Early versus delayed appendicectomy for appendiceal phlegmon or abscess.

BACKGROUND: This is an update of a Cochrane review first published in 2017. Acute appendicitis (inflammation of the appendix) can be simple or complicated. Appendiceal phlegmon and appendiceal abscess are examples of complicated appendicitis. Appendiceal phlegmon is a diffuse inflammation in the bottom right of the appendix, while appendiceal abscess is a discrete inflamed mass in the abdomen that contains pus. Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms (e.g. abdominal pain, loss of appetite, nausea, and vomiting) and avoid complications (e.g. peritonitis (infection of abdominal lining)). Surgery for people with appendiceal phlegmon or abscess may be early (immediately after hospital admission or within a few days of admission), or delayed (several weeks later in a subsequent hospital admission). The optimal timing of appendicectomy for appendiceal phlegmon or abscess is debated. OBJECTIVES: To assess the effects of early appendicectomy compared to delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 11 June 2023, together with reference checking to identify additional studies. SELECTION CRITERIA: We included all individual and cluster-randomised controlled trials (RCTs), irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs that randomised 828 participants to early or delayed appendicectomy for appendiceal phlegmon (7 trials) or appendiceal abscess (1 trial). The studies were conducted in the USA, India, Nepal, and Pakistan. All RCTs were at high risk of bias because of lack of blinding and lack of published protocols. They were also unclear about methods of randomisation and length of follow-up. 1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon We included seven trials involving 788 paediatric and adult participants with appendiceal phlegmon: 394 of the participants were randomised to the early appendicectomy group (open or laparoscopic appendicectomy as soon as the appendiceal mass resolved within the same admission), and 394 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed open or laparoscopic appendicectomy several weeks later). There was no mortality in either group. The evidence is very uncertain about the effect of early appendicectomy on overall morbidity (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.19 to 2.86; 3 trials, 146 participants; very low-certainty evidence), the proportion of participants who developed wound infections (RR 0.99, 95% CI 0.48 to 2.02; 7 trials, 788 participants), and the proportion of participants who developed faecal fistulas (RR 1.75, 95% CI 0.36 to 8.49; 5 trials, 388 participants). Early appendicectomy may reduce the abdominal abscess rate (RR 0.26, 95% CI 0.08 to 0.80; 4 trials, 626 participants; very low-certainty evidence), reduce the total length of hospital stay by about two days (mean difference (MD) -2.02 days, 95% CI -3.13 to -0.91; 5 trials, 680 participants), and increase the time away from normal activities by about five days (MD 5.00 days; 95% CI 1.52 to 8.48; 1 trial, 40 participants), but the evidence is very uncertain. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess We included one trial involving 40 paediatric participants with appendiceal abscess: 20 were randomised to the early appendicectomy group (emergent laparoscopic appendicectomy), and 20 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed laparoscopic appendicectomy 10 weeks later). There was no mortality in either group. The trial did not report on overall morbidity, various complications, or time away from normal activities. The evidence is very uncertain about the effect of early appendicectomy on the total length of hospital stay (MD -0.20 days, 95% CI -3.54 to 3.14; very low-certainty evidence). AUTHORS' CONCLUSIONS: For the comparison of early versus delayed open or laparoscopic appendicectomy for paediatric and adult participants with appendiceal phlegmon, very low-certainty evidence suggests that early appendicectomy may reduce the abdominal abscess rate. The evidence is very uncertain whether early appendicectomy prevents overall morbidity or other complications. Early appendicectomy may reduce the total length of hospital stay and increase the time away from normal activities, but the evidence is very uncertain. For the comparison of early versus delayed laparoscopic appendicectomy for paediatric participants with appendiceal abscess, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy. Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery, and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities and length of hospital stay.

Cholangiocarcinoma combined with biliary obstruction: an exosomal circRNA signature for diagnosis and early recurrence monitoring.

Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.

BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking. METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1. RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect. CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.