tbuckley/cabot-search huggingface dataset:
Rectal Cancer, Version 2.2015
Authors: Al B. Benson, Alan P. Venook, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Axel Grothey, Howard S. Hochster, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Lucille A. Leong, Edward Lin, Wells A. Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, Deborah Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2015)

The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.
Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study.
Authors: M Markman, M F Brady, N M Spirtos, P Hanjani, S C Rubin
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the response rate of intraperitoneal (i.p.) paclitaxel in patients with small-volume residual carcinomas of the ovary, fallopian tube, or peritoneum. PATIENTS AND METHODS Eligibility criteria included patients with one of the cancers noted above, with the largest residual disease 0.5 cm or less in maximum diameter at the end of second-look surgery, and prior treatment with systemic paclitaxel was permitted. The treatment plan was paclitaxel 60 mg/m2 i.p. weekly for 16 weeks, followed by surgical evaluation in patients without evidence of disease progression. RESULTS Of 80 patients entered onto the study, 76 were eligible, of whom 86% were considered to be potentially cisplatin-sensitive. Although five patients (7%) did not complete the first course of therapy because of catheter leakage or blockade, 53 patients (70%) received all 16 planned courses. Only 14 patients (18%) received fewer than 11 courses. Treatment was well tolerated, which included only moderate abdominal pain (grade 2, 12 patients; grade 3, one patient) and minimal neutropenia (grade 2, three patients; grade 3, one patient). Of 28 assessable patients with microscopic disease at the start of i.p. therapy, 17 patients (61%) achieved a surgically defined complete response (CR). Only one of 31 patients (3%) with any macroscopic disease achieved a CR. Of the eligible patients, 18 of 76 (24%) achieved a CR. CONCLUSION Salvage i.p. paclitaxel is tolerable and active in patients with microscopic residual disease. The impact of this treatment strategy on survival remains to be assessed in a phase III trial.
Prognostic factors for overall survival with sunitinib as first-line therapy in patients with metastatic renal cell carcinoma (mRCC)
Authors: S. Patil, R. A. Figlin, T. E. Hutson, M. D. Michaelson, S. Négrier, S. T. Kim, X. Huang, R. J. Motzer
Journal: Journal of Clinical Oncology (2009)

5042 Background: Sunitinib demonstrated superior progression-free survival (PFS; the primary endpoint) over interferon-alfa (IFN-α) as first-line mRCC therapy (NEJM 2007;356:115). Median overall survival (OS) with sunitinib compared to IFN-α was: 26.4 vs. 21.8 months (HR=0.821; P=0.051 by unstratified log-rank test; Proc ASCO 2008;26, May 20 suppl; abstr 5024). An analysis of prognostic factors for OS was performed on data from this trial. Methods: 750 treatment-naïve mRCC patients were randomized 1:1 to receive sunitinib or IFN-α. By Cox proportional hazards model, selected pretreatment variables were evaluated univariately and in a multivariate model for each treatment arm. Multivariate models for each treatment arm were based on a stepwise algorithm with a type I error of 0.25 for entry and 0.15 for elimination. Further elimination was applied to identify variables significant at P&lt;0.05. Results: In multivariate analysis of sunitinib patients, factors associated with longer OS include: interval from diagnosis to treatment ≥1 yr, ECOG PS of 0, lower corrected calcium, absence of bone metastases, lower lactic dehydrogenase (LDH), and higher hemoglobin (Hgb) ( table ). For the IFN-α treatment arm, male gender, absence of bone or lymph node metastases, lower LDH, higher Hgb, lower corrected calcium, higher neutrophil count, and interval from diagnosis to treatment ≥1 yr were associated with longer OS. Conclusions: For patients in the sunitinib treatment arm, prognostic factors identified were similar to the factors previously identified in the MSKCC risk groups (J Clin Oncol 2002;20:289). Additional prognostic factors were identified for the IFN-α arm. Further studies are warranted to independently validate these findings as well as to identify tumor-specific prognostic factors. [Table: see text] [Table: see text]
Does a rapid diagnosis of Clostridium difficile infection impact on quality of patient management?
Authors: F. Barbut, L. Surgers, C. Eckert, B. Visseaux, M. Cuingnet, C. Mesquita, N. Pradier, A. Thiriez, N. Ait-Ammar, A. Aifaoui, E. Grandsire, V. Lalande
Journal: Clinical Microbiology and Infection (2013)
Continuous venovenous haemofiltration (CVVHDF) in cancer patients with acute renal failure (ARF): Results of a retrospective study with multivariate analysis
Authors: T. Berghmans, A.-P. Meert, E. Markiewicz, J.-P. Sculier
Journal: Journal of Clinical Oncology (2004)

8198 Background: To assess the role of CVVHDF in cancer patients admitted for ARF in an oncological intensive care unit (ICU). Methods: Retrospective study of all patients with acute renal failure treated with CVVHDF in a medical ICU from a cancer hospital,. Multiple logistic regression was used for multivariate analysis, including all variables with a p value ≤ 0.2 in univariate analysis. Results: From 01/97 until 12/02, 32 cancer patients were treated for ARF with CVVHDF. Their principal characteristics were: male/female 23/9, median age 61 years, haematological/solid tumours 16/16, median APACHE II and IGS II scores 31/67. The number of organ failure was 1/2/3/4 in respectively 10/6/13/2 patients. Sixteen patients died in the ICU and 15 were discharged alive from the hospital. In univariate analysis, variables adversely associated with hospital mortality were: renal failure of renal origin, bone marrow transplant, increasing number of organ failure, reduced lymphocyte count, elevated bilirubin and lower creatinine levels, increased thromboplastin time, younger age, increased APACHE II and IGS II, ARDS and mechanical ventilation. In multivariate analysis, 2 models were used including either APACHE II or IGS II. The number of organ failure was found as a significant prognostic factor in the 2 models (p ≤ .01). Conclusions: CVVHDF is effective in the treatment of ARF in cancer patients. The increasing number of organ failures was the single independent poor predictive factor for hospital mortality. Cancer characteristics and general gravity scores were not predictive factors. No significant financial relationships to disclose.
Longitudinal changes in regular physical activity (PA) in subjects with and without COPD: Findings from the Copenhagen City heart study
Authors: Anouk W. Vaes, Judith Garcia-Aymerich, Peter Lange, Marta Benet, Jacob L. Marrot, Frits M.E. Franssen, Jørgen Vestbo, Emiel F.M. Wouters, Peter Schnohr, Martijn A. Spruit
Journal: European Respiratory Journal (2013)

Background  To date, little is known about longitudinal changes in PA in subjects with and without COPD. Therefore, we aimed to determine whether and to what extent regular PA may change over time in a large cohort of subjects with and without COPD.   Methods  Subjects of the Copenhagen City Heart Study with at least 2 consecutive observations (time interval: 5 to 10 yrs) were selected. PA level was measured using a questionnaire. Subjects were stratified according to baseline PA into three groups: low (light PA such as walking or biking for  4 hrs/wk or more vigorous activity for > 2hrs/wk).   Results  Data of 1,270 subjects with COPD (58% men, 56±10 yrs, FEV 1 : 67±18%pred) and 8,734 subjects without COPD (42% men, 49±13 yrs, FEV 1 : 91±15%pred) were used, resulting in 16,659 repeated observations (with COPD: 1,733; without COPD: 14,926). The proportion of subjects with COPD with moderate/high baseline PA who had a decline in PA during follow up, was significantly higher compared to subjects without COPD with similar baseline PA (p   Conclusion  Longitudinal decrease in PA occurs more often in subjects with COPD. Therefore, PA needs to be assessed and stimulated by healthcare providers in subjects with COPD.  This study was financially supported by 9Stichting De Weijerhorst9.
Intensive weekly combination chemotherapy for patients with intermediate-grade and high-grade non-Hodgkin's lymphoma.
Authors: J W Sweetenham, G M Mead, J M Whitehouse
Journal: Journal of Clinical Oncology (1991)

High response and overall survival rates have been reported for second- and third-generation combination chemotherapy regimens used in the treatment of advanced intermediate- and high-grade non-Hodgkin's lymphoma (NHL). Results with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy have been particularly impressive, although this regimen produces considerable toxicity. We have devised a similar regimen, which differs from previously reported weekly regimens in that it includes etoposide given at 14-day intervals. The doses of methotrexate and prednisolone were lower in our regimen than those used in MACOP-B. Alternating cycles of cyclophosphamide, doxorubicin, and etoposide (week 1) and methotrexate, bleomycin, and vincristine (week 2) were given for a total of 12 weeks, with continuous oral prednisolone and prophylactic antibiotics. We report here the first 61 patients entered onto this study. The overall response rate is 84% (57% complete remission [CR], 27% partial remission [PR]). With a median follow-up of 32 months for surviving patients, the actuarial overall survival at 3 years is 47%, and the failure-free survival is 45%. The dose-limiting toxicity of this regimen was mucositis. Five deaths occurred during chemotherapy, two of which were due to sepsis. The dose intensities of cyclophosphamide and doxorubicin in this regimen are considerably lower than those in MACOP-B. However, because of the inclusion of etoposide, the projected average relative dose intensity for our regimen is higher than that for MACOP-B. Our regimen has produced inferior results to those reported for MACOP-B. This may be because the addition of etoposide has failed to compensate for the lower doses of doxorubicin and cyclophosphamide. Alternatively, it may reflect differences in the presenting features of the patient populations.
The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle
Authors: Emmy Manders, Silvia Rain, Harm-Jan Bogaard, M. Louis Handoko, Ger J.M. Stienen, Anton Vonk-Noordegraaf, Coen A.C. Ottenheijm, Frances S. de Man
Journal: European Respiratory Journal (2015)

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction.
Genomic and epigenomic profiling of hepatocellular carcinoma
Authors: Hiroyuki Aburatani
Journal: Clinical Cancer Research (2006)

A100   Recent progress in microarray technology has enabled a comprehensive functional genomics analysis of cancer, i.e. gene expression profiles, allelic copy number, and DNA methylation. We have applied an integrated approach to elucidate a molecular basis of liver cancer as well as to identify novel therapeutic and/or diagnostic targets.For the allelic dosage analysis, we used a Affymetrix genotyping array to detect chromosomal aberrations in an allelic manner by a newly developed Genome Imbalance Map algorithm. We have observed that uniparental disomy (UPD) is not a rare event and gives rise to loss of heterozygosity (LOH), which cannot be identified by the conventional array CGH analysis because UPD regions do not show any total copy number changes (Midorikawa 2006). Homozygous deletion, which is not easy to detect in fresh tumors due to contamination of normal tissues, has been detected within LOH regions in several tumors and are currently under study for their relevance in tumor progression.Besides chromosomal deletion, DNA methylation is another mechanism for gene silencing. Therefore, we used a genome tiling array, coupled with methylated DNA immunoprecipitation (Me-DIP), to analyze genome-wide methylation profiles. Methylation was not restricted in CpG islands, and showed differential patterns among various tissues and between cancer versus normal tissues. In 6q24-25, which contains imprinting gene clusters, we observed reduced levels of PLAGL1 expression due to loss of the unmethylated allele. Obviously, methylation of the remaining allele in the LOH regions could inactivate both alleles as well. Integration of gene expression, copy number changes and DNA methylation will be presented.
Routine imaging studies for the posttreatment surveillance of breast and colorectal carcinoma.
Authors: A R Kagan, R J Steckel
Journal: Journal of Clinical Oncology (1991)

Current recommendations on follow-up procedures for patients who have been treated for cancer include imaging studies and other laboratory tests at relatively frequent intervals. At least two questions should be asked to evaluate the benefits of this practice for patients: Do frequent routine surveillance tests detect recurrences "earlier" in asymptomatic patients? and Does earlier treatment of these recurrences reduce morbidity or prolong survival? The practical import of surveillance with imaging and laboratory tests for recurrence in patients with cancer of the breast and colon is discussed. Reported autopsy data, findings at elective reoperation, and clinical data have been examined to ascertain the justification for routine periodic tests in the treated but asymptomatic patient. It is concluded that earlier detection of a local recurrence or of metastatic disease through periodic tests in the asymptomatic patient with breast or colon cancer rarely alters the treatment or the outcome. A notable exception is regular screening mammography following treatment for adenocarcinoma of the breast.
HER2 testing by local, central, and reference laboratories in the NCCTG N9831 Intergroup Adjuvant Trial
Authors: E. A. Perez, V. J. Suman, N. E. Davidson, S. Martino, P. A. Kaufman, W. L. Lingle, P. J. Flynn, J. N. Ingle, D. Visscher, R. B. Jenkins
Journal: Journal of Clinical Oncology (2004)

567 Background: N9831 is evaluating trastuzumab as adjuvant therapy for patients with HER2 positive resected breast cancer. Accurate determination of HER2 status is essential to select patients most likely to benefit from therapy. An earlier report from this study found poor concordance between HER2 findings of local laboratories and central laboratory (JNCI 94:855,2002). Eligibility criteria were modified in early 2002 to require central review for HER2 status. This report provides data of HER2 testing concordance following this modification. Methods: Eligible women were allowed entry to N9831 based on the local laboratory determination that the tumor was strongly HER2+ by immunohistochemistry (IHC) or HER2 gene amplification by fluorescence in situ hybridization (FISH). Local laboratory testing was confirmed by central testing (Mayo Clinic) using IHC (Dako Herceptest™) and FISH (Vysis PathVysion™). Cases where central testing results were not 3+ by IHC and not amplified by FISH (HER2:CEP17 ratio <2) were sent to another reference laboratory (LabCorp) for testing. Results: 967cases were reviewed by the central laboratory. Local testing methods included IHC (49% HercepTest™ and 26% non-HercepTest™) and FISH (25%). There were 827 (85.5%) patient samples found to be either 3+ or FISH+ by central testing. Concordance between central and local testing when the same method was used was 79% for HercepTest™, 69% for non-HercepTest™, and 85% for FISH. Of the 140 discordant cases, 130 were re-tested at LabCorp and 10 cases (7.7%) were discordant, i.e., found to be 3+ or FISH+. The agreement between central review and LabCorp was 97% (126/130) for IHC (0,1+ or 2+) and 95.2% (119/125) for FISH (not amplified). Conclusions: There was a high level of discordance between local and central laboratories for both IHC and FISH. When a reference laboratory tested the discordant cases, there was high degree of agreement in both the IHC and FISH findings. These data show that HER2 testing by experienced laboratories improves patient selection for trastuzumab therapy. Supported by the Breast Cancer Research Foundation, Genentech, National Cancer Institute (CA25224). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly; Merck; Pfizer; Vysis, Inc.; Wyeth Merck Aventis; Pfizer; Sanofi Genentech
Facial hyperpigmentation: causes and treatment
Authors: N.A. Vashi, R.V. Kundu
Journal: British Journal of Dermatology (2013)

Journal Article Facial hyperpigmentation: causes and treatment Get access N.A. Vashi, N.A. Vashi Department of Dermatology Boston University School of Medicine Boston Medical Center 609 Albany St J602 Boston MA 02118 U.S.A Correspondence Neelam A. Vashi. E‐mail: nvashi@bu.edu Search for other works by this author on: Oxford Academic Google Scholar R.V. Kundu R.V. Kundu Department of Dermatology Northwestern University Feinberg School of Medicine 676 N. St Clair Street Suite 1600 Chicago IL60611 U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue s3, 1 October 2013, Pages 41–56, https://doi.org/10.1111/bjd.12536 Published: 01 October 2013
Real-life asthma impairment: SABA use depends on smoking phenotype
Authors: Richard Martin, David Price, Andrew McIvor, Gary Wong, Jerry Krishnan, Jonathan D. Campbell, Leif Bjermer, Marc Miravitlles, Alison Chisholm, Annie Burden
Journal: European Respiratory Journal (2013)

Background : Asthma impairment is defined by short-acting beta-agonist (SABA) use, symptoms, functional limitations, and pulmonary function. Objective measures of impairment rely on SABA records but the Respiratory Effectiveness Group believe SABA use may vary by management step and smoking status.

Methods: Real-life study pooling records from the UK’s Optimum Patient Care & Clinical Practice Research Databases for asthma patients aged 16–70yrs. Average daily SABA use was evaluated over one year (total annual dose prescribed/365) and split by management step (inhaled corticosteroid [ICS] initiation or step up) and smoking status (current, non- and ex-smoker).

Results: For both ICS initiation and step-up populations, the distribution of SABA dosage varied significantly by smoking status (p<0.001). More current smokers used ≥800µg, and fewer ≤200µg SABA daily than non- or ex-smokers.

View this table:

ICS Initiation*





View this table:

ICS Step-up*





Conclusions: Average SABA use is higher among ICS step-up compared with ICS initiation patients. Current smokers use more SABA than non- or ex-smokers, irrespective of management step. Further work is required to set meaningful SABA thresholds for objective measures of real-life asthma impairment.
Antioxidant activity of pomegranate juice reduces lung injury secondary to secondary to acute and chronic cigarette smoke exposure in an animal model
Authors: Ahmad Husari, Marwan Sabban
Journal: European Respiratory Journal (2013)

Cigarette smoke exposure (CSE) creates an increased oxidative burden in the lungs. Pomegranate (Punica granatum L.) Juice (PJ) possesses potent antioxidant activities that are attributed to its polyphenols. The study aims to determine the effects of PJ supplementation on the damaging effects of acute and chronic CSE in an animal model.  Methods: Male C57BL/6J mice were divided to four different groups: control, CSE, CSE + PJ and PJ. CSE groups received daily exposure, 5 days per week, for different time points (3 days, 1 and 3 months). PJ groups received daily 80 μmol /kg while other groups received placebo. At the end of the experiments, different parameters were studied: a) oxidative stress (OS), c) histological evaluation of the lung by H&E, d) apoptosis using TUNEL assay, and e) expression levels of IL-1 beta, IL-6 and TNF-alpha by RT-PCR method.  Results: Acute exposure (3 days): A significant increase in OS, IL-1 beta, IL-6, TNF-alpha expression was noted in the CSE only group when compared to control. PJ significantly reduced OS and the expression of inflammatory mediators. TUNEL staining demonstrated significant apoptosis in CSE lungs, which was diminished in the CSE + 80 μmol PJ group  Chronic exposure (3 months): Lung sections demonstrated multifocal alveolar emphysematous changes that were significantly reduced in the CSE + PJ group.  Conclusion: In this animal model, exposure to CSE resulted in lung injury. PJ supplementation attenuated the expression of inflammatory mediators observed in the acute CSE animal model and reduced emphysematous changes noted in the chronic animal model.