bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant Therapy with Trastuzumab for HER-2/neu-Positive Breast Cancer
Authors: Gonzalez-Angulo Ana M. , Hortobágyi Gabriel N. , Esteva Francisco J. 
Published: September 2006

Abstract

Learning Objectives
After completing this course, the reader will be able to: Select appropriate adjuvant therapy for patients with HER-2/neu-positive breast cancer.Monitor trastuzumab therapy for cardiac toxicity.Discuss the controversies that remain in the treatment of HER-2/neu-positive breast cancer.
Access and take the CME test online and receive 1 AMA PRA category 1 creditTM at CME.TheOncologist.com
Breast cancer is the most common cancer in women in the U.S. and western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. In experimental models, transfection of the her-2/neu gene results in transformation of mammary epithelial cells. In human breast cancer, amplification of the her-2/neu gene results in protein over expression and poor prognosis. Patients whose tumors have her-2/neu gene amplification have a shorter disease-free survival time than patients whose tumors exhibit a normal her-2/neu gene copy number. her-2/ neu gene amplification identifies a biologically unique subset of aggressive breast tumors that are sensitive to growth inhibition and apoptosis induced by anti-HER-2/neu-targeted therapies. The first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with metastatic HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. However, potential cardiotoxicity requires careful patient selection. Here, we review the recently completed clinical trials of adjuvant trastuzumab in the adjuvant setting. HER-2/neu testing, patient selection, cardiotoxicity, duration of therapy, and directions for future research are discussed.
Molecular Classification of Breast Cancer: Limitations and Potential
Authors: Pusztai Lajos , Mazouni Chafika , Anderson Keith , Wu Yun , Symmans W. Fraser 
Published: September 2006

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the technical variables that affect accuracy of estrogen receptor immunohistochemistry.Describe emerging methods to quantify estrogen receptor expression and predict the prognosis of estrogen receptor-positive patients.Discuss limitations of current gene expression-based molecular classification of breast cancer.Explain the conceptual differences between unsupervised molecular class discovery methods and supervised clinical outcome prediction models such as multigene prognostic signatures.Interpret results of DNA microarray literature as they relate to diagnosis and prognosis of breast cancer.
Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Reverse transcription polymerase chain reaction and DNA microarrays are increasingly used in the clinic and in clinical research as prognostic or predictive tests. Results from these tests led to novel risk stratification methods and to new molecular classification of breast cancer. Some of these tools already complement existing diagnostic tests and can aid medical decision making in some situations. Better understanding of the molecular classes of breast cancer, independent of their prognostic and predictive values, may also lead to new biological insights and eventually to better therapies that are directed toward particular molecular subsets. However, there is substantially less experience with these emerging technologies than with the more established methods, the accuracy of which is often overestimated. This review discusses some of the limitations and strengths of current gene expression-based molecular classification of breast cancer. To provide context for this discussion, we also briefly examine the performance of estrogen receptor immunohistochemistry, which represents an essential part of the routine diagnostic workup for all breast cancer patients.
Thymoma: Benign Appearance, Malignant Potential
Authors: Riedel Richard F. , Burfeind William R. 
Published: September 2006

Abstract
Thymoma is a rare tumor with a largely indolent growth pattern. It does, however, have malignant potential as a result of its ability to invade locally and metastasize regionally. Often associated with a number of immune- and nonimmune-mediated paraneoplastic syndromes, patient outcomes are directly related to stage of disease and the ability to achieve a complete surgical resection. Surgery is the mainstay of treatment, with adjuvant radiation recommended for invasive thymoma. Sensitive to both chemotherapy and radiation, durable responses are achievable in incompletely resected and inoperable patients. We present two cases of thymoma followed by a general discussion with an emphasis on treatment for both early and advanced-stage disease.
Role of Minimally Invasive Surgery in Gynecologic Cancers
Authors: Schlaerth Alan C. , Abu-Rustum Nadeem R. 
Published: September 2006

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the different minimally invasive surgical options for patients diagnosed with cervical, endometrial, or ovarian cancer.List the benefits and limitations of a minimally invasive surgical approach in patients with gynecologic cancers.Identify the clinical criteria that are useful in determining whether a patient with a gynecologic cancer is an appropriate candidate for a minimally invasive surgery.
Access and take the CME test online and receive 1 AMA PRA category 1 creditTM at CME.TheOncologist.com
The role of minimally invasive surgery in the management of gynecologic cancers continues to expand. Radical vaginal trachelectomy with laparoscopic pelvic lymphadenectomy has emerged as a safe, reasonable option for women with early-stage cervical cancer desiring fertility preservation. Similarly, laparoscopically assisted radical vaginal hysterectomy has been systematically described, is feasible, and can be offered to women with early-stage cervical cancer who do not desire future childbearing. In the treatment of early-stage endometrial cancer, the surgical approach of laparoscopic hysterectomy, peritoneal washings, and pelvic and para-aortic lymph node dissection, with or without an omentectomy, is being compared with the same surgery performed via laparotomy in the cooperative Gynecologic Oncology Group LAP 2 study, which has completed accrual, and appears to be a reasonable surgical option. In ovarian cancer, minimally invasive surgery has been incorporated to manage early-stage, advanced-stage, and recurrent disease, as well as second-look procedures. Hand-assisted laparoscopy has also recently been described in managing larger volume primary and recurrent gynecologic cancers. Extraperitoneal laparoscopy for para-aortic and pelvic lymph node dissections has been shown to yield adequate nodal counts and to be safe and feasible in the management of gynecologic cancers.
What Is the Current State-of-the-Art Imaging for Detection and Staging of Cholangiocarcinoma?
Authors: Slattery James M. , Sahani Dushyant V. 
Published: September 2006

Abstract
Cholangiocarcinoma is an adenocarcinoma that arises from the bile duct epithelium and is the second most common primary hepatobiliary cancer, after hepatocellular cancer, with approximately 2,500 cases annually in the U.S. However, cholangiocarcinoma remains a relatively rare disease, accounting for &lt;2% of all human malignancies. Although the entire biliary tree is potentially at risk, tumors involving the biliary confluence or the right or left hepatic ducts (hilar cholangiocarcinoma) are most common and account for 40%–60% of all cases. Most patients present with advanced disease that is not amenable to surgical treatment. The median survival time for patients with intrahepatic cholangiocarcinoma without involvement of the hilum varies among centers from 18–30 months. The median survival time for patients with perihilar cholangiocarcinoma is slightly less, varying from 12–24 months. Despite the overall poor prognosis, survival after surgical treatment of hilar cholangiocarcinoma has improved during the past 10–15 years. This review highlights the imaging features of cholangiocarcinoma, with particular emphasis on the imaging techniques that can best assess tumor resectability and guide the surgeon regarding the potential extent of resection required in operable candidates.
Disseminated Intravascular B-Cell Lymphoma: Clinicopathological Features and Outcome of Three Cases Treated with Anthracycline-Based Immunochemotherapy
Authors: Bouzani Maria , Karmiris Themis , Rontogianni Dimitra , Delimpassi Susanna , Apostolidis John , Mpakiri Maria , Nikiforakis Emmanuel 
Published: September 2006

Abstract
The purpose of this study was to evaluate the use of combination anthracycline-based immunochemotherapy in intravascular lymphoma (IVL). This is an extremely rare, disseminated, and aggressive extranodal CD20+ non-Hodgkin's lymphoma (NHL) with poor outcome following anthracycline-based chemotherapy. From a population of 700 newly diagnosed patients with NHL who were registered and followed up at our unit between 1990 and 2005, three cases (0.4%) have been classified as IVL. Among the patients, there were two men and one woman, with a median age of 52 years. We have assessed the clinicopathological characteristics, response to therapy, and outcome. All patients presented with systemic symptoms and disseminated disease. All patients received anthracycline-based chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab (immunochemotherapy). Complete remission was achieved in all three patients, and currently all remain progression free with a follow-up of 24–45 months. In conclusion, anthracycline-based immunochemotherapy induces durable remissions in patients with IVL, an ultimately fatal disease, suggesting that the clinical course of this disease may be altered with immunochemotherapy.
Advances in the Therapy of Chronic Idiopathic Myelofibrosis
Authors: Arana-Yi Cecilia , Quintás-Cardama Alfonso , Giles Francis , Thomas Deborah , Carrasco-Yalan Antonio , Cortes Jorge , Kantarjian Hagop , Verstovsek Srdan 
Published: September 2006

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Discuss the clinical manifestations of myelofibrosis with myeloid metaplasia and recent developments in the understanding of its pathogenesis.Discuss the most recent clinical trials involving novel therapies for myelofibrosis with myeloid metaplasia.Propose an algorithm-based approach to the treatment of patients with myelofibrosis with myeloid metaplasia.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.comThe molecular basis of chronic idiopathic myelofibrosis (CIMF) has remained elusive, thus hampering the development of effective targeted therapies. However, significant progress regarding the molecular mechanisms involved in the pathogenes is of this disease has been made in recent years that will likely provide ample opportunity for the investigation of novel therapeutic approaches. At the fore front of these advances is the discovery that 35%–55% of patients with CIMF harbor mutations in the Janus kinase 2 tyrosine kinase gene. Until very recently, the management of patients with CIMF involved the use of supportive measures, including growth factors, transfusions, or interferon, and the administration of cyto-reductive agents, such as hydroxyurea and anagrelide. However, several trials have demonstrated the efficacy of antiangiogenic agents alone or in combination with corticosteroids. In addition, the use of reduced-intensity conditioning allogeneic stem cell transplantation has resulted in prolonged survival and lower transplant-related mortality.
Prophylaxis of Irinotecan-Induced Diarrhea with Neomycin and Potential Role for
UGT1A1*28
Genotype Screening: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: de Jong Floris A. , Kehrer Diederik F. S. , Mathijssen Ron H. J. , Creemers Geert-Jan , de Bruijn Peter , van Schaik Ron H. N. , Planting André S. Th. , van der Gaast Ate , Eskens Ferry A. L. M. , Janssen Jos Th. P. , Ruit Jan B. , Verweij Jaap , Sparreboom Alex , de Jonge Maja J. A. 
Published: September 2006

Abstract
Objective. Delayed-type diarrhea is a common side effect of irinotecan and is associated with a bacterial-mediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestine. Based on a pilot study, we hypothesized that concomitant administration of the antibiotic neomycin would diminish exposure of the gut to SN-38 and ameliorate the incidence and severity of diarrhea.
Patients and Methods. Patients were treated with irinotecan in a multicenter, double-blind, randomized, placebo-controlled trial. Eligible patients received irinotecan (350 mg/m2 once every 3 weeks) combined with neomycin (660 mg three times daily for three consecutive days, starting 2 days before chemotherapy) or combined with placebo. Blood samples were obtained for additional pharmacokinetic and pharmacogenetic analyses.
Results. Sixty-two patients were evaluable for the toxicity analysis. Baseline patient characteristics, systemic SN-38 exposure, and UGT1A1*28 genotype status (i.e., an additional TA repeat in the promoter region of uridine diphosphate-glucuronosyltransferase isoform 1A1) were similar in both arms. Although distribution, severity, and duration of delayed-type diarrhea did not differ significantly between arms, grade 3 diarrhea tended to be less frequent in the neomycin arm. The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2–3 diarrhea. In the neomycin arm, grade 2 nausea was significantly more common.
Conclusion. Our results do not suggest a major role for neomycin as prophylaxis for irinotecan-induced delayed-type diarrhea. It is suggested that the UGT1A1*28 genotype status could be used as a screening tool for a priori prevention of irinotecan-induced delayed-type diarrhea.
A Short‐Term Clinical and Microbial Evaluation of Periodontal Therapy Associated With Amalgam Overhang Removal
Authors: Roman‐Torres Caio Vinicius Gonçalves , Cortelli Sheila Cavalca , de Araujo Marcelo Werneck Barata , Aquino Davi Romeiro , Cortelli José Roberto 
Published: September 2006

Background: This study evaluated the effect of periodontal therapy plus amalgam overhang removal (PT+AOR) on periodontal status and the presence of Actinobacillus actinomycetemcomitans and Streptococcus mutans and compared two microbiological sampling techniques.Methods: Molar teeth with Class II overhang restorations were selected as the test group, and homologous sound teeth were selected as the control group. Periodontal probing depth (PD), clinical attachment level (CAL), and plaque and gingival indices were measured, and restorations were evaluated using radiographs and clinical exploration at baseline (T1) and 90 days after PT+AOR (T2). Microbial samples were taken with dental floss and paper points at T1 and T2. S. mutans and A. actinomycetemcomitans were detected using culture and commercial kits.Results: Mean values of plaque and gingival indices did not show statistically significant differences between test and control teeth between T1 and T2. At T2, the mean CAL decreased among test teeth, and the number of test teeth positive for A. actinomycetemcomitans showed a decrease, whereas positive samples for S. mutans increased. At T1, an association between the two sampling techniques for both bacteria was found. At T2, dental floss presented low sensitivity values for A. actinomycetemcomitans, whereas paper points showed low sensitivity for S. mutans.Conclusions: PT+AOR showed a beneficial effect on clinical parameters and a decrease of A. actinomycetemcomitans. At T1, both sampling techniques showed appropriate results. At T2, the use of paper points was a more sensitive sampling technique for isolate A. actinomycetemcomitans, whereas dental floss was found to be an alternative sampling method for isolate S. mutans.
Additional Effect of Dentifrices on the Instant Efficacy of Toothbrushing
Authors: Paraskevas S. , Timmerman M.F. , van der Velden U. , van der Weijden G.A. 
Published: September 2006

Background: Inconclusive evidence exists in the literature with regard to the additional effect of the use of dentifrice on plaque removal. The present study was undertaken to test whether the use of dentifrice during toothbrushing contributes to the instant cleaning efficacy of the brushing procedure.Methods: Three groups of patients, 40 subjects each, were randomly assigned to one of three dentifrices that differed with respect to the relative dentin abrasivity (RDA) value. After a 48‐hour plaque accumulation, subjects brushed under supervision in a split‐mouth order with or without the use of dentifrice (total time = 2 minutes).Results: Plaque reductions varied between 51% and 58% for the three dentifrices. The overall analysis showed a mean difference of 3% in plaque reduction in favor of brushing without dentifrice (P = 0.017). The type of dentifrice did not influence this observed difference (P = 0.506). Also, the order of the brushing procedure (starting the brushing procedure with or without dentifrice) had no interaction with the effect of dentifrice on the brushing (P = 0.187).Conclusions: The use of dentifrice does not contribute to the instant mechanical plaque removal during manual toothbrushing. A higher dentifrice abrasivity does not seem to contribute to increased plaque removal with a manual toothbrush. It appears that the mechanical action provided by the use of a toothbrush is the main factor in the plaque‐removing process.
Relationship Between Salivary Melatonin and Severity of Periodontal Disease
Authors: Cutando Antonio , Galindo Pablo , Gómez‐Moreno Gerardo , Arana Carlos , Bolaños Jorge , Acuña‐Castroviejo Darío , Wang Hom‐Lay 
Published: September 2006

Background: Melatonin possesses antioxidant, free‐radical scavenging, and immunoenhancing properties that promote fibroblast activity and bone regeneration. The aim of this study was to examine the possible links between salivary melatonin levels and the severity of periodontal disease using the community periodontal index (CPI).Methods: Thirty‐seven patients with different degrees of periodontal disease were studied. Salivary and plasma melatonin levels (by radioimmunoassay), salivary/plasma melatonin ratio, and CPI status were collected for each patient. The Spearman correlation coefficient was used to analyze relationships among variables.Results: Data showed a significant correlation between CPI and salivary/plasma melatonin ratios. When saliva volume was controlled for, a significant correlation (P <0.05) was found between lower salivary melatonin and a worse CPI. This finding suggests that melatonin may act as a protector against free radicals produced by inflammatory periodontal diseases.Conclusions: Salivary melatonin levels varied according to the degree of periodontal disease. As the degree of periodontal disease increased, the salivary melatonin level decreased, indicating that melatonin may act to protect the body from external bacterial insults. Therefore, melatonin may be potentially valuable in the treatment of periodontal diseases, although further research is required to validate this hypothesis.
Superior Effect of MD05, Beta‐Tricalcium Phosphate Coated With Recombinant Human Growth/Differentiation Factor‐5, Compared to Conventional Bone Substitutes in the Rat Calvarial Defect Model
Authors: Poehling Sylke , Pippig Susanne D. , Hellerbrand Klaus , Siedler Michael , Schütz Andreas , Dony Carola 
Published: September 2006

Background: MD05 consists of beta‐tricalcium phosphate (β‐TCP) coated with recombinant human growth/differentiation factor‐5 (rhGDF‐5) and is under evaluation as an osteoinductive and osteoconductive bone graft material for use in dental and maxillofacial applications. The objective of this study was to compare the bone regenerative properties of MD05 with those of conventional commercially available bone substitutes.Methods: Full‐thickness, 6‐mm diameter, calvarial critical‐size defects (two per animal) were created in adult Sprague‐Dawley rats. Groups of rats were implanted with the following: 1) MD05; 2) bovine bone mineral; 3) bovine bone mineral with collagen; 4) bovine bone mineral with synthetic peptide, 5) β‐TCP (from two different manufacturers); or 6) no filling material (sham controls). Blinded macroscopic analysis, histopathologic analysis, and histomorphometric analysis were carried out 6 weeks after implantation.Results: New bone formation assessed histomorphometrically was about five times greater with MD05 than with the other bone substitutes tested, and bone repair was well advanced in MD05‐filled defects after 6 weeks. The extent of fibrous tissue and residual implant were significantly lower in the MD05 group. In contrast to the other materials, the use of MD05 was associated with the complete osseous bridging of the defect and with the presence of normal bone marrow. The osteoinductive effect of rhGDF‐5 was apparent from the more pronounced bone ingrowth observed with MD05 compared to the β‐TCP carrier alone. All implants showed good biocompatibility.Conclusion: MD05 achieved superior bone regeneration compared to conventional materials and is a promising new bone substitute for dental and maxillofacial applications.
Impaired Masticatory Behavior in Subjects With Reduced Periodontal Tissue Support
Authors: Johansson Anders S. , Svensson Krister G. , Trulsson Mats 
Published: September 2006

Background: Mechanoreceptors situated in the periodontal ligament provide detailed information about intensive and spatial aspects of tooth loads, which support the neural control of masticatory forces. We asked whether a reduced periodontal ligament due to periodontitis, and, thus, an altered mechanoreceptive innervation of the teeth, would affect masticatory behavior when subjects used incisors to hold and split food.Methods: We tested 11 subjects with reduced periodontal tissue support that rendered 30% to 70% alveolar bone loss for at least one pair of opposing anterior incisors. Forces were recorded when subjects used their affected incisors to hold half of a peanut for ∼4 seconds and then split it. Age‐ and gender‐matched healthy subjects served as the control group. None of the participants showed acute oral symptoms or massive periodontal inflammation.Results: The test group used greater force when holding food between the teeth (1.1 ± 0.4 N [ mean ± 1 SD]) compared to the control group (0.4 ± 0.2 N). Hold forces used by subjects in the test group were also more variable, both within and between trials. The increase in bite force applied to split the peanut was slower and more hesitant for subjects in the test group compared to the control group.Conclusions: Reduced periodontal tissue support accompanies impaired regulation of masticatory forces. Faulty mechanoreceptive innervation of the periodontal ligament explains the elevated hold force, whereas a change in biting strategy due to the weakened support of the teeth may account for the more defensive food‐splitting behavior.