BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的研究结果表明，缺氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，这导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性特征。

BACKGROUND & AIMS: :Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.

背景与目标： ：最近在肺腺癌中，主要在东亚患者中，报道了HER2基因的酪氨酸激酶结构域中的活化突变。我们的研究旨在评估白人患者肺腺癌中HER2突变的发生率和性质。通过PCR单链构象多态性分析和外显子19和20的直接测序，评估了403例肺腺癌中HER2基因的突变状态。我们发现9例（2.2％）病例中存在HER2突变。突变中的七个（78％）位于776-779位密码子（YVMA）的框架重复/插入中，另外两个为碱基取代，导致氨基酸变化。先前发现在776-779碱基处的热点突变是亚洲患者中最常见的HER2突变。在传统的肺腺癌（CLA）和具有支气管肺泡特征（ABAFs）的肺腺癌之间，突变的分布存在显着差异。 113个ABAF中有7个（6.2％）和290个CLA中有2个（0.7％）被突变了（p = 0.0025）。此外，HER2突变的频率在女性（4.1％）比男性（1.8％）和从不吸烟者（3.1％）要高出吸烟者（1.9％），但差异无统计学意义。还研究了该系列肿瘤的EGFR和K-ras突变。在43（10.7％）例中观察到EGFR突变，在110（27.3％）例中观察到K-ras突变。发现EGFR，HER2和K-ras突变是相互排斥的事件。 HER2突变在一部分肺腺癌患者中的存在增加了用HER2特异性激酶抑制剂治疗这些患者的希望。

BACKGROUND & AIMS: :Following surgery, the hormone dependence of breast tumors is exploited for therapy using antagonists such as tamoxifen, although occasional hormone-resistant clones do appear. Another chemotherapeutic strategy uses microtubule inhibitors such as taxanes. Unfortunately, these agents elicit toxicities such as leukocytopenia, diarrhea, alopecia, and peripheral neuropathies and are also associated with the emergence of drug resistance. We have previously described a tubulin-binding, natural compound, noscapine, that was nontoxic and triggered apoptosis in many cancer types albeit at 10 mumol/L or higher concentrations depending on the cell type. We now show that a synthetic analogue of noscapine, 9-bromonoscapine, is approximately 10-fold to 15-fold more potent than noscapine in inhibiting cell proliferation and induces apoptosis following G2-M arrest in hormone-insensitive human breast cancers (MDA-MB-231). Furthermore, a clear loss of mitochondrial membrane potential, release of cytochrome c, activation of the terminal caspase-3, and the cleavage of its substrates such as poly(ADP-ribose) polymerase, suggest an intrinsic apoptotic mechanism. Taken together, these data point to a mitochondrially mediated apoptosis of hormone-insensitive breast cancer cells. Human tumor xenografts in nude mice showed significant tumor volume reduction and a surprising increase in longevity without signs of obvious toxicity. Thus, our data provide compelling evidence that 9-bromonoscapine can be useful for the therapy of hormone-refractory breast cancer.

背景与目标： ：手术后，尽管偶尔出现激素抵抗性克隆，但利用他莫昔芬等拮抗剂开发了乳腺肿瘤的激素依赖性疗法。另一种化学治疗策略是使用微管抑制剂，例如紫杉烷类。不幸的是，这些药物引起毒性，例如白细胞减少，腹泻，脱发和周围神经病，并且还与耐药性的出现有关。先前我们已经描述了微管蛋白结合的天然化合物Noscapine，尽管在10μmol/ L或更高的浓度（取决于细胞类型）下，但在许多类型的癌症中均无毒并引发细胞凋亡。我们现在显示，Noscapine的合成类似物9-bromonoscapine在抑制细胞增殖方面比Noscapine的效力高约10倍至15倍，并在激素不敏感的人类乳腺癌（MDA-MB）中引起G2-M阻滞后诱导凋亡-231）。此外，线粒体膜电位的明显损失，细胞色素c的释放，末端caspase-3的活化以及其底物（如聚（ADP-核糖）聚合酶）的裂解表明了内在的凋亡机制。综上所述，这些数据表明了激素不敏感的乳腺癌细胞由线粒体介导的凋亡。裸鼠中的人类肿瘤异种移植物显示出明显的肿瘤体积减少和寿命的惊人增加，而没有明显的毒性迹象。因此，我们的数据提供了令人信服的证据，表明9-溴莫可可碱可用于治疗激素难治性乳腺癌。

BACKGROUND & AIMS: STUDY DESIGN:A cross-sectional study of the spine in 40 young adults after solid organ transplantation in childhood. OBJECTIVE:To evaluate the impact of organ transplantation and long-term immunosuppressive treatment on growing spine using magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA:A review of the current literature reveals no systematic evaluation of the spine after transplantation in childhood. METHODS:A total of 40 adult patients (mean age 22.1 years, range, 16.0-27.0), who received either kidney, liver, or heart transplant as children, were evaluated. Mean follow-up after transplantation was 11.2 years (range 3.0-18.0). All patients filled in a questionnaire, underwent an interview and physical examination, as well as had MRI of the spine. Standing spinal radiographs were taken from patients with a rib hump > or = 6 degrees. RESULTS:There were 8 (20%) patients who had a history of vertebral fracture. Eleven (28%) patients reported frequent back pain at rest. There were 15 (38%) patients who had scoliosis > 10 degrees (range 10 degrees -69 degrees ). On MRI, narrowed disc spaces were noted in 32 (80%) patients, and irregular endplates were noted in 24 (60%). There were 14 (35%) patients who had at least 1 compressed or wedged vertebra (> 20%). Patients treated for acute rejection had wedged vertebrae, speckled or black disc spaces, and irregular endplates more often than patients without rejections. Males had wedged vertebrae more often than females (P = 0.0067). CONCLUSIONS:Back pain, scoliosis, wedged vertebrae, and narrowed, degenerated disc spaces are common after solid organ transplantation in childhood.

背景与目标： 研究设计：儿童实体器官移植后对40位年轻人的脊柱进行的横断面研究。
目的：利用磁共振成像（MRI）评估器官移植和长期免疫抑制治疗对生长中脊柱的影响。
背景资料摘要：对当前文献的回顾表明，儿童期移植后没有对脊柱进行系统评价。
方法：总共评估了40名成年患者（平均年龄22.1岁，范围16.0-27.0），他们从小就接受了肾脏，肝脏或心脏移植手术。移植后的平均随访时间为11.2年（范围3.0-18.0）。所有患者均填写了问卷，接受了访谈和体格检查，并对脊柱进行了MRI检查。肋骨隆起>或= 6度的患者拍摄站立式脊柱X光片。
结果：有8例（20％）有椎体骨折病史。 11名（28％）患者报告休息时经常出现背痛。脊柱侧弯> 10度（范围10度-69度）的患者为15（38％）。在MRI上，发现32例（80％）患者的椎间盘间隙变窄，发现24例（60％）的不规则端板。有14名（35％）患者至少有1块受压或楔入的椎骨（> 20％）。接受急性排斥反应的患者比没有排斥反应的患者更经常出现椎体楔形，斑点或黑色椎间盘间隙以及不规则的终板。男性比女性更经常楔住椎骨（P = 0.0067）。
结论：儿童实体器官移植后，背部疼痛，脊柱侧弯，椎骨楔形和椎间盘狭窄变窄是常见的。

BACKGROUND & AIMS: PURPOSE:To demonstrate the utility of a new concept of intraoperative use of high frequency ultrasound (hfioUS) in maximizing the extent of resection (EOR) of intracerebral high-grade tumors. MATERIALS AND METHODS:22 Patients harboring an intracerebral high-grade tumor were retrospectively included in this study (14 primary tumors, 8 metastasis). 14 of them had a perilesional edema equal or greater to lesion volume, 3 had previously received radiotherapy. Following macroscopic tumor debulking, the small (11 × 31 mm) L15 - 7io (Philips, Bothell, USA) high-frequency probe (7 - 15 MHz) was introduced into the resection cavity and its walls were meticulously scanned to search for tumor remnants. Postoperative MR scan was evaluated by a board-certified independent neuroradiologist, who assessed the EOR. RESULTS:Gross total resection was achieved in 21 patients (95.5 %). One patient had a small tumor remnant (6 × 4 × 3 mm) of a very large (80 × 60 × 74 mm) anaplastic astrocytoma, detected in the postoperative MR scan. A permanent postoperative hemiparesis was diagnosed in one patient with a metastasis in the motor area, while the other patients recovered without permanent neurological deficits from the surgery. CONCLUSION:The hfioUS probe allowed in this study a precise detection of the tumor and a detailed discrimination between normal, pathological and edematous tissue in all 22 cases. :ZIEL:: Darstellung eines neuen intraoperativen Konzepts basierend auf Hochfrequenz-Ultraschall (hfioUS) zur Maximierung der Resektion hochgradiger intrazerebraler Tumoren. MATERIAL UND METHODEN:22 Patienten mit hochgradigen intrazerebralen Tumoren (14 primäre Tumoren, 8 Metastasen) wurden retrospektive in diese Studie eingeschlossen. 14 dieser Patienten zeigten ein perifokales Ödem gleich oder größer als das Läsionsvolumen, 3 Patienten erhielten präoperativ bereits Radiotherapie. Nach der makroskopischen Tumorentfernung wurde die hfioUS-Messsonde L15 – 7io (Philips, Bothell, USA) mit einer Größe von 11 × 31 mm in die Tumorhöhle eingeführt und die Wände dieser nach Tumorresten untersucht. Postoperative MRTs wurden von einem unabhängigen Neuroradiologen bezüglich Resektionsgrad ausgewertet. ERGEBNISSE:Eine makroskopische Totalresektion wurde bei 21 Patienten (95.5 %) erreicht. Ein Patient mit einem großen anaplastischen Astrozytom (80 × 60 × 74 mm) zeigte einen kleinen Resttumor (6 × 4 × 3 mm) im postoperativen MRT. Eine permanente postoperative Hemiparese zeigte sich bei einem Patient mit einer Metastase im motorischen Areal, die restlichen Patienten erholten sich postoperative ohne permanentes neurologisches Defizit von der Operation. SCHLUSSFOLGERUNG:In dieser Studie erlaubte die hfioUS-Messsonde bei allen 22 Fällen eine präzise Darstellung des Tumors und eine detaillierte Unterscheidung zwischen regelrechtem, pathologischem und ödematösem Hirnparenchym.

背景与目标： 目的：证明术中使用高频超声（hfioUS）这一新概念在最大限度地扩大脑内高级别肿瘤的切除范围（EOR）方面的实用性。
材料与方法：本研究回顾性纳入了22例脑内高度肿瘤患者（14例原发肿瘤，8例转移瘤）。其中14例病灶周围水肿等于或大于病灶体积，3例以前接受过放射治疗。在宏观肿瘤消灭之后，将小的（11×31 mm）L15-7io（Philips，Bothell，USA）高频探头（7-15 MHz）引入切除腔，并对其壁进行仔细扫描以寻找肿瘤残留物。术后MR扫描由经董事会认证的独立神经放射科医生评估，该医师评估了EOR。
结果：21例患者全切除了（95.59％）。一名患者在术后MR扫描中发现了一个很小的肿瘤残留（6××4××3×mm）很大的（80××60××74×mm）间变性星形细胞瘤。一名患有运动区转移的患者被诊断出永久性术后偏瘫，而另一名患者则因手术而没有永久性神经功能缺损而康复。
结论：在本研究中，hfioUS探针可对所有22例患者的肿瘤进行精确检测，并对正常，病理和水肿组织进行详细区分。
：ZIEL :: Darstellung eines neuenneuopern Konzepts basierend auf Hochfrequenz-Ultraschall（hfioUS）zur Maximierung der Resektion hochgradiger intrazerebraler Tumoren。
材料和方法：22顽固性复发性脑卒中患者是图斯雷布雷伦·图莫伦（14 primture Tumoren，8 Metastasen）。 14位患者的抗癌药和放射线治疗的3位患者的放射治疗。 US-Messsonde L15 – 7io（菲利普斯，美国，博塞尔）的Nach der makroskopischen Tumorentfernung战争发生在Tumorhöhleeingeführt和Wände死者中。术后的MRT会引起神经放射。
ERGEBNISSE：21位患者（Eat makroskopische Totalresektion wurde bei）（95.5％）erreicht。术后进行MRT时，患者应接受astroplasttom（80×60×74 mm）和zeigte einen kleinen Resttumor（6×4×3 mm）的手术。永久性手术后半永久患者的脑部转移，再进行永久性患者永久性神经外科手术后永久性手术。
SCHLUSSFOLGERUNG：在Dieser Studie erlaubte die HfioUS-Messsonde bei allen中，在肿瘤与细节研究方面的进展，以及在病理学和病理学上的发展。

BACKGROUND & AIMS: OBJECTIVES:Pancreatic endocrine tumors (PETs) share numerous features with gastrointestinal neuroendocrine (carcinoid) tumors. Targets of novel therapeutic strategies previously assessed in carcinoid tumors were analyzed in PETs (44 cases). METHODS:Activating mutations in EGFR, KIT, and PDGFRA and nonresponse mutations in KRAS were evaluated. Copy number of EGFR and HER-2/neu was quantified by fluorescence in situ hybridization. Expression of EGFR, PDGFRA, VEGFR1, TGFBR1, Hsp90, SSTR2A, SSTR5, IGF1R, mTOR, and MGMT was measured immunohistochemically. RESULTS:Elevated EGFR copy number was found in 38% of cases but no KRAS nonresponse mutations. VEGFR1, TGFBR1, PDGFRA, SSTR5, SSTR2A, and IGF1R exhibited the highest levels of expression in the largest percentages of PETs.Anticancer drugs BMS-754807 (selective for IGF1R/IR), 17-(allylamino)-17-demethoxygeldanamycin (17-AAG, targeting Hsp90), and axitinib (directed toward VEGFR1-3/PDGFRA-B/KIT) induced growth inhibition of human QGP-1 PET cells with IC50 values (nM) of 273, 723, and 743, respectively. At growth-inhibiting concentrations, BMS-754807 inhibited IGF1R phosphorylation; 17-AAG induced loss of EGFR, IGF1R, and VEGFR2; and axitinib increased p21(CDKN1A) expression without inhibiting VEGFR2 phosphorylation. CONCLUSIONS:Results encourage further research into multidrug strategies incorporating inhibitors targeting IGF1R or Hsp90 and into studies of axitinib combined with conventional chemotherapeutics toxic to tumor cells in persistent growth arrest.

背景与目标： 目的：胰腺内分泌肿瘤（PET）与胃肠道神经内分泌（类癌）肿瘤具有许多特征。以前在类癌肿瘤中评估过的新治疗策略的靶标已在PET（44例）中进行了分析。
方法：评估EGFR，KIT和PDGFRA的激活突变以及KRAS的无应答突变。通过荧光原位杂交定量EGFR和HER-2 / neu的拷贝数。免疫组织化学法检测EGFR，PDGFRA，VEGFR1，TGFBR1，Hsp90，SSTR2A，SSTR5，IGF1R，mTOR和MGMT的表达。
结果：38％的病例发现EGFR拷贝数升高，但没有KRAS无反应突变。 VEGFR1，TGFBR1，PDGFRA，SSTR5，SSTR2A和IGF1R在最大百分比的PET中表现出最高的表达水平。抗癌药BMS-754807（对IGF1R / IR选择性），17-（烯丙胺基）-17-去甲氧基格尔德霉素（17-靶向Hsp90的AAG和axitinib（针对VEGFR1-3 / PDGFRA-B / KIT）诱导人QGP-1 PET细胞的生长抑制，IC50值（nM）分别为273、723和743。在抑制生长的浓度下，BMS-754807抑制了IGF1R磷酸化。 17-AAG诱导的EGFR，IGF1R和VEGFR2丢失；阿昔替尼在不抑制VEGFR2磷酸化的情况下增加p21（CDKN1A）的表达。
结论：结果鼓励对结合靶向IGF1R或Hsp90的抑制剂的多药策略和阿昔替尼与常规化学治疗药物联合治疗对持续生长停滞有毒的肿瘤细胞进行进一步研究。

BACKGROUND & AIMS: :Infectious pancreatic necrosis virus (IPNV), a type species of aquabirnaviruses in the family Birnaviridae, is an etiological agent of infectious pancreatic necrosis and has been isolated from epizootics of cultured salmonids. In the present study, an epithelioma papulosum cyprini (EPC) cell line persistently infected with IPNV (PI-EPC) was experimentally established by subculturing EPC cells surviving IPNV infection, and was characterized. PI-EPC cells were morphologically indistinguishable from EPC, but continued to grow and yield IPNV. PI-EPC cells showed no cytopathic effect due to IPNV inoculation, and susceptibility of PI-EPC cells against heterologous viruses was not different from that of EPC cells. Only one cell of 10(3.5) PI-EPC cells produced IPNV at approximately 10(0.5) 50% tissue culture infectious dose (TCID50)/cell/day, which was approximately 1,000 times lower than that of normal EPC cells. PI-EPC cells that did not yield IPNV (N-PI-EPC) were screened. The IPNV genome was detected from both PI-EPC and N-PI-EPC cells, and the IPNV VP2 structural protein was detected from both cell lines, but no other IPNV proteins were observed by Western blot analysis with anti-IPNV serum. Thus, multiplication of IPNV in PI-EPC cells was regulated by some host cell factors, except interferon.

背景与目标： ：传染性胰腺坏死病毒（IPNV）是Birnaviridae家族中一种水痘病毒的类型物种，是传染性胰腺坏死的病原体，已从养殖鲑鱼的流行病中分离出来。在本研究中，通过继代培养在IPNV感染后存活的EPC细胞，通过实验建立了持续感染IPNV（PI-EPC）的塞浦路斯青皮上皮细胞（EPC）细胞系，并对其进行了表征。 PI-EPC细胞在形态上与EPC没有区别，但继续生长并产生IPNV。 PI-EPC细胞没有因IPNV接种而引起的细胞病变作用，并且PI-EPC细胞对异源病毒的敏感性与EPC细胞没有什么不同。 10（3.5）PI-EPC细胞中只有一个细胞以约10（0.5）50％组织培养物感染剂量（TCID50）/细胞/天产生IPNV，这比正常EPC细胞低约1,000倍。筛选不产生IPNV的PI-EPC细胞（N-PI-EPC）。从PI-EPC和N-PI-EPC细胞中都检测到IPNV基因组，并且从两个细胞系中都检测到了IPNV VP2结构蛋白，但用抗IPNV血清进行的蛋白质印迹分析未观察到其他IPNV蛋白。因此，除干扰素外，PI-EPC细胞中IPNV的增殖受某些宿主细胞因子的调节。

BACKGROUND & AIMS: :We carried out the first meta-analysis comparing the technical success and clinical outcomes of endoscopic ultrasound-guided drainage (EUD) and conventional transmural drainage (CTD) for pancreatic pseudocysts. We searched PubMed, Embase, Scopus, and the Cochrane library to identify relevant prospective trials. The technical success rate, short-term (4-6 weeks) success, and long-term (at 6 months) success in symptoms and the radiologic resolution of pseudocysts, complication rates, and death rates were compared. Two eligible randomized-controlled trials and two prospective studies including 229 patients were retrieved. The technical success rate was significantly higher for EUD than for CTD [risk ratio (RR)=12.38, 95% confidence interval (CI): 1.39-110.22]. When CTD failed because of the nonbulging nature of pseudocysts, a crossover was carried out to EUD (n=18), which was successfully performed in all these cases. All patients with portal hypertension and bleeding tendency were subjected to EUD to avoid severe complications. EUD was not superior to CTD in terms of short-term success (RR=1.03, 95% CI: 0.95-1.11) or long-term success (RR=0.98, 95% CI: 0.76-1.25). The overall complications were similar in both groups (RR=0.98, 95% CI: 0.52-1.86). The most common complications were bleeding and infection. There were two deaths from bleeding after CTD. The short-term and long-term treatment success of both methods is comparable only if proper drainage modality is selected in specific clinical situations. For bulging pseudocysts, either EUD or CTD can be selected whereas EUD is the treatment of choice for nonbulging pseudocysts, portal hypertension, or coagulopathy.

背景与目标： ：我们进行了首次荟萃分析，比较了胰腺假性囊肿的内镜超声引导引流术（EUD）和常规透壁引流术（CTD）的技术成功率和临床结果。我们搜索了PubMed，Embase，Scopus和Cochrane库，以确定相关的前瞻性试验。比较了技术上的成功率，短期（4-6周）成功率和长期（6个月时）症状的成功率以及假性囊肿的放射学分辨率，并发症发生率和死亡率。检索了两项合格的随机对照试验和两项前瞻性研究，其中包括229例患者。 EUD的技术成功率显着高于CTD [风险比（RR）= 12.38，95％置信区间（CI）：1.39-110.22]。当CTD由于假性囊肿的非膨隆性而失败时，便与EUD进行了交叉（n = 18），在所有这些情况下均成功进行了交叉。所有患有门静脉高压症和出血倾向的患者均应接受EUD治疗，以避免严重的并发症。就短期成功率（RR = 1.03，95％CI：0.95-1.11）或长期成功率（RR = 0.98，95％CI：0.76-1.25）而言，EUD并不优于CTD。两组的总并发症相似（RR = 0.98，95％CI：0.52-1.86）。最常见的并发症是出血和感染。 CTD后有两人因出血死亡。仅当在特定的临床情况下选择了适当的引流方式时，这两种方法的短期和长期治疗成功率才具有可比性。对于隆起的假性囊肿，可以选择EUD或CTD，而EUD是不隆起的假性囊肿，门脉高压或凝血病的治疗选择。

BACKGROUND & AIMS: PURPOSE:Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). METHODS:The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. RESULTS:Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). CONCLUSIONS:These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

背景与目标： 目的：糖尿病是怀疑为胰腺癌的危险因素，但有关它是该疾病的危险因素还是结果仍存在疑问。这项研究从NCI胰腺癌队列联合会（PanScan）收集的数据中前瞻性地检查了糖尿病与胰腺腺癌风险之间的关联。
方法：汇集的数据包括使用嵌套病例对照研究设计的来自十二个队列的1,621例胰腺腺癌病例和1,719例匹配的对照。所有分析均排除在胰腺癌诊断时间（<2年）内被诊断出患有糖尿病的受试者。所有分析均根据年龄，种族，性别，研究，饮酒，吸烟，BMI和胰腺癌家族史进行了调整。
结果：自我报告的糖尿病与胰腺癌风险增加40％相关（OR = 1.40，95％CI：1.07，1.84）。该关联因糖尿病持续时间而异；持续时间为2-8年的患者风险最高（OR = 1.79，95％CI：1.25，2.55）;糖尿病9年没有相关性（OR = 1.02，95％CI：0.68，1.52）。
结论：这些发现为糖尿病与胰腺癌风险之间的关系提供了支持。糖尿病持续时间最长的患者缺乏相关性可能反映了低胰岛素血症，需要进一步研究。

BACKGROUND & AIMS: :Objective: To determine the effect of electro-acupuncture (EA) treatment on serum levels of interferon-γ (IFN-γ) in rats with 7,12-dimethylbenz(α)anthracene (DMBA)-induced breast tumors. Methods: Twenty five female Wistar rats were divided randomly into 5 groups: normal group (N; neither DMBA-induced nor treated with EA); control group (C; DMBA-induced only); EA 3 days : (DMBA-induced + EA for 3 days); EA 5 days: (DMBA-induced + EA for 5 days); EA 10 days: (DMBA-induced + EA for 10 days) group. Animals were acclimatized from day 1 to day 7. Subcutaneus injections of DMBA 10mg/kg BW was administered every second day, from days 7 to 35. Acupuncture was performed every second day from day 42. Rats were sacrificed on the second day after the last acupuncture, breast tumors excised and stained histological sections were analysed by light microscopy. At sacrifice, blood was extracted from the heart for measurement of serum IFN-γ by ELISA. Results: All of the DMBA-induced rats developed tumors. Electro-acupuncture significantly increased IFN-γ levels in DMBA induced rats, when compared to control group. Conclusions: Our findings suggest that EA significantly increases IFN-γ levels in DMBA-induced breast tumors.

背景与目标： ：目的：确定电针治疗对血清中干扰素-γ（IFN-γ）水平的影响
在患有7,12-二甲基苯并（α）蒽（DMBA）诱导的乳腺肿瘤的大鼠中。方法：25名女性Wistar
将大鼠随机分为5组：正常组（N；既不是DMBA诱导的，也不是用EA治疗的）。控制
组（C；仅DMBA诱导）； EA 3天：（DMBA诱导的EA 3天）； EA 5天：（DMBA诱导的EA
5天）; EA 10天：（DMBA诱导的EA 10天）组。从第1天到第7天使动物适应环境。
从第二天到第7天至第35天，皮下注射DMBA 10mg / kg体重。
从第42天起每隔第二天进行一次。最后一次针刺后第二天将大鼠处死，
通过光学显微镜分析切除的肿瘤和染色的组织学切片。牺牲时，血液被抽出
从心脏通过ELISA测定血清IFN-γ。结果：所有DMBA诱导的大鼠均出现肿瘤。
与对照组相比，电针显着增加了DMBA诱导的大鼠的IFN-γ水平。
结论：我们的发现表明，EA可以显着增加DMBA诱导的乳腺肿瘤中的IFN-γ水平。

BACKGROUND & AIMS: BACKGROUND:The ideal neoadjuvant treatment protocol for patients with pancreatic cancer (PDAC) remains unclear. We evaluated the efficacy and safety of neoadjuvant hypofractionated chemoradiotherapy with S-1 for patients with resectable (R) and borderline resectable (BR) PDAC. METHODS:Eligibility criteria included patients with R and BR PDAC, performance status 0-1, and age 20-85 years. Hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) was delivered 5 days/week for 2 weeks prior to pancreatectomy. RESULTS:Fifty-seven patients were enrolled in this study, including 33 R and 24 BR [19 BR tumors with portal vein contact (BR-PV) and 5 BR tumors with arterial contact (BR-A)]. The total rates of protocol treatment completion and resection were 91% (50/57) and 96% (55/57), respectively. Seven patients failed to complete S-1 due to cholangitis (n = 5) or neutropenia (n = 2). The most common grade 3 toxicities [Common Terminology Criteria for Adverse Events (CTCAE) version 4.0] were anorexia (7%), nausea (5%), neutropenia (4%), and leukopenia (4%). No patient experienced grade 4 toxicity. Pathologically negative margins (R0) were achieved in 54 of 55 patients (98%) who underwent pancreatectomy. Pathological response was classified as Evans grade I in 8 patients (15%), IIa in 31 patients (56%), IIb in 14 patients (25%), III in 1 patient (2%), and IV in 1 patient (2%), and operative morbidity (Clavien-Dindo grade IIIb or less) was observed in 4 patients (8%). The 1- and 2-year overall survival (OS) rates were 91 and 83% in R patients, respectively, and 77 and 58% in BR patients, respectively (p = 0.03). CONCLUSION:Neoadjuvant S-1 with concurrent hypofractionated radiotherapy is tolerable and appears promising for patients with R and BR PDAC.

背景与目标： 背景：胰腺癌（PDAC）患者理想的新辅助治疗方案尚不清楚。我们评估了可切除（R）和边缘可切除（BR）PDAC患者使用S-1的新辅助超分割放化疗的疗效和安全性。
方法：入选标准包括R和BR PDAC，表现状态0-1和20-85岁的患者。在胰腺切除术之前的2周中，每周5天，每次S-5（60 mg / m2）进行次分割放射束放射疗法（10份30 Gy）。
结果：57例患者入选本研究，包括33例R和24例BR [19例门静脉接触的BR肿瘤（BR-PV）和5例动脉接触的BR肿瘤（BR-A）]。方案治疗完成和切除的总比率分别为91％（50/57）和96％（55/57）。由于胆管炎（n = 5）或中性粒细胞减少症（n = 2），七名患者未能完成S-1。最常见的3级毒性[不良事件通用术语标准（CTCAE）4.0版]为厌食症（7％），恶心（5％），中性粒细胞减少症（4％）和白细胞减少症（4％）。没有患者经历过4级毒性。 55例接受胰腺切除术的患者中有54例（98％）达到了病理学阴性切缘（R0）。病理反应分为Evans I级：8例（15％），IIa≥31例（56％），IIb≥14例（25％），IIIb≥1例（2％），IV≥1例（2 ％），并且在4例患者（8％）中观察到了手术发病率（Clavien-Dindo IIIb级或更低）。 R患者的1年和2年总生存率（OS）分别为91％和83％，BR患者分别为77％和58％（p = 0.03）。
结论：新辅助S-1联合并发次分割放疗是可以耐受的，对于R和BR PDAC的患者似乎很有希望。

BACKGROUND & AIMS: :The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.

背景与目标： ：制造挑战和血清半衰期短阻碍了双特异性T细胞结合抗体的潜力。我们通过用体外转录的药理优化，编码抗体的核苷修饰的mRNA治疗小鼠，从而规避了这些局限性。我们实现了抗体的持续内源性合成，与相应的纯化双特异性抗体一样有效地消除了晚期肿瘤。由于药物mRNA的生产速度很快，因此该方法可以加速新型双特异性抗体的临床开发。

BACKGROUND & AIMS: :According to the World Health Organization classification of pituitary tumors, only tumors with systemic metastasis must be considered as carcinomas. Invasive tumors with multiple recurrences are only classified as aggressive tumors or "atypical adenomas". To illustrate the problems encountered in the pathological diagnosis of pituitary carcinoma and in patient management, we present two male patients operated on for an aggressive prolactin pituitary adenoma with and without metastasis. In case 1, 5 surgeries, 3 irradiations, increased doses of dopamine agonists, and trials of temozolomide and carboplatine-VP16 failed to control tumor progression and the appearance of metastases which lead to death 16 years after onset. In case 2, based on the initial diagnosis of an aggressive-invasive adenoma that was resistant to dopamine agonists, gamma-Knife irradiation was initially performed on the intra-cavernous remnant. Eight years after onset, the remnant remained stabilized and the plasma PRL normalized under dopamine agonist. From these 2 cases alongside other cases found in the literature, we propose that the association of certain clinical signs (male sex, dopamine-resistant hyperprolactinemia), radiological signs (invasive macro or giant tumor on MRI) and histological signs (angiogenesis, Ki-67 > 3%, p53 positive, mitoses >2 per high power field, vascular invasion, up-regulation of genes related to invasion and proliferation, and allelic loss of chromosome 11) might suggest aggressiveness and be suspicious of malignancy before the appearance of metastasis. The early detection of an aggressive phenotype of a prolactin pituitary tumor should permit the earlier establishment of the optimum therapeutic strategy associating surgery and radiotherapy to delay or inhibit metastasis.

背景与目标： ：根据世界卫生组织垂体瘤分类，只有具有全身转移的肿瘤才可被视为癌。具有多次复发的浸润性肿瘤仅分类为浸润性肿瘤或“非典型腺瘤”。为了说明垂体癌的病理诊断和患者管理中遇到的问题，我们介绍了两名男性患者，他们患有侵袭性催乳素垂体腺瘤，有无转移。在病例1、5的手术，3的放射线，增加的多巴胺激动剂剂量以及替莫唑胺和卡铂-VP16的试验中，未能控制肿瘤的进展和转移的出现，从而导致发病后16年死亡。在案例2中，基于对多巴胺激动剂有抵抗力的侵略性腺瘤的初步诊断，最初对海绵体内残余物进行了伽玛刀照射。发病八年后，在多巴胺激动剂作用下，残余物保持稳定，血浆PRL正常化。从这2例病例以及文献中发现的其他病例中，我们建议将某些临床体征（男性，多巴胺耐药性高泌乳素血症），放射体征象（MRI上的浸润性大肿瘤或巨瘤）与组织学征象（血管生成，Ki- 67> 3％，p53阳性，每个高倍视野中的有丝分裂> 2，血管浸润，与浸润和增殖相关的基因上调，以及11号染色体的等位基因丢失，这可能表明其具有侵略性，并且在出现转移之前怀疑是恶性的。泌乳素垂体瘤侵袭性表型的早期检测应允许较早建立最佳的治疗策略，以结合手术和放疗来延迟或抑制转移。

BACKGROUND & AIMS: A 70-year-old man was admitted to the hospital because of sudden, upper abdominal and back pain. Laboratory and image data indicated acute pancreatitis. Shortly after the admission, pancreatic and liver abscess with bacteremia developed. Antibiotic therapy seemed effective. A month later, spontaneous fistulization of the pancreatic abscess to the duodenal bulb was found by gastroduodenal fiberscopy. Injection of contrast medium into the duodenal orifice showed that the fistula was draining the abscess and that no other fistula formed from the abscess. Endoscopic retrograde cholangiopancreatogram indicated no fistula formation to the pancreatic duct. The pancreatic abscess became smaller and was not visible using computerized tomography and ultrasonography 3 months later and thereafter. Closure of the duodenal orifice was ascertained by the endoscopy. It is suggested that retrograde infection from the fistula was prevented by the single fistulization to the acidic duodenal bulb, which is not supposed to allow most bacterial growth. Pancreatic abscess usually necessitates operative treatment, even with fistulization to the alimentary tract. It seems likely that the single, small fistulization to the bulb, in addition to the lack of underlying disease and medical and nutritional support, facilitated the spontaneous healing process.

背景与目标： 一名70岁的男子因突然，上腹部和背部疼痛入院。实验室和图像数据表明急性胰腺炎。入院后不久，胰腺和肝脓肿发展为菌血症。抗生素治疗似乎有效。一个月后，通过胃十二指肠纤维镜检查发现胰腺脓肿自发形成十二指肠球。造影剂注入十二指肠孔显示瘘管正在排脓，而脓肿未形成其他瘘管。内镜逆行胰胆管造影显示胰管未形成瘘管。 3个月后及以后，胰腺脓肿变小，使用计算机断层扫描和超声检查无法观察到。通过内窥镜检查确定十二指肠口的闭合。提示通过对酸性十二指肠球进行单次瘘管造瘘可以防止从瘘管逆行感染，这不应使大多数细菌生长。胰腺脓肿通常需要手术治疗，即使在消化道有瘘管的情况下也是如此。除缺乏潜在的疾病以及医疗和营养支持外，球囊单一，小的瘘管似乎也促进了自发愈合过程。

BACKGROUND & AIMS: :Solid and papillary epithelial neoplasm (SPENP) of the pancreas is a rare pancreatic tumour of low malignant potential, that is seen mostly in young females. The aetiology and pathogenesis is unclear but it is considered to be arising from primordial pancreatic cells. We report two cases of SPENP who had palpable abdominal lumps and were diagnosed on histopathology. In the first case, the tumour was unresectable and patient died within one year. In the second case, at laprotomy the patient had perineurial as well as capsular infiltration but after wide resection of the growth, patient has been doing well for the past 6 months. Since SPENP is a low grade malignant neoplasm, it should be treated aggressively with complete resection and metastatectomy. Prognosis after adequate surgery is good. A clinicopathological study and brief review of literature is presented.

背景与目标： ：胰腺的乳头状和乳头状上皮性肿瘤（SPENP）是一种罕见的低恶性潜能的胰腺肿瘤，多见于年轻女性。病因和发病机制尚不清楚，但被认为起源于原始胰腺细胞。我们报告了2例SPENP患者，他们有明显的腹部肿块，并经组织病理学确诊。在第一种情况下，肿瘤无法切除，患者在一年内死亡。在第二种情况下，在腹膜切开术中，患者有尿道周和囊膜浸润，但是在广泛切除生长后，患者在过去的6个月中一直表现良好。由于SPENP是低度恶性肿瘤，因此应通过彻底切除和转移切除术积极治疗。适当手术后预后良好。提出了临床病理学研究和文献简要回顾。