bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Incidence among Korean-American Immigrants in the United States and Native Koreans in South Korea
Authors: Lee Joanne , Demissie Kitaw , Lu Shou-En , Rhoads George G.
Published: August 2017

Background

While previous studies demonstrated contrasting patterns of cancer risk among migrant populations from different ethnic groups in the United States, few studies have focused on the Korean-American population. This study compares cancer incidence rates between Korean-Americans, whites, and blacks in the United States and native Koreans.

Methods

Data from the Surveillance, Epidemiology, and End Results (SEER) program and International Association for Research on Cancer were used to calculate age-standardized incidence rates among whites, blacks, and Korean Americans in the United States and native Koreans.

Results

The risk of stomach, liver, gallbladder, larynx, and esophageal cancer has sharply declined in Korean-American men compared with their native counterparts while prostate, colon, and rectum cancer risk has increased. In women, stomach, liver, gallbladder, and cervical cancers have declined, and breast, lung, colon, rectum, and endometrial cancers have increased. Cancer rates for stomach, liver, gallbladder, and esophagus are higher in native Koreans compared to US whites. Recently, cancer rates for Korean-American immigrants have increased for prostate, breast, colon, and rectal cancers.

Conclusions

The study provides evidence that the risk of cancers common in Western countries is higher for Korean Americans than for their native counterparts. Recent trends among Korean Americans also revealed a stronger Western profile.
Need for an Improved Molecular/Genetic Classification for CD30+ Lymphomas Involving the Skin
Authors: Droc Claudia , Cualing Hernani D. , Kadin Marshall E.
Published: August 2017

Background

The spectrum of diseases that constitute the CD30+ lymphomas, with lymphomatoid papulosis (LyP) at one end, and anaplastic large-cell lymphoma (ALCL) at the other end, shows variable morphology, immunophenotype, and clinical behavior. The border between these diseases is sometimes difficult to establish and there are many grey zones in their classification.

Methods

We reviewed the clinical and research literature and guided by our experiences attempted to discern molecular and phenotypic criteria to improve the classification and identify molecular targets for therapy of CD30-positive cutaneous lymphomas.

Results

Functional studies of ALCL cell lines clonally derived from LyP have revealed loss of growth inhibition by transforming growth factor beta (TGF-β), due to TGF-β receptor mutations. Studies of genetic variants of the CD30 promoter showed distinct microsatellite alleles associated with development of LyP and lymphoma progression. Studies of LyP and cutaneous ALCL tissues and cell lines suggest a dual role for CD30/CD30 ligand interactions in regression of LyP and progression to lymphoma. CD30 signaling activates NF-κB in cell lines derived from cutaneous ALCL but not anaplastic lymphoma kinase (ALK)-positive systemic ALCL in which growth arrest occurs through cell cycle inhibitor p21WAF1/Cip1. Other likely biomarkers of disease progression include differential expression of Bcl-2, fascin, cutaneous lymphocyte antigen, and T-cell receptor clonality. These may lead to improved classification, diagnoses, and therapeutic targets.

Conclusions

The current clinicopathologic classification of CD30+ cutaneous lymphoproliferative disorders is insufficient. Incorporating genetic and molecular criteria would better define the borders between benign/malignant and aggressive/nonaggressive disorders.
Evidence-Based Medicine for Rare Diseases: Implications for Data Interpretation and Clinical Trial Design
Authors: Behera Madhusmita , Kumar Ambuj , Soares Heloisa P. , Sokol Lubomir , Djulbegovic Benjamin
Published: August 2017

Background

The randomized, controlled trial (RCT) is the “gold standard” for establishing the effect of any intervention. This approach, however, is often not feasible with rare diseases such as cutaneous T-cell lymphoma.

Methods

We review the principles of evidence-based medicine to see which are particularly pertinent to the study of rare diseases.

Results

When an RCT is not feasible, attention is given to determining all the available prior data. Evaluation of the new data and the historic base requires attention to biases, but can allow estimation of a “true” study result.

Conclusions

Even when an RCT cannot be performed because of insufficient cases, utilization of evidence-based methodology can help minimize bias and maximize the truth of observed new data.
High-Risk Benign Breast Lesions: Current Strategies in Management
Authors: Kiluk John V. , Acs Geza , Hoover Susan J.
Published: August 2017

Background

High-risk benign breast lesions can create confusion for both the patient and the clinician. This paper reviews the characteristics of these lesions to help direct appropriate management.

Methods

The authors reviewed the literature regarding high-risk breast lesions and include management guidelines that we employ at our institute.

Results

High-risk breast lesions offer varying degrees of increased risk for the future development of breast cancer. Chemoprevention may be used to help decrease the risks from some lesions.

Conclusions

The management of high-risk benign breast lesions can be confusing. Clinicians should assess the risk of future breast cancer and develop a proper screening and prevention strategy for each individual patient.
Recent Advances in Breast-Specific Imaging
Authors: Berman Claudia G.
Published: August 2017

Background

Imaging the breast is a vital component not only for breast cancer screening, but also for diagnosis, evaluation, treatment, and follow-up of patients with breast cancer.

Methods

The author reviews recent advances and also provides her personal experience in describing the status of digital mammography, computer-aided detection, dedicated magnetic resonance imaging (MRI), and positron-emission mammography for evaluating the breast.

Results

Full-field digital mammography is superior to standard mammography in women under 50 years of age and in those with dense breasts. Computer-aided detection assists inexperienced mammographers and enhances detection of microcalcifications in dense breasts. Breast MRI is useful in preoperative evaluation, clarification of indeterminate mammograms, and follow-up of BRCA mutation carriers. The specificity of MRI remains problematic, however. Positron-emission mammography promises enhanced detection of ductal carcinoma in situ (DCIS), even when not associated with microcalcifications, and should aid surgical planning.

Conclusions

These four significant advances in breast imaging have all improved the sensitivity of detecting breast abnormalities. Cost issues, however, may limit the widespread application of these advances.
Proteomic Approach to Breast Cancer
Authors: Laronga Christine , Drake Richard R.
Published: August 2017

Background

Breast cancer is the most common cancer affecting women worldwide. Despite tremendous advances in screening, diagnosis, and treatment, the causes of this disease remain elusive and complex. Proteomics is a rapidly developing field that can explore the heterogeneity of breast cancer and supplement the wealth of information gained from genomics.

Methods

This article serves as an overview of the application of matrix-assisted laser desorption/ionization source with a time-of-flight (MALDI-TOF) proteomic techniques as applied to breast cancer. Examples of the clinical applicability of MALDI-TOF mass spectrometry are provided but represent only a fraction of the potential uses yet to be discovered. In addition, a brief summary of the bioinformatics issues that surround proteomics is included.

Results

Mass spectrometry has provided new proteomic approaches to unravel the complexities of clinical specimens relevant to breast cancer diagnostics. In particular, MALDI-TOF mass spectrometry analysis has been used to differentiate cancer profiles from benign profiles in samples from sera, plasma, tissue, nipple fluid, and ductal lavage. Some discriminating proteins have subsequently been identified.

Conclusions

Mass spectrometry applications to breast cancer diagnostics continue to be developed but are evolving faster than bioinformatics/statistical analysis can adapt. The future of these techniques in terms of clinical investigation is limitless, but in terms of general applicability, these applications are currently cost-prohibitive.
Orthopedic Surgery Options for the Treatment of Primary Osteosarcoma
Authors: Marulanda German A. , Henderson Eric R. , Johnson David A. , Letson G. Douglas , Cheong David
Published: August 2017

Background

Osteosarcoma is the most common malignant primary neoplasm of bone. Orthopedic procedures are essential components in the multidisciplinary treatment of osteosarcoma. Limb-salvaging procedures offer adequate disease control comparable to the results obtained by amputations. This review discusses the advantages and disadvantages of the various types of amputations and the limb-salvaging techniques for the treatment of osteosarcoma.

Methods

The authors analyzed the characteristics of limb-salvaging procedures and amputations for osteosarcoma. Qualitative and quantitative studies published in the English language that are listed in the National Library of Medicine were used as the basis for this review. In addition, a review of an expandable prosthesis is included.

Results

Limb-salvaging techniques have acceptable rates of disease control. However, amputation remains a valid procedure in selected cases of osteosarcoma in most parts of the world. Orthopedic oncology surgeons have various materials, procedures, and techniques available to achieve disease control and improve function in patients with osteosarcoma.

Conclusions

The surgical management of patients with osteosarcoma is challenging. No difference in survival has been shown between amputations and adequately performed limb-salvaging procedures. Optimal tumor resection and a functional residual limb with increased patient survival are the goals of modern orthopedic oncology.
Outpatient Chemotherapy plus Radiotherapy in Sarcomas: Improving Cancer Control with Radiosensitizing Agents
Authors: Anderson Pete , Aguilera Dolly , Pearson Margaret , Woo Shaio
Published: August 2017

Background

Cancer control by radiotherapy (RT) can be improved with concurrent chemotherapy. Outpatient strategies for sarcomas that combine chemotherapy and RT are possible since supportive care and RT techniques have improved.

Methods

The current status of non-anthracycline chemotherapy in combination with radiation for high-risk sarcoma is reviewed.

Results

Ifosfamide with mesna and newer activated ifosfamide agents (ZIO-201 and glufosfamide) have high potential to improve sarcoma cancer control. In Ewing's sarcoma and osteosarcoma, high-dose ifosfamide with mesna (2.8 g/m2/day of each x 5 days; mesna day 6) can be safely given to outpatients using continuous infusion. Reducing ifosfamide nephrotoxicity and central nervous system side effects are discussed. Other outpatient radiosensitization regimens include gemcitabine (600–1000 mg/m2/dose IV over 1 hour weekly x 2–3 doses), temozolomide (75 mg/m2/daily x 3–6 weeks), or temozolomide (100 mg/m2/dose daily x 5) + irinotecan (10 mg/m2/dose daily x 5 x 2 weeks). In osteosarcoma with osteoblastic metastases on bone scan, samarium (1 mCi/kg; day 3 of RT) and gemcitabine (600 mg/m2IV over 1 hour day 9 of RT) is a radiosensitization strategy. Future drugs for radiosensitization include beta-D-glucose targeted activated ifosfamide (glufosfamide) and sapacitabine, an oral nucleoside with in vitro activity against solid tumors including sarcomas.

Conclusions

The potential to treat major causes of sarcoma treatment failure (local recurrence and distant metastases) with concurrent chemotherapy during radiation should be considered in high-grade sarcomas.
Current Issues in Adolescent and Young Adult Cancer Survivorship
Authors: Soliman Hatem , Agresta Samuel V.
Published: August 2017

Background

Overall, the survival rate for cancer patients has continued to improve over the past several decades. However, those aged 15 to 29 years have not experienced the same improvements in survival. This review explores some of the challenges faced by adolescent and young adult (AYA) cancer patients and their survivorship needs.

Methods

Using the OVID Medline database from 1966 to present, a variety of search terms including “adolescent,” “young adult,” and “cancer survivorship” were entered. Articles related to those obtained by the search were also collected. Additional data were obtained from the SEER database AYA monograph, the Childhood Cancer Survivorship Study, the Report of the Adolescent and Young Adult Oncology Progress Review Group, and the Long-Term Follow-Up Recommendations of the Children's Oncology Group.

Results

Cancer patients in this age-group are at increased risk for second malignancies, cardiotoxicity, and reproductive difficulties. Few data exist concerning intellectual and other psychosocial issues for this specific patient population.

Conclusions

More research is needed to develop accurate data on treatment and survivorship for AYA patients. A separate cancer discipline focusing on improving outcomes in treatment and survivorship among AYA patients should be developed in major academic cancer centers.
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.
Surgical Intervention of Nonvertebral Osseous Metastasis
Authors: Attar Samer , Steffner Robert J. , Avedian Raffi , Hussain Waqas M.
Published: August 2017

Background

Nonvertebral osseous metastases can result in pain and disability. The goals of surgical intervention are to reduce pain and to improve function if nonsurgical treatment fails. The indications for proceeding with surgical intervention depend on anatomic location, amount of local destruction, extent of skeletal and visceral disease and, most important, the patient's performance status and life expectancy.

Methods

This article reviews the evaluation and treatment of metastatic nonvertebral osseous lesions from the perspective of the orthopedic surgeon, based mainly on an assessment of the surgical literature.

Results

This article summarizes the approaches to preoperative evaluation, patient selection, and medical optimization. Guidelines for estimating osseous stability and fracture risk are discussed, and surgical implants and their relation to postoperative outcomes are examined. This review also describes less invasive ablative procedures currently available.

Conclusions

The surgical management of nonvertebral osseous metastases involves multidisciplinary collaboration. The surgical construct must be a stable, reliable, and durable intervention that is individually tailored and matched to a patient's prognosis and performance status.
The Role of Bone-Seeking Radionuclides in the Palliative Treatment of Patients with Painful Osteoblastic Skeletal Metastases
Authors: Tomblyn Michael
Published: August 2017

Background

Pain from skeletal metastases represents a major burden of advanced disease from solid tumors. Analgesic medications, bisphosphonates, hormonal agents, cytotoxic chemotherapy, and external beam radiotherapy are all effective treatments. However, patients often suffer from diffuse painful metastases and respond poorly to these standard therapies. Bone-seeking radionuclides can specifically target osteoblastic lesions to offer palliation of pain.

Methods

This article offers a narrative review of bone-seeking radionuclides, examines the evidence of safety and efficacy for the treatment of painful skeletal metastases, and presents guidelines for their appropriate use in this patient population.

Results

Seven bone-seeking radionuclides have shown evidence of both safety and efficacy in reducing pain from diffuse skeletal metastases. 153Sm-EDTMP and 89Sr are most commonly used in the United States and have been safely utilized for both repeat dosing as well as concurrent dosing with cytotoxic chemotherapy.

Conclusions

Targeted bone-seeking radionuclides are underutilized in the treatment of painful diffuse osteoblastic metastases. Several new agents are in active clinical investigation, and the pending approval of the first alpha-emitting radionuclide (223Ra) may offer a new class of agents that provide greater efficacy and less toxicity than those currently available for routine clinical use.
Genetic Risk Assessments in Individuals at High Risk for Inherited Breast Cancer in the Breast Oncology Care Setting
Authors: Pal Tuya , Vadaparampil Susan T.
Published: August 2017

Background

It has become increasingly common to consider BRCA mutation status when determining optimal cancer risk management and treatment options in order to improve patient outcomes. Knowledge about the risk for hereditary cancer at or as close as possible to the time of diagnosis allows patients access to the most risk reduction options available.

Methods

This paper illustrates the role of genetic risk assessment for hereditary breast cancer, using hereditary breast and ovarian cancer (HBOC) syndrome as a model due to germline mutations in the BRCA1 and BRCA2. Specifically, the value of genetic counseling and testing for HBOC across the cancer prevention and control continuum is outlined as it pertains to breast cancer.

Results

In recognition of the importance of risk assessment for hereditary breast cancer, leading health professional organizations have developed specific guidelines and recommendations to providers for identification of women at increased risk for carrying a BRCA mutation.

Conclusions

Institutional efforts specific to genetic counseling and testing have resulted in the implementation of a model driven by physician recommendation as a referral system for high-risk breast cancer patients. Establishing an infrastructure to support research, education, and outreach initiatives focused on BRCA genetic counseling and testing will provide information that can improve the delivery of cancer genetics services.
Axillary Staging Prior to Neoadjuvant Chemotherapy: The Roles of Sentinel Lymph Node Biopsy and Axillary Ultrasonography
Authors: Lee Marie Catherine , Joh Jennifer E. , Chau Alec
Published: August 2017

Background

Clinical evaluation of the axilla is an area of controversy in current breast cancer research and management. Evidence of axillary metastasis on biopsy affects all modalities of cancer therapeutics and is central to breast cancer staging. Neoadjuvant chemotherapy is standard therapy for patients with locally advanced breast cancer and considered for patients with early-stage breast cancer.

Methods

This article discusses axillary ultrasonography for axillary staging relative to neoadjuvant chemotherapy, reviews advances in sentinel lymph node (SLN) biopsy techniques, and explores an integrated approach to axillary staging. Techniques for staging the axilla after a breast cancer diagnosis relative to the use of neoadjuvant chemotherapy are also discussed.

Results

There is increasing support in the literature for routine axillary ultrasonography and percutaneous biopsy in the evaluation of regional nodal metastasis for breast cancer. SLN biopsy and axillary node dissection continue to be the standards for definitive staging.

Conclusions

Axillary ultrasonography (with or without biopsy) and SLN biopsy are safe and feasible options for breast cancer staging and may facilitate treatment decisions for surgery, chemotherapy, and radiation therapy. Multidisciplinary review may also significantly influence treatment and timing of staging and therapy. An integrated approach to diagnosis and treatment is beneficial for both patients and providers.
The Changing Face of Mastectomy: An Oncologic and Cosmetic Perspective
Authors: Laronga Christine , Lewis Jaime D. , Smith Paul D.
Published: August 2017

Background

The history of surgical treatment of breast cancer is rich with contributions from many surgeons over the centuries. Among the recent advances in technique is the nipple-sparing mastectomy, which reflects the emerging focus on cosmetic outcomes.

Methods

We took a backward glance at the literature illustrating the evolution of surgical management of breast cancer, culminating with nipple-sparing mastectomy. The growing clinical data with nipple-sparing mastectomy are explored.

Results

The demand for nipple-sparing mastectomy has been steadily increasing at many institutions. Based on the clinical data reported, nipple-sparing mastectomy is an oncologically safe procedure for selected women who have or are at high risk for breast cancer.

Conclusions

For women facing mastectomy and their surgeons, the optimal aesthetic result centers on preservation of the nipple. However, nipple-sparing mastectomy is technically challenging, with long-term safety not yet confirmed. Evidence-based data are needed to document local tumor recurrence, distant metastasis, cosmetic outcomes, patient satisfaction, and procedural complications.
Accelerated Partial Breast Irradiation: A Review and Description of an Early North American Surgical Experience with the Intrabeam Delivery System
Authors: Deneve Jeremiah L. , Hoefer Richard A. , Harris Eleanor E. R. , Laronga Christine
Published: August 2017

Background

Targeted intraoperative radiation therapy (IORT) as an alternative to whole breast irradiation (WBI) has been described for patients with early-stage breast cancer. The randomized phase III TARGiT trial demonstrated similar recurrence rates to WBI and a lower overall toxicity profile on short-term follow-up. We report on our early North American surgical experience using the Intrabeam radiotherapy delivery system and review the current literature.

Methods

Prospectively gathered estrogen receptor-positive, clinically node-negative patients with invasive breast cancer < 3 cm receiving IORT using the Intrabeam system were reviewed. IORT-related effects and early postoperative outcome were assessed. A literature review was also performed.

Results

Forty-two patients (median age 71 years) underwent lumpectomy, sentinel lymph node (SLN) biopsy, and concurrent IORT from January 2011 to July 2011. Ninety-one percent of patients had invasive ductal histology with a median tumor size of 1.0 cm. This review highlights the patient selection criteria, describes commercially available accelerated partial breast irradiation (APBI) treatment options, and discusses outcomes for the variety of APBI techniques currently utilized in clinical practice as well as an istitutional review of our early surgical experience using the Intrabeam radiotherapy delivery system.

Conclusions

While a variety of APBI techniques are currently available for clinical use, our early North American operative experience with IORT shows it is well tolerated with low morbidity. Delivery of IORT adds moderate operative time and may require creating subcutaneous tissue flaps. The addition of WBI may be necessary in situations for positive residual margins or microscopic nodal disease in patients who do not undergo additional surgery.
Menopausal Symptoms in Young Survivors of Breast Cancer: A Growing Problem without an Ideal Solution
Authors: Murthy Vijayashree , Chamberlain Ronald S.
Published: August 2017

Background

New breast cancers occur in 25% to 30% of women < 50 years of age. These young women undergo ablative surgery, chemotherapy, or hormonal/targeted treatment. These treatments have resulted in increased survival but at the expense of early menopause, marked by distressing vasomotor symptoms, sexual dysfunction, decreased metabolism, and musculoskeletal and cardiovascular effects.

Methods

A comprehensive literature search was performed using PubMed. This article reviews the evidence-based approaches to the treatment of these distressing symptoms in young breast cancer survivors.

Results

Menopausal symptoms in young patients are typically more severe due to the abrupt and rapid decrease in estrogen, and chemotherapy and hormones worsen these symptoms. Evidence supporting the efficacy of most complementary therapies is scarce. Behavioral modification and yoga may be helpful in mild cases of vasomotor symptoms, whereas newer antidepressants are promising in moderate to severe cases, and stellate ganglion block may be used in refractory cases. Local vaginal moisturizers, and in refractory cases low-dose estrogen creams, may ameliorate most urogenital symptoms. Bisphosphonates, vitamin D, and calcium can treat osteoporosis, and weight-bearing exercises decrease bone mineral density loss and help to control weight. Smoking cessation, exercise, and dietary modifications should be recommended to all young patients to decrease cardiac morbidity. At present, there is insufficient evidence to support any natural agent as a viable alternative to hormone replacement therapy to treat these symptoms.

Conclusions

No single agent can ameliorate vasomotor, cardiac, skeletal, and sexual concerns of young breast cancer survivors coping with menopausal symptoms. Quality-of-life research involving premenopausal breast cancer survivors is lacking. Further study is needed to identify safe and effective treatments for menopausal symptoms and to confirm their long-term safety in young breast cancer survivors.