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BMC Cancer Mar 2015Patient response to chemotherapy for ovarian cancer is extremely heterogeneous and there are currently no tools to aid the prediction of sensitivity or resistance to... (Review)
Review
BACKGROUND
Patient response to chemotherapy for ovarian cancer is extremely heterogeneous and there are currently no tools to aid the prediction of sensitivity or resistance to chemotherapy and allow treatment stratification. Such a tool could greatly improve patient survival by identifying the most appropriate treatment on a patient-specific basis.
METHODS
PubMed was searched for studies predicting response or resistance to chemotherapy using gene expression measurements of human tissue in ovarian cancer.
RESULTS
42 studies were identified and both the data collection and modelling methods were compared. The majority of studies utilised fresh-frozen or formalin-fixed paraffin-embedded tissue. Modelling techniques varied, the most popular being Cox proportional hazards regression and hierarchical clustering which were used by 17 and 11 studies respectively. The gene signatures identified by the various studies were not consistent, with very few genes being identified by more than two studies. Patient cohorts were often noted to be heterogeneous with respect to chemotherapy treatment undergone by patients.
CONCLUSIONS
A clinically applicable gene signature capable of predicting patient response to chemotherapy has not yet been identified. Research into a predictive, as opposed to prognostic, model could be highly beneficial and aid the identification of the most suitable treatment for patients.
Topics: Animals; Antineoplastic Agents; Drug Resistance, Neoplasm; Female; Humans; Ovarian Neoplasms; Predictive Value of Tests
PubMed: 25886033
DOI: 10.1186/s12885-015-1101-8 -
The Cochrane Database of Systematic... Mar 2015Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing.
OBJECTIVES
The objective of this review was to assess the effects of honey compared with alternative wound dressings and topical treatments on the of healing of acute (e.g. burns, lacerations) and/or chronic (e.g. venous ulcers) wounds.
SEARCH METHODS
For this update of the review we searched the Cochrane Wounds Group Specialised Register (searched 15 October 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9); Ovid MEDLINE (1946 to October Week 1 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October 2014); Ovid EMBASE (1974 to 13 October 2014); and EBSCO CINAHL (1982 to 15 October 2014).
SELECTION CRITERIA
Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint.
DATA COLLECTION AND ANALYSIS
Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. All data have been subsequently checked by two more authors.
MAIN RESULTS
We identified 26 eligible trials (total of 3011 participants). Three trials evaluated the effects of honey in minor acute wounds, 11 trials evaluated honey in burns, 10 trials recruited people with different chronic wounds including two in people with venous leg ulcers, two trials in people with diabetic foot ulcers and single trials in infected post-operative wounds, pressure injuries, cutaneous Leishmaniasis and Fournier's gangrene. Two trials recruited a mixed population of people with acute and chronic wounds. The quality of the evidence varied between different comparisons and outcomes. We mainly downgraded the quality of evidence for risk of bias, imprecision and, in a few cases, inconsistency.There is high quality evidence (2 trials, n=992) that honey dressings heal partial thickness burns more quickly than conventional dressings (WMD -4.68 days, 95%CI -5.09 to -4.28) but it is unclear if there is a difference in rates of adverse events (very low quality evidence) or infection (low quality evidence).There is very low quality evidence (4 trials, n=332) that burns treated with honey heal more quickly than those treated with silver sulfadiazine (SSD) (WMD -5.12 days, 95%CI -9.51 to -0.73) and high quality evidence from 6 trials (n=462) that there is no difference in overall risk of healing within 6 weeks for honey compared with SSD (RR 1.00, 95% CI 0.98 to 1.02) but a reduction in the overall risk of adverse events with honey relative to SSD. There is low quality evidence (1 trial, n=50) that early excision and grafting heals partial and full thickness burns more quickly than honey followed by grafting as necessary (WMD 13.6 days, 95%CI 9.82 to 17.38).There is low quality evidence (2 trials, different comparators, n=140) that honey heals a mixed population of acute and chronic wounds more quickly than SSD or sugar dressings.Honey healed infected post-operative wounds more quickly than antiseptic washes followed by gauze and was associated with fewer adverse events (1 trial, n=50, moderate quality evidence, RR of healing 1.69, 95%CI 1.10 to 2.61); healed pressure ulcers more quickly than saline soaks (1 trial, n= 40, very low quality evidence, RR 1.41, 95%CI 1.05 to 1.90), and healed Fournier's gangrene more quickly than Eusol soaks (1 trial, n=30, very low quality evidence, WMD -8.00 days, 95%CI -6.08 to -9.92 days).The effects of honey relative to comparators are unclear for: venous leg ulcers (2 trials, n= 476, low quality evidence); minor acute wounds (3 trials, n=213, very low quality evidence); diabetic foot ulcers (2 trials, n=93, low quality evidence); Leishmaniasis (1 trial, n=100, low quality evidence); mixed chronic wounds (2 trials, n=150, low quality evidence).
AUTHORS' CONCLUSIONS
It is difficult to draw overall conclusions regarding the effects of honey as a topical treatment for wounds due to the heterogeneous nature of the patient populations and comparators studied and the mostly low quality of the evidence. The quality of the evidence was mainly downgraded for risk of bias and imprecision. Honey appears to heal partial thickness burns more quickly than conventional treatment (which included polyurethane film, paraffin gauze, soframycin-impregnated gauze, sterile linen and leaving the burns exposed) and infected post-operative wounds more quickly than antiseptics and gauze. Beyond these comparisons any evidence for differences in the effects of honey and comparators is of low or very low quality and does not form a robust basis for decision making.
Topics: Administration, Topical; Apitherapy; Burns; Honey; Humans; Leg Ulcer; Pressure Ulcer; Randomized Controlled Trials as Topic; Surgical Wound Infection; Varicose Ulcer; Wound Healing; Wounds and Injuries
PubMed: 25742878
DOI: 10.1002/14651858.CD005083.pub4 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740 -
Cancer Medicine Jan 2015Metastasis to the periocular soft tissue of the orbit is a rare manifestation of metastatic cancer. Infiltrating lobular breast cancer (ILBC) is a special breast cancer... (Meta-Analysis)
Meta-Analysis Review
Metastasis to the periocular soft tissue of the orbit is a rare manifestation of metastatic cancer. Infiltrating lobular breast cancer (ILBC) is a special breast cancer subtype, which accounts for 10-15% of all mammary carcinomas and for ~1% of all malignancies. Here, we report on a high frequency of lobular breast cancer in patients with orbital metastases identified in an original series of metastatic tumor specimens and by a systematic literature review. A series of 14 orbital metastases was compiled from formalin-fixed paraffin-embedded archival tissues. All cases were subjected to histological re-review and detailed immunophenotypical characterization. In addition, we performed a meta-analysis of 68 previously published case reports describing orbital metastases, with special reference to breast cancer subtypes. Based on clinical history, histomorphology, immunophenotype, and/or comparison with matched primary tumors, orbital metastases were derived from breast cancer in 8/14 cases, seven of which were classified as metastatic lobular breast cancer. Other entities included non-small cell lung cancer (4/14), infiltrating ductal breast cancer (1/14), prostate cancer (1/14) and adenocarcinoma of the esophagus (1/14). In line with this original series of orbital metastases, lobular breast cancer was the most common malignancy in 72 patients with orbital metastases described in 68 independent case reports. In conclusion, lobular breast cancer represents the cancer subtype with the highest prevalence among orbital metastases. The high frequency of ILBC in orbital metastases illustrates the special metastatic behavior of this tumor entity and may have implications for the understanding of the organotropism of metastatic lobular breast cancer.
Topics: Biopsy; Breast Neoplasms; Carcinoma, Lobular; Female; Humans; Magnetic Resonance Imaging; Neoplasm Grading; Neoplasm Staging; Orbital Neoplasms
PubMed: 25355547
DOI: 10.1002/cam4.331 -
The Cochrane Database of Systematic... Apr 2014Fingertip entrapment injuries, which involve lacerations to the pulp and nail and often a fracture of the underlying bone, commonly occur in children, usually as the... (Review)
Review
BACKGROUND
Fingertip entrapment injuries, which involve lacerations to the pulp and nail and often a fracture of the underlying bone, commonly occur in children, usually as the result of a crushing injury. Treatment is either conservative (wound cleaning and fingertip dressing)or surgical (repair of lacerations, reduction and stabilisation of fractures); however, no consensus currently exists regarding the most appropriate treatment modality.
OBJECTIVES
To assess the effects (benefits and harms) of surgical and conservative interventions for fingertip entrapment injuries in children. We aimed to compare: different methods of conservative treatment; surgical versus conservative treatment; different methods of surgical treatment; and different methods of management after initial conservative or surgical treatment.
SEARCH METHODS
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, the World Health Organization Clinical Trials Registry Platform and reference lists of articles up to 30 April 2013. We did not apply any restrictions based on language or publication status.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing interventions for treating fingertip entrapment injuries in children.The primary outcomes were fingertip function, nail growth, nail deformity and adverse events such as infection.
DATA COLLECTION AND ANALYSIS
Two authors independently screened studies for inclusion, assessed the risk of bias in each included trial and extracted data.We resolved disagreements through discussion.
MAIN RESULTS
We included two RCTs examining a total of 191 young children, 180 of whom were included in the analyses. The two trials tested different comparisons. Both trials were at high risk of bias, particularly from lack of blinding of participants and personnel, and of outcome assessment. The trials did not record fingertip function, nail growth or nail deformity. The quality of the evidence for the reported outcomes was judged to be 'low' using the GRADE approach (i.e. further research is very likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate).One trial compared a seven-day course of antibiotics with no antibiotics after formal surgical repair of fingertip entrapment injuries.One child in each group had an infection at day seven (1/66 antibiotic group versus 1/69 no antibiotic group; RR 1.05, 95% CI 0.07 to 16.37). Both participants with infections had a more severe injury (partial fingertip amputation).The other trial compared two different dressings (silicone net and paraffin gauze) for use after either surgical or initial conservative management of fingertip entrapment injuries. It reported that two of 20 children in the silicone group versus one of 25 in the paraffin group had complications of wound infection (RR 2.50, 95% CI 0.24 to 25.63) and that one of 20 children in the silicone group versus two of 25 in the paraffin group had skin necrosis (RR 0.63, 95% CI 0.06 to 6.41). All complications healed with conservative treatment. The results for mean healing times and mean number of dressing changes were similar between groups but benefits of either silicone or paraffin dressings could not be excluded (silicone mean 4.1 weeks versus paraffin mean 4.0 weeks;MD 0.10 weeks, 95% CI-0.61 to 0.81); (silicone mean 4.3 dressing changes versus paraffin mean 4.2 dressing changes; MD 0.10, 95% CI -0.57 to 0.77). The trial found that a silicone dressing was less likely to adhere to the wound or cause distress for the child at the one-week dressing change.
AUTHORS' CONCLUSIONS
There is a lack of evidence from RCTs to inform all key treatment decisions for the management of fingertip entrapment injuries in children.Given that the quality of evidence is low from one trial, we do not have conclusive evidence that prophylactic use of antibiotics after surgical repair fails to reduce risk of infection. The two children who experienced infection had more severe wounds.Similarly, the low quality evidence from one trial has not enabled us to draw firm conclusions regarding the effect on healing time or complications (infection, skin necrosis) at four-week follow-up between a silicone net dressing and a paraffin gauze dressing when applied post-surgery or after simple wound irrigation; however, the silicone net dressing may be easier to remove in the first week.Further RCTs are required in this area, preferably comparing surgical with conservative methods of managing fingertip entrapment injuries. Outcome assessment should include fingertip function, nail growth and nail deformity for a minimum of three months posttreatment.
Topics: Anti-Bacterial Agents; Bandages; Child; Child, Preschool; Finger Injuries; Humans; Infant; Paraffin; Randomized Controlled Trials as Topic; Silicones; Time Factors; Wound Healing
PubMed: 24788568
DOI: 10.1002/14651858.CD009808.pub2 -
The Cochrane Database of Systematic... Jan 2014Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. Two main strategies are used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics.
OBJECTIVES
The objective of this review was to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers.
SEARCH METHODS
In May 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 24 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4); Ovid MEDLINE (1948 to Week 3 May 2013); Ovid MEDLINE (In-Process & Other Non-indexed Citations, 22 May 2013); Ovid EMBASE (1980 to Week 20 2013); and EBSCO CINAHL (1982 to 17 May 2013). No language or publication date restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs) recruiting people with venous leg ulceration, evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two review authors while working independently.
DATA COLLECTION AND ANALYSIS
Information on the characteristics of participants, interventions and outcomes was recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one review author and were checked by a second. Data were pooled when appropriate.
MAIN RESULTS
Forty-five RCTs reporting 53 comparisons and recruiting a total of 4486 participants were included, Many RCTs were small, and most were at high or unclear risk of bias. Ulcer infection status at baseline and duration of follow-up varied across RCTs. Five RCTs reported eight comparisons of systemic antibiotics, and the remainder evaluated topical preparations: cadexomer iodine (11 RCTs reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antiseptics Cadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care.
AUTHORS' CONCLUSIONS
At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.
Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Humans; Occlusive Dressings; Randomized Controlled Trials as Topic; Varicose Ulcer; Wound Healing
PubMed: 24408354
DOI: 10.1002/14651858.CD003557.pub5 -
International Journal of Clinical and... 2013The targeted treatment of advanced non-small-cell lung cancer (NSCLC) depends on confirmation of activating somatic EGFR mutation. The aim of the study was to evaluate... (Review)
Review
EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence.
The targeted treatment of advanced non-small-cell lung cancer (NSCLC) depends on confirmation of activating somatic EGFR mutation. The aim of the study was to evaluate the incidence of EGFR mutations in NSCLC detected in cytological and histological material and present literature review on European EGFR mutation incidence. 273 patients with confirmed NSCLC were entered into the study: 189 histological, paraffin-embedded materials, 12 fresh and 72 fixed cytological specimens. DNA was extracted from both types of material and the EGFR mutation in exons 18-21 was analyzed by direct sequencing. In addition the EGFR gene copy number in cases with sufficient histological material (110 patients) was evaluated by fluorescent in situ hybridization (FISH) technique. The percentage of EGFR somatic mutations was 10.62%. FISH positive results (amplification or high polysomy of EGFR gene) were identified in 33 patients (30.0%). The strongest clinicopathological correlation with the EGFR mutation was found for histological type (adenocarcinoma; p < 0.01), gender (females; p < 0.01) and FISH positive result (p < 0.05). This is the first, single institution study that estimates the EGFR mutation incidence in the Polish population. Cytological material recovered from fixed preparations and stained with hematoxylin and eosin showed DNA quality comparable to fresh tumor cells and histological samples.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; DNA Mutational Analysis; ErbB Receptors; Female; Gene Amplification; Gene Dosage; Gene Frequency; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Male; Middle Aged; Mutation; Poland
PubMed: 24294366
DOI: No ID Found -
PloS One 2013The objective of the present study was to conduct a systematic review and meta-analysis of published literature investigating the survivin expression and its effects on... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The objective of the present study was to conduct a systematic review and meta-analysis of published literature investigating the survivin expression and its effects on bladder cancer prognosis.
MATERIALS AND METHODS
We carefully searched online Pubmed, Cochrane Library and SCOPUS database from August 1997 to May 2013.
RESULTS
A total of 14 articles met the eligibility criteria for this systematic review. The eligible studies included a total of 2,165 patients with a median number of 155 patients per study (range: 17-726). Of the 14 studies, nine evaluated immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. In non-muscle invasive bladder tumor, the pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.81; 95% confidence interval [CI], 1.30-2.52), progression-free survival (pooled HR, 2.12; 95% CI, 1.60-2.82), cancer-specific survival (pooled HR, 2.01; 95% CI, 1.32-3.06), and overall survival (pooled HR, 1.53; 95% CI, 1.02-2.29). The overall HRs by survivin status were robust across advanced stages. When only adjusted survival data were included, statistically significant differences were identified for all survival subgroup analyses. There was no between-study heterogeneity in the effect of survivin status on the majority of meta-analyses. There was no clear evidence of publication bias in this meta-analysis.
CONCLUSIONS
Survivin expression indicates worse prognosis in patients with bladder cancer but the results should be interpreted with caution. It is necessary that better-designed studies with standardized assays need to provide a better conclusion about the relationship between survivin expression and the outcome of patients with bladder cancer.
Topics: Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Inhibitor of Apoptosis Proteins; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Survivin; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 24204662
DOI: 10.1371/journal.pone.0076719 -
PloS One 2013The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC.
METHODS
Relevant studies were identified by searching PubMed, Embase and Web of Science databases until June 2012. The association of p16 methylation with both overall survival (OS) and disease-free survival (DFS) was preformed. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses, sensitivity analysis and publication bias were also conducted.
RESULTS
A total of 18 studies containing 2432 patients met the inclusion criteria and had sufficient survival data for quantitative aggregation. The results showed that p16 methylation was an indicator of poor prognosis in NSCLC. The HR was 1.36 (95% CI: 1.08-1.73, I(2) = 56.7%) and 1.68 (95% CI: 1.12-2.52, I(2) = 38.7%) for OS and DFS, respectively. Subgroup analyses were carried out. The HRs of fresh and paraffin tissue were 1.50 (95% CI: 1.11-2.01) and 1.10 (95% CI: 0.77-1.57). The pooled HR was 1.40 (95% CI: 1.02-1.92) for methylation-specific PCR (MSP) and 1.26 (95% CI: 0.87-1.82) for quantitative MSP (Q-MSP). The combined HR of the 16 studies reporting NSCLC as a whole indicated that patients with p16 hypermethylation had poor prognosis. No significant association was found when adenocarcinoma subtype pooled. When seven studies on DFS were aggregated, the HR was 1.68 (95% CI: 1.12-2.52) without significant heterogeneity. Moreover, no obvious publication bias was detected on both OS and DFS.
CONCLUSION
The meta-analysis findings support the hypothesis that p16 methylation is associated with OS and DFS in NSCLC patients. Large well-designed prospective studies are now needed to confirm the clinical utility of p16 methylation as an independent prognostic marker.
Topics: Carcinoma, Non-Small-Cell Lung; DNA Methylation; Epigenesis, Genetic; Gene Silencing; Genes, p16; Humans; Lung Neoplasms; Neoplasm Staging; Odds Ratio; Prognosis; Promoter Regions, Genetic; Publication Bias
PubMed: 23372805
DOI: 10.1371/journal.pone.0054970 -
The Cochrane Database of Systematic... Apr 2012Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non-surgical and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non-surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first-choice treatment.
OBJECTIVES
To evaluate the effects of non-surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail.
SEARCH METHODS
We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles.
SELECTION CRITERIA
Randomised controlled trials of non-surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow-up period of at least one month.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non-surgical interventions, and 19 were on surgical interventions.The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies.None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications - infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes.Surgical interventions were better at preventing recurrence than non-surgical interventions with gutter treatment (or gutter removal), and they were probably better than non-surgical treatments with orthonyxia (brace treatment).In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation.In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69).None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone-iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time.
AUTHORS' CONCLUSIONS
Surgical interventions are more effective than non-surgical interventions in preventing the recurrence of an ingrowing toenail.In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes.Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time.
Topics: Combined Modality Therapy; Humans; Nails, Ingrown; Phenol; Postoperative Care; Randomized Controlled Trials as Topic; Secondary Prevention; Toes
PubMed: 22513901
DOI: 10.1002/14651858.CD001541.pub3