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Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National center for Tumor Diseases, Heidelberg

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World Journal of Gastroenterology 2015年第16期21卷 4911-4918页

作者： Anne Katrin Berger Stefanie Zschaebitz Christine Komander Dirk Jger Georg Martin Haag National center for Tumor Diseases Heidelberg University Hospital NCT clinical Cancer Registry German Cancer Research Center

AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National center for Tumor Diseases,***:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National center for Tumor Diseases Heidelberg,Germany between January 2006 and *** requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or *** clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of *** times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were *** and safety were *** factors including ECOG PS,age and previousperioperative treatment were ***:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to *** times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,*** differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not sho

关键词： Gastroesophageal cancer Old patients Palliative chemotherapy Toxicity Eastern CooperativeOncology Group performance status

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Comparative Analysis of Continuous versus Intermittent Proton Pump Inhibitor Therapy in Patients with Upper Gastrointestinal Bleeding Due to Ulcers

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Open Journal of Gastroenterology 2024年第3期14卷 99-107页

作者： Abraamyan Feruza Misra P. Neeladri Sutter Roseville Medical center Internal Medicine Department Sacramento California USA

Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bleeding ulcers recommend a continuous infusion of proton pump inhibitors (PPI). However, studies comparing intermittent dosing of PPI therapy show that this regimen achieves similar clinical benefits. If the clinical efficacy remains equivalent, intermittent dosing will be more cost-effective for patients and the health care system. Our research study aims to analyze the comparative effectiveness of intermittent versus continuous PPI therapy after endoscopic treatment in patients with UGIB, focusing on such endpoints as rebleeding risk at 3-and 7-day mortality rates. Methods: Resources searched included MEDLINE, EMBASE, PUBMED, and the Cochrane Central Register of Controlled trials databases from January 2010 through December 2023 with the inclusion of meta-analysis, systematic review, review, or ACG guideline recommendations. Results of the analysis show how recommendations regarding high vs. low PPI regimen changed over time: from no difference in regimen in 2010 to recommending continuous regimen in 2012 to declaring insufficient evidence between choosing one regimen over another in 2013 to determine that both regimens were comparable to each other in 2014-2018 and finally to recommending both regimens in 2021. To conclude, our review shows that in patients with bleeding ulcers and high-risk endoscopic findings, intermittent PPI therapy is non-inferior to continuous PPI infusion for three days, seven days bleeding risk or mortality rates;however, it remains challenging to determine the most optimal intermittent regimen due to heterogeneity of RCTs included in meta-analyses, and further trials will need to be performed.

关键词： Upper Gastrointestinal Bleeding PPI Continuous Intermittent Bolus Regimens Review

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A Measure for Assessing Functions of Time-Varying Effects in Survival Analysis

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Open Journal of Statistics 2014年第11期4卷 977-998页

作者： Anika Buchholz Willi Sauerbrei Patrick Royston center for Medical Biometry and Medical Informatics Medical Center - University of Freiburg Freiburg Germany MRC clinical trials Unit at University College London London UK

A standard approach for analyses of survival data is the Cox proportional hazards model. It assumes that covariate effects are constant over time, i.e. that the hazards are proportional. With longer follow-up times, though, the effect of a variable often gets weaker and the proportional hazards (PH) assumption is violated. In the last years, several approaches have been proposed to detect and model such time-varying effects. However, comparison and evaluation of the various approaches is difficult. A suitable measure is needed that quantifies the difference between time-varying effects and enables judgement about which method is best, i.e. which estimate is closest to the true effect. In this paper we adapt a measure proposed for the area between smoothed curves of exposure to time-varying effects. This measure is based on the weighted area between curves of time-varying effects relative to the area under a reference function that represents the true effect. We introduce several weighting schemes and demonstrate the application and performance of this new measure in a real-life data set and a simulation study.

关键词： Cox Model Measure of Distance Survival Analysis Time-Varying Effects

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Inferior mesenteric arteriovenous fistula during treatment with bevacizumab in colorectal cancer patient: A case report

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World Journal of Gastrointestinal Oncology 2020年第11期12卷 1364-1371页

作者： Ayako Doi Hiroyuki Takeda Kumiko Umemoto Ryosuke Oumi Shinji Wada Shingo Hamaguchi Hidefumi Mimura Hiroyuki Arai Yoshiki Horie Takuro Mizukami Naoki Izawa Takashi Ogura Takako EguchiNakajima Yu Sunakawa Department of clinical Oncology St.Marianna University School of MedicineKanagawa 216-8511Japan Department of Gastroenterology St.Marianna University School of MedicineKanagawa 216-8511Japan Department of Radiology St.Marianna University School of MedicineKanagawa 216-8511Japan Innovation center for Next Generation clinical trials and iPS Cell Therapy Kyoto University HospitalKyoto 606-8507Japan

BACKGROUND Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula(IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer(mCRC) after colon *** SUMMARY An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after *** Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.

关键词： Metastatic cancer Colon surgery Chemotherapy Fistula formation Inferior mesenteric artery Interventional radiology Case report

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Rare tumors: a blue ocean of investigation

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Frontiers of Medicine 2023年第2期17卷 220-230页

作者： Shuhang Wang Peiwen Ma Ning Jiang Yale Jiang Yue Yu Yuan Fang Huilei Miao Huiyao Huang Qiyu Tang Dandan Cui Hong Fang Huishan Zhang Qi Fan Yuning Wang Gang Liu Zicheng Yu Qi Lei Ning Li clinical Trial center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Phase I clinical Trial center Fujian Medical University Cancer Hospital/Fujian Cancer HospitalFuzhou 350014China Key Laboratory of Molecular Epigenetics of the Ministry of Education Northeast Normal UniversityChangchun 130024China GenePlus-Shenzhen Shenzhen 518118China

Advances in novel drugs,therapies,and genetic techniques have revolutionized the diagnosis and treatment of cancers,substantially improving cancer patients’*** rare tumors account for a non-negligible number,the practice of precision medicine and development of novel therapies are largely hampered by many *** low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and *** exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines,insufficient biomarkers for prognosis/efficacy,and inability to identify potential novel therapies in clinical ***,by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas,we proposed a definition of rare tumor in China,including 515 tumor types with incidences of less than 2.5/100000 per *** also summarized the current diagnosis process,treatment recommendations,and global developmental progress of targeted drugs and immunotherapy agents on the status ***,we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by *** this informative report,we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

关键词： rare tumors diagnosis flowchart treatment strategy clinical trials recommendation

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Consensus on the clinical diagnosis and treatment of grade 3 pancreatic neuroendocrine tumors

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胰腺病学杂志(英文) 2024年第2期07卷 97-105页

作者： Chen Jie Wu Wenming Bai Chunmei Chi Yihebali Huo Li Jiang Liming Ji Yuan Luo Jie Li Jie Li Jingnan Lou Wenhui Shao Chenghao Shen Lin Wang Feng Wang Yu Xue Ling Xu Jin Yuan Chunhui Yu Xianjun Yin Xiaoyu Zhao Hong Zhu Xiongzeng Zhao Yupei Centre for Neuroendocrine Tumors Fudan University Shanghai Cancer Center Shanghai China Department of General Surgery State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China Department of Medical Oncology Peking Union Medical College Hospital Chinese Academy of Medical Science &amp Peking Union Medical College Beijing China Department of Medical Oncology National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare Diseases Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing China Department of Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Pathology Zhongshan Hospital Fudan University Shanghai China Department of Pathology China-Japan Friendship Hospital Beijing China Department of Gastroenterological Oncology Beijing Cancer Hospital Peking University Cancer Hospital &amp Institute Beijing China Department of Gastroenterology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing China Department of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai China Department of Pancreatic-Biliary Surgery Second Affiliated Hospital of Naval Medical University Shanghai China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital &amp Department of Nuclear Medicine Nanjing First Hospital Nanjing Medical University Nanjing China Depar

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

关键词： clinical diagnosis Grade 3 Pancreatic neuroendocrine tumors Treatment

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High incidence of nasopharyngeal cancer: similarity for 60% of mitochondrial DNA signatures between the Bidayuhs of Borneo and the Bai-yue of Southern China

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Chinese Journal of Cancer 2012年第9期31卷 455-456页

作者： Joseph Wee Tam Cam Ha Susan Loong Chao-Nan Qian Department of Radiation Oncology National Cancer Centre Singapore Division of clinical trials&Epidemiological Sciences National Cancer Centre Singapore Duke-NUS Graduate Medical School State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Van Andel Research Institute

Populations in Southern China (Bai-yue) and Borneo (Bidayuh) with high incidence of nasopharyngeal cancer (NPC) share similar mitochondrial DNA signatures, supporting the hypothesis that these two populations may share the same genetic predisposition for NPC, which may have first appeared in a common ancestral reference population before the sea levels rose after the last ice age.

关键词：线粒体DNA 中国南方相似性婆罗洲发病率鼻咽癌签名遗传易感性

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Inhibition of xanthine oxidase alleviated pancreatic necrosis via HIF-1α-regulated LDHA and NLRP3 signaling pathway in acute pancreatitis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3591-3604页

作者： Juan Rong Chenxia Han Yan Huang Yiqin Wang Qi Qiu Manjiangcuo Wang Shisheng Wang Rui Wang Juqin Yang Xia Li Chenggong Hu Zhiyao Chen Lihui Deng Wei Huang Qing Xi Dan Du West China center of Excellence for Pancreatitis Institute of Integrated Traditional Chinese and Western MedicineWest China Hospital/West China Medical SchoolSichuan UniversityChengdu 610041China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Advanced Mass Spectrometry center Research Core FacilityFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610213China Proteomics-Metabolomics Platform Research Core FacilityInstitutes for Systems GeneticsWest China HospitalSichuan UniversityChengdu 610093China Biobank West China HospitalSichuan UniversityChengdu 610093China West China School of Nursing Sichuan UniversityChengdu 610041China Department of Critical Care Medicine West China HospitalSichuan UniversityChengdu 610041China

Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment *** inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains ***,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger *** first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP *** also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time ***,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and *** mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-***,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP *** results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

关键词： Xanthine oxidase inhibitor Multi-omics HIF-1a Necrotizing acute pancreatitis Lactate Therapeutic target NLRP3 Metabolic flux

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Pilot Study on the Intercalibration of a Categorisation System for FAIRer Digital Objects Related to Sensitive Data in the Life Sciences

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Data Intelligence 2022年第2期4卷 196-211页

作者： Christian Ohmann Romain David Mónica Cano Abadia Florence Bietrix Jan-Willem Boiten Steve Canham Maria Luisa Chiusano Walter Dastrù Arnaud Laroquette Dario Longo Michaela Theresia Mayrhofer Maria Panagiotopoulou Audrey Richard Pablo Emilio Verde European clinical Research Infrastructure Network (ECRIN) 2. European Research Infrastructure on Highly Pathogenic Agents (ERINHA AISBL) 3. Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) 4. European Infrastructure for Translational Medicine (EATRIS) 5. European Advanced Translational Research Infrastructure (EATRIS)/Lygature European Marine Biological Resource Centre (EMBRC)—Department of Agricultural Sciences University Federico II of Naples via Università Department of Molecular Biotechnology and Health Sciences Molecular Imaging Center University of Torino European Marine Biological Resource Centre (EMBRC) 9. European Research Infrastructure for Biological and Biomedical Imaging (Euro-Bio Imaging) coordination Centre for clinical trials Heinrich Heine University Düsseldorf Ringgold standard institution

Sharing sensitive data is a specific challenge for research infrastructures in the field of life sciences. For that reason a toolbox has been developed, providing resources for researchers who wish to share and use sensitive data, to support the workflows for handling these kinds of digital objects. Common and community approved annotations are required to be compliant with FAIR principles(Findability, Accessibility,Interoperability, Reusability). The toolbox makes use of a tagging(categorisation) system, allowing consistent labelling and categorisation of digital objects, in terms relevant to data sharing tasks and activities. A pilot study was performed within the Horizon 2020 project EOSC-Life, in which 2 experts from 6 life sciences research infrastructures were recruited to independently assign tags to the same set of 10 to 25 resources related to sensitive data management and data sharing(in total 110). Summary statistics of agreement and observer variation per research infrastructure are provided. The pilot study has shown that experts were able to attribute tags but in most cases with a considerable observer variation between experts. In the context of CWFR(Canonical Workflow Frameworks for Research), this indicates the necessity for careful definition,evaluation and validation of parameters and processes related to workflow descriptions. The results from this pilot study were used to tackle this issue by revising the categorisation system and providing an updated version.

关键词： Sensitive data CWFR EOSC-Life Life sciences Toolbox Categorisation system Tagging FAIR

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CIMAvax^(█)EGF vaccine therapy for non-small cell lung cancer:A weighted log-rank tests-based evaluation

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Modern Chemotherapy 2013年第3期2卷 51-56页

作者： Carmen Viada Gonzalez Jean-Francois Dupuy Martha Fors López Patricia Lorenzo Luaces Gisela González Marinello Elia Neninger Vinagera Beatriz García Verdecia Tania Crombet-Ramos clinical trials Department Center of Molecular ImmunologyHavanaCuba National Institute of Applied Sciences of Rennes RennesFrance National Coordinator center of clinical Trial HavanaCuba Hermanos Ameijeiras Hospital HavanaCuba

Time-to-event has become one of the primary endpoints of many clinical trials. Comparing treatments and therapies using time-to-event (or “survival”) data requires some care, since survival differences may occur either early or late in the follow-up period, depending on various factors such as the initial potency or the duration of efficacy of the drugs. In this work, we investigate the effect of the CIMAvax?EGF vaccine therapy on the survival of patients with non-small cell lung cancer, using stratified and unstratified weighted log-rank tests. Weighted log-rank tests are designed to identify early and late survival differences between treatments. Using these tests, we conclude that the vaccine is more efficient than the standard therapy among patients less than 60 years of age.

关键词： Log-Rank Test Fleming-Harrington Test Stratified Tests

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