bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activated Stat-3 in Melanoma
Authors: Messina Jane L. , Yu Hua , Riker Adam I. , Munster Pamela N. , Jove Richard L. , Daud Adil I. 
Published: August 2017

Background Recent studies have demonstrated that the Src-Stat pathway may play an important role in melanoma. We examined the expression of phosphorylated Stat-3 (pStat-3), activated Stat-1 (pStat-1) and interferon alpha receptor subunit 1(IFNAR-1) in human melanocytic neoplasms. Methods Compound nevi (6), dysplastic nevi (4), congenital nevi (2), primary melanoma (14), and sentinel lymph node metastasis (40) were examined. Specimens were evaluated for phospho-Stat-1 (pStat-1), phospho-Stat-3 (pStat-3), and IFNAR-1 by immunohistochemistry. Staining was scored from 1 to 3 based on a composite score that took into account both the percentage of tumor cells staining and the intensity of stained cells. Results Normal melanocytes or benign nevi expressed little pStat-1, pStat-3, or IFNAR-1. In primary cutaneous melanoma, 6 of 14 skin biopsies showed activated Stat-3. However, in melanoma metastatic to regional lymph nodes, 16 of 26 had activated Stat-3 but only 6 of 23 had activated Stat-1. Melanoma tumors had high levels of either pStat-3 or pStat-1 but not both. All melanoma specimens but not benign melanocytes had cytoplasmic IFNAR-1 staining. An increase in Stat-3 activity was seen in melanoma but not in benign nevi or skin melanocytes. There appeared to be an inverse correlation between the levels of pStat-3 and pStat-1 in a given specimen. Conclusions The relationship between activated Stat-3 and biological behavior of melanocytic lesions observed in this study warrants further exploration.
Treatment Options for Limited or Symptomatic Metastatic Melanoma
Authors: Mcloughlin James M. , Zager Jonathan S. , Sondak Vernon K. , Berk Lawrence B. 
Published: August 2017

Background Patients who develop metastatic melanoma often have limited effective treatment options. However, a select group of patients will benefit from aggressive surgery or a multidisciplinary approach, depending on the site of metastasis. Methods The current literature was reviewed and summarized regarding the collective recommendations for staging and treating patients with metastatic melanoma. Results A thorough preoperative staging includes positron-emission tomography, MRI of the brain, and CT of the chest, abdomen, and pelvis. Tumor biology ultimately determines the success of intervention. A long disease-free interval is a good indicator of potential benefit from resection of metastatic disease. If surgery is performed, no less than a complete resection will affect the overall survival of the patient. Surgery and other multimodality treatment options can be used for symptomatic palliation but will not affect survival. Chemotherapy and radiation are often used to control the symptoms of brain and bony metastases but have limited if any impact on survival. Conclusions A select group of patients with metastatic melanoma will benefit from aggressive surgery. Identifying which patients will benefit from treatment requires good clinical judgment and a thorough radiologic evaluation to identify the true extent of disease.
Endometrial Cancer and Lynch Syndrome: Clinical and Pathologic Considerations
Authors: Meyer Larissa A. , Broaddus Russell R. , Lu Karen H. 
Published: August 2017

Background Approximately 2% to 5% of endometrial cancers may be due to an inherited susceptibility. Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, an autosomal-dominant inherited cancer susceptibility syndrome caused by a germline mutation in one of the DNA mismatch repair genes, accounts for the majority of inherited cases. Lynch syndrome is associated with early onset of cancer and the development of multiple cancer types, particularly colon and endometrial cancer. Methods The current status of knowledge regarding Lynch syndrome-associated endometrial cancer and methods for diagnosis, screening, and prevention of cancers is reviewed. Results The lifetime cumulative risk of endometrial cancer for women with Lynch syndrome is 40% to 60%, which equals or exceeds their risk of colorectal cancer. No current evidence suggests either a survival advantage or disadvantage to endometrial cancer that is associated with Lynch syndrome when these cases are compared with sporadic cases. A combination of family and personal medical history and tumor testing provides an efficient basis for diagnosing Lynch syndrome in women with endometrial cancer. Current gynecologic cancer screening guidelines for women with Lynch syndrome include annual endometrial sampling and transvaginal ultrasonography beginning at age 30 to 35 years. Conclusions Diagnosing endometrial cancer patients with Lynch syndrome has important clinical implications for the individual and family members. Screening and prevention practices can decrease the likelihood of developing additional cancers.
The Use of Minimally Invasive Surgery for Endometrial Cancer
Authors: Humphrey Marcia M. , Apte Sachin M. 
Published: August 2017

Background Endometrial cancer is the most common gynecologic malignancy in the United States. Surgical staging is an integral component in the treatment of this disease. Minimally invasive surgical techniques have been utilized with increasing frequency in its management. Methods This article reviews the use of minimally invasive surgery for the treatment of endometrial cancer. Results Prospective trials and retrospective analyses have demonstrated the safety and feasibility of laparoscopy in performing hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic lymphadenectomy for surgical staging in endometrial cancer. The use of minimally invasive techniques does not appear to have an adverse impact on survival, and it improves quality of life in the postoperative period. Robotic surgery has been used in the management of this disease with promising preliminary results. Conclusions Laparoscopy is a safe and effective approach for surgical staging of selected patients with endometrial cancer. Further studies and cost-benefit analyses are required to determine if the use of robotics improves outcomes over standard laparoscopy and can extend the benefits of minimally invasive surgery to a larger proportion of patients with this common gynecologic malignancy.
Non-Endometrioid Adenocarcinoma of the Uterine Corpus: A Review of Selected Histological Subtypes
Authors: Mendivil Alberto , Schuler Kevin M. , Gehrig Paola A. 
Published: August 2017

Background Understanding the etiology, presentation, evaluation, and management of selected non-endometrioid endometrial adenocarcinomas of the uterine corpus is needed to define optimal treatment regimens. Methods The pathology and treatment of selected non-endometrioid endometrial adenocarcinomas of the uterus are reviewed and summarized. Results The most common non-endometrioid histology is papillary serous (10%), followed by clear cell (2% to 4%), mucinous (0.6% to 5%), and squamous cell (0.1% to 0.5%). Some non-endometrioid endometrial carcinomas behave more aggressively than the endometrioid cancers such that even women with clinical stage I disease often have extrauterine metastasis at the time of surgical evaluation. Therefore, when technically and medically feasible, comprehensive surgical staging is helpful for women with non-endometrioid endometrial cancer histology. Comprehensive surgical staging includes hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and cytological evaluation of the abdominal cavity. While whole abdominal radiotherapy has a limited role in early-stage uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC), there may be a role for postoperative chemotherapy and volume-directed radiotherapy in both early-stage UPSC and CC. In the setting of optimally debulked advanced-stage disease, a combination of radiation and chemotherapy may be indicated. In the setting of recurrent disease or in women with residual disease after surgery, a platinum-based regimen or enrollment in a clinical trial is recommended. Conclusions UPSC and CC are managed similarly since sufficient data to separate treatment recommendations are lacking. Because both histologies are associated with a high rate of recurrence, adjuvant therapy is recommended even in women with early-stage disease. The remaining cell types should be treated similar to endometrioid or other low-grade histologies.
Health Literacy Demands of Written Health Information Materials: An Assessment of Cervical Cancer Prevention Materials
Authors: Helitzer Deborah , Hollis Christine , Cotner Jane , Oestreicher Nancy 
Published: August 2017

Background Health literacy requires reading and writing skills as well as knowledge of health topics and health systems. Materials written at high reading levels with ambiguous, technical, or dense text, often place great comprehension demands on consumers with lower literacy skills. This study developed and used an instrument to analyze cervical cancer prevention materials for readability, comprehensibility, suitability, and message design. Methods The Suitability Assessment of Materials (SAM) was amended for ease of use, inclusivity, and objectivity with the encouragement of the original developers. Other novel contributions were specifically related to “comprehensibility” (CAM). The resulting SAM + CAM was used to score 69 materials for content, literacy demand, numeric literacy, graphics, layout/typography, and learning stimulation variables. Expert reviewers provided content validation. Inter-rater reliability was “substantial” (κ = .77). Results The mean reading level of materials was 11th grade. Most materials (68%) scored as “adequate” for comprehensibility, suitability, and message design; health education brochures scored better than other materials. Only one-fifth were ranked “superior” for ease of use and comprehensibility. Conclusions Most written materials have a readability level that is too high and require improvement in ease of use and comprehensibility for the majority of readers.
Tumor Biomarkers in Melanoma
Authors: Ugurel Selma , Utikal Jochen , Becker Jüurgen C 
Published: August 2017

Background Morphologic and histopathologic markers have been the backbone for the classification and prognostic assessment of melanoma. Availability of an increasing number of molecular markers, however, provides the potential for refining diagnostic and prognostic categories in this disease. Methods We reviewed the recent data that are accumulating concerning gene expression and genetic profiling and related these to clinical aspects of the disease. Results Multiple biomarkers have now been described, and their biologic significance is being established. In addition, several candidate molecules involved in mela-noma pathogenesis have been identified. Conclusions The process of biomarker identification and validation is providing a rapidly changing molecular view of melanoma, a strategy that is necessary for developing truly stratified or even personalized prevention or management.
Sentinel Lymph Node Biopsy for Melanoma: Indications and Rationale
Authors: Phan Giao Q. , Messina Jane L. , Sondak Vernon K. , Zager Jonathan S. 
Published: August 2017

Background The disease status of regional lymph nodes is the most important prognostic indicator for patients with melanoma. Sentinel lymph node biopsy (SLNB) was developed as a technique to surgically assess the regional lymph nodes and spare node-negative patients unnecessary and potentially morbid complete lymphadenectomies. Methods We reviewed the literature on SLNB for cutaneous mela-noma to provide insight into the rationale for the current widespread use of SLNB. Results Multiple studies show that the status of the SLN is an important prognostic indicator. Those with positive SLNs have significantly decreased disease-free and melanoma-specific survival compared with those who have negative SLNs. In the Multicenter Selective Lymphad-enectomy Trial I (MSLT-I), in which patients with intermediate-thickness mela-noma were randomized to SLNB (and immediate completion lymphadenectomy if the SLN was positive) vs observation (and a lymphadenectomy only after presenting with clinically evident recurrence), the 5-year survival rate was 72.3% for patients with positive sentinel nodes and 90.2% for those with negative sentinel nodes (P < .001). Although overall survival was not increased in patients who underwent SLNB compared with those who were randomized to observation, patients who underwent SLNB had a significantly increased 5-year disease-free survival rate compared with those who underwent observation alone (78.3% in the biopsy group and 73.1% in the observation group; P = .009). For those with nodal metastases, patients who underwent SLNB and immediate lymphadenectomy had an increased overall 5-year survival rate compared with those who had lymphadenectomy only after presenting with clinically evident disease (72.3% vs 52.4%; P = .004). Moreover, other studies show that for patients with thin melanomas ≤ 1.0 mm, the overall survival rate is significantly worse for those with positive SLNs compared to those with negative SLNs. For thin melanomas, Breslow depth ≥ 0.76 mm and increased mitotic rate have been shown to be associated with an increased incidence of SLN metastases. Conclusions SLNB provides important prognostic and staging data with minimal morbidity and can be used to identify regional node-negative patients who would not benefit from a complete nodal dissection. In our opinion, SLNB should be performed on most patients (with acceptable surgical and anesthesia risk) who have melanomas with a Breslow depth ≥ 0.76 mm.
Fertility and Reproductive Considerations in Premenopausal Patients with Breast Cancer
Authors: Lee M. Catherine , Gray Jhanelle , Han Hyo Sook , Plosker Shayne 
Published: August 2017

Background Approximately 10% of all new breast cancer diagnoses occur in young women. Although lacking medical comorbidities, these patients often have unique issues with regard to their reproductive health that merit special consideration. As breast cancer outcomes continue to improve, quality of life for patients and their families after breast cancer treatment has come to the forefront of cancer research, particularly in the growing field of oncofertility. Methods This article reviews the literature on the singular situations and controversies faced by premenopausal breast cancer patients. Results Data on amenorrhea and the effects of modern chemotherapeutic agents on amenorrhea are limited, although the role of tamoxifen in amenorrhea is more clearly defined as increasing the rate of amenorrhea across several studies. At the forefront of studies on fertility and premenopausal breast cancer patients are investigations on fertility preservation via ovarian protection and on assisted reproductive technologies. The use of gonadotropin-releasing hormone analogs for ovarian protection remains controversial and continues to be investigated. Conclusions Early integration of assessment and counseling regarding fertility preservation is part of the multidisciplinary approach in the care of the premenopausal breast cancer patient and is key to optimizing both cancer treatment and fertility plans for the future. Because of the many ongoing biological, practical, and ethical controversies surrounding oncofertility, eligible patients should be strongly encouraged to participate in clinical trials and studies to further increase our knowledge in this growing field.
Promoter Hypermethylation in Prostate Cancer
Authors: Park Jong Y. 
Published: August 2017

Background The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. Methods This review discusses current information on methylated genes associated with prostate cancer development and progression. Results Over 30 genes have been investigated for promoter methylation in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is reviewed. Conclusions These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use.
Outcomes from Unrelated Donor Hematopoietic Stem Cell Transplantation
Authors: Perez Lia Elena 
Published: August 2017

Background Allogeneic hematopoietic cell transplantation (HCT) offers a curative treatment option for management of a variety of hematologic malignancies. While sibling donors have been the gold standard for adult patients in need of an HCT, not all patients have a suitable family donor. The availability of unrelated volunteer donor registries and alternative stem cell sources has expanded the wide application of this procedure. Methods PubMed and MEDLINE were searched for human trials and the English language from 2001 to 2011. Factors influencing transplantation outcomes involving unrelated donors over the last decade are discussed, and feasible alternative stem cell sources when a matched unrelated donor is not available are reviewed. Results HCT using a matched unrelated donor offers outcomes comparable to sibling HCT due to current molecular-based HLA typing and improvements in conditioning regimens and/or supportive care. The primary factor that contributes to improved outcome is the degree of donor-to-recipient HLA matching. The selection of younger unrelated donors has also been associated with improved outcomes in HCT. Evidence supports the universal application of matched unrelated donors even in high-risk leukemia and/or older patients. In adult patients without a matched related donor, other promising options as stem cell source includes mismatched unrelated donors, umbilical cord blood units, and haploidentical donors. Conclusions With current methodologies for molecular HLA typing and supportive care tools, outcomes of transplants with matched unrelated donors are comparable to those achieved with sibling donors. Alternative stem cell donors when a matched unrelated donor is not available are feasible expanding the stem cell donor pool.
Clinical and Laboratory Prognostic Indicators in Chronic Lymphocytic Leukemia
Authors: Sagatys Elizabeth M. , Zhang Ling 
Published: August 2017

Background The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous, with some patients experiencing rapid disease progression and others living for decades without requiring treatment. The Rai and Binet clinical staging systems are used to define disease extent and predict survival. The pathology laboratory also provides important prognostic information. Methods A review of the literature was performed on the subject of staging in CLL from clinical and pathologic standpoints. This article also reviews currently available diagnostic approaches related to disease prognosis and to timing of treatment and follow-up in patients with CLL. Results Novel biological and cytogenetic features such as immunoglobulin heavy-chain variable gene segment [IgVH], genomic aberrations including del(17p13), del(11q23), del(13q14), and trisomy 12, serum markers (thymidine kinase and beta-2 microglobulin), and cellular markers (CD38 and ZAP70) have become increasingly important in predicting prognosis at the time of diagnosis. Conclusions Current prognostic factors directly or indirectly influence the management of patients with CLL and help to predict treatment-free and overall survival.
Front-Line Therapy for Chronic Lymphocytic Leukemia
Authors: Desai Sheetal , Pinilla-Ibarz Javier 
Published: August 2017

Background Historically, alkylator-based therapy has been used to treat patients with chronic lymphocytic leukemia (CLL). More effective therapies, such as the use of monoclonal antibodies in combination with chemotherapy, have been shown to prolong both progression-free survival and overall survival. Improvements in the identification of prognostic markers for CLL, as well as novel combinations for chemoimmunotherapy regimens, have improved the outcome for patients with CLL. Methods We examine the diagnosis of CLL, the role of prognostic factors in determining treatment goals, and current data on frontline management of CLL. Results The benefits of single-agent and combination therapies are associated with prolonged progression-free and overall survival. While more aggressive management may therefore be warranted, each patient's comorbidities and performance status must be weighed against the benefits, availability, cost, treatment goals, and incidence of adverse effects associated with each therapy. Conclusions New single agents and novel treatment combinations have shown promising results in phase I/II studies. The ultimate therapeutic goals of prolonged survival and improved quality of life will be validated only by ongoing clinical and laboratory research and by continuous enrollment of patients in clinical trials.
Hematopoietic Stem Cell Allografting for Chronic Lymphocytic Leukemia: A Focus on Reduced-Intensity Conditioning Regimens
Authors: Kharfan-Dabaja Mohamed A. , Bazarbachi Ali 
Published: August 2017

Background Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only known treatment modality that currently offers a potential cure to patients with chronic lymphocytic leukemia (CLL). A better understanding of the role of adoptive immunotherapy and its consequent bona fide graft-vs-leukemia (GVL) effect has resulted in a reduction of the ablative intensity and toxicity of preparative allo-HCT regimens. Methods The authors review the published data of reduced-intensity conditioning (RIC) allo-HCT in patients with CLL. Results RIC allo-HCT has reduced the transplant associated morbidity and mortality of the procedure and has consequently broadened applicability of allo-HCT to patients with CLL who are generally of more advanced age (> 60 years) and who often have associated comorbidities. Conclusions Published literature supports the use of RIC allo-HCT for these patients once a suitable donor is identified, provided they fulfill acceptable consensus criteria for hematopoietic stem cell allografting. Several studies have shown that T-cell-replete RIC allo-HCT is also capable of overcoming the adverse effect of poor prognostic factors in CLL such as del(17p), unmutated IgVH, or ZAP-70 expression. Continued clinical trials to identify the optimal regimen for RIC allo-HCT for patients with CLL are warranted.