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Ovarian cancer is a major cause of morbidity and mortality in females. Due to the unremarkable symptoms associated with early ovarian cancer, many patients are already in the advanced stages at first diagnosis. Recent studies have shown that the lymph node ratio (LNR) has a certain value in predicting the prognosis of patients with ovarian cancer. However, preoperative chemotherapy may lead to changes in the LNR, and thus, the predictive value of the LNR in such patients is unclear. Therefore, this study examined the predictive value of the LNR in ovarian cancer patients undergoing preoperative chemotherapy.A total of 208 patients with stage IIIC ovarian cancer, who were treated in the Fourth Clinical Medical College of Xinxiang Medical University, Xinxiang Central Hospital from January 2014 to January 2016, were recruited for this study. The median LNR was 0.32. Patients with LNR0.32 were defined as the control group and those with LNR ≥0.32 were defined as the observation group. The prognosis of the two groups was compared.The LNR in the observation group was significantly higher than that of the control group (0.63±0.21 vs. 0.19±0.08; P=0.000). Patients in the observation group showed significantly higher postoperative recurrence rates (51.92% vs. 22.12%; P=0.000), greater incidences of postoperative metastasis (43.27% vs. 17.31%; P=0.000), and significantly increased postoperative mortality (36.54% vs. 11.54%; P=0.000) compared to the control group. The survival function showed that the overall survival, recurrence-free survival, and metastasis-free survival were all significantly shorter in the observation group compared to the control group (P=0.000). The receiver operating characteristic curves showed that the LNR had certain diagnostic value for postoperative recurrence [area under the curve (AUC) =0.658; 95% confidence interval (CI): 0.582 to 0.734; P=0.000], postoperative metastasis (AUC =0.640; 95% CI: 0.560 to 0.720; P=0.001), and postoperative mortality (AUC =0.653; 95% CI: 0.569 to 0.737; P=0.001) in patients with stage IIIC ovarian cancer treated with preoperative chemotherapy.The LNR has good prognostic value in patients with locally advanced ovarian cancer treated with preoperative chemotherapy.

Ovarian cancer is the most lethal gynecological malignancy. Because of the lack of specific clinical symptoms, approximately 70% of women diagnosed with the disease have metastases beyond the regional lymph nodes. The most common metastatic sites of ovarian cancer are peritoneum, liver and lung, while brain metastasis that indicates a worse prognosis is rarely seen. This is a case report of a 73-year-old woman who was initially diagnosed with stage IIIC ovarian cancer and developed brain metastasis 10 years later. After surgical treatment and chemotherapy, the quality of life of the patient was significantly improved, and the survival time was prolonged.

Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. There are only a few reports on intertrigo-like eruptions caused by PLD. We describe the first case of severe bullous erythema, including intertrigo-like eruptions with angioedema, induced by PLD in Japan. We present the case of a 53-year-old woman who was diagnosed with stage IIIC ovarian cancer. After receiving three cycles of PLD, the patient developed swelling of the upper lip and painful erythema with blisters and erosions on the axilla, upper back, flank and wrists. The patient was diagnosed with angioedema and severe skin lesions, including intertrigo-like eruptions induced by PLD. Although treatment with oral prednisolone and topical steroids was effective against these eruptions, the administration of PLD was discontinued because of its ineffectiveness against the primary disease. Several risk factors, such as obesity, perspiration and racial differences, may contribute toward a severe manifestation such as that seen in our patient. Moreover, our case was the first accompanied by angioedema. The mechanism of coexistence of intertrigo-like eruptions and angioedema is not clear; further studies are required to clarify the pathological mechanism of intertrigo-like eruptions.

Objectives: In ovarian cancer patients, recurrent malignant ascites reduces quality of life and is associated with a poor prognosis. There is a lack of guidance in the literature regarding the placement of a tunneled peritoneal catheter in this patient population. We evaluated the outcomes of ovarian cancer patients who underwent tunneled peritoneal catheter placement for recurrent malignant ascites. Methods: We queried the institutional interventional radiology records from 5/2009 to 5/2020 for female patients with ovarian cancer who had a tunneled peritoneal catheter placed for malignant ascites. We evaluated patient characteristics, number of paracentesis procedures recorded prior to placement, complications, and the time between placement and death. Descriptive statistics were performed. Results: 30 patients were identified. The mean age was 68 (range, 42-88). 77% of patients were White and the average BMI was 26. 56.7% of patients had stage IIIC ovarian cancer and the 83.3% had papillary serous adenocarcinoma. Patients had a mean of four lines (range, 0-11) of chemotherapy before undergoing tunneled peritoneal catheter placement. The mean number of paracentesis performed prior to peritoneal catheter placement was two (range, 0-6). There were six minor complications (20%), including two catheter-related infections requiring removal and four instances of catheter dysfunction requiring revision. The median time of catheter placement to death was 44 days (range, 3-151). Conclusions: The complication rate of tunneled peritoneal catheter placement is low, as evidenced by no major complications found in this patient population. The short period from catheter placement until patient death suggests that tunneled peritoneal catheters should be pursued earlier in the disease course if patients have symptomatic, recurrent ascites.

// Wenqian Li 1 , Xiaoxue Zhang 1 , Ji Wang 1 , Mengchen Li 1 , Canhui Cao 1 , Jiahong Tan 1 , Ding Ma 1 and Qinglei Gao 1 1 Cancer Biology Research Center (Key Laboratory of The Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of China Correspondence to: Ding Ma, email: dma@tjh.tjmu.edu.cn Qinglei Gao, email: qlgao@tjh.tjmu.edu.cn Keywords: ovarian cancer; CAF; exosomes; TGFβ1; epithelial-mesenchymal transition Received: May 09, 2017 Accepted: August 26, 2017 Published: October 06, 2017 ABSTRACT Cancer-associated fibroblasts (CAF), a major component of the tumor microenvironment, play an important role in interacting with neoplastic cells to promote ovarian cancer progression. Exosomes are nano-sized vesicles that mediate the cross-talk between different cell types. An increasing number of studies have focused on the fact that tumor cell-derived exosomes influence stromal cells. However, the mechanism by which CAF-derived exosomes modulate cancer cells in ovarian cancer remains obscure. To investigate the role of CAF exosomes in ovarian cancer, we examined the exosomal content of paired primary, metastatic and normal fibroblasts from seven stage IIIC ovarian cancer patients by ELISA. We found that in ovarian CAF-derived exosomes, TGFβ1 was upregulated compared to normal omentum fibroblasts (NOF). Exosomes derived from CAF were taken up by ovarian SKOV-3 and CAOV-3 cell lines during co-culture and induced malignant behaviors in cancer cells, including an enhanced migration and invasion ability and the promotion of epithelial-mesenchymal transition (EMT) by activating the SMAD signaling pathway. Our results indicate that the role of TGFβ1 in CAF exosomes triggers ovarian cancer cells into a more aggressive phenotype, suggesting that targeting CAF exosomes could be a potential treatment in ovarian cancer.

Objective. To compare the functional activity of natural killer cells in peripheral blood and ascites from patients with different stages of colorectal and ovarian cancers and benign ovarian tumors. Material and methods. The study included 10 patients with stage IIIC ovarian cancer (FIGO, 2009), 5 patients with benign ovarian tumors (BOTs), and 15 patients with colorectal cancer (T2–4N0–2M0 ). The control group consisted of 5 healthy donors. To evaluate the number and functional activity of NK-cells in peripheral blood and ascites, the FACS Canto II Flow Cytometer was used. Results. In peripheral blood of patients with ovarian and colorectal cancers, the relative number of activated NK-cells capable of secreting granzyme B (GB) (CD56 + CD107a + GB + PF-) was significantly lower and the proportion of degranulated NK-cells (CD56 + CD107a + GB- PF-) was higher than those of healthy donors. Low total NK-cell counts in peripheral blood were a distinctive feature of ovarian cancer patients (p< 0.05). The proportion of activated peripheral blood NK-cells, containing granules of cytolytic enzymes GB and perforin (PF) increased with tumor growth. However, lymph node metastasis in patients with colorectal cancer did not affect the level and activation of NK-cells. The comparative analysis of NK-populations in patients with benign and malignant ovarian tumors revealed that the level of CD56 + cells was significantly higher in tumor ascites compared to peripheral blood. In patients with BTs, the levels of CD56 + CD107a + and activated CD56 + CD107a + GB-PF-degranulated cells was higher in ascites than in blood. In patients with ovarian cancer, the level of degranulated cells was higher in peripheral blood than in malignant ascites. Conclusion. The tumor cells and tumor microenvironment were found to affect the number and the functional activity of NK-cells. The accumulation of free fluid within the peritoneal cavity in patients with both benign and malignant ovarian tumors resulted in significantly decreased levels of NK-cells in peripheral blood and increased levels in ascites. The differences in the functional activity of NK-cells in ascites and peripheral blood of patients with ovarian cancer require further investigation of the lymphocyte receptor status and possibly cytokine-producing function of NK-cells.

Introduction/Background The goal of this video to demonstrate step-by-step paraoartic lymphadenectomy Methodology It is important to recognize the landmarks to open the spaces and mobilize the bowel. It is important to open the space laterally until the ureters and superiorly until left renal vein. In addition, the procedure should be performed systemically to accomplish a complete lymphadenectomy Results In the video a successful para-aortic lymphadenectomy performed for stage IIIC ovarian cancer Conclusion Para-aortic lymphadenectomy needs an expert surgeon with major blood vessels to achieve a successful procedure with minimal or no complications Disclosure Nothing to disclose

Until now, there has been progress in the treatment of ovarian cancer, but ovarian carcinoma is still a cause of high mortality. Various factors have been known to be associated with a poor prognosis, such as the absence of symptoms, lack of an effective screening tool, diagnosis of the disease that was only detected after an advanced stage, high recurrence of disease resistant to chemotherapy. There are more than 70% of cases detected in advanced stage, with long-term survival of only 15-30%; while those detected in early stages, the survival reaches 90%. The recurrence risk of IIIC stage disease is as high as 40% -50%. However, there is a small group of patients who can recover after standard therapy. There is variability in the recurrence-free period and survival, so it is difficult to predict the outcome with certainty. Ovarian cancer patients with the same characteristics can show a different prognosis, related to high molecular heterogeneity of tumor genetics. We report a rare case that is a 56-year-old woman who has experienced a 5-year free disease after complete remission after standard chemotherapy from stage IIIC ovarian cancer. The disease-free period of up to 5 years after therapy may be related to factors that can be predictors of prognosis, such as age at diagnosis, body mass index, physical performance, cancer cell biology, and the success of surgical response and chemotherapy in these patients.

Objective Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis. Methods A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded. Results Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p =.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0months, p =.0097) and overall survival was shorter (median 31.7 vs. 61.3months, p =.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS. Conclusion The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

Despite advances in therapy, ovarian cancer remains the most lethal gynecological malignancy and prognosis has not substantially improved over the past 3 decades. Immunotherapy is a promising new treatment option. However, the immunosuppressive cancer microenvironment must be overcome for immunotherapy to be successful. Here, we present a unique case of spontaneous regression of ovarian carcinoma after septic peritonitis. A 79-year-old woman was diagnosed with stage IIIc ovarian cancer. The omental cake biopsy was complicated by sepsis. Although the patient recovered, her physical condition did not allow further treatment for her ovarian cancer. After 6 months, spontaneous regression of the tumor was observed during surgery. Analysis of the immune infiltrate in the tissues showed a shift from a pro-tumorigenic to an anti-tumorigenic immune response after sepsis. Strong activation of the immune system during sepsis overruled the immunosuppressive tumor microenvironment and allowed for a potent anti-tumor immune response. More understanding of immunological responses in cases with cancer and septic peritonitis might be crucial to identify potential new targets for immunotherapy.

Objective: To evaluate Risk of Malignancy Index (RMI) as a triage tool for ovarian cancer in Dr. Cipto Mangunkusumo Hospital. Method: This is a retrospective study conducted from January 2008-December 2012 in patients diagnosed with ovarian mass. Patients admitted for surgery due to ovarian masses were included to this study. RMI 3 score was calculated based on ultrasonography examination in Dr. Cipto Mangunkusumo Hospital, CA-125 test and menopausal status. Patients without final pathological report and incomplete data were excluded from study. Data were analysed using SPSS 20 to evaluate RMI result and final pathlogical report in benign and malignant case. Result: From 882 patients identified with ovarian masses from cancer registry, only 99 patients aged 17-70 y.o were included in this study. Most of the patients were nully-parity (28.3%), non-menopausal women (60.6%), normal body mass index (40.4%), and with stage IIIC ovarian cancer (33.3%). Ultrasonography examination showed that most of patients had solid mass and ascites (19.2%). Meanwhile, CA-125 showed that patients with

Objective.The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer.Methods.Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions.Results.Cytoreduction to no visible disease (P<0.0001) and complete response to platinum-based chemotherapy (P<0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17±1months) than in those with Stage II1A disease (36±8months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup.Conclusions.Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy.

The report describes a rare case of a patient with a calcified cerebellar metastasis arising from a primary ovarian cancer. The patient was a 33-year-old woman with a long history of stage IIIc ovarian cancer who had undergone transabdominal hysterectomy and bilateral oophorectomy followed by chemotherapy with gemcitabine hydrochloride. Incidentally, computed tomography (CT) revealed a cerebellar tumor with calcification. The size of the tumor gradually increased, and lateral suboccipital craniotomy was performed for gross total removal of the tumor. The histological diagnosis was ovarian mucinous adenocarcinoma. The patient's postoperative course was uneventful, and she was discharged two days after surgery. Brain metastases from ovarian cancer are rare. In the review of metastatic brain tumors arising from a primary ovarian cancer in the Department of Obstetrics and Gynecology at our institution, this phenomenon was noted in only 10 cases (0.24%) of 4,158 patients with ovarian cancer seen at our center over a period of 8 years. Moreover, only three cases of calcified metastatic brain tumor have been reported previously. In conclusion, complete tumor resection may be an acceptable approach for patients with calcified metastatic tumors both for therapeutic considerations and to obtain tissue for confirmation of histopathological diagnosis. Metastatic brain tumors can be calcified, and should be considered within the differential diagnosis of calcified intracranial lesions to avoid any delay in diagnosis or treatment.

Granulocyte-colony stimulating factor (G-CSF)-producing cancer has been reported to occur in various organs. It has an aggressive nature and shows resistance to conventional treatments, however, its clinical features are not well known because of the small number or reported cases. We report G-CSF-producing squamous cell carcinoma arising in malignant-transformed ovarian mature cystic teratoma. An 80-year-old woman underwent suboptimal surgical excision of stage IIIC ovarian cancer. Prior to the treatment, the patient presented severe granulocytosis and elevated serum G-CSF concentration. With the help of histopathological and immunohistochemical studies, we diagnosed this case to be a poorly differentiated squamous cell carcinoma developed in ovarian mature cystic teratoma, which highly expressed G-CSF. During radiation therapy, the patient died from rapid growth of residual tumor and peritoneal dissemination 2 months after surgery. This is the first case of G-CSF-producing squamous cell carcinoma arising in malignant-transformed ovarian mature cystic teratoma, and its prognosis was very poor.

Objective Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy. Methods Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests. Results Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P =0.018). Conclusions Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.

Meningeal dissemination is rare in the clinical course of ovarian carcinoma, and its prognosis is poor. Although it is treated by the intrathecal administration of methotrexate (MTX) and/or total brain irradiation, these treatments are usually ineffective. We report a 58-year-old woman with stage IIIc ovarian cancer who had received nine courses of adjuvant chemotherapy after surgery. But her carbohydrate antigen (CA) 125 serum level had increased further (38.9 U/ml) after five courses of biweekly paclitaxel (Taxol; Bristol-Myers Squibb, Tokyo, Japan; BT) maintenance therapy. Fainting occurred, with a few seconds of unconsciousness, as did severe headaches. However, results of head computed tomography (CT), head magnetic resonance imaging, and electroencephalogram were normal. Lumbar puncture (LP) was performed. The opening pressure was 30 cmH2O or greater. Meningeal dissemination of the ovarian cancer was diagnosed, as adenocarcinoma cells were found by cerebrospinal fluid (CSF) cytology. We started chemotherapy with intrathecal injections of MTX and hydrocortisone acetate. Establishing a diagnosis of carcinomatous meningitis may be difficult. Clinical signs and biological data are not conclusive. In this patient, CSF cytology was very effective in establishing the diagnosis, and the intrathecal administration of MTX and hydrocortisone was very effective.

After observing disparate rates of cytoreduction, we initiated efforts to improve outcomes through feedback and education, and we reassessed outcomes.Outcomes from group A (2006 and 2007, n=105) were compared with those from the cohort predating quality-improvement efforts (group B, 2000 to 2003, n=132). All stage IIIC ovarian cancer patients at our institution were evaluated for tumor dissemination, age, performance status, surgical complexity, residual disease (RD), morbidity, and mortality. A surgical complexity score previously described was used to categorize extent of operation.No significant differences in age, performance status, or extent of disease were observed between cohorts. Surgical complexity increased after initiation of quality improvement (mean surgical complexity score, 5.5 to 7.1; p0.001), rates of optimal RD (1 cm) improved from 77% to 85% (p=0.157), and rates of complete resection of all gross disease rose from 31% to 43% (p=0.188). In the subset of patients with carcinomatosis most likely to benefit from extended surgical resection, radical procedures were used more frequently (63% versus 79%; p=0.028), rates of optimal debulking (RD1 cm) increased (64% to 79%), and the rate of RD=0 increased from 6% to 24% (p=0.006). When disease was noted on the diaphragm, procedures to remove the disease were more frequently used (38% to 64%; p=0.001). The rates of major perioperative morbidity (group B, 21% versus group A, 20%; p=0.819) and 3-month mortality (8% versus 6%; p=0.475) were not affected despite this more aggressive surgical approach.Analysis of outcomes with appropriate feedback and education is a powerful tool for quality improvement. We observed improvements in rates of cytoreduction and use of specific radical procedures, with no increase in morbidity as a result of this process.

Purpose:The significance of investigations of thoracic cavities as well as pleural biopsy and intrathoracic washing cytology through transdiaphragmatic thoracoscopy for stage IIIc ovarian cancer with diaphragmatic metastases was assessed as a prospective pilot study.Subjects and Methods:Eligibility criteria were established to include patients with stage IIIc ovarian cancer in whom pleural effusions were not detected preoperationally, but prominent diaphragmatic metastases were observed when the abdomen was opened and those who submitted consent. Transdiaphragmatic thoracoscopy was performed after diaphragm stripping. Then, biopsy of the lesion suspected to be disseminated or the plural membrane of the thoracic opening was performed followed by washing cytology using physiological saline.Results:Ten subjects were enrolled. Disseminated lesions were observed on plural membranes, and positive results were obtained in biopsy and washing cytology in 3 subjects. In addition, positive results were seen with biopsy alone in 2 subjects and with washing cytology alone in 2 subjects. Hence, a total of 7 subjects (70.0%) were up-staged to the level of stage IV. Postoperational complications were not observed in any of these cases.Conclusions:It was suggested that stage IIIc ovarian cancer with prominent diaphragmatic metastasis may advance to the level of stage IV from a clinical point of view even if carcinomatous pleural effusions are not detected pre-operationally. Therefore, it is thought that this operational method is useful in the management of progressive ovarian cancer.

Objectives To identify proteins unique to metastatic ovarian cancer and test their potential involvement in cell adhesion. Methods We purified plasma membrane from paired metastatic and primary tumor tissues from patients with stage IIIC ovarian cancer. Membrane proteins unique to metastases were identified by liquid chromatographic mass spectrometry (LC-MS). The role of one of the identified proteins, ovarian cancer immuno-reactive antigen domain containing 1 (OCIAD1) in cell adhesion was determined in the presence of LPA using both over-expression and down regulation approaches. Results We identified a differentially expressed 29 kDa protein as OCIAD1 over-expressed in metastatic tissues, when compared to primary tumor tissues. OCIAD1 over-expression in HEY ovarian cancer cells increased LPA-induced, but not basal level cell adhesion to extracellular matrix proteins collagen I and laminin 10/11. This enhancement was not blocked by LY294002 and GF109203X, suggesting that OCIAD1 does not use PKC and PI3K signaling pathways to exert its effect on adhesion. In addition, LPA induced cell adhesion to collagen I was unaffected by paclitaxel (5 µM) in OCIAD1 overexpressing cells. Conclusions This is the first report that OCIAD1 is over-expressed in metastatic ovarian cancer tissues. The effect of OCIAD1 on cell adhesion may be related to its function in ovarian cancer. Failure of paclitaxel to affect ovarian cancer cell adhesion in presence of OCIAD1 raises the possibility of OCIAD1's role in tumor metastasis. Ongoing studies using a mouse orthotopic LPA-dependent ovarian cancer metastasis model are focused on strategies to inhibit the potential role of OCIAD1 in tumor metastasis.

The characteristics of women presenting with asymptomatic ovarian or peritoneal cancer diagnosed following evaluation for abnormal cervicovaginal cytology are currently undefined. We present a case of a 51-year-old woman with asymptomatic stage IIIC ovarian cancer whose diagnosis was triggered by evaluation for adenocarcinoma and atypical glandular cells of undetermined significance (AGUS) on cervical cytology. We also present a case of a 53-year-old woman with AGUS cervical cytology on two occasions, found to have stage III peritoneal cancer at exploratory laparotomy. We conducted a systematic search for articles to enable a review of asymptomatic cases of ovarian and peritoneal cancer, which presented via abnormal cervicovaginal cytology. The mean age at presentation with peritoneal cancer was 47.8 years old, which is similar to that of ovarian cancer of 50.5 years. Staging was provided in 13 cases, 11 of which (85%) were at least stage IIIA or greater. In terms of age greater than 50 years old, cervicovaginal cytology interpreted as AGUS, having a negative initial work-up, and advanced disease stage at presentation, the two cases presented are consistent with the literature. Abnormal cervicovaginal cytology as a presenting diagnostic criterion of cancer of the ovary or peritoneum is often representative of advanced disease.

// Ikhlak Ahmed 1 , Thasni Karedath 1 , Simeon S. Andrews 1 , Iman K. Al-Azwani 2 , Yasmin Ali Mohamoud 2 , Denis Querleu 3 , Arash Rafii 4 , Joel A. Malek 1, 2 1 Department of Genetic medicine, Weill Cornell Medicine-Qatar, Education City, Ar-Rayyan, Qatar 2 Genomics Core, Weill Cornell Medicine-Qatar, Education City, Ar-Rayyan, Qatar 3 Department of Gynecologic Oncology, Universite Montepllier 1, Montpellier, France 4 Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Ar-Rayyan, Qatar Correspondence to: Joel A. Malek, e-mail: jom2042@qatar-med.cornell.edu Keywords: circular RNA, ovarian cancer, peritoneal metastasis, lymph node metastasis, miRNA Received: December 07, 2015 Accepted: April 02, 2016 Published: April 22, 2016 ABSTRACT Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.

Dear Editor, Systemic chemotherapy has not been established for metastatic brain tumors from primary ovarian cancer. Here, we report our experience with an important case in which the efficacy of systemic chemotherapy was enhanced and prolonged survival with a good quality of life (QOL) was achieved by using nifedipine to inhibit P-glycoprotein. The patient was a 53-year-old woman. In July 1998, she underwent an optimal surgery for stage IIIc ovarian cancer (serous adenocarcinoma). In August 2006, the disease recurred as metastasis in the para-aortic lymph nodes. Although these lesions disappeared after chemotherapy with paclitaxel plus carboplatin (CBDCA), four metastatic brain tumors were observed in July 2007: a lesion in the cerebellar vermis; an asymptomatic nodular lesion in the left basal ganglion; and an asymptomatic nodular lesion in the right and left cerebellar hemisphere, each. These lesions disappeared after Gamma Knife radiosurgery. In June 2008, yet another asymptomatic metastatic lesion was found in the cortex of the apical portion of the right temporal lobe, which disappeared after Gamma Knife radiosurgery. However, in March 2011, another asymptomatic metastatic lesion (8×5 mm) was observed in the medial portion of the sensory region of the right parietal lobe (Fig. 1a). We opted to administer systemic chemotherapy, anticipating that it would not only have therapeutic effects on brain metastases but also exert a preventive effect against both metastasis to other organs and recurrence. Pegylated liposomal doxorubicin (PLD) plus CBDCA, which has been shown to be effective for recurrent ovarian cancer, was selected. However, because of the previously reported poor outcomes for brain metastasis from primary ovarian cancer [3], we decided to combine PLD plus CBDCA with nifedipine in the hope of increasing the anti-cancer drug efficacy. The patient provided informed consent and was prescribed a sustained-release nifedipine tablet (20 mg) to be taken every morning and evening for 7 days, starting on day 1 of each cycle of chemotherapy. After two cycles, contrast-enhanced magnetic resonance imaging (MRI) showed a 75 % reduction in lesion size (Fig. 1b). After four cycles, the lesion was no longer visible on contrast-enhanced computed tomography (CT) (Fig. 1c). After five cycles, its disappearance was confirmed by contrast-enhanced MRI (Fig. 1d). The serum cancer antigen 125 level, which was 162.7 U/ml initially, normalized to 19.3 U/ml after three cycles. There were no variations in blood pressure during nifedipine treatment and no adverse events such as palpi tations, nausea, or facial f lushing. The chemotherapy-related adverse events were minor. Treatment was completed after seven cycles in November 2011. As of this writing, the patient is completely independent in her activities of daily living, with a performance status of 0. She has a good QOL and is under outpatient management. * Toru Yanase toyanase@gmail.com

OBJECTIVE Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival. METHODS A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival. RESULTS The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001). CONCLUSION Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis. LEVEL OF EVIDENCE II-2.

A 52-year-old woman with stage IIIC ovarian cancer and stage IA uterine cancer experienced recurring alopecia areata of her eyebrows, eyelashes, arms, legs, and pubic area beginning 5 months after completing chemotherapy with paclitaxel and carboplatin. The condition recurred in a cyclic fashion over the ensuing months. Alopecia is a well-recognized adverse event associated with chemotherapy; however, to our knowledge, this cyclic pattern of alopecia has not been reported in a patient with cancer. Our report of a cancer survivor who experienced cyclic alopecia areata indicates that this condition may be related to autoimmune changes instigated by chemotherapy. Oncology health care practitioners should evaluate unusual clinical cases of alopecia for underlying pathology.

Background. One of the unfortunate complications associated with the use of Penrose drains is slipping down of the drain into the peritoneal cavity because of incomplete placement of skin sutures to secure the drain. Case. A 49-year-old woman with the International Federation of Gynecology and Obstetrics (FIGO) stage IIIc ovarian cancer underwent bilateral salpingo-oophorectomy, total hysterectomy, partial omentectomy, and pelvic and para-aortic lymph nodes removal. On the third postoperative day, one of the Penrose drains slipped down, leaving it inside the patient. The intraperitoneal Penrose drain was successfully retrieved under endoscopic guidance through vaginal cut stump. She went home on the 9th day after the initial operation and started to receive postoperative adjuvant chemotherapy on the 17th day. Conclusion. The endoscopic-guided retrieval through vaginal cut stump of an intraperitoneal retained Penrose drain is an excellent option.

We report on a 45-year-old patient with stage IIIc ovarian cancer, multiple brain metastases, and meningitis carcinomatosa. After three courses of initial chemotherapy, consisting of docetaxel and carboplatin, the patient underwent interval cytoreductive surgery, consisting of hyster-ectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and retroperitoneal lymphadenectomy. Then five courses of the same chemotherapy were given as adjuvant treatment. At the completion of the primary therapy, she achieved a complete remission. Ten months after the completion of the initial treatment, multiple brain metastases with meningitis carcinomatosa were detected. After four courses of the same chemotherapy, she again had a complete response, confirmed by cranial enhanced magnetic resonance imaging (MRI), and she felt well, with relief from the debilitating neurologic symptoms for 4 months. After this 4 months, her disease recurred, with meningitis carcinomatosa, and she requested supportive care only. She died 4 months after this recurrence. Chemotherapy can help to prolong life for some patients with multiple brain metastases and meningitis carcinomatosa from ovarian cancer.

The objective of this study was to evaluate the impact of systematic pelvic and para-aortic lymphadenectomy on survival in patients with advanced ovarian cancer.We retrospectively analyzed the data of 189 consecutive patients with FIGO stage IIIC ovarian cancer between 2000 and 2011, who underwent primary cytoreductive surgery followed by platinum- and taxane-based chemotherapy. All patients were classified into two groups - patients who underwent systematic pelvic and para-aortic lymphadenectomy and those who did not. Progression-free (PFS) and overall survival (OS) times were analyzed using Kaplan-Meier method and Cox proportional hazards model.Patients who underwent systematic lymphadenectomy had significantly improved PFS (22 versus 9 months, p0.01) and OS (66 versus 40 months, p0.01). In patients with no gross residual disease (NGR) or residual disease 0.1-1cm (GR-1), the median OS time of those who had lymphadenectomy was significantly longer than those who did not (86 versus 46 months, p=0.02). However, in patients with residual disease1cm (GR-B), there was no significant difference in OS according to lymphadenectomy (39 versus 40 months, p=0.50). Among patients with NGR, the median OS time of those who underwent systematic lymphadenectomy was significantly longer than those who did not undergo lymphadenectomy (not yet reached [96] and 56 months, p0.01). No significant difference of OS between patients with and without lymphadenectomy was observed in the subgroup of patients with GR-1 (50 versus 38 months, p=0.44). The performance of lymphadenectomy was a statistically significant and independent predictor of improved OS in addition to the status of residual disease and the performance of radical cytoreductive procedures (hazard ratio, 0.34; [95% CI, 0.23-0.52]; p0.01).Systematic lymphadenectomy may have a therapeutic value and be significantly associated with improved survival in stage IIIC ovarian cancer patients with grossly no visible residual disease.

Objective To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction. Methods Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with 2cm IP spread and negative nodes (IP/RP−); and >2cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used. Results Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23–2.30; HR 1.38, 95% CI 1.04–1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24–2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85–1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29months, respectively, vs. 48months in the RP group (p=0.0007) and median OS of 63 and 79months vs. "not reached," respectively (p=0.0038). Conclusions Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.

Background. Systemic sclerosis is a rare, chronic, multisystem, and autoimmune disease. There is an overall increased risk of malignancy in patients with systemic sclerosis. However, multiple cancers of the female genital tract in patients with SSc are a very rare event. Our aim is to present a case of SSc and multiple cancers of the female genital tract, with prolonged survival following current treatment strategies.Case. The patient, a 43-year-old nulliparous premenopausal Greek woman suffering from systemic sclerosis, presented with a history of abdominal pain and abnormal uterine bleeding. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, appendectomy, and pelvic lymph node dissection. The histopathology revealed synchronous primary cancers of the endometrium and left ovary. The final diagnosis was stage Ib endometrial cancer endometrioid type and stage IIIc ovarian cancer endometrioid type. She underwent postoperative adjuvant chemotherapy and remains well without evidence of disease 89 months after initial surgery.Conclusion. Although our patient was diagnosed at advanced stage disease, prolonged survival may be related with radical surgery and postoperative adjuvant chemotherapy according to current treatment strategies.

We report a case of recurrent ovarian cancer in which desensitization for a carboplatin hypersensitivity reaction proved useful. The patient was a 65-year-old woman who presented with a recurrence of stage IIIc ovarian cancer. The initial chemotherapy consisted of 6 courses of paclitaxel and carboplatin. Recurrence in the pelvis, splenic hilum and para-aortic lymph nodes was detected 19 months after the final day of treatment. The patient was treated with docetaxel-carboplatin therapy for the recurrence, but a Grade 3 hypersensitivity reaction to carboplatin was observed during the second course. Carboplatin desensitization was commenced with the third course and 6 courses were completed with no evidence of hypersensitivity reaction. The antitumor effect showed a complete response and the patient has had a disease-free survival thus far. Desensitization for patients diagnosed with a carboplatin hypersensitivity reaction appeared to be a key method of treatment for prolonging the survival time of patients with recurrent ovarian cancer.

To assess the feasibility and efficacy of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) without adjuvant chemotherapy for relapsed or persistent advanced ovarian cancer.This observational study included stage IIIC ovarian cancer patients due to undergo CRS (interval debulking or recurrent surgery) followed by HIPEC with oxaliplatin (460 mg/m2) for 30 min.Twenty-two patients (12 interval debulking procedures and 10 recurrence procedures) were enrolled between September 2003 and September 2007. HIPEC was not performed in four patients because of operative findings. No patient received adjuvant chemotherapy after HIPEC. Patients were followed up routinely until recurrence or death. Median peritoneal cancer index at surgery was 6 (range: 1-18). Before HIPEC, all patients had completeness of cytoreduction scores of 0 or 1. Median length of hospital stay was 21 days (range 13-65). Ten patients (55.6%) had CTCAE grade 3-4 toxicity, including three patients (16.7%) requiring reoperation. No postoperative mortality was observed. With a median follow-up of 38 months (CI 95% 23.8-39.2), median overall survival was not reached. The 3-year overall survival rate was 83% (CI 95% 54-95). Median disease-free survival was, respectively, 16.9 months (CI 95% 10.2-23.2) and 10 months (CI 95% 4.5-11.3) for patients undergoing interval debulking or recurrence surgery.HIPEC without adjuvant chemotherapy is both feasible and safe, but with a high rate of grade 3-5 toxicity. Survival results are encouraging but should be confirmed in a randomized trial.

Introduction:Ovarian cancer spreads via the retroperitoneal lymphatics, and these lymph nodes frequently contain metastasis. A subset of patients whose disease was classified as stage IIIC has retroperitoneal lymph node metastases in the pelvic and/or para-aortic lymph nodes without intraperitoneal carcinomatosis and was upstaged from stage I to IIIB diseases based on these findings. Patients undergoing cytoreductive surgery for advanced-stage ovarian cancer undergo concomitant retroperitoneal lymphadenectomy in an effort to improve their survival.Methods:Stratification of patients with stage IIIC ovarian cancer by lymph node status and presence and extent of metastatic disease in the peritoneal cavity has been performed. Studies have determined the impact on disease-free and overall survivals of the resection of retroperitoneal lymph nodes as part of primary and secondary cytoreductive operations.Results:The overall survival of patients with stage IIIC ovarian cancer based on retroperitoneal lymph node metastasis without peritoneal carcinomatosis is 58% to 84% compared with 18% to 36% for those with macroscopic peritoneal carcinomatosis. Although the performance of a pelvic and para-aortic lymphadenectomy in patients with stage IIIC to IV diseases has been reported to prolong survival, an international randomized study did not confirm this finding. Patients who undergo secondary resection of isolated recurrent lymph node metastasis have a better survival than those with more extensive recurrent disease.Conclusions:These data support the stratification of patients with stage IIIC ovarian cancer based on the finding of metastasis to the retroperitoneal lymph nodes without peritoneal carcinomatosis versus those who have peritoneal carcinomatosis. The International Federation of Gynecology and Obstetrics Committee should consider modifying the ovarian cancer staging system by further stratifying stage III disease. Although systematic lymphadenectomy during primary cytoreductive surgery does not appear to improve overall survival, resection of isolated lymph node metastasis and recurrences in lymph nodes may be associated with a survival benefit.

Objectives: The aim of this study was to assess the prognostic factor of radical surgery in patients with stage IIIc ovarian cancer. Study design: Fifty-two patients were subjected to the study. The complete resection or optimal primary cytoreductive surgery (OPCS) was set as the maximum effort, and the accomplishment rate and prognosis were assessed. In addition, the poor prognosis cases among the OPCS-accomplished were evaluated with several factors based on univariate and multivariate analyses. Results: The OPCS accomplishment rate was 84.6%. A worse prognosis was obtained in the more-than-4-weeks-delayed postoperative chemotherapy group, assessing poor-outcome cases in the OPCS group. A case that required more than three colon resections was the significant factor for the delay of postoperative chemotherapy. Conclusions: OPCS should be performed with maximum effort to improve the prognosis of stage IIIc ovarian cancer. We should avoid any delay in starting postoperative chemotherapy. In cases that require more than three colon resections, it seems that ‘perioperative management’ should be reconsidered and that priority should be given to postoperative management so that chemotherapy can be started soon after the operation.

The rationale for ip administration as an adjunct to surgery is firmly based on theoretical and pharmacokinetic grounds. The superiority of combined ip and intravenous chemotherapy over intravenous chemotherapy alone has been established in randomized trials in stage IIIc ovarian cancer patients. Intraoperative ip cytotoxic therapy results in a definite pharmacological advantage, since high peritoneal concentrations are achieved with limited systemic absorption. At present, however, it is not clearly established to what extent this PK advantage will result in enhanced anticancer activity and, ultimately, in a survival benefit. Preclinical models show that direct penetration into tumour tissue is limited to a few millimeters. Furthermore, the limited exposure time of intraoperative chemoperfusion could limit cytotoxic activity despite high local concentrations. Among the cytotoxic agents currently used, the pharmacodynamic aspects of the platinum compounds are the best studied both with and without associated hyperthermia. Newer agents such as the taxanes and the camptothecins appear promising for ip chemoperfusion during or immediately after surgery. Pharmacodynamic aspects of HIPEC needing further preclinical study-including mathematical modeling - are the establishment of tumour tissue penetration of the newer agents and its relation to hyperthermia, the definition of the relative contribution of direct penetration versus vascular supply by absorbed drug, and the efficacy of combined ip and intravenous regimens. Ultimately, however, randomised trials of ip chemotherapy with surgery will have to provide the evidence base to further build upon.

However, extravasation of pegylated liposomal doxorubicin is generally accompanied by a mild cutaneous reaction that is reversible in a few days. 2 Here, we describe a severe, recall cutaneous reaction to pegylated doxorubicin in a site of previous drug extravasation after the resumption of treatment. A 58-year-old woman with platinum-resistant ovarian cancer was treated at our institution with pegylated liposomal doxorubicin. She had received bilateral oophorectomy and hysterectomy for stage IIIC ovarian cancer with macroscopic residual disease in the peritoneum, the retrocrural lymph nodes, and the retroperitoneum. Use of six cycles of first-line chemotherapy with carboplatin (area under curve [AUC] 6) and paclitaxel (175 mg/m 2 ) on day 1 every 21 days gave a partial response. The disease progressed for the next 5 months, after which she received second-line chemotherapy with topotecan (1·5 mg/m 2

Objective To report a case of gestational carrier pregnancy with oocytes from a stage IIIc ovarian cancer patient. Design Case report. Setting University hospital. Patient A 38-year-old woman with stage IIIc ovarian cancer. Intervention(s) Controlled ovarian stimulation, cancer surgery, and IVF-ET to a gestational carrier. Main Outcome Measure(s) Oocyte fertilization and pregnancy. Result(s) Singleton term delivery occurred after transfer of three frozen–thawed embryos. Conclusion(s) Cryopreservation of embryos derived from IVF of oocytes obtained from ovarian cancer patients should be an option for their future fertility.

Background . Altretamine has reported efficacy in the treatment of recurrent ovarian cancer following platinum-based therapy. This report presents the cases of two long-term survivors with recurrent ovarian cancer given oral altretamine. Cases . Two patients diagnosed with stage IIIC ovarian cancer underwent optimal cytoreductive surgery. Both women were subsequently treated with platinum-based chemotherapy. One had persistent cancer documented 2 months post therapy, while the other was disease-free for 22 months before recurring. Both received altretamine in a salvage setting. Each of these women achieved a prolonged response to third-line altretamine therapy, and one of whom was disease-free for 4 years and the other remains disease-free over 7 years following initiation of salvage therapy. Conclusion . Outpatient-administered oral altretamine can provide a prolonged disease-free interval with minimal toxicity.

We present a possible adverse reaction related to long-term use of Doxil® in female patients. We believe that long-term use of Doxil® may predispose female patients to oral squamous cell carcinoma. The patients in this report were not exposed to the common risk factors related to oral cancer formation such as smoking or alcohol consumption. Both patients were 59-year-old females. The first patient was diagnosed in 2001 with stage IIIC ovarian cancer. Seven years following treatment with Doxil®, she was diagnosed with stage III squamous cell carcinoma of the right maxilla. The second patient was diagnosed with Kaposi’s sarcoma with evidence of spread to the lungs. Four years following treatment with Doxil® she was diagnosed with stage I squamous cell carcinoma of the left maxilla. A literature review did not reveal any report on Doxil® and predisposition to oral cancer; however, we found an abstract that was presented at the last annual meeting of the American Society of Clinical Oncology (ASCO) by Cannon et al. When we combine the data from Cannon et al. and the data presented here, a total of six female patients developed an epithelial carcinoma of the oral cavity following long-term treatment with Doxil®. We believe that a large-scale study should be initiated on patients that were treated with Doxil® for more than 3 years, since these patients might be at risk for developing secondary cancer of the oral cavity.

Ovarian carcinosarcomas are rare gynecologic malignancies associated with an overall poor survival. The best way to obtain a good control of the disease seems to be complete cytoreduction; association of adjuvant platinum based chemotherapy was extrapolated from therapeutic guidelines for advanced epithelial ovarian cancer and seems to be effective in carcinosarcomas too. However the most important prognostic factor remains complete cytoreduction at the moment of diagnosis. We present the case of a 55 years old patient diagnosed with stage IIIC ovarian cancer in whom an R0 resection was performed. The histopathological findings revealed the presence of ovarian carcinosarcoma. At an one year follow up the patient is free of any recurrent disease.

e15507 Background: Intraperitoneal chemotherapy in stage III ovarian cancer is indicated following the results of the GOG 172 study but the ambulatory application of the scheme in 24 hours continuous infusion is not feasible. Following expert recommendations (Walker, ASCO 2009 Educational Book), we evaluated the feasibility of administrating a modified GOG 172 regime in an ambulatory form. Methods: Between September 2009 and October 2010, ten patients diagnosed with stage IIIC ovarian cancer and optimal cytoreduction received the following treatment in ambulatory form: IV paclitaxel (135mg/m2/3hrs Day 1), followed by IP cisplatin (60-75mg/m2 Day 2), plus IP paclitaxel (60mg/m2 Day 8). Cycles were administered every 21 days, up to a maximum of six cycles. The tolerance for this treatment was evaluated according to the CTC for Adverse Event 3.0. Results: Population Characteristics: Mean age (47 years; range 26-64). PS (0: 4 pt; 1: 6 pt). Pathology (Papillary: 7 Pts; Mucinous, Endometroid and Poorly Differentiated: 1 pt each). N-positives: 4 pt; N-negatives: 6 pt. Intestinal resection: 1pt. In all cases, treatment was applied according to the specified parameters. Total number of cycles administered: 37 (mean cycles per pt 3 range 2-6). The average time of treatment application was 3 hours per day (9 hours total). Toxicity (G3-4): Leukopenia (2 pts). Toxicity (G1-2): Alopecia (10 pts), Anemia (9 pts), Myalgia (8 pts), Neurologic (7 pts), Fatigue (6 pts), Nausea and vomiting (6pt), Renal (2 pts), Allergy (1 pt), Pain at Catheter site (1 pt). With an average follow up time of 16 months (Range: 9-26), none of the patients have died. Three patients have progressed after the Intraperitoneal chemotherapy, while seven are alive without evidence of disease after the treatment. Conclusions: 1) The modified GOG 172 scheme can be safely applied in an ambulatory form. 2) The time required for applying the treatment is similar to that of other frequently used treatments (BEP, paclitaxel – trastuzumab, R-CHOP, b-FOL). 3) Patient tolerance was very good. 4) With an average follow-up of 16 months, all 10 patients are alive and 7 of them remain free of disease.

e15568 Background: The efficacy of PDS for advanced ovarian cancer has recently been challenged by data suggesting equivalent clinical outcomes for neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS). The strongest known predictor of prolonged survival in either group is the ability to achieve complete resection (CR) to no residual disease. PDS that results in a CR is associated with the longest overall survival of any sequence of treatment. The aim of this study was to determine what type of surgical approach is required to successfully perform PDS. Methods: All women with newly diagnosed stage IIIC epithelial ovarian carcinoma treated at our institution from 2000 to 2010 were identified. Pathology was prospectively reviewed by a faculty gynecologic pathologist. Treatment planning was discussed and documented at our weekly multidisciplinary tumor board conference. Data was retrospectively extracted from computerized medical records. Results: 344 (86%) of 401 women underwent PDS. Optimal debulking was achieved in 278 patients (81%): 35% had CR while 46% had 0.1-1.0 cm residual disease. 56 stage IIIC pts (19%) had a suboptimal surgical outcome with ≥ 1.0 cm. Compared to those having a CR, patients with 0.1-1.0 cm residual were more likely to require splenectomy (17 v 5%; P = 0.002) and transverse colectomy (19 v 10%; P = 0.042), with comparable rates of rectosigmoid resection (41 v 39%; P = 0.712) and en bloc pelvic resection including total peritonectomy (26 v 30%; P = 0.050). Patients undergoing CR were more likely to have diaphragmatic surgery (31 v 20; P = 0.068) and lymphadenectomy (67 v 33%; P < 0.001). Conclusions: PDS is the preferred treatment of stage IIIC epithelial ovarian cancer at high-volume centers demonstrating >75% rates of optimal cytoreduction. Tumor biology may lead to the need for more aggressive upper abdominal procedures in patients with 0.1-1.0 residual. Diaphragm resection, stripping or ablation is more often required in order to achieve CR. Since subclinical macroscopic nodal metastases are often present, lymphadenectomy is also frequently performed to ensure that all possible disease has been resected.

Ovarian cancer is the leading cause of death among female reproductive tract cancers and the fifth most common overall cause of cancer death among women, with 22,430 newly diagnosed cases and 15,280 cause-specific deaths estimated in the United States in 2007.1 In Korea, it marks the eighth most common female cancer (3.6%) among 43,627 new total female cancer cases, and cancer death (3.1%) among 24,014 cause-specific deaths.2 In 1983, Chen et al. reported the incidence of retroperitoneal lymph node metastases in untreated cases of ovarian carcinoma. The incidence of positive para-aortic nodes in Stage I disease was 18.2%; in Stage II, 20.0%; in Stage III, 41.9%; and in Stage IV, 66.7%. The corresponding incidence of pelvic node metastasis was 9.1% in Stage I, 10.0% in Stage II, 12.9% in Stage III, and 33.3% in Stage IV. In total, the incidence of para-aortic node metastasis overall was 37.7% and of pelvic node metastasis, 14.8%.3 Direct relationships between nodal metastasis and clinical stage, tumor grade, and histologic type of tumor have been demonstrated. Grade 3 tumors were associated most frequently with nodal involvement, with an incidence of 52.5% positive para-aortic nodes and 15.5% positive pelvic nodes of. In patients with serous type malignancy, the frequencies of positive para-aortic/pelvic nodes were 44.4%/16.7%, respectively; 50.0%/10.0% in the undifferentiated type, 25.0%/25.0% in the clear cell type, and 14.3%/14.3%. in the mucinous type. In the series, 32 patients (52.5%) had positive retroperitoneal nodal involvement. Therefore, they concluded that selective biopsies of the para-aortic and pelvic lymph nodes should be part of any "staging laparotomy" for ovarian carcinoma.3 Thereafter, the GOG study confirmed that surgical exploration for early stage carcinoma of the ovary should include biopsies of the retroperitoneal pelvic and para-aortic lymph nodes, excision of the infracolic omentum, biopsies of pelvic and abdominal peritoneum, including the right diaphragm, and peritoneal cytologic studies.4 Therefore in 1986, the International Federation of Gynecology and Obstetrics (FIGO) cancer committee announced that initial comprehensive surgical staging according to FIGO staging systems with maximal cytoreductive surgery for patients with ovarian cancer is important for determining the diagnosis and in identifying prognostic factors.5 Since then, surgery has played a key role in the management of this disease, in which the presence of metastatic disease in retroperitoneal lymph nodes is indicative of a poor prognosis.6 However Carino et al.7 noticed that a significant increase in survival (p=0.04) was found for patients classified as stage IIIC only according to lymph node involvement, compared to patients with peritoneal stage IIIC with positive lymph nodes (3-year survival: 46% vs. 12%). A small increase in survival was observed for node (-) patients compared to node (+) patients, for both stage III and IV, even with the same residual tumor size, but the difference was not statistically significant. A Japanese study also reported that relatively good survival was observed for patients with intraperitoneal tumors limited to the pelvis and lymph node involvement who had underwent systematic aortic and pelvic lymphadenectomy. In other words, Stage III disease based only on lymph node positivity had fairly good survival.8 Baek et al.9 reported almost the same results in this issue. They studied a relatively large numbers of 272 patients with stage IIIC epithelial ovarian cancer who had underwent cytoreductive surgery according to the FIGO guidelines, followed by platinum based chemotherapy from September 1989 to September 2006. The median follow-up period was 37 months, and they observed that patients with stage IIIC disease due to positive nodes only had significantly longer disease-free survival (DFS) and overall survival (OS) compared to other stage IIIC patients (p

BackgroundThe aim of this study was to find out the long-term survival of patients with primary International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC IIIC) in a population-based patient cohort treated in Norway in 2002.Patients and MethodsAll 198 women with a diagnosis of EOC IIIC who underwent surgery were included. The data were derived from notifications to the Norwegian Cancer Registry and medical, surgical, and histopathologic records. The hospitals were grouped into teaching hospitals (THs) and nonteaching hospitals (NTHs). The follow-up period was from 0 to 106 months.ResultsThe long-term survival at 8 years was 15% for women operated on at THs and 10% for women operated on at NTHs (P < .05). The median survival was 35.6 months at THs and 23.4 months at NTHs (P < .05). After simultaneous adjustment for 4 prognostic factors (age, histologic type, grade of differentiation, and residual disease), the risk of death within 8 years at NTHs was unchanged, with a hazard ratio of 1.38 (95% confidence interval [CI], 1.00-1.89), compared with THs.ConclusionPatients operated on for EOC IIIC at THs achieved better long-term survival than did patients operated on at NTHs. Centralization of EOC IIIC surgery should be introduced in all countries to improve outcomes for this patient group.