Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia.

To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians' discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age.

Evaluation of Local Retinal Function in Light-Damaged Rats Using Multifocal Electroretinograms and Multifocal Visual Evoked Potentials.

Electroretinograms (ERGs) are often used to evaluate retinal function. However, assessing local retinal function can be challenging; therefore, photopic and scotopic ERGs are used to record whole-retinal function. This study evaluated focal retinal function in rats exposed to continuous light using a multifocal ERG (mfERG) system. The rats were exposed to 1000 lux of fluorescent light for 24 h to induce photoreceptor degeneration. After light exposure, the rats were reared under cyclic light conditions (12 h: 5 lux, 12 h: dark). Photopic and multifocal ERGs and single-flash and multifocal visual evoked potentials (mfVEPs) were recorded 7 days after light exposure. Fourteen days following light exposure, paraffin-embedded sections were prepared from the eyes for histological evaluation. The ERG and VEP responses dramatically decreased after 24 h of light exposure, and retinal area-dependent decreases were observed in mfERGs and mfVEPs. Histological assessment revealed severe damage to the superior retina and less damage to the inferior retina. Considering the recorded visual angles of mfERGs and mfVEPs, the degenerated area shown on the histological examinations correlates well with the responses from multifocal recordings.

Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

BACKGROUND: Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. CASE PRESENTATION: Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. CONCLUSIONS: Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

Long-term outcomes of postoperative taxane/platinum chemotherapy for early stage cervical cancer: a retrospective study.

BACKGROUND: Taxane/platinum (TP)-based combination chemotherapy is standard for the treatment of metastatic or recurrent cervical cancer. The aim of this study was to investigate the efficacy of postoperative TP therapy in early stage cervical cancer. METHODS: A retrospective review of patients with FIGO IB-IIB stage cervical cancer who were treated with radical hysterectomy and displayed surgical-pathological risk factors was performed. 122 patients were identified between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to investigate predictors of survival. RESULTS: The median follow-up period was 82.4 months. The postoperative adjuvant therapy was TP in 82 (67.2%) patients, other chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to the postoperative adjuvant therapy. The estimated 5-year overall survival was 95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT group, and 100% in the NFT group. No significant difference of survival was observed in the subgroups. However, when analyzing only patients who displayed high-risk factors, non-TP adjuvant therapy (including RT and other chemotherapies) was independently associated with shorter survival on multivariate analysis. In the TP group, multivariate analysis revealed that a positive surgical margin was a significant predictor of shorter survival. CONCLUSIONS: Postoperative TP is effective in patients with surgically treated early stage cervical cancer. In these populations, a positive surgical margin could be associated with poor prognosis.

[Safety and Efficacy of Cisplatin Treatment after Carboplatin Hypersensitivity Reactions in Gynecologic Malignancies].

To investigate the safety and efficacy of cisplatin(CDDP)treatment after carboplatin(CBDCA)hypersensitivity reactions (CHSR)in gynecologic malignancies, we retrospectively reviewed the clinical records of 544 patients who underwent paclitaxel and CBDCA therapy(TC therapy). CHSR was observed in 18 patients. Eight patients were administered weekly paclitaxel and CDDP therapy(wTP therapy)continuously, to confirm that there was no CDDP hypersensitivity followingintravenous administration of 10 mgCDDP. At the onset of CHSR, the patients had received a median of 9 TC therapy cycles, and the median number of CBDCA administrations was 14. The frequency of CHSR was significantly higher in patients who received 7 cycles or more of TC therapy and CBDCA administration(p<0.0001). The median number of wTP therapy administrations was 8. Although CDDP hypersensitivity reactions were observed in 2 patients, their symptoms were mild(Grade 2, CTCAE v4.0). Of the 6 patients who received wTP therapy and had evaluable disease sites, 1, 2, 2 and 1 patients showed CR, PR, SD, and PD, respectively. The median progression-free survival in these 6 patients was 9.5 months. For patients with the platinum- sensitive disease who have CHSR, CDDP could improve their prognosis.

The usefulness of 18F-FDG-PET/CT in discriminating benign from malignant ovarian teratomas.

BACKGROUND: The present study investigates the usefulness of 18F-FDG-PET/CT (PET/CT) in distinguishing between benign and malignant ovarian teratomas. METHODS: This study includes 4 mature teratomas (MTs) with malignant transformation, 8 immature teratomas (ITs), and 16 MTs that were diagnosed after surgical resection. Preoperative tumor marker values, MRI findings, PET/CT SUVmax values, and other clinical parameters were retrospectively compared with those of 14 patients who had MTs. RESULTS: The median CA125 was significantly higher for ITs than for MTs (P = 0.04). The median AFP was significantly higher for ITs than for MTs (P = 0.0034). The median SUVmax values for MTs with malignant transformation, ITs, and MTs were 18.3 (5.3-23.3), 6.0 (3.6-22.6), and 1.1 (1.0-15.5), respectively. SUVmax was significantly higher in MTs with malignant transformation and ITs than in MTs (P = 0.004, P = 0.0007). With a cut-off SUVmax of 3.6 to distinguish between benign and malignant MTs, sensitivity was 100 %, specificity was 81 %, positive predictive value was 80 %, negative predictive value was 100 %, and diagnostic accuracy was 89 % (AUC 0.94). However, one patient with an MT had a high SUVmax corresponding to values in the central nervous system (CNS). CONCLUSIONS: 18F-FDG-PET/CT has a high diagnostic accuracy in distinguishing between benign and malignant ovarian teratomas. Thus, PET/CT may be useful in cases where the diagnosis is unclear on MRI and other clinical findings. However, some MTs with abundant CNS tissue may have a high SUVmax. Therefore, the diagnosis of a benign or malignant lesion should be made carefully in conjunction with other clinical findings.

Uterine leiomyosarcoma well-controlled with eribulin mesylate.

Uterine leiomyosarcoma is a rare type of malignant gynecological tumor and has a poor prognosis; therefore, this tumor is often difficult to treat. Some new drugs have been approved during the past several years in Japan and are expected to be efficacious. Eribulin, one of these drugs, is a natural product of halichondrin B, which is isolated from a marine sponge. A recent clinical trial comparing eribulin with dacarbazine to target liposarcoma and leiomyosarcoma indicated that overall survival (OS) was prolonged by treatment with eribulin. We report a case of uterine progressive leiomyosarcoma that responded to eribulin. A 57-year-old woman was suspected of having leiomyosarcoma based on an endometrial biopsy and imaging examinations. Although the tumor grew toward the uterine artery on the right side of the uterine cervix, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy to obtain an outcome of no gross residual disease. However, the margin of the right side of the uterine cervix was histologically positive, so leiomyosarcoma stage IIB (pT2bcN0cM0, FIGO2008) was diagnosed. Gemcitabine and docetaxel therapy was administered postoperatively. However, after three cycles, the residual tumor progressed. Other anticancer drugs were administered but were ineffective. We administered eribulin (1.4 mg/m2) as a fourth-line regimen, and the mass decreased by 32% after four cycles. However, the residual tumor continued to grow after eight cycles. The only adverse event associated with eribulin treatment was mild, grade 2 neutropenia. For our patient, eribulin was effective for her recurrent leiomyosarcoma. In selecting chemotherapy, there are currently no fixed guidelines; we should consider the characteristics and adverse events associated with each drug and patient performance status and comorbidities. In this patient, eribulin was associated with few adverse events, an easy route of administration and a good quality of life. Therefore, eribulin is expected to be efficacious for the treatment of gynecologic sarcoma.

The frequent shift to intermediate flora in preterm delivery cases after abnormal vaginal flora screening.

The effect of screening and treatment for abnormal vaginal flora on the reduction of preterm deliveries remains controversial. We evaluated whether this screening and treatment reduces the preterm delivery rate for general-population pregnant women. Pregnant women of the Intervention group (n = 574) underwent the screening test and the treatment of vaginal metronidazole during the early second trimester, and those of the Control group (n = 1,161) did not. We compared the preterm delivery rate between these two groups. We also compared the profiles of vaginal flora of the preterm delivery cases with those of the pregnant women with a normal course. There was no significant difference in the preterm delivery rate between these two groups. However, in the preterm delivery cases, a frequent shift to intermediate flora was observed not before but after the screening in the Intervention group. This shift may explain why most of the previous studies failed in regard to the prevention of preterm deliveries.