International Trends in Decision-making Regarding Risk-reducing Salpingo-oophorectomy for Hereditary Breast and Ovarian Cancer Syndrome

遺伝性乳がん卵巣がん症候群に対するリスク低減卵巣卵管摘出術への意思決定に関する海外の動向


Emotions of patients with hereditary breast and ovarian cancer syndrome after risk reducing salpingo-oophorectomy

遺伝性乳癌卵巣癌症候群と診断された乳癌罹患患者のリスク低減卵管卵巣摘出術後の思い


Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy

Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. The patients' median age was 60 (range 33-80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m) before treatment had a poor prognosis (p = 0.016 and p < 0.001). Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

International Journal of Clinical Oncology


Exploring the Psychological Adjustment of Female Cancer Survivors in Terms of Femininity

女性性からみた女性がんサバイバーの心理的適応の探求

The purpose of this study is to explore the psychological adjustments female cancer survivors undergo with respect to their femininity. Semi-structured interviews were performed with 29 female cancer(breast or gynecologic cancer)survivors in their20s to50s. Qualitative descriptive study data was interpreted according to Krippendorff's content analysis method.As a result, six categories were generated as psychological adjustments utilized by female cancer survivors from the viewpoint of femininity : "I like the way I am" ; "I am charming as a woman" ; "I live independently as a woman" ; "I am expanding my life as a woman" ; "I can feel connected with someone" ; and "I have graduated from pessimism." These could be interpreted as psychological adaptations that reflect feminine emotions and reflect the strength and resilience of female cancer survivors. In order for female cancer survivors to adjust to living with cancer in a psychologically healthy way, it was suggested that nursing support was important to restore the feelings of the survivors from the perspective of these feminine characteristics.


海外文献における遺伝性腫瘍に関する遺伝カウンセリングの動向

海外文献における遺伝性腫瘍に関する遺伝カウンセリングの動向


Resveratrol suppresses proliferation and induces apoptosis of uterine sarcoma cells by inhibiting the Wnt signaling pathway.

Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.


Current status of chromosomal analysis in couples with recurrent miscarriage at Tokushima University Hospital

徳島大学病院産科婦人科における不育症患者に対する染色体検査の実施状況

Modern Trends in Obstetrics & Gynecology


Can systematic lymphadenectomy be omitted for low-risk endometrial cancer?

The objective of this study was to identify pathological indicators that could be used to identify a subgroup of patients with apparent stage I endometrial cancer who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer patients underwent primary surgery at Tokushima University Hospital. We retrospectively evaluated their clinical records and histopathological factors. Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade 1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty-four patients with a T1a endometrium-limited lesion did not exhibit lymph node metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph node metastasis, and these 3 cases exhibited approximately 50% myometrial invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy remain alive without recurrence. Systematic lymphadenectomy could be omitted for patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J. Med. Invest. 65:221-224, August, 2018.

The Journal of Medical Investigation : JMI


See and treat LEEP biopsy for cervical intraepithelial neoplasia grade 2/3

European Journal of Gynaecological Oncology


Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells.

Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling . Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.


Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma .

Effective chemotherapeutic strategies for uterine sarcoma are lacking; existing therapies achieve poor response rates. Previous studies have identified the prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) as a potential anticancer treatment; however, its effectiveness in uterine sarcoma has not been examined. Furthermore, the molecular mechanisms underlying the cytotoxic mechanism of 15d-PGJ2 remain unclear. Here, we evaluated the effects of 15d-PGJ2 alone and in combination with the tyrosine kinas inhibitor (TKI) dasatinib in uterine sarcoma cell lines (MES-SA, MES-SA/DX5 and SKN). 15d-PGJ2 inhibited cell growth and increased apoptosis. Western blotting demonstrated that 15d-PGJ2 treatment increased MEK and ERK phosphorylation, and decreased levels of phosphorylated AKT. Dasatinib in combination with 15d-PGJ2 significantly reduced cell proliferation compared with 15d-PGJ2 alone, and repressed both the AKT and MAPK pathways. The cell growth inhibition rate in the PGJ2 was 21.5±12.0, 35.3±5.4 and 28.3±4.2%, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the cell growth inhibition rate in the combination therapy was significantly higher compared with 15d-PGJ2 alone (MES-SA; 64.2±0.8, MES-SA/DX5;23.9±8.2 and SKN; 41.4±17.6%). The PGJ2 IC determined by MTT assay was 27.41,10.46 and 17.38 µmol/l, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the dasatinib IC was 6.68,17.30 and 6.25 µmol/l, respectively. Our findings demonstrate that 15d-PGJ2 suppresses proliferation by inactivating the AKT pathway in uterine sarcoma. Furthermore, combining 15d-PGJ2 with dasatinib produced a synergistic effect on cancer cell inhibition by repressing 15d-PGJ2-mediated activation of MAPK signaling, and further repressing AKT signaling. These results suggest that 15d-PGJ2 could be used in combination with dasatinib as a potential therapeutic approach for uterine sarcoma.


A case of metastatic orbital tumor with severe pain

激痛を伴いマイラゲルの合併症と鑑別を要した転移性眼窩腫瘍の1例

Japanese Journal of Clinical Ophthalmology


Resection of the vaginal vault for vaginal recurrence of cervical cancer after hysterectomy and brachytherapy

We describe our experiences with vaginal vault resection for vaginal recurrence of cervical cancer after hysterectomy and radiotherapy. After operative treatment, the rate of vaginal vault recurrence of uterine cervical cancer is reported to be about 5%. There is no consensus regarding the treatment for these cases. Between 2004 and 2012, eight patients with vaginal vault recurrence underwent removal of the vaginal wall via laparotomy after hysterectomy and radiotherapy. The median patient age was 45 years (range 35 to 70 years). The median operation time was 244.5 min (range 172 to 590 min), the median estimated blood loss was 362.5 mL (range 49 to 1,890 mL), and the median duration of hospitalization was 24.5 days (range 11 to 50 days). Two patients had intraoperative complications: a grade 1 bowel injury and a grade 1 bladder injury. The following postoperative complications were observed: one patient had vaginal vault bleeding, three patients developed vesicovaginal fistulae, and one patient had repeated ileus. Two patients needed clean intermittent catheterization. Local control was achieved in five of the eight cases. Vaginal vault resection is an effective treatment for vaginal recurrence of cervical cancer after hysterectomy and radiotherapy. However, complications of this procedure can be expected to reduce quality of life. Therefore, this operation should be selected with great care.


The presentation of an asymptomatic ovarian carcinosarcoma caught by BRCA1 mutation surveillance program


卵巣に発生した悪性リンパ腫の1例

卵巣に発生した悪性リンパ腫の1例


Ovarian teratoma with gliomatosis peritonei: 10 case reports


嚢胞状骨盤リンパ節転移を認めた子宮頸癌の1例

嚢胞状骨盤リンパ節転移を認めた子宮頸癌の1例

関東連合産科婦人科学会誌

関東連合産科婦人科学会誌


Lobular endocervical glandular hyperplasia を伴うadenocarcinoma in situ および子宮体癌を認めた重複癌の 1 例

The Journal of the Japanese Society of Clinical Cytology


Evaluation of residual disease in patients with cervical cancer treated by concurrent chemoradiotherapy

子宮頸癌同時化学放射線療法後の局所残存再発症例の検討

Objective : The objective of this study was to investigate the usefulness of cytology for detecting locoregional recurrence in cervical cancer patients treated by concurrent chemoradiotherapy (CCRT).
Study Design : This was a retrospective study of patients with stage Ib-IVa cervical cancer treated by CCRT. At our hospital, CCRT for cervical cancer failed in 14 patients. The cytologic and pathologic findings and MRI results before and after CCRT were evaluated, and the therapeutic response and status of local control were assessed on the basis of these evaluations.
Results : The evaluations could be completed in 14 patients (including 5 with squamous cell carcinoma, 5 with adenosquamous carcinoma, and 4 with adenocarcinoma), and the accuracy of cytology for the detection of recurrence was 50% (7/14). The reason for the false-negative cytological results in the remaining patients was necrotic change in the outer layer, and the presence of local residual diseases in these patients was confirmed by pathological evaluation and/or MRI.
Conclusion : Combined evaluation by cytology, pathologic examination, and MRI is useful for predicting residual disease in cervical cancer patients treated by CCRT.

目的 : 子宮頸癌に対して同時化学放射線療法 (CCRT) が広く行われている. しかし, 照射後の局所制御困難例もあり, 追加治療として根治的子宮全摘術が行われるようになってきた. このため, 局所腫瘍残存や局所再発症例の早期識別が重要である. そのための検査として細胞診, 組織診および画像診断について比較検討を行った.
方法 : 2005 年から 6 年間に当院で初回治療として根治的 CCRT を施行した子宮頸癌Ib 期∼IVa 期症例中, 局所残存もしくは局所制御後再発をきたした 19 例中, 細胞診未施行の 5 例を除外し, 14 例を対象とし, 後方視的に検討した.
成績 : 年齢中央値 43 歳 (32∼68 歳). 組織型は扁平上皮癌 5 例, 腺扁平上皮癌 5 例, 腺癌 4 例であった. 局所残存再燃症例の細胞診陽性率は 50% (7/14) であった. 細胞診陰性例では上皮細胞が経時的に減少し, 壊死組織および組織球が主体となっていた. 細胞診陽性例のなかには, MRI では病巣の描出を認めない症例も 2 例含まれていた.
結論 : 子宮頸癌 CCRT 後の局所判定は, 手術療法が必要な症例の早期識別のため行い, 細胞診, 組織診, MRI の併用による総合的な判断が重要であると考えられた.


Usefulness of intraoperative imprint cytology in ovarian germ cell tumors

This study retrospectively investigated the usefulness of intraoperative diagnosis based on imprint cytology and frozen sections for ovarian germ cell tumor. Intraoperative studies were reviewed for 23 cases with ovarian germ cell tumor treatment for which both frozen sections and imprint cytology were available. Final histopathologic diagnoses were compared with those based on intraoperative examinations. Underlying pathologies included dysgerminoma (n = 6), yolk sac tumor (n = 1), non-gestational choriocarcinoma (n = 1), mature cystic teratoma with malignant transformation (n = 1), immature teratoma (n = 11), and mixed germ cell tumor (n = 3). Discrepancies between intraoperative imprint cytology and definitive histologic diagnosis were seen in 6 of the 23 cases. Accuracy was 54.5% (6/11) for immature teratoma and 91.7% (11/12) for other tumors. Cytologic examination facilitated accurate diagnosis in both of our cases, and intraoperative diagnosis by frozen section proved inaccurate. These results demonstrate that intraoperative assessment based on imprint cytology for immature teratoma has a relatively lower sensitivity, but an acceptable sensitivity for other germ cell tumors. Diagnostic approaches combining frozen sections and imprint cytology are advisable to improve the yield for intraoperative diagnosis.


低悪性度子宮内膜間質肉腫が術後5年で急速な進展をきたした1例

低悪性度子宮内膜間質肉腫が術後5年で急速な進展をきたした1例


卵巣未熟奇形腫術後化学療法中に生じたgrowing teratoma syndromeを腹腔鏡下手術で診断し得た一例

Japanese Journal of Gynecologic and Obstetric Endoscopy

日本産科婦人科内視鏡学会雑誌


当院におけるプラチナ耐性再発卵巣癌に対するドキシルの使用経験

当院におけるプラチナ耐性再発卵巣癌に対するドキシルの使用経験

Modern Trends in Obstetrics & Gynecology


The possibility of vertical transmission of human papillomavirus through maternal milk

Human papillomavirus (HPV) DNA has been detected in the oral cavity of infants and breast cancer tissue, suggesting its vertical transmission through maternal milk. We determined whether HPV is detected in maternal milk and is vertically transmitted by breast-feeding. Informed consent was obtained, and maternal milk samples (n=80) were analysed for high-risk HPV DNA. In 43 women, this DNA was measured in the uterine cervix. In women with positive samples, this DNA was measured in the oral cavities of their children. The domain including HPV E6 and E7 was amplified by polymerase chain reaction using consensus primers, and HPV serotype determined by electrophoresis after restriction enzyme digestion. High-risk HPV-16 was detected in two of 80 samples (2.5%), and in these two cases, high-risk HPV was not detected in the uterine cervix or oral cavity of the child. It was concluded that the infection of HPV in maternal milk is rare (2/80); vertical transmission through maternal milk was not detected in this study (0/80). HPV infection through maternal milk may occur, but its likelihood is low.


A case of ovarian cancer developing shortly after initiation of TNF antagonist therapy

間質性肺炎を合併した皮膚筋炎に対してTNF拮抗薬使用中に発症した卵巣癌の1例

Japanese Journal of Gynecological Oncology


Gene gun-mediated skin transfection with FL gene suppresses the growth of murine fibrosarcoma.

Particle-mediated transfection is known as an efficient method of non-viral gene transfer. Flt3 ligand (FL) is a growth factor for hematopoietic progenitors; it promotes the growth of dendritic cells (DC). DCs are powerful antigen-presenting cells (APCs) and show a remarkable capacity to stimulate antigen-specific T-cell responses. In this study, we intended to investigate the suppressive effect on tumor growth by gene gun-mediated transfer of FL in a murine model. C57BL/6J mice were injected intradermally with MCA205 cells. DNA (pNGVL-hFLex)-coated gold particles were delivered to the mouse skin surrounding the target tumor. The expression of FL was determined by RT-PCR. Analyses by immunohistochemistry and fluorescence-activated cell sorter (FACS) revealed an increase in the number of DC after treatment with FL. Gene gun-mediated pNGVL-hFLex transfer significantly inhibited the growth of the MCA205 tumor. FL transfer markedly increased the number of CD11c(+) DCs in the tumor tissue. Further, the FL-transfected mice exhibited a significantly higher number of CD80(+) MHC-II cells. We successfully performed FL therapy using an in vivo gene gun in order to effectively mobilize DCs in situ and induce suppressive immunity.

The Journal of Medical Investigation : JMI


The impact of systematic para-aortic and pelvic lymphadenectomy on survival in patients with optimally debulked ovarian cancer.

The objective of this study was to verify the impact of systematic retroperitoneal lymphadenectomy on survival in patients with ovarian cancer.

The Journal of Obstetrics and Gynaecology Research


Desensitization treatment with cisplatin after carboplatin hypersensitivity reaction in gynecologic cancer

Platinum-based chemotherapy is the standard regimen for the treatment of gynecologic cancers; however, hypersensitivity reactions (HR) to platinum often lead to discontinuation of this effective treatment. Here we performed a desensitization protocol for platinum infusion in 3 patients who required platinum re-administration after developing HR. Two patients (Case 1 and 2) were treated with the desensitization protocol successfully without developing HR during the subsequent 3 courses. Case 3 tolerated desensitization well for 2 courses, but in the 3(rd) course, she developed severe HR immediately after the initiation of cisplatin infusion because the desensitization protocol was unintentionally omitted. These cases show the usefulness and effectiveness of the desensitization protocol for the continuation of platinum treatment in patients who have undergone an extended number of treatments.


当院における過去3年間の腹腔鏡下手術を施行した子宮外妊娠症例の検討

当院における過去3年間の腹腔鏡下手術を施行した子宮外妊娠症例の検討


子宮頸癌Ⅰb2-Ⅲb期に対する術前化学療法 手術(NAC-S)とConcurrent chemoradiotherapy (CCRT)の比較

Japanese Journal of Cancer and Chemotherapy


卵巣癌に対する化学療法中に発症した治療関連骨髄異形成症候群の2 例

卵巣癌に対する化学療法中に発症した治療関連骨髄異形成症候群の2 例


A case of ovarian endometrioid adenocarcinoma with a yolk sac tumor component.

Endometrioid adenocarcinoma of the ovary coexists very rarely with yolk sac tumor (YST). This unusual mixed tumor is thought to be a rare variant of endometrioid ovarian carcinoma because of its aggressive behavior, lack of response to chemotherapy, and unfavorable prognosis. We report a case of ovarian endometrioid adenocarcinoma with a YST component in a postmenopausal woman. The patient was treated by surgery and a combination of bleomycin, etoposide, and cisplatin and taxol and carboplatin. She has been clinically free of tumor for 20 months. Immunohistochemically, the YST component reacted for alpha-fetoprotein. YST areas were negative for both CA125 and sex-hormone receptors. Cytokeratin7 and epithelial membrane antigen were negative in YST, but positive in endometrioid adenocarcinoma. The occurrence of this unusual case suggests that even somatic carcinomas may acquire an extraembryonal germ cell differentiation.

International Journal of Gynecological Cancer


Mismatch repair deficiency in young patients of reproductive age with endometrial cancer and atypical endometrial hyperplasia

生殖年齢期に発生した子宮内膜癌・異型内膜増殖症におけるミスマッチ修復蛋白発現に関する検討

MPA therapy is widely administered to patients with early-stage endometrial cancer and atypical endometrial hyperplasia (AEH) who desire a fertility-preserving treatment modality. We examined the relationship between MMR protein expression and the effects of MPA therapy, risk of relapse, prognosis, and familial history in 21 patients. We observed MMR deficiency in 7 patients (MLH1: 4, PMS2: 5, MSH2: 2, and MSH6: 2). All patients with lymph node metastasis or who died had MLH1 deficiency. In 13 of 21 patients, we performed MPA therapy for fertility preservation and confirmed MMR deficiency in 2. After the initial treatment, ovarian cancer developed in 2 patients, one of whom had Peutz-Jeghers syndrome. Due to the small sample size of this study, we found no significant association between MMR deficiency and the effects of MPA therapy or the risk of relapse. Many young patients with endometrial tumors may have inherited diseases, although not necessarily with MMR deficiency. Therefore, clinical assessment considering their past history and family history should be performed prior to each treatment. Our findings will serve as a catalyst for future studies with larger sample sizes.

妊孕性温存療法希望の早期子宮体癌および異型内膜増殖症症例にMPA療法を行うも不応や再燃症例も経験する．徳島大学産科婦人科で初回治療を行った若年子宮体癌および異型内膜増殖症21症例を対象にミスマッチ修復(mismatch repair;MMR)蛋白発現と，MPA療法の効果，再燃リスク，および予後との関連について検討した．MMR蛋白の発現欠失は7例で認め，MLH1欠失4例，PMS2欠失5例，MSH2欠失2例，MSH6欠失2例であった．リンパ節転移例と再発原病死例はいずれもMLH1欠失例であった．MPA療法施行13例中，MMR欠失を2例で認めたが，いずれもMPA奏効・無病生存例であった．初回治療後，異時性卵巣癌発症を2例に認め，このうちの1例はPeutz-Jeghers症候群であった．本検討では対象例が少なく，MMR蛋白発現とMPA療法の効果および再燃リスクとの間に有意な関連は確認できなかった．しかしMMR欠失を認めなくとも， 遺伝性疾患を背景にもつハイリスク症例もあり，家族歴を考慮した適切な医学的管理が必要であると考えられた．


嚢胞状帝王切開瘢痕部が着床部結節から成っていた一例

嚢胞状帝王切開瘢痕部が着床部結節から成っていた一例

Modern Trends in Obstetrics & Gynecology


カルチノイド成分を合併した粘液生卵巣癌の1例

カルチノイド成分を合併した粘液生卵巣癌の1例