-
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 -
World Journal of Surgical Oncology May 2023This is a letter to the editor on a study by Jambor et al. on the role of staging laparoscopy in identifying occult and distant metastases in pancreatic adenocarcinoma...
This is a letter to the editor on a study by Jambor et al. on the role of staging laparoscopy in identifying occult and distant metastases in pancreatic adenocarcinoma patients. In this study, inclusion of staging laparoscopy as an adjunct to computed tomography resulted in an absolute risk reduction of 12.5% for non-therapeutic laparotomy. The study found no correlation between the presence of occult and distant metastases, and serum CA 19-9 level, tumour size or location, which was in significant contrast to a number of other studies. This was likely due to the smaller sample size of the study and restriction to a single high-volume referral centre. It is also noted that staging laparoscopy cannot detect vascular invasion, lymph node involvement and deep hepatic metastases. The sensitivity of peritoneal lavage cytology in detecting occult metastases is low as well. Inclusion of biomarkers like peritoneal lavage tumour DNA may improve sensitivity. Hence, even as this study adds to the evidence supporting staging laparoscopy, further studies on improving the sensitivity of staging laparoscopy are warranted.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Neoplasm Staging; Laparoscopy
PubMed: 37198653
DOI: 10.1186/s12957-023-02975-1 -
Frontiers in Immunology 2023Acute Respiratory Distress Syndrome (ARDS) is a devastating pulmonary inflammatory disorder, commonly precipitated by sepsis. Glucocorticoids are immunomodulatory...
Impaired alveolar macrophage 11β-hydroxysteroid dehydrogenase type 1 reductase activity contributes to increased pulmonary inflammation and mortality in sepsis-related ARDS.
BACKGROUND
Acute Respiratory Distress Syndrome (ARDS) is a devastating pulmonary inflammatory disorder, commonly precipitated by sepsis. Glucocorticoids are immunomodulatory steroids that can suppress inflammation. Their anti-inflammatory properties within tissues are influenced by their pre-receptor metabolism and amplification from inactive precursors by 11β-hydroxysteroid dehydrogenase type-1 (HSD-1). We hypothesised that in sepsis-related ARDS, alveolar macrophage (AM) HSD-1 activity and glucocorticoid activation are impaired, and associated with greater inflammatory injury and worse outcomes.
METHODS
We analysed broncho-alveolar lavage (BAL) and circulating glucocorticoid levels, AM HSD-1 reductase activity and Receptor for Advanced Glycation End-products (RAGE) levels in two cohorts of critically ill sepsis patients, with and without ARDS. AM HSD-1 reductase activity was also measured in lobectomy patients. We assessed inflammatory injury parameters in models of lung injury and sepsis in HSD-1 knockout (KO) and wild type (WT) mice.
RESULTS
No difference in serum and BAL cortisol: cortisone ratios are shown between sepsis patients with and without ARDS. Across all sepsis patients, there is no association between BAL cortisol: cortisone ratio and 30-day mortality. However, AM HSD-1 reductase activity is impaired in patients with sepsis-related ARDS, compared to sepsis patients without ARDS and lobectomy patients (0.075 v 0.882 v 0.967 pM/hr/10 AMs, p=0.004). Across all sepsis patients (with and without ARDS), impaired AM HSD-1 reductase activity is associated with defective efferocytosis (r=0.804, p=0.008) and increased 30-day mortality. AM HSD-1 reductase activity negatively correlates with BAL RAGE in sepsis patients with ARDS (r=-0.427, p=0.017). Following intra-tracheal lipopolysaccharide (IT-LPS) injury, HSD-1 KO mice demonstrate increased alveolar neutrophil infiltration, apoptotic neutrophil accumulation, alveolar protein permeability and BAL RAGE concentrations compared to WT mice. Caecal Ligation and Puncture (CLP) injury in HSD-1 KO mice results in greater peritoneal apoptotic neutrophil accumulation compared to WT mice.
CONCLUSIONS
AM HSD-1 reductase activity does not shape total BAL and serum cortisol: cortisone ratios, however impaired HSD-1 autocrine signalling renders AMs insensitive to the anti-inflammatory effects of local glucocorticoids. This contributes to the decreased efferocytosis, increased BAL RAGE concentrations and mortality seen in sepsis-related ARDS. Upregulation of alveolar HSD-1 activity could restore AM function and improve clinical outcomes in these patients.
Topics: Animals; Mice; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Glucocorticoids; Hydrocortisone; Cortisone; Macrophages, Alveolar; Receptor for Advanced Glycation End Products; Pneumonia; Hydroxysteroid Dehydrogenases; Anti-Inflammatory Agents; Respiratory Distress Syndrome; Sepsis
PubMed: 37180160
DOI: 10.3389/fimmu.2023.1159831 -
Cancer Diagnosis & Prognosis 2023Patients with pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal lavage cytology (CY) reportedly have poor prognoses. However, the value of diagnosis of...
BACKGROUND/AIM
Patients with pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal lavage cytology (CY) reportedly have poor prognoses. However, the value of diagnosis of suspicious for malignancy on CY is unknown. This study aimed to elucidate the prognostic impact of CY by focusing on CY subgroups.
PATIENTS AND METHODS
Data were collected from 231 resectable PDAC patients who underwent curative-intent resection. Patients were divided into three CY-based groups: negative (CY0), suspicious for malignancy (CY-S), and positive (CY1). Clinicopathological characteristics and prognostic factors were analyzed.
RESULTS
CY1 and CY-S were diagnosed in 7.8% and 3.9% of the patients, respectively. The CY1 group had significantly larger tumors and higher frequencies of distal tumors, anterior pancreatic tissue invasion, retropancreatic tissue invasion, and R1 resection than the CY0 group. Patient characteristics did not differ between the CY0 and CY-S groups. The CY1 group exhibited worse survival than the CY0 and CY-S groups (median survival time: 18.8 vs. 39.6 months, p=0.0021 and vs. 62.2 months, p=0.018). Multivariate analysis for survival indicated that a tumor size >2 cm, preoperative CA19-9 value >100 U/ml, CY1, lymph node metastasis, R1 resection, and lack of adjuvant chemotherapy were associated with poor prognosis. Both the CY1 and CY-S groups had higher frequencies of peritoneal recurrence than the CY0 group (50% vs. 11.8%, p<0.001 and 44.4% vs. 11.8%, p=0.019).
CONCLUSION
The prognosis of the CY1 group was poor. Although CY-S was associated with a higher frequency of peritoneal recurrence than CY0, the long-term outcomes of patients with surgical treatment were acceptable.
PubMed: 37168974
DOI: 10.21873/cdp.10221 -
Frontiers in Immunology 2023Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1...
INTRODUCTION
Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survival.
METHODS
RAW264.7 cells and peritoneal macrophages collected from C57BL/6 wild-type (WT) mice were exposed to 5- and 10-Gray (Gy) radiation. C57BL/6 WT and CIRP-/- mice underwent 10-Gy total body irradiation (TBI). TREM-1 expression on RAW264.7 cells and peritoneal macrophages in vitro and in vivo were evaluated by flow cytometry. eCIRP levels in cell culture supernatants and in peritoneal lavage isolated from irradiated mice were evaluated by Western blotting. We also evaluated 30-day survival in C57BL/6 WT, CIRP-/- and TREM-1-/- mice after 6.5-Gy TBI.
RESULTS
The surface protein and mRNA levels of TREM-1 in RAW264.7 cells were significantly increased at 24 h after 5- and 10-Gy radiation exposure. TREM-1 expression on peritoneal macrophages was significantly increased after radiation exposure in vitro and in vivo. eCIRP levels were significantly increased after radiation exposure in cell culture supernatants of peritoneal macrophages in vitro and in peritoneal lavage in vivo. Moreover, CIRP-/- mice exhibited increased survival after 6.5-Gy TBI compared to WT mice. Interestingly, TREM-1 expression on peritoneal macrophages in CIRP-/- mice was significantly decreased compared to that in WT mice at 24 h after 10-Gy TBI. Furthermore, 30-day survival in TREM-1-/- mice was significantly increased to 64% compared to 20% in WT mice after 6.5-Gy TBI.
CONCLUSION
Our data indicate that ionizing radiation increases TREM-1 expression in macrophages via the release of eCIRP, and TREM-1 contributes to worse survival after total body irradiation. Thus, targeting TREM-1 could have the potential to be developed as a novel medical countermeasure for radiation injury.
Topics: Animals; Mice; Inflammation; Macrophages; Mice, Inbred C57BL; Radiation Injuries; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 37168858
DOI: 10.3389/fimmu.2023.1151250 -
The American Surgeon Oct 2023Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared...
BACKGROUND
Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared to ultrasonography. However, whether both moderately hypotensive (systolic blood pressure [SBP] < 90 mmHg) and severely hypotensive (SBP < 70 mmHg) patients benefit from DPA/DPL is unclear. We hypothesized DPA/DPL used within the first hour increases risk of death for severely vs moderately hypotensive BTPs.
METHODS
The 2017-2019 Trauma Quality Improvement Program database was queried for BTPs ≥ 18 years old with hypotension upon arrival. We compared moderately and severely hypotensive groups. A multivariable logistic regression analysis was performed controlling for age, comorbidities, emergent operation, blood transfusions, and injury profile.
RESULTS
From 134 hypotensive patients undergoing DPA/DPL, 66 (49.3%) had severe hypotension. Patients in both groups underwent an emergent operation (43.9% vs 58.8%, = .09) in a similar amount of time (median, 42-min vs 54-min, = .11). Compared to the moderately hypotensive group, severely hypotensive patients had a higher rate and associated risk of death (84.8% vs 50.0%, < .001) (OR 5.40, CI 2.07-14.11, < .001). The strongest independent risk factor for death was age ≥ 65 (OR 24.81, CI 4.06-151.62, < .001).
DISCUSSION
Among all BTPs undergoing DPA/DPL within the first hour of arrival, an over 5-fold increased risk of death for patients with severe hypotension was demonstrated. As such, DPA/DPL within this group should be used with caution, particularly for older patients, as they may be better served by immediate surgeries. Future prospective research is needed to confirm these findings and elucidate the ideal DPA/DPL population in the modern era of ultrasonography.
Topics: Humans; Adolescent; Abdominal Injuries; Peritoneal Lavage; Peritoneum; Wounds, Nonpenetrating; Hypotension
PubMed: 37154296
DOI: 10.1177/00031348231175132 -
Advanced Science (Weinheim,... Jul 2023Peritoneal metastasis (PM) is the mostcommon form of distant metastasis and one of the leading causes of death in gastriccancer (GC). For locally advanced GC, clinical...
Peritoneal metastasis (PM) is the mostcommon form of distant metastasis and one of the leading causes of death in gastriccancer (GC). For locally advanced GC, clinical guidelines recommend peritoneal lavage cytology for intraoperative PM detection. Unfortunately, current peritoneal lavage cytology is limited by low sensitivity (<60%). Here the authors established the stimulated Raman molecular cytology (SRMC), a chemical microscopy-based intelligent cytology. The authors firstly imaged 53 951 exfoliated cells in ascites obtained from 80 GC patients (27 PM positive, 53 PM negative). Then, the authors revealed 12 single cell features of morphology and composition that are significantly different between PM positive and negative specimens, including cellular area, lipid protein ratio, etc. Importantly, the authors developed a single cell phenotyping algorithm to further transform the above raw features to feature matrix. Such matrix is crucial to identify the significant marker cell cluster, the divergence of which is finally used to differentiate the PM positive and negative. Compared with histopathology, the gold standard of PM detection, their SRMC method could reach 81.5% sensitivity, 84.9% specificity, and the AUC of 0.85, within 20 minutes for each patient. Together, their SRMC method shows great potential for accurate and rapid detection of PM from GC.
Topics: Humans; Peritoneal Neoplasms; Stomach Neoplasms; Peritoneal Lavage; Microscopy; Artificial Intelligence
PubMed: 37114845
DOI: 10.1002/advs.202300961 -
Annals of Medicine and Surgery (2012) Apr 2023Hydatid cyst is a parasitic disease that is transmitted from animals to humans caused by the larval stage , especially . A complication of a hydatid cyst of the liver is...
UNLABELLED
Hydatid cyst is a parasitic disease that is transmitted from animals to humans caused by the larval stage , especially . A complication of a hydatid cyst of the liver is its rupture, either traumatic or spontaneously.
CASE PRESENTATION
A 19-year-old male presented with an acute abdomen for 12 h. After clinical assessment, contrast-enhanced computed tomography showed a rupture of the anterior wall of the hepatic hydatid cyst with intra-abdominal and pelvic dissemination. Exploratory laparotomy was performed with the evacuation of the daughter cyst and peritoneal lavage. The patient recovered well and was discharged with albendazole therapy.
CLINICAL DISCUSSION
Hydatid cyst rupture is a rare but serious complication. Computed tomography has high sensitivity in demonstrating cyst rupture. The patient underwent laparotomy, where disseminated cysts were evacuated, and the anterior wall of the cyst was deroofed, along with the removal of a ruptured laminated membrane. Emergency surgery plus albendazole therapy are recommended protocols for cases like ours.
CONCLUSIONS
A patient from an endemic region with acute presentation of right upper quadrant pain can have spontaneously ruptured hydatidosis as a differential diagnosis. Intraperitoneal rupture and dissemination of hydatid cysts of the liver can be life-threatening if intervention is delayed. Immediate surgery is life-saving and prevents complications.
PubMed: 37113932
DOI: 10.1097/MS9.0000000000000383 -
Clinical Epigenetics Apr 2023The detection of peritoneal metastasis (PM) is limited by current imaging tools. In this prospective study, we aimed to evaluate the sensitivity and specificity of...
Peritoneal cell-free DNA as a sensitive biomarker for detection of peritoneal metastasis in colorectal cancer: a prospective diagnostic study: A prospective diagnostic study.
BACKGROUND
The detection of peritoneal metastasis (PM) is limited by current imaging tools. In this prospective study, we aimed to evaluate the sensitivity and specificity of peritoneal cell-free DNA (cfDNA) for diagnosis of PM.
METHODS
Colorectal cancer (CRC) patients with/without PM were enrolled. The cfDNA experimental personnel and statists were blinded to the diagnosis of PM. Ultradeep sequencing covering large genomic regions (35000X, Next-generation sequencing) of cfDNA in peritoneal lavage fluid (FLD) and matched tumor tissues was performed.
RESULTS
A total of 64 cases were recruited prospectively and 51 were enrolled into final analysis. In training cohort, 100% (17/17) PM patients obtained positive FLD cfDNA, comparing to 5/23 (21.7%) in patients without PM. Peritoneal cfDNA had a high sensitivity of 100% and specificity of 77.3% for diagnosis of PM (AUC: 0.95). In validation group of 11, 5/6 (83%) patients with PM obtained positive FLD cfDNA, comparing to 0/5 in non-PM (P = 0.031) with a sensitivity of 83.3% and specificity of 100%. Positive FLD cfDNA was associated with poor recurrence-free survival (P = 0.013) and was preceding radiographic evidence of recurrence.
CONCLUSIONS
Peritoneal cfDNA is a promising sensitive biomarker for earlier detection of PM in CRC than current radiological tools. It can potentially guide selection for targeted therapies and serve as a surrogate instead of laparoscopic explore in the future. Trial Registration Chinese Clinical Trial Registry at chictr.org.cn (ChiCTR2000035400). URL: http://www.chictr.org.cn/showproj.aspx?proj=57626.
Topics: Humans; Biomarkers, Tumor; Cell-Free Nucleic Acids; Colorectal Neoplasms; DNA Methylation; Mutation; Peritoneal Neoplasms; Prospective Studies
PubMed: 37072801
DOI: 10.1186/s13148-023-01479-9 -
Frontiers in Immunology 2023Neutrophil extracellular traps (NETs) can cause acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by inducing macrophage pyroptosis. The purpose of this...
Alpha-linolenic acid pretreatment alleviates NETs-induced alveolar macrophage pyroptosis by inhibiting pyrin inflammasome activation in a mouse model of sepsis-induced ALI/ARDS.
BACKGROUND
Neutrophil extracellular traps (NETs) can cause acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by inducing macrophage pyroptosis. The purpose of this study was to find out whether pretreatment of alpha-linolenic acid (ALA) could inhibit NETs-induced macrophage pyroptosis in sepsis-induced ALI/ARDS, as well as to identify which inflammasome is involved in this process.
METHODS
LPS was instilled into the trachea to establish sepsis-induced ALI/ARDS in a mouse model. Lung injury was assessed by microscopic examination of lung tissue after hematoxylin and eosin staining, pathology score, and bronchoalveolar lavage fluid (BALF) total protein concentration. The level of NETs in lung tissue was detected by MPO-DNA ELISA. Purified NETs, extracted from peritoneal neutrophils, induced macrophage pyroptosis . Expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in the lung tissue and bone marrow-derived macrophages (BMDMs) were determined by western blotting or ELISA. Specks of Pyrin/ASC were examined by confocal immunofluorescence microscopy. Mefv (Pyrin) mice were used to study the role of Pyrin in the process of sepsis-induced ALI/ARDS.
RESULTS
ALA alleviated LPS-induced lung injury. ALA reduced the level of NETs, pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC), and IL-1β in the lung tissue of sepsis mice. , NETs increased the expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β significantly in BMDMs. Pyrin protein was found to be higher and form the inflammasome with ASC in NETs challenged-BMDMs. Knockout of Mefv (Pyrin) gene fully restored the increased expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β and . Lung injury was alleviated significantly in Mefv (Pyrin)-/- mice as well. ALA suppresses all the NETs-induced changes as mentioned above.
CONCLUSION
Our study is the first to demonstrate Pyrin inflammasome driving NETs-induced macrophage pyroptosis, and ALA may reduce ALI/ARDS by inhibiting the activation of the Pyrin inflammasome-driven macrophage pyroptosis.
Topics: Animals; Mice; Inflammasomes; Macrophages, Alveolar; Pyrin; alpha-Linolenic Acid; NLR Family, Pyrin Domain-Containing 3 Protein; Extracellular Traps; Pyroptosis; Lipopolysaccharides; Acute Lung Injury; Mice, Knockout; Respiratory Distress Syndrome; Sepsis; Caspases
PubMed: 37051243
DOI: 10.3389/fimmu.2023.1146612