ABSTRACT
BACKGROUND: Incidentally found polyps on surgical pathology after colectomy is an underreported phenomenon, and management guidelines are lacking. Elucidation of the significance of incidental polyps is needed to determine if post-operative endoscopic surveillance modification is warranted. We sought to determine the relationship between incidental polyp on colectomy specimen and findings on post-operative colonoscopy. MATERIALS AND METHODS: A multi-institutional retrospective review was performed on patients that underwent colorectal resection from 2018-2019. Surgical pathology was reviewed for polyps and assigned as expected or incidental based on pre-operative colonoscopy. If performed, post-operative colonoscopy was reviewed for new lesion identification. The odds of detecting new lesion on post-operative colonoscopy was compared between cases with incidental polyp on surgical specimen and patients without incidental findings. RESULTS: In 243 colorectal resections, incidental polyps were identified in 55 cases (22.6%). Post-operative colonoscopy was completed in 65 cases (26.7%) with new polyp detected in 24 cases (9.88%). Of those, 10 had an incidental polyp previously identified on surgical specimen while 14 did not. The presence of incidental surgical specimen polyp was associated with a greater than two-fold higher odds of detecting new polyp on post-operative colonoscopy (odds-ratio 2.76, 95% confidence interval 1.15-6.63;P = 0.023). CONCLUSION: This analysis revealed a high frequency of incidental polyps on surgical specimens with an increased rate of newly found lesions on post-operative colonoscopy. Incidental polyps may be a risk factor for other missed lesions still within the patient. Therefore, providers should consider surveillance interval modification on an individual basis in the setting of incidental surgical specimen polyps.
Subject(s)
Colonic Polyps , Colectomy/adverse effects , Colonic Polyps/diagnosis , Colonic Polyps/pathology , Colonic Polyps/surgery , Colonoscopy , Humans , Retrospective Studies , Risk FactorsABSTRACT
Oncolytic immunotherapy is a promising novel therapeutic for cancer, and further preclinical studies may maximize its therapeutic efficacy. In this study, we construct a novel oncolytic vaccinia virus (VV) expressing a superagoinst IL-15, a fusion protein of IL-15 and IL-15Ralpha. This virus, named vvDD-IL15-Rα, possesses similar replication efficiency as the parental virus vvDD yet leads to significantly more regression of the disease and extends the survival of mice bearing MC38 colon or ID8 ovarian cancer. This novel virus elicits potent adaptive antitumor immunity as shown by ELISPOT assays for interferon-gamma-secreting CD8+ T cells and by the rejection of tumor implants upon re-challenge in the mice, which were previously cured by vvDD-IL15-Rα treatment. In vivo cell depletion assays with antibodies showed that this antitumor activity is highly dependent on CD8+ T cells but much less so on CD4+ T cells and NK cells. Finally, the combination of the oncolytic immunotherapy with anti-PD-1 antibody dramatically improves the therapeutic outcome compared to either anti-PD-1 alone or vvDD-IL15-Rα alone. These results demonstrate that the IL-15-IL-15Rα fusion protein-expressing OV elicits potent antitumor immunity, and rational combination with PD-1 blockade leads to dramatic tumor regression and prolongs the survival of mice bearing colon or ovarian cancers.
Subject(s)
Interleukin-15 Receptor alpha Subunit/genetics , Interleukin-15/genetics , Neoplasms/therapy , Programmed Cell Death 1 Receptor/genetics , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Combined Modality Therapy , Female , Humans , Immunity, Innate/drug effects , Immunity, Innate/immunology , Immunotherapy/methods , Interferon-gamma/genetics , Interleukin-15/administration & dosage , Interleukin-15 Receptor alpha Subunit/administration & dosage , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Mice , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/pathology , Oncolytic Virotherapy/methods , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Xenograft Model Antitumor AssaysABSTRACT
Oncolytic viral therapy is a promising approach to treat many malignancies, including breast, colorectal, hepatocellular, and melanoma. The best results are seen when using "targeted and armed" viruses. These are viruses that have been genetically modified to selectively replicate within cancer cells and express specific transgenes that alter the tumor microenvironment to inhibit tumor progression. The products of these transgenes induce cell death, make the virus less virulent, compromise tumor vascularity, and are capable of modulating or enhancing the immune system-such as cytokines and chemokines. In addition, oncolytic viruses can induce anti-vascular effects and disrupt the extracellular matrix to improve viral spread within the tumor. Oncolytic viruses also improve crosstalk between fibroblasts, cytokine-induced killer cells, and cancer cells within the microenvironment, leading to enhanced tumor cell death.