A Case Report of Occult Breast Cancer Detected by Diagnostic Laparoscopy for Suspected Ovarian Cancer.

Diagnostic laparoscopy is useful in the management of gynecological cancers; however, it can occasionally result in the detection of other malignancies. Occult breast cancer (OBC) is metastatic breast cancer without a recognized primary breast lesion. We report a rare case of OBC that was detected laparoscopically. A 64-year-old female presented to our hospital with back pain. Magnetic resonance imaging (MRI) revealed a 50 mm multicystic tumor with an internal nodule in the right ovary. Positron emission tomography/computed tomography showed abnormal accumulation in multiple lymph nodes, moderate accumulation in the ovarian tumor nodule, and no accumulation in the breasts. Ovarian cancer was suspected, and a diagnostic laparoscopy was performed. Laparoscopically, a cystic tumor in the right ovary and 10 mm nodule in the right round ligament were observed and partially resected. Immunohistopathologically, the nodules of the round ligament exhibited features consistent with those of breast cancer, but the ovarian tumor was a seromucinous borderline tumor. MRI revealed no breast lesions. Therefore, the malignancy was diagnosed as an OBC.

Successful resection of growing teratoma syndrome in the abdominal wall with reconstruction using tensor fascia lata muscle flap: A case report and literature review.

While cancer cure is the primary goal, fertility preservation is also a cornerstone of the underlying principle of treatment for ovarian germ cell tumors. Growing teratoma syndrome (GTS) presents with growth of mature teratomas during or after chemotherapy. We report a case of successful treatment of GTS in the anterior abdominal wall involving reconstruction. A 23-year-old woman with a suspected right ovarian mature teratoma with torsion underwent emergency laparoscopically assisted extracorporeal ovarian cystectomy. Histopathological findings revealed a grade 1 immature teratoma. After two months, postoperative α-fetoprotein (AFP) levels increased, and disseminated lesions developed not only in the pelvic cavity but also in the abdominal wound where the tumor had been extracted using an extracorporeal technique at the time of primary surgery. The patient underwent laparoscopic right salpingo-oophorectomy, excision of multiple peritoneal nodules, and biopsy of abdominal wall mass. The left rectus abdominis muscle tumor could not be removed. All of these nodules were diagnosed as metastatic immature teratomas. Although the patient received three cycles of chemotherapy, the residual tumor in the abdominal wall grew remarkably despite post-chemotherapy normalization of AFP levels. Both rectus abdominis muscles involving the residual tumors were removed and reconstructed using a left tensor fascia lata muscle flap. Histopathologically, the residual tumors were identified as mature teratomas with no immature elements, resulting in GTS. The patient got pregnant without the need of fertility treatment and gave birth uneventfully by cesarean section. Thus, reconstruction with a tensor fascia lata muscle flap facilitated complete removal of GTS while preserving fertility.

Computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography findings for the diagnosis of malignant struma ovarii: A case report.

Malignant struma ovarii (MSO) is an extremely rare disease arising from struma ovarii. Preoperative diagnosis is still challenging due to the lack of criteria for imaging findings. Herein, we report a case of MSO with suggestive imaging findings for a 50-year-old woman who presented with a pelvic tumor. The tumor did not typically show characteristic imaging findings of struma ovarii; however, the findings implied colloids of thyroid tissue within solid components on the magnetic resonance imaging (MRI) and computed tomography. Additionally, the solid components showed hyperintensity on diffusion-weighted image and hypointensity on apparent diffusion coefficient maps. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Histopathological examination revealed MSO of the right ovary, pT1aNXM0. The distribution of papillary thyroid carcinoma tissue corresponded to restricted diffusion area on MRI. In conclusion, the coexistence of imaging findings suggesting thyroid tissue and restricted diffusion in the solid component on MRI could indicate MSO.

Giant retroperitoneal dedifferentiated liposarcoma mimicking ovarian cancer: A case report.

Retroperitoneal liposarcoma is a rare tumor, and its dedifferentiated subtype and a larger diameter are associated with a poor prognosis. However, there are few reports of retroperitoneal liposarcomas, both with a dedifferentiated subtype and a diameter of >30 cm. We report a case of a giant retroperitoneal liposarcoma with a dedifferentiated subtype. A 78-year-old woman presented to our hospital with abdominal distension and loss of appetite. Computed tomography and magnetic resonance imaging findings revealed a 35-cm-diameter solid tumor in the peritoneal cavity. CA125 (64.8 U/mL) and HE4 (229.0 pmol/L) were elevated preoperatively raising suspicion for ovarian malignancy. However, intraoperative findings revealed that the tumor originated in the retroperitoneal cavity. Reductive surgery for the tumor and partial resection of the sigmoid colon and left ureter were performed, and pathological examination confirmed a retroperitoneal dedifferentiated liposarcoma. Although her symptoms improved postoperatively, she died 11 months after surgery due to disease progression.

Successful nedaplatin desensitization therapy in a patient with platinum-sensitive recurrent ovarian cancer: A case report and literature review.

Desensitization protocols of platinum-based agents are recommended for patients with a history of hypersensitivity reaction (HSR). Herein, we report the first case of a successful desensitization therapy with nedaplatin after HSR to carboplatin and nedaplatin for platinum-sensitive recurrent ovarian cancer. A 53 year-old woman was diagnosed with stage IIIC serous carcinoma of the ovary and underwent primary debulking surgery followed by an adjuvant chemotherapy. The tumor relapsed 4 times in 10 years after the initial treatment, and platinum-based chemotherapy was performed on each occasion. HSR to carboplatin without and with desensitization protocol occurred during the 9th cycle of treatment and 2nd cycle of retreatment, respectively. Additionally, HSR to nedaplatin occurred during the 16th cycle of nedaplatin treatment. A four-step desensitization protocol with nedaplatin was conducted without occurrence of any severe adverse event. Nedaplatin desensitization regimen could be a new alternation for HSR to platinum-based agents.

Robot-assisted laparoscopic hysterectomy for early-stage endometrial cancer with massive uterine leiomyomas: A case report.

INTRODUCTION AND IMPORTANCE: Compared to conventional laparoscopic surgery, robot-assisted surgery enables precise operation, with the aid of high-resolution 3D images and articulated forceps, even in cases where the uterus is very large. CASE PRESENTATION: A 48-year-old woman with severe obesity was referred to our hospital with atypical genital bleeding for half a year. She was diagnosed with multiple uterine leiomyomas and early endometrial cancer with presumed advanced stage classification (stage IA). Robot-assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node biopsy were performed. Due to the difficulty of removing the uterus transvaginally, the umbilical incision was extended by 7 cm, which allowed the uterine tissue removal without shredding or leakage into the pelvic cavity. The patient was discharged 5 days postoperatively, with no postoperative complications. CLINICAL DISCUSSION: Robot-assisted surgery has often been used for the management of early-stage endometrial cancer. Robot-assisted laparoscopic hysterectomy has significantly fewer intraoperative and postoperative complications than laparoscopic and abdominal hysterectomy. CONCLUSION: Improving this surgical procedure allows for safe and easy robot-assisted uterine malignant tumor removal even in cases where the patient presents with severe obesity and huge uterine leiomyomas.

Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients.

Progesterone is used to treat uterine endometrial cancer in young patients wishing to preserve their fertility as well as in advanced or recurrent patients, but its response rate is limited. The antitumor effect of progesterone is mediated by progesterone receptor (PR) binding. Hence, loss of progesterone's therapeutic effect, i.e., development of progesterone resistance, is mainly due to decreased PR expression. However, little is known about underlying mechanisms that regulate PR expression. Immunohistochemistry analysis of specimens from 31 young, endometrial cancer patients showed that elevated PR expression significantly increased (P < 0.05) rates of progression-free and overall survival. We investigated mechanisms of regulating PR expression and suppressing cell proliferation using genistein, a chemotherapeutic agent against different cancers. Genistein inhibits cell growth by inducing cell cycle arrest in G2 and apoptosis; moreover, it upregulates prolonged expression of PR-B and forkhead box protein O1, regardless of estrogen receptor alpha expression in endometrial cancer cells. Genistein-induced PR expression decreases CCAAT/enhancer binding protein beta expression and activates c-Jun N-terminal kinase pathway, rather than causing epigenetic alterations of the PR promoter. Therefore, increased PR expression is an important antitumor effect of genistein. This may help to improve the response rates of fertility-sparing treatments for young patients.

Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis.

CONTEXT: Progesterone resistance including progesterone receptor (PR) deficiency contributes to the pathophysiology of endometriosis; however, whether the PR expression levels in ovarian endometrioma (OE) correlate with the postoperative recurrence of endometriosis remains unclear. OBJECTIVE: This study aimed to investigate the association between PR expression levels in OE and the recurrence of endometriosis. METHODS: OE specimens were obtained from 132 patients who underwent conservative surgery for endometriosis. The PR expression levels were evaluated using the H score after immunohistochemical staining. RESULTS: Of the 132 patients, 36 (27.3%) experienced recurrence and 96 (72.7%) did not. No differences were observed in the patient characteristics between the recurrence and nonrecurrence groups except for follow-up period. PR immunoreactivity in the epithelial cells (ECs) was statistically significantly lower in the recurrent group than in the nonrecurrent group (P < .01); however, this change was not observed in the stromal cells. Moreover, multivariable logistic regression analysis revealed that the H score of PR in ECs was an independent factor and was statistically significantly associated with the recurrence of endometriosis (P = .01). Furthermore, we divided the patients into PR-negative or PR-positive groups. The cumulative recurrence rate in the negative PR group was statistically significantly higher than that in the positive PR group (P = .046). CONCLUSION: Low PR expression levels in OE-ECs may predict the recurrence of endometriosis. The PR status in OE-ECs is associated with the pathophysiology of the recurrence of endometriosis, and optimized postoperative management for endometriosis may be provided by referring to the PR status.

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.

Primary Ovarian Leiomyoma Associated with Multiple Uterine Leiomyomas.

Ovarian leiomyomas are very rare. We report the case of a primary ovarian leiomyoma accompanied by multiple uterine leiomyomas. A 50-year-old woman was referred to our department for heavy menstruation, and a hot spot in the uterine lumen was observed on positron emission tomography-computed tomography (PET-CT). Cervical and endometrial cytology and tumor marker tests were negative. Pelvic magnetic resonance imaging revealed an endometrial polyp and submucosal leiomyoma in the uterine lumen and a 5-cm right ovarian tumor. Laparoscopic total hysterectomy, right salpingo-oophorectomy, and left salpingectomy were performed for radical treatment. Histopathology showed that ovarian tumors contained interlacing bundles of fusiform cells encircled by normal ovarian tissue. Immunohistochemical staining showed strong and diffuse positive staining for α-smooth muscle actin. We diagnosed the tumor as a primary ovarian leiomyoma because the leiomyoma was localized in the ovary and was larger than the size of uterine leiomyomas. No metastatic lesion was found on PET-CT. There was no tumor recurrence at the 6-month follow-up.

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.

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.

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.

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.

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.

Endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy: A case report.

Malignant transformation of diaphragmatic endometriosis is rare. We present a case of endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy. A 59-year-old primigravida woman who had undergone abdominal hysterectomy for adenomyosis at the age of 47 years was referred to our hospital for investigation of a tumor on the surface of the liver. An integrated positron emission tomography-computed tomography scan revealed a 3-cm nodule on the surface of the liver with abnormal fluorine-18-deoxyglucose accumulation. Partial resection of the diaphragm and liver was performed. Histopathological examination revealed an endometrioid carcinoma arising from diaphragmatic endometriosis. We additionally performed laparoscopic bilateral salpingo-oophorectomy and partial omentectomy. The resected tissues revealed no malignancy. Adjuvant chemotherapy with paclitaxel and carboplatin was administered. In cases of diaphragmatic tumors, endometriosis and its associated malignancies should be considered. Laparoscopic surgery is effective in patients with such conditions.

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.

Primary osteosarcoma of the uterine corpus: A case report.

Pure osteosarcoma arising from the uterus is extremely rare. Only 15 cases of this type of cancer have been reported to date. Most patients showed local or lung metastasis early after surgery and died within a year of treatment initiation, regardless of multimodality therapy, indicating that this tumor is aggressive with a poor prognosis. Herein, we report the first clinical experience treated with a combination of docetaxel and gemcitabine for local and lung metastasis from primary osteosarcoma of the uterus. Although the disease was considered stable after three cycles of treatment, new metastatic lesions appeared in the lungs after six cycles. The patient was asymptomatic for 13 months; however, she died two months after symptom recurrence. Our case demonstrates that a combined regimen of docetaxel and gemcitabine may be a sound therapeutic option to control primary osteosarcoma of the uterus.

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.