bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Survey of Medical Choices in Caring for Terminally ill Patients in Italy, a Cross-Sectional Study
Authors: Cocconi Giorgio , Caminiti Caterina , Zaninetta Giovanni , Passalacqua Rodolfo , Cascinu Stefano , Campione Francesco , Todeschini Renata , Zani Sergio , d'Aloia Tiberio , Migone Luigi 
Published: February 2018

Aims and background In Italy, euthanasia and assisted suicide remain illegal but have been the subject of constant debate. Such discussions, however, seem to take relatively little account of physicians' views and attitudes. Methods and study design We used an anonymous questionnaire to survey the attitudes and practices concerning euthanasia and the care of terminally ill patients of 5000 Italian physicians from among the approximately 20,000 members of seven of the most important Italian scientific societies. They were asked to complete an anonymous questionnaire consisting of 15 items, which also collected demographic and professional information. Results The response rate was 23.5%, and 855 questionnaires were returned. The respondents (75% males) had a median age of 51 years and 47% practiced medicine in a hospital or university setting. The survey showed that the attitude of Italian physicians towards caring for terminal patients is generally against the practice of euthanasia insofar as 84% and 87%, respectively, would, on a theoretical basis, be unwilling to prescribe or administer lethal drugs. Only 1.2-2% of the physicians declared that they had resorted at least once to active euthanasia practices consisting of the prescription and/or direct administration of lethal drugs during their professional lives, and 0.5–0.9% during the previous year. The main factor significantly influencing the opinions and behaviors of the physicians was religion. Conclusions To our knowledge, this is the first Italian survey investigating the opinions and practices on euthanasia of a large sample of physicians from all over the country, belonging to various medical specialties. Our findings confirm the considerable influence of religion on physician's opinions and practice concerning end-of-life care.
Interval Cancers in Breast Cancer Screening: Comparison of Stage and Biological Characteristics with Screen-Detected Cancers or Incident Cancers in the Absence of Screening
Authors: Caumo Francesca , Vecchiato Francesca , Strabbioli Marzia , Zorzi Manuel , Baracco Susanna , Ciatto Stefano 
Published: February 2018

Aims and background To analyze stage distribution and biological features of interval cancers observed in Verona mammography screening compared to screen-detected cancers and “clinical” cancers occurring in the absence of screening, as provided by the Veneto Cancer Registry. Methods and study design Screen-detected cancers were identified in the screening archives. Interval cancers and clinical cancers (occurring in women never screened or not yet invited) were identified through the local cancer registry. Studied variables were age, stage, pathological pT and pN category, histological grading, estrogen and progesterone receptor status, and proliferation index (Ki67). Results We compared 95 interval cancers, 761 screen-detected cancers, and 1873 clinical cancer cases. Interval cancers had more aggressive features than screen-detected cancers, the difference being statistically significant for pT (P = 10–6), pN (P = 0.0003), grading (P = 0.007), estrogen receptors (P = 0.0006), and progesterone receptors (P = 0.00005), but not for Ki67 (P = 0.18). The features of interval cancers were not more aggressive than those of clinical cancers for pT (P = 0.84), pN (P = 0.33), grading (P = 0.61), estrogen receptors (P = 0.48), and progesterone receptors (P = 0.69), and were better for Ki67 (P = 0.02). In contrast, screen-detected cancers showed significantly better features than clinical cancers, for all studied variables: pT (P = 10–6), pN (P = 10–6), grading (P = 10–6), estrogen receptors (P = 10–5), progesterone receptors (P = 10–6), and Ki67 (P = 10–6). Conclusions Our findings are consistent with the length biased sampling hypothesis of interval cancers having a faster growth rate and a less favorable presentation than screen-detected cancers. Compared to clinical cancers, interval cancers had similar features, whereas screen-detected cancers had definitely more favorable features. This finding suggests, rather than a faster growth rate for interval cancers, a slower growth rate for screen-detected cancers, which, together with diagnostic anticipation, may explain a certain degree of overdiagnosis.
Radiotherapy Alone or with Concomitant Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer: Definitive Results of a Phase III Study with a Follow-Up Period of up to Ten Years
Authors: Grazia Ruo Redda Maria , Ragona Riccardo , Ricardi Umberto , Beltramo Giancarlo , Rampino Monica , Gabriele Pietro , Allis Simona , La Porta Maria Rosa , Moro Gregorio , Melano Antonella , Gabriele Anna Maria , Tessa Mariella , Fossati Piero , Orecchia Roberto 
Published: February 2018

Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial. Materials and methods From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin. Results The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04). Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.
Male Breast Lesions: Which Abnormalities Really Need Core Needle Biopsy?
Authors: Bazzocchi Massimo , Vianello Elena , Linda Anna , Londero Viviana , Zuiani Chiara 
Published: February 2018

Aims and background The purpose of the study was to identify clinical, mammographic or sonographic abnormalities of the male breast that require histological characterization. Methods and study design Clinical and imaging features of 31 male patients with breast lesions were retrospectively evaluated and correlated with core needle biopsy results. Results Seven of 31 (22.6%) lesions proved to be malignant and 24 of 31 (77.4%) benign, with a benign/malignant ratio of 4.4:1. In the case of a suspicious clinical presentation (firm mass, nipple retraction) and/or the presence of risk factors for breast cancer (BRCA2 mutation, previous breast cancer), core needle biopsy always demonstrated malignancy. All malignant lesions identified on mammography (4 of 7) appeared as a mass. Benign lesions detected on mammography (21 of 24) presented as an area of increased density (20 of 21) more frequently than a mass (1 of 21). Conclusions Sonographic features of cancers were not different from those of benign lesions. Clinical and mammographic findings, along with patient history, can be useful in the identification of male breast lesions that require core needle biopsy.
Influence of Recombinant Human Growth Hormone (rhGH) on Proliferation of Hepatocellular Carcinoma Cells with Positive and Negative Growth Hormone Receptorsin Vitro
Authors: Li Suyi , Hou Guiqing , Wang Ying , Su Xiangyu , Xue Lexun 
Published: February 2018

Aims and background Recombinant human growth hormone (rhGH) is increasingly used in the clinic because it promotes the synthesis of proteins. However, rhGH is able to increase malignant transformation and tumor recurrence. The aim of this study was to investigate the effects of rhGH on hepatocellular carcinoma (HCC) cells with positive and negative growth hormone receptors (GHR) in order to guide its clinical application. Methods and study design Cells of the human HCC cell lines Bel-7402 (GHR+) and SMMC-7721 (GHR-) as well as human umbilical vein endothelial cell line ECV304 cells in the exponential growth phase were harvested and divided into experimental and control groups. After the human HCC cells were cultured alone or co-cultured with ECV304 cells under the different treatments, cell cycle phase, proliferation index, and expression levels of vascular endothelial growth factor (VEGF) mRNA and proteins were determined. Results In the Bel-7402 GHR+ cells treated with rhGH, both the percentage of cell in G2-M phase and the proliferation index were higher than those of controls (P <0.05); this was not the case in the SMMC-7721 GHR- cells treated with rhGH (P >0.05). Although there was no difference in the cell doubling times between ECV304 cells co-incubated with Bel-7721 GHR- cells treated with rhGH and without rhGH, the doubling times of ECV304 cells co-incubated with Bel-7402 GHR+ cells, when treated with rhGH, were significantly shortened compared to those of controls (P <0.05). The cell doubling times of ECV304 cells co-incubated with Bel-7721 GHR- or Bel-7402 GHR+ cells which were treated with bevacizumab were longer than those of controls and of cells with rhGH (P <0.05). The VEGF mRNA and protein expression levels were higher in Bel-7402 GHR+ cells treated with different doses of rhGH than controls (P <0.05 or P <0.01); however, there was no statistically significant difference in the expression levels of VEGF mRNA and proteins between SMMC-7721 GHR- cells treated with rhGH and controls. Conclusions rhGH can induce VEGF secretion and stimulate proliferation of Bel-7402 GHR+ cells in vitro, but has little effect on the proliferation of SMMC-7721 GHR-cells, suggesting that rhGH may be applied safely to treatment for the catabolic state in patients with GHR-negative HCC.
Attenuated Salmonella Typhimurium Carrying TRAIL and VP3 Genes Inhibits the Growth of Gastric Cancer Cells in Vitro and in Vivo
Authors: Cao Hong-Dan , Yang Yin-Xue , Lü Lin , Liu Shao-Ning , Wang Pi-Long , Tao Xiao-Hong , Wang Li-Juan , Xiang Ting-Xiu 
Published: February 2018

Background Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and apoptin (VP3) of chicken anemia virus can selectively induce apoptosis in human tumor cell lines by two different pathways. Salmonella not only delivers functional genes to mammalian cells but also possesses antitumor activity and therefore could be adopted as a novel vector for anticancer therapy. Materials and methods TRAIL and VP3 genes were cloned into a pBudCE4.1 vector and delivered by attenuated Salmonella typhimurium into gastric cancer cells, and their expression and antitumor effects in nude mice were monitored by Western blot, fluorescence microscopy, MTT assay, TUNEL staining, and immunohistochemistry. Results pBud-VP3 and pBud-TRAIL-VP3 plasmids were constructed to express TRAIL and apoptin in gastric cancer cells, leading to inhibition of cancer cell proliferation after 48 hours (P <0.05). TRAIL and VP3 genes in pBudCE4.1 vector were also successfully delivered by attenuated S. typhimurium into gastric cancer cells in vivo, in which both TRAIL and apoptin were expressed. In vivo data indicated that S. typhimurium carring pBud-TRAIL-VP3 induced significant cell growth inhibition and tumor regression (P <0.05). Moreover, expression of TRAIL and apoptin increased the expression of caspase-3 and caspase-9, resulting in enhanced apoptosis. Conclusion Delivery of TRAIL and VP3 genes by attenuated S. typhimurium can significantly inhibit the growth of gastric cancer cells in vitro and in vivo.
Overexpression of Smac/DIABLO in Hep-2 Cell Line: Possible Role in Potentiating the Sensitivity of Chemotherapeutic Drugs
Authors: Lu Sumei , Xu Wei , Fan Zhaomin , Liu Wenwen , Li Jianfeng , Wang Haibo 
Published: February 2018

Aims and background The major obstacles for tumor chemotherapy are drug resistance and/or adverse effects on the host. In the present study we investigated the role of the second mitochondria-derived activator of caspase (Smac/DIABLO) in the action of cisplatin (DDP), 5-fluorouracil (5-FU), and the combination of both in Hep-2 cells. Methods and study design Hep-2 laryngeal carcinoma cells exposed to DDP, 5-FU and the combination of both were investigated. Cell viability was determined by MTT assay. Apoptosis was measured by Ho.33342 and PI double staining and flow cytometry. The expression of Smac/DIABLO at the mRNA and protein level was assayed by RT-PCR and Western blotting. Results DDP, 5-FU and the combination of both drugs reduced the cell survival rates in a concentration- and time-dependent manner. The drug combination not only exerted a stronger inhibitory effect, but also at a lower concentration compared with the single drugs. Apoptosis was concomitant in a caspase-dependent manner. The expression of Smac/DIABLO increased significantly at both mRNA and protein levels after cell exposure to the combination compared with single drugs. Conclusions Smac/DIABLO plays a pivotal role in attaining a synergistic effect in Hep-2 cells in response to this combined strategy.
Mesenteric Cyst: Report of a Case Resulting in Pseudomyxoma Peritonei
Authors: Zappa Luis , Sugarbaker Paul H 
Published: February 2018

Background A mesenteric cyst may have an embryonic, traumatic, neoplastic or infectious origin. In rare cases mesenteric cysts may contain neoplastic epithelium. A mesenteric cyst has not previously been recorded as the cause of pseudomyxoma peritonei. Methods A patient who developed widespread mucinous intraperitoneal tumor as a result of a ruptured mesenteric cyst is reported. A literature review of the clinical features, diagnosis, treatment, and prognosis of the mesenteric cyst is presented. Results This patient was treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Her recovery was uneventful and she remains well two years after treatment. Conclusion Mesenteric cyst is a rare cause of pseudomyxoma peritonei. The definite treatment of a ruptured neoplastic mesenteric cyst can, by analogy, be compared to the treatment for pseudomyxoma peritonei of appendiceal origin. The results of cytoreductive surgery with perioperative intraperitoneal chemotherapy are expected to be good.
Is there a Specific Magnetic Resonance Phenotype Characteristic of Hereditary Breast Cancer?
Authors: Trecate Giovanna , Manoukian Siranuosh , Suman Laura , Vergnaghi Daniele , Marchesini Monica , Agresti Roberto , Ferraris Cristina , Peissel Bernard , Scaramuzza Davide , Bergonzi Silvana 
Published: February 2018

Aims and background The aim of the study was to investigate the growth rate of inherited breast cancer, to analyze its T2 signal intensity besides kinetic and morphologic aspects, and to verify whether there is any correlation between magnetic resonance imaging phenotype and BRCA status. Methods Between June 2000 and September 2009, we enrolled 227 women at high genetic risk for breast cancer in a surveillance program, within a multicenter project of the Istituto Superiore di Sanità (Rome). Results Thirty-four cancers were detected among 31 subjects. One patient refused magnetic resonance imaging because of claustrophobia. Compared with sporadic disease, hereditary cancer showed some differences, in terms of biologic attitude and semeiotic patterns. These differences were mainly registered for magnetic resonance imaging, where the most frequent radiological variant was represented by the very high T2 signal intensity (73%). Moreover, the size of 8 of the neoplasms showed a significant increase in less than one year, 5 of them in less than 6 months. Six lesions were in BRCA1 patients and the remaining in BRCA2. Furthermore, cancers with a high growth rate also demonstrated a significant increment in T2 signal intensity. Conclusions Our results confirmed the high growth rate within BRCA-related breast cancers, especially for BRCA1 mutation carriers. In our experience, we found a specific imaging phenotype, represented by the high T2 signal intensity of hereditary breast cancer. To our knowledge, this is the first report that points out this new semeiotic parameter, which is usually typical of benign lesions. Considering the correlation between high growth rate and high T2 signal intensity, the former seems to be related to the absence of induction of a desmoplastic reaction that could somehow restrict cancer growth.
Metastatic Breast Cancer Shows Different Immunohistochemical Phenotype According to Metastatic Site
Authors: Koo Ja Seung , Jung Woohee , Jeong Joon 
Published: February 2018

Aims and background The study was performed to assess the status of immunohistochemical markers in primary and metastatic breast cancer and to determine the organ-specific characteristics of metastatic breast cancer. Methods Samples from 13 cases of paired primary and metastatic breast cancer and 34 cases of metastatic breast cancer were included. Results In the analysis of 13 cases of paired primary and metastatic breast cancer, estrogen receptor and progesterone receptor loss were noted in 1 (7.7%) case each. Androgen receptor loss and gain was noted in 2 (15.4%) cases, respectively. HER-2 showed 100% concordance with primary and metastatic tumors. C-kit was demonstrated in only 2 (15.4%) cases of metastatic breast cancer. In the analysis of 34 cases of metastatic breast cancer, when classified into triple-negative type (ER-, PR-, and HER-2-), HER-2+ type, and ER+ or PR+/HER-2- type according to immunohistochemical stain results, HER-2 type (66.7%) in brain metastasis and ER+ or PR+/HER-2- type (75.0%) in liver metastasis were predominant. Bone metastasis was composed of triple negative type (44.4%) and ER+ or PR+/HER-2- type (55.6%), and lung metastasis showed all of three subtypes in similar proportions. Conclusions Metastatic breast cancer shows different immunohistochemical phenotypes according to metastatic site (P = 0.048).
Glycosyl-Phosphatidylinositol-Anchored Interleukin-2 Expressed on Tumor-Derived Exosomes Induces Antitumor Immune Response in Vitro
Authors: Zhang Jiamo , Zhang Yao , Luo Chunli , Xia Yuguo , Chen Honglin , Wu Xiaohou 
Published: February 2018

Aims and background Tumor-derived exosomes (TEXs) have been considered as a new kind of cancer vaccine, but the antitumor effects are not satisfactory. In order to improve the efficacy of TEXs, we investigated whether exosomes derived from glycosyl-phosphatidylinositol-anchored interleukin 2 (GPI-IL-2) gene-modified bladder cancer cells can increase the antitumor effects. Methods and study design We transfected melanoma antigen-1 (MAGE-1)-expressing T24 tumor cells with a plasmid encoding GPI-IL-2 and prepared the TEXs. Exosomes expressing GPI-IL-2 were characterized by electron microscope and Western blot analysis. Results IL-2 was present on the cell surface in the GPI-anchored form as demonstrated by fluorescent microscope and ELISA analyses. Exosomes expressing GPI-IL-2 naturally contained bioactive GPI-IL-2 and tumor-associated antigen MAGE-1. Moreover, exosomes expressing GPI-IL-2-pulsed dendritic cells could induce the proliferation of T cells and the antigen-specific cytotoxic T-lymphocyte immune response more efficiently. Conclusions GPI-IL-2 gene-modified tumor cells can make the TEXs contain GPI-IL-2, resulting in increased antitumor effects. Our study provided a feasible approach for exosome-based tumor immunotherapy.
Successful Treatment with the Fully Human Antibody Panitumumab after a Severe Infusion Reaction with Cetuximab
Authors: Brugger Wolfram 
Published: February 2018

Aims and background There are only limited data on the safety and efficacy of panitumumab in patients who experienced severe infusion reactions during cetuximab antibody therapy. Case report We report the case of a 69-year-old woman with chemotherapy-refractory metastatic colorectal cancer who received single-agent cetuximab treatment but experienced a severe reaction during the first infusion, despite premedication with corticosteroids/antihistamines. Cetuximab was discontinued and treatment with panitumumab initiated approximately 14 days later (without premedication); no infusion reactions occurred and there was a rapid improvement in her general condition. She experienced a partial response that was sustained for 7 months before progression. Conclusions This case supports the use of panitumumab in patients with chemotherapy-refractory metastatic colorectal cancer and suggests that panitumumab may be used in some patients with prior infusion reactions to cetuximab.
EGFR Polysomy in Squamous Cell Carcinoma of the Thyroid. Report of Two Cases and Review of the Literature
Authors: Bonetti Luca Reggiani , Lupi Massimo , Trani Margherita , Trani Nicoletta , Sartori Giuliana , Schirosi Laura , Bettelli Stefania , Zanelli Giuliana , Maccio Livia , Maiorana Antonio 
Published: February 2018

Aims and background Primary squamous cell carcinoma of the thyroid gland (PSCCT) is an uncommon malignancy characterized by a poor prognosis. A radical surgical approach combined with radiotherapy or chemotherapy is the generally accepted treatment for this tumor. The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor modulating the cell proliferation and biological progression of many human epithelial tumors. The EGFR overexpression in PSCCT suggests an additional therapeutic option for the treatment of this tumor. Methods and study design The clinicopathological features and immunohistochemical profiles of two cases of primary squamous cell carcinoma of the thyroid in a 66-year-old and an 83-year-old woman are presented. EGFR status was valued in both cases. Results Overexpression of EGFR protein was detected in 50% and 75% of the tumor cell membranes. EGRF gene polysomy was detected in both tumors. Conclusions Pharmaceuticals targeting EGFR may help to provide the rationale for an additional, novel therapeutic option for this rare tumor, especially when other therapeutic options have been exhausted.