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Bioscience Reports Oct 2018The significance of perineural invasion (PNI) present in penile cancer (PC) is controversial. In order to clarify the predictive role of PNI in the inguinal lymph node... (Meta-Analysis)
Meta-Analysis
The significance of perineural invasion (PNI) present in penile cancer (PC) is controversial. In order to clarify the predictive role of PNI in the inguinal lymph node (ILN) metastases (ILNM) and oncologic outcome of patients, we performed this meta-analysis and systematic review. The search of PubMed, Embase, and Web of Science was conducted for appropriate studies, up to 20 January 2018. The pooled odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were applied to evaluate the difference in ILNM and oncologic outcome between patients present with PNI and those who were absent. A total of 298 in 1001 patients present with PNI were identified in current meta-analysis and systematic review. Significant difference was observed in ILNM between PNI present and absent from patients with PC (OR = 2.98, 95% CI = 2.00-4.45). Patients present with PNI had a worse cancer-specific survival (CSS) (HR = 3.58, 95% CI = 1.70-7.55) and a higher cancer-specific mortality (CSM) (HR = 2.20, 95% CI = 1.06-3.82) than those cases without PNI. This meta-analysis and systematic review demonstrated the predictive role of PNI in ILNM, CSS, and CSM for PC patients.
Topics: Aged; Aged, 80 and over; Humans; Inguinal Canal; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Odds Ratio; Penile Neoplasms; Penis; Prognosis; Proportional Hazards Models; Retrospective Studies; Treatment Outcome
PubMed: 30279203
DOI: 10.1042/BSR20180333 -
Oncotarget Aug 2018Identifying patients with high risk of biochemical recurrence after radical prostatectomy is of immense value in clinical practice. Assessment of prognostic significance...
Identifying patients with high risk of biochemical recurrence after radical prostatectomy is of immense value in clinical practice. Assessment of prognostic significance of specific clinicopathological features plays an important role in surgical management after prostatectomy. The purpose of our meta-analysis was to investigate the association between the six pathological characteristics and the prognosis of prostate cancer. We carried out a systematic document retrieval in electronic databases to sort out appropriate studies. Outcomes of interest were gathered from studies comparing biochemical recurrence-free survival (BCFS) in patients with the six pathological traits. Studies results were pooled, and hazard ratios (HRs) combined with corresponding 95% confidence intervals (CIs) for survival were used to estimate the effect size. 29 studies (21,683 patients) were enrolled in our meta-analysis. All the six predictors were statistically significant for BCFS with regard to seminal vesicle invasion (HR = 1.97, 95% CI = 1.79-2.18, < 0.00001), positive surgical margin (HR = 1.79, 95% CI = 1.56-2.06, < 0.00001), extracapsular extension (HR = 2.03, 95% CI = 1.65-2.50, < 0.0001), lymphovascular invasion (HR = 1.85, 95% CI = 1.54-2.22, < 0.00001), lymph node involvement (HR = 1.88, 95% CI = 1.37-2.60, = 0.0001) and perineural invasion (HR = 1.59, 95% CI = 1.33-1.91, < 0.00001). Subgroup analysis showed that all the six predictors had significantly relationship with poor BCFS. The pooled results demonstrated that the six clinical findings indicated a worse prognosis in patients with prostate cancer. In conclusion, our results show several clinicopathological characteristics can predict the risk of biochemical recurrence after radical prostatectomy. Prospective studies are needed to further confirm the predictive value of these features for the prognosis of prostate cancer patients after radical prostatectomy.
PubMed: 30181813
DOI: 10.18632/oncotarget.22459 -
Translational Oncology Oct 2018CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations....
BACKGROUND
CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors.
METHODS
We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model.
RESULTS
We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion.
CONCLUSION
The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.
PubMed: 30071442
DOI: 10.1016/j.tranon.2018.07.008 -
PloS One 2018Perineural dexamethasone has been shown to prolong the duration of local anesthetic (LA) effect in regional anesthesia; however, the use of perineural dexamethasone as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perineural dexamethasone has been shown to prolong the duration of local anesthetic (LA) effect in regional anesthesia; however, the use of perineural dexamethasone as an adjuvant to to the transversus abdominis plane (TAP) block remains controversial. This meta-analysis sought to assess the efficacy of dexamethasone in prolonging the TAP block and enhancing recovery after abdominal surgery.
METHODS
We identified and analyzed 9 RCTs published on or before September 30, 2017, regardless of the original language, after searching the following 6 bibliographic databases: PubMed, EMBASE, Medline, Springer, Ovid, and the Cochrane Library. databases. These studies compared the effects of perineural dexamethasone mixed with local anesthetic versus local anesthetic alone in the TAP block. The Cochrane Collaboration's Risk of Bias Tool was used to evaluate the methodological quality of each RCT. The primary outcomes were the time until the first request for postoperative analgesics and the analog pain scores at 2, 6, 12, and 24 h after surgery. The secondary outcomes were the analgesic consumption and the incidence of nausea and vomiting on the first day after surgery. We used Trial Sequential Analysis (TSA) to control for random errors.
RESULTS
Perineural dexamethasone prolonged the duration of LA effect in the TAP block [mean difference (MD): 2.98 h; 95% confidence interval (CI): 2.19 to 3.78] and reduced analog pain scores at 2 h [MD: -1.15; 95% CI: -2.14 to -0.16], 6 h [MD: -0.97; 95% CI: -1.51 to -0.44], and 12 h [MD: -0.93; 95% CI: -1.14 to -0.72] postoperatively. Furthermore, the use of perineural dexamethasone was associated with less analgesic consumption [standard mean difference: -1.29; 95% CI: -1.88 to -0.70] and a lower incidence of nausea and vomiting [odds ratio: 0.28; 95% CI: 0.16 to 0.49] on the first day after surgery.
CONCLUSION
Dexamethasone prolongs the LA effect when used as an adjuvant in the TAP block and improves the analgesic effects of the block.
Topics: Abdominal Muscles; Adjuvants, Anesthesia; Anesthetics, Local; Dexamethasone; Humans; Nerve Block
PubMed: 29902215
DOI: 10.1371/journal.pone.0198923 -
Journal of Cancer 2018Pancreatic solid pseudopapillary tumors (SPTs) are rare neoplasms with low-grade malignancy. The main treatment for them is surgical resection. However, some SPTs...
Pancreatic solid pseudopapillary tumors (SPTs) are rare neoplasms with low-grade malignancy. The main treatment for them is surgical resection. However, some SPTs relapse after resection. The risk factors associated with the recurrences of resected SPTs remain controversial to date. We performed a systematic review and meta-analysis to identify the risk factors of the recurrences of pancreatic SPTs. We searched PubMed, EMBASE, and the Cochrane Library from their inception to December 2017. Studies that focused on the risk factors of postoperative relapses of pancreatic SPTs were enrolled. Combined ORs with 95% CIs were calculated to evaluate the effects of relevant factors investigated in eligible studies. Heterogeneity among combined results was assessed by Cochran's Q test and by the degree of inconsistency (I). Statistical analyses were performed by Review Manager (version 5.3) using random effects models. We included 10 studies, which enrolled 1091 patients. The pooled results suggested that patients with larger tumors (diameter > 5cm), lymphovascular invasion, lymph node metastasis, synchronous metastasis and positive margin were prone to suffer from the recurrences of SPTs. In addition, some factors like gender, location of tumors, perineural invasion, calcification and capsular invasion did not show any correlation with the relapses of resected SPTs. Factors including a larger tumor size (diameter > 5cm), lymphovascular invasion, lymph node metastasis, synchronous metastasis and positive margin may increase the risk of recurrences of resected pancreatic SPTs. All SPTs should be excised and patients with high-risk features should undergo a long-term follow-up.
PubMed: 29896274
DOI: 10.7150/jca.24491 -
Asian Journal of Surgery Jan 2019Primary duodenal adenocarcinoma (PDAC) is a rare malignancy. The aim of this study was to evaluate the published evidence for resection with curative intent in patients... (Meta-Analysis)
Meta-Analysis
Primary duodenal adenocarcinoma (PDAC) is a rare malignancy. The aim of this study was to evaluate the published evidence for resection with curative intent in patients with PDAC. A literature search was conducted in PubMed and EMBASE databases for eligible studies that reported 5-year overall survival (OS) after surgical resection of PDAC from January 1990 to January 2018. Independent prognostic factors related to OS were evaluated using meta-analytical techniques. Odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were calculated as appropriate. Thirty-seven observational studies comprising a total of 1728 patients who underwent resection for PDAC were reviewed. The overall 30-day postoperative mortality was 3.2% (range, 0-16.0%) and the median 5-year OS was 46.4% (range, 16.6-71.1%). Surgical resection significantly improved the prognosis as compared with the palliative therapy (OR 15.76, P < 0.001). Lymph node metastasis (HR 2.58, P < 0.001), poor tumor differentiation (HR 1.43, P = 0.05), perineural invasion (HR 2.21, P = 0.002), and lymphovascular invasion (HR 2.18, 95% CI 1.18-4.03; P = 0.01) were found to be independently associated with decreased OS after surgical resection. The present study provides evidence that surgical resection can be performed safely for PDAC patients and offers a favorable long-term outcome. Tumor-specific factors have prognostic significance.
Topics: Adenocarcinoma; Confidence Intervals; Databases, Bibliographic; Digestive System Surgical Procedures; Duodenal Neoplasms; Humans; Lymphatic Metastasis; Observational Studies as Topic; Odds Ratio; Prognosis; Proportional Hazards Models; Survival Rate; Time Factors; Treatment Outcome
PubMed: 29802028
DOI: 10.1016/j.asjsur.2018.04.005 -
Scandinavian Journal of Pain Jan 2018Treatment of pain following major limb amputations is often a clinical challenge in a patient population consisting mainly of elderly with underlying diseases....
BACKGROUND AND AIMS
Treatment of pain following major limb amputations is often a clinical challenge in a patient population consisting mainly of elderly with underlying diseases. Literature on management of acute post-amputation pain is scarce. We performed a systematic review on this topic to evaluate the efficacy and safety of analgesic interventions for acute pain following major limb amputation.
METHODS
A literature search was performed in PubMed, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews using the following key words: [(amputation) AND (pain OR analgesi* OR pain relief)] AND (acute OR postoperative). Randomized controlled studies (RCTs) and observational studies investigating treatment of acute pain following major amputations for any indication (peripheral vascular disease, malignant disease, trauma) were included. The review was performed according to the standards described in the PRISMA statement. The Cochrane quality assessment tool was used to evaluate the risk of bias in the RCTs.
RESULTS
Nineteen studies with total of 949 patients were included. The studies were generally small and heterogeneous on outcomes, study designs and quality. There were 16 studies on epidural or continuous perineural analgesia (CPI). Based on five RCTs (n=268) and two observational studies (n=49), epidural analgesia decreased the intensity of acute stump pain as compared to systemic analgesics, during the first 24 h after the operation. Based on one study epidural analgesia caused more adverse effects like sedation, nausea and motor block than continuous perineural local anesthetic infusion. Based on one RCT (n=21) and eight observational studies (n=501) CPI seemed to decrease opioid consumption as compared to systemic analgesics only, on the first three postoperative days, and was well tolerated. Only three trials investigated systemic analgesics (oral memantine, oral gabapentine, iv ketamine). Ketamine did not decrease acute pain or opioid consumption after amputation as compared to other systemic analgesics. Gabapentin did not decrease acute pain when combined to epidural analgesia as compared to epidural analgesia and opioid treatment, and caused adverse effects.
CONCLUSIONS
The main finding of this systematic review is that evidence regarding pain management after major limb amputation is very limited. Epidural analgesia may be effective, but firm evidence is lacking. Epidural causes more adverse effects than CPI. The results on efficacy of CPI are indecisive. The data on adjuvant medications combined to epidural analgesia or CPI is limited. Studies on efficacy and adverse effects of systemic analgesics for amputation pain, especially concentrating on elderly patients, are needed.
Topics: Acute Pain; Amputation, Surgical; Analgesia, Epidural; Analgesics; Chemotherapy, Adjuvant; Humans; Pain Management; Pain, Postoperative
PubMed: 29794290
DOI: 10.1515/sjpain-2017-0170 -
British Journal of Anaesthesia Feb 2018I.V. and perineural dexamethasone have both been found to prolong loco-regional analgesia compared with controls without dexamethasone. It is unclear whether perineural... (Meta-Analysis)
Meta-Analysis
Co-administration of dexamethasone with peripheral nerve block: intravenous vs perineural application: systematic review, meta-analysis, meta-regression and trial-sequential analysis.
BACKGROUND
I.V. and perineural dexamethasone have both been found to prolong loco-regional analgesia compared with controls without dexamethasone. It is unclear whether perineural administration offers advantages when compared with i.v. dexamethasone.
METHODS
A systematic literature search was performed to identify randomized controlled double-blind trials that compared i.v. with perineural dexamethasone in patients undergoing surgery. Using the random effects model, risk ratio (for binary variables), weighted mean difference (for continuous variables) and 95% confidence intervals were calculated. We applied trial sequential analysis to assess the risks of type I and II error, meta-regression for the study of the doseresponsive relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system.
RESULTS
We identified 10 randomized controlled double-blind trials (783 patients). When using conventional meta-analysis of nine low risk of bias trials, we found a statistically significantly longer duration of analgesia, our primary outcome with perineural dexamethasone (241 min, 95%CI, 87, 394 min). When trial sequential analysis was applied, this result was confirmed. Meta-regression did not show a dose-response relationship. Despite the precision in the results, using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE), we assessed the quality of the evidence for our primary outcome as low.
CONCLUSIONS
There is evidence that perineural dexamethasone prolongs the duration of analgesia compared with i.v. dexamethasone. Using GRADE, this evidence is low quality.
Topics: Administration, Intravenous; Dexamethasone; Humans; Hypnotics and Sedatives; Injections; Nerve Block; Peripheral Nerves; Randomized Controlled Trials as Topic
PubMed: 29406171
DOI: 10.1016/j.bja.2017.11.062 -
BMC Urology Feb 2018Although numerous studies have shown that perineural invasion (PNI) is linked to prostate cancer (PCa) risk, the results have been inconsistent. This study aimed to... (Meta-Analysis)
Meta-Analysis Review
Perineural invasion as an independent predictor of biochemical recurrence in prostate cancer following radical prostatectomy or radiotherapy: a systematic review and meta-analysis.
BACKGROUND
Although numerous studies have shown that perineural invasion (PNI) is linked to prostate cancer (PCa) risk, the results have been inconsistent. This study aimed to explore the association between PNI and biochemical recurrence (BCR) in patients with PCa following radical prostatectomy (RP) or radiotherapy (RT).
METHODS
According to the PRISMA statement, we searched the PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang databases from inception to May 2017. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were extracted from eligible studies. Fixed or random effects model were used to calculate pooled HRs and 95% CIs according to heterogeneity. Publication bias was calculated by Begg's test.
RESULTS
Ultimately, 19 cohort studies that met the eligibility criteria and that involved 13,412 patients (82-2,316 per study) were included in this meta-analysis. The results showed that PNI was associated with higher BCR rates in patients with PCa after RP (HR=1.23, 95% CI: 1.11, 1.36, p<0.001) or RT (HR=1.22, 95% CI: 1.12, 1.34, p<0.001). No potential publication bias was found among the included studies in the RP group (p-Begg = 0.124) or the RT group (p-Begg = 0.081).
CONCLUSIONS
This study suggests that the presence of PNI by histopathology is associated with higher risk of BCR in PCa following RP or RT, and could serve as an independent prognostic factor in patients with PCa.
Topics: Humans; Male; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peripheral Nerves; Predictive Value of Tests; Prostatectomy; Prostatic Neoplasms
PubMed: 29390991
DOI: 10.1186/s12894-018-0319-6 -
The Cochrane Database of Systematic... Nov 2017Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone.
OBJECTIVES
To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events.
AUTHORS' CONCLUSIONS
Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.
Topics: Anesthetics, Local; Arm; Dexamethasone; Glucocorticoids; Humans; Injections, Intravenous; Leg; Nerve Block; Neuromuscular Blocking Agents; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors
PubMed: 29121400
DOI: 10.1002/14651858.CD011770.pub2