Dalilah Fortin

Current Concepts in the Management of Esophageal Perforations: A Twenty-Seven Year Canadian Experience

BACKGROUND Perforation of the esophagus remains a challenging clinical problem. METHODS A retrospective review was performed of patients diagnosed with an esophageal perforation admitted to the London Health Sciences Centre from 1981 to 2007. Univariate and multivariate logistic regression was used to determine which factors had a statistically significant effect on mortality. RESULTS There were 119 patients; 15 with cervical, 95 with thoracic, and 9 with abdominal perforations. Fifty-one percent of all the perforations were iatrogenic and 33% were spontaneous. Multivariate logistic regression analysis revealed that patients with preoperative respiratory failure requiring mechanical ventilation had a mortality odds ratio of 32.4 (95% confidence interval [CI] 3.1 to 272.0), followed by malignant perforations with 20.2 (95% CI 5.4 to 115.6), a Charlson comorbidity index of 7.1 or greater with 19.6 (95% CI 4.8 to 84.9), the presence of a pulmonary comorbidity with 13.9 (95% CI 2.9 to 97.4), and sepsis with 3.1 (95% CI 1.0 to 10.1). A wait time of greater than 24 hours was not associated with an increased risk of mortality (p=0.52). CONCLUSIONS Malignant perforations, sepsis, mechanical ventilation at presentation, a higher overall burden of comorbidity, and a pulmonary comorbidity have a significant impact on the overall survival. Time to treatment is not as important. Restoration of intestinal continuity, either by primary repair or by excision and reanastomosis can be attempted even in patients with a greater time from perforation to treatment with respectable morbidity and mortality rates.

Human Alveolar Epithelial Cells Attenuate Pulmonary Microvascular Endothelial Cell Permeability under Septic Conditions

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are characterised by high-protein pulmonary edema and severe hypoxaemic respiratory failure due to increased permeability of pulmonary microvascular endothelial cells (PMVEC). Alveolar epithelial cells (AEC) contribute importantly to normal alveolar function, and AEC dysfunction in ALI/ARDS is associated with worse outcomes. We hypothesized that AEC can modulate human PMVEC barrier function, and investigated the effects of AEC presence on human PMVEC barrier under septic conditions in vitro. PMVEC isolated from human lung were treated in vitro with septic stimulation (lipopolysaccharide [LPS], a mixture of clinically-relevant cytokines [cytomix], or plasma from patients with severe sepsis), and the trans-PMVEC leak of Evans Blue dye-labeled albumin assessed. PMVEC septic responses were compared in the presence/absence of co-cultured A549 epithelial cell line or primary human AEC. Septic stimulation with LPS, cytomix, or septic plasma induced marked PMVEC hyper-permeability (10.2±1.8, 8.9±2.2, and 3.7±0.2 fold-increase vs. control, respectively, p<0.01 for all). The presence of A549 cells or primary human AEC in a non-contact co-culture model attenuated septic PMVEC hyper-permeability by 39±4% to 100±3%, depending on the septic stimulation (p<0.05). Septic PMVEC hyper-permeability was also attenuated following treatment with culture medium conditioned by previous incubation with either naïve or cytomix-treated A549 cells (p<0.05), and this protective effect of A549 cell-conditioned medium was both heat-stable and transferable following lipid extraction. Cytomix-stimulated PMN-dependent PMVEC hyper-permeability and trans-PMVEC PMN migration were also inhibited in the presence of A549 cells or A549 cell-conditioned medium (p<0.05). Human AEC appear to protect human PMVEC barrier function under septic conditions in vitro, through release of a soluble mediator(s), which are at least partly lipid in nature. This study suggests a scientific and potential clinical therapeutic importance of epithelial-endothelial cross talk in maintaining alveolar integrity in ALI/ARDS.

Management of Tumors Involving the Chest Wall Including Pancoast Tumors and Tumors Invading the Spine

Bronchogenic carcinomas involving the chest wall include tumors invading the ribs and spine, as well as Pancoast tumors. In the past, such neoplasms were considered to be incurable, but with new multimodality regimens, including induction chemoradiation followed by surgery, they can now be completely resected and patients can benefit from prolonged survival. The most important prognostic factors are the completeness of resection and the pathologic nodal status.

Transarterial embolization of intralobar pulmonary sequestration in a young adult with hemoptysis

Intralobar pulmonary sequestration is a rare congenital malformation characterized by the presence of dysplastic lung that does not communicate with the tracheobronchial tree, and has aberrant systemic arterial supply. While most are asymptomatic, they rarely can present with hemoptysis, which has been traditionally managed with surgical resection of the sequestration. We report a case of an 18-year-old male who presented with acute large-volume hemoptysis on a background of recurrent minor episodes of hemoptysis, due to intralobar sequestration. He was successfully treated with transarterial embolization with a combination of polyvinyl alcohol (PVA) particles, gelfoam and coils. Transarterial embolization can be effective in managing emergent hemoptysis from pulmonary sequestration.

3D human lung histology reconstruction and registration to in vivo imaging.

Stereotactic ablative radiotherapy (SABR) delivers high-dose-per-fraction radiotherapy to tumours and spares surrounding tissue. It is effective for early-stage non-small cell lung cancer. However, SABR causes radiationinduced lung injuries that mimic recurring cancer, confounding detection of recurrences and early salvage therapy. We have previously developed radiomics-based recurrence detection. However, our radiomics system needs to be validated against histologic markers of viable tumour post-SABR. In this paper, our goals were to develop semiautomatic (1) 2D reconstruction of pseudo whole-mount (PWM) tissue sections from scanned slides, (2) 3D reconstruction and registration of PWM sections to pre-surgery computed tomography (CT), and (3) quantitative registration error measurement. Lobectomy tissue sections on standard 1” × 3” slides were obtained from patients who underwent SABR. Our graphical user interface allows interactive stitching of the sections into PWMs. Using our developed 3D Slicer-based thin-plate spline warping tool, we performed 3D PWM reconstruction and registered them to CT via correspondence of homologous intrinsic landmarks. The target registration error for 229 fiducial pairs defining vessels and airways was calculated for 56 PWMs reconstructed from 9 patients. We measured a mean of 7.33 mm, standard deviation of 4.59 mm and root mean square of 8.65 mm. This proof-of-principle study demonstrates for the first time that it is feasible to register in vivo human lung CT images with histology, with no modifications to the clinical pathology workflow other than videography to document gross dissection. Ongoing work to automate this process will yield a tool for histologic lung imaging and radiomics validation.

RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy: RBCs & postpneumonectomy respiratory failure

Pneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy.