bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of nausea, vomiting, and diarrhea in oncologic patients at the emergency department
Authors: Ferrer Perez A. I. , Vidal Losada M. J. , Serrano Solares S. , Tobeña Puyal M. , Pajares Bernad I. , Lopez Sanchez D. , Ruiz-Echarri Rueda M. , Millastre Bocos E. , Lambea Sorrosal J. , Tres Sanchez A. 
Published: August 2020

e20727 Background: Nausea, vomiting, and diarrhea are very common in cancer patients under palliative treatment. These usually can be controlled on an outpatient basis, although they can become extremely debilitating for the patient. It is not uncommon that patients come to the emergency department because of the rebelliousness of these symptoms. The aim of this study is to describe cancer patient population which consults for nausea, vomiting, or diarrhea in the Emergency Department (ED) of a tertiary hospital, their causes and clinical management. Methods: From October 2007 to October 2008, all cancer patients attended at the Emergency Department of our hospital were prospectively collected. The reasons for consultation, diagnosis and clinical management in the SE are described Results: Of 560 patients enrolled, 440 patients were stage IV disease. 54.8% of them ( 307 patients) were under palliative chemotherapy treatment at the time of consultation. 5.9% consulted for nausea or vomiting (33 patients), 3.6% (20 patients) consulted for diarrhea, 0.7% (4 patients) consulted for both. 57.5% of patients (19 patients) with nausea or vomiting, 90% (18 patients) with diarrhea and 100% (4 patients) with both symptoms were receiving chemotherapy at that moment. The most frequent causes of these symptoms were chemotherapy toxicity (52.6%) and acute abdominal pathology (15.8%). 24 patients (72.7%%) who consulted for nausea or vomiting, 12 patients (60%) who consulted for diarrhea and 3 patients (75%) who consulted for vomiting and diarrhea required at least 24 hours of hospitalization. Conclusions: Vomiting and diarrhea are very prevalent symptoms in oncology patients, but they are not frequent causes of demanding emergency attention. The most important etiology of these situations is the chemotherapy toxicity, followed by acute abdominal pathology. Most patients attended in ED because of these symptoms require hospitalization. No significant financial relationships to disclose.
End-of-life care: Empowering cancer patients with information and choices
Authors: Tucker K. 
Published: August 2020

e20739 Background: Terminally ill patients want information and choices, including aid in dying, as they confront death due to cancer and other terminal illnesses. Physicians treating such patients want to feel safe in having candid conversations with patients about their wishes and to provide aid in dying when appropriate. Methods: Review the law governing end of life decision making, including aid in dying. Review the data from Oregon, which has more than 10 years experience with a regulated practice. Review what has been learned in OR, and how that is transferring to other states making aid in dying an end of life option. Results: Oregon's experience shows that when aid in dying is a legal option for mentally competent terminally ill patients overall end of life care improves. Conversations between physicians and patients are more open and candid; Referrals to hospice increase and occur earlier; clinician enrollment in CE for pain and symptom management increase; rx of strong pain medication increase; more patients die at home; patients are comforted to have aid in dying as an option; there is no negative impact on the practice of medicine. Conclusions: Terminally ill patients should be able to recieve comprehensive counseling about all end of life options. There is a growing trend of support for expanding end of life options to include aid in dying for mentally competent terminally ill patients who find themselves trapped in an unbearable dying process. No significant financial relationships to disclose.
The use of cannabinoids (CBs) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN): A retrospective review
Authors: Gingerich J. , Wadhwa D. , Lemanski L. , Krahn M. , Daeninck P. J. 
Published: August 2020

e20743 Background: CIPN is a common toxicity associated with the use of chemotherapy (CT) agents such as platinums, taxanes and vinca alkaloids. Patients (pts) may suffer from pain that adversely affects their quality of life, regardless of their disease trajectory. Preclinical research has shown CBs to be effective in preventing CIPN. CBs can be beneficial for cancer pain, although their specific benefit in pts with CIPN remains unknown. Methods: A retrospective chart review was conducted to identify all pts with CIPN treated with CBs at our institution between 7/07–10/08. Results: Eight pts were identified; 6 were male. Six pts had received platinum-based CT. Four had colon cancer. Four pts had metastatic disease. The median time to CIPN treatment (post-chemotherapy) was 4 months (0–84 months). All pts had 2+ neuropathy based on the NCI-CTC for Adverse Events. Pain improved in 7/8 pts with CB treatment. In those who responded, the improvement was as much as 7 points on an 11 point VAS. Two pts who transiently stopped treatment noted increased CIPN symptoms. Three pts eventually stopped treatment (1 due to side effects). Conclusions: Treatment with CBs appears to benefit some pts with CIPN. Further research is needed to explore the optimal use of CBs in pts with CIPN. No significant financial relationships to disclose.
Systematic review of response evaluation in gastrointestinal stromal tumors
Authors: Verma S. , Macdonald B. 
Published: August 2020

e21500 Background: Our purpose was to conduct an evidence-based systematic review of the literature on the accuracy of 18FDG PET - CT(PET) and contrast enhanced computer tomography (CT) in assessment of response to imatinib therapy in advanced gastrointestinal stromal tumor (GIST) Methods: A systematic review of the literature between January 2000 and December 2008 was performed on Medline and EMBASE. Inclusion criteria included prognostic studies or diagnostic studies using CT or PET to determine response to imatinib. Only articles with Level 1B or higher were included. The following variables were extracted: imaging modality (PET, In-line PET/CT, CT), response criteria used EORTC,RECIST criteria, or novel criteria), and the clinical outcome (time-to-treatment failure (TTF), time to progression (TTP), progression free survival (PFS), disease specific survival (DSS), and/or overall survival). The number of responders and non-responders was extracted from the data, and the reported log rank statistics for the Kaplan Meier curves were used to determine the strength of correlation between the responders and the clinical outcomes. Results: Five articles met the strict criteria for Level 1B evidence. Four articles met the inclusion criteria for In-line PET/CT. In these four articles the log rank correlation between In-line PET/CT response criteria described by the EORTC and the outcome measure of TTF ranged between. p=0.002 -0.04, a very high degree of positive correlation. A subset of four articles met the strict methodological inclusion criteria for CT using RECIST criteria. The log rank correlation for RECIST ranged from p=0.100 - 0.74, no significant correlation. Only one of the articles met the criteria for prospectively applying novel CHOI criteria with CT in a validating cohort. The log rank correlation with the TTF was p=0.0002, a very high degree of positive correlation. Conclusions: In-line PET/CT using EORTC criteria accurately predicts the response to imatinib in terms of TTF or PFS across four Level 1B studies. CT using RECIST criteria has a poor correlation with TTF in well designed studies and is not a useful predictor of response; consistently poor across four Level 1B studies. CT using CHOI criteria shows promise in a single Level 1B study No significant financial relationships to disclose.
Validation of genotyping of gastrointestinal stromal tumor in Japan
Authors: Takahashi T. , Nishida T. , Sakurai S. , Kanda T. , Sawaki A. , Wada R. , Hasegawa T. , Hirota S. 
Published: August 2020

e21502 Background: Most gastrointestinal stromal tumors (GIST) have activating mutations in the KIT or PDGFRA gene. Genotyping of GIST is important in Dx and Tx of GIST. Methods of genotyping using genomic DNA extracted from paraffin-embedded specimens are diverse and not standardized. We did validation study of genotyping using special reference to sequencing data obtained from cDNA from fresh GIST samples. Methods: Three DNA extraction methods (QIAamp, DEXPAT, or original) and four PCR methods (Ex Taq, AmpliTaq condition-1, AmpliTaq condition-2, or QIAGEN Tag) were compared using 20 paraffin-embedded specimens with special reference to sequencing data obtained from cDNA from corresponding 20 fresh GIST samples. After DNA extraction, KIT exon 9, 11, 13 and 17, and PDGFRA exon 12 and 18 were amplified by each PCR method using specific primers and directly sequenced. Results: In evaluation of PCR method, the protocol with Ex Taq showed 100% amplication of DNA and sequence agreement, the protocol with QIAGEN Tag 99%, and the protocol with AmpliTaq condition-2 86% agreement, and the protocol with AmpliTaq condition-1 showed much less amplication and higher disagreement. For the DNA extraction, the protocol with QIAamp showed best DNA extraction and its DNA sequence data were consistent with reference sequence in 98%, DNA sequence obtained using DEXPAT showed 33% consistency, and 89% of DNA sequence data obtained from an original method was agreed with reference data. Some modifications improved DNA amplication but inconsistent sequence data also increased probably due to miss-PCR. Conclusions: Each DNA extraction method had different quantity of DNA and four PCR methods showed different quality. Using this validation study, a standard genotyping method in Japan was established. No significant financial relationships to disclose.
A phase II study of imatinib mesylate as adjuvant treatment for curatively resected high-risk localized gastrointestinal stromal tumors
Authors: Kang B. , Lee J. , Ryu M. , Im S. , Park S. , Kang W. , Kim T. , Oh D. , Jung K. , Kang Y. 
Published: August 2020

e21515 Background: In our previous study, the presence of c-kit mutation as well as tumor size and mitotic count was an independent poor risk factor for relapse after curative resection of primary localized GIST. The patients with all the 3 poor risk factors had only 30% of 2 year relapse free survival rate (RFSR). (Kim, et al. Clin Cancer Res, 2004) It is also well known that c-kit exon 11 mutant GISTs respond better to imatinib treatment than the other mutant or wild type GISTs. Therefore, the patients who have primary localized GISTs with large size, high mitotic count, and c-kit exon 11 mutation may be the best candidate of adjuvant imatinib treatment. In this phase II study, we have evaluated the efficacy and safety of adjuvant imatinib for this patient group. Methods: Patients who underwent complete resection of a primary GIST with 1) c-kit exon 11 mutation, and 2) ≥10 mitoses/50 HPF, or tumor size ≥10 cm, or ≥5 mitoses/50 HPF and tumor size ≥5 cm were eligible. Patients received imatinib 400mg p.o. daily until recurrence of disease, intolerable toxicities, or for 2 years. The primary end point was relapse-free survival (RFS). Results: A total of 47 patients from 4 centers in Korea were enrolled. The median age was 57.0 years. Stomach was the most common primary site (n=31). Median primary tumor size was 7.5cm and median mitoses index was 12/50 HPF. With a median follow-up of 26.9 months, the median RFS and overall survival (OS) have not yet been reached. RFSR was 97.7% at 1-year and 92.7% at 2-years. Six relapses (12.8%) were documented among the 47 patients. The treatments were generally well tolerated. Grade 3–4 toxicities included neutropenia 27.7%, rash 8.5%, constipation 4.3%, anorexia 2.1%, vomiting 2.1%, and pruritis 2.1%. There were no episode of febrile neutropenia and treatment-related death. Conclusions: Postoperative adjuvant imatinib for 2 years were safe and could prolong the RFS in patients with high-risk of recurrence following complete surgical resection of the primary GIST. However, it remains unknown if this benefit in RFS can be translated into OS benefit. So, further follow-up is needed with comparison of OS with historical controls who could be use imatinib after recurrence. [Table: see text]
Breast sarcomas: Is now the time to change our mind?
Authors: Galaychuk I. 
Published: August 2020

e21524 Background: Primary breast sarcoma usually was considered a rare malignant disease [Adem et al., 2004]. The aim of this study is to show the incidence of breast sarcoma in the region with female population of about 600,000. Methods: Retrospective comparative analysis of breast sarcoma and breast cancer incidence in female of Ternopil region for 2000 - 2008. Descriptive statistical method was used. Results: The total of 101 cases of breast sarcoma was diagnosed in female of 39 - 76 years of age. Every year about 11 (6–18) primary breast sarcomas and 256 (233–279) patients with primary breast cancer were detected. The incidence rate of breast sarcoma was 1.14 per 100,000 women in 2000, 2.94 (in 2001), 1.48 (2002), 0.99 (2003), 2.16 (2004), 1.67 (2005), 2.53 (2006), 2.03 (2007) and 1.87/100,000 in 2008. The incidence of breast cancer was ranged from 37.3 to 46.4 per 100,000 of female population. Breast sarcoma consisted of 2.5% of the breast malignancies in 2000, 6.5% (in 2001), 3.3% (2002), 2.6% (2003), 5.4% (2004), 4.1% (2005), 5.9% (2006), 4.4% (2007) and 4.7% in 2008. Pathohistologic examination revealed angiosarcoma in 92.1% of cases. Thus, our findings are significantly different than data of other authors: f.e., the incidence of primary breast sarcoma is at 45 new cases per 10 million women [Confavreux et al., 2003], or 17 new cases per million women [Moore and Kinne, 1996], and breast sarcoma accounting for 0.0006% of breast malignancies which were diagnosed in 1910–2000 [Adem, 2004]. Taking into account all historical and recent data we can suggest beginning of biological changing in correlation between breast malignant tumors–carcinoma and sarcoma. Conclusions: Our statistical finding shows that incidence of breast sarcoma is 1.87 (0.99–2.94) per of 100,000 female population, and now sarcomas consist of 4.4% (2.5–6.5%) of all malignant breast tumors. Angiosarcoma is a most common (92.1%) morphological type of breast sarcomas. No significant financial relationships to disclose.
In vitro sequence-dependent interaction between paclitaxel and gefitinib in human lung cancer cell lines
Authors: Cheng H. , Wu Y. , An S. , Dong S. , Chen H. , Zhang X. , Guo A. 
Published: August 2020

e22025 Background: Cytotoxicity chemotherapy has been standard first line treatment for advanced NSCLC. Clinical trials comparing first line EGFR TKI therapy over cytotoxicity chemotherapy are under investigation in phase III trials. The aim of this study is to test the hypothesis that paclitaxel followed by gefitinib would be superior to the opposite order in EGFR TKI resistant cell lines because of cell signaling pathway and cell cycle interaction. Methods: we have used EGFR-TKI resistant human lung cancer cell lines A549, H1975 and H1650 as an in vitro model for defining the differential effects of opposite sequence of combination of cytotoxic drug and anti- EGFR agents on cell growth, signaling pathway, cell cycle distribution and induction of apoptosis. Results: Paclitaxel 24 hours followed by gefitinib 72 hours in A549, H1975 and H1650 cells produced synergistic effects, while the reverse sequence produced antagonistic effects. Exposure to paclitaxel resulted in an increased pEGFR and pAKT level, this increase of phosphorylation can be inhibited by the following gefitinib exposure, while the reverse sequence resulted in no change in EGFR and AKT phosphorylation. We confirmed that gefitinib arrested the cells in G1, paclitaxel arrested cells in S phase. The sequence of paclitaxel followed by gefitinib cause cells arrested in G1, while the reverse sequence cause cells arrested in S and G2 phase. Conclusions: These findings suggest that the sequence of paclitaxel followed by gefitinib may be superior to the reverse sequence in gefitinib resistant NSCLC, and support the investigation of these sequential treatment in the clinical setting. This work was supported by the grants from the National Natural Science Foundation of China (No. 30772531). No significant financial relationships to disclose.
MicroRNA for circulating tumor cells detection in breast cancer: In silico and in vitro analysis
Authors: Medina Villaamil V. , Blanco Calvo M. , Díaz Prado S. M. , Antolín Novoa S. , Calvo Martínez L. , Santamarina Caínzos I. , Haz Conde M. , Antón Aparicio L. M. , Valladares-Ayerbes M. 
Published: August 2020

e22027 Background: Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in breast cancer (bc) patients. Deregulation of microRNAs (miRNAs) is frequent in tumors, including breast cancer. It is suggested miRNAs play a role in tumor progression. We hypothesized that miRNAs may constitute a promising new class of cancer biomarkers for CTC detection. Our objective has been to identify miRNAs potentially useful for CTC detection. Methods: Phase I preclinical study was performed by means of computational tools for miRNAs profiling including MIRGATOR, MIRBASE, SMIRNAdb, GeneHUB-GEPIS, MICRORNA.ORG, and MIRNAMAP. In silico data were used to identify and prioritize miRNAs highly expressed in breast cancer, but absent in hematopoietic-derived sources. Selected miRNAs were evaluated by means of qRT-PCR in breast cancer and Hematopoietic cell lines, normal blood, and blood from breast cancer patients. Results: Computational tools identify a set of miRNAs highly expressed in breast cancer sources in relation to hematopoietic samples. Among these were miR-141, miR-200c, miR-196a, miR-203, miR-200a, miR-200b, miR-32, miR-375, miR-31, miR-193a, and miR-205. For instance, relative expression of miR-32 was 104 higher in bc cell lines (N= 5) than in normal PB (N = 19) using qRT-PCR. In a preliminary analysis of PB from bc patients (stage IV) higher relative expression levels for selected miRNAs were found comparing with age-matched controls’ blood. Conclusions: Our results suggest that miRNA bioinformatic approach is a useful high-throughput method to select bc-associated miRNAS. The selected miRNAs should be further evaluated for their potential as markers for CTC detection. We next investigate if blood miRNA profile could predict tumor progression and survival. Supported by grants PI06/1541 and PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III. No significant financial relationships to disclose.
Localization of erythropoietin receptor mRNA in primary breast tumors by laser capture microdissection
Authors: Miller C. P. , Loeb K. , Edlefsen K. , Urban N. , Blau C. A. 
Published: August 2020

e22036 Background: Adverse effects of erythropoiesis stimulating agents on tumor progression and/or survival were observed in recent Phase III clinical trials, however, mechanisms are not understood. Whether tumor erythropoietin receptor (EpoR) expression is associated with erythropoietin-dependent tumor progression remains unclear, owing in part to the lack of specificity of commercial antibodies for protein detection. To overcome issues of protein detection, we previously optimized a quantitative RTPCR approach for reliable measurements of low level EpoR mRNA in primary tumor samples, and observed a 30-fold range of EpoR expression among panels of both breast and head and neck cancer samples. Methods: To test whether EpoR mRNA is expressed in tumor epithelial cells, we performed laser capture microdissection to fractionate 3 breast tumors into tumor epithelial enriched vs. depleted fractions. In each fraction, lineage marker and EpoR mRNA expression was normalized to 3 endogenous control genes. Results: Vascular endothelial markers in tumor epithelial-enriched fractions were reduced by an average of 15.3-fold (vascular endothelial cadherin) and 18.5-fold (platelet cell adhesion molecule 1) while the stromal marker vimentin was reduced by 14.7-fold. EpoR expression was enriched by 4.9-, 7.2-, and 1.1-fold in epithelial enriched fractions. Conclusions: Despite the depletion of endothelial cells, EpoR mRNA was at the same level or enriched in tumor epithelial fractions. These results demonstrate that malignant epithelial cells are a major source of EpoR mRNA in primary tumors. Applying this approach to additional breast cancer specimens as well as other cancer types will improve our understanding of erythropoietin-associated tumor progression. [Table: see text]
APC germ-line allele-specific expression in familial adenomatous polyposis
Authors: Castellsague E. , González S. , Blanco I. , Guinó E. , Lázaro C. , Gruber S. , Capella G. 
Published: August 2020

e22037 Background: About 13% of Familial Adenomatous Polyposis (FAP) families and 70% of Attenuated FAP families remain with unknown molecular pathogenic cause after APC and MYH mutational analyses. Also, mutations can affect specific allele expression (ASE) at the germline level. The aim of the study was to determine the presence of germline ASE in the APC gene in FAP and AFP with and without detectable APC or MYH mutations. Methods: Germline RNA from fresh frozen and/or cultured lymphocytes of 17 APC/MYH-negative Polyposis (7 FAP, 10 AFAP) families (21 individuals) and 35 APC-mutated Polyposis (30 FAP, 5 AFAP) families (60 individuals) was analyzed. Fourteen controls were also studied. ASE was investigated by single nucleotide primer extension (SNuPE) of rs2229992 APC coding SNP. Results: In controls ASE was 1.04± 0.3. We found that 17% (3 of 17) APC/MYH(-) FAP and AFAP families showed ASE (range=1.17–1.39) and ASE co-segregated with disease. ASE was more intense in short-cultured lymphocytes except for two cases and completely reversed by puromycin treatment. Eleven of 35 (31%) APC-FAP/AFAP harbored ASE (range=1.20–7.76), and the mutant allele was underexpressed in each case. ASE was restricted to splicing (4 families), nonsense (3 families) and frameshift (3 families) mutations outside of exon 15. Puromycin reversed ASE in all cases analyzed. Conclusions: APC ASE is present in a significant proportion (17%) of APC/MYH(-) FAP or AFAP. ASE, due to nonsense-mediated decay (NMD), is present in APC-FAP and is associated with specific mutation location, similar to reports for other hereditary syndromes. No significant financial relationships to disclose.