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The Cochrane Database of Systematic... Jun 2021It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or recurrent setting following transurethral resection of a bladder tumor. This is an update of a Cochrane Review first published in 2012. Since that time, several randomized controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To assess the comparative effectiveness and toxicity of intravesical gemcitabine instillation for NMIBC.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Library, MEDLINE, Embase, four other databases, trial registries, and conference proceedings to 11 September 2020, with no restrictions on the language or status of publication.
SELECTION CRITERIA
We included RCTs in which participants received intravesical gemcitabine for primary or recurrent NMIBC.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the included studies and extracted data for the primary outcomes: time to recurrence, time to progression, grade III to V adverse events determined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0), and the secondary outcomes: time to death from bladder cancer, time to death from any cause, grade I or II adverse events determined by the CTCAE v5.0 and disease-specific quality of life. We performed statistical analyses using a random-effects model and rated the certainty of the evidence using GRADE.
MAIN RESULTS
We included seven studies with 1222 participants with NMIBC across five comparisons. This abstract focuses on the primary outcomes of the three most clinically relevant comparisons. 1. Gemcitabine versus saline: based on two years' to four years' follow-up, gemcitabine may reduce the risk of recurrence over time compared to saline (39% versus 47% recurrence rate, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.54 to 1.09; studies = 2, participants = 734; I = 49%; low-certainty evidence), but the CI included the possibility of no effect. Gemcitabine may result in little to no difference in the risk of progression over time compared to saline (4.6% versus 4.8% progression rate, HR 0.96, 95% CI 0.19 to 4.71; studies = 2, participants = 654; I = 53%; low-certainty evidence). Gemcitabine may result in little to no difference in the CTCAE grade III to V adverse events compared to saline (5.9% versus 4.7% adverse events rate, risk ratio [RR] 1.26, 95% CI 0.58 to 2.75; studies = 2, participants = 668; I = 24%; low-certainty evidence). 2. Gemcitabine versus mitomycin: based on three years' follow-up (studies = 1, participants = 109), gemcitabine may reduce the risk of recurrence over time compared to mitomycin (17% versus 40% recurrence rate, HR 0.36, 95% CI 0.19 to 0.69; low-certainty evidence). Gemcitabine may reduce the risk of progression over time compared to mitomycin (11% versus 18% progression rate, HR 0.57, 95% CI 0.32 to 1.01; low-certainty evidence), but the CI included the possibility of no effect. We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to mitomycin (RR 0.51, 95% CI 0.13 to 1.93; very low-certainty evidence). The analysis was only based on recurrent NMIBC. 3. Gemcitabine versus Bacillus Calmette-Guérin (BCG) for recurrent (one-course BCG failure) high-risk NMIBC: based on 6 months' to 22 months' follow-up (studies = 1, participants = 80), gemcitabine may reduce the risk of recurrence compared to BCG (41% versus 97% recurrence rate, HR 0.15, 95% CI 0.09 to 0.26; low-certainty evidence) and progression over time (16% versus 33% progression rate, HR 0.45, 95% CI 0.27 to 0.76; low-certainty evidence). We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to BCG (RR 1.00, 95% CI 0.21 to 4.66; very low-certainty evidence). In addition, the review provides information on the comparison of gemcitabine versus BCG and gemcitabine versus one-third dose BCG. AUTHORS' CONCLUSIONS: Based on findings of this review, gemcitabine may have a more favorable impact on recurrence and progression-free survival than mitomycin but we are very uncertain as to how major adverse events compare. The same is true when comparing gemcitabine to BCG in individuals with high risk disease who have previously failed BCG. The underlying low- to very low-certainty evidence indicates that our confidence in these results is limited; the true effects may be substantially different from these findings; therefore, better quality studies are needed.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; BCG Vaccine; Bias; Cause of Death; Confidence Intervals; Deoxycytidine; Disease Progression; Drug Administration Schedule; Humans; Mitomycin; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Saline Solution; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 34125951
DOI: 10.1002/14651858.CD009294.pub3 -
European Urology Oct 2021Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are... (Meta-Analysis)
Meta-Analysis
CONTEXT
Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates.
OBJECTIVE
To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD.
EVIDENCE ACQUISITION
A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist.
EVIDENCE SYNTHESIS
A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p < 0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p < 0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p = 0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen.
CONCLUSIONS
Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence.
PATIENT SUMMARY
We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.
Topics: Captopril; Humans; Injections, Intralesional; Male; Mitomycin; Recurrence; Tamoxifen; Triamcinolone; Urethra; Urethral Stricture
PubMed: 34275660
DOI: 10.1016/j.eururo.2021.06.022 -
European Urology Focus May 2023The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer (NMIBC) have not become accepted.
OBJECTIVE
To assess the treatment outcomes of chemoablation for NMIBC and to compare its safety with that of the standard treatment, transurethral resection of bladder tumors (TURBT) followed by intravesical therapy.
EVIDENCE ACQUISITION
Multiple databases were queried in July 2022 for studies investigating the complete response (CR) rates and adverse events in NMIBC patients treated with chemoablation using mitomycin C (MMC), gemcitabine, epirubicin, or bacillus Calmette-Guérin.
EVIDENCE SYNTHESIS
Overall, 23 studies comprising 1199 patients were eligible for this meta-analysis. Among these studies, 20 assessed the efficacy of chemoablation and three compared the treatment outcomes of MMC chemoablation versus standard treatment. Among patients treated with weekly administration of any agent, the pooled CR rates at initial assessment were 50.9% (95% confidence interval [CI]: 45.9-55.9) for the marker lesion and 47.5% (95% CI: 36.5-58.7) for well-selected NMIBC (ie, small tumors and/or a small number of tumors). Novel regimens for chemoablation such as MMC-gel (70.6%, 95% CI: 60.1-79.3) and an intensive MMC regimen (64.7%, 95% CI: 56.2-72.3) provided better CR rates in well-selected NMIBC patients. Comparable CR rates were noted irrespective of tumor multiplicity, whereas tumor size <5 mm was associated with a higher CR rate than tumor size ≥5 mm (odds ratio: 0.36, 95% CI: 0.17-0.79). The novel intensive MMC regimen resulted in lower rates of dysuria and urinary frequency than standard treatment.
CONCLUSIONS
Despite the lack of long-term outcomes, chemoablation appears to be a promising treatment option for well-selected NMIBC patients and can potentially help avoid unnecessary TURBT, specifically in some elderly patients with intermediate-risk NMIBC. Further well-designed studies with larger cohorts are necessary to address the differential tolerability and long-term anticancer efficacy of this resurging approach.
PATIENT SUMMARY
Bladder instillation therapy has a potential ablative effect for well-selected non-muscle-invasive bladder cancer. This can lead to the omission of an unnecessary surgical treatment.
Topics: Humans; Aged; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Mitomycin; Gemcitabine; Administration, Intravesical
PubMed: 36517409
DOI: 10.1016/j.euf.2022.12.003 -
The Cochrane Database of Systematic... Sep 2021Cholangiocarcinoma (cancer in the bile duct) is an aggressive tumour for which surgical resection is a mainstay of treatment. Despite complete resection, recurrences of... (Review)
Review
BACKGROUND
Cholangiocarcinoma (cancer in the bile duct) is an aggressive tumour for which surgical resection is a mainstay of treatment. Despite complete resection, recurrences of the cancer are common and lead to poor prognosis in patients. Postoperative adjuvant chemotherapy given after surgical resection may reduce the risk of cancer recurrence by eradicating residual cancer and micrometastatic lesions. The benefits and harms of postoperative adjuvant chemotherapy versus placebo, no intervention, or other adjuvant chemotherapies are unclear.
OBJECTIVES
To assess the benefits and harms of postoperative adjuvant chemotherapy versus placebo, no intervention, or other adjuvant chemotherapies for people with cholangiocarcinoma after curative-intent resection.
SEARCH METHODS
We performed electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science for trials that met the inclusion criteria up to 28 April 2021.
SELECTION CRITERIA
Randomised clinical trials irrespective of blinding, publication status, or language comparing postoperative adjuvant chemotherapy versus placebo, no intervention, or a different postoperative adjuvant chemotherapy regimen for participants with curative-intent resection for cholangiocarcinoma.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods to develop and conduct the review. We conducted meta-analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CI). We assessed risk of bias according to predefined domains suggested by Cochrane. We rated the certainty of evidence using the GRADE approach and presented outcome results in a summary of findings table.
MAIN RESULTS
We included five published randomised clinical trials. The trials included 931 adults (18 to 83 years old) who underwent curative-intent resection for cholangiocarcinoma. Four trials compared postoperative adjuvant chemotherapy (mitomycin-C and 5-fluorouracil (5-FU); gemcitabine; gemcitabine plus oxaliplatin; or capecitabine) versus no postoperative adjuvant chemotherapy (surgery alone) in 867 participants with cholangiocarcinoma only. A fifth trial compared postoperative adjuvant S-1 (a novel oral fluoropyrimidine derivative) chemotherapy versus gemcitabine in 70 participants with intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma (64 participants), and gallbladder carcinoma (6 participants). We assessed all of the included trials at overall high risk of bias. One trial was conducted in France, three in Japan, and one in the United Kingdom. We could not perform all planned comparison analyses due to lack of data. Three trials used intention-to-treat analyses. Another trial used per-protocol analysis. In the remaining trial one participant in the intervention group and one in the control group were lost to follow-up. However, the outcomes of these two participants were not described. Postoperative adjuvant chemotherapy versus no postoperative adjuvant chemotherapy We are very uncertain as to whether postoperative adjuvant chemotherapy has little to no effect on all-cause mortality versus no postoperative adjuvant chemotherapy (RR 0.92, 95% CI 0.84 to 1.01; 4 trials, 867 participants, very low-certainty evidence). We are very uncertain of the effect of postoperative adjuvant chemotherapy on serious adverse events (RR 17.82, 95% CI 2.43 to 130.82; 1 trial, 219 participants, very low-certainty evidence). The trial indicated that postoperative adjuvant chemotherapy could increase serious adverse events, as 19/113 (20.5%) of participants developed an adverse event, compared to 1/106 (1.1%) of participants in the no-postoperative adjuvant chemotherapy group. None of the included trials reported data on health-related quality of life, cancer-related mortality, time to recurrence of the tumour, and non-serious adverse events in participants with only cholangiocarcinoma. Adjuvant S-1 chemotherapy (fluoropyrimidine derivative) versus adjuvant gemcitabine-based chemotherapy The only available trial analysed all participants with intrahepatic, perihilar cholangiocarcinoma and gallbladder carcinoma together, with data on participants with cholangiocarcinoma not provided separately. The authors reported that one-year overall mortality after adjuvant S-1 therapy was lower than with adjuvant gemcitabine-based therapy following major hepatectomy for biliary tract cancer. There were no differences in two-year overall mortality.
FUNDING
two trials received support from drug companies; one trial received funding from the Japan Society of Clinical Oncology; one trial received support from "Programme Hospitalier de Recherche Clinique (PHRC2009) and Ligue Nationale Contre le Cancer"; and one trial did not provide information on support or sponsorship. We identified six ongoing randomised clinical trials.
AUTHORS' CONCLUSIONS
Based on the very low-certainty evidence found in four trials in people with curative-intent resection for cholangiocarcinoma, we are very uncertain of the effects of postoperative adjuvant chemotherapy (mitomycin-C and 5-FU; gemcitabine; gemcitabine plus oxaliplatin; or capecitabine) versus no postoperative adjuvant chemotherapy on mortality. The effects of postoperative adjuvant chemotherapy compared with no postoperative adjuvant chemotherapy on serious adverse events are also very uncertain, but the result of the single trial showed 20% higher occurrences of haematologic adverse events. We assessed the certainty of the evidence as very low due to overall high risk of bias, and imprecision. Due to insufficient power of the only identified trial, the best postoperative adjuvant chemotherapy regimen in people with only cholangiocarcinoma could not be established. We also lack randomised clinical trials with outcome data on adjuvant S-1 chemotherapy versus adjuvant gemcitabine-based chemotherapy in people with cholangiocarcinoma alone. There is a need for further randomised clinical trials designed to be at low risk of bias and with adequate sample size exploring the best adjuvant chemotherapy treatment after surgery in people with cholangiocarcinoma.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemotherapy, Adjuvant; Cholangiocarcinoma; Humans; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Young Adult
PubMed: 34515993
DOI: 10.1002/14651858.CD012814.pub2 -
Journal of Clinical Medicine Aug 2023Although topical medical therapy and selective-laser-trabeculoplasty represent the treatments of choice to reduce intraocular pressure, many patients do not achieve... (Review)
Review
Although topical medical therapy and selective-laser-trabeculoplasty represent the treatments of choice to reduce intraocular pressure, many patients do not achieve adequate glaucoma control; therefore, they require further options and eventually surgery. Trabeculectomy is still considered the gold standard, but the surgical management of glaucoma has undergone continuous advances in recent years, XEN-gel-stent has been introduced as a safer and less traumatic means of lowering intraocular pressure (IOP) in patients with open-angle glaucoma (OAG). This study aimed to review the effectiveness and safety of clinical data on XEN-stent in OAG patients with a Synthesis-Without-Meta-analysis (SWiM) methodology. A total of 339 studies were identified following a literature search adhering to PRISMA guidelines and, after evaluation, 96 studies are discussed. XEN63 and XEN45 device data were collected both short and long term. In addition, this document has evaluated different aspects related to the XEN implant, including: its role compared to trabeculectomy; the impact of mitomycin-C dose on clinical outcomes; postoperative management of the device; and the identification of potential factors that might predict its clinical outcomes. Finally, current challenges and future perspectives of XEN stent, such as its use in fragile or high myopia patients, were discussed.
PubMed: 37629380
DOI: 10.3390/jcm12165339 -
Chinese Medicine 2020Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to... (Review)
Review
BACKGROUND
Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to identify potential pharmacokinetic or pharmacodynamic interactions from the existing literature to ensure their effective and safe combination usage in cancer patients.
METHODS
A systematic search was conducted on nine major Chinese and English databases, including China Journal Net, Allied and Complementary Medicine Database, and Ovid MEDLINE, etc., to identify clinical, animal, and in-vitro studies that evaluate the effect of combined use of Lingzhi or Yunzhi with cytotoxic drugs. The Jadad scale was used to assess the quality of clinical studies.
RESULTS
This search identified 213 studies, including 77 clinical studies that reported on the combined use of cytotoxic drugs with Yunzhi (n = 56) or Lingzhi (n = 21). Majority of these clinical studies demonstrated modest methodological quality. In clinical practice, the most commonly used cytotoxic drugs with Lingzhi were cisplatin, 5-fluorouracil (5-FU) and paclitaxel, whereas Tegafur/uracil (UFT)/Tegafur, 5-FU, and mitomycin were the ones used more often with Yunzhi. Only two clinical pharmacokinetic studies were available showing no significant interactions between Polysaccharide K (PSK) and Tegafur. From the pharmacodynamic interactions perspective, combination uses of Yunzhi/Lingzhi with cytotoxic drugs in clinical practice could lead to improvement in survival (n = 31) and quality of life (n = 17), reduction in tumor lesions (n = 22), immune modulation (n = 38), and alleviation of chemotherapy-related side effects (n = 14) with no reported adverse effects.
CONCLUSION
Our findings suggest that the clinical combination use of Lingzhi or Yunzhi with cytotoxic drugs could enhance the efficacy and ameliorate the adverse effects of cytotoxic drugs, leading to improved quality of life in cancer patients. More high quality clinical studies including pharmacokinetic herb-drug interactions studies are warranted to verify these observations and mechanisms involved. Based on the high quality clinical data, pharmacoepidemiology methods and bioinformatics or data mining could be adopt for further identification of clinical meaningful herb-drug interactions in cancer therapies.
PubMed: 32724333
DOI: 10.1186/s13020-020-00356-4 -
Bioengineering (Basel, Switzerland) Apr 2024Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic... (Review)
Review
Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), have been used to mitigate post-surgical fibrosis, but these have unpredictable outcomes. Therefore, there is a need to develop novel treatments which provide increased effectiveness and specificity. This review aims to provide insight into the pathophysiology behind wound healing in glaucoma surgery, as well as the current and promising future wound healing agents that are less toxic and may provide better IOP control.
PubMed: 38790314
DOI: 10.3390/bioengineering11050446 -
The Cochrane Database of Systematic... Nov 2022Radiotherapy and chemotherapy are used to improve survival in colorectal cancer but adverse effects can be a problem. Severe adverse effects may result in dose reduction... (Review)
Review
BACKGROUND
Radiotherapy and chemotherapy are used to improve survival in colorectal cancer but adverse effects can be a problem. Severe adverse effects may result in dose reduction or cessation of treatment, which have an impact on survival. Coriolus versicolor (Trametes versicolor or 'Turkey Tail') mushroom and its extracts have been used by cancer patients to help with adverse effects.
OBJECTIVES
To assess the effects of adjunctive Coriolus versicolor (Trametes versicolor) and its extracts on adverse effects and on survival during colorectal cancer treatment (chemotherapy and radiotherapy) compared with no adjunctive treatment.
SEARCH METHODS
We searched databases including CENTRAL, MEDLINE, Embase, AMED and CINAHL, Chinese and Japanese databases, and trials registers to 12th April 2022 without restriction of language or publication status. We screened reference lists and attempted to contact researchers in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the efficacy and safety of Coriolus versicolor and its extracts in adult participants with a confirmed diagnosis of colorectal cancer, in addition to conventional treatment. Interventions included any preparation of Coriolus versicolor (raw, decoction, capsule, tablet, tincture, extract, injection), any part of the fungus (cap, stem, mycelium or whole), in any dose or regimen. Outcomes included adverse events rates, survival, disease progression and recurrence, response rates and quality of life.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected studies, extracted outcome data, and assessed risk of bias. We evaluated the overall certainty of evidence using the GRADE approach.
MAIN RESULTS
We included seven parallel RCTs (1569 participants). Six studies (1516 participants) were conducted in Japan and one study (53 participants) in China. Studies included both male and female participants with colorectal cancer (five studies), colon cancer (one study) or rectal cancer (one study). Participants were diagnosed with cancer ranging from stage II to stage IV. Coriolus was used in the form of an extract in all seven studies and was generally used after curative resection, although in one study it was used preoperatively. Duration of treatment with the extract varied between four weeks and three years. Chemotherapeutic regimens in six studies consisted of an oral fluoropyrimidine which was preceded by weekly intravenous 5-Fluorouracil (5-FU) in one study, by mitomycin C in two studies, and which was combined with folinic acid (Leucovorin) in two studies and with radiotherapy preoperatively in one study. XELOX (oxaliplatin intravenous infusion and capecitabine) was used in the remaining study. We found very low-certainty evidence of little to no effect of adjunctive treatment with Coriolus (in the form of an extract, polysaccharide-Krestin, PSK) on withdrawal from treatment due to adverse events (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.45 to 2.34; 703 participants; 3 studies;). We are uncertain whether adjunctive Coriolus versicolor and its extracts compared to usual care alone resulted in a difference in adverse events including neutropenia (RR 0.41, 95% CI 0.24 to 0.71; 133 participants; 3 studies; very low certainty), oral cavity disorders such as oral dryness and mucositis (RR 0.37, 95% CI 0.13 to 1.03; 1022 participants; 5 studies; very low certainty), nausea (RR 0.73, 95% CI 0.44 to 1.22; 969 participants; 4 studies; very low certainty), diarrhoea (RR 0.77, 95% CI 0.32 to 1.86; 1022 participants; 5 studies; very low certainty), and fatigue (RR 0.76; 95% CI 0.33 to 1.78; 133 participants; 3 studies; very low certainty). We found low-certainty evidence of a small effect of adjunctive Coriolus on improved survival at five years compared with no adjunctive care (RR 1.08, 95% CI 1.01 to 1.15; 1094 participants; 3 studies; number needed to benefit (NNTB) = 16 (95% Cl 9 to 70). The effect at earlier time points was unclear.
AUTHORS' CONCLUSIONS
Due to the very low certainty of evidence, we were uncertain about the effect of adjunctive Coriolus (in the form of an extract PSK) on adverse events resulting from conventional chemotherapy for colorectal cancer. This includes effects on withdrawal of treatment due to adverse events and on specific adverse outcomes such as neutropenia and nausea. The uncertainty in the evidence also means that it was unclear whether any adverse events were due to the chemotherapy or to the extract itself. While there was low-certainty evidence of a small effect on overall survival at five years, the influence of reduced adverse effects on this could not be determined. In addition, chemotherapy regimens used in assessing this outcome do not reflect current preferred practice.
Topics: Adult; Female; Humans; Male; Agaricales; Colorectal Neoplasms; Drug-Related Side Effects and Adverse Reactions; Nausea; Neutropenia; Trametes; Randomized Controlled Trials as Topic
PubMed: 36445793
DOI: 10.1002/14651858.CD012053.pub2 -
The Cochrane Database of Systematic... Aug 2020Primary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child's life and is not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child's life and is not associated with other systemic or ocular abnormalities. PCG results in considerable morbidity even in high-income countries.
OBJECTIVES
To compare the effectiveness and safety of different surgical techniques for PCG.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2020, Issue 4); Ovid MEDLINE; Embase.com; PubMed; metaRegister of Controlled Trials (mRCT) (last searched 23 June 2014); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 27 April 2020.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs comparing different surgical interventions in children under five years of age with PCG.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We included 16 trials (13 RCTs and three quasi-RCTs) with 587 eyes in 446 children. Eleven (69%) trials were conducted in Egypt and the Middle East, three in India, and two in the USA. All included trials involved children younger than five years of age, with follow-up ranging from six to 80 months. The interventions compared varied across trials. Three trials (on 68 children) compared combined trabeculotomy and trabeculectomy (CTT) with trabeculotomy. Meta-analysis of these trials suggests there may be little to no evidence of a difference between groups in mean IOP (mean difference (MD) 0.27 mmHg, 95% confidence interval (CI) -0.74 to 1.29; 88 eyes; 2 studies) and surgical success (risk ratio (RR) 1.01, 95% CI 0.90 to 1.14; 102 eyes; 3 studies) at one year postoperatively. We assessed the certainty of evidence as very low for these outcomes, downgrading for risk of bias (-1) and imprecision (-2). Hyphema was the most common adverse outcome in both groups (no meta-analysis due to considerable heterogeneity; I = 83%). Two trials (on 39 children) compared viscotrabeculotomy to conventional trabeculotomy. Meta-analysis of 42 eyes suggests there is no evidence of between groups difference in mean IOP (MD -1.64, 95% CI -5.94 to 2.66) and surgical success (RR 1.11, 95% CI 0.70 to 1.78) at six months postoperatively. We assessed the certainty of evidence as very low, downgrading for risk of bias and imprecision due to small sample size. Hyphema was the most common adverse outcome (38% in viscotrabeculotomy and 28% in conventional trabeculotomy), with no evidence of difference difference (RR 1.33, 95% CI 0.63 to 2.83). Two trials (on 95 children) compared microcatheter-assisted 360-degree circumferential trabeculotomy to conventional trabeculotomy. Meta-analysis of two trials suggests that mean IOP may be lower in the microcatheter group at six months (MD -2.44, 95% CI -3.69 to -1.19; 100 eyes) and at 12 months (MD -1.77, 95% CI -2.92 to -0.63; 99 eyes); and surgical success was more likely to be achieved in the microcatheter group compared to the conventional trabeculotomy group (RR 1.59, 95% CI 1.14 to 2.21; 60 eyes; 1 trial at 6 months; RR 1.54, 95% CI 1.20 to 1.97; 99 eyes; 2 trials at 12 months). We assessed the certainty of evidence for these outcomes as moderate due to small sample size. Hyphema was the most common adverse outcome (40% in the microcatheter group and 17% in the conventional trabeculotomy group), with greater likelihood of occurring in the microcatheter group (RR 2.25, 95% CI 1.25 to 4.04); the evidence was of moderate certainty due to small sample size (-1). Of the nine remaining trials, no two trials compared the same two surgical interventions: one trial compared CTT versus CTT with sclerectomy; three trials compared various suturing techniques and adjuvant use including mitomycin C, collagen implant in CTT; one trial compared CTT versus Ahmed valve implant in previously failed surgeries; one trial compared CTT with trabeculectomy; one trial compared trabeculotomy to goniotomy; and two trials compared different types of goniotomy. No trials reported quality of life or economic data. Many of the included trials had limitations in study design, implementation, and reporting, therefore the reliability and applicability of the evidence remains unclear.
AUTHORS' CONCLUSIONS
The evidence suggests that there may be little to no evidence of difference between CTT and routine conventional trabeculotomy, or between viscotrabeculotomy and routine conventional trabeculotomy. A 360-degree circumferential trabeculotomy may show greater surgical success than conventional trabeculotomy. Considering the rarity of the disease, future research would benefit from a multicenter, possibly international trial, involving parents of children with PCG and with a follow-up of at least one year.
Topics: Child, Preschool; Glaucoma; Glaucoma Drainage Implants; Humans; Hyphema; Infant; Infant, Newborn; Intraocular Pressure; Mitomycin; Postoperative Complications; Randomized Controlled Trials as Topic; Sclera; Trabecular Meshwork; Trabeculectomy; Treatment Outcome
PubMed: 32816311
DOI: 10.1002/14651858.CD008213.pub3 -
BMJ Open May 2022To compare the effectiveness and safety of the six interventions for neovascular glaucoma. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the effectiveness and safety of the six interventions for neovascular glaucoma.
DESIGN
A systematic review and network meta-analysis.
METHODS
Randomised controlled trials and cohort studies which compared the six interventions in neovascular glaucoma were identified using the following databases searched up to 1 September 2020: PubMed, Cochrane Library, Embase and Web of Science. The quality assessment was conducted by using the Cochrane risk of bias tool and the Newcastle-Ottawa scale. The primary outcome measure was the weighted mean differences for intraocular pressure reduction. Secondary one was ORs for success rate. Outcome measures were reported with a 95% CI and p<0.05 was considered statistically significant. Network meta-analysis was performed using Stata V.15.0.
RESULTS
Twenty-three studies involving a total of 1303 patients were included. The types of surgical treatments included Ahmed glaucoma valve (AGV) implant surgery, AGV combined with intravitreal anti-vascular endothelial growth factor (AGV +IVAV), cyclophotocoagulation (CPC), cyclocryotherapy (CCT), trabeculectomy with mitomycin (Trab(MMC)) and Trab(MMC) combined with IVAV (Trab(MMC)+IVAV). Network meta-analysis showed that in comparison with AGV, AGV +IVAV (MD=4.74, 95% CI 1.04 to 8.45) and Trab(MMC)+IVAV (MD=6.19, 95% CI 0.99 to 11.40) showed a favourable effect in intraocular pressure reduction (IOPR) 6 months after surgery. Compared with CCT, AGV (OR=-0.17, 95% CI -0.53 to -0.05), AGV +IVAV (OR=-0.10, 95% CI -3.48 to -1.19), CPC (OR=-0.12, 95% CI -0.53 to -0.05), Trab(MMC) (OR=3.54, 95% CI 1.15 to 10.91) and Trab(MMC)+IVAV (OR=5.78, 95% CI 2.29 to 14.61) showed a superior impact in success rate. The order of efficacy as best intervention ranked as follows: Trab(MMC)+IVAV (IOPR 6 months after surgery, surface under the cumulative ranking (SUCRA)=88.1), CPC (IOPR 12 months after surgery, SUCRA=81.9), AGV +IVAV (IOPR 12 months after surgery, SUCRA=79.9) and AGV +IVAV (success rate, SUCRA=92.7). Adverse events were also summarised in detail.
CONCLUSION
In the treatment of neovascular glaucoma, AGV+IVAV and CPC were more effective in IOPR and success rate than the other four interventions. Additionally, AGV+IVAV is superior to CPC concerning the success rate in the long-term treatment. However, considering the limitations of this review, more high-quality trials, especially those surgical interventions not mentioned in this review, should be carried out in the future to further confirm the current findings.
Topics: Glaucoma Drainage Implants; Glaucoma, Neovascular; Humans; Intraocular Pressure; Network Meta-Analysis; Trabeculectomy; Treatment Outcome
PubMed: 35613778
DOI: 10.1136/bmjopen-2021-051794