tbuckley/cabot-search huggingface dataset:
Some immunohistochemical parameters in primary and recurrent soft tissue sarcomas.
Authors: Evgeniya M. Nepomnyashchaya, Oleg Ivanovich Kit, Elena Petrovna Ulianova, Inna Arnoldovna Novikova, Larisa Nikolaevna Vashchenko, Timur A. Aliev, Tatiana Valeryevna Ausheva, Galina I. Zakora, Ekaterina I. Zolotareva, Elena S. Bondarenko, Elena A. Andreyko
Journal: Journal of Clinical Oncology (2018)

e23533 Background: The purpose of the study was to reveal some immunohistochemical parameters in primary and recurrent soft tissue sarcomas. Methods: The study included patients with primary (n = 30) and recurrent (n = 29) sarcomas. Sections of tissues embedded in paraffin blocks were studied by immunohistochemistry; the staining was performed using the Thermo Scientific autostainer. The Reveal Polyvalent HRP-DAB Detection System was used to visualize the immunohistochemical reaction. Proliferative activity (Ki-67), factors of apoptosis and proapoptosis (bcl2, bax) and angiogenesis (CD34) were determined. Statistical processing of the data was performed using STATISTICA 7.0 (StatSoftInc., USA). Results: Ki-67 in primary sarcomas was 30.7±9.2% and in recurrent sarcomas – 35.5±8.72%, t˃2. (P˃0.05). Proliferative activity in recurrent sarcomas was higher than in primary sarcomas, but the χ2 index was not statistically significant. The Ki-67 expression in the nuclei of tumor cells ranged from 5% to 45%. CD34 in primary sarcomas was 12.2±0.94, in recurrent sarcomas – 9.18±1.6 (P˂0.05); VEGF levels were 10.6±1.88 and 8.12±1.6 respectively (P˂0.05). Some decrease in angiogenesis factors in recurrent tumors could be explained by the adjuvant chemotherapy contributing to the suppression of the tumor growth. The apoptotic factors bax and bcl2 in primary tumors amounted to 7.67±2.3 and 4.42±1.46, respectively; the bax expression was absent in 3 cases, that of bcl2 – in 2 cases. The bax/bcl2 ratio was 1.68±0.54. The levels of bax and bcl2 in recurrent tumors were 1.68±0.54 and 4.28±0.67; the bax expression was absent in 4 cases, that of bcl2 – in 7 cases. The bax/bcl2 ratio was 0.60±0.15. The bax levels in primary sarcomas were statistically significantly higher compared to recurrent sarcomas (7.67±2.3 vs. 1.68±0.54, P˂0.05), while the bcl2 levels were similar (4.42±1.46 and 4.28±0.67, respectively). Conclusions: The immunohistochemical study of parameters of the proliferative activity, apoptosis, proapoptosis and angiogenesis factors revealed some characteristics of primary and recurrent sarcomas of soft tissues.
Abstract 21379: Transfemoral vs Transapical Transcatheter Aortic Valve Replacement: Analysis Of The Nationwide Inpatient Sample and National Readmission Database From 2011-2014
Authors: Aditya Mantha, Afnan R Tariq
Journal: Circulation (2017)

Introduction: Transfemoral (TF) and transapical (TA) techniques for transcatheter aortic valve replacement have been validated in clinical trials. However, the impact of the choice of approach modality on resource utilization, mortality, and readmissions in clinical practice remains unclear. Methods: Patients who underwent transcatheter aortic valve replacement (ICD 9: 35.05, 35.06) in the 2011-2014 National Readmission Database (NRD) and the Nationwide Inpatient Sample (NIS) Databases for whom readmission data was available were analyzed. The NRD and NIS are all-payer inpatient databases maintained by the Healthcare Cost and Utilization Project (HCUP) that estimate more than 35 million annual U.S. hospitalizations. Mortality, readmission, and GDP-adjusted cost were evaluated using hierarchical linear models adjusting for socioeconomic, demographic and comorbidity measured by Elixhauser Index. Results: 38,929 patients underwent TAVR during the study period, 8,643 (22%) received a TA approach while 30,285 (78%) received a TF approach. TA patients were more likely female (52% vs 46%, P&lt;0.001), more likely from ZIP codes with median income below the national median (48% vs 44%, P&lt;0.001), and had higher Elixhauser Index (CI: 6.5 vs 6.1, P&lt;0.001). The TA approach was associated with higher adjusted mortality at discharge (6.7% vs 3.8% OR=1.7, P&lt;0.001), higher cost ($65,591 vs $56,595, β=0.14 , P&lt;0.001), and longer stays (11 vs 8.3 days, IRR=1.28, P&lt;0.001). All-cause readmission was significantly higher in TA patients within 30 days (20% vs 16%, OR=1.27, P&lt;0.001). Conclusion: In this study of 38,929 U.S. patients who underwent TAVR from 2011-2014, after adjustment for demographics, comorbidities, and hospital level variation, the TA approach was 14% more expensive, had 27% higher odds of readmission within 30 days, 28% longer length of stay, and 70% greater odds of mortality compared to TF approach. Our findings support the preference for the TF approach where technically feasible.
Clinical outcome and prognostic factors for Asian patients treated in a phase I study at the National University Cancer Institute, Singapore (NCIS).
Authors: Vaishnavi Muthu, Ross A. Soo, Wei-Peng Yong, Soo-Chin Lee, Andrea Li Ann Wong, Wee-Joo Chng, David SP Tan, Valerie Heong, Boon Cher Goh, Bee Choo Tai, Cheng Ean Chee
Journal: Journal of Clinical Oncology (2018)

e18748 Background: Patient selection for phase I (P1) trials in oncology is challenging. A typical inclusion criterion for P1 studies is 'life expectancy > 3 months', however overall survival (OS) of patients (pts) with advanced solid malignancies is difficult to predict. The Royal Marsden Hospital (RMH) prognostic score showed that low albumin, high LDH and > 2 sites of metastasis were independent prognostic factors for OS in P1 trial pts. A similar risk score has not been validated in Asian pts. In order to better select Asian pts for P1 trials, we aim to develop a similar prognostic score at an academic P1 trial unit in Singapore. Methods: Retrospective review of electronic medical records of P1 trial pts from October 2013 to July 2017 at the National University Cancer Institute, Singapore. Pt characteristics and survival data were collected. Results: We analyzed 174 pts treated in 14 P1 studies. Median age and BMI were 61 yrs (range: 23-82) and 21.9 (range: 13.4-35.2), respectively. Pt characteristics were summarized as follows: age > 60 (58%), male (52%), ECOG 0-1 (98%), comorbidities ≥2 (36%), no. of prior therapies ≥3 (60%, range: 0-13), no. of metastatic sites ≥3 (44%). Multivariable analysis of 11 factors indicated that low albumin ( < 35 g/L) (HR: 2.03, 95% CI: 1.27 – 3.27, p < 0.003), LDH > upper normal limit (HR: 1.69, 95% CI: 1.09 – 2.64, p < 0.020) and upper GI tumor type (HR: 2.86, 95% CI: 1.34 – 6.1, p < 0.006) were independent negative prognostic factors for OS. Adjusting for tumor type, low albumin and high LDH remained independent prognostic factors for OS with > 2 sites of metastasis at the threshold of significance (HR: 1.44, 95% CI: 0.94 – 2.22, p < 0.094). OS according to the RMH prognostic score revealed that pts with a score of 2–3 had a significantly shorter OS compared to pts with a score of 0–1 (4.9 months vs 13.9 months, HR: 2.67, 95% CI: 1.71 – 4.15, p < 0.001). Conclusions: Our study confirms that objective clinical parameters such as albumin, LDH and number of metastatic sites, may be used as markers of overall survival for Asian pts in P1 trials.
Post-operative breast pain in an ethnically diverse population.
Authors: Tamie L. Kerns, Patricia Nishimoto, Jacqui Mitchell, Dustin L Boyer, Mary P Johnson, Brenda S Santos, Michael B Lustik, Antoinette D Hemmings, Catherine M Miloni, Ellen G PerezSealey, Eileen C Itamotogaza, Jami Aya Fukui
Journal: Journal of Clinical Oncology (2018)

e22183 Background: Prevalence rates for persistent pain following breast cancer surgery range 25-60%. The wide range is attributed to differences in the definition of persistent pain, the measure used to assess pain and prospective vs retrospective assessment. There are a few studies that have looked at factors predicting persistent breast pain. The preliminary data suggest differences among ethnic groups with Asians and African-Americans disproportionally under/over reporting pain, respectively. Methods: Women diagnosed from 2015-2016 with breast cancer at Tripler Army Medical Center were contacted to assess the incidence of persistent breast pain and effect on quality of life. Patients were contacted by introduction letters prior to a telephone interview to complete the Breast Pain Questionnaire. Descriptive statistical analysis was conducted. Results: Of the one hundred breast cancer patients, 44 were available to participate in the telephone interview. 61% of patients reported ongoing breast complaints since their treatment. Breast pain accounted for negative effects on sex, sleep, and work in 18%, 42%, and 15% of patients studied, respectively. When dichotomized as Pacific Islanders versus other ethnicities, 43% of Pacific Islanders reported severe pain compared to 5% of other ethnicities (p = 0.053). Those identified as Asian never reported more than mild pain. Two-third of those reporting pain described it as ‘tenderness and/or aching’ but Pacific Islanders were less likely to describe the pain as tenderness. Conclusions: These results highlight a clinically underappreciated patient concern within cancer care delivery. The contrasts in ethnic perception of pain, which are multidimensional, malleable and shaped by culture, influence the difficulty in fully defining persistent breast pain. Larger studies are needed to translate knowledge and science into clinical practice for reduction in ethnic disparities of pain and to personalize pain management for all individuals.
Guarding against dispassion for doctors in the NHS
Authors: Archik Das, Rodger Charlton
Journal: Journal of the Royal Society of Medicine (2018)

Compassion has always been a vital component of healthcare anywhere in the world. With numerous definitions in a variety of contexts, it cannot simply be prescribed, measured or given in a bottle. When our patients are ill, great attention is paid to the verbal and non-verbal communication presented by a doctor and the manner in which they are delivered. However, with an ever-growing demand on the NHS workforce, numerous patient surveys across the UK have accused doctors for lacking compassion in their practice, amid the strains of their modern-day commitments. The concept of being caring to our patients is highlighted from the first walks of medical school or indeed any healthcare professional’s training programme, meaning that patients will always be our prime audience for compassion. Yet, so often in medical training, it is emphasised how important it is to demonstrate a personal detachment between oneself and the patient and not to get too emotionally involved. So despite numerous challenges, how do we find the correct balance to optimise our day-to-day service and stay sensitive to the needs of our patients? This article reflects upon compassion from multiple perspectives in the NHS pertinent to doctors of all settings and experience levels, exploring the barriers, internal conflicts and facilitators of its delivery. We examine the objective evidence of measures that have been put in place to overcome these challenges and summarise key considerations to optimise the enablement of a workforce to deliver compassion at universally higher standards in future practice.
Dose Reduction May Jeopardize Efficacy of Abiraterone Acetate
Authors: F.J. Sherida H. Woei-A-Jin, Tine Van Nieuwenhuyse, Nielka P. van Erp, Benoit Beuselinck, Stephanie Stroobants, Dirk Jan A.R. Moes, Susanne Osanto, Isabel Spriet
Journal: Journal of Clinical Oncology (2018)
Comprehensive genomic profiling of gastric cancer to reveal distinctive genomic alterations between peritoneal metastasis (PM) patients (pts) and non-PM pts.
Authors: Rongbo Lin, Xianchao Guo*, Ying Chen, Hui Li, Jie Liu, Shen Zhao, Jiaqing Yu, Nanfeng Fan
Journal: Journal of Clinical Oncology (2018)

e16063 Background: PM is the main cause of death in gastric cancer. PM of gastric cancer is difficult to diagnose in its early stage due to lack of obvious clinical signs and symptoms. Comprehensive genome analysis of the primary tumor provides a new strategy for uncovering the pathogenesis and molecular diagnosis of PM. Methods: DNA was extracted from FFPE samples of the primary tumors from 10 pts with PM and 9 pts without PM (non-PM). Comprehensive genomic profiling was performed using a 1.24M size panel covering exon regions of 1,346 genes based next generation sequencing assay. Somatic Mutations were analyzed to investigate the difference of molecular features between the gastric pts with or without PM. Results: The most frequently mutated genes were TP53, RAD50, ZFHX4. In addition, frequent mutations in chromatin remodeling genes such as KDM5A, KMT2C, KAT6A and HDAC2 were detected. Mutations of GPI, JAK3, PRSS8 and IDH3G are more common in non-PM pts than in PM pts (p < 0.05). Four mutations (PRDM1, c.950G > A; XPC, c.1315G > C; CD68, c.554A > C; ACVR1B, c.1345C > A) were only identified in PM pts. Conclusions: Comprehensive genomic profiling of gastric cancer reveals distinctive genomic alterations between PM pts and non-PM pts. Several possible candidate genes that may be helpful forPM of gastric cancer were identified in this small cohort. Expanded prospective cohorts are warranted to further elucidate these findings.
P05.86 Hippocampal sparing in primary central nervous system lymphoma. Is it routinely possible?
Authors: T Zinicola, S Chiesa, F Beghella Bartoli, F Catucci, M Giraffa, D Marchesano, S Hohaus, G C Mattiucci, V Valentini, M Balducci
Journal: Neuro-Oncology (2018)

Whole brain radiotherapy (WBRT) has been the radiation treatment of choice for patients with primary central nervous system lymphoma (PCNSL). Neurocognitive functions (NCFs) decline is surely one of the main significant complications which may occur. It has been widely shown that neurocognitive decline is mainly caused by the radiation-induced injury to the hippocampus. The conformal hippocampal avoidance during the course of WBRT might provide meaningful NCFs preservation. Our study aims to investigate the correlation between the site of (Primary Central Nervous System Lymphoma) PCNSL lesions and the hippocampal region in order to explore the feasibility of routinely sparing of the hippocampus during a WBRT to prevent neurocognitive decline. Patients (> 18 years, ECOG <4) with pathologically proven PCNSL and MRI image pre-treatment were retrospectively reviewed. All patients had received high-dose of methotrexate (HD-MTX) before WBRT. T1-weighted, post-contrast axial MR image sets obtained prior to cranial irradiation were imported on Varian Eclipse treatment planning system, version 11 (Varian Medical Systems) and registered with the simulation CT. The hippocampus as well as each PCNSL lesions were contoured. Three dimensional envelopes surrounding the hippocampus were generated adding 5, 10, and 15 mm and the distance of brain lesions were recorded as <5 mm, 5 to <10 mm, 10 to <15 mm, and >15 mm from the hippocampus. The minimum margin of 5 mm was taken into account for systematic setup error and dose fall-off between whole brain clinical target volume and the hippocampus. Thirty-eight patients were treated between 2005 and 2018 and 36 pts with 57 lesions were eligible for this study. PCNSL lesions’ locations were: deep brain structures (26%), parietal lobe (23%), frontal lobe (19%), temporal lobe (14%), occipital lobe (7%), brainstem (5%), other sites (6%). Nine patients were affected by multiple lesions. In 18/57 lesions (31.6%) the distance from the hippocampus region was less than 5 mm and seven of them (12.3%) involved the hippocampus. Lesions over 15 mm from the hippocampus were observed in 30 cases (52.6%), while only the 15,8% was between 5 and 15 mm. These data show that routinely sparing of the hippocampus region is not recommended. Anyway, it should be considered in selected patients, when the spatial distribution of PCNSL is far more than 5 mm from the lesion.
Legalise illicit drugs to protect health, say former heads of state
Authors: Richard Hurley
Journal: BMJ (2018)

Current efforts to control drugs such as cannabis, cocaine, and heroin are causing huge avoidable harm, and governments have a duty to investigate the effect of legalising their supply, former world leaders and others have said.

Legal controls could reduce social and health harms among people who take such drugs and would disrupt organised crime and reduce the violence innate to the criminal market, says a report from the Global Commission on Drug Policy, which also considers how such regulation might be achieved.1

“The process . . . must be cautious, incremental and evidence-based, guided at all times by the principles of protecting and promoting human rights, public health, sustainable development, and peace and security,” the report says.

“Often misrepresented as …
Predictive factors of surgical morbidity for early-stage cervical cancer management: A prospective multicentric cohort of 228 patients.
Authors: Vincent Balaya, Patrice Mathevet, Charlotte Ngo, Laurent Magaud, Cyrille Huchon, Fabrice Lecuru
Journal: Journal of Clinical Oncology (2018)

e17506 Background: The aim of this study was to assess the post-operative morbidity of patients who have undergone a radical surgery for early-stage cervical cancer and to determine the predictive factors of complication. Methods: We analyzed the data of a french prospective multicentric cohort on sentinel node biopsy for cervical cancer. Patients who have undergone radical hysterectomy or radical trachelectomy were included between 2009 and 2012 from 23 French oncologic centers. Results: A total of 228 patients were included. The median age were 43 years [22 – 85]. 192 patients had a radical hysterectomy and 36 a radical trachelectomy. 91,4 % of patients had a stage IB1 disease. There were 67,7% of epidermoid carcinoma and 30,2 % of adenocarcinoma. The urinary, lymphovascular and neurologic complications rates were respectively 30,7%, 25,4% and 21,5%. In a multivariate analysis, the predictive factors of lymphovascular complications were: a previous pelvic surgery (ORa = 3,3; IC95% = [1,6; 6,8], p = 0,001), a one-time surgery (ORa = 7,7; IC95% = [1,6; 33,3], p = 0,01), an associated vaginal complication (ORa = 2,7; IC95% = [1,05; 7,12], p = 0,04) and an adjuvant radiotherapy (ORa = 4,6; IC95% = [1,9; 11,3], p = 0,001). In a multivariate analysis, the predictive factors of neurologic complications were BMI < 25 kg/m2 (ORa = 2; IC95% = [0,9; 1,6], p = 0,07) and age < 45 years (ORa = 5; IC95% = [1,4; 20], p = 0,01). Conclusions: These complications rates were less important than that found in the literature. The main complications were urinary infections and lower limb lymphedema. The nerve-sparing technique is the most important key to improve the functional outcomes for the surgical management for early-stage cervical cancer.
Neoadjuvant chemotherapy with mFOLFOXIRI alone for cT4 and fixed cT3 rectal cancer: Results from a single arm phase II study (FORTUNE).
Authors: Jianwei Zhang, Yue Cai, Huabin Hu, Dianke Chen, Jian Xiao, Jiayu Ling, Wang Wenjing, Ping Lan, Lei Wang, Meijin Huang, Xiaojian Wu, Liang Kang, Jianping Wang, Yanhong Deng
Journal: Journal of Clinical Oncology (2017)

3607 Background: Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in locally advanced rectal cancer (LARC), it delays administration of systemic chemotherapy. About 30% of patients still developed distant metastases, which is the main obstacle for improving survival of LARC. Besides, preoperative radiation causes lots of concerns about anal and sexual functions. We aimed to explore the efficacy of preoperative chemotherapy with mFOLFOXIRI in LARC rather than consistent use of chemoradiotherapy. Methods: Patients with fixed cT3 or cT4 rectal cancer evaluated by pelvic MRI participated in this trial. All candidates were to receive 4-6 cycles of mFOLFOXIRI. MRI will be performed to assess clinical responses. Patients with stable/progressive disease were to have radiation before surgery, whereas responders were to have immediate total mesorectal excision (TME). Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX was recommended. The primary endpoint is the ratio of tumor downstaging to ypT 0-2 N 0 M 0 .The secondary endpoint included pathologic complete response rate, 3-year disease free survival rate and safety. Results: Between August 2014 and September 2016, 83 patients were enrolled and 80 participants had received TME. Three refused surgery after chemotherapy, because the tumor location is too low to perform sphincter-preserving operation. Of 80 patients completing at least 4 cycles of preoperative chemotherapy, two received short-term radiation before TME, and 10 patients underwent long-term chemoradiotherapy after MRI evaluation. The pCR rate of the whole group was 15 of 80 (18.8%) and the tumor downstaging rate was 43.8%. Among patients without chemoradiotherapy, the pCR rate and tumor downstaging were 14.3% and 41.4%, respectively. And the chemo-related toxicity was all tolerable. Conclusions: Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. The result was promising and further phase III study is warranted to validate this experience. Clinical trial information: NCT02217020.
Therapeutic pathomorphism of non-small cell lung cancer (NSCLC) as a result of neoadjuvant chemoimmunotherapy (nCIT) with tumor necrosis factor (TNFÎ±1).
Authors: Yuri Lazutin, Sergey P. Pyltsin, Tamara G. Ayrapetova, Pavel A. Anistratov, Igor A. Leyman, Anna V. Chubaryan, Igor N. Turkin, Oleg N. Stateshny, A. S. Shogenov, Liubov Yu Vladimirova, M. A. Gappoeva, S. G. Beleckiy, M. Afaunov, Rukiyat Isaeva
Journal: Journal of Clinical Oncology (2018)

e24323 Background: The purpose of the study was to reveal morphological changes in tissues of NSCLC after various nPCT regimens. Methods: The study included 64 pts with stage IIb-IIIa NSCLC divided into two groups: main group – 32 pts, 2 cycles of nPCIT with recombinant hybrid protein of TNFα1; control group - 32 pts, 2 cycles of conventional PCT. CR in 3 (9,4%) and 2 (6.2%) cases, PR in 14 (43.7%) and 13 (40.6%), SD in 13 (40.6%) and 14 (43.7%), PD in 2 (6.2%) and 3 (9.4%), respectively. 29 (90.6%) pts in each group received surgery. Pts with PR had squamous cell carcinoma in 28.5% and 21.4%, adenocarcinoma in 17.9% in both groups. Tumor tissue samples of pts with PR were studied by immunohistochemistry with staining for: CD3+ lymphocytes, CD20+ lymphocytes,CD34+ endothelial cells. An original 3-point scale of IHC expression in CD34+and CD3+cell specimens was used for the evaluation. Results: The expression of CD34+cells in the main group was weak in 69.2% and moderate in 30.8% (p = 0.044), with no strong expression; in thr control – moderate in 54.5% and strong in 45.5%. Weak CD3+expression in the main group prevailed over strong expression (53.8% vs 7.7%, p = 0.014) and in comparison with the control group (18.3%, p = 0.034). Moderate CD3+expression was observed in 38.4% and 36.4%, respectively; strong expression – 7.7% and 45.4%, respectively (p = 0.017). Thus, therapeutic pathomorphism in the nCIT group involved necrosis of up to 70-80% of tumor, with weak inflammation and no fibrosis. The endothelial vascular reaction was weak in 69.2% or moderate in 30.8%, T-lymphocytic infiltration – weak in 53.8% and moderate in 38.4%. The control group demonstrated other manifestations of therapeutic pathomorphism – up to 50% of tumor tissue was preserved with small necrosis foci. Conclusions: The study showed that recombinant hybrid protein of tumor necrosis factor-alpha-thymosin-alpha1 in addition to the conventional chemotherapy had a significant damaging effect on the tumor due to its cytotoxic and anti-angiogenic action.
Edoxaban Versus Warfarin in Latin American Patients With Atrial Fibrillation
Authors: Ramón Corbalán, José Carlos Nicolau, José López-Sendon, Armando Garcia-Castillo, Rodrigo Botero, Gustavo Sotomora, Manuel Horna, Christian T. Ruff, Rose A. Hamershock, Laura T. Grip, Elliott M. Antman, Eugene Braunwald, Robert P. Giugliano
Journal: Journal of the American College of Cardiology (2018)