tbuckley/cabot-search huggingface dataset:
Integrating Evidence-Based Medicine for Treatment of Spinal Metastases Into a Decision Framework: Neurologic, Oncologic, Mechanicals Stability, and Systemic Disease
Authors: Ori Barzilai, Ilya Laufer, Yoshiya Yamada, Daniel S. Higginson, Adam M. Schmitt, Eric Lis, Mark H. Bilsky
Journal: Journal of Clinical Oncology (2017)

Patients with cancer are frequently affected by spinal metastases. Treatment is palliative, with the principle goals of pain relief, preservation of neurologic function, and improvement in quality of life. In the past decade, we have witnessed a dramatic change in the treatment paradigms due to the development of improved surgical strategies and systemic and radiation therapy. The most important change to these paradigms has been the integration of spinal stereotactic radiosurgery (SSRS), allowing delivery of tumoricidal radiation doses with sparing of nearby organs at risk. High-dose SSRS provides durable tumor control when used either as definitive therapy or as a postoperative adjuvant therapy. Integration of SSRS has fundamentally changed the indications for and type of surgery performed for metastatic spine tumors. Although the role for surgical intervention is well established, a clear trend toward less-aggressive, often minimally invasive techniques has been observed. Targeted therapies are also rapidly changing the way cancer is being treated and have demonstrated improved survival for a number of malignancies. As these treatment decisions become more complex, a multidisciplinary approach including medical oncologists, radiation oncologists, surgeons, interventionalists, and pain specialists is required. In this article, the current evidence affecting the treatment of spinal metastases is integrated into a decision framework that considers four principal assessments of a patient's spine disease: NOMS (neurologic, oncologic, mechanical instability, and systemic disease).
Hepatic stimulator substance resists hepatic ischemia/reperfusion injury by regulating Drp1 translocation and activation
Authors: Chao Zhang, Jing Huang, Wei An
Journal: Hepatology (2017)

Ischemia/reperfusion injury, induced by abnormal mitochondrial fission–related apoptosis, is a major concern in liver transplantation settings. Our previous studies have demonstrated that hepatic stimulator substance (HSS) is an antiapoptotic effector and could protect liver from ischemia/reperfusion injury. However, the underlying mechanism remains unclear. In the present study, we report that in vitro and in vivo HSS could regulate mitochondrial fission and hepatocyte apoptosis during liver ischemia/reperfusion injury by orchestrating the translocation and activation of dynamin‐related protein 1 (Drp1). Using a mouse model of ischemia/reperfusion‐induced liver injury, we found that HSS‐haploinsufficient (HSS +/− ) mice displayed exacerbated liver damage based on their increased serum aminotransferase levels, cell structural destruction, and apoptosis levels compared to wild‐type (HSS +/+ ) littermates. Disruption of HSS markedly increased cyclin‐dependent kinase 1 (CDK1) and Bax expression, accompanied by elevated phosphorylated Drp1 and release of cytochrome c . In parallel in vitro studies, we found that HSS could inhibit the expression of CDK1 and that HSS inhibits hepatocyte apoptosis through its suppression of CDK1/cyclin B–mediated phosphorylation at Ser‐616 of Drp1, thereby decreasing Drp1 accumulation in mitochondria and Drp1‐mediated activation of the mitochondrial fission program. On the contrary, knockdown of HSS increased CDK1 as well as Drp1 phosphorylation and aggravated hepatocellular apoptosis. Mechanistic investigation showed that HSS was able to reduce the stability and translation of CDK1 mRNA by modulating the expression of several microRNAs (miRs), including miR‐410‐3p, miR‐490‐3p, and miR‐582‐5p. Conclusion: Our data reveal a novel mechanism for HSS in regulating the mitochondrial fission machinery and further suggest that modulation of HSS may provide a therapeutic approach for combating liver damage. (H epatology 2017;66:1989–2001)
Clinicopathological features and management of patients with primary malignant mediastinal germ cell tumor: 10 year’s experience in Peruvian patients.
Authors: Cindy Elizabeth Alcarraz, Zaida Morante, Gerson Mejia, Edgar Amorin, Silvia P Neciosup, Luis Mas, Henry L. Gómez, Jule Franve Vasquez Chavez
Journal: Journal of Clinical Oncology (2016)

e13088 Background: Primary malignant mediastinal germ cell tumor (PMMGCT) are rare and have poor prognosis with particularly different biology from those of other germ cell tumor. The aim of this study was to evaluate the clinicopathological features, different types of treatment response and survival these patients. Methods: Forty-six patients with PMMGCT who were treated at the Instituto Nacional de Enfermedades Neoplasicas, from 2003 to 2012. Overall survival (OS) curves were estimated using the Kaplan-Meier method and comparisons were done using the log-rank test. A p-value < 0.05 was considered statistically significant. Results: Forty-six men and 2 women with a median age of 23 [range: 3-68] were identified, of whom 17 (35.4%) had pure seminoma, 11 (22.9%) had non-seminomatous, 11 (22.9%) had mixed histology and 9 (18.8%) were not determined of histologic type. Thirty-one (64.6%) had tumor located at mediastinum, 7 (14.6%) had lung metastases and /or effusion and 10 (20.8%) had distant metastases. Thirty-five (72.9%) patients received chemotherapy (ChT) first, 6 (12.5%) underwent surgical resection followed by ChT, 2 (4.2%) concurrent ChT and radiotherapy (RT), 1 (2.1%) RT followed by ChT and 4 (8.3%) no treatment. Twenty eight (63.6%) achieved objective response, 22 (50%) underwent surgery after ChT consolidation of which 17 (77.2%) were negative for tumor histology. The 5-yrs median progression-free survival was 73.4% and overall survival was 60.1%. By univariate analysis was determined that the high level of AFP at diagnosis (p = 0.002) and surgical consolidation (p = 0.042) were prognostic factors for OS and PFS. Conclusions: Young men were the most affected population. The mediastinum restricted location and pure seminoma histology are more frequent. The high level of AFP and surgical resection were significant factors for survival but not independently.
Targeting Adenosine in BRAF-Mutant Melanoma Reduces Tumor Growth and Metastasis
Authors: Arabella Young, Shin Foong Ngiow, Jason Madore, Julia Reinhardt, Jennifer Landsberg, Arash Chitsazan, Jai Rautela, Tobias Bald, Deborah S. Barkauskas, Elizabeth Ahern, Nicholas D. Huntington, Dirk Schadendorf, Georgina V. Long, Glen M. Boyle, Michael Hölzel, Richard A. Scolyer, Mark J. Smyth
Journal: Cancer Research (2017)

Increasing evidence exists for the role of immunosuppressive adenosine in promoting tumor growth and spread in a number of cancer types, resulting in poor clinical outcomes. In this study, we assessed whether the CD73-adenosinergic pathway is active in melanoma patients and whether adenosine restricts the efficacy of clinically approved targeted therapies for commonly mutated BRAFV600E melanoma. In AJCC stage III melanoma patients, CD73 expression (the enzyme that generates adenosine) correlated significantly with patients presenting nodal metastatic melanoma, suggesting that targeting this pathway may be effective in advanced stage disease. In addition, dabrafenib and trametinib treatment of CD73+ BRAFV600E-mutant melanomas caused profound CD73 downregulation in tumor cells. Inhibition of BRAF and MEK in combination with the A2A adenosine receptor provided significant protection against tumor initiation and metastasis formation in mice. Our results suggest that targeting adenosine may enhance therapeutic responses for melanoma patients receiving targeted or immune-based therapies. Cancer Res; 77(17); 4684-96. ©2017 AACR.
French comment on article Long-term clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms in 423 cases: a retrospective study1 Suivi clinique à long terme après dissection sous muqueuse pour 423 tumeurs colorectales: une étude rétrospective
Journal: Endoscopy (2017)

La dissection sous muqueuse (DSM) est une technique de résection qui permet d’avoir une meilleure analyse carcinologique de la lésion par rapport à la mucosectomie. Elle est associée dans la littérature à un taux de récidive plus faible. Les données concernant le risque de récidive à long terme sont cependant peu nombreuses. Dans cette étude rétrospective réalisée dans un centre japonais avec une forte activité de DSM (National Cancer Center Hospital à Tokyo) les auteurs ont analysé le taux de récidive après le suivi à long terme de 423 lésions colorectales (adénomes, adénocarcinomes). La perforation (3 %, dont un cas opéré au niveau du caecum) et le saignement retardé (1 %) étaient les deux complications rapportées.
DNA Copy Number Gains of TCF4 (E2-2) Are Associated with Poor Outcome in Diffuse Large B-Cell Lymphoma
Authors: Keenan Hartert, Saber Tadros, Alyssa Bouska, Dalia Moore, Christine Pak, Tayla Heavican, Chih Long Liu, Andrew J. Gentles, Elena M Hartmann, Robert Kridel, Karin Ekstrom Smedby, Gunnar Juliusson, Richard Rosenquist, Randy D Gascoyne, Andreas Rosenwald, Martin Bast, Julie M Vose, Matthew Lunning, Timothy C. Greiner, Scott J Rodig, Javeed Iqbal, Ronald Levy, Ash A. Alizadeh, Michael R Green
Journal: Blood (2016)
Demographic study of gastrointestinal cancers in northeast of Iran: Report of 12000 patients.
Authors: Maryam Salehi, Soudabeh Shahidsales, Seyed Amir Aledavood, Hakimeh Baseri
Journal: Journal of Clinical Oncology (2016)

e13061 Background: This study was aimed to determine the relative frequency, mean age and sex ratio of the four types of gastrointestinal cancers (GI) among 12,000 patients referred to two referral center of Oncology, during 1985-2012 in Mashhad, Iran Methods: This cross- sectional study was conducted in Mashhad, Iran. The data of 11471 patients with GI cancers were obtained.The duration of study was categorized into five periods: 1985-1990, 1991-1995, 1996-2000, and 2001-2005 and after 2006. GI cancers were studied include: esophageal, stomach, intestinal and colorectal. Results: Esophageal cancer (5,744 cases, relative frequency of 50.1%) was the most frequent cancer overall and in all intervals followed by stomach (30%), colorectal (18.4%) and intestinal (1.6%). Relative frequency of GI cancers had significant differences among five intervals (p < 0.001), the relative frequency of esophageal cancer was decreasing but in colorectal cancer was increasing during 3 decades. Mean age at the time of diagnosis was 59.9±13.5years (male: 60.9±13.5, female: 58.3±13.2). There was significant difference in mean age for all cancers dividing by sex (p < 0.001).Mean age of esophageal, stomach, intestinal and colorectal cancers was 61.8±12, 61.8±11.9, 42.4±21.5, 53.1±15.3 years, respectively. The mean age of patients had significant differences among cancer types (p < 0.001).Mean age of all cancers was significantly rising during 5 periods intervals (p < 0.001).Mean age at the time of diagnosis for all cancers except colorectal cancer, was significantly higher in men (p < 0.001).Male to female sex ratios in our study for esophageal, stomach, intestinal and colorectal cancers were 1.15, 3.21, 1.48 and 1.27 respectively. Conclusions: Esophageal cancer was the most common gastrointestinal cancer in the whole duration of this study. Gender differences observed in the relative frequency and in the mean age at the time of diagnosis of cancers.Age at diagnosis for esophageal and stomach cancers was about 60 years and for colorectal cancer about 50 years.
Hormone replacement therapy (HRT) among BRCA mutation carriers.
Authors: Nicole Centers, Olga Ivanov, Cynthia Buffington, Aileen Caceres
Journal: Journal of Clinical Oncology (2017)

1561 Background: BRCA mutation carriers are often offered risk-reducing surgery (oophorectomy, hysterectomy) and medication regimens (hormone modulators, chemotherapy) in a preventative format. These therapies cause premature menopause and associated symptoms including reduced libido and sexuality. Hormone replacement therapy (HRT) is beneficial in alleviating climacteric symptoms of menopause. However, due to high risk for breast cancer in BRCA mutation carriers, many within the healthcare community oppose the use of HRT, despite recent studies that fail to demonstrate an adverse effect on oncologic outcomes. The purpose of this study was to identify current HRT practices among BRCA1,2 mutation carriers. Methods: The study population included 763 BRCA1,2 mutation carriers (52% previvors, 48% survivors) who are members of Facing Our Risk of Cancer Empowered, a support, education, and advocacy group for individuals with gene mutations. Data was collected via an online survey that included questions pertaining to patient characteristics, preventative procedures, menopausal status and symptoms, HRT use, and provider recommendations. Results: According to the survey findings, 73% of BRCA mutation carriers were postmenopausal (59% previvors, 88% survivors) and, among these, 81% had become menopausal prematurely due to risk-reducing surgery or medications. Major postmenopausal concerns of BRCA mutation carriers involved low libido/sexuality (78%) and an increased risk for weight gain (83%), cardiovascular disease (77%), and osteoporosis (65%). Despite the high incidence of premature menopause and associated symptomatology of the population, HRT usage was low (13% previvors, 28% survivors). According to the survey respondents, only 26% of healthcare providers for the previvors and 8% for the survivors favored HRT use. Conclusions: High rates of premature menopause with related symptoms occur among BRCA1,2 mutation carriers in association with cancer preventative therapies. Despite the young age of this postmenopausal population, only a small percentage are on HRT. These findings suggest the need for improved education to patients and providers regarding HRT and cancer risk, as well as the exploration of HRT options.
Nabpaclitaxel plus gemcitabine in subjects with advanced pancreatic cancer who have cholestatic hyperbilirubenemia secondary to bile duct obstruction.
Authors: Uwe Pelzer, Lilianna Wislocka, Sven Bischoff, Anja JÃ Â¼hling, Marianne Sinn, Jana Kaethe Striefler, Marcus Bahra, Bernd Dörken, Hanno Riess
Journal: Journal of Clinical Oncology (2016)

e15717Background: The combination of nabpaclitaxel/gemcitabine (AG) is one standard of care treatment for patients (pts) with advanced pancreatic adenocarcinoma (APC). Only insufficient data accord...
Abstract 15279: Early Rule-Out of Myocardial Infarction is Facilitated by Soluble FMS-Like Tyrosine Kinase-1
Authors: Till Keller, Francisco Ojeda, Tanja Zeller, Stergios Tzikas, Christoph Bickel, Stephan Baldus, Karl Lackner, Thomas Münzel, Stefan Blankenberg
Journal: Circulation (2011)

Background: Acute chest pain is one of the most common causes for admission to an emergency department. Up to one third of these patients suffer an acute coronary syndrome (ACS) whereas a large pro...
Adjuvant chemoradiation alone versus chemoradiation after curative resection for pancreatic cancer: feasibility results of a randomised EORTC/FFCD/GERCOR study (40013/22012/0304)
Authors: J Van Laethem, E Van Cutsem, P Hammel, F Mornex, D Azria, G Van Tienhoven, Marc Peeters, Marleen Praet, Budach, K Haustermans
Journal: Journal of Clinical Oncology (2008)
Trends in treatment patterns and outcomes for DCIS patients: A SEER population-based analysis.
Authors: Mathias Worni, Rachel A Greenup, Aimee M Mackey, Igor Akushevich, Shelley E. Hwang
Journal: Journal of Clinical Oncology (2014)

1007 Background: Ductal carcinoma in situ (DCIS) is considered a precursor lesion of invasive ductal cancer of the breast, and current therapy aims to prevent progression to invasive disease. However, the impact of contemporary treatment options on breast-cancer survival remains poorly defined. Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was queried from 1991-2010 for patients with DCIS. Age-adjusted incidence rates were calculated, and trends in treatment patterns were analysed using the Cochran Armitage trend test. Survival analyses were performed with inverse probability weight (IPW) adjusted competing risk analysis for cancer specific (CSS) and cox proportional hazard regression analysis for overall survival (OS). Results: 121,080 DCIS patients were included in the analysis. Age-adjusted incidence rates increased from 23.2/100,000 females in 1992 to 36.4/100,000 in 2010. Highest incidence rate was found among females age 60-79 years in 2010 (83.8/100,000). Most patients were treated with lumpectomy and radiation therapy (breast conservation therapy, BCT) (43.0%), followed by lumpectomy alone (26.5%), unilateral (23.8%) or bilateral mastectomy (4.5%), and no treatment (2.3%). Rates of unilateral mastectomy significantly decreased from 1991 (44.9%) to 2010 (19.3%), as did lumpectomy alone (29.8% to 22.3%), while increased rates of BCT (24.2% to 46.8%) and bilateral mastectomy (0% to 8.5%) were observed (p for trend <0.001 for all comparisons). On IPW adjusted analysis, CSS was superior to BCT compared to mastectomy (hazard ratio HR: 1.16, 95% CI: 1.00-1.33, p=0.048) while no difference was found for lumpectomy alone over mastectomy (HR: 0.90, CI: 0.77-1.05, p=0.17). Compared to mastectomy, patients undergoing BCT demonstrated improved OS (HR: 1.17, CI: 1.12-1.22, p<0.001) while patients undergoing lumpectomy alone demonstrated worse OS (HR: 0.79, CI: 0.76-0.83, p<0.001). Conclusions: The incidence of DCIS in females continues to rise, particularly in women 60-79. There has been a significant shift in treatment patterns towards BCT and bilateral mastectomy. Using IPW adjustment, CSS and OS were best for patients undergoing BCT compared to all other treatment groups.
Alterations in the levels of oxidative damage in sporadic colorectal cancer
Authors: J Sheridan, H Mulcahy, E Fox, D Leahy, K Sheahan, J Hyland, D O'Donoghue, J O'Sullivan
Journal: Endoscopy (2006)

Oxidative DNA damage can be caused by reactive oxygen species (ROS), and 8-oxo-dG is a key biomarker of oxidative DNA damage. The base-excision repair pathway (BER) is the major pathway for repair of oxidative damage, the mis-match repair (MMR) system being an important backup repair pathway. Using tissue microarrays and immunohistochemistry, we examined levels and localization of 8-oxo dG in matched tumour and normal tissues from 47 sporadic colorectal cancers. Loss of mis-match repair proteins, MLH1 and MSH2 was assessed to determine interactions between BER and MMR pathways. Total 8-oxo-dG positivity were significantly elevated in normal mucosa (mean 70.1 [SD 23.9]) compared to tumour (36.9 [38.9]) (p<0.001). Individual levels, both in epithelial and stromal cells were greater in normal than tumour (p<0.001 in each case). Total intensity levels were also significant in each case (p<0.001). There was no association between 8-oxo-dG and loss of mis-match repair proteins in tumours (p=0.7). Increased ROS and inflammation may contribute to the increased levels of 8-oxo-dG in normal tissue with subsequent promotion of genomic instability and consequent risk of cancer development.
A potential role of pemetrexed (PMTX) for the treatment (Tx) of thymidylate synthase (TS) negative primary brain tumors and systemic malignancies with CNS metastasis.
Authors: Lyndon J. Kim, James J Evans, Kevin D. Judy, Christopher Farrell, David W. Andrews
Journal: Journal of Clinical Oncology (2017)

e13519 Background: Fluoropyrimidne analogue Capecitabine, a TS inhibitor, can cross blood brain barrier and has been used for the Tx of breast cancer with brain metastasis (mets). An antifolate Methotrexate (MTX), which also inhibits TS, has been used for the Tx of PCNSL secondary to it's excellent CNS penetration. MTX analogue, PMTX inhibits purine synthesis via TS and DHFR, and pyrimidine synthesis via GARFT, thus, making it a viable Tx option for CNS malignancies. Methods: We have treated 40 pts with previously heavily treated recurrent primary and systemic malignancies with CNS mets based on the molecular profiling. 26/40 pts were found to have TS negative expression (5/12 GBM, 5/5 AA, 1/1 Gr II Astrocytoma (A), 5/7 meningioma, 1/3 PCNSL, 1/2 Esthesioneuroblastoma, 1/1 chordoma, and 7/9 brain mets) and 10/26 TS negative pts were treated with PMTX. MRI was performed every 2-3 mo for tumor response. Results: Total pts: 10. M:F 6:4. Age: 48-88 yo. Median age: 61.9 yo. Tx period: 7/14–1/17. 1/1 GBM pt: stable disease (SD) x 4 mo. 1/2 AA pts: SD x 4 mo, 1/2 pts: tumor progression. 1 Gr. II A pt, SD x 7 mo. 2/2 meningioma pts: SD x 2 and 4 mo. Both pts also received concurrent cisplatin (also ERCC1 negative). 3/3 pts: squamous cell Ca of skin with skull base/brain mets responded x 24 mo, 24 mo and 3 mo respectively (1 PR and 2 SD), 2 pts: still receiving Tx. 1 pt: 26 mo reponder, died of nontumor related issue. 1/1 chordoma pt: SD x 11 mo. Toxicities: very mild except 2 pts (Gr. 3-4) who also received cisplatin. Conclusions: TS negative expression is commonly found in most of secondary malignancies with brain mets and in non-GBM primary brain tumors. PMTX appears to have a favorable efficacy for the Tx of TS negative primary and systemic malignancies with CNS mets. Albeit small cohort, overall response was 90% (PR:1, SD:8). Tx was particularly effective for squamous cell ca with brain mets and responses were durable in all spectrum. Due to favorable tolerance and response, especially in the elderly pts with squamous cell with brain mets, PMTX could be an excellent Tx option for TS negative CNS malignancies. PMTX trial for TS negative CNS malignancies should be considered.
62 Follow-up of patients with isolated active ileitis: increasing development of overt crohn’s disease over time
Authors: R Stack, S O’Donnell, N O’Morain, M Hussey, A O’Connor, N Breslin, A Alakkari, D McNamara, BM Ryan
Journal: Gut (2017)

Background  Increased TI intubation at colonoscopy had led to increased identification of mild ileal inflammation. Patients with co-called Isolated Active ileitis (IAI) have mild TI inflammation, no chronicity on histology, and do not fulfil criteria for a diagnosis of Crohn’s Disease (CD). Causes include CD, NSAID use or infection. The natural history of IAI has remained unclear.  Aim  Long term follow up of a cohort of patients diagnosed as IAI, to assess evolution to CD, persistent IAI and Self-Limiting Ileitis (SLI).  Method  IAI patients were reviewed at a 10 year interval by means of clinical follow up, endoscopy, histology and small bowel imaging (SBI).  Results  50 patients; Median age 48 years; 16/50 (32%) male. At time of follow up, 29/50 (58%) had a follow up ileocolonoscopy with 16/29 (55%) showing persistent ileitis on histology. 38/50 had formal SBI with inflammatory changes on 11/38 (29%). Of the original cohort, SLI, persistent IAI and CD was reported in 7/50 (14%), 7/50 (14%) and 14/50 (28%), respectively. 22/50 patients were lost to follow up. 4 patients developed strictures and 3 required surgery. Predominant presenting symptoms included pain and diarrhoea in all groups, with no statistical difference in smoking, NSAID use and family history amongst the 3 subgroups.  Conclusions  Over time a significant portion of patients with IAI evolve to overt small bowel CD. Neither presenting complaint nor clinical risk factors were predictive of disease progression, suggesting these all patients should be under surveillance for disease progression.
Abstract 17864: Final Results of the Inspire Trial With the Novel Mguard Stent for SVG and Thrombus-Containing Lesions
Authors: Jose de Ribamar Costa, Alexandre Abizaid, Fausto Feres, Ricardo Costa, Rodolfo Staico, Dimytri Siqueira, Galo Maldonado, Amanda Sousa, J Eduardo Sousa
Journal: Circulation (2010)

Background: Disturbances of coronary flow due to distal embolization of thrombus/platelet agreggates are associated with worse immediate and long-term prognosis after PCI. Treatment of SVG and PCI ...