Hemostatic spray (TC-325) vs. standard endoscopic therapy for non-variceal gastrointestinal bleeding: A meta-analysis of randomized controlled trials
Endoscopy international open. 2023;11(3):E288-e295
Background and study aims Hemospray (TC-325) is a mineral powder with adsorptive properties designed for use in various gastrointestinal bleeding (GIB) scenarios. We conducted a systematic review & meta-analysis of randomized controlled trials (RCTs) comparing TC-325 to standard endoscopic therapy (SET) for non-variceal GIB (NVGIB). Methods Multiple databases were searched through October 2022. Meta-analysis was performed using a random-effects model to determine pooled relative risk (RR) and proportions with 95 % confidence intervals (CI) for primary hemostasis, hemostasis failure, 30-day rebleeding, length of stay (LOS), and need for rescue interventions. Heterogeneity was assessed using I (2) %. Results Five RCTs with 362 patients (TC-325 178, SET 184) - 123 females and 239 males with a mean age 65 ± 16 years). The most common etiologies were peptic ulcer disease (48 %), malignancies (35 %), and others (17 %). Bleeding was characterized as Forrest IA (7 %), IB (73 %), IIA (3 %), and IIB (1 %). SET included epinephrine injection, electrocautery, hemoclips, or a combination. No statistical difference in primary hemostasis between TC-325 compared to SET, RR 1.09 (CI 0.95-1.25; I (2) 43), P = 0.2, including patients with oozing/spurting hemorrhage, RR 1.13 (CI 0.98-1.3; I (2) 35), P = 0.08. Failure to achieve hemostasis was higher in SET compared to TC-325, RR 0.30 (CI 0.12-0.77, I (2) 0), P = 0.01, including patients with oozing/spurting hemorrhage, RR 0.24 (CI 0.09 - 0.63, I (2) 0), P = 0.004. We found no difference between the two interventions in terms of rebleeding, RR 1.13 (CI 0.62-2.07, I (2) 26), P = 0.8 and LOS, standardized mean difference (SMD) 0.27 (CI, -0.20-0.74; I (2) 62), P = 0.3. Finally, pooled rate of rescue interventions (angiography) was statistically higher in SET compared to TC-325, RR 0.68 (CI 0.5-0.94; I (2) 0), P = 0.02. Conclusions Our analysis shows that for acute NV GIB, including oozing/spurting hemorrhage, TC-325 does not result in higher rates of primary hemostasis compared to SET. However, lower rates of failures were seen with TC-325 than SET. In addition, there was no difference in the two modalities when comparing rates of rebleeding and LOS.
Small-Diameter Transjugular Intrahepatic Portosystemic Shunt versus Endoscopic Variceal Ligation Plus Propranolol for Variceal Rebleeding in Advanced Cirrhosis
Background Some studies have shown that transjugular intrahepatic portosystemic shunt (TIPS) placement within 72 hours of admission improves survival in patients at high risk who present with acute variceal bleeding. However, the role of small-diameter covered TIPS in the secondary prophylaxis of variceal bleeding is still debatable. Purpose To compare the efficacy of 8-mm TIPS and endoscopic variceal ligation (EVL) plus propranolol in the prevention of variceal rebleeding among participants with advanced cirrhosis. Materials and Methods Between June 2015 and December 2018, participants admitted to the hospital for variceal bleeding were considered for enrollment in this randomized controlled trial (ClinicalTrials.gov). Participants with Child-Pugh class B or C cirrhosis were randomly assigned to receive an 8-mm covered TIPS or EVL and propranolol. The primary end point was recurrent variceal bleeding assessed using Kaplan-Meier curve analysis. Secondary end points included survival and overt hepatic encephalopathy (HE) assessed using Kaplan-Meier curve analysis. Results A total of 100 participants were enrolled, with 50 randomly assigned to the EVL plus propranolol group (median age, 54 years; IQR, 45-60 years; 29 male, 21 female) and 50 randomly assigned to the TIPS group (median age, 49 years; IQR, 43-56 years; 32 male, 18 female). The median follow-up period was 43.4 months. In the TIPS group, variceal rebleeding risk was reduced compared with variceal rebleeding risk in the EVL plus propranolol group (hazard ratio [HR], 0.31; 95% CI: 0.14, 0.69; P = .008), but the incidence of overt HE was higher in the TIPS group (30.0% vs 16.0%, P = .03). No differences in survival were observed between the two groups (1-year survival: TIPS, 98.0%; EVL plus propranolol, 92.0%; 3-year survival: TIPS, 94.0%; EVL plus propranolol, 85.7%; HR, 0.52; 95% CI: 0.19, 1.42; P = .22). Conclusion When compared with EVL plus propranolol, 8-mm TIPS led to reduced variceal rebleeding but did not impact overall survival in participants with Child-Pugh class B or C cirrhosis. Clinical trial registration no. NCT02477384 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barth in this issue.
Hemostatic powder vs. standard endoscopic treatment for gastrointestinal tumor bleeding: A multicenter randomized trial
BACKGROUND & AIMS Current guidelines vary as to their recommendations addressing the role of hemostatic powders when managing patients with malignant gastrointestinal (GI) bleeding as these are based on very-low to low quality evidence in large part due to a paucity of randomized trial data. METHODS This was a patient- and outcome assessor-blinded multicenter randomized controlled trial. Patients presenting with active bleeding from an upper or lower GI lesion suspected to be malignant at index endoscopy between June 2019 and January 2022 were randomly allocated to receive either TC-325 alone or standard endoscopic treatment (SET). The primary outcome was 30-day rebleeding, while secondary objectives included immediate hemostasis and other clinically relevant endpoints. RESULTS Overall, 106 patients comprised the study population (55 TC-325 and 51 SET, after 1 exclusion in the TC-325 and 5 in the SET group). Baseline characteristics and endoscopic findings did not differ between groups. Thirty-day rebleeding was significantly lower in the TC-325 (2.1% TC-325 versus 21.3% SET,OR=0.09[0.01, 0.80],P=.003). Immediate hemostasis rates were 100% in the TC-325 versus 68.6% in the SET group (OR=1.45[0.93, 2.29],P < .001). Other secondary outcomes did not differ between the two groups. Independent predictors of 6-month survival included the Charlson comorbidity index (HR=1.17[1.05, 1.32], P =.007), and receiving an additional non endoscopic hemostatic or oncological treatment during 30 days after the index endoscopy (HR=0.16 [0.06, 0.43], P <.001) after adjustment for functional status, Glasgow-Blatchford score, and an upper GI source of bleeding. CONCLUSION The TC-325 hemostatic powder results in greater immediate hemostasis rates followed by lower 30-day rebleeding rates when compared to contemporary SET. (ClinicalTrials.gov number,NCT03855904).
Comparison of High Ligation Versus Low Ligation of the Inferior Mesenteric Artery (IMA) on Short-Term and Long-Term Outcomes in Sigmoid Colon and Rectal Cancer Surgery: A Meta-analysis
This study was done to compare the perioperative outcomes and long-term outcomes between low ligation and high ligation of the inferior mesentric artery (IMA) in sigmoid colon and rectal cancer surgery. This study was conducted following the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A literature search was performed in electronic databases including PubMed, CINAHIL, EMBASE, and Web of Science to identify studies published between January 1, 2015, and April 30, 2023. The outcomes assessed in this meta-analysis included postoperative complications (anastomotic leakage, surgical site infection, and postoperative ileus), intraoperative outcomes (duration of surgery in minutes, total intraoperative blood loss in milliliters, total lymph nodes harvested, and total number of metastatic lymph nodes), recovery outcomes (time to first flatus and length of hospital stay), and long-term outcomes (five-year mortality rate and disease-free survival rate). A total of 17 studies were included in this meta-analysis. Of these, six were randomized control trials (RCTs) and 11 were retrospective cohort studies. This meta-analysis suggests that lower ligation may be associated with a lower risk of anastomotic leakage compared to higher ligation in patients undergoing colon cancer surgery. However, there was no significant difference between the two techniques in terms of surgical site infection, postoperative ileus, total lymph nodes harvested, number of metastatic lymph nodes, duration of surgery, intraoperative blood loss, and length of hospital stay. Time to first flatus was significantly shorter in patients who underwent lower ligation. Additionally, there were no significant differences in the five-year mortality rate and disease-free survival rate between the two techniques. The results of this study indicate that both techniques are comparable in most aspects and suggest that the choice of technique should be based on individual patient factors and surgeon preference.
Comparing Tubeless and Tubed Approaches in Percutaneous Nephrolithotomy for Moderate Renal Calculi: Outcomes on Safety, Efficacy, Pain Management, Recovery Time, and Cost-Effectiveness
Introduction This study focuses on investigating the effect of routine nephrostomy tube placement in patients with moderate renal calculi of size 2.5 cm or less who undergo uncomplicated percutaneous nephrolithotomy (PCNL) procedures. Previous studies have not specified whether only uncomplicated cases were included in the analysis, which may affect the results. This study aims to provide a clearer understanding of the effect of routine nephrostomy tube placement on blood loss in a more homogeneous patient population. Materials and methods A prospective randomized controlled trial (RCT) was conducted at our department over 18 months, dividing 60 patients with a single renal or upper ureteric calculus of size ≤2.5 cm into two groups: 30 patients in each group (group 1: tubed PCNL, group 2: tubeless PCNL). The primary outcome was the drop in perioperative hemoglobin level and the number of packed cell transfusions necessary. The secondary outcome included the mean pain score, analgesic requirement, length of hospital stay, time to return to normal activities, and the total cost of the procedure. Results The two groups were comparable in age, gender, comorbidities, and stone size. The postoperative hemoglobin level was significantly lower in the tubeless PCNL group (9.56 ± 2.13 gm/dL) compared to the tube PCNL group (11.32 ± 2.35 gm/dL) (p = 0.0037), and two patients in the tubeless group required blood transfusion. The duration of surgery, pain scores, and analgesic requirement were comparable between the two groups. The total procedure cost was significantly lower in the tubeless group (p = 0.0019), and the duration of hospital stay and time to return to daily activities were significantly shorter in the tubeless group (p < 0.0001). Conclusions Tubeless PCNL is a safe and effective alternative to conventional tube PCNL, with the advantages of shorter hospital stay, faster recovery, and lower procedure costs. Tube PCNL is associated with less blood loss and the need for transfusions. Patient preferences and bleeding risk should be considered when choosing between the two procedures.
Polyethylene glycol-coated haemostatic patch for prevention of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy: randomized clinical trial
BJS open. 2023;7(2)
BACKGROUND The potential of haemostatic patches to reduce the rate of postoperative pancreatic fistula remains unclear. The aim of this trial was to evaluate the impact of a polyethylene glycol-coated haemostatic patch on the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. METHODS In this randomized, single-centre, clinical trial, patients undergoing pancreatoduodenectomy were randomized 1 : 1 to receive pancreatojejunostomy reinforced with two polyethylene glycol-coated haemostatic patches (patch group) or without any reinforcement (control group). The primary outcome was clinically relevant postoperative pancreatic fistula, defined as grade B/C according to International Study Group of Pancreatic Surgery criteria, within 90 days. Key secondary outcomes were length of hospital stay, total rate of postoperative pancreatic fistula, and overall complication rate. RESULTS From 15 May 2018 to 22 June 2020, 72 patients were randomized, and 64 were included in the analyses (31 in the patch group and 33 in the control group). The risk of clinically relevant postoperative pancreatic fistula was reduced by 90 per cent (OR 0.10, 95 per cent c.i. 0.01 to 0.89, P = 0.039). Moreover, the use of the polyethylene glycol-coated patch retained its protective effect on clinically relevant postoperative pancreatic fistula in a multivariable regression model, significantly reducing the risk of clinically relevant postoperative pancreatic fistula by 93 per cent (OR 0.07, 95 per cent c.i. 0.01 to 0.67, P = 0.021), regardless of patient age, sex, or fistula risk score. The incidence of secondary outcomes did not significantly differ between the groups. One patient died within 90 days in the patch group versus three patients in the control group. CONCLUSIONS A polyethylene glycol-coated haemostatic patch reduced the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. REGISTRATION NUMBER NCT03419676 (http://www.clinicaltrials.gov).
Fibrin-based haemostatic agents for reducing blood loss in adult liver resection
The Cochrane database of systematic reviews. 2023;8(8):Cd010872
BACKGROUND Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.
Adults undergoing liver resection (22 randomised controlled trials, n= 2,945).
Fibrin-based haemostatic agents (FBHAs).
No intervention. Non-FBHAs.
FBHAs vs. no intervention (6 RCTs, 1,001 participants): It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58; 95% CI [0.89, 7.44] 4 trials), serious adverse events (RR 0.96; 95% CI [0.88, 1.05] 4 trials), postoperative transfusion (RR 1.04; 95% CI [0.77, 1.40] 5 trials), reoperation (RR 2.92, 95% CI [0.58, 14.61] 2 trials), or postoperative bile leak (RR 1.00; 95% CI [0.67, 1.48] 4 trials), as the certainty of evidence was very low for all these outcomes. FBHAs vs. non-FBHAs (16 RCTs, 1,944 participants): It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03; 95% CI [0.62, 1.72] 11 trials), postoperative transfusion (RR 0.92; 95% CI [0.68, 1.25] 7 trials), reoperation (RR 0.48; 95% CI [0.25, 0.90] 3 trials), or postoperative bile leak (RR 1.15; 95% CI [0.60, 2.21] 9 trials), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99; 95% CI [0.95, 1.03] 9 trials, low-certainty evidence).
Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial
INTRODUCTION Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. METHODS This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment. DISCUSSION The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs. TRIAL REGISTRATION ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.
Efficacy of self-assembling peptide in mitigating delayed bleeding after advanced endoscopic resection of gastrointestinal lesions: A meta-analysis
Endoscopy international open. 2023;11(5):E553-e560
Background and study aims Advanced endoscopic resection techniques carry a risk of delayed bleeding (DB). A novel fully synthetic self-assembling peptide (SAP) has shown promising results in mitigating this risk. In this meta-analysis, we evaluated all available data and analyzed the effectiveness of SAP in reducing DB after advanced endoscopic resection of gastrointestinal luminal lesions. Patients and methods Electronic databases (PubMed, Embase, and Cochrane Library) from January 2010 through October 2022 were searched for publications addressing the use of SAP solution in patients undergoing advanced endoscopic resection of gastrointestinal lesions. Pooled proportions were calculated using fixed (inverse variance) and random-effects (DerSimonian-Laird) models. Results The initial search identified 277 studies, of which 63 relevant articles were reviewed. The final analysis included data from six studies comprising 307 patients that met inclusion criteria. The pooled rate of DB was 5.73 % (95 % confidence interval [CI] = 3.42-8.59). Mean patient age was 69.40 years ± 1.82. The weighted mean size of resected lesions was 36.20 mm (95 % CI = 33.37-39.02). Endoscopic submucosal dissection was used in 72.69 % (95 % CI = 67.62-77.48), while endoscopic mucosal resection was used in 26.42 % (95 % CI = 21.69-31.44) of the procedures. Among the 307 patients, 36 % were on antithrombotic medications. No adverse events (AEs) were attributable to using SAP, with a pooled rate of 0.00 % (95 % CI = 0.00-1.49). Conclusions SAP solution appears promising in reducing post-procedural DB after advanced endoscopic resection of high-risk gastrointestinal lesions with no reported AEs.
LigaSure technique for splenectomy: A systematic review and meta-analysis
BACKGROUND This study aimed to clarify the optimal management of the LigaSure technique and conventional techniques during splenectomy. METHODS All databases, including CBM, CNKI, WFPD, Medline, EMBASE, PubMed, and Cochrane databases up to April 2023, were searched for relevant studies comparing the LigaSure technique with conventional techniques. Six studies, extracted by 2 independent reviewers, were evaluated for blood loss, operative time, conversion, mortality, hospital stay, and transfusion. RESULTS The blood loss was significantly higher in the convention group than in the LigaSure group (WMD = -48.98, 95% CI: -62.41 to -35.55, P < .00001). Meanwhile, the mean operative time was significantly shorter in LigaSure group than in convention group (WMD = -10.57; 95% CI: -12.35 to -8.78), P < .00001). No significant differences were found regarding the conversion rate, hospital stay, morbidity, and transfusion. CONCLUSIONS The LigaSure technique has comparable effects to conventional techniques, but to some extent reduces blood loss and operative time.