocarcinoma, but the prevalence of ALK rearrangements is not as well characterized in long-term ex-smokers (quit >10 years prior to diagnosis). Accurate and timely diagnosis of ALK-rearranged tumors is of clinical importance given the remarkable response to targeted inhibitors. ALK gene rearrangement may be detected by fluorescence in situ hybridization (FISH), and abnormal expression of ALK protein may be detected by immunohistochemistry (IHC), the latter of which is faster and less expensive. The aim of this study is to evaluate the prevalence of ALK rearrangement in non-smokers and long-term ex-smokers with lung adenocarcinoma and to assess the performance of IHC for the detection of ALK+ tumors when compared to FISH. Two hundred fifty-one cases of resected lung adenocarcinoma were retrospectively reviewed, including non-smokers (n = 79) or long-term ex-smokers (n = 172). ALK IHC and ALK FISH were performed on each case. Four cases demonstrated ALK rearrangement by FISH (4/251; 1.6 %). All cases were non-smokers (4/79; 5.1 %), and all were positive for ALK by IHC. No additional cases were considered positive by IHC, and only 26 (10.4 %) cases were considered equivocal using a conservative approach to interpretation, resulting in a sensitivity of 100 % and specificity of 89.5 %. ALK rearrangement was not observed in lung adenocarcinoma arising in long-term ex-smokers, whereas it is seen in up to 5.1 % of lifetime non-smokers. ALK IHC using the 5A4 antibody demonstrates high sensitivity, supporting its use as a screening test.

Lung cancer is the leading cause of cancer-related death worldwide, and the majority of cases (77%) are not diagnosed until the disease has spread to regional lymph nodes or distant sites.Even among Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma patients who have been diagnosed early and where there has been no spread to lymph nodes, recurrence after surgical intervention is high.Improved understanding of the molecular alterations involved in aggressivity and recurrence of these tumors may provide better biomarkers for the identification of patients who would benefit from adjuvant chemotherapy.By comparing the expression of microRNAs in advanced Stage II/III tumors with those expressed in earlier Stage I tumors, we aimed to identify differentially expressed molecular biomarkers that could underly progression and recurrence of Stage I tumors.This pilot study utilized TaqMan qPCR assays to assess the expression of microRNAs in tumor tissue, matched normal tissue and plasma samples from Stage I and Stage II/III lung adenocarcinoma patients.Seven microRNAs were identified from plasma that could distinguish between patients with Stage I and Stage II/III adenocarcinoma.The up-regulation of miR-29a in plasma of patients with later-stage adenocarcinoma would result in enhanced expression of several molecules involved in integrin signaling, migration and proliferation.Analysis of differential expression of microRNAs in later-stage compared to early-stage lung adenocarcinoma implicates focal adhesion and ECM-receptor pathways in progression and recurrence.Plasma miR-29a is a promising biomarker that can be assessed non-invasively and whose clinical utility should be pursued.

Castleman's disease (CD) is a rare, non-clonal disease of the lymph nodes that may develop at a single site (unicentric form) or multiple sites (multicentric form) throughout the body. Histopathologically, CD is differentiated into a hyaline vascular variant, a plasma cell variant and a mixed cell type. Classically, unicentric CD is of the hyaline vascular variety while multicentric disease is of the plasma cell or mixed cellularity forms. We report an asymptomatic patient whose imaging revealed isolated left hilar lymphadenopathy. After thoracotomy, lymph node excision biopsy was performed, and histopathological examination revealed plasma cell histology. Unicentric plasma cell presentation is a rarely seen variant of CD.

Recurrence after lung cancer surgery is high, even among Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma patients diagnosed early as Stage I, where there has been no spread to lymph nodes.Understanding the biological underpinnings of aggressivity and recurrence in this subset of tumours may enable the identification of patients who would benefit from adjuvant therapy.The purpose of this study was to identify differentially expressed molecular biomarkers that might underlie recurrence of Stage I tumours by comparing gene expression in later-stage tumours with those expressed in early-stage tumours.Gene expression in tissue biopsy samples from five Stage I and five Stage II/III NSCLC adenocarcinoma patients was analysed using an oligonucleotide microarray containing 17,000 probes printed in duplicate.Analyses were performed on total RNA isolated from tumour tissue of each patient using universal human RNA as a reference.Compared to normal tissues, the transcriptome of Stage I NSCLC adenocarcinomas showed enrichment in general pathways in cancer, whereas in Stage II/III more specific cancer pathways such as focal adhesion and ECM-receptor interaction pathways were enriched and components of the PPAR signalling pathway were depleted.Relative to early-stage NSCLC, Stage II/III adenocarcinomas showed up-regulation of genes of the basic transcriptional and translational machinery, particularly the "cancer testis antigen" PASD1 transcription factor.The actin cytoskeleton re-organisation and interleukin-6 pathways were also up-regulated whereas there was a generalized down-regulation of immune effectors and genes involved in immune system development.This small-scale transcriptome study provides important information about the pathways and molecules likely to be involved in the more metastatic propensity of those Stage I NSCLC adenocarcinomas that recur.

# 1 Is laparoscopic sleeve gastrectomy a reasonable stand-alone procedure for super morbidly obese patients? {#article-title-2} Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a well established standard of care in the treatment of obesity and its associated comorbidities. Laparoscopic sleeve

We report a case of post-pneumonectomy right to left shunting via patent foramen ovale (PFO) and bronchopleural fistula (BPF). Although the latter complication is well-known following pneumonectomy, the former is quite rare. In terms of post-pneumonectomy complications, no case has been reported, in which right to left shunting via PFO and BPF were synchronous. Low awareness of post-pneumonectomy PFO often results in delay of the appropriate management, like in our experience. The rarity and the complexity of our case as well as literature review of the post-pneumonectomy right to left shunting via PFO are summarized.With our case of post-pneumonectomy right to left shunting via PFO and BPF reviewed, we would like to show the rarity of our case and to enlighten all of the thoracic surgeons for early detection of this hemodynamic complication following pneumonectomy.

Objective: To compare endoscopic stapling versus external transcervical approaches in the treatment of Zenker diverticulum.Design: A 10-year retrospective institutional review was performed to identify all patients treated for Zenker diverticulum.Setting: Academic tertiary care centre.Methods: Patients treated surgically for Zenker diverticulum were identified through an electronic records search. Patient charts were reviewed, and patients were interviewed at follow-up.Main Outcome Measures: Patient age, sex, duration of symptoms, procedural time, time to oral liquids, length of posttreatment hospital stay, and post procedure patient satisfaction were recorded and compared.Results: Ten patients treated endoscopically were compared with eight patients treated via an external approach. There were no significant differences in patient age, sex, and duration of symptoms. The external technique took significantly longer (110.88 +/- 59.61 minutes) than the staple technique (19.50 +/- 6.47 minutes) (p < .0001). There was no significant difference in time to full oral liquids (p = .11). The postsurgical hospital stay (4.71 +/- 1.98 days) was significantly longer for the external technique compared with the staple technique (2.30 +/- 2.83) (p = .03). Patient symptom relief was reported as completely resolved or improved in all cases, regardless of treatment type.Conclusions: Endoscopic stapling of Zenker diverticulum achieves operative success and patient satisfaction comparable to those of traditional external transcervical techniques, with significantly decreased operative times and hospital stays, allowing for more efficient use of resources.

Epidermal growth factor receptor is a trans-membrane glycoprotein with an extracellular epidermal growth factor binding domain and an intracellular tyrosine kinase domain that regulates signaling pathways to control cellular proliferation. Epidermal growth factor receptor binding to its ligand results in autophosphorylation by intrinsic tyrosine/kinase activity, triggering several signal transduction cascades. Constitutive or sustained activation of these sequences of downstream targets is thought to yield more aggressive tumor phenotypes. Mutations in epidermal growth factor receptor have been discovered in association with some lung cancers. Lung adenocarcinomas with mutated epidermal growth factor receptor have significant responses to tyrosine kinase inhibitors, although for unselected patients it does not appear to have a survival benefit. However, in a subset of patients (non-smoking Asian women with adenocarcinoma, particularly with a bronchioloalveolar carcinoma), there appears to be a significant survival advantage. Both EGFR mutation and gene amplification status may be important in determining which tumors will respond to tyrosine kinase inhibitors.

The need to change Japan's current health care system has recently motivated discussions about the introduction of nurse practitioners (NPs). This system might not be familiar to Japanese physicians; however, their roles have been valued greatly in Canada, which introduced programs for NPs in 1960s. We would like to introduce amazing roles that are performed by an NP in one Canadian thoracic surgery ward, and to refer to the feasibility of NPs providing clinical services for thoracic surgery in Japan.