RESUMO
Uncontrolled activation of tumor necrosis factor receptor-associated factor (TRAF) proteins may result in profound tissue injury by linking surface signals to cytokine release. Here we show that a ubiquitin E3 ligase component, Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by destabilizing a sentinel TRAF inhibitor, Fbxl2. Fbxo3 and TRAF protein in circulation positively correlated with cytokine responses in subjects with sepsis, and we identified a polymorphism in human Fbxo3, with one variant being hypofunctional. A small-molecule inhibitor targeting Fbxo3 was sufficient to lessen severity of cytokine-driven inflammation in several mouse disease models. These studies identified a pathway of innate immunity that may be useful to detect subjects with altered immune responses during critical illness or provide a basis for therapeutic intervention targeting TRAF protein abundance.
Assuntos
Proteínas F-Box/metabolismo , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Sepse/imunologia , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Animais , Ceco/imunologia , Ceco/cirurgia , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Motivos F-Box/genética , Proteínas F-Box/genética , Humanos , Imunomodulação , Inflamação/genética , Camundongos , Camundongos Endogâmicos C57BL , Polimorfismo Genético , Estabilidade Proteica , Infecções por Pseudomonas/genética , Pseudomonas aeruginosa/genética , RNA Interferente Pequeno/genética , Sepse/genética , Transgenes/genéticaRESUMO
BACKGROUND: Empty Pelvis Syndrome, subsequent to the removal of pelvic organs, results in the descent of the small bowel into an inflamed pelvic cavity, leading to the formation of adhesions and subsequent small bowel obstruction. However, no effective measures have been previously described. OBJECTIVE: Describe a simple and autologous solution to prevent "Empty Pelvis Syndrome," small bowel obstruction, and adhesions by utilizing the cecum to occlude the pelvis. DESIGN: Mobilization of the right colon to lower the cecum into the pelvic cavity to occlude the superior pelvic ring to some degree and changing the direction of the terminal ileum. SETTINGS: Hospital Universitario Fundación Jiménez Díaz, Department of General Surgery, Colorectal Service. PATIENTS: Eight anonymized patients were included in this study, each with varying colorectal pathologies. Patients were above 18 years old. MAIN OUTCOME MEASURES: Percent of blockage of the superior pelvic ring produced by the descended cecum recorded in percentage; the amount of small intestine descended past the superior pelvic ring recorded in cm. RESULTS: The mobilization of the cecum achieved partial occlusion of the superior pelvic ring. The descent of the small bowel beyond this landmark ranged from 0 to 4.9 cm. LIMITATIONS: Given the small number of patients included in this study, these results cannot be generalized to the whole of the population. A bladder emptying protocol prior to CT scans was not implemented, resulting in variations in measurements among patients. CONCLUSION: The cecum-to-pelvis technique is a simple method that can serve as an autologous solution to EPS (enteropelvic fistula) and help reduce postoperative complications such as SBO (small bowel obstruction) and adhesions. It is not essential to completely occlude the superior pelvic ring to achieve successful outcomes.
Assuntos
Ceco , Pelve , Complicações Pós-Operatórias , Humanos , Ceco/cirurgia , Pelve/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Aderências Teciduais/prevenção & controle , Aderências Teciduais/etiologia , Adulto , Obstrução Intestinal/prevenção & controle , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , IdosoRESUMO
AIM: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short-term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. METHOD: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. RESULTS: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). CONCLUSION: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.
Assuntos
Doença de Crohn , Íleo , Fenótipo , Complicações Pós-Operatórias , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Feminino , Estudos Retrospectivos , Masculino , Adulto , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Pessoa de Meia-Idade , Íleo/cirurgia , Adulto Jovem , Ceco/cirurgia , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Laparoscopia/efeitos adversos , Duração da Cirurgia , Tempo de Internação/estatística & dados numéricos , Fatores de TempoRESUMO
BACKGROUND: Despite the minimally invasive approach and early rehabilitation, abdominal-perineal resection (APR) remains a procedure with high morbidity, notably due to postoperative trapped bowel ileus and perineal healing complications. Several surgical techniques have been described for filling the pelvic void to prevent abscess formation and ileus by trapped bowel loop. OBJECTIVE: The aim of our study was to compare the post APR complications for cancer of two of these techniques, omentoplasty and cecal mobilization, in a single-center study from an expert colorectal surgery center. PATIENTS: From 2012 to 2022, 84 patients were included, including 58 (69%) with omentoplasty and 26 (31%) with cecal mobilization. They all underwent APR at Bordeaux University Hospital Center. SETTINGS: A propensity score was used to avoid confounding factors as far as possible. Patient and procedure characteristics were initially comparable. RESULTS: The 30-day complication rate was significantly higher in the cecal mobilization group (53.8% vs. 5.2% p < 0.01), as was the rate of pelvic abscess (34.6% vs. 0% p < 0.001). CONCLUSION: These findings suggest that, when feasible, omentoplasty should be considered the preferred method for pelvic reconstruction following APR.
Assuntos
Ceco , Omento , Complicações Pós-Operatórias , Protectomia , Pontuação de Propensão , Humanos , Feminino , Masculino , Omento/cirurgia , Pessoa de Meia-Idade , Idoso , Ceco/cirurgia , Protectomia/efeitos adversos , Protectomia/métodos , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
An 8-year-old cat was presented for an acute history of anorexia, marked abdominal pain, and hyperthermia. Ultrasonography showed a cecal perforation with focal steatitis and adjacent free gas bubbles, consistent with focal peritonitis. Surgery confirmed the imaging findings. An enterectomy was performed with the removal of the cecum and ileocolic valve, and anastomosis between the ileum and colon was performed. Histology revealed transmural enteritis and chronic severe pyogranulomatous peritonitis with intralesional plant fragments.
Assuntos
Doenças do Gato , Doenças do Ceco , Perfuração Intestinal , Ultrassonografia , Animais , Gatos , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/cirurgia , Doenças do Gato/diagnóstico , Doenças do Ceco/veterinária , Doenças do Ceco/diagnóstico por imagem , Doenças do Ceco/cirurgia , Ceco/diagnóstico por imagem , Ceco/cirurgia , Ceco/lesões , Perfuração Intestinal/veterinária , Perfuração Intestinal/cirurgia , Perfuração Intestinal/diagnóstico por imagem , Peritonite/veterinária , Peritonite/diagnóstico por imagem , Peritonite/etiologia , Ultrassonografia/veterináriaRESUMO
Inflammation accompanies most pathological processes, while the lymphatic system takes part in both the development and resolution of inflammation. We studied the contractile function of rat lymph nodes after cecal ligation and puncture (CLP). In 24 h after CLP, the mesenteric lymph nodes were removed and placed in the myograph chamber. After CLP, the lymph nodes showed lower tension than lymph nodes from sham-operated animals (control). The expression of inducible NO synthase, cyclooxygenase-2, and cystathionine-γ-lyase was observed in the lymph nodes of CLP rats. NO, prostaglandins, and H2S formed during inflammation inhibited contractile activity of smooth muscle cells in the capsule of the lymph nodes, which manifested itself in inhibition of phase contractions and a decrease in the tone of their capsule.
Assuntos
Sepse , Ratos , Animais , Inflamação , Contração Muscular , Punções , Ceco/cirurgiaRESUMO
OBJECTIVES: Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy. This study aims to explore the effects of maresin 1 (MaR1), an anti-inflammatory and pro-resolving lipid mediator, on sepsis-induced neuroinflammation and cognitive impairment. METHODS: Mice were randomly assigned to 4 groups: A sham group (sham operation+vehicle), a cecal ligation and puncture (CLP) group (CLP operation+vehicle), a MaR1-LD group (CLP operation+1 ng MaR1), and a MaR1-HD group (CLP operation+10 ng MaR1). MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation, then every other day for 7 days. Survival rates were monitored, and serum inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6] were measured 24 h after operation using enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed 7 days after operation using the Morris water maze (MWM) test and novel object recognition (NOR) task. The mRNA expression of TNF-α, IL-1ß, IL-6, inducible nitric oxide synthase (iNOS), IL-4, IL-10, and arginase 1 (Arg1) in cortical and hippocampal tissues was determined by real-time reverse transcription PCR (RT-PCR). Western blotting was used to determine the protein expression of iNOS, Arg1, signal transducer and activator of transcription 6 (STAT6), peroxisome proliferator-activated receptor gamma (PPARγ), and phosphorylated STAT6 (p-STAT6) in hippocampal tissue. Microglia activation was visualized via immunofluorescence. Mice were also treated with the PPARγ antagonist GW9662 to confirm the involvement of this pathway in MaR1's effects. RESULTS: CLP increased serum levels of TNF-α, IL-1ß, and IL-6, and reduced body weight and survival rates (all P<0.05). Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α, IL-1ß, and IL-6 levels, improved body weight, and increased survival rates (all P<0.05). No significant difference in efficacy was observed between the 2 doses (all P>0.05). MWM test and NOR task indicated that CLP impaired spatial learning, which MaR1 mitigated. However, GW9662 partially reversed MaR1's protective effects. Real-time RT-PCR results demonstrated that, compared to the sham group, mRNA expression of TNF-α, IL-1ß, and iNOS significantly increased in hippocampal tissues following CLP (all P<0.05), while IL-4, IL-10, and Arg1 showed a slight decrease, though the differences were not statistically significant (all P>0.05). Compared to the CLP group, both 1 ng and 10 ng MaR1 decreased TNF-α, IL-1ß, and iNOS mRNA expression in hippocampal tissues and increased IL-4, IL-10, and Arg1 mRNA expression (all P<0.05). Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group (P<0.05). Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group (both P<0.05). Western blotting results showed that, compared to the CLP group, both 1 ng and 10 ng MaR1 down-regulated the iNOS expression, while up-regulated the expression of Arg1, PPARγ, and p-STAT6 (all P<0.05). However, the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγ compared to the MaR1-LD group (all P<0.05). CONCLUSIONS: MaR1 inhibits the classical activation of hippocampal microglia, promotes alternative activation, reduces sepsis-induced neuroinflammation, and improves cognitive decline.
Assuntos
Ceco , Disfunção Cognitiva , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos , Sepse , Fator de Necrose Tumoral alfa , Animais , Camundongos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Sepse/complicações , Sepse/metabolismo , Ligadura , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Ceco/cirurgia , Masculino , Interleucina-6/metabolismo , Interleucina-1beta/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/etiologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Arginase/metabolismo , Punções/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologiaRESUMO
AIMS: Acute lung injury (ALI) induced by sepsis and its complications have high morbidity and mortality rates globally. The objective of this study was to enhance our understanding of the underlying mechanism of ALI by identifying potential splicing events that are regulated in this condition. MATERIALS AND METHODS: The CLP mouse model was utilized for mRNA sequencing, and the expression and splicing data were analyzed. Verification of the changes in expression and splicing induced by CLP was conducted using qPCR and RT-PCR. RESULTS: Our results showed that splicing-related genes were regulated, suggesting that splicing regulation may be a key mechanism in ALI. We also found that more than 2900 genes displayed alternative splicing in the lungs of mice with sepsis. Using RT-PCR, we verified that TLR4 and other genes had differential splicing isoforms in the lungs of mice with sepsis. We confirmed the presence of TLR4-s in the lungs of mice with sepsis using RNA-fluorescence in situ hybridization. CONCLUSION: Our results suggest that sepsis-induced ALI can significantly alter splicing in the lungs of mice. The list of DASGs and splicing factors is valuable for further study in the search for new treatment approaches for sepsis-induced ALI.
Assuntos
Lesão Pulmonar Aguda , Sepse , Camundongos , Animais , Processamento Alternativo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Hibridização in Situ Fluorescente , Pulmão/metabolismo , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Punções/efeitos adversos , Ligadura/efeitos adversos , Ceco/cirurgia , Ceco/metabolismo , Sepse/complicações , Sepse/genética , Sepse/metabolismoRESUMO
Sepsis results from a heavy-handed response to infection that may culminate in organ failure and death. Many patients who survive acute sepsis become immunosuppressed and succumb to opportunistic infections. Therefore, to be successful, sepsis immunotherapies must target both the initial and the protracted phase of the syndrome to relieve early immunopathology and late immunosuppression, respectively. Invariant NKT (iNKT) cells are attractive therapeutic targets in sepsis. However, repeated treatments with α-galactosylceramide, the prototypic glycolipid ligand of iNKT cells, result in anergy. We designed a double-hit treatment that allows iNKT cells to escape anergy and exert beneficial effects in biphasic sepsis. We tested the efficacy of this approach in the sublethal cecal ligation and puncture mouse model, which mirrors polymicrobial sepsis with progression to an immunosuppressed state. Septic mice were treated with [(C2S, 3S, 4R)-1-O-(α-d-galactopyranosyl)-N-tetracosanoyl-2-amino-1,3,4-nonanetriol] (OCH), a TH2-polarizing iNKT cell agonist, before they received α-galactosylceramide. This regimen reduced the morbidity and mortality of cecal ligation and puncture, induced a transient but robust IFN-γ burst within a proinflammatory cytokine/chemokine landscape, transactivated NK cells, increased MHC class II expression on macrophages, and restored delayed-type hypersensitivity to a model hapten, consistent with recovery of immunocompetence in protracted sepsis. Structurally distinct TH2-polarizing agonists varied in their ability to replace OCH as the initial hit, with their lipid chain length being a determinant of efficacy. The proposed approach effectively exploits iNKT cells' versatility in biphasic sepsis and may have translational potentials in the development of new therapies.
Assuntos
Imunoterapia/métodos , Células T Matadoras Naturais/imunologia , Sepse/imunologia , Células Th2/imunologia , Animais , Ceco/cirurgia , Células Cultivadas , Anergia Clonal , Modelos Animais de Doenças , Galactosilceramidas/imunologia , Humanos , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/transplante , Sepse/terapiaRESUMO
Sepsis is a life-threatening organ dysfunction caused by a dysfunctional host response to infection. Neutrophils play a protective role by releasing antibacterial proteins or by phagocytizing bacteria. However, excess neutrophils can induce tissue damage. Recently, a novel intercellular communication pathway involving extracellular vesicles (EVs) has garnered considerable attention. However, whether EVs secreted by macrophages mediate neutrophil recruitment to infected sites has yet to be studied. In this study, we assessed the chemotactic effect of EVs isolated from mouse Raw264.7 macrophages on mouse neutrophils and found that CXCL2 was highly expressed in these EVs. By regulating CXCL2 in Raw264.7 macrophages, we found that CXCL2 on macrophage EVs recruited neutrophils in vitro and in vivo. The CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway and induced tissue damage. This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.
Assuntos
Quimiocina CXCL2/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos/imunologia , NADPH Oxidase 4/metabolismo , Neutrófilos/imunologia , Proteína Quinase C/metabolismo , Sepse/imunologia , Animais , Ceco/cirurgia , Modelos Animais de Doenças , Doenças do Sistema Imunitário , Transtornos Leucocíticos , Camundongos , Camundongos Endogâmicos C57BL , Ativação de Neutrófilo , Transdução de SinaisRESUMO
Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.
Assuntos
Aloe , Emodina , Sepse , Camundongos , Animais , Emodina/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Punções/efeitos adversos , Ligadura/efeitos adversos , Sepse/tratamento farmacológico , Sepse/etiologia , Ceco/cirurgia , Modelos Animais de DoençasRESUMO
Winslow's foramen hernia, or Blandin's hernia, is a rare internal hernia with a non-specific clinical presentation and its diagnosis may be difficult. The hernia occurs across the omental hiatus, bounded by the inferior vena cava posteriorly and the portal triad anteriorly. CT imaging provides several diagnostic clues in this condition. Prompt surgical management allows reduction before complications arise. We present a case of caecal internal herniation through Winslow's foramen in a patient who underwent gastrojejunal bypass about ten years ago. Laparoscopy with reduction of the caecal bascule and closure of the foramen is performed successfully.
La hernie du foramen de Winslow, ou hernie de Blandin, est une hernie interne rare, avec une présentation clinique non spécifique et son diagnostic peut être difficile. La hernie se produit au travers de l'hiatus omental, limité par la veine cave inférieure en arrière et la triade portale en avant. L'imagerie médicale par tomodensitométrie nous fournit plusieurs indices diagnostiques dans cette pathologie. La prise en charge chirurgicale rapide permet une réduction avant la survenue de complications. Nous présentons un cas de hernie interne caecale par le foramen de Winslow chez un patient ayant bénéficié d'un bypass gastro-jéjunal une dizaine d'années auparavant. Une laparoscopie avec réduction de la bascule caecale et fermeture du foramen est réalisée avec succès.
Assuntos
Doenças do Ceco , Hérnia , Herniorrafia , Procedimentos de Cirurgia Plástica , Humanos , Doenças do Ceco/diagnóstico , Doenças do Ceco/cirurgia , Ceco/cirurgia , Hérnia/diagnóstico , Veia Cava Inferior/cirurgia , Herniorrafia/métodosRESUMO
Background/aim: The development of postoperative adhesion after abdominal surgery is sometimes a severe problem. Our study investigates the effectiveness of exogenous surfactant application in preventing adhesion development in the experimental adhesion model. Materials and methods: This randomized-controlled interventional study was carried out in the animal laboratory of Kahramanmaras Sütçü Imam University between March 1 and March 31, 2020. An experimental intra-abdominal adhesion model was established in 24 adult female rats by cecal abrasion. Rats were randomly divided into four groups. Groups I, II, and III were taken intraperitoneally as beractant, poractant, and calfactant applied groups, respectively. Group IV was the control group. Relaparotomy was performed in all groups on the 15th postoperative day, and intra-abdominal adhesions were scored macroscopically according to the Canbaz scoring system. In addition, the cecal regions were evaluated microscopically and scored according to the Zühlke microscopic classification system. The scores of the groups were compared statistically. Results: The Zühlke adhesion development score was significantly lower in the exogenous surfactant applied groups. In addition, when the surfactant-applied groups were compared among themselves, it was seen that the adhesion score in the beractant group was significantly better than the other surfactant types (p < 0.01). Conclusion: Our study results showed that prophylactic intraperitoneal surfactant application significantly reduced postoperative adhesion development, particularly beractant.
Assuntos
Complicações Pós-Operatórias , Tensoativos , Animais , Aderências Teciduais/prevenção & controle , Ratos , Feminino , Tensoativos/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Modelos Animais de Doenças , Produtos Biológicos/farmacologia , Fosfolipídeos/farmacologia , Ceco/cirurgiaRESUMO
Malignant tumor occurring in the inguinal region are relatively infrequent, and metastatic tumor is extremely rare. We report a case of inguinal hernial sac metastasis of cecal cancer resected with TAPP approach. The case is a 80's man. One year and 6 months after cecal cancer surgery, contrast-enhanced computer tomography(CT)examination revealed a solitary tumor in the right inguinal canal. We diagnosed inguinal hernia sac metastasis of cecal cancer and performed surgery. The mass in the hernia sac was resected with the TAPP approach. Histopathological findings were consistent with peritoneal metastasis directly to the inguinal hernia sac. The patient has been alive without 2 years after metastasectomy. It is necessary to treat patients with a history of malignant disease with keeping the possibility of inguinal hernia sac metastasis in mind.
Assuntos
Neoplasias do Ceco , Hérnia Inguinal , Masculino , Humanos , Hérnia Inguinal/cirurgia , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/patologia , Peritônio/patologia , Peritônio/cirurgia , Neoplasias do Ceco/cirurgia , Herniorrafia , Ceco/cirurgiaRESUMO
The patient was a 90-year-old man. He was referred to our department with a diagnosis of ascending colon cancer after lower gastrointestinal endoscopy for a positive stool occult blood test. Lower gastrointestinal endoscopy revealed a type 1 tumor 30 mm in the ascending colon and a type 3 tumor 50 mm in the cecum. Biopsy revealed Group 5(tub1)for the ascending colon lesion, but Group 2 for the cecum lesion. The patient was clinically diagnosed as having overlapping ascending colon cancer and cecum cancer, and a right hemicolectomy of the colon was performed. Histopathological examination revealed ascending colon cancer and primary malignant lymphoma of the cecum.
Assuntos
Neoplasias do Colo , Linfoma , Masculino , Humanos , Idoso de 80 Anos ou mais , Colo Ascendente/cirurgia , Colo Ascendente/patologia , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Ceco/cirurgia , BiópsiaRESUMO
Historically, murine models of inflammation in biomedical research have been shown to minimally correlate with genomic expression patterns from blood leukocytes in humans. In 2019, our laboratory reported an improved surgical sepsis model of cecal ligation and puncture (CLP) that provides additional daily chronic stress (DCS), as well as adhering to the Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines. This model phenotypically recapitulates the persistent inflammation, immunosuppression, and catabolism syndrome observed in adult human surgical sepsis survivors. Whether these phenotypic similarities between septic humans and mice are replicated at the circulating blood leukocyte transcriptome has not been demonstrated. Our analysis, in contrast with previous findings, demonstrated that genome-wide expression in our new murine model more closely approximated human surgical sepsis patients, particularly in the more chronic phases of sepsis. Importantly, our new model of murine surgical sepsis with chronic stress did not reflect well gene expression patterns from humans with community-acquired sepsis. Our work indicates that improved preclinical murine sepsis modeling can better replicate both the phenotypic and transcriptomic responses to surgical sepsis, but cannot be extrapolated to other sepsis etiologies. Importantly, these improved models can be a useful adjunct to human-focused and artificial intelligence-based forms of research in order to improve septic patients' morbidity and mortality.
Assuntos
Modelos Animais de Doenças , Leucócitos/metabolismo , Fenótipo , Sepse/genética , Transcriptoma , Adulto , Fatores Etários , Idoso , Animais , Ceco/cirurgia , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/metabolismo , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Punções , Sepse/sangue , Fatores SexuaisRESUMO
INTRODUCTION: Current surgical guidelines for the treatment of intra-abdominal sepsis recommend interventional source control as the key element of therapy, alongside resuscitation and antibiotic administration. Past trials attempted to predict the success of interventional source control to assess whether further interventional therapy is needed. However, no predictive score could be developed. MATERIALS AND METHODS: We utilized an established murine abdominal sepsis model, the cecal ligation and puncture (CLP), and performed a successful surgical source control intervention after full development of sepsis, the CLP-excision (CLP/E). We then sought to evaluate the success of the source control by characterizing circulating neutrophil phenotype and functionality 24 h postintervention. RESULTS: We showed a significant relative increase of neutrophils and a significant absolute and relative increase of activated neutrophils in septic mice. Source control with CLP/E restored these numbers back to baseline. Moreover, main neutrophil functions, the acidification of cell compartments, such as lysosomes, and the production of Tumor Necrosis Factor-alpha (TNF-α), were impaired in septic mice but restored after CLP/E intervention. CONCLUSIONS: Neutrophil characterization by phenotyping and evaluating their functionality indicates successful source control in septic mice and can serve as a prognostic tool. These findings provide a rationale for the phenotypic and functional characterization of neutrophils in human patients with infection. Further studies will be needed to determine whether a predictive score for the assessment of successful surgical source control can be established.
Assuntos
Neutrófilos , Sepse , Animais , Ceco/cirurgia , Modelos Animais de Doenças , Humanos , Ligadura , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/patologia , Sepse/patologiaRESUMO
Bacterial lipoprotein (BLP)-induced tolerance represents an essential regulatory mechanism during bacterial infection and has been shown to protect against microbial sepsis. This protection is generally attributed to BLP-tolerized monocytes/macrophages characterized by hyporesponsiveness in producing inflammatory cytokines and, simultaneously, an augmented antimicrobial activity. However, the contribution of polymorphonuclear neutrophils (PMNs), another major player in innate immunity against bacterial infection, to BLP tolerance-afforded protection against microbial sepsis has not been identified. In this study, we report that induction of BLP tolerance protected mice against cecal ligation and puncture-induced polymicrobial sepsis, with significantly improved survival. Importantly, BLP tolerization via i.p. injection triggered an early PMN recruitment even before bacterial infection and promoted further PMN influx into the infectious site (i.e., the peritoneal cavity upon cecal ligation and puncture-associated septic challenge). Notably, this early PMN influx was mediated by BLP tolerization-induced PMN chemoattractant CXCL2-formed concentration gradient between the circulation and peritoneal cavity. Critically, blockage of PMN influx with the CXCR2 antagonist SB225002 abolished BLP tolerance-afforded protection and rendered BLP-tolerized mice more vulnerable to microbial infection with impaired bacterial clearance and increased overall mortality. Thus, our results highlight that an early recruitment of PMNs in the infectious site, as an important cellular mechanism, contributes to BLP tolerance-afforded protection against microbial sepsis.
Assuntos
Neutrófilos/imunologia , Sepse/imunologia , Animais , Proteínas de Bactérias/imunologia , Ceco/cirurgia , Movimento Celular , Células Cultivadas , Quimiocina CXCL2/metabolismo , Modelos Animais de Doenças , Tolerância Imunológica , Imunidade Inata , Lipoproteínas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos de Fenilureia/farmacologia , Receptores de Interleucina-8B/antagonistas & inibidoresRESUMO
BACKGROUND: A history of abdominal surgery is associated with difficulty in colonoscopy insertion. Few studies have reported effective colonoscopy insertion for patients who underwent abdominal surgery due to stomach cancer. AIM: We aimed to compare the impact of supine position (SP) and left lateral position (LLP) as the starting position of colonoscopy insertion in patients who underwent abdominal surgery due to stomach cancer. METHODS: This was a prospective, randomized controlled trial. Patients undergoing colonoscopy for screening or post-polypectomy surveillance after gastrectomy due to stomach cancer were enrolled and randomized to the SP or LLP group as the starting position of colonoscopy insertion. All colonoscopic examinations were performed with a transparent cap. The primary outcome was to compare the cecal intubation time between the two groups. RESULTS: A total of 224 patients were enrolled. The mean cecal intubation time was not significantly different between the SP and LLP groups (364.5 s versus 306.9 s; p = 0.105). In patients with a lower body mass index (< 21 kg/m2) or who underwent gastrectomy within three years, the mean cecal intubation time of the LLP group was shorter than the SP group. In the multivariate analysis for the factors affecting to increase in the cecal intubation time (> 5 min), the starting position was not an independent factor. CONCLUSION: Either the SP or LLP could serve as a possible starting position of colonoscopy insertion for patients who underwent abdominal surgery due to stomach cancer.
Assuntos
Colonoscopia , Neoplasias Gástricas , Ceco/cirurgia , Gastrectomia , Humanos , Estudos Prospectivos , Neoplasias Gástricas/cirurgiaRESUMO
To evaluate the clinical features, surgical management, and prognosis of ileocecal duplication in children. A total of 115 patients diagnosed with ileocecal duplication at Beijing Children's Hospital between January 2010 and June 2021 were retrospectively reviewed. Ileocecal duplications were divided into ileal intraluminal (n = 41), ileal extraluminal (n = 24), ileocecal valve (n = 11), cecal intraluminal (n = 18), and cecal extraluminal (n = 3) types according to their locations. Median age at diagnosis was 9.5 (0.1-169.2) months. Intussusception was only observed preoperatively in patients with the ileal intraluminal (8/41), ileocecal valve (4/11), and cecal intraluminal (7/18) types (P = 0.004). Ileocecal resection and ileocolostomy and cyst excision without ileocecal resection were performed in 41 (35.7%) and 74 (64.3%) patients, respectively. The proportions of cyst excision without ileocecal resection performed in patients with different types were 78.0% (32/41), 91.7% (22/24), 27.3% (3/11), 27.8% (5/18), and 100.0% (3/3) (P < 0.001). Time of oral intake (P = 0.003) and hospital stay after surgery (P < 0.001) were significantly shorter in patients undergoing cyst excision without ileocecal resection. There were no significant differences in the complications, growth, and stool frequency (older than 4 years) between patients undergoing different surgical procedures. Regarding the stool consistency (older than 4 years), there was a lower proportion of dry stool in patients undergoing cyst excision (P = 0.008). CONCLUSIONS: Ileocecal duplications at specific locations are prone to intussusception and can influence the surgical procedure choice. At mid-term follow-up, the children's growth and defecation patterns do not seem to be affected by ileocecal resection. WHAT IS KNOWN: ⢠How to address ileocecal duplication has always been challenging in clinical management. ⢠Children who have an ileocecal resection can develop some early postoperative complications. WHAT IS NEW: ⢠Ileocecal duplications at specific locations are prone to intussusception and can influence the surgical procedure choice. ⢠Children's growth and defecation patterns do not seem to be affected by ileocecal resection.