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Journal of Blood Medicine 2019Bleeding remains one of the most serious complications of laparoscopic cholecystectomy and can increase mortality. Even if several patient-related and intraoperative...
Bleeding remains one of the most serious complications of laparoscopic cholecystectomy and can increase mortality. Even if several patient-related and intraoperative factors increase the risk of bleeding, complete hemostasis should be achieved at the end of each surgical procedure. Although irrigation is a standard step, its importance is often underestimated. This commentary highlights the efficacy of peritoneal lavage in identifying bleeding sources and the effect of saline temperature.
PubMed: 31695538
DOI: 10.2147/JBM.S215438 -
Cancers Mar 2023Despite intensive scientific efforts, the therapy of peritonitis is presently limited to symptomatic measures, including infectious source control and broad-spectrum...
Despite intensive scientific efforts, the therapy of peritonitis is presently limited to symptomatic measures, including infectious source control and broad-spectrum antibiotics. Promising therapeutic approaches to reduce morbidity and mortality are still missing. Within the early phase of abdominal sepsis, apoptosis of neutrophil granulocytes is inhibited, which is linked to tissue damage and septic shock. TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent to stimulate neutrophil apoptosis. However, the underlying mechanisms have not been elucidated so far. The objective of the present study was to characterize the molecular mechanisms of TRAIL-stimulated apoptosis in early abdominal sepsis. Therefore, the murine sepsis model Colon ascendens stent peritonitis (CASP) was applied in wild type (WT) and TRAIL knock-out (TRAIL-/-) C57/BL6j mice. Neutrophil granulocytes were isolated from spleen, blood, bone marrow, and peritoneal lavage using magnetic-activated cell sorting. Neutrophil maturation was analyzed by light microscopy, and apoptotic neutrophils were quantified by fluorescence-activated cell sorting (FACS). Western blot and FACS were used to investigate expression changes in apoptotic proteins and TRAIL receptors. The impact of TRAIL-induced apoptosis was studied in vitro. In septic mice (CASP 6 h), the number of neutrophils in the BM was reduced but increased in the blood and peritoneal lavage. This was paralleled by an increased maturation of neutrophils from rod-shaped to segmented neutrophils (right shift). In vitro, extrinsic TRAIL stimulation did not alter the apoptosis level of naïve neutrophils but stimulated apoptosis in neutrophils derived from septic WT and TRAIL-/- mice. Neutrophils of the bone marrow and spleen showed enhanced protein expression of anti-apoptotic Flip, c-IAP1, and McL-1 and reduced expression levels of pro-apoptotic Bax in neutrophils, which might correlate with apoptosis inhibition in these cells. CASP increased the expression of intrinsic TRAIL in neutrophils derived from the bone marrow and spleen. This might be explained by an increased expression of the TRAIL receptors DR5, DcR1, and DcR2 on neutrophils in sepsis. No differences were observed between septic or naïve WT and TRAIL-/- mice. In conclusion, the present study shows that neutrophil granulocytes are sensitive to TRAIL-stimulated apoptosis in the early stage of abdominal sepsis, emphasizing the promising role of TRAIL as a therapeutic agent.
PubMed: 36980658
DOI: 10.3390/cancers15061773 -
International Journal of Surgery Case... Nov 2021Enteric fever is one of the major public health problems mainly in developing countries. Gallbladder perforation is very unusual. Enteric fever rarely causes gallbladder...
INTRODUCTION AND IMPORTANCE
Enteric fever is one of the major public health problems mainly in developing countries. Gallbladder perforation is very unusual. Enteric fever rarely causes gallbladder perforation. We report a case of gallbladder perforation due to enteric fever in an adult patient.
CASE PRESENTATION
A 50-year-old female without any medical illness presented with a history of intermittent fever for two weeks and three days duration of severe abdominal pain. Upper abdominal tenderness and guarding were found in the abdominal examination. Ultrasonography showed thickening of the gallbladder wall and pericholecystic fluid collection. Magnetic resonance cholangiopancreatography revealed a distended gallbladder with sludge, diffuse wall thickening, and contained perforation with a mild amount of free fluid seen in the abdomen. With the diagnosis of type II gallbladder perforation, percutaneous ultrasonography-guided drainage was done. The culture of bile revealed positivity for Salmonella Typhi. Intra-venous antibiotic (ceftriaxone and gentamicin) was administered for 14 days. Four weeks later, cholecystectomy with peritoneal lavage was done. She was discharged on the 8th postoperative day.
CLINICAL DISCUSSION
Preoperative diagnosing of gallbladder perforation is challenging. The accurate treatment and precise timing of the surgery remain important. In most cases, cholecystectomy and abdominal lavage are adequate to treat gallbladder perforation.
CONCLUSIONS
Gallbladder perforation is a life-threatening surgical problem. The clinician should have a high index of awareness about this unusual surgical entity due to enteric fever and early diagnosis with prompt surgical intervention is necessary to improve patient outcomes.
PubMed: 34741857
DOI: 10.1016/j.ijscr.2021.106553 -
World Journal of Surgical Oncology Aug 2021The optimal treatment in patients with gastric cancer and peritoneal disease remains controversial. Some guidelines indicate palliative treatment only, while others...
BACKGROUND
The optimal treatment in patients with gastric cancer and peritoneal disease remains controversial. Some guidelines indicate palliative treatment only, while others consider surgical treatment in case of positive lavage cytology (CY+) or limited peritoneal disease. Here, we analyzed the role of peritoneal disease in patients with gastric cancer, and the prognostic relevance of response to neoadjuvant therapy.
METHODS
In this retrospective cohort analysis, we analyzed patients with adenocarcinoma of the stomach or esophago-gastric junction from a single center operated between 2011 and 2019. According to histology and lavage cytology, patients were classified into four risk groups: (A) no peritoneal disease, (B) CY+ who converted to negative lavage cytology (CY-) after neoadjuvant chemotherapy, (C) CY+ without conversion after chemotherapy, and (D) patients with visible peritoneal metastasis.
RESULTS
Overall, n = 172 patients were included. At initial presentation, n = 125 (73%) had no peritoneal disease, and about a third of patients (n = 47, 27%) had microscopic or macroscopic peritoneal disease. Among them, n = 14 (8%) were CY+ without visible peritoneal metastasis, n = 9 converted to CY- after chemotherapy, and in n = 5 no conversion was observed. Median overall survival was not reached in patients who had initially no peritoneal disease and in patients who converted after chemotherapy, resulting in 3-year survival rates of 65% and 53%. In contrast, median overall survival was reduced to 13 months (95% CI 8.7-16.7) in patients without conversion and was 16 months (95% CI 12-20.5) in patients with peritoneal metastasis without difference between the two groups (p = .364). The conversion rate from CY+ to CY- was significantly higher after neoadjuvant treatment with FLOT (5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel) compared to ECF (epirubicin, cisplatin, and 5-fluorouracil) (p = 0.027).
CONCLUSION
Conversion of CY+ to CY- after neoadjuvant chemotherapy with FLOT is a significant prognostic factor for a better overall survival. Surgical treatment in well-selected patients should therefore be considered. However, peritoneal recurrence remains frequent despite conversion, urging for a better local control.
Topics: Humans; Induction Chemotherapy; Neoplasm Recurrence, Local; Peritoneal Lavage; Prognosis; Retrospective Studies; Stomach Neoplasms
PubMed: 34404403
DOI: 10.1186/s12957-021-02351-x -
Journal For Immunotherapy of Cancer Nov 2020Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal...
BACKGROUND
Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC.
METHODS
PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay.
RESULTS
JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8 T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8 T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcriptional signatures within the tumor microenvironment. Notably, JX cooperates with immune checkpoint inhibitors (ICIs), anti-programmed death-1, anti-programmed death-ligand 1, and anti-lymphocyte-activation gene-3 to elicit a stronger anticancer immunity that eliminates peritoneal metastases and malignant ascites of colon cancer compared with JX or ICI alone.
CONCLUSIONS
Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.
Topics: Animals; Carcinoma; Colonic Neoplasms; Humans; Immune Checkpoint Inhibitors; Male; Mice; Oncolytic Viruses; Peritoneal Neoplasms; Rats; Vaccinia virus
PubMed: 33199510
DOI: 10.1136/jitc-2020-000857 -
Cells Dec 2021Tet methylcytosine dioxygenase 2 (Tet2) mediates demethylation of DNA. We here sought to determine the expression and function of Tet2 in macrophages upon exposure to...
Tet methylcytosine dioxygenase 2 (Tet2) mediates demethylation of DNA. We here sought to determine the expression and function of Tet2 in macrophages upon exposure to lipopolysaccharide (LPS), and in the host response to LPS induced lung and peritoneal inflammation, and during induced peritonitis. LPS induced expression in mouse macrophages and human monocytes in vitro, as well as in human alveolar macrophages after bronchial instillation in vivo. Bone marrow-derived macrophages from myeloid Tet2 deficient () mice displayed enhanced production of IL-1β, IL-6 and CXCL1 upon stimulation with several Toll-like receptor agonists; similar results were obtained with LPS stimulated alveolar and peritoneal macrophages. Histone deacetylation was involved in the effect of Tet2 on IL-6 production, whilst methylation at the promoter was not altered by Tet2 deficiency. mice showed higher IL-6 and TNF levels in bronchoalveolar and peritoneal lavage fluid after intranasal and intraperitoneal LPS administration, respectively, whilst other inflammatory responses were unaltered. induced stronger production of IL-1β and IL-6 by Tet2 deficient peritoneal macrophages but not in peritoneal lavage fluid of mice after in vivo intraperitoneal infection. mice displayed enhanced bacterial growth during peritonitis, which was associated with a reduced capacity of peritoneal macrophages to inhibit the growth of in vitro. Collectively, these data suggest that Tet2 is involved in the regulation of macrophage functions triggered by LPS and during infection.
Topics: Animals; Anti-Bacterial Agents; Chemokine CXCL1; DNA-Binding Proteins; Dioxygenases; Escherichia coli; Gene Expression Regulation; HEK293 Cells; Histone Deacetylases; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Ligands; Lipopolysaccharides; Lung; Macrophages; Mice; Models, Biological; Myeloid Cells; Nod2 Signaling Adaptor Protein; Peritonitis; Toll-Like Receptors
PubMed: 35011643
DOI: 10.3390/cells11010082 -
Cancers May 2021Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the...
Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-β1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients.
PubMed: 34065529
DOI: 10.3390/cancers13102505 -
Biomedicine & Pharmacotherapy =... Aug 2019Bilirubin is an endogenous substance derived from heme catabolism. In this study, we aimed to assess the anti-inflammatory activity of bilirubin, and to determine the...
Bilirubin is an endogenous substance derived from heme catabolism. In this study, we aimed to assess the anti-inflammatory activity of bilirubin, and to determine the mechanism thereof. The anti-inflammatory activity of bilirubin was evaluated using lipopolysaccharide (LPS)-treated peritoneal macrophages (PMs) and Raw264.7 cells, and mice with alum-induced peritonitis. The mRNA and proteins of NOD-like receptor family pyrin domain containing 3 (Nlrp3) and inflammatory cytokines were determined using qPCR and Western blotting, respectively. Distribution of phosphorylated (p) p65 [a NF-κB (nuclear factor-κB) subunit] in the cytoplasm and nucleus were evaluated by immunofluorescence analysis and electrophoretic mobility shift assay. Bilirubin prior to LPS treatment decreased protein expressions of Nlrp3, pro-interleukin (IL)-1β and mature IL-1β in PMs, whereas bilirubin post LPS treatment showed no effects. Bilirubin prior to LPS treatment dose-dependently repressed expressions of Nlrp3 and IL-1β, and inhibited translocation of p-p65 to nucleus in Raw264.7 cells. Bilirubin treatment decreased myeloperoxidase activity and reduced the levels of inflammatory cytokines (i.e., IL-1β, TNFα and IL-6) in lavage fluid in mice with alum-induced peritonitis. This was accompanied by a lower mortality rate. In addition, the mRNAs of Nlrp3 and IL-1β in peritoneal exudates cells were decreased, and the levels of p-p65 and mature IL-1β proteins were reduced. In conclusion, bilirubin acted on inflammation and alleviated alum-induced peritonitis through inactivation of Nlrp3 inflammasome.
Topics: Alum Compounds; Animals; Bilirubin; DNA; Inflammasomes; Interleukin-1beta; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Peritonitis; RAW 264.7 Cells; Signal Transduction
PubMed: 31121485
DOI: 10.1016/j.biopha.2019.108973 -
Journal of Immunology (Baltimore, Md. :... Jun 2021Cyclic nucleotides cAMP and cGMP are important regulators of immune cell functions. Phosphodiesterases (PDEs) hydrolyze cAMP and/or cGMP and, thus, play crucial roles in...
Cyclic nucleotides cAMP and cGMP are important regulators of immune cell functions. Phosphodiesterases (PDEs) hydrolyze cAMP and/or cGMP and, thus, play crucial roles in cyclic nucleotide homeostasis. Abnormal alterations of PDE expression have been implicated in several diseases. To understand the function of PDEs in macrophages, we screened for all PDE genes in both peritoneal and alveolar macrophages from C57BL/6J mice and found that PDE4B and PDE10A are highly induced by LPS. A number of PDE4 inhibitors have been used clinically for the treatment of inflammatory lung diseases. However, the role of PDE10A in inflammation is still poorly understood. We therefore investigated the role of PDE10A in macrophage inflammatory response in vitro and acute lung inflammation in vivo. We found that LPS induces a sustained PDE10A expression in macrophages, which is different from a transient induction by PDE4B. PDE10A inhibition blocked LPS-induced MCP-1 expression, but not TNF-α, whereas PDE4B inhibition blocked LPS-induced TNF-α expression, but not MCP-1. In addition, PDE10A inhibition or deficiency decreased LPS-induced HIF-1α protein expression and subsequently suppressed MCP-1 expression. In vivo, PDE10A expression was also elevated in lung tissue after LPS exposure. Global PDE10A knockout or systemic administration of the PDE10A inhibitor TP-10 in mice significantly suppressed inflammatory molecule levels in the lung tissue and bronchoalveolar lavage fluid as well as inflammatory cell infiltration. These findings show that PDE10A plays a critical role in lung inflammation by promoting the activation of resident macrophages and infiltration of neutrophils.
Topics: Administration, Inhalation; Animals; Female; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphoric Diester Hydrolases; Pneumonia
PubMed: 34117108
DOI: 10.4049/jimmunol.2001026 -
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