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Cell & Bioscience Nov 2023Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer...
BACKGROUND
Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer progression via the intrinsic oncogenic pathways. However, the role of m6A in regulating host immune cell function during anti-tumor immunity needs comprehensive analysis. This study aimed to investigate the role of METTL3, a catalytic subunit of the methyltransferase complex, in regulating host immune cell response against OC.
METHODS
In this study, myeloid-specific Mettl3 gene knockout (Mettl3-cKO) mice were bred using the Cre-LoxP system. Intraperitoneally injection of ID8 cells was used as a syngeneic OC model. Furthermore, the compositions of immune cell populations were analyzed by flow cytometry and single-cell sequencing. Moreover, chemokines and cytokines secretion were assessed using ELISA. Lastly, the role of METTL3 in regulating IL-1β secretion and inflammasome activation in bone marrow-derived macrophages cocultured with ID8 cells was specified by ELISA and immunoblotting.
RESULTS
It was revealed that OC cell growth was enhanced in Mettl3-cKO mice. Furthermore, a shift of decreased M1 to increased M2 macrophage polarization was observed during OC progression. Moreover, Mettl3 depletion in myeloid lineage cells increased secretion of CCL2 and CXCL2 in peritoneal lavage fluild. Interestingly, Mettl3 deficiency enhanced IL-1β secretion induced by viable ID8 cells independent of inflammasome activation and cell death. Therefore, OC cells in tumor-bearing mice trigger a slight inflammatory response with a low-to-moderate secretion of pro-inflammatory cytokines and chemokines.
CONCLUSION
This study provides new insights into METTL3-mediated m6A methylation, which regulates host immune response against OC.
PubMed: 37932814
DOI: 10.1186/s13578-023-01149-6 -
International Journal of Clinical... Jul 2021The prognostic value of positive intraoperative peritoneal cytology and lavage cytology, including the differences in their prognostic impact, in colorectal cancer is...
BACKGROUND
The prognostic value of positive intraoperative peritoneal cytology and lavage cytology, including the differences in their prognostic impact, in colorectal cancer is controversial. We aimed to investigate the prognostic values of positive peritoneal cytology and lavage cytology findings for colorectal cancer and compare their prognostic impact.
METHODS
We retrospectively evaluated 592 clinical stage II-IV colorectal cancer patients who underwent peritoneal cytology (n = 225) or lavage cytology (n = 367) between November 1993 and December 2018. The prognostic factors for cancer-specific survival were identified, and the differences in cancer-specific survival were examined between the patients.
RESULTS
The cytology-positive rate was 10.8% (64/592), 17.8% (40/225), and 6.5% (24/367) in the overall, peritoneal cytology, and lavage cytology groups, respectively. Both positive peritoneal cytology (hazard ratio: 2.196) and lavage cytology (hazard ratio: 2.319) were independent prognostic factors. The peritoneal cytology-positive group showed significantly poorer cancer-specific survival than the cytology-negative group (5-year: 3.5% vs. 59.5%; 10-year: 3.5% vs. 46.1%, p < 0.001). Similar results were obtained for lavage cytology (5-year: 14.1% vs. 73.9%; 10-year: 4.7% vs. 63.5%, p < 0.001). The cancer-specific survival was not significantly different between the peritoneal cytology-positive and lavage cytology-positive groups (p = 0.058). Both positive peritoneal and lavage cytology were associated with poorer cancer-specific survival across all colorectal cancer stages.
CONCLUSIONS
Positive peritoneal and lavage cytology are associated with worse cancer-specific survival in colorectal cancer. The prognostic impact was comparable between positive lavage and peritoneal cytology. Thus, cytology should be a standard assessment modality for colorectal cancer.
Topics: Colorectal Neoplasms; Cytodiagnosis; Humans; Neoplasm Staging; Peritoneal Lavage; Prognosis; Retrospective Studies
PubMed: 33844111
DOI: 10.1007/s10147-021-01918-8 -
The British Journal of Surgery Jun 2023The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic peritoneal lavage or sigmoid resection. The aim of this analysis was to identify risk factors for treatment failure in patients with Hinchey III perforated diverticulitis.
METHODS
This was a post hoc analysis of the SCANDIV trial and LOLA arm. Treatment failure was defined as morbidity requiring general anaesthesia (Clavien-Dindo grade IIIb or higher) within 90 days. Age, sex, BMI, ASA fitness grade, smoking status, previous episodes of diverticulitis, previous abdominal surgery, time to surgery, and surgical competence were all tested in univariable and multivariable logistic regression analyses using an interaction variable.
RESULTS
The pooled analysis included 222 patients randomized to laparoscopic lavage and primary resection (116 and 106 patients respectively). Univariable analysis found ASA grade to be associated with advanced morbidity in both groups, and the following factors in the laparoscopic lavage group: smoking, corticosteroid use, and BMI. Significant factors for laparoscopic lavage morbidity in multivariable analysis were smoking (OR 7.05, 95 per cent c.i. 2.07 to 23.98; P = 0.002) and corticosteroid use (OR 6.02, 1.54 to 23.51; P = 0.010).
CONCLUSION
Active smoking status and corticosteroid use were risk factors for laparoscopic lavage treatment failure (advanced morbidity) in patients with perforated diverticulitis.
Topics: Humans; Adrenal Cortex Hormones; Diverticulitis; Diverticulitis, Colonic; Intestinal Perforation; Laparoscopy; Peritoneal Lavage; Peritonitis; Randomized Controlled Trials as Topic; Reoperation; Treatment Failure; Treatment Outcome
PubMed: 37202860
DOI: 10.1093/bjs/znad114 -
Diagnostic Cytopathology Jun 2021We aimed to assess the sensibility, specificity, and predictive values of cytology of the fluid sediment in patients with pelvic endometriosis diagnosed based on...
BACKGROUND
We aimed to assess the sensibility, specificity, and predictive values of cytology of the fluid sediment in patients with pelvic endometriosis diagnosed based on laparoscopic-guided biopsy.
METHODS
Between January 2017 and September 2018, 71 specimens of peritoneal fluid collected by laparoscopy were evaluated. Fifty-three patients were diagnosed laparoscopically and histologically with endometriosis, and 18 were considered controls (without suspicious endometriosis lesions). We calculated the sensitivity, specificity, the positive and negative predictive value, and the accuracy of endometrial-like cells (ELC) and hemosiderin-laden macrophages (HLM) in the fluid sediment.
RESULTS
Of the 50 patients with endometriosis, 32 (64%) had HLM, 9 (18%) had ELC, and 7 (14%) had both elements. Of the 18 patients without endometriosis, 3 (16%) had HLM, 2 (11%) had ELC, and 1 (5%) had both ELC and HLM. The sensitivity of the cytology of peritoneal fluid sediment for the diagnosis of endometriosis, based on the presence of ELC, was 18%, the specificity was 83%, the positive predictive value was 82%, the negative predictive value was 28.7%, and the accuracy was 36.8%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy based on the presence of HLM were 64%, 83%, 91%, 45.5%, and 69.1%, respectively.
CONCLUSION
The study of peritoneal fluids obtained laparoscopically from women undergoing evaluation for endometriosis may identify patients with the disease.
Topics: Adolescent; Adult; Ascitic Fluid; Cytodiagnosis; Endometriosis; Female; Humans; Middle Aged; Peritoneal Lavage; Sensitivity and Specificity; Young Adult
PubMed: 33555651
DOI: 10.1002/dc.24721 -
Journal of Investigative Surgery : the... Jun 2022The role of Ca-125 in endometrial cancer is not fully known. Some authors have reported high Ca-125 levels in patients with recurrent or advanced endometrial cancer,...
Correlation of Preoperative Serum and Intraoperative Peritoneal Lavage Fluid Ca-125 Levels with Postoperative Tumor Histology in Patients with Endometrial Cancer: A Prospective-Controlled Study.
BACKGROUND
The role of Ca-125 in endometrial cancer is not fully known. Some authors have reported high Ca-125 levels in patients with recurrent or advanced endometrial cancer, whereas others have stated that Ca-125 levels and the advance of the disease were not correlated in endometrial cancer. This makes it inevitable for clinicians to search for different measurement methods or interpretation of the present tumor markers. The aim of this study was to evaluate the relationship between Ca-125 values of the serum and abdominal lavage fluid and postoperative histopathological parameters in patients with endometrial carcinoma.
METHODS
The study included patients who were diagnosed with endometrial cancer in the Gynecology Clinic and were planned to undergo surgery. The correlations of clinicopathological parameters with preoperative values of Ca-125 measured from serum and abdominal lavage fluid were investigated. The Spearman correlation test was applied in the analysis of correlations of serum and abdominal lavage fluid Ca-125 values with postoperative tumor characteristics.
RESULTS
The serum Ca-125 values were determined to be positively correlated with surgical stage, tumor diameter, and lymph node involvement (p = 0.03; p = 0.04; and p = 0.01, respectively). No correlation was determined between tumor grade and serum Ca-125 level. The level of Ca-125 in the abdominal lavage fluid was observed to be correlated with surgical stage and tumor grade, but not with tumor diameter or lymph node involvement (p = 0.01, p = 0.04, respectively).
CONCLUSIONS
The value of Ca-125 in the abdominal lavage fluid has a positive correlation with the surgical stage and tumor grade in patients with endometrial carcinoma.
Topics: Ascitic Fluid; Biomarkers, Tumor; CA-125 Antigen; Endometrial Neoplasms; Female; Humans; Neoplasm Staging; Peritoneal Lavage; Preoperative Period; Prospective Studies
PubMed: 34991426
DOI: 10.1080/08941939.2021.2024307 -
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 -
Annals of Surgical Oncology Apr 2021The clinical role of peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, partly due to its low sensitivity. This study...
BACKGROUND
The clinical role of peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, partly due to its low sensitivity. This study aimed to develop a new biomarker, defined as peritoneal lavage tumor DNA (ptDNA), using DNAs extracted from peritoneal lavage samples from patients with PDAC.
METHODS
Samples were collected intraoperatively from 89 PDAC patients who underwent pancreatectomy between 2012 and 2017. Droplet digital polymerase chain reaction (PCR) was used to measure ptDNA for detection of KRAS mutations. The ptDNA status and clinical characteristics were retrospectively evaluated.
RESULTS
Positive ptDNA was found in 41 patients, including all 9 patients positive for CY (CY+) and 32 patients negative for CY (CY-). The mutant allele frequency was significantly higher in the CY+ patients than in the CY- patients. The disease-free survival (DFS) and overall survival (OS) were significantly poorer in the high-ptDNA group than in the low-ptDNA group (median DFS, 11.0 vs. 18.8 months; p = 0.007; median OS, 28.7 vs not reached; p = 0.001). The survival curves of DFS and OS in the CY+ group were almost equal to those in the CY- and high-ptDNA group. In a multivariable analysis, ptDNA was an independent predictive factor for DFS (p = 0.025) and OS (p = 0.047). The estimated cumulative incidence of peritoneal recurrence was 45.5% in the high-ptDNA group. The ptDNA biomarker had a much higher sensitivity for peritoneal recurrence than CY, whereas CY had higher specificity.
CONCLUSIONS
As a promising biomarker, ptDNA may predict poor prognosis and peritoneal recurrence in PDAC, resolving the controversy surrounding CY.
Topics: Biomarkers; Carcinoma, Pancreatic Ductal; DNA; Humans; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Peritoneal Lavage; Peritoneal Neoplasms; Prognosis; Retrospective Studies
PubMed: 32875467
DOI: 10.1245/s10434-020-08990-w -
Journal of Laparoendoscopic & Advanced... Feb 2020Although gastric carcinoma is the fifth most commonly diagnosed cancer, optimal treatment of perforated cancer remains debated. The study was conducted according to...
Although gastric carcinoma is the fifth most commonly diagnosed cancer, optimal treatment of perforated cancer remains debated. The study was conducted according to the guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. An electronic systematic search was conducted using MEDLINE databases (PubMed, EMBASE, and Web of Science) by matching the terms "perforated gastric cancer," "gastric cancer perforated," "perforation AND gastric cancer," and "perforated gastric tumor." Fifteen studies published between 1995 and 2018 and including 964 patients matched the inclusion criteria for this systematic review. There were 4 publications from Japan, 3 from Turkey, and 1 from China, Germany, Hong Kong, Italy, Nepal, Serbia, South Korea, and Taiwan, respectively. The sample size of the individual studies ranged from 8 to 514 patients. Perforated gastric carcinoma was rare and more prevalent in elderly males, preoperative diagnosis was uncommon, and the distal stomach was most frequently involved. Mortality was 11.4% and 1.9%, respectively, in one-stage versus two-stage gastrectomy ( = .010). Curative treatment by omental patch repair and staged gastrectomy yielded acceptable 5-year survival rates. There were no significant differences in the recurrence rate and pattern between perforated and nonperforated gastric cancer if a curative operation was performed. Use of laparoscopy was mentioned only in one study. Future studies should evaluate the role of laparoscopic surgery and clarify the indications for hyperthermic intraperitoneal chemotherapy and extensive peritoneal lavage protocols to decrease gastric cancer cell shed in the surgical field and increase long-term survival.
Topics: Gastrectomy; Humans; Hyperthermia, Induced; Laparoscopy; Neoplasm Recurrence, Local; Peritoneal Lavage; Peritonitis; Prevalence; Prognosis; Recurrence; Stomach Neoplasms; Survival Rate; Treatment Outcome
PubMed: 31545122
DOI: 10.1089/lap.2019.0507 -
World Journal of Surgery Mar 2023The prognostic impact of positive peritoneal lavage cytology on pancreatic cancer is unclear. Therefore, this study aimed to evaluate its impact in resectable pancreatic...
BACKGROUND
The prognostic impact of positive peritoneal lavage cytology on pancreatic cancer is unclear. Therefore, this study aimed to evaluate its impact in resectable pancreatic body and tail cancer.
METHODS
Between January 2006 and December 2019, 97 patients with pancreatic body and tail cancer underwent peritoneal lavage cytology and curative resection at our institution. We analyzed the impact of positive peritoneal lavage cytology on clinicopathological factors and on the prognosis of pancreatic body and tail cancer.
RESULTS
Malignant cells were detected in 14 patients (14.4%) using peritoneal lavage cytology. In these patients, the tumor diameter was significantly larger (p < 0.001) and anterior serosal invasion (p = 0.034), splenic artery invasion (p = 0.013), lympho-vessel invasion (p = 0.025), and perineural invasion (p = 0.008) were significantly more frequent. The R1 resection rate was also significantly higher in patients with positive peritoneal lavage cytology than in negative patients (p = 0.015). Positive peritoneal lavage cytology had a significantly poor impact on overall survival (p = 0.001) and recurrence-free survival (p < 0.001). This cytology was also an independent poor prognostic factor for recurrence (p = 0.022) and was associated with peritoneal dissemination and liver metastasis.
CONCLUSIONS
Positive peritoneal lavage cytology is considered to be indicative of more systemic disease in patients with resectable pancreatic body and tail cancer than in patients with negative peritoneal lavage cytology. Early detection of pancreatic cancer before it develops micrometastases is important to improve prognosis, and CY+ patients require more intensive multimodality treatment than standard treatment for resectable pancreatic cancer.
Topics: Humans; Peritoneal Lavage; Prognosis; Retrospective Studies; Peritoneal Neoplasms; Pancreatic Neoplasms
PubMed: 36357802
DOI: 10.1007/s00268-022-06818-0 -
Journal of Obstetrics and Gynaecology :... Apr 2020The aim of this study was to evaluate cytokine levels (IL-2, IL-8, TNF-α, IL-5, IL-6 and IL-10) in the peritoneal fluid in non-neoplastic tumours, benign ovarian...
The aim of this study was to evaluate cytokine levels (IL-2, IL-8, TNF-α, IL-5, IL-6 and IL-10) in the peritoneal fluid in non-neoplastic tumours, benign ovarian neoplasms and malignant ovarian neoplasms. Peritoneal fluid or ascites was collected from 117 patients with neoplastic and non-neoplastic ovarian tumours. Cytokine levels were assessed by ELISA. The unpaired groups were compared by the Kruskal-Wallis test with Dunn's post-test. Higher IL-6 levels were found in malignant neoplasms when compared to non-neoplastic tumours (=.0241). There was no significant difference in the evaluation of other cytokines. Therefore, higher IL-6 levels in peritoneal fluid are related to the diagnosis of ovarian cancer. Further studies should be performed to evaluate the profile of cytokines in the peritoneal fluid of patients with ovarian tumours, and may be a new diagnostic strategy and a future target for treatment.Impact statement Cytokines can be dosed in both the serum and peritoneal fluid, and in the ascitic fluid of women with ovarian neoplasia. Elevated levels of IL-6 were found in the ascitic fluid of patients with malignant ovarian tumours. To our knowledge, this is the first study in the literature that evaluates a large panel of cytokines in the peritoneal fluid (and not only in ascites), comparing non-neoplastic tumours, benign neoplasms and malignant ovarian neoplasms. The cytokine dosage in the peritoneal fluid should be considered to map a profile of inflammatory cytokines that permeate the peritoneal cavity of patients with ovarian cancer. The dosage of these cytokines can be a potential pre-surgical tumour marker. In addition, a better understanding of the pattern of cytokines around ovarian neoplasia may be targeted for further studies in the development of new therapies for ovarian cancer.
Topics: Adolescent; Adult; Aged; Ascites; Ascitic Fluid; Biomarkers, Tumor; Child; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-2; Interleukin-5; Interleukin-8; Middle Aged; Ovarian Neoplasms; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 31476946
DOI: 10.1080/01443615.2019.1633516