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JAMA Surgery Feb 2021Perforated colonic diverticulitis usually requires surgical resection, with significant morbidity. Short-term results from randomized clinical trials have indicated that... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Perforated colonic diverticulitis usually requires surgical resection, with significant morbidity. Short-term results from randomized clinical trials have indicated that laparoscopic lavage is a feasible alternative to resection. However, it appears that no long-term results are available.
OBJECTIVE
To compare long-term (5-year) outcomes of laparoscopic peritoneal lavage and primary resection as treatments of perforated purulent diverticulitis.
DESIGN, SETTING, AND PARTICIPANTS
This international multicenter randomized clinical trial was conducted in 21 hospitals in Sweden and Norway, which enrolled patients between February 2010 and June 2014. Long-term follow-up was conducted between March 2018 and November 2019. Patients with symptoms of left-sided acute perforated diverticulitis, indicating urgent surgical need and computed tomography-verified free air, were eligible. Those available for trial intervention (Hinchey stages
INTERVENTIONS
Patients were assigned to undergo laparoscopic peritoneal lavage or colon resection based on computer-generated, center-stratified block randomization.
MAIN OUTCOMES AND MEASURES
The primary outcome was severe complications within 5 years. Secondary outcomes included mortality, secondary operations, recurrences, stomas, functional outcomes, and quality of life.
RESULTS
Of 199 randomized patients, 101 were assigned to undergo laparoscopic peritoneal lavage and 98 were assigned to colon resection. At the time of surgery, perforated purulent diverticulitis was confirmed in 145 patients randomized to lavage (n = 74) and resection (n = 71). The median follow-up was 59 (interquartile range, 51-78; full range, 0-110) months, and 3 patients were lost to follow-up, leaving a final analysis of 73 patients who had had laparoscopic lavage (mean [SD] age, 66.4 [13] years; 39 men [53%]) and 69 who had received a resection (mean [SD] age, 63.5 [14] years; 36 men [52%]). Severe complications occurred in 36% (n = 26) in the laparoscopic lavage group and 35% (n = 24) in the resection group (P = .92). Overall mortality was 32% (n = 23) in the laparoscopic lavage group and 25% (n = 17) in the resection group (P = .36). The stoma prevalence was 8% (n = 4) in the laparoscopic lavage group vs 33% (n = 17; P = .002) in the resection group among patients who remained alive, and secondary operations, including stoma reversal, were performed in 36% (n = 26) vs 35% (n = 24; P = .92), respectively. Recurrence of diverticulitis was higher following laparoscopic lavage (21% [n = 15] vs 4% [n = 3]; P = .004). In the laparoscopic lavage group, 30% (n = 21) underwent a sigmoid resection. There were no significant differences in the EuroQoL-5D questionnaire or Cleveland Global Quality of Life scores between the groups.
CONCLUSIONS AND RELEVANCE
Long-term follow-up showed no differences in severe complications. Recurrence of diverticulitis after laparoscopic lavage was more common, often leading to sigmoid resection. This must be weighed against the lower stoma prevalence in this group. Shared decision-making considering both short-term and long-term consequences is encouraged.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01047462.
Topics: Aged; Colectomy; Diverticulitis, Colonic; Female; Humans; Intestinal Perforation; Laparoscopy; Male; Norway; Peritoneal Lavage; Sweden
PubMed: 33355658
DOI: 10.1001/jamasurg.2020.5618 -
Current Protocols in Immunology Dec 2020This article presents assays that allow induction and measurement of activation of different inflammasomes in mouse macrophages, human peripheral blood mononuclear cell...
This article presents assays that allow induction and measurement of activation of different inflammasomes in mouse macrophages, human peripheral blood mononuclear cell (PBMC) cultures, and mouse peritonitis and endotoxic shock models. Basic Protocol 1 describes how to prime the inflammasome in mouse macrophages with different Toll-like receptor agonists and TNF-α; how to induce NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation by their corresponding stimuli; and how to measure inflammasome activation-mediated maturation of interleukin (IL)-1β and IL-18 and pyroptosis. Since the well-established agonists for NLRP1 are inconsistent between mice and humans, Basic Protocol 2 describes how to activate the NLRP1 inflammasome in human PBMCs. Basic Protocol 3 describes how to purify, crosslink, and detect the apoptosis-associated speck-like protein containing a CARD (ASC) pyroptosome. Formation of the ASC pyroptosome is a signature of inflammasome activation. A limitation of ASC pyroptosome detection is the requirement of a relatively large cell number. Alternate Protocol 1 is provided to stain ASC pyroptosomes using an anti-ASC antibody and to measure ASC specks by fluorescence microscopy in a single cell. Intraperitoneal injection of lipopolysaccharides (LPS) and inflammasome agonists will induce peritonitis, which is seen as an elevation of IL-1β and other proinflammatory cytokines and an infiltration of neutrophils and inflammatory monocytes. Basic Protocol 4 describes how to induce NLRP3 inflammasome activation and peritonitis by priming mice with LPS and subsequently challenging them with monosodium urate (MSU). The method for measuring cytokines in serum and through peritoneal lavage is also described. Finally, Alternate Protocol 2 describes how to induce noncanonical NLRP3 inflammasome activation by high-dose LPS challenge in a sepsis model. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Priming and activation of inflammasomes in mouse macrophages Basic Protocol 2: Activation of human NLRP1 inflammasome by DPP8/9 inhibitor talabostat Basic Protocol 3: Purification and detection of ASC pyroptosome Alternate Protocol 1: Detection of ASC speck by immunofluorescence staining Basic Protocol 4: Activation of canonical NLRP3 inflammasome in mice by intraperitoneal delivery of MSU crystals Alternate Protocol 2: Activation of noncanonical NLRP3 inflammasome in mice by intraperitoneal delivery of LPS.
Topics: Animals; Cell Culture Techniques; Disease Models, Animal; Humans; Immunoassay; Inflammasomes; Leukocytes, Mononuclear; Macrophages; Mice; Peritonitis; Pyroptosis; Shock, Septic
PubMed: 33017103
DOI: 10.1002/cpim.107 -
Frontiers in Immunology 2021Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or...
Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or even opposite effects on the development of lupus nephritis. Substantial evidence has shown that macrophage M2 polarization is beneficial to individuals with chronic kidney disease. Further, it has been reported that PD-1 ligands (PD-Ls) contribute to M2 polarization of macrophages and their immunosuppressive effects. Total glucosides of paeony (TGP), originally extracted from Radix Paeoniae Alba, has been approved in China to treat some autoimmune diseases. Here, we investigated the potentially therapeutic effects of TGP on lupus nephritis in a pristane-induced murine model and explored the molecular mechanisms regulating macrophage phenotypes. We found that TGP treatment significantly improved renal function by decreasing the urinary protein and serum creatinine, reducing serum anti-ds-DNA level and ameliorating renal immunopathology. TGP increased the frequency of splenic and peritoneal F4/80CD11bCD206 M2-like macrophages with no any significant effect on F4/80CD11bCD86 M1-like macrophages. Immunofluorescence double-stainings of the renal tissue showed that TGP treatment increased the frequency of F4/80Arg1 subset while decreasing the percentage of F4/80iNOS subset. Importantly, TGP treatment increased the percentage of both F4/80CD11bPD-L1 and F4/80CD11bPD-L2 subsets in spleen and peritoneal lavage fluid as well as the kidney. Furthermore, TGP augmented the expressions of CD206, PD-L2 and phosphorylated STAT6 in IL-4-treated Raw264.7 macrophages while its effects on PD-L2 were abolished by pretreatment of the cells with an inhibitor of STAT6, AS1517499. However, TGP treatment did not affect the expressions of STAT1 and PD-L1 in Raw264.7 macrophages treated with LPS/IFN-γ , indicating a possibly indirect effect of TGP on PD-L1 expression on macrophages . Thus, for the first time, we demonstrated that TGP may be a potent drug to treat lupus nephritis by inducing F4/80CD11bCD206 and F4/80CD11bPD-L2 macrophages through IL-4/STAT6/PD-L2 signaling pathway.
Topics: Animals; B7-H1 Antigen; Biomarkers; Cell Line; Disease Susceptibility; Female; Glucosides; Humans; Interleukin-4; Lupus Nephritis; Macrophage Activation; Macrophages; Mice; Paeonia; Programmed Cell Death 1 Ligand 2 Protein; STAT6 Transcription Factor; Signal Transduction; Terpenes
PubMed: 34290705
DOI: 10.3389/fimmu.2021.683249 -
Emergency Medicine Clinics of North... Nov 2021Occult abdominal injuries are common and can be associated with increased risk of morbidity and mortality. Patients with a delayed presentation to care or who are... (Review)
Review
Occult abdominal injuries are common and can be associated with increased risk of morbidity and mortality. Patients with a delayed presentation to care or who are multiply injured are at increased risk of this type of injury, and a high index of suspicion must be maintained. A careful combination of history, physical examination, laboratory, and imaging can be quite helpful in mitigating the risk of a missed occult abdominal injury.
Topics: Abdomen; Abdominal Injuries; Delayed Diagnosis; Emergency Service, Hospital; Hematologic Tests; Humans; Liver Function Tests; Missed Diagnosis; Peritoneal Lavage; Physical Examination; Radiation Dosage; Risk Factors; Wounds, Nonpenetrating
PubMed: 34600638
DOI: 10.1016/j.emc.2021.07.009 -
The Surgeon : Journal of the Royal... Dec 2021Whether peritoneal lavage is beneficial for the postoperative outcomes of appendectomy is debatable. This study is a meta-analysis of randomized controlled trials (RCTs)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whether peritoneal lavage is beneficial for the postoperative outcomes of appendectomy is debatable. This study is a meta-analysis of randomized controlled trials (RCTs) that aimed to determine whether peritoneal lavage leads to improved appendectomy outcomes.
METHODS
PubMed, Embase, and Cochrane Library databases were searched for articles published before September 2020. The meta-analysis calculated the pooled effect size by using a random effects model. The primary outcome was the incidence of intra-abdominal abscess. Secondary outcomes were the incidence of surgical-site infection, hospital stay duration, operation time, and readmission incidence.
RESULTS
Eight RCTs involving 1487 patients were reviewed. The lavage group had a nonsignificantly lower incidence of intra-abdominal abscess (risk ratio [RR]: 0.81; 95% confidence interval [CI]: 0.55-1.18) and surgical-site infection (RR: 0.73; 95% CI: 0.31-1.72) than did the nonirrigation group. Furthermore, the lavage group showed a nonsignificantly shorter hospital stay duration and lower readmission incidence than did the nonirrigation group. However, the lavage group required significantly more operation time than did the nonirrigation group (mean difference: 7.59 min; 95% CI: 4.67-10.50).
CONCLUSION
Our study revealed that performing peritoneal lavage has no advantage over suction or drainage only in appendectomy. Moreover, peritoneal lavage significantly increased operation time. Consequently, for improving efficiency and reducing operation time, we suggest skipping peritoneal irrigation during appendectomy. However, the available evidence is of variable quality; therefore, high-quality prospective RCTs are required in the future.
Topics: Abdominal Abscess; Appendectomy; Appendicitis; Drainage; Humans; Peritoneal Lavage
PubMed: 33589397
DOI: 10.1016/j.surge.2021.01.001 -
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 -
Frontiers in Immunology 2022The peritoneal cavity contains many site-specific immune cells which constitute a unique immune microenvironment. However, it is unclear how the local immune signature...
BACKGROUND
The peritoneal cavity contains many site-specific immune cells which constitute a unique immune microenvironment. However, it is unclear how the local immune signature is altered in patients with peritoneal metastases (PM).
METHODS
Peritoneal lavage fluid or ascites were obtained from 122 patients with various stages of gastric cancer (GC). Cells recovered from peritoneal fluids were immunostained with mAbs for lymphocyte-, macrophage- and tumor cell-specific antigens and the frequencies of leukocyte subsets and antigen expression levels were evaluated with multi-color flowcytometry.
RESULTS
The proportions of CD8(+) T cells, CD3(+)CD56(+) NKT-like cells, and CD3(-)CD56(+) NK cells to CD45(+) leukocytes were significantly reduced in patients with PM compared to those without PM. In patients with PM, the rates of CD8 (+) T cells and NKT-like cells correlated inversely with the tumor leukocyte ratio (TLR), the relative frequency of CD326(+) tumor cells to CD45(+) leukocytes. In contrast, the proportion of CD19(+) B cells was significantly increased in patients with PM, and their proportion correlated positively with the TLR and peritoneal carcinomatosis index (PCI) score. In patients with PM, CD14(+) macrophages tended to be increased with enhanced expression of CD14, CD16 and a M2-macrophage marker, CD163. In particular, macrophages in patients with high TLR contained many granules with high side scatter and CD14 expression in their flow profile compared to those without PM.
CONCLUSION
PM are accompanied by a drastic change in phenotypes of lymphocyte and macrophage in the peritoneal cavity, which might be involved in the development and progression of intraperitoneal tumor growth.
Topics: CD8-Positive T-Lymphocytes; Humans; Killer Cells, Natural; Peritoneal Cavity; Peritoneal Neoplasms; Stomach Neoplasms; Tumor Microenvironment
PubMed: 36119051
DOI: 10.3389/fimmu.2022.969468 -
World Journal of Emergency Surgery :... Mar 2023Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with intra-abdominal infections (IAIs) remains controversial. This study aims to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of IOPL in patients with IAIs.
METHODS
The databases of PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, and CBM databases were searched from inception to December 31, 2022. Random-effects models were used to calculate the risk ratio (RR), mean difference, and standardized mean difference. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence.
RESULTS
Ten RCTs with 1318 participants were included, of which eight studies on appendicitis and two studies on peritonitis. Moderate-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (0% vs. 1.1%; RR, 0.31 [95% CI, 0.02-6.39]), intra-abdominal abscess (12.3% vs. 11.8%; RR, 1.02 [95% CI, 0.70-1.48]; I = 24%), incisional surgical site infections (3.3% vs. 3.8%; RR, 0.72 [95% CI, 0.18-2.86]; I = 50%), postoperative complication (11.0% vs. 13.2%; RR, 0.74 [95% CI, 0.39-1.41]; I = 64%), reoperation (2.9% vs. 1.7%; RR,1.71 [95% CI, 0.74-3.93]; I = 0%) and readmission (5.2% vs. 6.6%; RR, 0.95 [95% CI, 0.48-1.87]; I = 7%) in patients with appendicitis when compared to non-IOPL. Low-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (22.7% vs. 23.3%; RR, 0.97 [95% CI, 0.45-2.09], I = 0%) and intra-abdominal abscess (5.1% vs. 5.0%; RR, 1.05 [95% CI, 0.16-6.98], I = 0%) in patients with peritonitis when compared to non-IOPL.
CONCLUSION
IOPL with saline use in patients with appendicitis was not associated with significantly decreased risk of mortality, intra-abdominal abscess, incisional surgical site infection, postoperative complication, reoperation, and readmission compared with non-IOPL. These findings do not support the routine use of IOPL with saline in patients with appendicitis. The benefits of IOPL for IAI caused by other types of abdominal infections need to be investigated.
Topics: Humans; Peritoneal Lavage; Abdominal Abscess; Peritonitis; Surgical Wound Infection; Appendicitis; Randomized Controlled Trials as Topic
PubMed: 36991507
DOI: 10.1186/s13017-023-00496-6 -
Surgical Endoscopy Oct 2022This study aimed to compare laparoscopic lavage and sigmoidectomy as treatment for perforated diverticulitis with purulent peritonitis during a 36 month follow-up of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study aimed to compare laparoscopic lavage and sigmoidectomy as treatment for perforated diverticulitis with purulent peritonitis during a 36 month follow-up of the LOLA trial.
METHODS
Within the LOLA arm of the international, multicentre LADIES trial, patients with perforated diverticulitis with purulent peritonitis were randomised between laparoscopic lavage and sigmoidectomy. Outcomes were collected up to 36 months. The primary outcome of the present study was cumulative morbidity and mortality. Secondary outcomes included reoperations (including stoma reversals), stoma rates, and sigmoidectomy rates in the lavage group.
RESULTS
Long-term follow-up was recorded in 77 of the 88 originally included patients, 39 were randomised to sigmoidectomy (51%) and 38 to laparoscopic lavage (49%). After 36 months, overall cumulative morbidity (sigmoidectomy 28/39 (72%) versus lavage 32/38 (84%), p = 0·272) and mortality (sigmoidectomy 7/39 (18%) versus lavage 6/38 (16%), p = 1·000) did not differ. The number of patients who underwent a reoperation was significantly lower for lavage compared to sigmoidectomy (sigmoidectomy 27/39 (69%) versus lavage 17/38 (45%), p = 0·039). After 36 months, patients alive with stoma in situ was lower in the lavage group (proportion calculated from the Kaplan-Meier life table, sigmoidectomy 17% vs lavage 11%, log-rank p = 0·0268). Eventually, 17 of 38 (45%) patients allocated to lavage underwent sigmoidectomy.
CONCLUSION
Long-term outcomes showed that laparoscopic lavage was associated with less patients who underwent reoperations and lower stoma rates in patients alive after 36 months compared to sigmoidectomy. No differences were found in terms of cumulative morbidity or mortality. Patient selection should be improved to reduce risk for short-term complications after which lavage could still be a valuable treatment option.
Topics: Diverticulitis; Diverticulitis, Colonic; Follow-Up Studies; Humans; Intestinal Perforation; Laparoscopy; Peritoneal Lavage; Peritonitis; Treatment Outcome
PubMed: 35606544
DOI: 10.1007/s00464-022-09326-3