An artificial intelligence-assisted diagnostic system improves the accuracy of image diagnosis of uterine cervical lesions.

The present study created an artificial intelligence (AI)-automated diagnostics system for uterine cervical lesions and assessed the performance of these images for AI diagnostic imaging of pathological cervical lesions. A total of 463 colposcopic images were analyzed. The traditional colposcopy diagnoses were compared to those obtained by AI image diagnosis. Next, 100 images were presented to a panel of 32 gynecologists who independently examined each image in a blinded fashion and diagnosed them for four categories of tumors. Then, the 32 gynecologists revisited their diagnosis for each image after being informed of the AI diagnosis. The present study assessed any changes in physician diagnosis and the accuracy of AI-image-assisted diagnosis (AISD). The accuracy of AI was 57.8% for normal, 35.4% for cervical intraepithelial neoplasia (CIN)1, 40.5% for CIN2-3 and 44.2% for invasive cancer. The accuracy of gynecologist diagnoses from cervical pathological images, before knowing the AI image diagnosis, was 54.4% for CIN2-3 and 38.9% for invasive cancer. After learning of the AISD, their accuracy improved to 58.0% for CIN2-3 and 48.5% for invasive cancer. AI-assisted image diagnosis was able to improve gynecologist diagnosis accuracy significantly (P<0.01) for invasive cancer and tended to improve their accuracy for CIN2-3 (P=0.14).

CD70 antibody-drug conjugate: A potential novel therapeutic agent for ovarian cancer.

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3 , P < .01; SKOV3cisR: 232.2 vs 584.9 mm3 , P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma. OBJECTIVE: This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma. STUDY DESIGN: Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models). RESULTS: CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm3; relative reduction, 84.7%; P<.001). CONCLUSION: Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.

Fathers' participation in the HPV vaccination decision-making process doesn't increase parents' intention to make daughters get the vaccine.

INTRODUCTION: The HPV vaccination rate in Japan has been dismally low. Our previous survey work found that mothers in Japan, who have a strong influence over their daughters, often are receptive to the fathers' participation in the family's decision-making process about getting their daughter HPV vaccinated. METHODS: We conducted a survey to investigate the nature of the influence of fathers' participation on the mother's decision-making process. From an internet survey panel, we selected a pool of 1,499 eligible mothers who had 12-18 years old daughters. The mothers were randomized into three Groups. To the mothers in Group A, we gave an educational leaflet regarding HPV vaccination and a second leaflet which recommended that they talk with their husbands about the vaccination. To Group B, we gave only the educational leaflet. No leaflets were sent to Group C. A structured survey questionnaire was then distributed through the internet to the mothers. RESULTS: In Groups A, B, and C, their intention to have their daughter receive the HPV vaccine was 21.6%, 20.7% and 8.2%, respectively. The percent of Group A mothers who thought their husband's opinion was important for when they made the decision was significantly higher (70%) than in Group B (56.6%) or Group C (47.1%). CONCLUSIONS: The fathers' participation in the mothers' decision-making does not increase the likelihood of HPV vaccination for their daughters. On the other hand, the educational leaflet proved to be effective for this cause.

Time-dependent changes of the intention of mothers in Japan to inoculate their daughters with the HPV vaccine after suspension of governmental recommendation.

In Japan, the trend for cervical cancer at younger ages has been increasing. As a countermeasure, the HPV vaccine was introduced as a routine vaccination in April 2013. However, the Ministry of Health, Labour and Welfare (MHLW) announced a "Suspension of its active inoculation recommendation for HPV vaccine" in June 2013. In 2016, 32 months after that suspension, we conducted survey via Internet and compared the results with our previous ones conducted at 9 and 23 months after suspension (in 2014 and 2015, respectively). We examined the 'time-dependent change' of the 'intention of mothers to inoculate their daughters with the HPV vaccine' in terms of efficacy of external decision-making support. 17.5% of mothers in the first survey replied that they would inoculate their daughters under the current circumstances, 12.1% in the second survey, and 6.7% in the third, showing a consistent decrease in willingness over time (p = 0.03, p < 0.01). If the government recommendation were to be reintroduced, 22.5% of mothers in the first survey replied they would inoculate their daughters, 21.0% in the second survey, which indicated no significant difference (p = 0.65) over the first interval; however, this was significantly decreased to 12.2% in the third survey (p < 0.01). Our study revealed that the intention to inoculate their daughters has been declining among Japanese mothers over time triggered by the suspension.

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.

Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).

PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m2, respectively; level 2: 100 and 1000 mg/m2) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity. RESULTS: A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m2 irinotecan and 1000 mg/m2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%. CONCLUSIONS: Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

Realistic fear of cervical cancer risk in Japan depending on birth year.

OBJECTIVE: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. METHODS: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. RESULTS: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994-1999 was reduced to 0.56-0.70, however, the rate in those born in 2000-2003 was 0.98-1.0, almost the same risk as before introduction of the vaccine. DISCUSSION: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

Treatment and repair of uterine scar dehiscence during cesarean section.

The incidence of cesarean section (c-section) has increased worldwide. Because the major risk factor for uterine scar dehiscence (USD) is a previous c-section, the rate of this complication has also increased. Its clinical significance and management strategies are unclear. Here, we discuss USD particularly pertaining to its surgical treatment.

Pregnancy management for a patient with graft occlusion after right iliac artery bypass surgery.

We describe an extremely rare case of a pregnant woman who had a successful delivery despite developing bypass graft occlusion after right external iliac bypass surgery. External and common iliac artery bypass surgery is often performed when arteriosclerosis obliterans or thromboangiitis obliterans result in iliac artery occlusion or when revascularization is required because of iliac artery injury. Because arteriosclerosis obliterans and thromboangiitis obliterans rarely develop in young women or girls, most physicians have little experience with graft occlusion after iliac artery bypass surgery. Here we describe and discuss the published work pertaining to this extremely rare case.