bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathologic grading of medulloblastomas
Authors: Eberhart Charles G. , Kepner James L. , Goldthwaite Patricia T. , Kun Larry E. , Duffner Patricia K. , Friedman Henry S. , Strother Douglas R. , Burger Peter C. 
Published: August 2002

AbstractBACKGROUNDMedulloblastomas are small cell embryonal tumors of the cerebellum found predominantly in children, only slightly more than half of whom survive. Predicting favorable outcome has been difficult, and improved stratification clearly is required to avoid both undertreatment and overtreatment. Patients currently are staged clinically, but no pathologic staging system is in use. Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcome for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia. Therefore, the authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results.METHODSMedulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan–Meier and log‐rank analyses.RESULTSIncreasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival.CONCLUSIONSModerate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility. Cancer 2002;94:552–60. © 2002 American Cancer Society.
Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma
Authors: Bandoh Nobuyuki , Hayashi Tatsuya , Kishibe Kan , Takahara Miki , Imada Masanobu , Nonaka Satoshi , Harabuchi Yasuaki 
Published: August 2002

AbstractBACKGROUNDMany researchers have attempted to correlate p53 mutation and spontaneous apoptosis with the effectiveness of radiochemotherapy and with prognosis in several malignancies.METHODSThe current study group consisted of 70 Japanese patients with maxillary sinus squamous cell carcinoma (SCC). Fifty seven patients were treated with radiochemotherapy followed by total or partial maxillectomy, and the remaining13 patients were treated with radiotherapy alone. Tumor biopsy specimens at pretreatment status were examined for apoptosis‐related proteins such as p53 protein, Fas, bax, bcl‐x, and apoptosis using immunohistologic methods. The proportion of apoptotic cells labeled by single stranded DNA antibody was expressed as an apoptotic index (AI). p53 mutations at exons 5 through 8 were analyzed by direct sequence on polymerase chain reaction amplified products obtained from laser microdissected tissues. The effectiveness of radiochemotherapy was investigated histologically on surgically dissected specimens.RESULTSp53 mutations were identified in 20 (29%) of 70 patients. p53 protein was overexpressed in 39 patients (56%), Fas in 20 patients (29%), bax in 40 patients (57%), and bcl‐x in 33 patients (47%). Overexpression of bax was associated with negativity of bcl‐x (P = 0.015) and with high AI (P = 0.024). Low AI and/or p53 mutation in the pretreatment tissues correlated with low histologic effectiveness of radiochemotherapy (P = 0.048, P = 0.019, respectively). Kaplan‐Meier analysis as well as univariate analysis using the Cox proportional hazards model showed that low histologic effectiveness of radiochemotherapy (P = 0.0281, P = 0.0284, respectively), p53 mutations (P = 0.0095, P = 0.0187, respectively), negativity of bax (P = 0.0069, P = 0.0191, respectively), and low AI (P = 0.0134, P = 0.0407, respectively) were significantly related to worse disease‐free survival. Multivariate analysis showed AI as an independent factor predicting for disease‐free survival (P = 0.0455).CONCLUSIONSThe p53 mutations, expression of bax, and levels of spontaneous apoptosis have prognostic value in maxillary sinus SCC; AI especially is an independent factor for disease‐free survival. A high level of spontaneous apoptosis induced by overexpression of bax may increase sensitivity of radiochemotherapy resulting in good prognosis, while p53 mutation may lead to resistance against radiochemotherapy. resulting in poor prognosis. Cancer 2002;94:1968–80. © 2002 American Cancer Society.DOI 10.1002/cncr.10388
The panorama of opioid‐related cognitive dysfunction in patients with cancer
Authors: Lawlor Peter G. 
Published: August 2002

AbstractBACKGROUNDOpioids have an essential role in the management of pain in cancer patients, particularly those with advanced disease. Cognitive dysfunction is a recognized complication of opioid use. However, misconceptions and controversy surround the nature and prevalence of its occurrence. A projected increase in the aging cancer population highlights the need for a better understanding of this phenomenon.METHODSA critical appraisal of the literature evidence in relation to the pattern, pathophysiology, assessment, impact, and management of cognitive dysfunction due to opioid use in cancer pain management is given.RESULTSStudies in cancer patients with less advanced disease reveal subtle evidence of cognitive impairment, largely related to initial dosing or dose increases. In advanced cancer, opioid‐induced cognitive dysfunction usually occurs in the form of delirium, a multifactorial syndrome. The presence of both cognitive impairment and delirium frequently is misdiagnosed or missed. Potential risk factors include neuropathic and incidental pain, opioid tolerance, somatization of psychologic distress, and a history of drug or alcohol abuse. Elevation of opioid metabolites with renal impairment may contribute to cognitive dysfunction. Recognition of opioid‐related cognitive dysfunction is improved by objective screening. Successful management requires either dose reduction or a change of opioid, in addition to addressing other reversible precipitants such as dehydration or volume depletion.CONCLUSIONSOpioid‐related cognitive dysfunction tends to be subtle in the earlier stages of cancer, whereas delirium, a more florid form with behavioral disturbance is likely to be present in the advanced cancer population. In patients with advanced disease, an optimal management approach requires careful clinical assessment, identification of risk factors, objective monitoring of cognition, maintenance of adequate hydration, and either dose reduction or switching to a different opioid. Cancer 2002;94:1836–53. © 2002 American Cancer Society.DOI 10.1002/cncr.10389
The PedsQL™ in pediatric cancer
Authors: Varni James W. , Burwinkle Tasha M. , Katz Ernest R. , Meeske Kathy , Dickinson Paige 
Published: August 2002

AbstractBACKGROUNDThe Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health‐related quality of life (HRQOL) in children and adolescents ages 2–18 years. The PedsQL 4.0 Generic Core Scales are multidimensional child self‐report and parent proxy‐report scales developed as the generic core measure to be integrated with the PedsQL disease specific modules. The PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients. The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer specific HRQOL.METHODSThe PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module were administered to 339 families (220 child self‐reports; 337 parent proxy‐reports).RESULTSInternal consistency reliability for the PedsQL Generic Core Total Scale Score (α = 0.88 child, 0.93 parent report), Multidimensional Fatigue Total Scale Score (α = 0.89 child, 0.92 parent report) and most Cancer Module Scales (average α = 0.72 child, 0.87 parent report) demonstrated reliability acceptable for group comparisons. Validity was demonstrated using the known‐groups method. The PedsQL distinguished between healthy children and children with cancer as a group, and among children on‐treatment versus off‐treatment. The validity of the PedsQL Multidimensional Fatigue Scale was further demonstrated through hypothesized intercorrelations with dimensions of generic and cancer specific HRQOL.CONCLUSIONSThe results demonstrate the reliability and validity of the PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module in pediatric cancer. The PedsQL may be utilized as an outcome measure in clinical trials, research, and clinical practice. Cancer 2002;94:2090–106. © 2002 American Cancer Society.DOI 10.1002/cncr.10427
Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas
Authors: Aigner Thomas , Müller Susanna , Neureiter Daniel , Illstrup Duane M. , Kirchner Thomas , Björnsson Johannes 
Published: August 2002

AbstractBACKGROUNDConventional chondrosarcoma is the second most common malignant solid tumor of bone, and its management still poses a challenge for the orthopedic surgeon. Currently, tumor grade is the only parameter of prognostic significance besides stage and, possibly, resection margins. Additional independent prognostic markers therefore would be highly valuable for patient management.METHODSIn the current study, the authors evaluated biologic markers for various chondrocytic phenotypes by histochemical and immunohistochemical technology in a large series of clinically well defined cases of enchondromas and conventional chondrosarcomas, each with at least 5 years of clinical follow‐up.RESULTSThe authors' results confirm the strong correlation between clinical behavior and cell differentiation as expressed by marker genes. The phenotypes of the tumor cells are the biologic substrate of the histopathologic appearance of the neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and long survival. Conversely, collagen Type I, together with cell spindling, indicates a transition to a more proliferative, so‐called “dedifferentiated” phenotype, which clearly is associated with a poorer prognosis. The changes in cellular phenotypes are accompanied by changes in proliferative activity. Thus, low‐grade neoplasms showing mainly mature and terminally differentiated (hypertrophic) chondrocytes display only scant proliferation whereas less differentiated chondrosarcomas with biologically dedifferentiated chondrocytes show significantly higher proliferative activity, a feature that is also highly correlated with prognosis.CONCLUSIONSThese data indicate that molecular markers are to a large extent the biologic basis of the conventional grading, rather than representing independent prognostic markers. The authors' results further indicate that COL1 has significant value in the distinction between enchondromas and low‐grade chondrosarcomas including these that are histologically similar. Further understanding of chondrocytic phenotypes will be a promising way to provide new tumor markers for better understanding, diagnosis, and treatment of chondroid neoplasms. Cancer 2002;94:2273–81. © 2002 American Cancer Society.DOI 10.1002/cncr.10461
Depression and functional status as predictors of death among cancer patients
Authors: Stommel Manfred , Given Barbara A. , Given Charles W. 
Published: August 2002

AbstractBACKGROUNDThe current study examined the extent to which depression and functional limitations contribute to the mortality of newly diagnosed cancer patients. The analysis focused on differences in survival times among cancer patients with new experiences of depressive symptoms and functional limitations and patients with a history of such limitations.METHODSData for the current analysis came from two panel studies conducted in Michigan between 1993 and 1997, including 871 adult (≥ 21 years of age) breast, colon, lung, and prostate carcinoma patients. Information came from four separate sources: the intake patient interview, a self‐administered questionnaire, medical record audits, and the Death Certificate Registry of Michigan's Department of Community Health. With time to death as the primary outcome (followup of 571 days), data were analyzed using Kaplan‐Meier product limit estimates and the Cox proportional hazard model.RESULTSCancer patients who, after diagnosis, report only new depressive symptoms or functional limitations, have the same survival chances as those who report none. Cancer patients with either previous emotional problems or previous physical limitations face, within the first 19 months after diagnosis, a 2.6 times greater hazard of dying than patients without prior problems. Patients with both previous emotional problems and physical limitations before diagnosis have a 7.6 times greater hazard of dying within that time frame.CONCLUSIONSThe current data show cancer patients with prior limitations and emotional problems have worse survival chances than would be expected on the basis of their cancer diagnosis alone. While depressive symptoms and functional limitations are common short‐run responses to a cancer diagnosis and initial treatment, patients with no prior history of such problems appear to be more resilient. Cancer 2002;94:2719–27. © 2002 American Cancer Society.DOI 10.1002/cncr.10533
Prognostic factors for death after an isolated local recurrence in patients with early‐stage breast carcinoma
Authors: Lê Monique G. , Arriagada Rodrigo , Spielmann Marc , Guinebretière Jean‐Marc , Rochard France 
Published: August 2002

AbstractBACKGROUNDThe authors analyzed the outcome of patients with early‐stage breast carcinoma after an isolated local recurrence, taking into account initial tumor characteristics and the type of initial treatment and local salvage treatment.METHODSOne hundred five patients were studied who presented with a breast tumor measuring ≤ 25 mm and who subsequently developed an isolated local recurrence (breast or chest wall) as the first tumor event. A second series included 335 patients who developed distant metastases as the first event. Cox models that took into account potential prognostic factors were used to estimate the risk of death. First, survival rates were compared after an isolated local recurrence and after a diagnosis of distant metastases; and, second, effects of initial treatments and local or systemic treatments of local recurrences were analyzed.RESULTSThe 10‐year survival rate was 56% (95% confidence interval, 45–65%) after an isolated local recurrence compared with 9% (95% confidence interval, 7–13%) after distant metastasis as the first event. Three independent prognostic factors for the risk of death after local recurrence were identified: histologic tumor grade, patient age at the time of diagnosis with the primary tumor, and disease free interval until recurrence. The type of initial treatment and local salvage treatment did not influence the risk of death. Systemic treatments of local recurrence had different effects according to the patient's menopausal status. In premenopausal patients, ovarian suppression and chemotherapy significantly decreased the risk of death. In postmenopausal women, systemic treatments did not affect the risk of death.CONCLUSIONSIsolated local recurrences in patients with early‐stage breast carcinoma carry a moderately good prognosis. The outcome of patients is not affected by the type of initial treatment or local salvage treatment. After a local recurrence, ovarian suppression or chemotherapy had a beneficial effect in premenopausal patients. Cancer 2002; 94:2813–20. © 2002 American Cancer Society.DOI 10.1002/cncr.10572
Cholinergic innervation of the chick basilar papilla
Authors: Zidanic Michael 
Published: August 2002

AbstractAntibodies directed against choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine (ACh) and a specific marker of cholinergic neurons, were used to label axons and nerve terminals of efferent fibers that innervate the chick basilar papilla (BP). Two morphologically distinct populations of cholinergic fibers were labeled and classified according to the region of the BP they innervated. The inferior efferent system was composed of thick fibers that coursed radially across the basilar membrane in small fascicles, gave off small branches that innervated short hair cells with large cup‐like endings, and continued past the inferior edge of the BP to ramify extensively in the hyaline cell area. The superior efferent system was made up of a group of thin fibers that remained in the superior half of the epithelium and innervated tall hair cells with bouton endings. Both inferior and superior efferent fibers richly innervated the basal two thirds of the BP. However, the apical quarter of the chick BP was virtually devoid of efferent innervation except for a few fibers that gave off bouton endings around the peripheral edges. The distribution of ChAT‐positive efferent endings appeared very similar to the population of efferent endings that labeled with synapsin antisera. Double labeling with ChAT and synapsin antibodies showed that the two markers colocalized in all nerve terminals that were identified in BP whole‐mounts and frozen sections. These results strongly suggest that all of the efferent fibers that innervate the chick BP are cholinergic. J. Comp. Neurol. 445:159–175, 2002. © 2002 Wiley‐Liss, Inc.
Experience‐dependent plasticity of zinc‐containing cortical circuits during a critical period of postnatal development
Authors: Land Peter W. , Shamalla‐Hannah Lorraine 
Published: August 2002

AbstractDistinctive subsets of glutamatergic neurons in cerebral cortex sequester the transition metal zinc within the synaptic vesicles of their axon terminals. In the present study we used histochemical localization of synaptic zinc to investigate normal postnatal development and experience‐dependent plasticity of zinc‐containing circuits in somatosensory barrel cortex of rats. First, we found that zinc‐containing cortical circuits are dynamically reorganized between postnatal day (P) 0 and P28. Whereas most cortical laminae exhibited idiosyncratic increases in zinc histochemical staining with advancing age, lamina IV barrels were darkly reactive early in life and then lost much of their complement of synaptic zinc during postnatal weeks 2–4. Second, we established that sensory experience plays a major role in sculpting the zinc‐containing innervation of cortical barrels. Trimming a particular facial whisker arrested the normal postnatal decline in synaptic zinc in the corresponding, deprived barrel. This resulted in more intense zinc staining in deprived barrels compared with adjacent, nondeprived barrels. Notably, the influence of experience on development of zinc circuits was most robust during a critical period extending from about P14, when an effect of whisker trimming first could be observed, through P28, after which time chronic deprivation no longer resulted in heightened levels of synaptic zinc in lamina IV. These findings indicate that sensory input can have a marked influence on development of cortical circuits, including those within lamina IV, throughout the first postnatal month. J. Comp. Neurol. 447:43–56, 2002. © 2002 Wiley‐Liss, Inc.
Establishment of left‐right asymmetric innervation in the lancelet oral region
Authors: Kaji Takao , Aizawa Shinichi , Uemura Masanori , Yasui Kinya 
Published: August 2002

AbstractLancelets (amphioxus) exhibit a remarkable asymmetric development in the anterior body region, which is reflected in the peripheral nervous system even at adulthood. Not all of the anterior nerves are involved, but the left third to fifth nerves are clearly asymmetric. To trace the developmental process responsible for asymmetric innervation, the peripheral nerves in the anterior region were studied in pre‐ and mid‐metamorphic larvae, 1‐cm‐long juveniles, and in adults by using whole‐mount immunostaining. The mouth changes in size and location during larval life before moving ventrally and, in conjunction with this change, nerves in the oral region are also modified. The left second nerve initially innervates the oral region, but this connection is secondarily lost. As the mouth expands and shifts posteriorly, the left fifth to ninth nerves join the left third and fourth in the innervation of the oral region. The left third to sixth nerves anastomose with the oral nerve ring, which encircles the mouth on the left side. In the juveniles and adults, there are two nerve plexuses that run parallel to the margin of the oral hood. The innermost of these, the “inner oral‐hood nerve plexus”, is asymmetrically connected with the left third to fifth nerves on both sides. The other, the “outer oral‐hood nerve plexus”, is ipsilaterally connected with the third to seventh nerves on both sides. The velar nerve ring is also innervated asymmetrically by the left fourth and fifth nerves. From these observations, we suggest that the oral nerve ring is the precursor of both the inner oral‐hood nerve plexus and the velar nerve ring, and that the asymmetric innervation retained in adult lancelets is related to the early anastomosis of the left nerves with the oral nerve ring. We also show that, contrary to the persistent asymmetric innervation, the axonal patterns of the anterior peripheral nervous system in developing lancelets can change. J. Comp. Neurol. 435:394–405, 2001. © 2001 Wiley‐Liss, Inc.
Development of the perforating pathway: An ipsilaterally projecting pathway between the medial septum/diagonal band of Broca and the cingulate cortex that intersects the corpus callosum
Authors: Shu Tianzhi , Shen Wei‐Bin , Richards Linda J. 
Published: August 2002

AbstractThe perforating pathway (PFP) intersects the corpus callosum perpendicularly at the midline in the dorsoventral axis. Therefore axons in either the PFP or the corpus callosum make different axonal guidance decisions in the same anatomical region of the developing cortical midline. The mechanisms underlying these axonal choices are not known. To begin to identify these guidance mechanisms, we characterized the development of these two pathways in detail. The development of the corpus callosum and its pioneering projections has been described elsewhere (Shu and Richards [2001] J. Neurosci. 21:2749–2758; Rash and Richards [2001] J. Comp. Neurol. 434:147–157). Here we examine the development, origins, and projections of axons that make up the PFP. The majority of axons within the PFP originate from neurons in the medial septum and diagonal band of Broca complex. These neurons project in a topographic manner to the cingulate cortex. In contrast to previous reports, we find that a much smaller projection originating from the cingulate cortex also contributes to this pathway. The pioneering projections of the PFP and the corpus callosum arrive at the corticoseptal boundary at around the same developmental stage. These findings show that ipsilaterally projecting PFP axons and contralaterally projecting callosal axons make distinct guidance decisions at the same developmental stage when they reach the corticoseptal boundary. J. Comp. Neurol. 436:411–422, 2001. © 2001 Wiley‐Liss, Inc.