Identical twins with mature cystic teratomas treated with laparoscopic surgery: Two case reports.

Mature cystic teratomas are the most common among all ovarian neoplasms, representing 30-40% of the cases. However, to the best of our knowledge, there have been only two reports of mature cystic teratomas occurring in identical twins to date. We herein report a case of identical twins with mature cystic teratomas who were treated with laparoscopic surgery. A 32-year-old woman was referred to our hospital due to a tumor in the right ovary. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Two years later, the identical twin of the abovementioned patient was referred to our hospital also due to a right ovarian tumor. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Therefore, for early diagnosis, it may be important to consider the possibility of mature cystic teratoma in the identical twin of a patient, even in the absence of symptoms.

Prognostic impact of primary tumor SUVmax on preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography in endometrial cancer and uterine carcinosarcoma.

The objective of the present study was to investigate the usefulness of the maximum standardized uptake value (SUVmax) of the primary tumor on preoperative 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) as a prognostic indicator in patients with endometrial neoplasms. A total of 75 patients with endometrial cancer or uterine carcinosarcoma who underwent surgical treatment were included in the present study. All patients underwent preoperative PET/CT, and the correlation between the SUVmax of the primary tumor and clinical outcomes was analyzed. The SUVmax was significantly higher in patients with stage II/III disease, a histology of grade 3 endometrioid adenocarcinoma and carcinosarcoma, a positive lymph node (LN) status, positive lymph-vascular space involvement (LVSI), and deep (≥1/2) myometrial invasion. Receiver operating characteristic curve analysis revealed that the optimal cut-off values of SUVmax for predicting a positive LN, LVSI and deep myometrial invasion were 7.49, 6.45 and 6.45, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with those of patients with a low SUVmax using the cut-off value of 7.30. However, no significant difference was observed in the OS or PFS between the high and low SUVmax groups when analyzed in carcinosarcoma patients alone. Finally, multivariate analyses demonstrated that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in 55 endometrioid adenocarcinoma patients; however, not in all patients, including those with carcinosarcoma. The present findings demonstrated that the SUVmax of the primary tumor may be a useful biomarker for predicting clinical outcomes of patients with endometrial cancer, although its prognostic impact appears to be limited in patients with uterine carcinosarcoma.

Primary tumor SUVmax on preoperative FDG-PET/CT is a prognostic indicator in stage IA2-IIB cervical cancer patients treated with radical hysterectomy.

The objective of the present study was to investigate the prognostic value of 18F-fluoro-2-deoxy-D-glucose (FDG) uptake by primary tumors on positron emission tomography/computed tomography (PET/CT) in surgically resectable cervical cancer. A total of 59 patients with stage IA2-IIB cervical cancer who underwent preoperative FDG-PET/CT, followed by radical hysterectomy and lymphadenectomy, were included in the study. The maximum standardized uptake value (SUVmax) of the primary tumor was measured, and the association between the SUVmax and clinicopathological factors or patient outcomes was analyzed. The SUVmax was significantly higher in patients with an advanced stage, lymph node metastasis, lymph-vascular space involvement and large tumors. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with patients with a low SUVmax, using an optimal cut-off value of 7.36 for OS and 5.59 for PFS obtained from receiver operating characteristic curve analysis. Similarly, OS and PFS in patients with a high SUVmax were significantly lower in 39 patients with stage IB using a cut-off value of 7.90 and 6.69 for OS and PFS, respectively. Finally, multivariate analyses showed that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in all patients and those with stage IB alone. These findings demonstrated that a high SUVmax on preoperative PET/CT was correlated with unfavorable clinical outcomes in patients receiving radical hysterectomy, suggesting that the SUVmax of the primary tumor may be a prognostic indicator for surgically-treated, early-stage invasive cervical cancer.

Clinicopathologic Factors of Cervical Adenocarcinoma Stages IB to IIB.

OBJECTIVE: The aim of this study was to clarify the clinicopathologic factors of stages IB to IIB cervical adenocarcinoma. METHODS: Several clinicopathologic factors were compared between 35 patients who underwent radical hysterectomy and pelvic lymphadenectomy due to cervical adenocarcinoma stages IB to IIB and 77 patients with squamous cell carcinoma (SCC). RESULTS: In patients with adenocarcinoma, univariate analysis demonstrated that International Federation of Gynecology and Obstetrics stage, tumor size, and lymphovascular space invasion were significantly associated with progression-free survival (PFS), whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with overall survival (OS). However, multivariate analysis revealed that FIGO stage was the only significant factor for PFS in patients with adenocarcinoma. In patients with SCC, univariate analysis demonstrated that FIGO stage and lymph node metastasis were significantly associated with PFS, whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with OS. Multivariate analysis revealed that lymph node metastasis was the only significant factor for PFS and OS in patients with SCC. In 26 patients who were positive for high-risk human papillomavirus (HPV), including both adenocarcinoma and SCC patients, univariate and multivariate analyses revealed that HPV18 was significantly associated with poorer PFS compared with non-HPV18. There was a significant difference in distribution of HPV genotype between adenocarcinoma and SCC. CONCLUSIONS: Careful treatment may be necessary for the patients with lymphovascular space invasion in early-stage cervical adenocarcinoma. The presence of HPV18 may have an influence on the prognosis of early-stage cervical carcinoma.

AG490, a Jak2 inhibitor, suppressed the progression of murine ovarian cancer.

Ovarian cancer is the major cause of cancer death among female genital malignancies, and requires developing novel therapeutic measures. Immune escape and acquisition of tolerance by tumor cells are essential for cancer growth and progression. An immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) overexpression in tumors is essential for host immune tolerance. Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) pathway is involved in various kinds of tumor biology. Thus, we examined the effects of STAT1 inhibition by AG490 (a JAK2 inhibitor) on ovarian cancer progression in mice. In vitro study, IFN-γ treatment up-regulated Ido mRNA expression with STAT1 activation in OV2944-HM-1 cells, whereas AG490 treatment significantly inhibited this effect with the suppression of STAT1 phosphorylation. In vivo model, OV2944-HM-1 cells were intraperitoneally/subcutaneously transplanted into syngeneic immunocompetent female mice. AG490 treatment significantly suppressed subcutaneous tumor growth, compared with control. Consistently, in mice intraperitoneally inoculated HM-1 cells, the same treatment significantly improved survival rate with the reduced number of intraperitoneal tumors. Actually, intratumoral IDO expression was significantly suppressed with the reduction of STAT1 activation in AG490-treated mice. Moreover, in tumor microenvironment of mice treated with AG490, the accumulation of anti-tumor leukocytes such as CD8(+) T-cells, M1 macrophages, and NK cells was apparently exaggerated with the reciprocal reduction of regulatory T cells. Furthermore, intratumoral expression of anti-tumor cytokines such as IL-1α, IL-1ß and IL-12 expression was significantly enhanced in mice treated with AG490. Collectively, JAK/STAT signal pathways may be good molecular target for immunotherapy of ovarian cancer.

Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months.

Acute fatty liver of pregnancy associated with fetal mitochondrial trifunctional protein deficiency.

Acute fatty liver of pregnancy (AFLP) is a devastating disorder of the maternal liver in the third trimester. Recent studies have demonstrated an association between AFLP and fetal fatty acid oxidation disorders. Here, we report a case of AFLP caused by fetal mitochondrial trifunctional protein (TFP) deficiency. A 21-year-old parous woman presented with nausea, genital bleeding and abdominal pain at 33 weeks of gestation. Laboratory data revealed hepatic failure and disseminated intravascular coagulopathy. The patient underwent emergency cesarean section and was diagnosed with AFLP from the clinical characteristics. She was successfully treated with frequent plasma exchange. The newborn presented severe heart failure and died on the 39th day after birth. Tandem mass spectrometry indicated long-chain fatty acid oxidation disorder. Gene analysis demonstrated homozygous mutation in exon 13 of HADHB, the gene responsible for mitochondrial TFP deficiency. The parents carried a heterozygous mutation at the same location in HADHB.

Ovarian steroid cell tumor, not otherwise specified, producing testosterone.

Steroid cell tumor, not otherwise specified, is a rare type of ovarian sex cord-stromal tumor with malignant potential. Some of these tumors produce testosterone. We describe a case of steroid cell tumor of the ovary associated with virilization. A 23-year-old nulliparous woman was found to have an ovarian tumor when she visited her primary doctor for virilization and oligomenorrhea. Magnetic resonance imaging revealed a solid left ovarian tumor 40 mm in size. Her laboratory data revealed elevated testosterone with normal levels of gonadotropins, estradiol, dehydroepiandrosterone sulfate and cortisol. She underwent left adnexectomy. On histopathologic and immunohistochemical analyses, the tumor was diagnosed as steroid cell tumor, not otherwise specified, without malignant behavior. After removal of the tumor, serum testosterone level decreased, and there have been no signs of recurrence.

Adverse perinatal and neonatal outcomes in patients with chronic abruption-oligohydramnios sequence.

AIM: Chronic abruption-oligohydramnios sequence (CAOS) is a clinical condition with lasting vaginal bleeding and oligohydramnios because of chronic placental abruption, which seems to cause preterm labor and neonatal chronic lung disease (CLD). This prompted us to explore the correlation between perinatal/neonatal outcomes and CAOS. METHODS: Patients with suspected risk of abortion with recurrent vaginal bleeding were divided into CAOS and non-CAOS groups, and we compared the perinatal/neonatal outcomes between these two groups. To examine the impact of chorioamnionitis (CAM) on the prognosis of CAOS, we also compared outcomes between the CAOS group and gestational-age-matched preterm labor due to CAM (CAM group). RESULTS: In the CAOS and non-CAOS groups, initial vaginal bleeding was seen at the first trimester. However, its duration was significantly longer in the CAOS group. Additionally, neonatal birthweight was lower, and small-for-gestational-age (SGA) incidence was higher in the CAOS group. CLD was observed in most infants from CAOS patients. In the comparison between CAOS and CAM groups, birthweight was lower and SGA incidence was higher in the CAOS group. Moreover, CLD incidence and neonatal mortality were significantly higher, despite the lower incidence of severe CAM in the CAOS group. Finally, multivariate analysis demonstrated that duration of bleeding was a significant predictive factor for CAOS. CONCLUSIONS: Our observations demonstrated that patients with CAOS were a high-risk group for poor perinatal/neonatal outcomes. Moreover, episodes of recurrent and prolonged uterine bleeding were predictive factors for CAOS. During the first trimester, prolonged bleeding is an important sign as one symptom of CAOS.

Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. Our prior study showed that tumoral IDO overexpression is involved in disease progression and impaired patient survival in human ovarian cancer, although its mechanism remains unclear. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. Indoleamine 2,3-dioxygenase cDNA was transfected into the murine ovarian carcinoma cell line OV2944-HM-1, establishing stable clones of IDO-overexpressing cells (HM-1-IDO). Then HM-1-IDO or control vector-transfected cells (HM-1-mock) were i.p. transplanted into syngeneic immunocompetent mice. The HM-1-IDO-transplanted mice showed significantly shortened survival compared with HM-1-mock-transplanted (control) mice. On days 11 and 14 following transplantation, the tumor weight of peritoneal dissemination and ascites volume were significantly increased in HM-1-IDO-transplanted mice compared with those of control mice. This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-ß and interleukin-10 in ascites. Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-ß secretion. These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity. Therefore, IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.

Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer.

OBJECTIVE: The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. RESULTS: Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.

Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells.

Using seven monoclonal SN38-resistant subclones established from ME180 human cervical squamous cell carcinoma cells, we examined the demethylation effects of 5-aza-2'-deoxycytidine (5-aza-CdR) on the SN38-sensitivity of the cells as well as the expression of death-associated protein kinase (DAPK) in the SN38-resistant cells. The DAPK expression levels were evaluated among parent ME180 cells, SN38-resistant ME180 cells and cisplatin-resistant ME180 cells by methylation-specific DAPK-PCR, quantitative RT-PCR and western blot analysis. The SN38-resistant cells co-treated with SN38 and 5-aza-CdR strongly exhibited enhanced SN38-sensitivities resembling those found in the parent cells. In the SN38-resistant subclones, no relationships were found between the restored SN38 sensitivity and hypermethylation of the DAPK promoter, DAPK mRNA expression, DAPK protein expression and induction of DAPK protein after 5-aza-CdR treatment, unlike the strong suppression of 5-aza-CdR-induced DAPK protein expression in the cisplatin-resistant subclones. These findings indicate that reversibly methylated molecules, but not DAPK, may regulate SN38 resistance, and that demethylating agents can be strong sensitizing anticancer chemotherapeutic drugs for SN38-resistant cancers.