-
Cancer Letters Jan 2023Peritoneal metastasis is one of the most frequent causes of death in several types of advanced cancers; however, the underlying molecular mechanisms remain largely...
Peritoneal metastasis is one of the most frequent causes of death in several types of advanced cancers; however, the underlying molecular mechanisms remain largely unknown. In this study, we exploited multicolor fluorescent lineage tracking to investigate the clonality of peritoneal metastasis in mouse xenograft models. When peritoneal metastasis was induced by intraperitoneal or orthotopic injection of multicolored cancer cells, each peritoneally metastasized tumor displayed multicolor fluorescence regardless of metastasis sites, indicating that it consists of multiclonal cancer cell populations. Multicolored cancer cell clusters form within the peritoneal cavity and collectively attach to the peritoneum. In vitro, peritoneal lavage fluid or cleared ascitic fluid derived from cancer patients induces cancer cell clustering, which is inhibited by anticoagulants. Cancer cell clusters formed in vitro and in vivo are associated with fibrin formation. Furthermore, tissue factor knockout in cancer cells abrogates cell clustering, peritoneal attachment, and peritoneal metastasis. Thus, we propose that cancer cells activate the coagulation cascade via tissue factor to form fibrin-mediated cell clusters and promote peritoneal attachment; these factors lead to the development of multiclonal peritoneal metastasis and may be therapeutic targets.
Topics: Mice; Animals; Humans; Peritoneum; Thromboplastin; Fibrinogen; Peritoneal Neoplasms; Cluster Analysis; Fibrin
PubMed: 36404569
DOI: 10.1016/j.canlet.2022.215983 -
BMJ Open Jul 2020Intra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal...
INTRODUCTION
Intra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal lavage (IOPL) was proposed in 1905, it has been widely used in the surgery practice. However, the effectiveness of IOPL in patients with IAIs has always been controversial. Our objective is to identify whether it is beneficial to flush the abdominal cavity with saline in IAIs surgery through a comprehensive systematic review and meta-analysis.
METHODS AND ANALYSIS
This protocol is reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Electronic databases (including the Cochrane library, MEDLINE, EMBASE, Web of Science, etc) and clinical trial registry platforms will be searched from inception to 8 September 2019. Randomised controlled trials, quasi-randomised clinical trials and cohort studies comparing IOPL and suction alone in IAIs will be included. The primary outcomes are mortality and abscess rate. Two independent reviewers will screen literature, collect data and assess risk of bias of included studies. Discussion or a third reviewer will be referred for any disagreements. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. We will perform meta-analysis using random-effects model. Subgroup analysis, sensitivity analysis and publication bias will be conducted if data are enough.
ETHICS AND DISSEMINATION
Ethical approval is not required for this systematic review and meta-analysis protocol. Results of this study will be published in a peer-reviewed journal, presented at relevant conferences and disseminated to local and international policy makers.
PROSPERO REGISTRATION NUMBER
CRD42019145109.
Topics: Humans; Intraabdominal Infections; Peritoneal Lavage; Publication Bias; Research Design; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 32690517
DOI: 10.1136/bmjopen-2019-036273 -
Journal of Leukocyte Biology Jun 2024Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection...
Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection following radiation injury remains poorly examined. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that dysregulates host immune system responses such as phagocytosis. We hypothesized that radiation-induced eCIRP release impairs macrophage phagocytosis of bacteria. Adult healthy mice were exposed to 6.5-Gy total body irradiation (TBI). Primary peritoneal macrophages isolated from adult healthy mice were exposed to 6.5-Gy radiation. eCIRP-neutralizing monoclonal antibody (mAb) was added to the cell culture prior to irradiation. Bacterial phagocytosis by peritoneal macrophages was assessed using pHrodo Green-labeled E. coli 7 days after irradiation ex vivo and in vitro. Bacterial phagocytosis was also assessed after treatment with recombinant murine CIRP (rmCIRP). Rac1 and ARP2 protein expression in cell lysates and eCIRP levels in the peritoneal lavage were assessed by Western blotting. Bacterial phagocytosis by peritoneal macrophages was significantly decreased after irradiation compared to controls ex vivo and in vitro. Rac1 and ARP2 expression in the peritoneal macrophages were downregulated after TBI. TBI significantly increased eCIRP levels in the peritoneal cavity. rmCIRP significantly decreased bacterial phagocytosis in a dose-dependent manner. eCIRP mAb restored bacterial phagocytosis by peritoneal macrophages after irradiation. Ionizing radiation exposure impairs bacterial phagocytosis by macrophages after irradiation. Neutralization of eCIRP restores the phagocytic ability of macrophages after irradiation. Our findings elucidate a novel mechanism of immune dysfunction and provide a potential new therapeutic approach for limiting infection after radiation injury.
PubMed: 38920274
DOI: 10.1093/jleuko/qiae132 -
World Journal of Surgical Oncology Oct 2023To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a...
BACKGROUND
To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer.
METHODS
A total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell's C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots.
RESULTS
This study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis.
CONCLUSION
We have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.
Topics: Humans; Retrospective Studies; Peritoneal Neoplasms; Stomach Neoplasms; Nomograms; Peritoneum; Claudins
PubMed: 37833730
DOI: 10.1186/s12957-023-03188-2 -
Cancers Mar 2022Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.p. dissemination in abdominal cancers and may help uncover critical information...
Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.p. dissemination in abdominal cancers and may help uncover critical information about future successful clinical treatments. i.p. cellular composition is studied in preclinical models addressing a wide spectrum of other pathophysiological states such as liver cirrhosis, infectious disease, autoimmunity, and aging. The peritoneal cavity is a multifaceted microenvironment that contains various immune cell populations, including T, B, NK, and various myeloid cells, such as macrophages. Analysis of the peritoneal cavity is often obtained by euthanizing mice and performing terminal peritoneal lavage. This procedure inhibits continuous monitoring of the peritoneal cavity in a single mouse and necessitates the usage of more mice to assess the cavity at multiple timepoints, increasing the cost, time, and variability of i.p. studies. Here, we present a simple, novel method termed in vivo intraperitoneal lavage (IVIPL) for the minimally invasive monitoring of cells in the peritoneal cavity of mice. In this proof-of-concept, IVIPL provided real-time insights into the i.p. tumor microenvironment for the development and study of ovarian cancer therapies. Specifically, we studied CAR-T cell therapy in a human high-grade serous ovarian cancer (HGSOC) xenograft mouse model, and we studied the immune composition of the i.p. tumor microenvironment (TME) in a mouse HGSOC syngeneic model.
PubMed: 35406547
DOI: 10.3390/cancers14071775 -
Neurologia Medico-chirurgica Sep 2022Treatment for pediatric hydrocephalus aims not only to shrink the enlarged ventricle morphologically but also to create an intracranial environment that provides the... (Review)
Review
Treatment for pediatric hydrocephalus aims not only to shrink the enlarged ventricle morphologically but also to create an intracranial environment that provides the best neurocognitive development and to deal with various treatment-related problems over a long period of time. Although the primary diseases that cause hydrocephalus are diverse, the ventricular peritoneal shunt has been introduced as the standard treatment for several decades. Nevertheless, complications such as shunt infection and shunt malfunction are unavoidable; the prognosis of neurological function is severely affected by such factors, especially in newborns and infants.In recent years, treatment concepts have been attempted to avoid shunting, mainly in the context of pediatric cases. In this review, the current role of neuroendoscopic third ventriculostomy for noncommunicating hydrocephalus is discussed and a new therapeutic concept for post intraventricular hemorrhagic hydrocephalus in preterm infants is documented. To avoid shunt placement and achieve good neurodevelopmental outcomes for pediatric hydrocephalus, treatment modalities must be developed.
Topics: Cerebrospinal Fluid Shunts; Child; Humans; Hydrocephalus; Infant; Infant, Newborn; Infant, Premature; Neuroendoscopy; Third Ventricle; Treatment Outcome; Ventriculostomy
PubMed: 36031350
DOI: 10.2176/jns-nmc.2022-0100 -
Cureus Aug 2022Background Ninety-five percent (95%) ethyl alcohol (ethanol) has been used as a standard cytological fixative but it is expensive, difficult to procure, and has...
Background Ninety-five percent (95%) ethyl alcohol (ethanol) has been used as a standard cytological fixative but it is expensive, difficult to procure, and has addictive properties. Alternate substitutes like methanol, which give similar results to ethanol, have toxic potential. Honey, a known preservative, is an eco-friendly fixative and is of great value when ethanol is unavailable and economizing on cost is necessary. The present study was done to assess and compare the fixation property and cytomorphological features of smears fixed in 20% honey in comparison to 95% ethyl alcohol and to determine whether the former can be used as an alternative cytological fixative in routine practice. Material and methods The present prospective study was done in the cytology section of the Department of Pathology for one and a half years on 300 cytological samples comprising 100 samples each of various body fluids (peritoneal, pleural, bronchoalveolar lavage, and urine), cervical smears, and fine-needle aspiration samples. The smears from all the 300 cytological samples were fixed separately in 95% ethanol and 20% unprocessed natural honey for a minimum of 15 minutes and were then stained with Papanicolaou (Pap) stain. The cytomorphological parameters of both the smears were compared based on set criteria. Relevant statistical analysis was done using the student t-test, chi-square test, and test of agreement (kappa statistics). Results A comparable and good-quality staining pattern, preservation of morphology, and crisp nuclear and cytoplasmic staining were observed between the two fixatives for all three types of samples with a strong agreement between them (kappa value varying between 0.896 and 0.942) and a p-value of <0.05. Conclusion Natural honey is a readily available and non-toxic alternative to ethanol as a cytological fixative and can be used in routine practices, especially in resource-constrained settings.
PubMed: 36148184
DOI: 10.7759/cureus.28149 -
Clinical Immunology (Orlando, Fla.) Sep 2023Metrnl play an immunocytokine-like role in several diseases, which is also known as meteorin-like because it is homologous to the neurotrophic factor meteorin (Metrn)....
Protective role of the novel cytokine Metrnl/ interleukin-41 in host immunity defense during sepsis by promoting macrophage recruitment and modulating Treg/Th17 immune cell balance.
BACKGROUND
Metrnl play an immunocytokine-like role in several diseases, which is also known as meteorin-like because it is homologous to the neurotrophic factor meteorin (Metrn). Although the expression and function of Metrnl, including neurotrophic, immunomodulatory, and insulin resistance functions in different tissues have been extensively studied, its role in sepsis has remained largely limited.
METHODS
The present work analyzed the levels of Metrnl and cytokines in the circulation, such as tumor necrosis factor (TNF-α), interleukin (IL-1)β, IL-6, IL-8, together with IL-10 among septic adult patients. Clinical information was obtained from such patients, including sofa score, procalcitonin(PCT)count, and C-reactive count (CRP) within 24 h when entering the intensive care unit (ICU). We constructed a sepsis model in Metrnl-deficient or normal wild-type mice using cecal ligation and perforation to study its functions in bacterial burden, survival, cytokine/chemokine generation, peritoneal lavage fluid neutrophils, macrophage and lymphocyte recruitment, and Treg/Th17 immune cell balance after CLP-induced sepsis.
RESULTS
The expression of Metrnl was remarkably elevated in the early phase of sepsis clinically. Its serum content in patients dying of sepsis slightly decreased relative to that in survivors. Furthermore, the concentration of Metrnl in septic cases when entering the ICU independently predicted the 28-day mortality. For septic patients who had low serum Metrnl content (≤ 274.40 pg/mL), the death risk increased by 2.3 folds relative to those who had a high serum content. It is reported that Metrnl is probably insufficient among patients dying of sepsis. Additionally, the content of Metrnl in the serum of septic patients when entering the ICU is markedly and negatively related to the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17, PCT, and Sofa score. Collectively, Metrnl could be a potential therapeutic target for sepsis. A low-lethality non-severe sepsis (NSS) model was constructed, which suggested that Metrnl insufficiency elevated the death rate and reduced bacterial clearance during sepsis. For Metrnl-deficient mice, impaired sepsis immunity defense might be related to decreased macrophage recruitment and Treg/Th17 lymphocyte imbalance. Recombinant Metrnl administered to Metrnl-deficient mice abolished the immunity defense impairment following NSS while protecting the high-lethality severe sepsis (SS) model in wild-type (WT) mice. In addition, Metrnl-induced sepsis prevention was intricately associated with the increased recruitment of peritoneal macrophages and modulation of the Treg/TH17 immune cell balance. Furthermore, CCL3 exposure in Metrnl-deficient mice reduced peritoneal bacterial loads while improving survival during sepsis partially by promoting the recruitment of peritoneal macrophages. Furthermore, Metrnl regulated the polarization of M1 macrophages through the ROS signaling pathway and promoted macrophage phagocytosis, thereby killing Escherichia coli.
CONCLUSIONS
The present proof-of-concept work suggests that Metrnl-mediated recruitment of macrophages significantly affects sepsis defense in the host and modulates the Treg/Th17 immune cell balance. Findings in this work shed more light on the development of host-directed treatments that can be used to manipulate host immunity to treat sepsis.
Topics: Animals; Mice; Cytokines; Interleukin-6; Interleukin-8; Interleukins; Macrophages; Sepsis; T-Lymphocytes, Regulatory; Th17 Cells; Tumor Necrosis Factor-alpha
PubMed: 37423488
DOI: 10.1016/j.clim.2023.109690 -
European Journal of Trauma and... Feb 2024Emergency treatment of acute diverticulitis remains a hazy field. Despite a number of clinical studies, randomized controlled trials (RCTs), guidelines and surgical... (Review)
Review
PURPOSE
Emergency treatment of acute diverticulitis remains a hazy field. Despite a number of clinical studies, randomized controlled trials (RCTs), guidelines and surgical societies recommendations, the most critical hot topics have yet to be addressed.
METHODS
Literature research from 1963 until today was performed. Data regarding the principal RCTs and observational studies were summarized in descriptive tables. In particular we aimed to focus on the following topics: the role of laparoscopy, the acute care setting, the RCTs, guidelines, observational studies and classifications proposed by literature, the problem in case of a pandemic, and the importance of adapting treatment /place/surgeon conditions.
RESULTS
In the evaluation of these points we did not try to find any prospective evolution of the concepts achievements. On the contrary we simply report the individuals strands of research from a retrospective point of view, similarly to what Steve Jobes said: "you can't connect the dots looking forward; you can only connect them looking backwards. So you have to trust that the dots will somehow connect in your future". We have finally obtained what can be defined "a narrative review of the literature on diverticulitis".
CONCLUSIONS
Not only evidence-based medicine but also the contextualization, as also the role of 'competent' surgeons, should guide to novel approach in acute diverticulitis management.
Topics: Humans; Evidence-Based Medicine; Diverticulitis; Laparoscopy; Anastomosis, Surgical; Critical Care; Peritonitis
PubMed: 37747500
DOI: 10.1007/s00068-023-02362-1 -
American Journal of Translational... 2022Chronic pelvic pain (CPP) and infertility are the common characteristics of endometriosis. Macrophages and related inflammation play important roles in endometriosis...
Chronic pelvic pain (CPP) and infertility are the common characteristics of endometriosis. Macrophages and related inflammation play important roles in endometriosis pain. TRPV1 and TRPA1 form a heteromeric channel which is related to endometriosis pain. In the present study, the inflammation-mediated macrophage polarization along with TRPV1/TRPA1 heteromers in endometriosis was investigated and . Macrophage polarization and TRPV1/TRPA1 heteromers in endometriosis tissue of patients were assayed, and was further investigated in endometriosis mice by co-culturing macrophages derived from mice in different groups with human endometrium cells. Our results indicated that macrophage polarization, as CD86 and CD206 positive macrophages, were accompanied by TRPV1/TRPA1 heteromers in endometriosis tissues of patients with pain. Inflammatory factors in peritoneal lavage fluid and serum of mice were correlated with TRPV1/TRPA1 expression in endometriosis tissues of mice as well as macrophage polarization which tended to be consistent with TRPV1/TRPA1 heteromers in endometriosis tissue. Moreover, macrophage polarization in enterocoelia induced ectopic endometrial cells migration with the increase in TRPV1/TRPA1 heteromers. Our results suggest that endometriosis-induced celiac inflammation might mediate macrophage polarization along with the increase of TRPV1/TRPA1 heteromers, which may play a key role in endometriosis pain.
PubMed: 35702089
DOI: No ID Found