Laparoscopic Sacrohysteropexy for Pelvic Organ Prolapse and the Technique Used for Uterine Preservation: A Case Report.

Pelvic organ prolapse (POP) is prevalent among middle-aged and older women, and its prevalence is expected to increase in Japan in the future. Laparoscopic surgery for POP is covered by insurance and is currently a minimally invasive procedure. There are multiple treatment approaches for the uterus, especially sacrohysteropexy, for patients who wish to preserve their uterus. This approach requires an understanding of its anatomical characteristics, including how the arm is threaded. However, specific techniques for uterine preservation have not yet been thoroughly investigated or reported. Here, we discuss the innovative operative techniques for uterine preservation and mesh application achieved by laparoscopic sacrohysteropexy performed at our hospital. A 34-year-old woman presented at our hospital with a uterine prolapse in the hope of undergoing laparoscopic sacrohysteropexy. The anterior vaginal wall was dissected, the mesh fixed, and the right and left intrauterine foramina next to the cervix were deployed and released. The anterior vaginal wall mesh penetrated the released mesentery and was integrated with the mesh of the posterior vaginal wall. It was fixed to the anterior aspect of the cape angle by using a subperitoneal tunnel. This surgical case is currently under follow-up, with no recurrence to date. We elaborate upon the ingenious insertion site of the port for the preservation of the uterus, the secure fixation of the mesh to the uterus, and the traction method. Unlike laparoscopic sacrocolpopexy and sacrocervicopexy, laparoscopic sacrohysteropexy necessitates at least the aforementioned techniques. At our institution, we perform sacrohysteropexy following the method outlined in this case. A more efficient technique is expected to emerge as larger-scale studies accumulate additional cases, ultimately leading to widespread acceptance and standardization of the approach.

Does maternal oxygen administration during non-reassuring fetal status affect the umbilical artery gas measures and neonatal outcomes?

PURPOSE: To clarify whether maternal oxygen administration during vaginal delivery improves umbilical artery (UA) gas measurements and neonatal outcomes. METHODS: Singleton pregnancies requiring operative vaginal delivery or emergency cesarean section (CS) due to non-reassuring fetal status (NRFS) during vaginal delivery at our hospital from 2018 to 2021 were retrospectively investigated. Intrapartum fetal wellbeing was evaluated based on the 5-tier fetal heart rate (FHR) pattern which is a delivery management method widely used in Japan. Operative vaginal deliveries or emergency CS was performed under integrated judgment in NRFS. Patients were divided into the oxygen group to whom oxygen (10 L/min) was supplied by a facemask and the room air group. The UA gas measurements and neonatal outcomes were compared. The oxygen administration was classified by conditions before and after the coronavirus disease 2019 pandemic. As a secondary evaluation, stratification of FHR pattern levels and factors associated with UA pH < 7.15 were examined. RESULTS: A total of 250 patients required obstetric surgical delivery due to NRFS, including 140 (56%) and 110 (44%) in the oxygen and room air groups, respectively. No differences in maternal background factors were found between both groups, except for maternal age. UA gas measurements and neonatal outcomes also showed no significant differences. No significant factors were extracted in the multivariate analysis for UA pH < 7.15. CONCLUSIONS: Trans-maternal oxygen administration for intrapartum NRFS did not affect neonatal cord blood gasses or neonatal outcomes. Thus, routine oxygen administration for intrapartum NRFS may not always be necessary.

Retrospective study of the efficacy and safety of docetaxel/carboplatin combination therapy as postoperative adjuvant chemotherapy for nonsquamous cell carcinoma of the cervix.

OBJECTIVE: Optimal adjuvant chemotherapy for nonsquamous cervical carcinoma has not yet been established. This study investigated the efficacy and safety of docetaxel/carboplatin (DC) for early-stage nonsquamous cell cervical carcinoma after radical hysterectomy (RH). METHODS: We evaluated 157 patients with stage IB-IIB nonsquamous cervical carcinoma with intermediate risk and high risk treated at our institution with DC after type II or III RH from 2007 to 2021. Patients received docetaxel (60-70 mg/m2) and carboplatin (area under the curve 5-6) every 3 weeks for six cycles. The primary endpoint was 2 year recurrence-free survival (RFS) and the secondary endpoint was adverse events (AEs). RESULTS: There were 106 intermediate-risk and 51 high-risk patients. The high-risk patients included 11 with positive parametrial involvement, 20 with pelvic lymph node metastases, and 20 with both parametrial involvement and pelvic lymph node metastases. The 2 year RFS rates for intermediate-risk, high-risk, and positive pelvic lymph nodes were 94.8% (95% confidence interval [CI], 87.9-97.8), 80.1% (95% CI, 64.1-89.5), and 74.5% (95% CI, 55.4-86.4), respectively. Sixteen patients had recurrence, including local recurrence (n = 6), distant metastasis (n = 9), and local and distant metastasis (n = 1). Hematologic toxicity was the most frequent AE, especially leukopenia and neutropenia. Nausea and constipation were the most frequent nonhematologic toxicities. CONCLUSION: DC therapy at our institution showed good 2 year RFS, and postoperative adjuvant therapy with DC therapy is suggested as a useful strategy for patients with nonsquamous cervical carcinoma.

Risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer: a single-institution 10-year experience.

BACKGROUND: For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35-40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. METHODS: To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011-21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. RESULTS: The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016-17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). CONCLUSION: Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie's risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.

Utility of molecular subtypes and genetic alterations for evaluating clinical outcomes in 1029 patients with endometrial cancer.

BACKGROUND: We investigated the utility of a molecular classifier tool and genetic alterations for predicting prognosis in Japanese patients with endometrial cancer. METHODS: A total of 1029 patients with endometrial cancer from two independent cohorts were classified into four molecular subtype groups. The primary and secondary endpoints were relapse-free survival (RFS) and overall survival (OS), respectively. RESULTS: Among the 265 patients who underwent initial surgery, classified according to immunohistochemistry, patients with DNA polymerase epsilon exonuclease domain mutation had an excellent prognosis (RFS and OS), patients with no specific molecular profile (NSMP) and mismatch repair protein deficiency had an intermediate prognosis, and those with protein 53 abnormal expression (p53abn) had the worst prognosis (P < 0.001). In the NSMP group, mutant KRAS and wild-type ARID1A were associated with significantly poorer 5-year RFS (41.2%) than other genomic characteristics (P < 0.001). The distribution of the subtypes differed significantly between patients with recurrence/progression and classified by sequencing (n = 764) and patients who underwent initial surgery (P < 0.001). Among patients with recurrence/progression, 51.4% had the opportunity to receive molecular targeted therapy. CONCLUSIONS: A molecular classifier is a useful tool for determining prognosis and eligibility for molecularly targeted therapy in patients with endometrial cancer.

Predictive model for the preoperative assessment and prognostic modeling of lymph node metastasis in endometrial cancer.

Lymph node metastasis (LNM) is a well-established prognostic factor in endometrial cancer (EC). We aimed to construct a model that predicts LNM and prognosis using preoperative factors such as myometrial invasion (MI), enlarged lymph nodes (LNs), histological grade determined by endometrial biopsy, and serum cancer antigen 125 (CA125) level using two independent cohorts consisting of 254 EC patients. The area under the receiver operating characteristic curve (AUC) of the constructed model was 0.80 regardless of the machine learning techniques. Enlarged LNs and higher serum CA125 levels were more significant in patients with low-grade EC (LGEC) and LNM than in patients without LNM, whereas deep MI and higher CA125 levels were more significant in patients with high-grade EC (HGEC) and LNM than in patients without LNM. The predictive performance of LNM in the HGEC group was higher than that in the LGEC group (AUC = 0.84 and 0.75, respectively). Patients in the group without postoperative pathological LNM and positive LNM prediction had significantly worse relapse-free and overall survival than patients with negative LNM prediction (log-rank test, P < 0.01). This study showed that preoperative clinicopathological factors can predict LNM with high precision and detect patients with poor prognoses. Furthermore, clinicopathological factors associated with LNM were different between HGEC and LGEC patients.

Whole-genome analysis of human papillomavirus 67 isolated from Japanese women with cervical lesions.

BACKGROUND: Human papillomavirus (HPV) type 67 is phylogenetically classified into Alphapapillomavirus species 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67. METHODS: Total cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences. Variant lineages/sublineages were assigned through viral whole-genome phylogenetic analysis. The transcriptional activity of the virus early promoter was assessed by luciferase reporter assays in cervical cancer cell lines. RESULTS: Phylogenetic analyses of HPV67 genomes from Japan (n = 12) revealed that 11 belonged to lineage A (sublineage A1, n = 9; sublineage A2, n = 2) and one belonged to lineage B. All cancer cases contained sublineage A1 variants, and one of these contained an in-frame deletion in the E2 gene. The long control region of the HPV67 genome did not induce transcription from the virus early promoter in HeLa cells, but showed weak transcriptional activity in CaSki cells. CONCLUSIONS: The single detection of HPV67 in cervical cancer and precancer specimens strongly suggests the carcinogenic potential of this rare genotype. The phylogenetic analysis indicates a predominance of lineage A variants among HPV67 infections in Japan. Since only 23 complete genome sequences of HPV67 had been obtained until now, the newly determined genome sequences in this study are expected to contribute to further functional and evolutionary studies on the genetic diversity of HPV67.

Assessment of the value of measuring soluble fms-like tyrosine kinase-1 and placental growth factor levels following administration of tadalafil to treat fetal growth restriction.

PURPOSE: The aim of this study was to measure the blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) before and after tadalafil treatment in patients with fetal growth restriction. MATERIALS AND METHODS: Maternal blood was collected from 13 women before and 2 weeks after tadalafil administration in the TADAFER II trial. The tadalafil treatment was conducted in addition to the conventional FGR treatment. As a control, maternal blood was also collected from 11 women before and 2 weeks after conventional treatment for fetal growth restriction. Blood sFlt-1 and PlGF were measured and the sFlt-1/PlGF ratio was calculated. Student's t-test was used to statistically analyze differences in the sFlt-1 and PlGF levels, and in the sFlt-1/PlGF ratios. RESULTS: In both treatment groups, the levels of sFlt-1 and PlGF before and after treatment were not significantly different from each other. The sFlt-1/PlGF ratio was 2.0 ± 1.0 before and 17.6 ± 11.3 after treatment in the control group (p=.04). The sFlt-1/PlGF ratio was 2.2 ± 1.1 before and 22.2 ± 10.6 after tadalafil treatment in the tadalafil group (p=.06). The sFlt-1/PlGF ratios before and after tadalafil treatment were significantly increased in the control group. In both treatment groups, the sFlt-1/PlGF ratios before and after treatment were less than 38. CONCLUSIONS: We conclude that the levels of sFlt-1 and PlGF were not significantly different as a result of tadalafil treatment. Further studies are needed to understand the mechanism of action of tadalafil in the treatment of fetal growth restriction.

Survey on spontaneous miscarriage and induced abortion surgery safety at less than 12 weeks of gestation in Japan.

AIM: In Japan, dilatation and curettage (D&C) is a common procedure for spontaneous miscarriage and induced abortion, and its safety has long been an issue. Electric vacuum aspiration (EVA) is also common, but manual vacuum aspiration (MVA) was introduced recently, with medical abortions using mifepristone or misoprostol which are not yet legally accepted. This nationwide retrospective study surveyed the surgical methods and complications associated with spontaneous miscarriage and induced abortion at less than 12 weeks of gestation in Japan to assess their safety, in comparison with a similar survey for induced abortions in 2012. METHODS: Questionnaires were sent to 4176 facilities with a license for induced abortion surgeries in 2019. The questions included were the methods used, number of spontaneous miscarriages and induced abortions, and number of complications (uterine perforation, incomplete abortion, and gross bleeding requiring blood transfusion). RESULTS: Responses were received from 1706 facilities (40.9%). Although EVA with sharp curettage was the most common surgical method, which was used for 11 953 spontaneous miscarriages (28.9%) and 24 045 induced abortions (37.3%), the most common surgical method per facility was D&C, and the rates of D&C for spontaneous miscarriages (38.4%) and induced abortions (44.7%) performed in general hospitals were significantly higher than those in clinics (24.1% and 22.0%, respectively). There was no significant difference in the complication incidence rate among surgical methods for spontaneous miscarriages. However, in induced abortion surgery, the total complication and incomplete abortion incidence rates for D&C were significantly higher than those for EVA without sharp curettage (47/15 162 [0.31%] vs. 29/18 693 [0.16%], p = 0.00362, 45/15 162 [0.30%] vs. 27/18 693 [0.14%], p = 0.00285, respectively). There was no significant difference in the complication incidence rate between MVA and other surgical methods for each abortion surgery. CONCLUSION: In Japan, especially in general hospitals, D&C is still widely used for miscarriage and induced abortion surgery. Its complication-incidence rates significantly decreased compared with that of the nationwide survey in 2012, but were still significantly higher than EVA without sharp curettage. Few facilities used MVA, but its complication rate was comparable with those of other surgical methods.

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk-reducing surgery for hereditary breast and ovarian cancer.

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk-reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results.

Study for risks of amniocentesis in anterior placenta compared to placenta of other locations.

OBJECTIVE: This study aimed to compare the risks of amniocentesis between anteriorly located placentas and placentas in other locations and assess the factors that cause procedure-related complications. MATERIALS AND METHODS: We prospectively studied women with singleton pregnancies who underwent amniocentesis between 2014 and 2020. The amniocentesis puncture sites were determined using ultrasonography. Women were classified into two groups according to their placental location. Medical records were retrospectively reviewed and characteristics and complications were compared between the groups of patients with different placental locations. RESULTS: During the study period, 629 women underwent amniocentesis. Three cases (0.5%) of premature rupture of membranes and one case (0.3%) of fetal loss within four weeks of amniocentesis were found. Puncture failure was observed in 14 cases (2.2%). Puncture failure included procedures with failure to obtain an adequate sample and procedures requiring more than three needle insertions. There was no significant difference in the frequency of puncture failure between the two groups. Logistic regression analysis revealed that uterine myoma (odds ratio [OR] 11.92; 95% CI, 3.04-45.17) and tenting membrane (OR 33.57; 95% CI, 6.45-178.41) were associated with puncture failure. CONCLUSION: Anteriorly located placenta is not a risk factor for amniocentesis-related adverse outcomes. Instead, puncture failure frequently occurs in case of uterine myoma and tenting membrane. If puncture failure occurs, or if the puncture is difficult to perform, then the procedure should be considered technically difficult and postponed until it can be more easily performed.

Preoperative Magnetic Resonance Imaging versus Intraoperative Frozen Section Diagnosis for Predicting the Deep Myometrial Invasion in Endometrial Cancer: Our Experience and Literature Review.

AIM: The present study was designed to directly compare the diagnostic performance of preoperative magnetic resonance imaging (MRI) and intraoperative frozen section (FS) diagnoses in predicting deep myometrial invasion (MI) of endometrial cancer. METHODS: Using MRI findings and FS diagnoses, 194 patients with surgically staged endometrial cancer were evaluated for deep MI between 2006 and 2018. Definitive histological diagnosis of paraffin sections of excised tissues was used as the gold standard approach. RESULTS: Of 194 cases, 53 (27.3%) cases were finally diagnosed as having deep MI (≥50%). There was 82% total agreement between MRI and FS diagnoses in predicting deep MI, with a kappa value of 0.54 (95% confidence interval [CI] = 0.40-0.67, moderate agreement). The sensitivity of FS diagnosis (0.66, 95% CI = 0.52-0.78) for predicting deep MI was lower than that of MRI (0.77, 95% CI = 0.63-0.87; p = 0.21), while the specificity of FS (0.98, 95% CI = 0.93-0.99) was significantly higher than that of MRI (0.88, 95% CI = 0.81-0.93; p = 0.001). Overall, the accuracy of FS (0.89, 95% CI = 0.84-0.93) was higher than that of MRI (0.85, 95% CI = 0.79-0.90), although the difference did not reach statistical significance (p = 0.23). The accuracy (0.95, 95% CI = 0.90-0.97) was very high in cases with concordant MRI and FS results. CONCLUSIONS: MRI and FS showed different diagnostic characteristics for predicting deep MI, with a higher specificity observed for FS and the greatest accuracy obtained in concordant cases. Thus, our findings recommend the addition of FS diagnosis, either alone or in conjunction with MRI, to MI evaluation.

Recent Prevalence of Human T-cell Leukemia Virus Type 1 Carrier Associated with Horizontal Transmission in Pregnant Japanese Women.

The current study was conducted to examine the number of human T-cell leukemia virus type 1 (HTLV-1) carriers and how horizontal transmission affected the prevalence of HTLV-1 carriers among pregnant Japanese women in 2019. We requested 2,214 obstetrical facilities to provide information on HTLV-1 tests for pregnant women who delivered in 2019. The estimated number of HTLV-1 carriers among pregnant Japanese women was 952. At least 10% or more of the carriers acquired HTLV-1 through horizontal transmission.

Infective endocarditis due to Streptococcus agalactiae in the puerperal period.

Streptococcus agalactiae, also known as group B Streptococcus, is a species of bacteria occasionally detected in the vagina and/or rectum of pregnant women. This report describes the case of a 33-year-old woman who developed infective endocarditis on puerperal day 17, owing to group B Streptococcus, and required lifesaving surgery. The patient was rushed to our hospital with chief complaints of fever and fatigue. After hospitalization, antibiotics were administered; however, the symptoms did not improve. Following a detailed examination, vegetation was found in the heart, suggestive of infective endocarditis. Surgical removal of the vegetation improved the patient's condition. The development of group B Streptococcus infection and infective endocarditis in a pregnant woman with no risk factors is rare. This case confirms that this patient's life was saved by a timely diagnosis and appropriate therapeutic intervention.

The routine use of prophylactic Bakri balloon tamponade contributes to blood loss control in major placenta previa.

OBJECTIVE: To verify the blood loss control effect of routine prophylactic Bakri balloon tamponade on major and minor placenta previa (PP). METHODS: We conducted a retrospective cohort study of all singleton pregnancies that involved cesarean section (CS) for PP at our hospital. All participants were divided into Bakri balloon (underwent routine prophylactic use just after placenta removal) and non-balloon groups, and into major and minor PP groups. Clinical outcomes in major and minor PP were compared between balloon and non-balloon groups. RESULTS: The balloon and non-balloon groups contained 74 and 89 patients, respectively. There were 41 and 33 (balloon group) and 48 and 41 (non-balloon group) major and minor PP cases, respectively. Intraoperative and perioperative blood losses of major PP were significantly lower in the balloon group than the non-balloon group (1045 ml versus 1553 ml, P = 0.016; and 1189 ml versus 1810 ml, P = 0.006, respectively). The frequency of massive postpartum hemorrhage (>500 ml) with major PP was lower in the balloon group than in the non-balloon group (2.4% versus 16.7%, P = 0.027), but with no significant difference with minor PP. CONCLUSION: Routine prophylactic use of Bakri balloon tamponade during and after CS is effective in controlling blood loss in major PP.

Current status of cervical cytology during pregnancy in Japan.

In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.

Analysis of preventability of malignancy-related maternal death from the nationwide registration system of maternal deaths in Japan.

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II-IV in 9, and the performance status was 3-5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24-30] (19-40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant.

Issues of infant feeding for postnatal prevention of human T-cell leukemia/lymphoma virus type-1 mother-to-child transmission.

BACKGROUND: Nationwide antenatal human T-cell leukemia/lymphoma virus type-1 (HTLV-1) antibody screening has been conducted in Japan. The purpose of our study was to clarify the issues related to feeding options to prevent postnatal mother-to-child transmission. METHODS: Of the pregnant carriers at 92 facilities in Japan between 2012 and 2015, 735 were followed prospectively. Among the children born to them, 313 (42.6%) children were followed up to the age of 3 and tested for HTLV-1 antibodies. The mother-to-child transmission rate was calculated for each feeding option selected before birth. RESULTS: Among the 313 pregnant carriers, 55.0, 35.1, 6.1, and 3.8% selected short-term breast-feeding (≤3 months), exclusive formula feeding, frozen-thawed breast-milk feeding, and longer-term breast-feeding, respectively. Despite short-term breast-feeding, 8-18% of the mothers continued breast-feeding for 4-6 months. The mother-to-child transmission rate with short-term breast-feeding was 2.3% (4/172), and its risk ratio compared with that of exclusive formula feeding was not significantly different (0.365; 95% CI: 0.116-1.145). Because of the small number of children who were fed by frozen-thawed breast-milk, their mother-to-child transmission rate was not statistically reliable. CONCLUSIONS: Pregnant HTLV-1 carriers tended to select short-term breast-feeding in Japan. While short-term breast-feeding was not always easy to wean within 3 months, it may be a viable option for preventing postnatal mother-to-child transmission because the vertical transmission rate with short-term breast-feeding was not significantly higher than that with exclusive formula feeding. Increasing the follow-up rates for children born to pregnant carriers may provide clearer evidence of preventative effects by short-term breast-feeding and frozen-thawed breast-milk feeding.

High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer.

Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.

Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

BACKGROUND: Screening of pregnant women carrying human T-lymphotropic virus type 1 (HTLV-1) has a crucial role in reducing the number of HTLV-1 carriers. A national HTLV-1 screening program for pregnant women was started in 2011 in Japan. The purpose of this study is to report on the implementation of this nationwide screening program. METHODS: This was a retrospective repeated cross-sectional study. We used datasets from surveys of HTLV-1-antibody-positive pregnant women performed by the Japan Association of Obstetricians and Gynecologists in 2011, 2013, and 2016. Outcomes for evaluation included the number of persons (pregnant women) who conducted the screening test, the number of positive persons (women) identified by these tests, and the proportion of positive persons to the number of persons (women) who conducted the tests. RESULTS: Numbers of target facilities changed yearly: 1857 in 2011, 2544 in 2013, and 2376 in 2016. The mean number of screening-test participants increased per facility, but the median increased or decreased. The mean number of positive individuals identified decreased. Multivariate analysis results revealed the number of screenings was slightly reduced yearly, although areas (Kanto and Kinki) and high volume in facility types increased. Regarding the positive rates, some areas (Hokkaido/Tohoku, Kanto, and Chugoku/Shikoku) exhibited decreases or increases by facility type. The number of western blotting (WB) implementations decreased in 2016, positive rates identified by WB decreased in 2016 in all areas, and the number of facility types increased. The number of PCR participants increased in 2016 in Kanto and Kinki, but a decrease in facility type was observed. Positive rates were decreased in all areas (except the central region) but facility types were increased. CONCLUSIONS: The nationwide screening program for HTLV-1 in Japan was almost fully implemented. However, regional variations in screening tests were observed during this implementation. Thus, some incentives are needed to encourage proper implementation across all regions.