野村 弘行

This study shows that the newly designed self-administered questionnaire is a useful tool to assess the risk of hereditary cancer for patients with gynecologic cancer.A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients. Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups. A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20-25% risk and three patients (2.9%) had a 5-10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5-10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5-10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91). In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.

AimTo examine the usefulness of the neutrophil : lymphocyte (N/L) ratio as a cost-effective and simple diagnostic marker of mature cystic teratoma (MCT) with malignant transformation (MT). MethodsA retrospective chart review was performed between 1998 and 2013 of 12 MCT patients with MT and between 2009 and 2013 of 130 patients with benign MCT. Data were collected on age, tumor size, white blood cell count with differential counts, tumor marker levels, and presenting features. ResultsOlder age, greater tumor size, higher CA19-9 or CA125, higher neutrophil count, and higher N/L ratio were associated with MT on univariate analysis. White blood cell count; lymphocyte count; and the tumor marker squamous cell carcinoma antigen were not associated with MT. Older age (median), larger tumor size (10 cm), and high N/L ratio (5.0) were predictors of MT (hazard ratio, 11.51, 5.87, and 11.11, respectively). Six of 12 patients were diagnosed with MT on preoperative magnetic resonance imaging and five of 12 had an N/L ratio 5.0. ConclusionsNeutrophil : lymphocyte ratio is a potential preoperative diagnostic marker of MT. The optimal cut-off should be determined in future large-scale studies.

We investigated whether UGT1A1 polymorphisms are associated with the prognosis of ovarian cancer patients treated with irinotecan. UGT1A1 genotypes were analyzed in 11 stage I ovarian clear cell carcinoma patients who received irinotecan as first-line therapy. Progression-free survival, overall survival and adverse events were also assessed for each genotype. Three patients harbored UGT1A1*1/*6 while another three harbored UGT1A1*1/*28. Two patients with a wildtype genotype experienced recurrence and one died, whereas no recurrence or death was observed in patients with heterozygous genotypes. Adverse events tended to be more severe in patients with UGT1A1*6 and *28, although progression-free survival and overall survival rates tended to be better than in wild-type; the differences were not significant. We conclude that UGT1A1 polymorphisms have the potential to be a prognostic marker of irinotecan treatment.

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3% BRCA1), 8 (3.5% BRCA2), 6 (2.6% mismatch repair genes), 3 (1.3% RAD51D), 2 (0.9% ATM), 1 (0.4% MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Trousseau症候群は悪性腫瘍に伴う血液凝固線溶異常により血栓塞栓症を生じる病態であり、進行例が多く予後不良である。当科でも2006〜2014年に5例の脳梗塞を発症したTrousseau症候群を経験した。年齢の中央値は63歳(54〜69歳)で、合併悪性腫瘍は子宮体癌2例、卵巣癌2例、子宮頸癌1例であり、組織型は類内膜腺癌2例、漿液性腺癌2例、扁平上皮癌1例であった。4例は進行再発癌、1例は早期癌であった。病態はいずれも多発脳梗塞によるものであり、脳出血の症例はなかった。感染性心内膜炎との鑑別に難渋した進行再発例の1例を除く全症例でヘパリンナトリウムによる抗凝固療法を開始したが、手術不能な進行再発癌の4例は原疾患の治療が奏効せず、発症後約2ヵ月以内に死亡した。手術で腫瘍を完全摘出できた早期の卵巣癌の1例は予後良好であり、手術可能な症例では原疾患の摘除により予後改善の可能性があることが示唆された。(著者抄録)

Purpose Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC. Patients and Methods Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m2 on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m2 plus carboplatin area under the curve 6.0mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression free survival. Secondary end points were overall survival, overall response rate, and adverse events. Results Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC. Conclusion No significant survival benefit was found for CPT- P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC. (C) 2016 by American Society of Clinical Oncology

重複癌は2つ以上の臓器または組織に異なる種類の癌腫が発生するものであり、子宮体部および卵巣に同時発生する例もしばしば経験される。臨床的には一方の癌による転移との鑑別に苦慮することも少なくないが、両者では臨床的な取扱いや経過が異なるため、その鑑別は重要である。そこで、2002年から2015年に当院において経験した子宮体部・卵巣同時発生重複癌40症例の臨床病理学的背景を検討した。臨床的には診断時の平均年齢は48.5歳と比較的若年者が多く、病理学的には高分化、早期の症例が多数を占め、組織型は子宮体部・卵巣ともに類内膜腺癌が最も多かった。類内膜腺癌重複癌の症例では85.1%で子宮内膜症の併存を認めた。(著者抄録)

Aim: There is poor evidence regarding effective treatment for recurrent endometrial cancer. We treated patients with recurrent endometrial cancer with docetaxel-cisplatin (DP) therapy as second-line or third-line chemotherapy. We aimed to evaluate the feasibility and efficacy of DP therapy for patients with recurrent endometrial cancer. Patient and Methods: We included 26 patients diagnosed with recurrent endometrial cancer, who underwent DP chemotherapy at our Institution. Docetaxel at 70 mg/m(2) and cisplatin at 60 mg/m(2) were administered by intravenous injection every 3 weeks. We retrospectively analyzed the clinicopathological factors associated with the response rate (RR) and prognosis. We also analyzed the adverse effects of DP therapy. Results: Median follow-up was 33.8 months and the median number of therapy cycles was six. Grade 3 or 4 adverse effects included leukopenia (66%), neutropenia (81%), anemia (9%), diarrhea (12%), general fatigue (12%), liver dysfunction (4%), peripheral neuropathy (4%), and hyponatremia (4%). RR was 58% and the median progression-free survival (PFS) was 7.5 months. The group with a treatment-free interval of 6 months or more tended to have better PFS than that with less than 6 months (p=0.01). The group with a platinum-free interval of 6 months or more had significantly better PFS than that with less than 6 months (p=0.09). Although the history of taxane usage was not relevant to prognosis, a taxane-free interval of 12 months or more was associated with a tendency for better PFS (p=0.06). Conclusion: DP therapy was fully feasible and demonstrated efficacy for patients with recurrent endometrial cancer.

Objective. The objective of this study is to evaluate the detection rate and diagnostic accuracy of sentinel lymph node (SN) mapping using hysteroscopic sub-endometrial injection of 99m-Technetium labeled phytate (Radio-isotope; RI method) and subserosal Indocyanine green (ICG) injection (Dye method) in patients with endometrial cancer. Methods. From April 2009 to December 2012, prospective evaluation of 57 Japanese endometrial cancer patients undergoing SN mapping using RI method combined with Dye method was done. To combine RI method or no was determined by a status of RI supply of the tracer injection day. As for 32 cases, both (RI + Dye) methods were used and 23 cases were performed only in Dye method. The primary endpoint was estimation of sensitivity and negative predictive value (NPV) of SN, and analysis of the distribution of SNs with metastasis. Results. At least one SN was detected in 100% and average number of detected SNs was 6.0 in RI + Dye method. Sensitivity and NPV were 100%, 100%, respectively. From results of SN mapping, 62.8% of SNs were present in pelvic and 37.1% in para-aortic lymph nodes (PAN). Total 563% of lymph nodes with metastasis were present in pelvic and 43.8% in PAN; and the distribution has no difference with SN mapping results (P = 0.602). Among 13 cases with metastatic SNs, 76.9% cases showed metastasis in PAN. Conclusions. This SN mapping procedure for endometrial cancer patients revealed high detection rate, sensitivity, NPV, and also indicated the importance of the SN exploration in PAN area. (C) 2015 Elsevier Inc. All rights reserved.

BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.

後腹膜リンパ節郭清術後に発生する感染性リンパ嚢胞は術後合併症の一つである。治療は抗生剤投与を基本とし、リンパ嚢胞ドレナージを施行する。今回われわれは当院で発生した感染性リンパ嚢胞の臨床的背景、治療方法について後方視的に検討した。2012年1月から2015年3月までに当院で入院加療を要した感染性リンパ嚢胞症例30例を対象とし、ドレナージ方法、刺入部位について検討した。ドレナージ療法は発生部位によっては穿刺が困難である症例を認めた。また抗生剤のみで治療された群(ドレナージ不要群)と抗生剤治療では改善を得られずドレナージが必要となった群(ドレナージ必要群)の2群に分類し、ドレナージ施行の有無に関与する因子について検討したところ、ドレナージ必要群においてリンパ嚢胞径が大きかったことからドレナージ療法の是非は嚢胞径が判断基準となる可能性が示唆された。術後感染性リンパ嚢胞の治療には嚢胞径、発生部位を考慮して適切な治療計画のもと、ドレナージの必要性を検討すべきである。(著者抄録)

AimManagement of atypical polypoid adenomyoma (APAM) is complicated because it can sometimes coexist with atypical endometrial hyperplasia (AEH) or endometrioid adenocarcinoma. It is often difficult to assess myometrial invasion in APAM complicated with endometrial cancer. We encountered three patients who, contrary to magnetic resonance imaging, did not have myometrial invasion on hysteroscopic transcervical resection (TCR) and therefore could have fertility preserved, and consequently could become pregnant. MethodsWe removed the polypoid lesion and a 3-5mm-thick layer of the normal inner membrane at the root of the polypoid lesion, and then performed total curettage. Several pathological diagnostic procedures were then carried out on each of these resected specimens. Thereafter, high-dose medroxyprogesterone acetate (MPA) was initiated. ResultsAll three patients underwent hysteroscopic transcervical tumor resection. The pathological diagnoses were as follows: patient 1, G1 endometrioid adenocarcinoma (EMG1)+APAM; patients 2,3, AEH+APAM. No findings of myometrial invasion in the resected root specimen were observed in any patient. In all cases, high-dose MPA was initiated. After the disappearance of tumors, each patient achieved pregnancy. Complications such as placenta accreta were not observed at the time of delivery. ConclusionIn patients with APAM and AEH or EMG1, TCR may aid accurate diagnosis when myometrial invasion is unclear on diagnostic imaging.

Objective: Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers. Methods: Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers. Results: Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II. Conclusions: These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

Objective: This study aimed to evaluate the efficacy of paclitaxel and carboplatin in patients with completely or optimally resected uterine carcinosarcoma. Materials and Methods: We conducted a single-arm multicenter prospective phase II trial at 20 Japanese medical facilities. Eligible patients had histologically confirmed uterine carcinosarcoma without prior chemotherapy or radiotherapy. Patients received 6 courses of 175 mg/m(2) paclitaxel over 3 hours, followed by a 30-minute intravenous administration of carboplatin at an area under the serum concentration-time curve of 6. Results: A total of 51 patients were enrolled in this study, 48 of whom underwent complete resection and 3 of whom underwent optimal resection. At 2 years, the progression-free survival and overall survival rates were 78.2% (95% confidence interval [CI], 64.1%-87.3%) and 87.9% (95% CI, 75.1%-94.4%), respectively. At 4 years, these rates were 67.9% (95% CI, 53.0%-79.0%) and 76.0% (95% CI, 60.5%-86.1%), respectively. Although 15 patients showed disease recurrence during the follow-up period (median, 47.8 months; range, 2.1-72.8 months), a total of 40 (78.4%) patients completed the 6 courses of treatment that had been planned. Conclusions: The combination of paclitaxel and carboplatin was a feasible and effective postoperative adjuvant therapy for patients with completely or optimally resected uterine carcinosarcoma.

Purpose of investigation: This study aimed to assess the role of omentectomy in the surgical therapy of endometrial cancer. Materials and Methods: A retrospective study was performed in 98 patients who were pathologically diagnosed with endometrial cancer and had initially undergone surgical therapy at the present institution. This study analyzed the relationship between omental metastasis and clinicopathological factors. Results: Omental metastasis was detected in nine patients (9%). On univariate analysis, significant number of omental metastatic lesions were detected in few cases by positive peritoneal cytology, adnexal metastasis, gross dissemination, and lymphovascular space involvement. On multivariate analysis, adnexal metastasis were a significant risk factor. The sensitivity of the special histological type and the specificity of the macroscopic peritoneal dissemination and adnexal metastasis were all high. Conclusion: Omentectomy plays a significant role in determining the exact surgical staging in cases with non-endometrioid cancer, adnexal metastasis, and macroscopic peritoneal dissemination.

Objective: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third-line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. Materials and Methods: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. Results: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and >= 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI >= 3 months than for TFI 0-3 months (795 days vs. 281 days, p <0.001). Finally, according to univariate (HR = 0.256; p <0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. Conclusions: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

The aim of this study was to investigate the impact of the histological findings on the treatment of malignant ovarian tumors in pregnant women. This is a retrospective study of 41 patients diagnosed and treated for ovarian malignancy during pregnancy between 1985 and 2010. The median age of the study group was 30 years old, ranging from 20 to 41. Thirty-eight (92 %) patients were diagnosed with stage I, and one (2 %) with each of stages II, III, and IV. Twenty-five (61 %) patients had borderline malignancy, 8 (20 %) were diagnosed with epithelial ovarian cancer, 7 (17 %) with germ cell tumor, and one with sex cord stromal tumor. All patients received primary surgery; 7 (17 %) patients had cystectomy, 32 (78 %) had unilateral salpingo-oophorectomy, and 3 (7 %) underwent hysterectomy with bilateral salpingo-oophorectomy. Thirty-one (76 %) patients delivered live newborns; 21 had borderline tumor (84 %), 2 had ovarian cancers (25 %), and 8 had non-epithelial tumor (100 %). Six cases were terminated in order to perform the standard treatment for ovarian malignancy and 2 cases aborted spontaneously. In pregnant women, ovarian cancer is exceptionally less frequent compared with non-pregnant women, i.e. age-matched, statistically-corrected controls based on the Japanese annual report [8/33 (24 %) vs. control (60 %); ovarian cancer/(ovarian cancer + borderline tumor), P = 0.001]. The pregnant women with ovarian cancer chose to prioritize treatment of ovarian cancer at the sacrifice of their babies while those with borderline tumor or non-epithelial tumor were able to successfully deliver live newborns.

Clear cell carcinoma of the ovary (CCC) is a histologic subtype of epithelial ovarian cancer with a distinct clinical behavior. There are marked geographic differences in the prevalence of CCC. The CCC is more likely to be detected at an early stage than high-grade serous cancers, and when confined within the ovary, the prognosis is good. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. Cytoreductive surgery should be performed for patients with stage II, III, or IV disease. An international phase III study to compare irinotecan/cisplatin and paclitaxel/carboplatin as adjuvant chemotherapy for stage IIV CCC has completed enrollment (GCIG/JGOG3017). Considering the frequent PIK3CA mutation in CCC, dual inhibitors targeting PI3K, AKT in the mTOR pathway, are promising. Performing these trials and generating the evidence will require considerable international collaboration.

To address the role of cancer-stroma interactions, we performed gene expression profiling of both cancer and stroma, using matching samples of endometrial cancer (EC), and analyzed the relationship between the gene expression pattern and prognosis in EC. Sixty EC cases were included in this study (38 nonrecurrent and 22 recurrent). Cancer and stroma were separated by performing laser capture microdissection, and microarray analysis was performed separately on cancer and stromal cells. Genes related with progression-free survival (PFS) in cancer and stroma were analyzed using the Cox regression model, and we established a formula, based on the gene expression pattern of cancer and stroma, to predict recurrence using logistic regression. We estimated the accuracy of the formula using the 0.632 method. All cases were classified based on the 79 selected genes of cancer and stroma related to PFS, based on unsupervised clustering. A total of 143 genes in cancer, and 79 genes in stroma were significantly related with PFS. The estimated area under the curve of receiver operating characteristics curve in cancer and stroma to predict recurrence were 0.800 and 0.758, respectively. Based on the 79 genes of cancer, the 22 recurrent cases were divided into two groups, which generally correlated with the histological grade. In contrast, based on the 79 genes of stroma, the 22 recurrent cases displayed homogeneous gene expression, unrelated to the histological grade. We conclude that gene expression profiles of cancer and stroma can predict the recurrence of EC and stromal that gene expression does not depend on the cancer grade. (C) 2014 Wiley Periodicals, Inc.

Aim One of the important risk factors for recurrence of endometrial cancer is lymph node metastasis. The regional lymph nodes are pelvic lymph nodes (PLN) and para-aortic lymph nodes (PAN). PAN metastasis was often detected in the cases with PLN metastasis. However, PAN metastasis not associated with PLN metastasis was identified in a few cases. We focused on nine cases with PAN metastasis and without PLN metastasis. Material and Methods The subjects of this study were 260 cases that were diagnosed with endometrial cancer. The initial treatments were surgery, including pelvic and para-aortic lymphadenectomy. Nine of these cases had PAN metastasis but did not have PLN metastasis. We retrospectively analyzed the clinicopathological factors and prognosis in cases with PLN-PAN+ cases. Results A total of 91 (35%) cases were identified as positive for either PLN or PAN. PAN metastases were detected in 62.6% of the cases that had some regional lymph node metastases and 3.5% of all cases were PLN- and PAN+. In all PLN-PAN+ cases, PAN swelling was not detected by preoperative chest-abdominal computed tomography scan. There were no clear trends among risk factors of regional lymph node metastasis. The 5-year progression-free survival was 87.1% for PLN-PAN- cases, 67.5% for PLN+PAN- cases, 44.4% for PLN-PAN+ cases, and 33.2% for PLN+PAN+ cases. Conclusion During diagnosis and treatment for endometrial cancer, PLN-PAN+ cases should also be considered because the prognosis in PLN-PAN+ cases tended to be lower than that in PLN-PAN- cases and PLN+PAN- cases.

Glycosylation is an important post-translational modification, in which attachment of glycans to proteins has effects on biological functions and carcinogenesis. Analysis of human chorionic gonadotropin, a glycoprotein hormone produced by placental trophoblasts and trophoblastic tumors, has contributed to the diagnosis and treatment of trophoblastic disease, resulting in reduced incidence and mortality. However, alterations of the glycan structure itself in choriocarcinoma have not been characterized. We established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC(3)-1), which mimics the clinical pathohistology in vivo, to examine the tumorigenesis and pathogenesis of choriocarcinoma. In this study, the alterations of glycan structures in the development of choriocarcinoma were examined by performance of comprehensive glycan profiling in clinical samples and in iC(3)-1 cells using a conventional microarray and the recently introduced lectin microarray. Microarray comparison showed significant upregulation of several characteristic glycogenes in the iC(3)-1 cells as compared to the parental HTR8/SVneo cells. The lectin array showed increased -2-6-sialic acid, Gal1-4GlcNAc, GlcNAc1-3GalNAc, and decreased -1-6 core fucose, high mannose, GalNac1-4Gal, GALNAc (Tn antigen) and Gal1-3Gal in choriocarcinoma tissue compared to normal villi. This is the first report of a lectin array analysis in choriocarcinoma and provides useful information for understanding of the disease.

Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma. Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma.

This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. Nine of 102 (8.8) families were regarded as having hereditary breastovarian cancer syndrome, two families (2.0) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

Ovarian cancer has a poor prognosis because early detection is difficult and recurrent ovarian cancer is usually drug-resistant. The morbidity and mortality of ovarian cancer are high worldwide and new methods of diagnosis and therapy are needed. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression that are involved in carcinogenesis, metastasis, and invasion. Thus, miRNAs are likely to be useful as diagnostic and prognostic biomarkers and for cancer therapy. Many miRNAs have altered expression in ovarian cancer compared to normal ovarian tissues and these changes may be useful for diagnosis and treatment. For example, deficiencies of enzymes including Dicer and Drosha that are required for miRNA biogenesis may be adverse prognostic factors; miRNAs such as miR-214 and miR-31, which are involved in drug resistance, and the miR-200 family, which is implicated in metastasis, may serve as biomarkers; and transfection of downregulated miRNAs and inhibition of upregulated miRNAs may be effective for treatment of ovarian cancer. Chemotherapy targeting epigenetic mechanisms associated with miRNAs may also be effective to reverse gene silencing.

Irinotecan is a key chemotherapeutic drug used to treat many tumors, including cervical and ovarian cancers however, irinotecan can cause toxicity, particularly in the presence of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms, which are associated with reduced enzyme activity. Here, we investigated the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28) and their relationships with irinotecan-induced adverse events in patients with gynecologic cancer, who are treated with lower doses of irinotecan than patients with other types of solid tumors. Fifty-three female patients treated with irinotecan and 362 female patients not treated with irinotecan were screened for UGT1A1*6, UGT1A1*27 and UGT1A1*28. Homozygosity for UGT1A1*6 or heterozygosity for UGT1A1*6/*28 was associated with a high risk of severe absolute neutrophil count decrease or diarrhea (odds ratios: 16.03 and 31.33, respectively). In contrast, serum bilirubin levels were not associated with irinotecan toxicity. Homozygosity for UGT1A1*6/*6 and heterozygosity for UGT1A1*6/*28 were associated with an increased risk of absolute neutrophil count and/or diarrhea in Japanese gynecologic cancer patients, despite the lower doses of irinotecan used in these patients. UGT1A1*6 and UGT1A1*28 are potential predictors of severe absolute neutrophil decrease and diarrhea caused by low-dose irinotecan in gynecologic cancer patients. © 2013 The Japan Society of Human Genetics All rights reserved 1434-5161/13.

The medical liquid crystal display (LCD) monitor is a conventionally used imaging device for diagnosis and during endoscopic surgery. Recently, a medical organic electroluminescence panel, the organic light-emitting diode (OLED) monitor, was made available commercially. The advantages of the OLED monitor include good color reproducibility, high contrast, and high video responsiveness. In this nonclinical study, we compared the clinical usefulness and image quality of the OLED monitor and those of the LCD monitor using videos of gynecologic endoscopic surgeries. Monitors were set for blind evaluation. Five evaluators with varying experience in endoscopic surgery evaluated 21 surgery videos played simultaneously on an OLED monitor and two LCD monitors for 2 to 3 minutes twice. Evaluators judged 13 clinical usefulness indices and 11 image quality indices using a 5-point scale (1, very good; 5, very poor) for each video. The mean scores of clinical usefulness indices of the OLED monitor and the LCD monitors 1 and 2 were 2.2 to 2.7, 2.1 to 3.3, and 3.0 to 3.2, respectively. Of seven indices measured, five including motion response, the ability to differentiate organs, recognize lesions, and reproduce actual images, and the general impression of picture quality were statistically superior with use of the OLED monitor compared with the LCD monitor 1, and two including ability to distinguish blood vessels and the ureters were statistically superior with use of the LCD monitor 1 compared with the OLED monitor. The mean scores of image quality indices of the OLED monitor and the LCD monitors 1 and 2 were 1.8 to 3.2, 2.6 to 3.6, and 2.8 to 4.0, respectively. Each index of the OLED monitor was superior to or comparable with those of the LCD monitors. We conclude that the OLED monitor is superior to the LCD monitors insofar as several video presentation characteristics required in gynecologic endoscopic surgery. These findings suggest that the OLED monitor is expected to contribute detailed assessment of organs and the operative field. Journal of Minimally Invasive Gynecology (2013) 20, 522-528 (C) 2013 AAGL. All rights reserved.

早期体がん症例に対する術後療法としての放射線骨盤照射(EBRT)は全生存を改善せず,有害事象をもたらすことから,推奨されない.術後療法としての化学療法の標準基準はAP療法であり,JGOG2043(AP療法,TC療法,DP療法のRCT)の解析結果が待たれる.術後に化学療法と放射線療法を併用し,再発や原癌死に関するハザード比が低下したとする報告があり,また複数のRCTが進行中である.(著者抄録)

Gestational choriocarcinoma is a malignant trophoblastic tumor that usually occurs in the uterus after pregnancy. The tumor is curable with advanced chemotherapy, but the molecular mechanism of choriocarcinoma tumorigenesis remains unclear. This is partly because the low incidence makes it difficult to obtain clinical samples for investigation and because an appropriate choriocarcinoma cell model to study the tumorigenesis has not been developed. We have established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC(3)-1), that possesses unique characteristics compared to other choriocarcinoma cell lines, including production of tumors that consist of the two types of cells commonly found in choriocarcinoma and mimicking of the clinical pathology. Existing trophoblast cell lines utilized in previous choriocarcinoma studies have had significantly dissimilar gene expression profiles. Therefore, it is important to choose an appropriate cell line for a particular study based on the characteristics of the cell line. In this study, to clarify the genetic characteristics of iC(3)-1 and to explore the tumorigenesis mechanism, we examined the gene profile of iC(3)-1 compared to those of existing cell lines and normal placental tissue. Bioinformatics analysis showed that several characteristic genes, IGF1R, CHFR, MUC3A, TAF7, PARK7, CDC123 and PSMD8, were significantly upregulated in iC(3)-1 compared to BeWo and JEG3 cells. Interestingly, HAS2, CD44 and S100P were significantly upregulated in iC(3)-1 compared to parental HTR8/SVneo cells and normal third trimester placenta. Choriocarcinoma samples also showed immunoreactivity to HAS2, CD44 and S100. In summary, the gene expression profile of iC(3)-1 suggests that studies using this cell line can make an important contribution to improved understanding of choriocarcinoma tumorigenesis. (C) 2012 Elsevier Ltd. All rights reserved.

Natural Orifice Translumenal Endoscopic Surgery(NOTES)は体表面に傷を残さない夢の手術として注目が集まっている。軟性内視鏡を自然孔(口、肛門、腟、膀胱など)から挿入後、管腔壁を経て体腔内に到達し、診断・処置を行う手術方法である。我々は、当院倫理委員会およびNOTES研究会の審査を受けたプロトコールに従い十分なインフォームドコンセントを得て、63歳女性の右卵巣嚢腫および胆石症に対し、婦人科・外科2領域同時手術を施行した症例を経験した。臍部の創は臍輪内に留まり、臍部単孔式腹腔鏡手術に比べて整容性に優れ、術後の疼痛も軽度であった。また術後の短期的・長期的合併症はいずれも認めなかった。本術式は、創部の整容性と疼痛の軽減に関して臍部単孔式腹腔鏡手術に優る有用性が期待されるが、今後の症例集積による安全性と有効性の評価を進める必要があると考えられた。(著者抄録)

子宮体癌は子宮体部や底部から発生することが一般的であるが,まれに体部下部から頸部上部,つまりlower uterine segment(LUS)もしくは峡部と呼ばれる領域から発生する子宮体癌が存在する.子宮峡部から発生する子宮体癌(以降,子宮峡部癌)は子宮体癌全体の3〜3.5%とまれであり,これまで小規模の報告しか存在しない.近年,子宮峡部癌が遺伝性腫瘍であるLynch症候群との関連があると報告され注目されている.一般的な子宮体癌でのLynch症候群の頻度は1〜2%といわれているが,米国の報告によると子宮峡部癌のうち29%がLynch症候群とされ,高頻度にMSH2の変異が存在するとしている.今後わが国をはじめ,より大規模な調査において子宮峡部癌の臨床病理学的特徴やLynch症候群との関連についてさらに検討する必要がある.(著者抄録)

Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

新規皮弁である両側陰部大腿臀溝双葉皮弁を用いた手術を行い、腟機能温存の可能性が期待される2例を経験した。症例1は45歳で、2〜3年前より外陰部の違和感を認めていた。数ヵ月前より腫瘤と疼痛を認めた。細胞診診断は扁平上皮癌であった。病期は外陰癌、FIGO Stage Ib期相当で、広汎外陰摘出術、腟壁部分切除術皮弁を用いた植皮術、尿道部分切除術を施行した。現在、術後約3年経過しており再発兆候を認めていない。症例2は42歳で、数ヵ月継続する難治性の外陰部そう痒感で受診した。複数部位の細胞診を採取し疑陽性であったため、麻酔下で外陰部生検を施行した。細胞診診断は異型腺細胞で、乳房外Paget病と診断した。広汎外陰摘出術、腟壁全摘出術、肛門皮膚粘膜切除術、人工肛門造設術、有形性皮弁を用いた植皮術を施行した。術後から約1年6ヵ月経過しているが、再発兆候を認めていない。