Abundance of mitochondrial superoxide dismutase is a negative predictive biomarker for endometriosis-associated ovarian cancers.

Background:Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are both classified as endometriosis-associated ovarian cancers (EAOCs). Despite the high rates of recurrence and mortality of EAOC, only a few prognostic biomarkers have been reported. Mitochondrial superoxide dismutase (SOD2) plays an important role in maintaining mitochondrial function through oxidative stress tolerance and contributes to chemotherapeutic resistance.Methods:To clarify the clinical significance of SOD2 in EAOC, SOD2 expression was semi-quantitatively investigated by immunohistochemical analysis in 61 primary EAOC cases, and the correlations between SOD2 expression and clinicopathological data and survival were analyzed.Results:Forty-six (75%) cases expressed high levels of SOD2. High SOD2 expression was associated with a poor prognosis on both univariate and multivariate analyses after adjusting for variables such as age, International Federation of Gynecology and Obstetrics (FIGO) stage, blood markers, histological type, and completion of treatment. There were 14 fatalities from 15 recurrences among 46 cases with high SOD2 expression. In contrast, only one recurrence and no fatalities were seen among 15 cases with low SOD2 expression.Conclusion:Increased SOD2 expression is a predictive biomarker for worse prognosis in EAOC. The therapeutic efficacy of the current standard therapeutic protocol for EAOC is limited; thus, mitochondrial SOD2 should be a therapeutic target for SOD2-abundant EAOC.滋賀医科大学令和元年

Antioxidants and Therapeutic Targets in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinomas (OCCCs) are resistant to conventional anti-cancer drugs; moreover, the prognoses of advanced or recurrent patients are extremely poor. OCCCs often arise from endometriosis associated with strong oxidative stress. Of note, the stress involved in OCCCs can be divided into the following two categories: (a) carcinogenesis from endometriosis to OCCC and (b) factors related to treatment after carcinogenesis. Antioxidants can reduce the risk of OCCC formation by quenching reactive oxygen species (ROS); however, the oxidant stress-tolerant properties assist in the survival of OCCC cells when the malignant transformation has already occurred. Moreover, the acquisition of oxidative stress resistance is also involved in the cancer stemness of OCCC. This review summarizes the recent advances in the process and prevention of carcinogenesis, the characteristic nature of tumors, and the treatment of post-refractory OCCCs, which are highly linked to oxidative stress. Although therapeutic approaches should still be improved against OCCCs, multi-combinatorial treatments including nucleic acid-based drugs directed to the transcriptional profile of each OCCC are expected to improve the outcomes of patients

Successful conservative treatment for massive uterine bleeding with non-septic disseminated intravascular coagulation after termination of early pregnancy in a woman with huge adenomyosis: case report.

BACKGROUND:Adenomyosis is a benign gynecological condition in which endometrial tissue or endometrial-like tissue develops within the uterine myometrium. Few cases of disseminated intravascular coagulation has been reported in the patients with adenomyosis. Although hysterectomy is indicated for refractory massive uterine bleeding in the patients with advanced uterine adenomyosis, conservative treatment is often desired in women in the late reproductive age. Recently such cases are increasing due to the social trend of late marriage.CASE PRESENTATION:A 37-year-old woman with huge adenomyosis, gravida 2 para 0, was referred to our hospital to terminate her pregnancy. Acute, non-septic, disseminated intravascular coagulation (DIC) developed after early pregnancy was terminated in a woman with huge adenomyosis. Massive bleeding and DIC occurred 3 days after the dilatation and curettage. There was no evidence of infection as the cause of the DIC, because neither bacteria nor endotoxin could be detected in her blood, and antithrombin 3 (AT3), which would be expected to decrease in septic patients, was not decreased. Hemorrhage in the adenomyotic tissue after the termination presumably developed inflammation, with numerous microthrombi and necrosis in the adenomyotic tissue, which subsequently promoted coagulation and fibrinolysis, leading to the onset of massive uterine bleeding and DIC. Although severe hyperfibrinolysis is observed in peripheral blood, the fibrinolysis state in the uterine myometrium is considered to be even more severe. The newly formed clots for hemostasis under the uterine mucosa could be removed due to the excessive activation of fibrinolytic system happened in the adjacent myometrium, leading to the onset of massive uterine bleeding. Massive bleeding and DIC resolved quickly after the patient was treated with nafamostat mesilate, which is effective for both excessive coagulation and fibrinolysis.CONCLUSIONS:Adenomyosis could cause massive bleeding and DIC when pregnancy is terminated. Massive bleeding was considered to occur because the excessive fibrinolysis system inside adenomyosis affected the adjacent endometrium. Before considering hysterectomy to control refractory uterine bleeding, nafamostat mesilate should be considered as one option, thinking the pathophysiology of the massive bleeding due to uterine adenomyosis

Prevalence, definition, and etiology of cesarean scar defect and treatment of cesarean scar disorder : A narrative review

Background: Cesarean scar defects (CSD) are caused by cesarean sections and cause various symptoms. Although there has been no previous consensus on the name of this condition for a long time, it has been named cesarean scar disorder (CSDi). Methods: This review summarizes the definition, prevalence, and etiology of CSD, as well as the pathophysiology and treatment of CSDi. We focused on surgical therapy and examined the effects and procedures of laparoscopy, hysteroscopy, and transvaginal surgery. Main findings: The definition of CSD was proposed as an anechoic lesion with a depth of at least 2 mm because of the varied prevalence, owing to the lack of consensus. CSD incidence depends on the number of times, procedure, and situation of cesarean sections. Histopathological findings in CSD are fibrosis and adenomyosis, and chronic inflammation in the uterine and pelvic cavities decreases fertility in women with CSDi. Although the surgical procedures are not standardized, laparoscopic, hysteroscopic, and transvaginal surgeries are effective. Conclusion: The cause and pathology of CSDi are becoming clear. However, there is variability in the prevalence and treatment strategies. Therefore, it is necessary to conduct further studies using the same definitions.journal articl

A novel surgical treatment for labial adhesion – The combination of Z- and Y-V-plasty : A case report.

Labial adhesion is characterised by complete or partial fusion of the labia minora. It occurs rarely in postmenopausal women. Although various methods have been proposed, there is no established treatment for postmenopausal patients with labial adhesions due to its low prevalence in this age group. Severe cases require surgical intervention, and the postoperative recurrence rate is relatively high at 14–20%. In this study, a novel therapeutic method was designed to treat labial adhesions: a combination of Z- and Y-V-plasty. An 82-year-old woman was diagnosed with severe long labial adhesion during an episode of urinary tract infection. The labia could not be separated manually; hence, Z-plasty was performed on the ventral side and Y-V-plasty on the anal side under general anaesthesia. No recurrence was noted eight months postoperatively. This method is relatively easy and produced the desired therapeutic effect with decreased risk of recurrence. This is a novel approach for postmenopausal patients with severe labial adhesion

Decreased Fertility in Women with Cesarean Scar Syndrome Is Associated with Chronic Inflammation in the Uterine Cavity.

Chronic inflammation in cesarean scar defect contributes to secondary infertility in women with cesarean scar syndrom; however, it remains unclear about the situation of inflammation in uterine cavity in women with cesarean scar syndrome. This ambidirectional cohort study aimed to explore the effect of inflammation in the uterine cavities of women with cesarean scar syndrome on infertility at a single university hospital. The frequency of chronic endometritis in infertile patients was retrospectively compared between the cesarean scar syndrome group and non-cesarean scar syndrome group. The frequency of endometriosis was also investigated in patients with cesarean scar syndrome who underwent laparoscopy. The level of tumor necrosis factor-α and interleukin-1β in the uterine cavity was prospectively evaluated in the cesarean scar syndrome group and in women with a history of cesarean section (control group) using an enzyme-linked immunosorbent assay. There was a significant difference in the incidence of chronic endometritis between the cesarean scar syndrome and non-cesarean scar syndrome groups (65.8% and 46.0%, respectively, p = 0.0315). Endometriosis was detected in 51 (70%) patients with laparoscopy. Tumor necrosis factor-α and interleukin-1β levels in the cesarean scar syndrome group were significantly higher than those in the control group (p = 0.0002 and p = 0.0217, respectively). Our findings suggest that one cause of secondary infertility in women with cesarean scar syndrome is embryo implantation failure-associated chronic endometritis, endometriosis, and chronic inflammation in the uterine cavity

Pregnancy outcomes after hysteroscopic surgery in women with cesarean scar syndrome.

Cesarean scar defect often causes postmenstrual abnormal uterine bleeding, dysmenorrhea, chronic pelvic pain, and infertility, which are collectively known as cesarean scar syndrome (CSS). Several studies have reported that hysteroscopic surgery can restore fertility in women with CSS. The study aimed to identify factors that influence subsequent pregnancy following hysteroscopic surgery. Therefore, we studied 38 women with secondary infertility due to CSS who underwent hysteroscopic surgery at Shiga University of Medical Hospital between July 2014 and July 2019. Our hysteroscopic procedure included inferior edge resection and superficial cauterization of the cesarean scar defect under laparoscopic guidance. Patients were followed up for 3 to 40 months after surgery. Surgery was successful in all cases and no complications were observed. Twenty-seven patients (71%) became pregnant (pregnant group), while 11 (29%) did not (non-pregnant group). Baseline characteristics of age, body mass index, gravidity, parity, previous cesarean section, presence of endometriosis, retroflex uterus, and preoperative residual myometrial thickness were not significantly different between the groups. However, the median residual myometrium thickness was significantly higher after surgery than before surgery in the pregnant group (1.9 [1.1-3.6] vs 4.9 [3.4-6.6] mm, P<0.0001), whereas this difference was not significant in the non-pregnant group. Of those who became pregnant, 85% conceived within 2 years of surgery. Although three pregnancies resulted in abortion and one is ongoing at the time of writing, 23 pregnancies resulted in healthy babies at 35-38 gestational weeks by scheduled cesarean sections with no obstetrical complications due to hysteroscopic surgery. The average birth weight was 3,076 g. Our findings support that hysteroscopic surgery is a safe and effective treatment for secondary infertility due to CSS. The thickness of the residual myometrium may be a key factor that influences subsequent pregnancy in women with CSS

An abdominal-sacral approach with preoperative embolisation for vulvar solitary fibrous tumour : a case report.

Background:Solitary fibrous tumours (SFTs) in the female genital tract are uncommon. Resection of these tumours is controversial because it can cause life-threatening haemorrhage. We report a case of vulvar SFT that was excised in a combined abdominal-sacral approach after preoperative embolisation.Case presentation:At another hospital, an inoperable intrapelvic tumour was diagnosed in a 34-year-old woman. Computed tomography and magnetic resonance imaging showed that the uterus, urinary bladder and rectum were compressed laterally by a pelvic tumour with a maximum diameter of 11 cm. This mass was hypervascular and had a well-defined border. Transperineal biopsy was performed, and immunostaining revealed that the mass was an SFT. The tumour was supplied by feeding vessels from the right iliac arteries. First, we embolised the feeding vessels. Second, we performed surgical resection in a combined abdominal-sacral approach; no blood transfusion was necessary, and no perioperative complications occurred. The final pathological diagnosis was SFT that was positive for CD34 and signal transducer and activator of transcription 6 according to immunohistochemical staining.Conclusion:During a year of follow-up, the disease did not recur. Treatment of pelvic SFT should aim at complete resection through various approaches after careful measures are taken to prevent haemorrhage

CTが診断契機となったディスジャーミノーマIA期の再発症例

　ディスジャーミノーマの術後経過観察において、腫瘍マーカーや内診による身体診察が推奨される一方、CT検査での全身検索については一定の見解が得られていない。今回、ディスジャーミノーマIA期術後に、CTが診断契機となったディスジャーミノーマIA期の傍大動脈リンパ節への単独再発症例を経験したので報告する。　症例は17歳、未妊。下腹部痛を主訴に来院した。MRIで臍高に達する右卵巣の充実性腫瘍を認めた。血液検査にてLDH、ALP、CA125、β-human chorionic gonadotropin(β-hCG)は高値を示したが、α-fetoprotein(AFP)は正常値であった。ディスジャーミノーマを疑い、右付属器切除および大網切除を施行した。術前のCTおよび腹腔内検索でリンパ節腫大や播種性病変を認めなかったため、リンパ節生検は省略した。術後病理でディスジャーミノーマIA期と診断され、術後化学療法は行わず、1ヵ月間隔で経過観察した。術後いずれの腫瘍マーカーも陰性化し、身体診察でも異常を認めず経過したが、術後6ヵ月で虫垂炎を発症。その際に撮影されたCTで、偶発的に傍大動脈リンパ節腫大を認めた。腹腔鏡下傍大動脈リンパ節摘出および虫垂切除術を施行し、ディスジャーミノーマの傍大動脈リンパ節への遠隔再発と診断された。術後BEP療法を3コース行い、現在再発なく経過している。　リンパ節郭清および術後補助化学療法が省略されたディスジャーミノーマIA期は再発のリスクが高いことを認識し、CT検査を含む厳重な経過観察が必要であることが示唆された。(著者抄録