Immunohistochemical p16 overexpression and Rb loss correlate with high-risk human papillomavirus infection in endocervical adenocarcinomas.

AIMS: p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect. METHODS AND RESULTS: We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR-HPV infection by mRNA in-situ hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR-HPV was detected in 83 of 108 ECA cases (77%), including five HPV-associated adenocarcinomas in situ and 78 invasive HPV-associated adenocarcinomas. All 83 HPV-positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV-independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV-independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR-HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR-HPV infection correlated with better prognosis among invasive ECAs. CONCLUSIONS: The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR-HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy.

Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma.

Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7-30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and ß-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p < 0.0001) and high CDK8 expression (p = 0.0014) were independent predictors of poor prognosis. MED12 mutation status was not significantly associated with CDK8 expression (p = 0.6873) and DSS (p = 0.8075). In conclusion, our data suggest that CDK8 expression may identify a subset of ULMS patients with a poor prognosis.

Resolution of large pelvic lymphocele after incidental intracystic hemorrhage caused by percutaneous catheter drainage: Case report.

We report the case of a large pelvic lymphocele after an ovarian cancer operation, which incidentally vanished after bleeding resulting from percutaneous catheter drainage. The patient was a 74-year-old woman with stage IVB ovarian cancer who underwent surgery including pelvic lymph node dissection. Three months after surgery, computed tomography revealed a large (13-cm diameter) pelvic lymphocele with associated bilateral hydronephrosis and left femoral vein thrombosis. The lymphocele was repeatedly drained by percutaneous aspiration, and the day after the second procedure, the drainage fluid became bloody. The catheter was clamped for 3 days and then removed. The lymphocele volume gradually decreased, and it was not seen on a computed tomography scan 70 days after drainage. The lymphocele did not recur prior to her death. In this case, the intracystic hemorrhage was considered to have served as a blood patch for lymph leakage.

Long-term follow up after sentinel node biopsy alone for early-stage cervical cancer.

OBJECTIVE: Sentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy. METHODS: We performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed. RESULTS: The median age of the patients was 34 years (range, 21-73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25-145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate. CONCLUSIONS: SNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate.

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA).

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Difficulty of cervical cancer diagnosis during pregnancy: A case series analysis of the clinicopathological characteristics and prognosis of cervical cancer diagnosed during pregnancy or within 6 months after parturition.

Due to the recent trend of women having children at an older age, the number of pregnancies complicated by cervical cancer has increased. In the present study, the clinical characteristics of patients with cervical cancer complicated by pregnancy were analyzed. The clinicopathological characteristics and prognosis of patients with cervical cancer during pregnancy who underwent treatment at Kyushu University Hospital from January 2008 to December 2017 were assessed retrospectively from their medical records. The medical information of patients diagnosed within 6 months after parturition was also evaluated as these patients were considered to be affected by cervical cancer during pregnancy. A total of 19 women were diagnosed with cervical cancer during pregnancy (median age, 33 years), three of whom were diagnosed as negative for intraepithelial lesion or malignancy at the initial visit to a previous clinic after pregnancy. The tumor stage was IA1 in one patient, IB1 in 16 patients, IB2 in one patient and IVB in one patient. The median gestational age at the time of cervical cancer diagnosis was 13 weeks. One patient died of cervical cancer during the follow-up period. An additional 12 patients were diagnosed within 6 months after parturition. The median age of these patients was 35.5 years. Cancer screening was performed in 10 patients during pregnancy, none of whom were diagnosed with cervical cancer, including three patients who were negative for intraepithelial lesion or malignancy. Of the 12 patients, one had tumor stage IA1, eight had IB1, two had IB2 and one had IIB. Three patients experienced recurrence, of whom one died of cervical cancer. Advanced cervical cancer was diagnosed both during pregnancy and within 6 months after parturition. Diagnosis of cervical cancer during pregnancy is difficult even at an advanced stage; however, rapid diagnosis and prompt multidisciplinary treatment are critical. Therefore, it is necessary to improve the accuracy of cervical cancer diagnosis, and to characterize tumor cells and their microenvironment, during pregnancy.

YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer.

Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.

Evaluation of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer: a single-institution experience.

BACKGROUND: To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. METHODS: Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. RESULTS: Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12-146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. CONCLUSION: Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation.

Prognosis of bulky pTIIB cervical cancer treated by radical hysterectomy comparing adenocarcinoma with squamous cell carcinoma using propensity score matching.

OBJECTIVE: To investigate whether radical hysterectomy (RAH) can effectively treat true Stage IIB (pTIIB) cervical adenocarcinoma (AC) because FIGO (clinical) Stage IIB cervical cancer is rarely treated with RAH and radiotherapy has unfavorable effects on AC. METHODS: We retrospectively analyzed data for 82 patients with Stage pTIIB cervical cancer who underwent RAH at our institution between January 1997 and December 2017. The end points were disease-free survival (DFS) and overall survival (OS) among squamous cell carcinoma (SCC) (n = 60) and AC (n = 22) patients. Kaplan-Meier survival analysis with and without propensity score matching was conducted to identify the impact of RAH. RESULTS: Para-aortic lymph node metastasis and tumor diameter were significant factors for recurrence, and adjuvant chemotherapy prevented recurrence on multivariate analysis. After propensity score matching, there was no significant difference in DFS and OS between the groups. Five-year DFS and OS of the SCC group were 0.505 (95% confidence interval [CI] 0.268-0.702) and 0.619 (95% CI 0.351-0.803), respectively, and those of the AC group were 0.444 (95% CI 0.232-0.638) and 0.602 (95% CI 0.351-0.782), respectively. CONCLUSION: Bulky Stage pTIIB cervical cancer is hard to cure, but RAH plus adjuvant therapy might be an option for radio-resistant pTIIB cervical AC.

Identification of genes associated with endometrial cell ageing.

Ageing of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine ageing are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine ageing. Gene expression patterns were assessed by two RNA-sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5- and 8-week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20s and 40s (10 cases each). In the secretory phase samples, 3,3'- diaminobenzidine staining intensities of IL17RB, CXCL12 and CXCL14 for patients in their 40s were significantly higher than that for patients in their 20s, as detected by a Mann-hitney U test. These results suggest that these genes are candidate markers for endometrial ageing and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.

Diagnostic benefit of cytological and histopathological examinations for recurrent vaginal cancer metastasizing to the duodenum: A case report.

This is the first case report of a vaginal squamous cell carcinoma that metastasized to the duodenum. Cytological and histopathological examinations are useful for the diagnosis of a duodenal metastasis.

Potential alternative progestin therapy for low-grade endometrial stromal sarcoma: A case report.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor that sometimes recurs and advances. Hormonal treatment, especially high-dose progestins and aromatase inhibitors (AIs), has demonstrated efficacy against these tumors. Because the standard treatment period is uncertain and hormonal treatment is effective, hormonal agents are likely to be used long-term, especially when a residual tumor is present. However, the long-term use of high-dose progestins and AIs may cause thromboembolism, as well as musculoskeletal stiffness and pain. Dienogest, a relatively new progestin, has demonstrated safety after long-term administration; it also appears to have a more favorable long-term safety profile compared with other progestins and AIs. We encountered a young patient with recurrent LG-ESS that metastasized to the liver and exhibited resistance to high-dose medroxyprogesterone acetate (MPA). The patient was successfully treated with dienogest monotherapy. This is the first report describing the efficacy of dienogest against recurrent and metastatic LG-ESS that is resistant to MPA and other agents.

Is Adjuvant Therapy Necessary for Patients with Intermediate-Risk Cervical Cancer after Open Radical Hysterectomy?

INTRODUCTION: Adjuvant therapy is usually recommended for patients with intermediate-risk cervical cancer (deep stromal invasion [DSI], lymphovascular space invasion [LVSI], and bulky tumor) after radical hysterectomy. However, we previously reported that DSI, LVSI, and bulky squamous cell carcinoma (SCC) were not correlated with prognosis in multivariate analysis; therefore, the indications we use for adjuvant therapy include complete stromal invasion, not DSI or LVSI or bulky SCC. The objective of this study was to evaluate the adequacy of our therapeutic strategy for cervical cancer after radical hysterectomy. METHODS: We performed 321 type III open radical hysterectomies for cervical cancer between 2001 and 2013. Eighty-two patients with DSI, LVSI, or bulky SCC did not receive adjuvant therapy after radical hysterectomy under informed consent. We retrospectively evaluated the prognosis of these 82 patients. RESULTS: Forty-two patients had >2/3 DSI and 35 patients had 1/3-2/3 DSI. Five patients had LVSI alone. The mean patient age was 43 years (range, 27-72). Six patients (7%) experienced recurrence during a median follow-up period of 84 months (range, 1-206). Two of the 6 patients with recurrence suffered cervical cancer-related deaths, but the remaining 4 cases are alive without evidence of disease after treatment during a follow-up period of 87-165 months. The 5-year disease-free survival rate was 92.6%, and the 5-year overall survival rate was 96.3%. CONCLUSIONS: Adjuvant therapy for DSI, LVSI, or bulky SCC after open radical hysterectomy might not be necessary. Further data collection is warranted to determine the standard of care for patients with intermediate-risk cervical -cancer.

Sectioning protocol determines accuracy of intraoperative pathological examination of sentinel lymph node in cervical cancer: A systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to July 30, 2019, for studies concerning SLNB with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator for evaluation. RESULTS: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0.77 (95% CI 0.66-0.85) with high heterogeneity (I2 = 69.73%). Two representative sectioning protocols for FSE were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected) and latitudinal (L-protocol, SLN was cut at intervals). Meta-regression showed that FSE protocol was the only source of heterogeneity (p < 0.001). The pooled sensitivity was 0.86 (95% CI 0.79-0.91, I2 = 0%) and 0.59 (0.46-0.72, I2 = 58.47%) for FSE using L- (13 studies, 650 patients) and E- (13 studies, 1047 patients) protocol, respectively. Among the available data, marcometastases (>2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0.97 (95% CI 0.89-0.99) if only marcometastases were considered. These findings were robust to sensitivity analyses. CONCLUSION: The sectioning protocol determines the accuracy of FSE in SLNB. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements.

Safety evaluation of abdominal trachelectomy in patients with cervical tumors ≥2 cm: a single-institution, retrospective analysis.

OBJECTIVE: For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm. METHODS: We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study. RESULTS: We attempted trachelectomy in 212 patients. Among the 135 patients with tumors <2 cm, trachelectomy was successful in 120, one of whom developed recurrence and none of whom died of their disease. Among 77 patients with tumors ≥2 cm, trachelectomy was successful in 62, 2 of whom developed recurrence and 1 of whom died of her disease. The overall relapse rate after trachelectomy was 1.6% (0.8% in <2 cm group and 3.2% in ≥2 cm group), and the mortality rate was 0.5% (0% in <2 cm group and 1.6% in ≥2 cm group). Recurrence-free survival (p=0.303) and overall survival (p=0.193) did not differ significantly between the <2 cm and ≥2 cm groups. CONCLUSIONS: Abdominal trachelectomy with intraoperative frozen sections of sentinel lymph nodes and cervical margins is oncologically safe, even in patients with tumors ≥2 cm.

Retrospective analysis of treatment and prognosis for uterine leiomyosarcoma: 10-year experience of a single institute.

AIM: Uterine leiomyosarcoma (ULMS) is a highly aggressive and lethal disease. This malignancy remains the most common type of uterine sarcoma, affecting approximately 0.4/100 000 women each year. Our aim was to assess the treatment and prognosis of ULMS patients. METHODS: A total of 14 patients were treated at our institution between January 2008 and July 2017. We retrospectively analyzed their clinicopathological variables, treatment and prognosis. RESULTS: The median patient age was 63 years (range, 35-83 years). The largest group of patients had stage IB disease (stage IB, n = 8; IIB, n = 2; IIIB, n = 1; IVB, n = 3) and the largest group by histological subtype was ordinary (ordinary, n = 11; myxoid, n = 2; epithelioid, n = 1). Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed for all patients, with additional surgical procedures (e.g., tumor resection, lymphadenectomy) performed if necessary. Twelve patients received adjuvant chemotherapy (ACT) consisting of gemcitabine and docetaxel. Ten patients experienced recurrence and received multidisciplinary therapies, including tumor resection, chemotherapy, radiation and targeted therapies. The median observation period was 17 months (range, 5-75 months), and 11 patients were alive (without disease, n = 5; with disease, n = 6). Intriguingly, five of eight stage IB patients who received postoperative ACT were alive without disease. CONCLUSION: ULMS is rare but is associated with a poor prognosis, even if multidisciplinary therapies are administered. However, ACT appears to be effective in improving the prognosis of patients with stage IB disease.

Serous carcinoma of the uterine cervix: Clinicopathological features differing from serous carcinomas of other female organs.

AIM: Serous carcinoma of the uterine cervix (USCC) is a very rare malignant tumor, while this histological subtype is common in the ovary, fallopian tube, uterine corpus and peritoneum. Because of its rarity, details of the clinicopathological features of USCC are largely unknown. We retrospectively analyzed the clinicopathological characteristics of five cases of pure USCC. METHODS: We reviewed the medical records and pathological specimens of five USCC cases who were treated at the Gynecology Service of the National Hospital Organization Kyushu Cancer Center, Japan, between 2000 and 2017. The clinicopathological features were also compared with those of serous carcinomas of the endometrium and ovary who were treated during the same period. RESULTS: Five patients were treated at our hospital between 2000 and 2017. Three tumors were stage IB1, one was stage IIB, and one was stage IVB. The median follow-up time was 104 months (range 26-210). Four patients other than stage IVB were treated with radical hysterectomy and have been free of relapse. One patient with stage IVB tumor was treated with platinum-based combination chemotherapy and is currently on maintenance therapy with bevacizumab and remains free of relapse. CONCLUSION: USCC has a distinctive clinicopathological feature that differentiates it from serous carcinomas of other female organs. USCC had been thought to be a poor prognostic disease; however, it could be curable if it is not accompanied by lymph node metastasis or peritoneal dissemination. We might conquer USCC even if it is accompanied by lymph node metastasis with the use of multimodal therapy.

Reduction in HPV16/18 prevalence among young women with high-grade cervical lesions following the Japanese HPV vaccination program.

The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12-16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population-level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1-3 (CIN1-3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012-2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6-year period were observed in CIN1 (50.0% to 0.0%, Ptrend  < .0001) and CIN2-3/AIS (83.3% to 45.0%, Ptrend  = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18-attributable CIN2-3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch-up vaccination (P = .04). The HPV16/18 prevalence in CIN2-3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18-positive CIN/AIS in Japan; however, our data did not support catch-up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch-up vaccination before age 20 years.

Amide proton transfer imaging for differentiating benign ovarian cystic lesions: Potential of first time right.

PURPOSE: To investigate whether amide proton transfer (APT) imaging is useful to differentiate benign ovarian cystic lesions. MATERIALS AND METHODS: This prospective study enrolled a total of 19 lesions in 18 patients with benign ovarian cystic lesion: serous cystadenoma (SCA), n = 4; mucinous cystadenoma (MCA), n = 9; or functional cyst (FC), n = 6. APT imaging was performed with three different presaturation pulse durations: 0.5, 1.0 and 2.0 s. APT signal was defined as magnetization transfer ratio asymmetry at 3.5 ppm. The SI ratios of cyst to muscle calculated on T1- and T2-weighted images were defined as T1- and T2-ratios. Apparent diffusion coefficient (ADC) maps were also generated. We compared the three cystic lesion groups' APT signals, T1-ratio, T2-ratio, and ADC. RESULTS: When using 2.0 s of presaturation, the APT signals were 1.41 ±â€¯0.71% in SCA, 5.15 ±â€¯1.92% in MCA and 8.52 ±â€¯1.17% in FC. Significant differences were observed between SCA and MCA (p < .01) and MCA and FC (p < .05), as well as between SCA and FC (P <  .0001). When 1.0 s presaturation pulse was used, similar results were obtained. On the other hand, ADC value shows significance only between SCA (2.91±0.03×10-3 mm2/s) and MCA (2.59 ±â€¯0.49 × 10-3 mm2/s, p < .05). Further, there was no significant difference in the T1-ratio, T2-ratio among the three groups. CONCLUSIONS: APT imaging might be useful for the non-invasive diagnosis of benign ovarian cystic lesions. With the use of the longer presaturation pulse as possible, APT imaging may provide an early and correct diagnosis of ovarian cystic lesions without additional follow-up studies.