Three-dimensional CT imaging in extensor tendons using deep learning reconstruction: optimal reconstruction parameters and the influence of dose.

The purpose of this study was to assess the optimal reconstruction parameters and the influence of tube current in extensor tendons three-dimensional computed tomography (3D CT) using deep learning reconstruction, using iterative reconstruction as a reference. In the phantom study, a cylindrical phantom with a 3 mm rod simulated an extensor tendon was used. The phantom images were acquired at tube current of 50, 100, 150, 200, and 250 mA. In the clinical study, CT scans of hand tendons were performed on nine hands from eight patients. All images were reconstructed using advanced intelligent clear-IQ engine (AiCE) parameters (body, body sharp, brain CTA, and brain LCD) and adaptive iterative dose reduction three dimensional (AIDR 3D). The objective image quality for tendon detectability was evaluated by calculating the low-contrast object specific contrast-to-noise ratio (CNRLO) in the phantom study and CNR and coefficient of variation (CV) in the clinical study. In the phantom study, CNRLO (at 200 mA) of AiCE parameters (body, body sharp, brain CTA, and brain LCD) and AIDR 3D were 5.2, 5.3, 5.3, 5.8, and 5.0, respectively. In the clinical study, AiCE brain CTA was higher CNR and lower CV values compared to other reconstruction parameters. AiCE without dose reduction may be an effective strategy for further improving the image quality of extensor tendons 3D CT. Our study suggests that the AiCE brain CTA is more suitable for extensor tendons 3D CT compared to other AiCE parameters.

3D-Image-Guided Multi-Catheter Interstitial Brachytherapy for Bulky and High-Risk Stage IIB-IVB Cervical Cancer.

This study aimed to evaluate the efficacy and safety of computed tomography-magnetic resonance imaging (CT-MRI)-guided multi-catheter interstitial brachytherapy for patients with bulky (≥4 cm) and high-risk, stage IIB-IVB advanced cervical cancer. Eighteen patients who underwent concurrent chemoradiotherapy with multi-catheter interstitial brachytherapy between September 2014 and August 2020 were enrolled. The prescribed dose of external beam radiotherapy was 45-50.4 Gy, and the brachytherapy high-dose-rate aim was 25-30 Gy per 5 fractions. The endpoints were four-year local and pelvic control rates, four-year disease-free and overall survival rates, and the adverse events rate. The median follow-up period was 48.4 months (9.1-87.5 months). Fifteen patients received concurrent cisplatin therapy (40 mg/m2, q1week). Four (22.2%), seven (38.9%), and seven (38.9%) patients had stage II, III, and IV cervical cancer, respectively. Pelvic and para-aortic lymph node metastases were observed in 11 (61.1%) and 2 (11.1%) patients, respectively. The median pre-treatment volume was 87.5 cm3. The four-year local control, pelvic control, disease-free survival, and overall survival rates were 100%, 100%, 81.6%, and 87.8%, respectively. Three (16.7%) patients experienced grade 3 adverse events, and none experienced grade 4-5 adverse events. CT-MRI-guided multi-catheter interstitial brachytherapy could be a promising treatment strategy for locally advanced cervical cancer.

Protocol for a modified vaginal pipe for total laparoscopic hysterectomies: Experimental research.

BACKGROUND: The Vagi-Pipe® is a useful device for performing a total laparoscopic hysterectomy. The conventional model of the Vagi-Pipe® is unable to grasp the uterus during colpotomy for recovery of the resected uterus. However, the modified C-Type Vagi-Pipe® model has a shape that allows insertion into the vagina without removing the uterus manipulator. In this study, we will prospectively investigate the safety and efficacy of the C-Type Vagi-Pipe® in total laparoscopic hysterectomies. MATERIALS AND METHODS: In total, 25 female subjects aged between 20 and 60 years with uterine fibroids or adenomyosis will be included. Patients with complications regarded as unsuitable for this study by the investigators will be excluded. The C-Type Vagi-Pipe® will be used rather than the conventional Vagi-Pipe® when performing a total laparoscopic hysterectomy. The primary endpoint will be safety and the secondary endpoints will be operation time, bleeding volume, and presence of complications. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review boards. Written informed consent will be obtained from all patients before registration in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals.

Peroxisome proliferator-activated receptor-γ coactivator 1α-mediated pathway as a possible therapeutic target in endometriosis.

STUDY QUESTION: Is a peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-mediated pathway involved in the development of endometriosis? SUMMARY ANSWER: PGC-1α plays critical roles in inflammation and cell proliferation of endometriotic tissues and may be involved in the development of endometriosis. WHAT IS KNOWN ALREADY: Expression levels of PGC-1α are higher in ovarian endometrioma (OE) than normal endometrium (NE). PGC-1α also stimulates aromatase activity and promotes local estrogen biosynthesis in OE. STUDY DESIGN, SIZE, DURATION: This is a case-controlled biological study using endometrial cells and tissues derived from 23 women with, and 10 women without, OE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ectopic endometriotic and eutopic endometrial stromal cells (SCs) were isolated and maintained in culture. PGC-1α was either overexpressed in the cells or knocked down using siRNA. The expression of PGC-1α and other factors during endometriosis was examined using real-time PCR and western blotting, cell proliferation was measured using Cell Counting Kit-8 (WST-8) assays and transcriptional activity was assessed using luciferase reporter assays. MAIN RESULTS AND THE ROLE OF CHANCE: PGC-1α overexpression promoted the proliferation of OESCs in a time-dependent manner (P < 0.01 versus control) but not NESCs. PGC-1α stimulated aromatase (P < 0.01 versus control) and interleukin (IL)-6/IL-8 mRNA expression levels (P < 0.05 versus control for each) and led to inhibitor kappa B phosphorylation protein expression and upregulation of the apoptosis inhibitors X-linked inhibitor of apoptosis protein and survivin at mRNA level (P < 0.05 versus control for each). HX531, a selective retinoid-X receptor-α (RXRα) antagonist, suppressed the PGC-1α-induced cell proliferation (P < 0.05 versus control), aromatase/IL-6/IL-8/survivin mRNA expression (P < 0.05 versus control for each) and transcription reporter activity of PGC-1α in a dose-dependent manner (P < 0.01 versus control). Moreover, HX531 downregulated PGC-1α-induced aromatase-promoter PI.3-II transcripts in OESCs, and PGC-1α knockdown reduced aromatase, IL-6/IL-8 and antiapoptotic factors mRNA expression (P < 0.05 versus control for each). Notably, the Histogram score, which was used for quantifying RXRα status, was markedly higher in OE than in NE tissue (P < 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Only OE tissues were included in this study, while peritoneal and deep infiltrating endometriotic tissues were not. Therefore, these findings might not be generalized to other types of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: In OESC, PGC-1α stimulated cell proliferation and was involved in local estrogen biosynthesis, inflammation and apoptosis, and these effects of PGC-1α were inhibited by HX531. The suppression of PGC-1α-induced proliferation by HX531 in OESCs but not NESCs suggests that the PGC-1α-RXRα axis could play critical roles in promoting endometriosis. This is the first report of a relationship between PGC-1α and inhibitor of apoptosis proteins in endometriosis. Based on these findings, the PGC-1α-mediated pathway could represent a potential target in molecular therapy of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The study is supported in part by Grants-in-Aid for Scientific Research (15 K10681 and 15 K10726) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan). The authors have no conflicts of interest to disclose.

Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer.

Estrogen-related receptor alpha (ERRα), which shares structural similarities with estrogen receptors, is associated with tumor progression in endometrial cancer, but little is known about the detailed underlying mechanism. We investigated whether ERRα, in cooperation with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), could participate in epithelial-mesenchymal transition (EMT) in endometrial cancer through cancer-stromal interactions. Two endometrial cancer cell lines, Ishikawa and HEC-1A, transfected with ERRα/PGC-1α expression plasmids or silenced for ERRα expression, were co-cultured with telomerase-transformed human endometrial stromal cells (T-HESCs). We found that EMT-associated factors including vimentin, Snail, and zinc finger E-box binding homeobox 1 were upregulated in cancer cells overexpressing ERRα/PGC-1α and that transforming growth factor-beta (TGF-ß) was induced in T-HESCs in the same conditions. In contrast, ERRα knockdown suppressed EMT-associated factors in cancer cells and TGF-ß in T-HESCs. ERRα/PGC-1α overexpression increased the expression of EMT-associated factors after TGF-ß exposure; however, it decreased E-cadherin at protein level. ERRα knockdown suppressed EMT-associated factors in the presence of TGF-ß, whereas E-cadherin remained unchanged. Matrigel invasion assays revealed that ERRα knockdown attenuated the stimulation of migration and invasion by TGF-ß. These findings suggest that ERRα is a potential target for inhibiting TGF-ß-induced EMT through cancer-stromal interactions in endometrial cancer.

Retroperitoneal fibrosis after chemo-radiotherapy for cervical cancer: A case report.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by proliferation of fibro-inflammatory tissue in the retroperitoneum. Multiple studies have reported on the idiopathic cases of the disease, but reports of RPF secondary to irradiation are very limited. Herein, we report the case of a 47-year-old woman who complained of lower abdominal pain 14 months after chemo-radiotherapy for cervical cancer. Computed tomography showed a soft-tissue mass spreading in the presacral space. Biopsy of the lesion revealed fibro-inflammatory tissue without malignancy. Retrospective imaging findings showed that the lesion was consistent with the irradiation field. We diagnosed the patient with RPF caused by radiotherapy. We started oral administration of prednisolone at a dose of 30 mg/day. After 3 months, scans showed a remarkable reduction in lesion size. Prednisolone was tapered to a maintenance dose of 5 mg/day, which is ongoing. The patient is doing well with no recurrence to date.

Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells.

PURPOSE: The estrogen-related receptor (ERR) α is structurally similar to classical estrogen receptors (ERs), but is considered to be an orphan nuclear receptor. We previously found that ERRα regulates uterine endometrial cancer progression. Here, we investigated the efficacy of XCT790, a selective inverse agonist of ERRα, on endometrial cancer cells in vitro and in vivo. METHODS: HEC-1A and KLE, ERα-negative endometrial cancer cells exhibiting high ERRα expression levels, and HEC-1A cell-derived xenograft model mice were treated with XCT790. Transcriptional activity and cell proliferation were examined using luciferase, WST-8 and colony formation assays, respectively. Cell cycle progression was evaluated using flow cytometry, immunofluorescence cytochemistry and Western blotting. Apoptosis was evaluated using a caspase-3/7 activity assay. RESULTS: We found that XCT790 significantly inhibited ERRα-induced in vitro transcriptional activity, including that of the vascular endothelial growth factor (VEGF) gene, in a concentration-dependent manner (p < 0.05). We also found that XCT790 suppressed colony formation and cell proliferation in a concentration and time-dependent manner (p < 0.01) without cytotoxicity, and induced apoptosis (p < 0.01). XCT790 was found to cause cell cycle arrest at the mitotic phase. Akt and mTOR phosphorylation was found to be inhibited by XCT790, but PI3K levels were not found to be significantly affected. Combination therapy of XCT790 with paclitaxel elicited a synergistic inhibitory effect. Additionally, we found that XCT790 significantly inhibited in vivo tumor growth and angiogenesis, and induced apoptosis without a reduction in body weight, in xenograft models (p < 0.01). CONCLUSIONS: From our data we conclude that XCT790 has an anti-tumor effect on endometrial cancer cells in vitro and in vivo. As such, it may serve as a novel therapeutic agent for endometrial cancer.

Massive prolapsed submucous fibroid treated with laparoscopic surgery: A case report.

Prolapsed uterine fibroids are pedunculated submucous fibroids that prolapse through the cervical canal. Herein, we describe the laparoscopic treatment of massive prolapsed submucous fibroids. A 47-year-old woman had experienced frequent urination and abnormal vaginal bleeding for 7 years. She presented with persistent lower abdominal pain. The uterine fundus was palpable at 3 cm above the umbilicus. Vaginal examination revealed a dark purple and easily bleeding mass in her vagina. Pelvic magnetic resonance imaging revealed a large mass prolapsing from the uterine endometrium, which occupied the cervical canal and vagina, without evidence of malignancy. Under a preoperative diagnosis of uterine fibroids with edematous degeneration, we performed laparoscopic uterine artery cutting, transvaginal removal of the fibroid by twisting, and total laparoscopic hysterectomy. Histopathological examination revealed leiomyoma with partial ischemia. Six days postoperatively, the patient was discharged without complications. This approach may be appropriate for the treatment of massive prolapsed submucous fibroids.

Successful Laparoscopic Surgery without Neuromuscular Blockade in a Patient with Malignant Hyperthermia Susceptibility.

Malignant hyperthermia (MH) is a life-threatening clinical syndrome of hypermetabolism involving skeletal muscle. Susceptibility to MH is inherited in an autosomal dominant manner. Its common trigger is exposure to volatile anesthetic agents or depolarizing muscle relaxants. Deep neuromuscular blockade using muscle relaxants can improve the quality of surgical conditions and prevent cardiorespiratory adverse events during laparoscopic surgery. Here we report a case of successful laparoscopic surgery under anesthetic management without neuromuscular blockade in an MH-susceptible patient. A 22-year-old woman with a family history of MH underwent laparoscopic excision of ovarian endometrioma under total intravenous anesthesia and a posterior transversus abdominis plane block. The surgery was completed uneventfully. Our experience suggests that this type of anesthetic management is useful when performing laparoscopic surgery in MH-susceptible patients.

Dienogest therapy during the early stages of recurrence of endometrioma might be an alternative therapeutic option to avoid repeat surgeries.

AIM: We aimed to evaluate whether hormonal therapy immediately after postsurgical recurrence of ovarian endometrioma controls disease progression and can be an alternative therapeutic option to avoid multiple repeat surgeries. METHODS: We enrolled 146 patients treated for endometrioma at the University Hospital of Kyoto Prefectural University of Medicine between 2009 and 2015. After laparoscopic cystectomy using the stripping technique, opening of cul-de-sac obliterations and complete resection of the deep infiltrating endometriosis lesions, the patients either received no treatment (n = 83), oral contraceptives (OC; n = 32) or dienogest (DNG; n = 27), depending on their medical history. Four patients were excluded because they changed their regimens during the follow-up period. All patients were followed up every 3 months. Patients who developed recurrence of endometrioma immediately received DNG, OC or gonadotropin-releasing hormone agonist. RESULTS: Overall, 16 patients developed a recurrence of the endometrioma (12 in the nontreatment group, three in the OC group and one in the DNG group). The 11 patients with recurrence were treated with DNG immediately after the diagnosis of recurrent endometrioma. Among them, seven patients continued treatment with DNG (2 mg) for 24 months. After 24 months of treatment with DNG, complete resolution of recurrent endometrioma was achieved in four (57.1%) of seven patients. There was no improvement in the three patients who received OC and one patient who underwent secondary surgery. CONCLUSION: DNG therapy early after recurrence of postsurgical endometrioma appears to be viable for reducing the risk of repeated surgery.

Long-term survival with bevacizumab in heavily pretreated and platinum-resistant mucinous ovarian cancer: A case report.

The prognosis of patients with recurrent and platinum-resistant ovarian cancer is quite poor. Randomized trials have shown that bevacizumab (BEV) can be effective, even in platinum-resistant ovarian cancer, but only a few such cases of long-term survival with BEV have been reported. Furthermore, there is no consensus on how many cycles of BEV should be administered. Herein, we report a case of refractory mucinous ovarian cancer showing long-term survival after six cycles of weekly paclitaxel with BEV followed by 26 cycles of BEV maintenance. Although six prior chemotherapy regimens resulted in progressive disease, the BEV treatment controlled the patient's ascites and improved her performance status. For a further 30 months and 32 cycles of BEV, neither progression of the disease nor severe adverse events have been observed. Our case demonstrates that BEV administration could result in a favorable outcome in heavily pretreated and platinum-resistant ovarian cancer patients.

Apocrine Adenocarcinoma of the Vulva: A Case Report and Review of the Literature.

Primary vulvar adenocarcinomas are very rare. We describe the rare case of primary vulvar apocrine adenocarcinoma, a histologically rare subtype of vulvar adenocarcinoma. A 57-year-old Japanese woman presented with an enlarging vulvar mass. A dark-red, hemorrhagic, ulcerated tumor was on the right side of the anterior labial commissure measuring approximately 3.5 × 3.5 cm. Preoperative biopsy showed poorly differentiated carcinoma with partial differentiation to adenocarcinoma. Systemic examination revealed lymph node metastases in both inguinal regions and no other primary source. We performed radical vulvectomy and bilateral inguinal and pelvic lymphadenectomy. Histopathologic diagnosis was apocrine adenocarcinoma of the vulva with inguinal lymph node metastases, pT1bN2bM0. Surgical margins were negative. The patient received no adjuvant chemotherapy or radiation. Inguinal lymph node recurrence occurred after six months. Reresection and adjuvant tomotherapy were performed. After a further 12 months of observation, no rerecurrence was observed. The patient is now on follow-up.

Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer.

Estrogen-related receptor (ERR)α presents structural similarities with estrogen receptor (ER)α. However, it is an orphan receptor not binding to naturally occurring estrogens. This study was designed to investigate the role of ERRα in endometrial cancer progression. Immunohistochemistry analysis on 50 specimens from patients with endometrial cancer showed that ERRα was expressed in all examined tissues and the elevated expression levels of ERRα were associated with advanced clinical stages and serous histological type (p < 0.01 for each). ERRα knockdown with siRNA suppressed angiogenesis via VEGF and cell proliferation in vitro (p < 0.01). Cell cycle and apoptosis assays using flow cytometry and western blot revealed that ERRα knockdown induced cell cycle arrest during the mitotic phase followed by apoptosis initiated by caspase-3. Additionally, ERRα knockdown sensitized cells to paclitaxel. A significant reduction of tumor growth and angiogenesis was also observed in ERRα knockdown xenografts (p < 0.01). These findings indicate that ERRα may serve as a novel molecular target for the treatment of endometrial cancer.

Loss of AF-6/afadin induces cell invasion, suppresses the formation of glandular structures and might be a predictive marker of resistance to chemotherapy in endometrial cancer.

BACKGROUND: AF-6/afadin plays an important role in the formation of adherence junctions. In breast and colon cancer, loss of AF-6/afadin induces cell migration and cell invasion. We aimed to elucidate the role of AF-6/afadin in human endometrial cancer. METHODS: Morphology and AF-6/afadin expression in endometrial cancer cell lines was investigated by 3-dimensional culture. We used Matrigel invasion assay to demonstrate AF-6/afadin knockdown induced invasive capability. Cell proliferation assay was performed to estimate chemoresistance to doxorubicin, paclitaxel and cisplatin induced by AF-6/afadin knockdown. The associations between AF-6/afadin expression and clinicopathological status were determined by immunohistochemical analysis in endometrial cancer tissues. Informed consent was obtained from all patients before the study. RESULTS: The majority of cell clumps in 3-dimensional cultures of Ishikawa cells that strongly expressed AF-6/afadin showed round gland-like structures. In contrast, the cell clumps in 3-dimensional cultures of HEC1A and AN3CA cells-both weakly expressing AF-6/afadin-showed irregular gland-like structures and disorganized colonies with no gland-like structures, respectively. AF-6/afadin knockdown resulted in reduced number of gland-like structures in 3-dimensional cultures and enhancement of cell invasion and phosphorylation of ERK1/2 and Src in the highly AF-6/afadin-expressing endometrial cancer cell line. Inhibitors of MAPK/ERK kinase (MEK) (U0126) and Src (SU6656) suppressed the AF-6/afadin knockdown-induced invasive capability. AF-6/afadin knockdown induced chemoresistance to doxorubicin, paclitaxel and cisplatin in Ishikawa cells, not in HEC1A. Immunohistochemical analysis showed that AF-6/afadin expression was significantly associated with myometrial invasion and high histological grade. CONCLUSIONS: AF-6/afadin regulates cell morphology and invasiveness. Invasive capability is partly regulated through the ERK and Src pathway. The inhibitors to these pathways might be molecular-targeted drugs which suppress myometrial invasion in endometrial cancer. AF-6/afadin could be a useful selection marker for fertility-sparing therapy for patients with atypical hyperplasia or grade 1 endometrioid adenocarcinoma with no myometrial invasion. AF-6/afadin knockdown induced chemoresistance especially to cisplatin. Therefore, loss of AF-6/afadin might be a predictive marker of chemoresistance to cisplatin.

G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis.

OBJECTIVE: To demonstrate the effects of the selective G protein-coupled estrogen receptor 1 (GPER) agonist G-1 in human ovarian endometriotic stromal cells (ESCs). DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): A total of 33 patients with ovarian endometrioma. INTERVENTION(S): Endometriotic stromal cells from ovarian chocolate cysts were treated with the GPER agonist G-1. MAIN OUTCOME MEASURE(S): The primary outcomes were cell proliferation, measured using the WST-8 assay; cell cycle, as analyzed using flow cytometry, fluorescent immunocytochemistry, and cytotoxicity; caspase activity, as measured by fluorescent and luminescent enzyme assays; and protein expression levels, as determined by Western blot analysis. RESULT(S): G-1 suppressed ESC proliferation in a concentration-dependent manner. The inhibitory effect was not blocked when GPER signaling pathways, including the GPER itself, were inhibited. G-1 induced cell cycle arrest and accumulation in the sub-G1 phase in ESCs. Immunofluorescence analysis demonstrated that G-1 interrupted microtubule assembly at the mitotic phase. G-1 also induced caspase-3-dependent apoptosis without significant cytotoxicity. CONCLUSION(S): G-1 suppressed proliferation and induced apoptosis in ESCs, suggesting the potential use of this compound as a therapeutic drug for the treatment of endometriosis.

Dienogest reduces HSD17ß1 expression and activity in endometriosis.

Endometriosis is an estrogen-dependent disease. Abnormally biosynthesized estrogens in endometriotic tissues induce the growth of the lesion and worsen endometriosis-associated pelvic pain. Dienogest (DNG), a selective progesterone receptor agonist, is widely used to treat endometriosis and efficiently relieves the symptoms. However, its pharmacological action remains unknown. In this study, we elucidated the effect of DNG on enzymes involved in local estrogen metabolism in endometriosis. Surgically obtained specimens of 23 ovarian endometriomas (OE) and their homologous endometrium (EE), ten OE treated with DNG (OE w/D), and 19 normal endometria without endometriosis (NE) were analyzed. Spheroid cultures of stromal cells (SCs) were treated with DNG and progesterone. The expression of aromatase, 17ß-hydroxysteroid dehydrogenase 1 (HSD17ß1), HSD17ß2, HSD17ß7, HSD17ß12, steroid sulfatase (STS), and estrogen sulfotransferase (EST) was evaluated by real-time quantitative PCR. The activity and protein level of HSD17ß1 were measured with an enzyme assay using radiolabeled estrogens and immunohistochemistry respectively. OESCs showed increased expression of aromatase, HSD17ß1, STS, and EST, along with decreased HSD17ß2 expression, when compared with stromal cells from normal endometria without endometriosis (NESCs) (P<0.01) or stromal cells from homologous endometrium (EESCs) (P<0.01). In OESCs, DNG inhibited HSD17ß1 expression and enzyme activity at 10(-7) M (P<0.01). Results of immunohistochemical analysis displayed reduced HSD17ß1 staining intensity in OE w/D (P<0.05). In conclusion, DNG exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and HSD17ß1, contributing to a therapeutic effect of DNG on endometriosis.

Clear cell carcinoma arising from cesarean section scar endometriosis: case report and review of the literature.

Introduction. The incidence of endometriosis affecting skin tissue represents only 0.5-1.0% of all endometriosis cases. A malignancy in the abdominal wall arising from endometriosis following cesarean section is even rarer; only 21 cases have previously been reported. The therapeutic strategy has not been determined because of the limited cases. We report a case of clear cell adenocarcinoma arising in the abdominal wall from endometriosis tissues following cesarean section and review previous literature to achieve the optimal treatment and better prognosis. Case Presentation. A 60-year-old woman presented with a growing mass at the left side of a cesarean section scar. Radical resection of the abdominal wall mass was performed. Histopathological examination showed a clear cell adenocarcinoma. Benign endometrium-like tissues were found adjacent to the cancer lesion in the excised specimen, suggesting malignant transformation from endometriosis of the abdominal wall. Discussion. Local resection was performed in 10 cases (47.6%) and total abdominal hysterectomy or oophorectomy was conducted in 11 cases (52.4%). No malignant lesions were observed in either the uterus or adnexa that were resected. These cases may be expected to increase with increasing incidence of cesarean section. The significance of the extensional resection should be further elucidated.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography-positive lymph node endometriosis masquerading as lymph node metastasis of a malignant tumor.

Endometriosis is defined as the presence of endometrium-like tissues at extrauterine sites, most commonly in the abdominal cavity. Lymph node endometriosis is a rare but clinically important type of endometriosis that can mimic lymph node metastasis of a malignant tumor. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing malignant tumors, although it occasionally shows false positive results in tissues with high metabolic activity caused by severe inflammation. In the present report, we describe a case of lymph node endometriosis that mimicked lymph node metastasis of a malignant tumor and showed a positive result on (18)F-FDG PET/CT. The findings of the present case suggest that lymph node endometriosis could present as swollen lymph nodes with (18)F-FDG PET/CT-positive results and provide important information for determining an appropriate treatment strategy.

Late, isolated metastasis from poorly differentiated gastric cancer to the uterine cervix.

•Metastases from extrapelvic organs to the uterine cervix are rare.•Cervical metastases from the stomach are often accompanied by extrauterine metastases.•We report a case of cervical metastasis of gastric cancer, occurring 10 years after the first surgical treatment.

Pharmacokinetics of mirabegron, a ß3-adrenoceptor agonist for treatment of overactive bladder, in healthy Japanese male subjects: results from single- and multiple-dose studies.

BACKGROUND: Mirabegron is a human ß3-adrenoceptor agonist for the treatment of overactive bladder. The pharmacokinetic profile of mirabegron has been extensively characterized in healthy Caucasian subjects. OBJECTIVE: The objective of this study was to evaluate the pharmacokinetics, dose-proportionality, and tolerability of mirabegron following single and multiple oral doses in healthy Japanese male subjects. The results were compared with those reported in non-Japanese (primarily Caucasian) subjects. METHODS: Two studies were conducted. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study (Study 1), mirabegron oral controlled absorption system (OCAS) tablets were administered at single doses of 50, 100, 200, 300, and 400 mg, with eight subjects (six active, two placebo) per dose group (Part I), and once daily for 7 days at 100 and 200 mg with 12 subjects (eight active, four placebo) per group (Part II). In an open-label, three-period, single-ascending dose study (Study 2), mirabegron OCAS was administered to 12 subjects at 25, 50, and 100 mg in an intra-subject dose-escalation design. Plasma and/or urine samples were collected up to 72 h after the first and last dose and analyzed for mirabegron. Pharmacokinetic parameters were determined using non-compartmental methods. Tolerability assessments included physical examinations, vital signs, 12-lead electrocardiogram, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event (AE) monitoring. RESULTS: Forty and 24 young male subjects completed Part I and II, respectively, of Study 1. Twelve young males completed Study 2. After single oral doses (25-400 mg), maximum plasma concentrations (C max) were reached at approximately 2.8-4.0 h postdose. Plasma exposure (C max and area under the plasma concentration-time curve) of mirabegron increased more than dose proportionally at single doses of 25-100 mg and approximately dose proportionally at high doses of 300 and 400 mg. A more than dose proportional increase in plasma exposure was noted in the body of the same individual. Mirabegron accumulated twofold upon once-daily dosing relative to single-dose data. Steady state was reached within 7 days. Mirabegron was generally well-tolerated at single doses up to 400 mg and multiple doses up to 200 mg. The AE with the highest incidence was increased pulse rate at 400 mg in Study 1. CONCLUSIONS: Mirabegron OCAS exhibits similar single- and multiple-dose pharmacokinetic characteristics and deviations from dose proportionality in healthy Japanese male subjects compared with those observed in non-Japanese (primarily Caucasian) subjects in previous studies.