tbuckley/cabot-search huggingface dataset:
Effect of bevacizumab in first-line chemotherapy on progression-free survival in advanced ovarian clear cell carcinoma.
Authors: Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Makio Shozu
Journal: Journal of Clinical Oncology (2020)

e18086 Background: Advanced ovarian clear cell carcinoma (ACCC, stage III/IV disease) is a rare tumor characterized by chemoresistance. To evaluate the efficacy of bevacizumab (Bev) for ACCC, we investigated the survival outcome of first-line treatment before and after the approval of Bev for ovarian cancer treatment in November 2013 in Japan. Methods: We recruited 28 consecutive patients diagnosed with ACCC at our institution between 2007 and 2018. We performed cytoreductive surgery and administered paclitaxel-carboplatin chemotherapy (paclitaxel: 80 mg/m 2 + carboplatin area under the curve 2.0–3.0 mg/mL/min, weekly without break) as first-line chemotherapy. Bev (15 mg/kg/3 weeks) was also administered after its approval. We compared progression-free survival (PFS) between Bev+ group (n = 18) and Bev- group (n = 10) using the Kaplan–Meier method and a Cox regression model. Results: Patients characteristics were similar between the Bev- and Bev+ groups. The median age was 54 years and 53 in the Bev- and Bev+ groups (p = 0.810), respectively. Three (30%) and 4 (22%) patients in the Bev- and Bev+ groups had stage IV disease (p = 0.674), respectively. The performance status (PS) was ≥2 in 1(10%) and 5 (28%) patients in the Bev- and Bev+ groups (p = 0.375), respectively. Peritoneal cancer index was 5.5 and 5.5 in the in Bev- and Bev+ groups (p = 0.727), respectively. Primary debulking surgery was performed in 10 (100%) and 11 (61%) patients in the Bev- and in Bev+ groups, respectively. Surgical complexity score was 9 and 9 in the Bev- and in Bev+ groups (p = 0.700), respectively. Completeness of resection was higher in the Bev- group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev+ group received ≥21 cycles of Bev. The median PFS increases from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis revealed that Bev use (p = 0.005) and PS &lt; 2 (p = 0.035) were independent prognostic factors for PFS; however, completeness of resection was not a prognostic factor (p = 0.052). Conclusions: Bev in first-line chemotherapy improves the survival outcome of ACCC. [Table: see text]
Patterns and prognostic factors of malignant ascites in hospitalized patients with advanced stage cancer.
Authors: Shanila Ahmed, Mir Ibrahim Sajid, Risha Fayyaz, Faiza Ilyas, Noreen Nasir
Journal: Journal of Clinical Oncology (2020)

e24141 Background: Ascites is a shared pathological manifestation of numerous diseases, the primary (81%) disease being hepatic cirrhosis. Ascites is termed “malignant” when it is associated with cancers. It can manifest as abdominal swelling, abdominal pain, nausea and vomiting, anorexia and fatigue. Our study aimed at identifying baseline characteristic in patients who present to our hospital with malignant ascites as the first sign of advanced stage cancers and the factors that can affect outcomes in such patients. Methods: This is a retrospective study which includes all the patients who had been diagnosed with malignant ascites at our institute between the years 2012 and 2016.The diagnosis was made either on the basis of cytological examination or medical imaging or both. Patients who were younger than 18 years and who developed ascites due to diseases other than malignancy were excluded from the study. A total of 150 patients were shortlisted using these criteria. Results: The mean age of the sample was 56.52 years with 101 (67%) of the patients being female, 54 (36%) diabetic, 55 (37%) hypertensive, 26 (52%) and 12 (8%) had ischemic heart disease. The most prevalent tumor reported was ovarian cancer 47 (31%) with the highest frequency of metastasis reported in the peritoneal region 34 (23%). Among symptoms, the most prevalent were abdominal distension 127 (85%), abdominal pain 99 (66%), 41 (27%) nausea, 44 (29%) vomiting and 32 (21%) reported weight change. Paracentesis was done in 139 (92%) for palliation of symptoms .Surgery was performed on 11 (7%) of the patients, whereas 70 (47%) of the patients were switched to chemotherapy with Carboplatin-Taxol constituting the major chemotherapeutic regimen. Majority 93 (62%) of the patients were discharged in a stable condition. The median survival following diagnosis of ascites was three months. Ovarian cancer favored longer survival while low serum albumin, low serum protein and liver metastases adversely affected survival. The independent prognostic factors for survival were cancer type, liver metastases and serum albumin. Conclusions: The identified independent prognostic factors should be used to select patients for multimodality therapy for adequate palliation.
Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors
Authors: Anita Gul, Tyler F. Stewart, Charlene M. Mantia, Neil J. Shah, Emily Stern Gatof, Ying Long, Kimberly D. Allman, Moshe C. Ornstein, Hans J. Hammers, David F. McDermott, Michael B. Atkins, Michael Hurwitz, Brian I. Rini
Journal: Journal of Clinical Oncology (2020)

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.
自发性食管穿孔31例临床分析
Authors: 贺建胜, 束余声, 石维平, 史宏灿
Journal: BMJ (2010)

自发性食管穿孔是胸外科少见但比较凶险的急性疾病,由于临床重视不够,常延误诊治.我院自1996年1月至2008年12月共收治该病31例,现报道如下. 1.对象与方法: (1)研究对象:31例中,男性27例、女性4例,年龄34～80岁,平均59岁,均有呕吐病史,发病到确诊时间为4 h～7 d;均有胸痛和发热,23例有呼吸困难,8例可触及颈部皮下气肿,5例伴感染性休克。
密歇根大学医学院的人文医学教育
Authors: 黄晓明, 彭斌, 沈菁, 潘慧
Journal: BMJ (2012)

加强人文社会科学教育是医学教育的未来方向.通过考察美国密歇根大学医学院的人文医学教育,从课程设置、人文教学内容、人文教学特点等方面介绍了西方一流医学院校的人文医学教育现状,对处于转型期的我国医学院校医学教育改革有一定启示作用。
Completion time in prostate cancer treated with proton beam therapy: Do interruptions matter?
Authors: Shaakir Hasan, Lane Rosen, Henry Tsai, Christopher Sinesi, George E Laramore, Mark V. Mishra, Charles B. Simone, Daniel Gorovets
Journal: Journal of Clinical Oncology (2020)

e17553 Background: The association between completion time of proton therapy(PT) in prostate cancer and biochemical control is unknown. Methods: We queried the multi-institutional, prospectively collected, proton collaborative group registry for prostate cases treated definitively with PT. Kaplan meier methodology was used for biochemical failure free (bFF) rates and multivariable regression analyses (MVA) were used to identify correlates of treatment interruptions (TI) and bF. Results: After exclusion, 2794 men with 693 low, 869 favorable intermediate, 627 unfavorable intermediate, and 605 high risk prostate cancers had available data. The median age was 68 years(40-92), 90% were white and 8% were black. Androgen deprivation therapy (ADT) was given to 676 patients, 312 treatments were hypofractionated, and median EQD2 dose = 75(74-86) GyE 1.5 . Kaplan-meier median follow-up was 79 months. In total 900 patients (32%) had at least one TI. Shorter treatments (HR = 0.95 per day, P &lt; 0.01) and high risk (HR = 0.72, P &lt; 0.04) cases were less likely to have Tis on MVA. There was no difference in 5-year bFF rate with (92.7) and without (93.1%) TIs. In a subset of only high risk patients treated with ADT (n = 385), the 5-year bFF was 83% without TIs and 75% with TIs (HR = 2.10, P = 0.06). This discrepancy was significant with multivariable binomial regression (HR = 2.36, P = 0.03), and the bF difference was greatest when &gt; 5 treatment days were missed per receiver operating characteristic curve. Conclusions: Largely, there was no correlation between TIs and bF in prostate cancer treated with PT, however completion time may play a more significant role in high risk disease.
鉴别诊断的重要性
Authors: 陈仕银, 黄文娟
Journal: BMJ (2012)

我是一名工作第二年的全科住院医生,最近在内科轮转期间,一名乏力并上消化道出血的病人让我留下了深刻的印象.这是一名38岁的女性.因“乏力、胸闷、气促1年,黑便、呕血9天”入院.患者1年前开始无明显诱因出现四肢乏力,发音不清楚,偶有胸闷、气促,无胸痛、肌痛等.曾在其他医院诊断为“多发性肌炎”并给予甲泼尼龙、甲氨蝶呤等治疗,无明显好转. 关键词：诊断
Camrelizumab in advanced or metastatic solid tumor patients with microsatellite instability–high/mismatch repair-deficient: Results from an open-label exploratory study.
Authors: Jingde Chen, Ming Quan, Zhiqin Chen, Tianmei Zeng, Yandong Li, Ying Zhou, Yanan Hai, Yong Gao
Journal: Journal of Clinical Oncology (2020)

e15140 Background: PD-1 checkpoint inhibitor has been shown a significant effect in patients (pts) with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumor. Herein, we assessed the efficacy and safety of camrelizumab, a PD-1 checkpoint inhibitor, in advanced or metastatic solid tumor pts with MSI-H/dMMR. Methods: Pts with MSI-H/dMMR solid tumor who had received at least one line of prior systemic chemotherapy were recruited in this single-arm exploratory study. Pts received camrelizumab (200mg, ivd, D1/2W) until disease progression or intolerable toxicity. Response was assessed every 8 weeks. The primary endpoint was objective response rate (ORR) according to RECIST v1.1 criteria. This study was registered at Chinese Clinical Trial Registry, ChiCTR-OIC-17013249. Results: From November 2017 to February 27, 2019, 12 eligible pts were recruited, which covered 9 cancer types. The median age was 58 (range 27-72) years; male/female was 58.3/41.7%. 11 pts were confirmed as MSI-H status, and 1 patient as d-MMR status. All pts were included in efficacy and safety analysis. 2 pts achieved complete response (CR), 6 pts partial response (PR), 4 pts stable disease (SD), yielding the ORR of 66.7% (95% CI: 34.9-90.1), and the disease control rate of 100% (95% CI 73.5-100) at best. What’s more, cancer types of CR pts covered rectal cancer and bladder cancer (1 patient each); PR pts included colon cancer, liver cancer, endometrial cancer, ureteric cancer, intrahepatic cholangiocarcinoma, and small intestine cancer (1 patient each); SD pts contained 3 colon cancer pts and 1 retroperitoneal leiomyosarcoma patient. The overall incidence of adverse incidences (AEs) was 100%. The incidence of Grade ≥3 AEs was 58.3%, which mainly included anemia (16.7%), increased γ-transglutaminase (16.7%), increased alkaline phosphatase (16.7%), increased blood bilirubin (16.7%). As of Oct 30, 2019, 11 pts were still on study medication. Conclusions: Camrelizumab resulted in encouraging objective response and tolerable toxicity in MSI-H/dMMR advanced or metastatic solid tumor. The survival benefits will be further observed. Clinical trial information: ChiCTR-OIC-17013249 .
Prediction of histologic and molecular subsets of soft tissue sarcoma using deep learning.
Authors: Ari Rosenberg, Sara Kochanny, James Dolezal, Cindy Wang, Heather Chen, Jakob Nikolas Kather, Alexander T. Pearson
Journal: Journal of Clinical Oncology (2020)

e23529 Background: Soft tissue sarcomas (STS) are histologically and molecularly heterogenous with variable biologic behavior and differential therapeutic responses. Molecular analysis of STS is commonly utilized to identify targetable mutations or identify STS subtypes that have predictive and prognostic implications. To address the challenge of rapid, accurate classification of STS subtypes, we sought to develop an approach using a form of artificial intelligence called deep learning to identify meaningful hidden information directly from digital H+E slide images. We trained a deep learning model using genotype and phenotype data from The Cancer Genome Atlas (TCGA) and companion diagnostic digital H+E slide images, in order to identify therapeutic biomarkers and prognostic molecular subtypes. Methods: Digital whole slide images (WSIs) from TCGA were downloaded and regions of tumor were annotated by pathologists. WSIs were carved into 604 um by 604 um square tiles within the tumor region and saved at an image size of 598 px by 598 px for a resolution of ~1um/px. These tiles were used as input to a deep convolution neural network (Xception model pretrained on imagenet). Performance results are reported at the as the average of three-fold cross-validation, averaged at the patient level. Results: 206 sarcomas available through the TCGA were used as training set. Sarcoma histologies include 80 leiomyosarcoma (LMS) (27 uterine LMS and 53 non-uterine LMS), 50 dedifferentiated liposarcoma (DDLPS), 44 undifferentiated pleomorphic sarcoma (UPS), 72 myxofibrosarcoma (MFS), and 10 synovial sarcoma (SS). FNCLCC grade 1 (n = 14), grade 2 (n = 112), and grade 3 (n = 80). Histology could be predicted automatically with very high accuracy for LMS (Area under Receiver-operator curve (AUROC) 0.93 and 0.95 for uterine and non-uterine LMS respectively), DDLPS (AUROC 0.70), UPS (AUROC 0.76), and MFS (AUROC 0.76). FNCLCC grade could be predicted for grade 3, 2, 1 with AUROC of 0.79, 0.73, and 0.81 respectively. High vs. low mitotic rate (threshold 15) could be predicted with AUROC of 0.70. Within non-uterine LMS, prognostic molecular cluster could be predicted with AUC of 0.62 for cluster with worse recurrence-free and disease specific survival. Within DDLPS, DNA methylation cluster 2 associated with worse disease specific survival was predicted with AUC of 0.80. Conclusions: Deep learning algorithm analysis of histologic slides was able to predict clinically meaningful characteristics and molecular clusters with reasonable accuracy. Retrospective and prospective validation is needed.
Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function
Authors: Shih-Ying Wu, Fei Xing, Sambad Sharma, Kerui Wu, Abhishek Tyagi, Yin Liu, Dan Zhao, Ravindra Pramod Deshpande, Yusuke Shiozawa, Tamjeed Ahmed, Wei Zhang, Michael Chan, Jimmy Ruiz, Thomas W. Lycan, Andrew Dothard, Kounosuke Watabe
Journal: The Journal of Experimental Medicine (2020)

Up to 40% of lung cancer patients develop brain metastasis, and the median survival of these patients remains less than 6 months. Smoking is associated with lung cancer. However, how smoking impacts the development of brain metastasis remains elusive. We examined 281 lung cancer patients with distant metastasis and found that smokers exhibited a significantly high incidence of brain metastasis. We found that nicotine enhanced brain metastasis, while a depletion of microglia suppressed this effect in vivo. Nicotine skewed the polarity of microglia to the M2 phenotype, thereby increasing the secretion of IGF-1 and CCL20, which promoted tumor progression and stemness. Importantly, nicotine enhanced the expression of SIRPα in microglia and restricted their phagocytic ability. We also identified a compound, parthenolide, that suppressed brain metastasis by blocking M2 polarization. Our results indicate that nicotine promotes brain metastasis by skewing the polarity of M2 microglia, which enhances metastatic tumor growth. Our results also highlight a potential risk of using nicotine for tobacco cessation.
Spontaneous epidural haematoma of the lumbar spine presenting as radiculopathy: report of one case
Authors: Aibing Huang, Gang Ju, Ting Lu, Hongguang Liu, Haijun Li
Journal: BMJ (2019)

自发性腰椎黄韧带内血肿临床罕见，可造成神经根或硬膜囊受压，引起临床症状。本文报道1例自发性腰椎黄韧带内血肿引起神经根性症状患者的临床资料，采用MRI脊神经根成像技术获得诊断，手术治疗后压迫症状消失。
Access to innovation through the French Expanded-Access Program and clinical trials in patients with malignant melanoma.
Authors: Claire Christen, Laetitia Belgodere, Bernard Guillot, Ghania Kerouani-Lafaye, Liora Brunel, Florence Turcry, Adrien Monard, Francoise Grude, Gaëlle Guyader, Lotfi Boudali, Nicolas Albin
Journal: Journal of Clinical Oncology (2020)

e22030 Access to innovation through the French Expanded-Access Program and clinical trials in patients with malignant melanoma Background: The arrival of immunotherapy (IT) and targeted therapy (TT) has constituted a revolution in the treatment of metastatic melanoma (MM) since the 2010s. The major challenge was to allow these new treatments to make them available as soon as possible. France has effective tools such as clinical trials (CT) and an expanded-access program (EPA) (through temporary use authorizations (ATU) and temporary use recommendations (RTU)) allowing the use of innovative drug without marketing authorization (MA) in case of therapeutic “dead-end”. Methods: Real-time data collection of nominal and cohort ATU, RTU (between 01/09/2009 and 01/09/2019), and CT authorizations (from 01/12/2017 to 01/09/2019) filed and evaluated by the French national agency for medicines and health products safety (ANSM) in the MM from internal databases. Clinical data of the cATU come from the summary reports produced by the laboratory. Results: 45 CT were authorized in MM, including 51% in early phases and 44% in phase II/III, mainly in the metastatic stage (86%) and with an industrial promoter (73%). IT and TT (63% and 24% respectively) are the most used in experimental arms, mostly in combination. Through the EPA, 3 RTUs were authorized in the adjuvant treatment of MM, 14 drugs benefited of a nATU and 5 obtained a cATU. This has treated 6538 patients (28% of nATU and 72% of cATU). The anti-PD1 and combination therapy of BRAF and MEK inhibitors are the most used, mainly in combination. 80% of the indications are from the second line. The duration of availability of the ATU is 9,85 months before obtaining the MA. Efficacy data in patients receiving cATU of vemurafenib and combination of cobimetinib and vemurafenib showed respectively the following objective response rate (ORR): at 8 weeks of treatment, ORR = 57,7% and 54,7%; at 20 weeks, ORR = 36,7% and 54,7% (IR criteria). For pembrolizumab, at 12 weeks, ORR = 29,7% and at 24 weeks, ORR = 40% (irRC criteria). All of these drugs obtained a MA and an inscription on the reimbursement list after the health technology assessment. Conclusions: Thanks to CT and the French EPA, patients were able to benefit from innovative treatments at an early stage of MM.
Clinicopathologic analysis of MMR gene mutations and uterine adenocarcinomas: An updated population-based study.
Authors: Aifen Wang, Robert W. Holloway, Jinsong Yang, Zhe Pei, Yan Sun, Yingyan Zhao
Journal: Journal of Clinical Oncology (2020)

e18100 Background: Endometrial carcinoma frequently harbors genetic alterations in genes encoding mismatch repair (MMR) enzymes, a finding which has important implications for adjuvant therapy. The aim of this study is to determine an optimal screening strategy to detect MMR mutations for each histologic subtype of endometrial carcinoma (EC). Methods: We performed a comparative analysis of the demographic, clinical, pathologic, and molecular data, including MLH1, MLH3, PMS1, PMS2, MSH2, MSH3, MSH6, and EPCAM, for 562 patients from The Cancer Genome Atlas database (TCGA), stratified by tumor histologic subtype. Results: Molecular data was available for 562 patients, of which 162 (28.8%) had tumors that were positive for MMR mutations. We did not separate somatic and germline mutation. Of these tumors, the penetrate rate of FIGO grade 3 endometrioid endometrial carcinoma (EEC G3) (84/184, 45.7%) was significantly higher than the one of uterine serous carcinoma (USC) (35/156, 22.4%) ( p &lt; 0.001), grade 2 (EEC G2) (26/129, 20.2%) ( p &lt; 0.001), and grade 1 (EEC G1) (17/93, 18.3%) ( p &lt; 0.001). Of EEC G3 tumors, patients with MMR gene mutations were significantly older ( p = 0.024) or had lower BMI's than MMR mutation noncarriers ( p = 0.028). Of 562 endometrial carcinomas, alterations in MSH2 (n = 55), MSH6 (n = 54), MSH3 (n = 50) were the most frequent mutations. There were no differences in overall survival and progression-free interval between MMR mutation carriers and nonmutation carriers (p &gt; 0.05) except that PFI with MMR gene mutation was higher than with MMR proficiency in EEC G3 ( p = 0.014). Conclusions: EEC G3 harbored the most MMR mutations among EC. EEC G3 and USC could be more considered to screen MMR mutation due to more MMR mutations occurred in EEC G3 and USC than did among EEC G2 and EEC G1. Besides MLH1, MSH2, MSH6, PMS2 and EPCAM mutation , MLH3, MSH3, PMS1 mutation could be screened in patients with newly diagnosed endometrial carcinoma. [Table: see text]
Identification of CCN1 transferred by extracellular vesicles derived from breast cancer cells responsible for doxorubicin-resistance.
Authors: Sujin Yang, Jinhai Tang
Journal: Journal of Clinical Oncology (2020)

e12623 Background: The anthracycline drug, doxorubicin, is one of the most frequently used chemotherapeutic drugs for breast cancer. However, not all patients respond to doxorubicin-containing combination chemotherapy due to chemo-resistance (natural or acquired). Preceding researches have shown that extracellular vesicles (EVs) can be readily harvested from peripheral blood for further biological analysis and thus perform an attractive source of tumor derived materials for identification of chemo-resistance factors. This study aims to provide a theoretical basis to use CCN1-containing EVs as new biomarkers and therapeutic targets for doxorubicin-resistance in breast cancer. Methods: A strategy combining RNA-sequencing technique and bioinformatic analysis was used to determine the level of differential expressed mRNAs in EVs samples from cellular supernatant (n = 4) and blood serum (n = 8) from chemo-resistant and chemo-sensitive patients. Serial gene expression analysis in patients (n = 203) who treated with neoadjuvant (GSE32603) were also employed to identified drug-resistance-related proteins. The expression of CCN1 was detected in doxorubicin-resistant cell lines (MCF-7/DOX),MCF-7 and their EVs by RT-qPCR and western blot. Then, we used cell apoptosis and immunofluorescence stain to confirm the ability of CCN1-containing EVs in conferring drug resistance. Immunohistochemistry stain and RT-qPCR were used to prove the expression level of CCN1 in tumor tissues from breast cancer patients (n = 80) and in serum EVs from patients treated with the whole neoadjuvant chemotherapy. Results: We combined the differentially expressed mRNAs from three datasets and found identified CCN1 as a drug-resistance-related factor in breast cancer. The expression level of CCN1 is much higher in MCF-7/DOX cells and their EVs compared with MCF-7 cells and their EVs. The addition of CCN1-containing EVs has been found significantly increase the resistance to doxorubicin in sensitive cells. Moreover, a higher expression level of CCN1 was detected in the progressive disease (PD)/stable disease (SD) group than in the partial response (PR)/complete response (CR) group both in tissues and serum EVs. Conclusions: All These findings demonstrate that CCN1-containing EVs appear to be essential in conferring resistance to doxorubicin. More importantly, we exhibit the potential applications of CCN1-containing EVs for predicting the efficiency and outcome of patients treated with doxorubicin-based chemotherapy.