A rare case of extraluminal interstitial pregnancy treated with laparoscopic cornuotomy.

We report an extremely rare case of an extraluminal interstitial pregnancy. A 36-year-old nulliparous woman visited our hospital during the fifth week of gestation. Although no intrauterine gestational sac (GS) was identified, transabdominal ultrasonography revealed a GS-like cyst was detected in the right uterine horn. She underwent laparoscopic surgery for a suspected interstitial ectopic pregnancy. After laparoscopic cornuotomy, dye leakage was observed from the fimbria rather than the incision site. Finally, the patient was diagnosed with a right extraluminal interstitial pregnancy. Hysterosalpingography performed at three postoperative months revealed bilateral tubal passage. She conceived 7 months after surgery, with safe delivery by elective cesarean section at 38 weeks.

A Preclinical Evaluation towards the Clinical Application of Oxygen Consumption Measurement by CERMs by a Mouse Chimera Model.

We have developed an automated device for the measurement of oxygen consumption rate (OCR) called Chip-sensing Embryo Respiratory Measurement system (CERMs). To verify the safety and the significance of the OCR measurement by CERMs, we conducted comprehensive tests using a mouse model prior to clinical trials in a human in vitro fertilization (IVF) program. Embryo transfer revealed that the OCR measured by CERMs did not compromise the full-term development of mice or their future fertility, and was positively correlated with adenosine triphosphate (ATP) production and the mitochondrial membrane potential (ΔΨm), thereby indirectly reflecting mitochondrial oxidative phosphorylation (OXPHOS) activity. We demonstrated that the OCR is independent of embryo morphology (the size) and number of mitochondria (mitochondrial DNA copy number). The OCR correlated with the total cell numbers, whereas the inner cell mass (ICM) cell numbers and the fetal developmental rate were not. Thus, the OCR may serve as an indicator of the numbers of trophectoderm (TE) cells, rather than number or quality of ICM cells. However, implantation ability was neither correlated with the OCR, nor the embryo size in this model. This can probably be attributed to the limitation that chimeric embryos contain non-physiological high TE cells counts that are beneficial for implantation. CERMs can be safely employed in clinical IVF owing to it being a safe, highly effective, non-invasive, accurate, and quantitative tool for OCR measurement. Utilization of CERMs for clinical testing of human embryos would provide further insights into the nature of oxidative metabolism and embryonic viability.

Development of a new clinically applicable device for embryo evaluation which measures embryo oxygen consumption.

STUDY QUESTION: Does a new system-the chip-sensing embryo respiration monitoring system (CERMs)-enable evaluation of embryo viability for potential application in a clinical IVF setting? SUMMARY ANSWER: The system enabled the oxygen consumption rate of spheroids, bovine embryos and frozen-thawed human embryos to be measured, and this rate corresponded to the developmental potential of embryos. WHAT IS ALREADY KNOWN: To date, no reliable and clinically suitable objective evaluation methods for embryos are available, which circumvent the differences in inter-observer subjective view. Existing systems such as the scanning electrochemical microscopy (SECM) technique, which enables the measurement of oxygen consumption rate in embryos, need improvement in usability before they can be applied to a clinical setting. STUDY DESIGN, SIZE, DURATION: This is a prospective original research study. The feasibility of measuring the oxygen consumption rate was assessed using CERMs for 9 spheroids, 9 bovine embryos and 30 redundant frozen-thawed human embryos. The endpoints for the study were whether CERMs could detect a dissolved oxygen gradient with high sensitivity, had comparable accuracy to the SECM measuring system with improved usability, and could predict the development of an embryo to a blastocyst by measuring the oxygen consumption rate. The relationship between the oxygen consumption rate and standard morphological evaluation was also examined. PARTICIPANTS/MATERIALS, SETTING, METHODS: We developed a new CERMs, which enables the oxygen consumption rate to be measured automatically using an electrochemical method. The device was initially used for measuring a dissolved oxygen concentration gradient in order to calculate oxygen consumption rate using nine spheroids. Next, we evaluated data correlation between the CERMs and the SECM measuring systems using nine bovine embryos. Finally, the oxygen consumption rates of 30 human embryos, which were frozen-thawed on 2nd day after fertilization, were measured by CERMs at 6, 24, 48, 72 and 96 h after thawing with standard morphological evaluation. Furthermore, the developed blastocysts were scored using the blastocyst quality score (BQS), and the correlation with oxygen consumption rate was also assessed. MAIN RESULTS AND THE ROLE OF CHANCE: The device enabled the oxygen consumption rate of an embryo to be measured automatically within a minute. The oxygen concentration gradient profile showed excellent linearity in a distance-dependent change. A close correlation in the oxygen consumption rates of bovine embryos was observed between the SECM measuring system and CERMs, with a determination coefficient of 0.8203 (P = 0.0008). Oxygen consumption rates of human embryos that have reached the blastocyst stage were significantly higher than those of arrested embryos at 48, 72 and 96 h after thawing (P = 0.039, 0.004 and 0.049, respectively). Thus, in vitro development of frozen-thawed human embryos to the blastocyst stage would be predicted at 48 h after thawing (day 4) by measuring the oxygen consumption using CERMs. Although a positive linear relationship between BQS and the oxygen consumption rate was observed [the determination coefficient was R(2) = 0.6537 (P = 0.008)], two blastocysts exhibited low oxygen consumption rates considering their relatively high BQS. This suggests that morphology and metabolism in human embryos might not correlate consistently. LIMITATIONS, REASONS FOR CAUTION: Transfer of the embryo and pregnancy evaluation was not performed. Thus, a correlation between oxygen consumption and the in vivo viability of embryos remains unknown. Clinical trials, including embryo transfer, would be desirable to determine a threshold value to elect clinically relevant, quality embryos for transfer. We utilized frozen-thawed human embryos in this study. The effect of these manipulations on the respiratory activity of the embryo is also unknown. WIDER IMPLICATIONS OF THE FINDINGS: Selection of quality embryos, especially in a single embryo transfer cycle, by CERMs may have an impact on obtaining better clinical outcomes, albeit with clinical trials being required. Furthermore, the early determination of quality embryos by CERMs may enable the omission of long-term in vitro embryo culture to the blastocyst stage. CERMs is scalable technology that can be integrated into incubators and/or other embryo evaluation systems, such as the time-lapse systems, due to its chip-based architecture. Thus, CERMS would enable automatic measurement of oxygen consumption, under 5% CO2, in the near future, in order to reduce oxidative stress from exposure to atmospheric air. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Health and Labor Sciences Research Grant (H24-Hisaichiiki-Shitei-016). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer.

BACKGROUND: Pelvic exenteration has attained an important role in the treatment of advanced or recurrent cervical cancer for obtaining a complete cure or longer disease-free survival. The purpose of this study was to evaluate patients undergoing pelvic exenteration and to determine the clinical features associated with outcome and survival. METHODS: We retrospectively analyzed the records of 12 patients who underwent pelvic exenteration for uterine cervical cancer between July 2002 and August 2011. RESULTS: Two patients had primary stage IVA cervical adenocarcinoma and 10 patients had recurrent cervical cancer. Eight patients underwent anterior pelvic exenteration, 3 patients underwent total pelvic exenteration, and 1 patient underwent posterior pelvic exenteration. With a median duration of follow-up of 22 months (range 3-116 months), 5 patients were alive without recurrence. Of 5 patients with no evidence of disease, 4 were recurrent or residual tumor, all of whom had common factors, such as a tumor size ≤ 30 mm, negative surgical margins, complete resection, and no lymph node involvement. The 5-year overall survival rate for 12 patients was 42.2 %. Ileus was the most common complication (42 %) and post-operative intestinal anastomosis leaks developed in 3 patients, but no ureteral anastomosis leaks occurred. CONCLUSIONS: Pelvic exenteration is a feasible surgical procedure in advanced and/or recurrent cervical cancer patients with no associated post-operative mortality, and the only therapeutic option for complete cure or long-term survival; however, post-operative complications frequently occur.

Feasibility study of gemcitabine plus docetaxel in advanced or recurrent uterine leiomyosarcoma and undifferentiated endometrial sarcoma in Japan.

BACKGROUND: Uterine leiomyosarcoma (LMS) and undifferentiated endometrial sarcoma (UES) are rare, aggressive malignancies. Both are treated similarly; however, few chemotherapy agents are effective. Recently, the combination of gemcitabine (900 mg/m(2), days 1 and 8) plus docetaxel (100 mg/m(2), day 8) with granulocyte colony-stimulating factor (G-CSF, 150 µg/m(2), days 9-15) has been shown to have activity in LMS. In Japan, neither prophylactic G-CSF at a dose of 150 µg/m(2) nor docetaxel at a dose of 100 mg/m(2) are approved for use. For this reason, we evaluated the combination of 900 mg/m(2) gemcitabine plus 70 mg/m(2) docetaxel regimen without prophylactic G-CSF support in advanced or recurrent LMS and UES in Japanese patients. METHODS: Eligible women with advanced or recurrent LMS and UES were treated with 900 mg/m(2) gemcitabine on days 1 and 8, plus 70 mg/m(2) docetaxel on day 8, every 3 weeks. The primary endpoint was overall response rate, defined as a complete or partial response. RESULTS: Of the eleven women enrolled, 10 were evaluated for a response. One complete response and 2 partial responses were observed (30 %) with an additional 4 (40 %) having stable disease. Mean progression-free survival was 5.4 months (range 1.3-24.8 months), and overall survival was 14 months (range 5.3-38.4 months). Grade 4 neutropenia was the major toxicity (50 %). The median number of cycles was 5 (range 2-18). Twenty-two cycles (44 %) employed G-CSF. CONCLUSION: The gemcitabine plus docetaxel regimen without prophylactic G-CSF support was tolerable and highly efficacious in Japanese patients with advanced or recurrent LMS and UES.

Small cell carcinoma of the uterine cervix: clinical outcome of concurrent chemoradiotherapy with a multidrug regimen.

Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with advanced stage disease, the response rate was 75% (complete response, 1; partial response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.

Hysteroscopic inspection and total curettage are insufficient for discriminating endometrial cancer from atypical endometrial hyperplasia.

Endometrial cancer (EC) is the most prevalent gynecologic malignancy in Japan. Atypical endometrial hyperplasia (AEH) is viewed as the premalignant lesion of EC, however it is often difficult to distinguish EC from AEH. The rate of concurrent EC in women diagnosed preoperatively with AEH based on endometrial biopsy was reported as 17-52%. Although hysteroscopic inspection and total curettage are considered as useful methods to make diagnosis of endometrial lesions, there is no report using this combined method to discriminate EC from AEH. The purpose of this study was to examine whether hysteroscopic inspection and total curettage improve the prevalence of EC among women diagnosed preoperatively with AEH. We reviewed 22 patients who underwent hysteroscopic inspection and total curettage and were diagnosed with AEH before undergoing hysterectomy between November 2001 and May 2011. The diagnosis made with the hysterectomy specimens revealed AEH in 10 patients (45.5%), endometrial hyperplasia without atypia in 3 (13.6%), and endometrioid adenocarcinoma, the most common type of EC, in 9 (40.9%). Endometrioid adenocarcinoma included 7 patients without myometrial invasion (31.8%) and 2 patients with superficial myometrial invasion (9.1%). There was no hysteroscopic finding that was specific for EC or AEH. In conclusion, about 41% of women who underwent hysterectomy under a diagnosis of AEH were found to have coexisting adenocarcinoma, although the prevalence of EC among those women was similar to that in earlier reports with endometrial biopsy. Accordingly, we must be careful in planning the therapeutic strategy for women with a preoperative diagnosis of AEH.

Individualized radical hysterectomy procedure using intraoperative electrical stimulation for patients with cervical cancer.

OBJECTIVE: In this study, by monitoring the varied distributions of nerve fascicles using intraoperative electrical stimulation (IES), we sought to establish an individualized operation based on the patient's unique nerve distribution pattern, and to determine whether this technique would result in a higher preservation rate. MATERIALS/METHODS: Radical hysterectomy was performed from 2002 to 2010. Patients in group A are the 48 cases from 2002 to 2007 in which nerve-sparing radical hysterectomy using IES as our previous report was performed. Patients in group B are the 38 cases from 2008 to 2010 in which we used our new method, which was individualized to each patient. Urodynamic study (UDS) was used to confirm nerve preservation. Nerve preservation was defined as confirming distinct detrusor contraction during urinary voiding. RESULTS: In group B, nerve preservation rate was higher than in group A (75% vs 9 0%, P = 0.067). We classified the case-by-case nerve anatomy as whether the nerve fascicle was mainly on the medial side or on the lateral side of the deep uterine vein. The lateral type anatomy was observed unilaterally in 6 cases and bilaterally in 1 case. In summary, the lateral type anatomy was observed in 8 (29%) of 28 sides. In the cases evaluated by UDS, the positive predictive value of IES was 95% in group A and 100% in group B. CONCLUSIONS: Our method of IES showed a high positive predictive value of nerve preservation as confirmed by UDS. By delineating the nerve tract in detail using IES, it is possible to individualize the operation based on each patient's anatomy, with an improved nerve preservation rate.