Prophylactic clipping to prevent delayed colonic post-polypectomy bleeding: meta-analysis of randomized and observational studies
Surgical endoscopy. 2021
BACKGROUND AND AIMS Delayed post-polypectomy bleeding (DPPB) is a commonly described adverse event following polypectomy. Prophylactic clipping may prevent DPPB in some patient subgroups. We performed a meta-analysis to assess both the efficacy and real-world effectiveness of prophylactic clipping. METHODS We performed a database search through March 2020 for clinical trials or observational studies assessing prophylactic clipping and DPPB. Pooled risk ratios (RR) were calculated using random effects models. Subgroup, sensitivity, and meta-regression analyses were performed to elucidate clinical or methodological factors associated with effects on outcomes. RESULTS A total of 2771 citations were screened, with 11 randomized controlled trials (RCTs) and 9 observational studies included, representing 24,670 colonoscopies. DPPB occurred in 2.0% of patients overall. The pooled RR of DPPB was 0.47 (95% CI 0.29-0.77) from RCTs enrolling only patients with polyps ≥ 20 mm. Remaining pooled RCT data did not demonstrate a benefit for clipping. The pooled RR of DPPB was 0.96 (95% CI 0.61-1.51) from observational studies including all polyp sizes. For patients with proximal polyps of any size, the RR was 0.73 (95% CI 0.33-1.62) from RCTs. Meta-regression confirmed that polyp size ≥ 20 mm significantly influenced the effect of clipping on DPPB. CONCLUSION Pooled evidence demonstrates a benefit when clipping polyps measuring ≥ 20 mm, especially in the proximal colon. In lower-risk subgroups, prophylactic clipping likely results in little to no difference in DPPB.
Role of prophylactic hemoclip placement in prevention of delayed post-polypectomy bleeding for large colon polyps: a meta-analysis of randomized controlled trials
Annals of gastroenterology. 2021;34(3):392-398
BACKGROUND Polypectomy is a widely used and effective procedure to treat precancerous polyps. Delayed post-polypectomy bleeding (DPPB), a common complication of polypectomy, may diminish the utility of this procedure. Previous data on the efficacy of hemoclips has been conflicting, therefore we aimed to collectively evaluate and analyze the data to reach a definitive conclusion on the efficacy of using hemoclips to prevent incidences of DPPB in patients with large polyps (≥10 mm). METHODS We identified a total of 261 studies based on our previously defined search strategy. After screening, we included 6 randomized controlled trials. A meta-analysis was performed comparing the use of prophylactic application of hemoclips to a standard group without prophylactic clip placement for large polyps. RESULTS We found a statistically significant reduction in the incidence of DPPB when using hemoclips for large polyps. The overall incidence of DPPB was lower in the hemoclip group compared to the standard group for all large polyps ≥10 mm (relative risk 0.51, 95% confidence interval 0.35-0.75; P=0.01; I (2)=0%). CONCLUSIONS The use of hemoclips in achieving hemostasis for large polyps has a beneficial effect and appears to prevent DPPB. This reinforces the routine clinical practice of using hemoclips in polypectomy procedures.
Pure Red Cell Aplasia and Other Haematological Diseases Associated With Thymoma: A Case Series and Systematic Review
Frontiers in medicine. 2021;8:759914
Background: Thymoma-associated haematological diseases (HDs), such as pure red cell aplasia (PRCA) and Good's syndrome, are extremely rare, and due to the paucity of large-scale studies, the characteristics, remission after thymectomy, and long-term evaluation remain undetermined. Methods: We retrospectively assessed patients with thymoma and associated HDs from Jan 2005 to Dec 2020. All patients received thymectomy and/or additional treatments for HDs. A comparison with thymoma-associated myasthenic gravis (MG), and a systematic review from PubMed/MEDLINE and Embase were conducted. Results: In the median follow-up of 56 months, 130 patients were enrolled. Patients with thymoma-associated MG (n = 46) and HDs [n = 8; PRCA (n = 5), PRCA and Good's syndrome (n = 2) and autoimmune haemolytic anaemia (n = 1)] were evaluated. Patients with MG had a significantly higher remission rate after thymectomy (50 vs. 17%; p = 0.0378) as compared to those with other autoimmune diseases. Two of seven patients with PRCA experienced remission with thymectomy alone, and an additional two patients achieved remission with thymectomy plus immunosuppressive therapy (IST). In the systematic review, 60 studies (case reports, n = 46; case series including the present study, n = 14) were evaluated. Forty-four percent of patients were diagnosed with PRCA after thymoma, and 61% achieved remission with thymectomy plus IST; however, Good's syndrome was unaffected. Conclusions: Our study indicates that patients with thymoma-associated autoimmune diseases other than MG have a lower remission rate than those with MG. Remission of thymoma-associated PRCA can be achieved by thymectomy and IST. This study provides insight into extremely rare but puzzling autoimmune manifestations.
Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review
Frontiers in oncology. 2021;11:727010
More than 40 tyrosine kinase inhibitors (TKIs) have received hematological or oncological indications over the past 20 years, following the approval of imatinib, and many others are currently being tested in clinical and preclinical level. Beyond their common toxicities, no certain agent from this large class of molecularly targeted therapies was strongly associated with "off-target" impairment of neuromuscular transmission, and although myasthenia gravis (MG) is a well-characterized autoimmune disorder, only few sporadic events proven by serologically detected causative autoantibodies and/or by positive electrophysiological tests are reported in the literature. Herein, we present the first case of anti-MUSK (+) MG in a woman with metastatic BRAF-mutant melanoma after long-term treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Triggered by this report, a systematic literature review was conducted, summarizing all other cancer cases that developed MG, after exposure to any type of targeted agent and regardless of the underlying malignancy. All available data on the clinical diagnosis, the potential of administered TKIs to induce a seropositive myasthenic syndrome, the immune and non-immune-mediated pathogenesis of postsynaptic damage, and the challenging management of this neuromuscular toxicity were collected and discussed. In the presented case, MG was confirmed by both autoantibodies and nerve-conduction tests, while its reactivation after TKIs rechallenge supports a more than coincidental association. The following review identified 12 cancer cases with TKI-related MG in six case reports and one case series. In most of them, the myasthenia diagnosis was challenging, since the clinical symptomatology of fatigable weakness was not corroborating with consistent laboratory and electrophysiological findings. In fact, anti-AchR titers were positive in five and anti-MuSK only in the abovementioned individual. The symptomatology corresponded to TKI discontinuation and standard treatment with pyridostigmine and prednisolone; intravenous immunoglobulin was added only in three, and two required mechanical ventilation. In an era where TKIs will be prescribed more frequently for various malignancies, even in combinations with immune-checkpoint inhibitors, this report synthesizes their risk for neuromuscular complications and increases the clinicians' awareness in order to extend the on-treatment and overall survival of TKI-treated cancer patients.
Potentially Overestimated Efficacy of Nanoparticle Albumin-bound Paclitaxel compared with Solvent-based Paclitaxel in Breast Cancer: A Systemic Review and Meta-analysis
Journal of Cancer. 2021;12(17):5164-5172
Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has exhibited clinical efficacy in breast cancer treatment, but toxicities can be yielded more at the same time. We did this meta-analysis aiming to unambiguously compare nab-PTX with conventional solvent-based paclitaxel (sb-PTX) in breast cancer patients of all stages. Method: Pubmed, Embase and Cochrane Library were searched for head-to-head randomized controlled trials of nab-PTX and sb-PTX in breast cancer. Risk ratio (RR) with 95% confidence interval was used for dichotomous variables while Hazard ratio (HR) was used for time-to-event outcomes. Results: Our review finally included 9 studies with 3508 patients. Nab-PTX showed a benefit on objective response rate (ORR) (RR=1.22 [1.04-1.43], P=0.01) as well as non-inferiority compared with sb-PTX in disease control rate (DCR) (RR=1.01 [0.98-1.04], P=0.44), overall survival (OS) (HR=0.99 [0.93-1.05], P=0.81) and disease free survival/progression free survival (DFS/PFS) (HR=0.92 [0.81-1.05], P=0.21). However, when it comes to toxicities (fatigue, nausea or vomiting, peripheral sensory neuropathy and adverse event related discontinuation), results favored sb-PTX (RR=2.89 [1.07-7.8], 3.15 [1.78-5.59], 2.11 [1.32-3.37], 2.02 [1.61-2.53]; P<0.05). Patients with metastatic tumors or undergoing conventional schedule responses better to nab-PTX than the compared groups (RR of ORR in metastatic vs early or locally advanced patients: 1.46 [1.09-1.96] vs 1.01 [0.94-1.08]; conventional vs dose dense group: 1.59 [1.23-2.06] vs 1.01 [0.91-1.12]). Conclusions: Nab-PTX can improve ORR compared with paclitaxel and should be given priority to when aiming to reduce tumor load in breast cancer. Sb-PTX of dose dense schedule is recommended when toxicity of nab-PTX is hard to bear for breast cancer patients.
Effects of Fibrin Sealant on Seroma Reduction for Patients with Breast Cancer Undergoing Axillary Dissection: Meta-Analysis of Randomized Controlled Trials
Ann Surg Oncol. 2020
BACKGROUND Seroma formation is common in patients with breast cancer after axillary dissection. Fibrin sealant, containing fibrinogen and thrombin, has been developed to improve wound healing. We conducted a systematic review and meta-analysis to evaluate the efficacy of fibrin sealants in reducing seroma among patients with breast cancer undergoing axillary dissection. METHODS We searched the PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs) published up to April 2020. Pooled estimates of the outcomes were computed using a random-effects model. The primary outcomes were incidence and volume of seroma, while the secondary outcomes were volume and duration of drainage, incidence of infection, and length of hospital stay. RESULTS We reviewed 23 RCTs that included 1640 patients. Compared with the control group, the fibrin sealant group had no significant differences in the incidence of seroma, length of hospital stay, or incidence of surgical site infection. Significant intergroup differences were discovered in lower volume of seroma (weighted mean difference [WMD] - 71.88, 95% confidence interval [CI] - 135.58 to - 8.19), volume of drainage (WMD - 73.24, 95% CI - 107.32 to - 39.15), and duration of drainage (WMD - 0.84, 95% CI - 1.50 to - 0.19). CONCLUSIONS Fibrin sealants provide limited benefits in reducing the volume of seroma and the volume and duration of drainage. Therefore, after shared decision making, surgeons may apply fibrin sealants to patients with breast cancer undergoing axillary dissection.
Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: A meta-analysis
Scientific reports. 2020;10(1):530
The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69-3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07-3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62-0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54-0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC.
Patients with metastatic breast cancer, (5 studies), (n= 1,554).
Nanoparticle albumin-bound (nab)-paclitaxel chemotherapy, (n=774).
Solvent-based (sb)-taxanes chemotherapy: sb-paclitaxel, (n=606) and docetaxel, (n=174).
When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of overall response rate (ORR) (OR 2.39), disease control rate (DCR) (OR 1.89), and progression-free survival (PFS) (HR 0.75). Nab-paclitaxel also showed significantly longer overall survival (OS) (HR 0.73) than docetaxel. Adverse events (AEs) and dose discontinuation rate (DDR) were comparable between the two arms.
Polyglycolic acid sheets decrease post-endoscopic submucosal dissection bleeding in early gastric cancer: a systematic review and meta-analysis
J Dig Dis. 2020
Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer (EGC). However, post-ESD bleeding remains a serious issue particularly in patients continued antithrombotic agent treatment or undergone a large mucosal resection (>4 cm). It has been suggested that ulcer bed induced by ESD covered with polyglycolic acid (PGA) sheets can prevent post-ESD bleeding. However, the effectiveness of this procedure has been questioned. To this end, Pubmed, Cochrane library and Embase databases were searched for studies on the effects of PGA sheets shielding on inpatients with EGC and high risk bleeding using post-ESD bleeding rate as the primary outcome. Among the four included studies with 212 lesions in the PGA sheets group and 208 lesions in the control group, post-ESD bleeding rate was significantly lower in the PGA sheet group than in the control group (4.9% vs. 13.7%, risk ratio (RR) 0.33, 95% confidence interval (CI) 0.16-0.69, P = 0.003). Subgroup analysis showed application of PGA sheets effectively reduced the post-ESD bleeding rate in patients receiving antithrombotic agents (5.5% vs. 14.5%, RR 0.39, 95% CI 0.18-0.83, P = 0.01). However, although application of PGA sheets tended to decrease post-ESD bleeding rate in patients who underwent large mucosal resections, the difference was not significantly different (3.0% vs. 9.6%, RR 0.43; 95% CI 0.08-2.23, P = 0.31) and need to be further confirmed.
Hyperfibrinolysis in Patients with Solid Malignant Neoplasms: A Systematic Review
Seminars in thrombosis and hemostasis. 2020
Solid malignant neoplasms have the capability of disturbing the fibrinolytic system, leading to primary hyperfibrinolysis, a paraneoplastic syndrome that potentially results in severe bleeding. Yet, the full extent of primary hyperfibrinolysis in solid malignant neoplasms is unknown. Thus, the purpose of this study was to systematically review the current literature regarding clinical manifestations, biochemical diagnosis, and treatment of primary hyperfibrinolysis in patients with solid malignant neoplasms. The review was performed in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, Scopus, and Web of Science were searched on December 5, 2019, without time limits. Studies were included if they comprised at least one biochemical marker of fibrinolysis in addition to fibrinogen degradation products such as D-dimer, and furthermore included a correlation between biochemical marker and clinical outcome. In total, 12 studies were included. All studies were case reports including a total of 21 patients. Prostate cancer was the most frequently represented cancer type (76%), and the majority of cancer patients had metastatic disease (81%). Spontaneous bleeding was the clinical presentation in the majority of patients (76%), and the most frequently localization for the bleedings was subcutaneous. Antifibrinolytic agents were the most commonly used treatment and ceased bleedings in 80% of patients. Three patients died of uncontrolled bleedings. In conclusion, primary hyperfibrinolysis induced by solid malignant neoplasms is a rare but potentially life-threatening condition that should be considered, especially in patients with metastatic disease presenting with serious, spontaneous subcutaneous bleedings. A standardized diagnostic strategy is strongly needed.
Intraoperative balloon occlusion of the aorta for blood management in sacral and pelvic tumor resection: A systematic review and meta-analysis
Surgical oncology. 2020;35:156-161
BACKGROUND Neoplasms of the sacrum and pelvis are challenging to manage due to their complex vascularity and size and are at high risk of bleeding during resection. Intra-aortic balloon occlusion (IABO) has been used in trauma to control massive blood loss, but its efficacy and safety in oncologic sacral and pelvic surgery are unknown. The primary objective of this systematic review and meta-analysis was to assess the effectiveness of IABO in providing hemorrhage control during resection of sacral and pelvic tumors. METHODS This PROSPERO pre-registered study meta-analyzed all studies reporting on the use of IABO in the setting of pelvic and sacral tumour resection, in accordance with the PRISMA guidelines. The primary outcome of the meta-analysis was intraoperative blood loss, with secondary outcomes consisting of transfusion volume, post-operative blood loss, operative time, complication rate, and mortality. RESULTS Across studies, IABO was associated with a large, significant reduction in intraoperative blood loss (SMD -0.81, 95% CI -1.01 to -0.60, P < 0.0001) and transfused red blood cell volume (SMD 0.92, 95% CI -1.30 to -0.53, P < 0.0001). Two studies reported that complication rates were comparable between patients receiving IABO and patient receiving conventional surgery (Odds ratio = 1.29, 95% CI: 0.59 to 2.83, P = 0.52). All studies descriptively reported improved visualization of the operative field with IABO. CONCLUSIONS Our findings demonstrated that IABO is an effective technique to decrease blood loss and transfusion requirements during sacral and pelvic tumor surgery. Future clinical trials should be conducted to establish the safety of this method and explore potential contraindications.