Serous tubal intraepithelial carcinoma (STIC) is considered the precursor of pelvic serous carcinomas and the earliest malignant alteration in BRCA mutation-positive women. Recently, risk-reducing salpingo-oophorectomy (RRSO) is being performed in BRCA mutation-positive women and STIC is often discovered incidentally in the fallopian tubes. A 62-year-old woman underwent bilateral salpingo-oophorectomy (BSO) for ovarian cysts. Ten months later, cytological screening for the endometrium revealed adenocarcinoma. No atypical tissue was detected by the endometrial curettage. Imaging tests and hysteroscopy found no abnormal findings. She underwent hysterectomy and was diagnosed with STIC originating from the intrauterine portion of the residual fallopian tube. Here, the authors report the first case of STIC being detected during an endometrial cytological examination after BSO. Although STIC associated with the BRCA mutation usually involves the distal fallopian tube, the present case suggests that the intrauterine portion of the fallopian tube should be removed or cauterized during RRSO.

The prognostic significance of peritoneal washing cytology in gynecologic neoplasms is controversial. The presence of neoplastic cells in peritoneal washings is currently part of the Federation of Gynecology and Obstetrics and American Joint Committee on Cancer TNM staging systems in cases of ovarian and fallopian tube neoplasms without metastasis beyond the pelvis. In this study, we retrospectively reviewed all cases of ovarian and fallopian tube neoplasms in which cytologic studies were performed. The utility of cytology in tumor staging and the relationship between cytology results and patient outcome are studied. All cases of ovarian and fallopian tube neoplasms in our institution between July 2002 and July 2012 were reviewed. Primary tumor characteristics including type and pelvic extension were collected, categorized, and correlated with peritoneal washing cytology. Final tumor staging was reviewed and the impact of positive cytology was evaluated. A total of 120 cases of ovarian and fallopian tube neoplasms without extrapelvic metastasis were identified within the study period. Peritoneal washing cytology was positive in 24% (29/120) of neoplasms and upstaged the tumor 83% (24/29) of the time when positive. Overall, 20% (24/120) of reviewed cases were upstaged based on positive cytology results. Peritoneal washing cytology remains a useful staging tool for ovarian and fallopian tube neoplasms limited to the pelvic cavity. Positive cytology results in upstaging in a significant proportion of the cases regardless of the tumor type. A larger study is needed to analyze follow-up data to determine if upstaging based on positive cytology adversely affects outcome.

BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS) is used for contraception and heavy menstrual bleeding. A long-term hormone therapy can modify the risk of gynecologic cancers. Little is known about the impact of LNG-IUS use on the risk for invasive and borderline ovarian tumor subtypes or for primary fallopian tube carcinoma. We examined the associations of LNG-IUS use with these tumors.
MATERIAL AND METHODS: We identified from the national Medical Reimbursement Registry of Finland the women aged 30-49 years who had used LNG-IUS for menorrhagia in 1994-2007, and from the Finnish Cancer Registry ovarian cancers and primary fallopian tube carcinomas diagnosed before the age of 55 and by the end of 2013.
RESULTS: A total of 77 invasive ovarian cancers and seven primary fallopian tube carcinoma cases were diagnosed in a cohort of 93 843 LNG-IUS users during the follow-up of 1 083 126 women-years. The LNG-IUS users had decreased risk for both invasive ovarian cancer [standardized incidence ratio (SIR) 0.59, 95% confidence interval (CI) 0.47-0.73] and for borderline ovarian tumors (SIR 0.76, 95% CI 0.57-0.99) as compared to the background population. The risk of primary fallopian tube carcinoma was not increased (SIR 1.22, 95% CI 0.49-2.50). Decreased risks for mucinous (SIR 0.49, 95% CI 0.24-0.87), endometrioid (SIR 0.55, 95% CI 0.28-0.98), and serous ovarian carcinomas (SIR 0.75, 95% CI 0.55-0.99) were seen in LNG-IUS users.
CONCLUSIONS: LNG-IUS use associated with decreased risk for both invasive and borderline ovarian tumors. The incidence of primary fallopian tube carcinoma did not significantly differ between LNG-IUS users and the background population.

The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows-(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the 'flow charts' have been improved and placed near the beginning of the guidelines; (3) the 'basic points', including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

AIM: To compare the efficacies and side effects of intravenous and oral dexamethasone (IV-D and PO-D) for paclitaxel-associated hypersensitivity reaction (P-HSR) prophylaxis in patients with primary ovarian, fallopian tube and peritoneal carcinomas (POC/PFTC/PPC) receiving a first cycle of paclitaxel plus carboplatin (TC).
METHODS: In this double-blind randomized controlled trial, patients with POC/PFTC/PPC receiving a first cycle of TC were randomly allocated in a 1:1 ratio to either the IV-D or PO-D groups. Those were followed at 28 days. Primary outcomes were incidence of overall and severe P-HSRs. Secondary outcomes included incidence of dexamethasone-related side effects, other chemotherapy-related adverse events (AEs), and quality-of-life (QoL).
RESULTS: A total of 288 patients were enrolled from February to July 2015, of whom 281 were eligible for analysis, including 140 allocated to IV-D and 141 to PO-D. There was no significant difference in P-HSR rate between the IV-D and PO-D groups (17.9% vs. 19.1%, P = 0.780). Severe P-HSR occurred in one women in the IV-D group (0.7% vs. 0%, P = 0.498). There were no significant differences in other chemotherapy-related AEs and QoL scores. However, women in the PO-D had more side effects from short-term corticosteroid use than those in the IV-D group, especially acne (10.6% vs. 2.1%, P = 0.004).
CONCLUSIONS: IV-D and PO-D have similar efficacies for preventing P-HSR. However, short-term IV-D may be associated with fewer side effects than PO-D. IV-D is thus suggested for P-HSR prophylaxis in patients with POC/PFTC/PPC receiving a first cycle of TC.

Renal cell carcinoma (RCC), the most common type of kidney cancer in adult, rarely metastasizes to the ovary or fallopian tube, and most cases published in the literature were case reports. Herein, we describe the clinicopathological features of 9 cases of RCC metastatic to the ovary (n = 8) or the fallopian tube (n = 1). The patients' age at the onset of primary renal tumor was available in 8 patients, ranging from 37 to 73 years (mean, 51 years; median, 50 years). Ovarian metastasis was detected prior to or concurrently with the primary renal tumors in 3 patients, and after the diagnosis of renal tumors in 6 patients. The histotypes of the RCCs were clear cell (n = 7), chromophobe (n = 1), and unclassified (n = 1). Immunohistochemical stainings were performed on the sections containing metastatic tumors in 4 cases. Interestingly, pagetoid intraepithelial spread in the tubal mucosa was observed in the case of RCC metastatic to the fallopian tube. Among the 8 patients with follow-up data, 5 died of disease and 3 were alive with disease, with a follow-up period ranging from 3.7 months to 17 years (mean, 77 months; median, 53 months) after the diagnosis of primary kidney tumors. Diagnostically, metastatic RCC may mimic primary ovarian tumors clinically, morphologically, or immunophenotypically. Pathologists should also keep in mind that both ovarian and kidney tumors express PAX8 and PAX2, the markers commonly used to diagnose metastatic RCC. In addition, chromophobe RCC only rarely metastasizes, but it can be a diagnostic challenge when it metastasizes to the ovary.

Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p < 0.001). No differences in tubal injury or inflammation were seen when comparing the sporadic serous cancer group and the control group or within the hereditary group. STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.

OBJECTIVE: With the 2013 International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and primary peritoneal cancer, the number of substages changed from 10 to 14. Any classification of a malignancy should easily assign patients to prognostic groups, refer patients to individualized treatments, and allow benchmarking and comparison of patients and results between centers. The stage should reflect survival in particular. The objective of the study was to validate these requirements of the revised FIGO staging on a high number of ovarian cancer patients.
MATERIALS AND METHODS: Demographic, surgical, histological, and survival data from 4036 ovarian cancer patients were used in the analysis. Five-year survival rates (5YSR) and hazard ratios for the old and revised FIGO staging were calculated using Kaplan-Meier curves and Cox regression.
RESULTS: A total of 1532 patients were assigned to new stages. Stages IA and IC1 had similar survival (5YSR, 87%); and stages IB, IC2, and IC3 had similar survival (5YSR, 75%-80%). Stage IIC was omitted, resulting in similar survival in stages IIA and IIB (5YSR, 61% and 65%). Of 1660 patients in stage IIIC, 79 were restaged: In 16 cases, IIIC was down-staged to IIIA1, as they had only been stage IIIC owing to lymph node metastases; and in 63 cases, IIIC was down-staged to IIIB, as they had lymph node metastases and abdominal tumor of less than 2 cm. The 5YSR in stage IIIC was unchanged (22%). Stage IV (5YSR, 14% ) was restaged as IVA (13%) and IVB (13%). Both were different from IIIC; P < 0.0001.
CONCLUSION: With introduction of new substages, staging becomes more demanding. Second, as fewer patients are allocated to each substage, statistical power is diminished, resulting in uncertainty in the results. Despite this, and most importantly, the revised coding adequately reflects survival, as there was a clear graphical and statistical tendency for poorer survival with increasing stage.

INTRODUCTION: Molecular pathological research has contributed to improving the knowledge of different subtypes of ovarian cancer. In parallel with the implementation of the new FIGO staging classification, the WHO classification was revised. The latter is mainly based on the histopathological findings and defines the actual type of tumor. It has, therefore, also an important impact on prognosis and therapy of the patient.
MATERIALS AND METHODS: The new WHO Classification of Ovarian Cancer published 2014 by Robert Kurman and co-authors is summarized. The major changes compared to the hitherto existing classification are presented.
RESULTS: The new classification eliminates the previous focus of mesothelial origin of ovarian cancer. Instead, it features a discussion of tubal carcinogenesis of hereditary and some other high-grade serous carcinomas. The previously assumed pathogenesis pathway may be correct for some, but not for all, serous cancers. The new classification was established to classify ovarian cancer in a more consistent way. The earlier transitional cell type of ovarian cancer has been removed while seromucinous tumors have been added as a new entity. The role of some borderline tumors as one possible step in the progression from benign to invasive lesions is incorporated. The article summarizes the essential updates concerning serous, mucinous, seromucinous, endometrioid, clear-cell, and Brenner tumors.
CONCLUSION: The new WHO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes. The tubal origin of hereditary and some non-hereditary high-grade serous cancers is mentioned in contrast to the hitherto theory of mesothelial origin of tumors. Seromucinous tumors represent a new entity.

OBJECTIVE: This study aimed to identify the prognostic factors for primary fallopian tube carcinoma.
METHODS: A retrospective analysis was conducted of the patients treated with primary surgery and adjuvant chemotherapy at the Obstetrics and Gynecology Hospital of Fudan University from February 2003 to December 2010. Cox proportional hazards model was used for univariate and multivariate survival analysis.
RESULTS: Included in this study were 101 patients with a median follow-up of 64 months and a mean age of 57 years. Latzko triad symptom of abdominal pain, vaginal bleeding or discharge, and palpable pelvic mass was reported in 14 patients, and elevated CA 125 (≥ 35 U/mL) was found in 63. Four patients were classified as grade 1, 31 were grade 2, and 66 were grade 3. The distribution of International Federation of Gynecology and Obstetrics stage was 33 at stage I, 28 at stage II, 39 at stage III, and 1 at stage IV. Ninety patients underwent optimal tumor debulking in which residual tumor was no larger than 1 cm, and 67 patients received no fewer than 6 cycles of postoperative chemotherapy with paclitaxel and carboplatin (TP)-based regimen. Recurrence occurred in 44 patients after a median of 20 months (range, 1-72 months). The 5-year overall survival rate was 67.7%, and the 5-year disease-free survival was 57.4%. Multivariate analysis revealed that International Federation of Gynecology and Obstetrics stage (I-II) [hazard ratio (HR), 2.670; 95% confidence interval (CI), 1.316-5.418; P = 0.007 vs HR, 2.716; 95% CI, 1.416-5.211; P = 0.003], pelvic lymphadenectomy (HR, 0.274; 95% CI, 0.136-0.555; P < 0.001 vs HR, 0.449; 95% CI, 0.227-0.888; P = 0.021), and cycles (≥ 6) of chemotherapy (HR, 0.480; 95% CI, 0.246-0.937; P = 0.031 vs HR, 0.521; 95% CI, 0.276-0.985; P = 0.045) might serve as independent predictors of both overall survival and disease-free survival.
CONCLUSIONS: Preoperative diagnosis of fallopian tube carcinoma is difficult due to the silent course of this neoplasm. Comprehensive surgical staging including pelvic lymphadenectomy followed by adequate cycles of chemotherapy is an important strategy to improve patients' prognosis.

OBJECTIVES: The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications.
MATERIALS AND METHODS: Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data.
RESULTS: Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation.
CONCLUSIONS: Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.

UNLABELLED: Intratubal teratoma is a very rare condition. The authors believe to present the first case of a completely intratubal mature cystic teratoma with a contralateral intraovarian teratoma. Preoperative ultrasound examination allowed the intraoperative diagnosis of this rare condition, hence allowing appropriate surgical management.
MATERIALS AND METHODS: A 19-year-old woman presented with a history of pelvic pain and severe dysmenorrhea. Ultrasound examination initially suggested bilateral ovarian dermoids. Upon laparoscopy, the distal left fallopian tube was obstructed and contained an inflammatory mass adhered to the rectosigmoid. The left ovary was entirely normal. A contralateral intraovarian dermoid was also identified.
CONCLUSION: Although rare, when an intratubal mass is identified, consideration of intratubal dermoid should be given. Preoperative ultrasound can be of critical importance to the intraoperative diagnosis.

OBJECTIVE: The aim of the study was to evaluate the activity and tolerability of iniparib monotherapy in women with BRCA1 or BRCA2-associated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
METHODS AND MATERIALS: Eligible patients had advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, germline BRCA1 or BRCA2 mutation, measurable disease, and at least 1 previous treatment regimen of platinum/taxane chemotherapy. Patients received iniparib 8 mg/kg intravenously on days 1 and 4 weekly, with imaging every 8 weeks. Treatment continued until disease progression or adverse events (AEs) prohibited further therapy. Common Terminology Criteria for AEs v3.0 was used to grade AEs. The primary endpoint was tumor response. The study was conducted with a Simon 2-stage design with 12 and 23 patients planned in the first and second stage, respectively. The study was designed to distinguish between 10% and 30% responding with types 1 and 2 error of 0.10.
RESULTS: Twelve patients were treated on study, with median exposure to iniparib of 7.5 weeks. The median number of previous chemotherapeutic regimens was 7. Treatment-related AEs (≥10%) included asthenia (83.3%), constipation (25%), diarrhea (25%), nausea (25%), abdominal pain (16.7%), and decreased hemoglobin (16.7%). All treatment-related AEs were grades 1 or 2 with the following 2 exceptions: 1 grade 3 diarrhea and 1 grade 3 hypertension. One patient had stable disease lasting 2 cycles; the remaining 11 patients had progressive disease. The study did not proceed to second stage enrollment.
CONCLUSIONS: Iniparib did not show significant activity in this heavily pretreated ovarian cancer population, all of whom had BRCA1 or BRCA2 mutations.

Primary fallopian tube carcinoma is rare and accounts for 0.14-1.8% of all malignancies of the female genital tract. It has been found to be associated with nulliparity and subfertility, as well as with pelvic inflammatory disease. High parity has been reported to be protective but not in our 3 cases. History of pregnancy and the use of oral contraceptives decrease the PFTC risk significantly in literature. PFTC has been described in high-risk breast-ovarian cancer families with germ-line BRCA-1 and BRCA-2 mutations. Symptoms are nonspecific and include abdominal pelvic pain, vaginal bleeding and watery discharge. However, diagnosis is rarely achieved pre-operative because of misleading imaging. In many cases, the diagnosis is made incidentally on histopathology after surgery for an un-related condition commonly being an ovarian carcinoma.

Ovarian cancer is the seventh most common cancer diagnosis among women worldwide. The International Federation of Gynecology and Obstetrics recently significantly revised staging criteria for cancer of the ovary. The latest revision was based on the concept that high-grade serous tubal intraepithelial carcinoma (STIC) may be the origin of some high-grade serous carcinomas of the ovary and peritoneum. Therefore, staging criteria for the ovary, fallopian tube, and peritoneum have been unified. Understanding this background and other important revised points are essential for radiologists concerned with imaging diagnosis in gynecologic oncology. Through this review, we introduce the STIC theory and show examples of diseases in accordance with the new staging criteria based on magnetic resonance imaging (MRI) and computed tomography (CT) results.

Fallopian adenocarcinoma is a rare malignancy arising in the epithelium of the fallopian tube. Fallopian tube epithelium has been proposed as a tissue origin for high-grade serous ovarian carcinoma, the deadliest gynecologic malignancy. Given the commonalities in dissemination and treatment of these malignancies, we contemplated the possibility of similar patterns of gene expression underlying their progression. To reveal potential similarities or differences in the gene expression of fallopian adenocarcinoma and high-grade serous ovarian carcinoma, we tested expression of the fractalkine receptor (CX3CR1) and its ligand, fractalkine (CX3CL1), in the specimens of normal and pathologic fallopian tube using immunohistochemistry. Our data show that CX3CR1 is expressed in the normal, cancer adjacent normal, inflammatory, and malignant fallopian epithelium. CX3CL1 was expressed only by the normal and cancer adjacent normal fallopian tube epithelium; its expression was largely lost in the inflammatory and malignant fallopian epithelium. In opposite, both CX3CR1 and CX3CL1 are expressed in high-grade serous ovarian carcinoma. These findings are consistent with an idea that fallopian adenocarcinoma and high-grade serous ovarian carcinoma, although currently thought to arise from the same organ, may not share similar molecular characteristics.

OBJECTIVE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of veliparib combined with PLD and carboplatin (CD) in patients with recurrent, platinum-sensitive epithelial ovarian cancer. To determine the tolerability at the MTD combined with bevacizumab.
METHODS: Patients received PLD (30mg/m(2), IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7 (intermittent) or days 1-28 (continuous). Standard 3+3 design was used in the dose escalation phase with DLTs based on the first cycle. Once the MTDs were determined, cohorts of 6 patients were enrolled to each regimen with bevacizumab (10mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4cycles of treatment in the bevacizumab cohorts.
RESULTS: In the dose-escalation phase, 27 patients were treated at 3 dose levels with DLTs noted in 6 patients including grade 4 thrombocytopenia (n=4), and prolonged neutropenia >7days (n=3). At the MTD of veliparib (80mg p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At MTD, 12 additional patients were treated with bevacizumab with 9 patients experiencing DLTs including grade 4 thrombocytopenia (n=4), prolonged neutropenia >7days (n=1), grade 3 hypertension (n=5), and grade 5 sepsis (n=1).
CONCLUSIONS: The MTD of veliparib combined with CD is 80mg p.o. b.i.d. in women with recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs were noted in 9 out of 12 patients. Lower doses of veliparib will need to be considered when given in combination with platinum-based therapies.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

OBJECTIVES: Changes in cognitive function have been identified in and reported by many cancer survivors. These changes have the potential to impact patient quality of life and functional ability. This prospective longitudinal study was designed to quantify the incidence of change in cognitive function in newly diagnosed ovarian cancer patients throughout and following primary chemotherapy.
METHODS: Eligible patients had newly diagnosed, untreated ovarian cancer and had planned to receive chemotherapy. Web-based and patient reported cognitive assessments and quality of life questionnaires were conducted prior to chemotherapy, prior to cycle four, after cycle six, and six months after completion of primary therapy.
RESULTS: Two-hundred-thirty-one evaluable patients entered this study between May 2010 and October 2011. At the cycle 4 time point, 25.2% (55/218) of patients exhibited cognitive impairment in at least one domain. At the post-cycle 6 and 6-month follow up time points, 21.1% (44/208) and 17.8% (30/169) of patients, respectively, demonstrated impairment in at least one domain of cognitive function. There were statistically significant, but clinically small, improvements in processing speed (p<0.001) and attention (p<0.001) but not in motor response time (p=0.066), from baseline through the six-month follow up time period.
CONCLUSIONS: This was a large, prospective study designed to measure cognitive function in ovarian cancer. A subset of patients had evidence of cognitive decline from baseline during chemotherapy treatment in this study as measured by the web-based assessment; however, changes were generally limited to no more than one domain.

BACKGROUND: The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer.
METHODS: Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing.
RESULTS: Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas).
CONCLUSIONS: In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers.

High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre-metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed 'serous tubal intraepithelial carcinoma' or STIC. Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall short of STIC but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high-grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of FTSCs were capable of multipotent differentiation and that the tumours derived from transformed FTSCs shared the histological and molecular features of HGSC. We also demonstrated that altered expression of some biomarkers seen in transformed FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and transformed FTSCs showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen in vivo. Biomarkers unique to STIC relative to normal tubal epithelium provide a basis for novel detection approaches to early HGSC, but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed FTSCs may provide unique early targets for prevention strategies. Central to these efforts has been the ability to clone and perpetuate multipotent FTSCs.

Primary Fallopian Tube Carcinomas are rare and share many clinical and histo- pathological features with primary peritoneal and high grade serous carcinomas of ovary. The three have a considerable overlap in pathogenesis and clinical course leading to the view of them being a single entity. Due to the same reason, International Federation of Obstetrics and Gynecology (FIGO) 2014, in the latest staging have staged them collectively with the clause of designating the primary wherever possible. Presenting symptoms of fallopian tube carcinoma are vague. The diagnosis is generally made in retrospect in women operated for adnexal mass. Imaging studies have not shown to be of much help in pre-operative diagnosis. Management strategies are same for all three regardless of their ovarian, tubal, or peritoneal derivation. Due to rarity, no randomized trials are available exclusively for FTC and most treatment strategies have been extrapolated from epithelial ovarian cancers. In recent times, there has been a rapidly increasing body of evidence supporting the tubal origin for all high grade serous carcinomas of ovary. This has led to growing interest in the strategy of prophylactic salpingectomy rather than salpingooophorectomy as a preventive measure for ovarian carcinomas.

A 64-year-old Japanese woman had rapidly progressing bilateral palmar contracture associated with severe pain on both palms over the previous 8 weeks, without a history of arthritis in any joints. We suspected palmar fibromatosis or fasciitis without polyarthritis. Because palmar fibromatosis is known to be associated with cancer, we performed cancer screening and the patient was subsequently diagnosed with fallopian tube cancer. This is the first case report of palmar fibromatosis or fasciitis without polyarthritis associated with fallopian tube cancer. The characteristic rapid progression of palmar contracture is a key finding that suggests the potential existence of a malignancy.

BACKGROUND: Readmission within 30days is a measure of care quality. Ovarian cancer patients are at high risk for readmission, but specific risk factors are not defined. This study was designed to determine risk factors in patients with ovarian cancer receiving upfront surgery and chemotherapy.
METHODS: The study population was enrolled to GOG 0218. Factors predictive of admission within 30days of a previous admission or 40days of cytoreductive surgery were investigated. Categorical variables were compared by Pearson chi-square test, continuous variables by Wilcoxon-Mann-Whitney test. A logistic regression model was used to evaluate independent prognostic factors and to estimate covariate-adjusted odds. All tests were two-tailed, α=0.05.
RESULTS: Of 1873 patients, 197 (10.5%) were readmitted, with 59 experiencing >1 readmission. One-hundred-forty-four (73%) readmissions were post-operative (readmission rate 7.7%). Significant risk factors include: disease stage (stage 3 vs 4, p=0.008), suboptimal cytoreduction (36% vs 64%, p=0.001), ascites, (p=0.018), BMI (25.4 vs 27.6, p<0.001), poor PS (p<0.001), and higher baseline CA 125 (p=0.017). Patients readmitted within 40days of surgery had a significantly shorter interval from surgery to chemotherapy initiation (22 versus 32days, p<0.0001). Patients treated with bevacizumab had higher readmission rates in the case of patients with >1 readmission. On multivariate analysis, the odds of re-hospitalization increased with doubling of BMI (OR=1.81, 95% CI: 1.07-3.07) and PS of 2 (OR=2.05, 95% CI 1.21-3.48).
CONCLUSION: Significant risk factors for readmission in ovarian cancer patients undergoing primary surgery and chemotherapy include stage, residual disease, ascites, high BMI and poor PS. Readmissions are most likely after the initial surgical procedure, a discrete period to target with a prospective intervention.

Leiomyomas from the fallopian tube are very rare and usually asymptomatic but may cause symptoms by torsion or obstruction. Herein, we describe the detailed imaging findings of tubal leiomyoma with myxoid degeneration. Tubal leiomyoma appeared as a well-defined juxtauterine tumor marginated by low-signal rims with intervening bridging vessels between the tumor and uterus. A tubal mass showing heterogeneous speckled high signals with intermediate signal background on T2-weighted image without diffusion restriction could suggest the probability of tubal leiomyoma with mxoid degeneration.

OBJECTIVES: Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy for bevacizumab.
METHODS: Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The presence of ascites was determined prospectively. Chi-square and Wilcoxon-Mann-Whitney tests compared baseline variables between subgroups. Survival was estimated by Kaplan-Meier method, and Cox proportional hazard models were used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on survival.
RESULTS: Treatment arms were balanced with respect to ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221 (20%) did not. Those with ascites were more likely to have: poorer performance status (p<0.001); serous histology (p=0.012); higher baseline CA125 (p<0.001); and suboptimal cytoreduction (p=0.004). In multivariate survival analysis, ascites was prognostic of poor OS (Adjusted HR 1.22, 95% CI 1.00-1.48, p=0.045), but not PFS. In predictive analysis, patients without ascites treated with bevacizumab had no significant improvement in either PFS (AHR 0.81, 95% CI 0.59-1.10, p=0.18) or OS (AHR 0.94, 95% CI 0.65-1.36, p=0.76). Patients with ascites treated with bevacizumab had significantly improved PFS (AHR 0.71, 95% CI 0.62-0.81, p<0.001) and OS (AHR 0.82, 95% CI 0.70-0.96, p=0.014).
CONCLUSIONS: Ascites in women with advanced ovarian cancer is prognostic of poor overall survival. Ascites may predict the population of women more likely to derive long-term benefit from bevacizumab.

BACKGROUND: Olaparib (AZD2281), a PARP-1/2 inhibitor, has been extensively investigated in clinical trials. However, limited clinical data are available about its long-term safety and anti-tumour activity.
METHODS: Patients had first participated in a phase I study of olaparib combined with carboplatin and/or paclitaxel. They continued with olaparib monotherapy in their best interest if they failed to tolerate the combination due to the treatment-related adverse events (TRAEs). Safety data were collected by physical examination and regular laboratory evaluations. Disease evaluations were performed by CT scan.
RESULTS: At data cutoff, 21 patients were included; 10 with breast, 9 with ovarian and 2 with fallopian tube cancer of whom 16 patients had a BRCA mutation (13 BRCA1; 3 BRCA2). TRAEs were mostly haematological and most prominent shortly after switching from combination to monotherapy, probably due to carry-over effects of chemotherapy. Over time, both severity and frequency of TRAEs decreased. Responses to olaparib were durable with a median treatment duration of 52 (range 7-183) weeks. In total, nine (43%) patients were still on study at data cutoff.
CONCLUSION: Continued long-term daily olaparib was found to be safe and tolerable. Encouragingly, patients who showed a favourable response on earlier combination therapy maintained this response on olaparib monotherapy.

OBJECTIVES: Combining histone deacetylase inhibitors and chemotherapy is synergistic. This phase I study combined escalating vorinostat doses with constant doses of carboplatin and gemcitabine for the treatment of recurrent platinum-sensitive ovarian cancer. The objectives of this study were to determine the maximally tolerated dose of this combination; secondary objectives included preliminary response rate of this regimen and toxicity profile.
METHODS: Fifteen patients with relapsed ovarian cancer were enrolled into this phase I study. Doses of carboplatin and gemcitabine were AUC 4 on day 1 and 1000 mg/m(2) on days 1 and 8, respectively; cycles were administered every 21 days. Vorinostat was tested using four different schedules. The first dose level (DL A) tested vorinostat as daily oral dosing from days 1 to 14. DL B tested twice daily (BID) vorinostat dosing on days 1-3 and 8-10. DL C tested BID vorinostat dosing on days 1, 2, 8, and 9, starting vorinostat 1 day prior to initiation of carboplatin and gemcitabine, and DL D tested vorinostat on days 1 and 2 with chemotherapy starting on day 2.
RESULTS: All four DLs tested resulted in dose-limiting toxicities, and no MTD was determined. Toxicities were mostly hematologic. Seven patients were evaluable for RECIST assessment, and six of them had partial responses (PR) via RECIST.
CONCLUSIONS: Combination of carboplatin, gemcitabine, and vorinostat has activity in relapsed platinum-sensitive ovarian cancer, but was difficult to combine because of hematologic toxicities in this phase I study. No maximally tolerated dose was found, and the study was terminated early.

OBJECTIVE: The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL).
METHODS: Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly.
RESULTS: Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma.
CONCLUSIONS: Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration.

Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture ("surgical spill") is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB).