-
Frontiers in Oncology 2021Over many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral...
OBJECTIVE
Over many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral squamous cell carcinoma (OSCC) but also provided inconsistencies, making clinical application difficult. The 8th TNM staging system of OSCC has acknowledged the importance of some histopathological features, by incorporating depth of invasion (DOI) to T category and extranodal extension (ENE) to N category. The aim of this systematic review with meta-analysis is to determine the most clinically relevant histopathological features for risk assessment and treatment planning of OSCC and to elucidate gaps in the literature.
METHODS
A systematic review was conducted using PRISMA guidelines, and the eligibility criteria were based on population, exposure, comparison, outcome, and study type (PECOS). PubMed, Cochrane, Scopus, and Web of Science were searched for articles exploring the impact of histopathological features on OSCC outcomes with Cox multivariate analysis. Pooled data were subjected to an inverse variance method with random effects or fixed effect model, and the risk of bias was evaluated using quality in prognosis studies (QUIPS). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.
RESULTS
The study included 172 articles published from 1999 to 2021. Meta-analyses confirmed the prognostic potential of DOI, ENE, perineural invasion, lymphovascular invasion, and involvement of the surgical margins and brought promising results for the association of bone invasion, tumor thickness, and pattern of invasion with increased risk for poor survival. Although with a small number of studies, the results also revealed a clinical significance of tumor budding and tumor-stroma ratio on predicted survival of patients with OSCC. Most of the studies were considered with low or moderate risk of bias, and the certainty in evidence varied from very low to high.
CONCLUSION
Our results confirm the potential prognostic usefulness of many histopathological features and highlight the promising results of others; however, further studies are advised to apply consistent designs, filling in the literature gaps to the pertinence of histopathological markers for OSCC prognosis.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.
PubMed: 34858861
DOI: 10.3389/fonc.2021.784924 -
BMC Anesthesiology Sep 2021Peripheral injection of dexmedetomidine (DEX) has been widely used in regional anesthesia to prolong the duration of analgesia. However, the optimal perineural dose of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Peripheral injection of dexmedetomidine (DEX) has been widely used in regional anesthesia to prolong the duration of analgesia. However, the optimal perineural dose of DEX is still uncertain. It is important to elucidate this characteristic because DEX may cause dose-dependent complications. The aim of this meta-analysis was to determine the optimal dose of perineural DEX for prolonged analgesia after brachial plexus block (BPB) in adult patients undergoing upper limb surgery.
METHOD
A search strategy was created to identify suitable randomized clinical trials (RCTs) in Embase, PubMed and The Cochrane Library from inception date to Jan, 2021. All adult patients undergoing upper limb surgery under BPB were eligible. The RCTs comparing DEX as an adjuvant to local anesthetic (LA) with LA alone for BPB were included. The primary outcome was duration of analgesia for perineural DEX. Secondary outcomes included visual analog scale (VAS) in 12 and 24 h, consumption of analgesics in 24 h, and adverse events.
RESULTS
Fifty-seven RCTs, including 3332 patients, were identified. The subgroup analyses and regression analyses revealed that perineural DEX dose of 30-50 μg is an appropriate dosage. With short-/intermediate-acting LAs, the mean difference (95% confidence interval [CI]) of analgesia duration with less than and more than 60 μg doses was 220.31 (153.13-287.48) minutes and 68.01 (36.37-99.66) minutes, respectively. With long-acting LAs, the mean differences (95% CI) with less than and more than 60 μg doses were 332.45 (288.43-376.48) minutes and 284.85 (220.31-349.39) minutes.
CONCLUSION
30-50 μg DEX as adjuvant can provides a longer analgesic time compared to LA alone and it did not increase the risk of bradycardia and hypotension.
Topics: Brachial Plexus Block; Dexmedetomidine; Dose-Response Relationship, Drug; Humans; Hypnotics and Sedatives; Randomized Controlled Trials as Topic; Time Factors
PubMed: 34583650
DOI: 10.1186/s12871-021-01452-0 -
Pain Physician Sep 2021Perineural (PN) dexamethasone (DEX) administration can prolong the analgesic time of a brachial plexus block. However, its efficacy and safety are controversial due to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perineural (PN) dexamethasone (DEX) administration can prolong the analgesic time of a brachial plexus block. However, its efficacy and safety are controversial due to its off-label use and different routes of administration.
OBJECTIVES
This meta-analysis aimed to assess the safety and efficacy of PN versus intravenous (IV) dexamethasone.
STUDY DESIGN
Systematic review and meta-analysis of randomized controlled trials (RCTs).
SETTING
Relevant studies were found through a comprehensive literature search of PubMed, Web of Science, Ovid, EMBASE, and the Cochrane Library (from the inception until January 2020).
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was conducted to identify RCTs comparing PN and IV dexamethasone in brachial plexus block. A randomized effect model was used in the meta-analysis and the subgroup analysis was performed with adrenaline stratification. The quality of evidence and the strength of recommendations were graded by GradePro version 3.6.1.
RESULTS
Twelve RCTs with a total of 1,345 subjects were included. We found that PN dexamethasone could prolong the duration of analgesia (mean difference [MD]: 131.82 minutes, 95% confidence interval [CI] [38.96, 224.68], I2 = 82%, P = 0.005), motor block (MD: 218.85 minutes, 95% CI [113.65,324.05], I2 = 72%, P < 0.0001) and sensory block (MD: 209.57 minutes, 95% CI [72.64, 346.50], I2 = 87%, P = 0.003) in the main analysis with significant difference. In the absence of epinephrine, there were no significant differences between PN dexamethasone and IV dexamethasone. Except for adverse-effects, no significant differences were observed in secondary outcomes. PN dexamethasone had slightly higher adverse-effects; however, these could be altered if a sensitivity analysis was conducted.
LIMITATIONS
There was high heterogeneity among included studies.
CONCLUSIONS
PN dexamethasone can prolong the duration of analgesia, sensory block, and motor block, when compared with IV dexamethasone. In a subgroup analysis without epinephrine, the 2 routes of administration were equivalent to topical anesthesia. There were no differences in secondary outcomes, except for adverse effects, which could be altered if a sensitivity analysis was conducted. Therefore, despite the advantages of PN dexamethasone, caution is needed due to its off-label character. While the results of this study are promising, additional large and well-designed RCTs are needed to validate these initial findings and their implications.
Topics: Administration, Intravenous; Analgesia; Brachial Plexus Block; Dexamethasone; Humans; Randomized Controlled Trials as Topic
PubMed: 34554686
DOI: No ID Found -
World Journal of Surgery Jan 2022The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy.
METHOD
A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy.
RESULTS
Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20-1.43, p = 0.209). High heterogeneity (I > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion.
CONCLUSION
Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.
Topics: Chemotherapy, Adjuvant; Cohort Studies; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34545418
DOI: 10.1007/s00268-021-06309-8 -
Medicine Aug 2021Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB).
METHODS
We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796.
RESULTS
After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05).
CONCLUSIONS
This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.
Topics: Adjuvants, Anesthesia; Adrenergic alpha-2 Receptor Agonists; Anesthesia, Local; Dexamethasone; Dexmedetomidine; Glucocorticoids; Humans; Nerve Block; Peripheral Nerves; Randomized Controlled Trials as Topic
PubMed: 34449500
DOI: 10.1097/MD.0000000000027064 -
Frontiers in Oncology 2021A significant number of recently published research has outlined the contribution of perineural invasion (PNI) to clinical outcomes in oral tongue squamous cell...
OBJECTIVES
A significant number of recently published research has outlined the contribution of perineural invasion (PNI) to clinical outcomes in oral tongue squamous cell carcinoma (OTSCC), but some results remain conflicting. This study aimed to determine whether patients with OTSCC with PNI have a worse prognosis than those without PNI.
MATERIALS AND METHODS
PubMed, Embase, and the Cochrane Library were queried for potentially eligible articles published up to December 2020. The primary outcomes were the hazard ratio (HR) for locoregional recurrence, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). The random-effect model was used in all analyses.
RESULTS
Seventeen studies (4445 patients) were included. Using adjusted HRs, the presence of PNI was associated with a higher risk of locoregional recurrence (HR=1.73, 95%CI: 1.07-2.79, P=0.025, I = 33.1%, P=0.224), worse OS (HR=1.94, 95%CI: 1.39-2.72, P<0.001, I = 0.0%, P=0.838), worse DFS (HR=2.13, 95%CI: 1.53-2.96, P<0.001, I = 48.4%, P=0.071), and worse CSS (HR=1.93, 95%CI: 1.40-2.65, P<0.001, I = 25.5%, P=0.251). PNI had an impact on locoregional recurrence in early-stage OTSCC but not in all stages, and on OS, DFS, and CSS in all-stage and early-stage OTSCC. The sensitivity analyses showed that the results were robust.
CONCLUSION
The presence of PNI significantly affects the locoregional recurrence and survival outcomes among patients with OTSCC.
PubMed: 34322385
DOI: 10.3389/fonc.2021.683825 -
Neurobiology of Pain (Cambridge, Mass.) 2021Obesity has been associated with increased chronic pain susceptibility but causes are unclear. In this review, we systematize and analyze pain outcomes in rodent models... (Review)
Review
Obesity has been associated with increased chronic pain susceptibility but causes are unclear. In this review, we systematize and analyze pain outcomes in rodent models of obesity as these can be important tools for mechanistic studies. Studies were identified using MEDLINE/PubMed and Scopus databases using the following search query: (((pain) OR (nociception)) AND (obesity)) AND (rat OR (mouse) OR (rodent))). From each eligible record we extracted the following data: species, strain, sex, pain/obesity model and main behavioral readouts. Out of 695 records 33 were selected for inclusion. 27 studies assessed nociception/acute pain and 17 studies assessed subacute or chronic pain. Overall genetic and dietary models overlapped in pain-related outcomes. Most acute pain studies reported either decreased or unaltered responses to noxious painful stimuli. However, decreased thresholds to mechanical innocuous stimuli, i.e. allodynia, were frequently reported. In most studies using subacute and chronic pain models, namely of subcutaneous inflammation, arthritis and perineural inflammation, decreased thresholds and/or prolonged pain manifestations were reported in obesity models. Strain comparisons and longitudinal observations indicate that genetic factors and the time course of the pathology might account for some of the discrepancies observed across studies. Two studies reported increased pain in animals subjected to high fat diet in the absence of weight gain. Pain-related outcomes in experimental models and clinical obesity are aligned indicating that the rodent can be an useful tool to study the interplay between diet, obesity and pain. In both cases weight gain might represent only a minor contribution to abnormal pain manifestation.
PubMed: 34195483
DOI: 10.1016/j.ynpai.2021.100066 -
Gland Surgery May 2021The benefits of neoadjuvant chemotherapy (NCT) in pancreatic cancer (PC) have been realized and gradually accepted. FOLFIRINOX and gemcitabine and nab-paclitaxel (GA)...
Head-to-head comparison between FOLFIRINOX and gemcitabine plus nab-paclitaxel in the neoadjuvant chemotherapy of localized pancreatic cancer: a systematic review and meta-analysis.
BACKGROUND
The benefits of neoadjuvant chemotherapy (NCT) in pancreatic cancer (PC) have been realized and gradually accepted. FOLFIRINOX and gemcitabine and nab-paclitaxel (GA) are the two most widely used regimens for PC NCT.
METHODS
The literature was systematically reviewed by searching MEDLINE, EMBASE, Web of Science and the Cochrane Library for studies published until September 2020.
RESULTS
Eight studies were eligible for the meta-analysis. Compared to GA, neoadjuvant FOLFIRINOX significantly prolonged overall survival [hazard ratio (HR) =0.65, 95% confidence interval (95% CI): 0.55-0.77; P<0.001]. FOLFIRINOX provided better survival benefits in the first three years after surgery; however, the 4- and 5-year survival probabilities of the two strategies were similar based on a conservative estimation in the random effect model. The perioperative parameters analysed included perineural invasion (PNI), lymphovascular invasion (LVSI), R0 status, postoperative complications and resection rate. The PNI rate was marginally elevated in the GA group compared with the FOLFIRINOX cohort [79.8% 70.5%, odds ratio (OR) =0.70, 95% CI: 0.47-1.06, P=0.09], which may account for the potential survival benefits of FOLFIRINOX.
CONCLUSIONS
The results of our meta-analysis suggest that FOLFIRINOX is non-inferior to GA in patients who are FOLFIRINOCX capable.
PubMed: 34164301
DOI: 10.21037/gs-21-16 -
Annals of Surgical Oncology Dec 2021The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy.
METHODS
A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes.
RESULTS
We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4-34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0-37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable.
CONCLUSIONS
In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Pancreatic Neoplasms; Prospective Studies
PubMed: 34142290
DOI: 10.1245/s10434-021-10276-8 -
European Journal of Vascular and... Aug 2021Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was to assess the effect of perineural catheters (PNCs) on post-operative pain, post-operative morphine requirement, in-hospital mortality, long term phantom limb pain, and chronic stump pain.
METHODS
A systematic review using PubMed, EMBASE via OVID and the Cochrane library from database inception (1946) to 20 October 2020 was performed according to PRISMA guidelines. Studies involving patients undergoing MLLA which reported on post-operative morphine requirement, pain scores, in-hospital mortality, phantom limb pain (PLP), and chronic stump pain were included. Studies comparing PNC use with epidural or wound site local anaesthetic infusions were excluded. Outcome data were extracted from individual studies and meta-analysis was performed using a random effects (Mantel-Haenszel) model for dichotomous data using an odds ratio (OR) summary statistic with 95% confidence intervals (CI), and with an inverse variance random effects model for continuous data using a standardised mean difference (SMD) summary statistic with 95% CIs. Sensitivity analyses were performed for post-operative pain scores and post-operative morphine requirement. Study quality was assessed using the Downs and Black score, and outcomes were assessed using the GRADE tool.
RESULTS
Ten studies reporting on 731 patients were included, with 350 patients receiving a PNC and 381 receiving standard care. PNC use is associated with a reduction in post-operative pain (SMD -0.30, 95% CI -0.58 - -0.01, p = .040, I = 54%, GRADE quality of evidence: low) and post-operative morphine requirements (SMD -0.63, 95% CI -1.03 - -0.23, p = .002, I = 75%, GRADE quality of evidence: moderate), although the effect of PNC on reduced post-operative morphine requirements is lost on sensitivity analysis of randomised trials only (p = .40). No demonstrable effect was found on in-hospital mortality, PLP, or chronic stump pain (GRADE quality of evidence: low).
CONCLUSION
PNC use in amputees is associated with a significant reduction in post-operative pain scores and post-operative morphine requirements, although this latter finding is lost on sensitivity analysis of randomised trials only.
Topics: Amputation, Surgical; Amputation Stumps; Analgesics, Opioid; Anesthetics, Local; Catheters; Hospital Mortality; Humans; Lower Extremity; Morphine; Pain Measurement; Pain, Postoperative; Peripheral Nerves; Phantom Limb
PubMed: 34088614
DOI: 10.1016/j.ejvs.2021.03.008