tbuckley/cabot-search huggingface dataset:
FDG-PET based dose escalated adjuvant tomotherapy (image-guided intensity-modulated radiotherapy) utilizing 4D-CT planning for high-risk adrenocortical carcinoma (ACC): A case study.
Authors: Ujjal Mallick, S Ramamurty, Ruth Elizabeth Carr, Nick Willis, S Ball, R Bliss, Judith H. Mott, John B. Wilsdon, S Johnson
Journal: Journal of Clinical Oncology (2012)

e13522 Background: ACC is a rare endocrine malignancy with an annual incidence of 0.5-2/million/year. Surgery is the mainstay of treatment but relapse rate is high and the prognosis is dismal (20-50% 5 year survival). Adjuvant Radiotherapy improves local control in cases with high risk of local failure and dose escalation may achieve better results. Dose Escalation with 3-Dimensional computed tomography (CT) based radiotherapy is difficult for ACC due to unacceptable toxicity to several adjacent organs at risk (OARs) e.g., the kidneys, stomach bowel, liver, spinal cord. FDG-PET helps delineation of areas of higher metabolic activity and density of clonogenic cells within the target (Biological Target Volume or BTV) where focal dose escalation could be directed safely for improving local control as in other solid tumours. Tomotherapy (IMRT with daily image guidance) delivers precision radiotherapy with integrated boost to the BTV, lower dose to OARs, improved coverage of the targets, and better dose delivery across the targets which are essential for tumour control. 4-Dimensional CT for planning allows adequate Clinical Target Volume(CTV) coverage despite respiratory movements. Methods: A 63 year old lady had left adrenalectomy for an adrenocortical carcinoma measuring 29 x 18 x 25mm (TNM pT1NXMX) thought to be microscopically incompletely excised (R1) with a proliferation index ( Ki-67) of 40% for which adjuvant radiotherapy was advised. PET-CT, 4D-CT and Tomotherapy were used for planning. A total dose of 50.4Gy to PTV with a simultaneous integrated boost to BTV taking it up to 59.40Gy (1.98Gy/ fraction) in 30 daily fractions was prescribed. Results: Target dose and coverage were very satisfactory. The doses to OARs were well within tolerance despite dose escalation; she completed treatment with only grade- fatigue. She had metastatic disease at 11 months follow-up without local relapse. Conclusions: To our knowledge this is the first report of using FDG –PET based dose escalation, 4D CT and Tomotherapy in high risk ACC to improve local control and needs further study.
Generation of Human Fatty Livers Using Custom-Engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 Metabolism
Authors: Alexandra Collin de l’Hortet, Kazuki Takeishi, Jorge Guzman-Lepe, Kazutoyo Morita, Abhinav Achreja, Branimir Popovic, Yang Wang, Kan Handa, Anjali Mittal, Noah Meurs, Ziwen Zhu, Frank Weinberg, Michael Salomon, Ira J. Fox, Chu-Xia Deng, Deepak Nagrath, Alejandro Soto-Gutierrez
Journal: Cell Metabolism (2019)
Perceptions of chemotherapy influencing treatment decisions in women with hormone-positive tumors.
Authors: Tracey Proverbs-Singh, Kezhen Fei, Rebeca Franco, Nina Bickell
Journal: Journal of Clinical Oncology (2012)

e19621 Background: Women with hormone receptor positive (HR+) breast cancer can benefit from chemotherapy (CTX). Unnecessary therapy can adversely affect patient morbidity.. While tumor biology affects decision making, patient perception of cancer recurrence is also important. In this study we determine whether women with HR+ tumors (&gt;1cm) who undergo CTX, have stronger beliefs in the efficacy of CTX than women who do not get therapy. Methods: Women participating in a Breast Cancer Patient Assistance Trial in 2006-2010 were surveyed about their cancer knowledge and beliefs about its treatment; charts were abstracted 6 months later to measure treatments received. A Nottingham Prognostic indicator (NPI), which uses stage, tumor size, and lymph node involvement was calculated. Chi-square and logistic regression analyses examined associations between receipt of CTX and tumor stage, NPI, physician recommendation, patient demographics and beliefs about CTX. Results: Women with HR+ tumors 130/211(62%) received CTX and 197/211(93%) received hormonal therapy. Gene array analysis was performed in 46/211 (22%), and of these (7/46 [15%]) had high recurrence scores and received CTX. Women treated with CTX vs those without CTX were younger (mean 52.5 yrs vs 62.3 yrs, p&lt;0.0001), had higher stage cancer (stage II: 65% vs 23%, p&lt;0.0001), worse NPI (poor prognosis:15% vs 2% p&lt;0.0001), more physician recommended CTX (92% vs 34%, p&lt;0.0001) and increased concern about recurrence without CTX (very worried 70% vs 15%; p&lt;0.0001). Multivariate analysis found that physician recommendation, poor NPI and moderate NPI were most strongly associated with receiving CTX [RR= 3.2, (95% CI:1.8-5.6), 1.7, (95%CI:1.3-2.2); 1.6, (95%CI:1.2-2.0)], respectively, followed by women’s worry (RR=1.3; 95%CI: 1.0-1.6), and belief that CTX allows women to live longer (RR=1.1; 95%CI: 1.0 - 1.2). Older age was associated with less use of CTX (RR= 0.99; 95%CI: 0.978-.995). Conclusions: Physician recommendation, disease severity, concerns about recurrence and beliefs about CTX’s effectiveness influence the utilization of CTX in HR+ breast cancer. Patients may benefit from education to make informed decisions.
Prevalence of Pulmonary Embolism in Patients With Syncope
Authors: Patrick Badertscher, Jeanne du Fay de Lavallaz, Angelika Hammerer-Lercher, Thomas Nestelberger, Tobias Zimmermann, Marc Geiger, Orell Imahorn, Òscar Miró, Emilio Salgado, Michael Christ, Louise Cullen, Martin Than, F. Javier Martin-Sanchez, Salvatore Di Somma, W. Frank Peacock, Dagmar I. Keller, Juan Pablo Costabel, Joan Walter, Jasper Boeddinghaus, Raphael Twerenbold, Adriana Méndez, Boris Gospodinov, Christian Puelacher, Desiree Wussler, Luca Koechlin, Damian Kawecki, Nicolas Geigy, Ivo Strebel, Jens Lohrmann, Michael Kühne, Tobias Reichlin, Christian Mueller, Maria Rubini Giménez, Nikola Kozhuharov, Samyut Shrestha, Lorraine Sazgary, Beata Morawiec, Piotr Muzyk, Ewa Nowalany-Kozielska, José Bustamante Mandrión, Imke Poepping, Michael Freese, Kathrin Meissner, Caroline Kulangara, Carolina Isabel Fuenzalida Inostroza, Jaimi Greenslade, Tracey Hawkins, Katharina Rentsch, Arnold von Eckardstein, Andreas Buser, Wanda Kloos, Jana Steude, Stefan Osswald
Journal: Journal of the American College of Cardiology (2019)
Case-based discussion: a case of misdiagnosis of primary lung malignancy
Authors: Ran Wang, Thomas Lightburn, John Howells, Ihssan Tahan, Mohamad Bittar, Lipsita Patnaik, Reuben Tooze, Syed B Mehdi
Journal: Thorax (2019)

A 69-year-old man was initially referred to urology outpatient clinic for investigation of frank haematuria. His medical history included transurethral resection of prostate in 2008, autoimmune hepatitis, hyperlipidaemia and hypertension. He was an active smoker with a 52 pack-year history and drinks 12 units of alcohol per week. He worked as a librarian with no history of chemical or asbestos exposure. His regular prescription included azathioprine and ursodeoxycholic acid, amlodipine, alfuzosin and finasteride. He underwent a cystoscopy which was normal. Subsequently, a CT urogram was performed which demonstrated a 48 mm mass within the left adrenal gland, suspected of malignancy; however, no primary site had been identified. A subsequent CT of the thorax and abdomen displayed a 6.5 cm diameter mass within the base of the right upper lobe on the background of emphysema, with precarinal and right hilar lymph nodes, and multiple nodules in the middle lobe and left lower lobe (figure 1A). A large left adrenal mass was again identified. On further questioning, the patient described symptoms of breathlessness and lethargy but denied any chest pain or cough. There was no history of sputum production or haemoptysis. He did, however, report loss of appetite and had lost 3 kg of weight over the previous 4 weeks.



Figure 1 
(A) Initial CT thorax demonstrating a 6.5 cm diameter mass within the base of the right upper lobe, small precarinal and right hilar nodes and evidence of multiple intrapulmonary nodules; (B) PET CT demonstrating large necrotic mass at right upper lobe; (C) FDG avid intrapulmonary metastasis; (D) histopathological features of lymphomatoid granulomatosis under high power microscopy (40× objective, NIKON eclipse 80i).



With the symptoms of breathlessness and unintentional weight loss, in combination with a significant smoking history and suspicious radiological findings, metastatic bronchogenic carcinoma with a left adrenal metastasis was the most …
Activation of the PI3K/AKT signal transduction pathway is inversely associated with estrogen receptor levels and correlates with survival in hormone receptor-positive Her2/neu-negative breast cancer
Authors: A. M. Gonzalez-Angulo, B. T. Hennessy, F. Meric-Bernstam, Y. Lu, W. F. Symmans, G. N. Hortobagyi, G. B. Mills
Journal: Journal of Clinical Oncology (2007)

10588 Background: Hormone receptor-positive is the most common subtype of breast cancer. Despite the successes of antihormone therapy alone or combined with chemotherapy, a significant proportion of patients (30–40%) will have primary or acquired resistance to this treatment. There is a need to identify molecular markers to distinguish patients unlikely to benefit from therapy as well as novel targeted therapeutics that increase the response rate. Methods: We used a novel functional proteomics technology, reverse phase protein array (RPPA), to quantify expression and activation of 42 steroid and kinase signaling proteins in 64 hormone receptor-positive-Her2/neu-negative breast cancers from patients with stage I to III tumors managed with non-steroidal aromatase inhibitors ± chemotherapy. Unsupervised clustering analysis was used to molecularly group the tumors. Recurrence-free survival (RFS) was estimated with the Kaplan Meier product limit method and comparison was made using the Log-rank test. Correlation coefficients were used to look at the relationships between two variables. Results: Median age was 57 years (23–79). Sixteen patients (25%) had stage I tumors, 32 (50%) had stage II tumors and 16 (25%) had stage III tumors. There were two well-defined and distinct clusters of tumors: Group 1: ER high (n=25) and Group 2: PI3K/AKT activated (n=39). 3-year RFS estimates were 100% for group 1 and 59% for group 2 (p=0.04). There were thus clear inverse correlations between markers of activation of PI3K pathway and expression of ER (R for pAKT vs ER = -0.26, p=0.03). PIK3CA mutation was detected in 12/58 (21%) of hormone receptor-positive breast cancers and these tumors were found to have a proteomic signature distinct from PTEN loss with the former signature associated with a trend to improved RFS (p=0.06). Conclusion: Activation of the PI3K/AKT pathway in hormone receptor- positive-Her2/neu-negative breast cancer is inversely correlated with ER levels and associated with adverse outcome. At least in some cases, PI3K/AKT pathway activation, may be under the control of genomic aberrations. A validation set of 100 tumors treated with tamoxifen is on- going. No significant financial relationships to disclose.
Prognostic value of quantitative image analysis (QIA) for determination of proliferative index in mantle cell lymphoma (MCL) treated with sequential chemotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR)
Authors: R. Schaffel, C. Hedvat, J. Teruya-Feldstein, C. S. Portlock, C. H. Moskowitz, A. D. Zelenetz
Journal: Journal of Clinical Oncology (2009)

e19522 Background: Gene expression studies have demonstrated that the proliferation signature is the most important factor in determination of outcome in MCL. However, visual assessment of immunohistochemical staining is not standardized. QIA of MIB-1/Ki67 staining may have a greater reliability for determination of the PI. We tested the agreement between manual counting (MC) and QIA and its prognostic value in patients with MCL. Methods: 105 patients with MCL underwent therapy for de novo MCL, of these, 66 had slides stained with MIB-1 for the analysis. The PI was determined in three ways: 1) estimation by a hematopathologist using a microscope (manual count, MC); 2) visual estimation by an independent hematopathologist after whole slide digitization; and 3) QIA software (color deconvolution algorithm). The survival analysis was restricted to 47 patients that were treated with sequential therapy followed by upfront consolidation with HDT/ASCR. Results: A median of 612,394 cells per slide were analyzed by QIA. There was a good correlation between the QIA and both the MC under the microscope and digital image (0.9061, P&lt;0.001 and 0.9336, P&lt;0.001; Spearman test) as well as between the pathologists (0.897, P&lt;0.001). Based on a 30% cutoff, the agreements (kappa test) were: interobserver, 0.6 (80% of slides); between QIA and MC of visual image, 0.86 (94% of slides); and between the QIA and MC using standard microscopy, 0.72 (86% of slides). In the survival analysis, the median PI was 25% (0.7% to 74%). By QIA, 27 patients had a low PI (&lt;30%) and 20 patients had a high PI. At a median follow-up of 4.4 years, the 5 year overall survival (OS) and event free survival (EFS) were inferior in the high PI cohort (66% v 93%, P=0.003 and 0 v 71%, P&lt;0.001, respectively). In a Cox regression analysis, both OS and EFS were significantly associated with PI and not associated with either MIPI or inclusion of rituximab during therapy. No event was reported after 4.7 years of follow-up in the low-PI group. Conclusions: Digital image analysis of MIB-1/Ki67 staining is highly reproducible and further validates the prognostic significance of a high PI in MCL using a threshold of 30%. No significant financial relationships to disclose.
Concomitant chemoradiotherapy of cervical carcinoma.
Authors: Svetlana Shamshykeevna Naizabekova
Journal: Journal of Clinical Oncology (2013)

e16557 Background: In structure of cancer incidence among female population of Kyrgyzstan, cervical carcinoma takes the second place. incidence is 19.1 per 100 thousand of female population. growth of standardized cervical carcinoma index in Kyrgyzstan from 2002 to 2007 estimated as - 36.4% (from 14.0 to 19.1 per 100 thousand people). materials and methods. in the chemotherapy unit of the national center of oncology, ministry of health KR, from 2010 to 2012 were treated 51 patients with locally advanced cervical carcinoma IIb - stage IIIb with ftorafur as radiomodifier. all patients’ diagnosis were verified. histologically - squamous cell carcinoma. age of patients ranged from 29 to 74, median – 51 years. the main group consisted of patients with IIIb stage - 33 patients (64.7%), 18 patients with iib stage - 35.3%. all 51 patients with locally advanced cervical carcinoma received combined radiotherapy (external beam and intracavitary) on a radical program against ftorafur. ftorafur was taken orally dozed at 400 mg every 12 hours. absolute contraindications of use of ftorafur together with combined radiation therapy of patients with cervical carcinoma were not found. presence of severe comorbidity was one of the relative contraindication research results. evaluation of the effectiveness of the treatment was carried out according to WHO criteria, on the degree of regression of primary tumor. clinical results showed that complete regression occurred in 28 patients (54.9%), partial regression of the tumor in 16 patients (31.4%), stabilization of tumor in 7 (13.7%). objective response rates were 92.1%. side effects of the treatment were evaluated on a scale of toxicity (Common Toxicity Criteria NCIC). hematologic toxicity (anemia - 56.8%, leukopenia - 3,9%) I-II degree, gastrointestinal symptoms (nausea and vomiting - 3,9%) I-II toxicity. during the dynamical monitoring of patients, the III-IV toxicity stages were not found. conclusion. use of ftorafur as a radiomodifier together with concomitant radiation therapy on patients with locally advanced cervical carcinoma helped to accelerate the tumor regression. toxicity did not exceed I-II degrees. analysis of immediate results of treatment showed a high objective effect - 86.3% in the following category of patients.
Benefit of oncologist and geriatrician collaboration in the management of digestive cancer in elderly patients
Authors: T. Cudennec, E. Mitry, S. Moulias, C. Lepere, A. Lievre, L. Teillet, P. Rougier
Journal: Journal of Clinical Oncology (2007)

19667 Background: A standardized geriatric evaluation is essential for the multidisciplinary discussion of elderly patients with gastrointestinal cancer. A geriatric as well as an oncological evaluation are mandatory to offer to these patients the best therapeutic option and improve their prognosis as well as their quality of life. A Geriatric Intervention Team (GIT) composed by nurses and geriatrician is working in our hospital. One of its function is to evaluate elderly patients with digestive neoplasms in collaboration with the Digestive Oncology unit (DOU). Methods: The Mini Mental State Examination, the mini-Geriatric Depression Scale and the Get up and go timed test were used for the geriatric evaluation. Results: GIT was solicited for 124 pts over a 3-year period. Their mean age was 79,1 ± 6,3 years old (65 to 96), 45% were men. The neoplasic localizations were: colorectal (53%), pancreatic (17%), esophagus (11%), hepatic carcinoma (7%) and other (12%). There was a clear prevalence of cognitive disorders identified by the Folstein MMSE. Among 65 workable files (complete MMSE), 61% of the patients had an abnormal (&lt; 26). The observation of a time and/or space disorientation was noticed in 30% of the cases. The mini-GDS used to detect depression, was positive in 43% of the evaluations. The Timed Get Up and Go Test was used to evaluate the walking capacity self-sufficiency and the risk of falls. It was superior to 20 seconds in 40% of cases. For 77 geriatrics evaluation, the GIT was solicited before the decision of the best treatment to choose. In this population, we can clearly identify 3 clusters of patients: well-matched patients (34%) who received chimiotherapy; intermediate patients (26%) who needed a new geriatric assessment before decision; and frailed patients (40%) who received only palliative treatment. In the second group, after geriatrician intervention, 60% of patients finally received a chemotherapy. Conclusions: These results show the benefit of a close collaboration between geriatricians and oncologist. In the daily management of elderly patients, alteration are at least detected in 55% of patients by geriatric assessment. Moreover, the GIT is allow to securely classify the patients between the 3 categories and help to decision in the intermediate group. No significant financial relationships to disclose.
“Ghost Introgression” As a Cause of Deep Mitochondrial Divergence in a Bird Species Complex
Authors: Dezhi Zhang, Linfang Tang, Yalin Cheng, Yan Hao, Ying Xiong, Gang Song, Yanhua Qu, Frank E Rheindt, Per Alström, Chenxi Jia, Fumin Lei
Journal: Molecular Biology and Evolution (2019)

In the absence of nuclear-genomic differentiation between two populations, deep mitochondrial divergence (DMD) is a form of mito-nuclear discordance. Such instances of DMD are rare and might variably be explained by unusual cases of female-linked selection, by male-biased dispersal, by "speciation reversal" or by mitochondrial capture through genetic introgression. Here, we analyze DMD in an Asian Phylloscopus leaf warbler (Aves: Phylloscopidae) complex. Bioacoustic, morphological, and genomic data demonstrate close similarity between the taxa affinis and occisinensis, even though DMD previously led to their classification as two distinct species. Using population genomic and comparative genomic methods on 45 whole genomes, including historical reconstructions of effective population size, genomic peaks of differentiation and genomic linkage, we infer that the form affinis is likely the product of a westward expansion in which it replaced a now-extinct congener that was the donor of its mtDNA and small portions of its nuclear genome. This study provides strong evidence of "ghost introgression" as the cause of DMD, and we suggest that "ghost introgression" may be a widely overlooked phenomenon in nature.
Helen Salisbury: Poaching in practice
Authors: Helen Salisbury
Journal: BMJ (2019)

It’s uncontroversial to suggest that GP workloads have increased over the past 10 years.12 Work previously done in hospitals has shifted to primary care, and the population of older patients with complex medical needs has grown. Demand has risen, and patients have higher expectations of instant access. When I first started in general practice few people had mobile phones and, unless they were sick enough to stay in their homes, most patients didn’t ask to be called.

For stressed GPs, however, help is at hand. August is the end of the training year, and a newly …
Mortality rate after pneumatic dilatation for achalasia
Authors: Froukje B van Hoeij, Albert J Bredenoord
Journal: Gut (2019)

With great interest we have read the article ‘Outcomes of pneumatic dilatation and Heller’s myotomy for achalasia in England between 2005 and 2016’ of Harvey et al. 1 In this retrospective study, the efficacy and complication rate were compared between pneumatic dilatation (PD) and Heller’s myotomy (HM) over 10 years. The Hospital Episode Statistics (HES) database of England was used to include achalasia patients treated with PD or HM. Subjects were identified by the presence of an International Classification of Diseases (ICD-10) code for diagnosis and treatment. With the large sample …
High efficacy of paclitaxel (P), carboplatin (C) and concurrent thoracic radiation therapy (TRT) for locally advanced non-small cell lung cancer (NSCLC)
Authors: K. Kishi, A. Okazaki, H. Takaya, A. Miyamoto, S. Sakamoto, M. Kawabata, E. Tsuboi, S. Homma, K. Yoshimura
Journal: Journal of Clinical Oncology (2006)

17143 Background: Combined modality therapy with P, C and radiation for locally advanced NSCLC is active, but its clinical data are limited in Japan. The aim of this study is to evaluate feasibility and efficacy of the therapy in a Japanese general hospital. Methods: Patients with previously untreated and locally advanced NSCLC with stage IIIA and IIIB (PS 0–1, weight loss less than 5% over past 3 months) were treated with P (40 mg/m 2 on days 1,8,15, 22, 29, 36, 43), C (AUC 2 on days 1,8,15, 22, 29, 36, 43) and TRT (66 Gy/33fr over 6.5 weeks starting on day1). Results: Fifteen evaluable patients entered this study between December 2001 and March 2005. They were 12 males, 3 females, with median age 67 (57–76); 6 patients with ECOG PS 0, 9 with PS 1, 8 with stage IIIA, and 7 with IIIB. Chemotherapeutic agents were administered a median of 6 cycles (4–7) and 66 Gy of TRT done in 14 patients. It achieved 13 PRs, 1 SD and 1 PD with a response rate of 86.7%. Survival was 85.5% at 1 year, 66.0% at 2 year and 66.0% at 3 year. Eleven patients are still alive. A relapse occurred in 10 patients (66.7%) and 5 were disease-free (33.3%). The site of first relapse was distant in 5 patients, local in 3, and both local and distant in 2. Toxicity was mild: grade 3 neutropenia in 2 patients, grade 3 nausea in 1, and grade 3 esophagitis in 1. No grade 3/4 pneumonitis was observed. After completion of chemoradiotherapy scheduled, 2 patients received additional chemotherapy of PC and 1 underwent lobectomy. Conclusion: Although the number of patients is small in this study, concurrent PC and TRT for locally advanced NSCLC is feasible and highly effective for Japanese patients with good PS and minimal weight loss. No significant financial relationships to disclose.