Tomoyasu Kato

Anticancer effects of a chinese Herbal medicine, Juzen-taiho-to, in combination with or without 5-fluorouracil derivative on DNA-synthesizing enzymes in 1,2-dimethylhydrazine induced colonic cancer in rats

Juzen-taiho-to (JTT; [Shi-quan-da-bu-tang], a Japanese modified Chinese herbal prescription) in combination with an anticancer drug UFT (5-fluorouracil derivative) prevented the body weight loss and the induction of the colonic cancer in rats treated with a chemical carcinogen 1,2-dimethylhydrazine (DMH), and suppressed markedly the activity of thymidylate synthetase (TS) involved in the de novo pathway of pyrimidine synthesis in colonic cancer induced by DMH.

Clinicopathologic Association and Prognostic Value of Microcystic, Elongated, and Fragmented (MELF) Pattern in Endometrial Endometrioid Carcinoma

Microcystic, elongated, and fragmented (MELF) pattern is seen in the invasive front of some endometrial endometrioid carcinomas. Although MELF pattern can be expected as an indicator of patient outcomes, its prognostic significance remains unclear. This study was conducted to elucidate clinicopathologic features and the prognostic impact of MELF pattern in patients with endometrial endometrioid carcinoma. We retrospectively analyzed data of 479 consecutive patients with endometrial endometrioid carcinoma that had been surgically resected. In 45 of 427 patients (11%) with low-grade endometrioid carcinoma, MELF pattern was found, but it was found in none of the 52 patients with high-grade endometrioid carcinoma. Among the patients with low-grade endometrioid carcinoma, MELF pattern was associated significantly with larger tumor size, myometrial invasion of more than 50%, advanced International Federation of Gynecology and Obstetrics stages, lymphovascular space invasion, lymph node metastasis, papillary architecture, and mucinous differentiation. However, survival analysis revealed that the patients with MELF pattern showed no significantly worse prognosis than those without MELF pattern either in disease-specific survival or in recurrence-free survival. MELF was not a significant prognosticator after adjustment for International Federation of Gynecology and Obstetrics stage (disease-specific survival [hazard ratio, 1.47; 95% confidence interval, 0.28-7.67; P=0.64], recurrence-free survival [hazard ratio, 0.98, 95% confidence interval, 0.32-2.99, P=0.98]). Immunohistochemical analysis revealed that MELF pattern was positive for p16 and p21 and almost negative for Ki-67 labeling, which suggested that tumor cells in MELF pattern were involved in growth arrest or cellular senescence. We conclude that MELF pattern could have little impact on outcomes of patients with low-grade endometrial endometrioid carcinoma.

A novel prediction score for predicting the baseline risk of recurrence of stage I–II endometrial carcinoma

Objective To develop and validate a 3-year recurrence prediction score (RPS) system for predicting the baseline risk of recurrence of stage I–II endometrial carcinoma. Methods We reviewed 427 patients with International Federation of Gynecology and Obstetrics staging I–II endometrial carcinoma underwent surgery without any adjuvant therapy from 2005 to 2013. The patients were divided into 2 groups: the test cohort (n=251) comprising those who underwent surgery in odd-numbered years, and the validation cohort (n=176) comprising those who underwent surgery in even-numbered years. Multivariate analysis was performed using 7 candidate predictors to identify the risk factors for 3-year recurrence-free interval (RFI) in the test cohort. Each risk factor was scored based on logistic regression analyses of the test data set, and the sum of the risk factor scores was defined as the RPS system. We then applied the system in the validation cohort. Results Multivariate analysis revealed that the significant risk factors were age ≥60 years, pathological type II, positive cervical stromal invasion, and positive peritoneal cytology. In the test cohort, the 3-year RFI rates were 100%, 95.8%, 79.9%, and 33.3% for RPSs of 0, 1, 2, and 3, respectively. In the validation cohort, the 3-year RFI was significantly higher in the low-RPS group (RPS 0 or 1) than in the high-RPS group (RPS 2 or 3) (95.2% vs. 79.9%, p<0.01). Conclusions The RPS system shows significant reproducibility for predicting the baseline risk of recurrence. The system could potentially impact the choice of adjuvant therapy for stage I–II endometrial carcinoma.

Prognostic factors of synchronous endometrial and ovarian endometrioid carcinoma

Objective Gynecologists occasionally encounter synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC) patients who show favorable prognosis than locally advanced or metastatic disease patients. This study aimed to elucidate prognostic factors of SEO-EC and identify patients who have a sufficiently low risk of recurrence without receiving adjuvant chemotherapy. Methods We retrospectively reviewed 46 patients with pathologically confirmed SEO-EC who underwent surgery at the National Cancer Center Hospital between 1997 and 2016. Immunohistochemical evaluation of DNA mismatch repair (MMR) protein expression were performed for both endometrial and ovarian tumors. Patient outcomes were analyzed according to clinicopathologic factors. Results From the multivariate analysis, cervical stromal invasion indicated a worse prognosis for progression-free survival (hazard ratio [HR]=6.85; 95% confidence interval [CI]=1.50–31.1) and overall survival (HR=6.95; 95% CI=1.15–41.8). Lymph node metastasis and peritoneal dissemination did not significantly affect survival. MMR deficiency was observed in 13 patients (28.3%), with both endometrial and ovarian tumors showing the same MMR expression status. MMR deficiency was not significantly associated with survival. Of 23 patients with lesions confined to only the uterine body and adnexa, only 2 had recurrence in the group receiving adjuvant therapy, while none of the 10 patients who did not receive adjuvant therapy had recurrence. Conclusion SEO-EC patients with tumors localized to the uterine body and adnexa lesions had a low risk for recurrence and may not require adjuvant therapy. SEO-EC may have prognostic factors different from those of endometrial and ovarian cancer.

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.

Retrospective Analyses of Systemic Chemotherapy and Cytoreductive Surgery for Patients with Ovarian Metastases from Colorectal Cancer: A Single-Center Experience

Background: Ovarian metastases from colorectal cancers are relatively rare. Since most ovarian metastases are associated with metastases at other sites, the prognosis is usually poor. Few reports exist that describe the clinical course of colorectal cancer patients with ovarian metastasis, including the chemotherapy response. Methods: We retrospectively reviewed the clinical data of patients with ovarian metastases from colorectal cancer treated at the National Cancer Center Hospital, Tokyo, between January 2006 and December 2015. Results: Thirty-seven patients with ovarian metastases received palliative chemotherapy as first-line treatment. The objective response rate for systemic chemotherapy of ovarian metastases was significantly lower than that for other metastatic sites (23.5 vs. 63.6% for first-line, respectively, p = 0.0047). Following chemotherapy, the additional surgical resection of ovarian metastases was positively associated with longer overall survival (OS) compared to no surgical resection (43.1 vs. 17.0 months, respectively, p = 0.0016). Furthermore, cytoreductive surgery was also positively associated with longer OS, especially when other metastatic sites were well controlled. Conclusions: Ovarian metastases are less responsive to systemic chemotherapy compared to extra-ovarian metastases in patients with relapsed or metastatic colorectal cancer. Multidisciplinary treatment strategy, including systemic chemotherapy and cytoreductive surgery, may contribute to the prolongation of OS.

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.