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Malignant mixed Mullerian tumor of the fimbriated end of the fallopian tube: origin as an intraepithelial carcinoma.

BACKGROUND: A paucity of examples of malignant mixed Mullerian tumors (MMMT) of the fimbriated end of the fallopian tube has been reported. CASE: We report a first case of FIGO Stage IV primary MMMT, heterologous type, in the right fimbria of a 77-year-old woman associated with symptomatic pleural spread who succumbed with recurrent disease 12 months after resection and postoperative paclitaxel and carboplatin chemotherapy. CONCLUSIONS: The identification of intraepithelial carcinoma in this tumor lends support to a role of the epithelial component in fimbrial MMMT histogenesis as seen for MMMT at other anatomic sites. Comparison of the clinical management of these tumors shows prolonged survival of patients whose treatment included postoperative pelvic external radiotherapy.

Aged↗

A successfully treated case of primary tubal choriocarcinoma coexistent with viable intrauterine pregnancy.

BACKGROUND: Choriocarcinoma of the fallopian tube is extremely rare as is choriocarcinoma with a viable pregnancy. We present an unusual case of prima gravida at 33 weeks gestation that was diagnosed as having tubal choriocarcinoma which was successfully treated by chemotherapy. CASE: A 31-year-old prima gravida at 32(+3) weeks gestation was admitted complaining of dyspnea and blood tinged sputum. Suspecting a left adnexal malignant tumor with pulmonary metastasis, delivery of the baby for optimal treatment of the mother's tumor was planned. Cesarean delivery was performed because of induction failure. Tumorectomy with left salpingectomy and infracolic omentectomy was performed for a left tubal tumor. Microscopic findings revealed choriocarcinoma with extensive hemorrhage. Its FIGO stage was III and its WHO prognostic score 12, representing high risk. After 4 cycles of chemotherapy, serum beta-hCG level fell to the normal range. The patient and her baby remain disease-free 16 months after disease diagnosis. CONCLUSION: This is the first reported case of tubal choriocarcinoma coexistent with a viable pregnancy, in which the baby survived and the mother was successfully treated by chemotherapy.

Adult↗

Transfusion utilization during adnexal or peritoneal cancer surgery: effects on symptomatic venous thromboembolism and survival.

OBJECTIVE: To determine whether perioperative packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions during ovarian, tubal, or peritoneal cancer surgery increase the risk of symptomatic postoperative venous thromboembolism (VTE) and adversely affect overall survival. METHODS: We conducted a retrospective review of all cases of surgical exploration for resection of stage IIIC-IV adnexal/peritoneal cancer between November 1998 and May 2002 at Memorial Sloan-Kettering Cancer Center. Patients with a history of prior or active preoperative VTE were excluded. Routine intraoperative and postoperative VTE prophylaxis including lower extremity external pneumatic compression with or without postoperative subcutaneous heparin was utilized in all cases. Symptomatic postoperative VTE was diagnosed by lower extremity Doppler or computerized tomography (excluding cases with only ovarian vein thrombosis). Clinical parameters were examined by a logistic regression analysis to identify independent prognostic predictors of postoperative symptomatic VTE, which occurred within 30 days of surgery. Survival was calculated using the Kaplan-Meier method. RESULTS: In all, 174 patients underwent exploratory surgery, and 6 (3.4%) were excluded due to active or prior history of VTE. Of the remaining 168 patients, 71 (42%) received at least one perioperative transfusion of PRBC or FFP. Postoperative VTE was documented in 5 of 46 (11%) patients who received a postoperative transfusion compared to 3 of 122 (2.5%) patients who did not (P = 0.04; odds ratio, 4.8); moreover, VTE was noted in 3:16 (19%) patients who received postoperative FFP compared to 5:152 (3.3%) patients who did not (P = 0.01, odds ratio of 6.78). Age, stage, body mass index, length of the operation, blood loss, presence of ascites, volume of ascites, residual disease status, preoperative hemoglobin level and coagulation profile were not associated with increased risk for VTE. When survival results were stratified by transfusion utilization and controlling for optimal debulking status, perioperative transfusions had no apparent effect on overall survival. CONCLUSION: In women with stage IIIC-V disease, postoperative blood product transfusions particularly FFP were associated with increased risk of DVT and PE, but transfusions had no impact on overall survival.

Adult↗

Paraneoplastic cerebellar degeneration with fallopian tube adenocarcinoma.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is rarely caused by fallopian tube adenocarcinoma. CASE: We present a patient with PCD and fallopian tube cancer. Anti-Yo antibody, one of an anti-neuronal antibody, was positive in serum and cerebrospinal fluid. She was also positive for HLA A24, which is common in patients with PCD. Radical surgery did not significantly ameliorate her neurological impairment, although the dysarthria improved slightly. CONCLUSION: This case highlights the importance of detecting the underlying malignancy in patients with subacute neurological impairment and shows that fallopian tube cancer can potentially cause PCD.

Adenocarcinoma↗

Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers.

OBJECTIVE: To estimate the likelihood of occult cancer diagnosis at prophylactic oophorectomy in BRCA1 and BRCA2 carriers in different age groups and to determine the histopathology of these lesions. METHODS: We describe a series of 159 female BRCA1 or BRCA2 carriers who underwent prophylactic oophorectomy at the University Health Network, Toronto from January 1, 1992 to June 30, 2004. RESULTS: Seven (4.4%) occult cancers were detected at pathologic examination. None of the 159 subjects had clinical signs or symptoms of ovarian carcinoma prior to, or at the time of, surgery. Only two cancers were grossly visible at surgery. There were 94 BRCA1 carriers, of whom six were found to have an occult cancer (6.4%). In contrast, only one of the 65 BRCA2 carriers was found to have an occult cancer (1.5%). Three of the seven cases of occult malignancy involved the fallopian tube and not the ovaries. CONCLUSION: Approximately 6% of BRCA1 carriers and 2% of BRCA2 carriers who undergo prophylactic salpingo-oophorectomy will be found to have occult carcinomas if the ovaries and tubes are rigorously examined. A significant proportion of these appear to originate in the fallopian tube. No cancers were detected among women who had the operation at age 39 or younger.

Adult↗

Mesonephric adenocarcinoma of the vagina with a 3-year follow-up.

BACKGROUND: Mesonephric adenocarcinoma of the vagina is exceedingly rare, with only one well-documented case in the literature. Little is known regarding clinical presentation, pathological characteristics, therapy, or prognosis of the vaginal mesonephric adenocarcinoma. CASE: A 55-year-old woman presented with a polypoid mass at the right vaginal apex, extending to the right paravaginal tissue. The tumor was an adenocarcinoma with ductal and tubular pattern arising in a background of mesonephric remnants. Tumor cells showed immunoreactivity for pankeratin, epithelial membrane antigen (EMA), and calretinin. The right fallopian tube and one paravaginal lymph node were positive for metastases. The patient is disease-free 3 years after surgery, radiation therapy, and chemotherapy. CONCLUSION: We report the second case of mesonephric adenocarcinoma of the vagina with metastasis to the right fallopian tube and to one paravaginal lymph node.

Adenocarcinoma↗

A phase I trial of gemcitabine and topotecan in previously treated ovarian or peritoneal cancer: a Gynecologic Oncology Group study.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of the combination of gemcitabine and topotecan in women with previously treated epithelial ovarian, peritoneal, or fallopian tube cancer. METHODS: Patients with recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. Initial treatment was gemcitabine at a dose of 800 mg/m(2) on days 1, 8, and 15 and topotecan at a dose of 0.5 mg/m(2) on days 2-5, with cycles repeated every 28 days. Dose escalations were planned first for topotecan (Cohort I, Dose Levels 1-5) then for gemcitabine (Cohort II, Dose Levels 6-9) until the MTD was reached. RESULTS: Ten patients received a total of 29 cycles. When none of the first four patients could complete therapy as prescribed due to toxicity, doses for each drug were reduced by 1 day. The next six patients were treated at the modified schedule of gemcitabine days 1 and 8 and topotecan days 2-4 (Dose Level -1). Despite this modification, dose-limiting toxicities including neutropenia, thrombocytopenia, and stomatitis occurred at Dose Level -1, and the study was closed early. CONCLUSIONS: At both the initial dose schedule and an attenuated schedule, the combination of gemcitabine and topotecan produced dose-limiting toxicities in women with previously treated epithelial ovarian or peritoneal cancer.

Aged↗

Reclassification of a tubal leiomyosarcoma as an eGIST by molecular evaluation of c-KIT.

BACKGROUND: Extragastrointestinal stromal tumors (eGISTs) are rare mesenchymal-derived tumors arising outside of the GI tract. eGISTs are often histologically confused with leiomyosarcoma. Distinction between eGIST and leiomyosarcoma is critical because of the unique responsiveness of eGISTs to the molecularly targeted agent imatinib. CASE: A woman presented with a history of tubal spindle cell tumor that was initially diagnosed and treated as a leiomyosarcoma. Because of minimal response to sarcoma directed chemotherapy, the possibility that the tumor was in fact an eGIST was investigated and supported by immunohistochemical and mutational analyses of the c-Kit receptor tyrosine kinase. The patient currently has stable disease control on imatinib for the last 18 months. CONCLUSIONS: The possibility of eGIST should be considered in the differential diagnosis of tumors with a spindle cell morphology in the gynecologic tract especially when involving the ovary, fallopian tube, or uterine serosa.

Base Sequence↗

Influence of interval between primary surgery and chemotherapy on short-term survival of patients with advanced ovarian, tubal or peritoneal cancer.

OBJECTIVE: To investigate the impact on short-term survival of time between surgery and start of first chemotherapy cycle in patients with advanced ovarian cancer. METHODS: This prospective, population-based study comprised 371 patients with epithelial ovarian, tubal or peritoneal cancer diagnosed in 2002-2003. All patients underwent primary surgery, followed at different intervals by chemotherapy. The data were derived from notifications to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan-Meier plots were used to show differences in survival, and Cox regression analysis was used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs). RESULTS: No difference in survival between patient groups was seen when time between surgery and start of chemotherapy was divided into quartiles. The group of patients with no residual disease and an interval between surgery and start of chemotherapy equal to or more than 6 weeks had non-significantly worse survival (unadjusted HR = 1.86; adjusted HR = 1.35) than those with an interval of less than 6 weeks. Patients with residual disease after surgery and chemotherapy at an interval of less than 6 weeks had worse short-term survival than patients without residual disease and the same interval before chemotherapy: unadjusted HR = 3.66 (95% CI, 2.09-6.40) and adjusted HR = 2.36 (95% CI, 1.22-4.57). CONCLUSIONS: The interval between surgery and start of chemotherapy had no major impact on short-term survival after ovarian cancer. Patients might be included in chemotherapy trials when interval between surgery and start of chemotherapy is more than 6 weeks. Any further investigation of a possible effect of interval between surgery and start of chemotherapy should be performed as a randomized trial.

Aged↗

Aggressive multimodality treatment in transitional cell carcinoma of the parafallopian tube: report of 2 cases and review of the literature.

BACKGROUND: Primary carcinoma of the fallopian tube is a rare and aggressive cancer. Information regarding its epidemiologic, biologic, and prognostic characteristics is limited; consequently, no standard treatment has been developed. We report the case histories of 2 women with transitional cell carcinoma (TCC) of the parafallopian tube treated with aggressive multimodality therapy, and the literature is reviewed. CASES: Two women presented with stage IIB TCC of the parafallopian tube. Both were treated with cytoreductive surgery followed by adjuvant intravenous chemotherapy with cisplatin, gemcitabine, and paclitaxel. Our consolidation treatment consisted of intraperitoneal chemotherapy using the same agents, and 1 patient also received additional hyperthermic chemotherapy with docetaxel. Both patients remain free of disease. CONCLUSION: In these 2 cases, an aggressive, multimodality regimen proved to be feasible and effective in treating TCC of the parafallopian tube.

Antineoplastic Combined Chemotherapy Protocols↗

Negative laparoscopy is highly predictive of negative second-look laparotomy following chemotherapy for ovarian, tubal, and primary peritoneal carcinoma.

OBJECTIVE: To determine the negative predictive value of second-look laparoscopy compared to laparotomy for assessment of pathologic complete response (CR) in patients with epithelial ovarian, tubal, and peritoneal carcinoma who achieved a clinical CR. METHODS: Data were analyzed from patients who participated in two sequential phase II clinical trials following primary cytoreductive surgery. Both trials required surgical evaluation for pathologic CR in those patients who achieved clinical CR. Protocol specified that assessment begin with laparoscopy; if negative, conversion to laparotomy was required. Collection of peritoneal washings was performed laparoscopically. RESULTS: One hundred thirty-six patients entered the 2 sequential clinical trials. Ninety-nine patients achieved clinical CR and 95 underwent second-look surgery (SLO). Seventy patients began SLO with laparoscopy and converted to planned laparotomy after biopsies were negative. Eighteen cases were positive based on laparoscopy with frozen section. Five additional patients had peritoneal washings and/or permanent pathology positive based on laparoscopic findings, yielding a positive SLO rate of 32.9%. Four of the 52 patients who underwent laparotomy (7.7%) were found to have persistent disease that was not detected on laparoscopic biopsy or washings and represent false-negative laparoscopy; all four patients had disease at peritoneal-based sites. The sensitivity and negative predictive value for intraoperative diagnosis of persistent disease by laparoscopy were 66.6% and 82.7%, respectively. The sensitivity and negative predictive value of laparoscopic peritoneal biopsies and washings compared to laparotomy, as determined by final pathology, were 85.2% and 91.5%, respectively. CONCLUSION: A negative second-look laparoscopy with negative peritoneal pathology and cytology is 91.5% predictive of negative laparotomy and is associated with a low complication rate even in the setting of prior extensive cytoreductive surgery. The small increase in sensitivity and negative predictive value afforded by laparotomy does not warrant the increased morbidity.

Adult↗

Phase II evaluation of a 3-day infusion of topotecan in patients with recurrent ovarian or primary peritoneal cancer.

OBJECTIVE: To assess the efficacy and toxicity profile in patients treated with topotecan at 2.0 mg/m2/day x 3 days every 3 weeks. MATERIALS AND METHODS: Eligibility criteria included patients with recurrent primary peritoneal or epithelial ovarian cancer with > or =6 months elapsed from time of prior platinum treatment. Patients were required to have a performance status of < or =2 and normal hepatic and renal function. Response to therapy and toxicity was assessed using standard criteria. Chi-square and Student's t tests were used as appropriate. Survival was assessed with Kaplan-Meier method. RESULTS: All 40 patients enrolled were assessable for response. The mean age of the patients was 63.2 years (range 43-85). Median time to progression from initial treatment was 11.8 months. A total of 286 cycles of chemotherapy were administered with an average of 7.1 cycles per patient. Overall median time to progression (TTP) with 3-day topotecan treatment was 21 weeks (range 6-43 weeks). Of the 33 patients with measurable disease, 24% (11-42%, 95% CI) demonstrated a response. Seven patients had CA-125 evaluable disease with a response of 43% (10-89%, 95% CI). Median progression-free survival (PFS) was 16 weeks (range 12-21 weeks, 95% CI). Median overall survival was 106 weeks (range 76-117 weeks, 95% CI). Assessment of toxicity by patient showed 90% demonstrating grade 3/4 neutropenia with the vast majority being uncomplicated. No severe non-hematological toxicity was observed. CONCLUSION: Administration of topotecan as a 3-day regimen is feasible with demonstrable activity and tolerable toxicity. Critical comparison to the 5-day regimen in a randomized fashion is warranted.

Adult↗

Three sequential chemotherapy doublets for the treatment of newly diagnosed advanced müllerian malignancies: the modified triple doublet regimen.

OBJECTIVE: Previously, we reported the use of three sequential doublets (Triple Doublets) in the treatment of women with newly diagnosed and advanced stage müllerian malignancies. The surgically defined negative second look operation (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment regimen that were predicted to reduce toxicity and possibly increase efficacy. METHODS: Open label two-cohort study. Patients with a new diagnosis of Stages II-IV müllerian malignancy were eligible. After cytoreductive surgery, patients were treated with three sequential doublets including 3 cycles of carboplatin and gemcitabine, and 3 cycles of carboplatin and paclitaxel, and 3 cycles of doxorubicin and topotecan. After therapy, all women were clinically staged and evaluated at SLO if clinical staging was negative for residual disease. Primary endpoints were toxicity and negative SLO rate with rates of 60% and 40% defined a priori in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or Stage IV (cohort 2), respectively. RESULTS: Eighty-five eligible patients were enrolled with a median age of 52 years. Forty-seven and thirty-eight women were in cohorts 1 and 2, respectively. 723 cycles of chemotherapy were delivered with no toxic deaths. Grades 3 and 4 toxicities included neutropenia in 75% of patients and thrombocytopenia in 65% of patients during at least one cycle of therapy. Fever and neutropenia were seen in 3.5% of patients. All Grades 3 and 4 non-hematologic toxicities were seen at a frequency of <10%. Seventy women underwent SLO with a negative SLO rate of 53% with an additional 9% having microscopically positive procedures. Negative SLO rate was 74% in cohort 1 and 36% in cohort 2. CONCLUSIONS: Treatment with the modified triple doublet regimen is tolerable with an encouraging pathologic CR rate.

Adult↗

Inguinal node metastasis as the initial presentation of primary fallopian tube cancer.

BACKGROUND: An initial presentation of inguinal metastasis in primary fallopian tube cancer in an asymptomatic patient is uncommon. All previously described palpable lymphadenopathies in fallopian tube cancer have been associated with widely disseminated intra-abdominal disease. CASE: This is the first case of inguinal node metastasis from fallopian tube cancer in a 72-year-old asymptomatic patient with a previous hysterectomy with no evidence of intra-abdominal disease. The metastasis was detected in the contralateral inguinal area. CONCLUSION: Fallopian tube cancer can present with inguinal metastasis, although this is an uncommon occurrence. A high index of suspicion must be maintained, especially in asymptomatic patients with negative imaging studies.

Aged↗

Paclitaxel, carboplatin and pegylated liposomal doxorubicin in ovarian and peritoneal carcinoma: a phase I study of the Gynecologic Oncology Group.

PURPOSE: Based on the activity and tolerability of liposomal doxorubicin in platinum- and paclitaxel-resistant ovarian carcinoma, we conducted a phase I trial of pegylated liposomal doxorubicin with paclitaxel and carboplatin to determine the maximum tolerated dose (MTD) in chemotherapy naive ovarian, peritoneal and tubal carcinoma patients. METHODS: Three schedules were studied: paclitaxel, carboplatin and pegylated liposomal doxorubicin every 28 days; paclitaxel and carboplatin every 21 days with liposomal doxorubicin every 42 days; and weekly paclitaxel, carboplatin (AUC=5) every 21 days and liposomal doxorubicin every 42 days. The paclitaxel dose was 175 mg/m(2) over 3 h on an every 3-4 week schedule and 60 mg/m(2) when administered weekly. Based on the frequency of neutropenic sepsis, grade 4 thrombocytopenia and > or =grade 3 non-hematologic toxicity, the starting dose of liposomal doxorubicin of 20 mg/m(2) was escalated to determine the MTD. RESULTS: A total of 210 (21-day) cycles were administered to 37 patients. Dose-limiting toxicity (DLT) occurred when liposomal doxorubicin was administered at 40 mg/m(2). Because of treatment-related delays resulting in decreased paclitaxel/carboplatin dose intensity, administration was modified to be given every 21 days, with liposomal doxorubicin given every 42 days. Since neutropenia was the DLT of this schedule, the schema was further modified to administer paclitaxel weekly; however, weekly administration was inconsistent because of toxicity. CONCLUSION: Paclitaxel 175 mg/m(2), carboplatin (AUC=5) and pegylated liposomal doxorubicin 30 mg/m(2) are tolerable without supportive therapy. The usual dose intensity of paclitaxel/carboplatin was maintained by administering liposomal doxorubicin every other cycle.

Adenocarcinoma↗

Endosalpingosis as a cause of chronic pelvic pain.

Endosalpingosis, a condition characterized by ectopic oviduct epithelium, is diagnosed histologically by the appearance of benign ciliated and nonciliated columnar cells in an abnormal location. Endosalpingosis is typically without symptoms. Our unusual case report shows symptomatic endosalpingosis first seen with chronic pelvic pain. Various aspects of this disease will also be discussed.

Adult↗