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Langenbeck's Archives of Surgery Feb 2022In the last two decades, there has been a Copernican revolution in the decision-making for the treatment of Diverticular Disease.
BACKGROUND
In the last two decades, there has been a Copernican revolution in the decision-making for the treatment of Diverticular Disease.
PURPOSE
This article provides a report on the state-of-the-art of surgery for sigmoid diverticulitis.
CONCLUSION
Acute diverticulitis is the most common reason for colonic resection after cancer; in the last decade, the indication for surgical resection has become more and more infrequent also in emergency. Currently, emergency surgery is seldom indicated, mostly for severe abdominal infective complications. Nowadays, uncomplicated diverticulitis is the most frequent presentation of diverticular disease and it is usually approached with a conservative medical treatment. Non-Operative Management may be considered also for complicated diverticulitis with abdominal abscess. At present, there is consensus among experts that the hemodynamic response to the initial fluid resuscitation should guide the emergency surgical approach to patients with severe sepsis or septic shock. In hemodynamically stable patients, a laparoscopic approach is the first choice, and surgeons with advanced laparoscopic skills report advantages in terms of lower postoperative complication rates. At the moment, the so-called Hartmann's procedure is only indicated in severe generalized peritonitis with metabolic derangement or in severely ill patients. Some authors suggested laparoscopic peritoneal lavage as a bridge to surgery or also as a definitive treatment without colonic resection in selected patients. In case of hemodynamic instability not responding to fluid resuscitation, an initial damage control surgery seems to be more attractive than a Hartmann's procedure, and it is associated with a high rate of primary anastomosis.
Topics: Anastomosis, Surgical; Colostomy; Diverticulitis; Diverticulitis, Colonic; Humans; Intestinal Perforation; Laparoscopy; Peritoneal Lavage; Peritonitis
PubMed: 34557938
DOI: 10.1007/s00423-021-02288-5 -
International Journal of Surgery... Nov 2023Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing...
BACKGROUND
Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing the procedure's diagnostic accuracy, we aimed to systematically review the literature on operative techniques, followed by peritoneal lavage fluid assessment in gastric cancer patients. Specifically, we sought to indicate the most common characteristics of the procedure and cytological evaluation.
METHODS
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol for this systematic review was registered on PROSPERO database (CRD: 42022306746). On September 2022, a search was carried out using Embase, Medline ALL, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection.
RESULTS
The search identified 1632 studies on staging laparoscopy and 2190 studies on peritoneal fluid assessment. Some 212 studies were included. Open Hasson was the method of choice in accessing the peritoneal cavity in 65% of the studies, followed by establishing a pneumoperitoneum at 10-12 mmHg in 52% of reports. Most frequently, the patient was positioned supine (70%), while a 30° scope and three ports were used to assess the peritoneal cavity clockwise (72%, 77%, and 85%, respectively). Right and left upper abdomen quadrants were the predominant area of laparoscopic exploration (both 65%), followed by the primary tumor region (54%), liver and pelvis (both 30%), and small bowel and spleen (19% and 17%, respectively). Regions of peritoneal lavage and aspiration were limited to the pelvis (50%), followed by right and left upper abdomen quadrants (37.5% and 50%, respectively). No studies compared different methods of operative techniques or analysis of ascites/fluid.
CONCLUSIONS
This study indicates a high heterogeneity in the technique of staging laparoscopy and peritoneal fluid assessment in gastric cancer patients. Further research and initiatives to reach a consensus on the standardization of the procedure are warranted.
Topics: Humans; Stomach Neoplasms; Ascitic Fluid; Neoplasm Staging; Laparoscopy; Peritoneal Lavage
PubMed: 37581636
DOI: 10.1097/JS9.0000000000000632 -
The Journal of Clinical Investigation Dec 2021Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms...
Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms predict mortality in different infections, and anti-MIF antibody improves survival in experimental models when administered 8 hours after infectious insult. The recent description of a second MIF superfamily member, D-dopachrome tautomerase (D-DT/MIF-2), prompted closer investigation of MIF-dependent responses. We subjected Mif-/- and Mif-2-/- mice to polymicrobial sepsis and observed a survival benefit with Mif but not Mif-2 deficiency. Survival was associated with reduced numbers of small peritoneal macrophages (SPMs) that, in contrast to large peritoneal macrophages (LPMs), were recruited into the peritoneal cavity. LPMs produced higher quantities of MIF than SPMs, but SPMs expressed higher levels of inflammatory cytokines and the MIF receptors CD74 and CXCR2. Adoptive transfer of WT SPMs into Mif-/- hosts reduced the protective effect of Mif deficiency in polymicrobial sepsis. Notably, MIF-2 lacks the pseudo-(E)LR motif present in MIF that mediates CXCR2 engagement and SPM migration, supporting a specific role for MIF in the recruitment and accumulation of inflammatory SPMs.
Topics: Animals; Cytokines; Disease Models, Animal; Female; Flow Cytometry; Gene Expression Profiling; Inflammation; Intramolecular Oxidoreductases; Leukocyte Count; Macrophage Migration-Inhibitory Factors; Macrophages; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peritoneal Lavage; Phenotype; Protein Binding; RNA-Seq; Sepsis; Signal Transduction
PubMed: 34850744
DOI: 10.1172/JCI127171 -
Anesthesiology Jul 2021Sepsis is one of the leading causes of mortality in intensive care units, and sedation in the intensive care unit during sepsis is usually performed intravenously. The...
BACKGROUND
Sepsis is one of the leading causes of mortality in intensive care units, and sedation in the intensive care unit during sepsis is usually performed intravenously. The inhalative anesthetic sevoflurane has been shown to elicit protective effects in various inflammatory studies, but its role in peritonitis-induced sepsis remains elusive. The hypothesis was that sevoflurane controls the neutrophil infiltration by stabilization of hypoxia-inducible factor 1α and elevated adenosine A2B receptor expression.
METHODS
In mouse models of zymosan- and fecal-induced peritonitis, male mice were anesthetized with sevoflurane (2 volume percent, 30 min) after the onset of inflammation. Control animals received the solvent saline. The neutrophil counts and adhesion molecules on neutrophils in the peritoneal lavage of wild-type, adenosine A2B receptor -/-, and chimeric animals were determined by flow cytometry 4 h after stimulation. Cytokines and protein release were determined in the lavage. Further, the adenosine A2B receptor and its transcription factor hypoxia-inducible factor 1α were evaluated by real-time polymerase chain reaction and Western blot analysis 4 h after stimulation.
RESULTS
Sevoflurane reduced the neutrophil counts in the peritoneal lavage (mean ± SD, 25 ± 17 × 105vs. 12 ± 7 × 105 neutrophils; P = 0.004; n = 19/17) by lower expression of various adhesion molecules on neutrophils of wild-type animals but not of adenosine A2B receptor -/- animals. The cytokines concentration (means ± SD, tumor necrosis factor α [pg/ml], 523 ± 227 vs. 281 ± 101; P = 0.002; n = 9/9) and protein extravasation (mean ± SD [mg/ml], 1.4 ± 0.3 vs. 0.8 ± 0.4; P = 0.002; n = 12/11) were also lower after sevoflurane only in the wild-type mice. Chimeric mice showed the required expression of the adenosine A2B receptor on the hematopoietic and nonhematopoietic compartments for the protective effects of the anesthetic. Sevoflurane induced the expression of hypoxia-inducible factor 1α and adenosine A2B receptor in the intestine, liver, and lung.
CONCLUSIONS
Sevoflurane exerts various protective effects in two murine peritonitis-induced sepsis models. These protective effects were linked with a functional adenosine A2B receptor.
Topics: Anesthetics, Inhalation; Animals; Disease Models, Animal; Hypoxia-Inducible Factor 1; Male; Mice; Mice, Inbred C57BL; Peritonitis; Receptor, Adenosine A2B; Sepsis; Sevoflurane; Signal Transduction
PubMed: 33914856
DOI: 10.1097/ALN.0000000000003788 -
World Journal of Clinical Cases Jan 2023Necrotizing or severe pancreatitis represents approximately 10%-20% of acute pancreatitis. 30%-40% of patients with acute necrotizing pancreatitis (ANP) will develop...
Necrotizing or severe pancreatitis represents approximately 10%-20% of acute pancreatitis. 30%-40% of patients with acute necrotizing pancreatitis (ANP) will develop debris infection through translocation of intestinal microbial flora. Infected ANP constitutes a serious clinical condition and is complicated by severe sepsis with high mortality rates of up to 40% despite progress in current intensive care. The timely detection of sepsis is crucial. The Quick Sequential Organ Failure Assessment score, procalcitonin levels > 1.8 ng/mL and increased lactates > 2 mmol/L (> 18 mg/dL), indicate the need for urgent management. The escalated step-by-step management protocol starts with broad-spectrum antibiotics, percutaneous drainage or endoscopic management, and ends with surgical management if needed. The latter includes necrosectomy (either laparoscopic or traditional open surgery), peritoneal lavage and extensive drainage. This management protocol increases the chance of survival to approximately 60% in patients with otherwise fatal cases. Any treatment choice must be individualized, and the timing is critical.
PubMed: 36686342
DOI: 10.12998/wjcc.v11.i2.482 -
Annals of Medicine and Surgery (2012) Dec 2023
PubMed: 38098572
DOI: 10.1097/MS9.0000000000001444 -
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 -
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 -
Frontiers in Immunology 2022Polyphosphates are linear polymers of inorganic phosphates that exist in all living cells and serve pleiotropic functions. Bacteria produce long-chain polyphosphates,...
Polyphosphates are linear polymers of inorganic phosphates that exist in all living cells and serve pleiotropic functions. Bacteria produce long-chain polyphosphates, which can interfere with host defense to infection. In contrast, short-chain polyphosphates are released from platelet dense granules and bind to the chemokine CXCL4. Here, we report that long-chain polyphosphates induced the release of CXCL4 from mouse bone marrow-derived macrophages and peritoneal macrophages in a dose-/time-dependent fashion resulting from an induction of CXCL4 mRNA. This polyphosphate effect was lost after pre-incubation with recombinant exopolyphosphatase (PPX) Fc fusion protein, demonstrating the potency of long chains over monophosphates and ambient cations. In detail, polyphosphate chains >70 inorganic phosphate residues were required to reliably induce CXCL4. Polyphosphates acted independently of the purinergic P2Y1 receptor and the MyD88/TRIF adaptors of Toll-like receptors. On the other hand, polyphosphates augmented LPS/MyD88-induced CXCL4 release, which was explained by intracellular signaling convergence on PI3K/Akt. Polyphosphates induced Akt phosphorylation at threonine-308. Pharmacologic blockade of PI3K (wortmannin, LY294002) antagonized polyphosphate-induced CXCL4 release from macrophages. Intratracheal polyphosphate administration to C57BL/6J mice caused histologic signs of lung injury, disruption of the endothelial-epithelial barrier, influx of Ly6G polymorphonuclear neutrophils, depletion of CD11cSiglecF alveolar macrophages, and release of CXCL4. Long-chain polyphosphates synergized with the complement anaphylatoxin, C5a, which was partly explained by upregulation of C5aR1 on myeloid cells. C5aR1 mice were protected from polyphosphate-induced lung injury. C5a generation occurred in the lungs and bronchoalveolar lavage fluid (BALF) of polyphosphate-treated C57BL/6J mice. In conclusion, we demonstrate that polyphosphates govern immunomodulation in macrophages and promote acute lung injury.
Topics: Mice; Animals; Complement C5a; Anaphylatoxins; Platelet Factor 4; Polyphosphates; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Myeloid Differentiation Factor 88; Mice, Inbred C57BL; Immunologic Factors; Acute Lung Injury; Bacteria
PubMed: 36405694
DOI: 10.3389/fimmu.2022.980733 -
Molecular Medicine (Cambridge, Mass.) Jul 2023Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis...
BACKGROUND
Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study.
METHODS
IL-1β and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1β levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry.
RESULTS
Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH.
CONCLUSIONS
Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases.
Topics: Animals; Mice; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Lipopolysaccharides; Shock, Septic; Diabetes Mellitus, Type 2; Anti-Inflammatory Agents; Disease Models, Animal; Interleukin-1beta; Mice, Inbred C57BL
PubMed: 37400760
DOI: 10.1186/s10020-023-00671-0