tbuckley/cabot-search huggingface dataset:
Risk factors of hepatic failure after liver resection for perihilar cholangiocarcinoma: Importance of future liver remnant volume, body weight ratio, and impact on long-term survival.
Authors: Jong Woo Lee, Jae Hoon Lee
Journal: Journal of Clinical Oncology (2019)

348 Background: Hepatic resection for perihilar cholangiocarcinoma (PHCC) is associated with high postoperative mortality. Future liver remnant volume to total liver volume ratio has been used to anticipate the risks associated with liver resection for PHCC. We sought to investigate the independent factors associated with postoperative hepatic failure (PHLF) and assess predictive value of future liver remnant volume – body weight (FLRV/Wt) ratio after resection for PHCC. Methods: This study included 287 patients who underwent major hepatectomy including caudate lobectomy with bile duct resection for PHCC between 2008 and 2015 in single center. FLRV were calculated with CT volumetry and perioperative clinical and operative data were analyzed to identify independent determinants of PHLF (grade B/C according to the International Study Group of Liver Surgery criteria) and major postoperative complications (Dindo III to IV). Results: Combined Portal vein resection was performed in 18.8%. PHLF incidence was 13.6% and 90-day mortality was 3.5%. On multivariate analysis, predictors of PHLF (p &lt; 0.05) were FLRV/Wt ratio &lt; 0.5 (odds ratio [OR] 9.45), ICG R15 &gt; 15 (OR 3.72), BMI &lt; 25.0 (OR 6.41) and R1 resection (OR 3.97). There was no significant difference of survival between two groups divided by FLRV/Wt ratio (0.5) in Kaplan-Meier analysis. There was significant difference of survival according to PHLF. In without PHLF group, 1yr, 3yr, 5yr survival were 83.1%, 45.2%, 28.1%. In PHLF B group, 1yr, 3yr, 5yr survival were 66.7%, 40.7%, 20.7% respectively. Conclusions: Insufficient FLR volume (FLRV/Wt &lt; 0.5), ICG R15 (&lt; 15), BMI (&lt; 25) and R1 resection is associated with PHLF for patients with PHCC. We confirmed that PHLF is also associated with long term outcome. Preoperative assessment to patients with PHCC should be optimized to minimize the risk of PHLF. [Table: see text]
Novel radiomics signature predicts lymph node metastasis in T1 colorectal carcinoma.
Authors: Yanlei Ma, Sheng Zhang, Xinxiang Li, Tianye Niu
Journal: Journal of Clinical Oncology (2019)

506 Background: This study evaluates the predictive performance of radiomic features in metastasis of T1 colorectal carcinoma (CRC) to lymph nodes. Methods: A total of 10 200 CRC patients from our clinical cancer center included in this analysis. 225 eligible cases diagnosed with T1 CRC were included and divided into two groups: computed tomography (CT) image group (n = 82) and magnetic resonance image (MRI) group (n = 143) based on the preoperative image data available. A total of 548 radiomic features were extracted from each case and analyzed, and then a panel of radiomic features associated with lymph node metastases (LNM) were selected using Mann-Whitney U test. Combining these selected radiomic features and clinical data, the predictive performance for LNM was calculated using receiver operating characteristic (ROC) curves. Results: The prediction accuracy for LNM of T1 CRC could be improved to 0.88 by area under the receiver operating characteristic curve (AUC) through integration of one radiomic feature and three clinical indicators in CT group. In the group of contrast enhanced T1-weighted MRI (T1w-MRI), combination of two radiomic features and three clinical parameters present an AUC value of 0.85. In the group of T2-weighted MRI (T2w-MRI), combination of four radiomic features and five clinical characteristics identified T1 tumors with LNM with an AUC value of 0.87. Conclusions: The current study present a good predictive performance of combination of radiomic features with clinic characteristic in identifying T1 CRC with LNM, which may provide an important opportunity for us to make clinical treatment decision-making for T1 CRC patients.
Abstract OT1-1-08: PERSEPHONE: Duration of trastuzumab with chemotherapy in women with HER-2+ve early breast cancer
Authors: HM Earl, A-L Vallier, E Ogburn-Storey, DA Cameron, AM Wardley, D Miles, S Loi, L Hiller, HB Higgins, JA Dunn
Journal: Cancer Research (2013)

Abstract Background: PERSEPHONE is a randomised controlled trial comparing six months of trastuzumab to the standard 12 months in patients with HER2 positive early breast cancer. PERSEPHONE is funded by the NIHR HTA programme in the UK. Methods: 4000 patients (pts) will be randomised into the two arms (1:1). The power calculations assume that the disease-free survival (DFS) of the standard treatment (12 months trastuzumab) is 80% at 4 years. Randomisation of 4000 pts will allow the trial to prove non-inferiority of six months trastuzumab (5% 1-sided significance and 85% power). Non-inferiority is defined as ‘no worse than 3%’ below the control arm (12 month) 4 year DFS. Primary outcome is DFS, and secondary outcomes are overall survival (OS) non-inferiority; cost effectiveness; cardiac function and quality of life. Tumour blocks are collected to research molecular predictors of survival with respect to duration of trastuzumab treatment. Blood samples are analysed for single nucleotide polymorphisms (SNPs) as pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. PHARE, a similar trial from the Institut National du Cancer in France, closed to recruitment in 2010 and presented early data at ESMO 2012. Following this an unplanned interim analysis of PERSEPHONE was presented to the Data Monitoring and Safety Committee (DMSC). Results: PERSEPHONE commenced recruitment in October 2007. At abstract submission, 2781 pts (70%) had been randomised from 145 UK sites. Recruitment is due to complete in 2015 with the first planned interim analysis of the primary outcome mid-2016. The iDMSC reviewed all data available on HERA and PHARE as well as a PERSEPHONE interim analysis. There were no safety findings or signals that would warrant a change of the study plan and the high quality of data returns was noted. Conclusion: PERSEPHONE continues the active recruitment phase as planned. Preliminary but inconclusive PHARE data have reinforced interest in the PERSEPHONE trial both nationally and internationally. There has been full support from the Breast International Group (BIG) and the international breast cancer community to answer this important shorter duration question. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-08.
Transcriptional Feedback Links Lipid Synthesis to Synaptic Vesicle Pools in Drosophila Photoreceptors
Authors: Jessica W. Tsai, Ripsik Kostyleva, Pei-Ling Chen, Irma Magaly Rivas-Serna, M. Thomas Clandinin, Ian A. Meinertzhagen, Thomas R. Clandinin
Journal: Neuron (2019)
Abstract 169: Impact of Resistance to Intravenous Immune Globulin on Changes of Left Ventricular Myocardial Deformation Over Time in Children with Kawasaki Disease
Authors: Soo Jung Kang, Dong Keon Yon
Journal: Circulation (2015)

Introduction: This study aimed to assess the impact of resistance to intravenous immune globulin(IVIG) on left ventricular(LV) myocardial deformation in children with Kawasaki disease(KD) during the acute and convalescent phases of illness. Few studies have elucidated the impact of resistance to IVIG on the progressive changes of myocardial mechanics over time in patients with KD. Methods: We studied 26 patients with KD and 8 normal control subjects. Of the 26 patients, 16 were IVIG non-responders. Echocardiograms were obtained during the acute and convalescent phases of KD. Standard echocardiographic data and peak systolic global LV longitudinal strain[strain(ε)] were obtained using vector velocity imaging. Results: During the acute phase of KD, peak systolic global LV longitudinal ε decreased significantly in both IVIG non-responders(-21.18 % ± 3.97) and responders(-20.94 % ± 3.15) compared to controls(-24.99 % ± 2.23). Although in the acute phase, LV ejection fraction(EF) was significantly higher in the IVIG non-responders(55.38 % ± 5.14) compared to the responders(50.2 % ± 6.53), peak systolic global LV longitudinal ε was not significantly higher in the IVIG non-responders compared to the responders. During the convalescent phase, peak systolic global LV longitudinal ε tended to increase in non-responders(-21.62% ± 3.98) and responders(-21.83% ± 2.61) compared to the acute phase, but remained significantly decreased in both groups compared to controls. The increment of peak systolic global LV longitudinal ε from acute to convalescent phase tended to be smaller in the IVIG non-responders compared to the responders. The proportion of patients with coronary dilatations in both IVIG non-responders(4 of 16) and IVIG responders(2 of 10) did not differ significantly. Conclusions: The increment of peak systolic global LV longitudinal ε over time tended to be smaller in the IVIG non-responders compared to the IVIG responders. Resistance to IVIG may delay normalization of myocardial mechanics in IVIG non-responders. Further studies with larger number of patients, as well as long-term follow-up of myocardial deformation in KD are necessary.
A phase I/II study of RX-3117, an oral antimetabolite nucleoside, in combination with nab-paclitaxel (nab-pac) as first-line treatment of metastatic pancreatic cancer (met-PC): Preliminary results.
Authors: Hani M. Babiker, Peter J. Schlegel, Lee G. Hicks, Andrea J. Bullock, Nafisa Burhani, Ely Benaim, Christine Peterson, Callie Heaton, Allyson J. Ocean
Journal: Journal of Clinical Oncology (2019)

420 Background: RX-3117 is an oral small molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by cancer-enriched uridine cytidine kinase 2. Single agent RX-3117 has demonstrated efficacy in a phase III single agent clinical study of RX-3117 in met-PC and bladder cancer. RX-3117 in combination with nab-pac is being evaluated as first line treatment of met-PC cancer. Methods: This is a multicenter, open label phase I/II study (NCT03189914). Eligible subjects (aged ≥ 18 years) have histologically or radiologically proven met-PC with no prior therapies for metastatic disease, ECOG PS 0-1, and normal lab values. phase I identified the MTD dose that is being further evaluated in the phase II: RX-3117 (700 mg administered orally once-daily for 5 consecutive days with 2 days off per week) and nab-pac (125 mg/m 2 administered once weekly) for 3 weeks with 1 week off per 4-week cycle. The Safety Committee reviewed data from phase I before moving to phase II. The primary endpoint of phase II (dose expansion) is an adequate number of responders based on PFS at 4 months and/or objective clinical response per RECIST v1.1. Results: As of September 21, 2018, 8 phase I subjects and 13 phase II subjects were enrolled and treated (9 males and 12 females, median age 67 years). The most common (≥ 15%) related adverse events were nausea, diarrhea, fatigue, alopecia, decreased appetite, rash, vomiting, and anemia. Fourteen subjects had at least one on-study scan (after 2 cycles). One subject experienced a complete response (CR) after 6 cycles of therapy with normalization of CA19.9 (-76%). Three subjects exhibited a partial response (PR): two after 2 cycles (39-47%) and one after 4 cycles of therapy (36%). Eight subjects had stable disease for at least 2 months, and 4 subjects had PFS of at least 4 months. The disease control rate (CR+PR+SD) was 86% in evaluable subjects while the overall response rate (CR+PR) was 29%. Conclusions: RX-3117 in combination with nab-pac appears to be safe and well tolerated in subjects with met-PC. Antitumor activity per RECIST was observed in 12 subjects. Phase II of the clinical study is currently ongoing. Clinical trial information: NCT03189914.
Pediatric T-ALLs Developing into a Type 2 Relapse Originate from Cells That Carry the Potential of Variable Maturation into Subclones with Distinct Chromatin Landscapes
Authors: Büşra Erarslan-Uysal, Joachim B. Kunz, Tobias Rausch, Paulina Richter-Pechanska, Sebastian Waszak, Viktoras Frismantas, Beat Bornhauser, Martin Zimmermann, Martin Stanulla, Martin Schrappe, Gunnar Cario, Gabriele Escherich, Kseniya Bakharevich, Renate Kirschner-Schwabe, Cornelia Eckert, Tsvetomir Loukanov, Matthias Gorenflo, Martina U. Muckenthaler, Jean-Pierre Bourquin, Jan O. Korbel, Andreas E. Kulozik
Journal: Blood (2018)
Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer
Authors: D. Dong, L. Tang, Z -Y Li, M -J Fang, J -B Gao, X -H Shan, X -J Ying, Y -S Sun, J. Fu, X -X Wang, L -M Li, Z -H Li, D -F Zhang, Y. Zhang, Z -M Li, F. Shan, Z -D Bu, J. Tian, J.-F. Ji
Journal: Annals of Oncology (2019)

BackgroundOccult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients.Patients and methodsA total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability.ResultsRS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923–0.993], 0.941 (95% CI 0.904–0.977), 0.928 (95% CI 0.886–0.971), and 0.920 (95% CI 0.862–0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability.ConclusionCT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.
Tumor Identification of Less Aggressive or Indolent Lymphoma With Whole-Body 11C-Acetate PET/CT
Authors: Junichi Tsuchiya, Masahide Yamamoto, Hyeyeol Bae, Takumi Oshima, Tomohiro Yoneyama, Osamu Miura, Ukihide Tateishi
Journal: Clinical Nuclear Medicine (2019)

The aim of this study was to investigate the diagnostic performance of whole-body [C]acetate PET/CT in less aggressive or indolent lymphomas, wherein [F]FDG PET/CT would exhibit limited sensitivity.Between September 2016 and May 2018, we prospectively evaluated 17 patients (9 men, 8 women; mean age [range], 71 [45-87] years) with pathologically proven less aggressive or indolent lymphomas according to Non-Hodgkin's Lymphoma Classification Project, using both [F]FDG PET/CT and [C]acetate PET/CT (performed on the same day). Detected nodal lesions were recorded according to the Ann Arbor classification. Extranodal (EN) lesions were also evaluated. We compared whole-body lesion detection between [F] FDG PET/CT and [C]acetate PET/CT using the McNemar test.In all patients, significantly more nodal and EN lesions were detected using [C]acetate PET/CT than [F]FDG PET/CT (nodal: 84 vs 64 regions; P < 0.001; EN: 26 vs 19 regions, P = 0.039). Bone lesions were detected in 8 and 5 patients using [C]acetate PET/CT and [F]FDG PET/CT, respectively (P = 0.25). Among the 14 patients (82.4%) who underwent bone marrow biopsy, bone marrow involvement was detected with sensitivities of 100% (6/6 patients) and 80% (5/6 patients) using [C]acetate PET/CT and [F]FDG PET/CT, respectively. Multiple areas of focal uptake in the spleen of 1 patient were exhibited on [F]FDG PET/CT but not [C]acetate PET/CT.[C]acetate PET/CT exhibited greater sensitivity than [F]FDG PET/CT for lesion detection in patients with less aggressive or indolent lymphomas, thus promising applicability as a physiological tracer in the study of such lesions.
Systematic review of three decades of clinical trials in metastatic colorectal cancer: Making lemonade out of lemons?
Authors: Daniel Tannenbaum, Kanwal Pratap Singh Raghav, Robert Asa Horn, Michael J. Overman, Cathy Eng, Scott Kopetz, Benny Johnson, Van K. Morris, Christine Megerdichian Parseghian, George J. Chang, Jane Elizabeth Rogers, Susan Parker, Maria de los Angeles Lopez-Olivo, Arvind Dasari
Journal: Journal of Clinical Oncology (2019)

656 Background: Despite multiple trials of new agents in metastatic colorectal cancer (mCRC), long term outcomes remain poor. This study explores the changing trends in the design, interpretation and outcomes of phase III randomized controlled trials (RCT) in mCRC over time. Methods: Phase III RCTs of systemic therapy for mCRC with enrollment between 1986 and 2016 were identified through 4 electronic databases and grouped into 3 time periods (1986-1996 – T1; 1997-2006 – T2 &amp; 2007-2016 – T3). Study selection, quality appraisal and data collection were performed by 2 independent investigators. Study characteristics, primary and secondary endpoints, and authors’ interpretation of results and conclusions were analyzed. Improvement in overall survival (OS) was the difference between experimental and control arms. A study was deemed positive if it met its end point, was recommended for further study or for adoption for clinical use (p ≤ 0.05 significant for all analyses). Results: One hundred fifty trials (T1=36, T2=62, T3=52) with 77494 patients (T1=12406, T2=39158, T3=25930) were included. Although 1st line therapy trials continued to be the most common across all T, the percentage (%) of trials evaluating 3 rd line and beyond (T1=0, T2=3, T3=27) have increased significantly over time as have trials with targeted agents (T1=11, T2=34, T3=79). Although OS remains the most common primary end point, more trials in T2 &amp; T3 have used progression-free survival instead (14 vs 47 &amp; 44). The % of trials with negative results but interpreted as positive increased over time (T1=18; T2=42; T3=35). Across all T, the median improvement in OS (months, m) of these trials was significantly lower compared to the trials that met primary end point across all T (T1 = 0 vs 1.8 m, T2 = -0.1 vs 3.25, T3 = -0.25 vs 2.55). Conclusions: A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced CRC. Any interpretations of potential survival benefits from trials that have not met primary end point must be made with significant caution.
Abstract 12407: Plasma B-type Natriuretic Peptide Level is Useful to Predict Incidence for Both Types of Heart Failure With and Without Left Ventricular Systolic Dysfunction in the General Population
Authors: Ryosuke Komi, Fumitaka Tanaka, Kenyu Satoh, Yuuki Matsuura, Toshiyuki Onoda, Kozo Tanno, Masaki Ohsawa, Kuniaki Ogasawara, Kiyomi Sakata, Akira Okayama, Motoyuki Nakamura
Journal: Circulation (2017)

Aim: It remains unknown whether the predictive abilities of plasma B-type (BNP) are viable for either heart failure (HF) with preserved ejection fraction (HFpEF) or with reduced ejection fraction (...
Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy
Authors: Chris Miles, Gherardo Finocchiaro, Michael Papadakis, Belinda Gray, Joseph Westaby, Bode Ensam, Joyee Basu, Gemma Parry-Williams, Efstathios Papatheodorou, Casey Paterson, Aneil Malhotra, Jan Lukas Robertus, James S. Ware, Stuart A. Cook, Angeliki Asimaki, Adam Witney, Irina Chis Ster, Maite Tome, Sanjay Sharma, Elijah R. Behr, Mary N. Sheppard
Journal: Circulation (2019)

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort.We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria.Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents.SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death.