bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Value of Plasma D-Dimer Levels in Lung Carcinoma
Authors: Komurcuoglu Berna , Ulusoy Sadik , Gayaf Mine , Guler Arzu , Ozden Emel 
Published: February 2018

Aims and Backgrounds Plasma concentrations of several proteases of the coagulation system have been shown to predict prognosis in malignancy. The study was aimed to investigate the prognostic value of plasma D-dimer concentrations and some other coagulation factors in lung cancer. Methods Between 2004 and 2008, 100 newly diagnosed lung cancer patients and 25 healthy individuals serving as the control group were evaluated. The patients had no history of coagulation system disorders or anticoagulant therapy. Plasma D-dimer concentrations, prothrombin time, activated partial thromboplastin time, international normalized ratio and blood counts of the patients were obtained. Patient age, lung cancer stage, tumor histology, therapy modalities (surgery, chemotherapy and radiotherapy), therapy outcomes and survival durations of the patients were determined. Results The median age of the patients (86 males/14 females) was 67 years, and 15% had stage 2, 26% had stage 3A, 24% had stage 3B, and 35% had stage 4 disease. Histologic subtypes were non-small cell carcinoma (87%) and small cell carcinoma (13%). The median D-dimer level of the patients was 1250 ng/dl, which was significantly higher than that of the control group. Survival duration was significantly higher in patients with low D-dimer levels (P <0.05). D-dimer plasma levels predicted survival independently of the clinical stage of disease, histologic tumor type and performance status of the patient (HR = 5.1; 95% confidence interval, 1.015–1.19, P = 0.013). Plasma D-dimer level was significantly higher in metastatic disease (P <0.01). Conclusions The results suggest that D-dimer plasma levels might be useful to predict the clinical outcome and survival of patients with lung cancer.
Simultaneously Targeting Bcl-2 and Akt Pathways Reverses Resistance of Nasopharyngeal Carcinoma to TRAIL Synergistically
Authors: Li Shi-Sheng , Tang Qing-Lai , Wang Shu-hui , Chen Yue-Hong , Liu Jia-Jia , Yang Xin-Ming 
Published: February 2018

Aims and Background Despite progress in treatment techniques, the five-year survival rate of nasopharyngeal carcinoma (NPC) is disappointing. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can selectively induce apoptosis in most tumor cells while sparing normal cells. Given the antiapoptotic functions of Bcl-2 and Akt, we examined the effects of targeting these pathways alone or simultaneously on TRAIL apoptosis in NPC cell lines. Methods and Study Design We first tested the cytotoxic effect of TRAIL and the expression of death receptors, Bcl-2, Akt, and p-Akt on four NPC cell lines by MTT and Western blotting, respectively. Small interfering RNAs (siRNAs) targeting Bcl-2 and PI3–K inhibitor (LY294002) were used alone or combined with TRAIL in the cell lines and cytotoxicity was examined by MTT. Apoptosis rates, mitochondrial transmembrane potential, and apoptotic pathway signals were detected by flow cytometric analysis, DiOC6(3) assays, and Western blotting after the various combination treatments on CNE-2, the cell line that was most resistant to TRAIL. Results Although no direct correlation between the sensitivity to TRAIL and the relative expression levels of Bcl-2 and activated Akt was found in the NPC cell lines examined, siRNA mediated the downregulation of Bcl-2 and LY294002-induced inactivation of Akt, increasing the sensitivity of all examined NPC cell lines to TRAIL. Synergistic enhancement of TRAIL-mediated cytotoxicity was observed in combination treatment of Bcl-2 siRNA and LY294002 compared to cells treated with each treatment alone. The synergistic effects were mediated through increased apoptotic signaling of the mitochondrial pathway, as was evident from the more increased mitochondrial depolarization, activation of caspase-9 and caspase-3, and suppression of XIAP. Conclusions This study provides proof of principle that TRAIL combined with simultaneously targeting the Bcl-2 and Akt signaling pathways may have potential as a novel future treatment strategy for NPC.
Radiotherapy in Italy for Non-Small Cell Lung Cancer: Patterns of Care Survey
Authors: Ramella Sara , Maranzano Ernesto , Frata Paolo , Mantovani Cristina , Lazzari Grazia , Menichelli Claudia , Navarria Piera , Pergolizzi Stefano , Salvi Fabrizio 
Published: February 2018

Aims and Background Surveys in clinical practice are useful to find how current clinical approaches follow recommendations from evidence-based medicine, to stimulate discussion in a multidisciplinary team, and to hypothesize collaborative multi-centric trials. To assess management strategies for the use of radiotherapy in the treatment of lung cancer in Italy, in 2009, the Italian Society of Radiation Oncology Lung Cancer Study Group proposed the survey to all Italian radiation oncology institutions. Results were compared with literature data and international reports. Study Design Questionnaires on patterns of care of non-small cell lung cancer were sent to radiation oncology centers active at June 2009 and evaluated data recorded in 2008. Results A total of 65 of 143 Italian centers responded to the questionnaire. The responding centers reflect the distribution of radiotherapy centers throughout the country. Of the treated patients, 55.2% were stage III, and most cases had a good performance status. FDG-PET was routinely used by 51% of centers for diagnostic and contouring phases. Postoperative radiotherapy was prescribed to pN1 and pN2 patients in 42.2% and 98.5%, respectively. The possible use of neo-adjuvant concomitant chemoradiation was declared by 70% of responders. A sequential chemoradiation approach was actually used in 43.6% of cases, induction chemotherapy followed by concomitant radiochemotherapy in 42.4%, and upfront concomitant radiochemotherapy in only 14%. In 53% of the institutions, patients have a clinical examination by a radiation oncologist only after the beginning of chemotherapy and in 82.4% of cases they have already received 2–4 cycles of chemotherapy. Most of the institutions exclude elective nodal irradiation from routine application. Total dose and fractionation in adjuvant, neoadjuvant, curative and palliative settings confirm literature data. There were significant differences in treatment planning constraints applied for lung, esophageal and cardiac tissues. Of the responding centers, 41% had stereotactic therapy for primary inoperable lung cancer and for metastatic lesions. Conclusions In Italy, daily practice differs in some ways from the evidence supported by the results of meta-analyses/clinical trials as regards concurrent chemoradiation approaches. It could be postulated that there is an urgent need for groups that collaborate with the other societies involved in the treatment of non-small cell lung cancer in order to offer the best therapy to our patients.
A Feasibility Study of Neo-Adjuvant Low-Dose Fractionated Radiotherapy with Two Different Concurrent Anthracycline-Docetaxel Schedules in Stage IIA/B-IIIA Breast Cancer
Authors: Nardone Luigia , Valentini Vincenzo , Marino Lorenza , De Santis Maria Carmen , Terribile Daniela , Franceschini Gianluca , Balducci Mario , Mantini Giovanna , Mattiucci Giancarlo , Mulè Antonino , Belli Paolo , Masetti Riccardo 
Published: February 2018

Aims and Background The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination with two anthracycline-docetaxel regimens, in breast cancer treatment. Materials and Methods Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy (0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8–6 cycles) with concomitant neoadjuvant chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and expressed as tumor regression grade. Results Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant chemotherapy. No grade 3–4 breast toxicity was observed. Five patients had a clinical complete response. Seven patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment. Conclusions Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity. The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher histological response rates compared to the sequential application of the same two drugs.
Morbidity of Selective Lymph Node Biopsy for Melanoma: Meta-Analysis of Complications
Authors: Cigna Emanuele , Gradilone Angela , Ribuffo Diego , Gazzaniga Paola , Fino Pasquale , Sorvillo Valentina , Scuderi Nicolò 
Published: February 2018

Background and Aim Intraoperative lymphatic mapping and selective lymph node biopsy is accepted worldwide as the standard procedure for staging regional lymph nodes of 1–4 mm thick melanomas, as well as for other neoplasms. Although it is often stated that selective lymph node biopsy is a minimally invasive procedure associated with few complications, few data exist concerning the morbidity associated with the procedure. The present analysis was performed to evaluate the morbidity associated with selective lymph node biopsy in a long-term follow-up. Materials and Methods The study provides a review of 437 selective lymph node biopsies on 269 patients, operated on between the 1994 and the 2009, for the lymph node biopsy of head and neck, groin, axilla, upper and lower limbs and nodal basins. Patients’ history and follow-up were reviewed for 2 weeks after surgery, every 3 months for the first 2 years, every 4 months during the third year, and every 6 months subsequently, and postoperative morbidity was evaluated. Results After sentinel node biopsy, 14 patients developed one of the following complications: hematoma, 1 case (0.30%); lymphedema, 1 case (0.30%); seroma, 2 cases (0.61%); wound infection, 6 cases (1.83%); keloid scar, 2 cases (0.61%); and postoperative pain, 2 cases (0.61%). The total complication rate was 4.26%. Conclusions Selective lymph node biopsy for melanoma, as for other tumors, in respect to radical lymphadenectomy, is not a complications-free procedure but is usually not severe.
On the Diagnostic Accuracy of Stereotactic Vacuum-Assisted Biopsy of Nonpalpable Breast Abnormalities. Results in a Consecutive Series of 769 Procedures Performed at the Trento Department of Breast Diagnosis
Authors: Bernardi Daniela , Borsato Giuliana , Pellegrini Marco , Tuttobene Paolina , Fanto’ Carmine , Valentini Marvi , Aldovini Daniela , Ciatto Stefano 
Published: February 2018

Aims and Background To assess the diagnostic accuracy of stereotactic vacuum-assisted biopsy of nonpalpable breast lesions. Methods and Study Design 769 consecutive vacuum-assisted biopsy procedures were retrospectively reviewed. Positive predictive value for carcinoma (B5) at vacuum-assisted biopsy was assessed on the overall series and by age, lesion morphology and size, degree of suspicion and calendar period. The accuracy of vacuum-assisted biopsy was based on surgical histology or follow-up (no change at 12 months was assumed as negative). Results Lesions were depicted as isolated microcalcifications, opacity + microcalcifications, or opacity in 716 (93.1%), 28 (3.6%), or 25 (3.2%) cases, respectively. Vacuum-assisted biopsy was negative (B1 = 63; B2 = 319) in 382 (49.7%), borderline (B3) in 142 (18.5%), suspicious (B4) in 2 (0.3%), and positive (B5) in 243 (31.6%) cases (in situ = 185, 24.1%), invasive = 58 (7.5%)), respectively. Age (χ2df3 = 19.50; P <0.002), size (χ2df4 = 51.02; P = 10-6) and degree of suspicion (χ2df2 = 146.68; P = 10-6) were associated with a B5 outcome, no significant association was evident for morphology (χ2df2 = 0,47; P <0.78), whereas calendar period had a moderate but significant inverse association (χ2df2 = 6.12; P <0.04). The positive predictive value for surgically confirmed carcinoma (in situ or invasive) was 0% for B1, 0.7% for B2, 12.3% for B3, 100% for B4, 92.7% for in situ B5, and 94.6% for invasive B5. Conversion from in situ B5 to invasive was 12.3% and was insignificantly associated with size (χ2df2 = 0.95; P = 0.62) and histology grade (χ2df2 = 3.64; P = 0.16). Down-grading of vacuum-assisted biopsy lesions to a less severe histology occurred in 13 (7.2%) in situ and in 16 (28.6%) invasive carcinomas. B3 cases upgrading to more severe lesions was 0%, 4.5% or 16.0% in the presence of no, mild, or severe atypia. Conclusions The study confirmed a good performance of vacuum-assisted biopsy, possibly influenced by the local scenario (e.g., radiologist's and pathologist's interobserver variability and sampling modality). Conflicting results with the literature may have local explanations rather than being due to inadequate performance.
High Lapatinib Plasma Levels in Breast Cancer Patients: Risk or Benefit?
Authors: Cizkova Magdalena , Bouchalova Katerina , Friedecky David , Polynkova Adriana , Janostakova Anna , Radova Lenka , Cwiertka Karel , Trojanec Radek , Zezulova Michaela , Zlevorova Miloslava , Hajduch Marian , Melichar Bohuslav 
Published: February 2018

Aims and Background Lapatinib is a tyrosine kinase inhibitor targeting epidermal growth factor receptors 1 (EGFR/HER1) and 2 (HER2) used in the treatment of patients with HER2-positive breast cancer. The aim of the present study was to determine lapatinib plasma levels in breast cancer patients treated with lapatinib plus capecitabine. Patients and Methods We assessed lapatinib plasma levels in blood samples from 21 breast cancer patients treated with lapatinib plus capecitabine using the standard regimen in an expanded access program. Liquid chromatography tandem mass spectrometry was used for measuring lapatinib plasma concentrations. The validated method was applied for measurement of 55 plasma samples. Results The median lapatinib plasma level was 5.09 μg/mL, with large interindividual differences. Patients of lower weight tended to have higher lapatinib plasma levels (Spearman correlation coefficient R = −0.435, P = 0.055). One patient's lapatinib plasma levels were markedly higher than those of the others, with a median level of 11.25 μg/mL and repeatedly exceeding 7.80 μg/mL. The treatment was terminated after 8 months when hyperbilirubinemia occurred. Conclusions The lapatinib plasma levels reported here are twice as high as the clinically effective steady-state geometric mean maximum concentration. We conclude that increased lapatinib body levels occur when patients are in a nonfasting state at the time of drug intake and when lapatinib doses are not adjusted to low body weight or weight loss during treatment. In Europe, dose adjustments are not recommended in the case of hepatic function impairment. Thus, attention should be paid to changes in liver function test results in clinical practice, especially in patients of small stature and weight, given the risk of high plasma concentrations. Prospective lapatinib plasma level assessment in treated patients might be useful to confirm or refute the possible correlation of high lapatinib plasma levels with hepatic and/or other toxicities.
Radiation Therapy for Pituitary Metastasis: Report of Four Cases
Authors: Turaka Aruna , Parsons Rosaleen B , Buyyounouski Mark K 
Published: February 2018

Aims and Background To report the clinical outcomes of four patients with pituitary metastases treated with radiotherapy. Methods Retrospective chart review of four cases. Results The mean age of the patients was 66 years; two were women and two were men. The mean duration of symptoms at initial presentation of the primary tumor was 2.25 months. The location of the primary tumor was the breast in one case and the lung in three. Magnetic resonance imaging of the brain revealed sellar masses in all cases. The mean interval between the primary tumor diagnosis and the development of pituitary metastases was 22.5 months. The metastases were treated with radiation therapy (palliative/stereotactic/intensity modulated) at a mean dose of 3219 cGy. At the last follow-up, three patients were dead and one was alive. Conclusions Treatment with three-dimensional conformal radiotherapy or stereotactic radiotherapy is a suitable non-surgical option for patients with pituitary metastases.
Asbestos and SV40 in Malignant Pleural Mesothelioma from a Hyperendemic Area of North-Eastern Italy
Authors: Comar Manola , Zanotta Nunzia , Pesel Giuliano , Visconti Patrizia , Maestri Iva , Rinaldi Rosa , Crovella Sergio , Cortale Maurizio , De Zotti Renata , Bovenzi Massimo 
Published: February 2018

Aims and background Malignant mesothelioma is a fatal cancer of increasing incidence in north-eastern Italy. Together with asbestos, the polyomavirus SV40 was hypothesized to contribute to the onset of malignant mesothelioma. To investigate the putative role of SV40 in the individual susceptibility to asbestos-induced malignant mesothelioma, we conducted a molecular epidemiological study on a series of malignant mesothelioma patients from an area in north-eastern Italy hyperendemic for malignant pleural mesothelioma. Methods and study design We collected 63 mesothelioma samples from incidence cases of patients diagnosed with malignant pleural mesothelioma in the period 2009–2010. DNA was extracted from patients’ tissue biopsies using the BioRobot EZ1 Qiagen workstation. SV40 sequence detection and quantification was performed by specific real time PCR. The 74.6% of the 63 enrolled patients had a history of asbestos exposure. The epithelioid histotype was more prevalent in males (64.0%) and the mixed in females (61.5%) who showed significantly higher cancer co-morbidity (46.1% vs 12%, P = 0.005). SV40 was detected in 22% of MM tumors, with a low viral load. In SV40-positive patients, a threefold increased risk of asbestos exposure was observed, more evident in females (OR 4.32) than in males (OR 1.20). Conclusions Our findings indicate that a high prevalence of SV40 was present in malignant mesothelioma incident cases from an area hyperendemic for malignant mesothelioma in north-eastern Italy. Although asbestos is considered the main risk factor in malignant mesothelioma onset, a role for SV40 could be hypothesized.
Response to Concurrent Chemoradiotherapy as a Prognostic Marker in Elderly Patients with Locally Advanced Esophageal Cancer
Authors: Go Se-Il , Lee Won Sup , Kang Myung Hee , Song Haa-Na , Kim Moon Jin , Lee Min Jeong , Kim Hoon-Gu , Lee Gyeong Won , Kang Jung Hun , Lee Jeong-Hee , Kang Ki Mun , Jeon Kyung-Nyeo , Cho Jae Min , Jung Woon Tae , Ko Gyung Hyuck 
Published: February 2018

Aims and background Little is known about chemoradiotherapy in elderly patients with locally advanced esophageal cancer. We compared the efficacy and toxicity of chemoradiotherapy in elderly and non-elderly patients with locally advanced esophageal cancer and determined the variables affecting the treatment outcome in the elderly patients with locally advanced esophageal cancer who had received chemoradiotherapy. Methods Fifty-seven elderly patients (age ≥65 years) and 30 non-elderly patients (age <65 years) were reviewed retrospectively. Results The median age of the elderly group was 69 years and in the non-elderly group, 56.5 years. Although treatment compliance appeared to be poor, the response rate and median survival were similar in both the groups (elderly versus non-elderly; 84.4% vs 87.5%, and 11.2 months vs11.3 months) and so were G3/4 hematologic and non-hematologic toxicities. The treatment-related mortality of the elderly patients appeared to be higher than that of the non-elderly group (7.0% vs 3.3%), but did not reach statistical significance. In prognostic factor analysis, a major response to chemoradiotherapy was a good prognostic indicator in the elderly group (response versus non-response; median overall survival times of 19.5 vs 5.4 months, respectively, P <0.001). Conclusions The study suggests that chemoradiotherapy for locally advanced esophageal cancer in elderly patients, even though treatment compliance appears to be poor, is as safe and effective as in non-elderly patients and that the response to chemoradiotherapy is related to prognosis in elderly patients.
Palonosetron: An Evidence-Based Choice in Prevention of Nausea and Vomiting Induced by Moderately Emetogenic Chemotherapy
Authors: Celio Luigi , Agustoni Francesco , Testa Isabella , Dotti Katia , de Braud Filippo 
Published: February 2018

Aims and background In 2003, the second-generation, 5-HT3 receptor antagonist (5-HT3 RA) palonosetron was approved by the FDA for the prevention of nausea and vomiting associated with highly and moderately emetogenic chemotherapy. We reviewed the current knowledge on the role of palonosetron against acute and delayed emesis in patients with solid tumors undergoing single-day moderately emetogenic chemotherapy regimens. Methods A literature review in PubMed was performed to update currently available preclinical and clinical evidence on palonosetron, prioritizing randomized clinical trials. Results The distinct pharmacology of palonosetron provides a rationale behind the improved efficacy observed with the drug in prevention of delayed symptoms. This may be explained by allosteric binding properties and by palonosetron-triggered receptor internalization, which result in prolonged inhibition of the 5-HT3 receptor function. Very recent pharmacology experiments have also suggested that palonosetron would be able to differentially inhibit 5-HT3/neurokinin 1 (NK-1) receptor signaling cross-talk. In two recent meta-analyses, palonosetron was shown to be more effective than other available 5-HT3 RAs in preventing acute and delayed nausea and vomiting for both HEC and MEC. Recent findings also suggest that a single-day regimen of palonosetron plus dexamethasone (both drugs administered intravenously) may provide a reasonable therapeutic alternative to reduce the total dexamethasone dose administered in patients undergoing moderately emetogenic chemotherapy. Conclusions On the basis of accumulating data, the evidence-based international guidelines devised from the major organizations have been recently updated to recommend the use of palonosetron plus 3-day dexamethasone for the optimal prevention of nausea and vomiting due to moderately emetogenic chemotherapy. There is still a need to investigate the efficacy of palonosetron in combination with an NK-1 receptor antagonist and dexamethasone in well-designed randomized trials.