記述言語：日本語   出版者・発行元：中国四国産科婦人科学会  

2014年6月に女性生殖器腫瘍のWHO分類第4版が刊行され、新たにseromucinous tumorという分類が加えられた。改訂後5年が経過し、しばしば症例を経験するが、術前診断は容易ではない。そこで、我々はseromucinous borderline tumor(SMBT)の術前診断における画像検査や血液検査の特徴を示すことを目的とし、検討を行った。方法は、2006年3月から2019年4月までに当院で手術を行い、病理組織診断でSMBT、もしくは2014年改定によりSMBTに包括されたmullerian mixed-epitherial borderline tumor、endocervical-like mucinous borderline tumorと診断された21例を対象とし、診療録を参照し後方視的に検討した。対象年齢の年齢は中央値49歳、病期はI期20例(95.2%)、III期1例(4.8%)であった。血清中CA125は中央値63.2U/mLであり、35U/mL以上の異常高値を示した例は13例(61.9%)であった。腫瘍径は中央値6.0cmであった。MRI所見では15例(71.4%)において嚢胞内容液はT1強調画像で高信号を示し、子宮内膜症の存在を反映していた。T2強調画像では充実部分の低信号のコアとその周囲の高信号がSMBTの特徴とされるが、その所見を認めたのは8例(38.1%)であった。造影効果については既存の報告と同様に、様々な造影強度であった。今回SMBT21例の画像所見を中心に検討を行ったが、一定の特徴はあるものの非典型例も多数認めた。術前診断の精度向上にはさらなる症例の蓄積が望まれる。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged ≥70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

DOI： 10.3892/mco.2020.1989

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

DOI： 10.18926/AMO/58268

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記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

婦人科癌は治療法の進歩によりがんサバイバーが増え、がんサバイバーにとって、再発や死亡を防ぐことが重要である。がん治療終了後生活は生活習慣(食事、喫煙、飲酒)、運動などに注意することが大切とされているが、未だ婦人科領域におけるがん治療終了後生活の現状は把握されていない。そこでがん治療を行った229名の婦人科癌患者を対象に16項目のアンケートを用い、がん治療後の生活実態を調査した。定期的な外来検診を行った健康的な婦人科癌患者に直接アンケートを配布し、ボックスにて回収を行った(99.9%回収)。その結果、がん治療後食事量が減少した患者は24.0%、脂肪摂取が減った患者は34.9%、塩分量が減少した患者は24.9%、緑黄色野菜が増えた患者は47.2%であり、禁煙や喫煙減少した患者は59.2%、禁酒や飲酒量減少した患者は46.8%を占めており、がん治療終了後健康的な生活を送ることに多くのがんサバイバーが心掛けていることを認識できた。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7-16 months] in BRAF-mutant and 34 months (95% CI: 22-58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21-25 months) in BRAF-mutant and 38 months (95% CI: 24-42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

DOI： 10.18632/oncotarget.24735

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 (CI) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% CI = 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% CI = 80.6-97.5%) and a specificity of 97.9% (95% CI = 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 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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: This study aimed to investigate the correlation of sarcopenia findings with prognostic factors in patients with cervical cancer (CC) undergoing concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively collected data on body composition and clinicopathological features from the medical records of 60 patients with CC who underwent CCRT and analyzed correlations between prognosis and changes in body composition as measured by computed tomography (skeletal muscle and iliopsoas muscle [IM]). Statistical analyses were performed using the Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox proportional hazard regression was used for univariate and multivariate analyses. RESULTS: The median follow-up for all patients who were alive at the last follow-up was 33.5 months (range, 1-104 months). The PFS and OS rates were worse for patients with at least 15.0% than for those with less than 15.0% loss of skeletal muscle and IM from baseline (P < 0.001 for both). Furthermore, multivariate analyses showed that at least 15.0% loss of IM was an independent prognostic factor for PFS and OS (P = 0.002 for both). CONCLUSIONS: Sarcopenia (≥15.0% loss of IM from baseline) was revealed to be an important prognostic factor in patients with CC undergoing CCRT.

DOI： 10.1097/IGC.0000000000001127

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

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記述言語：日本語   出版者・発行元：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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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J05038&link_issn=&doc_id=20171221410019&doc_link_id=%2Fcv0mtrob%2F2017%2F006601%2F019%2F0109-0115%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2017%2F006601%2F019%2F0109-0115%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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) (physical well-being [PWB], social well-being, emotional well-being [EWB], and functional well-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patients with 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 χ 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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Collision tumors, which are characterized by the coexistence of two or more completely distinct and independent tumors in the uterine corpus, are very rare. A collision tumor is mainly composed of two distinct tumor types, epithelial and mesenchymal. To the best of our knowledge, there has only been a single case in which a choriocarcinoma with an endometrial carcinoma were coexistent but histologically distinct. We herein report the first case of a collision tumor in a 52-year-old woman, with a history of two pregnancies and two deliveries. The collision tumor was composed of three histologically distinct neoplasms in the uterine corpus, namely an endometrioid carcinoma, an undifferentiated carcinoma and a choriocarcinoma. The patient underwent hysterectomy, bilateral adnexectomy and pelvic lymph node dissection, followed by six cycles of adjuvant chemotherapy with paclitaxel/carboplatin due to the high risk of endometrial cancer, and an additional five cycles of chemotherapy with methotrexate, as the β-human chorionic gonadotropin level was beyond the normal range. Following adjuvant chemotherapy, the tumor markers were within normal limits and no relapses of the cancer have been observed during 1 year of follow-up. Diagnosing a collision tumor prior to surgery is difficult if the neoplasms are in close proximity, or if one of the tumors predominates. Careful pathological examination is crucial for accurately diagnosing the neoplasms in a collision tumor and ensuring appropriate management and a favorable prognosis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The Glasgow prognostic score (GPS) determined at pretreatment is important in the prediction of prognosis in various cancers. We investigated if the GPS used both at pretreatment and during concurrent chemoradiotherapy (CCRT) could predict the prognosis of patients with cervical cancer. METHODS: We collected GPS and clinicopathological data from the medical records of 91 patients who underwent CCRT for cervical cancer; their GPSs at pretreatment and during CCRT were retrospectively analyzed for correlations with recurrence and survival. Statistical analyses were performed using the Mann-Whitney U test. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. RESULTS: The median follow-up for all patients who were alive at the time of last follow-up was 38.0 months (range, 1-108 months). The DFS and OS rates of patients with a high GPS during CCRT (GPS 1 + 2; 55 patients; 60.4%) were significantly shorter than those for patients with a low GPS (GPS 0; 36 patients; 39.6%) (DFS, P < 0.001; OS, P < 0.001). Furthermore, multivariate analyses showed that high GPS during CCRT was an independent prognostic factor of survival for OS (P = 0.008). CONCLUSIONS: During CCRT, a high GPS was revealed to be an important predictor of survival for cervical cancer.

DOI： 10.1097/IGC.0000000000000485

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the present study was to identify the correlations between inflammation markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and C-reactive protein (CRP) and the prognosis in patients with recurrent cervical cancer. The associations among NLR, PLR and CRP and clinical characteristics and prognosis were examined in 32 patients receiving chemotherapy with recurrent cervical cancer following concurrent chemoradiation therapy (CCRT). The patient median survival time was 198 days (range, 42-1,022 days). Pretreatment NLR and PLR were significantly correlated with the recurrence of cervical cancer following CCRT (R=-0.538, P=0.002; and R=-0.542, P=0.001, respectively). Pretreatment PLR >322.0 was significantly associated with a poor prognosis for recurrent cervical cancer following CCRT by univariate and multivariate analyses (P=0.015 and P=0.029). These findings indicate that pretreatment PLR is an important predictor of prognosis in patients with recurrent cervical cancer following CCRT.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Placental mesenchymal dysplasia (PMD) rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.

DOI： 10.1155/2013/265159

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