tbuckley/cabot-search huggingface dataset:
Perioperative morbidity in metastatic gastrointestinal stromal tumors (GIST) undergoing surgery of residual disease following imatinib (IM)
Authors: A. Gronchi, M. Fiore, S. Radaelli, P. Coco, E. Fumagalli, S. Stacchiotti, P. Collini, E. Tamborini, S. Pilotti, P. G. Casali
Journal: Journal of Clinical Oncology (2007)

10043 Background: To review the morbidity of post-IM surgery of residual disease in a consecutive series of metastatic, IM- sensitive, GIST pts. Methods: Between November 2002 and September 2006, 29 pts with metastatic GIST were operated on, being progression- free on IM for at least 6 months. Median preoperative IM duration was 17 mos. Only patients deemed to be completely resectable on CT/MRI were considered for surgery. Major surgical procedures were generally excluded. Results: Surgery consisted in explorative laparotomy with resection of residual visible disease, omentectomy in 13 cases, intestinal resections in 10, minor hepatic resections in 7, radiofrequency ablations of liver nodules in 2, spleno-pancreatectomy in 2. Macroscopically complete surgery could be performed in 90% of pts. Median operative time was 180’ (range 120–420). Median post-surgery discharge time was 9 days (range 4–35). Median preoperative Hb level was 12.2 mg/dL and the median perioperative whole blood and fresh frozen plasma units required was 1.5 and 2.9 (range 0–16 and 0–44), respectively. In 28% of pts, there was post-operative ascites (daily peritoneal effusion of &gt;200 ml), which generally responded to medical therapy in one week. Postoperative levels of AST/ALT reached twice the baseline in 48% of pts, independently of whether liver resections had been carried out. Postoperative pneumonia was observed in 38% of patients. Major surgical complications occurred in 14% (one bleeding, one evisceration, and two anastomotic leakages). After a median follow up of 36 mos from surgery, PFS was 69% at 2 yrs (65% at 4 yrs from IM-onset). Conclusions: While this was a series of favorably selected patients, and major surgical procedures were preferably avoided, surgical perioperative morbidity turned out to be higher than expected. This reinforces the view that post-IM surgery of residual disease in metastatic GIST pts should be considered investigational, as long as its efficacy in improving prognosis is not demonstrated. [Table: see text]
Differences in spirometry of Greek smokers presenting in the smoking cessation program of a large municipal hospital. Effect of sex and age
Authors: Marios Kougias, Christina Goga, George Boulbasakos, Nikolaos Tatsis, Stavroula Boulia, George Tatsis
Journal: European Respiratory Journal (2013)

Greece ranks high in cigarette consumption in Europe. The purpose of this study is to highlight spirometric characteristics of Greek smokers, referring to our smoking cessation office.  METHODS  Fifty nine smokers -27 men/32 women- participated in our survey during the last semester. Spirometry was performed in all individuals.Data were analyzed using Spearman correlation analysis and independent samples t-test, using sex as grouping variable.  RESULTS  The mean age of the participants was 53.40±1.30. Cigarette consumption (packyears) was 49.39±2.90  FVC measured 92.73 % ± 2.4 % (men 83.16±3.61 vs women 94.21±2.79).  FEV1 was 89.16 % ± 2.33 (men 85.76±3.28 vs women 98.62 ±3.15 )  MMEF was 65.61 %±3.76 (men 54.72 ± 5.54 vs women 72.99 ±4.87).  FVC was correlated significantly with sex (SF= 0.26 at p = 0.048) and age (SF =0.38 at p=0.003). The same applied for FEV1(correlation for sex SF = 0.366 at p=0.004 and age SF=0.331 at p=0.010) and MMEF (correlation for sex SF = 0.276 at p=0.035 and age SF=0.287 at p=0.027).  Cigarette consumption(packyears) was correlated significantly with FEV1 (SF=0.285 at p=0.029) and FVC (SF 0.297 at p=0.022).  Men and women differed significantly in cigarette consumption (Levene factor 2.5 at p  Results are expressed as mean value ± standard error, SF=Spearman Factor  CONCLUSIONS  Spirometric values and cigarette consumption demonstrated significant differences between men and women smokers of different age groups, presenting to our smoking cessation office.
PWE-346 Lynch syndrome and application of the rcpath colorectal cancer dataset in the united kingdom
Authors: A Kaur, KJ Monahan, J Schofield, S Lishman, D Alsina, N Bason
Journal: Gut (2015)

<h3>Introduction</h3> Lynch syndrome is estimated to cause over 1,000 cases of colorectal cancer in the UK every year. Individuals that have Lynch syndrome have a lifetime risk of developing colorectal cancer or other Lynch associated cancers of &gt;35%. Yet fewer than 5% of individuals with the condition have been diagnosed in the UK. The Royal College of Pathologists (RCPath) cancer dataset (July 2014) mandates the use of immunohistochemistry or other testing for molecular features of Lynch syndrome in colorectal cancer or Lynch associated cancer patients under the age of 50, at the time of diagnosis. Performing this type of screening test for Lynch syndrome identifies those at greater risk of recurrence as well as family members at extended risk through early cascade testing. <h3>Method</h3> The strategy was developed by Bowel Cancer UK with advice from the Medical Advisory Board of the charity. We identified all NHS hospital trusts in England, health boards in Scotland and Wales and health and social care trusts in Northern Ireland. A freedom of information (FOI) request was submitted to each of these bodies in which a number of questions were asked to establish whether they were implementing the RCPath core dataset requirement, with regard to mismatch repair (MMR) testing for Lynch syndrome. As this was an FOI request respondents were required to respond within 20 working days. <h3>Results</h3> In England, 78% of trusts responded, 100% responded in Scotland and Northern Ireland; one health board in Wales did not respond. In England and Scotland 50% of hospital trusts and health boards currently do not follow the RCPath cancer dataset. 4 health boards in Wales do not, and all health and social care trusts in Northern Ireland stated they perform MMR testing to identify suspected Lynch syndrome patients. In England only 28 of those that did not perform testing stated they were intending to implement the dataset and two in Wales. Scotland is in the process of developing a nationally agreed protocol for implementation of the dataset. We found that among trusts and health boards that do test for Lynch syndrome many do not yet have in place a systematic reflex service, as mandated by RCPath. <h3>Conclusion</h3> Our findings show that the RCPath dataset may have already had some impact on the application of MMR testing for Lynch syndrome in patients diagnosed under the age of 50. However there is considerable variation in approach. We recommend that: England and Wales carry out a nationwide initiative to look at ways of delivering a consistent approach to reflex testing for Lynch syndrome; that all CCGs commission to reflect the RCPath cancer dataset thus ensuring providers are compliant with the dataset. <h3>Disclosure of interest</h3> None Declared.
New approaches to evaluating complex health and care systems
Authors: Tara Lamont, Nicholas Barber, John de Pury, Naomi Fulop, Stephanie Garfield-Birkbeck, Richard Lilford, Liz Mear, Rosalind Raine, Ray Fitzpatrick
Journal: BMJ (2016)

Tara Lamont and colleagues  discuss how researchers can help service leaders to evaluate rapidly changing models of care, with a range of approaches depending on needs and resources
Living in Thin Air: New Fruit Fly Research Pinpoints Genomic Hallmarks of Human High Altitude Adaptation
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2015)

Twenty-one percent, that is the amount of oxygen in the air that we breathe—with the exception of the extreme high-altitude dwellers on the Tibetan or Andean mountains. To get at the genetic roots of these thin air thrivers, a collaborative research team led by University of Chicago Professor Kevin White and University of California San Diego’s Jha et al. 2015 turned to a research workhorse, the fruit fly and identified a treasure trove of new genes—all told, over 100 genes that may be critical to high-altitude adaptation, with more than 40 similar genes found in humans. The results were published in the advanced online edition of Molecular Biology and Evolution. Using experimental evolution followed by whole-genome sequencing (dubbed “evolve and resequence”), the research team grew three fruit fly populations under severely hypoxic conditions over many generations. Sequencing the hypoxiatolerant flies (surviving on just 5% oxygen by the 13th generation) they identified 3,800 single mutations many of which mapped within 66 genomic regions and prioritized a total of 99 candidate fruit fly genes. Many of these were primarily associated with development of respiratory system in fruit flies. In addition, gene knockdown experiments of the targets significantly enhanced survival under severe hypoxic conditions. “In a tribute to legendary Sherpa mountaineers of Nepal, we named three of the previously unnamed fruit fly genes implicated in metabolic rewiring as Pasang Lhamu, Tenzing Norgay, and Phurba Tashi,” said Jha et al. (2015), a graduate student in Kevin White’s lab and the first author of the study. When the research team examined similar genes in highaltitude populations, they found several single mutation differences between high-altitude human populations and their lowland neighbors. Human comparative data from Andeans (n = 10), Sherpas (69) Tibetans (96), and Ethiopian highlanders (165) showed that of the 102 human genes that are similar to the 55 hypoxia genes in fruit fly, more than 40 appear to enable hypoxia tolerance in Sherpas, Tibetans, and Ethiopian highlanders. A smaller number (n = 21) of genes were shared in the Andean population, which may have been due to the small sample size (just ten individuals). Professor White explains, “These results show that, to our surprise, genetic variation in the same types of genes can produce hypoxia resistance in both humans and fruit flies. This result implies that even across hundreds of millions years of evolution, organisms can arrive at convergent solutions during adaptation to similar types of environmental change.” Armed with the new data, the team will pursue teasing out the individual contributions and functions of the candidate genes they have identified.
Screening for Endometrial Cancer in the Patient Receiving Tamoxifen for Breast Cancer
Authors: Richard R. Barakat
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.7.1967 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561245 Screening for Endometrial Cancer in the Patient Receiving Tamoxifen for Breast Cancer Richard R. BarakatxRichard R. BarakatSearch for articles by this author Show More Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.1999.17.7.1967 Full Text PDF Figures and Tables "Screening for Endometrial Cancer in the Patient Receiving Tamoxifen for Breast Cancer." Journal of Clinical Oncology, 17(7), p. 1967© 1999 by American Society of Clinical Oncology
Peritoneal mesothelioma treated by cytoreductive surgery and intra peritoneal hyperthermic perfusion: Clinical and translational study
Authors: M. Deraco, S. Kusamura, D. Baratti, P. Casali, A. Gronchi, N. Zaffaroni
Journal: Journal of Clinical Oncology (2004)

9729 Background: to report the NCI of Milan experience on treating Peritoneal Mesothelioma (PM) with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Secondary endpoints: 1) assessment of potential prognostic factors; 2) test of in vitro PM sensitivity to chemotherapies; 3) development of a gene therapy approach. Methods: Thirty eight PM patients underwent 40 consecutive procedures. Mean follow-up was 18,7 mths. 34 (89%) cases had malignant epithelioid disease. Twenty one (53%) cases received preoperative chemotherapy. The IPHP was performed with closed abdomen technique with cisplatin+mitomycin-C or cisplatin+doxorubicin through a heart-lung pump for 60 or 90 minutes at 42.5° C. Potential prognostic biological markers were evaluated on surgical 19 PM specimens. PM in vitro drug sensitivity was evaluated on primary cultures derived from surgical specimens. We established new PM cell lines for the development of a gene therapy approach, which aimed at the inhibition of cell survival factors. Results: 5-year overall and progression free survivals were 70% and 49%, respectively. The operative morbidity GIII, mortality and toxicity GIII/IV rates were 20%, 0% and 10%, respectively. PM cells largely expressed anti-apototic proteins belonging to bcl-2 and IAP family; most of the cases were negative for the expression of the pro-apototic factor SMAC/diablo. Reactivation of telomerase was found in 17/19 cases, which were positive for the expression of the hTERT catalytic subunit of the enzyme. The assessment of sensitivity profile of 7 PM primary cultures to a panel of drugs found a variable response rate for the different compounds. Conclusions: CRS+IPHP seems consistent with a potentially effective treatment for selected PM patients. Apoptosis related markers presented an apparent correlation with PM tumor cell biology, but the their prognostic significance is still undefined. Further definition of drug sensitivity profile and the development gene therapies will provide a possible biological rationale for the design of new clinical treatments. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AIRC (Italian Association of Cancer Research)
Differences in lung cancer clinical trial accrual between a public and university medical oncology clinic.
Authors: S. J. Vara, D. E. Gerber, A. Avila, J. Bolluyt, J. Yan, Y. Xie, J. H. Schiller
Journal: Journal of Clinical Oncology (2010)

9082 Background: Historically, fewer than 5% of adult cancer patients enter clinical trials. Several studies have suggested socioeconomic disparities in research participation. To evaluate these factors, we prospectively studied patterns of lung cancer clinical trial enrollment by patients treated at both a public clinical facility and an academic cancer center. Methods: From April 2008 through November 2009, we prospectively collected demographic, disease, and clinical trial participation data for lung cancer patients who were either newly referred or established with progressive disease at oncology clinics at Parkland Health and Hospital System, the primary public medical facility in Dallas County, and the Simmons Cancer Center, both of which are associated with the University of Texas Southwestern Medical Center. Univariate analysis and multivariate logistic regression were performed. Results: A total of 229 patients met criteria for analysis. Of these, 52% were female and 67% were seen in the private clinic. Thirty-eight patients (17%) enrolled in a clinical trial. Trial participation was significantly associated with clinical setting (25% for academic versus 10% for public; p=0.04), but was not significantly associated with gender (26% for men versus 15% for women; p=0.11) or disease stage (23% for stages III-IV versus 11% for stages I-II; p=0.18). Reasons for non-participation included inadequate performance status (11% vs. 28% academic vs. public), presence of brain metastases (9% vs. 12%), lack of study availability (8% vs. 17%), receiving treatment elsewhere (13% vs. 0%), presence of comorbidities (16% vs. 6%), patient preference (14% vs. 6%), absence of measurable disease (4% vs. 3%), and clinician preference (16% vs. 10%). Of these, inadequate performance status (P=0.009), lack of study availability (p=0.05), and patient receiving treatment elsewhere (p<0.001) were significantly associated with clinical setting. Conclusions: In this patient cohort, participation rates in lung cancer clinical trials were significantly higher at an academic cancer center than at a public hospital. Study availability for patient with poor performance status may in part account for this association. No significant financial relationships to disclose.
Peripheral Blood Stem Cell Transplantation From Unrelated Donors: A Comparison With Marrow Transplantation
Authors: O. Ringdén, M. Remberger, V. Runde, M. Bornhäuser, I.W. Blau, N. Basara, K. Hölig, D.W. Beelen, H. Hägglund, O. Basu, G. Ehninger, A.A. Fauser
Journal: Blood (1999)
Late effects: Ten years long term follow up of pediatric oncology patients - From nihilism to cautious optimism
Authors: A. Sachdeva, S. Sachdeva, R. Mohan, P. K. Pruthi, S. Gupta, S. Dhawan, J. Vineeta, S. P. Yadav, N. Singh
Journal: Journal of Clinical Oncology (2004)

8568 Background: We have seen spectacular improvement in the survival rates of pediatric patients suffering from cancer, but long term effects of the tumors as well as the treatment modalities uised remain a cause for concern especially in countries with limited resources. We have evaluated over a ten year period the long term effects of Anthracyclines in pediatric patients Methods: Non-invasive cardiological methods were used to detect these fatal side effects early. We evaluated 58 children in the age group of 1½ - 13 years admitted with various malignancies in the period 1992 –1997. They were treated for ALL (30), Wilms (10) Hodgkins Lymphoma (12), Neurblastoma(6). The doses ranged from 180 mg/mt2 to 350mg/mt2 of Doxorubicin. Their Echocardiograms and ECG was done at baseline before administration of Chemotherapy and then repeated 1year after the last injection of Anthracyclines.and for long term follow up they were evaluated again at 3 years The Left Ventricular Ejection Fraction (LVEF) was calculated. Cardiotoxicity was defined as decrease in left ventricular ejection fraction of more than 10% to a final left ventricular ejection fraction < or = 50%. Results: There were 32 males and 26 females. The LVEF decreased more than 10% to a level< or + 50% in 7 patients (12.06%). The LVEF decreased from 56 ± 1.8 to 53.86 ± 1.32 (> 0.01) in patent with no cardiotoxicity. For those who had a fall in LVEF the values were 58.36 ± 1.73 to 43.26 ± 2.1 (p <0.001). Out of the seven patients showing a significant fall in LVEF there was only one who had a anthracycline dose of less than 200mg/mt2. On evaluation at 3 years 52 responded. There were now 9(7+2) children who had satisfied the criteria of cardiotoxicity. Their LVEF were 59.26+1.58 to 47.89+1.46 to 46.35 +2.3 (p,.001). On using a cut off at 1 year of 5% fall in LVEF the sensitivity increased to 89% and the specificity of 69% for latter cardiotoxicity. Conclusions:Thus there is a need to revise the toxicity criteria and have a high index of suspicion. These patients need a long term follow up for improving their Quality of Life. No significant financial relationships to disclose.
Resolvins on the way to resolution
Authors: Peter A. Ward
Journal: The Journal of Experimental Medicine (2015)

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Insight from Peter Ward



Over the past several decades, lipid products have been found to exert both proinflammatory effects (e.g., prostaglandins and leukotrienes) and antiinflammatory activities (e.g., lipoxins and products derived from docosahexaenoic acid, including
Procarbazine and High-Dose Tamoxifen as a Second-Line Regimen in Recurrent High-Grade Gliomas: A Phase II Study
Authors: Alba A. Brandes, Mario Ermani, Sergio Turazzi, Elvira Scelzi, Franco Berti, Pietro Amistà, Antonino Rotilio, Claudio Licata, Mario V. Fiorentino
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m 2 /d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33 weeks for patients with AA (P = .006). The median survival time (MST) was 27 weeks for patients with GBM and 57 weeks for those with AA (P = .006). CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it was not followed by an increased TTP or MST.
Tamoxifen does not reduce the risk of lung cancer in women
Authors: J. D. Patel, R. G. Gray, J. A. Stewart, H. G. Skinner, J. H. Schiller
Journal: Journal of Clinical Oncology (2005)

7212 Background: Mounting evidence indicates that women have a different susceptibility to lung cancer than men. In particular, female never-smokers are more likely than male never-smokers to develop lung cancer. Moreover, women are more likely to be diagnosed with adenocarcinoma than are men. Coupled with the localization of estrogen receptors alpha and beta to lung cancer cells, gender differences in incidence point to a possible role for circulating estrogens in lung tumorigenesis. We sought to determine if use of the anti-estrogen tamoxifen decreases the risk of lung cancer. Methods: We examined incidence rates of second primary lung cancers by categories of tamoxifen treatment among women enrolled in randomized ECOG adjuvant breast cancer trials. Overall, there were 15,875 women in 14 studies from 1978–2002. The duration of tamoxifen treatment varied by study and was alternately categorized as ≤ 1, ≤2 or ≥5 years. Results: We identified 55 second-primary lung cancers over 97,225 person-years of follow-up. 27 second-primary lung cancers occurred among 6,478 women who did not receive tamoxifen versus 28 lung cancers among the 9,397 women who received tamoxifen of any duration. Compared to women without tamoxifen treatment, those treated for fewer than two years had an age-adjusted relative risk for lung cancer of 1.13 (95% CI 0.52–2.32). Similarly, among women treated with tamoxifen for ≥5 years the relative risk for subsequent lung cancer was 0.80 (95% CI 0.40–1.57). Conclusions: We did not observe a strong association between tamoxifen treatment and the risk of second-primary lung cancer in a sample of women who had received tamoxifen as adjuvant therapy for breast cancer. The results are similar to those previously reported (Fisher, JNCI 1998). However, the potential estrogenic activity of tamoxifen may argue for evaluating adjuvant breast cancer trials of aromatase inhibitors for incident second primary lung cancers. No significant financial relationships to disclose.