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European Journal of Surgical Oncology :... Jun 2024Gastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis...
INTRODUCTION
Gastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis (PC+) and free cancer cells in peritoneal lavage cytology (CY+). The current study aimed to present the outcomes of staging laparoscopy and the prognosis of PC+ and CY+ in a Swedish high-volume center.
MATERIALS AND METHODS
A cohort study including all consecutive patients with locally advanced gastric cancer who underwent staging laparoscopy between February 2008 and October 2022. The laparoscopy findings were categorized as PC+, PC-CY+ (positive cytology without peritoneal carcinomatosis) or negative laparoscopy (PC-CY-). The primary endpoint was overall survival (OS) stratified by laparoscopy findings. The secondary endpoint was OS within each laparoscopy finding group stratified by subsequent treatment.
RESULTS
Among 168 patients who underwent staging laparoscopy, 78 patients (46%) had PC-CY-, 29 patients (17%) had PC-CY+ and 61 patients (36%) had PC+. Decreased OS was observed for both PC-CY+ patients (aHR 2.14, 95% CI 1.13-4.06) and PC+ patients (aHR 5.36, 95% CI 3.21-8.93), compared to PC-CY-. Patients with PC-CY+ who converted to PC-CY- after chemotherapy and underwent tumor resection seemed to have a better prognosis compared to patients with persisting PC-CY+.
CONCLUSIONS
Staging laparoscopy is an important tool in the staging of locally advanced gastric cancer. Tumor resection for patients with PC-CY+ who convert to PC-CY- may lead to improved survival for these patients.
Topics: Humans; Stomach Neoplasms; Peritoneal Lavage; Peritoneal Neoplasms; Laparoscopy; Male; Female; Middle Aged; Neoplasm Staging; Aged; Sweden; Survival Rate; Prognosis; Retrospective Studies; Gastrectomy
PubMed: 38503223
DOI: 10.1016/j.ejso.2024.108059 -
Frontiers in Immunology 2024Pre-neutrophils, while developing in the bone marrow, transcribe the gene and synthesize Activin-A protein, which they store and release at the earliest stage of their...
BACKGROUND
Pre-neutrophils, while developing in the bone marrow, transcribe the gene and synthesize Activin-A protein, which they store and release at the earliest stage of their activation in the periphery. However, the role of neutrophil-derived Activin-A is not completely understood.
METHODS
To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model ( mice) and analyzed the immune response to Influenza A virus (IAV) infection. More specifically, evaluation of body weight and lung mechanics, molecular and cellular analyses of bronchoalveolar lavage fluids, flow cytometry and cell sorting of lung cells, as well as histopathological analysis of lung tissues, were performed in PBS-treated and IAV-infected transgenic animals.
RESULTS
We found that neutrophil-specific Activin-A deficiency led to exacerbated pulmonary inflammation and widespread hemorrhagic histopathology in the lungs of IAV-infected animals that was associated with an exuberant production of neutrophil extracellular traps (NETs). Moreover, deletion of the Activin-A receptor ALK4/ACVR1B in neutrophils exacerbated IAV-induced pathology as well, suggesting that neutrophils themselves are potential targets of Activin-A-mediated signaling. The pro-NETotic tendency of Activin-A-deficient neutrophils was further verified in the context of thioglycollate-induced peritonitis, a model characterized by robust peritoneal neutrophilia. Of importance, transcriptome analysis of Activin-A-deficient neutrophils revealed alterations consistent with a predisposition for NET release.
CONCLUSION
Collectively, our data demonstrate that Activin-A, secreted by neutrophils upon their activation in the periphery, acts as a feedback mechanism to moderate their pro-NETotic tendency and limit the collateral tissue damage caused by neutrophil excess activation during the inflammatory response.
Topics: Animals; Mice; Humans; Neutrophils; Lung; Influenza A virus; Pneumonia; Influenza, Human; Activins
PubMed: 38476229
DOI: 10.3389/fimmu.2024.1302489 -
Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response.Cell Reports Mar 2024Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of...
Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression. Conventional DCs also respond to BPI, while M-CSF-cultivated or peritoneal lavage macrophages do not. Subsequent to BPI stimulation of BMDCs, CD4 T cells predominantly secrete IL-22 and, when naive, preferentially differentiate into T helper 22 (Th22) cells. Congruent with the tissue-protective properties of IL-22 and along with impaired IL-22 induction, disease severity is significantly increased during dextran sodium sulfate-induced colitis in BPI-deficient mice. Importantly, physiological diversification of intestinal microbiota fosters BPI-dependent IL-22 induction in CD4 T cells derived from mesenteric lymph nodes. In conclusion, BPI is a potent activator of DCs and consecutive Th22 cell differentiation with substantial relevance in intestinal homeostasis.
Topics: Animals; Mice; Tumor Necrosis Factor-alpha; Cells, Cultured; T-Lymphocytes, Helper-Inducer; Dendritic Cells; Permeability
PubMed: 38457343
DOI: 10.1016/j.celrep.2024.113929 -
Chinese Journal of Cancer Research =... Feb 2024Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence...
OBJECTIVE
Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.
METHODS
In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.
RESULTS
Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. and were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0).
CONCLUSIONS
There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.
PubMed: 38455368
DOI: 10.21147/j.issn.1000-9604.2024.01.07 -
Trauma Surgery & Acute Care Open 2024Advanced Trauma Life Support (ATLS) focuses on care of injured patients in the first hour of resuscitation. Expanded demand for courses has led to a concurrent need for...
OBJECTIVES
Advanced Trauma Life Support (ATLS) focuses on care of injured patients in the first hour of resuscitation. Expanded demand for courses has led to a concurrent need for new instructors. Nurse practitioners and physician assistants (NPs/PAs) work on trauma services and duties include patient, staff, and outreach education. The goal of this project was to assess NP/PA self-reported knowledge and skills pertinent to ATLS and identify potential barriers to becoming instructors.
MATERIALS
This was a voluntary 91-question survey emailed to NP/PA lists obtained from professional societies and online social media channels. NPs/PAs completed a survey reflecting self-reported knowledge, experience, comfort level, and barriers to teaching ATLS interactive discussions and skills. Responses were recorded using a Likert scale and results were documented as percentages. Number of years of experience versus perceived knowledge and comfort teaching were compared using a χ test of independence.
RESULTS
There were 1696 completed surveys. Most NPs/PAs thought they had adequate knowledge and experience to teach interactive discussions and skills. Those with more years of experience and those who completed more ATLS courses had higher percentages. The number 1 barrier to teaching was lack of formal teaching experience followed by perceived hierarchy concerns. Experience and comfort with skills that fell below 50% were pediatric airway (49.5%), needle and surgical cricothyrotomy (49.8% and 44.8%), diagnostic peritoneal lavage (21.6%), and venous cutdown (20.8%).
CONCLUSION
NPs/PAs with experience in trauma reported having the knowledge and skill to teach ATLS. A majority are comfortable teaching interactive discussions and skills for which they are knowledgeable. The primary barrier to teaching was lack of formal teaching experience, which is covered in the ATLS Instructor course. Training NPs/PAs to become instructors would increase the instructor base and allow for increased promulgation of ATLS and trauma education.
LEVEL OF EVIDENCE
IV.
PubMed: 38450048
DOI: 10.1136/tsaco-2023-001195 -
European Journal of Surgical Oncology :... Apr 2024Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL...
INTRODUCTION
Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL is important given ongoing improvements in diagnostic imaging and treatment. As contemporary data from European centres are sparse, this retrospective cohort study aimed to assess the yield of DL in patients with potentially curable gastric cancer, and to identify predictive factors for peritoneal metastases.
METHODS
Patients with adenocarcinoma of the stomach, treated between January 2016 and December 2018, were identified from institutional databases of two high volume European Upper-GI centres. Patients who underwent a DL with peritoneal lavage for potentially curable disease after clinical staging with imaging (cT1-4N0-3M0) were included. The primary outcome was the proportion of patients with a positive DL, defined as macroscopic metastatic disease, positive peritoneal cytology washings (PC+) or locally irresectable disease.
RESULTS
Some 80 of 327 included patients (24.5%) had a positive DL, excluding these patients from neoadjuvant treatment (66 of 327; 20.2%) and/or surgical resection (76 of 327; 23.2%). In 34 of 327 patients (10.3%), macroscopic metastatic disease was seen, with peritoneal deposits in 30 of these patients. Only 16 of 30 patients with peritoneal disease had positive cytology. Some 41 of 327 patients (12.5%) that underwent DL had PC+ in the absence of macroscopic metastases and five patients (1.5%) had an irresectable primary tumour. Diffuse type carcinoma had the highest risk of peritoneal dissemination, irrespective of cT and cN categories.
CONCLUSION
The diagnostic yield of staging laparoscopy is high, changing the management in approximately one quarter of patients. DL should be considered in patients with diffuse type carcinoma irrespective of cT and cN categories.
Topics: Humans; Peritoneal Lavage; Stomach Neoplasms; Retrospective Studies; Peritoneal Neoplasms; Neoplasm Staging; Laparoscopy; Adenocarcinoma
PubMed: 38428107
DOI: 10.1016/j.ejso.2024.108233 -
Scientific Reports Feb 2024Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we...
Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we report the interactions between EVs and NETs during murine endotoxemia studied in situ directly in the vasculature (cremaster muscle, liver sinusoids) using intravital microscopy (IVM). We captured NETs and EV release in real time by both non- and polarized neutrophils in liver but not in cremaster vasculature. When comparing numbers of circulating EVs of various origin (nanoparticle tracking analysis-NTA, flow cytometry) with those interacting with endothelium and NETs (IVM) we observed that whereas platelet and monocyte/macrophage-derived EVs dominate in blood and peritoneal lavage, respectively, mostly neutrophil-derived EVs interact with the vascular lining, NETs and leukocytes. Despite the interaction, NETs do not affect EV formation as NET release inhibition did not alter EV release. However, EVs inhibit NETs formation and in particular, erythrocyte-derived EVs downregulate NET release and this effect is mediated via Siglec-E-dependent interactions with neutrophils. Overall, we report that EVs are present in NETs in vivo and they do modulate their release but the process in not bidirectional. Moreover, EVs isolated from body fluids might not reflect their importance in direct endothelial- and leukocyte-related interactions.
Topics: Mice; Animals; Extracellular Traps; Neutrophils; Inflammation; Leukocytes; Extracellular Vesicles
PubMed: 38409254
DOI: 10.1038/s41598-024-55081-x -
Alternative Therapies in Health and... Feb 2024Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical...
BACKGROUND
Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical surgery for elderly patients with colorectal cancer are still unclear.
METHODS
In accordance with computer-generated random allocation sequences, 116 elderly patients with colorectal cancer who received radical surgery were randomly grouped into the raltitrexed intraperitoneal perfusion group or the saline intraperitoneal perfusion group from January 2020 to December 2021 in the First Affiliated Hospital of Bengbu Medical University. t tests and χ2 tests were used to analyze the difference between the two groups of the clinical characteristics, pathological features, perioperative parameters, and carcinoembryonic antigen mRNA in the peritoneal lavage fluid.
RESULTS
No statistically significant differences in postoperative complications after radical surgery were observed between the two groups. No statistically significant differences in peripheral blood indexes were observed between the two groups before surgery or on the first and third days after surgery. One day after radical surgery, the alanine transaminase (54.33 ± 4.93 vs 51.01 ± 5.56) and aspartate transaminase (49.28 ± 4.30 vs 50.99 ± 3.88) in the peripheral blood were higher in the raltitrexed intraperitoneal perfusion group than in the saline intraperitoneal perfusion group. At the same time, no significant difference was found on the third day after surgery. No significant differences in side effects of chemotherapy were observed between the two groups. The positive rate of carcinoembryonic antigen mRNA in the raltitrexed intraperitoneal perfusion group (8.47%) was significantly lower than that in the saline intraperitoneal perfusion group (22.81%) after surgery.
CONCLUSION
Raltitrexed perfusion during radical surgery is safe and feasible for elderly patients with CRC and can reduce the positive rate of carcinoembryonic antigen mRNA in peritoneal lavage fluid, so it can be explored as a treatment option.
PubMed: 38401095
DOI: No ID Found -
ACS Nano Feb 2024Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective peritoneal models has hindered the exploration of the potential mechanisms...
Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process . Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.
Topics: Humans; Peritoneum; Stomach Neoplasms; Peritoneal Neoplasms; Ascites; Biomimetics; Extracellular Vesicles
PubMed: 38349890
DOI: 10.1021/acsnano.3c02285 -
Frontiers in Immunology 2024Various immune cell types play critical roles in sepsis with numerous distinct subsets exhibiting unique phenotypes even within the same cell population. Single-cell RNA...
INTRODUCTION
Various immune cell types play critical roles in sepsis with numerous distinct subsets exhibiting unique phenotypes even within the same cell population. Single-cell RNA sequencing (scRNA-seq) enables comprehensive transcriptome profiling and unbiased cell classification. In this study, we have unveiled the transcriptomic landscape of immune cells in sepsis through scRNA-seq analysis.
METHODS
We induced sepsis in mice by cecal ligation and puncture. 20 h after the surgery, the spleen and peritoneal lavage were collected. Single-cell suspensions were processed using a 10× Genomics pipeline and sequenced on an Illumina platform. Count matrices were generated using the Cell Ranger pipeline, which maps reads to the mouse reference transcriptome, GRCm38/mm10. Subsequent scRNA-seq analysis was performed using the R package Seurat.
RESULTS
After quality control, we subjected the entire data set to unsupervised classification. Four major clusters were identified as neutrophils, macrophages, B cells, and T cells according to their putative markers. Based on the differentially expressed genes, we identified activated pathways in sepsis for each cell type. In neutrophils, pathways related to inflammatory signaling, such as NF-κB and responses to pathogen-associated molecular patterns (PAMPs), cytokines, and hypoxia were activated. In macrophages, activated pathways were the ones related to cell aging, inflammatory signaling, and responses to PAMPs. In B cells, pathways related to endoplasmic reticulum stress were activated. In T cells, activated pathways were the ones related to inflammatory signaling, responses to PAMPs, and acute lung injury. Next, we further classified each cell type into subsets. Neutrophils consisted of four clusters. Some subsets were activated in inflammatory signaling or cell metabolism, whereas others possessed immunoregulatory or aging properties. Macrophages consisted of four clusters, namely, the ones with enhanced aging, lymphocyte activation, extracellular matrix organization, or cytokine activity. B cells consisted of four clusters, including the ones possessing the phenotype of cell maturation or aging. T cells consisted of six clusters, whose phenotypes include molecular translocation or cell activation.
CONCLUSIONS
Transcriptomic analysis by scRNA-seq has unveiled a comprehensive spectrum of immune cell responses and distinct subsets in the context of sepsis. These findings are poised to enhance our understanding of sepsis pathophysiology, offering avenues for targeting novel molecules, cells, and pathways to combat infectious diseases.
Topics: Mice; Animals; Pathogen-Associated Molecular Pattern Molecules; Gene Expression Profiling; Transcriptome; Cytokines; Sepsis
PubMed: 38343542
DOI: 10.3389/fimmu.2024.1347453