Diagnostic Utility of Hysteroscopic Biopsy in Cases of Suspected Lobular Endocervical Glandular Hyperplasia and Comparison with Cervical Conization.

BACKGROUND: Cervical cystic lesions encompass a range of benign and malignant pathologies. Magnetic resonance imaging or cytology alone cannot provide a definitive diagnosis, and conventional practice involves performing a cervical biopsy by conization to confirm the histology in cases exhibiting potential signs of lobular endocervical glandular hyperplasia (LEGH) or malignancy. However, as postoperative complications resulting from conization can impact future fertility and pregnancy, alternative diagnostic methods are needed for reproductive-age patients. This study aimed to establish the efficacy of a hysteroscopic biopsy for diagnosing cervical cystic lesions and compare it with conization. METHODS: Thirteen patients with cervical cystic lesions suspected of LEGH or malignancy underwent a hysteroscopic biopsy, while 23 underwent conization. Patient background information, preoperative evaluation, histology, and postoperative outcomes were collected and compared retrospectively. RESULTS: No significant differences were found between the hysteroscopy and conization groups in terms of mean patient age (45 vs. 48 years), operating time (23 vs. 35 min), blood loss (small amount vs. 43 mL), and postoperative hospitalization (1.1 vs. 1.6 days). CONCLUSION: A hysteroscopic biopsy allows for targeted resection of the cervix while maintaining diagnostic accuracy. It may serve as an efficient method for diagnosing cervical cystic lesions.

Development of an Algorithm to Differentiate Uterine Sarcoma from Fibroids Using MRI and LDH Levels.

BACKGROUND: This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. METHODS: One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined by four evaluators with different imaging experience and abilities, using a test set of 61 cases, including 14 cases of uterine sarcoma. RESULTS: From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroids, we found that all sarcomas were included in the group with a high T2WI and either a high T1WI, an unclear margin, or high LDH values. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings for T2WI, T1WI, margins, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators and the sensitivity of sarcoma detection ranged from 71% to 93%. CONCLUSION: We established an algorithm to distinguish uterine sarcoma if tumors in the myometrium with low T2WI and DWI are present.

Treatment for Locally Resectable Stage IIIC1 Cervical Cancer: A Retrospective, Single-Institution Study.

According to the revision of the FIGO 2018 staging system, cervical cancer with pelvic lymph node metastases was changed to stage IIIC1. We retrospectively analyzed the prognosis and complications of locally resectable (classified as T1/T2 by TNM classification of the Union for International Cancer Control) stage IIIC1 cervical cancer. A total of 43 patients were divided into three groups: surgery with chemotherapy (CT) (ope+CT group) (T1; n = 7, T2; n = 16), surgery followed by concurrent chemoradiotherapy (CCRT), or radiotherapy (RT) (ope+RT group) (T1; n = 5, T2; n = 9), and CCRT or RT alone (RT group) (T1; n = 0, T2; n = 6). In T1 patients, recurrence was observed in three patients, but there was no difference among the treatment groups, and no patients died. In contrast, in T2 patients, recurrence and death were observed in nine patients (8 in ope+CT; 1 in ope+RT), and recurrence-free survival and overall survival were lower in the ope+CT group (p = 0.02 and 0.04, respectively). Lymphedema and dysuria were more common in the ope+RT group. A randomized controlled trial comparing CT and CCRT as an adjuvant therapy after surgery in T1/T2 patients, including those with pelvic lymph node metastases, is currently underway. However, our data suggest that performing CT alone after surgery in T2N1 patients is likely to worsen the prognosis.

Risk factors for future osteoporosis in perimenopausal Japanese women.

OBJECTIVE: The aims of this study were to investigate trends in bone mineral density (BMD) loss and related factors in early postmenopausal women in Japan, identify risk factors for future osteoporosis, and predict osteoporosis before it occurs. METHODS: The study population consisted of women who were 50 to 54 years old at the time of the survey in 2002 or 2006. The study included a questionnaire and physical measurement findings (BMD, height, body weight [WT], body mass index [BMI], and handgrip strength). One hundred sixty-seven women continued to participate in the study and had BMD measurements at the 9- or 10-year follow-up of the Japanese Population-based Osteoporosis study. Statistical analyses were performed using Pearson correlation to examine each factor of physical measurement and BMD for lumbar spine (LS) and femoral neck (FN). The receiver operating characteristic curve of this data was also predictive of osteoporosis in 2011 for 2002 data; BMD at the age of 50 to 54 years was then used to predict the likelihood of being diagnosed with osteoporosis 9 and 10 years later. RESULTS: At the baseline in 2002 and 2006, WT, BMI, height, and handgrip strength were positively correlated with BMD. The optimal cutoff values for BMD in 2006 to predict osteoporosis in 2016 were LS less than 0.834 g/cm 2 and FN less than 0.702 g/cm 2 . These data were also predictive of osteoporosis in 2011 for 2002 data; applying this to the 2002 data, LS/FN had a sensitivity of 92%/100%, a specificity of 87%/81%, a positive predictive value of 55%/48%, and a negative predictive value of 98%/100%. The larger WT and BMI also resulted in a greater decrease in BMD of FN after 9 or 10 years. CONCLUSIONS: We have identified a cutoff value for BMD to predict future osteoporosis in menopausal women and found a negative correlation between WT and BMI in menopausal women and changes in BMD of the FN over the next 10 years.

Surgical skill and oncological outcome of laparoscopic radical hysterectomy: JGOG1081s-A1, an ancillary analysis of the Japanese Gynecologic Oncology Group Study JGOG1081.

OBJECTIVES: We investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH). METHODS: We previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review. RESULTS: After a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8-90.6) and five-year Overall Survival rate was 93.7% (87.5-96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12-5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence. CONCLUSIONS: Our new study has found that LRH surgical experience and skill trended to have better oncological outcomes.

Comparison of Surgical Results and Postoperative Recurrence Rates by Laparoscopic Sacrocolpopexy with Other Surgical Procedures for Managing Pelvic Organ Prolapse.

OBJECTIVES: Pelvic organ prolapse (POP) is relatively high for a gynecologic disease. Laparoscopic sacrocolpopexy (LSC) is currently the main surgical option for managing POP. The priority of the surgical treatment is preventing recurrence after the surgery. We presented the surgical outcome and recurrence rate of LSC and compared the data of LSC with that of other surgical procedures for managing POP to examine the effectiveness of LSC over other them. MATERIALS AND METHODS: We compared the results of 138 cases of LSC with other conventional procedures, namely 30 cases of total vaginal hysterectomy (TVH) combined with colporrhaphy anterior and posterior, 66 cases of the Manchester operation, and 68 cases of colpocleisis. We compared the age, body mass index, operative time, blood loss volume, postoperative hospital stay duration, rate of complications, recurrence rate, reoperation rate, and the cumulative recurrence rate after 10 years. RESULTS: The complication rate of LSC, TVH, the Manchester operation, and colpocleisis was 2.2%, 3.3%, 3.0%, and 4.4%; the recurrence rate 2.8%, 3.5%, 4.5%, and 8.7%; and the cumulative recurrence rate after 10 years 3.7%, 4.6%, 8.8%, and 18.2%. There was no significant difference between LSC and the other three groups. CONCLUSION: LSC seems to be an effective surgical option that requires a higher skill level than other surgical methods and has a longer operative time, lesser operative invasion, and a lower long-term recurrence rate. We will actively recommend LSC to those when appropriate.

Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma.

Recent studies have reported cancer-associated mutations in normal endometrium. Mutations in eutopic endometrium may lead to endometriosis and endometriosis-associated ovarian cancer. We investigated PIK3CA mutations (PIK3CAm) for three hotspots (E542K, E545K, H1047R) in eutopic endometrium in patients with ovarian cancer and endometriosis from formalin-fixed paraffin-embedded specimens by laser-capture microdissection and droplet digital PCR. The presence of PIK3CAm in eutopic endometrial glands with mutant allele frequency ≥ 15% were as follows: ovarian clear cell carcinoma (OCCC) with PIK3CAm in tumors, 20/300 hotspots in 11/14 cases; OCCC without PIK3CAm, 42/78 hotspots in 11/12 cases; high-grade serous ovarian carcinoma, 8/45 hotspots in 3/5 cases; and endometriotic cysts, 5/63 hotspots in 5/6 cases. These rates were more frequent than in noncancer nonendometriosis controls (7/309 hotspots in 5/17 cases). In OCCC without PIK3CAm, 7/12 (58%) cases showed multiple hotspot mutations in the same eutopic endometrial glands. In 3/54 (5.6%) cases, PIK3CAm was found in eutopic endometrial stroma. Multisampling of the OCCC tumors with PIK3CAm showed intratumor heterogeneity in three of eight cases. In two cases, PIK3CAm was detected in the stromal component of the tumor. Homogenous PIK3CAm in the epithelial component of the tumor matched the mutation in eutopic endometrial glands in only one case. Eutopic endometrial glands in ovarian cancer and endometriosis show high frequency of PIK3CAm that is not consistent with tumors, and multiple hotspot mutations are often found in the same glands. While the mutations identified in eutopic endometrium may not be driver mutations in the patient's cancer, these are still driver mutations but this specific clone has not undergone the requisite steps for the development of cancer.

Measures for Safe Laparoscopic Sacrocolpopexy: Preoperative Contrast-Enhanced Computed Tomography and Perioperative Ultrasonography.

Laparoscopic sacrocolpopexy is one of the most difficult laparoscopic surgical techniques. In this study, we report on our efforts to safely perform this procedure, which consists of suturing a piece of mesh onto the anterior longitudinal ligament using a nonabsorbent suture during mesh fixation onto the prepromontorium layer, which can lead to massive bleeding if a mistake is made, by performing preoperative and intraoperative image evaluation. Preoperative contrast-enhanced computed tomography was performed. Images in DICOM format were acquired, and three-dimensional vessel reconstruction was performed. After performing a peritoneal incision in the presacral area, ultrasonography was performed using a probe inserted through a 12-mm trocar into the abdominal cavity to re-confirm the absence of vessels near the planned suturing area. After ultrasonography, an Ethibond® suture was inserted through the anterior longitudinal ligament. In our hospital, 126 patients underwent the procedure, and none had a serious hemorrhage or required blood transfusion, indicating the safety of this modified procedure without separation of a wide presacral area. We believe that these techniques can be performed safely with minimal incision. However, we did not examine the efficacy of these techniques in this paper. Further studies are needed to determine whether this approach is suitable.

Research Article Quality of life after laparoscopic hysterectomy versus abdominal hysterectomy.

BACKGROUND: Laparoscopic surgery has been described as a minimally invasive surgery. The purpose of this study is to clarify its minimal invasive features using a patient questionnaire on the postoperative quality of life (QOL) over various time periods following either laparoscopic hysterectomy (LH) or abdominal hysterectomy (AH) and to compare the results. METHODS: This study enrolled 28 patients who underwent total hysterectomy for uterine fibroids in 2012 (14 AH cases and 24 LH cases) were enrolled in this study. The 36-Item Short Form Survey (SF-36) questionnaire was completed on postsurgical day 3; weeks 1, 2, and 4; and month 6. The results were compared between the two groups. RESULTS: Patients who underwent LH scored significantly higher on physical functioning on postoperative day 3 and week 2; physical role and bodily pain on day 3 and week 1; general health on postoperative day 3, weeks 1, 2, and 4, and month 6; social functioning on day 3; and emotional role on day 3 and week 1. No significant differences were found between vitality and mental health at any time point or in the categories above at any other time point. CONCLUSIONS: Postoperative QOL in LH cases was improved on day 3 and week 1; however, no significant differences between the LH and AH groups were found in most categories at week 4 and month 6. LH leads to superior short-term QOL early in the postoperative period relative to AH.

Ovarian cyst elevation using a metreurynter for laparoscopic cystectomy of a benign ovarian cyst during pregnancy.

BACKGROUND: A uterine manipulator cannot be used to elevate the ovary in benign ovarian surgery during pregnancy. This report describes our method of elevation of the ovary using a metreurynter with the success rate of the procedure and a comparison of surgical results and pregnancy outcomes between the successful and unsuccessful cases. METHODS: Between August 2003 and February 2020, 11 pregnant patients with a tumor found sunk in the Cul-de-sac underwent laparoscopic cystectomy for a benign ovarian cyst with a metreurynter. The surgical results, success and failure of the elevation by a metreurynter, pregnancy outcomes, and fetal status at delivery were evaluated. RESULTS: Elevation of ovarian tumors with a metreurynter was successful in nine cases. However, it was unsuccessful in the remaining two cases wherein the ovary was lifted with forceps while the uterus was in a compressed state. The operative time was also longer in these cases. The pregnancy prognosis, however, was good for both, successful and unsuccessful cases. CONCLUSIONS: The metreurynter is an inexpensive and practical obstetric device, and its optimal use allows the performance of a procedure with minimal burden on a pregnant uterus. Therefore, we recommend the appropriate use of this method to enable effective laparoscopic cystectomy of ovarian tumors during pregnancy.

A case report of bladder and intestinal endometriosis, and the relationship between sex hormone receptor expression and PIK3CA mutation analysis.

BACKGROUND: Extragonadal endometriosis is a rare condition, and its disease manifestation and long-term prognosis have not been elucidated. We report an extragonadal endometriosis case controlled by drug therapy for 14 years with analysis of the sex hormone receptor expression and PIK3CA mutation. CASE PRESENTATION: The patient was diagnosed with bladder endometriosis at age of 30 years, and underwent bilateral nephrostomy and GnRHa therapy with add-back therapy. The patient was switched to dienogest therapy at age 35 and had hematuria and bloody stools at age 38. PET-CT revealed a 6-cm mass in the bladder with fluorodeoxyglucose accumulation and the diagnosis of endometriosis in the bladder, sigmoid colon, and cecum was confirmed after the biopsy result. The lesion's tubular structures were positive for the estrogen receptor, but only 30% positive for the progesterone receptor, and the H1047R mutation in PIK3CA was found in tubular structures of the bladder lesion. GnRHa therapy caused the tumors to shrink. CONCLUSION: Decreased progesterone receptor expression and oncogenic mutations may influence the course of less common and rare site endometriosis. Rare site endometriosis often requires long-term hormone therapy, and management should be tailored to the patient's life stage, keeping in mind complications, such as decreased bone density.

Relationship between cervical elastography and spontaneous onset of labor.

Cervical elastography might be an objective method for evaluating cervical ripening during pregnancy, but its usefulness has not been fully investigated. We examined the significance of cervical elastography in the last trimester of pregnancy. Cervical elastography was performed at weekly checkups after 36 weeks of gestation in 238 cases delivered at our hospital from 2017 to 2018. The correlation with the onset time of natural labor, which is an index for judging maternal delivery preparation status, was examined. A total of 765 examinations were conducted, and cervical stiffness determined by cervical elastography was positively correlated with the Bishop score (r = 0.46, p < 0.0001). When examined separately for each week, only the examinations performed at 39 weeks were associated with the onset of spontaneous labor up to 7 days later (p = 0.0004). Furthermore, when stratified and analyzed by the Bishop score at 39 weeks of gestation, cervical elastography was associated with the occurrence of spontaneous labor pain for up to seven days in the groups with Bishop scores of 3-5 and 6-8 (p = 0.0007 and p = 0.03, respectively). In conclusion, cervical elastography at 39 weeks of pregnancy is useful for judging the delivery time.

A case of left renal atrophy following the development of an infected giant retroperitoneal chylous cyst after laparoscopic para-aortic lymphadenectomy for endometrial cancer.

Chylous leakage is caused by interruption of lymphatic vessels carrying triglyceride-rich lymph during para-aortic lymph node dissection in patients with gynecological malignancies. Our search of literature revealed no report like our case that the renal atrophy was late onset after healing of the chylous cyst infection. A case is 60-year-old. She was preoperatively diagnosed with endometrial cancer, endometrioid carcinoma FIGO grade 3, stage IA of the FIGO system. Laparoscopic-modified radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and partial omentectomy were performed. On the 16th postoperative day, a percutaneous drainage was performed, and revealed chylous effusion from the lymph cyst. The drainage tube was removed, and she discharged on the 34th postoperative day. On the 99th postoperative day, a follow-up plain CT to check for a recurrence of endometrial cancer revealed atrophy of left kidney. It is probable that the chylous leakage was the primary cause of renal atrophy. Therefore, it is crucial to prevent chylous leakage during surgery to avoid repeating the same complication again.

Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy.

Endometrial cysts (ECs) are thought to be the origin of endometriosis-associated ovarian cancer (EAOC). A hypothesis that the oxidative stress of iron in cysts causes "malignant transformation of ECs" has been proposed, but this has not been verified. Several population-based studies showed that endometriosis was a risk factor but did not reflect the "malignant transformation of ECs". A review showed that most patients were diagnosed with EAOC early in monitoring following detection of ECs, and that these cases might have been cancer from the start. Epidemiologically, EAOC was reduced by hysterectomy rather than by cystectomy of ECs. Gene mutation analyses identified oncogenic mutations in endometriosis and normal endometrium and revealed that the same mutations were present at different endometriotic lesions. It was also shown that most of the gene mutations found in endometriosis occurred in normal endometrium. Taking together, EAOC might be caused by eutopic endometrial glandular epithelial cells with oncogenic mutations that have undergone menstrual blood reflux and engrafted in the ovary, rather than by low-risk ECs acquiring oncogenic mutations and becoming malignant. This review discusses the mechanisms of EAOC development and targeted therapy based on genetic variation in EAOC with a focus on eutopic endometrium.

Superparamagnetic iron oxide as a tracer for sentinel lymph node detection in uterine cancer: a pilot study.

Sentinel lymph node (SLN) mapping using dye or radioisotopes has been performed in patients with uterine cancer. Superparamagnetic iron oxide (SPIO) can be handled safely and is taken up by lymph nodes (LNs); however, its efficacy in detecting SLNs in uterine cancer remains unknown. This pilot study evaluated the use of SPIO as a tracer for SLN detection in patients with uterine cancer. SPIO was injected into the uterine cervixes of 15 patients with uterine cancer scheduled for pelvic LN dissection. Magnetic resonance imaging (MRI) was performed preoperatively. Five patients also underwent radioisotope injection and single-photon emission computed tomography/computed tomography. Dissected LNs were stained with iron and examined pathologically. Of the radioisotope-positive LNs, 92% were also SPIO/MRI-positive. SPIO/MRI and iron staining were positively correlated. SLNs were identified by iron staining in 93% of cases. Iron staining was strongly positive in two of the five areas of LN metastasis; these were considered SLNs. Staining was negative or very weak in the other three areas and lymph flow disturbance was considered. SPIO and radioisotopes are taken up similarly by SLNs. SPIO/MRI and iron staining may thus be useful for detection of SLNs and diagnosis of LN metastasis in patients with uterine cancer.

Endometriosis-associated ovarian cancer occurs early during follow-up of endometrial cysts.

BACKGROUND: Endometriosis is a risk factor for ovarian cancer. Endometriosis-associated ovarian cancer (EAOC), most commonly clear cell carcinoma, is believed to develop from ovarian endometrial cysts. In this study, we reviewed published cases of EAOC considered to have developed from endometrial cysts, and focused on the observation period. METHODS: We searched for articles published since January 2000 that reported cases of ovarian cancer thought to have originated from endometrial cysts using PubMed, Web of Science, and Ichushi-Web. The period from the start of follow-up of the endometrial cyst to the diagnosis of ovarian cancer was calculated. RESULTS: Seventy-nine cases were identified from 32 articles. The median period from the diagnosis of endometrial cysts to the diagnosis of ovarian cancer was only 36 months. Approximately 75% of cases developed into cancer within 60 months and most cases developed within 120 months. CONCLUSION: Our results suggest that clinically detectable cysts subsequently diagnosed as ovarian cancer might already have contained cancer cells. Therefore, the mechanism of EAOC development needs to be re-examined and appropriate management guidelines need to be developed.

Effectiveness of laparoscopic ultrasonography in laparoscopic myomectomy.

INTRODUCTION: Laparoscopic myomectomy (LM) has become increasingly common in recent years because it minimizes invasiveness. However, myoma can recur after myomectomy. Therefore, we began using laparoscopic ultrasonography, which involves inserting a probe into the peritoneal cavity via a trocar and placing it in direct contact with the uterus. During surgery, this enables the detection of myomas as a small as 1 mm in diameter, which are often undetectable on MRI. Here, we report the effectiveness of laparoscopic ultrasonography. METHODS: The subjects were 26 women who underwent LM at our institution from February 2015 to December 2016. Preoperative MRI was performed, and all myomas detected on MRI were removed during LM. Laparoscopic ultrasonography was then performed to assess for residual myomas, which were removed. RESULTS: In six patients (23%), residual myomas were identified on laparoscopic ultrasonography after the first enucleation of the myomas detected on preoperative MRI. All detected residual myomas, the largest of which was less than 10 mm in diameter, were removed. CONCLUSION: Small myomas undetectable on preoperative MRI were detected on laparoscopic ultrasonography and removed.

Differential Diagnosis of Uterine Leiomyoma and Uterine Sarcoma using Magnetic Resonance Images: A Literature Review.

MRI plays an essential role in patients before treatment for uterine mesenchymal malignancies. Although MRI includes methods such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, the differentiation between uterine myoma and sarcoma always becomes problematic. The present paper discusses important findings to ensure that sarcomas are not overlooked in magnetic resonance (MR) images, and we describe the update in the differentiation between uterine leiomyoma and sarcoma with recent reports.

Clinical Determinants Affecting Indications for Surgery and Chemotherapy in Recurrent Ovarian Granulosa Cell Tumor.

BACKGROUND: Because reports on the management of recurrent granulosa cell tumor have been sparse, a consensus as to which patients should undergo surgical resection and which patients should be considered for chemotherapy has not been established. METHODS: A total of 21 tumor recurrences in eight patients with granulosa cell tumor were reviewed. RESULTS: Surgery was performed as the main treatment for 13 recurrences, while chemotherapy was chosen as the main treatment for eight recurrences. Complete tumor resection could be accomplished in 13 of 16 surgeries (81.3%), which include all the ten recurrences without involvement of liver or diaphragm and without ascites. The number of recurrent masses was significantly higher in the early recurrence group (progression free survival < 2 years) than in the late recurrence (progression free survival > 2 years). All cases with a solitary recurrent tumor at an extra-peritoneal site presented a significantly longer progression free survival. CONCLUSIONS: For patients with recurrent granulosa cell tumor, surgery may provide the best disease control. In cases with complete resection, the number of recurrent masses was the predictive factor for the next recurrence, and adjuvant chemotherapy might be considered in such cases.