Neutrophils promote tumor growth and metastasis at multiple stages of cancer progression. One mechanism through which this occurs is via release of neutrophil extracellular traps (NETs). We have ...previously shown that NETs trap tumor cells in both the liver and the lung, increasing their adhesion and metastasis following postoperative complications. Multiple studies have since shown that NETs play a role in tumor progression and metastasis. NETs are composed of nuclear DNA-derived web-like structures decorated with neutrophil-derived proteins. However, it is unknown which, if any, of these NET-affiliated proteins is responsible for inducing the metastatic phenotype. In this study, we identify the NET-associated carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) as an essential element for this interaction. Indeed, blocking CEACAM1 on NETs, or knocking it out in a murine model, leads to a significant decrease in colon carcinoma cell adhesion, migration and metastasis. Thus, this work identifies NET-associated CEACAM1 as a putative therapeutic target to prevent the metastatic progression of colon carcinoma.
Despite advances in cancer treatment, metastasis remains today the main cause of cancer death. Local control through complete surgical resection of the primary tumor continues to be a key principle ...in cancer treatment. However, surgical interventions themselves lead to adverse oncologic outcomes and are associated with significantly increased rates of metastasis. Neutrophils through release of neutrophil extracellular traps (NETs) in response to infections were shown to be able to capture circulating cancer cells, and in doing so, support the development of metastatic disease. To be able to intervene on this process, understanding the exact molecular nature of these mechanisms is crucial. We therefore hypothesize and demonstrate that beta1-integrin is an important factor mediating the interactions between circulating tumor cells and NETs. We show that beta1-integrin expression on both cancer cells and NETs is important for the adhesion of circulating tumor cells to NETs both in vitro and in vivo. Using a murine model of intra-abdominal sepsis to mimic the postoperative inflammatory environment, we show that beta1-integrin expression is upregulated in the context of inflammation in vivo. Ultimately, we show that this increased early cancer cell adhesion to NETs in vivo and this effect is abrogated when mice are administered DNAse 1. Our data therefore sheds light on the first molecular mechanism by which NETs can trap circulating tumor cells (CTCs), broadening our understanding of this process. What's new? Surgical removal of tumors can increase inflammation. When neutrophils respond to inflammatory signals, they sometimes form web-like projections called "neutrophil extracellular traps" (NETs). These NETs are able to enhance metastasis, because they bind circulating tumor cells (CTCs) and cause them to adhere to distant organs. In our study, the authors found that beta1-integrins play an essential role in the interaction between NETs and tumor cells. Then, they found that hepatic adhesion of CTCs in mice could be significantly reduced by blocking beta1-integrins. These results suggest that targeting beta1-integrins may help to reduce metastases.
Ambulatory bariatric surgery has recently gained interest especially as a potential way to improve access for eligible patients with severe obesity. Building on our previously published research, ...this follow-up study delves deeper in the evolving landscape of ambulatory bariatric surgery over a 3-year period, focusing on predictors of success/failure.BACKGROUNDAmbulatory bariatric surgery has recently gained interest especially as a potential way to improve access for eligible patients with severe obesity. Building on our previously published research, this follow-up study delves deeper in the evolving landscape of ambulatory bariatric surgery over a 3-year period, focusing on predictors of success/failure.In a prospective single-center follow-up study, we conducted a descriptive assessment of all eligible patients as per our established protocol, who underwent a planned same-day discharge (SDD) primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 03/01/2021 and 02/29/2024. Trends in SDD surgeries over time were assessed over six discrete 6 month intervals. Primary endpoint was defined as a successful discharge on the day of surgery without emergency department visit or readmission within 24 h. Secondary outcomes included 30-day postoperative morbidity.METHODSIn a prospective single-center follow-up study, we conducted a descriptive assessment of all eligible patients as per our established protocol, who underwent a planned same-day discharge (SDD) primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 03/01/2021 and 02/29/2024. Trends in SDD surgeries over time were assessed over six discrete 6 month intervals. Primary endpoint was defined as a successful discharge on the day of surgery without emergency department visit or readmission within 24 h. Secondary outcomes included 30-day postoperative morbidity.A total of 811 primary SG and 325 RYGB procedures were performed during the study period. Among them, 30% (n = 244) were SDD-SGs and 6% (n = 21) were SDD-RYGBs, respectively. At baseline, median age of the entire SDD cohort was 43 years old, 81% were females, and body mass index (BMI) was 44.5 kg/m2. The planned SDD approach was successful in 89% after SG (n = 218/244) and in 90% after RYGB (n = 19/21). Nausea/vomiting was the main reason for a failed SDD approach after SG (46%). The 30-day readmission rate was 1.5% (n = 4) for the entire SDD cohort including only one readmission in the first 24 h. The percentage of SDD-SGs performed as a proportion of total SGs increased over the initial five consecutive six-month intervals (14%, 25%, 24%, 38%, and 49%).RESULTSA total of 811 primary SG and 325 RYGB procedures were performed during the study period. Among them, 30% (n = 244) were SDD-SGs and 6% (n = 21) were SDD-RYGBs, respectively. At baseline, median age of the entire SDD cohort was 43 years old, 81% were females, and body mass index (BMI) was 44.5 kg/m2. The planned SDD approach was successful in 89% after SG (n = 218/244) and in 90% after RYGB (n = 19/21). Nausea/vomiting was the main reason for a failed SDD approach after SG (46%). The 30-day readmission rate was 1.5% (n = 4) for the entire SDD cohort including only one readmission in the first 24 h. The percentage of SDD-SGs performed as a proportion of total SGs increased over the initial five consecutive six-month intervals (14%, 25%, 24%, 38%, and 49%).Our SDD protocol for bariatric surgery demonstrates a favorable safety profile, marked by high success rate and low postoperative morbidity. These outcomes have led to a continued increase in ambulatory procedures performed over time especially SG.CONCLUSIONOur SDD protocol for bariatric surgery demonstrates a favorable safety profile, marked by high success rate and low postoperative morbidity. These outcomes have led to a continued increase in ambulatory procedures performed over time especially SG.
Background
Given its short procedure time and low morbidity, there is enthusiasm to perform sleeve gastrectomy (SG) in an outpatient setting. However, most relevant studies include an overnight stay ...at a medical facility (≤ 24-h). Hence, we investigated the feasibility and safety of a same-day discharge (SDD) protocol for laparoscopic SG.
Methods
In a prospective pilot study (02/01/2021–02/28/2022), all patients planned for SG were screened for eligibility. Patients met the inclusion criteria if they were ≤ 65 years old, without major comorbidity, and lived close to the hospital. Postoperatively, patients who met discharge criteria were sent home directly from the recovery room. Patients were called the same night and the next morning. Feasibility was defined as discharge on the day of surgery without emergency department (ED) visit or readmission within 24-h. Secondary outcomes, including 90-day morbidity, were compared to patients who met inclusion criteria but chose a same-day admission (SDA) approach during the same study period. Descriptive statistics are displayed as count (percentage) and median (interquartile range).
Results
A total of 320 patients were planned for SG during the study period, 229 of whom met eligibility criteria and underwent SG with 56 agreeing to SDD-SG while 173 opted for SDA-SG. Baseline characteristics were all similar between both groups except for obstructive sleep apnea being more prevalent in SDA-SG group (38.2% vs. 16.1%;
P
< 0.001). Operative characteristics including procedure time were similar between both groups. Successful SDD-SG was achieved in 54(96%) of patients with a median of 6.0(1.0) hours of stay in the recovery room. Ninety-day morbidity was similar between SDD-SG and SDA-SG groups (1.8% vs. 6.9%, respectively;
P
= 0.196).
Conclusion
A SDD protocol for laparoscopic SG was feasible and safe in selected patients. Larger studies that evaluate patient reported outcomes and include bypass-type procedures may be needed to guide safe use of ambulatory bariatric surgery.
Aim
To validate the Individualized Metabolic Surgery (IMS) score and assess long‐term remission of type 2 diabetes (T2D) after duodenal switch (DS)‐type procedures in patients with obesity. In ...addition, to help guide metabolic procedure selection for those patients categorized as having severe T2D.
Materials and Methods
This is a retrospective single cohort study of all patients with T2D and severe obesity, who underwent DS‐type procedures at a single institution from December 2010 to December 2018. Study endpoints included validating the IMS score in our cohort and evaluating the impact of DS‐type procedures on long‐term (≥ 5 years) remission of T2D, especially in patients with severe disease. A receiver operator characteristic curve was used to assess the accuracy of the IMS score using the area under the curve (AUC).
Results
The study cohort included 30 patients with complete baseline and long‐term glycaemic data after their index DS‐type surgery. Twelve patients (40%) were classified with severe T2D, and the distribution of IMS‐based severity groups was similar between our cohort and the original IMS study (P = .42). IMS scores predicted long‐term T2D remission with AUC = 0.77. Patients with IMS‐based severe diabetes achieved significantly higher long‐term remission after DS‐type procedures compared with gastric bypass and/or sleeve gastrectomy from the original IMS study (42% vs. 12%; P < .05).
Conclusions
The IMS score properly classifies the severity of T2D in our study cohort and adequately predicts its long‐term remission after DS‐type procedures. While T2D remission decreases with more severe IMS scores, long‐term remission remains high after DS‐type procedures among patients with severe disease.
The World Health Organization declared a pandemic when coronavirus disease 2019 (COVID-19) started to sweep the globe. Growing concerns for the safety of health care workers was raised when up to 80% ...of people with COVID-19 showed mild or no symptoms at all. Some surgical procedures will be inevitable during the pandemic, and proper safety measures must be in place to avoid transmission risks. Surgical smoke is a common by-product from the use of energy devices in the operating room. The effects of surgical smoke have been studied for more than 40 years, and potential health hazards have been reported. Chemicals, carcinogens and biologically active materials, such as bacteria and viruses, have been isolated in surgical smoke. To ensure the safety of operating room personnel, we must consider whether there is any concern of viral transmission from the inhalation of surgical smoke.
Several models have been introduced to improve and restructure surgical training, but continued barriers exist. Residents are uniquely positioned to offer perspective on practical challenges and ...needs of reformatting surgical education. This study aimed to establish a nationwide, Delphi consensus statement on the perceptions of Canadian residents regarding the future of general surgery training.
Canadian general surgery residents participated in a moderated focus group using the Nominal Group Technique to discuss early subspecialization, competency-based medical education, and transition to practice. Qualitative verbal data were transcribed, categorized into themes, and synthesized into recommendation statements. During an iterative Delphi survey, resident leaders ranked each statement on a 5-point Likert scale of agreement. The survey was terminated once consensus was achieved (≥2 survey rounds and Cronbach’s α ≥ 0.80).
A total of 66 statements were synthesized by 16 members of the Canadian Association of General Surgeons Resident Committee. A total of 49 residents participated in the Delphi consensus, which was achieved after 2 voting rounds (Cronbach’s α = 0.93). Participants agreed that (1) residency should focus on achieving standardized competencies and milestones based on resident ability to meet specific measurable metrics, (2) early streaming should be offered after “core” milestones and competencies have been achieved, and (3) an explicit period should allow transition-to-independent practice with tailored rotations, greater autonomy, and resident-run clinics. We identified 10 barriers to competency-based medical education implementation.
A nationwide consensus regarding the future of surgical training was established among current residents. These findings can inform and help implement guidelines and national curricula that meet the needs of the trainee and address the many challenges they face during their training.
Abstract
Targeting the dynamic tumor immune microenvironment can provide effective therapeutic strategies for cancer. Neutrophils (polymorphonuclear neutrophils, PMNs) are the predominant circulating ...leukocyte population in humans and are vital to fight infection. Despite mounting evidence that PMNs can promote tumor progression, depleting PMNs is not a viable therapeutic option. Neutrophil extracellular traps (NETs) are networks of extracellular neutrophil DNA fibers that are capable of trapping tumor cells and promoting their growth and their metastasis. Targeting NETs can therefore be a potentially successful therapeutic option to block the tumor promoting functions of PMNs. Here we demonstrate that circulating NET levels are elevated in esophageal, gastric and lung cancer patients compared to healthy controls. This increase correlates with disease stage and NET levels are independent predictors of advanced stage. Using pre-clinical murine models of lung and colon cancer, we observe elevated NET levels in tumor bearing mice compared to non-tumor bearing mice; these levels correlated with tumor size. NET levels significantly decrease following tumor resection or treatment with DNase1, a NET degrader, or neutrophil elastase inhibitor (NEi), a NET inhibitor. NET levels do not rise following tumor inoculation in peptidyl arginine deiminase-IV knock out (PAD4-/-) mice; PAD4 being an enzyme essential for citrullination of histones, a crucial step in NET release. Moreover, PMNs from tumor bearing mice are more primed for NETosis than PMNs from non-tumor bearing mice or NEi-treated or PAD4-/- tumor bearing mice. Finally, elevated in vivo hepatic adhesion and spontaneous liver and lung metastases are observed in tumor bearing mice compared to DNase1- or NEi-treated or PAD4-/- tumor bearing mice. Therefore, inhibiting NETs represents a promising strategy to impede metastatic dissemination in several types of cancer patients.
Citation Format: Roni F. Rayes, Jack G. Mouhanna, Ioana Nicolau, Phil Vourtzoumis, Carson Wong, Jules Eustache, France Bourdeau, Betty Giannias, Aya Siblini, Emma Lee, Veena Sangwan, Simon Rousseau, Daniela Quail, Logan Walsh, Nicholas Bertos, Jonathan Cools-Lartigue, Lorenzo E. Ferri, Jonathan D. Spicer. Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1508.
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