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World Journal of Surgery Sep 2017Individualised risk prediction is crucial if targeted pre-operative risk reduction strategies are to be deployed effectively. Radiologically determined sarcopenia has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individualised risk prediction is crucial if targeted pre-operative risk reduction strategies are to be deployed effectively. Radiologically determined sarcopenia has been shown to predict outcomes across a range of intra-abdominal pathologies. Access to pre-operative cross-sectional imaging has resulted in a number of studies investigating the predictive value of radiologically assessed sarcopenia over recent years. This systematic review and meta-analysis aimed to determine whether radiologically determined sarcopenia predicts post-operative morbidity and mortality following abdominal surgery.
METHOD
CENTRAL, EMBASE and MEDLINE databases were searched using terms to capture the concept of radiologically assessed sarcopenia used to predict post-operative complications in abdominal surgery. Outcomes included 30 day post-operative morbidity and mortality, 1-, 3- and 5-year overall and disease-free survival and length of stay. Data were extracted and meta-analysed using either random or fixed effects model (Revman 5.3).
RESULTS
A total of 24 studies involving 5267 patients were included in the review. The presence of sarcopenia was associated with a significant increase in major post-operative complications (RR 1.61 95% CI 1.24-4.15 p = <0.00001) and 30-day mortality (RR 2.06 95% CI 1.02-4.17 p = 0.04). In addition, sarcopenia predicted 1-, 3- and 5-year survival (RR 1.61 95% CI 1.36-1.91 p = <0.0001, RR 1.45 95% CI 1.33-1.58 p = <0.0001, RR 1.25 95% CI 1.11-1.42 p = 0.0003, respectively) and 1- and 3-year disease-free survival (RR 1.30 95% CI 1.12-1.52 p = 0.0008).
CONCLUSION
Peri-operative cross-sectional imaging may be utilised in order to predict those at risk of complications following abdominal surgery. These findings should be interpreted in the context of retrospectively collected data and no universal sarcopenic threshold. Targeted prehabilitation strategies aiming to reverse sarcopenia may benefit patients undergoing abdominal surgery.
Topics: Abdomen; Disease-Free Survival; Humans; Mortality; Postoperative Complications; Predictive Value of Tests; Radiology; Risk Factors; Sarcopenia; Survival Rate
PubMed: 28386715
DOI: 10.1007/s00268-017-3999-2 -
The Cochrane Database of Systematic... Mar 2017This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates.
OBJECTIVES
To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival.
SEARCH METHODS
We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010.
SELECTION CRITERIA
Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope.
DATA COLLECTION AND ANALYSIS
We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis.
MAIN RESULTS
This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (Sr) with Samarium-153 (Sm), Rhenium-186 (Re) and Phosphorus-32 (P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of Sm (0.5 versus 1.0 mCi).
AUTHORS' CONCLUSIONS
This update adds new evidence on efficacy of radioisotopes versus placebo, Sr compared with other radioisotopes, and dose-comparisons of Sm and Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.
Topics: Bone Neoplasms; Fractures, Bone; Humans; Hypercalcemia; Pain; Pain Measurement; Phosphorus Radioisotopes; Radioisotopes; Randomized Controlled Trials as Topic; Ruthenium Radioisotopes; Samarium; Spinal Cord Compression; Strontium Radioisotopes
PubMed: 28334435
DOI: 10.1002/14651858.CD003347.pub3 -
Cancer Treatment Reviews Mar 2017It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours.
METHODS
We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted.
RESULTS
Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes.
CONCLUSION
Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours.
Topics: Antimetabolites, Antineoplastic; Azacitidine; Cytidine; DNA Methylation; Decitabine; Humans; Hydralazine; Immune System; Methylation; Neoplasms; Procaine; Treatment Outcome
PubMed: 28189913
DOI: 10.1016/j.ctrv.2017.01.004 -
Jornal de Pediatria 2015This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential... (Review)
Review
OBJECTIVES
This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential association with pediatric stroke and cerebral palsy (CP).
SOURCES
Scientific articles published from 1993 to 2013, written in Portuguese, English, French, and Spanish, were selected and reviewed. The publications were searched in electronic databases, and also in the collections of local libraries. The terms "hereditary thrombophilia", "polymorphisms", "mutation", "pediatric strokes", and "cerebral palsy" were used for the research.
SUMMARY OF THE FINDINGS
The search in databases and in the bibliographic references retrieved 75 articles for inclusion in this review. Studies that investigated hereditary thrombophilias and their associations to CP and arterial and venous pediatric stroke presented contradictory results. The meta-analysis and case-control studies that showed positive results for this association described only slightly increased relative risks and sometimes had questionable conclusions. The association of two or more hereditary thrombophilias, or the association between thrombophilia and other specific clinical risk factors, suggest a higher risk of CP and pediatric stroke than isolated hereditary thrombophilia.
CONCLUSIONS
Larger, multicenter studies should be developed in order to elucidate the role of mutations leading to hereditary thrombophilia and the development of CP and pediatric stroke. The complex and multifactorial etiology of CP and stroke makes this an arduous and difficult task; however, the benefits generated by these studies are immeasurable.
Topics: Case-Control Studies; Cerebral Palsy; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Intracranial Thrombosis; Meta-Analysis as Topic; Mutation; Polymorphism, Genetic; Risk Factors; Stroke; Thrombophilia
PubMed: 25451211
DOI: 10.1016/j.jped.2014.08.004 -
Brachytherapy 2014To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer. (Review)
Review
PURPOSE
To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer.
METHODS
A literature search and a systematic review of the high-dose-rate (HDR) brachytherapy (monotherapy) prostate literature were performed on PubMed using "high-dose-rate, brachytherapy, prostate, monotherapy" as search terms. More than 80 articles and abstracts published between 1990 and 2013 were identified. Data tables were generated and summary descriptions created. Commentary and opinion was formulated through discussion and consensus based on the critical review of the literature and the author's combined personal experience and knowledge.
RESULTS
Thirteen articles reported clinical outcome and toxicity with followup ranging from 1.5 to 8.0 years. Results were available for all risk groups. A variety of dose and fractionation schedules were described. Prostate-specific antigen progression-free survival ranged from 79% to 100% and local control from 97% to 100%. The toxicity rates were low. Genitourinary toxicity, mainly frequency/urgency, was 0-16% (Grade 3). Gastrointestinal toxicity was 0-2% (Grade 3). Erectile function preservation was 67-89%. The radiobiological, clinical, and technical features of HDR brachytherapy were reviewed and discussed.
CONCLUSIONS
Consistently high local tumor control and low complications rates are reported with HDR monotherapy. It provides reproducible high-quality dosimetry, it has an advantage from a radiobiology perspective, and it has a good radiation safety profile. HDR brachytherapy is a safe and effective local treatment modality for prostate cancer.
Topics: Brachytherapy; Disease-Free Survival; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Tomography, X-Ray Computed
PubMed: 25085454
DOI: 10.1016/j.brachy.2014.03.002