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The evolution of cancer genomic medicine in Japan and the role of the national Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan national Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the national Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Incidence and Mortality of Cancers in Female Genital Organs—China,2022

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China CDC weekly 2024年第10期6卷 195-202,I0003,I0004页

作者： Kexin Sun Bingfeng Han Hongmei Zeng Shaoming Wang Li Li Ru Chen Rongshou Zheng Wenqiang Wei national Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Introduction:This study presented the incidence and mortality rates of cancers affecting the female genital organs in China,along with their trends spanning from 2010 to ***:700 population-based cancer registries provided relevant cancer incidence and mortality data for the year *** these,106 registries had continuous monitoring data suitable for trend analysis from 2010 to *** focused specifically on cancers affecting female genital organs(ICD10=C51-C54,C56)and projected their incidences and mortalities in China for 2022 based on data from 2018 and the trends observed from 2010 to ***-standardized incidence rate(ASIR)and mortality rate(ASMR)were calculated using Segi’s world standard ***:In 2022,there were an estimated 296,300 new cases and 104,900 deaths from female cancers in *** for vulva(C51),vagina(C52),cervix uteri(C53),corpus uteri(C54),and ovary(C56)were 0.32,0.23,13.83,6.84,and 5.68 per 100,000 *** for corpus uteri and ovary cancers were higher in urban *** for vulva,vagina,cervix,corpus uteri,and ovary cancers were 0.14,0.08,4.54,1.05,and 2.64 per 100,000 population,*** for ovarian cancer was higher in urban *** and ASMRs for most female genital organ cancers increased from 2010 to 2018,although the rate of increase for vulvar and cervical cancers in rural areas has slowed ***:Tailored cancer prevention and control programs specific to each region are necessary to address the growing disease burden.

关键词： ICD10 mortality organs

Mission of the national Cancer Center hospital in Japan to promote clinical trials for precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 1-3页

作者： Kazuaki Shimada Kenichi Nakamura Noboru Yamamoto Department of Hepatobiliary and Pancreatic Surgery National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan

Precision medicine is a growing field *** its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical *** main obstacles are associated... 详细信息

关键词： clinical Cancer overcome

Surgical Repair of Ventricular Septal Defect in Neonates: Indications and Outcomes

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Congenital Heart Disease 2024年第1期19卷 69-83页

作者： Jae Hong Lee Sungkyu Cho Jae Gun Kwak Hye Won Kwon Woong-Han Kim Mi Kyoung Song Sang-Yun Lee Gi Beom Kim Eun Jung Bae Department of Thoracic and Cardiovascular Surgery Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsanKorea Department of Thoracic and Cardiovascular Surgery Seoul National University Children’s HospitalSeoulKorea Department of Pediatrics Seoul National University Children’s HospitalSeoulKorea

Background:The optimal surgical timing and clinical outcomes of ventricular septal defect(VSD)closure in neo-nates remain *** aimed to evaluate the clinical outcomes of VSD closure in neonates(age≤30 days).Methods:We retrospectively reviewed 50 consecutive neonates who underwent VSD closure for isolated VSDs between August 2003 and June *** for the procedure included congestive heart failure/failure to thrive and pulmonary *** adverse events(MAEs)were deﬁned as the composite of all-cause mortality,reoperation,persistent atrioventricular block,and signiﬁcant(≥grade 2)valvular ***:The median age and body weight at operation were 26.0 days(interquartile range[IQR],18.8–28.3)and 3.7 kg(IQR,3.3–4.2),*** median follow-up duration was 110.4 months(IQR,56.8–165.0).Seven patients required preoperative respiratory support,andﬁve had signiﬁcant(≥grade 2)preoperative valvular *** early mortality occurred due to irreversible cardiogenic shock;no late mortality was *** reopera-tion was due to hemodynamically signiﬁcant residual VSD at 103.8 months *** overall survival,freedom from reoperation,and freedom from MAE at 15-years were 98.0%,96.3%,and 94.4%,***-operative mechanical ventilation was associated with a longer duration of postoperative mechanical ventilation(p<0.001)and a longer length of intensive care unit stay(p<0.001).Conclusions:VSD closure with favorable outcomes without morbidities is feasible even in ***,neonates requiring preoperative respiratory support may require careful postoperative management considering the long-term postoperative ***,surgical VSD closure might be indicated earlier in neonates with respiratory compromise.

关键词： Ventricular septal defect neonate early surgery neonatal surgery

Utilization of biomarkers for the prognostic prediction of cardiac arrest survivors using a multi-modal approach

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World Journal of Emergency Medicine 2024年第2期15卷 131-134页

作者： Changshin Kang Yeonho You Jung Soo Park Byeong Kwon Park Jae Kwang Lee Byung Kook Lee Department of Emergency Medicine College of MedicineChungnam National UniversityDaejeon 35015Republic of Korea Department of Emergency Medicine Chungnam National University HospitalDaejoen 35015Republic of Korea Department of Emergency Medicine Konyang University HospitalCollege of MedicineDaejeon 35015Republic of Korea Department of Emergency Medicine Chonnam National University Medical SchoolChonnam National University HospitalGwangju 61469Republic of Korea

International guidelines for post-cardiac arrest care recommend using multi-modal strategies to avoid the withdrawal of life-sustaining therapy(WLST)in patients with the potential for neurological recovery.[1]However,a clear methodology for multi-modal approaches has yet to be ***-specific enolase(NSE)is currently the only recommended biomarker,and the European Resuscitation Council(ERC)and the European SocietyofIntensiveCareMedicine(ESICM)have proposed a cutoff value of 60μg/L at 48 and/or 72 h after the return of spontaneous circulation(ROSC)as a multimodal prognostic tool for predicting poor neurological outcomes.

关键词： cardiac modal return

Comparative study between Embosphere®and Marine gel®as embolic agents for chemoembolization of hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 102-109页

作者： Hyo-Cheol Kim Jin Woo Choi Department of Radiology Seoul National University HospitalSeoul 03080South Korea

BACKGROUND While gelatin sponge particles and calibrated microspheres are commonly used as embolic materials in conventional transarterial chemoembolization(cTACE),direct comparisons between these embolic agents are *** To compare the efficacy and safety of superselective cTACE using Embosphere®or Marine gel®in patients with early-stage hepatocellular carcinoma(HCC).METHODS This retrospective study included 70 patients with small(<4 cm)HCC who underwent cTACE with Embosphere®(n=33)or Marine gel®(n=37)as the embolic agent at a single center between March 2021 and July *** radiologic images and clinical data were retrospectively reviewed,with an emphasis on tumor response,procedure-related complications,and local tumor *** primary index tumor was assessed on a 1-mo follow-up image,and local progression-free survival was obtained using the Kaplan-Meier method and was compared by the log-rank *** The median tumor size of both groups was 1.5 cm,and 69 patients achieved a complete response one month after *** cumulative local recurrence rate at 12 mo was 15.5%in the Embosphere®group and 14.4%in the Marine gel®*** local progression-free survival was not significantly different between the two groups(P=0.83).In the multivariate analysis,high serum alphafetoprotein was the only significant poor prognostic factor for local tumor progression(P=0.01).Postembolization syndrome occurred in 36.4%of the Embosphere®group and 35.1%of the Marine gel®group,and there were no cases of biloma,biliary duct dilation,or liver abscess in either *** Calibrated gelatin sponge particles(Marine gel®)and calibrated microspheres(Embosphere®)have similar outcomes in terms of tumor response for superselective cTACE of small HCC.

关键词： Hepatocellular carcinoma Chemoembolization Temporary embolic material Permanent embolic material Tumor response

Metformin-associated lactic acidosis:A mini review of pathophysiology,diagnosis and management in critically ill patients

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World Journal of Diabetes 2024年第6期15卷 1178-1186页

作者： Kay Choong See Department of Medicine National University HospitalSingapore 119228Singapore

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation,leading to metforminassociated lactic acidosis(MALA).As diabetes mellitus is a common chronic metabolic condition found in critically ill patients,pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency *** aim of this narrative mini review is therefore to update clinicians about MALA,and to provide a practical approach to its diagnosis and *** in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis,and confirmed when lactate exceeds 5 mmol/*** factors include those that reduce renal elimination of metformin(renal impairment from any cause,histamine-2 receptor antagonists,ribociclib)and excessive alcohol consumption(as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism).Treatment of MALA involves immediate cessation of metformin,supportive management,treating other concurrent causes of lactic acidosis like sepsis,and treating any coexisting diabetic *** MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement *** optimal time to restart metformin has not been *** is nonetheless reasonable to first ensure that lactic acidosis has resolved,and then recheck the kidney function post-recovery from critical illness,ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m^(2) or better before restarting metformin.

关键词： Acid-base equilibrium Biguanides Oxidative phosphorylation Pyruvic acid Renal replacement therapy

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

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World Journal of Clinical Cases 2024年第2期12卷 267-275页

作者： Chae Hwa Kwon Hyung Il Seo Dong Uk Kim Sung Yong Han Suk Kim Nam Kyung Lee Seung Baek Hong Ji Hyun Ahn Young Mok Park Byeong Gwan Noh BioMedical Research Institute Pusan National University HospitalBusan 49241South Korea Department of Surgery Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Internal Medicine Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Radiology Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Pathology and Biomedical Research Institute Pusan National University HospitalBusan 49241South Korea

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)*** To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative *** This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and *** impact of CCRT on advanced AoV cancer was *** The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,***-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate *** to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte *** Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV *** findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

关键词： Advanced ampulla of Vater cancer Adjuvant concurrent chemoradiotherapy Recurrence Survival Vater cancer

The learning curve for transurethral enucleation with bipolar energy for benign prostate hyperplasia:a single-surgeon experience of 494 patients

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Asian Journal of Andrology 2024年第3期26卷 288-294页

作者： Byeongdo Song Sang Hun Song Seong Jin Jeong Department of Urology Seoul National University Bundang HospitalSeongnam 13620Korea Department of Urology Seoul National University College of MedicineSeoul 03080Korea

This study was performed to investigate the learning curve of transurethral enucleation with bipolar energy(TUEB)for benignprostatic *** study involved 494 consecutive patients who underwent TUEB for benign prostatic hyperplasia fromAugust 2018 to March 2022 by one surgeon(SJJ,Seoul national University Bundang hospital,Seongnam,Korea).The patientswere followed up at 1 week,1 month,3 months,and 6 months *** evaluate the learning curve of TUEB,perioperativeparameters including the enucleation ratio(enucleated tissue weight/transitional zone volume),TUEB efficiency(enucleatedtissue weight/operation time),and enucleation efficiency(enucleated tissue weight/enucleation time)were *** and postoperative complications were also assessed,including the International Prostate Symptom Score(IPSS),IPSSquality-of-life(QoL)score,and uroflowmetry *** patients’median age was 72(interquartile range[IQR]:66–78)years,and the estimated prostate volume and transitional zone volume were 63.0(IQR:46.0–90.6)ml and 37.1(IQR:24.0–60.0)ml,*** enucleation ratio,TUEB efficiency,and enucleation efficiency were 0.60(IQR:0.46–0.54)g ml−1,0.33(IQR:0.22–0.46)g min−1,and 0.50(IQR:0.35–0.72)g min−1,respectively,plateauing after 70 *** functional outcomes,including total IPSS,IPSS QoL score,and uroflowmetry outcomes,significantly improved at 6 months after TUEB(all P<0.05),but without significant differences over the learning ***-five(13.2%)patients developed complications after TUEB,21.5%of whom experienced major complications(Clavien–Dindo grade≥3).The rate of major complications declined as the number ofTUEB cases increased(P=0.013).Our results suggest that the efficiency of TUEB stabilized within 70 procedures.

关键词： benign prostate hyperplasia learning curve perioperative efficiency prostate transurethral enucleation with bipolar energy