tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone with or without adjuvant chemotherapy in incidentally detected gallbladder carcinoma after simple cholecystectomy or in front of radical resection of BTC (ICC/ECC): A phase III study utilizing the German Registry of Incidental Gallbladder Carcinoma Platform (GR)—The AIO/CALGP/ACO-GAIN-Trial.
Authors: Thorsten Oliver Goetze, Ulli Simone Bankstahl, Sven A. Lang, Steffen Heeg, Wolf Otto Bechstein, Andreas Schnitzbauer, Ursula Pession, Daniel Reim, Sylvie Lorenzen, Tobias Keck, Alfred Königsrainer, Pompiliu Piso, Arndt Vogel, Claudia Pauligk, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2020)

TPS4653 Background: Currently, complete surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) including Gallbladder Cancer (GBC). Even after curative resection, 5-year OS is only 20–40%. GBC is relatively rare, but still the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. Gallbladder carcinoma is suspected preoperatively in only 30% of all pts, while the majority of cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. Encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase of GBC management and even in intrahepatic and extrahepatic cholangiocarcinoma. Especially because data regarding pure adjuvant chemotherapy in BTC`s are conflicting. Methods: This is a multicenter, randomized, controlled, open-label phase III study including pts with incidentally discovered GBCs after simple cholecystectomy in front of radical liver resection and pts with resectable/borderline resectable cholangiocarcinomas (ICC/ECC) scheduled to receive perioperative chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) or surgery alone followed by a therapy of investigator’s choice. Primary endpoint is OS; secondary endpoints are PFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. A total of N=333 patients with GBC or BTC will be included. Recruitment has just started; first patient in was on December 6, 2020. EudraCT number: 2017-004444-38. Clinical trial information: NCT03673072 .
Molecular validation of the 8th edition AJCC cancer staging system in patients with resected pancreatic cancer: Proposal of integrative translational staging system.
Authors: Sung Hwan Lee, Sunyoung S. Lee, Ju-Seog Lee
Journal: Journal of Clinical Oncology (2020)

e16765 Background: Even though the 8th edition AJCC cancer staging system for pancreatic cancer has validated with major clinicopathologic factors in multiple clinical cohorts, there is still an unmet need for integrative consideration using multi-omics data to stratify the patients with pancreatic cancer elaborately. Methods: We performed a comprehensive analysis and profiling using genomic, transcriptomic, and proteomic data from TCGA-PAAD and other translational cohorts (4 cohorts, n = 340). Molecular features and major subtypes were analyzed mutually with clinical and pathologic factors, especially the 8th AJCC staging system. Results: Aggressive molecular subtypes, basal-like and squamous subtype, were significantly associated with a higher nodal stage, but tumor size didn't show a clear association with molecular features. The activated stroma of pancreatic cancer microenvironment was significantly correlated with poor differentiation and large tumor size. The mutational pattern of KRAS and several transcriptomic pathways such as eptihelial-mesenchymal transition and DNA repair were differently presented in each clinical stage from the 8th AJCC TNM staging system. The optimal algorithm was identified to show significantly higher performance for the prediction for cancer relapse and cancer-specific survival in discovery and validation cohorts. The in silico prediction for molecular target agents and immunotherapy were performed for final clusters from optimal stratification system revealed from the integrative analysis. Conclusions: Our comprehensive multi-omics analysis reveals clear needs for the combination of clinical staging and molecular profiling and provides crucial evidence for precision strategy in patients with resectable pancreatic cancer.
应用自制针刀治疗微创腋臭术后皮瓣皱褶
Authors: 赵作钧, 王军玲, 梁伟中, 王秀艳, 洪苑, 徐欣, 艾红梅
Journal: BMJ (2011)

整形外科治疗腋臭目前多采用微创治疗,有关微创腋臭术后并发症报道中血肿、切口裂开、皮瓣坏死的报道较多[1].2005年6月到2009年6月本研究对6例术后由于皮瓣折叠愈合出现皮瓣皱褶的患者,采用自制针刀治疗取得满意疗效,现报道如下。
Hashimoto′s encephalopathy with disturbance of consciousness and dementia as initial symptoms: report of 2 cases and literature review
Authors: Xiaodan Fu, Lingying Yu, Xianfeng Zhang
Journal: BMJ (2016)

Two eases of Hashimoto′s encephalopathy(HE) are reported and relative literature is reviewed in this article. Both cases were female, with disturbance of consciousness and dementia as initial symptoms. Marked increase of anti-thyroid antibodies was found in serum of the patients. The symptoms disappeared after steroids and maintenance therapies. A total of 126 cases of HE in Chinese literature were retrieved from 2006 to 2015 through the databases of China National Knowledge Infrastructure and Wanfang Med Online.The male/female radio was 1∶6 with an average age of 51.3 years. The clinical manifestations included cognitive impairment (44.5%), epilepsy (38.3%), psychiatric disorders (27.3%), stroke-like symptoms (25.8%), disturbance of consciousness (24.2%), and extrapyramidal symptoms (20.3%). Good response to steroids was observed in 77.2% HE patients. Analysis indicates that HE is an autoimmune disease with the presence of neurological and psychiatric manifestations, elevated titers of anti-thyroid antibodies in serum and well response to steroids, with a good prognosis.


Key words: 
Braim diseases, Hashimoto′s diseases; Signs and symptoms
Use of antihypertensive drugs among community hypertensive patients in Shanghai
Authors: Jing-li Wang, Xiang-gui Xu, Jing-zhen Wang, Ning Mo, Yao-cheng Zhu
Journal: BMJ (2010)

Objective To investigate use of oral antihypertensive drugs among community hypertensive patients in Shanghai and find out factors related to their unreasonable use to direct their clinical use. Methods Seven hundred and three hypertensive patients were surveyed with questionnaire by stratified cluster sampling at three neighborhoods and one village of Dahua community, Baoshan district, Shanghai during April to June 2009 to understand their use of antihypertensive agents, including kinds and forms of drugs, rationale of drug use. Results Five hundred and eighty-two (82. 8% ) of 703 hypertensive patients interviewed were using antihypertensive drugs, 271 (38. 5% ) of them used only one kind of non-compound antihypertensive drug, 182 (25.9%) used one kind of compound agent, 311 (53.4%) used two or more kinds of drugs in combination, including 117 patients ( 16. 8% ) used two kinds of agents combined and 12 patients ( 1.6% ) used three kinds of agents combined. Two hundred and sixty-six (47.5%) patients took orally calcium-channel blockers and 205 ( 35.2% ) used compound agents. Conclusions Frequency of combined use of two or more kinds of antihypertensive agents is reasonable and significantly higher than that of use of one kind of drug at Dahua community in Shanghai. Calcium channel blocker plays a predominant role in treatment for hypertension, non-long-acting compound agents are used in a higher proportion. But,guidelines for hypertension prevention and treatment are not so well complied with in local hypertensive patients. So, it is suggested that training for community physicians and management for standard use of antihypertensive agents at community should be strengthened further.

Key words: 
Antihypertensive agent;  Questionnaire survey;  Community
Ramucirumab in patients with advanced HCC and elevated alpha-fetoprotein (AFP): Outcomes by treatment-emergent ascites.
Authors: Andrew X. Zhu, Masafumi Ikeda, Peter R. Galle, Tatsuya Yamashita, Josep Llovet, Kun Liang, Chunxiao Wang, Sachi Sakaguchi, Paolo Abada, Ryan C Widau, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2020)

4644 Background: REACH and REACH-2 investigated ramucirumab (RAM) vs placebo (PL) in patients (pts) with advanced HCC following sorafenib, with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. Ascites is common in HCC and associated with poorer outcomes. An exploratory analysis of outcomes by treatment-emergent (TE)-ascites was done. Methods: Pts with HCC, Child-Pugh A, ECOG PS ≤1, prior sorafenib, and no clinically meaningful ascites were randomized (REACH 1:1; REACH-2 2:1) to RAM 8 mg/kg or PL Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was done. OS and PFS were evaluated by Kaplan-Meier estimator and Cox models. Prognosis of TE-ascites in OS was evaluated by multivariate Cox models (adjusted for baseline ECOG PS, AFP, macrovascular invasion (MVI), and treatment [trt]). Results: Baseline characteristics were generally balanced between TE-ascites and non-ascites pts; however, more pts with ascites had MVI at baseline. Any-grade ascites was reported at a higher rate in RAM than PL (66 [21%] vs 33 [15%] pts, respectively), with most being low grade. Rate of Gr ≥3 ascites was similar between arms (15 [5%] vs 9 [4%] pts). Median time to onset (43 vs 47 days) and median duration of ascites (13 vs 18 days) were similar in RAM vs PL, with furosemide (22%) and spironolactone (19%) as most common trt and paracentesis (18%) as most common procedure for ascites in both arms. Ascites trended as a prognostic factor for OS after adjustment (with vs without; HR=1.3, 95% CI: 0.99, 1.62). Ascites was more commonly linked with hypoalbuminemia (odds ratio 4.9, 95% CI: 2.5, 9.3), but was not associated with proteinuria or hypertension. TEAEs occurred more frequently in pts with ascites in both arms. The most frequent Gr ≥3 TEAE in pts with ascites was hypertension. One RAM pt discontinued trt due to ascites. RAM trt was beneficial irrespective of presence of ascites (Table), and pts with ascites received more post-discontinuation therapy on RAM than PL (18% vs 6%). Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit in pts who did or did not experience TE-ascites. RAM was well tolerated and no new safety findings were observed. Clinical trial information: NCT011400347; NCT02435433 . [Table: see text]
Clinical significance of lipase detection in viral hepatitis patients
Authors: You-mei Yin, Yu-ming Dou, Li-xin Yu, Gui-tang Shen, Wei Wang, Li-li Zhang
Journal: BMJ (2012)

Lipase of 54/923 cases increased in viral hepatitis group with an abnormal rate of 5.85％.Lipase level of viral hepatitis patients gradually increased with the rising total bilirubin levels,and the difference was statistically significant (P ＜0.0l).Among 54 viral hepatitis cases with elevated lipase,11 died.The sustained abnormal rate of lipase (6/11) of the death group was statistically significant vs.4.65％ (2/43) of the survival group(P ＜0.01).Thus viral hepatitis could be concomitant with elevated lipase and elevated lipase might promote the progression of liver disease.The continuing rise of lipase is correlated with the severity and prognosis of the patients.

Key words: 
Hepatitis, viral, human; Lipase
Phenotype variants of invasive breast cancer differ in associations between the primary tumor size and its Ki-67 value.
Authors: Sven Kurbel, Branko Dmitrovic, Damir Vrbanec, Robert Separovic
Journal: Journal of Clinical Oncology (2020)

e12588 Background: Epidemiological studies report that Ki-67 values are higher in larger invasive breast cancers (IBC). This relation was investigated in 1040 consecutive IBC patients with various immunohistological phenotypes (ER+/-; HER2 0, 1+ to 3+), all treated at a single Croatian hospital. Methods: A scatter plot of 1040 Ki-67 values with their cancer diameter (in cms) have produced an LOWESS nonparametric curve that almost overlapped with the logarithmic function of the same data set (Ki-67% = 18.39+20.63*log(D), where D is a tumor diameter in cm). The next step in using this logarithmic function as a model, was to convert D values into log(D) for linear correlations, amenable to tests of significance. Results: Among all 1040 pts, only ER positive phenotype variants Ki-67% correlated with log(D): Among ER positive tumors, the HER2 expression has decreased the correlation significance and the slope of regression lines, suggesting that the HER2 presence increases Ki67% in small tumors, while larger tumors have Ki67% less augmented than among HER2 absent tumors. Thus the highest slope of the line was found among HER2 absent ER+ patients. Conclusions: Since only ER positive tumors have shown correlation of Ki67% with the log of their tumor size, tumor biology (estimated by Ki67%) of the ER negative IBCs seems unrelated with their size. This possibly suggests that the clinical course of ER negative IBC patients is less predictable due to some etiological distinction the ER positive and ER negative breast cancers. [Table: see text]
Performance of machine learning-augmented analysis of radiomics for the head and neck cancer histopathological diagnosis: A systematic review and meta-analysis.
Authors: Sotirios Bisdas, Jade Seguin, Diana Roettger, Daisuke Yoneoka, Faiq Shaikh
Journal: Journal of Clinical Oncology (2020)

e18526 Background: The imaging criteria used for head and neck cancers (HNC) staging are mostly anatomical with basic quantitative measures, such as size, and admittedly radiologists’ reading of images is dependent on their expertise level. Radiomics, a term referring to extracting and investigating higher dimensional data from images, has been suggested to address these shortcomings. Assisted by machine learning (ML), highly efficient prediction models could revolutionise our diagnostic practices. Our goal was to study the role of ML in the histopathological diagnosis of HNC based on radiomics. Methods: A systematic review and meta-analysis was conducted using electronic databases (PubMed, Scopus, EMBASE, Google Scholar) and including MRI, PET, and CT studies in patients with HNC. Our study was aimed only at diagnosis utilising radiomics and artificial intelligence (ML). A PRISMA diagram retracing the steps of this search process was completed. QUADAS-2 and EQUATOR checklists were completed. A weighted mean, a mean and a median of the performance indicators were recorded. Results: 7 studies were found eligible for meta-analysis. Patient sample sizes ranged between 2-107 patients (median: 18). CT was the most common modality used (4/7 studies). All but one studies were retrospective. Support vector machine and random forest techniques were the main ML techniques used but how the model was built was rarely described. Furthermore, studies did not make clear the exact number of patients in the testing set. Other issues included the reporting of the final model performance with few studies reporting confidence intervals and 2 studies not reporting the exact performance metrics. The accuracy values for the testing set ranged from 58% -94.1%. The meta-analysis showed an overall weighted-mean accuracy of 78.53%, a mean of 82.9% and a median of 84.4%. The weighted mean of the sensitivity was 76.5%, the mean was 83.3%, and for specificity was 83.9% and 88.5%., respectively. The AUC was 0.8. The neuroradiologists’ overall accuracy was 50.4% if weighted, and 54.5% if not, and the corresponding accuracy of the ML classifiers were 78.4% and 79.6%. The ML scored an accuracy of 20% higher than the radiologists. Conclusions: The results are overall encouraging, keeping in perspective the possible calculation biases and small number of studies. There is need for better documentation and standardisation of the applied ML models, which show initially superior performance compared to radiologists.
Five-year final results of a phase III study of CPX-351 versus 7+3 in older adults with newly diagnosed high-risk/secondary AML.
Authors: Jeffrey E. Lancet, Geoffrey L. Uy, Laura F. Newell, Tara L. Lin, Ellen K. Ritchie, Robert K. Stuart, Stephen Anthony Strickland, Donna Hogge, Scott R. Solomon, Dale Bixby, Jonathan E. Kolitz, Gary J. Schiller, Matthew Joseph Wieduwilt, Daniel H. Ryan, Stefan Faderl, Yu-Lin Chang, Jorge Cortes
Journal: Journal of Clinical Oncology (2020)

7510 Background: CPX-351 (Vyxeos; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of cytarabine [C] and daunorubicin [D], is approved by the FDA and EMA for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Primary analysis of the pivotal phase 3 study (NCT01696084) that formed the basis for these approvals evaluated patients (pts) aged 60-75 y with newly diagnosed high-risk/secondary AML and found that CPX-351 significantly improved median overall survival (OS) vs conventional 7+3, with a comparable safety profile. Here, we report the prospectively planned final 5-y follow-up results from this phase 3 study. Methods: Pts were randomized 1:1 to receive ≤2 induction cycles of CPX-351 (100 units/m 2 [C 100 mg/m 2 + D 44 mg/m 2 ] as a 90-min infusion on Days 1, 3, 5 [2nd induction: Days 1, 3]) or 7+3 (C 100 mg/m 2 /d continuously for 7 d + D 60 mg/m 2 on Days 1-3 [2nd induction: 5+2]). Pts achieving complete remission (CR) or CR with incomplete platelet or neutrophil recovery could receive up to 2 consolidation cycles. Pts could receive a hematopoietic cell transplant (HCT) at the physician’s discretion. Pts were followed until death or up to 5 y following randomization. Results: In total, 309 pts were randomized to CPX-351 (n = 153) or 7+3 (n = 156). The survival rate at 5 y was higher for CPX-351 vs 7+3 (18% vs 8%; Table). Among pts who died, the most common primary cause of death was progressive leukemia in both arms (CPX-351: 56%; 7+3: 53%). After a median follow-up of 60.65 mo, improved median OS with CPX-351 vs 7+3 was maintained: 9.33 vs 5.95 mo; Kaplan-Meier (KM) OS curves plateaued at ~30 mo. HCT was received by 53 (35%) vs 39 (25%) pts after CPX-351 vs 7+3; among these pts, the survival rate at 5 y was higher for CPX-351 vs 7+3 (52% vs 23%), and median OS landmarked from the HCT date was not reached for CPX-351 vs 10.25 mo for 7+3 (Table). Conclusions: After 5 y of follow-up, improved OS was maintained in this phase 3 study, supporting that CPX-351 has the ability to produce or contribute to long-term remission and survival in older pts with newly diagnosed high-risk/secondary AML. Clinical trial information: NCT01696084 . [Table: see text]
Covid-19: 146 researchers raise concerns over chloroquine study that halted WHO trial
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The BMJ A group of international researchers has raised methodological and data integrity concerns about a recent study on hydroxychloroquine and chloroquine in covid-19 patients, which led to the World Health Organization halting part of its trial.The observational study, published in the Lancet, 1 reported that inpatients with covid-19 who were treated with chloroquine or hydroxychloroquine (with or without a macrolide) showed an increased risk of dying in hospital and of de novo ventricular arrhythmia than patients who did not receive the drugs. 2WHO has been testing potential covid-19 treatments through its Solidarity Trial, involving over 400 hospitals in 35 countries.After the publication of the Lancet paper, which included patients from six continents, WHO announced that the hydroxychloroquine arm of the trial had been halted while the Data Safety Monitoring Board reviewed the data.In an open letter to the study's authors and the journal's editor, Richard Horton, however, 3 146 clinicians, medical researchers, statisticians, and ethicists have now highlighted 10 main concerns about the research.
TRIDENT-1: A global, multicenter, open-label Phase II study investigating the activity of repotrectinib in advanced solid tumors harboring <i>ROS1</i> or <i>NTRK1-3</i> rearrangements.
Authors: Robert Charles Doebele, Jessica Jiyeong Lin, Misako Nagasaka, Viola Weijia Zhu, Nashat Y. Gabrail, Lyudmila Bazhenova, Peter Meade Anderson, Benjamin J. Solomon, Arkadiusz Z. Dudek, Andrew William Pippas, Mihran Shirinian, Christina S Baik, Shanna Stopatschinskaja, D. Ross Camidge, Byoung Chul Cho, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2020)

TPS9637 Background: Repotrectinib is a next-generation ROS1/TRK inhibitor with &gt; 90-fold greater potency than crizotinib against ROS1 and &gt; 100-fold greater potency than larotrectinib against TRK. Preclinical studies demonstrated inhibitory activity of repotrectinib against ROS1 resistance mutations, including the solvent-front mutation (SFM) G2032R. In the phase 1 portion of the study, repotrectinib was found to be well tolerated with encouraging antitumor activity including a 91% confirmed overall response (cORR) in TKI-naïve ROS1+ NSCLC pts. In ROS1+ NSCLC pts who received 1 prior chemo and 1 prior TKI, the cORR was 57% at the clinical dose of 160 mg QD or above. Intra-cranial (IC) activity was observed in ROS1+ NSCLC pts with measurable CNS disease (100% IC-ORR in TKI-naïve and 75% IC-ORR in patients with 1 prior TKI). Encouraging antitumor activity was observed in pts with NTRK+ solid tumors. Methods: A global phase 2 study was initiated and is actively enrolling. The primary endpoint for the Phase 2 study is cORR assessed by BICR (Blinded Independent Central Review) using RECIST v1.1, in each expansion cohort in pts with advanced solid tumors that harbor a ROS1 or NTRK1/2/3 gene fusion. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), IC-ORR, IC-PFS, and quality of life assessments. All pts need to have RECIST 1.1 measurable disease confirmed by BICR and ECOG performance score ≤1. Repotrectinib is administered at 160 mg QD for 14 days and, if tolerated, the dose can be increased to 160 mg BID. Approximately 320 pts (≥12 years old) will be enrolled into 6 defined expansion cohorts, depending on the status of previous treatment with TKIs and cancer types (see table below). Clinical trial information: NCT03093116 . [Table: see text]