Drew Bethune

Fistulae of the internal thoracic vessels: report of two cases

Arteriovenous fistulae involving the internal thoracic vessels are extremely rare. The multiple causes, variable clinical presentation, and inconsistent delay of onset of clinical symptoms in addition to their rarity make their diagnosis difficult. However, the complications of untreated internal thoracic fistulae are potentially fatal, emphasizing the need to make a prompt and correct diagnosis. Once the diagnosis is made and the investigational workup complete, treatment consists of either surgical ligation and excision or percutaneous transcatheter embolization. We report two cases of patients with internal thoracic fistulae: one arising as a complication of a tube thoracostomy and the other following an anterior thoracotomy. The second case report describes a rupture of the internal thoracic fistulae, a complication not reported earlier.

Predicting EGFR mutation status in lung cancer:Proposal for a scoring model using imaging and demographic characteristics

ObjectiveTo determine if a combination of CT and demographic features can predict EGFR mutation status in bronchogenic carcinoma.MethodsWe 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.ResultsA 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.ConclusionsA 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.

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

BackgroundEsophagectomy 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.MethodsPatients 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.ResultsWe 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).ConclusionsEMR 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.

Reduction of traumatic macroglossia with base of tongue corticosteroid injection

A20-year-old male underwent elective urinary diversion by ileal conduit. Relevant medical history included developmental delay and Chiari II malformation, with associated hydrocephalus and lumbar myelomeningocele. His postoperative recovery was complicated by premature extubation that required reintubation. He was transferred to the Intensive Care Unit, where his condition worsened with the development of pneumothorax, sepsis, and severe macroglossia. Macroglossia was believed to be secondary to tongue-biting and traumatic reintubation. There was no history of macroglossia. The Otolaryngology–Head and Neck Surgery service was consulted to assess the patient’s macroglossia. At this time, the patient was sedated with an endotracheal tube in place. On examination, there was severe diffuse lingual swelling with 6 cm of the tongue protruding from the oral cavity. Concerns were raised with respect to the ability to secure the airway in the event of inadvertent extubation. Options for the control of macroglossia and airway protection were therefore discussed. Standard cervical tracheotomy for definitive airway management was precluded by anatomic variations that included marked flexion of the neck with a deep cleft between the mandible and the sternum. No significant extension of the neck was possible and the thyroid notch was palpated postero-inferior to the sternal notch. After consultation, the thoracic surgeons concluded that tracheotomy would require median sternotomy, which was deemed inappropriate at this time. Consequently, treatment of macroglossia itself was considered. The patient was administered 20 mg intravenous (IV) dexamethasone daily and bite blocks were used to decrease further tongue trauma. However, this management did not improve the macroglossia and was consequently discontinued after 48 hours (Fig 1). Alternate treatment was again considered as the potential for airway embarrassment continued. With this in mind, 200 mg of intramuscular (IM) triamcinolone acetonide (40 mg/cc)

Abstract B21: Investigating targeted driver mutations and PD-L1 expression for improved therapy of non-small cell lung cancer

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.

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.