bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘You don't bring me flowers any more’: an investigation into the experience of stigma by psychiatric in-patients
Authors: Bromley Joanna S. , Cunningham Sara J. 
Published: September 2004

Aims and MethodA structured interview-based questionnaire was used to measure the number of cards and gifts received by 40 people undergoing psychiatric in-patient treatment, compared with an age- and gender-matched group of medical in-patients. The study also assessed the amount of disclosure of admission and diagnosis to family and friends in the two groups.ResultsThe psychiatric patients received about half as many cards as the medical patients (60 v. 112). Gifts to the psychiatric patients were often practical in nature and seldom included luxury items such as flowers. Disclosure of admission for mental illness (compared with the physical illness group) was significantly lower, both to family members (139 v. 193, P=0.041) and friends (74 v. 332, P=0.0001).Clinical ImplicationsThe stigma of mental illness is reflected in the secrecy surrounding disclosure of hospital admission and the lack of tokens of support. Clinicians should be aware of the resulting sense of isolation and shame, and the consequences for mental health in view of reduced social networks increasing the risk of future relapse rates. Reduced contact with mentally ill patients has implications for society as a whole in maintaining the status quo of stigma.
Clinical Nature and Prognosis of Locally Recurrent Rectal Cancer After Total Mesorectal Excision With or Without Preoperative Radiotherapy
Authors: van den Brink Mandy , Stiggelbout Anne M. , van den Hout Wilbert B. , Kievit Job , Klein Kranenbarg Elma , Marijnen Corrie A.M. , Nagtegaal Iris D. , Rutten Harm J.T. , Wiggers Theo , van de Velde Cornelis J.H. 
Published: September 2004

Purpose To document the clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision (TME) with or without 5 × 5 Gy preoperative radiotherapy (PRT) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after local recurrence. Patients and Methods For 96 Dutch patients with a local recurrence who participated in a multicenter randomized clinical trial, data on treatments and follow-up were gathered from surgeons and radiation and medical oncologists. Twenty-three patients (24%) had previously been treated with PRT plus TME, and 73 patients (76%) had been treated with TME alone. Eighty-one patients (84%) were followed until death; median follow-up time of the alive patients after local recurrence was 21 months (range, 5 to 48 months). Results Survival after local recurrence in the PRT + TME group was significantly shorter than in the TME group (median survival, 6.1 v 15.9 months; hazard ratio for death, 2.1; P = .008). Patients with a local recurrence in the PRT + TME group had distant metastases more often (74% v 40%; P = .004), underwent surgical resection of local recurrence less often (17% v 35%; P = .11), and received radiotherapy for local recurrence at a total dose ≥ 45 Gy less often (4% v 42%; P = .001) than patients without PRT. In a multivariate analysis, the difference in survival after local recurrence between randomization groups was no longer statistically significant (hazard ratio for death of PRT, 1.53; P = .16). Conclusion The clinical nature and prognosis of patients with locally recurrent rectal cancer has changed since the introduction of PRT. The majority of patients who present with a local recurrence after previous PRT have simultaneous distant metastases, and median survival has decreased to 6 months.
Identification of Novel Prognosticators of Outcome in Squamous Cell Carcinoma of the Head and Neck
Authors: Wreesmann Volkert B. , Shi Weiji , Thaler Howard T. , Poluri Ashok , Kraus Dennis H. , Pfister David , Shaha Ashok R. , Shah Jatin P. , Rao Pulivarthi H. , Singh Bhuvanesh 
Published: September 2004

PurposeThe goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC).Patients and MethodsWe assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate χ2statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than .15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the χ2approximation of the final model by MCS.ResultsCGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P = .0009 to P = .01).ConclusionHNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.
Positron Emission Tomography in Combination With Sentinel Node Biopsy Reduces the Rate of Elective Neck Dissections in the Treatment of Oral and Oropharyngeal Cancer
Authors: Kovács Adorján F. , Döbert Natascha , Gaa Jochen , Menzel Christian , Bitter Klaus 
Published: September 2004

Purpose To assess the impact of a diagnostic ladder including [18F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Patients and Methods Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome. Results Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses. Conclusion Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard.
Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study
Authors: Thigpen J. Tate , Brady Mark F. , Homesley Howard D. , Malfetano John , DuBeshter Brent , Burger Robert A. , Liao Shu 
Published: September 2004

Purpose Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone. Patients and Methods Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m2 intravenously or doxorubicin 60 mg/m2 plus cisplatin 50 mg/m2 every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m2 doxorubicin. Results There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P = .004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P = .014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%). Conclusion Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.
Matched-Pair Analysis of Survival of Never Smokers and Ever Smokers With Squamous Cell Carcinoma of the Head and Neck
Authors: Pytynia Kristen B. , Grant Jonathan R. , Etzel Carol J. , Roberts Dianna B. , Wei Qingyi , Sturgis Erich M. 
Published: September 2004

Purpose To compare survival rates between patients with squamous cell carcinoma of the head and neck (SCCHN) without a history of smoking (never smokers) and those with a current or previous history of smoking (ever smokers). Patients and Methods Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever smokers according to sex, age, tumor site, overall stage, nodal stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results The never smokers had a greater overall survival (P = .020), disease-specific survival (P = .022), and recurrence-free survival (P = .016). Furthermore, matched-pair analysis demonstrated smoking was associated with a significant increase in risk of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P = .029), risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P = .034), and risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P = .023). Smoking was associated with three-fold increases in risk for overall death, death owing to disease, and recurrence after adjustment for cancer-associated symptom severity and alcohol use, but the 95% CI for these adjusted risk estimates each included the null. Conclusion Survival differed significantly between never smokers and ever smokers with SCCHN. These results are not substantively explained by differences in cancer-associated symptoms or alcohol use, but the CIs are wide and some imprecision remains. Regardless, possible fundamental differences in SCCHN between ever smokers and never smokers may exist, and further molecular characterization of these tumors is needed to determine whether biologic differences needing targeted therapies exist.
Effectiveness of Routine Visits and Routine Tests in Detecting Isolated Locoregional Recurrences After Treatment for Early-Stage Invasive Breast Cancer: A Meta-Analysis and Systematic Review
Authors: de Bock G.H. , Bonnema J. , van Der Hage J. , Kievit J. , van de Velde C.J.H. 
Published: September 2004

PurposeTo review the effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences in asymptomatic patients after treatment for early-stage invasive breast cancer.MethodsSystematic review and meta-analysis. The proportion of isolated locoregional recurrences diagnosed during routine visits or routine tests in asymptomatic patients was compared with the proportion of isolated locoregional recurrences in symptomatic patients.ResultsTwelve studies that involved a total of 5,045 patients and 378 isolated locoregional recurrences were identified. Pooling data showed an overall estimate of 40% of isolated locoregional recurrences diagnosed during routine visits or routine tests in asymptomatic patients (95% CI, 35 to 45). Of these, 47% (95% CI, 39 to 54) were diagnosed after mastectomy, and 36% (95% CI, 28 to 43) were diagnosed after breast-conserving therapy (relative risk, 1.327; 95% CI, 1.014 to 1.738). Apart from differences in therapy, we have not been able to discern subgroups of patients for whom results were different.ConclusionApproximately 40% of isolated locoregional recurrences are diagnosed during routine visits and routine tests in asymptomatic patients treated for early-stage invasive breast cancer. We could not assess whether these were detected by either physical examination or other tests, nor if the detection of asymptomatic isolated recurrences had any influence on potential for cure or quality of life. As the overall quality of the included studies and the overall incidence of isolated locoregional recurrences are low, this systematic review highlights the need for prospective comparative studies on cost-effective strategies for the follow-up of patients after a diagnosis of breast cancer.
Is Baseline Quality of Life Useful for Predicting Survival With Hormone-Refractory Prostate Cancer? A Pooled Analysis of Three Studies of the European Organisation for Research and Treatment of Cancer Genitourinary Group
Authors: Collette Laurence , van Andel George , Bottomley Andrew , Oosterhof Gosse O.N. , Albrecht Walter , de Reijke Theo M. , Fossà Sophie D. 
Published: September 2004

Purpose Patients with symptomatic metastatic hormone-resistant prostate cancer (HRPC) survive a median of 10 months and are often regarded as a homogeneous group. Few prognostic factors have been identified so far. We examined whether baseline health-related quality of life (HRQOL) parameters assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) were independent prognostic factors of survival and whether they bring extra precision to the predictions achievable with models based on clinical and biochemical factors only. Patients and Methods Data of 391 symptomatic (bone) metastatic HRPC patients from three randomized EORTC trials were used in multivariate Cox proportional hazards models. The significance level was set at α = .05. Results Of the 391 patients, 371 died, most of prostate cancer. Bone scan result, performance status, hemoglobin level, and insomnia and appetite loss as measured by the EORTC QLQ-C30 were independent predictors of survival. This model's area under the receiver operating curve was 0.65 compared with 0.63 without the two HRQOL factors. Conclusion Certain HRQOL sores, at baseline, seem to be predictors for duration of survival in HRPC. However, such measurements do not add to the predictive ability of models based only on clinical and biochemical factors.
Scintigraphic Response by 123I-Metaiodobenzylguanidine Scan Correlates With Event-Free Survival in High-Risk Neuroblastoma
Authors: Katzenstein Howard M. , Cohn Susan L. , Shore Richard M. , Bardo Dianna M.E. , Haut Paul R. , Olszewski Marie , Schmoldt Jennifer , Liu Dachao , Rademaker Alfred W. , Kletzel Morris 
Published: September 2004

Purpose To investigate whether response to induction therapy, evaluated by metaiodobenzylguanadine (MIBG) and bone scintigraphy, correlates with event-free survival (EFS) in children with high-risk neuroblastoma (NB). Patients and Methods Twenty-nine high-risk NB patients were treated prospectively with an intensive induction regimen and consolidated with three cycles of high-dose therapy with peripheral blood stem-cell rescue. The scintigraphic response was evaluated by MIBG and bone scans using a semi-quantitative scoring system. The prognostic significance of the imaging scores at diagnosis and following induction therapy was evaluated. Results A trend associating worse 4-year EFS rates for patients with versus without osteomedullary uptake on MIBG scintigraphs at diagnosis was seen (35% ± 11% v 80% ± 18%, respectively; P = .13). Similarly, patients with positive bone scans at diagnosis had worse EFS than those with negative scans, although the difference did not receive statistical significance (34% ± 10% v 83% ± 15%, respectively; P = .06). However, significantly worse EFS was observed in patients with a postinduction MIBG score of ≥ 3 compared to those with scores of less than 3 (0% v 58% ± 11%; P = .002). There was no correlation between bone scan scores and outcome following induction therapy. Conclusion MIBG scores ≥ 3 following induction therapy identifies a subset of NB patients who are likely to relapse following three cycles of high-dose therapy with peripheral blood stem-cell rescue, local radiotherapy, and 13-cis-retinoic acid. Alternative therapeutic strategies should be considered for patients with a poor response to induction therapy.
Pharmacogenetic Risk Factors for Osteonecrosis of the Hip Among Children With Leukemia
Authors: Relling Mary V. , Yang Wenjian , Das Soma , Cook Edwin H. , Rosner Gary L. , Neel Michael , Howard Scott , Ribeiro Raul , Sandlund John T. , Pui Ching-Hon , Kaste Sue C. 
Published: September 2004

Purpose One of the adverse effects of therapy for acute lymphoblastic leukemia (ALL) is osteonecrosis of the hip. Putative risk factors for osteonecrosis have included being female, white race, and older age. Our goal was to define possible genetic risk factors for osteonecrosis among children treated for newly diagnosed ALL. Methods Using a candidate gene approach, we determined the genotypes for 16 common polymorphisms in genes likely to affect the pharmacokinetics or pharmacodynamics of antileukemic medications in 64 children with ALL. Therapy included glucocorticoids and antifolates. Magnetic resonance imaging of both hips was used to diagnose osteonecrosis, and was performed at similar times from the start of ALL therapy (P = .61) in the 25 patients with and the 39 patients without osteonecrosis (median, 447 days and 443 days, respectively). Results In addition to age older than 10 years (odds ratio [OR], 24.2; P = .0001) and white race (OR, 11.1; P = .037), host factors for osteonecrosis included the vitamin D receptor FokI start site CC genotype (OR, 4.5; P = .045), and the thymidylate synthase low activity 2/2 enhancer repeat genotype (OR, 7.4; P = .049). Conclusion Because folate-related and vitamin D–receptor genetic variants have been associated with bone and vasculature morbidity, these pharmacogenetic associations likely reflect the interaction of antileukemic medications with germline sensitivity to drug actions, and might identify ALL patients at highest risk to develop osteonecrosis.
Microarray Gene Expression Profiling of B-Cell Chronic Lymphocytic Leukemia Subgroups Defined by Genomic Aberrations and VH Mutation Status
Authors: Haslinger Christian , Schweifer Norbert , Stilgenbauer Stephan , Döhner Hartmut , Lichter Peter , Kraut Norbert , Stratowa Christian , Abseher Roger 
Published: September 2004

Purpose Genomic aberrations and mutational status of the immunoglobulin variable heavy chain (VH) gene have been shown to be among the most important predictors for outcome in patients with B-cell chronic lymphocytic leukemia (B-CLL). In this study, we report on differential gene expression patterns that are characteristic for genetically defined B-CLL subtypes. Materials and Methods One hundred genetically well-characterized B-CLL samples, together with 11 healthy control samples, were analyzed using oligonucleotide arrays, which test for the expression of some 12,000 human genes. Results Aiming at microarray-based subclassification, class predictors were constructed using sets of differentially expressed genes, which yielded in zero or low misclassification rates. Furthermore, a significant number of the differentially expressed genes clustered in chromosomal regions affected by the respective genomic losses/gains. Deletions affecting chromosome bands 11q22-q23 and 17p13 led to a reduced expression of the corresponding genes, such as ATM and p53, while trisomy 12 resulted in the upregulation of genes mapping to chromosome arm 12q. Using an unsupervised analysis algorithm, expression profiling allowed partitioning into predominantly VH-mutated versus unmutated patient groups; however, association of the expression profile with the VH mutational status could only be detected in male patients. Conclusion The finding that the most significantly differentially expressed genes are located in the corresponding aberrant chromosomal regions indicates that a gene dosage effect may exert a pathogenic role in B-CLL. The significant difference in the partitioning of male and female B-CLL samples suggests that the genomic signature for the VH mutational status might be sex-related.
Bisphosphonates: Preclinical Review
Authors: Green Jonathan R. 
Published: September 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Describe the mechanism of action of first-generation and nitrogen-containing bisphosphonates. Explain how the mechanism of action of the bisphosphonates might directly affect tumor growth. Discuss how the bisphosphonates might be incorporated into both the prevention and treatment of cancer.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Bisphosphonates effectively inhibit osteoclast-mediated bone resorption and are integral in the treatment of benign and malignant bone diseases. The evolution of bisphosphonates over the past 30 years has led to the development of nitrogen-containing bisphosphonates (N-BPs), which have a mechanism of action different from that of the nonnitrogen-containing bisphosphonates. Studies conducted over the past decade have elucidated the mechanism of action and pharmacologic properties of the N-BPs. N-BPs exert their effects on osteoclasts and tumor cells by inhibiting a key enzyme in the mevalonate pathway, farnesyl diphosphate synthase, thus preventing protein prenylation and activation of intracellular signaling proteins such as Ras. Recent evidence suggests that N-BPs also induce production of a unique adenosine triphosphate analogue (Apppi) that can directly induce apoptosis. Our increased understanding of the pharmacologic effects of bisphosphonates is shedding light on the mechanisms by which they exert antitumor effects. As a result of their biochemical effects on protein prenylation, N-BPs induce caspase-dependent apoptosis, inhibit matrix metalloproteinase activity, and downregulate αvβ3 and αvβ5 integrins. In addition, zoledronic acid (Zometa®; Novartis Pharmaceuticals Corp.; East Hanover, NJ and Basel, Switzerland) exerts synergistic antitumor activity when combined with other anticancer agents. Zoledronic acid also inhibits tumor cell adhesion to the extracellular matrix and invasion through Matrigel™ and has antiangiogenic activity. A growing body of evidence from animal models demonstrates that zoledronic acid and other bisphosphonates can reduce skeletal tumor burden and prevent metastasis to bone. Further studies are needed to fully elucidate these biochemical mechanisms and to determine if the antitumor potential of bisphosphonates translates to the clinical setting.