Publications

OBJECTIVES

The management of complex colorectal polyps varies in practice. Accurate descriptions of the endoscopic appearance by using a standardized classification system (Paris classification) and size for complex colon polyps may guide subsequent providers regarding curative endoscopic resection vs. need for surgery. The accuracy of this assessment is not well defined. Furthermore, the factors associated with decisions for endoscopic vs. surgical management are unclear. To characterize the accuracy of physician assessment of polyp morphology, size, and suspicion for malignancy among physician subspecialists performing colonoscopy and colon surgery. In addition, we aimed to assess the influence of these polyp characteristics as well as physician type and patient demographics on recommendations for endoscopic vs. surgical resection of complex colorectal polyps.

METHODS

An online video-based survey was sent to gastroenterologists (GIs) and gastrointestinal surgeons affiliated with six tertiary academic centers. The survey consisted of high-definition video clips (30-60 s) of six complex colorectal polyps (one malignant) and clinical histories. Respondents were blinded to histology. Respondents were queried regarding polyp characteristics, suspicion for malignancy, and recommendations for resection.

RESULTS

The survey response rate was 154/317 (49%). Seventy-eight percent of respondents were attending physicians (91 GIs and 29 surgeons) and 22% were GI trainees. Sixteen percent of respondents self-identified as specialists in complex polypectomy. Accurate estimation of polyp size was poor (28.4%) with moderate interobserver agreement (k=0.52). Accuracy for Paris classification was 47.5%, also with moderate interobserver agreement (k=0.48). Specialists in complex polypectomy were most accurate, whereas surgeons were the least accurate in assigning Paris classification (66.0 vs. 28.7%, P<0.0001). Specialists in complex polypectomy were most likely to correctly identify the malignant lesion compared with other physicians (87.5 vs. 56.2%, P=0.008). Surgical removal of colon adenomas was recommended least frequently by specialists in complex polypectomy (3.1%) compared with nonspecialists in complex polypectomy (13.3%); surgeons were most likely to recommend surgical resection (17.2%, P=0.009). There were no differences in recommendations for endoscopic vs. surgical resection observed on the basis of years in practice, polyp morphology (polypoid vs. nonpolypoid), polyp location (right vs. left colon), or patient ASA class.

CONCLUSIONS

In this large survey of GIs and surgeons, physician specialty was strongly associated with accurate polyp characterization and a recommendation for endoscopic resection of complex polyps. Surgeons were most likely to recommend surgical resection of complex nonmalignant colorectal polyps compared with specialists in complex polypectomy who were the least likely. Therefore, collaboration with specialists in complex polypectomy may be helpful in determining the appropriate management of complex colon polyps. Further teaching is needed among all specialists to improve accurate communication and ensure optimal management of these lesions.

Tumor cells secrete factors that modulate macrophage activation and polarization into M2 type tumor-associated macrophages, which promote tumor growth, progression, and metastasis. The mechanisms that mediate this polarization are not clear. Macrophages are phagocytic cells that participate in the clearance of apoptotic cells, a process known as efferocytosis. Milk fat globule- EGF factor 8 (MFG-E8) is a bridge protein that facilitates efferocytosis and is associated with suppression of proinflammatory responses. This study investigated the hypothesis that MFG-E8-mediated efferocytosis promotes M2 polarization. Tissue and serum exosomes from prostate cancer patients presented higher levels of MFG-E8 compared with controls, a novel finding in human prostate cancer. Coculture of macrophages with apoptotic cancer cells increased efferocytosis, elevated MFG-E8 protein expression levels, and induced macrophage polarization into an alternatively activated M2 phenotype. Administration of antibody against MFG-E8 significantly attenuated the increase in M2 polarization. Inhibition of STAT3 phosphorylation using the inhibitor Stattic decreased efferocytosis and M2 macrophage polarization in vitro, with a correlating increase in SOCS3 protein expression. Moreover, MFG-E8 knockdown tumor cells cultured with wild-type or MFG-E8-deficient macrophages resulted in increased SOCS3 expression with decreased STAT3 activation. This suggests that SOCS3 and phospho-STAT3 act in an inversely dependent manner when stimulated by MFG-E8 and efferocytosis. These results uncover a unique role of efferocytosis via MFG-E8 as a mechanism for macrophage polarization into tumor-promoting M2 cells.

Canine intervertebral disk herniation (IVDH) is a common, naturally occurring form of spinal cord injury (SCI) that is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury mechanisms. Here, we characterized cerebrospinal fluid (CSF) cytokines, and chemokines in dogs with acute, surgically treated, thoracolumbar IVDH (n=39) and healthy control dogs (n=21) to investigate early inflammatory events after SCI. A bioplex system was used to measure interleukin (IL)-2, -6, -7, -8, -10, -15, and -18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), keratinocyte chemoattractant (KC)-like protein, IFN-γ-inducible protein-10, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha. Cytokine and chemokine concentrations in the CSF of healthy and SCI dogs were compared and, in SCI dogs, were correlated to the duration of SCI, behavioral measures of injury severity at the time of sampling, and neurological outcome 42 days post-SCI as determined by a validated ordinal score. IL-8 concentration was significantly higher in SCI cases than healthy controls (p=0.0013) and was negatively correlated with the duration of SCI (p=0.042). CSF MCP-1 and KC-like protein were positively correlated with CSF microprotein concentration in dogs with SCI (p<0.0001 and p=0.004). CSF MCP-1 concentration was negatively associated with 42-day postinjury outcome (p<0.0001). Taken together, these data indicate that cytokines and chemokines present after SCI in humans and rodent models are associated with SCI pathogenesis in canine IVDH.