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Frontiers in Immunology 2023Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1...
INTRODUCTION
Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survival.
METHODS
RAW264.7 cells and peritoneal macrophages collected from C57BL/6 wild-type (WT) mice were exposed to 5- and 10-Gray (Gy) radiation. C57BL/6 WT and CIRP-/- mice underwent 10-Gy total body irradiation (TBI). TREM-1 expression on RAW264.7 cells and peritoneal macrophages in vitro and in vivo were evaluated by flow cytometry. eCIRP levels in cell culture supernatants and in peritoneal lavage isolated from irradiated mice were evaluated by Western blotting. We also evaluated 30-day survival in C57BL/6 WT, CIRP-/- and TREM-1-/- mice after 6.5-Gy TBI.
RESULTS
The surface protein and mRNA levels of TREM-1 in RAW264.7 cells were significantly increased at 24 h after 5- and 10-Gy radiation exposure. TREM-1 expression on peritoneal macrophages was significantly increased after radiation exposure in vitro and in vivo. eCIRP levels were significantly increased after radiation exposure in cell culture supernatants of peritoneal macrophages in vitro and in peritoneal lavage in vivo. Moreover, CIRP-/- mice exhibited increased survival after 6.5-Gy TBI compared to WT mice. Interestingly, TREM-1 expression on peritoneal macrophages in CIRP-/- mice was significantly decreased compared to that in WT mice at 24 h after 10-Gy TBI. Furthermore, 30-day survival in TREM-1-/- mice was significantly increased to 64% compared to 20% in WT mice after 6.5-Gy TBI.
CONCLUSION
Our data indicate that ionizing radiation increases TREM-1 expression in macrophages via the release of eCIRP, and TREM-1 contributes to worse survival after total body irradiation. Thus, targeting TREM-1 could have the potential to be developed as a novel medical countermeasure for radiation injury.
Topics: Animals; Mice; Inflammation; Macrophages; Mice, Inbred C57BL; Radiation Injuries; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 37168858
DOI: 10.3389/fimmu.2023.1151250 -
Clinical Epigenetics Apr 2023The detection of peritoneal metastasis (PM) is limited by current imaging tools. In this prospective study, we aimed to evaluate the sensitivity and specificity of...
Peritoneal cell-free DNA as a sensitive biomarker for detection of peritoneal metastasis in colorectal cancer: a prospective diagnostic study: A prospective diagnostic study.
BACKGROUND
The detection of peritoneal metastasis (PM) is limited by current imaging tools. In this prospective study, we aimed to evaluate the sensitivity and specificity of peritoneal cell-free DNA (cfDNA) for diagnosis of PM.
METHODS
Colorectal cancer (CRC) patients with/without PM were enrolled. The cfDNA experimental personnel and statists were blinded to the diagnosis of PM. Ultradeep sequencing covering large genomic regions (35000X, Next-generation sequencing) of cfDNA in peritoneal lavage fluid (FLD) and matched tumor tissues was performed.
RESULTS
A total of 64 cases were recruited prospectively and 51 were enrolled into final analysis. In training cohort, 100% (17/17) PM patients obtained positive FLD cfDNA, comparing to 5/23 (21.7%) in patients without PM. Peritoneal cfDNA had a high sensitivity of 100% and specificity of 77.3% for diagnosis of PM (AUC: 0.95). In validation group of 11, 5/6 (83%) patients with PM obtained positive FLD cfDNA, comparing to 0/5 in non-PM (P = 0.031) with a sensitivity of 83.3% and specificity of 100%. Positive FLD cfDNA was associated with poor recurrence-free survival (P = 0.013) and was preceding radiographic evidence of recurrence.
CONCLUSIONS
Peritoneal cfDNA is a promising sensitive biomarker for earlier detection of PM in CRC than current radiological tools. It can potentially guide selection for targeted therapies and serve as a surrogate instead of laparoscopic explore in the future. Trial Registration Chinese Clinical Trial Registry at chictr.org.cn (ChiCTR2000035400). URL: http://www.chictr.org.cn/showproj.aspx?proj=57626.
Topics: Humans; Biomarkers, Tumor; Cell-Free Nucleic Acids; Colorectal Neoplasms; DNA Methylation; Mutation; Peritoneal Neoplasms; Prospective Studies
PubMed: 37072801
DOI: 10.1186/s13148-023-01479-9 -
World Journal of Emergency Surgery :... Mar 2023Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with intra-abdominal infections (IAIs) remains controversial. This study aims to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of IOPL in patients with IAIs.
METHODS
The databases of PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, and CBM databases were searched from inception to December 31, 2022. Random-effects models were used to calculate the risk ratio (RR), mean difference, and standardized mean difference. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence.
RESULTS
Ten RCTs with 1318 participants were included, of which eight studies on appendicitis and two studies on peritonitis. Moderate-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (0% vs. 1.1%; RR, 0.31 [95% CI, 0.02-6.39]), intra-abdominal abscess (12.3% vs. 11.8%; RR, 1.02 [95% CI, 0.70-1.48]; I = 24%), incisional surgical site infections (3.3% vs. 3.8%; RR, 0.72 [95% CI, 0.18-2.86]; I = 50%), postoperative complication (11.0% vs. 13.2%; RR, 0.74 [95% CI, 0.39-1.41]; I = 64%), reoperation (2.9% vs. 1.7%; RR,1.71 [95% CI, 0.74-3.93]; I = 0%) and readmission (5.2% vs. 6.6%; RR, 0.95 [95% CI, 0.48-1.87]; I = 7%) in patients with appendicitis when compared to non-IOPL. Low-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (22.7% vs. 23.3%; RR, 0.97 [95% CI, 0.45-2.09], I = 0%) and intra-abdominal abscess (5.1% vs. 5.0%; RR, 1.05 [95% CI, 0.16-6.98], I = 0%) in patients with peritonitis when compared to non-IOPL.
CONCLUSION
IOPL with saline use in patients with appendicitis was not associated with significantly decreased risk of mortality, intra-abdominal abscess, incisional surgical site infection, postoperative complication, reoperation, and readmission compared with non-IOPL. These findings do not support the routine use of IOPL with saline in patients with appendicitis. The benefits of IOPL for IAI caused by other types of abdominal infections need to be investigated.
Topics: Humans; Peritoneal Lavage; Abdominal Abscess; Peritonitis; Surgical Wound Infection; Appendicitis; Randomized Controlled Trials as Topic
PubMed: 36991507
DOI: 10.1186/s13017-023-00496-6 -
JCI Insight Jun 2023The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there...
The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there are no effective strategies to minimize the risk of colonization of preserved omental tissues by cancer cells that circulate in the peritoneal fluid. Normal saline is commonly administered into the peritoneal cavity for diagnostic and intraoperative lavage. Here we show that normal saline, when administered into the peritoneal cavity of mice, is prominently absorbed by the omentum, exfoliates its mesothelium, and induces expression of CX3CL1, the ligand for CX3CR1, within and surrounding the omental vasculature. Studies using CX3CR1-competent and CX3CR1-deficient mice showed that the predominant response in the omentum following saline administration is an accumulation of CX3CR1+ monocytes/macrophages that expand milky spots and promote neoangiogenesis within these niches. Moreover, saline administration promoted the implantation of cancer cells of ovarian and colorectal origin onto the omentum. By contrast, these deleterious effects were not observed following i.p. administration of lactated Ringer's solution. Our findings suggest that normal saline stimulates the receptivity of the omentum for cancer cells and that the risk of colonization can be minimized by using a biocompatible crystalloid for lavage procedures.
Topics: Animals; Mice; Saline Solution; Omentum; Ascitic Fluid; Embryo Implantation; Epithelium
PubMed: 37345662
DOI: 10.1172/jci.insight.167336 -
EBioMedicine Apr 2023Detecting free cancer cells from ascites and peritoneal lavages is crucial for diagnosing gastric cancer (GC). However, traditional methods are limited for early-stage...
BACKGROUNDS
Detecting free cancer cells from ascites and peritoneal lavages is crucial for diagnosing gastric cancer (GC). However, traditional methods are limited for early-stage diagnosis due to their low sensitivity.
METHODS
A label-free, rapid, and high-throughput technique was developed for separating cancer cells from ascites and peritoneal lavages using an integrated microfluidic device, taking advantage of dean flow fractionation and deterministic lateral displacement. Afterward, separated cells were analyzed using a microfluidic single-cell trapping array chip (SCTA-chip). In situ immunofluorescence for EpCAM, YAP-1, HER-2, CD45 molecular expressions, and Wright-Giemsa staining were performed for cells in SCTA-chips. At last, YAP1 and HER-2 expression in tissues was analyzed by immunohistochemistry.
FINDINGS
Through integrated microfluidic device, cancer cells were successfully separated from simulated peritoneal lavages containing 1/10,000 cancer cells with recovery rate of 84.8% and purity of 72.4%. Afterward, cancer cells were isolated from 12 patients' ascites samples. Cytological examinations showed cancer cells were efficiently enriched with background cells excluded. Afterwards, separated cells from ascites were analyzed by SCTA-chips, and recognized as cancer cells through EpCAM/CD45 expression and Wright-Giemsa staining. Interestingly, 8 out of 12 ascites samples showed HER-2 cancer cells. At last, the results through a serial expression analysis showed that YAP1 and HER-2 have discordant expression during metastasis.
INTERPRETATION
Microfluidic Chips developed in our study could not only rapidly detect label-free free GC cells in ascites and peritoneal lavages with high-throughput, they could also analyze ascites cancer cells at the single-cell level, improving peritoneal metastasis diagnosis and investigation of therapeutic targets.
FUNDING
This research was supported by National Natural Science Foundation of China (22134004, U1908207, 91859111); Natural Science Foundation of Shandong Province of China (ZR2019JQ06); Taishan Scholars Program of Shandong Province tsqn (201909077); Local Science and Technology Development Fund Guided by the Central Government (YDZX20203700002568); Applied Basic Research Program of Liaoning Province (2022020284-JH2/1013).
Topics: Humans; Stomach Neoplasms; Epithelial Cell Adhesion Molecule; Peritoneal Lavage; Ascites; Microfluidics; Single-Cell Analysis
PubMed: 36933411
DOI: 10.1016/j.ebiom.2023.104522 -
Clinics in Colon and Rectal Surgery Mar 2021Diverticulitis manifestations may cover a spectrum of mild local inflammation to diffuse feculent peritonitis. Up to 35% of patients presenting with diverticulitis will... (Review)
Review
Diverticulitis manifestations may cover a spectrum of mild local inflammation to diffuse feculent peritonitis. Up to 35% of patients presenting with diverticulitis will have purulent (Hinchey grade III) or feculent (Hinchey grade IV) contamination of the abdomen, with a high-associated morbidity and mortality. Surgical management may involve segmental resection with or without restoration of bowel continuity. However, emergency resection for diverticulitis can be associated with high mortality rates, as well as low stoma reversal rates at 1 year. Therefore, laparoscopic peritoneal lavage has been proposed for use in selected patients with purulent peritonitis. The topic of laparoscopic peritoneal lavage for the treatment of perforated diverticulitis in the literature has been controversial. Our review of the recent data show that laparoscopic lavage may be safe and feasible in select patients with similar rates of mortality and major morbidity. There is, however, a concern regarding an associated higher rate of postoperative abscess and early reintervention risk.
PubMed: 33642950
DOI: 10.1055/s-0040-1716702 -
Journal of Cancer Research and Clinical... Jun 2021Positive cytology from peritoneal washings obtained prior to potential resection of pancreatic cancer is associated with grim prognosis, equivalent to M1 disease. We...
INTRODUCTION
Positive cytology from peritoneal washings obtained prior to potential resection of pancreatic cancer is associated with grim prognosis, equivalent to M1 disease. We examine our experience with pancreatic cancer patients who underwent pre-resection lavage in an attempt to predict who would have malignant cells on peritoneal cytology.
METHODS
We conducted a retrospective review of patients undergoing pancreatectomy for pancreatic adenocarcinoma at a tertiary care institution from 1995 to 2019 and had pre-resection lavage performed. Demographic and clinicopathologic data were collected. Logistic regression models were used to identify predictors of positive cytology.
RESULTS
Three hundred ninety-nine patients underwent pancreatic resection and had lavage performed. Forty-three (10.8%) had positive peritoneal cytology. Those with positive cytology had higher median Ca19-9 value than those with negative cytology at diagnosis (368.5 vs 200 U/mL, p = 0.007) and after neoadjuvant therapy (100.3 vs 43 U/mL, p = 0.013). After controlling for preoperative therapy received, an initial Ca19-9 greater than 1220 U/mL (OR 2.72, 95% CI 1.07-6.89, p = 0.035), locally advanced disease (OR 4.86, 95% CI 1.31-18.09, p = 0.018), and BMI ≥ 25 kg/m (OR 2.67, 95% CI 1.04-6.97, p = 0.042) were associated with positive cytology in multivariate logistic regression model. The associated ROC curve had an AUC of 0.7507, suggesting adequate discrimination of those with positive peritoneal cytology.
CONCLUSION
Diagnostic laparoscopy remains an important adjunct to the workup, diagnosis, and staging of pancreatic adenocarcinoma. Patients with locally advanced disease, significantly elevated serum Ca19-9 at diagnosis, and BMI ≥ 25 kg/m may be at higher risk for positive peritoneal cytology, regardless of whether neoadjuvant therapy is administered.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cytodiagnosis; Female; Humans; Male; Middle Aged; Neoplasm Staging; Pancreatectomy; Pancreatic Neoplasms; Peritoneal Lavage; Peritoneal Neoplasms; Peritoneum; Predictive Value of Tests; Prognosis; Retrospective Studies
PubMed: 33389074
DOI: 10.1007/s00432-020-03471-9 -
Annals of Surgical Oncology Dec 2020Disease burden in patients with peritoneal carcinomatosis (PC) is difficult to estimate. We evaluate whether peritoneal cell-free tumor DNA can be used as a measure of...
BACKGROUND
Disease burden in patients with peritoneal carcinomatosis (PC) is difficult to estimate. We evaluate whether peritoneal cell-free tumor DNA can be used as a measure of disease burden.
PATIENTS AND METHODS
Malignant ascites or peritoneal lavage fluids were collected from patients with PC under approved IRB protocol. Cell-free DNA was extracted from peritoneal fluid. Droplet digital PCR (ddPCR) was performed using a commercially available KRAS G12/G13 screening kit. Mutant allele frequency (MAF) was calculated based on the numbers of KRAS wild-type and mutant droplets. Clinicopathological, treatment and outcome data were abstracted and correlated with MAF of cell-free KRAS mutant DNA.
RESULTS
Cell-free KRAS mutant DNA was detected in 15/37 (40%) malignant peritoneal fluids with a MAF of 0.1% to 26.2%. While peritoneal cell-free KRAS mutant DNA was detected in all the patients with KRAS mutant tumors (N = 10), 3/16 (19%) patients with KRAS wild-type tumors also had peritoneal cell-free KRAS mutant DNA. We also found that 71% (5/7) of patients with disease amenable to cytoreductive surgery (CRS) had a MAF of < 1% (median: 0.5%, range: 0.1-4.7%), while 75% (6/8) of patients with unresectable disease had a MAF of > 1% (median: 4.4%, range: 0.1-26.2%).
CONCLUSIONS
This pilot proof-of-principle study suggests that peritoneal cell-free tumor DNA detected by ddPCR may enable prediction of disease burden and a measure of disease amenable to CRS in patients with PC.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Humans; Peritoneal Neoplasms; Polymerase Chain Reaction
PubMed: 32648179
DOI: 10.1245/s10434-020-08832-9 -
Frontiers in Oncology 2021As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of... (Review)
Review
As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of patients to a very large extent. Peritoneal status and risk of peritoneal recurrence can be evaluated by peritoneal lavage cytology, photodynamic diagnosis, imaging examination, and pathologic analysis. Presently, there is no standard approach for preventing peritoneal recurrence after radical surgery; furthermore, controversies exist regarding the effects of some preventive methods. Among the preventive methods, there are high expectations about the potential of preoperative therapy, surgical skill improvement, hyperthermic intraperitoneal chemotherapy, and postoperative treatment to reduce the incidence of peritoneal recurrence after radical gastrectomy. This study aimed to analyze the results of previous studies on the risk assessment and preventive methods of peritoneal recurrence after radical gastrectomy in recent years. We hope to provide references for better approach to clinical diagnosis and treatment strategies for peritoneal recurrence after radical gastrectomy.
PubMed: 35047394
DOI: 10.3389/fonc.2021.778152 -
World Journal of Emergency Surgery :... Sep 2021Acute appendicitis is one of the most frequent abdominal surgical emergencies. Intra-abdominal abscess is a frequent post-operative complication. The aim of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute appendicitis is one of the most frequent abdominal surgical emergencies. Intra-abdominal abscess is a frequent post-operative complication. The aim of this meta-analysis was to compare peritoneal irrigation and suction versus suction only when performing appendectomy for complicated appendicitis.
METHODS
According to PRISMA guidelines, a systematic review was conducted and registered into the Prospero register (CRD42020186848). The risk of bias was defined to be from low to moderate.
RESULTS
Seventeen studies (9 RCTs and 8 CCTs) were selected, including 5315 patients. There was no statistical significance in post-operative intra-abdominal abscess in open (RR 1.27, 95% CI 0.75-2.15; I = 74%) and laparoscopic group (RR 1.51, 95% CI 0.73-3.13; I = 83%). No statistical significance in reoperation rate in open (RR 1.27, 95% CI 0.04-2.49; I = 18%) and laparoscopic group (RR 1.42, 95% CI 0.64-2.49; I = 18%). In both open and laparoscopic groups, operative time was lower in the suction group (RR 7.13, 95% CI 3.14-11.12); no statistical significance was found for hospital stay (MD - 0.39, 95% CI - 1.07 to 0.30; I = 91%) and the rate of wound infection (MD 1.16, 95% CI 0.56-2.38; I = 71%).
CONCLUSIONS
This systematic review has failed to demonstrate the statistical superiority of employing intra-operative peritoneal irrigation and suction over suction-only to reduce the rate of post-operative complications after appendectomy, but all the articles report clinical superiority in terms of post-operative abscess, wound infection and operative times in suction-only group.
Topics: Appendectomy; Appendicitis; Humans; Peritoneal Lavage; Postoperative Complications; Suction
PubMed: 34488825
DOI: 10.1186/s13017-021-00391-y