Shun-ichi Ikeda

Novel screening method for agents that overcome classical multidrug resistance in a human cell line

P-glycoprotein (P-gp) is involved in the transport of a wide variety of organic compounds including a fluorescent dye, rhodamine 6G (RG), as well as anti-cancer drugs. Agents that overcome classical multidrug-resistance (MDR) increased the accumulation of RG in a MDR cell line, KB-C1. The effect of agents on RG-accumulation in KB-C1 cells was highly correlated with their effect on the reversion of vincristine-resistance in KB-C1 cells. RG was detected on a fluorescence microplate reader with a rhodamine channel. This assay may become a useful method for the screening of agents that overcome classical MBR, since it is quick and simple.

Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma

Uterine papillary serous carcinoma (UPSC) is a rare and aggressive variant of endometrial carcinoma. Little is known about the pathological and biological features of this tumor. Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) expression have an important role in tumor behavior and clinical outcome, but their relevance in UPSC is not clear. In the present study, the immunohistochemical expression of HER2 and HR was assessed in 27 patients with Stage I disease, 13 with Stage II disease, 25 with Stage III disease, and 6 with Stage IV disease. Correlations between HER2 and HR expression and the clinicopathological parameters of UPSC were evaluated using Coxs univariate and multivariate analyses. For all patients, the 5‐year recurrence‐free survival (RFS) and overall survival (OS) rates were 51% and 66%, respectively; in patients with Stage I, II, III and IV disease, the RFS and OS were 67%/81%, 59%/77%, 43%/54% and 0%/0%, respectively. Of all 71 patients, 14% (10/71) were positive for HER2 and 52% (37/71) were positive for HR. Overexpression of HER2 was correlated with lower OS (P = 0.01), whereas HR overexpression was correlated with higher OS (P = 0.008). In multivariate models, HER2, HR, and histologic subtype were identified as independent prognostic indicators for RFS (P = 0.022, P = 0.018, and P = 0.01, respectively), but HR was the only independent factor associated with OS (P = 0.044). Thus, HER2 and HR are prognostic variables in UPSC, with HR an independent prognostic factor for OS. (Cancer Sci 2012; 103: 926–932)

Serous Adenocarcinoma of the Uterine Cervix: A Clinicopathological Study of 12 Cases and a Review of the Literature

Background/Aims: To determine the clinicopathological characteristics and potentially associated outcomes in patients diagnosed with serous adenocarcinoma of the uterine cervix. Methods: The records of surgically-treated patients with pathological stage pT1b–2b serous adenocarcinoma were reviewed. Results: Of 12 patients with serous adenocarcinoma who underwent radical hysterectomy, five had pT1b1N0 disease, two pT1b1N1, two pT1b2N0, and three pT2bN1. The 5-year overall survival rate for patients with or without parametrial involvement (pT2b vs. pT1b) was 0 and 89%, respectively. The 3-year recurrence-free survival rate for those with or without parametrial involvement was 33 and 89%, respectively. Four patients suffered recurrence, namely one of those who had pT1b (1/9, 11%) and 3 of those who had pT2b disease (100%). The sites of recurrence of pT2b disease were outside the pelvis in all 3 patients. Of these, 2 (67%) had peritoneal spread and 1 distant node metastasis. Conclusion: While patients with pathological stage pT1b disease may have a relatively favorable outcome after radical surgery, those with more advanced disease have a poor prognosis because of extra-pelvic recurrence.

Combination of squamous cell carcinoma‐antigen, carcinoembryonic antigen, and carbohydrate antigen 19‐9 predicts positive pelvic lymph nodes and parametrial involvement in early stage squamous cell carcinoma of the uterine cervix

Aim:  We examined the correlations between the pretreatment values of four tumor markers (squamous cell carcinoma [SCC]‐antigen, carcinoembryonic antigen [CEA], carbohydrate antigen [CA]19‐9, and CA125) and postsurgical high‐risk factors (parametrial involvement and positive pelvic lymph nodes) in women with SCC of the uterine cervix who had International Federation of Gynecology and Obstetrics clinical stage IB and IIA disease and underwent radical hysterectomy.

Knowledge, fatigue, and cognitive factors as predictors of lymphoedema risk-reduction behaviours in women with cancer

ObjectiveTo identify social–cognitive factors predicting lymphoedema risk-reduction behaviours (hereafter, self-care) after discharge among patients in Japan with breast or gynaecological cancers, using the extended model of the theory of planned behaviour.MethodsA cross-sectional questionnaire study was conducted in an oncology hospital. Items measured were (1) knowledge about self-care; (2) the Cancer Fatigue Scale; (3) social–cognitive factors in the theory of planned behaviour (attitudes, subjective norms, and perceived behavioural control); (4) self-care (limb hygiene, observation, articular movement, recommended risk-reduction behaviours in daily life, and diet and weight control); and (5) demographics. Of 202 respondents, 147 who had not been diagnosed with lymphoedema were eligible for statistical analysis (65.3% with gynaecological cancer, 34.7% with breast cancer).ResultsStructural equation modelling was used to examine a hypothesised model based on the theory of planned behaviour. The results revealed that a longer time since surgery, higher levels of fatigue, less knowledge, higher expected efficacy of self-care, and lower perceived behavioural control directly and significantly predicted less self-care behaviour.ConclusionsBesides education about self-care behaviour, levels of fatigue and perceived behavioural control should be taken into account to encourage female patients with cancer to perform self-care after discharge. Continuous psycho-educational programmes after discharge may help to facilitate self-care behaviours among long-term female cancer survivors.

Integrated extracellular microRNA profiling for ovarian cancer screening

A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.Screening methods for early detection of ovarian cancer is technically difficult. Here, the authors investigated circulating microRNA in human blood serum and developed a model using 10 microRNAs to discern between ovarian cancer and being ovarian tumors, solid tumors, and non-cancer patients.

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy

Objective Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Methods Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. Results FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Conclusion Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I–II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies.

Baseline risk of recurrence in stage I–II endometrial carcinoma

Objective Though there are no evidences that postoperative therapy improves overall survival (OS) in stage I–II endometrial carcinoma, many women receive postoperative radiation or chemotherapy. This study aimed to investigate the baseline risk of recurrence after complete resection without any adjuvant therapies and to suppose the validity of postoperative therapy for stage I–II endometrial carcinoma. Methods Charts for patients with stage I–II endometrial carcinoma who underwent operation without postoperative therapy between January 2005 and December 2011 were retrospectively reviewed and the baseline risk of recurrence and prognosis were assessed. Risk classifications were performed according to European Society for Medical Oncology (ESMO) clinical practice guidelines and Japanese guideline written by Japan Society of Gynecologic Oncology Group. Results Among 374 patients who underwent complete resection, 311 were evaluable. Five-year recurrence rates by ESMO and Japanese were 2.6% and 3.1% in low-risk, 9.2% and 6.6% in intermediate-risk and 13.5% and 13.8% in high-risk group (p=0.003 and 0.015, respectively). High-risk group had worse OS compared with low- and intermediate-risk groups (5-year OS, low: 97.9% and 97.6%, intermediate: 97.9% and 98.8%, and high: 89.5% and 87.5%; p=0.003 and 0.008, respectively). Independent predictive factors of recurrence were age over 60 years, type 2 (estrogen-independent) and peritoneal cytology. Conclusion ESMO and Japanese risk classification similarly stratify the baseline risk of recurrence. Patients with stage I–II endometrial carcinoma, especially low- and intermediate-risk diseases, have low recurrence rate and favorable OS, and the benefit of postoperative therapy might be small.

Information-seeking, information sources and ongoing support needs after discharge to prevent cancer-related lymphoedema

Objectives To compare gynaecological and breast cancer patients in their information-seeking behaviours, usefulness of information sources and ongoing care needs after discharge to prevent the onset of lymphoedema. Methods We conducted a consecutive cross-sectional survey in an oncology hospital. Adult patients with stage I, II or III gynaecological or breast cancer who had undergone lymph node dissection and had not been diagnosed with lymphoedema were eligible for inclusion. The survey explored physical health status, knowledge of self-care, information-seeking behaviours, information sources and need for ongoing care from an oncology hospital and/or community health centre. Results Among 254 patients recruited, 202 responded (79.5% response rate). In total, 147 patients were eligible for statistical analysis. Irrespective of cancer type, the most commonly sought information was lymph drainage. Information on preventing weight gain was sought more often by breast cancer patients than gynaecological cancer patients. Regardless of cancer type, the most common information sources were nurses at an oncology hospital. Gynaecological cancer patients perceived nurses at the oncology hospital as useful for understanding risks, symptoms and prevention of lymphoedema. Irrespective of cancer type, ongoing need for help with lymphoedema prevention was reported both from the oncology hospital and the community centre. Limb symptoms, poor health status and poor knowledge affected the ongoing needs of gynaecological cancer patients at the oncology hospital, whereas poor health status affected ongoing needs in community health centres among both types of cancer patients. Conclusions Both gynaecological and breast cancer patients reported ongoing care needs, but that details of information-seeking behaviours differed.

Uterine adenosarcoma in Japan: Clinicopathologic features, diagnosis and management

Uterine adenosarcoma is a rare malignancy with limited cohort data in Asian countries. This study evaluated the clinicopathologic features of Japanese patients with uterine adenosarcoma and their potential treatment challenges.