Outcomes and Prognostic Factors of Patients with Metastatic Colorectal Cancer Who Underwent Pulmonary Metastasectomy with Curative Intent: A Brazilian Experience.

BACKGROUND: We aimed to identify clinicopathological and molecular features associated with progression-free survival (PFS) and overall survival (OS) after pulmonary metastasectomy for metastatic colorectal cancer in a retrospective cohort in Brazil. MATERIALS AND METHODS: We did a retrospective review of thoracic surgeries performed in a single large academic hospital in Brazil from January 1985 to September 2019. Demographics, previously described prognostic factors, and clinicopathological and molecular characteristics were abstracted. Univariate Cox regression was performed for each variable, and, when significant, data were dichotomized to provide clinically meaningful thresholds. RESULTS: Records from 698 patients were reviewed. Fifty-eight patients underwent pulmonary metastasectomy with curative intent. Of those, 53.4% had a single metastatic lesion. The median size of the largest lesion was 1.5 cm. Results of RAS, RAF, and mismatch repair testing and of cytokeratin 20 (CK20) and CDX2 testing were available for 13.8% and 58.6% of the sample, respectively. Median PFS was 14 months, median OS was 58 months, and 5-year survival was 49.8%. Unfavorable prognostic factors for OS included disease-free interval (DFI) <24 months, synchronous presentation, size of the largest lesion ≥2 cm, and loss of CK20 expression. Presenting with more than one lesion was prognostic for PFS but not for OS. CONCLUSION: In this Brazilian cohort, our findings corroborate existing data supporting DFI, synchronous presentation, and number and size of lesions as prognostic factors. Furthermore, we found that loss of CK20 expression may be associated with more aggressive disease and shorter OS. Additional molecular prognostic factors after pulmonary metastasectomy for colorectal cancer should be further explored. IMPLICATIONS FOR PRACTICE: This study consolidates disease-free interval, synchronous presentation, and number and size of lesions as clinically relevant data that may help guide therapy for patients with colorectal cancer and lung metastases who are candidates for curative-intent metastasectomy. Additionally, in this sample, lack of cytokeratin 20 expression in metastases was associated with shorter progression-free survival and overall survival, suggesting that biomarkers also may have a role in guiding therapy in this setting and that additional biomarkers should be further explored.

Risk factors for post-transplant lymphoproliferative disease in patients with cystic fibrosis.

The objective of this study was to retrospectively analyze risk factors associated with post-transplant lymphoproliferative disease (PTLD) in a cohort of 112 lung transplant recipients with cystic fibrosis (CF). Prior to transplantation, patients were tested for Epstein-Barr virus (EBV), human herpesvirus (HHV types 1, 2, 3, 6, and 8), herpes zoster virus, and cytomegalovirus (CMV) serologies. PTLD diagnosis was established based on increased EBV viral charge plus clinical/radiographic findings and confirmed by biopsy. Negative EBV and HHV serologies at the time of lung transplantation (LTx) were significant risk factors associated with development of PTLD in patients with CF in the univariate logistic regression analysis (p < 0.05) and also in the multivariate analysis (odds ratio of 77.5 and 12.5, respectively). CMV serology, CMV mismatch, acute rejection in the first three months following LTx, HLA-A3 antigen expression, and female gender did not affect PTLD. Our study confirmed the presence of a strong association between negative EBV serology at the time of LTx and PTLD and suggested an independent effect of negative HHV serology on PTLD.

Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation.

OBJECTIVE: To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation. METHODS: To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens. RESULTS: Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi. CONCLUSIONS: Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.

Rejection and indirect revascularization of glycerin-preserved tracheal implant.

The objective of the following study was to evaluate antigenicity, malacia and revascularization in glycerin-preserved canine tracheal allografts. Trachea with six cartilage rings (2.4 to 3.1 cm) were distributed in three study groups: autograft (21), allograft (18) and glycerin-preserved (22). We implanted two segments from different groups in the greater omentum of dogs. After 28 days, latex was injected in the canine aorta before the segments were harvested. We evaluated number of sectors with functional vessels, number of vessels dyed in the submucosa, acute arteritis score, incidence of acute rejection, cartilage lesion score, and malacia. The autograft group had a larger number of dyed vessels than the glycerin-preserved group. The autograft group also had a higher average number of quadrants with functional vessels than the allograft group and the glycerin-preserved group. The allograft group had a higher mean score for acute arteritis than the autograft group and more acute rejection than the glycerin-preserved group. The cartilage lesion score did not show any significant difference between groups. Malacia was not observed in any tracheal segment. Overall, the glycerin-preserved tracheal implant had low antigenicity and good rigidity, but showed incomplete revascularization.

Novel silicone stent to treat tracheobronchial lesions: results of 35 patients.

We describe a case series of 35 patients with either benign (14) or malignant (21) tracheal stenosis who were treated using a novel silicone stent, the HCPA-1, designed to prevent migration. Between March 2001 and September 2008, 13 women and 22 men received 41 HCPA-1 stents. The median duration of stenting in benign cases was 457 days (range, 4-2,961 days). Successful stent removal with curative results was accomplished in 2 patients with tracheomalacia and 1 with post-intubation stenosis. In malignant cases, the median duration of stenting was 162 days (range, 1-1,279 days). Five patients had tumor progression with obstruction requiring repeated laser resection, dilatation, or additional stents. Two patients died due to airway obstruction despite bronchoscopic intervention. Twelve patients with malignant lesions died with the stent in place. At the end of the study, 3 patients with malignant disease remained alive; 2 were lost to follow-up. The HCPA-1 stent proved to be safe, with no severe complications during the study period, and effective in improving quality of life with relief of dyspnea.

Electrocautery versus 23% NaOH infiltration to induce subglottic stenosis in a canine experimental model.

Subglottic stenosis (SGS) is defined as the narrowing of the lower larynx. Difficulties in the management of subglottic stenosis, especially in the pediatric population, justify the development of experimental models. The objective of this study was to compare the two methods of experimental subglottic stenosis induction. Twenty-three dogs were randomly selected and assigned by lottery to either one of the two groups: Gp I (n = 10) of electrocoagulation; and Gp II (n = 13) of 23% NaOH injection. In Gp I, self-interruption electrocoagulation was applied to one point in each of the four quadrants of the cricoid cartilage. In Gp II, 0.2 ml of 23% NaOH was injected in the submucosal layer in the anterior and posterior portions of the cricoid cartilage. Once a week, endoscopy was performed and the caliber of the subglottic region was measured using endotracheal tubes, and the injection was repeated if there were no signs of subglottic stenosis. The animals were killed on day 21; animals that developed respiratory distress were killed before day 21. One animal in Gp I died on day 14 after the injection and during transportation; two animals in Gp II died, one on day 7 due to a tracheoesophageal fistula, and the other of unknown causes on day 5. Significant subglottic stenosis (over 51% obstruction) was found in 67% of the animals in Gp I and in 64% of those in Gp II (P = 0.99). Median time to development of significant stenosis was 21 days in both groups, and required either two or three injections. Mean time for the performance of the procedures was significantly shorter (P < 0.01) in Gp I (mean: 6.36 min) than in Gp II (mean: 14.88 min). Electrocoagulation and 23% NaOH injection in the subglottic region were effective in the development of significant subglottic stenosis in dogs, both methods leading to stenosis in the same period of time and after the same number of procedures. However, electrocoagulation was the fastest method.