BACKGROUND & AIMS: :Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemotherapy and chemoradiotherapy are new alternatives for locally advanced disease, particularly induction chemotherapy for patients with unresectable tumors. In recurrent/metastatic disease and after progression to platin-based regimens, no treatments other than best supportive care are currently available. Most SCCHN tumors overexpress the epidermal growth factor receptor (EGFR). This is a tyrosine kinase membrane receptor and has a clear implication in angiogenesis, tumor progression and resistance to different cancer treatments. Cetuximab is a monoclonal antibody that binds to EGFR and alters the tyrosine kinase-mediated signal transduction pathway. The drug is active in colon cancer and is currently being tested in SCCHN patients. For locally advanced disease, cetuximab/radiotherapy combination has demonstrated a benefit in survival when compared with radiotherapy alone as radical treatment. Cetuximab is an active treatment in platin-refractory patients with recurrent/metastatic disease.

背景与目标： ：外科手术和放射疗法是头颈部鳞状细胞癌（SCCHN）患者的标准治疗选择。化学疗法和放化疗是局部晚期疾病的新选择，特别是对于无法切除的肿瘤患者的诱导化疗。在复发/转移性疾病中，以及发展为以铂为基础的治疗方案之后，除最佳支持治疗外，目前尚无其他治疗方法。大多数SCCHN肿瘤过表达表皮生长因子受体（EGFR）。这是酪氨酸激酶膜受体，在血管生成，肿瘤进展和对不同癌症治疗的抗性中具有明显的含义。西妥昔单抗是与EGFR结合并改变酪氨酸激酶介导的信号转导途径的单克隆抗体。该药物在结肠癌中有活性，目前正在SCCHN患者中进行测试。对于局部晚期疾病，西妥昔单抗/放疗联合治疗与单纯放疗作为根治性治疗相比，已显示出生存获益。西妥昔单抗是铂类难治性复发/转移性疾病患者的积极治疗方法。

BACKGROUND & AIMS: :Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

背景与目标： ：口腔癌是一种具有某些已知原因的肿瘤。增生基因在其少数致病和预后因素中很重要。钙环蛋白是与细胞周期相关的基因，其功能尚不清楚。为了评估它们在鳞状细胞癌中的致病作用，已经研究了它的表达以及Haras和组蛋白H3的表达。从鳞状细胞癌（SCC）和良性病变的病理和正常粘膜中提取的RNA通过聚合酶链反应（PCR）进行逆转录和扩增。仅在SCC中，病理黏膜中所有三个基因的表达均得到增强。这表明它们可能参与其发病机理，并为区分恶性和良性病变提供了另一个参数。

BACKGROUND & AIMS: :Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma cell line, DDM-1.13. Six patients were enrolled in the phase I trial. Autologous DCs were generated in vitro from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were pulsed with melanoma cell lysate from a cloned and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.

背景与目标： ：免疫疗法已显示出令人兴奋的癌症治疗新观点。我们研究的目的是评估用来自新开发的黑素瘤细胞系DDM-1.13的裂解物脉冲的自体树突状细胞（DC）对晚期结直肠癌患者进行疫苗接种的毒性和可能的​​不良反应。一期试验招募了六名患者。在粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白介素-4（IL-4）的存在下，由外周血单核细胞体外产生自体DC。用来自克隆和选择的黑色素瘤细胞系的黑色素瘤细胞裂解液对DC进行脉冲处理，该黑色素瘤细胞系富含MAGE-A抗原的表达，而黑色素瘤分化抗原（酪氨酸酶，MART-1和gp100）的表达不足。在大腿近端皮内注射疫苗，每两周间隔注射五种给定的疫苗。每种疫苗均包含3-5 x 10（6）个DC。六名患者中有五名接受了全部五种疫苗的治疗。所有患者对治疗的耐受性良好，没有观察到疫苗相关的不良反应。事实证明，使用这种基于DC的癌症疫苗进行治疗是安全且无毒的。

BACKGROUND & AIMS: PURPOSE:The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. EXPERIMENTAL DESIGN:In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. RESULTS:UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. CONCLUSIONS:UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.

背景与目标： 目的：在中国最常见的泌尿生殖系统恶性肿瘤是膀胱移行细胞癌（TCC）。尽早诊断出新发和复发性膀胱癌，然后及时进行治疗，将有助于降低死亡率。目前，临床上尚无令人满意的膀胱癌标记物。迫切需要更好的诊断方法。
实验设计：在这项研究中，我们使用了全面的表达序列标签分析，基因表达的序列分析和微阵列分析，并迅速发现了候选标记物，尿路上皮癌相关1（UCA1）。对UCA1基因进行了表征，并通过逆转录PCR与尿沉渣一起分析了其作为尿液标记物的性能。这项研究总共包括212位个体，其中94位患有膀胱癌，33位输尿管/盆腔癌以及85位正常和其他泌尿系统疾病对照。
结果：UCA1被鉴定为TCC中上调的新型非编码RNA基因，是迄今鉴定到的最具TCC特异性的基因。全长cDNA为1439 bp，序列分析表明它属于人内源性逆转录病毒H家族。临床测试表明，UCA1检测对膀胱癌的诊断具有高度特异性（91.8％，78 of 85）和非常敏感（80.9％，76 of 94），对于浅表G2-G3患者特别有价值（敏感性91.1％，41） 45）。在没有TCC的各种泌尿系统疾病中，它表现出出色的鉴别诊断性能。
结论：UCA1是膀胱癌非常敏感和特异的独特标志物。它可能对术后无创性随访产生重要影响。这项研究还突出了通过将计算机隔离方法与基于RNA检测方案的转化临床测试相集成的新癌症诊断测定方法的捷径。

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： ：几种针对分子的疗法已在临床试验中用于治疗头颈部鳞状细胞癌（HNSCC）。其中，针对表皮生长因子受体（EGFR）的疗法已得到最广泛的研究，某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发现与临床反应相关的分子标志。在这里，作者总结了相关的临床发现，并着重报道了针对HNSCC的EGFR靶向治疗药物的分子相关研究。作者尤其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针对EGFR的临床研究的数据，他们预期这将是头颈癌研究和治疗界感兴趣的数据。

BACKGROUND & AIMS: OBJECTIVES:We evaluated the functional and oncological outcomes of transoral laser microsurgery (TLM) in patients with previously untreated supraglottic carcinoma compared with the outcomes in salvage cases after radiation-based treatment. METHODS:We conducted a retrospective case-control study at a single academic tertiary care institution. The functional outcomes were stratified by prior irradiation and were assessed at baseline, less than 1 week after operation, and at last follow-up. RESULTS:Five patients underwent TLM for previously untreated disease, and 5 previously irradiated patients underwent salvage TLM for local failure. No patient required tracheostomy. There was no local recurrence after TLM as primary therapy, and none of those patients required radiotherapy. One salvage patient developed local recurrence. The duration of feeding tube dependence (p = 0.049) and the rates of chronic aspiration (more than 1 month after operation; p = 0.048) were significantly higher in the salvage TLM cases than in the previously untreated cases. The median scores on the PSS-HN Understandability of Speech were 75 ("usually understandable") in the salvage group and 100 ("always understandable") in the previously untreated group. CONCLUSIONS:Both local control and function were better in the previously untreated patients than in the salvage patients. Our findings provide support for the use of TLM as a primary treatment modality for selected supraglottic carcinomas, but also suggest a potential for functional recovery in both previously untreated and salvage cases.

背景与目标： 目的：我们评估了先前未经治疗的声门上癌患者经口激光显微外科手术（TLM）的功能和肿瘤学结果，与基于放射治疗的抢救病例的结果相比。
方法：我们在一家单一的三级学术机构中进行了一项回顾性病例对照研究。功能结局通过事先照射进行分层，并在基线，手术后不到1周和最后一次随访时进行评估。
结果：5例接受过TLM的患者先前未接受过治疗，而5例接受过放射线的患者则接受了TLM进行局部衰竭治疗。没有患者需要气管切开术。 TLM作为主要疗法后没有局部复发，而且这些患者均不需要放疗。一名抢救患者出现局部复发。抢救性TLM病例的进食管依赖性持续时间（p = 0.049）和慢性误吸率（术后1个月以上； p = 0.048）显着高于先前未治疗的病例。挽救组的PSS-HN语音可理解性中位数为75（“通常可理解”），以前未治疗的组为100（“始终可理解”）。
结论：先前未治疗的患者的局部控制和功能均优于抢救患者。我们的发现为TLM作为选定的声门上癌的主要治疗手段提供了支持，但也暗示了先前未治疗和挽救病例的功能恢复潜力。

BACKGROUND & AIMS: BACKGROUND:This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. METHODS:Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (M1) and the elderly (aged≥75y). RESULTS:A total of 4,217 patients with mRCC were identified, including 1,533 patients with M1 and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (≥75 vs.<75y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, M1, and elderly populations. CONCLUSION:This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in M1 and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age.

背景与目标： 背景：这项回顾性研究调查了瑞典转移性肾细胞癌（mRCC）患者在治疗前（2002-2005），早期（2006-2008）和晚期（2009-2012）的总生存（OS）和影响OS的因素。靶向治疗（TT）时代。
方法：瑞典的三个国家登记册确定了mRCC患者。中位数操作系统是使用Kaplan-Meier方法估算的。使用Cox比例风险回归进行多变量分析。对同步转移患者（M1）和老年人（年龄≥75岁）进行亚组分析。
结果：共鉴定出4,217例mRCC患者，其中1,533例M1患者和1,275例老年患者。对于2002年至2005年，2006年至2008年以及2009年至2012年诊断为mRCC的患者，中位OS​​为10.0、13.0和18.0个月。同样，M1和老年人口的OS中位数有所改善。老年患者接受TT的可能性较小（≥75vs. <75y）：18.3 vs. 63.5％（在2006-2008年）和28.6％vs. 55.9％（在2009-2012年）。 2009年至2012年，对mRCC的诊断，肾切除术和TT处方与总mRCC，M1和老年人口的OS改善相关。
结论：这项现实世界的研究表明，在TT时代后期，包括M1和老年人群，mRCC OS持续显着改善。对于所有mRCC患者，无论年龄大小，均应考虑TT。

BACKGROUND & AIMS: :Nuclear protein in testis (NUT)-midline carcinoma (NMC) is a rare, aggressive disease typically presenting with a single t(15;19) translocation that results in the generation of a bromodomain-containing protein 4 (BRD4)-NUT fusion. PER-624 is a cell line generated from an NMC patient with an unusually complex karyotype that gave no initial indication of the involvement of the NUT locus. Analysis of PER-624 next-generation transcriptome sequencing (RNA-Seq) using the algorithm FusionFinder identified a novel transcript in which Exon 15 of BRD4 was fused to Exon 2 of NUT, therefore differing from all published NMC fusion transcripts. The three additional exons contained in the PER-624 fusion encode a series of polyproline repeats, with one predicted to form a helix. In the NMC cell line PER-403, we identified the 'standard' NMC fusion and two novel isoforms. Knockdown by small interfering RNA in either cell line resulted in decreased proliferation, increased cell size and expression of cytokeratins consistent with epithelial differentiation. These data demonstrate that the novel BRD4-NUT fusion in PER-624 encodes a functional protein that is central to the oncogenic mechanism in these cells. Genomic PCR indicated that in both PER-624 and PER-403, the translocation fuses an intron of BRD4 to a region upstream of the NUT coding sequence. Thus, the generation of BRD4-NUT fusion transcripts through post-translocation RNA-splicing appears to be a common feature of these carcinomas that has not previously been appreciated, with the mechanism facilitating the expression of alternative isoforms of the fusion. Finally, ectopic expression of wild-type NUT, a protein normally restricted to the testis, could be demonstrated in PER-403, indicating additional pathways for aberrant cell signaling in NMC. This study contributes to our understanding of the genetic diversity of NMC, an important step towards finding therapeutic targets for a disease that is refractory to current treatments.

背景与目标： ：睾丸（NUT）-中线癌（NMC）中的核蛋白是一种罕见的侵袭性疾病，通常表现为单个t（15; 19）易位，导致含溴结构域的蛋白4（BRD4）-NUT融合的产生。 PER-624是由具有异常复杂核型的NMC患者产生的细胞系，未初步显示NUT基因座的参与。使用FusionFinder算法对PER-624下一代转录组测序（RNA-Seq）进行分析，发现了一种新颖的转录本，其中BRD4的第15外显子与NUT的第2外显子融合，因此不同于所有已发表的NMC融合转录本。 PER-624融合物中包含的三个附加外显子编码一系列聚脯氨酸重复序列，其中一个被预测会形成螺旋。在NMC细胞系PER-403中，我们确定了“标准” NMC融合蛋白和两种新型同工型。在任一细胞系中通过小分子干扰RNA敲低导致增殖减少，细胞大小增加和与上皮分化一致的细胞角蛋白表达。这些数据表明，PER-624中的新型BRD4-NUT融合蛋白编码的功能蛋白是这些细胞中致癌机制的核心。基因组PCR表明，在PER-624和PER-403中，易位将BRD4的内含子融合到NUT编码序列上游的区域。因此，通过易位后RNA剪接产生BRD4-NUT融合转录本似乎是这些癌的一个共同特征，以前尚未被人们认识到，其机制促进了融合的其他亚型的表达。最后，可以在PER-403中证实野生型NUT（通常限于睾丸的蛋白质）的异位表达，这表明NMC中异常细胞信号传导的其他途径。这项研究有助于我们了解NMC的遗传多样性，这是为目前治疗难以治疗的疾病寻找治疗靶标的重要一步。

BACKGROUND & AIMS: :Upregulation of lipogenesis is a hallmark of cancer and blocking the lipogenic pathway is known to cause tumor cell death by apoptosis. However, the exact role of lipogenesis in tumor initiation is as yet poorly understood. We examined the expression profile of key lipogenic genes in clinical samples of ductal carcinoma in situ (DCIS) of breast cancer and found that these genes were significantly upregulated in DCIS. We also isolated cancer stem-like cells (CSCs) from DCIS.com cell line using cell surface markers (CS24(-)CD44(+)ESA(+)) and found that this cell population has significantly higher tumor-initiating ability to generate DCIS compared with the non-stem-like population. Furthermore, the CSCs showed significantly higher level of expression of all lipogenic genes than the counterpart population from non-tumorigenic breast cancer cell line, MCF10A. Importantly, ectopic expression of SREBP1, the master regulator of lipogenic genes, in MCF10A significantly enhanced lipogenesis in stem-like cells and promoted cell growth as well as mammosphere formation. Moreover, SREBP1 expression significantly increased the ability of cell survival of CSCs from MCF10AT, another cell line that is capable of generating DCIS, in mouse and in cell culture. These results indicate that upregulation of lipogenesis is a pre-requisite for DCIS formation by endowing the ability of cell survival. We have also shown that resveratrol was capable of blocking the lipogenic gene expression in CSCs and significantly suppressed their ability to generate DCIS in animals, which provides us with a strong rationale to use this agent for chemoprevention against DCIS.

背景与目标： ：脂肪生成的上调是癌症的标志，已知阻断脂肪生成途径会通过凋亡导致肿瘤细胞死亡。然而，尚不清楚脂肪生成在肿瘤起始中的确切作用。我们检查了乳腺导管原位癌（DCIS）临床样品中关键脂肪形成基因的表达谱，发现这些基因在DCIS中显着上调。我们还使用细胞表面标记（CS24（-）CD44（）ESA（））从DCIS.com细胞系中分离了癌干样细胞（CSC），发现与该细胞群相比，该细胞群具有更高的产生DCIS的肿瘤启动能力与非茎状种群。此外，CSCs显示所有脂肪形成基因的表达水平均高于非致瘤性乳腺癌细胞系MCF10A的对应群体。重要的是，MCF10A中异源表达的主调节因子SREBP1在MCF10A中的异位表达显着增强了干样细胞的脂肪生成，并促进了细胞生长以及乳球形成。此外，SREBP1表达显着提高了来自MCF10AT的CSC在小鼠和细胞培养物中的细胞存活能力，MCF10AT是另一种能够产生DCIS的细胞系。这些结果表明，通过赋予细胞存活能力，脂肪生成的上调是DCIS形成的先决条件。我们还显示白藜芦醇能够阻断CSC中脂肪基因的表达，并显着抑制其在动物体内生成DCIS的能力，这为我们提供了使用这种药物化学预防DCIS的强大理由。

BACKGROUND & AIMS: :Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis. Although these pro-inflammatory factors in esophageal squamous cell carcinoma have been well-characterized with reference to protein-coding targets, their functional interactions with non-coding RNAs have only recently been gaining attention. Non-coding RNAs, especially microRNAs and long non-coding RNAs demonstrate potential as biomarkers and alternative therapeutic targets. In this review, we summarize the recent literature and concepts on non-coding RNAs that are regulated by/regulate nuclear factor kappa B and signal transducer and activator of transcription 3 in esophageal cancer progression. We also discuss how these recent discoveries can pave way for future therapeutic options to treat esophageal squamous cell carcinoma.

背景与目标： ：食管鳞状细胞癌是发展中国家第六大最常见的癌症。食管鳞状细胞癌的侵略性，其复发趋势以及晚期诊断出的患者生存前景差，迫切需要开发针对该疾病的新疗法。已知慢性炎症与癌症易感性有因果关系。核因子κB和信号转导子及转录激活子3是调节免疫力和炎症的转录因子，并逐渐成为肿瘤起始，进展和转移的关键调节剂。尽管这些食管鳞状细胞癌中的促炎因子已针对蛋白质编码靶标进行了很好的表征，但它们与非编码RNA的功能相互作用只是最近才受到关注。非编码RNA，尤其是microRNA和长的非编码RNA，具有作为生物标志物和替代治疗靶标的潜力。在这篇综述中，我们总结了关于非编码RNA的最新文献和概念，这些非编码RNA在食管癌进展中受核因子κB和信号转导子及转录激活子3的调控。我们还讨论了这些最新发现如何为将来治疗食管鳞状细胞癌的治疗选择铺平道路。

BACKGROUND & AIMS: PURPOSE:To investigate the epidemiology and clinicopathological management for ocular sebaceous carcinoma (OSC) in the UK. METHODS:Observational prospective cohort study of patients with newly-diagnosed OSC. The British Ophthalmological Surveillance Unit captured incident cases of OSC between 2008 and 2010. Incident and 6-month follow-up questionnaires from reporting ophthalmologists captured OSC demographic and clinical data. RESULTS:Data were available on 51 patients with unilateral OSC (response rate 85%). The UK estimated annual incidence was 0.41 cases per million population (95% CI 0.31 to 0.54). Median age was 70 years (SD 14, range 28-98) with 57% women. OSC location was upper lid (54%), lower lid (20%), multicentric (14%) and caruncle (12%). Most common misdiagnoses included chalazion (42%), basal cell carcinoma (30%) and blepharoconjunctivitis (16%), with median delay in diagnosis of 10 months (SD 9, range 0.5-36). Specialist ophthalmic pathologists performed diagnostics in 62%, with pagetoid/intraepithelial spread present in 39%. Misdiagnosis of chalazion (p=0.019) and pagetoid tumour spread (p=0.016) was associated with a significant diagnostic delay (one-way ANOVA/R(2)). Primary surgical management involved excision with reconstruction (49%), primary exenteration (10%) and Mohs surgery (8%). There were three deaths (out of 51) during the study period; one patient died of OSC-related disease and the other two due to other causes. CONCLUSIONS:This population-based prospective study confirms OSC as a rare cancer in the UK. Masquerade syndromes result in significant diagnostic delays and increase the risk of pagetoid tumour spread. There is considerable UK variation in pathological and surgical management, and ocular reconstruction and radical surgery is often required for OSC due to delayed presentation.

背景与目标： 目的：探讨英国眼皮脂腺癌（OSC）的流行病学和临床病理管理。
方法：对新诊断为OSC的患者进行观察性前瞻性队列研究。英国眼科监视部门捕获了2008年至2010年之间发生OSC的事件。来自报告眼科医师的事件和6个月的后续调查表捕获了OSC的人口统计和临床数据。
结果：有51例单侧OSC患者的数据（有效率85％）。英国估计的年发病率为每百万人口0.41例（95％CI为0.31至0.54）。中位年龄为70岁（SD 14，范围28-98），其中女性占57％。 OSC位置是上盖（54％），下盖（20％），多中心（14％）和and形（12％）。最常见的误诊包括睑板裂（42％），基底细胞癌（30％）和睑结膜炎（16％），中位诊断时间延迟10个月（SD 9，范围0.5-36）。专门的眼科病理学家对62％的患者进行了诊断，其中39％的患者出现了页面状/上皮内扩散。查拉净的错误诊断（p = 0.019）和页面状肿瘤扩散（p = 0.016）与显着的诊断延迟（单向ANOVA / R（2））相关。主要的外科手术管理包括切除术，重建术（49％），初次切除术（10％）和莫氏手术（8％）。在研究期间，有3例死亡（共51例）。一名患者死于OSC相关疾病，另一例死于其他原因。
结论：这项基于人群的前瞻性研究证实了OSC在英国是一种罕见的癌症。假面舞会综合症会导致严重的诊断延迟，并增加页面状肿瘤扩散的风险。英国在病理和手术管理上存在很大差异，由于延迟出现，OSC经常需要眼球重建和根治性手术。

BACKGROUND & AIMS: :Serous carcinomas most commonly arise within the uterine corpus or ovary/fallopian tube, but there are 2 prior case reports of primary vaginal serous carcinoma. We report 2 examples of high-grade serous carcinoma arising within the urethra or a urethral diverticulum (1 case each). Both neoplasms exhibited the classic morphologic features of high-grade serous carcinoma, and a combination of clinical, radiologic, and pathologic examination excluded other possible sites of primary neoplasm.

背景与目标： ：浆液性腺癌最常见于子宫体或卵巢/输卵管，但已有2例先前的原发性阴道浆液性癌病例报告。我们报告2例发生在尿道或尿道憩室内的高度浆液性癌的例子（每例1例）。两种肿瘤均表现出高级别浆液性癌的经典形态学特征，临床，影像学和病理学检查的结合排除了其他可能的原发性肿瘤部位。

BACKGROUND & AIMS: :Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n = 55) and mutation data (n = 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade (P = 0.002/0.035), ER-negative (P = 0.02/0.02), and ERBB2-amplified tumors (P < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs (P < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with TP53 mutation (P = 0.03) but not with PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both P < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels.Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. Clin Cancer Res; 23(17); 5210-7. ©2017 AACR.

背景与目标： 目的：乳腺导管原位癌（DCIS）的免疫微环境尚未得到充分探索，并且免疫细胞与DCIS遗传特征的关系尚不清楚。实验设计：我们量化了肿瘤相关淋巴细胞（TIL）并评估了PD通过免疫组织化学检测一组纯DCIS（分别为138和79例）中的-L1蛋白水平，其中一些具有拷贝数（n = 55）和突变数据（n = 20）。 DCIS（119/138，86％），平均TIL得分为5％（范围：0％-90％）。大多数DCIS对肿瘤细胞PD-L1染色呈阴性（89％），但25％的病例对免疫细胞染色呈阳性。我们观察到，与浸润性乳腺癌一样，高级别（P = 0.002 / 0.035），ER阴性（P = 0.02 / 0.02）和ERBB2放大的肿瘤（P < 0.001 / 0.048）。痤疮坏死与TILs呈显着正相关（P <0.0001），而与PD-L1无显着正相关。 TP53突变的患者的TILs评分显着更高（P = 0.03），而PIK3CA或GATA3突变的患者则没有。在具有拷贝数数据的情况下，基因组的比例改变和端粒失衡的数目均与TILs显着正相关（均P <0.001）。该结果与浸润性乳腺癌数据形成鲜明对比，后者的非整倍性与TIL水平无关。结论：尽管队列很小，但我们的数据提示了一种初步模型，通过该模型DCIS向浸润性癌进展可能涉及肿瘤拷贝数关系的改变免疫微环境，可能是通过肿瘤的免疫编辑。临床癌症研究； 23（17）; 5210-7。 ©2017 AACR。

BACKGROUND & AIMS: OBJECTIVE:To explore the prognostic value of the postsurgical half-life (HL) of serum alpha-fetoprotein (AFP). BACKGROUND:There is still a paucity of early surrogate indicators of clinical endpoints after liver resection of hepatocellular carcinoma (HCC). METHODS:The analysis was based on cohorts of 225 (exploration set) and 117 (validation set) treatment-naïve HCC patients undergoing curative liver resection. We defined 3 categories of AFP HL: early complete resolution of AFP, normal HL, and prolonged HL if the HL exceeded 7 days. Overall, probabilities of recurrence and survival were estimated and compared across the AFP HL categories. RESULTS:In the exploration cohort, 48 patients (21.3%) achieved early AFP complete resolution, 116 (51.6%) had normal HL, and 61 (27.1%) had prolonged HL. Long AFP HL was significantly associated with early postoperative recurrence (P < 0.001), as was microvascular invasion. Early recurrence within 2 years of resection was observed in 59% of the patients with prolonged AFP HL compared with only 29.3% of those with normal AFP HL (P < 0.001). A log-rank test followed by multivariate Cox analysis identified an independent function of prolonged AFP HL in predicting shorter recurrence-free survival and overall survival time after HCC resection (hazard ratios, 2.81 and 3.58; P < 0.001). When AFP HL analysis was applied to the validation cohort, the association between prolonged AFP HL and survival endpoints (hazard ratio, 11.63 and 16.39; P < 0.001) was confirmed.

背景与目标： 目的：探讨血清甲胎蛋白（AFP）的术后半衰期（HL）的预后价值。
背景：肝切除肝细胞癌（HCC）后仍缺乏临床终点的早期替代指标。
方法：该分析基于225例（探索组）和117例（验证组）未进行过根治性肝切除的未接受治疗的HCC患者的分析。我们定义了AFP HL的3个类别：AFP的早期完全消退，正常HL和如果HL超过7天则延长HL。总体而言，在AFP HL类别中估计并比较了复发和生存的可能性。
结果：在探索队列中，有48例（21.3％）的患者达到了AFP的早期完全缓解，HL正常的116例（51.6％），HL延长的61例（27.1％）。长期AFP HL与微血管浸润与术后早期复发显着相关（P <0.001）。 AFP HL延长的患者中有59％的患者在切除的2年内出现了早期复发，而AFP HL正常的患者只有29.3％的患者出现了早期复发（P <0.001）。对数秩检验和多变量Cox分析确定了AFP HL延长在预测肝癌切除术后较短的无复发生存期和总生存期方面具有独立的功能（危险比，2.81和3.58； P <0.001）。当将AFP HL分析应用于验证队列时，证实了延长的AFP HL与生存终点之间的关联（风险比分别为11.63和16.39； P <0.001）。

BACKGROUND & AIMS: BACKGROUND:The status of regional lymph nodes (LNs) is one of the most consistent predictors of survival in Merkel cell carcinoma (MCC). In cases of clinically localized disease, current practice involves sentinel lymph node (SLN) assessment. OBJECTIVES:To propose ultrasonography (US) followed by fine needle aspiration cytology (FNAC) and immunohistochemistry as a useful diagnostic tool in the pre-surgical management of patients with MCC. METHODS:US of LNs was performed in 75 patients with MCC (22 with stage III tumours; 53 with stage I-II). In patients with US suspected disease, US coupled with FNAC of the LN was performed. Smears were examined by routine cytological staining supplemented with immunohistochemical staining for cytokeratin 20. All patients underwent surgical removal of regional LNs. RESULTS:In all 22 patients with stage III tumours, US was indicative of tumour deposits and FNAC confirmed metastases to LNs. In 11 of 53 patients with localized MCC without clinical evidence of nodal disease, US revealed enlarged, equivocal nodes where FNAC was performed. Ten LNs were cytologically positive for metastases, and one was negative. Upon histological examination, the FNAC-negative case showed a metastasis 5 mm in diameter. In all the other 42 cases with no clinical or US evidence of LN involvement, only SLN biopsy was performed and in six cases small metastatic foci were detected. Ultimately, of the 53 stage I-II MCC, 17 had positive LN involvement. In 10 cases (59%) metastases were detected by FNAC, and in seven cases, were detected by SLN biopsy. CONCLUSIONS:In a selected subset (∼20%) of patients with MCC with clinically localized disease, US followed by FNAC in the suspect LN is a valid alternative to the classical protocol of SLN histological examination.

背景与目标： 背景：区域淋巴结（LNs）的状态是默克尔细胞癌（MCC）存活率最一致的预测指标之一。在临床上局部疾病的情况下，当前的实践涉及前哨淋巴结（SLN）评估。
目的：提出超声检查（US），然后进行细针穿刺细胞学检查（FNAC）和免疫组织化学，作为MCC患者术前治疗的有用诊断工具。
方法：我们对75例MCC患者（22例为III期肿瘤； 53例为I-II期）进行了LNs检查。在患有US可疑疾病的患者中，进行US联合LN的FNAC。通过常规细胞学染色和细胞角蛋白20的免疫组化染色检查涂片。所有患者均接受了手术切除局部LN。
结果：在所有22例III期肿瘤患者中，US提示有肿瘤沉积，并且FNAC证实转移至LNs。在53例没有局部淋巴结病临床证据的局部MCC患者中，US显示进行FNAC的肿大，模棱两可。 10个LN在转移学上在细胞学上均为阳性，而1个为阴性。经组织学检查，FNAC阴性病例显示直径为5毫米的转移灶。在没有临床或美国证据显示LN受累的所有其他42例病例中，仅进行了SLN活检，而在6例中，发现了小的转移灶。最终，在53个I-II期MCC中，有17个LN积极参与。 FNAC检测到10例（59％）转移，SLN活检检测到7例转移。
结论：在选定的一部分（约20％）患有临床局部疾病的MCC患者中，可疑LN中的US继之以FNAC，是经典SLN组织学检查方案的有效替代方案。