ABSTRACT
Postoperative epidural fibrosis (EF) is still a major limitation to the success of spine surgery. Fibrotic adhesions in the epidural space, initiated via local trauma and inflammation, can induce difficult-to-treat pain and constitute the main cause of failed back surgery syndrome, which not uncommonly requires operative revision. Manifold agents and methods have been tested for EF relief in order to mitigate this longstanding health burden and its socioeconomic consequences. Although several promising strategies could be identified, few have thus far overcome the high translational hurdle, and there has been little change in standard clinical practice. Nonetheless, notable research progress in the field has put new exciting avenues on the horizon. In this review, we outline the etiology and pathogenesis of EF, portray its clinical and surgical presentation, and critically appraise current efforts and novel approaches toward enhanced prevention and treatment.
ABSTRACT
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study. Tissue samples of resected pulmonary metastases and available corresponding primary tumors were collected and assessed for PD-1, PD-L1 and PD-L2 expression by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression patterns were correlated with clinical outcome parameters. PD-1 and PD-L1 expression was commonly found in TILs and tumor cells. Expression levels significantly differed between metastases and primary tumors. High PD-1 expression by TILs was associated with impaired overall survival (low vs high expression (mean, 95% CI): 78 mo (60-96) vs 35 mo (25-44); p = 0.011). Additionally, the subgroup of patients, who experienced an upgrading in their TILs/PD1 status between primary and metastasis had a worse survival outcome compared with patients with the same grade or a downgrading (34 mo (26-42) vs 96 mo (72-120); p = 0.004). Thus, PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Future, large-scale studies are warranted to validate the findings of this single-center, retrospective analysis.
ABSTRACT
BACKGROUND: Pulmonary metastasectomy (PM) is a standard procedure in the treatment of stage IV colorectal cancer (CRC). In most centers the indication for PM is solely based on clinical factors without taking the tumor biology into account. This results in diverse outcomes ranging from long-term remission to early recurrence. Inflammation is considered a hallmark of cancer development and progression. On the other hand the accessibility of CRC cells to the immune system reflects the grade of tumor aggressiveness. We sought to investigate the impact of cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2) expression in pulmonary metastases on different outcome parameters following PM. METHODS: From 04/2009 to 11/2013 53 patients with complete PM for CRC were included in this single-center study. Tissue samples of resected pulmonary metastases and available corresponding primaries were collected and assessed by immunohistochemistry for COX-2 and PGE2 expression of the tumor tissue and the peritumoral stroma. Results were correlated with clinical outcome parameters. RESULTS: COX-2 and PGE2 were detected in nearly every pulmonary CRC metastasis. Staining intensities of pulmonary metastases correlated only weakly with intensities found in primary tumors. When dividing metastases in high expressing and low expressing tumors, a trend towards longer recurrence free survival and improved survival was found in tumors with strong COX-2 and PGE2 staining. CONCLUSIONS: In conclusion, this pilot study shows that COX-2 and PGE2 are uniformly overexpressed in pulmonary metastases from CRC. High expression of COX-2 and PGE2 seems to reflect a beneficial tumor biology with late tumor recurrence and prolonged overall survival after PM.
