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.

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.

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.

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.

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.

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.

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.

Fibrosis in Preeclamptic Placentas Is Associated with Stromal Fibroblasts Activated by the Transforming Growth Factor-ß1 Signaling Pathway.

Although fibrosis is one of the most prominent pathologic features of preeclamptic (PE) placentas, its mechanism remains largely unknown. Consistent with previous reports, we observed overexpression of collagen; actin, α2, smooth muscle, aorta; connective tissue growth factor; and fibronectin in PE placentas compared with control ones. To investigate the mechanism of fibrosis in PE placentas, placental fibroblasts were isolated from PE placentas or normal pregnancies at delivery. The expression of fibrosis-related factors in fibroblasts was evaluated by real-time RT-PCR, Western blotting, enzyme-linked immunosorbent assay, and gene microarrays. An in vitro collagen gel contraction assay was also performed. Fibroblasts isolated from PE placentas showed higher expression levels of fibrosis-related factors compared with those from control ones. Global gene expression profiling of PE fibroblasts was contrasted with that of control ones and indicated an intimate association with transforming growth factor-ß1 (TGFB1) signaling. Furthermore, the PE fibroblasts expressed abundant phosphorylated SMAD family member 2 and showed higher expression levels of target genes of TGFB1 signaling compared with the control ones. The PE fibroblasts also had a greater ability to contract compared with the control ones. Contractility also depended on TGFB1 signaling. Our results suggest that TGFB1 signaling is activated in the fibroblasts in PE placentas and that these active fibroblasts contribute to fibrosis.

Pelvic abscess: A late complication of abdominal trachelectomy for cervical cancer.

AIM: Only a few reports of pelvic abscess as a late complication of trachelectomy have been published to date. To evaluate the cases of pelvic abscess as a late complication of abdominal trachelectomy for cervical cancer. METHODS: In June 2005, we began a clinical trial of abdominal trachelectomy at our institution. Written informed consent was obtained from all patients. We retrospectively reviewed the medical records of patients who underwent trachelectomy and extracted the data of patients who experienced pelvic abscess as a late complication. RESULTS: From June 2005 to September 2017, we performed 181 trachelectomies at our institution. In total, 15 pelvic abscesses occurred in 12 of these patients more than 1 month after trachelectomy. The median postoperative period before the onset of pelvic abscess was 51 months (range, 1-104 months). Among the 15 cases, abscess formed in the uterine adnexa in 12, in a pelvic lymphocyst in two, and in the uterus in one. Abscess drainage was performed in six cases. Three patients underwent laparotomy with salpingo-oophorectomy. CONCLUSION: It is possible that not only surgical removal of the uterine cervix but also the use of nonabsorbable suture in cervical cerclage and placement of an intrauterine device triggered post-trachelectomy infection. Pelvic abscess can occur as a late complication of abdominal trachelectomy.

Survey of the desire to have children and engage in sexual activity after trachelectomy among young Japanese women with early-stage cervical cancer.

AIM: To evaluate how the desire to have children and engage in sexual activity change after trachelectomy in Japanese women with early-stage cervical cancer who strongly desired to have children before surgery. METHODS: Desire to have children, coital pain, fear of sexual intercourse, sexual activity frequency and libido were assessed in cervical cancer patients who received follow-up after trachelectomy. An anonymous questionnaire survey was conducted via informed consent. RESULTS: Of the 151 patients who underwent trachelectomy at Kyushu University Hospital between 2005 and 2015, 46 patients were evaluated; the response rate was 30%. The desire to have children disappeared in 13 of 46 (28%) patients, and 14 (30%) patients experienced increased coital pain. Moreover, 19 (41%) patients experienced fear of sexual intercourse, and sexual frequency decreased in 24 (52%) patients. CONCLUSION: Trachelectomy is an important fertility-sparing surgical method; however, this study revealed loss of the desire to have children and/or to engage in sexual activity in some patients after surgery. Counseling about these issues is important and should be addressed.

Amide Proton Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association with Histologic Grade.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in estimating histologic grades of endometrioid endometrial adenocarcinoma (EEA). Materials and Methods The institutional review board approved this prospective study. Between June 2012 and March 2016, 32 patients with EEA underwent magnetic resonance (MR) imaging. After their surgical procedures, their EEAs were confirmed pathologically and classified into histologic grades: grade 1 (n = 11), grade 2 (n = 11), and grade 3 (n = 10). The APT signal intensities (SIs) and the mean and minimum apparent diffusion coefficients (ADCs) of the three grades were calculated and compared. Spearman rank correlation coefficient was also calculated between the APT SIs and histologic grades, and between the ADCs and histologic grades. Results The Spearman correlation coefficient with histologic grade of the APT SIs, the mean ADC, and the minimum ADC were 0.55 (P = .001), 0.03 (P = .84), and -0.30 (P = .09), respectively. The average APT SIs and the mean and minimum ADCs were 2.2% ± 0.2 (standard deviation), 0.9 × 10-3 mm2/sec ± 0.2, and 0.6 × 10-3 mm2/sec ± 0.1 for grade 1; 3.2% ± 0.3, 0.8 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 2; and 3.7% ± 0.3, 0.9 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 3, respectively. The APT SIs of grade 3 EEA were significantly higher than those of grade 1 EEA (P = .01), but other pairwise comparisons did not reveal any significant differences (P = .06-.51). The mean and minimum ADCs showed no significant differences among the three histologic grades (P =.13-.51). Conclusion The APT SI was positively correlated with the histologic grades of EEA. © RSNA, 2017 Online supplemental material is available for this article.

Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma.

AIMS: The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). METHODS AND RESULTS: We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. CONCLUSIONS: IMP3 expression in ULMS could be a marker of a poor prognosis.

Value of Intraoperative Cytological and Pathological Sentinel Lymph Node Diagnosis in Fertility-Sparing Trachelectomy for Early-Stage Cervical Cancer.

BACKGROUND AND OBJECTIVES: Trachelectomy, a fertility-sparing surgery for early-stage cervical cancer, can be performed only when there is no extrauterine extension present. Therefore, identifying the sentinel lymph nodes (SLNs) and using them to obtain an intraoperative pathologic diagnosis can provide information on the feasibility and safety of trachelectomy. Our aim was to assess the value of an intraoperative SLN diagnosis. METHODS: We retrospectively analyzed the accuracy of intraoperative imprint cytology and frozen-section examination in 201 patients at our institution in whom trachelectomy was planned. RESULTS: All patients could be evaluated for SLNs; a total of 610 SLNs were analyzed. Although the specificity of both imprint cytology and frozen-section examination was 100.0%, the sensitivity was only 58.6 and 65.5%, respectively. The diagnostic sensitivity was higher in 2-mm slices along the short axis than on bisection along the longitudinal axis. Imprint cytology correctly diagnosed 2 patients who had false-negative results on frozen section. The nature of the metastatic foci that caused an intraoperative false-negative diagnosis was either micrometastasis or isolated tumor cells. CONCLUSIONS: The accuracy of intraoperative SLN diagnosis requires improvement, especially when small metastatic foci are present.

Infertility after abdominal trachelectomy.

INTRODUCTION: Despite numerous reports on pregnancy outcomes after trachelectomy, there are few descriptions of fertility treatment after trachelectomy. Moreover, little is known about the differences in fertility outcomes between various radical trachelectomy procedures. The purpose of this report was to clarify the infertility problems that occur in patients who have previously undergone an abdominal trachelectomy. MATERIAL AND METHODS: We retrospectively investigated the medical records of 37 patients who received fertility treatments or were evaluated for menstrual disorders after trachelectomies in our institution between 2012 and 2016. RESULTS: Twenty-two of 37 patients had complications which affected fecundity. Six patients had cervical stenosis requiring surgical dilation, 4 had ovarian insufficiency, and 14 had Asherman's syndrome. CONCLUSIONS: In spite of efforts to preserve fertility, some patients have severe complications after trachelectomy, such as Asherman's syndrome, resulting in infertility. Clinicians should pay careful attention to the status of the endometrial cavity after trachelectomy.

Prognostic outcome and complications of sentinel lymph node navigation surgery for early-stage cervical cancer.

BACKGROUND: To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy. METHODS: A total of 139 patients who underwent SNNS using 99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group. RESULTS: The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median 40 months) in the SNNS group. CONCLUSIONS: Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted.

Oncologic and obstetric outcomes and complications during pregnancy after fertility-sparing abdominal trachelectomy for cervical cancer: a retrospective review.

BACKGROUND: Trachelectomy was developed as a fertility-sparing surgery for early-stage cervical cancer in patients of childbearing age. The purpose of this study is to evaluate oncologic and obstetric outcomes and complications after abdominal trachelectomy. METHODS: We began to perform abdominal trachelectomy in 2005. Our institutional review board approved this clinical study, and fully informed consent was obtained from each patient. The medical records of patients who underwent trachelectomy were retrospectively reviewed. RESULTS: We performed 151 abdominal trachelectomies (89 radical trachelectomies, 48 modified radical trachelectomies, and 14 simple trachelectomies). The median age of the patients was 33 years, and the median postoperative follow-up period was 61 months. Although one patient experienced recurrence at the preserved cervix, none died after treatment. A total of 61 patients attempted to conceive after trachelectomy, and 21 pregnancies were achieved in 15 women. Hence, the pregnancy rate among patients who attempted to conceive was 25%. Fifteen babies were delivered by cesarean section between gestational weeks 23 and 37. Six babies were delivered at term. Six cases of preterm premature rupture of the membranes occurred. Varices appeared around the uterovaginal anastomotic site in five patients. CONCLUSIONS: Our data indicate that the oncologic outcome was excellent but infertility treatment was necessary to achieve the majority of conceptions. Additionally, preterm premature rupture of the membranes and premature delivery were frequently observed. An improved pregnancy rate and prevention of complications during pregnancy are issues that should be addressed in future studies.

FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian tumors.

FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c-Myc, cyclin E, Notch and c-Jun. FBXW7 is a known tumor-suppressor gene, and mutations in FBXW7 have been reported in various human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes. We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBXW7 expression was negatively correlated with the malignant potential of ovarian tumors. That is to say, FBXW7 expression levels in ovarian cancer samples were significantly lower than those in borderline and benign tumors (P < 0.01). FBXW7 expression levels in serous carcinoma samples were the lowest among four major histological subtypes. In addition, p53-mutated ovarian cancer samples showed significantly lower levels of FBXW7 expression compared with p53 wild-type cancer samples (P < 0.001). DNA methylation arrays and bisulfite PCR sequencing experiments revealed that 5'-upstream regions of FBXW7 gene in p53-mutated samples were significantly higher methylated compared with those in p53 wild-type samples (P < 0.01). This data indicates that p53 mutations might suppress FBXW7 expression through DNA hypermethylation of FBXW7 5'-upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers, and was associated with p53 mutations and the DNA methylation status of the 5'-upstream regions of FBXW7.

Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin.

BACKGROUND: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy. METHODS: We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively. RESULTS: Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %; P < 0.0001), "no significant nausea" patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group. CONCLUSION: The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.