Chance diagnosis of mixed gonadal dysgenesis in an adult case of malignant gonadal germ cell tumor: a case report.

BACKGROUND: Mixed gonadal dysgenesis (MGD) is a subtype of the disorders of sex development (DSD) associated with sex chromosome abnormalities characterized by abnormal external genitalia, short stature, and primary amenorrhea. This disease is generally diagnosed from the neonatal stage to early childhood, and by puberty at the latest. Cases that are phenotypically female or those with ambiguous genitalia experience a high risk of gonadal tumor formation. As tumor risk is known to increase with age, prophylactic bilateral gonadectomy is recommended following early diagnosis. CASE PRESENTATION: Here we report a case of an adult Japanese woman diagnosed with MGD during treatment for a giant pelvic tumor. The patient initially visited a gynecology clinic during puberty for primary amenorrhea, at which time an abnormality was found with the external genitalia. However, a diagnosis of MGD was not made at this time, resulting in the development of a malignant gonadal germ cell tumor in adulthood. CONCLUSIONS: For early diagnosis of MGD and the prevention of gonadal tumor formation, it is essential that gynecologists fully understand MGD and other DSD.

Vaginal cancer diagnosed during pregnancy presenting a therapeutic dilemma: A case report.

BACKGROUND: Vaginal cancer is rare, accounting for only about 2% of all cancers of the female reproductive organs, and it is a disease that is rarely encountered in routine clinical practice. Vaginal cancer is mainly treated with radiation therapy or concurrent chemoradiotherapy (CCRT). However, in stage I-II cases, when the lesion is confined to the upper third of the vagina, surgical treatment may include total hysterectomy and vaginal resection with an adequate resection margin. We report a case of stage I vaginal cancer diagnosed at 13 weeks of gestation. There are very few reports on the diagnosis and treatment of vaginal cancer during pregnancy, and it was difficult to decide on a treatment plan; therefore, we report on the course of treatment followed for this patient. CASE PRESENTATION: The patient was a 38-year-old woman with a history of two pregnancies and zero births. The patient had thrombocytopenia and was diagnosed highly suspicious of myelodysplastic syndrome by bone marrow biopsy, and her platelet count remained at approximately 50,000/µL. At the time of the 11-week gestational checkup, a 4-cm pedunculated tumor was found in the right posterior vaginal fornix. Transvaginal tumor resection was performed at 13 weeks of gestation, and the patient was diagnosed with stage I vaginal cancer (squamous cell carcinoma). Because vaginal cancer was confined to the posterior vaginal wall fornix, radical surgery after abortion was suggested as a treatment plan. However, the patient strongly desired to continue the pregnancy, so the policy was to continue the pregnancy and follow-up. However, at 22 weeks of gestation, a recurrent tumor was found in the posterior fornix of the vagina. The lesion had invaded the paravaginal tissue, making radical surgery impossible. At 26 weeks of gestation, an elective cesarean section was performed because of giving priority to early therapeutic intervention to her recurrent vaginal cancer, and it was decided that CCRT with cisplatin would be administered from postpartum day 1. However, because of thrombocytopenia, chemotherapy could not be co-administered, and the treatment was completed with radiation alone. The therapeutic effect was partial response, but 13 weeks after the end of radiation therapy, we observed regrowth of the recurrent tumor and emergence of pelvic lymph node metastasis. The patient received palliative treatment but died 8 months after delivery due to a generally deteriorating condition, sepsis, and disseminated intravascular coagulation. CONCLUSIONS: In cases of malignant tumors associated with pregnancy, treatment policies should consider the perinatal prognosis at the same time as treatment for malignant tumors, and gynecologic oncologists, obstetricians, and neonatologists, from the standpoint of their respective specialties, should thoroughly discuss the "curative effect of treatment for malignant tumors" and the "prognosis of the child after birth" and consider the treatment plan for each case.

Undifferentiated Carcinoma After Laparoscopic Surgery for a Cystic Ovarian Tumour: A Case Study.

Background: Laparoscopic surgery for malignant tumours occasionally results in recurrence at the trocar insertion site or port-site metastasis (PSM). We report on a patient requiring emergency laparoscopic surgery for an ovarian tumour with a review of the relevant literature. Case Report: A 42-year-old woman developed sudden abdominal pain and underwent laparoscopic right adnexectomy because of a suspected ovarian cystic tumour rupture. The postoperative histological diagnosis was a mucinous borderline ovarian tumour; however, an undifferentiated carcinoma was detected at the port site eight months after the initial surgery. The histopathological diagnosis of the abdominal wall tumour at the port site differed from intraoperative pathological findings, which was contradictory to PSM definition. Postoperatively, she received three systemic chemotherapy courses but died consequent to tumour metastasis. Conclusion: This is an atypical PSM case with histopathological differences from the initial tumour. Careful preoperative diagnosis and intraoperative attention are essential in such cases.

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo.

Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells-referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute "artificial" ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

Ovarian mature cystic teratoma with fistula formation into the rectum: a case report.

BACKGROUND: While ovarian mature cystic teratomas are benign ovarian germ-cell tumors and the most common type of all ovarian tumors, the formation of fistulas into surrounding organs such as the bladder and the intestinal tract is extremely rare. This report documents a case of ovarian mature cystic teratoma with a rectal fistula, thought to be caused by local inflammation. CASE DESCRIPTION: A pelvic mass was diagnosed as an ovarian mature cystic teratoma of approximately 10 cm in diameter on transvaginal ultrasound and magnetic resonance examinations. Endoscopic examination of the lower gastrointestinal tract to investigate diarrhea revealed an ulcerative lesion with hair in the rectal wall adjacent to the ovarian cyst, and formation of a fistula from the ovarian teratoma into the rectum was suspected. Laparotomy revealed extensive inflammatory adhesions between a left ovarian tumor and the rectum. Left salpingo-oophorectomy and upper anterior resection of the rectum were performed. The final pathological diagnosis was ovarian mature cystic teratoma with no malignant findings, together with severe rectal inflammation and fistula formation with no structural disorders such as diverticulitis of the colon or malignant signs. DISCUSSION: The formation of fistulas and invasion into the neighboring organs are extremely rare complications for ovarian mature cystic teratomas. The invasion of malignant cells into neighboring organs due to malignant transformation of the tumor is reported as the cause of fistula formation into the neighboring organs. A review of 17 cases including the present case revealed that fistula formation due to malignant transformation comprised only 4 cases (23.5 %), with inflammation as the actual cause in the majority of cases (13 cases, 76.5 %). CONCLUSION: Although malignancy is the first consideration when fistula formation is observed between ovarian tumors and surrounding organs, in mature cystic teratoma, local inflammation is more likely than malignant transformation.

Highly improved accuracy of the revised PREoperative sarcoma score (rPRESS) in the decision of performing surgery for patients presenting with a uterine mass.

In 2014, we published an article titled "Novel uterine sarcoma preoperative diagnosis score predicts the need for surgery in patients presenting with a uterine mass" on the preoperative diagnosis of uterine sarcoma, in the SpringerPlus (Nagai et al. in SpringerPlus 2014, 3:678. doi:10.1186/2193-1801-3-678). Subsequently, we received several suggestions from readers, which were used to modify the statistical analysis methods and create a more precise preoperative diagnostic scoring system, which we present here as a supplemental report. The subjects were 63 patients who underwent surgical therapy for suspected uterine sarcoma (sarcoma group: 15 patients, benign group: 48 patients). Logistic regression analysis using the exact method was performed considering the subjects' preoperative age, serum lactate dehydrogenase levels, magnetic resonance imaging findings, and endometrial cytology findings. We then used parameter estimates obtained from this analysis to revise the PREoperative Sarcoma Score (PRESS). The revised PRESS (rPRESS) has a maximum score of 10 points and an optimal cut-off value of 4 points, as derived from a receiver operating characteristic curve. Using this, the accuracy, positive predictive value, and negative predictive value were 93.7, 92.3, and 94.0 %, respectively. The diagnostic precision of the rPRESS is better than that of the original PRESS.

Concomitant sentinel lymph node biopsy leading to abbreviated systematic lymphadenectomy in a patient with primary malignant melanoma of the vagina.

INTRODUCTION: Primary malignant melanoma of the vagina is an extremely rare disease affecting 3% of patients with malignant vaginal tumors. It is rare compared to primary malignant melanoma of the skin and its prognosis is unfavorable even in patients with Stage I disease. Here, we report a case of primary malignant melanoma of the vagina and discuss our experience with regard to previously published literature. CASE DESCRIPTION: The patient was a 59-year-old female with 2 prior pregnancies and child births. She was examined by a local doctor for swelling of the genitalia, and a 1.8 × 1.0 cm large tumor was detected on the left side of the vaginal wall. A biopsy indicated leiomyosarcoma, and she was referred to our hospital. The tumor was resected, and histopathology of the resected sample confirmed the diagnosis of malignant melanoma based on a positive surgical margin. Additional courses of treatment included left inguinal sentinel lymph node biopsy using an isotope and extended vaginectomy. Although the sentinel node was negative, we performed a modified radical hysterectomy and left vaginectomy during the third operation because the surgical margin was positive. We could not confirm whether the lesion in the extracted sample was malignant, and the final diagnosis was primary malignant melanoma of the vagina T4bN0M0 Stage IIc (UICC 2009). Postoperative adjuvant therapy consisted of 6 cycles of DAV-Feron therapy (dacarbazine, ACNU, vincristine, IFN- ß). After 5 months of postoperative adjuvant therapy, a 2 cm single lung metastasis was detected in the lower left lung. We performed a laparoscopic lower left lobectomy and are planning additional chemotherapy. DISCUSSION AND EVALUATION: Currently, surgical resection has the highest probability of improving the prognosis of patients when used as initial treatment for Stage I disease. By combining treatment with sentinel lymph node biopsy, we were able to accurately determine the stage of disease and thus avoid systematic lymph node dissection and further surgical treatments. CONCLUSION: Malignant melanoma of the vagina is very rare tumor so it is necessary to requires the integration of further cases.

Novel uterine sarcoma preoperative diagnosis score predicts the need for surgery in patients presenting with a uterine mass.

Preoperative diagnosis of uterine sarcoma is very difficult, and currently, its diagnostic accuracy is not satisfactory. It is therefore important to perform surgery and establish the pathological diagnosis if the clinical findings and various examination findings indicate possible uterine sarcoma. We investigated the accuracy of the combination of various types of predictors of uterine sarcoma and the novel PREoperative Sarcoma Score (PRESS) for avoiding unnecessary surgery while diagnosing uterine sarcoma. We retrospectively analyzed the clinical findings, blood tests, imaging studies (ultrasonography and magnetic resonance imaging [MRI]), and endometrial cytology of 63 suspected uterine sarcoma cases that underwent surgery from 2006 to 2012. These cases were also scored retrospectively using PRESS. We analyzed the number of unnecessary surgeries that could be avoided using PRESS. Of 63 cases, 15 were diagnosed with uterine sarcoma (sarcoma group), and 48 had benign tumors (benign group). Univariate analysis indicated age, serum lactate dehydrogenase (LDH) values, and MRI and endometrial cytology findings as significant predictors of uterine sarcoma in both groups. In contrast, multivariable analysis identified only age, serum LDH value, and endometrial cytology findings as significant predictors. Accordingly, the latter were placed as 2 points, and the remaining MRI finding as 1 point. The accuracy rate of prediction was 84.1%, and the positive and negative predictive values were 63.2% and 93.2% respectively when the PRESS was interpreted as "positive" when it was 3 points or higher. Using multiple predictors for the preoperative diagnosis of uterine sarcoma, our proposed PRESS score is beneficial in the clinical setting while making treatment decisions in suspected uterine sarcoma cases as well as avoiding unnecessary surgery.

Implantation of capillary structure engineered by optical lithography improves hind limb ischemia in mice.

We previously reported a novel optical lithographic technique for the construction of a capillary network consisting of endothelial cells. To investigate the feasibility of clinical application in the treatment of ischemic diseases, capillary structures were formed on scaffolds made from amniotic membrane (AM) and implanted into mice. The capillary network remained in place for at least 5 days and blood perfusion through the implanted capillaries was histologically detected in an ear flap model. Moreover, blood was observed flowing through the capillary network implanted in abdominal subcutaneous tissue of mice at 5 days after insertion. Implantation of the AM capillary structure into the ischemic hind limbs of mice significantly increased reperfusion compared with controls (AM only). Blood flow was restored in the ischemic limbs to the level of corresponding nonischemic limbs as early as 9 days after surgical implantation. The treatment reversed ischemic symptoms, and ambulatory impairment was significantly improved. Thus, the implantation of a capillary network engineered ex vivo could have therapeutic potential for ischemic diseases.

A comparison of the tube forming potentials of early and late endothelial progenitor cells.

The identification of circulating endothelial progenitor cells (EPCs) has revolutionized approaches to cell-based therapy for injured and ischemic tissues. However, the mechanisms by which EPCs promote the formation of new vessels remain unclear. In this study, we obtained early EPCs from human peripheral blood and late EPCs from umbilical cord blood. Human umbilical vascular endothelial cells (HUVECs) were also used. Cells were evaluated for their tube-forming potential using our novel in vitro assay system. Cells were seeded linearly along a 60 mum wide path generated by photolithographic methods. After cells had established a linear pattern on the substrate, they were transferred onto Matrigel. Late EPCs formed tubular structures similar to those of HUVECs, whereas early EPCs randomly migrated and failed to form tubular structures. Moreover, late EPCs participate in tubule formation with HUVECs. Interestingly, late EPCs in Matrigel migrated toward pre-existing tubular structures constructed by HUVECs, after which they were incorporated into the tubules. In contrast, early EPCs promote sprouting of HUVECs from tubular structures. The phenomena were also observed in the in vivo model. These observations suggest that early EPCs cause the disorganization of pre-existing vessels, whereas late EPCs constitute and orchestrate vascular tube formation.