Role of Stem Cells in Human Uterine Leiomyoma Growth

Uterine leiomyoma is the most common benign tumor in reproductive-age women. Each leiomyoma is thought to be a benign monoclonal tumor arising from a single transformed myometrial smooth muscle cell; however, it is not known what leiomyoma cell type is responsible for tumor growth. Thus, we tested the hypothesis that a distinct stem/reservoir cell-enriched population, designated as the leiomyoma-derived side population (LMSP), is responsible for cell proliferation and tumor growth.LMSP comprised approximately 1% of all leiomyoma and 2% of all myometrium-derived cells. All LMSP and leiomyoma-derived main population (LMMP) but none of the side or main population cells isolated from adjacent myometrium carried a mediator complex subunit 12 mutation, a genetic marker of neoplastic transformation. Messenger RNA levels for estrogen receptor-α, progesterone receptor and smooth muscle cell markers were barely detectable and significantly lower in the LMSP compared with the LMMP. LMSP alone did not attach or survive in monolayer culture in the presence or absence of estradiol and progestin, whereas LMMP readily grew under these conditions. LMSP did attach and survive when directly mixed with unsorted myometrial cells in monolayer culture. After resorting and reculturing, LMSP gained full potential of proliferation. Intriguingly, xenografts comprised of LMSP and unsorted myometrial smooth muscle cells grew into relatively large tumors (3.67 ± 1.07 mm(3)), whereas xenografts comprised of LMMP and unsorted myometrial smooth muscle cells produced smaller tumors (0.54 ± 0.20 mm(3), p<0.05, n = 10 paired patient samples). LMSP xenografts displayed significantly higher proliferative activity compared with LMMP xenografts (p<0.05).Our data suggest that LMSP, which have stem/reservoir cell characteristics, are necessary for in vivo growth of leiomyoma xenograft tumors. Lower estrogen and progesterone receptor levels in LMSP suggests an indirect paracrine effect of steroid hormones on stem cells via the mature neighboring cells

Considerations for performing microwave endometrial ablation (MEA) – Three cases with abnormal test results of endometrial tissue discovered by chance when performing MEA

Introduction Microwave endometrial ablation (MEA) is beginning to be used widely in Japan as a minimally invasive alternative to conventional total hysterectomy for functional hypermenorrhea, uterine fibroids, hypermenorrhea due to organic diseases such as uterine adenomyosis, and acute heavy uterine bleeding. Method MEA was introduced in our hospital in January 2016. It is performed after a screening via cytodiagnosis and histodiagnosis to ensure that there are no malignant diseases in the uterus. Histopathological examination by endometrial curettage during MEA revealed three cases of endometrial abnormalities. In all cases, radical surgery was performed, the postoperative course was good, and no recurrence was observed. Here, we report three cases in which abnormal endometrial tissue findings were observed in histopathologic examinations via total endometrial curettage during MEA. Conclusion When performing MEA, it is important to perform detailed examinations and careful monitoring of post-operative progress bearing in mind potential malignant uterine diseases

Efficacy and safety of an Aron Alpha method in managing giant ovarian tumors

Background: Giant malignant tumors have an increased risk of intraoperative rupture, which might lead to a worse disease condition and tumor recurrence. We performed a clinical study on patients with a giant ovarian mass who underwent laparoscopy combined with an Aron Alpha method. Methods: This retrospective clinical study spanned from January 2016 to September 2022 and included 23 patients with giant ovarian tumors treated with an Aron Alpha method. Results: The mean age of the subjects was 47.6 ± 17.8 years, mean tumor diameter 20.4 ± 5.8 cm, mean surgical duration 87.2 ± 33.1  min, and mean hemorrhage volume 94.1 ± 92.2 mL. No patient experienced intraoperative tumor rupture or surgery-related symptoms. Histopathology of excised samples revealed serous cyst adenoma and mucinous cystadenoma, mucinous cystadenoma of borderline malignancy and mature cystic teratoma, and endometriotic cyst adenoma in 6, 4, and 3 patients, respectively. The mean hospitalization period was 6.0 ± 1.2 days, and the hospitalization period was not extended in any subject. Conclusion: The Aron Alpha method allows tumor resection without capsular rupture and is a useful, minimally invasive surgical method for resecting giant ovarian tumors in which malignancy cannot be ruled out

Myoma with Hypermenorrhea Treated with Ultrasound-Guided Microwave Ablation of the Inflowing Blood Vessels to the Uterine Myoma: A Case

Microwave endometrial ablation (MEA) is a minimally invasive treatment for uterine myoma with hypermenorrhea, which can replace conventional hysterectomy. However, cases requiring additional treatment because of postoperative recurrence are often encountered. MEA cauterizes the endometrium and is not recommended for patients who wish to preserve fertility. We present the cases of a patient with myoma-related hypermenorrhea who underwent microwave ablation of the inflowing blood vessels to the uterine myoma under transvaginal ultrasound guidance. A 43-year-old woman was diagnosed with chronic myeloid leukemia and treated with dasatinib 2 years ago. Worsening hypermenorrhea was observed after treatment initiation. Ultrasound and pelvic magnetic resonance imaging revealed a uterine myoma. Therefore, she underwent MEA under transvaginal ultrasound guidance. Visual analog scale evaluation demonstrated considerable improvement in hypermenorrhea and dysmenorrhea; the myoma size showed reduction. The postoperative course was uneventful, and the patient was discharged on the day after surgery. No postoperative complications were observed. This patient is currently undergoing infertility treatment. The microwave ablation of myoma under transvaginal ultrasound guidance can effectively and safely reduce the myoma size. These findings suggest that this method is a novel treatment option for patients with myoma-related hypermenorrhea who wish to preserve their fertility and have children

Myoma with Hypermenorrhea Treated with Ultrasound-Guided Microwave Ablation of the Inflowing Blood Vessels to the Uterine Myoma: A Case

Microwave endometrial ablation (MEA) is a minimally invasive treatment for uterine myoma with hypermenorrhea, which can replace conventional hysterectomy. However, cases requiring additional treatment because of postoperative recurrence are often encountered. MEA cauterizes the endometrium and is not recommended for patients who wish to preserve fertility. We present the cases of a patient with myoma-related hypermenorrhea who underwent microwave ablation of the inflowing blood vessels to the uterine myoma under transvaginal ultrasound guidance. A 43-year-old woman was diagnosed with chronic myeloid leukemia and treated with dasatinib 2 years ago. Worsening hypermenorrhea was observed after treatment initiation. Ultrasound and pelvic magnetic resonance imaging revealed a uterine myoma. Therefore, she underwent MEA under transvaginal ultrasound guidance. Visual analog scale evaluation demonstrated considerable improvement in hypermenorrhea and dysmenorrhea; the myoma size showed reduction. The postoperative course was uneventful, and the patient was discharged on the day after surgery. No postoperative complications were observed. This patient is currently undergoing infertility treatment. The microwave ablation of myoma under transvaginal ultrasound guidance can effectively and safely reduce the myoma size. These findings suggest that this method is a novel treatment option for patients with myoma-related hypermenorrhea who wish to preserve their fertility and have children

Effects of Tetrafluoroborate and Bis(trifluoromethylsulfonyl)amide Anions on the Microscopic Structures of 1‑Methyl-3-octylimidazolium-Based Ionic Liquids and Benzene Mixtures: A Multiple Approach by ATR-IR, NMR, and Femtosecond Raman-Induced Kerr Effect Spectroscopy

The microscopic aspects of the two series of mixtures of 1-methyl-3-octylimidazolium tetrafluoroborate ([MOIm]­[BF₄])–benzene and 1-methyl-3-octylimidazolium bis­(trifluoromethylsulfonyl)­amide ([MOIm]­[NTf₂])–benzene were investigated by several spectroscopic techniques such as attenuated total reflectance IR (ATR-IR), NMR, and fs-Raman-induced Kerr effect spectroscopy (fs-RIKES). All three different spectroscopic results indicate that the anions more strongly interact with the cations in the [MOIm]­[BF₄]–benzene mixtures than in the [MOIm]­[NTf₂]–benzene mixtures. This also explains the different miscibility features between the two mixture systems well. The <i>x</i>_C₆H₆ dependences of the chemical shifts and the C–H out-of-plane bending mode of benzene are similar: the changes are large in the high benzene concentration (<i>x</i>_C₆H₆ > ∼0.6) compared to the low benzene concentration. In contrast, the linear <i>x</i>_C₆H₆ dependences of the first moments of the low-frequency spectra less than 200 cm^–1 were observed in both the [MOIm]­[BF₄]–benzene and [MOIm]­[NTf₂]–benzene systems. The difference in the <i>x</i>_C₆H₆ dependent features between the chemical shifts and intramolecular vibrational mode and the intermolecular/interionic vibrational bands might come from the different probing space scales. The traces of the parallel aromatic ring structure and the T-shape structure were found in the ATR-IR and NMR experiments, but fs-RIKES did not observe a clear trace of the local structure. This might imply that the interactions between the imidazolium and benzene rings are not strong enough to librate the imidazolium and benzene rings together. The bulk properties, such as miscibility, density, viscosity, and surface tension, of the two ionic liquid-benzene mixture series were also compared to the microscopic aspects

Age dependence of radiation-induced renal cell carcinomas in an Eker rat model

Exposure to carcinogens early in life may contribute to cancer development later in life. The amount of radiation exposure to children during medical procedures has been increasing, so it is important to evaluate the radiation risk of cancer in developing organs. Toward this goal, we assessed the risk of developing renal cell carcinoma using Eker rats as a kidney tumor model. F1 hybrids of male Eker (Tsc2 mutant) and female F344 rats were irradiated with 0.5 or 2 Gy gamma radiation on gestation days 15 and 19, and on postnatal days 5, 20, and 49. At 27 weeks of age, kidneys were examined for proliferative lesions. Preneoplastic lesions such as phenotypically altered tubules increased after postnatal irradiation as a function of age-at-irradiation, and hyperplasia were greatly increased after perinatal and postnatal irradiation. In contrast, development of adenoma and adenocarcinoma were evident in animals irradiated at perinatal ages, being maximal at gestational day 19. The frequency of LOH at the Tsc2 locus was unexpectedly low -0% (0 of 4) for the control, and 17% (6 of 35) for the irradiated group. Irrespective of LOH, the mTOR pathway, which is negatively regulated by the Tsc1/2 complex, was activated in both benign and malignant lesions, as evidenced by phosphorylation of S6 ribosomal protein and 4E-BP1. This suggests that the wild-type Tsc2 allele may be functionally inactivated. In conclusion, the actively growing kidney of (F344 X Eker) F1 rats (Tsc2+/-), at a perinatal age, is at risk for radiation-induced malignant transformation of the renal epithelium associated with mTOR activation