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。

BACKGROUND & AIMS: Pancreatic neoplasms harbor different prognoses according to their histological typea benign course for serous cystadenoma, a low malignant potential for intraductal papillary mucinous neoplasms (IPMN), and high aggressiveness for ductal adenocarcinoma (ADC). Transforming growth factor beta 1 (TGF beta 1) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta 1-latency-associated peptide (beta 1-LAP), its latent binding protein (LTBP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5). LTBP is thought to play a strategic role in the processing and active secretion of latent TGF beta 1 and its stockage in the extracellular matrix. Localization of beta 1-LAP and LTBP was assessed by immunohistochemistry using specific antibodies and expression of TGF beta 1 mRNA by reverse-transcriptase polymerase chain reaction analysis. beta 1-LAP was only slightly expressed in normal specimens, while LTBP was not detected. beta 1-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one carcinoma in situ. LTBP was detected only in stromal cells and in the surrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta 1-LAP was strongly expressed in the epithelial cells, while it was poorly detected in invasive IPMN; stromal cells were poorly or not all stained by beta 1-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benign IPMN and two of two cases with cystadenoma, while stroma was not immunostained. TGF beta 1 mRNA was strongly expressed in most of the tumors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta 1 in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta 1 efficiently, in contrast to ductal ADC as shown by the ability of the neoplastic cells to express both beta 1-LAP and LTBP.

背景与目标： 胰腺肿瘤根据其浆液性囊腺瘤的组织学类型，良性，导管内乳头状黏液性肿瘤（IPMN）的低恶性潜能和导管腺癌（ADC）的高侵袭性，具有不同的预后。转化生长因子beta 1（TGF beta 1）可能调节肿瘤的生长。本研究分析并比较了IPMN中导管腺癌（n = 10）中其前体β1-潜伏期相关肽（β1-LAP），其潜在结合蛋白（LTBP）和其mRNA的表达。 8），浆液性囊腺瘤（n = 2）和正常组织（n = 5）。 LTBP被认为在潜在的TGFβ1及其在细胞外基质中的储备中的加工和主动分泌中起着战略作用。使用特异性抗体通过免疫组织化学评估β1-LAP和LTBP的定位，并通过逆转录酶聚合酶链反应分析评估TGFβ1 mRNA的表达。 β1-LAP在正常标本中仅少量表达，而未检测到LTBP。在10例ADC患者中，有9例在肿瘤细胞的细胞质中检测到了β1-LAP。在所有情况下，除了原位癌中的一种，在肿瘤腺周围的基质细胞中均存在强烈的染色。 LTBP仅在基质细胞和周围的细胞外基质中检测到。在具有轻度不典型增生的IPMN和膀胱腺瘤中，β1-LAP在上皮细胞中强烈表达，而在侵袭性IPMN中则检测不到。除侵袭性IPMN外（n = 2），基质细胞几乎没有被β1-LAP染色。在3例良性IPMN的肿瘤细胞和2例囊性腺瘤的2例肿瘤细胞中检测到LTBP，而基质未进行免疫染色。 TGFβ1mRNA在大多数肿瘤中强烈表达，并且在不同类型的肿瘤之间未观察到表达差异。在ADC和IPMN或膀胱腺瘤中，TGF beta 1的表达没有定量差异。但是，与导管ADC相比，后者能有效分泌TGFβ1，而肿瘤细胞既能表达β1-LAP又能表达LTBP。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Under both conventional method (CM) and microwave (MW) irradiation (MWI) conditions, alkylation of 4,5-diphenylimidazole-2-thione (1) with halogeno-alkanols 2 or 5, chloroglycerol 11 and 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)-glycerol (8) in presence of sodium ethoxide or sodium acetate in alcohol afforded regioselectively the corresponding S-alkylated analogues 3, 6, 9, and 12; they also were obtained using MW in absence and presence of bentonite as solid support with no change in regioselectivity. In the presence of potassium carbonate in DMF, the bisalkylated analogues 4, 7, 10, and 13 were obtained except in case of compound 13 where it was accompanied with the imidazothiazine 14. A convenient approach for imidazo-[2,1-b]thiazines and thiazoles 14-16 could be achieved by intramolecular dehydrative ring closure of the S-hydroxyalkylated imidazoles 3, 6, and 12 using potassium carbonate in DMF under both conventional and microwave methods. Isopropylidenation of 12 and 13 and deprotection of 9 and 10 also were investigated.

背景与目标： ：在常规方法（CM）和微波（MW）照射条件下，均用卤代链烷醇2或5，氯甘油11和2,3-O-将4,5-二苯基咪唑-2-硫酮（1）烷基化在乙醇钠或乙酸钠存在下，在异丙醇中的异亚丙基-1-O-（对甲苯磺酰基）-甘油（8）选择性地提供相应的S-烷基化的类似物3、6、9和12；它们也可以在不存在和存在膨润土作为固体载体的情况下使用MW获得，其区域选择性没有变化。在DMF中存在碳酸钾的情况下，获得双烷基化的类似物4、7、10和13，除了化合物13与咪唑并噻嗪14结合的情况外。咪唑-[2,1-b]的简便方法噻嗪和噻唑14-16可以通过在传统方法和微波方法下使用碳酸钾在DMF中对S-羟烷基化的咪唑3、6和12进行分子内脱水闭环来实现。还研究了12和13的异亚丙基化和9和10的脱保护。

BACKGROUND & AIMS: :Vitamin D and its analogues exhibit potent antitumor effects in many tissues, including the pancreas. Normal and malignant pancreatic tissues were recently shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined associations between dietary intake of vitamin D, calcium, and retinol and subsequent risk for pancreatic cancer. We conducted prospective studies in cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses' Health Study), documenting incident pancreatic cancer through the year 2000. Diet was ascertained by semiquantitative food-frequency questionnaire. We identified 365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with participants in the lowest category of total vitamin D intake (<150 IU/d), pooled multivariate relative risks for pancreatic cancer were 0.78 [95% confidence interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for 300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI, 0.40-0.88) for >/=600 IU/d (P(trend) = 0.01). These associations may be stronger in men than women. After adjusting for vitamin D intake, calcium and retinol intakes were not associated with pancreatic cancer risk. In two U.S. cohorts, higher intakes of vitamin D were associated with lower risks for pancreatic cancer. Our results point to a potential role for vitamin D in the pathogenesis and prevention of pancreatic cancer.

背景与目标： 维生素D及其类似物在包括胰腺在内的许多组织中均显示出强大的抗肿瘤作用。最近显示正常和恶性胰腺组织表达高水平的维生素D1-α-羟化酶，可将循环中的25-羟基维生素D转化为活性1,25-二羟基维生素D。视黄醇和随后的胰腺癌风险。截至1986年，我们对46,771名40-75岁的男性（健康专业人员随访研究）和75,427名38-65岁的女性（队列1984年）（护士健康研究）进行了前瞻性研究，记录了胰腺癌的发生情况。到2000年。通过半定量食物频率问卷确定饮食。在16年的随访中，我们确定了365例胰腺癌事件病例。与总维生素D摄入量最低的类别（<150 IU / d）的参与者相比，胰腺癌的汇总多元相对风险为0.78 [95％置信区间（95％CI），0.59-1.01]，范围为150至299 IU / d，对于300至449 IU / d为0.57（95％CI，0.40-0.83），对于450至599 IU / d为0.56（95％CI，0.36-0.87），对于0.59（95％CI，0.40-0.88） > / = 600 IU / d（P（趋势）= 0.01）。这些联系在男性中可能比女性更强。在调整了维生素D的摄入量之后，钙和视黄醇的摄入量与胰腺癌的风险无关。在美国的两个队列中，维生素D的摄入量增加与胰腺癌的风险降低有关。我们的研究结果表明维生素D在胰腺癌的发病机理和预防中的潜在作用。