Faculty Profiles - NAKAMURA Keiichiro

Accuracy of four mononucleotide-repeat markers for the identification of DNA mismatch-repair deficiency in solid tumors

Yuko Takehara, Takeshi Nagasaka, Akihiro Nyuya, Tomoko Haruma, Junko Haraga, Yoshiko Mori, Keiichiro Nakamura, Toshiyoshi Fujiwara, C. Richard Boland, Ajay Goel

JOURNAL OF TRANSLATIONAL MEDICINE 16 2018.1

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC

Background: To screen tumors with microsatellite instability (MSI) arising due to DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are commonly used. In spite of its several strengths, the pentaplex assay is not robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome this challenge, we designed this study to develop and optimize a panel of four quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid tumors with dMMR, especially dMSH6.Methods: To improve the sensitivity for tumors with dMMR, we established a quasi-monomorphic variant range (QMVR) of 3-4 bp for the four Tetraplex markers. Thereafter, to confirm the accuracy of this assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR [45 MutL homolog (MLH) 1-deficient, 45 MutS protein homolog (MSH)2-deficient, and 15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set. In addition, we analyzed a cohort of 138 endometrial cancers (EC) by immunohistochemistry to determine MMR protein expression and validation of our new MSI assay.Results: Using the criteria of >= 1 unstable markers as MSI-positive tumor, our assay resulted in a sensitivity of 97.1% [95% confidence interval (Cl) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% Cl = 91.5-97.4%) for pMMR CRC specimens. Among the 138 EC specimens, 41 were dMMR according to immunohistochemistry. Herein, our Tetraplex assay detected dMMR tumors with a sensitivity of 92.7% (95% Cl = 80.6-97.5%) and a specificity of 97.9% (95% Cl = 92.8-99.4%) for pMMR tumors. With respect to tumors with dMSH6, in the CRC-validation set, Tetraplex detected | dMSH6 tumors with a sensitivity of 86.7% (13 of 15 dMSH6 CRCs), which was subsequently validated in the EC test set I as well (sensitivity, 75.0%; 6 of 8 dMSH6 ECs).Conclusions: Our newly optimized Tetraplex system will help offer a robust and highly sensitive assay for the identification of dMMR in solid tumors.

DOI： 10.1186/s12967-017-1376-4

Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability. International journal

Tomoko Haruma, Takeshi Nagasaka, Keiichiro Nakamura, Junko Haraga, Akihiro Nyuya, Takeshi Nishida, Ajay Goel, Hisashi Masuyama, Yuji Hiramatsu

PloS one 13 ( 4 ) e0195655 2018

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. MATERIALS AND METHODS: A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC). RESULTS: Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival. CONCLUSIONS: This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

DOI： 10.1371/journal.pone.0195655

骨盤腎と全身性強皮症を合併し治療方針の決定に難渋した子宮頸癌の1例

秋定幸, 春間朋子, 原賀順子, 依田尚之, 楠本知行, 中村圭一郎, 関典子, 増山寿, 平松祐司

現代産婦人科 66 ( 1 ) 109 - 115 2017.12

Language：Japanese Publisher：中国四国産科婦人科学会

今回比較的稀な先天奇形である骨盤腎と、全身性強皮症を合併した子宮頸癌IIB期の1例を経験した。症例は65歳3経妊3経産。前医での子宮頸部組織診で扁平上皮癌の診断で、精査加療目的に当科紹介となった。当科受診時の内診で子宮頸部に浸潤癌様腫瘤と軽度の子宮傍組織浸潤を認めた。MRI検査では子宮頸部に長径5.2cmの不整形腫瘤と両側閉鎖リンパ節の腫大を指摘され、PET/CT検査で同部位へのFDGの高集積を認めた。子宮頸癌IIB期(T2bN1M0)と診断した。同時化学放射線治療(CCRT)を行った場合、放射線照射領域内に左骨盤腎が入り、左腎臓は無機能腎となることが予想され、さらに化学療法で白金製剤を使用することから腎機能の悪化が懸念された。しかし病期、肥満を考慮し、本人と相談の上、腎機能の推移を慎重にモニタリングしながらCCRTを行う方針とした。しかしCCRT治療開始後(全骨盤18Gy照射、weekly Cisplatin 40mg/m21コース)、皮膚への色素沈着と手指硬化を認め全身性強皮症と診断された。全身性強皮症患者に対する放射線治療はGrade 3以上の晩期障害がコントロール群と比較し約2.5倍になったとの報告もあり、放射線科治療医と相談しCCRTの継続は困難と判断した。手術療法を行う方針とし、単純子宮全摘、両側付属器切除術、骨盤リンパ節郭清を施行した。術後病理検査では腫瘍の縮小を認めており、左閉鎖リンパ節に腫瘍の瘢痕があるものの、その他明らかなリンパ節転移は認めなかった。術後は化学療法を施行し治療後3ヵ月現在再発兆候なく経過観察中である。(著者抄録)

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The Influence of Adverse Effects on Quality of Life of Survivors of Gynecologic Cancer

Chiaki Omichi, Keiichiro Nakamura, Junko Haraga, Naoyuki Ida, Masayuki Saijo, Takeshi Nishida, Tomoyuki Kusumoto, Hisashi Masuyama

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 27 ( 9 ) 2014 - 2019 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objective: The objective of this observational study was to investigate correlations between adverse effects (lower-extremity lymphedema [LEL], dysuria, and severe gastrointestinal symptoms) and quality of life (QOL) (physicalwell-being [PWB], socialwell-being, emotional well-being [EWB], and functionalwell-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patientswith gynecologic cancer (GC).Methods: From August 2012 to October 2016, questionnaire responses and clinical data of 75 patients with GC were collected and assessed by treatment received. The chi(2) test was used to determine the significance of correlations.Results: Participants with LEL had significantly poorer QOL than did those without it in the domains of PWB at posttreatment1 (P = 0.026) and EWB at posttreatment2 (P = 0.020). Moreover, patients with 2 adverse effects (LEL plus dysuria or severe gastrointestinal symptoms) had significantly poorer QOL than did those with no or single adverse effect in the domains of PWB at posttreatment1 and posttreatment2 (posttreatment1: P = 0.049, P = 0.001; posttreatment2: P = 0.002, P = 0.028) and poorer QOL compared with those with no adverse effect in the domain of EWB at posttreatment1 (P = 0.017).Conclusions: Poorer QOL in emotional and physical domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical therapy not only on survival but also on the QOL of survivors.

DOI： 10.1097/IGC.0000000000001125

当院での悪性腫瘍手術における希釈式自己血輸血の現状

Reply to "Letter to the Editor" by M. Saijo et al. "Glasgow prognostic score is predictive of prognosis for patients with endometrial cancer ". International journal

Masayuki Saijo, Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

European journal of obstetrics, gynecology, and reproductive biology 216 260 - 260 2017.9

大平安希子, 原賀順子, 関典子, 依田尚之, 西條昌之, 大道千晶, 西田傑, 小川千加子, 楠本知行, 中村圭一郎, 増山寿

現代産婦人科 66 ( Suppl. ) S62 - S62 2017.9

腹腔鏡下子宮筋腫核出術後に生じた巨大parasitic myomaの一例

原賀順子, 玉田祥子, 田中梓菜, 楠本知行, 中村圭一郎, 増山寿, 平松祐司

日本産科婦人科内視鏡学会雑誌 33 ( Suppl.I ) 1164 - 1164 2017.8

腹腔鏡下子宮体がん手術単一施設同一術者での経験から

楠本知行, 依田尚之, 西條昌之, 原賀順子, 大道千晶, 西田傑, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 33 ( Suppl.I ) 352 - 352 2017.8

Gene expression profiles in BRAF V600E mutant colorectal cancer and association with SFRP2 methylation status

Kazuya Yasui, Takeshi Nagasaka, Toshiaki Toshima, Takashi Kawai, Kunitoshi Shigeyasu, Yoshiko Mori, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

巨大parasitic myomaの一例

玉田祥子, 田中梓菜, 早田桂, 楠本知行, 鎌田泰彦, 中村圭一郎, 関典子, 増山寿, 平松祐司

産婦人科手術 ( 28 ) 157 - 157 2017.6

子宮内膜癌再発に対する妊孕性温存治療後、生殖補助医療で妊娠し生児を得た一例

矢野肇子, 酒本あい, 安藤まり, 樫野千明, 松岡敬典, 長谷川徹, 早田桂, 小谷早葉子, 楠本知行, 鎌田泰彦, 中村圭一郎, 関典子, 増山寿, 中塚幹也, 平松祐司

現代産婦人科 65 ( 2 ) 217 - 221 2017.5

Language：Japanese Publisher：中国四国産科婦人科学会

近年40歳以下の若年子宮内膜癌患者は増加しており、その妊孕性温存が注目されている。我々は子宮内膜癌IA期発症後にmedroxyprogesterone acetate(MPA)による高用量黄体ホルモン療法後の再発に対し再度MPA療法を行い、生殖補助医療により生児を得た症例を経験したので報告する。症例は32歳女性既婚、未経妊。不正性器出血を主訴に前医を受診した。子宮内膜組織診でendometrioid adenocarcinoma、Grade 1と診断され、当科紹介となった。当院での精査で、子宮内膜癌IA期相当と診断、妊孕性温存希望のため、MPA療法を6ヵ月間行った。子宮内膜組織診で悪性所見の消失を確認後、妊娠を試みるも妊娠成立せず、初回治療から3年2ヵ月後に組織診断でendometrioid adenocarcinomaの再発が指摘された。依然挙児希望は強く、リスクを十分に説明した上で再度MPA療法を6ヵ月間行った。子宮内膜組織診で悪性所見の消失を確認し、不妊治療を再開した。生殖補助医療を選択し、GnRHアンタゴニスト法で14個の卵子を採取し体外受精した。受精後6日目に胚盤胞まで達した3AA胚1個を凍結した。子宮内膜組織診で陰性を確認後、ホルモン補充周期で凍結融解胚移植を行い、妊娠成立した。妊娠経過は順調で、妊娠40週4日に胎児機能不全の適応で帝王切開術を施行した。MPA療法は治療後1〜3年以内に再発する症例が多く、寛解後早期の不妊治療開始が推奨され、体外受精により妊娠する症例が多い。本症例のように子宮内膜癌再発後にMPA療法と生殖補助医療を行い、生児を得た症例の報告は散見されるが、本邦のガイドラインでは推奨されていないため、十分な説明と同意のもとに慎重に行われるべきである。(著者抄録)

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Glasgow prognostic score is a prognosis predictor for patients with endometrial cancer

Masayuki Saijo, Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY 210 355 - 359 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objective: This study investigated whether the inflammation-based Glasgow prognostic score (GPS) predicted the prognosis of patients with endometrial cancer (EC) in terms of progression-free survival (PFS) and overall survival (OS).Study design: Pretreatment GPS was examined to determine the correlations with recurrence and survival in 431 patients with EC. Statistical analyses were performed using the Mann-Whitney U test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses.Results: Median PFS and OS were 49.7 and 52.7 months, respectively. The follow-up range was I to 140 months. Kaplan-Meier analysis revealed that patients with EC cancer and high GPS (GPS 2) had a shorter PFS and OS than those with lower GPS (GPS 0 + 1) (PFS: P < 0.001; OS; P < 0.001). On multivariate analysis, GPS (GPS 2) was an independent predictor of both recurrence (P < 0.001) and survival (P < 0.001) for all cases of EC.Conclusion: GPS can be useful as an indicator of poor prognosis in patients with EC. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ejogrb.2017.01.024

Radical Hysterectomy Plus Concurrent Chemoradiation/Radiation Therapy Is Negatively Associated With Return to Work in Patients With Cervical Cancer

Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 27 ( 1 ) 117 - 122 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objective: Cervical cancer is one of the most common malignant diseases in working-age women. This study investigated the influence of adverse effects of various treatment modalities on return to work in women with cervical cancer.Methods: Questionnaires and clinical data from medical records of 97 patients with early stage (stages I and II) cervical cancer were collected and assessed by treatment received. The following treatment groups were analyzed for correlations between time to return to work and various adverse effects: radical hysterectomy (RH) alone, RH group (n = 29); concurrent chemoradiation therapy (CCRT)/radiation therapy (RT) alone, CCRT/RT group (n = 21); and RH + CCRT/RT group (n = 47). The chi(2) test was used to determine the significance of the correlations.Results: The mean age at the time of diagnosis was 43.0 years and the average interval since treatment was 4.5 years. The RH + CCRT/RT group was the most strongly negatively associated with return towork in employed patients who had undergone CCRT/RT group of cervical cancer (P = 0.012). There was a significant association between failure to return to work and lower extremity lymphedema (P = 0.049). A more than-6-month interval between treatment and return towork and reduced personal income occurred in a significantly higher percentage of patients in the RH + CCRT group than in the CCRT/RT group (P = 0.034 and P = 0.034).Conclusions: Of the treatments assessed, RH + CCRT/RT has the greatest negative effect on return to work in women with cervical cancer.

DOI： 10.1097/IGC.0000000000000840

Pretreatment prognostic nutritional index is a significant predictor of prognosis in patients with cervical cancer treated with concurrent chemoradiotherapy. International journal

Junko Haraga, Keiichiro Nakamura, Chiaki Omichi, Takeshi Nishida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Norihisa Katayama, Susumu Kanazawa, Yuji Hiramatsu

Molecular and clinical oncology 5 ( 5 ) 567 - 574 2016.11

Language：English Publishing type：Research paper (scientific journal)

This study investigated whether pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) are prognostic factors in patients with cervical cancer who undergo concurrent chemoradiotherapy (CCRT) and radiotherapy (RT). A total of 131 patients who underwent CCRT and RT for cervical cancer were retrospectively investigated and the correlations of NLR, PLR and PNI with clinical parameters and prognosis were assessed in CCRT and RT. The CCRT and RT groups had a median progression-free survival (PFS) of 41.82 and 24.72 months, respectively, and an overall survival of 49.70 and 29.56 months, respectively. At a cut-off value of NLR≥2.85, the PFS and OS in patients with higher NLR undergoing RT were significantly shorter compared with those in patients with lower NLR (P=0.029 and P=0.017, respectively). At a cut-off value for PNI of ≤48.55 in patients undergoing CCRT and ≤45.80 in patients undergoing RT, the PFS and OS in patients with lower PNI were significantly shorter compared with those in patients with higher PNI (PFS and OS with CCRT, P<0.001 and P<0.001, respectively; PFS and OS with RT, P=0.002 and P=0.008, respectively). Multivariate analyses also identified low PNI as an independent prognostic factor for PFS and OS in patients receiving CCRT. Therefore, low PNI was shown to predict poor prognosis in patients with cervical cancer.

Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells

Hisashi Masuyama, Keiichiro Nakamura, Etsuko Nobumoto, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF ONCOLOGY 49 ( 3 ) 1211 - 1220 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Epithelial ovarian cancer remains the most devastating gynecologic cancer with drug resistance and rapid recurrence. Pregnane X receptor (PXR) is a nuclear receptor that affects drug metabolism/efflux and drug-drug interaction through control of multiple drug resistance 1 (MDR1), which implies a major role in multidrug resistance, and other genes. We examined whether the inhibition of PXR-mediated pathway using siRNA interference and an antagonist for PXR could influence the paclitaxel and cisplatin cytotoxicity in ovarian cancer cells. PXR agonists, phthalate and pregnenolone had significant positive effects on cytochrome P450 (CYP) 3A4 expression and PXR-mediated transcription through the CYP3A4 promoter, whereas MDR1 expression and PXR-mediated transcription though the MDR1 promoter were significantly increased in the presence of paclitaxel or cisplatin. Downregulation of PXR suppressed the augmented MDR1 expression and PXR-mediated transcription by PXR ligands, and significantly enhanced cell growth inhibition and apoptosis in the presence of paclitaxel or cisplatin. Additionally, ketoconazole, a PXR antagonist, suppressed the augmented MDR1 expression and PXR-mediated transactivation by paclitaxel and cisplatin, and enhanced cell growth inhibition and apoptosis in their presence. In conclusion, inhibition of PXR-mediated pathways could be a novel means of augmenting sensitivity, or overcoming resistance to anticancer agents for ovarian cancer.

DOI： 10.3892/ijo.2016.3611

Dimethylesculetin ameliorates maternal glucose intolerance and fetal overgrowth in high-fat diet-fed pregnant mice via constitutive androstane receptor

Hisashi Masuyama, Takashi Mitsui, Jota Maki, Kazumasa Tani, Keiichiro Nakamura, Yuji Hiramatsu

MOLECULAR AND CELLULAR BIOCHEMISTRY 419 ( 1-2 ) 185 - 192 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice. Dimethylesculetin suppressed the mRNA expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and lipogenic genes, sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1, and enhanced CAR-mediated transcription. Blocking the CAR-mediated pathway abolished the effect of DE in vitro. DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in HFD-induced obese pregnant mice in vivo. Our data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.

DOI： 10.1007/s11010-016-2772-4

Return to work after cancer treatment of gynecologic cancer in Japan. International journal

Keiichiro Nakamura, Hisashi Masuyama, Takeshi Nishida, Junko Haraga, Naoyuki Ida, Masayuki Saijo, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

BMC cancer 16 558 - 558 2016.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Gynecologic cancer is one of the most common malignant diseases in working-age women. This study investigated whether several characteristics influence return to work after treatment of gynecologic cancer. METHODS: We investigated the correlations between return to work and several other characteristics in 199 gynecologic cancer survivors. Questionnaires were distributed to patients with cancer (≥1 year after treatment and age of <65 years) who visited Okayama University. Logistic regression analysis and receiver operating characteristic curves were used to determine whether each characteristic influenced return to work (no return to work or job change) in these gynecologic cancer survivors. RESULTS: For all patients, the mean age at the time of diagnosis was 47.0 years, and the average number of years after treatment was 4.5. Forty-four patients (53.7 %) who were non-regular employees continued to be employed at the same workplace. Non-regular employment had a significantly higher area under the curve (AUC) (0.726) than other characteristics in terms of negatively affecting return to work. Additionally, non-regular employment tended to have a higher AUC (0.618) than other characteristics in terms of job changes. CONCLUSIONS: Non-regular employment was the variable most likely to negatively affect return to work and job changes in employed patients who underwent treatment for gynecologic cancer.

DOI： 10.1186/s12885-016-2627-0

Glasgow prognostic score is an independent marker for poor prognosis with all cases of epithelial ovarian cancer

Chiaki Omichi, Keiichiro Nakamura, Junko Haraga, Hisashi Masuyama, Yuji Hiramatsu

CANCER MEDICINE 5 ( 6 ) 1074 - 1080 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Inflammatory markers are important prognostic factors in various cancers. This study investigated whether inflammatory markers of the Glasgow prognostic score (GPS) predicted progression-free survival (PFS) and overall survival (OS) for patients with all cases of epithelial ovarian cancer (OC). Pretreatment GPS was examined for the correlations with PFS and OS in 216 patients in all stages of epithelial OC. Statistical analyses were performed using the Mann-Whitney U-test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. For all patients, the median PFS was 35.1 months, and median OS was 46.7 months; follow-up range was 1-162 months. Kaplan-Meier analysis revealed that patients with high GPS (GPS 2) at pretreatment had a shorter PFS and OS than did patients with lower GPS (GPS 0 + 1) in for early, advanced, and all-stages of OC (PFS: P < 0.001 for early-, advanced- and all-stages; OS; P < 0.001 for early- and all-stage, P = 0.015 for advanced-stage). GPS (GPS 2) was also found to be an independent predictor of both recurrence (P = 0.002) and survival (P = 0.001) of all cases of epithelial OC by a multivariate analysis. GPS can serve as an indicator of poor prognosis in patients with all stages of epithelial OC, including early-stage disease and regardless of histology.

DOI： 10.1002/cam4.681

Neutrophil to lymphocyte ratio in the pre-treatment phase of final-line chemotherapy predicts the outcome of patients with recurrent ovarian cancer. International journal

Keiichiro Nakamura, Takeshi Nagasaka, Takeshi Nishida, Tomoko Haruma, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

Oncology letters 11 ( 6 ) 3975 - 3981 2016.6

Language：English Publishing type：Research paper (scientific journal)

Inflammation and tumor immunology are associated with prognosis in a variety of cancers. The aim of the present retrospective study was to identify associations between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), cancer antigen 125 (CA125) concentrations, tumor response, performance status (PS) and survival of patients that developed recurrent ovarian cancer subsequent to receiving chemotherapy. The NLR and PLR measured prior to fourth-line chemotherapy were significantly increased compared with those measured prior to second-line chemotherapy (P=0.029 and 0.049, respectively). By using receiver operating characteristic curves, the cut-off values were determined for the NLR, PLR and CA125 levels that were measured during the pre-treatment phase, which predicted the outcomes. According to univariate analyses, pre-treatment NLR >3.91, PLR >299.0 and PS 2 were each significantly associated with poor outcomes (P=0.001, 0.005 and 0.021, respectively). According to multivariate analyses, only pre-treatment NLR was associated with poor outcome (P=0.035). The present findings indicate that pre-treatment NLR is an important predictor of prognosis in patients with ovarian cancer that experience recurrence following chemotherapy.