bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separation Surgery for Spinal Metastases: Effect of Spinal Radiosurgery on Surgical Treatment Goals
Authors: Moussazadeh Nelson , Laufer Ilya , Yamada Yoshiya , Bilsky Mark H. 
Published: August 2017

BackgroundThe treatment of epidural spinal cord compression due to metastatic cancer represents an important clinical challenge. The NOMS (neurologic, oncologic, mechanical, and systemic) framework facilitates the determination of the optimal combination of systemic, radiation, and surgical therapies for individual patients. Spinal stereotactic radiosurgery (SRS) is an effective and safe modality for achieving durable control of local disease. Integrating SRS into the postoperative treatment plan allows surgical goals to be modified, thus decreasing the extent of tumor resection required.MethodsSeparation surgery is indicated for patients with spinal cord compression secondary to solid tumor metastases. During separation surgery, the spinal column is stabilized and the epidural tumor is resected without requiring significant vertebral body resection.ResultsTumor separation from the spinal cord allows patients to undergo postoperative SRS.ConclusionsThe combination of separation surgery and high-dose hypofractionated or single-fraction SRS results in high local tumor control at 1 year and is an effective palliative paradigm for this patient population.
Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Management of Peritoneal Carcinomatosis
Authors: Rajeev Rahul , Turaga Kiran K. 
Published: August 2017

BackgroundMalignant peritoneal disease can lead to significant debility due to bowel obstructions, ascites, and cancer cachexia. Moreover, inadequate imaging techniques can lead to the suboptimal detection of disease, and the poor vascularity of tumors can lead to a poor response to systemic chemotherapy. However, combination cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising novel treatment for patients with this disease.MethodsThe medical literature focusing on diagnostic updates and the management of peritoneal disease was reviewed. The application principles of HIPEC for use in peritoneal disease were also summarized.ResultsImprovements in imaging and the application of laparoscopic techniques have significantly increased the rate of diagnosis of early peritoneal disease with consequently less morbid cytoreductive procedures. Appropriate patient selection based on prognostic scores along with complete cytoreduction can identify a cohort of patients likely to derive durable benefit from this combination treatment.ConclusionsAdvances in diagnostic and therapeutic techniques, including surgical cytoreductive techniques, have demonstrated significant survival gains in patients with peritoneal disease. Although HIPEC can be used for the management of various types of histologies, further development of high-level evidence is necessary to advance the field.
Surgical Treatment for Leptomeningeal Disease
Authors: Volkov Andrey A. , Filis Andreas K. , Vrionis Frank D. 
Published: August 2017

Background Advancements in cancer treatment have led to more cases of leptomeningeal disease, which requires a multimodal approach. Methods Treatment modalities are reviewed from a neurosurgical standpoint, focusing on intrathecal chemotherapy and shunting devices. Potential complications and how to avoid them are discussed. Results The Ommaya reservoir and the chemoport are used for administering intrathecal chemotherapy. Use of ventriculo-lumbar perfusion can efficiently deliver chemotherapeutic agents and improve intracerebral pressure. Shunting systems, in conjunction with all of their variations, address the challenge of hydrocephalus in leptomeningeal carcinomatosis. Misplaced catheters, malfunction of the system, and shunt-related infections are known complications of treatment. Conclusions From an oncological perspective, the surgical treatment for leptomeningeal disease is limited; however, neurosurgery can be used to aid in the administration of chemotherapy and address the issue of hydrocephalus. Minimizing surgical complications is important in this sensitive patient population.
Quality-of-Life Assessment in Palliative Care
Authors: Mcmillan Susan C. 
Published: August 2017

Background Understanding the effects of cancer on the quality of life of affected patients is critical to clinical research as well as to optimal management and care. Methods Nine instruments for assessing quality of life in patients with cancer are identified, and their effectiveness during palliative care is analyzed. Results Most of the instruments included physical, functional, and symptom control, as well as psychologic and social aspects. Financial and spiritual aspects were included less often. While all but two of the instruments had adequate validity and reliability data published, only two - the Spitzer Quality-of-Life Index and the Hospice Quality-of-Life Index - were designed and validated for palliative care populations. Conclusions Although a variety of instruments is currently available, none is ideal for all palliative care settings. Further development and refinement of instruments are needed.
Therapeutic Options in the Management of Acute Myelogenous Leukemia in Adults
Authors: Saez Ruben A. 
Published: August 2017

BackgroundThe treatment of acute myelogenous leukemia has evolved in recent years due to advances in supportive care, the identification of prognostic factors, and the careful evaluation of chemotherapeutic modalities in randomized clinical trials.MethodsThe classification and prognostic features are reviewed, and the results from clinical trials have been evaluated with an emphasis on randomized trials and on both remission induction and postremission phases of management.ResultsThe combination of an anthracycline and standard-dose Ara-C form the basis of remission induction. High-dose Ara-C has greater toxicity. For postremission therapy, high-dose Ara-C improves results in those with good risk features or normal cytogenetics. Acute promyelocytic leukemia management includes all-trans-retinoic acid.ConclusionsOnce a patient relapses from a nontransplant approach, high-dose therapy and allogeneic marrow transplantation are considered. Autologous stem cell transplantation cures some patients who do not have a donor.
Biology of the Transition of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma
Authors: Lust John A. , Donovan Kathleen A. 
Published: August 2017

BackgroundApproximately 25% of patients with monoclonal gammopathy of undetermined significance (MGUS) eventually develop multiple myeloma (MM) or a related plasma cell disorder that is universally fatal. In this report, we examine the changes that occur in the clonal plasma cell that are likely to be important in the progression of MGUS to active myeloma.MethodsStudies that investigate the mechanisms involved in the multistep pathogenesis of monoclonal gammopathies are reviewed. Cytokines such as IL- 6 and IL-1β, adhesion molecules, viruses, and oncogenes including ras, bcl-2, Rb, and p53 are discussed.ResultsIL-1β is produced by plasma cells from virtually all MM patients but is undetectable in most MGUS patients. IL-1β has potent osteoclast activating factor activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. Subsequently, these “fixed” monoclonal plasma cells could now stimulate osteoclasts through the production of IL-1β and paracrine generation of IL-6 resulting in osteolytic disease. With continued progression of the myeloma, the monoclonal plasma cells may later acquire the ability to produce IL-6 in an autocrine fashion that will be manifested clinically by an elevated labeling index.ConclusionsA better understanding of the progression of MGUS to myeloma may lead to novel therapeutic strategies to prevent the development of MM.
Breast Cancer Care: Developments in 1998
Authors: Horton John 
Published: August 2017

Background Breast cancer is a significant cause of mortality and morbidity worldwide, although death rates in the United States and some other countries are beginning to fall. Methods Several sources of information in 1998, including publications and presentations at the 1998 meeting of the American Society of Clinical Oncology, are pertinent to contemporary breast cancer care. Results It is now possible to prescribe hormonal therapy that will reduce the incidence of breast cancer. Methods are available to reduce the morbidity from axillary node dissection, and improvements in adjuvant therapy and management of metastatic breast cancer are now at hand. Conclusions The information presented provides a broad-based platform for new standards of care for breast cancer that will serve as a sound base for further progress in this important disease.
Circulating Prostate Cancer Cells Detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR): What Do They Mean?
Authors: Moreno Jose G. , Gomella Leonard G. 
Published: August 2017

BackgroundMolecular techniques have been developed recently to assess for circulating tumor cells. This “molecular staging” of prostate cancer uses the reverse transcription-polymerase chain reaction (RT-PCR) to detect cells that contain PSA or PSMA in the bloodstream. Currently, the clinical application of this concept is controversial.MethodsThe authors discuss the current status of molecular biologic methods to detect circulating prostate cancer cells. They report on the limitations of the technology and the advances that will allow the quantification of these circulating cells.ResultsStudies generally indicate an increasing level of PSA RT-PCR positivity as disease advances. However, reports have been significantly diverse, and there is no clear explanation for this disparity.ConclusionsThe determination of the “circulating prostate cancer cell load” by RT-PCR or other techniques may prove to be useful in the management of patients with prostate cancer, but questions remain to be answered before we can develop and assess new therapeutic strategies that will advance the treatment of prostate cancer before metastasis becomes evident. A better understanding of the biology of tumor cells present in the circulatory system is also needed.
Neoadjuvant Therapy for Cancer of the Esophagus
Authors: Green Robert J. , Haller Daniel G. 
Published: August 2017

Background: The standard of care for esophageal cancer has historically been surgical resection. However, survival following surgical treatment of esophageal cancer remains poor. In inoperable patients, both radiation therapy and chemotherapy alone and in combination have been used with some success. Consequently, these therapies have been utilized in the neoadjuvant setting to improve palliation and prolong survival. Methods: The author reviewed the literature regarding clinical trials that employed neoadjuvant chemotherapy and radiation therapy in the treatment of squamous cell carcinoma and adenocarcinoma of the esophagus. Results: In most patients, surgery alone is noncurative therapy, even when performed with curative intent. Most phase III trials of neoadjuvant therapy have not been designed with adequate statistical power to detect clinically relevant improvement. The available data are insufficient to determine a benefit to preoperative radiation therapy alone. Preoperative chemotherapy with 5-FU plus cisplatin followed by surgery probably offers little or no improvement over surgery alone. Trials of combined preoperative chemoradiation therapy have yielded promising but not definitive results. Conclusions: Outside of a clinical trial, neoadjuvant therapy for esophageal cancer should be reserved for only a select group of patients. Future clinical trials may determine a role for neoadjuvant chemoradiation and identify more active chemotherapeutic agents and populations most likely to benefit.
Physician-Assisted Suicide: The Influence of Psychosocial Issues
Authors: Breitbart William , Rosenfeld Barry D. 
Published: August 2017

Background: Physician-assisted suicide (PAS) is perhaps the most compelling and clinically relevant mental health issue in palliative care today. The desire for death, the consideration of suicide, the interest in PAS, and the relationship of these issues to depression and other psychosocial issues appear to be of paramount importance. Methods: Psychiatric and psychosocial perspectives are used to understand the factors contributing to the interest in PAS, as well as to guide interventions in the clinical care of patients with advanced disease. Results: Research and clinical experience suggest that attending to issues of depression, social support, and other psychosocial issues in addition to pain and physical symptom control are critical elements in interventions that are useful in reducing the distress of patients who desire hastened death. Conclusions: Psychosocial and psychiatric issues are among the most powerful predictors of desire for death and interest in PAS. Evaluation and intervention in these areas, particularly depression, is a critical component of compassionate care.
Testing for Hereditary Risk of Ovarian Cancer
Authors: Frank Thomas S. 
Published: August 2017

Background Approximately one out of every 10 ovarian cancers is caused by inherited mutations in identified genes. The characterization of hereditary ovarian cancer as an autosomal dominant disorder of specific gene mutations is more specific and useful than descriptive clinical syndromes such as “Lynch II,” “site-specific ovarian cancer,” or “breast-ovarian cancer.” Methods The author reviewed recent studies of the biology, epidemiology, and medical management of hereditary ovarian cancer risk. Results Most hereditary ovarian cancer is attributable to two genes, BRCA1 and BRCA2, with other genes accounting for a smaller fraction. Women who inherit a mutation in any of these genes are far more likely than the general population to develop an epithelial malignancy of the ovary. Appropriate evaluation of family history can identify women most likely to have hereditary cancer risk, and genetic testing can definitively identify women with germline mutations that place them and their family at increased risk of ovarian cancer. Conclusions Hereditary risk assessment, including genetic testing, can enhance medical management when used appropriately and should be accompanied by patient education and counseling.
Stage B Prostate Cancer: Correlation of DNA Ploidy Analysis with Histological and Clinical Parameters
Authors: Mora Linda B. , Moscinski Lynn C. , Diaz José I. , Blair Pamela , Cantor Alan B. , Pow-Sang Julio M. 
Published: August 2017

Background The ability to accurately predict tumor behavior and patient survival is a problem in managing patients with prostate cancer. Prognostic variables in predicting death from tumor include prostate-specific antigen (PSA) level, histological grade, and clinical stage. Observer subjectivity is inherent in determining grade and stage; thus, criteria that are more objective are needed to identify patients for appropriate treatment. Methods The authors correlated flow cytometric nuclear DNA ploidy with Gleason score, PSA level, and recurrence risk in patients who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1993 for histopathologic stage B prostate cancer (T2, N0, M0). Results Of the tumors analyzed, 64% were DNA diploid with a low proliferative fraction, 25% were DNA diploid with a high proliferative fraction, and 11% were DNA aneuploid. DNA aneuploidy was associated with high Gleason grade (7–10). All Gleason grade 10 tumors were DNA aneuploid. Both DNA aneuploidy and high proliferative fraction (S+G2M) were statistically correlated with high Gleason grade and adverse prognosis but not with PSA level or patient age. Conclusions A direct relationship is shown between both DNA aneuploidy and a high proliferation index with aggressive biological behavior in stage B prostatic cancer. Objective tumor criteria are needed to choose treatment more selectively for individual patients.
Analyzing of incremental high utility pattern mining based on tree structures
Authors: Lee Judae , Yun Unil , Lee Gangin 
Published: August 2017

AbstractSince the concept of high utility pattern mining was proposed to solve the drawbacks of traditional frequent pattern mining approach that cannot handle various features of real-world applications, many different techniques and algorithms for high utility pattern mining have been developed. Moreover, several advanced methods for incremental data processing have been proposed in recent years as the sizes of recent databases obtained in the real world become larger. In this paper, we introduce the basic concept of incremental high utility pattern mining and analyze various relevant methods. In addition, we also conduct performance evaluation for the methods with famous benchmark datasets in order to determine their detailed characteristics. The evaluation shows that the less candidate patterns make algorithms faster.
Platelets in Wiskott-Aldrich syndrome: Victims or executioners?
Authors: Sereni Lucia , Castiello Maria Carmina , Villa Anna 
Published: August 2017

Abstract
Microthrombocytopenia is the clinical hallmark of WAS, a rare X-linked immunodeficiency that is characterized by eczema, autoimmunity, and cancer susceptibility. This disease is caused by mutations in the WAS gene, which is expressed in hematopoietic cells and regulates actin cytoskeleton remodeling thereby modulating various cellular functions, including motility, immunologic synapse assembly, and signaling. Despite extensive studies that have provided great insight into the relevance of this molecule to innate and cellular immunity, the exact mechanisms of microthrombocytopenia in WAS are still unknown. This review focuses on the recent progress made in dissecting the pathogenesis of platelet defects in patients with WAS and their murine counterparts. In parallel, we will provide an overview of the state-of-the art platelets as immune modulators at the interface between hemostasis and the immune system, which suggests that these cells may have a direct role in the pathogenesis of immune dysregulation in WAS.
First-in-Human Phase I Study of the Tamoxifen Metabolite Z-Endoxifen in Women With Endocrine-Refractory Metastatic Breast Cancer
Authors: Goetz Matthew P. , Suman Vera J. , Reid Joel M. , Northfelt Don W. , Mahr Michael A. , Ralya Andrew T. , Kuffel Mary , Buhrow Sarah A. , Safgren Stephanie L. , McGovern Renee M. , Black John , Dockter Travis , Haddad Tufia , Erlichman Charles , Adjei Alex A. , Visscher Dan , Chalmers Zachary R. , Frampton Garrett , Kipp Benjamin R. , Liu Minetta C. , Hawse John R. , Doroshow James H. , Collins Jerry M. , Streicher Howard , Ames Matthew M. , Ingle James N. 
Published: August 2017

Purpose Endoxifen is a tamoxifen metabolite with potent antiestrogenic activity. Patients and Methods We performed a phase I study of oral Z-endoxifen to determine its toxicities, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity. Eligibility included endocrine-refractory, estrogen receptor–positive metastatic breast cancer. An accelerated titration schedule was applied until moderate or dose-limiting toxicity occurred, followed by a 3+3 design and expansion at 40, 80, and 100 mg per day. Tumor DNA from serum (circulating cell free [cf); all patients] and biopsies [160 mg/day and expansion]) was sequenced. Results Of 41 enrolled patients, 38 were evaluable for MTD determination. Prior endocrine regimens during which progression occurred included aromatase inhibitor (n = 36), fulvestrant (n = 21), and tamoxifen (n = 15). Patients received endoxifen once daily at seven dose levels (20 to 160 mg). Dose escalation ceased at 160 mg per day given lack of MTD and endoxifen concentrations > 1,900 ng/mL. Endoxifen clearance was unaffected by CYP2D6 genotype. One patient (60 mg) had cycle 1 dose-limiting toxicity (pulmonary embolus). Overall clinical benefit rate (stable > 6 months [n = 7] or partial response by RECIST criteria [n = 3]) was 26.3% (95% CI, 13.4% to 43.1%) including prior tamoxifen progression (n = 3). cfDNA mutations were observed in 13 patients ( PIK3CA [n = 8], ESR1 [n = 5], TP53 [n = 4], and AKT [n = 1]) with shorter progression-free survival ( v those without cfDNA mutations; median, 61 v 132 days; log-rank P = .046). Clinical benefit was observed in those with ESR1 amplification (tumor; 80 mg/day) and ESR1 mutation (cfDNA; 160 mg/day). Comparing tumor biopsies and cfDNA, some mutations ( PIK3CA, TP53, and AKT) were undetected by cfDNA, whereas cfDNA mutations ( ESR1, TP53, and AKT) were undetected by biopsy. Conclusion In endocrine-refractory metastatic breast cancer, Z-endoxifen provides substantial drug exposure unaffected by CYP2D6 metabolism, acceptable toxicity, and promising antitumor activity.
Local Anesthetics Inhibit the Growth of Human Hepatocellular Carcinoma Cells
Authors: Le Gac Grégoire , Angenard Gaëlle , Clément Bruno , Laviolle Bruno , Coulouarn Cédric , Beloeil Hélène 
Published: August 2017

BACKGROUND:
Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic options. Retrospective studies have shown that the administration of local anesthetics (LAs) during cancer surgery could reduce cancer recurrence. Besides, experimental studies reported that LAs could inhibit the growth of cancer cells. Thus, the purpose of this study was to investigate the effects of LAs on human HCC cells.

METHODS:
The effects of 2 LAs (lidocaine and ropivacaine) (10−
2 to 10–6 M) were studied after an incubation of 48 hours on 2 HCC cell lines, namely HuH7 and HepaRG. Cell viability, cell cycle analysis, and apoptosis and senescence tests were performed together with unsupervised genome-wide expression profiling and quantitative real-time polymerase chain reaction for relevant genes.

RESULTS:
We showed that LAs decreased viability and proliferation of HuH7 cells (from 92% [P < .001] at 5 × 10−3 M to 40% [P = .02] at 10−
4 M with ropivacaine and from 87% [P < .001] to 37% [P = .02] with lidocaine) and HepaRG progenitor cells (from 58% at 5 × 10−
3 M [P < .001] to 29% at 10−
4 M [P = .04] with lidocaine and 59% [P < .001] with ropivacaine 5 × 10−
3 M) in concentration-dependent manner. LAs have no effect on well-differentiated HepaRG. Ropivacaine decreased the mRNA level of key cell cycle regulators, namely cyclin A2, cyclin B1, cyclin B2, and cyclin-dependent kinase 1, and the expression of the nuclear marker of cell proliferation MKI67. Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/β-catenin pathway. Both LAs increased apoptosis in Huh7 and HepaRG progenitor cells (P < .01).

CONCLUSIONS:
The data demonstrate that LAs induced profound modifications in gene expression profiles of tumor cells, including modulations in the expression of cell cycle–related genes that result in a cytostatic effect and induction of apoptosis.