bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exclusion Criteria vs Reality: Dual BRAF/MEK Inhibition and Radiotherapy in a Patient with Melanoma Metastatic to the Brain and ECOG 3
Authors: Márquez-Rodas Iván , Avilés-Izquierdo Jose-Antonio , Parra Verónica , Álvarez-González Ana , Borrego Pedro , Fernández-García Pilar , Guzmán-de-Villoria Juan-Adan , Jerez Yolanda , Martin Miguel 
Published: October 2015

Background Prognosis of metastatic melanoma is changing due to advances in immunotherapy and targeted therapy. However, management of patients with brain metastases in day-to-day practice continues to be a challenge. Case Report We describe a 40-year-old woman diagnosed with symptomatic brain metastases from cutaneous melanoma and Eastern Cooperative Oncology Group 3. She was treated, off label, with BRAF inhibitor (dabrafenib) + MEK inhibitor (trametinib) and radiotherapy. There was significant, long-lasting, response (17 months), no clinically relevant toxicity, and clear improvement in quality of life. Conclusions This case is an example of real-life application of advances in targeted therapy.
Tumor-Associated Trypsin Inhibitor in Patients with Endometrial Cancer
Authors: Kozakiewicz Barbara , Chądzyńska Małgorzata , Dmoch-Gajzlerska Ewa , Stefaniak Małgorzata 
Published: October 2015

Aim The aim of the study was to look for prognostic factors of metastasis or recurrence in patients with endometrial cancer. Methods Tumor-associated trypsin inhibitor (TATI) concentrations were measured in serum of 317 patients with endometrial cancer. The assay was done 7 times in each patient, from the moment of diagnosis until the start of follow-up after the completion of treatment. Observation of patients after treatment lasted from 0 to 16 years. Results The TATI levels in patients with adverse prognostic factors accumulated in the first 3 assays and then decreased to zero. Mean TATI concentrations were significantly higher in patients with clinically advanced disease (stage IIIB) than patients at stage I (Kruskal-Wallis p = 0.0446). An increase in the concentration by more than 10.6% in the first 3 assays was significantly correlated with disease relapse (Mann-Whitney Z = −6.06653, p = 0.00000) and local or distant recurrence (Mann-Whitney Z = −4.97475, p = 0.000001). A significant increase in the TATI level in the first 3 tests also occurred in patients who died during the study period (Kruskal Wallis p<0.001). In our series of patients with endometrial cancer, TATI proved to be a sensitive indicator of disease recurrence and distant metastasis, with a sensitivity of 84.4% and 75.7%, respectively. Conclusions TATI seems to behave as a prognostic factor in certain subgroups of patients with endometrial cancer.
Reducing Heart dose during Left Breast Cancer Radiotherapy: Comparison among 3 Radiation Techniques
Authors: D’Agostino Giuseppe R. , Diletto Barbara , Mantini Giovanna , Nardone Luigia , Mattiucci Gian Carlo , Catucci Francesco , Canna Roberta , Martino Antonella , Azario Luigi , Valentini Vincenzo 
Published: October 2015

Purpose Breast cancer survivors have a high risk of cardiac death as a consequence of heart irradiation during left breast tangential radiotherapy (RT). This study compares the cardiac dose delivered by standard 3D conformal tangential RT (CRT) to that delivered by prospective-gating RT (PGRT) or 5-field intensity-modulated RT (IMRT). Methods Patients with early left breast cancer, referred for adjuvant RT to our institution, were enrolled in this study. For each patient, 2 simulation computed tomography scans were acquired: the first during free breathing, and the second on prospective gating during deep inspiration breath-hold. The scans were monitored by the Varian RPM™ respiratory gating system. For each patient, 3 treatment plans were performed: a 3D-CRT and an IMRT plan, each based on the free-breathing scan, and a PGRT plan, based on the deep inspiration breath-hold scan. Dose-volume histograms were compared by means of the Friedman test. Results The median mean heart dose was 3 Gy (range 0.9-7.3 Gy) in the CRT plans, 1.9 Gy (range 0.5-3.6 Gy) in the PGRT plans, and 4.5 Gy (range 1.1-10.5 Gy) in the IMRT plans (p = 0.001). The mean heart V25 was 1.2% (range 0%-9.7%), 0% (range 0%-2.0%), and 0.2% (range 0%-7.3%) for CRT, PGRT, and IMRT plans, respectively (p<0.001). Conclusions Prospective-gating RT to the left breast offered the best protection of heart and lung, as well as a lower irradiation of the contralateral breast, compared to CRT or IMRT.
Surgical Approach to Primary Tumors of the Chest Wall in Children and Adolescents: 30 Years of Mono-Institutional Experience
Authors: Girelli Lara , Luksch Roberto , Podda Marta G. , Meazza Cristina , Puma Nadia , Scanagatta Paolo , Pecori Emilia , Diletto Barbara , Galeone Carlotta , Massimino Maura , Pastorino Ugo 
Published: October 2015

Aims and background Chest wall reconstruction after surgical resection for malignancies in children is a challenge for surgeons because of growth-related complications. The aim of this study is to analyze the surgical treatment and outcomes of 30 pediatric and adolescent patients treated at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, over a 30-year period. Methods Pediatric patients undergoing chest wall resection were retrospectively reviewed and selected for malignant primary tumor. Endpoints were survival, recurrences, and long-term results. We also reported the use of the innovative rib-like technique in 2 young patients. Results Twenty-one patients were male. Median age was 13.7 years. Eleven patients (37%) presented with a chest wall mass. Twenty-six (87%) had Ewing sarcoma family tumors. Twenty-eight (94%) received neoadjuvant chemotherapy after histologic diagnosis. One rib was resected in 13 cases; 2 or 3 contiguous ribs in 8 cases. No postoperative mortality was observed and the complication rate was 40%. Overall survival was 85.2% (95% confidence interval [CI] 65.2%-94.2%) at 5 and 10 years. Relapse occurred in 7 patients. The 5-year disease-free survival rate was 82% (95% CI 62%-92%). Conclusions Long-term survival is achievable for chest wall tumors in a high-volume referral center where a multimodal treatment should be set to reach the best result. As advances in medical treatment have increased survival, surgical techniques must ensure a lasting functional result. When refining the reconstruction techniques, such as the rib-like approach, it is necessary to expand the options of curative surgery for young patients.
Osteoblastic Progression during EGFR Tyrosine Kinase Inhibitor Therapy in Mutated Non-small Cell Lung Cancer: A Potential Blunder
Authors: Bersanelli Melissa , Bini Paola , Rabaiotti Enrico , Facchinetti Francesco , De Filippo Massimo , Bortesi Beatrice , Buti Sebastiano , Tiseo Marcello 
Published: October 2015

Aims and background Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI). Methods We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment. Results Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction. Conclusions The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.
Impact of Aspirin on Clinical Outcomes for African American Men with Prostate Cancer Undergoing Radiation
Authors: Osborn Virginia Wedell , Chen Shan-Chin , Weiner Joseph , Schwartz David , Schreiber David 
Published: October 2015

Aims and background Preclinical and clinical studies have suggested that aspirin (ASA) may exhibit antineoplastic activity. Particularly in prostate cancer, several reports have suggested that ASA plays a role in improved outcomes. Therefore, we studied the role of ASA in a uniquely African American population, which is known to harbor more aggressive and biologically different disease compared to the general population. Methods We identified 289 African American men with prostate cancer who were treated with definitive radiation therapy to a dose of ≥7560 cGy. The median follow-up was 76 months. Kaplan-Meier analysis was used to analyze biochemical failure-free survival (bFFS), distant progression-free survival (DMPFS), and prostate cancer-specific survival (PCSS). Multivariate Cox regression was used to analyze the impact of covariates on all endpoints. Results There were 147 men who were ASA+ and 142 who were ASA-. The 7-year bFFS was 80.9% for ASA+ men and 70.3% for ASA− men (p = 0.03). On multivariate analysis, ASA use was associated with a significant reduction in biochemical recurrences (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.34-0.93, p = 0.03). The 7-year DMPFS was 98.4% for ASA+ and 91.8% for ASA− men (p = 0.04). On multivariate analysis, ASA use was associated with a decreased risk of distant metastases (HR 0.23, 95% CI 0.06-0.91, p = 0.04). The 7-year PCSS was 99.3% for ASA+ and 96.9% for ASA− men (p = 0.07). Conclusions In this study, ASA use was associated with improved biochemical outcomes and reduced distant metastases. This indicates that ASA appears to play an important antineoplastic role in African American men.
Misregulation of the Dependence Receptor DCC and its Upstream lincRNA, LOC100287225, in Colorectal Cancer
Authors: Kazemzadeh Mina , Safaralizadeh Reza , feizi Mohammad Ali HosseinPour , Somi Mohammad Hossein , Shokoohi Behrooz 
Published: October 2015

Background Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. Methods We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. Results The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. Conclusions Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.
Management of Advanced Pancreatic Cancer in Daily Clinical Practice
Authors: Giuliani Jacopo , Piacentini Paolo , Bonetti Andrea 
Published: October 2015

Purpose The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. Methods A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. Results We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Conclusions Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.
Mass-Forming Extramedullary Hematopoiesis in Multiple Myeloma: 18F-FDG PET/CT is useful in Excluding Extramedullary Myeloma Involvement
Authors: Seo Minjung , Kim Hawk , Jo Jae-Cheol , Choi Yunsuk , Cha Hee Jeong , Lim Ji-Hun , Park Seol Hoon 
Published: October 2015

Aims and background Extramedullary hematopoiesis (EMH), a benign condition, is usually observed in patients with hematologic disorders. We report the first case of mass-forming EMH detected on a 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan in a patient with multiple myeloma (MM). Methods A 58-year-old woman underwent workup for bicytopenia, and was diagnosed with MM based on the results of bone marrow aspiration and serum protein electrophoresis. An 18F-FDG PET/CT scan revealed a paravertebral mass with mild FDG avidity, suggesting a tumorous condition. Results Biopsy was performed to exclude malignancy and the mass was eventually confirmed as EMH. Conclusions Differential diagnosis of a mildly FDG-avid paravertebral mass in MM should include EMH.
Factors Influencing Young Urologists’ Productivity and Academic Career Choice
Authors: Resorlu Berkan , Silay Mesrur Selcuk , Onem Kadir , Bayrak Omer , Sonbahar Adil Emrah , Acar Omer , Ergun Osman , Celik Orcun , Tefik Tzevat , Firdolas Fatih , Tandogdu Zafer 
Published: October 2015

Objective The objective of this study is to identify the variables that affect young urologists’ productivity and academic career choice. Patients and Methods We have conducted an internet-based national survey for urologists randomly sampled from the database of Turkish Urological Association and 110 physicians completed this survey. Participants were asked to answer three-page questionnaire including 37 questions, which takes around 5 min to complete. Questionnaire was consisting of four main sections: ‘demography’, ‘education’, ‘working conditions’ and ‘quality of life’. Results Increased dedicated research time, being interested in an academic career, being Fellow of the European Board of Urology (FEBU), having English proficiency, and greater numbers of manuscript publication during residency were associated with increased productivity after residency (p = 0.001, p = 0.028, p = 0.046, p<0.001 and p<0.001, respectively). The remaining variables including age at marriage, age at having a child, monthly salary, length of residency, having a mentor or role model during residency showed no significant relationship with manuscript publications. Twenty-nine physicians (26.4%) stated that they had once been interested in their residency but were no longer interested in academic urology. Reasons for this loss of academic interest included lack of effective mentor or role model (27.2%), bureaucracy (17%), financial issues (13.6%), mandatory rule to work in public hospitals (18.2%) or military hospitals (9%) and language problems (21.6%). Conclusions Our data indicate that increased time spent for research, being interested in an academic career, being an FEBU, having English proficiency, and greater publication during residency were associated with increased numbers of publications and academic career choice.
Chronic, Nonspecific, Postinfectious, Retroperitoneal Fibrosis and Ureteral Obstruction
Authors: Territo Angelo , Micali Salvatore , Manenti Antonio , Martorana Eugenio , Pirola Giacomo Maria , Bianchi Giampaolo 
Published: October 2015

Introduction Two cases of severe ureteral obstruction following nonspecific, postinfectious, chronic retroperitoneal fibrosis are described, which both originated by a primitive intestinal pathology. Patients This complication was observed in two women: first, 65 years old, submitted for ulcerative colitis to a total proctocolectomy, with ileo-pouch-anal anastomosis, complicated by an anastomotic fistula; and second, 66 years old, operated with an extended left hemicolectomy, for an adenocarcinoma of the recto-sigmoid colon complicated with a vaginal fistula. In these cases, computerized tomography demonstrated a unilateral hydronephrosis, secondary to a complete obstruction of the ureter; a subsequent nephro-ureterectomy became necessary. Histology demonstrated nonspecific inflammatory lesions. Discussions Postinfectious, chronic inflammation of the retroperitoneum acts on the ureteral and peri-ureteral tissues, inducing an inflammatory and then a fibrotic process. Conclusions We underline the opportunity of a precocious and radical treatment of every retroperitoneal infection.
‘Cupid and Psyche’: A Novel Technique for Robotic Hysterosacropexy in the Treatment of Pelvic Organ Prolapse
Authors: Dal Moro Fabrizio , Calpista Arturo , Mancini Mariangela 
Published: October 2015

Purpose The purpose of any surgical repair of pelvic organ prolapse (POP) is to restore pelvic anatomy, preserving urinary, intestinal and sexual functions while avoiding complications. We present a novel robotic approach to hysterosacropexy (HSP) in the treatment of POP. Methods In our technique (named ‘Cupid and Psyche’, recalling as it does the famous sculpture by Canova), the two branches of the MESH encircle the uterus from behind, lifting and supporting it. The aim of this technique is to resolve POP, minimizing the risk of vaginal erosion: the posterior ‘embrace’ of the uterus limits the direct contact of the mesh with the vagina, thus reducing any risk of erosion/extrusion at this level. We performed 10 cases of robotic HSP. Results All procedures are completed robotically. Median operative time (skin-to-skin) is 125 min [interquartile range (IQR) 85-145], including port placement, robot docking and console time. We have never had any cases of intraoperative or postoperative complications. With regard to short-term follow-up, analysis of outcomes is limited; in any case, we have never had any cases of MESH erosion or other complications, and no sexually active woman complained of dyspareunia. Conclusions Maintaining sufficient motility of the vagina is another advantage of ‘Cupid and Psyche’, avoiding as it does any negative effects on patients’ later sexual activity, granting more natural motility of both uterus and vagina but resolving the prolapse. Further prospective studies comparing the long-term functional outcomes of the various HSP techniques are needed to confirm these findings.
Robotic Surgery in Urology: The Italian Contribution
Authors: Porpiglia Francesco , Bertolo Riccardo 
Published: October 2015

The introduction of robotic technology has given a major boost to the urologic surgery by expanding the indications of minimally-invasive surgery. The Italian urological community has played a major role in this revolution, by contributing to the development and dissemination of technological innovation in urology, with several key publications stemming from this research. The most important revolution has been observed in radical prostatectomy, with robotic technology allowing to achieve better functional results. Nephron-sparing surgery has also been expanded, and leading Italian centers are being involved in international research groups focused on these topics. Major impact has been observed for pyeloplasty, where Italy has been a leader in the field with the introduction of robot-assisted single-site technique. In summary, the advent of robotics has improved collaborations between Italy and other Countries, with increased scientific activity, continuous improvement of surgical techniques and effective training of young urologists.
Nieuw fiscaal procesrecht op de Caribische eilanden
Authors: Barmentlo D.G. , Jongmans B. 
Published: October 2015

Nieuw fiscaal procesrecht op de Caribische eilanden: something old, something new
In de Caribische delen van het Koninkrijk overzee wordt in 2015, tien jaar na de invoering in Nederland, de tweede feitelijke instantie in belastingzaken ingevoerd. Daarmee wordt ook de mogelijkheid van cassatie bij de Hoge Raad der Nederlanden geopend. Op Aruba bestaat hoger beroep sinds 1 januari 2015. Per 30 juni 2015 hebben Bonaire, Sint Eustatius en Saba (de BES-eilanden) zich aangesloten bij de ‘Arubaanse regeling’. De verwachting is dat ook Curaçao en Sint Maarten snel, waarschijnlijk in 2015, zullen volgen. Cassatie bij de Hoge Raad is mogelijk zodra alle eilanden hoger beroep hebben ingevoerd.
Validation of the Lung Subtyping Panel in Multiple Fresh-Frozen and Formalin-Fixed, Paraffin-Embedded Lung Tumor Gene Expression Data Sets
Authors: Faruki Hawazin , Mayhew Gregory M. , Fan Cheng , Wilkerson Matthew D. , Parker Scott , Kam-Morgan Lauren , Eisenberg Marcia , Horten Bruce , Hayes D. Neil , Perou Charles M. , Lai-Goldman Myla 
Published: October 2015

Context
A histologic classification of lung cancer subtypes is essential in guiding therapeutic management.

Objective
To complement morphology-based classification of lung tumors, a previously developed lung subtyping panel (LSP) of 57 genes was tested using multiple public fresh-frozen gene-expression data sets and a prospectively collected set of formalin-fixed, paraffin-embedded lung tumor samples.

Design
The LSP gene-expression signature was evaluated in multiple lung cancer gene-expression data sets totaling 2177 patients collected from 4 platforms: Illumina RNAseq (San Diego, California), Agilent (Santa Clara, California) and Affymetrix (Santa Clara) microarrays, and quantitative reverse transcription–polymerase chain reaction. Gene centroids were calculated for each of 3 genomic-defined subtypes: adenocarcinoma, squamous cell carcinoma, and neuroendocrine, the latter of which encompassed both small cell carcinoma and carcinoid. Classification by LSP into 3 subtypes was evaluated in both fresh-frozen and formalin-fixed, paraffin-embedded tumor samples, and agreement with the original morphology-based diagnosis was determined.

Results
The LSP-based classifications demonstrated overall agreement with the original clinical diagnosis ranging from 78% (251 of 322) to 91% (492 of 538 and 869 of 951) in the fresh-frozen public data sets and 84% (65 of 77) in the formalin-fixed, paraffin-embedded data set. The LSP performance was independent of tissue-preservation method and gene-expression platform. Secondary, blinded pathology review of formalin-fixed, paraffin-embedded samples demonstrated concordance of 82% (63 of 77) with the original morphology diagnosis.

Conclusions
The LSP gene-expression signature is a reproducible and objective method for classifying lung tumors and demonstrates good concordance with morphology-based classification across multiple data sets. The LSP panel can supplement morphologic assessment of lung cancers, particularly when classification by standard methods is challenging.