Uterine Artery Embolization with Gelfoam for Acquired Symptomatic Uterine Arteriovenous Shunting.

PURPOSE: To evaluate the technical and clinical success rates and safety of bilateral gelfoam uterine artery embolization (UAE) for symptomatic acquired uterine arteriovenous shunting due to prior obstetric or gynecologic event. MATERIALS AND METHODS: This was a retrospective study of consecutive patients of reproductive age who presented with abnormal uterine bleeding after recent gynecologic procedures or obstetric events between January 2013 and February 2018. Bilateral UAE was performed in all patients using gelfoam slurry. Technical success was defined as angiographic resolution of arteriovenous shunting. Clinical success was defined as cessation of symptomatic bleeding, resolution on follow-up imaging, or minimal estimated blood loss (EBL) (<50 ml) on subsequent elective dilation and curettage (D&C) procedure. RESULTS: Eighteen patients (mean age, 32.8 ± 7.1 years) were included. Technical success and clinical success were experienced by 17/18 (94.4%) and 16/17 (94.1%) patients, respectively. Angiography demonstrated arteriovenous shunting in 18/18 (100%) patients, with early venous drainage. Seven of 18 (38.9%) patients underwent subsequent scheduled D&C due to remaining retained products of conception, with an EBL of 17.9 ± 15.6 ml. There was 1 minor complication of a self-limited vascular access groin hematoma (1/18, 5.6%) and 1 major complication (1/18, 5.6%) of a pulmonary embolism detected 3 days after UAE. The length of clinical follow-up was 19.3 ± 15.5 months, in which 41.2% (7/17) of the patients became pregnant. CONCLUSIONS: UAE with gelfoam alone for symptomatic uterine arteriovenous shunting is a feasible treatment option that has a high technical and clinical success rate with a low rate of complications.

Paraneoplastic thrombocytosis in ovarian cancer.

BACKGROUND: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. METHODS: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. RESULTS: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. CONCLUSIONS: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).

Significance of perioperative infection in survival of patients with ovarian cancer.

OBJECTIVES: Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer. METHODS: Patients who underwent primary cytoreductive surgery were included in the analysis (n = 276). The enumeration and speciation of pathogens, antimicrobial agents used, and sensitivity assay results were culled from medical records and correlated to clinicopathologic demographics and survival outcomes. Perioperative infection was determined as a positive microbiology result obtained within a 6-week postoperative period. RESULTS: The incidence of perioperative infection was 15.9% (common sites: urinary tract, 57.3%, and surgical wound, 21.4%). Commonly isolated pathogens were Enterococcus species (22.4%) and Escherichia coli (19.4%) in urinary tract infection, and Bacteroides fragilis, E. coli, and Klebsiella pneumoniae (all, 16%) in surgical wound infection. Imipenem represents one of the least resistant antimicrobial agents commonly seen in urinary tract and surgical wound infections in our institution. Perioperative infection was associated with diabetes, serous histology, lymph node metastasis, bowel resection, decreased bicarbonate, and elevated serum urea nitrogen in multivariate analysis. Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival (median time, 8.4 vs 17.6 months; P < 0.001), and decreased overall survival (29.0 vs 51.8 months; P = 0.011). Multivariate analysis showed that perioperative infections other than urinary tract infection remained a significant risk factor for decreased survival (progression-free survival, P = 0.02; and overall survival, P = 0.019). CONCLUSION: Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

Patient-reported symptoms and survival in ovarian cancer.

OBJECTIVE: While the development of an index of clinical symptoms to use for the detection and diagnosis of ovarian cancer is under active investigation, the role of clinical symptoms in survival after the initial diagnosis is poorly understood. The aim of this study was to correlate the type and extent of clinical symptoms with survival outcomes in ovarian cancer. METHODS: Medical records of 276 cases of primary epithelial ovarian, fallopian tube, and peritoneal cancers were evaluated. Thirty-one symptoms in 5 categories were cataloged. The significance of clinical symptoms in progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Overall, 93.5% of ovarian cancer patients expressed at least 1 symptom at the time of initial diagnosis. The 3 most common symptoms were abdominal pain (40.6%), increased abdominal size (33.7%), and bloating (21.7%). In survival analysis, weight loss (16.3%), nausea/vomiting (13.4%), and lower extremity edema (6.5%) were significantly associated with both decreased PFS and OS (all, P < 0.05). In multivariate analysis, lower extremity edema remained the strongest significant symptom, associated with increased surgical mortality rate, decreased response rate to adjuvant chemotherapy after primary cytoreductive surgery, and diminished survival outcomes (median PFS, 4.9 vs 15.3 months, P < 0.0001; and median OS, 5.9 vs 49.1 months, P < 0.001). Multiple symptoms were associated with poor survival outcomes (individual number of symptom ≤1 vs 2 vs ≥3; median PFS, 26.8 vs 17.4 vs 11.7 months [P < 0.001]; and median OS, 70 vs 41.6 vs 37.2 months [P < 0.001]). CONCLUSIONS: Lower extremity edema at initial diagnosis is a strong prognostic indicator of ovarian cancer patient.

Inferior vena cava filter placement and risk of hematogenous distant metastasis in ovarian cancer.

BACKGROUND: Recent studies have suggested that inferior vena cava (IVC) filter placement in cancer patients is associated with decreased survival time after insertion. Causality, however, is yet to be understood. This study evaluates (i) the patterns of recurrence or progression of disease; and (ii) survival outcomes of ovarian cancer patients who underwent IVC filter placement. METHODS: A total of 274 patients who underwent primary cytoreductive surgery for epithelial ovarian, fallopian tube, and primary peritoneal cancers were identified for analysis. Anatomic location of the first recurrence or progression of disease, progression-free survival, and overall survival were correlated to IVC filter placement status inserted during the perioperative period. RESULTS: Overall, 38 (13.9%) patients underwent perioperative IVC filter insertion, of which 37 (97.4%) were permanently placed. The most common indication was newly diagnosed venous thromboembolism (VTE) (52.6%). Patients with IVC filter placement for VTE were more likely to develop subsequent deep vein thrombosis (25% vs. 7.2%, odds ratio, 4.31, 95% confidence interval, 1.40-13.3, P = 0.019), have hematogenous distant metastasis as the site of first recurrence or progression of disease (12-mo hematogenous distant metastasis ratio, 45.2% vs. 13.6%, hazard ratio, 5.10, 95% confidence interval, 2.35-11.1, P < 0.001, multivariate analysis), and show decreased survival outcomes (median progression-free survival, 5.7 vs. 15.3 mo, P < 0.001: and median overall survival, 22.1 vs. 47.2 mo, P = 0.002, both multivariate analysis) when compared with patients without IVC filter placement. CONCLUSIONS: Our results suggested that IVC filter placement for VTE in the perioperative period of primary cytoreductive surgery for ovarian cancer may be associated with increased risk of hematogenous distant metastasis and resulted in decreased survival.

Multidrug resistance gene (MDR-1) and risk of brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer.

BACKGROUND: To evaluate risk factors that predict brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer. METHODS: All patients with FIGO stage I to IV who underwent initial cytoreductive surgery between January 1995 and January 2009 were evaluated. The tumor samples were evaluated for 7 markers including multidrug resistance gene (MDR-1), DNA aneuploidity and S-phase fraction, human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor, p53 mutation, epidermal growth factor receptor, and CD31. Biomarker expression was evaluated as a predictor of hematogenous metastasis to the following locations: (i) liver and spleen, (ii) lung, and (iii) brain. RESULTS: There were 309 cases identified during the period. Of those, 5 (1.6%, 95% CI: 0.2%-3.0%) women developed brain metastasis. Time to onset of brain metastasis was significantly longer than that for other recurrent sites (median time to recurrence after initial cytoreduction, brain vs. lung vs. liver, 21.4 vs. 12.6 vs. 11.0 months, P< 0.05). Significantly increased expression of MDR-1 was seen in tumors from women who developed brain metastasis (brain vs. nonbrain sites, 80% vs. 4.2%-24.3%, P= 0.004). In multivariate analysis, MDR-1 was the only significant variable associated with the risk of brain metastasis. MDR-1 expression predicted brain metastasis (receiver-operator-characteristic curve analysis, AUC 0.808, P= 0.018), and with a 10% positive expression of MDR-1 as the cutoff value, sensitivity, specificity, positive predictive value, negative predictive value, accuracy of prediction of brain metastasis were 80%, 86.1%, 15.4%, 99.3%, and 85.9%, respectively (odds ratio: 24.7, 95% CI: 2.64-232, P= 0.002). CONCLUSIONS: Increased expression of MDR-1 in the tumor tissue obtained at initial cytoreduction is associated with increased risk of developing brain metastases in women with epithelial ovarian, fallopian tube, or peritoneal cancer.