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Annals of Gastroenterological Surgery Nov 2022This study aimed to clarify the usefulness of tumor markers from peritoneal lavage in selecting patients with a high risk of recurrence and predicting site-specific...
AIM
This study aimed to clarify the usefulness of tumor markers from peritoneal lavage in selecting patients with a high risk of recurrence and predicting site-specific recurrence in patients with pancreatic cancer.
METHODS
The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 (sCEA/sCA 19-9) and paired peritoneal lavage CEA and CA 19-9 (pCEA/pCA 19-9) were measured in 90 patients with pancreatic cancer who underwent surgery. Using the cutoff values determined by maximally selected rank statistics for disease-free survival (DFS), the risk of recurrence and its patterns were evaluated in combination with different markers and different test specimens.
RESULTS
In univariate and multivariate analysis, an elevated pCA 19-9 level (>1.3 U/mL) was an independent prognostic marker for both DFS (hazard ratio [HR], 2.391; = .018) and overall survival (HR, 3.194; = .033). Combination analyses contributed to further stratification of a very high risk of recurrence. Of the 58 patients with resectable pancreatic cancer who underwent curative resection, elevated pCA19-9 was also associated with inferior DFS and overall survival (OS). Patients with elevated pCA 19-9 levels were more likely to have an earlier onset of peritoneal recurrence than those with normal pCA 19-9 levels ( = .048, Gehan-Breslow-Wilcoxon test).
CONCLUSION
pCA 19-9 is a reliable marker for predicting postoperative recurrence in patients with pancreatic cancer after surgery. Further risk stratification can be achieved by using combination assays. The combination of pCA 19-9 and sCA19-9 also serves as a predictor of recurrence site-specific recurrence.
PubMed: 36338582
DOI: 10.1002/ags3.12597 -
Cancer Reports (Hoboken, N.J.) Apr 2021Only few studies in literature have analyzed the clinical effects of peritoneal lavage status in biliary tract cancers. (Comparative Study)
Comparative Study
BACKGROUND
Only few studies in literature have analyzed the clinical effects of peritoneal lavage status in biliary tract cancers.
AIM
We aimed to assess the effect of cytology-positive peritoneal lavage on survival for patients with biliary tract cancer who underwent curative resection.
METHODS
The KHBO1701 study was a multi-institutional retrospective study that assessed the clinical effects of peritoneal lavage cytology in biliary tract cancers. Using clinicopathological data from 11 Japanese institutions, we compared long-term outcomes between patients with cytology-positive and cytology-negative peritoneal lavage.
RESULTS
Of 169 patients who underwent curative resection, 164 were cytology-negative, and five were cytology-positive. The incidence of portal invasion and preoperative carbohydrate antigen 19-9 levels were higher in the cytology-positive group than in the cytology-negative group. The incidence of peritoneal metastatic recurrence was also higher, and overall survival tended to be worse in the cytology-positive group. In contrast, recurrence-free survival was similar between the cytology-negative and cytology-positive groups.
CONCLUSIONS
The positive status of peritoneal lavage cytology could moderately affect the survival of patients with biliary tract cancers. Given that surgical resection is the only curative treatment option, it may be acceptable to resect biliary tract cancers without other non-curative factors, regardless of peritoneal lavage cytology status.
Topics: Aged; Biliary Tract Neoplasms; CA-19-9 Antigen; Disease-Free Survival; Female; Humans; Incidence; Japan; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peritoneal Lavage; Peritoneal Neoplasms; Peritoneum; Prognosis; Retrospective Studies
PubMed: 33283475
DOI: 10.1002/cnr2.1323 -
Theranostics 2021Peritonitis is one of the most common causes of sepsis, a serious syndrome characterized by a dysregulated systemic inflammatory response. Recent evidence suggests that...
Peritonitis is one of the most common causes of sepsis, a serious syndrome characterized by a dysregulated systemic inflammatory response. Recent evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as a proinflammatory mediator and could play an important role in the pathogenesis of sepsis. This work aims to analyze the role and the therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis. The level of extracellular GzmA as well as GzmA activity were analyzed in serum from healthy volunteers and patients with confirmed peritonitis and were correlated with the Sequential Organ Failure Assessment (SOFA) score. Peritonitis was induced in C57Bl/6 (WT) and GzmA mice by cecal ligation and puncture (CLP). Mice were treated intraperitoneally with antibiotics alone or in combination serpinb6b, a specific GzmA inhibitor, for 5 days. Mouse survival was monitored during 14 days, levels of some proinflammatory cytokines were measured in serum and bacterial load and diversity was analyzed in blood and spleen at different times. Clinically, elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen and GzmA did not affect bacterial replication in macrophages indicating that GzmA has no role in bacterial control. Analysis of GzmA in lymphoid cells following CLP showed that it was mainly expressed by NK cells. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα. Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis and provide solid evidences about its therapeutic potential for the treatment of this severe pathology.
Topics: Aged; Aged, 80 and over; Animals; Cytokines; Disease Models, Animal; Female; Granzymes; Humans; Inflammation Mediators; Interleukin-6; Killer Cells, Natural; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Molecular Targeted Therapy; Peritonitis; Precision Medicine; Sepsis; Serpins; Toll-Like Receptor 4
PubMed: 33664861
DOI: 10.7150/thno.49288 -
Journal of Inflammation Research 2023Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or...
PURPOSE
Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30-50%. Therefore, novel strategies to treat sepsis are urgently needed.
METHODS
Andrographolide (AD), the main active ingredient of , reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms.
RESULTS
Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity.
CONCLUSION
These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.
PubMed: 37822531
DOI: 10.2147/JIR.S422342 -
Pakistan Journal of Medical Sciences 2022To identify the percentage of ovarian cancers with positive peritoneal cytology and to correlate the positive cytology with the prognostic factors.
OBJECTIVES
To identify the percentage of ovarian cancers with positive peritoneal cytology and to correlate the positive cytology with the prognostic factors.
METHODS
This retrospective, cross-sectional study, evaluated the data of surgical specimens of malignant ovarian tumors, received in the Department of Pathology, Dow University of Health Sciences over a period of three years. The peritoneal cytology was correlated with these prognostic parameters: the size of the tumor, stage, capsular invasion, omental, and lymph node metastasis.
RESULTS
Eighty malignant ovarian tumors were diagnosed. Serous carcinoma was the most common ovarian tumor, diagnosed in 24(30.0%) cases, followed by endometrioid carcinoma in 17(21.25%) and Granulosa cell tumor in 11 (13.75%) cases. The mean age of the patients was 41.91 years (range 7-71 years). The mean size of the tumors was 10.03 cm (SD 5.62 cm). The ovarian capsular invasion was present in 27(33.75%) tumors. Peritoneal cytology was positive in 10/24 cases, with a detection rate of 41.66%. Omentum was involved in 12/34(35.29%) cases. Lymph node dissection was performed in three cases, two were reported as positive for metastasis. Peritoneal cytology significantly correlated with the tumor size (p=0.045), and with ovarian capsular invasion (p=0.054) and omental metastasis (p=0.052). Most of the tumors were staged as FIGO stage IA.
CONCLUSION
Peritoneal cytology correlates with the tumor size, stage, and omental metastasis of the malignant ovarian tumors. It should be routinely performed at the time of surgery for the optimal staging of the patients.
PubMed: 35035413
DOI: 10.12669/pjms.38.1.4393 -
Frontiers in Oncology 2021Gastric cancer with only peritoneal lavage cytology (GC-CY) is a special type of gastric cancer, which is defined as stage IV. The pre-treatment systemic...
Predictive Effect of Systemic Immune-Inflammation Index Combined With Prognostic Nutrition Index Score on Efficacy and Prognosis of Neoadjuvant Intraperitoneal and Systemic Paclitaxel Combined With Apatinib Conversion Therapy in Gastric Cancer Patients With Positive Peritoneal Lavage Cytology: A...
BACKGROUND
Gastric cancer with only peritoneal lavage cytology (GC-CY) is a special type of gastric cancer, which is defined as stage IV. The pre-treatment systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) are representative blood indexes of systemic inflammatory response and nutritional status. However, the clinical significance of combined detection of these two indexes is still unclear. This study aims to evaluate the clinical value of the new score system by combining SII and PNI (SII-PNI score) as a predictor of efficacy and prognosis after neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel combined with Apatinib conversion therapy for GC-CY patients.
METHODS
We registered a prospective clinical study involving 36 GC-CY patients from April 2018 to August 2019 (NCT03718624). All patients underwent re-laparoscopic exploration after treatment. According to free cancer cells (FCCs) status, these patients were divided into FCCs group and non-FCCs group. The SII-PNI score ranged from 0 to 2 as follows: score of 2, high SII (≥512.1) and low PNI (≤52.9); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI.
RESULTS
All patients underwent re-laparoscopic exploration after 3 cycles of NIPS paclitaxel and Apatinib conversion therapy. Among them, 28 cases (77.78%) were in non-FCCs group, and 8 cases (22.22%) were in FCCs group. The SII-PNI score of non-FCCs patients was significantly lower than that of FCCs patients (p=0.041). The prognosis of patients with high SII-PNI score was significantly worse than that of patients with low SII-PNI score (p<0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting overall survival and progression-free survival (p=0.001, 0.002).
CONCLUSION
Pretreatment SII-PNI score is an important predictor for the efficacy of GC-CY patients after NIPS paclitaxel combined with Apatinib conversion therapy, which can help to identify high-risk groups and predict prognosis.
PubMed: 35127498
DOI: 10.3389/fonc.2021.791912 -
Journal of Gastrointestinal Surgery :... Dec 2020Adhesion formation contributes to postoperative complications in abdominal and gynaecological surgery. Thus far, the prevention and treatment strategies have focused on...
BACKGROUND
Adhesion formation contributes to postoperative complications in abdominal and gynaecological surgery. Thus far, the prevention and treatment strategies have focused on mechanical barriers in solid and liquid form, but these methods are not in routine use. As autologous fat grafting has become popular in treatment of hypertrophic scars because of its immunomodulatory effects, we postulated that fat grafting could also prevent peritoneal adhesion through similar mechanisms.
METHODS
This was a control versus intervention study to evaluate the effect of fat grafting in the prevention on peritoneal adhesion formation. An experimental mouse model for moderate and extensive peritoneal adhesions was used (n = 4-6 mice/group). Adhesions were induced mechanically, and a free epididymal fat graft from wild type or CAG-DsRed mice was injected preperitoneally immediately after adhesion induction. PET/CT imaging and scaling of the adhesions were performed, and samples were taken for further analysis at 7 and 30 days postoperation. Macrophage phenotyping was further performed from peritoneal lavage samples, and the expression of inflammatory cytokines and mesothelial layer recovery were analysed from peritoneal tissue samples.
RESULTS
Fat grafting significantly inhibited the formation of adhesions. PET/CT results did not show prolonged inflammation in any of the groups. While the expression of anti-inflammatory and anti-fibrotic IL-10 was significantly increased in the peritoneum of the fat graft-treated group at 7 days, tissue-resident and repairing M2 macrophages could no longer be detected in the fat graft at this time point. The percentage of the continuous, healed peritoneum as shown by Keratin 8 staining was greater in the fat graft-treated group after 7 days.
CONCLUSIONS
Fat grafting can inhibit the formation of peritoneal adhesions in mice. Our results suggest that fat grafting promotes the peritoneal healing process in a paracrine manner thereby enabling rapid regeneration of the peritoneal mesothelial cell layer.
Topics: Adipose Tissue; Animals; Humans; Mice; Peritoneal Diseases; Peritoneum; Positron Emission Tomography Computed Tomography; Postoperative Complications; Tissue Adhesions
PubMed: 31823326
DOI: 10.1007/s11605-019-04425-4 -
Cell Death & Disease Jan 2021Apoptosis inhibitor of macrophage (AIM) modulates the signaling in inflammatory responses, including infection, cancer, or other immune diseases. Recent studies suggest...
Apoptosis inhibitor of macrophage (AIM) modulates the signaling in inflammatory responses, including infection, cancer, or other immune diseases. Recent studies suggest that like interleukin-10 (IL-10), AIM is involved in alternatively activated (M2) macrophage polarization. We aimed to understand whether and how AIM is involved in IL-10-induced inhibition of inflammasome activation and resolution of inflammation. First, we demonstrated that IL-10 induced increases in mRNA and protein expression of AIM in murine bone marrow-derived macrophages (BMDM). In addition, genetic and pharmacologic inhibition of STAT3 (signal transducer and activator of transcription 3) reduced IL-10-induced AIM expression. We also found that IL-10-induced STAT3 activity enhanced the AIM promoter activity by directly binding the promoter of the AIM gene. Additionally, reduction of LPS/adenosine triphosphate (ATP)-induced IL-1β production and caspase-1 activation by IL-10 was reversed in BMDM from AIM mice. Treatment of BMDM from both wild type (WT) and IL-10 mice with recombinant AIM showed the inhibitory effects on IL-1β and IL-18 production and caspase-1 activation. Endogenous and exogenous AIM inhibited apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) speck formation. In LPS-induced acute peritonitis, inhibition of IL-1β and IL-18 production in peritoneal lavage fluid (PLF) and serum, reduction of caspase-1 activation in peritoneal macrophages, and reduction of numbers of neutrophils and peritoneal macrophages in PLF by administration of IL-10 were not evident in AIM mice. Our in vitro and in vivo data reveal a novel role of AIM in the inhibition of inflammasome-mediated caspase-1 activation and IL-1β and IL-18 production.
Topics: Animals; Apoptosis Regulatory Proteins; Cells, Cultured; Immunomodulation; Inflammasomes; Interleukin-10; Macrophages; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Receptors, Scavenger
PubMed: 33414479
DOI: 10.1038/s41419-020-03332-w -
Cells Sep 2020Cytokeratin-19 (CK19) has been proven to be commonly expressed by cancer cells in a variety of solid tumors and may serve as a suitable marker of metastases in gastric...
Cytokeratin-19 (CK19) has been proven to be commonly expressed by cancer cells in a variety of solid tumors and may serve as a suitable marker of metastases in gastric cancer (GC). Since objective assessment of peritoneal lavage or fluid for free cancer cells (FCC) is essential for clinical decision making in patients with GC, it is important to develop a quantitative and reproducible method for such evaluation. We assessed the possible application of One-Step Nucleic Acid amplification (OSNA) assay as a rapid method for FCC detection in intraoperative peritoneal lavage or fluid of GC patients. Seventy-eight intraoperative peritoneal lavage or fluid samples were eligible for the analysis by conventional cytology and OSNA examination. The concentration of CK19 mRNA in intraoperative peritoneal lavage and fluid was compared with the conventional cytological assessment. CK19 mRNA concentration was detected by OSNA assay. For peritoneal lavage samples, sensitivity and specificity were 83.3% and 87.8%, respectively. In peritoneal fluid, significantly higher CK19 values were observed in patients with serosal infiltration (medians: 100 copies/µL vs. 415.7 copies/µL; = 0.0335) and lymph node metastases (medians: 2.48 copies/µL vs. 334.8 copies/µL). OSNA assay turns out to be an objective, fast, and reproducible quantitative method of FCC assessment.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Intraoperative Period; Keratin-19; Male; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating; Nucleic Acid Amplification Techniques; Peritoneal Lavage; RNA, Messenger; Stomach Neoplasms
PubMed: 32992913
DOI: 10.3390/cells9102168 -
Frontiers in Immunology 2022(, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. Gasdermin D (GSDMD) is...
(, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. Gasdermin D (GSDMD) is involved in cytokine release and cell death, indicating an important role in controlling the microbial infection. This study investigated the protective role of GSDMD in mice infected with SEZ and examined the role of GSDMD in peritoneal macrophages in the infection. GSDMD-deficient mice were more susceptible to intraperitoneal infection with SEZ, and the white pulp structure of the spleen was seriously damaged in GSDMD-deficient mice. Although the increased proportion of macrophages did not depend on GSDMD in both spleen and peritoneal lavage fluid (PLF), deficiency of GSDMD caused the minor release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) during the infection . , SEZ infection induced more release of IL-1β, IL-18, and lactate dehydrogenase (LDH) in wild-type macrophages than in GSDMD-deficient macrophages. Finally, we demonstrated that pore formation and pyroptosis of macrophages depended on GSDMD. Our findings highlight the host defense mechanisms of GSDMD against SEZ infection, providing a potential therapeutic target in SEZ infection.
Topics: Mice; Animals; Pyroptosis; Phosphate-Binding Proteins; Streptococcus equi; Interleukin-18; Intracellular Signaling Peptides and Proteins; Macrophages; Cytokines
PubMed: 36311722
DOI: 10.3389/fimmu.2022.1005925