BACKGROUND & AIMS: :Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

背景与目标： : 脊髓NMDA受体激活后过度兴奋可能导致慢性疼痛。天然衍生的哺乳动物肽组织蛋白可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物 [Ser1] 组织蛋白 (SHG) 可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型 (CCI) 诱发神经病理性疼痛。鞘内注射SHG可显着减轻由CCI引起的痛觉过敏和异常性疼痛，几乎使反应正常化。这些结果表明，天然肽组织粒蛋白可能是神经性疼痛管理的新型辅助手段。

BACKGROUND & AIMS: :Wound healing is a complex process resulting from an interplay of processes including coagulation, inflammation, angiogenesis, and epithelialization. The chemokine family has been shown to contain members that are potent regulators of many of these pathways. Because we have previously shown that chemokines "pool" in biologic wound dressings, we studied the levels of CXC and CC chemokines, along with key inflammatory mediators, serially from a group of patients undergoing therapy for chronic venous leg ulcers. After 8 weeks, all patients had marked clinical healing of their ulcers (median 63.3% reduction in size) with two of 10 completely healed. Wound fluids extracted from dressings showed high levels of platelet factor-4 and interferon-gamma-inducible protein, with a trend toward increases in the ratio of the sums of the angiogenic versus angiostatic CXC chemokines (p = 0.082) in the tissues collected from the center of the ulcers during wound closure. Neutrophil-activating peptide-2 and interleukin-8 accounted for the most changes in wound fluid angiogenic chemokines, with significant differences both as compared with baseline levels and with patients' plasma level noted at various time points between weeks 0 and 8. The level of angiostatic chemokines, interferon-y inducible protein 10 and platelet-activating-4, fell most significantly between weeks 0 and 3 as compared with plasma levels. The observed shift toward angiogenic CXC chemokines suggests that effective healing in chronic venous insufficiency ulcers appears to "move" the ulcer bed toward a state more conducive to epithelialization,characteristic of the proliferative phase of wound healing. CC chemokines were also elevated at baseline in the wound fluid samples as compared with the patients' plasma levels. Macrophage inflammatory protein-1 (3 and regulated on activation, normal T expressed and secreted (RANTES) levels decreased with healing, whereas there were significant increases in the tissue levels of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 a over the first 4 weeks of therapy (p< or = 0.05 for both). Coincident with these changes was a steady increase in the ratio of interleukin-1 R/interleukin-1 receptor antagonist protein in the ulcer center tissues, which also correlated with healing (p < 0 .05) as compared with a decreasing ratio at the ulcer edge, and a biphasic response in the wound fluids. These findings suggest that advanced wound care techniques help move the ulcer from a chronic inflammatory state into one more characteristic of the late inflammatory/early proliferative phase of wound healing. Chemokines may play a critical role in the pathogenesis of chronic venous ulcers through their effects on angiogenesis and/or the progression of inflammatory reactions at the site of injury.

背景与目标： 伤口愈合是一个复杂的过程，由凝血、炎症、血管生成和上皮形成等过程的相互作用产生。趋化因子家族已被证明包含许多这些途径的有效调节剂。因为我们以前已经表明趋化因子在生物伤口敷料中 “聚集”，所以我们连续研究了一组接受慢性静脉腿部溃疡治疗的患者的CXC和CC趋化因子以及关键炎症介质的水平。8周后，所有患者的溃疡临床愈合明显 (中位63.3% 缩小)，其中10例中有2例完全愈合。从敷料中提取的伤口液显示出高水平的血小板因子-4和干扰素-γ 诱导蛋白，在伤口闭合期间从溃疡中心收集的组织中，血管生成与血管抑制CXC趋化因子 (p = 0.082) 的总和比率呈增加趋势。中性粒细胞激活肽-2和interleukin-8占伤口流体血管生成趋化因子的最大变化，与基线水平和患者血浆水平相比，在第0周和第8周之间的不同时间点存在显着差异。与血浆水平相比，血管抑制趋化因子，干扰素y诱导蛋白10和血小板活化4的水平在第0周和第3周之间下降最明显。观察到的向血管生成CXC趋化因子的转变表明，慢性静脉功能不全溃疡的有效愈合似乎使溃疡床 “移至” 更有利于上皮形成的状态，这是伤口愈合增生期的特征。与患者血浆水平相比，伤口液体样品中的CC趋化因子在基线时也升高。巨噬细胞炎性蛋白-1 (3) 和受激活调节，正常T表达和分泌 (RANTES) 水平随愈合而降低，而在治疗的前4周内，单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1 a的组织水平显着增加 (两者p <或 = 0.05)。与这些变化同时发生的是，interleukin-1 R/interleukin-1受体拮抗剂蛋白的比例在溃疡中心组织，与溃疡边缘的比率降低相比，这也与愈合相关 (p <0.05)，和伤口液体中的双相反应。这些发现表明，先进的伤口护理技术有助于将溃疡从慢性炎症状态转移到伤口愈合的晚期炎症/早期增生期的另一个特征。趋化因子可能通过其对血管生成的影响在慢性静脉溃疡的发病机理中发挥关键作用和/或损伤部位炎症反应的进展。

BACKGROUND & AIMS: :Several molecular-targeted therapeutics have been tested in clinical trials for the treatment of head and neck squamous cell carcinoma (HNSCC). Of these, therapeutics targeting the epidermal growth factor receptor (EGFR) have been studied most extensively and some agents have demonstrated measurable clinical effectiveness. However, molecular studies designed to define HNSCC patient subcohorts of likely responders to EGFR-targeted therapy have not identified molecular signatures that correlate with clinical response. Here, the authors summarise the relevant clinical findings and highlight reported molecular correlative studies for EGFR-targeted therapeutics for HNSCC. The authors focus especially on molecular markers evaluated for association with clinical response and include data from EGFR-targeted clinical studies in other cancer sites that they anticipate will be of interest to the head and neck cancer research and treatment communities.

背景与目标： : 几种分子靶向疗法已在治疗头颈部鳞状细胞癌 (HNSCC) 的临床试验中进行了测试。其中，针对表皮生长因子受体 (EGFR) 的疗法已被最广泛地研究，并且一些药物已证明可测量的临床有效性。然而，旨在定义可能对EGFR靶向治疗有反应的HNSCC患者亚组的分子研究尚未确定与临床反应相关的分子特征。在这里，作者总结了相关的临床发现，并重点报道了针对HNSCC的EGFR靶向治疗的分子相关研究。作者特别关注评估与临床反应相关的分子标志物，并包括来自其他癌症部位的EGFR靶向临床研究的数据，他们预计头颈癌症研究和治疗社区将对此感兴趣。

BACKGROUND & AIMS: :Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to 50% of persons with AIDS. The purpose of this pilot study was to examine the effects of ice massage to reduce neuropathic pain and improve sleep quality and to determine the feasibility of a larger study. A repeated measures design was used. The three treatments consisted of ice massage, dry-towel massage, and presence. Consecutive sampling was used to select 33 persons with AIDS who had neuropathic pain. Although the results of the study were negative, there was a decrease in pain intensity over time with both the ice massage and towel massage, suggesting that the intervention has some clinical benefit.

背景与目标： : 周围神经性疼痛是一种独特的慢性疼痛形式，困扰多达50% 的艾滋病患者。这项初步研究的目的是检查冰按摩减轻神经性疼痛和改善睡眠质量的效果，并确定进行更大规模研究的可行性。使用了重复测量设计。这三种治疗方法包括冰按摩，干毛巾按摩和在场。连续抽样选择33例患有神经性疼痛的艾滋病患者。尽管研究结果为阴性，但随着时间的推移，冰按摩和毛巾按摩的疼痛强度有所降低，这表明该干预措施具有一定的临床益处。

BACKGROUND & AIMS: CONTEXT:Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. OBJECTIVES:This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. METHODS:In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. RESULTS:The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. CONCLUSION:This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

背景与目标：

BACKGROUND & AIMS: :The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

背景与目标： 内脏疼痛的感知是一个复杂的过程，涉及脊髓和高阶脑结构。越来越多的证据表明肠道菌群是大脑和行为的关键调节剂，但肠道细菌是否在内脏敏感性中起作用尚待确定。我们使用无菌小鼠 (GF) 评估内脏敏感性，脊髓基因表达和与疼痛相关的大脑结构。GF小鼠表现出内脏超敏反应，并伴有脊髓中Toll样受体和细胞因子基因表达的增加，这通过出生后用常规定植 (CC) 的微生物群定植而标准化。在GF小鼠中，前扣带回皮层 (ACC) 和导水管周围灰色 (涉及疼痛处理的区域) 的体积分别减少和扩大，并且ACC的树突状变化明显。这些发现表明，正常的内脏疼痛感需要肠道菌群。

BACKGROUND & AIMS: BACKGROUND & AIMS:Some patients with chronic hepatitis B virus (HBV) infection progress to hepatocellular carcinoma (HCC). However, the long-term effect of nucleos(t)ide analogue (NA) therapy on progression to HCC is unclear. METHODS:Therefore, we compared chronic hepatitis B patients who received NA therapy to those who did not, using a propensity analysis. RESULTS:Of 785 consecutive HBV carriers between 1998 and 2008, 117 patients who received NA therapy and 117 patients who did not, were selected by eligibility criteria and propensity score matching. Factors associated with the development of HCC were analyzed. In the follow-up period, HCC developed in 57 of 234 patients (24.4%). Factors significantly associated with the incidence of HCC, as determined by Cox proportional hazards models, include higher age (hazard ratio, 4.36 [95% confidence interval, 1.33-14.29], p=0.015), NA treatment (0.28 [0.13-0.62], p=0.002), basal core promoter (BCP) mutations (12.74 [1.74-93.11], p=0.012), high HBV core-related antigen (HBcrAg) (2.77 [1.07-7.17], p=0.036), and high gamma glutamyl transpeptidase levels (2.76 [1.49-5.12], p=0.001). CONCLUSIONS:NA therapy reduced the risk of HCC compared with untreated controls. Higher serum levels of HBcrAg and BCP mutations are associated with progression to HCC, independent of NA therapy.

背景与目标：

BACKGROUND & AIMS: :The feasibility of using a subcutaneously implanted portal system attached to a conventional 16-gauge epidural catheter has been evaluated in 50 patients with sever pain associated with cancer. This technique allowed for the percutaneous epidural administration of morphine at 8-12-hourly intervals for pain control. The mean duration of implantation was 12 weeks and the longest period a portal remained in situ was 36 weeks. Five portals had to be removed for various reasons. The injection system has blocked on eight occasions due to catheter blockage (six times) and portal blockage (two occasions). These patients have continued to obtain excellent analgesia when either catheter or portal were replaced. In a cadaver, 300 injections were simulated using either 22-gauge Huber point needles or disposable needles (25 gauge) and the injectate examined by both light and scanning electron microscopy. Both needle types resulted in particulate contamination which was greater with the recommended Huber point needles.

背景与目标： : 已在50例与癌症相关的严重疼痛患者中评估了使用固定在常规16号硬膜外导管上的皮下植入门静脉系统的可行性。该技术允许以8-12小时的间隔经皮硬膜外施用吗啡以控制疼痛。植入的平均持续时间为12周，而原位保留的最长时间为36周。由于各种原因，必须删除五个门户。由于导管阻塞 (六次) 和门静脉阻塞 (两次)，注射系统有八次阻塞。当更换导管或门静脉时，这些患者继续获得出色的镇痛效果。在尸体中，使用22号Huber点针或一次性针 (25号) 模拟300注射，并通过光学和扫描电子显微镜检查注射物。两种类型的针头都会导致颗粒污染，推荐的Huber点针头会更大。

BACKGROUND & AIMS: :Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).

背景与目标： : 美国 (20世纪70年代1985年) 和瑞士 (1988-1993) 的精神科医生和心理治疗师合法使用MDMA作为处方药，以提高心理治疗的有效性。早期报告表明，它在治疗创伤相关疾病中很有用。最近，第一个完成的MDMA辅助心理治疗PTSD的初步研究取得了令人鼓舞的结果。旨在测试MDMA辅助心理治疗在治疗耐药的PTSD患者中的安全性和有效性; 我们的随机，双盲，活性安慰剂对照试验招募了12名患者接受低剂量 (25 mg，加12.5 mg补充剂量) 或全剂量MDMA (125 mg，加62.5 mg补充剂量)。MDMA在三个实验课程中进行，并散布在每周的非基于药物的心理治疗课程中。使用的结果指标是临床医生管理的PTSD量表 (CAPS) 和创伤后诊断量表 (PDS)。在基线，第二次和第三次MDMA疗程 (治疗结束) 后三周以及2个月和1年随访时对患者进行评估。我们发现MDMA辅助心理治疗可以在临床环境中安全施用。未发生与药物相关的严重不良事件。尽管有临床和统计学上显着的自我报告 (PDS) 改善 (p = 0.066)，但我们没有看到CAPS评分的统计学显着降低 (p = 0.014)。在1年的随访中，CAPS评分进一步提高。此外，三个MDMA会话比两个更有效 (p = 0.016)。

BACKGROUND & AIMS: :Neuropathic pain is a result of complex interactions between peripheral and central mechanisms with multiple potential therapeutic targets. However, the complexity of these mechanisms and relative youth of translational pain research, which is in its infancy, have prevented translation of successful basic bench research to human therapy. Most of the clinically available neuropathic pain treatments are borrowed from other therapeutic areas, such as antidepressants and antiepileptics, or involve application of older therapy, such as opioids. Exceptions are ziconotide, tapentadol, and the high-concentration capsaicin patch. Similar to all other analgesic agents, these provide only partial pain relief in subsets of patients. The standard of care for patients with chronic neuropathic pain is multimodal and multidisciplinary. For most patients to achieve and maintain satisfactory pain relief a combination of therapeutic agents is necessary, providing the empiric basis for rational polypharmacy, which has become a standard approach as well.

背景与目标： 神经性疼痛是周围和中枢机制与多个潜在治疗靶点之间复杂相互作用的结果。然而，这些机制的复杂性以及尚处于起步阶段的转化疼痛研究的相对年轻，阻碍了成功的基础研究转化为人类治疗。大多数临床上可用的神经性疼痛治疗方法都是从其他治疗领域借来的，例如抗抑郁药和抗癫痫药，或者涉及应用较旧的治疗方法，例如阿片类药物。齐康宁、他喷他多和高浓度辣椒素贴剂是例外。与所有其他镇痛剂相似，这些镇痛剂仅可部分缓解患者的疼痛。慢性神经性疼痛患者的护理标准是多模式和多学科。为了使大多数患者达到并保持令人满意的疼痛缓解，必须结合治疗剂，为合理的多药治疗提供经验基础，这也已成为一种标准方法。

BACKGROUND & AIMS: :Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. This disease is strongly associated with tobacco smoking. The aim of this manuscript was to establish an in vitro model that mimics the chronic exposures of alveolar epithelial type II cells to the tobacco-specific nitrosamine carcinogen, NNK. Immortalized non-neoplastic alveolar epithelial cells type II, (E10 cells), from BALB/c mice were exposed to low concentration of NNK (100 pM) during 5, 10, 15, and 20 cycles of 48 h. NNK-transformed cells showed an increase of proliferation rate and motility. Moreover, these cells underwent epithelial-to-mesenchymal transition (EMT). Increased migratory capacity and EMT were correlated to the time of exposure to NNK. NNK-transformed cells were tested for their growth and metastatic capacity in vivo. Subcutaneous injection of cells exposed to NNK for 20 cycles (E10-NNK20 clone) into BALB/c mice led to the formation of subcutaneous tumors that arose after 40 ± 17 d in all animals, which died 95 ± 18 d after cell inoculation, with lymph nodes and lung metastasis. The morphological characteristics of tumors were compatible with metastatic undifferentiated carcinoma. Cells exposed to NNK for 5-10 cycles did not display metastatic capacity, while those exposed for 15 cycles displayed low capacity. Our results show that prolonged exposures to NNK led the cells to increasingly acquire malignant properties. The cellular model presented in this study is suitable for studying the molecular events involved in the different stages of malignant transformation.

背景与目标： : 肺癌是全世界男性和女性癌症相关死亡率的主要原因。这种疾病与吸烟密切相关。本手稿的目的是建立一个体外模型，该模型模拟肺泡上皮II型细胞对烟草特异性亚硝胺致癌物NNK的慢性暴露。来自BALB/c小鼠的永生化的非肿瘤性II型肺泡上皮细胞 (E10细胞) 在48  h的5、10、15和20个周期中暴露于低浓度的NNK (100  pM)。NNK转化的细胞显示出增殖速率和运动能力的增加。此外，这些细胞经历了上皮-间质转化 (EMT)。迁移能力和EMT的增加与NNK暴露时间相关。测试NNK转化的细胞在体内的生长和转移能力。在BALB/c小鼠中皮下注射暴露于NNK 20个周期的细胞 (E10-NNK20克隆) 导致所有动物皮下肿瘤的形成，该肿瘤在40  ±   17 d后出现，在细胞接种后95  ±   18 d死亡，并伴有淋巴结和肺转移。肿瘤的形态特征与转移性未分化癌相容。暴露于NNK 5-10个周期的细胞未显示转移能力，而暴露于15个周期的细胞显示低容量。我们的结果表明，长时间暴露于NNK导致细胞越来越多地获得恶性特性。本研究中提出的细胞模型适用于研究恶性转化不同阶段涉及的分子事件。

BACKGROUND & AIMS: :Increasing healthcare expenditure is a matter of concern in many countries, particularly in relation to the underlying drivers of such escalation that include ageing, medical innovation, and changes in the burden of disease, such as the growing prevalence of chronic diseases. Most healthcare systems in developed countries have been designed to 'cure' acute episodes, rather than to 'manage' chronic conditions, and therefore they are not suitably or efficiently organized to respond to the changing needs and preferences of users. New models of chronic care provision have been developed to respond to the changing burden of disease and there is already considerable practical experience in several different countries showing their advantages but also the difficulties associated with their implementation. In this paper, we focus on the Spanish experience in terms of policy changes and pilot studies focused on testing the feasibility of moving towards chronic care models. In particular, we discuss a framework that identifies and analyses ten key prerequisites to achieving high performing chronic care-based healthcare systems and apply it to the current Spanish National Health System (NHS). We find that the design of the Spanish NHS already meets some of these pre-requisites. However, other features are still in their early stages of development or are being applied only in limited geographical and clinical contexts. We outline the policies that are being implemented and the pathway that the Spanish NHS is taking to address the crucial challenge of the transition towards an optimal health system focused on chronic care. Given the current evidence and trends, we expect that the pathway for developing a chronicity strategy being followed by the Spanish NHS will significantly transform its current healthcare delivery model in the next few years.

背景与目标： : 在许多国家，医疗保健支出的增加是一个令人关注的问题，特别是在这种升级的潜在驱动因素方面，包括老龄化、医疗创新和疾病负担的变化，例如慢性病的日益流行。发达国家的大多数医疗保健系统旨在 “治愈” 急性发作，而不是 “管理” 慢性病，因此它们没有适当或有效地组织起来以应对用户不断变化的需求和偏好。已经开发了新的长期护理模式，以应对不断变化的疾病负担，几个不同国家已经有相当多的实践经验，显示了它们的优势，但也显示了与实施相关的困难。在本文中，我们着重于西班牙在政策变化方面的经验，并着重于测试转向慢性病模式的可行性的试点研究。特别是，我们讨论了一个框架，该框架确定并分析了实现高性能的基于慢性护理的医疗保健系统的十个关键先决条件，并将其应用于当前的西班牙国家卫生系统 (NHS)。我们发现西班牙NHS的设计已经满足了其中一些先决条件。但是，其他功能仍处于开发的早期阶段，或者仅在有限的地理和临床环境中应用。我们概述了正在实施的政策以及西班牙NHS为应对向以长期护理为重点的最佳卫生系统过渡的关键挑战而采取的途径。鉴于目前的证据和趋势，我们预计西班牙NHS遵循的制定慢性病策略的途径将在未来几年内显着改变其当前的医疗保健模式。

BACKGROUND & AIMS: INTRODUCTION:Significant malnutrition exists in a high percentage of patients with head and neck cancer. Malnutrition is associated with defects in immune function that may impair the host response to malignancy. Malnutrition and immunosupression make patients highly susceptible to postoperative infections and complications. OBJECTIVES:Some studies of patients receiving immuno-nutrition in the perioperative period in head and neck cancer have shown beneficial effects on clinical outcome and inmune status. The authors carried out a systematic review of randomised control trials to determine whether perioperative immunonutrition has a role in the treatment of head and neck cancer. METHODS:14 trials of polymeric nutritional supplementation with immunonutrition were identified. Two studies compared two types of immunonutrition. RESULTS:A reduction in the length of postoperative hospital stay was seen in some trials, but the reason for this reduction is not clear. Some studides showed statistical differences with less complications in arginine-enhanced group and also showed a significant decrease of fistula complications in patients treated with a high arginine dose enhanced formula, if compared with a medium dose of arginine. CONCLUSION:[corrected] Those planning future studies face challenges. A suitable powered clinical trial is required before firm recommendations can be made on the use of immunonutrition in head and neck cancer patients postoperatively.

背景与目标：

BACKGROUND & AIMS: :Spindle cell rhabdomyosarcoma is an uncommon subtype of embryonal rhabdomyosarcoma. Found almost exclusively in children, these tumors are classically located in the paratesticular and head and neck regions. Morphologically these lesions can resemble several other benign or malignant soft-tissue spindle cell lesions, especially smooth muscle or myofibroblastic tumors, and thus immunohistochemical staining is often needed to prove skeletal muscle differentiation. Although there is extensive literature reporting the genetics of embryonal rhabdomyosarcoma, little is reported specific to the spindle cell subtype. Below we present the case of a 7-month-old male presenting with a large posterior neck mass that was diagnosed as spindle cell rhabdomyosarcoma. Karyotype evaluation revealed a t(6;8) (p12;q11.2) chromosomal translocation within the lesion. We review the histologic and immunohistochemical diagnosis of these tumors and discuss the genetics of rhabdomyoscarcomas.

背景与目标： : 梭形细胞横纹肌肉瘤是胚胎性横纹肌肉瘤的一种罕见亚型。这些肿瘤几乎只在儿童中发现，通常位于睾丸旁和头颈部区域。从形态上讲，这些病变可能类似于其他几种良性或恶性软组织梭形细胞病变，尤其是平滑肌或肌纤维母细胞瘤，因此通常需要免疫组织化学染色来证明骨骼肌的分化。尽管有大量文献报道了胚胎横纹肌肉瘤的遗传学，但很少有针对梭形细胞亚型的报道。下面我们介绍一名7个月大的男性，其后颈部肿块较大，被诊断为梭形细胞横纹肌肉瘤。核型评估显示病变内有t(6;8) (p12;q11.2) 染色体易位。我们回顾了这些肿瘤的组织学和免疫组织化学诊断，并讨论了横纹肌肉瘤的遗传学。

BACKGROUND & AIMS: INTRODUCTION:Expression of the DLL4 (a notch pathway ligand) by tumor-associated endothelium is a postulated marker of vascular maturity and functionality. As vascular functionality is an important parameter defining chemotherapy and oxygen intra-tumoral distribution, we investigated the role of DLL4 expression in tumour vasculature in the efficacy of radio-chemotherapy for HNSCC patients. MATERIALS AND METHODS:Sixty-five biopsy specimens from HNSCC patients with inoperable disease were immunohistochemically examined using anti-CD31 (pan-endothelial cell marker) and anti-DLL4 antibodies and the vascular density (VD) was recorded. Patients were treated with platinum based hypofractionated accelerated conformal radiotherapy. The median follow-up period was 24 months (4-80 months). RESULTS:Using the 33rd and 66th percentiles cases were grouped in three categories of low, medium and high CD31+ or DLL4+ VD. The percentage of vessels expressing DLL4 (DLL4-ratio) ranged from 17 to 100 % (mean 71 %), showing substantial variation among cases. In accordance with previous published studies, a biphasic pattern of association of CD31+ VD with poor outcome was noted. Cases with a medium VD had a significantly better local relapse free survival (LRFS) compared to cases of high VD (p = 0.0005, HR 0.15) and of low VD (p = 0.02, HR 0.28). High DLL4/CD31 ratio defined improved LRFS in both these subgroups of poor prognosis. CONCLUSIONS:The expression of DLL4 is associated with reduced radio-resistance, presumably by reducing hypoxia and improving chemotherapy accessibility. Using the combination of CD31 and DLL4 staining, a classification is suggested so that HNSCCs are categorized in sub-groups to be targeted by different anti-angiogenic and hypoxia targeting agents.

背景与目标：