tbuckley/cabot-search huggingface dataset:
The mutation status of the epidermal growth factor receptor (EGFR) as a selection criterion for therapy with EGFR tyrosine kinase inhibitors (TKI’s) in non-small cell lung cancer (NSCLC)
Authors: A. Mathy, P. Nederlof, L. Boerrigter, L. Van ’t Veer, D. De Jong, P. Baas, S. Burgers, N. Van Zandwijk
Journal: Journal of Clinical Oncology (2006)

10073 Background: Somatic mutations in the EGFR gene have been shown to be closely associated with a favorable response to small-molecule TKI’s, while K-ras mutations seem to be associated with primary resistance. We present an exploratory study confirming the importance of mutation status for response on anti EGFR therapy. Methods: Mutations in the EGFR TK domain were looked for in tumor material extracted from two series of patients with advanced NSCLC. In the first series, mutations were determined in patients with an objective response or clearly progressive under gefitinib therapy. In the second series, EGFR mutations were determined prospectively in an enriched population (two of three characteristics: female gender, non-smoking status, bronchoalveolar -or adenocarcinoma pathology). The presence of a mutation was the criterion for treatment with TKI’s. Response assessment was done according to RECIST. K-Ras mutations were determined retrospectively. Results: In the retrospective series, 15 biopsies were analyzed, belonging to 3 complete responders and 12 non-responders (gefitinib). All three responders harbored an EGFR mutation, none had a K-ras mutation. None of the non-responders had an EGFR mutation. Three of them had a K-ras mutation. In the prospective (enriched) series, 13 out of 41 patients (tumors) possessed an EGFR mutation. Eleven of them swiftly responded on erlotinib or gefitinib, 1 had stable disease, 1 stopped treatment due to severe toxicity. K-ras mutations were not found in this set. In a single EGFR mutation positive patient survival has extended over 40 months since start of therapy. Conclusions: Our findings corroborate other groups’ conclusions that EGFR mutations are a powerful indicator of response to TKI’s and that K-ras mutations are associated with resistance. [Table: see text]
Incidence of and Mortality From Malignant Melanoma by Anatomical Site
Authors: Lee, J. A. H., Yongchaiyudha, S.
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Incidence of and Mortality From Malignant Melanoma by Anatomical Site Get access J. A. H. Lee, M.D., J. A. H. Lee, M.D. Department of Epidemiology and International Health and Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98105 Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Yongchaiyudha, M.D. S. Yongchaiyudha, M.D. Department of Epidemiology and International Health and Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98105 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 1, July 1971, Pages 253–263, https://doi.org/10.1093/jnci/47.1.253 Published: 01 July 1971 Article history Received: 17 February 1971 Accepted: 12 April 1971 Published: 01 July 1971
Early gastric cancer: The importance of early diagnosis on prognosis of gastric carcinoma.
Authors: T. Bouca-Machado, H. Santos Sousa, E. Lima-da-costa, J. Pinto-de-Sousa, J. Preto, J. Sousa-Rodrigues, J. Costa-Maia
Journal: Journal of Clinical Oncology (2011)

29 Background: The aim of this study was to evaluate the characteristics of early gastric cancer (EGC) in comparison to advanced tumors and its role in patient's prognosis. Methods: This study was related to 1,272 patients admitted with gastric or gastroesophageal junction carcinoma in our department, between January 1988 and December 2008. During this period the incidence of EGC was 12.68% (3.62% T0, 42.75% T1a and 53.62% T1b). Several clinical, pathological and staging parameters were evaluated according to classification in EGC and advanced tumors. Results: Significant differences were observed in location (p&lt;0.001); type of resection surgery (p&lt;0.001) and of lymphadenectomy (p=0.008 for Siewert and p&lt;0.001 for Japanese classifications) with less radical surgery in EGC patients. This type of tumors presented characteristics associated with a better prognosis in the following pathological parameters: tumor dimensions (p&lt;0.001), macroscopic form (p&lt;0.001), Ming's classification (p&lt;0.001), venous invasion (p&lt;0.001) and lymphatic permeation (p&lt;0.001). The 5-year survival rate of this series was 33.7%. There were significant differences in survival curves according to classification in EGC and advanced tumors (73% at 5 years and 26% at 5 years, respectively). Cox-regression analysis identified age, T and lymph node ratio as independent prognostic factors. There was no significant differences in age (cut-off 45 years), but there was significant differences in lymph node metastasis (p&lt;0.001). In 23.87% of EGC there was lymph node involvement, with significant differences (p=0.002) according to the depth wall invasion [T0 (100% N0), T1a (91.5% N0, 8.5% N1), T1b (60.8% N0, 21.6% N1, 13.5% N2, 4.1% N3a)]. Conclusions: The EGC percentage in our series was lower in comparison with other countries with high incidence of gastric cancer. The prognosis of the patients with gastric carcinoma continues to be gloomy mainly due to the late diagnosis and, given that the surgical treatment doesn't seem plausible of achieving a margin of significant additional progression, the need for an early diagnosis emerges if an improvement in patient survival is desired. No significant financial relationships to disclose.
Parathyroid surgery can be safely performed in a community hospital by experienced parathyroid surgeons: A retrospective cohort study
Authors: Vladimir K. Neychev, Maher Ghanem, Stuart L. Blackwood, Patricia Aragon Han, Roghayeh Fazeli, Eric Schneider, Alireza Najafian, Dov C. Bloch, Michael C. Bard, Jay H. Klarsfeld, Martha A. Zeiger, Richard J. Lipton
Journal: International Journal of Surgery (2015)
Usefulness of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in predicting outcomes for adolescents and young adults (AYAs) with hematologic malignancies (HM) undergoing allogeneic stem cell transplant (alloSCT)
Authors: W. A. Wood, A. M. Deal, D. T. Moore, J. Whitley, A. Sharf, J. S. Serody, D. A. Gabriel, T. C. Shea
Journal: Journal of Clinical Oncology (2009)

7034 Background: The HCT-CI was developed to help predict overall survival (OS) and non-relapse mortality (NRM) in pts undergoing alloSCT, a procedure with significant toxicity. AYAs with cancer (ages 16–40) have been identified by the NCI as a high-risk group, but it is not known whether the HCT-CI is a useful predictor of outcomes in this relatively healthy population. Methods: All pts ages 16–39 at the time of alloSCT from 1992–2008 were included. HCT-CI was retrospectively calculated for pts with complete data available. Univariable Cox regression models were used to examine the association between covariates and OS and NRM. Results: 62 evaluable pts included 38 males and 24 females. 50 (81%) were Caucasian, 9 (15%) African American, and 3 (5%) other. Diseases included AML (23), CML (14), ALL (14), and other (11). All comorbidities had a frequency of &lt;5% in this population except for pulmonary dysfunction (69%), hepatic dysfunction (27%), infection (19%), and psychiatric disturbance (10%). When dichotomized into categories of 0–2 (32) and &gt;3 (30), the HCT-CI was significantly associated with OS (p = 0.0006) and marginally with NRM (p = 0.07). Because pulmonary dysfunction appeared to be the most important contributor to the HCT-CI, the diffusing capacity adjusted for hemoglobin and alveolar volume (DLCO/VA adj) was examined independently. When dichotomized into categories of &lt;80% and &gt;80% of normal, the DLCO/VA adj alone was also significantly associated with OS (p = 0.008), but not with NRM (p = 0.2). Conclusions: AYAs with HM undergoing alloSCT have a limited number of comorbidities in the HCT-CI. Pulmonary dysfunction is most prevalent, and the DLCO/VA adj alone appears to be nearly as predictive for OS as the HCT-CI. The discrepancy between the predictiveness for OS and NRM may reflect pre-treatment or disease status of this population at the time of transplant. No significant financial relationships to disclose.
Nuclear Morphometry and Prognosis in Favorable Histology Wilms' Tumor: A Prospective Reevaluation
Authors: Norman E. Breslow, Alan W. Partin, Benjamin R. Lee, Katherine A. Guthrie, J. Bruce Beckwith, Daniel M. Green
Journal: Journal of Clinical Oncology (1999)

PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MV f = (0.02 × AGE) + (1.17 × SNRF) + (90.6 × LEFD) − 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of “MV f is greater than −0.35” as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of “MV f is greater than −0.35” were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.
Azithromycin, a novel maintenance therapy in patients with chronic non-CF suppurative lung disease
Authors: Simon Twite, Paul Stockton, Sanjeev Agarwal
Journal: European Respiratory Journal (2011)

Patients with bronchiectasis experience lower respiratory tract infections with decline in quality of life. The British Thoracic Society statement indicates that Macrolides may have disease-modifying activity. A definite recommendation for there use is not made in non-CF bronchiectasis. We present experience of Azithromycin in non-CF bronchiectaisis as well as other respiratory diseases at a large district general teaching hospital.  137 patients were identified on maintenance Azithromycin therapy during a 12 month period. 66% received Azithromycin 250mg daily. Azithromycin provided a significant improvement in the mean time between exacerbations/rescue antibiotics, in patients with non-CF bronchiectasis as well as other lung conditions. The mean time to exacerbation was 64 days, without Azithromycin (range 30-360 days) versus 304.5 days, with Azithromycin (range 14-582 days). 48 patients required no rescue antibiotics. Where Azithromycin was electively withdrawn, the patients clinically worsened. This strategy is therefore not recommended. Treatment failure due to side effects only occurred in those patients on a 500mg three times weekly regime. Discussion in the literature raises concerns with atypical mycobacteria, potential for increased colonisation rates and drug resistance. No such concerns were seen in this series. In this series, Azithromycin provided clinical improvement in patients with other non-CF lung disease processes but further studies are needed in this population.  The recommended regime from this study, in those patients with non-CF bronchiectasis is Azithromycin 250mg PO daily.
Authors' response
Authors: T. M. Fishbein, M. Zasloff
Journal: Gut (2011)

We have reviewed the letter to the editor by Janse et al 1 sent in response to Fishbein et al 2 in Gut 2008. Our paper reported an association of NOD2 gene polymorphisms with immunologic complications of intestinal transplantation. It was a prospective study in which all sample tissues were uniformly collected, analysed by one method and an extensive clinical outcomes database was prospectively set up to monitor outcomes. It also included significant mechanistic studies demonstrating that the antimicrobial sensing system was …
Abstract 11097: Racial Differences in Clinical Outcomes in Elderly Patients With Atrial Fibrillation
Authors: Rajesh Kabra, Peter Cram, Saket Girotra, Mary Vaughan-Sarrazin
Journal: Circulation (2014)

Introduction: Atrial fibrillation (AF) is associated with stroke and death, but the effect of race on these outcomes is not known. Methods: Medicare administrative data from 2010-2011 were used to identify patients with newly diagnosed AF who were categorized based on race as white, black and Hispanic. Racial differences in the primary outcome of death and secondary outcomes of stroke and the composite of stroke and death were assessed using Cox proportional hazard models. Results: Among 517,941 patients with newly diagnosed AF, 452,986 (87%) were whites, 36,425 (7%) were blacks and 28,530 (6%) were Hispanics. The mean age was 79 ± 8 years and 40.5% were males. Over a mean follow-up period of 0.9 years per patient, 68,250 (15.1%) whites, 7665 (20%) blacks and 4814 (16.9%) Hispanics died. Stroke was diagnosed in 6,509 (1.4%) whites, 843 (2.3%) blacks and 507 (1.8%) Hispanics. Compared to whites, blacks had a significantly higher hazard of death (Hazard Ratio [HR] =1.43; 95% CI 1.40-1.47; p&lt;0.001), stroke (HR=1.69; 95% CI 1.57-1.81; p&lt;0.001), and the composite outcome (HR= 1.46; 95% CI 1.43-1.49; p&lt;0.001). After controlling for pre-existing co-morbidities, the higher hazard of death (HR 0.99; 95% CI 0.97-1.01; p=0.41) and the composite outcome (HR=1.02; 95% CI 0.99-1.04; p=0.135) in blacks were eliminated and the relative hazard of stroke (HR=1.44; 95% CI 1.34-1.55; p&lt;0.001) was reduced compared to the whites. Similarly, Hispanics had a higher risk of death (HR= 1.13; 95% CI 1.10-1.17; p&lt;0.001), stroke (HR=1.26; 95% CI, 1.15-1.38; p&lt;0.001) and the composite outcome (HR= 1.15; 95% CI 1.12-1.18; p&lt;0.001), as compared to whites. The relative hazard of death and the composite outcome were noted to be lower in Hispanics, compared to whites, after controlling for pre-existing co- morbidities (HR= 0.93; 95% CI 0.92-0.96; p&lt;0.001 and HR= 0.95; 95% CI 0.92-0.97; p&lt;0.001 respectively). The relative hazard of stroke was also attenuated (HR=1.15; 95% CI 1.05-1.26; p=0.002). Conclusions: In an elderly Medicare population with newly diagnosed AF, the risks of death and stroke are higher in blacks and Hispanics, as compared to whites. This is likely due to increased co-morbidities in blacks and Hispanics.
Very-high-dose cisplatin with bleomycin infusion as initial treatment of advanced head and neck cancer.
Authors: I Haines, G Bosl, D Pfister, R Spiro, F Gerold, R Sessions, J Shah, E Strong, B Vikram, L Harrison
Journal: Journal of Clinical Oncology (1987)

Fifty-one patients with locally advanced squamous cancer of the head and neck (SCHN) were treated with up to three cycles of very-high-dose cisplatin, 187.5 mg/m2 (administered over five days) in hypertonic saline, and bleomycin infusion, 60 U/m2 (administered over five days), prior to definitive local therapy, in an attempt to improve complete remission (CR) and overall response rates. After chemotherapy, patients underwent surgery if the tumor was resectable for cure, (unless the operation involved total laryngectomy), and/or locoregional radiation therapy. Twelve patients (24%) achieved CR and 23 (45%) partial remission (PR) for an overall response rate of 69%. Thirty-nine of the 51 patients are evaluable following chemotherapy and locoregional treatment, and 28 (72%) have achieved disease-free status. Seven of these 28 (25%) have subsequently relapsed. Eleven of the 51 patients (22%) have died at median follow-up of 10+ months (3+ to 24+). Nausea and vomiting (94%) was the most severe acute toxicity. Myelosuppression was mild and nephrotoxicity was effectively prevented by the 3% saline diuresis. Bleomycin was withheld in 12 of 49 (24%) because of deterioration in pulmonary function tests. Ototoxicity in 12 of 49 (25%) and neurotoxicity in 19 of 49 (39%) were the most significant long-term toxicities. Very-high-dose cisplatin and bleomycin in this study was an effective chemotherapy regimen, but not more so than more conventional doses of cisplatin. Toxicity from both drugs was significant.
A genomic classifier to improve prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy.
Authors: Eric A. Klein, Kasra Yousefi, Zaid Haddad, Voleak Choeurng, Christine Buerki, Andrew J. Stephenson, Jianbo Li, Michael W. Kattan, Cristina Magi-Galluzzi, Elai Davicioni
Journal: Journal of Clinical Oncology (2015)

154 Background: Surgery is a standard first line therapy for most intermediate-high risk men diagnosed with prostate cancer. While clinical factors such as tumor grade, stage and prostate specific antigen (PSA) are currently used to identify patients at risk of cancer recurrence, novel biomarkers that can improve risk stratification and distinguish local from systemic recurrence are needed. The Decipher Genomic Classifier (GC) is a validated model for predicting men at risk of metastasis. We evaluated its performance in predicting metastatic disease within 5 years after surgery (rapid metastasis, RM) in an independent cohort. Methods: Tumors and clinicopathologic data were obtained from a cohort of 2,641 RP patients treated between 1987-2008 at Cleveland Clinic. The final study cohort consisted of 15 RM patients and 154 patients as non-RM controls who met the following criteria: 1) preoperative PSA&gt;20 ng/mL, stage pT3 or margin positive, or Gleason score ≥8; 2) pathologic node negative; 3) undetectable post-RP PSA; 4) no neoadjuvant or adjuvant therapy; and 5) minimum 5 year follow-up for the controls. Results: RM patients developed metastasis with a median of 2.3 (IQR: 0.8-5) years. In multivariable analysis, GC was a significant predictor of RM (OR=1.48, p=0.018) after adjusting for clinical risk factors. GC had the highest c-index, 0.77, compared to the Stephenson model (c-index 0.75) and CAPRA-S (c-index 0.72) as well as a panel of previously reported prostate cancer biomarkers unrelated to GC. Integration of GC into the Stephenson nomogram increased the c-index from 0.75 (95% CI: 0.65-0.85) to 0.79 (95% CI: 0.68-0.89). Conclusions: GC was independently validated as a genomic metastasis signature for predicting RM in a cohort of high-risk men treated with RP and managed conservatively without any adjuvant therapy. Integration of GC into clinical nomograms led to improvement in prediction of RM. GC may further allow identification of men most at risk for metastatic progression who should be considered for multimodal therapy or inclusion in clinical trials.
HAL-RAR (Doppler guided haemorrhoid artery ligation with recto-anal repair) is a safe and effective procedure for haemorrhoids. Results of a prospective study after two-years follow-up
Authors: Carlos Hoyuela, Fernando Carvajal, Montserrat Juvany, Daniel Troyano, Miquel Trias, Antoni Martrat, Jordi Ardid, Joan Obiols
Journal: International Journal of Surgery (2016)
Adenosine but not the A2A adenosine receptor agonist, CGS 21680 attenuates the endothelial cell barrier disruption induced by lipopolysaccharide
Authors: Joyce Gonzales, Alexander Verin
Journal: European Respiratory Journal (2011)

Rationale:  Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are severe disorders. Pulmonary injury is at the endothelial cell (EC) barrier with increased permeability. Our  in vitro  studies demonstrate that adenosine protects from the bacterial toxin lipopolysaccharide (LPS) induced barrier dysfunction.   Hypothesis:  Based on the known activation of the A2A adenosine receptor (A2AR) with adenosine it was hypothesized that the A2A agonist, CGS 21680 (CGS), would attenuate the LPS disrupted EC barrier  in vivo .   Methods:  Control and A2AR knock out (KO) mice were given normal saline (NS) or LPS intratracheally. NS or CGS was instilled intravenously (IV) at the same time or 3hrs later. At 22 hours Evans Blue Dye albumin (EBD) was instilled IV, at 24hrs the samples were collected. Bronchoalveolar lavage (BAL) was done and the lungs harvested. Cell counts, protein and EBD extravasation were analyzed.   Results:  LPS caused an increased number of cells in the LPS/adenosine treated mice and the KO mice treated with CGS at 3hrs consistently demonstrated a decreased cell count. LPS challenge increased the protein in BAL and EBD from lung, the protein and EBD were significantly attenuated in the LPS/adenosine treated mice but not in the CGS treated mice.   Conclusions:  Adenosine significantly attenuates the LPS induced EC barrier dysfunction in mice. The A2AR agonist, CGS, attenuates the cell count but not the protein or EBD extravasation. Other adenosine receptors or mechanisms may be involved in the significant improvement of protein and EBD barrier disruption that occurs with adenosine treatment.