Novel Strategy for the Management of Cervical Multicystic Diseases.

PURPOSE: To investigate the clinical practices of diagnosing multicystic cervical lesions as a means to develop a more appropriate diagnostic algorithm for gastric-type adenocarcinoma (GAS) and its precursors. METHODS: Clinical information for 159 surgically treated patients for multicystic disease of the uterine cervix was collected from 15 hospitals. We performed a central review of the MRI and pathological findings. The MRI findings were categorized into four types including two newly proposed imaging features based on the morphology and distribution of cysts, and the diagnosis accuracy was assessed. Among the four MRI types, types 1 and 2 were categorized as benign lesions that included LEGH; type 3 were precancerous lesions (with an assumption of atypical LEGH); and type 4 were malignant lesions. RESULTS: The central pathological review identified 56 cases of LEGH, seven with GAS, four with another form of carcinoma, and 92 with benign disease. In clinical practice, over-diagnosis of malignancy (suspicion of MDA) occurred for 12/19 cases (63.2%) and under-diagnosis of malignancy occurred for 4/11 (36%). Among the 118 patients who had a preoperative MRI and underwent a hysterectomy, type 3 or 4 MRI findings in conjunction with abnormal cytology were positively indicative of premalignancy or malignancy, with a sensitivity and specificity of 61.1% and 96.7%, respectively. CONCLUSIONS: Although the correct preoperative diagnosis of cervical cancer with a multicystic lesion is challenging, the combination of cytology and MRI findings creates a more appropriate diagnostic algorithm that significantly improves the diagnostic accuracy for differentiating benign disease from premalignancy and malignancy.

A nationwide birth year-by-year analysis of effectiveness of HPV vaccine in Japan.

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.

A potential means to help the HPV vaccine penetrate the Japanese public while under the continued suspension of governmental recommendation.

In Japan, the government's recommendation for the HPV vaccine has been suspended for almost 8 years. A questionnaire survey was conducted in the Tsubaki Women's Clinic, Matsuyama, Japan, to examine responses of the mothers of girls eligible for HPV vaccine before and after their doctor provided them an informative leaflet explaining the need for cervical cancer prevention.Among the 53 mothers who admitted to imposing some preconditions before being willing to encourage their daughters' HPV vaccination, 21 (40%) mothers became more willing to vaccinate their daughters immediately after receiving the cervical cancer prevention linkage explanation provided by their doctor, and seven of the mothers (33%) even returned to the clinic to get their daughter vaccinated during our study period. Logistical regression analysis revealed that having initial preconditions required for their daughters' HPV vaccination was an independent variable influencing the mothers' change of willingness to get their daughters vaccinated immediately after receiving the explanation using the leaflet.We have found that to achieve maximum effectiveness, we can use an appropriate leaflet even under suspension of the governmental recommendation. Our future efforts should be focused on those mothers who are less likely to impose preconditions on their daughter's vaccination.

The last strategy for re-dissemination of HPV vaccination in Japan while still under the suspension of the governmental recommendation.

In Japan, the governmental recommnendation of HPV vaccine has been suspended since June 2013, due to media reports of alleged adverse vaccination events. Although evidence of effectiveness and safety of the HPV vaccine has been universally demonstrated, and the medical and academic organizations across Japan have requested the resumption of the government's recommendation, the Japanese government has not changed their official stance towards the HPV vaccine. Under the current suspension of the national government's recommendation, one local government Isumi City started sending a leaflet containing information of cervical cancer and HPV vaccine, but not recommendation for the vaccine, to the tagted girls born in the fiscal year (FY) 2003. The cumulative vaccination rate of them reached 10.07% (14/139), which was significantly higher than that (0.00%) for girls born in FY 2002 who did not receive such a leaflet (p < 0.001). We sincerely ask the national government to change their stance towards the HPV vaccine. We also strongly suggest that, in the meantime, local governments immediately begin to provide an appropriate information of cervical cancer and HPV vaccine to the targeted girls and their parents in a way similar to what Isumi City has now shown to be effective.

A survey of Japanese mothers on the effectiveness of the Ministry of Health, Labor and Welfare's revised HPV vaccine leaflet.

Introduction: In June of 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) suspended its position of strong recommendation for the routine immunization of young girls against the Human Papilloma Virus (HPV) because of reports of adverse reactions after the vaccination. For the next four years, the MHLW's website warned about the significance of these adverse events. In January of 2018, MHLW's website was modified to reflect a less negative stance. We have studied public awareness of MHLW's revised leaflet in Japanese women whose daughters were of the targeted age for receiving the HPV vaccine and how this awareness influenced their intentions to get their daughters vaccinated. Materials and Methods: From June to December of 2018, a survey was conducted through the Departments of Obstetrics and Gynecology at 14 different medical facilities. The questionnaire was distributed to women whose daughters were of the HPV-vaccine-targeted age. The survey measured their responses before and after being presented with the 2018-revised MHLW leaflet. Responses from 384 mothers were analyzed. Results: Before being presented with the leaflet, the survey found that the percentage of responder's daughters already vaccinated was 6.5% (24/372). After reading the MHLW leaflet, an additional 6.9% (24/346) responded "I want to get my daughter vaccinated immediately", and 37.6% (130/346) responded "I have positive feelings about HPV vaccination". Discussion: By presenting the new MHLW leaflet at obstetrics and gynecology facilities, we expect to be able to effectively increase the HPV vaccination rate in Japan.

Changing attitudes in Japan toward HPV vaccination: a 5-year follow-up survey of obstetricians and gynecologists regarding their current opinions about the HPV vaccine.

In Japan, the governmental recommendation for HPV vaccination was suspended in June 2013 because of media reports of so-called adverse vaccine events. The HPV vaccination rate in Japan prior to this suspension was almost 70%, but fell afterward to almost zero. To explore ways to bolster HPV vaccination, between 2014 and 2019 we conducted three serial surveys of the opinions of obstetricians and gynecologists about HPV vaccination. This study aimed to discuss the changing attitudes found in this 5-year follow-up survey. In August 2014, January 2017, and June 2019, we posted questionnaires to about 570 obstetricians and gynecologists practicing in Osaka, Japan. All three surveys used the same structured and closed-ended questionnaire, including questions about their personal opinions regarding HPV vaccination. We compared our new results to those of the previous two surveys. The response rate for the latest survey was 51.1% (293/573), which was equivalent to the previous two surveys. Among the responders, 83.3% (244/293) now thought that the Japanese government should restart its HPV vaccine recommendation, and 84.6% (248/293) were already recommending HPV vaccines for teenagers in their daily care. Eleven of 30 doctors (36.7%) had their own teenage daughters vaccinated against HPV after the suspension of recommendation. The rate has maintained an increasing trend from the previous two surveys. This study indicated that the attitude of obstetricians and gynecologists in Japan toward HPV vaccination has changed positively over 5 years. The results should serve as an encouragement to resume the governmental recommendation of HPV vaccines.

HPV vaccination in Japan: results of a 3-year follow-up survey of obstetricians and gynecologists regarding their opinions toward the vaccine.

BACKGROUND: In Japan, the cervical cancer preventative HPV vaccination rate has dramatically declined, directly as a result of repeated broadcasts of so-called adverse events and the resulting suspension of the government's recommendation. Our previous survey of obstetricians and gynecologists in Japan regarding their opinions toward HPV vaccination revealed that these key specialists were as negatively influenced by the reports of purported negative events as were the general population. Here, we report a 3-year follow-up survey of these clinicians. METHODS: We reused the same questionnaire format as used in our 2014 survey, but added new questions concerning opinions regarding a WHO statement and reports of a Japanese nation-wide epidemiological study related to the adverse events, released in 2015 and 2016, respectively. RESULTS: The response rate was 46% (259/567): 5 (16.1%) of 31 doctors had inoculated their own teenaged daughters during the time period since the previous survey, despite the continued suspension of the governmental recommendation, whereas in the previous survey none of the doctors had done so. Among the respondents, the majority claimed awareness of the recent pro-vaccine WHO statement (66.5%), and of the report of a Japanese epidemiological study (71.5%), and a majority affirmed they currently held positive opinions of the safety (72.7%) and effectiveness (84.3%) of the HPV vaccine. CONCLUSIONS: Our re-survey of Japan's obstetricians and gynecologists regarding their opinions about the HPV vaccine found that their opinions have changed, potentially leading to a more positive future re-engagement for HPV vaccination in Japan.

Antagonistic control of the turnover pathway for the global regulatory sRNA CsrB by the CsrA and CsrD proteins.

The widely conserved protein CsrA (carbon storage regulator A) globally regulates bacterial gene expression at the post-transcriptional level. In many species, CsrA activity is governed by untranslated sRNAs, CsrB and CsrC in Escherichia coli, which bind to multiple CsrA dimers, sequestering them from lower affinity mRNA targets. Both the synthesis and turnover of CsrB/C are regulated. Their turnover requires the housekeeping endonuclease RNase E and is activated by the presence of a preferred carbon source via the binding of EIIA(Glc) of the glucose transport system to the GGDEF-EAL domain protein CsrD. We demonstrate that the CsrB 3' segment contains the features necessary for CsrD-mediated decay. RNase E cleavage in an unstructured segment located immediately upstream from the intrinsic terminator is necessary for subsequent degradation to occur. CsrA stabilizes CsrB against RNase E cleavage by binding to two canonical sites adjacent to the necessary cleavage site, while CsrD acts by overcoming CsrA-mediated protection. Our genetic, biochemical and structural studies establish a molecular framework for sRNA turnover by the CsrD-RNase E pathway. We propose that CsrD evolution was driven by the selective advantage of decoupling Csr sRNA decay from CsrA binding, connecting it instead to the availability of a preferred carbon source.