RESUMO
BACKGROUND: Post-operative colorectal venous thromboembolism (VTE) rates range between 1 and 3%. Often, surgeons utilize risk assessment models, like the modified Caprini, to determine need for prophylaxis. However, studies reveal additional unaccounted risk factors like preoperative serum albumin level, perioperative blood transfusion, emergency surgery, and preoperative steroid use. METHODS: This was a multicenter, retrospective study conducted between January 2021-December 2021. The primary endpoint was to assess the VTE rate within 30 days post-operatively. RESULTS: Overall, incidence rate was 1.75%. Of these, 53% underwent urgent/emergent surgery and 60% had perioperative blood transfusions. Twelve patients had a known preoperative serum albumin level, with 66% being less than 3.5 âg/dL. Only 30% of patients had a high Caprini risk score. No patient had preoperative steroid use. CONCLUSION: The study suggests considering urgent/emergent surgeries, low preoperative albumin levels, and blood transfusions for enhanced VTE screening and prophylaxis in post-operative colorectal patients.
Assuntos
Complicações Pós-Operatórias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Incidência , Albumina Sérica/análise , Transfusão de Sangue/estatística & dados numéricosRESUMO
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.
Assuntos
Pólipos do Colo , Colectomia/efeitos adversos , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Colonoscopia , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
Assuntos
Subunidade alfa de Receptor de Interleucina-15/genética , Interleucina-15/genética , Neoplasias/terapia , Receptor de Morte Celular Programada 1/genética , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Imunoterapia/métodos , Interferon gama/genética , Interleucina-15/administração & dosagem , Subunidade alfa de Receptor de Interleucina-15/administração & dosagem , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Terapia Viral Oncolítica/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
Assuntos
Neoplasias , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos , Microambiente Tumoral/imunologia , Animais , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapiaRESUMO
Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3+ cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A+Foxp3+ and ex-Th17 Foxp3+ cells are converted from IL-17A+Foxp3neg cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A+, ex-Th17 and iTreg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing Treg cell subsets. Although all Foxp3-expressing subsets are immunosuppressive, glycolysis is a prominent metabolic pathway exerted only by IL-17A+Foxp3+ cells. Transcriptome analysis and flow cytometry of IL-17A+Foxp3+ cells indicate that Folr4, GARP, Itgb8, Pglyrp1, Il1rl1, Itgae, TIGIT and ICOS are Th17-to-Treg cell transdifferentiation-associated markers. Tumour-associated Th17-to-Treg cell conversion identified here provides insights for targeting the dynamism of Th17-Treg cells in cancer immunotherapy.