Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR.

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.

Molecular profiling of non-small cell lung cancer.

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.

Optimal management of postoperative parenchymal air leaks.

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.

Digital Air Leak Monitoring for Lung Resection Patients: A Randomized Controlled Clinical Trial.

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.

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma: a Canadian experience.

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.

CONTEXTE: La mucosectomie endoscopique est de plus en plus utilisée en première intention pour l'oesophage de Barrett avec dysplasie de haut grade (DHG) et pour l'adénocarcinome intramuqueux. Nous avons passé en revue notre expérience du traitement endoscopique de l'oesophage de Barrett avec DHG et de l'adénocarcinome intramuqueux dans notre établissement aux plans des taux d'éradication, des complications et des récurrences à long terme. MÉTHODES: Nous avons procédé à une revue rétrospective de tous les cas d'oesophage de Barrett dysplasique ou d'adénocarcinome intramuqueux d'un seul centre adressés pour mucosectomie endoscopique entre octobre 2010 et août 2014. Nous avons effectué les mucosectomies endoscopiques à l'aide d'un endoscope muni d'un capuchon, et les interventions étaient répétées tous les 3 mois jusqu'àéradication ou progression de la maladie. RÉSULTATS: En tout, 28 patients ont été recensés : 16 présentaient un oesophage de Barrett dysplasique (14 DHG, 1 dysplasie de bas grade, 1 dysplasie intermédiaire) et 12 présentaient un adénocarcinome intramuqueux. Une éradication complète de la DHG a été obtenue chez 11 patients sur 14 (79 %). Chez 3 patients sur 12 (25 %) initialement adressés pour un adénocarcinome intramuqueux, la mucosectomie a révélé un adénocarcinome envahissant. Huit patients sur 9 (89 %) atteints d'un adénocarcinome intramuqueux avéré ont subi le traitement d'éradication avec succès, et 1 patient a dû subir une oesophagectomie de sauvetage. Des complications sont survenues chez 2 patients sur 28 (7 %); les 2 patients ont présenté des sténoses oesophagiennes corrigées par dilatation. La durée médiane du suivi a été de 371 jours. CONCLUSION: Notre expérience confirme l'innocuité de la mucosectomie endoscopique comme traitement de première intention chez les patients présentant un oesophage de Barrett dysplasique ou un adénocarcinome intramuqueux dans le contexte d'un suivi à court terme.

Endoscopic mucosal resection versus esophagectomy for intramucosal adenocarcinoma in the setting of barrett's esophagus.

BACKGROUND: 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. METHODS: Patients diagnosed with IMC from 2005 to 2013 were identified retrospectively. Beginning in 2009, preferred initial therapy for IMC transitioned from esophagectomy to EMR. Esophagectomy was performed either through a transthoracic or transhiatal technique. EMR was repeated until resolution of IMC on pathology or progression of disease. Continuous data are expressed as mean (SD) and analyzed using Student's t test. Categorical data are presented as number (%) and analyzed using Fisher's exact test. RESULTS: We identified 23 patients; 12 patients underwent esophagectomy and 11 patients underwent EMR as initial therapy. Patients were similar with respects to age, gender, and comorbidity index. Most tumors arose from short segment (vs long segment) Barrett's (esophagectomy: 9 (75%) vs. EMR: 10 (91%), p = 0.59) and one patient in each group had superficial invasion into the submucosa (T1sm1), the remainder having mucosal disease. Esophagectomy was associated with 7 (58%) minor complications and 2 (17%) major complications (respiratory failure, anastomotic leak), whereas there were no complications related to EMR (p < 0.01). EMR successfully eradicated IMC in 10 patients (91%) with one progressing to esophagectomy. Patients required 2 (1) endoscopies to achieve eradication. There was one mortality in each group on long-term follow-up (log-rank test, p = 0.62). CONCLUSIONS: EMR was successful in eradicating IMC in 10/11 patients with similar long-term recurrence and mortality to esophagectomy patients. Patients with IMC may benefit from EMR as initial therapy by obviating the need for a complex and morbid operation.

Considering the feasibility of introducing nurse practitioners into Japanese thoracic services.

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.

Colopleural fistula with atypical presentation as a complication of diaphragmatic hernia repair.

We report a 40-year-old woman with a surgical history of right hepatectomy. She underwent diaphragmatic hernia repair, and a colopleural fistula developed as a complication. The fistula was treated conservatively with drainage and antibiotic treatment. There are two points in our case to note: the first is that the patient showed no physical symptoms, and the second is that conservative treatment was successful. Colopleural fistula with specific points in our patient is reviewed.

Pulmonary hyalinizing granuloma.

OBJECTIVE: To present clinical and pathologic features of pulmonary hyalnizing granuloma through analyzing three cases found in our institution and reviewing cases reported in the English language literature. METHODS AND RESULTS: Three cases of pulmonary hyalnizing granuloma identified at our institution during the past ten years were reviewed. In the first case, the patient presented with concurrent pulmonary hyalinizing granuloma and histoplasmosis. In the second case, the patient presented with a 5.5 cm lung mass and a separate smaller lesion radiologically resembling bronchogenic carcinoma. There was very prominent polyclonal lymphocytic proliferation at the periphery especially of the smaller lesion likely representing an early stage of the disease process. In the third case, the patient presented with multiple subpleural plaque-like lesions in addition to nodular lesions of the lung. All cases also demonstrated various degrees of lymphocytic infiltration within the lesions. The English literature has been reviewed through searching the PubMed. CONCLUSION: Since patients with pulmonary hyalinizing granuloma demonstrated a spectrum of clinical presentations, radiologic changes and histologic features with a variety of associated clinical disorders, pulmonary hyalnizing granuloma is more in keeping with a clinicopathologic entity rather than a specific pathologic disease.

Ten-year follow-up of a province-wide cohort of surgical lung cancer patients in Nova Scotia.

BACKGROUND: After a diagnosis of lung carcinoma, survival is poor for all patients. We sought to assess 10-year survival and predictors of outcome after surgery for lung cancer in Nova Scotia. METHODS: We identified all patients n = 130) undergoing resection for lung cancer in Nova Scotia in 1994 from the Nova Scotia Cancer Registry and hospital charts and followed them prospectively for 10 years. We used Cox proportional hazards modelling to identify predictors of survival. RESULTS: The patients' mean age at operation was 67.7 (standard deviation [SD] 8.2) years, and 70% of the patients were men. Most of the operations n = 80, 61.5%) were performed in Halifax, and adenocarcinoma n = 55, 42.3%) was the most common histologic type. At the time of surgery, 66.9% of the cases were stage 1, 20.0% were stage 2 and 13.1% were stage 3. Survival at 5 and 10 years was 34% and 13%, respectively. Age of 70 years or older (hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.20-2.68), large cell carcinoma (HR 2.27, 95% CI 1.31-3.94) and stage 3 cancer (HR 2.21, 95% CI 1.25-3.90) were significant independent predictors of survival. Hospital site was not associated with any difference in survival (p = 0.66), although there was a trend toward differential rates of lymph node sampling across sites (p = 0.06). The presence of node sampling was associated with improved survival in a separate multivariate model (HR 0.51, 95% CI 0.29-0.89). CONCLUSION: Actuarial survival after resection of lung carcinoma in Nova Scotia in 1994 was 34% at 5 years and 13% after 10 years. Age, stage and histology are independent predictors of survival; lymph node sampling was associated with greater survival.

Evidence-based review of the surgical management of hyperhidrosis.

The great majority of the currently available evidence supporting sympathectomy for primary hyperhidrosis is observational, coming from a variety of prospective and restrospective clinical series as well as comparative studies. A cumulative experience in over 6000 patients suggests that ETS is a safe, reproducible, and effective procedure, and most patients are satisfied with the results of the surgery. The currently available experimental data comes from clinical trials that compared alternative levels of sympathetic chain disruption; these trials speak only to the relative merits of one surgical technique over another and do not provide an assessment of the overall impact of surgery in the general population of patients with primary hyperhidrosis. Furthermore, it is difficult to compare series and generalizability is compromised by a lack of uniform definitions and measures at both the exposure and outcome levels. There is marked heterogeneity with respect to study population and entry criteria, with significant variability of site and severity of excess sweating as well as the degree of preoperative conservative management of hyperhidrosis before surgical referral. Also the operative approach varies widely among studies, and the optimal procedure remains elusive: unilateral versus staged nonsimultaneous bilateral versus concomitant bilateral sympathectomy; ganglionic resection versus ablation using electrocoagulation or harmonic scalpel; clipping of the chain to maintain reversibility in the event of intolerable symptoms versus permanent disruption. In addition, the lack of uniform outcome measures makes these data difficult to interpret, and standardized metrics of surgical results are necessary, such as objective quantification of sweating by gravimetry or use of the SF-36 Health Survey Questionnaire as an estimate of patient quality of life. A multicenter, adequately powered, randomized controlled trial comparing surgical to medical management of hyperhidrosis is unlikely given the current enthusiasm for same-day thoracoscopic sympathectomy among surgeons, a largely positive literature replete with encouraging results, and well-informed hyperhidrosis patients who want to be cured of a socially debilitating illness. Future clinical trials in this area will likely compare surgical techniques. For such comparisons, procedures must be standardized and outcome measures validated for both symptoms of the disease and surgical complications. Finally, the studies must have large numbers of patients and adequate long-term follow-up if they are to detect differences in results among procedures with very high technical success rates.

Penetrating chest trauma secondary to a composite hockey stick injury.

Hockey is enjoyed by millions of people around the world and is a sport in which aggression is encouraged and injuries are common. Although body-checking is the most common cause of injury in hockey today, hockey sticks are associated with up to 14% of injuries. We report a case of chest trauma requiring surgical intervention secondary to the penetration of a composite hockey stick into a player's thoracic cavity.

Teaching practicing surgeons critical appraisal skills with an Internet-based journal club: A randomized, controlled trial.

BACKGROUND: The effectiveness of interventions for developing critical appraisal skills in practicing physicians has not been studied, despite the documented importance of reading the literature in caring for patients and in continuing professional development. The objective of this study was to evaluate whether an Internet-based intervention would lead to enhanced critical appraisal skills in practicing surgeons. METHODS: General surgeons who agreed to participate were randomized into 2 groups. The intervention was a curriculum in critical appraisal skills that included a clinical and methodologic article, a listserve discussion, and clinical and methodologic critiques. The control group received only the clinical articles. The primary outcome measure was a previously validated 2-hour test of critical appraisal. RESULTS: Of the 55 surgeons who completed the examination, subjects in the intervention group performed better on the test of critical appraisal skills than those in the control group (mean score: intervention group, 58% +/- 8 vs control group, 50% +/- 8), with a large effect size of 1.06 standard deviation units (t+3.92, P <.0001). Training conditions accounted for 22% of the variance in total scores. CONCLUSIONS: A multifaceted, Internet-based intervention resulted in improved critical appraisal skills of practicing general surgeons.