Value of High-Frequency Ultrasound for Differentiating Invasive Basal Cell Carcinoma from Non-invasive Types

The purpose of the study was to evaluate the value of high-frequency ultrasound (HFUS) for differentiating invasive basal cell carcinomas (BCCs) from non-invasive BCCs. We established a prediction model based on ultrasound features and validated it further. One hundred patients in the pilot cohort and another 43 in the validation cohort were evaluated. All patients underwent HFUS examinations by the same radiologist, and then were divided on the basis of pathology into invasive and non-invasive types. With respect to growth pattern, 60.5% of invasive BCCs had an irregular pattern, whereas 89.5% of non-invasive BCCs had a nodular or crawling pattern (p < 0.001). As for the layers involved, the more invasive BCCs broke through the dermis compared with non-invasive BCCs (23.3% vs. 1.8%) (p < 0.001). With respect to intralesional hyperechoic spot distribution, invasive and non-invasive BCCs tended to be clustered and absent/scattered-like, respectively (55.8% vs. 91.2%) (p < 0.001). On the basis of the aforementioned features, a prediction model was established with accuracies of 84.0% and 76.7%, respectively, in the pilot and validation cohorts. HFUS holds promise for the differentiation of the invasiveness of BCCs and is helpful in its clinical management.     

Fluorescence In Situ Hybridization to Visualize Genetic Abnormalities in Interphase Cells of Acinar Cell Carcinoma, Ductal Adenocarcinoma, and Islet Cell Carcinoma of the Pancreas

OBJECTIVE: To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.PATIENTS AND METHODS: Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS. These FISH probes were used with control probes to distinguish among various kinds of chromosome abnormalities of number and structure.RESULTS: FISH abnormalities were observed in 12 (80%) of 15 patients with pancreatic cancer: 5 of 5 patients with acinar cell carcinoma, 5 of 5 patients with ductal adenocarcinoma, and 2 (40%) of 5 patients with islet cell carcinoma. All 3 specimens of pancreatic tissue without neoplasia had normal FISH results. Gains of CTNNB1 due to trisomy 3 occurred in each tumor with acinar cell carcinoma but in none of the other tumors in this study. FISH abnormalities of all other cancer genes studied were observed in all forms of pancreatic tumors in this investigation.CONCLUSION: FISH abnormalities of CTNNB1 due to trisomy 3 were observed only in acinar cell carcinoma. FISH abnormalities of genes implicated in familial cancer, tumor progression, and the 5-fluorouracil pathway were common but were not associated with specific types of pancreatic cancer.5FU = 5-fluorouracil; FISH = fluorescence in situ hybridization; ND-FISH = interphase FISH to detect abnormalities of chromosome number and structure; SSC = standard saline citratePancreatic cancer afflicts more than 200,000 new patients worldwide each year, including more than 37,600 in the United States.^1-4 Surgery seldom cures pancreatic cancer and effective chemotherapies are largely unknown.⁵ Survival varies among patients with pancreatic cancer but is often measured in months.^6,7 Thus, novel genetic research of pancreatic cancer is urgently needed to help establish accurate diagnoses and to develop effective treatments for this important public health problem.This investigation used fluorescence in situ hybridization (FISH) to visualize chromosomal loci in interphase nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas. Acinar cell carcinoma and ductal adenocarcinoma, which are nonendocrine tumors, and islet cell carcinomas, which are neuroendocrine tumors, reportedly occur in less than 1%, 95%, and 5%, respectively, of patients with pancreatic cancer.^3,8,9 In 2 retrospective studies of large series of patients, median survival for unresected ductal adenocarcinoma was 3 months⁸; for unresected acinar cell carcinoma, 25 months⁸; for nonfunctional islet cell carcinoma, 26 months⁹; and for functional islet cell carcinoma, 54 months.⁹Although some genetic studies of pancreatic cancer have been published, most focus on ductal adenocarcinoma. An assortment of genetic procedures have been attempted to investigate pancreatic cancer, including family history studies,¹ conventional cytogenetic techniques,¹⁰ interphase FISH,^11-13 comparative genomic hybridization,¹⁴ RNA expression analyses,^15,16 and evaluation of sequence variations.¹⁷ These studies implicate a variety of point mutations and chromosomal anomalies in most, if not all, patients with pancreatic cancer. Nevertheless, the biology of various forms of pancreatic cancer remains poorly understood, and this problem precludes efforts to establish novel genetic treatments for these disorders.This investigation used interphase FISH to visualize genetic abnormalities in individual normal and neoplastic cells in acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.¹⁸ This research project was specifically designed to detect genetic abnormalities that have been shown via other genetic technologies to be associated with acinar cell carcinoma of the pancreas, familial pancreatic cancer, tumor progression in pancreatic cancer, or genes linked with the molecular pathway of 5-fluorouracil (5FU) chemotherapy.     

致敏的脐血源树突状细胞诱导CTL特异杀伤白血病细胞的实验研究

探讨脐血单个核细胞（MNC）诱导的树突状细胞（DC）通过负载冻融的HL-60、K562细胞抗原体外诱导产生细胞毒性T淋巴细胞（CTL）对HL-60、K562的杀伤作用。取脐血12份,分离MNC。在MNC中加入细胞因子GM-CSF（granulocyte monocyte colony-stimulating factor）、IL-3（interleukin 3）、SCF（stemcell factor）和EPO培养4周。使用CD83、CD1a、CD11C和CDw123单克隆抗体、流式细胞仪测定培养前后脐血DC抗原变化及扩增情况。DC通过负载HL-60、K-562白血病细胞抗原致敏T淋巴细胞产生CTL^3H-TdR掺入试验测定DC免疫刺激活性,MTT法观察CTL对HL-60、K562细胞的特异性杀伤活性。结果表明：新鲜脐血CD1a^＋、CD11c^＋、CD83^＋、CDw123^＋细胞数分别为0．27×10^5／ml、5．87×10^5／ml、1．94×10^5／ml、2．73×10^5／ml。加入上述细胞因子培养的脐血MNC分化为CD1a^＋、CD11C^＋、CD83^＋、CDw123^＋DC,经培养2—4周,DC数明显增多,分别达11．02×10^5／ml、28．24×10^5／ml、10．57×10^5／ml、18．7×10^5／ml,此后逐渐减少。细胞因子诱导脐血DC具有免疫刺激活性,且DC与CBMNC细胞比例为1：40时的刺激活性最佳。冻融法得到的HL-60、K562白血病细胞抗原致敏DC诱导的CTL对HL-60、K562细胞的杀伤率分别为（42．04±8．46）％和（31．25±11．07）％,与实验组比较有显著性差异（P〈0．01）。结论：加入细胞因子GM—CSF、IL-3、SCF和EPO培养2-4周的脐血MNC可分化为cD1a^＋、CD11C^＋、CD83^＋、CDw123^＋DC。冻融法得到的HL-60、K562白血病细胞抗原致敏DC,其诱导的CTL对HL-60、K562细胞具有特异的杀伤作用。脐血DC作为抗原呈递细胞在肿瘤免疫治疗上将起到重要作用。     

Ultrasound Image Classification of Ductal Carcinoma In Situ (DCIS) of the Breast: Analysis of 705 DCIS Lesions

The Japan Association of Breast and Thyroid Sonology (JABTS) proposed, in 2003, a conceptual classification system for non-mass abnormalities to be applied in addition to the conventional concept of masses, to facilitate detecting ductal carcinoma in situ (DCIS) lesions. The aim of this study was to confirm the utility of this system and to clarify the distribution of these findings in DCIS lesions. Data on 705 surgically treated DCIS lesions from 16 institutions in Japan were retrospectively reviewed. All 705 DCIS lesions could be classified according to the JABTS classification system. The most frequent findings were hypo-echoic areas in the mammary gland (48.6%), followed by solid masses (28.0%) and duct abnormalities (10.2%) or mixed masses (8.1%). Distortion (1.3%), clustered microcysts (1.4%) and echogenic foci without a hypo-echoic area (2.5%) were uncommon. These results suggest that the concept of non-mass abnormalities is useful in detecting DCIS lesions.     

鳞状细胞癌抗原、糖类抗原125检测在宫颈鳞癌中的应用价值

目的探讨肿瘤标志物鳞状细胞癌抗原（SCC）与糖类抗原125（CA125）检测在宫颈鳞状细胞癌中的应用价值。方法对经临床病理确诊的85例宫颈鳞状细胞癌患者、60例宫颈上皮内瘤样病变（CIN）患者以及45例健康妇女,采用雅培微粒子免疫分析仪IMX和罗氏电化学发光分析仪E170分别检测血清SCC和CA125数值,比较分析二者改变的临床意义。结果与正常对照组及CIN组相比,宫颈鳞癌组治疗前血清SCC水平及阳性率均较高（P〈0.05）;而CA125在三组间无统计学差异（P〉0.05）。在国际妇产科联盟（Federation International of Gynecology andObstetrics,FIGO）分期中,SCC水平及阳性率随分期上升而增加（P〈0.05）;而CA125仅浓度改变有统计学差异（P〈0.05）。SCC和CA125在不同病理分级中均无显著改变（P〉0.05）。宫颈鳞癌患者治疗前后的血清SCC改变,差异有统计学意义（P〈0.05）;而血清CA125无统计学差异（P〉0.05）。结论 SCC测定可作为宫颈鳞癌诊断的辅助指标,用于病情进展、治疗效果的监测。而CA125在宫颈鳞癌诊疗中的意义不大,二者联合检测可以提高对宫颈鳞癌诊断的敏感性。     

Sonographic Findings of High‐Grade and Non–High‐Grade Ductal Carcinoma In Situ of the Breast

Objective. The purpose of this study was to differentiate between high‐grade and non–high‐grade ductal carcinoma in situ (DCIS) of the breast on sonography. Methods. From October 2003 to August 2009, 76 DCIS lesions in 73 women who underwent sonography and mammography were included in this study. Lesions were confirmed by mastectomy, breast‐conserving surgery, or surgical biopsy. Images were analyzed by 2 radiologists with consensus and were correlated with histologic grades. Results. Of the 76 lesions, 44 were classified as high‐‐grade and 32 as non–high‐grade DCIS. Fifty‐seven lesions (75.0%) were identified on sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal changes in 4, and architectural distortion in 3. All cases with false‐negative findings on sonography (n = 19) showed microcalcifications on mammography. On sonography, masses were more frequently found in non–high‐grade (62.5%) than high‐grade DCIS (22.7%; P < .01). No significant difference was seen in the sonographic features of masses between high‐grade and non–high‐grade DCIS. Microcalcifications were more common in high‐grade (43.2%) than non–high‐grade (3.1%) DCIS (P = .02). Most sonographically visible microcalcifications had associated findings such as ductal changes (n = 11), a mass (n = 7), or a hypoechoic area (n = 5). The detection rate of microcalcifications on sonography was higher in high‐grade (62.9%) than non–high‐grade DCIS (25.0%; P = .023). Conclusions. Microcalcifications with associated ductal changes (11 of 31 [35.5%]) were the most common sonographic findings in high‐grade DCIS. An irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26 [50.0%]) was the most frequent finding in non–high‐grade DCIS.     

Cell Types Obtained from the Epidural Space of Patients with Low Back Pain/Radiculopathy

Background:   We investigated if correlations exist between medical history, tissue abnormalities, and cell types retrieved from the epidural space of patients with chronic low back pain (LBP) and chronic radicular pain (RP).
Methods:   Approval was obtained from the Institutional Review Board for the Protection of Human Subjects to study 191 patients undergoing epiduroscopy. Visual inspection was performed and abnormal areas were identified. A specimen obtained from the area using a cytology brush was processed by the Thin Prep technique. Patients were divided into four groups based on the presence or absence and intensity of LBP and RP. The gender and age of the patients were recorded, as was any history of prior back surgery. Areas of tissue abnormalities were rated according to changes in vascularity and amount of fat, fibrosis, and inflammation. Stenosis was assessed from magnetic resonance imaging or computerized tomography scan images. Cytologic assessments included notations of the presence or absence of erythrocytes, leukocytes, cell groups, lipocytes, spindled cells, and large round cells.
Results:   There was a significant difference in the number of patients from whom big round cells were obtained who had a high degree of LBP compared with the number of patients who had a high degree of both LBP and RP.
Conclusions:   The findings provide a foundation for future studies of cells obtained from similar patients with the goal of furthering the understanding of the pathogenesis of LBP/RP.     

LASIK治疗近视并发症的临床观察及处理

准分子激光原位角膜磨镶术 (ＥｘｃｉｍｅｒＬａｓｅｒｉｎｓｉｔｕＫｅｒａｔｏｍｉｌｅｕｓｉｓ,ＬＡＳＩＫ)治疗近视的安全性、有效性已被大量的临床资料证实[1,2 ] 。但其手术复杂同时存在一定的并发症[3 ] 。现将本院从 1998年开展ＬＡＳＩＫ以来的病例所发生的常见并发症作一初步分析。1　资料与方法1.1　一般资料　本组病例均为临床随访半年至 1年以上的患者 ,共 896例 (162 6只眼 ) ,男性 4 0 7例 (796只眼 ) ;女性 4 89例 (830只眼 ) ;平均年龄 2 6.15 (18～5 0 )岁。屈光范围 :- 2 .0 0～ - 2 2 .0 0Ｄ ,最大散光 :-5 .0 0Ｄ。按…     

Caring for Patients Treated With Checkpoint Inhibitors for the Treatment of Metastatic Merkel Cell Carcinoma

ObjectiveTo provide an overview for oncology nurses about Merkel cell carcinoma and its management with immunotherapy.Data SourcesA literature search was conducted from 2013 to the present using search terms including “Merkel cell carcinoma,” “avelumab,” “pembrolizumab,” “immune-mediated adverse events,” and “infusion-related reactions.” Clinical experience of the authors was also considered.ConclusionOncology nurses can expect to manage an increasing number of patients with Merkel cell carcinoma because of increased incidence of the disease, as well as evolving immunotherapy treatment paradigms. Both avelumab and pembrolizumab possess favorable safety profiles but are associated with immune-mediated and infusion-related reactions.Implications for Nursing PracticeOncology nurses need to understand Merkel cell carcinoma and be able to recognize the signs and symptoms of immune-mediated adverse events and infusion-related reactions associated with treatment to provide early intervention.     

A Suppressor T Cell of the Mixed Lymphocyte Reaction Specific for the HLA-D Region in Man

The mixed lymphocyte reaction (MLR) is the proliferative response of one individual's lymphocytes cultured in the presence of another individual's lymphocytes. In man, the MLR is elicited by cell surface antigens coded for by the HLA-D gene locus. This locus is among a cluster of genes which are located on the sixth chromosome and which include genes coding for the major histocompatibility antigens HLA-A, B, and C as well as HLA-D. If the stimulator cell possesses D locus antigens not present in the responder, the lymphocytes of the latter will undergo blast transformation resulting in DNA synthesis which can be measured. A vigorous response in the MLR to allogeneic cells is the rule among healthy individuals.We describe studies of a 23-yr-old man whose lymphocytes respond normally to mitogens and soluble antigens but fail to respond to allogeneic cells in the MLR. His medical history is unremarkable except that he received thymic irradiation as an infant. HLA typing revealed that he is homozygous for HLA-A2, B12, and Cw5 as well as for the D locus antigen Dw4. When his lymphocytes were added to the responder lymphocytes of other persons homozygous for the same HLA antigens, their responses to allogeneic cells but not mitogens were suppressed by 50-95%. Their responses to a soluble antigen, tetanus toxoid, were suppressed to a lesser degree. These inhibitory effects were mediated by a relatively radioresistant thymus-derived (T) lymphocyte.Further studies of the requirements for MLR suppression revealed that only persons heterozygous or homozygous for the Dw4 antigen were inhibited by the suppressor T cell. This effect was not altered by differences in the HLA-A, B, or C antigens between the suppressor and responder. It is concluded that genes in or near the HLA-D locus code not only for antigens (primarily on bone marrow-derived (B) cells), that elicit the MLR, but also for structures on T cells, or possibly macrophages, which are recognized by MLR suppressor T cells.     

膀胱癌并前列腺增生经尿道同期电切术的临床观察

【目的】探讨膀胱癌并前列腺增生症患者同期行经尿道膀胱肿瘤加前列腺电切术治疗的可行性及疗效。【方法】对27例膀胱癌并前列腺增生患者，行同期经尿道膀胱肿瘤加前列腺电切术并随访观察疗效。【结果】随访5～60个月，5例术后复发，平均19个月，无尿道及前列腺窝种植转移。【结论】膀胱癌并前列腺增生患者同期行经尿道电切术疗效确定，未观察到有前列腺窝及尿道种植转移。     

电镜包埋后肝细胞HBVDNA原位杂交及观察

应用电镜包埋后原位分子杂交技术，对１０例人肝癌及癌周组织，分别采用ＨＢＶＤＮＡ探针进行了包埋后原位分子杂交。结果显示：６例标本呈阳性反应．其中在肝癌细胞内ＨＢＶＤＮＡ少见阳性标志．在癌周肝细胞内ＨＢＶＤＮＡ呈强弱不等的阳性反应，其分布特征，核内主要呈散在型，核外呈局部的密集型。提示ＨＢＶＤＮＡ的分布特点可能与其复制的不同时期有关．并对ＨＢＶ的致癌性进行了初步讨论．     

增殖细胞核抗原表达与鼻咽癌放射敏感性关系的研究

[目的]探讨增殖细胞核抗原(PCNA)的表达与鼻咽癌(NPC)放射敏感性的关系.[方法]采用PCNA抗体进行ABC法免疫组化染色.检测108例患者初行放疗前鼻咽癌组织中PCNA表达情况,显微镜下计数阳性细胞,计算增殖指数(PI),并将所有病例按照PI值的高低以25%为界划分两组;高PCNA表达者(HPI)>25%,低P...     

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

Background

There is a need to better characterise cell-based therapies in preclinical models to help facilitate their translation to humans. Long-term high-resolution tracking of the cells in vivo is often impossible due to unreliable methods. Radiolabelling of cells has the advantage of being able to reveal cellular kinetics in vivo over time. This study aimed to optimise the synthesis of the radiotracers [⁸⁹Zr]Zr-oxine (8-hydroxyquinoline) and [⁸⁹Zr]Zr-DFO-NCS (p-SCN-Bn-Deferoxamine) and to perform a direct comparison of the cell labelling efficiency using these radiotracers.

Procedures

Several parameters, such as buffers, pH, labelling time and temperature, were investigated to optimise the synthesis of [⁸⁹Zr]Zr-oxine and [⁸⁹Zr]Zr-DFO-NCS in order to reach a radiochemical conversion (RCC) of >95 % without purification. Radio-instant thin-layer chromatography (iTLC) and radio high-performance liquid chromatography (radio-HPLC) were used to determine the RCC. Cells were labelled with [⁸⁹Zr]Zr-oxine or [⁸⁹Zr]Zr-DFO-NCS. The cellular retention of ⁸⁹Zr and the labelling impact was determined by analysing the cellular functions, such as viability, proliferation, phagocytotic ability and phenotypic immunostaining.

Results

The optimised synthesis of [⁸⁹Zr]Zr-oxine and [⁸⁹Zr]Zr-DFO-NCS resulted in straightforward protocols not requiring additional purification. [⁸⁹Zr]Zr-oxine and [⁸⁹Zr]Zr-DFO-NCS were synthesised with an average RCC of 98.4 % (n = 16) and 98.0 % (n = 13), respectively. Cell labelling efficiencies were 63.9 % (n = 35) and 70.2 % (n = 30), respectively. ⁸⁹Zr labelling neither significantly affected the cell viability (cell viability loss was in the range of 1–8 % compared to its corresponding non-labelled cells, P value > 0.05) nor the cells’ proliferation rate. The phenotype of human decidual stromal cells (hDSC) and phagocytic function of rat bone-marrow-derived macrophages (rMac) was somewhat affected by radiolabelling.

Conclusions

Our study demonstrates that [⁸⁹Zr]Zr-oxine and [⁸⁹Zr]Zr-DFO-NCS are equally effective in cell labelling. However, [⁸⁹Zr]Zr-oxine was superior to [⁸⁹Zr]Zr-DFO-NCS with regard to long-term stability, cellular retention, minimal variation between cell types and cell labelling efficiency.

     

Telavancin In Vitro Activity against a Collection of Methicillin-Resistant Staphylococcus aureus Isolates,Including Resistant Subsets,from the United States

Telavancin had MIC₅₀, MIC₉₀, and MIC₁₀₀ values of 0.03, 0.06, and 0.12 μg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 μg/ml) or daptomycin (1 to 2 μg/ml) had telavancin MIC₅₀ (0.06 μg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC₅₀, 0.03 μg/ml). However, telavancin had MIC₉₀ and MIC₁₀₀ results of 0.06 and 0.12 μg/ml (100% susceptible), respectively, regardless of the MRSA subset.     

In Situ Measurement of Acoustic Attenuation for Focused Ultrasound Ablation Surgery Using a Boiling Bubble at the Focus

ObjectiveAcoustic attenuation in the propagation path of focused ultrasound ablation surgery determines the energy loss toward the focal region and is critical to the consequent treatment outcomes. In situ non-invasive, reliable, and accurate measurement is challenging for multi-layered heterogeneous tissues within the focusing angle.MethodsA novel measurement approach is proposed and its performance is evaluated using ex vivo porcine tenderloin and bovine heart. A big boiling bubble (i.e., larger than a few millimeters in size) was produced at the focus as a strong reflector inside the tissue, and the echo amplitudes were used to determine the acoustic attenuation. Two models, acoustic ray and energy loss, were developed to derive the equivalent acoustic attenuation coefficient for a focused beam.ResultsThe measured acoustic attenuation coefficients of ex vivo porcine tenderloin and bovine heart at 0.97 MHz and a thickness of 3 cm are 0.159 ± 0.002 and 0.250 ± 0.005 Np/cm, respectively, which are all within the scope of measured values in the literature. In addition, the echo amplitude is sensitive to the conditions of the propagation path, and the inverse acoustic attenuation coefficient of the silicone gel pad placed in front of the tissue sample was 0.807 ± 0.002 Np/cm, which is comparable to the measurement using the insertion substitution method, 0.766 ± 0.003 Np/cm.ConclusionOur proposed approach could determine the tissue acoustic attenuation for focused ultrasound ablation surgery reliably and accurately in situ. The easy operating protocol may allow clinical translation and adoption for improved safety and efficacy.