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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 -
The Cochrane Database of Systematic... Jan 2010After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated and some important clinical questions were unanswered.
OBJECTIVES
We initiated a meta-analysis seeking updated individual patient data (IPD) from all randomised controlled trials (RCTs) to assess the effect of chemoradiotherapy on all outcomes. We pre-specified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics.
SEARCH STRATEGY
We supplemented MEDLINE, LILACS and CANCERLIT searches with information from trial registers, by handsearching relevant meeting proceedings and by discussion with relevant trialists and organisations. Searches were updated until October 2009.
SELECTION CRITERIA
Both published and unpublished trials were eligible for inclusion provided the patients had been randomised between radiotherapy (with or without surgery) versus concomitant chemoradiotherapy (with or without surgery); that the method of randomisation precluded prior knowledge of the treatment to be assigned; and that the trial had completed patient recruitment before the date of the final analyses.
DATA COLLECTION AND ANALYSIS
We carried out a quantitative meta-analysis using updated information from individual patients from all available RCTs. We sought data from all patients randomised in all eligible trials. We obtained updated information on survival, recurrence and date of last follow up. To avoid potential bias, we requested information for all randomised patients, including those who had been excluded from the investigators' original analyses.
MAIN RESULTS
Eighteen trials were identified and 15 of these were eligible for inclusion in the main analysis. On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio (HR) = 0.81, P < 0.001). A larger survival benefit was seen for the two further trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = 0.017) and non-platinum based (HR = 0.77, P = 0.009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival (DFS). There was a suggestion of a difference in the size of the survival benefit with tumour stage, but not across other patient subgroups. Acute haematological and gastro-intestinal toxicity were increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity.
AUTHORS' CONCLUSIONS
These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy this requires testing in RCTs.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Humans; Mitomycin; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms
PubMed: 20091664
DOI: 10.1002/14651858.CD008285 -
The Cochrane Database of Systematic... Oct 2005Trabeculectomy is performed as a treatment for glaucoma to lower the intraocular pressure (IOP). Mitomycin C (MMC) is an antimetabolite used during the initial stages of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Trabeculectomy is performed as a treatment for glaucoma to lower the intraocular pressure (IOP). Mitomycin C (MMC) is an antimetabolite used during the initial stages of a trabeculectomy to prevent excessive postoperative scarring and thus reduce the risk of failure.
OBJECTIVES
To assess the effects of intraoperative MMC compared to placebo in trabeculectomy.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1985 to 20 March 2005), SIGLE (1980 to December 2004), the National Research Register (Issue 1, 2005), LILACS (29 March 2005) and reference lists of articles. We also contacted researchers in the field.
SELECTION CRITERIA
We included randomised trials of intraoperative MMC compared to placebo in trabeculectomy surgery.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We contacted trial investigators for missing information.
MAIN RESULTS
Eleven trials, involving a total of 698 participants, were included. The trials enrolled three types of participants (high risk of failure, trabeculectomy combined with cataract surgery, no previous surgical intervention). Mitomycin C appears to reduce the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean IOP was significantly reduced at 12 months in all three participant groups receiving MMC compared to placebo. No significant increase in permanent sight-threatening complications was detected. However, none of the trials were large enough or of sufficient duration to address the long-term risk of bleb infection and endophthalmitis which has been reported in observational studies. Some evidence exists that MMC increases the risk of cataract.
AUTHORS' CONCLUSIONS
Intraoperative MMC reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean IOP at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following MMC, there was insufficient power to detect any increase in other serious side effects such as endophthalmitis.
Topics: Antimetabolites; Cicatrix; Glaucoma; Humans; Intraoperative Period; Mitomycin; Randomized Controlled Trials as Topic; Trabeculectomy; Treatment Failure
PubMed: 16235305
DOI: 10.1002/14651858.CD002897.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 -
Acta Ophthalmologica Nov 2020Favourable outcome after glaucoma surgery depends on proper control of the inflammatory response. Failing filtration bleb and consequently increased intraocular pressure...
Needling after trabeculectomy - does augmentation by anti-metabolites provide better outcomes and is Mitomycin C better than 5-Fluoruracil? A systematic review with network meta-analyses.
PURPOSE
Favourable outcome after glaucoma surgery depends on proper control of the inflammatory response. Failing filtration bleb and consequently increased intraocular pressure is an important cause of continuous visual field deterioration after uncomplicated glaucoma surgery. The present systematic review and meta-analysis aimed to compare the effects of employing either Mitomycin C (MMC), 5-Fluoruracil (5-FU) or no anti-metabolite in needling revision of trabeculectomies.
METHODS
We performed a systematic literature search in PubMed, Cochrane and EMBASE to identify randomized and non-randomized trials published between year 2000 and March 2019 comparing the efficacy of needling filtering blebs when using no anti-fibrotic agent, MMC or 5-FU in patients with glaucoma. Efficacy was defined as intraocular pressure at 12 months or latest follow-up, rate of complications, rates of success and the number of re-needling cases. Comparisons were made using network meta-analyses.
RESULTS
We identified one randomized trial and five retrospective trials. Twelve months after needling revision of trabeculectomy, no significant difference was observed when comparing the effect of the use of MMC with 5-FU or without any use of anti-metabolite on intraocular pressure, complication rates, qualified success, complete success or number of re-needling cases.
CONCLUSION
We found no significant difference in the efficacy of using either MMC, 5-FU or no anti-metabolite in needling revision of trabeculectomies. The number of studies meeting our inclusion criteria was limited. Considering the design of studies, only one was randomized leading to an overall low quality of evidence on the subject matter. Further research is warranted.
Topics: Fluorouracil; Glaucoma; Humans; Immunosuppressive Agents; Intraocular Pressure; Mitomycin; Network Meta-Analysis; Nucleic Acid Synthesis Inhibitors; Postoperative Complications; Trabeculectomy
PubMed: 32352646
DOI: 10.1111/aos.14452 -
The Cochrane Database of Systematic... Aug 2021Glaucoma is one of the leading largely preventable causes of blindness in the world. It is usually addressed first medically with topical intraocular pressure-lowering... (Review)
Review
BACKGROUND
Glaucoma is one of the leading largely preventable causes of blindness in the world. It is usually addressed first medically with topical intraocular pressure-lowering drops or by laser trabeculoplasty. In cases where such treatment fails, glaucoma-filtering surgery such as trabeculectomy, is commonly considered. Surgeons can differ in their technique when performing trabeculectomy, for example, the choice of the type of the conjunctival flap (fornix- or limbal-based). In a fornix-based flap, the surgical wound is performed at the corneal limbus; while in a limbal-based flap, the incision is further away. Many studies in the literature compare fornix- and limbal-based trabeculectomy with respect to outcomes and complications.
OBJECTIVES
To assess the comparative effectiveness of fornix- versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on intraocular pressure (IOP) control and complication rates (adverse effects).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 3); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 23 March 2021. There were no restrictions to language or year of publication.
SELECTION CRITERIA
We included RCTs comparing the benefits and complications of fornix- versus limbal-based trabeculectomy for glaucoma, irrespective of glaucoma type, publication status, and language. We excluded studies on children less than 18 years of age, since wound healing is different in this age group and the rate of bleb scarring postoperatively is high.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as per Cochrane criteria. MAIN RESULTS: We did not identify any new eligible studies for this review update. As presented in the original review, we included six trials with a total of 361 participants. Two studies were conducted in the USA and one each in Germany, Greece, India, and Saudi Arabia. The participants of four trials had open-angle glaucoma; one study included participants with primary open-angle or primary closed-angle glaucoma, and one study did not specify the type of glaucoma. Three studies used a combined procedure (phacotrabeculectomy). Trabeculectomy with mitomycin C (MMC) was performed in four studies, and trabeculectomy with 5-fluorouracil (5-FU) was performed in only one study. None of the included trials reported trabeculectomy failure at 24 months. Only one trial reported the failure rate of trabeculectomy as a late complication. Failure was higher among participants randomised to the limbal-based surgery: 1/50 eyes failed trabeculectomy in the fornix group compared with 3/50 in the limbal group (Peto odds ratio 0.36, 95% confidence interval (CI) 0.05 to 2.61)); therefore we are very uncertain as to the relative effect of the two procedures on failure rate. Four studies including 252 participants provided measures of mean IOP at 12 months. In the fornix-based surgeries, mean IOP ranged from 12.5 to 15.5 mmHg and similar results were noted in limbal-based surgeries with mean IOP ranging from 11.7 to 15.1 mmHg without significant difference. Mean difference was 0.44 mmHg (95% CI -0.45 to 1.33; 247 eyes) and 0.86 mmHg, (95% CI -0.52 to 2.24; 139 eyes) at 12 and 24 months of follow-up, respectively. Neither of these pooled analyses showed a statistically significant difference in IOP between groups (moderate certainty evidence). One trial reported number of anti-glaucoma medications at 24 months of follow-up with no difference noted between surgical groups. However, three trials reported the mean number of anti-glaucoma medications at 12 months of follow-up without significant difference in the mean number of postoperative IOP-lowering medications between the two surgical techniques. Mean difference was 0.02, (95% CI -0.15 to 0.19) at 12 months of follow-up (high certainty evidence). Because of the small numbers of events and total participants, the risk of many reported adverse events was uncertain and those that were found to be statistically significant may have been due to chance. For risk of bias assessment: although all six trials were randomised selection bias was mostly unclear, with unclear random sequence generation in four of the six studies and unclear allocation concealment in five of the six studies. Attrition bias was encountered in only one trial which also suffered from reporting bias. All other trials had an unclear risk of reporting bias as there was no access to study protocols. All included trials were judged to have high risk of detection bias due to lack of masking of the outcomes. Trabeculectomy is quite a standard procedure and unlikely to induce bias due to surgeon 'performance', hence performance bias was not evaluated.
AUTHORS' CONCLUSIONS
The main result of this review was that there was uncertainty as to the difference between fornix- and limbal-based trabeculectomy surgeries due to the small number of events and confidence intervals that cross the null. This also applied to postoperative complications, but without any impact on long-term failure rate between the two surgical techniques.
Topics: Child; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Sclera; Trabeculectomy
PubMed: 34437715
DOI: 10.1002/14651858.CD009380.pub3 -
The Cochrane Database of Systematic... Apr 2018Biliary tract cancers are a group of rare heterogeneous malignant tumours. They include intrahepatic and extrahepatic cholangiocarcinomas, gallbladder carcinomas, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Biliary tract cancers are a group of rare heterogeneous malignant tumours. They include intrahepatic and extrahepatic cholangiocarcinomas, gallbladder carcinomas, and ampullary carcinomas. Surgery remains the optimal modality of therapy leading to long-term survival for people diagnosed with resectable biliary tract carcinomas. Unfortunately, most people with biliary tract carcinomas are diagnosed with either unresectable locally-advanced or metastatic disease, and they are only suitable for palliative chemotherapy or supportive care.
OBJECTIVES
To assess the benefits and harms of intravenous administration of gemcitabine monotherapy or gemcitabine-based chemotherapy versus placebo, or no intervention, or other treatments (excluding gemcitabine) in adults with advanced biliary tract carcinomas.
SEARCH METHODS
We performed electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science up to June 2017. We also checked reference lists of primary original studies and review articles manually, for further related articles (cross-references).
SELECTION CRITERIA
Eligible studies include randomised clinical trials, irrespective of language or publication status, comparing intravenous administration of gemcitabine monotherapy or gemcitabine-based combination to placebo, to no intervention, or to treatments other than gemcitabine.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We assessed risks of bias of the included trials using definitions of predefined bias risk domains, and presented the review results incorporating the methodological quality of the trials using GRADE.
MAIN RESULTS
We included seven published randomised clinical trials with 600 participants. All included trials were at high risk of bias, and we rated the evidence as very low quality. Cointerventions were equally applied in three trials (gemcitabine plus S-1 (a combination of tegafur, gimeracil, and oteracil) versus S-1 monotherapy; gemcitabine plus S-1 versus gemcitabine monotherapy versus S-1 monotherapy; and gemcitabine plus vandetanib versus gemcitabine plus placebo versus vandetanib monotherapy), while four trials compared gemcitabine plus cisplatin versus S-1 plus cisplatin; gemcitabine plus mitomycin C versus capecitabine plus mitomycin C; gemcitabine plus oxaliplatin versus chemoradiotherapy; and gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive care. The seven trials were conducted in India, Japan, France, China, Austria, South Korea, and Italy. The median age of the participants in the seven trials was between 50 and 60 years, and the male/female ratios were comparable in most of the trials. Based on these seven trials, we established eight comparisons. We could not perform all planned analyses in all comparisons because of insufficient data.Gemcitabine versus vandetanibOne three-arm trial compared gemcitabine versus vandetanib versus both drugs in combination. It reported no data for mortality, health-related quality of life, or tumour progression outcomes. We rated the increased risk of serious adverse events, anaemia, and overall response rate as very low-certainty evidence.Gemcitabine plus cisplatin versus S-1 plus cisplatinFrom one trial of 96 participants, we found very low-certainty evidence that gemcitabine can lower the risk of mortality at one year when used with cisplatin versus S-1 plus cisplatin (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 0.98; P = 0.04; participants = 96). The trial did not report data for serious adverse events, quality of life, or tumour response outcomes. There is very low-certainty evidence that gemcitabine plus cisplatin combination leads to a higher risk of high-grade thrombocytopenia compared with S-1 plus cisplatin combination (RR 5.28, 95% CI 1.23 to 22.55; P = 0.02; participants = 96).Gemcitabine plus S-1 versus S-1From two trials enrolling 151 participants, we found no difference between the two groups in terms of risk of mortality at one year or risk of serious adverse events. Gemcitabine plus S-1 combination was associated with a higher overall response rate compared with S-1 alone (RR 2.46, 95% CI 1.27 to 4.75; P = 0.007; participants = 140; trials = 2; I = 0%; very low certainty of evidence). Neither of the trials reported data for health-related quality of life or time to progression of the tumour.Gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive careOne three-arm trial compared gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive care. It reported no data for serious adverse events, health-related quality of life, or tumour progression. We rated the evidence for mortality and for overall response rate as of very low certainty.Gemcitabine plus oxaliplatin versus 5-fluorouracil plus cisplatin plus radiotherapyOne trial of 34 participants compared gemcitabine plus oxaliplatin versus 5-fluorouracil plus cisplatin plus radiotherapy. It reported no data for quality of life, overall response rate, or tumour progression outcomes. We rated the evidence for mortality and serious adverse events as of very low certainty.Gemcitabine plus mitomycin C versus capecitabine plus mitomycin COne trial of 51 participants compared gemcitabine plus mitomycin C versus capecitabine plus mitomycin C. It reported no data for serious adverse events, quality of life, or tumour progression. We rated the evidence for mortality, overall response rate and thrombocytopenia as of very low certainty.We also identified three ongoing trials evaluating outcomes of interest for our review, which we can incorporate in future updates.For-profit bias: there was a high risk of for-profit bias in two trials (because of industry sponsorship) while there was a low risk of for-profit bias in another three trials, and unclear risk in two trials.
AUTHORS' CONCLUSIONS
In adults with advanced biliary tract carcinomas, the effects of gemcitabine or gemcitabine-based chemotherapy are uncertain on mortality and overall response compared with a range of inactive or active controls. The very low certainty of evidence is due to risk of bias, lack of information in the analyses and hence large imprecision, and possible publication bias. The confidence intervals do not rule out meaningful benefits or lack of effect of gemcitabine in all comparisons but one on mortality where gemcitabine plus cisplatin is compared with S-1 plus cisplatin. Gemcitabine-based regimens showed an increase in non-serious adverse events (particularly haematological toxicities). Further randomised clinical trials are mandatory, to further explore the best therapeutic options for adults with advanced biliary tract carcinomas.
Topics: Ampulla of Vater; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Capecitabine; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Humans; Male; Mitomycin; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Piperidines; Quinazolines; Randomized Controlled Trials as Topic; Tegafur; Gemcitabine
PubMed: 29624208
DOI: 10.1002/14651858.CD011746.pub2 -
Urologia Internationalis 2023The high recurrence of a urethral stricture after direct vision internal urethrotomy (DVIU) has been a problem for years. Mitomycin C (MMC) is an excellent antifibrosis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The high recurrence of a urethral stricture after direct vision internal urethrotomy (DVIU) has been a problem for years. Mitomycin C (MMC) is an excellent antifibrosis antigen that has been used in many fields, but its effect on a urethral stricture remains controversial. The purpose of this review was to investigate the effectiveness of MMC in reducing the recurrence rate of a urethral stricture after the first urethrotomy.
METHODS
Common databases were searched for publications prior to November 30, 2020. Randomized controlled and cohort trials were all included. Recurrence and success rates after the first urethrotomy of the posterior urethra were the main outcomes. Revman 5.3 was used for statistical analysis. Two evaluation systems, the Cochrane risk of bias tool and the Newcastle Ottawa Scale, were used to examine the risk of bias for RCTs and all studies. The quality of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation standard.
RESULTS
Sixteen trials were included, the reporting quality of which was generally poor, and the evidence level was very low to moderate. The addition of MMC could significantly reduce the recurrence rate of urethral strictures (risk ratio [RR] = 0.42; 95% confidence interval [CI]: 0.26, 0.67; p = 0.0002; 9 trials; 550 participants). The results of the subgroup analysis suggested that the effect of MMC combined with DVIU was significant in short (≤2 cm) anterior urethral strictures (RR = 0.39; 95% CI: 0.20, 0.78; p = 0.008), >12-month follow-up (RR = 0.45; 95% CI: 0.26, 0.76; p = 0.003). It also increased the success rate of the first urethrotomy procedure for posterior urethral contracture (RR = 0.74; 95% CI: 0.65, 0.84; p < 0.00001; 7 trials; 342 participants). Low-dose local injection of MMC was the most commonly used method.
CONCLUSION
MMC combined with DVIU is a promising way to reduce the long-term recurrence rate of a short-segment anterior urethral stricture. It also increases the success rate of the first urethrotomy of the posterior urethra. However, more high-quality randomized controlled trials are needed.
Topics: Humans; Urethral Stricture; Urethra; Mitomycin; Recurrence
PubMed: 34670219
DOI: 10.1159/000518977 -
Scientific Reports Aug 2022Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical... (Meta-Analysis)
Meta-Analysis
Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.
Topics: Administration, Topical; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Eye Neoplasms; Fluorouracil; Humans; Interferon alpha-2; Mitomycin; Retrospective Studies; Treatment Outcome
PubMed: 35987957
DOI: 10.1038/s41598-022-18545-6 -
Experimental Eye Research Apr 2022Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven... (Review)
Review
Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven treatment is lowering intraocular pressure (IOP), the most important risk factor. Glaucoma filtration surgery (GFS) can effectively lower IOP. However, approximately 10% of all surgeries fail yearly due to excessive wound healing, leading to fibrosis. GFS animal models are commonly used for the development of novel treatment modalities. The aim of the present review was to provide an overview of available animal models and anti-fibrotic drug candidates. MEDLINE and Embase were systematically searched. Manuscripts until September 1st 2021 were included. Studies that used animal models of GFS were included in this review. Additionally, the snowball method was used to identify other publications which had not been identified through the systematic search. Two hundred articles were included in this manuscript. Small rodents (e.g. mice and rats) are often used to study the fibrotic response after GFS and to test drug candidates. Due to their larger eyes, rabbits are better suited to develop medical devices. Novel drugs aim to inhibit specific pathways, e.g. through the use of modulators, monoclonal antibodies, aqueous suppressants or gene therapy. Although most newly studied drugs offer a higher safety profile compared to antimetabolites, their efficacy is in most cases lower when compared to MMC. Current literature on animal models and potential drug candidates for GFS were summarized in this review. Future research should focus on refining current animal models (for example through the induction of glaucoma prior to undertaking GFS) and standardizing animal research to ensure a higher reproducibility and reliability across different research groups. Lastly, novel therapies need to be further optimized, e.g. by conducting more research on the dosage, administration route, application frequency, the option of creating combination therapies, or the development of drug delivery systems for sustained release of anti-fibrotic medication.
Topics: Animals; Fibrosis; Filtering Surgery; Glaucoma; Intraocular Pressure; Mice; Mitomycin; Models, Animal; Pharmaceutical Preparations; Rabbits; Rats; Reproducibility of Results
PubMed: 35114212
DOI: 10.1016/j.exer.2022.108972