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Ovarian tumours in children and adolescents are rare diseases. Although the majority of tumours are benign, the diagnosis and management present various challenges that require a wide range of expertise. The multidisciplinary team ensures not only accurate diagnosis and correct and minimally invasive management, but also minimal psychological impact and the preservation of fertility. This article outlines the multidisciplinary team approach to ovarian masses in children and adolescents. The team includes paediatric oncologists, gynaecological surgeons, pathologists, radiologists, fertility experts, geneticists and psycho-social services., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy"., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma tumor affecting mainly young adult males. It rarely has an ovarian involvement., Case: A 29-year-old woman presented to her gynecologist for amenorrhoea. The laboratory results demonstrated a menopausal status and the ultrasound revealed a large mass of the right ovary. The right ovary was completely removed by laparoscopy. Pathology, cytology and immunochemistry revealed a DSRCT. In January 2009 a left salpingo-oophorectomy and a right salpingectomy were performed via laparoscopy. After 35 months from diagnosis there was no clinical evidence of disease recurrence., Conclusion: DSRCT is a rare ovarian tumor in adolescence with a general poor outcome. Every ovarian mass regardless of age should be approached with caution.

Vascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarray of clinical samples (N=86), tumour cell immunohistochemical staining of AKT/mTOR downstream targets, pS6 and p4E-BP1, together with tumour cell staining of VEGF-A and pVEGFR2 were semi-quantified. A correlation was found between the marker for VEGFR2 activation (pVEGFR2) and a downstream target of AKT/mTOR signalling (pS6) (R=0.29; P=0.002). Additional gene expression analysis in an independent cDNA microarray dataset (N=24) showed a negative correlation (R=-0.73, P<0.0001) between the RPS6 and the VEGFR2 gene, which is consistent as the gene expression and phosphorylation of S6 is inversely regulated. An activated tumour cell VEGFR2/AKT/mTOR pathway was associated with increased incidence of ascites (chi(2), P=0.002) and reduced overall survival of cisplatin-taxane-based patients with serous histology (N=32, log-rank test, P=0.04). These data propose that VEGF-A signalling acts on tumour cells as a stimulator of the AKT/mTOR pathway. Although VEGF-A inhibitors are classified as anti-angiogenic drugs, these data suggest that the working mechanism has an important additional modality of targeting the tumour cells directly.

Optimal cytoreductive surgery is essential in the treatment of ovarian cancer. Unfortunately many patients do not receive optimal treatment, despite numerous guidelines. The survival of patients receiving optimal surgery is twice the survival of patients receiving suboptimal surgery. There is no difference in complication rates between optimal and non-optimal surgery. An estimated 10% of the operated patients will have some kind of treatment-related morbidity. One of the most serious complications is acute abdomen in the postoperative period. Despite a long list of life-threatening situations there is sometimes also the unexpected complication, such as forgotten pain medication.

Purpose: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865., Experimental Design: Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC)., Results: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors., Conclusion: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.

Small cell carcinoma of the ovary is a rare type of ovarian carcinoma with a poor prognosis. Two types should be distinguished: the hypercalcemic type and the pulmonary type. We report the case history of a 54-year-old woman with both a Stage IIIC small cell carcinoma, pulmonary type and a well-differentiated endometrioid adenocarcinoma of the left ovary in combination with a Brenner tumor in the right ovary. A review of the literature on small cell carcinoma of the ovary is given and the findings of our patient are brought into perspective in terms of both histopathogenesis and treatment outcome.

Malignant mixed müllerian tumour (MMMT) of the ovary is a rare and aggressive tumour with a poor prognosis. We present a case of a 57-year-old woman with a large pelvic mass, omental cake, ascites and pleural effusions, clinically highly suspect of an ovarian neoplasm. Paracentesis and ultrasound-guided biopsy of the ovary were negative for malignant disease. Therefore a CT-guided true cut biopsy was performed. The latter gave a histopathologic diagnosis of an endometrioid adenocarcinoma of the ovary. However after cytoreductive surgery anatomopathologic examination revealed a malignant mixed müllerian tumour of the ovary with heterologous differentiation. Apparently only one of the two components was found in the puncture. Adjuvant chemotherapy, active against the sarcomatous and the carcinomatous component, was given. At present the patient is well and disease free 35 months after the initial diagnosis. Cytological examination of ascites may be negative in the presence of malignant disease. If a tumour consists of two components, puncture can miss one, which may lead to undertreatment. Punctures should be discouraged as a diagnostic tool in patients in whom an ovarian malignancy is suspected.

An ovarian mass in a premenopausal patient has many differential diagnoses. In young patients the mass is most likely to be benign. Sometimes patients with an abdominal mass will present as acute abdomen. If the patients have an IUD and a positive test for serum HCG, an ectopic ovarian pregnancy has to be suspected. However one also has to take into consideration the possibility of an ovarian germ cell tumour. The latter occurs in young patients, presents as an ovarian mass and can produce HCG. The preoperative and even intraoperative diagnosis are difficult. In these cases where there is a suspected ovarian mass and no clear diagnosis a laparoscopic approach should be considered. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. The approach and treatment modalities of an ovarian pregnancy are discussed.

Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neo-adjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. In patients with an estimated total metastatic tumor load of >100 g, the presence of at least two of the following relative indications for neo-adjuvant chemotherapy are considered to be necessary: 1) uncountable (>100) peritoneal metastases, 2) estimated metastatic tumor load of >1000 g, 3) presence of large (>10 g) peritoneal metastatic plaques, 4) large volume ascites, and 5) World Health Organization (WHO) status II or III. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). The strategy of neo-adjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC 55971 trial is currently addressing this issue. We will review the studies on primary chemotherapy, interval debulking surgery, and the indications for primary chemotherapy followed by interval debulking surgery, and ongoing trials., (Copyright 2000 Wiley-Liss, Inc.)

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Since 1989, we have been treating advanced epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary cytoreductive surgery in approximately half of the patients with stage III-IV disease. Selection of neoadjuvant chemotherapy was based on disease-related characteristics (eg, metastatic tumor load, stage of disease, performance status). Since 1993, open laparoscopy also has been used to aid in evaluating operability. A retrospective analysis of 338 patients was conducted to compare outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those observed during 1980 to 1988, when all patients underwent primary cytoreductive surgery. Crude 3-year survival rates were higher and postoperative mortality rates were lower during the second time period compared with the first. Overall, the results suggest that neoadjuvant chemotherapy results in survival rates in selected patients with advanced ovarian cancer that are comparable with those associated with primary cytoreductive surgery. Patients with stage IV disease, total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped peritoneal metastases, and/or a poor performance status are probably the best candidates for this alternative approach. A prospective randomized study of neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.

The occurrence of disseminated tumors of the appendix is a rare event. Usually appendix tumors are very small, located on the inside of the appendix, and can be pathologically diagnosed. Adenocarcinoid is an uncommon variant of carcinoid tumors that usually arises in the appendix. This report describes a case of a primary adenocarcinoid of the appendix in a patient who was preoperatively diagnosed to have uterus myomatosus but was intraoperatively found to instead have disseminated ovarian carcinoma. This case demonstrates that the clinical picture can be misleading, and that surgeons therefore always have to wait for the final pathological report before making a final diagnosis.

Objective: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer., Study Design: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics., Results: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients., Conclusions: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer.

Objective: This study was aimed at comparison of neoadjuvant chemotherapy with primary debulking surgery in advanced ovarian carcinoma., Methods: Retrospective analysis of 285 patients with advanced ovarian carcinoma treated between 1980 and 1997 was performed., Results: In the period 1980-1988 all patients underwent primary debulking surgery and 82% were cytoreduced to less than 0.5 cm largest residual tumor mass (n = 112). Analysis of this group of patients showed that some subgroups of patients (e.g., Stage IV disease or a total metastatic tumor load of more than 1000 g prior to debulking surgery) had a poor survival despite cytoreduction to no or less than 1 g of total residual tumor load. The complication rate was high especially in the group with unfavorable prognosis (postoperative mortality, 6%). In the period 1989-1997 (n = 173) the patients were surgically evaluated to receive primary chemotherapy (43%) or primary debulking surgery (57%). Prognostic variables were similar for both treatment periods. The actuarial crude survival was higher in the second time period (3-year crude survival of 26% +/- 4. 3 and 42% +/- 4.6 for the first and second time periods, respectively; P = 0.0001). The postoperative mortality was 0% during the second time period. From 1993 on, the decision to give neoadjuvant chemotherapy or to perform primary debulking surgery in patients with clinically obvious metastatic disease was made with the help of an open laparoscopy (n = 77). Median duration of the laparoscopy, blood loss, and hospital stay due to this procedure were 25 min, 10 ml, and 2 days. Primary and interval debulking surgery was performed in 36 and 63% of this subgroup of patients, respectively., Conclusion: In this retrospective analysis over two different time periods, crude survival was higher when treating about half of the patients with advanced ovarian carcinoma with primary chemotherapy instead of primary debulking surgery. The role of neoadjuvant chemotherapy should be evaluated in a prospective randomized study., (Copyright 1998 Academic Press.)

Objective: Our purpose was to evaluate the effectiveness, benefits, and potential side effects of the use of the cavitational ultrasonic surgical aspirator for cytoreduction of advanced ovarian cancer., Study Design: Forty patients with stage IIC to IV ovarian carcinoma were randomized to undergo ultraradical cytoreductive surgery with (group 1, 20 patients) or without (group 2, 20 patients) the use of the CUSA 200 cavitational ultrasonic surgical aspirator (Valleylab, Boulder, Colo). Preoperative and postoperative information and follow-up data were collected prospectively and compared between both groups., Results: The amount of residual tumor after debulking surgery, the duration of the operation, and the rate of perioperative complications were comparable in both study groups. The amount of perioperative blood loss was significantly lower (1450 ml vs 1650 ml, p=0.02) in group 1. These patients had less morbidity (p<0.05), and could be discharged from the hospital significantly sooner (14 days vs 16 days, p=0.031). CA 125 levels 1 and 2 months after surgery were significantly lower in the group with cavitational ultrasonic surgical aspirator (p<0.01 and p<0.01, respectively), suggesting more successful cytoreduction. However, this is not reflected in a better disease-free or overall survival., Conclusion: Cavitational ultrasonic surgical aspirator-assisted cytoreductive surgery of advanced ovarian carcinoma is more effective in eradicating disease, reduces morbidity, and is cost beneficial.