A single institution's experience with minimally invasive surgery for ovarian cancer, and a systematic meta-analysis of the literature.

BACKGROUND: This study assesses the feasibility of minimally invasive surgery (MIS) for well-selected epithelial ovarian cancer (EOC) patients. METHODS: We performed a review of data prospectively collected from a single center from 2017 to 2022. Only patients with histologically confirmed EOC, with a tumor diameter of less than 10 cm, were eligible. We also performed a meta-analysis of similar studies comparing the outcomes of laparoscopy and laparotomy. We used MINORS (Methodological Index for Non-Randomized Studies) to assess the risk of bias and calculated the odds ratio or mean difference. RESULTS: Eighteen patients were included; 13 in re-staging group, four in PDS group, and one in IDS group. All achieved complete cytoreduction. One case was converted to laparotomy. The median number of removed pelvic lymph nodes was 25 (range 16-34), and 32 (range 19-44) for para-aortic nodes. There were two (15.4%) intraoperative urinary tract injuries. The median follow-up was 35 months (range 1-53). Recurrence was observed in one case (7.7%). Thirteen articles for early-stage ovarian cancer were included in our meta-analysis. Analysis of the pooled results found that MIS had a higher frequency of spillage (OR, 2.15; 95% CI 1.27-3.64). No differences were observed in recurrence, complications, or up-staging. CONCLUSIONS: Our experience supports the possibility of conducting MIS for EOC in well-selected patients. Except for spillage, our meta-analysis findings are consistent with previous reports, the majority of which were also retrospective. Ultimately, randomized clinical trials will be needed to authenticate the safety.

Attitudes and behaviors of obstetricians and gynecologists toward HPV vaccination: a 7-year follow-up survey in Japan.

BACKGROUND: In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys. METHODS: The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019. RESULTS: A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization. CONCLUSION: This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine.

PD-1+ Tim3+ tumor-infiltrating CD8 T cells sustain the potential for IFN-γ production, but lose cytotoxic activity in ovarian cancer.

Persistent exposure to tumor antigens results in exhausted tumor-infiltrating T cells (TILs) that express the immune checkpoint molecules, PD-1 and Tim3, and lack anti-tumor immunity. To examine the exhausted status of TILs in ovarian cancer, the potential for cytokine production, proliferation and cytotoxicity by purified PD-1+ Tim3+ CD8 TILs was assessed. The production of IFN-γ and TNF-α by PD-1+ Tim3+ CD8 TILs remained the same in an intracellular cytokine staining assay and was higher in a cytokine catch assay than that by PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. %Ki67+ was higher in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- CD8 TILs. However, patients with high PD-1+ Tim3+ CD8 TILs had a poor prognosis. The potential for cytotoxicity was then examined. %Perforin+ and %granzyme B+ were lower in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. To observe the potential for direct cytotoxicity by T cells, a target cell line expressing membrane-bound anti-CD3scFv was newly established and a cytotoxic assay targeting these cells was performed. The cytotoxicity of PD-1+ Tim3+ CD8 TILs was significantly lower than that of PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. Even though PD-1+ Tim3+ CD8 TILs in ovarian cancer showed a sustained potential for cytokine production and proliferation, cytotoxicity was markedly impaired, which may contribute to the poor prognosis of patients with ovarian cancer. Among the impaired functions of exhausted TILs, cytotoxicity may be an essential target for cancer immunotherapy.

Clinical importance of the expression of CD4+CD8+ T cells in renal cell carcinoma.

OBJECTIVE: CD4+CD8+ T cells are expressed in some cancer patients including those with renal cell carcinoma (RCC). However, no reports have mentioned the clinical importance of this expression. We evaluated the expression of CD4+CD8+ T cells in patients with various cancer types to clarify clinical characteristics and prognostic importance significantly correlating with these T cells. METHODS: Expression of CD4+CD8+ T cells was evaluated using flowcytometry in tissue-infiltrating lymphocytes extracted from 260 cancer tissues including 104 RCC samples. RNA sequencing and characterization and regression (Citrus) was used to determine characteristics. The prognostic importance of CD4+CD8+ T cells was evaluated by Cox regression analysis. RESULTS: Among eight cancer types, expression of CD4+CD8+ T cells was significantly highest in RCC patients. According to the expression of CD4+CD8+ T cells in adjacent normal tissue-infiltrating lymphocytes, 24 patients (23.1%) were defined as being positive for CD4+CD8+ with an expression higher than 9.29% in RCC patients. Citrus showed CD8+PD-1+TIM-3+CD103- T cells to be a specific subpopulation of CD4+CD8+ T cells. RNA sequencing revealed that CD4+CD8+ T cells had significantly lower diversity than the other T cells and shared most T-cell receptor clones with CD8+ not CD4+ T cells. Expression of CD4+CD8+ T cells was identified as an independent predictor of overall survival (hazard ratio: 0.11, 95% confidence interval: 0.01-0.86, P = 0.035) in multivariate analysis. CONCLUSIONS: The expression of CD4+CD8+ T cells was significantly up-regulated in RCC patients and correlated significantly with prognostic importance in surgically treated RCC patients.

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.

Obstetric outcome in patients with a unicornuate uterus after laparoscopic resection of a rudimentary horn.

AIM: Previous studies have shown adverse obstetric outcomes of the laparoscopic resection of a rudimentary horn. Our study aimed to investigate the obstetric outcome in our institution and to review previous studies. METHODS: Using a retrospective analysis, data were reviewed from singleton pregnancies with maternal uterine anomalies at a medical center in Osaka, Japan, between January 2011 and March 2016. The uterine anomaly cases were divided into a 'postlaparoscopic resection of the rudimentary horn' group (study group) and an 'other uterine anomalies' (bicornuate uterus, uterine didelphys and unicornuate uterus) group (control group). Primary outcomes of interest were differences in obstetric outcomes, such as spontaneous preterm birth rate, small for gestational age (SGA) infant rate and hypertensive disorders of pregnancy (HDP) rate between the study and the control group, and the secondary outcome of interest was mode of delivery in the study group. RESULTS: Data from 40 deliveries were included in the study (7 deliveries: study group, 33 deliveries: control group). No significant difference was observed between the two groups in terms of either mean gestational weeks at delivery (36.4 weeks vs 37.1 weeks; P = .38), cesarean delivery rate (57.1% vs 57.5%; P = 1.0), SGA infant rate (<10th percentile) (0% vs 24.2%; P = .31) and HDP rate (0.0% vs 3.0%; P = 1.0). Three of seven cases with postlaparoscopic resection of the rudimentary horn were able to deliver vaginally without complications. CONCLUSION: Our study shows that the obstetric outcome observed in the study group was similar to that observed in the control group.

The efficacy of surgical treatment of recurrent or persistent cervical cancer that develops in a previously irradiated field: a monoinstitutional experience.

BACKGROUND: There are no guidelines about the selection of recurrent cervical cancer patients for salvage surgery. METHODS: Patients who developed recurrent or persistent cervical cancer in a previously irradiated field and were subsequently treated with salvage surgery (the surgery group) or palliative care alone (the palliative group) were identified. Patient characteristics, treatment-related complications, and survival were retrospectively compared between the two groups. RESULTS: A total of 79 patients (surgery group, n = 51; palliative group, n = 28) were identified. In the surgery group, no intraoperative complications or treatment-related deaths occurred. Eleven patients (21.6%) experienced severe postoperative complications. After a median follow-up period of 41.5 months, 23 patients (45.1%) had developed recurrent disease, predominantly at distant sites, and 19 patients (37.3%) had died of disease progression. The estimated 3-year progression-free survival (PFS) and overall survival rates of the surgery group were 50.4 and 56.5%, respectively. In the palliative group, all of the patients died of disease progression. Positive surgical margins and lymph node metastasis were found to be independent prognostic factors for PFS in the surgery group. Among the patients with no or one poor prognostic factor, the patients in the surgery group survived significantly longer than those in the palliative group. However, among the patients with 2 poor prognostic factors, the surgery group and palliative group displayed similar survival periods. CONCLUSIONS: Salvage surgery is a curative treatment in recurrent or persistent cervical cancer patients. However, considering its high surgical complication rate, salvage surgery should only be offered to carefully selected patients.

Long-term survival in small-cell carcinoma of the endometrium with liver and brain metastases.

Small-cell carcinoma (SmCC) of the endometrium is an extremely rare cancer and has a poor prognosis. Because long-term survival is rare, there is a paucity of data on the advanced disease stages. Thus, a standard treatment has not been established. We describe an extremely rare case of long-term survival in SmCC of the endometrium with liver and brain metastases. We provided multidisciplinary treatment, including brain surgery, subsequent whole-brain radiotherapy, gynecologic surgery, and adjuvant chemotherapy (irinotecan hydrochloride+cisplatin). The patient was treated successfully and has survived for more than 12 years with no evidence of the disease. Irinotecan hydrochloride+cisplatin chemotherapy was effective for controlling the liver metastases, and the resection of brain metastases and radiotherapy were effective for the treatment of brain metastases in our case. We reviewed the pertinent literature of advanced SmCC of the endometrium.

Successful conservative management of placenta percreta: Investigation by serial magnetic resonance imaging of the clinical course and a literature review.

Placenta percreta is a rare condition that presents a risk of massive intraoperative hemorrhage. To decrease maternal morbidity in such cases, conservative management was recently adopted as an option. Nevertheless, severe morbidity occurs in 42% of cases. In addition, the clinical course of conservative management remains unclear. We encountered a case of placenta percreta that was successfully treated by conservative management without complications or other clinical interventions. Serial magnetic resonance imaging (MRI) was performed to investigate the natural course of conservative management of placenta percreta. MRI on postoperative day (POD) 99 showed a decrease in placental size without gadolinium enhancement. MRI on POD 162 showed that the residual placenta was approximately 4 cm in size without gadolinium enhancement. On POD 265, the placenta had almost disappeared. This is the first series of MRI of conservative management of placenta percreta without clinical interventions. We present our case and a literature review.

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.

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.