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Wan J, Li XM, Gu J
Primary choriocarcinoma of the fallopian tube: a case report and literature review.
Eur J Gynaecol Oncol. 2014; 35(5):604-7 [PubMed] Related Publications

Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Primary fallopian tube choriocarcinoma is an extremely rare occurrence, especially in women over 50 years of age. This article concerns a case of tubal choriocarcinoma developing in a 54-year-old woman, which the authors present together with a brief review of the literature. The woman presented with irregular vaginal bleeding for two months, following three months of amenorrhea. Transvaginal dopolar and pelvic computed tomography (CT) scan showed an adnexal cystomic-solid mass. Her serum human chorionic gonadotropin (hCG) levels were 29,1116 mIU/ml. The patient underwent hysterectomy and bisalpingo-oophorectomy. Histology was suggestive of tubal choriocarcinoma. Immunohistochemistry tests were positive for the hCG, Ki 67, CK, PLAP, and negative for CD30, supporting the diagnosis of choriocarcinoma. A combination of 5-Fu and KSM was administrated postoperatively. After four cycles of chemotherapy, her serum hCG level fell to the normal range. The patient remains disease-free 14 months after disease diagnosis.

Kalampokas E, Sofoudis C, Boutas I, et al.
Primary fallopian tube carcinoma: a case report and mini-review of the literature.
Eur J Gynaecol Oncol. 2014; 35(5):595-6 [PubMed] Related Publications

Primary fallopian tube carcinoma (PFTC) is an uncommon gynecologic tumor, responsible for 0.14% to 1.8% of genital malignancies, with a mean incidence of 3.6 per million women per annum. The factors that contribute to its appearance are not well-known. Overall survival percentages for patients with PFTC are generally low. Although the preoperative diagnosis rarely occurs and it is usually first confirmed by the pathologist, an earlier diagnosis occurs with early clinical manifestation and prompt investigation leading to better prognosis. Both PFTC and epithelial ovarian cancer (EOC) are treated with similar surgical and chemotherapy methods. The authors report a case of a patient with bilateral high grade serous carcinoma of the fallopian tube, whose initial presentation was bilateral cystic adnexal masses and serosanguinous discharge, with no other pelvic involvement. This article also reviews in brief and presents updates of this rare gynecological malignancy.

Topolovec Z, Mrcela M, Sijanović S, et al.
Primary serous papillary adenocarcinoma of the fallopian tube.
Acta Clin Croat. 2014; 53(2):242-5 [PubMed] Related Publications

Fallopian tube cancer is least common of all gynecologic tumors, with the mean age at onset between 54 and 63 years. This case report presents a 67-year-old female, gravida 1, para 1, with primary adenocarcinoma of the fallopian tube, detected and diagnosed preoperatively in clinical stage IIIc. The patient was asymptomatic, with only mild vaginal discharge of amber color and normal measured value of CA 125. The diagnosis was based on routine clinical and ultrasound examination, followed by surgery, surgical-pathological staging of the disease, and finally paclitaxel and platinum based chemotherapy. The patient has been in remission for nine years now.

Cass I, Walts AE, Barbuto D, et al.
A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers.
Gynecol Oncol. 2014; 134(3):492-7 [PubMed] Related Publications

OBJECTIVE: To compare the frequency and distribution of candidate precursors of serous carcinoma in the fallopian tubes of BRCA mutation carriers to BRCA non-mutation carriers (controls) at risk-reducing bilateral salpingo-oophorectomy (RRSO).
METHODS: 78 BRCA carriers (52 BRCA1, 26 BRCA2) and 23 controls underwent RRSO. Fallopian tubes were serially cross-sectioned, and adnexa were entirely submitted and examined by two gynecologic pathologists blinded to BRCA mutation status. The presence and location of serous tubal intraepithelial carcinoma (STIC), p53 overexpression (≥ 6 consecutively stained nuclei), Ki67 overexpression, atypia/low grade dysplasia and epithelial hyperplasia were compared between BRCA carriers and controls. Patient age was dichotomized: ≤ 50 and >50 years.
RESULTS: 9 (12%) BRCA carriers had occult carcinoma: 8 STIC and 1 stage IC tubal carcinoma with STIC. No occult carcinomas or STIC was seen in controls. STIC involved the distal tube in all cases and was multifocal in three cases. STIC was more common in women >50 (p=0.06). P53 overexpression was common in BRCA carriers (30%) and controls (43%) (p=0.5) and did not correlate with age. Only 5/9 (55%) of STIC exhibited p53 overexpression. 2 patients had Ki67 overexpression: both BRCA1 carriers with STIC. No difference in the frequency of atypia/low grade dysplasia or hyperplasia was observed between BRCA carriers and controls.
CONCLUSIONS: STIC is the dominant precursor of serous fallopian tube carcinoma in BRCA carriers. There is insufficient evidence to support p53 overexpression alone as a putative precursor. Atypia/low grade dysplasia and epithelial hyperplasia are not pre-neoplastic lesions of serous fallopian tube carcinoma.

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Suidan RS, Ramirez PT, Sarasohn DM, et al.
A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer.
Gynecol Oncol. 2014; 134(3):455-61 [PubMed] Related Publications

OBJECTIVE: To assess the ability of preoperative computed tomography (CT) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal (>1cm residual disease) primary cytoreduction in advanced ovarian, fallopian tube, and peritoneal cancer.
METHODS: This was a prospective, non-randomized, multicenter trial of patients who underwent primary cytoreduction for stage III-IV ovarian, fallopian tube, and peritoneal cancer. A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery, respectively. Four clinical and 20 radiologic criteria were assessed.
RESULTS: From 7/2001 to 12/2012, 669 patients were enrolled; 350 met eligibility criteria. The optimal debulking rate was 75%. On multivariate analysis, three clinical and six radiologic criteria were significantly associated with suboptimal debulking: age ≥ 60 years (p=0.01); CA-125 ≥ 500 U/mL (p<0.001); ASA 3-4 (p<0.001); suprarenal retroperitoneal lymph nodes >1cm (p<0.001); diffuse small bowel adhesions/thickening (p<0.001); and lesions >1cm in the small bowel mesentery (p=0.03), root of the superior mesenteric artery (p=0.003), perisplenic area (p<0.001), and lesser sac (p<0.001). A 'predictive value score' was assigned for each criterion, and the suboptimal debulking rates of patients who had a total score of 0, 1-2, 3-4, 5-6, 7-8, and ≥ 9 were 5%, 10%, 17%, 34%, 52%, and 74%, respectively. A prognostic model combining these nine factors had a predictive accuracy of 0.758.
CONCLUSIONS: We identified nine criteria associated with suboptimal cytoreduction, and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score. These results may be helpful in pretreatment patient assessment.

Related: Ovarian Cancer

Penson RT, Moore KM, Fleming GF, et al.
A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.
Gynecol Oncol. 2014; 134(3):478-85 [PubMed] Related Publications

OBJECTIVE: Vascular endothelial growth factor (VEGF) receptor-mediated signaling contributes to ovarian cancer pathogenesis. Elevated VEGF expression is associated with poor clinical outcomes. We investigated ramucirumab, a fully human anti-VEGFR-2 antibody, in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Primary endpoints were progression-free survival at 6 months (PFS-6) and confirmed objective response rate (ORR).
METHODS: Women who received ≥ 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of <12 months with measurable disease were eligible. Patients received 8 mg/kg ramucirumab intravenously every 2 weeks.
RESULTS: Sixty patients were treated; one patient remained on study as of September 2013. The median age was 62 years (range: 27-80), and median number of prior regimens was 3. Forty-five (75%) patients had platinum refractory/resistant disease. Thirty-nine patients (65.0%) had serous tumors. PFS-6 was 25.0% (n=15/60, 95% CI: 14.7-37.9%). Best overall response was: partial response 5.0% (n=3/60), stable disease 56.7% (n=34/60), and progressive disease 33.3% (n=20/60). The most common treatment-emergent adverse events possibly related to study drug were headache (65.0%; 10.0% Grade ≥ 3), fatigue (56.7%; 3.3% Grade ≥ 3), diarrhea (28.3%; 1.7% Grade ≥ 3), hypertension (25.0%; 3.3% Grade ≥ 3), and nausea (20.0%; no Grade ≥ 3). Two patients experienced intestinal perforations (3.3% Grade ≥ 3). Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion, including increased VEGF-A, PlGF and decreased sVEGFR-2.
CONCLUSIONS: Although antitumor activity was observed, the predetermined efficacy endpoints were not met.

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Rabban JT, Garg K, Crawford B, et al.
Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.
Am J Surg Pathol. 2014; 38(6):729-42 [PubMed] Related Publications

Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

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Hunter SM, Ryland GL, Moss P, et al.
Genomic aberrations of BRCA1-mutated fallopian tube carcinomas.
Am J Pathol. 2014; 184(6):1871-6 [PubMed] Related Publications

Intraepithelial carcinomas of the fallopian tube are putative precursors to high-grade serous carcinomas of the ovary and peritoneum. Molecular characterization of these early precursors is limited but could be the key to identifying tumor biomarkers for early detection. This study presents a genome-wide copy number analysis of occult fallopian tube carcinomas identified through risk-reducing prophylactic oophorectomy from three women with germline BRCA1 mutations, demonstrating that extensive genomic aberrations are already established at this early stage. We found no indication of a difference in the level of genomic aberration observed in fallopian tube carcinomas compared with high-grade serous ovarian carcinomas. These findings suggest that spread to the peritoneal cavity may require no or very little further tumor evolution, which raises the question of what is the real window of opportunity to detect high-grade serous peritoneal carcinoma arising from the fallopian tube before it spreads. Nonetheless, the similarity of the genomic aberrations to those observed in high-grade serous ovarian carcinomas suggests that genetic biomarkers identified in late-stage disease may be relevant for early detection.

Coleman RL, Moon J, Sood AK, et al.
Randomised phase II study of docetaxel plus vandetanib versus docetaxel followed by vandetanib in patients with persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: SWOG S0904.
Eur J Cancer. 2014; 50(9):1638-48 [PubMed] Article available free on PMC after 01/06/2015 Related Publications

BACKGROUND: Vandetanib is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET, which has demonstrated clinical activity as a single agent and in combination with taxanes. We explored the efficacy, safety and toxicity of docetaxel and vandetanib in women with recurrent ovarian cancer (OC).
METHODS: Women with refractory or progressive OC were randomised 1:1 to docetaxel (75 mg/m(2), IV)+vandetanib (100mg daily, PO, D+V) or docetaxel (75 mg/m(2), D). Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents (as primary therapy) were allowed. The primary end-point was progression free survival (PFS). The study had 84% power to detect a PFS hazard ratio of 0.65, using a one-sided P of 0.1. This corresponds to an increase in median PFS from 3.6 months to 5.6 months. Patients progressing on D were allowed to receive single agent vandetanib (D → V).
RESULTS: 131 Patients were enrolled; two were excluded. 16% had received prior anti-angiogenic therapy. The median PFS estimates were 3.0 mos (D+V) versus 3.5 (D); HR: 0.99 (80% CI: 0.79-1.26). 61 Patients on D+V were assessable for toxicity; 20(33%) had treatment-related Grade (G) 4 events, primarily haematologic. Similarly, 17 (27%) of 64 patients receiving D had G4 events, primarily haematologic. 27 Evaluable patients crossed-over to V. 1/27(4%) experienced a G4 event. G3 diarrhoea was observed in 4% D → V patients. Median OS was 14 mos (D+V) versus 18 mos (D → V); HR(OS): 1.25 (80% CI: 0.93-1.68). Crossover vandetanib response was 4% (1/27 evaluable patients). High plasma IL-8 levels were associated with response to D+V.
CONCLUSIONS: Combination docetaxel+vandetanib did not prolong PFS relative to docetaxel alone in OC patients. No unexpected safety issues were identified.

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Alvarez RD, Sill MW, Davidson SA, et al.
A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: a gynecologic oncology group study.
Gynecol Oncol. 2014; 133(3):433-8 [PubMed] Article available free on PMC after 01/06/2015 Related Publications

OBJECTIVE: The purpose of this phase II trial was to evaluate the toxicity and antitumor activity of EGEN-001 in platinum resistant recurrent ovarian cancer.
METHODS: Eligible patients had weekly IP infusion of EGEN-001 at a dose of 24mg/m(2). Toxicity and antitumor activity were evaluated using CTCAE and RESIST criteria, respectively. Co-primary endpoints were tumor response and survival without progression (PFS) for at least 6months. Survival without progression before going onto a subsequent therapy (EFS) for at least six months was also considered.
RESULTS: A total of 58 EGEN-001 cycles were administered to 20/22 enrolled patients (median 2cycles, range 1-9). The most frequently associated adverse events related specifically to EGEN-001 treatment were grade 1/2 fatigue, fever, chills, abdominal pain, nausea, vomiting, anemia, thrombocytopenia, and leukopenia. Three of 20 EGEN-001 treated patients evaluable for toxicity elected to withdraw from the study motivated in part by grade 1 treatment related toxicities. There were no patients with partial or complete response (0%; 90% CI 0-10.9%). Seven (35%) of 16 patients evaluable for response had stable disease, and 9 (45%) had progressive disease. Six (30%) patients had a PFS of greater than six months, although three had gone off study and onto other therapies before six months. The estimated six-month EFS was 15%. The median PFS and OS were 2.89 and 9.17months, respectively.
CONCLUSION: EGEN-001 at the dose and schedule evaluated was associated with some but limited activity and was seemingly less tolerated in platinum resistant recurrent ovarian cancer patients.

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Nanaiah SP, Rathod PS, Rajkumar NN, et al.
Primary carcinoma of the fallopian tube: a review of a single institution experience of 8 cases.
ScientificWorldJournal. 2014; 2014:630731 [PubMed] Article available free on PMC after 01/06/2015 Related Publications

AIMS AND OBJECTIVES: To evaluate the clinicopathologic features, response to cytoreductive surgery and adjuvant platinum-based chemotherapy with or without paclitaxel.
MATERIALS AND METHODS: A retrospective observational study of 8 women with a histopathologic diagnosis of primary fallopian tube carcinoma (PFTC) from January 2000 to February 2013.
RESULTS: 4/8 (50%) of the women were in the early stage and an intraoperative frozen section was 100% effective in identifying fallopian tube carcinoma and then a staging laparotomy was performed. All 4/8 cases in the early stage had received and responded to single agent carboplatin and all are alive without clinical, radiological, or biochemical evidence of recurrence at the end of 2 years and the longest survivor has completed 13 years. Primary optimal cytoreductive surgery was achievable in 3/4 (75%) in advanced disease. All showed response to adjuvant paclitaxel and carboplatin (T+C), but all had succumbed to the disease following recurrence with mean progression-free survival of 19 months (range 15-21 months) and mean overall survival of 27 months (range 22-36 months).
CONCLUSION: The pivotal role played by a frozen section in diagnosing PFTC which is rare needs to be reemphasized, therefore justifying a primary staging laparotomy in an early stage. Prolonged survival observed in this group following an optimum tailored adjuvant single agent carboplatin is worth noting.

Suprasert P, Manopunya M, Cheewakriangkrai C
Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.
Asian Pac J Cancer Prev. 2014; 15(3):1145-8 [PubMed] Related Publications

BACKGROUND: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

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Reade CJ, McVey RM, Tone AA, et al.
The fallopian tube as the origin of high grade serous ovarian cancer: review of a paradigm shift.
J Obstet Gynaecol Can. 2014; 36(2):133-40 [PubMed] Related Publications

Research published over the past 10 years has suggested that most "ovarian cancer," and specifically the high-grade serous carcinoma (HGSC) subtype of ovarian cancer, actually originates in the fallopian tube. In this review, we examine the evidence supporting the tubal origin hypothesis for HGSC, and discuss the clinical implications of our improved understanding of the pathogenesis of ovarian cancer. We searched Medline R and Medline in-process and non-indexed citations from inception to December 15, 2012, to identify all English or French language articles discussing the origins of HGSC. Articles and findings were summarized descriptively. A step-wise transformation from normal epithelium to a lesion with the ability to invade and metastasize has been demonstrated within the fallopian tube. Intraepithelial or early invasive carcinoma of the fallopian tube is frequently identified in BRCA mutation carriers who undergo prophylactic risk-reducing salpingo-oophorectomy. In both BRCA mutation carriers and women from the general population, pre-invasive changes within the fimbriated end of the fallopian tube appear in association with early HGSC. Molecular and genetic studies, as well as in vitro and animal models, have also supported a tubal origin for HGSC. Whether the removal of fallopian tubes (salpingectomy) at the time of pelvic surgery for other reasons will lead to reductions in mortality from ovarian cancer is currently unknown, but it is an important area for future clinical research.

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Herzog TJ, Monk BJ, Rose PG, et al.
A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube.
Gynecol Oncol. 2014; 132(3):517-25 [PubMed] Related Publications

OBJECTIVE: To determine the safety and efficacy of the novel combination of docetaxel, oxaliplatin, and bevacizumab as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube after initial debulking surgery.
METHODS: Eligible patients (stage IB-IV) were treated with 6 cycles of oxaliplatin (85 mg/m(2)), docetaxel (75 mg/m(2)), and bevacizumab (15 mg/kg) every 3 weeks, followed by single-agent bevacizumab 15 mg/kg every 3 weeks to complete one year of therapy. The primary endpoint was 12-month progression-free survival (PFS).
RESULTS: A total of 132 patients (80 with measurable disease at baseline; 52 with non-measurable, evaluable disease at baseline) enrolled and received study treatment. At diagnosis, 76.5% of patients had stage III disease and 20% had stage IV. 62.9% were optimally cytoreduced. The most common grade 3/4 adverse events were neutropenia (42.4%), leukopenia (13.6%), hypertension (8.3%), fatigue (6.1%), and nausea (6.1%). One patient (0.8%) had a fatal gastrointestinal perforation. The best overall confirmed response rate (complete response+partial response [measurable disease subgroup]) was 58.6% (95% CI 49%, 67%). CA-125 response rates for the measurable and non-measurable disease subgroups were 83.0% and 81.5%, respectively. The 12-month PFS rate for the measurable disease subgroup was 65.7% (95% CI 53.4%, 76.7%); median PFS was 16.3 (95% CI 12.6, 19.6) months. Median overall survival was 47.3 (95% CI 34.1, upper limit not applicable) months.
CONCLUSIONS: This novel treatment regimen may provide a promising therapeutic approach for women with ovarian, primary peritoneal, or fallopian tube carcinoma. No unanticipated safety concerns were identified.

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Battelli C, Campo M, Buss MK, et al.
Safety and outcome of patients treated with a modified outpatient intraperitoneal regimen for epithelial ovarian, primary peritoneal or fallopian tube cancer.
Chemotherapy. 2013; 59(4):251-9 [PubMed] Related Publications

BACKGROUND: Despite the survival benefit of intraperitoneal (IP) chemotherapy observed in GOG172, significant toxicity and poor treatment completion rates have prevented the widespread acceptance of this regimen. Here, we report our experience with a modified outpatient GOG172 regimen.
METHODS: Eligible patients had stage III, optimally debulked epithelial ovarian, fallopian tube or primary peritoneal cancer that underwent IP port placement for administration of a modified GOG172 regimen consisting of: (i) intravenous paclitaxel 135 mg/m² on day 1 over 3 h; (ii) intraperitoneal cisplatin 75 mg/m² on day 2, and (iii) intraperitoneal paclitaxel 60 mg/m² on day 8. Day 8 IP paclitaxel was omitted until tolerance of the first cycle of IP cisplatin had been established.
RESULTS: Four or more cycles of IP chemotherapy were completed by 72.5% (29) of 40 eligible patients; 20% of patients exhibited catheter-related complications requiring port removal and discontinuation of IP chemotherapy. Grade 3-4 hematologic, metabolic and gastrointestinal toxicities occurred in 36, 8 and 21% of the patients, respectively. With a median follow-up of 47.7 months, progression-free and overall survival was comparable to GOG172.
CONCLUSIONS: This modified outpatient GOG172 regimen is associated with less toxicity and improved completion rates compared to the original GOG172 regimen.

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Narasimhaiah A, Ansari M, Haritwal A, Awasthi S
Fallopian tube papilloma--case report of a rare tumor.
Kathmandu Univ Med J (KUMJ). 2013 Jul-Sep; 11(43):250-2 [PubMed] Related Publications

Fallopian tube neoplasms are rare. We report a rare case of fallopian tube papilloma discovered incidentally in a 45 year old female, operated for procidentia. Right tube was dilated at the infundibular region, with friable grey white tissue in the lumen. Microscopy showed delicate branching papillae lined by a single layer of epithelium resembling tubal lining. There were no features to suggest a reactive hyperplasia in response to inflammation or of aggressive behaviour.

Nasser S, Arsenic R, Lohneis P, et al.
A case of primary peritoneal carcinoma: evidence for a precursor in the fallopian tube.
Anticancer Res. 2014; 34(1):407-12 [PubMed] Related Publications

BACKGROUND: Primary high-grade serous peritoneal carcinoma (PPSC) is a rare malignancy with an ambiguous pathogenesis.
CASE REPORT: We report on a 51-year-old woman presenting with a routine smear test cytology suspicious of adenocarcinoma. She underwent hysteroscopy, laparsocopy with multiple biopsies and bilateral salpingoophorectomy. She was diagnosed with a serous tubal intraepithelial carcinoma in situ (STIC) in the right fallopian tube. Subsequently, she underwent radical surgery and was diagnosed with peritoneal high-grade serous carcinoma. Interestingly, both ovaries remained histologically tumour-free.
DISCUSSION: High-grade serous carcinomas that arise on the peritoneum with tumour-free ovaries are rare. The findings in this case, coupled with current evidence, strongly suggest a precursor lesion in the fallopian tube (STIC lesions). The clinical implications of this theory reside in the potential for improving early detection strategies. Nonetheless, more data on precursor lesions in the fallopian tubes and their transformation to serous carcinoma are required to plan for future screening methods.

Velişcu A, Marinescu B, Costoiu L, et al.
Bilateral primary fallopian tube carcinoma: a case report.
Rom J Morphol Embryol. 2013; 54(4):1183-7 [PubMed] Related Publications

Primary cancer of the fallopian tube is a very rare tumor nowadays, accounting for approximately 0.14-0.3% of all tumors of the female genital tract. From these, bilateral primary cancer is found in less than 25% of all cases. We report here a case of bilateral primary cancer of the fallopian tube in a 48-year-old woman, associating uterine fibromatosis.

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Karst AM, Jones PM, Vena N, et al.
Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers.
Cancer Res. 2014; 74(4):1141-52 [PubMed] Related Publications

The fallopian tube is now generally considered the dominant site of origin for high-grade serous ovarian carcinoma. However, the molecular pathogenesis of fallopian tube-derived serous carcinomas is poorly understood and there are few experimental studies examining the transformation of human fallopian tube cells. Prompted by recent genomic analyses that identified cyclin E1 (CCNE1) gene amplification as a candidate oncogenic driver in high-grade serous ovarian carcinoma, we evaluated the functional role of cyclin E1 in serous carcinogenesis. Cyclin E1 was expressed in early- and late-stage human tumor samples. In primary human fallopian tube secretory epithelial cells, cyclin E1 expression imparted malignant characteristics to untransformed cells if p53 was compromised, promoting an accumulation of DNA damage and altered transcription of DNA damage response genes related to DNA replication stress. Together, our findings corroborate the hypothesis that cyclin E1 dysregulation acts to drive malignant transformation in fallopian tube secretory cells that are the site of origin of high-grade serous ovarian carcinomas.

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Martin LP, Sill M, Shahin MS, et al.
A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
Gynecol Oncol. 2014; 132(3):526-30 [PubMed] Related Publications

OBJECTIVE: This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer.
PATIENTS AND METHODS: Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of <12 months or a second recurrence, and adequate bone marrow and organ function. Patients received rilotumumab 20mg/kg IV every 14 days until evidence of unacceptable toxicity or disease progression. The study utilized co-dual primary endpoints of tumor response and six-month PFS to assess the efficacy of rilotumumab. Secondary endpoints included the frequency and severity of adverse events and the duration of progression-free and overall survival.
RESULTS: Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2-14%), and two women had 6-month PFS (6.5%; 90% CI 1.1-19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual.
CONCLUSION: Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian cancer.

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Bahar-Shany K, Brand H, Sapoznik S, et al.
Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma.
Gynecol Oncol. 2014; 132(2):322-7 [PubMed] Related Publications

OBJECTIVES: Ovulation-related inflammation is suspected to have a causal role in ovarian carcinogenesis, but there are no human models to study the molecular pathways. Our aim is to develop such an ex-vivo model based on human fallopian tube (FT) epithelium exposed to human follicular fluid (FF).
METHODS: FT epithelium was dissociated from normal surgical specimens. FF was obtained from donors undergoing in-vitro fertilization. The cells were cultured on collagen-coated Transwells and incubated with FF for various periods of time. The transcriptomic changes resulting from FF treatment were profiled using Affymetrix expression arrays. Specific characteristics of the FT pre-cancerous lesions were studied using immunohistochemistry, immunofluorescence, RT-PCR and XTT assay.
RESULTS: We show that FF exposure causes up-regulation of inflammatory and DNA repair pathways. Double stranded DNA breaks are induced. There is a minor increase in cell proliferation. TP53, which is the hallmark of the precursor lesion in-vivo, is accumulated. Levels of expression and secretion of Interleukin-8 are significantly increased.
CONCLUSIONS: Our model addresses the main non-genetic risk factor for ovarian cancer, namely the impact of ovulation. This study demonstrates the biological implications of in-vitro exposure of human FT epithelial cells to FF. The model replicates elements characterizing the precursor lesions of ovarian cancer, and warrants further investigation of the linkage between repeated exposure to ovulation-related damage and accumulation of neoplastic changes.

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Buza N, Rutherford T, Hui P
Genotyping diagnosis of nongestational choriocarcinoma involving fallopian tube and broad ligament: a case study.
Int J Gynecol Pathol. 2014; 33(1):58-63 [PubMed] Related Publications

A 22 year-old G1P1 woman presented to the emergency room with clinical impression of "ruptured right adnexal mass" and underwent a right salpingo-oophorectomy to rule out ectopic pregnancy. Instead, gross and microscopic examination revealed a pure choriocarcinoma involving the right fallopian tube and broad ligament. On the basis of the patient's age, recent history of delivery, last menstrual period for 10 weeks, large tumor mass, and possible pelvic lymph node metastasis, the patient promptly started to receive 8 cycles of multiagent chemotherapy regimen with a working diagnosis of high-risk gestational choriocarcinoma. Subsequent DNA genotyping analysis showed that the tumor cells had an identical genetic profile to that of the normal tissue of the patient, therefore establishing a final diagnosis of nongestational choriocarcinoma. Six months after the initial presentation, a second surgery was performed to remove a persistent right para-adnexal mass, which showed only necrotic tissue upon microscopic examination. The patient received 1 additional cycle of multiagent chemotherapy. She was alive without evidence of recurrence 26 months after the initial diagnosis.

Xiao P, Peng JJ, Li Y, et al.
Unusual calcifying fibrous tumor in the fallopian tube: review and discussion of the differential diagnosis.
Int J Gynecol Pathol. 2014; 33(1):40-4 [PubMed] Related Publications

Calcifying fibrous tumor (CFT) is a rare benign soft tissue tumor of unknown etiology and extremely rare in female reproductive system. We present a case of unusual CFT in the ampulla of fallopian tube occurring in a middle-aged female patient with multiple uterine leiomyomas. A hysterectomy was performed on a 48-year-old woman for uterine leiomyomas. At surgery, a solitary, well-defined nodule, measuring 1.0 cm in diameter, was incidentally observed on the wall of ampulla of right fallopian tube. The lesion of fallopian tube was resected totally. Histologically, this lesion was unencapsulated and composed of hyalinized collagenous fibrous tissue with psammomatous calcification and focal lymphoplasmacytic infiltrate. Sparsely fibroblast-like spindle cells were scattered in the dense hyalinized background with bland nuclei. By immunohistochemistry, vimentin was diffusely positive in most cells, and a focal reactivity for CD34 was also observed in spindle cells. However, they were negative for cytokeratin (AE1/AE3), S-100 protein, CD117, DOG1, SMA, desmin, and ALK. The Ki-67 labeling index of the lesion was <1%. A diagnosis of primary CFT of fallopian tube was made. To our knowledge, this is the first report of CFT occurring in female reproductive tract. Awareness of CFT and its distinctive features is important to avoid a diagnostic pitfall caused by histologic similarities to other spindle cell or calcifying lesions in unusual locations. Although marginal excision is usually adequate for most of CFT, long-term follow-up is suggested as delayed recurrence might occur infrequently.

Pennington KP, Walsh T, Harrell MI, et al.
Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas.
Clin Cancer Res. 2014; 20(3):764-75 [PubMed] Article available free on PMC after 01/02/2015 Related Publications

PURPOSE: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain.
EXPERIMENTAL DESIGN: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway.
RESULTS: Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Nonserous ovarian carcinomas had similar rates of homologous recombination mutations to serous carcinomas (28% vs. 31%, P = 0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic homologous recombination mutations was highly predictive of primary platinum sensitivity (P = 0.0002) and improved overall survival (P = 0.0006), with a median overall survival of 66 months in germline homologous recombination mutation carriers, 59 months in cases with a somatic homologous recombination mutation, and 41 months for cases without a homologous recombination mutation.
CONCLUSIONS: Germline or somatic mutations in homologous recombination genes are present in almost one third of ovarian carcinomas, including both serous and nonserous histologies. Somatic BRCA1/2 mutations and mutations in other homologous recombination genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of homologous recombination mutations in nonserous carcinomas supports their inclusion in PARP inhibitor clinical trials.

Related: Ovarian Cancer

Anton A, Schott S, Kaip G, et al.
Ki-67 and p53 expression of the fallopian tube mucosa in breast cancer patients with hereditary risk.
Arch Gynecol Obstet. 2014; 289(5):1079-85 [PubMed] Related Publications

PURPOSE: The fallopian tube has been implicated as a site of origin of sporadic and BRCA1-related ovarian cancer. To investigate if Ki-67 or p53 is altered in BRCA1 mutation carriers, we have studied the expression of these markers in morphologically normal mucosa in the fallopian tube and fimbriae.
METHODS: Prophylactic adnexectomy specimens from 24 patients (eight BRCA1 mutation carriers, eight non-mutation carriers, and eight with unknown BRCA1 status), were scored by automated image analysis for the amount of Ki-67 and wild-type p53 expression. All patients had a history of breast cancer and a family history of breast or ovarian cancer.
RESULTS: In the fimbriae, a median of 0.42 % Ki-67 and 0.04 % p53-positive epithelial cells was present, compared to a median of 0.36 % for Ki-67 and 0.05 % for p53 in the fallopian tube. Ki-67 expression decreased significantly with age (r = -0.45, p = 0.028). In contrast, p53 expression was not age-dependent for the whole group of patients (r = 0.25, p = 0.25). Subgroup analysis revealed a difference for p53 expression of the BRCA1 mutation carriers with respect to age (median 0.039 vs. 0.082 % for age less or greater than 50.5 years). Consequently, the p53/Ki-67 ratio showed an age-dependent increase, which was accelerated in the BRCA1-positive patients.
CONCLUSIONS: Ki-67 and p53 expression varies in morphologically normal tubal epithelial cells depending on age and BRCA1 mutation status. This may reflect an altered and age-dependent DNA repair in BRCA1 mutation carriers and may be related to increased risk of ovarian cancer arising in the fallopian tube.

Related: Breast Cancer BRCA1 MKI67 Ovarian Cancer TP53

Sehouli J, Olschewski J, Schotters V, et al.
Prognostic role of early versus late onset of bone metastasis in patients with carcinoma of the ovary, peritoneum and fallopian tube.
Ann Oncol. 2013; 24(12):3024-8 [PubMed] Related Publications

BACKGROUND: Bone metastases are a rare manifestation in the management of ovarian cancer and thought to be associated with a poor prognosis as sign of distant spread. Only few data exist on this rare condition. The present study aimed to more information on this very distinct patient collective.
PATIENTS AND METHODS: A retrospective chart review was carried out including all patients who had been treated from 1994 to 2009 for histologically confirmed ovarian, peritoneal and fallopian tube cancer. Overall, 1717 cases were detected and screened. Patients with bone metastasis were identified and analyzed regarding survival as well as various clinical variables.
RESULTS: A total of 26 women who had been diagnosed with bone metastases ante mortem could be identified, resulting in an incidence of 1.50%. The majority of patients presented multiple bone lesions (80.8%) and bone spread was symptomatic in 62.5% of the cases. Mean overall survival from primary diagnosis of EOC was 50.5 months (range: 2.5-142.5 months). Median overall survival after diagnosis of bone metastases was 7.2 months. When divided into two subsets depending on timepoint diagnosis of bone metastases, there was a significant difference in overall survival. The mean overall survival from primary diagnosis of EOC in the early-onset group (n = 8), defined as occurence of bone manifestation within 12 months, was 11.2 months. The mean overall survival in the late-onset group (n = 15) was 78.4 months (P = 0.000001).
CONCLUSIONS: The time interval from diagnosis to appearance of bone metastases is a prognostic factor in ovarian cancer. While early onset bone spread has a strong negative prognostic impact, late-onset bone diagnosis of bone metastases hardly influences the prognosis at all. This finding should be considered in the management of patients with bone metastases from ovarian cancer.

Related: Ovarian Cancer

Dietl J
Revisiting the pathogenesis of ovarian cancer: the central role of the fallopian tube.
Arch Gynecol Obstet. 2014; 289(2):241-6 [PubMed] Related Publications

BACKGROUND: Among all gynecological malignancies, ovarian cancer is associated with the highest rate of mortality. Recent findings now propose a pivotal role for the fallopian tube during ovarian cancer pathogenesis.
NEW INSIGHTS: Until recently, ovarian cancer was thought to derive from the ovarian surface epithelium. Nevertheless, attempts to define a precursor lesion from this tissue failed. Instead, prophylactic surgery performed on BRCA mutation carriers and subsequent histological analyses revealed a characteristic pre-neoplastic alteration at the fimbriated end of the fallopian tubes, the so-called serous tubal intraepithelial carcinoma (STIC). By morphology and molecular genetics, STIC was found to resemble serous ovarian cancer. As STIC can also be detected in >60 % of BRCA-unrelated serous ovarian carcinomas, it is now considered to be the precursor of the most common ovarian cancer subtype.
CONSEQUENCES: Based on this hypothesis, a salpingectomy, i.e., the removal of the post-reproductive fallopian tubes may remove the actual site of tumorigenesis and thereby prevent spreading over the ovarian surface and throughout the peritoneum. Consequently, prophylactic salpingectomy might protect against serous ovarian cancer. Moreover, the procedure interrupts the connection between the uterine cavity and the lesser pelvis. Hence, it prevents the ascension of exfoliated endometrial cells which will likely reduce the incidence of endometrioid and clear cell ovarian cancers. Increasing evidence suggests that serous ovarian cancer originates from the fimbriated distal end of the fallopian tube, whereas the ovary gets only involved at a later stage.
CONCLUSION: Given the lack of suitable screening or early detection strategies for ovarian cancer, post-reproductive salpingectomy deserves serious consideration as a prophylactic intervention that will likely confer significant protection against an often deadly disease.

Related: Ovarian Cancer

Hagemann AR, Novetsky AP, Zighelboim I, et al.
Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer.
Gynecol Oncol. 2013; 131(3):535-40 [PubMed] Article available free on PMC after 01/02/2015 Related Publications

OBJECTIVE: We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC).
METHODS: Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500 mg/m(2) IV and bevacizumab 15 mg/kg IV were administered every 3 weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS).
RESULTS: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Median follow-up was 25.7 months (range, 3.0-47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38-71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25-59), 18 stable disease (53%; 35-70) and 2 progressive disease (6%; 1-20). Median PFS was 7.9 months (95% CI, 4.6-10.9), with a median OS of 25.7 months (95% CI, 15.4-29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6 months prior to enrollment. Grade 3-4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment.
CONCLUSIONS: Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.

Related: Ovarian Cancer Pemetrexed Bevacizumab (Avastin)

Patrao L, Sa J, Fonseca-Moutinho JA, et al.
Left fallopian tube primitive serous adenocarcinoma presenting as a cardiac tamponade - a case report and review of literature.
Eur J Gynaecol Oncol. 2013; 34(3):261-2 [PubMed] Related Publications

A 61-year-old woman presented to the emergency room complaining of anterior left thoracic pain and shortness of breath even after minor efforts. Her previous medical history was unremarkable. Pulmonary angiographic tomography showed a moderate bilateral pleural effusion that had collapsed inferior lung lobes, a large pericardial effusion, and several enlarged lymph nodes in the anterior mediastinum. Echocardiogram (ECG) showed a considerable pericardial effusion with some degree of heart function impairment. Pericardiocentesis and thoracocentesis revealed neoplastic cells in both pericardial and pleural fluids. Abdominal and pelvic ultrasound showed a complex cystic mass with a 13-cm diameter located at left adnexal region and another complex cystic tumor with five-cm diameter at right adnexal region, with small amount of peritoneal effusion. Surgical staging was performed. Pathologic diagnosis was primitive left fallopian tube serous adenocarcinoma with peritubal involvement and multiple peritoneal and lymphatic metastases (FIGO Stage IV; TNM pT3c M1). Chemotherapy was initiated. Death occurred 25 months after diagnosis, with secondary dissemination (breast and lung). No recurrence of pericardial effusion was registered after chemotherapy, suggesting a high susceptibility of pericardial metastasis.

Katsumata N, Yasuda M, Isonishi S, et al.
Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial.
Lancet Oncol. 2013; 14(10):1020-6 [PubMed] Related Publications

BACKGROUND: 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.
METHODS: This randomised controlled trial was done at 85 centres in Japan. Patients with stage II-IV ovarian cancer were randomly assigned to receive conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min and paclitaxel 180 mg/m(2) on day 1) or dose-dense treatment (carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2) on days 1, 8, and 15). The treatments were repeated every 3 weeks for six cycles; responding patients had three additional cycles. The randomisation was done centrally by telephone or fax, stratified by residual disease, stage, and histological type. The primary endpoint was progression-free survival; overall survival was a secondary endpoint. Long-term information on adverse events was not collected. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00226915.
FINDINGS: 637 patients were enrolled, of whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the conventional regimen). Median follow-up was 76·8 months (IQR 68·9-85·6). Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group (28·2 months [95% CI 22·3-33·8] vs 17·5 months [15·7-21·7]; hazard ratio [HR] 0·76, 95% CI 0·62-0·91; p=0·0037). Median overall survival was 100·5 months (95% CI 65·2-∞) in the dose-dense treatment group and 62·2 months (52·1-82·6) in the conventional treatment group (HR 0·79, 95% CI 0·63-0·99; p=0·039).
INTERPRETATION: Dose-dense treatment offers better survival than conventional treatment and is a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer.

Related: Carboplatin Ovarian Cancer Paclitaxel

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