In the published article, Fig. 2 was published incorrectly.

Adolescent and young adult (AYA) patients are generally defined as being from 15 to 39 years old. For preservation of fertility in AYA cancer patients, the best-known guideline in this field was released by the American Society of Clinical Oncology (ASCO) in 2006. However, the ASCO guideline is not necessarily applicable to Japanese cancer patients. The Japan Society for Fertility Preservation (JSFP) was formed in 2012, and a system and guideline for fertility preservation in Japanese AYA cancer patients plus children was released in July 2017. According to this guideline, patients should receive psychological and social support from health care providers such as doctors, nurses, psychologists, pharmacists, and social workers. In 2013, the American Society for Reproductive Medicine stated that freezing oocytes is a method that has passed beyond the research stage. However, freezing ovarian tissue is still a research procedure. While slow freezing of ovarian tissue is generally performed, rapid freezing (vitrification) is more popular in Japan. We have developed a new closed technique for ovarian tissue cryopreservation. It has been suggested that optical coherence tomography might be applied clinically to measure the true ovarian reserve and localize follicles in patients undergoing ovarian tissue transplantation. Combining gonadotropin-releasing hormone agonist therapy with anticancer agents might be useful for ovarian protection and it is expected that discussion of such combined treatment will continue in the future. This article outlines practical methods of fertility preservation using assisted reproductive techniques for AYA cancer patients in Japan.
Adolescent* ; Antineoplastic Agents ; Asian Continental Ancestry Group ; Child ; Cryopreservation ; Fertility Preservation* ; Fertility* ; Freezing ; Gonadotropin-Releasing Hormone ; Health Personnel ; Humans ; Japan* ; Medical Oncology ; Methods ; Oocytes ; Ovarian Reserve ; Pharmacists ; Psychology ; Reproductive Medicine ; Reproductive Techniques, Assisted ; Social Work ; Social Workers ; Tissue Transplantation ; Tomography, Optical Coherence ; Transplants ; Vitrification ; Young Adult*

Oxycodone controlled-release (CR) tablets are used as a first-line opioid analgesic for cancer pain. However, use of oxycodone CR tablets is associated with toxicities such as drowsiness and constipation, leading to deterioration of the quality of life (QOL), especially in patients with gynecologic cancer. In contrast, fentanyl has a superior toxicity profile while still showing a strong analgesic effect. Although fentanyl has been approved for switching from opioid, there have been no Japanese studies of patients with gynecologic cancer who were switched to transdermal fentanyl after experiencing toxicity during therapy with oxycodone CR. More importantly early introduction of palliative therapy for pain has not been adopted routinely in the management of gynecologic cancer. Thus, it appears that treatment for patients with gynecologic cancer remains unsatisfactory at present. We conducted research into improvement of the toxicity profile and pain control with the aim of improving QOL for patients with gynecologic cancer. We showed that pain, drowsiness, and constipation could be significantly improved in gynecologic cancer patients as a result of switching to transdermal fentanyl therapy at an early stage.

Objective: This study aimed to assess gynecologic oncologists (GOs)’ perceptions and attitudes toward cancer survivorship to help improve survivor care. Methods: We conducted a web-based questionnaire survey about survivorship issues for the GOs belonging to the Japan Gynecologic Oncology Group. We analyzed the proactiveness of the participants toward addressing 25 survivor issues. In addition, the practice patterns and barriers to care for survivors’ long-term health issues, such as second primary cancer (SPC) and lifestyle-related diseases (LSRD), and return-to-work (RTW) support were assessed. Results: We received 313 responses. The respondents had a mean of 22 years of physician experience. The ratio of men to women was approximately 7:3, and 84.7% worked at facilities for multidisciplinary cancer treatment. The respondents’ proactiveness for addressing psychosocial problems was significantly lower than physical and gynecological issues (p<0.01 by χ2 test). However, most GOs tried to contribute to such issues according to patients’ demands. Women GOs were more proactively involved in some survivorship issues than the men (p<0.05 by logistic regression analysis). The rates of the respondents who proactively discussed SPC, LSRD, and RTW were unexpectedly high (60.7%, 36.1%, and 52.4%, respectively). However, the GOs only provided verbal support for these issues in many cases. Conclusion The Japanese GOs were enthusiastic about survivorship care. However, their tendency to deal with survivors’ problems through their own knowledge and judgments raises concerns about the quality of care. Therefore, creating survivorship care guidelines and enhancing multidisciplinary collaboration should be prioritized.

Objective: Previously, we reported that insulinoma-associated protein 1 (INSM1) immunohistochemistry (IHC) showed high sensitivity for neuroendocrine carcinoma of the uterine cervix and was an effective method for histopathological diagnosis, but that its specificity remained to be verified. Therefore, the aim was to verify the specificity of INSM1 IHC for a large number of non-neuroendocrine neoplasia (NEN) of the cervix. Methods: RNA sequences were performed for cell lines of small cell carcinoma (TCYIK), squamous cell carcinoma (SiHa), and adenocarcinoma (HeLa). A total of 104 cases of formalin-fixed and paraffin-embedded specimens, 16 cases of cervical NEN and 88 cases of cervical non-NEN, were evaluated immunohistochemically for conventional neuroendocrine markers and INSM1. All processes without antigen retrieval were performed by an automated IHC system. Results: The transcripts per million levels of INSM1 in RNA sequences were 1505 in TCYIK, 0 in SiHa, and HeLa. INSM1 immunoreactivity was shown only in the TCYIK. Immunohistochemical results showed that 15 cases of cervical NEN showed positive for INSM1; the positivity score of the tumor cell population and the stain strength for INSM1 were high. Two of the 88 cases of cervical non-NENs were positive for INSM1 in one case each of typical adenocarcinoma and squamous cell carcinoma. The sensitivity of INSM1 for cervical NEN was 94%; specificity, 98%; the positive predictive value, 88%; and the negative predictive value, 99%. Conclusion INSM1 is an adjunctive diagnostic method with excellent specificity and sensitivity for diagnosing cervical NEN. Higher specificity can be obtained if morphological evaluation is also performed.

OBJECTIVESThere is a growing need to evaluate the performance status of the activities of daily living (ADL) of the elderly in the rapidly aging Japanese society. The purpose of this study was to verify the usefulness of our new scoring sheet for assessing present ADL status and to clarify whether or not the assessed ADL status can predict the future risk of adverse conditions related to falls.

METHODSThe validation study was performed using 116 non-handicapped community-dwelling Japanese elderly at least 60 years of age. Of those subjects, 44 were also analyzed for the relationship between baseline ADL status and subsequent risk of adverse conditions related to falls.

RESULTSThe daily living performance score sheet had good internal consistency, with a Cronbach's alpha of 0.82 and a sequential hierarchical structure that reflected the difficulty of the activities. The total score was significantly and positively associated with six of eight subscale scores on the Short-Form 36-Item Health Survey (P < 0.01). In the follow-up study, every one-point decrease in total score was significantly associated with a 39% elevated risk of a stumble or fall (P = 0.022) and also borderline significantly associated with higher risks of a fall, anxiety while walking indoors, and anxiety while walking outdoors (P < 0.10).

CONCLUSIONOur new scoring sheet can reliably and comprehensively assess present ADL status. The assessed ADL could predict the future risk of adverse conditions related to falls.

Objective: Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). Methods: In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. Results: We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. Conclusion These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.

Objective: In this study we sought to investigate the clinical factors that affect postprogression survival (PPS) in patients with recurrent or persistent clear cell carcinoma (CCC).We utilized the JGOG3017/Gynecological Cancer InterGroup data to compare paclitaxel plus carboplatin (TC) and irinotecan plus cisplatin (CPT-P) in the treatment of stages I to IV CCC. Methods: We enrolled 166 patients with recurrent or persistent CCC and assessed the impact of variables, including platinum sensitivity, treatment arm, crossover chemotherapy, primary stage, residual tumor at primary surgery, performance status, ethnicity, and tumor reduction surgery at recurrence on the median of PPS in patients with recurrent or persistent CCC. Results: A total of 77 patients received TC, and 89 patients received CPT-P. The median PPS for patients with platinum-resistant disease was 10.9 months, compared with 18.8 months for patients with platinum-sensitive disease (hazard ratio [HR]=1.88; 95% confidence interval [CI]=1.30–2.72; log-rank p<0.001). In the multivariate analysis, the platinum sensitivity (resistant vs. sensitivity; HR=1.60; p=0.027) and primary stage (p=0.009) were identified as independent predictors of prognosis factors for PPS in recurrent or persistent CCC. Conclusions Our findings revealed that platinum sensitivity and primary stage are clinical factors that significantly affect PPS in patients with recurrent or persistent CCC as wellas other histologic subtypes of ovarian cancer. PPS in patients with recurrent CCC should establish the basis for future clinical trials in this population.

The purpose of this study is to clarify factors related to the effect of daikenchuto on constipation during pregnancy. The subjects were 21 patients who had constipation during pregnancy and received 15 g/day of daikenchuto. Based on the constipation score that was created independently, the score values before administration, 2 weeks and 4 weeks after administration were retrospectively investigated. Furthermore, from the outcome of the oral status at 4 weeks, we divided the patients into 2 groups (12 in the improvement group and 11 in the non-improvement group), and attempted to extract factors that were considered to be related to efficacy. The total constipation score decreased significantly before and after administration of daikenchuto, and the concomitant symptoms of constipation scores were low, especially such as abdominal distension and abdominal pain. A comparison of the backgrounds of the improved group and the non-improved group revealed that the proportion of the patients with a history of surgery (laparotomy or laparoscopic surgery) was significantly higher in the improvement group. In addition, there were no particular problems with the pregnancy and delivery course of the 23 patients. Daikenchuto was considered to be highly effective against constipation during pregnancy, especially in pregnant women with a history of surgery.

We aimed to clarify the significance of using Kampo therapy centered on kamishoyosan and tokishakuyakusan together with general infertility treatment. The subjects were 41 women who visited a Kampo outpatient clinic for infertility and received general infertility treatment with Kampo therapy (Kampo group). The control group was 781 women who received only general infertility treatment at the same time (non-Kampo group). In comparing both groups, we conducted a retrospective survey on the pregnancy rate by cycle and the pregnancy rate by prescription. The pregnancy rate in the first cycle was 24.4% in the Kampo group and 8.5% in the non-Kampo group, and the pregnancy rate was higher in the Kampo group (P = 0.003). There was no difference in pregnancy rates after the second cycle. The pregnancy rate by prescription was 26.7% for kamishoyosan, 22.2% for tokishakuyakusan, and 8.5% for the non-Kampo group. In the comparison between the first cycle pregnant group and the non-pregnant group, the qi counter flow score was clearly higher in the first cycle pregnant group (P = 0.012). It is suggested that combined use of Kampo therapy including kamishoyosan and tokishakuyakusan may be effective from an early stage. Meanwhile, if pregnancy does not occur even after the combined use of Kamp therapy, it would be an opportunity to consider stepping up as Western medical therapy.