bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus
Authors: Halfon Philippe , Bourlière Marc , Pénaranda Guillaume , Deydier Romaric , Renou Christophe , Botta-Fridlund Danielle , Tran Albert , Portal Isabelle , Allemand Isabelle , Rosenthal-Allieri Alessandra , Ouzan Denis 
Published: July 2005

Abstract

Background
In patients with chronic hepatitis C virus, liver biopsy is the gold standard for assessing liver disease stage; nevertheless, it is prone to complications, some of them serious. Non-invasive methods have been proposed as surrogate markers for liver fibrosis. It was shown that serum hyaluronic acid (HA) level increases with the development for liver fibrosis. The aim of this study was to evaluate the diagnostic value of HA as well as to determine the HA level cut-off for predicting the presence or absence of fibrosis, severe fibrosis, and cirrhosis.

Results
405 patients with chronic hepatitis C were prospectively included with biomarker measurement and liver biopsy done the same day: 151 in the training set (only biopsy lengths of 25 mm or more) and 254 in the validation set. For the discrimination of significant fibrosis, severe fibrosis, and cirrhosis in the training set, the areas under curve (AUCs) were 0.75 ± 0.03, 0.82 ± 0.02, and 0.89 ± 0.03, respectively. Absence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 16, 25, and 50 μg/l, respectively (with negative predictive values of 82%, 89%, and 100%, in the same order). Presence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 121, 160, and 237 μg/l, respectively (with positive predictive values of 94%, 100%, and 57%, in the same order).

Conclusion
In the validation set, HA was accurate in predicting significant fibrosis, severe fibrosis, and cirrhosis with AUCs of 0.73, 0.77, and 0.97, respectively. Moreover, accurate HA level cut-offs were defined for predicting significant fibrosis, severe fibrosis, and cirrhosis. Thus, the study supports that HA level may be clinically useful as a non-invasive marker for liver fibrosis and/or cirrhosis.
Improved Hepatic Toxicity Profile of Portal Vein Adjuvant Hepatic Infusional Chemotherapy
Authors: Faynsod Moshe , Wagman Lawrence D. , Longmate Jeff , Carroll Mary , Leong Lucille A. 
Published: July 2005

Purpose To determine whether floxuridine (FUDR) can be delivered with low hepatic toxicity through the portal vein (PV) as an adjuvant to surgically treated colorectal metastases. Patients and Methods Fifty-one patients undergoing complete resection and/or ablation for colorectal hepatic metastases were prospectively enrolled at a National Cancer Institute–designated comprehensive cancer center. Two sequential phase II trials were performed. Each trial included complete surgical treatment followed by sequential, alternating (22 patients) or concurrent (29 patients) regional PV FUDR and systemic fluorouracil (FU) with leucovorin chemotherapy. Results Fifty percent of patients were male. The mean age at diagnosis was 57 years. The mean number of lesions resected was three (range, one to 11 lesions). The stage at diagnosis was II, III, and IV in 16.9%, 52.8%, and 28.3% of patients, respectively. One- and 3-year overall survival rates were 92.7% and 41.8%, respectively. The 1- and 3-year disease-free survival rates were 64.5% and 19%, respectively. The site of first recurrence was hepatic in 35.9% of patients. Treatment was terminated early in 24 patients (17 patients progressed, two refused treatment, and five had nonhepatic toxicities). Fifty-five percent of patients received 75% to 100% of the planned FUDR courses, and 72% received greater than 50% of the planned FUDR dose. Only four patients required dose reductions of FUDR because of grade 3 hepatic toxicity. No patient required biliary stenting or had discontinuation of PV infusion because of hepatic toxicity. Conclusion The delivery of PV FUDR and FU with leucovorin can be performed with a high percentage of expected drug delivery and a low drug-induced hepatic toxicity rate, while achieving acceptable overall and disease-free survival.
Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results—EORTC 22921
Authors: Bosset Jean-François , Calais Gilles , Mineur Laurent , Maingon Philippe , Radosevic-Jelic Ljiljana , Daban Alain , Bardet Etienne , Beny Alexander , Briffaux Antoine , Collette Laurence 
Published: July 2005

Purpose The European Organisation for Research and Treatment of Cancer (EORTC) trial evaluated the addition of chemotherapy (CT) to preoperative radiation (preop RT) and the value of postoperative CT for improving the survival in patients with T3-4 resectable rectal cancer. Patients were allocated to the following four arms: arm 1, preop RT 45 Gy in 5 weeks; arm 2, preop RT plus two 5-day CT courses (fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d) in the first and fifth week of RT; arm 3, preop RT plus four postoperative CT courses; and arm 4, preop RT and CT plus postoperative CT. We investigated the effect of adding CT on the pathologic parameters. Patients and Methods One thousand eleven patients were entered onto the trial; 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms 2 and 4). We analyzed the differences in tumor size, tumor node stage, number of retrieved nodes, and histologic features such as lymphatic, venous, and perineural invasions, tumor differentiation, and tumor type. Results After preop RT-CT, tumors were smaller (P < .0001), had less advanced pT (P < .001) and pN stages (P < .001), had small numbers of examined nodes (P = .046), and less frequent LVN invasions (P ≤ .008). Mucinous tumors increased after preop RT-CT (P < .001). Conclusion In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces downsizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.
Phase I Trial of Systemic Oxaliplatin Combination Chemotherapy With Hepatic Arterial Infusion in Patients With Unresectable Liver Metastases From Colorectal Cancer
Authors: Kemeny Nancy , Jarnagin William , Paty Philip , Gönen Mithat , Schwartz Lawrence , Morse Meroë , Leonard Gregory , D’Angelica Michael , DeMatteo Ronald , Blumgart Leslie , Fong Yuman 
Published: July 2005

Purpose To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. Patients and Methods Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. Results The MTD for patients in group A was Oxal 100 mg/m2, CPT-11 150 mg/m2, and FUDR 0.12 mg/kg × 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m2, LV 400 mg/m2, and FU 1,400 mg/m2 by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. Conclusion Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.
Phase II Multicenter Study of the Antiepidermal Growth Factor Receptor Monoclonal Antibody Cetuximab in Combination With Platinum-Based Chemotherapy in Patients With Platinum-Refractory Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
Authors: Baselga José , Trigo José M. , Bourhis Jean , Tortochaux Jacques , Cortés-Funes Hernán , Hitt Ricardo , Gascón Pere , Amellal Nadia , Harstrick Andreas , Eckardt André 
Published: July 2005

Purpose To evaluate the efficacy and safety of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Ninety-six eligible patients received cetuximab (initial dose of 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) followed by platinum chemotherapy at the same dose and schedule at which progressive disease was documented before entry onto the study. Results The response rate, based on an independently read assessment, in the intent-to-treat population was 10%, with a disease control rate (complete response, partial response [PR], and stable disease) of 53%. The median time to progression and overall survival were 85 and 183 days, respectively; both were longest in patients achieving a PR (median, 203.5 and 294 days, respectively). Treatment was well tolerated. The most common cetuximab-related adverse events were skin reactions, particularly an acne-like rash. Conclusion The combination of cetuximab and platinum chemotherapy is an active and well-tolerated approach to the treatment of this poor-prognosis patient population with platinum-refractory recurrent or metastatic SCCHN for whom there are no recommended standard therapeutic options.
Phase II Multicenter Study of the Epidermal Growth Factor Receptor Antibody Cetuximab and Cisplatin for Recurrent and Refractory Squamous Cell Carcinoma of the Head and Neck
Authors: Herbst Roy S. , Arquette Matthew , Shin Dong M. , Dicke Karel , Vokes Everett E. , Azarnia Nozar , Hong Waun Ki , Kies Merrill S. 
Published: July 2005

Purpose This multicenter phase II study was undertaken to define the efficacy and safety of cetuximab, an antiepidermal growth factor receptor chimeric human and murine monoclonal antibody, administered with cisplatin to patients with refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods One hundred thirty-two patients were to receive two 3-week cycles with cisplatin/paclitaxel or cisplatin/fluorouracil. Patients (n = 30) with a complete or partial response continued standard therapy. Seventy-six patients with stable disease (SD; n = 51) or progressive disease (PD/1; n = 25) received combination therapy with cetuximab (400 mg/m2 intravenously on day 1, then 250 mg/m2/wk) and cisplatin (75 or 100 mg/m2 intravenously on day 1 every 3 weeks). The protocol was subsequently amended to enroll patients who had developed PD within 90 days after platinum-based therapy (PD/2; n = 54). Results Five patients (20%) in PD/1, three patients (6%) in PD/2, and nine patients (18%) with SD achieved an objective response. Median duration of response was 4.2, 4.1, and 7.4 months for the PD/1, PD/2, and SD groups, respectively, with median overall survival times of 6.1, 4.3, and 11.7 months. The most common toxicities were anemia, acne-like skin rash, leukopenia, fatigue and malaise, and nausea and vomiting. Seven patients (5%) developed a grade 3 or 4 hypersensitivity reaction to cetuximab. Conclusion Cetuximab and cisplatin is an active regimen in refractory SCCHN. The relative contribution of cetuximab is better defined in a single-agent trial. Cetuximab did not exacerbate cisplatin toxicity but was associated with skin rash in a majority of patients and occasional serious allergic reactions. Further study of this compound is warranted.
Phase I and Pharmacodynamic Study of the Oral MEK Inhibitor CI-1040 in Patients With Advanced Malignancies
Authors: LoRusso Patricia M. , Adjei Alex A. , Varterasian Mary , Gadgeel Shirish , Reid Joel , Mitchell David Y. , Hanson Lorelei , DeLuca Pamela , Bruzek Laura , Piens Jill , Asbury Peggy , Van Becelaere Keri , Herrera Roman , Sebolt-Leopold Judith , Meyer Mark B. 
Published: July 2005

Purpose This phase I study was undertaken to define the toxicity, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD), and clinical activity of CI-1040, a small-molecule inhibitor of the dual-specificity kinases MEK(mitogen-activated protein kinase kinase) -1 and MEK2 , in patients with advanced malignancy. Patients and Methods CI-1040 was tested in multiple daily dosing frequencies administered for 21 days repeated every 28 days leading ultimately to continuous administration, and effect of food on absorption was tested. Single dose and steady-state pharmacokinetics were assessed during cycle 1 and phosphorylated extracellular receptor kinase (pERK) levels were assessed in WBCs and also in tumor tissue from selected patients. Results Seventy-seven patients received CI-1040 at dose levels ranging from 100 mg QD to 800 mg tid. Grade 3 asthenia was dose limiting at the highest dose level tested, 800 mg tid administered with food. Ninety-eight percent of all drug-related adverse events were grade 1 or 2 in severity; most common toxicities included diarrhea, asthenia, rash, nausea, and vomiting. Plasma concentrations of CI-1040 and its active metabolite, PD 0184264, increased in a less than dose proportional manner from 100 to 800 mg QD. Administration with a high-fat meal resulted in an increase in drug exposure. The MTD and recommended phase II dose was 800 mg BID administered with food. Sixty-six patients were assessable for response. One partial response was achieved in a patient with pancreatic cancer and 19 patients (28%) achieved stable disease lasting a median of 5.5 months (range, 4 to 17 months). Inhibition of tumor pERK (median, 73%; range, 46% to 100%) was demonstrated in 10 patients. Conclusion CI-1040 was well tolerated at 800 mg BID administered with food. Both target suppression and antitumor activity were demonstrated in this phase I study.
Clinicopathologic and Genetic Profile of Intracranial Marginal Zone Lymphoma: A Primary Low-Grade CNS Lymphoma That Mimics Meningioma
Authors: Tu Pang-hsien , Giannini Caterina , Judkins Alexander R. , Schwalb Jason M. , Burack Richard , O'Neill Brian P. , Yachnis Anthony T. , Burger Peter C. , Scheithauer Bernd W. , Perry Arie 
Published: July 2005

PurposeAlthough rare overall, marginal zone B-cell lymphoma (MZBCL) is the most common primary low-grade CNS lymphoma reported in the literature. The aim of this study is to elucidate the biology and genetic features of this unusual tumor.Patients and MethodsFifteen CNS MZBCLs were studied clinically, pathologically, and genetically, including fluorescent in situ hybridization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 18 probes.ResultsCNS MZBCLs preferentially affect middle-aged women (female-to-male ratio, 4:1), with 93% presenting as dural-based masses mimicking meningioma. Ten patients with 1 to 7.6 years of follow-up after diagnosis showed no evidence of disease after radiation and/or chemotherapy. Like MZBCLs outside of the CNS, they consisted of CD20+, CD3−small B lymphocytes with varying degrees of plasmacytic differentiation and predominantly κ light-chain restriction (78%). Lymphoid follicles with follicular colonization were seen in three patients and deposition of amyloid was noted in samples from two patients, one of which was tumefactive. Neither Bcl-6 protein nor Epstein-Barr virus–encoded RNA was expressed. Trisomy 3 was detected in six of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected.ConclusionOur data suggest that intracranial MZBCL is an indolent primary CNS lymphoma that typically presents as a meningioma-like dural-based mass. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality that may contribute to the pathogenesis of this CNS lymphoma.
Lymphocyte-Rich Classical Hodgkin's Lymphoma: Clinical Presentation and Treatment Outcome in 100 Patients Treated Within German Hodgkin's Study Group Trials
Authors: Shimabukuro-Vornhagen Alexander , Haverkamp Heinz , Engert Andreas , Balleisen Leopold , Majunke Peter , Heil Günther , Eich Hans Theodor , Stein Harald , Diehl Volker , Josting Andreas 
Published: July 2005

Purpose To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-rich classical Hodgkin's lymphoma (LRCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL). Patients and Methods From a total of 2,715 patients with biopsy-proven HL treated within the trials HD7 to HD12 of the German Hodgkin's Study Group, 100 patients (4%) with LRCHL, 145 patients (5%) with lymphocyte-predominant HL (LPHL), 1,688 patients (62%) with nodular sclerosis, 731 patients (27%) with mixed cellularity, and 23 patients (1%) with lymphocyte depletion were identified. Patients with LRCHL had a median age of 38 years (range, 16 to 74 years). Results Compared with other histologic subtypes, patients with LRCHL are, on average, older and usually present with early stages of disease (stage I, 34%; stage II, 46%). The median time of follow-up was 32.2 months (95% CI, 28.2 to 37.0 months). Complete and partial remission was achieved in 96 patients (96%) and four patients (4%), respectively, with LRCHL. The event-free and overall survival rates were 97% (95% CI, 96.7% to 96.9%) and 97% (95% CI, 96.8% to 97.0%), respectively, at 30 months. Only three patients died; all of the deaths were caused by treatment-related toxicities. Conclusion LRCHL is a distinct subtype of CHL, with features of CHL and LPHL, and is a rare entity accounting for only 4% of HLs. LRCHL has a different pattern of clinical presentation and age and sex distribution than other CHLs. It is associated with an excellent prognosis if treated with current treatment regimens. When treating patients with LRCHL, great attention should be paid to avoid acute toxicities.
Potential impact of dare county landfills on Alligator River National Wildlife Refuge
Authors: Winger Parley V. , Lasier Peter J. , Augspurger Tom 
Published: July 2005

Abstract
Runoff of leachate from East Lake and Dare County Construction and Demolition Debris landfills has the potential to impact wildlife resources at Alligator River National Wildlife Refuge, Dare and Hyde Counties, North Carolina. Sediment quality of samples collected in August 2000 at 14 locations down-gradient from the landfills was assessed by measuring metal and organic contaminants in the sediments, chronic toxicity of solid-phase sediment (28-d static-renewal exposures; survival and growth as test endpoints) and acute toxicity of sediment porewater (96-h static exposures) to Hyalella azteca (Crustacea: Amphipoda). In addition, contaminant bioaccumulation from 4 sediments was determined using 28-d exposures of Lumbriculus variegatus (freshwater oligochaete). Although survival was not impaired, length of H. azteca was significantly reduced in sediments from 5 locations. Pore water from 4 locations was acutely toxic to H. azteca. Metals and a few polycyclic aromatic hydrocarbons (PAHs) were bioaccumulated by L variegatus from the sediments. Several metals and PAHs exceeded sediment quality guidelines, and metals in porewater from several sites exceeded water quality criteria for the protection of aquatic wildlife. Runoff of leachate from the landfills has reduced sediment quality and has the potential to adversely affect wildlife resources at Alligator River National Wildlife Refuge.
The Impact of mining activities on mongolia's protected areas: A status report with policy recommendations
Authors: Farrington John D. 
Published: July 2005

Abstract
Mongolia's protected areas cover 20.5 million ha or 13.1 % of its national territory. Existing and proposed protected areas, however, are threatened by mining. Mining impacts on Mongolia's protected areas are diverse and include licensed and unlicensed mineral activities in protected areas, buffer zone disturbance, and prevention of the establishment of proposed protected areas. Review of United States, Canadian, and Australian policies revealed 9 basic approaches to resolving conflicts between protected areas and mining. Four approaches suitable for Mongolia are granting land trades and special dispensations in exchange for mineral licenses in protected areas; granting protected status to all lapsed mineral licenses in protected areas; voluntary forfeiting of mineral licenses in protected areas in exchange for positive corporate publicity; and prohibiting all new mineral activities in existing and proposed protected areas. Mining is Mongolia's most important industry, however, and the long-term benefits of preserving Mongolia's natural heritage must be considered and weighed against the economic benefits and costs of mining activities.
Two simple algorithms for refining mammalian receptor selection in ecological risk assessments
Authors: Tannenbaum Lawrence V. 
Published: July 2005

Abstract
Although guidelines exist for selecting appropriate ecological receptors for risk assessments at contaminated sites, it can be demonstrated that many of the mammals commonly evaluated are spatially irrelevant. Terrestrial risk assessments could be simplified and made more efficient, though, if mammals that are initially considered were screened for their spatial relevance. This article presents 2 simple algorithms that each demonstrate that most mammalian receptors are not spatially relevant for the overwhelming majority of hazardous waste and other contaminated sites. The algorithms use readily available and curiously overlooked spatial distribution (e.g., animal density) information and suggest that contaminated sites need to be 80 to 100 acres in size to justify the inclusion of most mammalian receptors. Given that hazardous waste sites are generally much smaller than this, many ecological risk assessments (ERA) could reasonably dispense with incorporating mammals entirely. An awareness on the part of decision makers and risk managers of the nonsuitability of many mammalian receptors evaluated in terrestrial ERAs could significantly impact the perceived need to monitor or remediate sites. This article also examines the anticipated challenges of regulators and other decision makers when entertaining the notion of a spatial relevance screen for mammals.