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Yoshiyuki Yamamoto Motohide Uemura Masashi Fujita Kazuhiro Maejima Yoko Koh Makoto Matsushita Kosuke Nakano Yujiro Hayashi Cong Wang Yu Ishizuya Toshiro Kinouchi Takuji Hayashi Kyosuke Matsuzaki Kentaro Jingushi Taigo Kato Atsunari Kawashima Takeshi Ujike Akira Nagahara Kazutoshi Fujita Ryoichi Imamura Hidewaki Nakagawa Norio Nonomura 《Cancer science》2019,110(2):617-628
Reliable biomarkers for renal cell carcinoma (RCC) have yet to be determined. Circulating tumor DNA (ctDNA) is an emerging resource to detect and monitor molecular characteristics of various tumors. The present study aims to clarify the clinical utility of ctDNA for RCC. Fifty‐three patients histologically diagnosed with clear cell RCC were enrolled. Targeted sequencing was carried out using plasma cell‐free DNA (cfDNA) and tumor DNA. We applied droplet digital PCR (ddPCR) to validate detected mutations. cfDNA fragment size was also evaluated using a microfluidics‐based platform and sequencing. Proportion of cfDNA fragments was defined as the ratio of small (50‐166 bp) to large (167‐250 bp) cfDNA fragments. Association of mutant allele frequency of ctDNA with clinical course was analyzed. Prognostic potential was evaluated using log‐rank test. A total of 38 mutations across 16 (30%) patients were identified from cfDNA, including mutations in TP53 (n = 6) and VHL (n = 5), and median mutant allele frequency of ctDNA was 10%. We designed specific ddPCR probes for 11 mutations and detected the same mutations in both cfDNA and tumor DNA. Positive ctDNA was significantly associated with a higher proportion of cfDNA fragments (P = .033), indicating RCC patients with ctDNA had shorter fragment sizes of cfDNA. Interestingly, the changes of mutant allele frequency in ctDNA concurrently correlated with clinical course. Positive ctDNA and fragmentation of cfDNA were significantly associated with poor cancer‐specific survival (P < .001, P = .011). In conclusion, our study shows the clinical utility of ctDNA status and cfDNA fragment size as biomarkers for prognosis and disease monitoring in RCC. 相似文献
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Kenji Tamura Kosei Hasegawa Noriyuki Katsumata Koji Matsumoto Hirofumi Mukai Shunji Takahashi Hiroyuki Nomura Hironobu Minami 《Cancer science》2019,110(9):2894-2904
Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death‐1, inhibiting binding to programmed death‐ligand 1 or 2 (PD‐L1 or PD‐L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2‐week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression‐free survival, and safety. PD‐L1 expression and microsatellite‐instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression‐free survival was 5.6, 3.4, and 1.4 months, and 6‐month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD‐L1‐positive (n = 5/15; 33%) versus PD‐L1‐negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI‐high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD‐L1 expression in cervical cancer and MSI‐high in corpus cancer may predict clinical activity of nivolumab in these cancers. 相似文献
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Yu Han Koh Jeremy Granger Thomas P Cundy Hilary AP Boucaut Day Way Goh 《Journal of pediatric surgery》2019,54(12):2631-2635
BackgroundSurgical techniques for fixation of the testis are varied and subject to ongoing debate. Non-sutured techniques may avoid the theoretical morbidities of sutured fixation of the testis yet are criticized for insufficient prophylaxis against future torsion. This study aims to compare outcomes between sutured (point-fixation) versus Jaboulay fixation.MethodsEmergency scrotal explorations performed at a tertiary hospital in the state of South Australia between February 2002 and December 2017 were analyzed to identify cases of testicular torsion. Primary outcome measures included future testicular torsions and return to theater episodes following initial testicular fixation. Secondary outcome measures included re-presentations and post-operative complications.ResultsA total of 482 scrotal compartments were explored in 244 boys with acute testicular torsion. Testis fixation was performed using sutured point-fixation in 58.4% and Jaboulay tunica plication in 41.6%. No future testicular torsion occurred regardless of fixation technique. There were no significant differences in returns to theater (0.4% versus 1.2%, p = 0.12), re-presentations (6.9% versus 6.0%, p = 0.83), and post-operative complications (1.7% versus 1.8%, p = 1.0) in testes that previously underwent sutured or Jaboulay fixation, respectively.ConclusionJaboulay testicular fixation techniques are comparable with sutured point-fixation techniques in effectiveness and morbidity.Type of StudyTreatment Study.Level of EvidenceLevel III. 相似文献
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Kenji Yamada Michinori Ito Hironori Kobayashi Yuki Hasegawa Seiji Fukuda Seiji Yamaguchi Takeshi Taketani 《Brain & development》2019,41(7):638-642
Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is classically caused by a congenital defect in electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH). Flavin adenine dinucleotide synthase (FADS) deficiency caused by mutations in FLAD1 was recently reported as a novel riboflavin metabolism disorder resembling MADD. Here, we describe a Japanese boy with FADS deficiency due to a novel mutation (p.R249*) in FLAD1. In the asymptomatic male infant born at full term, newborn screening showed positive results with elevated C5 and C14:1 acylcarnitine levels and an increased C14:1/C2 ratio. Biochemical studies were unremarkable except for lactic acidosis (pH 7.197, lactate 61 mg/dL). A diagnosis of MADD was suspected because of mild abnormalities of the acylcarnitine profile and apparent abnormalities of urinary organic acids, although mutations in the ETFA, ETFB, ETFDH, and riboflavin transporter genes (SLC52A1, SLC52A2, and SLC52A3) were not detected. Administration of riboflavin and L-carnitine was initiated at one month of age based on the diagnosis of “biochemical MADD” despite a lack of symptoms. Nevertheless, the acylcarnitine profile was not normalized. Symptoms resembling bulbar palsy, such as vocal cord paralysis and dyspnea with stridor, were present from 3 months of age. At 4 months of age, he became bedridden because of hypoxic-ischemic encephalopathy due to fulminant respiratory failure with aspiration pneumonia. At 2 years and 5 months of age, a homozygous c.745C > T (p.R249*) mutation in the FLAD1 gene was identified, confirming the diagnosis of FADS deficiency. His severe clinical course may be caused by this nonsense mutation associated with poor responsiveness to riboflavin. Persistent lactic acidosis and neuropathy, such as bulbar palsy, may be important for diagnosing FADS deficiency. Although the biochemical findings in FADS deficiency are similar to those in MADD, their clinical symptoms and severity may not be identical. 相似文献
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Shinichi Sakamoto Katsuhito Miyazawa Takahiro Yasui Taro Iguchi Misuzu Fujita Hiroaki Nishimatsu Takuro Masaki Toru Hasegawa Hatsuki Hibi Takashi Arakawa Ryosuke Ando Yoshinari Kato Noritaka Ishito Satoshi Yamaguchi Ryoji Takazawa Masao Tsujihata Makoto Taguchi Koichiro Akakura Akira Hata Tomohiko Ichikawa 《International journal of urology》2019,26(1):96-101
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