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Biomedical subjects

Robert L Coleman

Publications and source records attributed to Robert L Coleman.

At least 19 recordsLinked to original sources
PubMed2007

Metronomic chemotherapy enhances the efficacy of antivascular therapy in ovarian cancer.

Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic taxanes alone and in combination with AEE788-a dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) inhibitor-in an orthotopic mouse model of ovarian cancer. Growth-modulating effects of metronomic and maximum tolerated dose (MTD) regimens on overall survival were tested in vivo using both chemotherapy-sensitive (HeyA8 and SKOV3ip1) and chemotherapy-resistant (HeyA8-MDR) models. Treated tumors were stained for microvessel density (CD31), proliferation index (proliferating cell nuclear antigen), and apoptosis (terminal deoxyribonucleotide transferase-mediated nick-end labeling). The cytotoxic effects of MTD and metronomic dosing were tested with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of metronomic regimens on circulating endothelial precursors (CEP) and tumor-specific cell-free DNA levels were assessed. In vivo, metronomic docetaxel resulted in significant reduction of tumor growth in the taxane-sensitive cell lines, whereas metronomic docetaxel plus AEE788 had an additive effect resulting in significant prolongation in survival. Combination therapy was effective even in the taxane-resistant model. Metronomic chemotherapy alone and combined with AEE788 resulted in a decrease in the proliferative index and microvessel density of treated tumors, whereas combination therapy increased the apoptotic index (P < 0.001). In vitro, metronomic taxanes caused endothelial cell toxicity at 10- to 100-fold lower concentrations compared with MTD dosing. Metronomic regimens inhibited mobilization of CEPs (P < 0.05) and led to a decrease in cell-free DNA levels (P < 0.05). Our results suggest that metronomic taxane chemotherapy with dual EGFR and VEGFR inhibition is highly efficacious and should be considered for future clinical trials.

Angiogenesis Inhibitors↗
PubMed2007

Early changes in CA125 after treatment with pegylated liposomal doxorubicin or topotecan do not always reflect best response in recurrent ovarian cancer patients.

PURPOSE: To examine early changes in CA125 relative to objective response in patients with recurrent ovarian cancer treated with pegylated liposomal doxorubicin (PLD) or topotecan and to compare the CA125 trends between the two chemotherapeutics. PATIENTS AND METHODS: Patients with recurrent ovarian cancer, all of whom had measurable or evaluable disease, were randomized to receive 50 mg/m2 PLD every 28 days (n = 239) or 1.5 mg/m2 topotecan for 5 days every 21 days (n = 235) as part of a previously reported multicenter study. CA125 measurements were obtained prior to therapy and with each cycle of administration. Assessable patients underwent radiographic evaluation for response after two cycles of therapy. Objective responses were compared to trends in CA125 values at the end of cycles 1 and 2. CA125 changes were categorized as baseline (+/-10%), +/- 10%-25% variance, and > 25% variance. RESULTS: Among patients treated with PLD, 50% of complete responders (CR) and 41% of partial responders (PR) had increases in CA125 from baseline to cycle 1. Increases in CA125 were also seen in topotecan-treated patients; however, fewer patients had increases (20% and 8%, respectively). Overall, 15% of responding patients (CR + PR) receiving PLD and 6% receiving topotecan had elevated CA125 after two cycles of therapy. For those patients achieving a partial response, 19% of PLD-treated patients and 8% of topotecan-treated patients had CA125 levels above baseline at cycle 2. CONCLUSIONS: Considerable intrapatient variation in CA125 values is present among responding patients. Early increases in CA125 may not predict ultimate outcome, especially in PLD-treated patients.

Adult↗
PubMed2006

Intraperitoneal delivery of liposomal siRNA for therapy of advanced ovarian cancer.

PURPOSE: Intravenous (IV) delivery of siRNA incorporated into neutral liposomes allows efficient delivery to tumor tissue, and has therapeutic efficacy in preclinical proof-of-concept studies using EphA2-targeting siRNA. We sought to determine whether intraperitoneal (IP) delivery of these siRNA complexes was as effective at delivery and therapy as IV delivery. EXPERIMENTAL DESIGN: SiRNA was incorporated into the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). Alexa555-siRNA-DOPC was injected IP into nude mice bearing established ovarian tumors, and organs were collected for microscopic fluorescent examination. Subsequently, therapeutic efficacy of the IP versus IV routes was directly compared. RESULTS: Alexa555-siRNA in DOPC liposomes injected IP was diffusely distributed into intraperitoneal ovarian tumors. Delivery was also seen deeply into the liver and kidney parenchyma, suggesting that the predominant means of distribution was through the vasculature, rather than direct diffusion from the peritoneal cavity. In mice with orthotopic ovarian tumors, treatment with combined paclitaxel and IP EphA2-targeting siRNA-DOPC reduced tumor growth by 48-81% compared to paclitaxel/control siRNA-DOPC IP (HeyA8: 0.34 g v 0.66 g; SKOV3ip1: 0.04 v 0.21, p<0.01). This reduction was comparable to concurrently-treated mice with paclitaxel and EphA2 siRNA-DOPC injected IV, which showed a reduction in growth by 45-69% compared to paclitaxel/control siRNA-DOPC injected IV (HeyA8: 0.23g v. 0.42g; SKOV3ip1: 0.04 v. 0.13 g). CONCLUSIONS: IP injection of siRNA incorporated in DOPC allows intra-tumoral delivery and has therapeutic efficacy in orthotopic ovarian tumors. These findings may have therapeutic implications for siRNA-based strategies.

Animals↗
PubMed2006

The use of adjuvant radiation therapy in early endometrial cancer by members of the Society of Gynecologic Oncologists in 2005.

OBJECTIVES: To determine current patterns of care for early stage endometrial cancer by the members of the Society of Gynecologic Oncologists (SGO). METHODS: A survey detailing the use of adjuvant radiation in early stage endometrial cancer was conducted. Details of surgery, indications for staging, and use of adjuvant radiation for cases primarily seen by the respondent and for those cases referred postoperatively without staging information were collected and compared to a similar survey from 1999. RESULTS: The practice demographics of the respondents are similar to the 1999 survey. SGO members are now more likely to perform complete surgical staging during all surgeries for endometrial cancer than in 1999 (71% vs. 48%; P<0.0001). A higher percentage of respondents now describe surgery as a complete lymphadenectomy (76% vs. 44%: P<0.0001) and believe this is therapeutic (71% vs. 66%: P=0.04). Approximately half of SGO members now use laparoscopic assisted staging in the primary treatment of endometrial cancer. Since 1999, there is a significant decrease in the recommendation for postoperative RT. In almost all cases where RT is recommended, the use of vaginal RT is now more common than pelvic RT. In all situations, consult recommendations for additional intervention were more likely if complete surgical staging had not been performed, suggesting that all patients with endometrial cancer would benefit from surgery by a gynecologic oncologist. CONCLUSIONS: There is an increase in complete surgical staging of endometrial cancer, an increase in the use of laparoscopy, and a marked decrease in the use of pelvic RT since 1999.

Endometrial Neoplasms↗
PubMed2006

Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.

OBJECTIVE: To evaluate fundal injection of blue dye and radiocolloid for lymphatic mapping and sentinel node identification in women with high-risk endometrial cancer. METHODS: At laparotomy, 18 women with high-risk endometrial cancer had isosulfan blue and technitium-99 radiocolloid injected into the uterine fundus subserosally. Sentinel nodes were then identified either by direct observation of blue dye, by radioactive counts using a handheld gamma counter, or by a combination of both methods. The number and location of sentinel node(s) were recorded and compared with the final lymph node specimens after hysterectomy and selective lymphadenectomy. RESULTS: A sentinel node was identified in only 8 (45%) of the cases. Four patients had sentinel nodes only in the pelvis, 2 had sentinel nodes in the pelvis and above the bifurcation of the aorta, and 2 patients had sentinel nodes above the bifurcation of the aorta only. Seven (88%) patients had unilateral drainage of dye and the radiocolloid; the other patient had bilateral drainage. No patients had metastatic disease to sentinel or nonsentinel lymph nodes. CONCLUSIONS: Subserosal fundal injection of blue dye and the radiocolloid is a poor technique for identifying sentinel lymph nodes in patients with high-risk endometrial cancer.

Adult↗
PubMed2006

Antiangiogenic and antitumor effects of SRC inhibition in ovarian carcinoma.

Src, a nonreceptor tyrosine kinase, is a key mediator for multiple signaling pathways that regulate critical cellular functions and is often aberrantly activated in a number of solid tumors, including ovarian carcinoma. The purpose of this study was to determine the role of activated Src inhibition on tumor growth in an orthotopic murine model of ovarian carcinoma. In vitro studies on HeyA8 and SKOV3ip1 cell lines revealed that Src inhibition by the Src-selective inhibitor, AP23846, occurred within 1 hour and responded in a dose-dependent manner. Furthermore, Src inhibition enhanced the cytotoxicity of docetaxel in both chemosensitive and chemoresistant ovarian cancer cell lines, HeyA8 and HeyA8-MDR, respectively. In vivo, Src inhibition by AP23994, an orally bioavailable analogue of AP23846, significantly decreased tumor burden in HeyA8 (P = 0.02), SKOV3ip1 (P = 0.01), as well as HeyA8-MDR (P < 0.03) relative to the untreated controls. However, the greatest effect on tumor reduction was observed in combination therapy with docetaxel (P < 0.001, P = 0.002, and P = 0.01, for the above models, respectively). Proliferating cell nuclear antigen staining showed that Src inhibition alone (P = 0.02) and in combination with docetaxel (P = 0.007) significantly reduced tumor proliferation. In addition, Src inhibition alone and in combination with docetaxel significantly down-regulated tumoral production of vascular endothelial growth factor and interleukin 8, whereas combination therapy decreased the microvessel density (P = 0.02) and significantly affected vascular permeability (P < 0.05). In summary, Src inhibition with AP23994 has potent antiangiogenic effects and significantly reduces tumor burden in preclinical ovarian cancer models. Thus, Src inhibition may be an attractive therapeutic approach for patients with ovarian carcinoma.

Adenosine Triphosphate↗
PubMed2006

Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.

PURPOSE: Focal adhesion kinase (FAK) plays a critical role in ovarian cancer cell survival and in various steps in the metastatic cascade. Based on encouraging in vitro results with FAK silencing, we examined the in vivo therapeutic potential of this approach using short interfering RNA (siRNA) in the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). EXPERIMENTAL DESIGN: Therapy experiments of FAK siRNA with or without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8MDR in nude mice. Additional experiments with a cisplatin-resistant cell line (A2780-CP20) were also done. Assessments of angiogenesis (CD31), cell proliferation (proliferating cell nuclear antigen), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) were done using immunohistochemical analysis. RESULTS: A single dose of FAK siRNA-DOPC was highly effective in reducing in vivo FAK expression for up to 4 days as assayed by Western blot and immunohistochemical analysis. Therapy experiments were started 1 week after injection of the ovarian cancer cells. Treatment with FAK siRNA-DOPC (150 mug/kg twice weekly) reduced mean tumor weight by 44% to 72% in the three cell lines compared with the control group (Ps < 0.05 for HeyA8, A2780-CP20, and SKOV3ip1). When FAK siRNA-DOPC was combined with docetaxel, there was even greater reduction in mean tumor weight in all models (all Ps < 0.05). Similar results were observed in combination with cisplatin. Treatment with FAK siRNA-DOPC plus docetaxel resulted in decreased microvessel density, decreased expression of vascular endothelial growth factor and matrix metalloproteinase-9, and increased apoptosis of tumor-associated endothelial cells and tumor cells. CONCLUSIONS: Taken together, these findings suggest that FAK siRNA-DOPC plus docetaxel or platinum might be a novel therapeutic approach against ovarian cancer.

Animals↗
PubMed2006

Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.

Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify beta-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.

Animals↗
PubMed2006

Role of appendectomy at the time of primary surgery in patients with early-stage ovarian cancer.

OBJECTIVE: To determine whether appendectomy is warranted in patients with apparent early-stage ovarian cancer who undergo surgery for staging and cytoreduction and to determine the complication rate associated with appendectomy in such patients. METHODS: We reviewed the medical records of all patients who underwent appendectomy at the time of primary surgery for ovarian cancer at The University of Texas M. D. Anderson Cancer Center between January 1992 and December 2004 and who did not meet any of the following exclusion criteria: stage III or IV ovarian cancer, appendectomy as part of a second-look procedure or secondary tumor-reductive surgery, primary appendiceal cancer, primary gastrointestinal malignancy with metastasis to the appendix, incomplete clinicopathologic data, appendicitis as a preoperative diagnosis, primary fallopian tube cancer, primary peritoneal cancer, or documented dual primary tumors. RESULTS: Fifty-seven patients were included in this analysis. The median age was 47 years (range, 13-75). Median follow-up was 53 months (range, 3-147). Histologic diagnoses were as follows: invasive epithelial carcinoma, 35 patients (61%); tumor of low malignant potential, 15 patients (26%); malignant germ cell tumor, 4 patients (7%); and other, 3 patients (5%). Twenty-three patients (40%) had pure mucinous tumors. Forty-six patients (81%) had stage I and 11 patients (19%) had stage II disease. The median CA-125 level was 36.2 U/mL (range, 7-7900). No patient had evidence of appendiceal involvement. No patient suffered an intraoperative or postoperative complication directly related to appendectomy. CONCLUSIONS: Appendectomy at the time of surgery for apparent early-stage ovarian cancer is not associated with complications but should not be routinely recommended.

Adolescent↗
PubMed2006

CA-125 response in patients with recurrent ovarian or primary peritoneal cancer treated with pegylated liposomal doxorubicin or topotecan.

OBJECTIVE: Recent additions of novel chemotherapeutics, such as pegylated liposomal doxorubicin (PLD) and topotecan (TPT), have provided clinicians with multiple options for treating recurrent ovarian cancer. Evaluating treatment response in patients without radiographic or physically measurable disease is problematic, thereby CA-125 values may be the only available objective criteria. It has been advocated that several cycles of novel agents are required prior to an observed CA-125 response. In this study, we sought to gain insight into response patterns regarding CA-125 in responders vs. non-responders and to determine whether specific "cut-off" values could help predict ultimate clinical response. METHODS: Patients with recurrent ovarian cancer who received either single agent PLD, TPT, or both were included. CA-125 levels were evaluated prior to initiation of chemotherapy and thereafter for each additional cycle. The Rustin criteria were utilized to evaluate CA-125 response. RESULTS: Fifty-four of 120 patients were judged to be responders. When comparing responders to non-responders, as expected, the majority of responders demonstrated a decrease after each of the first 4 cycles. However, nearly 50% of responders who received PLD demonstrated an increase in CA-125 after cycle 1. There were no responders who demonstrated two successive rises in CA-125. CONCLUSION: The majority of patients with recurrent ovarian cancer who will ultimately manifest a CA-125 response to novel agents, such as TPT or PLD, will demonstrate a decrease following each cycle. An initial increase in CA-125 should not mandate discontinuation of current therapy, but a successive rise over two or more cycles reliably predicts that a treatment response ultimately is unlikely.

Adult↗
PubMed2006

A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy. STUDY DESIGN: Women (n = 519) were randomized (4:1) to receive alvimopan 12 mg (n = 413) or placebo (n = 106) > or = 2 hours before the operation then twice daily for 7 days (hospital and home). Adverse events were monitored up to 30 days after the last dose of study drug was administered. Efficacy was assessed for 7 postoperative days. RESULTS: Overall, the most common adverse events were nausea, vomiting, and constipation; < 5% of patients discontinued use because of adverse events. Alvimopan significantly accelerated the time to first bowel movement (hazard ratio, 2.33; P <.001). Average time to first bowel movement was reduced by 22 hours, with more frequent bowel movement and better bowel movement quality found in the treatment cohort. CONCLUSION: Alvimopan has a safety profile that is similar to that of placebo and provides significantly improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy.

Adult↗
PubMed2006

Electrothermal bipolar coagulation for pelvic exenterations.

OBJECTIVES: The morbidity associated with pelvic exenteration is high; however, patients undergoing this procedure have no other curative treatment options. Excessive blood loss is a common complication of this procedure. We evaluated whether use of an electrothermal bipolar coagulator (LigaSure Atlas, ValleyLab, Boulder, Colorado, USA) during pelvic exenteration is safe and whether it reduces intraoperative blood loss, intraoperative blood transfusion requirements, and length of hospital stay. METHODS: Between September 2003 and January 2005, 12 patients underwent pelvic exenteration (total, anterior, or posterior) performed using the electrothermal bipolar coagulator. Estimated blood loss, transfusion requirements, length of hospital stay, and complications necessitating reoperation were evaluated. RESULTS: The mean age was 55 years (range, 30-77), the mean estimated blood loss was 1931 ml (range, 1300-1500 ml), the mean number of units of packed red blood cells transfused intraoperatively was 3.4 U (range, 2-12 U), the mean operative time was 609 min (range, 400-940 min), and the mean length of hospital stay was 19.9 days (range, 7-27). There were no intraoperative complications related to the electrothermal bipolar coagulator use. None of the patients had any complications necessitating reoperation. CONCLUSIONS: Use of the electrothermal bipolar coagulator device during pelvic exenteration is safe and may decrease blood loss and the number of units of blood that must be transfused intraoperatively.

Adult↗
PubMed2006

Total laparoscopic radical hysterectomy and lymphadenectomy: the M. D. Anderson Cancer Center experience.

OBJECTIVE: To retrospectively evaluate the feasibility and morbidity of total laparoscopic radical hysterectomy and lymphadenectomy. METHODS: We performed a retrospective review of all patients who underwent a total laparoscopic radical hysterectomy at our institution between May 2004 and August 2005. Data collected included age, body mass index, stage, histopathologic subtype, tumor grade, estimated blood loss, perioperative blood transfusions, number and status of lymph nodes obtained, status of surgical margins, length of hospital stay, time to resumption of normal bladder function, intraoperative and postoperative complications, and disease-free interval. RESULTS: Twenty patients underwent total laparoscopic radical hysterectomy during the study period. None of the surgeries required conversion to laparotomy. The median patient age was 41.5 years (range, 25-76). Eighteen patients had cervix cancer (5 stage IA2 and 13 stage IB1), and 2 had endometrial cancer (1 stage IB and 1 stage IIIA). Among those with cervix cancer, 12 had adenocarcinoma, 4 squamous cell carcinoma, and 2 adenosquamous carcinoma. The median weight was 70 kg (range, 49-112). The median number of resected pelvic lymph nodes was 13 (range, 9-26). One patient had nodal disease. The surgical margins were free of disease in all cases. The median blood loss was 200 ml (range, 25-700 ml). Only 1 patient required an intraoperative blood transfusion (1 U packed red blood cells). The median length of hospital stay was 1 day (range, 1-5). There were 3 short-term complications--unintentional cystotomy, pulmonary embolus, and pneumomediastinum with subcutaneous emphysema. There were 2 long-term complications--vaginal eviscerations and a lymphocyst. The median time to resumption of normal bladder function was 16 days (range, 13-29). The median follow-up time was 8 months range (1-16). All patients remain free of disease at the time of this report. CONCLUSIONS: Total laparoscopic radical hysterectomy can be performed safely with minimal blood loss and postoperative morbidity, and patients undergoing this procedure may be discharged after an overnight stay in the hospital.

Adenocarcinoma↗
PubMed2006

The role of maintenance therapy and novel taxanes in ovarian cancer.

OBJECTIVES: Despite several studies reporting various degrees of success, the role of maintenance chemotherapy in ovarian cancer remains controversial. This article reviews the available data and the controversy surrounding maintenance therapy. In addition, the role of novel taxanes, which may offer an improved therapeutic index and reduced toxicity relative to conventional therapies in this setting, is discussed. METHODS: The available randomized clinical data on extended or maintenance therapy in ovarian cancer are reviewed. RESULTS: Available data indicate that patients with ovarian cancer undergoing taxane maintenance chemotherapy exhibit a reduced recurrence rate and a longer progression-free survival. CONCLUSIONS: While an additional randomized trial is needed to confirm these benefits and establish maintenance therapy as the standard of care, the authors conclude that maintenance therapy is a valuable option that should be discussed with patients until further data are available. The Gynecologic Oncology Group 212 trial is a randomized clinical trial that is designed to answer whether taxane maintenance therapy offers a survival advantage as well as to determine the impact of such a therapeutic regimen on a patient's quality of life. This trial is also designed to address some of the questions regarding the role of a novel taxane in maintenance therapy in ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Historical progress in the initial management of ovarian cancer: intraperitoneal chemotherapy.

Despite measured improvement in survival with the introduction of the platinates and taxanes in treatment of advanced ovarian cancer, little additional progress has been made with conventional cytotoxic agents. Recently, the Gynecologic Oncology Group (GOG) published data from a study evaluating the merits of intraperitoneal chemotherapy in women with advanced, optimally cytoreduced ovarian cancer. They documented a significant advantage in progression-free and overall survival for the experimental regimen, a combination of intravenous paclitaxel and intraperitoneal cisplatin and paclitaxel, compared with standard intravenous cisplatin and paclitaxel chemotherapy. The intraperitoneal regimen was substantially more toxic and was associated with reduced short-term quality of life. The GOG trial joins six other published phase III trials since 1994 comparing intravenous with intraperitoneal chemotherapy in advanced-stage epithelial ovarian cancer. A recent meta-analysis suggests a 21% reduction in the hazard for progression (four studies) and death (seven studies). Reluctance to adopt a new standard of care is rooted in toxicity concerns. Further evaluation is warranted to clarify unanswered questions regarding administration schedule, agents, techniques, number of courses, and patient eligibility for intraperitoneal chemotherapy.

Carcinoma↗
PubMed2006

Usefulness of preoperative lymphoscintigraphy in patients who undergo radical hysterectomy and pelvic lymphadenectomy for cervical cancer.

OBJECTIVE: The purpose of this study was to assess the value of preoperative lymphoscintigraphy before intraoperative lymphatic mapping for sentinel lymph node identification during radical hysterectomy. STUDY DESIGN: Fifty patients underwent intraoperative lymphatic mapping on our institutional review board-approved protocol. The location of sentinel lymph nodes that were found on lymphoscintigraphy and intraoperative lymphatic mapping were compared. RESULTS: Fifteen of 21 patients (71%) with solitary sentinel lymph nodes that were found on lymphoscintigraphy had multiple sentinel lymph node basins found during the operation. Thirteen of 25 patients (52%) with unilateral sentinel lymph node basins that were found on lymphoscintigraphy had bilateral sentinel lymph nodes at intraoperative lymphatic mapping. Of 15 patients with 2 sentinel lymph node locations that were identified on lymphoscintigraphy, 12 patients (80%) had > or = 3 found during the operation. Of the sentinel lymph nodes that were located on the external iliac basin (n = 47) on lymphoscintigraphy, only 20 lymph nodes (43%) were found at that location during the operation. Concordance between the 2 methods was poor. Seven of the 9 patients with lymph node metastases had disease that was limited to the sentinel lymph nodes. CONCLUSION: Preoperative lymphoscintigraphy adds little value over intraoperative lymphatic mapping for sentinel lymph node identification during radical hysterectomy.

Adult↗
PubMed2006

Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary.

OBJECTIVE: To analyze the clinical behavior of patients with stage II-IV low-grade serous carcinoma of the ovary seen at our institution who underwent primary surgery followed by platinum-based chemotherapy. METHODS: Patients with stage II-IV low-grade serous carcinoma of the ovary from 1978 to 2003 were identified using existing databases. Clinicopathologic information was obtained from medical records. Progression-free survival and overall survival were estimated by the method of Kaplan and Meier. The log-rank test was used to compare differences between survival curves. Univariable and multivariable analyses were performed using Cox proportional hazards regression. RESULTS: We identified 112 eligible patients. Median age was 43 years.; 90% had stage III disease. Preoperative serum CA 125 was elevated in 86% of patients. The most common sites of extraovarian disease were omentum, fallopian tubes, pelvic peritoneum, and uterus. Response rate to platinum-based chemotherapy in 10 evaluable patients (15% of patients with gross residual disease) was 80%, and 42 patients underwent second-look surgery: microscopically negative findings, 2 (5%); microscopically positive disease, 13 (33%); macroscopically positive disease, 24 (62%); and insufficient information, 3 (7%). Median progression-free survival and overall survival times were 19.5 and 81.8 months. Persistent disease after primary chemotherapy was the only factor associated with shorter overall survival time (hazard ratio 3.46, 95% confidence interval 2.00-5.97, P<.001). CONCLUSION: Metastatic low-grade serous carcinoma of the ovary is characterized by young age at diagnosis and prolonged overall survival. Segregating women with this diagnosis in future clinical trials is warranted.

Adolescent↗