Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference − 0.43, 95% confidence interval [CI] − 0.75 to – 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.

     

Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: a systematic review.

PURPOSE: To assess the safety and efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), alone or combined with opioids, for the treatment of cancer pain. PATIENTS AND METHODS: Forty-two trials involving 3,084 patients met inclusion criteria: eight compared NSAID with placebo; 13 compared one NSAID with another; 23 compared NSAID with opioid, NSAID or opioid versus NSAID plus opioid combinations, or NSAID plus opioid combinations versus NSAID plus opioid combinations; and nine studies assessed the effect of increasing NSAID dose. RESULTS: Sixteen studies lasted 1 week or longer and 11 evaluated a single dose. Seven of eight trials demonstrated superior efficacy of single doses of NSAID compared with placebo. Only four of 13 studies reported increased efficacy of one NSAID compared with another; four other studies found that one NSAID had fewer side effects than one or more others. Thirteen of 14 studies found no difference, or minimal clinical difference, when comparing an NSAID plus opioid combination versus either drug alone. Comparisons between various NSAID plus opioid combinations were inconclusive. Four studies demonstrated increased efficacy with increased NSAID dose, without dose-dependent increases in side effects. CONCLUSION: Heterogeneity of study methods and outcomes precluded meta-analyses. Short duration of studies undermines generalization of findings on efficacy and safety. On the basis of limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID compared with another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no significant difference, or at most a slight but statistically significant advantage, compared with either single entity.     

Clinical pharmacology and pharmacotherapy of opioid switching in cancer patients

Pain is one of the most common and often most feared symptoms in patients with cancer. Ongoing or progressive pain is physically debilitating and has a marked impact on quality of life. Since a third of the population will die from cancer, and of these, 80% will experience severe pain in their final year of life, effective treatment of cancer-related pain remains both a high priority and an ongoing challenge in clinical practice. Individuals with moderate to severe cancer-related pain require treatment with strong analgesics, namely opioids. There is evidence to support the therapeutic maneuver of opioid switching in clinical practice, but further evidence is needed to elucidate the underlying mechanisms for interindividual differences in response to different opioids. Large, robust clinical trials will be needed if clinical differences among side-effect profiles of different opioids are to be clearly demonstrated. This review discusses candidate genes, which contribute to opioid response; many other genes have also been implicated in "pain" from animal or human studies. In order to continue to evaluate the genetic contributions to both pain susceptibility and analgesic response, further candidate genes need to be considered. Good pain control remains a high priority for clinicians and patients, and there is much work to be done to further individualize analgesic therapy for patients with cancer.     

Intravenous Flurbiprofen Axetil Enhances Analgesic Effect of Opioids in Patients with Refractory Cancer Pain by Increasing Plasma b-Endorphin

Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofenaxetil and opioids, and evaluate the relationship between refractory pain relief and plasma β-endorphin levels incancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups,60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receivingthe combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, painrelief, quality of life improvement and side effects were evaluated. Furthermore, plasma β-endorphin levelswere measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenousflurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% whenmorphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effectincreased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase inplasma β-endorphin levels. After the treatment, plasma β-endorphin level in group B was 62.4±13.5 pg/ml, whichwas higher than that in group A (45.8±11.2 pg/ml) (p<0.05). Conclusions: Our results suggest the combination ofintravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasmaβ-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.     

The level of patient-reported outcome reporting in randomised controlled trials of brain tumour patients: A systematic review

BackgroundTo determine the net clinical benefit of a new treatment strategy, information on both survival and patient-reported outcomes (PROs) is required. However, to make an adequately informed decision, PRO evidence should be of sufficiently high quality.ObjectiveTo investigate the methodological quality of PRO reporting in randomised controlled trials (RCTs) in patients with brain tumours, and to assess the proportion of studies that should impact clinical decision-making.MethodsWe conducted a systematic literature search in several databases covering January 2004 to March 2012. We selected relevant RCTs and retrieved the following data: (1) basic trial demographics and PRO characteristics, (2) quality of PRO reporting and (3) risk of bias. Studies that should impact clinical decision-making based on their methodological robustness were analysed systematically.ResultsWe identified 14 RCTs, representing over 3000 glioma patients. Only two RCTs (14%) satisfied sufficiently many key methodological criteria to provide high-quality PRO evidence, and should therefore impact clinical decision-making. Important methodological limitations in other studies were lack of reporting of the extent (43%) and reasons (86%) of missing data and statistical approaches to handle this (71%). PRO results were not interpreted in 79% of the studies and clinical significance was not discussed in 86%. Studies with high-quality PRO evidence generally showed lower risk of bias.ConclusionsInvestigators involved in brain tumour research should pay special attention to methodological challenges identified in current work. The level of PRO reporting should continue to improve in order to facilitate a critical appraisal of study results.     

Analgesic effects of cyclooxygenase 2 inhibitors

Traditional pain management strategies for cancer pain have relied on the use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant analgesics. However, the substantial adverse effects associated with their use has left many patients without dependable options for effective treatment. Recent advances in the understanding of pain and its pathophysiologic mechanisms have led to the development of novel therapeutics. Cyclooxygenase(Cox)-2-specific inhibitors (coxib) have an established efficacy in the treatment of chronic and acute pain comparable to that of traditional NSAIDs without the degree of gastrointestinal complication or the platelets inhibitor effect of traditional NSAIDs. Numerous studies have shown that coxibs are efficacious in the management of chronic and acute pain in various clinical settings including postoperative pain. The superior safety profile of coxibs in conjunction with a comparable efficacy to nonselective NSAIDs supports the use of coxibs in balanced analgesic regimens and provides the potential to incorporate coxibs into the pain management algorithm used to treat cancer pain.     

Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review.

BACKGROUND AND PURPOSE: The purpose was to develop a systematic review that would address the following question: what is the role of radiopharmaceuticals in the palliation of metastatic bone pain in adults with uncomplicated, multifocal painful bone metastases whose pain is not controlled with conventional analgesic regimens? The outcomes of interest are pain response, analgesic consumption, overall survival, adverse effects and quality of life. MATERIALS AND METHODS: A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes. RESULTS: Six randomized phase III trials, two randomized phase II trials and one randomized crossover trial of strontium-89 were reviewed. A randomized phase III trial comparing strontium-89 plus cisplatin with strontium-89 plus placebo reported a significantly higher proportion of patients experiencing pain relief for a significantly longer duration with strontium-89 plus cisplatin. A randomized phase III trial comparing adjuvant strontium-89 with placebo following radiotherapy reported a higher proportion of pain-free patients with strontium-89. Patients who received strontium-89 also experienced fewer new sites of bone pain. A second, but underpowered study failed to confirm these results. In one randomized trial of strontium-89 versus radiotherapy (hemibody or local), patients treated with strontium-89 developed fewer new sites of pain. In a second trial comparing strontium-89 versus local radiotherapy, median overall survival was improved with radiotherapy, while pain response and time-to-progression were similar in the two groups. One randomized phase III trial reported no difference in pain relief between strontium-89 and placebo. Three randomized phase III trials and two randomized phase II trials investigating samarium-153 were reviewed. In a randomized phase III trial of three different doses of samarium-153, the pain responses were similar for all three doses. In a randomized phase III trial of two different doses of samarium-153 versus placebo, the complete pain response rate was significantly higher with the higher dose of samarium-153 compared with placebo. In a randomized phase III trial comparing samarium-153 with placebo, significant differences favouring samarium-153 were reported for pain and opiate use. In addition, one randomized phase III trial, two randomized phase II trials, one randomized crossover trial and 13 phase II or phase I trials of rhenium, one phase I trial of tin-117 m and one phase II trial of phosphorus-32 were reviewed. The majority of patients treated in trials of radiopharmaceuticals where histology was specified had metastatic breast cancer (approximately 5-10% of patients reported), metastatic hormone-refractory prostate cancer (80-90% of patients reported) or metastatic lung cancer (5-10% of patients reported). Information on histologic subtype was not available for a significant proportion of patients treated on trials (30-40% of patients reported). CONCLUSIONS: Use of single-agent radiopharmaceuticals (strontium-89 and samarium-153) should be considered as a possible option for the palliation of multiple sites of bone pain from metastatic cancer where pain control with conventional analgesic regimens is unsatisfactory and where activity on a bone scan of the painful lesions is demonstrated. Ongoing clinical research should seek to establish the benefit of newer radiopharmaceuticals and radiopharmaceuticals in combination with other systemic therapies.     

Nordic walking for women with breast cancer: A systematic review

Nordic walking (NW) seems to be an interesting rehabilitation strategy for women with breast cancer (BC). No review article that has synthesised and summarised the existing scientific evidence about the effect of NW on BC survivors has been published so far. A systematic review was conducted aimed at identifying the characteristics and methodological quality of the studies that have analysed the effects of NW on women with BC. The critical appraisal of the randomised controlled trials (RCTs) was retrieved from the Physiotherapy Evidence Database (PEDro). The methodological quality of the uncontrolled studies was evaluated by means of the Quality Assessment Tool for Before–After Studies with No Control Group. Nine investigations (four RCTs and five quasi‐experimental studies) were included in the final analysis. The RCTs showed a fair methodological quality, while the quasi‐experimental studies obtained a score ranging from “fair” to “poor”. Judging from the findings of the analysed studies, NW had a significant and positive impact on a number of BC symptoms, including lymphedema, physical fitness, disability and morbid perceptions. No adverse effects were reported. However, due to the methodological limitations observed, further research is needed to confirm such findings.     

Oxycodone and the challenge of neuropathic cancer pain: a review

In order to evaluate the potential role of oxycodone in cancer pain management, neuropathic cancer pain was selected as a model for difficult pain syndromes. A nonsystematic, yet exhaustive, review of the literature provided the relevant evidence for the discussion. Ten randomized controlled trials (RCTs) and 5 open-label studies on oxycodone and cancer pain, 3 RCTs and 1 open-label study on oxycodone and neuropathic pain, and 2 RCTs on oxycodone and visceral pain were identified and reviewed. Additionally, 5 basic research studies that contributed to our knowledge of the specific mechanisms of action of oxycodone were also reviewed. Finally, recent evidence-based reviews of RCTs on neuropathic pain were selected (6 reviews), and specific RCTs on neuropathic cancer pain were also identified (2 trials). The review of the literature shows that the management of neuropathic cancer pain has changed dramatically in the last few years thanks to new approaches and novel drugs. The vast majority of these new drugs have been proven to be useful in 'benign' neuropathic pain syndromes. The intrinsic difficulties in performing RCTs in cancer pain have traditionally justified the acceptance of drugs already known to be effective in benign neuropathic pain, in spite of insufficient evidence in malignant neuropathic pain. Therefore, a case is made for the development of specific guidelines for the management of both simple and complex cases of neuropathic cancer pain. An example of one of such clinical guidelines is provided, in which the role of oxycodone is particularly relevant given the existing evidence.     

稳定性运动治疗慢性非特异性腰痛疗效的Meta分析

目的通过Meta分析的方法比较稳定性运动和常规运动治疗慢性非特异性腰痛的临床疗效。方法计算机检索PubMed、The Cochrane Library、PEDro、CNKI、CBM和VIP数据库,搜集稳定性运动治疗腰痛疗效的相关随机对照试验(randomized controlled trial,RCT),检索时限均为2009年1月至2019年8月。由2位研究者独立筛选文献、提取资料、质量评价及风险评估后,采用RevMan 5.3软件进行Meta分析。结果共纳入18个RCT,共计1125例。Meta分析结果表明,稳定性运动与常规运动相比,能显著改善患者短期疼痛[MD=-8.73,95%CI(-12.88,-4.58),Z=4.13,P<0.0001]和短期功能障碍[MD=-5.75,95%CI(-7.30,-4.20),Z=7.27,P<0.00001]。但在改善患者中期疼痛[MD=1.9,95%CI(-0.93,4.74),Z=1.31,P=0.19]和长期疼痛[MD=-4.08,95%CI(-11.58,3.41),Z=1.07,P=0.29]方面差异无统计学意义。结论稳定性运动与常规运动均可改善腰痛患者的疼痛和功能障碍,稳定性运动的短期疗效更优,中、长期疗效差异无统计学意义。     

Malignant lymphomas (ML) and HIV infection in Tanzania

Background

To determine the efficacy and safety of heparin (unfractionated heparin (UFH) or low-molecular-weight-heparin (LMWH)) and fondaparinux in improving the survival of patients with cancer.

Methods

We conducted in January 2007 a comprehensive search for relevant randomized clinical trials (RCTs). We used a standardized form to extract in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, thromboembolic events, and bleeding events. We assessed the methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology

Results

Of 3986 identified citations, we included 5 RCTs, none of which evaluated fondaparinux. The quality of evidence was moderate for survival, low for major and minor bleeding, and very low for DVT. Heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95%CI = 0.65–0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95%CI = 0.38–0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95%CI = 0.60–1.06) or patients with advanced cancer (HR = 0.84; 95%CI = 0.68–1.03). The increased risk of bleeding with heparin was not statistically significant (relative risk (RR) = 1.78; 95%CI = 0.73–4.38).

Conclusion

This review suggests a survival benefit of heparin in cancer patients in general, and in patients with limited small cell lung cancer in particular.     

羟考酮控释片治疗中重度肺癌疼痛的临床观察

目的：观察盐酸羟考酮控释片（奥施康定）治疗中重度肺癌疼痛的疗效,不良反应及患者生活质量改善情况,同时观察不同心理状态对疼痛程度和镇痛疗效的影响.方法：应用盐酸羟考酮控释片治疗76例中重度肺癌疼痛患者,盐酸羟考酮控释片起始剂量5mg/12h或10mg/12h,根据疼痛缓解程度调整剂量,直至达到满意镇痛效果,对其镇痛疗效,不良反应进行观察和评估.采用生活质量量表EORTCQLQ-C30（V3.0）中文版对肺癌疼痛患者镇痛治疗前后的生活质量进行评估.观察不同心理状态对疼痛强度和镇痛效果的影响.结果：入组的76例患者中,有74例可评价疗效和安全性,其中67例（90.5%）达到满意的疼痛缓解,平均达有效维持剂量时间为2.4天.消极悲观者疼痛程度重、镇痛效果差,积极乐观者疼痛程度轻、镇痛效果佳.主要不良反应为便秘、恶心呕吐、头晕、排尿困难、嗜睡.在疼痛缓解的同时,肺癌疼痛患者的生活质量得到了明显改善.结论：心理状态与疼痛程度和镇痛疗效密切相关;盐酸羟考酮控释片治疗中重度肺癌疼痛安全有效,能明显改善肺癌疼痛患者的生活质量.     

Palliative uses of methylphenidate in patients with cancer: a review.

PURPOSE: Cancer is, unfortunately, often a terminal disease. The goal of therapy for many patients with cancer is palliation of symptoms common at the end of life, including pain, depression, and cognitive dysfunction. Methylphenidate is a psychostimulant most commonly used in the treatment of attention deficit hyperactivity disorder. In this report, we review the use of methylphenidate in the palliative care of patients with cancer. METHODS: This review was written on the basis of a computerized literature search of Medline. We considered all English language publications from 1966 to present using the following key words: methylphenidate, palliative care, and cancer. Forty-nine articles were identified as being relevant for this review. RESULTS: On the basis of this review, we came to the conclusion that methylphenidate is used to ameliorate opioid-induced somnolence, to augment the analgesic effects of opioids, to treat depression, and to improve cognitive function in patients with cancer. CONCLUSION: The medical literature supports the palliative use of methylphenidate in the care of patients with cancer. Further placebo-controlled trials are needed to elucidate the precise role that methylphenidate will have in providing symptom relief to dying patients.     

The use of anti-inflammatory drugs in cancer pain

The role of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain has been well established in the treatment of mild pain and also alone or in association with opioids for the treatment of moderate to severe pain. Acutely, NSAIDs may be more than mild analgesics, and may provide additional analgesia when combined with opioids. However, NSAIDs have ceiling effects and there is no therapeutic gain from increasing dosages beyond those recommended.As there is no clearly superior NSAID, the choice should be based on experience and the toxicity profile that probably relates to the COX-1:COX-2 ratio. Among the older drugs, ibuprofen seems to have these properties.Non-steroidal anti-inflammatory drugs have been shown to have an opioid-sparing effect. Although the value of a simple narcotic-sparing effect may be questioned in cancer pain treatment, the use of NSAIDs may be useful when the increase in opioid dosage determine the occurrence of opioid toxicity. Like opioids, NSAIDs should not be considered analgesics for a specific type or cause of pain. There is a lack of evidence for any difference between different routes of NSAIDs administration.The long-term toxicity of NSAIDs in cancer pain is poorly defined due to a lack of studies. A variety of strategies have been used in an attempt to reduce the risks associated with NSAID therapy. Those NSAIDs that are weak COX-1 inhibitors may be preferred. In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications.     

Treatment of cancer pain with transdermal fentanyl

Pain is a feature of many cancers, particularly in the advanced stages at which the palliative care approach to symptom control achieves the best outcomes. The holistic approach generally dictates that any treatment of the cancer per se has symptom control as the primary objective at this advanced stage. Pain, which invariably increases with disease progression, is treated with opioids and adjuvant analgesic drugs together with physical therapies. Orally administered opioid drugs are used preferentially because of cost and convenience, but other routes of administration (subcutaneous, rectal, spinal) are also possible. More recently, transdermal fentanyl has been evaluated in the treatment of moderate to severe cancer pain. The rate of fentanyl absorption is constant (after a lag period), and the dose is altered by increasing or decreasing the area of skin covered by the patch (size and/or number of patches). The dosing interval for these systems is generally 3 days. The extent of pain relief provided by transdermal fentanyl and sustained release morphine formulations is similar, with quality-of-life instruments showing no consistent preference for either formulation. Open studies have suggested a lower risk of constipation. Transdermal fentanyl is effective in the treatment of severe cancer pain, particularly when the oral route is unavailable.     

Has the quality of health-related quality of life reporting in cancer clinical trials improved over time? Towards bridging the gap with clinical decision making

BACKGROUND: Previous work highlighted a number of methodological constraints when reporting health-related quality of life (HRQOL) outcomes from randomized controlled trials (RCTs). Given this, the objective of this study was to investigate whether the quality of such HRQOL reports has improved over time. MATERIALS AND METHODS: On the basis of a predefined set of criteria, 159 RCTs with a HRQOL end point, published between 1990 and 2004 were identified and analyzed. Each study was evaluated by a number of issues (e.g. sample size and industry sponsorship) and by the "minimum standard checklist for evaluating HRQOL outcomes in cancer clinical trials". RESULTS: The quality of HRQOL reports, as measured by the overall checklist score, was independently related to more recently published studies (P < 0.0001). This relationship was independent of industry funded, HRQOL end point (primary versus secondary), cancer disease site, size of the study and HRQOL difference between treatment arms. While only 39.3% of studies published between 1990 and 2000 (89/159 RCTs) were identified as being probably robust, thus likely to support clinical decision making, this percentage was 64.3% for studies published after 2000 (70/159 RCTs). CONCLUSION: Since we found a significant learning curve in HRQOL trial reporting since 1990, it can be expected that HRQOL data will increasingly impact on clinical decision making and treatment policies in the near future.     

Opioids for metastatic bone pain

Metastatic bone pain is characteristic of cancer pain. Satisfactory analgesic effects are achieved in more than 70% of patients with cancer pain who receive a combination of nonsteroidal anti-inflammatory drugs and opioids, according to the WHO therapeutic guidelines. Morphine, oxycodone, and fentanyl are commonly administered opioids. We found that the mean dose of oxycodone to achieve analgesic effects was 55 mg, and at doses of 相似文献   

Challenges in cancer pain management--bone pain

Whilst not strictly a neuropathic injury, cancer-induced bone pain (CIBP) is a unique state with features of neuropathy and inflammation. Recent work has demonstrated that osteoclasts damage peripheral nerves (peptidergic C fibres and SNS) within trabeculated bone leading to deafferentation. In addition, glia cell activation and neuronal hyperexcitability within the dorsal horn, are all similar to a neuropathy. Gabapentin and carbamazepine (both anti-convulsants that modulate neuropathy) are effective at attenuating dorsal horn neuronal excitability and normalizing pain-like behaviours in a rat model of CIBP. However alterations in neuroreceptors in the dorsal horn do not mimic neuropathy, rather only dynorphin is upregulated, glia cells are active and hypertrophic and c-fos expression is increased post-noxious behavioural stimulus. CIBP perhaps illustrates best the complexity of cancer pains. Rarely are they purely neuropathic, inflammatory, ischaemic or visceral but rather a combination. Management is multimodal with radiotherapy, analgesics (opioids, NSAIDs), bisphosphonates, radioisotopes and tumouricidal therapies. The difficulty with opioids relates to efficacy on spontaneous pain at rest and movement-related pain. Potential adjuvants to standard analgesic therapies for CIBP are being explored in clinical trials and include inhibitors of glutamate release.     

Adjuvant and neoadjuvant therapies in resectable pancreatic cancer: a systematic review of randomized controlled trials

The timing of surgery and antineoplastic therapies in patients with resectable non-metastatic pancreatic cancer is still a controversial matter of debate, with special regard to neoadjuvant approaches. Following the criteria of the PRISMA statement, a literature search was conducted looking for RCTs focusing on adjuvant and neoadjuvant therapies in resectable pancreatic cancer. The quality of the available evidence was assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Data extraction was carried out by two independent investigators. The search led to the identification of 2830 papers of which 14 RCTs focusing on adjuvant and neoadjuvant treatment of resectable pancreatic cancer eligible for the systematic review. Risk of bias was estimated “unclear” in 3 studies and “high” in 5 studies. Median age ranged between 53 and 66. Overall survival in the surgery-only arms ranged between 11 and 20.2 months; in the adjuvant treatment arms 12.5–29.8 months; and in the neoadjuvant setting 9.9–19.4 months. Neoadjuvant protocols should be offered only in randomized clinical trials comparing the standard of care (surgery followed by adjuvant treatments) to a neoadjuvant approach followed by surgery and adjuvant treatment.     

氟比洛芬酯联合吗啡自控静脉镇痛治疗肝癌半肝切除术后疼痛的疗效观察

目的:观察氟比洛芬酯注射液联合吗啡自控静脉镇痛（patient-controlled intravenous analgesia,PCIA）治疗半肝切除术后疼痛的镇痛效果及不良反应。方法:半肝切除术患者50例,按照随机数字表法分为单纯吗啡PCIA对照组和氟比洛芬酯注射液联合吗啡PCIA实验组,每组25 例,连续观察72小时。分别就两组治疗后疼痛缓解、吗啡用量、爆发痛镇痛起效时间和不良反应等方面进行评价。结果:对照组疼痛缓解率为88.0%;实验组疼痛缓解率为92.0%,两组镇痛作用无显著性差异（P>0.05）。实验组在减少阿片类止痛药剂量,缓解疼痛时间,减轻阿片类药物引起恶心、便秘、嗜睡、谵语、延长排气发生率方面明显优于对照组(P<0.05)。结论:氟比洛芬酯注射液与吗啡联合治疗肝癌半肝切除术后疼痛,可减少阿片类药物用量,降低阿片类不良反应,促进术后恢复。