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Concept: Fallopian tube cancer

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The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.

Concepts: Cancer, Lung cancer, Cancer staging, Lymph node, Gynecology, Prognosis, Fallopian tube cancer, Obstetrics and gynaecology

27

Primary fallopian tube carcinoma (PFTC) is a rare tumor, and it is very difficult to diagnose preoperatively. The aims of this study were to evaluate the clinicopathologic features of primary fallopian tube carcinoma (PFTC) and to review the current available literature on PFTC.

Concepts: Cancer, The Current, Fallopian tube, Fallopian tube cancer

27

To identify and review cases of isolated fallopian tube torsion (FTT) at our institution to further characterize diagnosis and management.

Concepts: Retrospective, Fallopian tube, Fallopian tube cancer

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The present study investigated the clinico-pathological features of fallopian tube malignancy (FTM) and elucidated the biological behavior of this disorder. Data were compiled concerning FTM from 68 patients from 7 institutes. The patients included 60 cases with fallopian tube carcinoma and 8 cases with fallopian tube carcinosarcoma. The clinical stage was stage III or higher in 72% of the cases. A complete response or partial response was achieved in 56 and 10 of the 68 patients with FTM, respectively, indicating a response rate of 97.1%. The median observation period for FTM was 41 months (3 to 126 months). Three of the 19 patients with stage I/II disease (16%) and 31 of the 49 patients with stage III/IV disease (63%) experienced recurrence, with a median progression-free survival of 17.5 months, and a 3-year overall survival of 77.2%. Regarding the site of recurrence, local intraperitoneal recurrence (26.2%) and solitary recurrences in lymph nodes (19.0%) and in the liver (16.7%) were relatively frequent. Secondary debulking surgery (SDS) was performed in 15 patients (44%) out of the 34 recurrent FTMs. Conversely, recurrence was associated with ascites (carcinomatous peritonitis) in 4 of the 34 recurrent patients, but all 4 patients died. The median survival period after recurrence was 28 months: 7.5 and 30 months with and without ascites, respectively (P<0.001). A univariate analysis showed that prognosis was significantly correlated only with whether SDS could be performed. These results suggest that since FTM frequently results in solitary recurrence, aggressive recurrence treatment including SDS could improve prognosis.

Concepts: Cancer, Cancer staging, Lymph node, Lymph, Univariate, Fallopian tube, Fallopian tube cancer, Recurrence relation

4

The epithelial lining of the fallopian tube is of critical importance for human reproduction and has been implicated as a site of origin of high-grade serous ovarian cancer. Here we report on the establishment of long-term, stable 3D organoid cultures from human fallopian tubes, indicative of the presence of adult stem cells. We show that single epithelial stem cells in vitro can give rise to differentiated organoids containing ciliated and secretory cells. Continuous growth and differentiation of organoids depend on both Wnt and Notch paracrine signalling. Microarray analysis reveals that inhibition of Notch signalling causes downregulation of stem cell-associated genes in parallel with decreased proliferation and increased numbers of ciliated cells and that organoids also respond to oestradiol and progesterone treatment in a physiological manner. Thus, our organoid model provides a much-needed basis for future investigations of signalling routes involved in health and disease of the fallopian tube.

Concepts: Cell, Disease, Stem cell, Cellular differentiation, Menstrual cycle, Adult stem cell, Fallopian tube, Fallopian tube cancer

2

The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. We report the long-term follow-up results for survival.

Concepts: Cancer, Metastasis, Lung cancer, Uterus, Chemotherapy, Chemotherapy regimens, Fallopian tube, Fallopian tube cancer

1

Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-α to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease. Here we describe the rationale and design of FORWARD I (NCT02631876), the first randomized, multicenter Phase III study to compare the safety and efficacy of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in women with folate receptor-α-positive, platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients will be randomized in a 2:1 ratio. The primary end point is progression-free survival, and key secondary objectives include comparison of overall response rates, overall survival and duration of response.

Concepts: Vitamin D, Cancer, Metastasis, Chemotherapy, Hereditary nonpolyposis colorectal cancer, BRCA2, Fallopian tube, Fallopian tube cancer

0

We wished to ascertain if atropine is useful for suppressing the pain suffered during four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) when assessing infertility in women. A total of 252 patients were divided into two groups to receive or not receive atropine (0.5 mg) injection 30 min before 4D-HyCoSy. Pain was evaluated using a numerical rating scale (NRS): during 4D-HyCoSy; upon two-dimensional transvaginal sonography; before catheter insertion; upon insertion and fixation of the catheter into the uterine cavity; 30 min after 4D-HyCoSy. According to the degree of patency of Fallopian tubes, the six patterns observed were integrated further into three patient groups: all-negative (both Fallopian tubes were negative), positive-and-negative (one Fallopian tube showed patency and the other showed stenosis or non-patency), and all-positive (both Fallopian tubes showed stenosis or non-patency). We compared the NRS scores and prevalence of side-effects other than pain between the atropine-injection and non-atropine-injection groups within the three groups mentioned above. The NRS score showed no significant differences among the groups at any time point (all p > 0.05). The difference prevalence of side-effects other than pain was significant between the atropine-injection and atropine-non-injection groups (p = 0.012). These data suggest that atropine does not reduce pain in patients during 4D-HyCoSy. However, atropine may reduce the prevalence of other side-effects during 4D-HyCoSy, which needs a further, large, prospective, multi-cohort study to verify. This article is protected by copyright. All rights reserved.

Concepts: Uterus, Dimension, Gynecology, Female reproductive system, All rights reserved, Fallopian tube, Fallopian tube cancer, Copyright

0

A 59-year-old woman developed a rash and severe arthralgia, which primarily affected her fingers. She displayed digital arthritis and nodules on the hands, chest, face, and oral cavity. Blood samples were normal. Skin biopsies revealed histiocytic proliferation. The surface marker profile and clinical findings were consistent with multicentric reticulohistiocytosis, which may occur as a paraneoplastic phenomenon. On workup, she was diagnosed with an otherwise asymptomatic stage IVC fallopian tube cancer. She experienced little effect of prednisolone, but her condition improved on antineoplastic treatment.

Concepts: Lung cancer, Biopsy, Small cell carcinoma, Fallopian tube, Fallopian tube cancer, Paraneoplastic syndrome

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Objective: Our goal was to determine the ex-vivo drug resistance assay, as well as the cytokine production, in response to platinum-based chemotherapy treatment in primary culture cells established from the tumor tissue of ovarian or fallopian tube carcinoma patients, and to predict the clinical responses to chemotherapy. Methods: Sensitivity to the platinum-based drug was analyzed in two ovarian cancer cell lines and 19 tumor samples using the primary cell culture obtained from 19 patients having ovarian or fallopian tube cancer that had undergone surgery from 2014 to 2017. Results: Our findings in the ovarian cancer cell lines showed that SKOV3 cells displayed 10-fold greater resistance to cisplatin and 5.8 times more resistance to carboplatin than A2780 cells. SKOV3 cells displayed platinum-induced IL-6 and IL-8 overproduction whereas wild type A2780 displayed no detectable cytokine production. Regarding the primary cell culture obtained from patients, ex-vivo drug resistance assay results revealed that although extreme drug resistance was correlated with late stage ovarian cancer (P= 0.031), it could not independently predict or alter the outcomes of patients with ovarian or fallopian tube cancer. No relationship was found between basal cytokine secretion and the clinical parameters. However, carboplatin-induced IL-6 and IL-8 production had a significant association with the clinical response to chemotherapy (P=0.016 and P=0.038 respectively). Carboplatin-induced IL-8 overproduction was correlated with FIGO staging III-IV (P=0.026), but no correlation between carboplatin-induced IL-6 and FIGO staging (P= 0.061) was noted. Conclusion: These results suggest that cytokine production in response to platinum-based chemotherapy in primary culture cells may be useful as a predictive marker for the therapeutic outcomes among ovarian or fallopian tube cancer patients.

Concepts: Cell, Cancer, Metastasis, Oncology, Cell biology, Chemotherapy, Cell culture, Fallopian tube cancer