bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual colonoscopy in stenosing colorectal cancer
Authors: Coccetta Marco , Migliaccio Carla , La Mura Francesco , Farinella Eriberto , Galanou Ioanna , Delmonaco Pamela , Spizzirri Alessandro , Napolitano Vincenzo , Cattorini Lorenzo , Milani Diego , Cirocchi Roberto , Sciannameo Francesco 
Published: November 2009

Abstract

Background
Between 5 and 10% of the patients undergoing a colonoscopy cannot have a complete procedure mainly due to stenosing neoplastic lesion of rectum or distal colon. Nevertheless the elective surgical treatment concerning the stenosis is to be performed after the pre-operative assessment of the colonic segments upstream the cancer.
The aim of this study is to illustrate our experience with the Computed Tomographic Colonography (CTC) for the pre-operative assessment of the entire colon in the patients with stenosing colorectal cancers.

Methods
From January 2005 till March 2009, we observed and treated surgically 43 patients with stenosing colorectal neoplastic lesions. All patients did not tolerate the pre-operative colonoscopy. For this reason they underwent a pre-operative CTC in order to have a complete assessment of the entire colon. All patients underwent a follow-up colonoscopy 3 months after the surgical treatment. The CTC results were compared with both macroscopic examination of the specimen and the follow-up coloscopy.

Results
The pre-operative CTC showed four synchronous lesions in four patients (9.3% of the cases). The macroscopic examination of the specimen revealed three small sessile polyps (3 - 4 mm in diameter) missed in the pre-operative assessment near the stenosing colorectal cancer. The follow-up colonoscopy showed four additional sessile polyps with a diameter between 3 - 11 mm in three patients.
Our experience shows that CTC has a sensitivity of 83,7%.

Conclusion
In patients with stenosing colonic lesions, CTC allows to assess the entire colon pre-operatively avoiding the need of an intraoperative colonoscopy. More synchronous lesions are detected and treated at the time of the elective surgery for the stenosing cancer avoiding further surgery later on.
Virological pattern of hepatitis B infection in an HIV-positive man with fatal fulminant hepatitis B: a case report
Authors: Bagaglio Sabrina , Albarello Luca , Biswas Priscilla , Uberti-Foppa Caterina , Fortis Claudio , Morsica Giulia 
Published: November 2009

AbstractIntroductionThere seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.Case presentationA 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.ConclusionThis case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.
Y-Box–Binding Protein YB-1 Identifies High-Risk Patients With Primary Breast Cancer Benefiting From Rapidly Cycled Tandem High-Dose Adjuvant Chemotherapy
Authors: Gluz Oleg , Mengele Karin , Schmitt Manfred , Kates Ronald , Diallo-Danebrock Raihana , Neff Frauke , Royer Hans-Dieter , Eckstein Niels , Mohrmann Svjetlana , Ting Evelyn , Kiechle Marion , Poremba Christopher , Nitz Ulrike , Harbeck Nadia 
Published: November 2009

PurposeTo investigate the potential of Y-box–binding protein YB-1, a multifunctional protein linked to tumor aggressiveness and multidrug resistance, to identify patients with breast cancer likely to benefit from dose-intensified chemotherapy regimens.Patients and MethodsYB-1 was immunohistochemically determined in 211 primary tumors from the prospective, randomized West German Study Group WSG-AM-01 trial in high-risk (≥ 10 involved lymph-nodes) breast cancer (HRBC). Predictive impact of YB-1 was assessed by multivariate survival analysis, including time-varying factor-therapy interactions.ResultsAt median follow-up of 61.7 months, patients receiving rapidly cycled tandem high-dose therapy (HD; two cycles [2×] epirubicin 90 mg/m2and cyclophosphamide 600 mg/m2every 14 days, followed by 2× epirubicin 90 mg/m2, cyclophosphamide 3,000 mg/m2, and thiotepa 400 mg/m2every 21 days) had better disease-free survival (DFS; hazard ratio [HR] = 0.62; 95% CI, 0.44 to 0.89) and overall survival (OS; HR = 0.59; 95% CI, 0.4 to 0.89) than those receiving conventional dose-dense chemotherapy (DD; 4× epirubicin 90 mg/m2and cyclophosphamide 600 mg/m2, followed by 3× cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2every 14 days). High YB-1 was associated with aggressive tumor phenotype (negative steroid hormone receptor status, positive human epidermal growth factor receptor 2 and p53 status, high MIB-1, unfavorable tumor grade) and poor OS (median 78 v 97 months; P = .01). In patients with high YB-1, HD yielded a 63-month median DFS (P = .001) and a 46-month median OS advantage (P = .002) versus DD. In multivariate models, patients with high B-1 receiving HD (v DD) had one third the hazard rate after 20 months for DFS and one sixth after 40 months for OS.ConclusionIn a randomized prospective cancer therapy trial, for the first time, a strong predictive impact of YB-1 on survival has been demonstrated: enhanced benefit from HD (v DD) therapy occurs in HRBC with high YB-1. Future trials could therefore address optimal chemotherapeutic strategies,taking YB-1 into account.
Hodgkin's Lymphoma in Adolescents Treated With Adult Protocols: A Report From the German Hodgkin Study Group
Authors: Eichenauer Dennis A. , Bredenfeld Henning , Haverkamp Heinz , Müller Horst , Franklin Jeremy , Fuchs Michael , Borchmann Peter , Müller-Hermelink Hans-Konrad , Eich Hans T. , Müller Rolf-Peter , Diehl Volker , Engert Andreas 
Published: November 2009

Purpose The standard of care for adolescent patients with Hodgkin's lymphoma (HL) is undefined, particularly the choice between pediatric and adult protocols. Thus, we compared risk factors and outcome of adolescents and young adults treated within study protocols of the German Hodgkin Study Group (GHSG). Patients and Methods Three thousand seven hundred eighty-five patients treated within the GHSG studies HD4 to HD9 were analyzed; 557 patients were adolescents age 15 to 20 years, and 3,228 patients were young adults age 21 to 45 years. Results Large mediastinal mass and involvement of three or more lymph node areas were more frequent in adolescents (P < .001). The incidence of other risk factors did not differ significantly between age groups. With a median observation time of 81 months for freedom from treatment failure (FFTF) and 85 months for overall survival (OS), log-rank test showed no significant differences between age groups regarding FFTF (P = .305) and a superior OS (P = .008) for adolescents. Six-year estimates for FFTF and OS were 80% and 94%, respectively, for adolescents and 80% and 91%, respectively, for young adults. After adjustment for other predictive factors, Cox regression analysis revealed age as a significant predictor for OS (P = .004), with a higher mortality risk for young adults. Secondary malignancies were more common in young adults (P = .037). Conclusion Outcome of adolescent and young adult patients treated within GHSG study protocols is comparable. These data suggest that adult treatment protocols exhibit a safe and effective treatment option for adolescent patients with HL. However, longer follow-up, including assessment of late toxicity, is necessary for final conclusions.
Dose-Dense Adjuvant Doxorubicin and Cyclophosphamide Is Not Associated With Frequent Short-Term Changes in Left Ventricular Ejection Fraction
Authors: Morris Patrick G. , Dickler Maura , McArthur Heather L. , Traina Tiffany , Sugarman Steven , Lin Nancy , Moy Beverly , Come Steven , Godfrey Laura , Nulsen Benjamin , Chen Carol , Steingart Richard , Rugo Hope , Norton Larry , Winer Eric , Hudis Clifford A. , Dang Chau T. 
Published: November 2009

Purpose Doxorubicin and cyclophosphamide (AC) every 3 weeks has been associated with frequent asymptomatic declines in left ventricular ejection fraction (LVEF). Dose-dense (dd) AC followed by paclitaxel (P) is superior to the same regimen given every third week. Herein, we report the early cardiac safety of three sequential studies of ddAC alone or with bevacizumab (B). Patients and Methods Patients with HER2-positive breast cancer were treated on two trials: ddAC followed by P and trastuzumab (T) and ddAC followed by PT and lapatinib. Patients with HER2-normal breast cancer were treated with B and ddAC followed by B and nanoparticle albumin–bound P. Prospective LVEF measurement by multigated radionuclide angiography scan before and after every 2 week AC for 4 cycles and at month 6 from all three trials were aggregated to determine the early risks of cardiac dysfunction. Results From January 2005 to May 2008, 245 patients were enrolled. The median age was 47 years (range, 27 to 75 years). Median LVEF pre-ddAC was 68% (range, 52% to 82%). LVEF post-ddAC was available in 241 patients (98%) and the median was unchanged at 68% (range, 47% to 81%). Per protocol no patients were ineligible for subsequent targeted biologic therapy based on LVEF decline post-ddAC. In addition, LVEF was available in 222 patients (92%) at 6 months, at which time the median LVEF was similar at 65% (range, 24% to 80%). Within 6 months of initiating chemotherapy, three patients (1.2%; 95% CI, 0.25% to 3.54%) developed CHF, all of whom received T. Conclusion Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.
Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects
Authors: Treviño Lisa R. , Shimasaki Noriko , Yang Wenjian , Panetta John C. , Cheng Cheng , Pei Deqing , Chan Diana , Sparreboom Alex , Giacomini Kathleen M. , Pui Ching-Hon , Evans William E. , Relling Mary V. 
Published: November 2009

PurposeMethotrexate plasma concentration is related to its clinical effects. Our aim was to identify the genetic basis of interindividual variability in methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia (ALL).Patients and MethodsWe performed a genome-wide analysis of 500,568 germline single-nucleotide polymorphisms (SNPs) to identify how inheritance affects methotrexate plasma disposition among 434 children with ALL who received 3,014 courses of methotrexate at 2 to 5 g/m2. SNPs were validated in an independent cohort of 206 patients.ResultsAdjusting for age, race, sex, and methotrexate regimen, the most significant associations were with SNPs in the organic anion transporter polypeptide, SLCO1B1. Two SNPs in SLCO1B1, rs11045879 (P = 1.7 × 10−10) and rs4149081 (P = 1.7 × 10−9), were in linkage disequilibrium (LD) with each other (r2= 1) and with a functional polymorphism in SLCO1B1, T521C (rs4149056; r2> 0.84). rs11045879 and rs4149081 were validated in an independent cohort of 206 patients (P = .018 and P = .017), as were other SLCO1B1 SNPs residing in different LD blocks. SNPs in SLCO1B1 were also associated with GI toxicity (odds ratio, 15.3 to 16.4; P = .03 to .004).ConclusionA genome-wide interrogation identified inherited variations in a plausible, yet heretofore low-priority candidate gene, SLCO1B1, as important determinants of methotrexate's pharmacokinetics and clinical effects.
Cyclophosphamide, Epirubicin, and Fluorouracil Versus Dose-Dense Epirubicin and Cyclophosphamide Followed by Paclitaxel Versus Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Node-Positive or High-Risk Node-Negative Breast Cancer
Authors: Burnell Margot , Levine Mark N. , Chapman Judith-Anne W. , Bramwell Vivien , Gelmon Karen , Walley Barbara , Vandenberg Ted , Chalchal Haji , Albain Kathy S. , Perez Edith A. , Rugo Hope , Pritchard Kathleen , O'Brien Patti , Shepherd Lois E. 
Published: November 2009

Purpose Cyclophosphamide, epirubicin, and fluorouracil (CEF) and doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) are commonly used adjuvant regimens in women with early breast cancer. In a previous trial in women with locally advanced breast cancer, 3 months of high-dose epirubicin and cyclophosphamide (EC) administered every 2 weeks (dose-dense) was equivalent to 6 months of CEF. We hypothesized that 3 months of paclitaxel after dose-dense EC (EC/T) would be superior to CEF or AC/T. Methods After lumpectomy or mastectomy, women 60 years of age or younger with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive CEF, EC/T, or AC/T for 6 months. This article reports the interim analysis for recurrence-free survival (RFS), which was planned after 227 recurrences. Results A total of 2,104 patients were enrolled. The median follow-up is 30.4 months. Hazard ratios for recurrence are as follows: AC/T versus CEF, 1.49 (95% CI, 1.12 to 1.99), P = .005; AC/T versus EC/T, 1.68 (95% CI, 1.25 to 2.27), P = .0006; and EC/T versus CEF, 0.89 (95% CI, 0.64 to 1.22), P = .46. Three-year RFS rates for CEF, EC/T, and AC/T are 90.1%, 89.5%, and 85.0%, respectively. There was more febrile neutropenia with CEF (22.3%) and EC/T (16.4%) compared with AC/T (4.8%), but more neuropathy with the last two regimens. Conclusion Three-weekly AC/T is significantly inferior to CEF or EC/T in terms of RFS. It is too early to detect any difference between CEF and dose-dense EC/T.
Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Authors: Makhija Sharmila , Amler Lukas C. , Glenn Dana , Ueland Frederick R. , Gold Michael A. , Dizon Don S. , Paton Virginia , Lin Chin-Yu , Januario Thomas , Ng Kimmie , Strauss Andreas , Kelsey Stephen , Sliwkowski Mark X. , Matulonis Ursula 
Published: November 2009

Purpose Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer. Patients and Methods Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting. Results One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm. Conclusion Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.
Survival Effect of Venous Thromboembolism in Patients With Multiple Myeloma Treated With Lenalidomide and High-Dose Dexamethasone
Authors: Zangari Maurizio , Tricot Guido , Polavaram Latha , Zhan Fenghuang , Finlayson Ashlie , Knight Robert , Fu Tommy , Weber Donna , Dimopoulos Meletios A. , Niesvizky Ruben , Fink Louis 
Published: November 2009

Purpose We conducted a retrospective analysis of the survival effect of venous thromboembolism (VTE) development in patients with multiple myeloma (MM). Methods Two identically designed, multicenter, double-blind, phase III clinical trials (MM-009 and MM-010) were conducted in Europe and the United States to assess the effect of lenalidomide in combination with dexamethasone versus dexamethasone plus placebo in patients with relapsed or refractory MM, after failing at least one prior line of treatment. In this retrospective analysis, we evaluated incidence and survival effect of thromboembolism in 353 patients randomly assigned to receive 25 mg of lenalidomide on days 1 through 21 of a 28-day cycle, plus 40 mg of oral dexamethasone on days 1 through 4, 9 through 12, and 17 through 20 for the first four cycles; after the fourth cycle, 40 mg of dexamethasone was administered on days 1 through 4 only. Results Seventeen percent of patients experienced a thromboembolic episode. The development of VTE did not significantly affect overall survival (P = .90) or time to progression (P = .34). No significant survival impact was observed in a subgroup of patients who received prophylactic anticoagulation (overall survival P = .7, time to progression P = .1). Conclusion Patients with MM treated with lenalidomide and high-dose dexamethasone who developed a VTE did not experience shorter overall survival or time to progression.
Neoadjuvant Chemotherapy Shows Similar Response in Patients With Inflammatory or Locally Advanced Breast Cancer When Compared With Operable Breast Cancer: A Secondary Analysis of the GeparTrio Trial Data
Authors: Costa Serban Dan , Loibl Sibylle , Kaufmann Manfred , Zahm Dirk-Michael , Hilfrich Jörn , Huober Jens , Eidtmann Holger , du Bois Andreas , Blohmer Jens-Uwe , Ataseven Beyhan , Weiss Erich , Tesch Hans , Gerber Bernd , Baumann Klaus H. , Thomssen Christoph , Breitbach Georg Peter , Ibishi Shaip , Jackisch Christian , Mehta Keyur , von Minckwitz Gunter 
Published: November 2009

Purpose Neoadjuvant chemotherapy followed by mastectomy is the treatment of choice in patients with inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC), but it is considered less effective in these diseases than in operable breast cancer (OBC). We report a prospective comparison of the GeparTrio trial of patients with IBC (cT4 days) or LABC (cT4a-c or cN3; stage IIIB or IIIC) and patients with OBC (cT2-3). Patients and Methods Participants were stratified by stage and were randomly assigned to six or eight cycles of docetaxel/doxorubicin/cyclophosphamide (TAC) or to two cycles of TAC followed by four cycles of vinorelbine/capecitabine. We present results of a secondary aim of the study, which was to compare pathologic complete response (pCR; ie, no remaining invasive/noninvasive tumor in breast and lymph nodes) in different stage groups. Results A total of 287 patients with IBC (n = 93) or LABC (n = 194) and 1,777 patients with OBC were entered onto the trial. At baseline, parameters were as follows for the three types of cancer, respectively: median tumor sizes: 8.0 cm, 7.0 cm, and 4.0 cm (P < .001); multiple lesions: 31.2%, 27.3%, and 19.6% (P < .001); nodal involvement: 86.6%, 71.2%, and 51.6% (P < .001); grade 3: 44.4%, 30.4%, and 39.9% (P = .178); lobular-invasive type: 7.5%, 17.5%, and 13.3% (P = .673); negative hormone receptor status: 38.0%, 20.0%, and 36.4% (P = .008); and positive human growth factor receptor 2 status: 45.1%, 38.9%, and 35.7% (P = .158). Response rates for IBC, LABC, and OBC, respectively, were 8.6%, 11.3%, and 17.7% for pCR (P = .002); 71.0%, 69.6%, and 83.4% for overall response by physical or sonographic examination (P < .001); and 12.9%, 33.0%, and 69.9% for breast conservation (P < .001). All P values were for IBC and LABC versus OBC. However, tumor stage itself was not an independent predictor for pCR in multivariable analysis (odds ratio, 1.51; 95% CI, 0.88 to 2.59; P = .13). Conclusion No evidence of a difference in response to neoadjuvant chemotherapy was found by tumor stage when analysis was adjusted for baseline characteristics.
NOA-04 Randomized Phase III Trial of Sequential Radiochemotherapy of Anaplastic Glioma With Procarbazine, Lomustine, and Vincristine or Temozolomide
Authors: Wick Wolfgang , Hartmann Christian , Engel Corinna , Stoffels Mandy , Felsberg Jörg , Stockhammer Florian , Sabel Michael C. , Koeppen Susanne , Ketter Ralf , Meyermann Richard , Rapp Marion , Meisner Christof , Kortmann Rolf D. , Pietsch Torsten , Wiestler Otmar D. , Ernemann Ulrike , Bamberg Michael , Reifenberger Guido , von Deimling Andreas , Weller Michael 
Published: November 2009

Purpose The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas. Patients and Methods Patients (N = 318) were randomly assigned 2:1:1 (A:B1:B2) to receive conventional radiotherapy (arm A); procarbazine, lomustine (CCNU), and vincristine (PCV; arm B1); or temozolomide (arm B2) at diagnosis. At occurrence of unacceptable toxicity or disease progression, patients in arm A were treated with PCV or temozolomide (1:1 random assignment), whereas patients in arms B1 or B2 received radiotherapy. The primary end point was time to treatment failure (TTF), defined as progression after radiotherapy and one chemotherapy in either sequence. Results Patient characteristics in the intention-to-treat population (n = 274) were balanced between arms. All histologic diagnoses were centrally confirmed. Median TTF (hazard ratio [HR] = 1.2; 95% CI, 0.8 to 1.8), progression-free survival (PFS; HR = 1.0; 95% CI, 0.7 to 1.3, and overall survival (HR = 1.2; 95% CI, 0.8 to 1.9) were similar for arms A and B1/B2. Extent of resection was an important prognosticator. Anaplastic oligodendrogliomas and oligoastrocytomas share the same, better prognosis than anaplastic astrocytomas. Hypermethylation of the O6-methylguanine DNA-methyltransferase (MGMT) promoter (HR = 0.59; 95% CI, 0.36 to 1.0), mutations of the isocitrate dehydrogenase (IDH1) gene (HR = 0.48; 95% CI, 0.29 to 0.77), and oligodendroglial histology (HR = 0.33; 95% CI, 0.2 to 0.55) reduced the risk of progression. Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm. Conclusion Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas. IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation.