Maria C. Bell

Comparison of outcomes and cost for endometrial cancer staging via traditional laparotomy, standard laparoscopy and robotic techniques

OBJECTIVES The study purpose was to compare hysterectomy and lymphadenectomy completed via robotic assistance, laparotomy, and laparoscopy for endometrial cancer staging with respect to operative and peri-operative outcomes, complications, adequacy of staging, and cost. METHODS One hundred and ten patients underwent hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy for endometrial cancer staging. All cases were performed by a single surgeon, at a single institution (40 robotic, 40 laparotomy, and 30 laparoscopic) and were retrospectively reviewed to compare demographics and peri-operative variables including, operative time, estimated blood loss, lymph node count, hospital stay, complications, and return to normal activity. Additionally, a cost comparison between all three modalities was performed. RESULTS Patients undergoing robotic assisted hysterectomy and staging experienced longer operative time than the laparotomy cohort with no difference in comparison to the laparoscopic cohort (184 min, 108.6 min, 171 min, p<0.0001, p=0.14). Estimated blood loss was significantly reduced for the robotic cohort in comparison to the laparotomy cohort and comparable to laparoscopic cohort (166 cc, 316 cc, 253 cc, p=0.01, p=0.25). The complication rate was lowest in the robotic cohort (7.5%) relative to the laparotomy (27.5%) and laparoscopic cohorts (20%) (p=0.015, p=0.03). Average return to normal activity for the robotic patients was significantly shorter than those undergoing laparotomy (24.1 days versus 52 days, p<0.0001) and those undergoing laparoscopy (31.6 days, p=0.005). Lymph node retrieval did not differ between the 3 groups (robotic 17 nodes, laparotomy 14 nodes, laparoscopic 17 nodes). The total average cost for hysterectomy with staging completed via laparotomy was

Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study

12,943.60, for standard laparoscopy

Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

7569.80, and for robotic assistance

Expression and Functions of Transmembrane Mucin MUC13 in Ovarian Cancer

8212.00. The difference in cost between laparotomy and robotic cohorts was significant p=0.0001 while there was no statistically significant difference in cost between laparoscopy and robotic cohorts p=0.06. CONCLUSIONS Robotic hysterectomy provides comparable node retrieval to laparotomy and laparoscopic procedures in the case of the experienced laparoscopic surgeon. While robotic hysterectomy takes longer to perform than hysterectomy completed via laparotomy, it is equivalent to laparoscopic hysterectomy and provides the patient with a more expeditious return to normal activity with reduced post-operative morbidity. Additionally, the average cost for hysterectomy and staging was highest for laparotomy, followed by robotic, and least for standard laparoscopy.

Curcumin suppresses human papillomavirus oncoproteins, restores p53, Rb, and PTPN13 proteins and inhibits benzo[a]pyrene-induced upregulation of HPV E7.

PURPOSE To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. PATIENTS AND METHODS Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. RESULTS In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). CONCLUSION Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.

Pathologic Findings at Risk-Reducing Salpingo-Oophorectomy: Primary Results From Gynecologic Oncology Group Trial GOG-0199

BackgroundChemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells.MethodsCisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid) (PLGA) nanoparticle formulation of curcumin (Nano-CUR) was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods.ResultsCurcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre-treatment lowered β-catenin expression and transcriptional activity. Nano-CUR was successfully generated and physico-chemical characterization of Nano-CUR indicated an average particle size of ~70 nm, steady and prolonged release of curcumin, antibody conjugation capability and effective inhibition of ovarian cancer cell growth.ConclusionCurcumin pre-treatment enhances chemo/radio-sensitization in A2780CP ovarian cancer cells through multiple molecular mechanisms. Therefore, curcumin pre-treatment may effectively improve ovarian cancer therapeutics. A targeted PLGA nanoparticle formulation of curcumin is feasible and may improve the in vivo therapeutic efficacy of curcumin.

Physical strain and urgent need for ergonomic training among gynecologic oncologists who perform minimally invasive surgery

MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon and cancer. However, the expression and functions of MUC13 in ovarian cancer are unknown. In the present study, the expression profile and functions of MUC13 were analyzed to elucidate its potential role in ovarian cancer diagnosis and pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used to determine the expression profile of MUC13 by immunohistochemistry using ovarian cancer tissue microarrays and 56 additional epithelial ovarian cancer (EOC) samples. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with the normal ovary/benign tissues. Among all ovarian cancer types, MUC13 expression was specifically present in EOC. For the functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous MUC13 expression induced morphologic changes, including scattering of cells. These changes were abrogated through c-Jun NH(2) kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (P < 0.05) increases in cell motility, proliferation, and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our findings show the aberrant expression of MUC13 in ovarian cancer and that its expression alters the cellular characteristics of SKOV-3 cells. This implies a significant role of MUC13 in ovarian cancer.

Is Bilateral Lymphadenectomy For Midline Squamous Carcinoma Of The Vulva Always Necessary? An Analysis From Gynecologic Oncology Group (GOG) 173

Curcumin has great potential as a chemopreventive and chemotherapeutic agent; however, its effects on human papillomavirus (HPV)‐associated molecular events are inadequately explored. This study examined the effects of curcumin on HPV‐associated pathways involved in developing cervical cancer. We demonstrate for the first time that curcumin treatment suppresses cervical cancer cell growth in a three‐dimensional raft culture system. Curcumin also inhibits tumorigenic characteristics as shown by decreases in both clonogenic potential and cell motility. Additionally, our findings show that curcumin treatment inhibits the transcription of HPV16 E6/E7 as early as 6 h posttreatment and restores the expression of tumor suppressor proteins p53, retinoblastoma protein, and PTPN13. While smoking is a recognized risk factor for cervical cancer, the molecular effects of smoke carcinogens on the expression of HPV E6/E7 oncogenes are not well known. We show for the first time that exposure to benzo[a]pyrene (BaP), a tobacco carcinogen, increases the expression of HPV E7 oncoprotein suggesting a molecular link between smoking and cervical cancer. Importantly, curcumin decreases the BaP induced increase in the expression of HPV E7 oncoprotein. The results of this study clearly demonstrate that curcumin alters HPV‐associated molecular pathways in cervical cancer cells. These novel findings imply that curcumin may be an effective chemopreventive and therapeutic agent for cervical cancer prevention and treatment. Mol. Carcinog.

Risk factors for HPV infection among American Indian and white women in the Northern Plains.

PURPOSE Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study. PARTICIPANTS AND METHODS This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participants mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression. RESULTS Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P < .001) were associated with detection of clinically occult neoplasms at RRSO. For 387 women with negative BRCA1/2 mutation testing and normal CA-125 levels, findings at RRSO were benign. CONCLUSION Clinically occult cancer was detected among 2.6% of high-risk women undergoing RRSO. BRCA1/2 mutation, postmenopausal status, and abnormal preoperative CA-125 and/or TVU were associated with cancer detection at RRSO. These data can inform management decisions among women at high risk of ovarian/tubal cancer.

Combined Staining of TAG-72, MUC1, and CA125 Improves Labeling Sensitivity in Ovarian Cancer: Antigens for Multi-targeted Antibody-guided Therapy

OBJECTIVES There is limited data regarding physical strain and minimally invasive gynecologic surgery (MIS). We sought to evaluate ergonomic strain among gynecologic oncologists. METHODS An online survey was sent to all physician members of the Society of Gynecologic Oncology in North America in 2010. The survey contained 42 questions and data was analyzed using univariate and bivariate analyses with summary statistics, t-tests, and chi-squared test. RESULTS There were 260 respondents (31.2%) to the survey. Case mix was 26% benign and 64% oncologic surgery. Over 52% of respondents had been in practice for greater than 11 years and 52% practice in an academic setting. Physical discomfort related to MIS was reported in 88% (216/244) of surgeons with 52% reporting persistent pain. Increased pain symptoms were associated with surgeons height, glove size, age and female gender. Patient body mass index (BMI) was associated with pain symptoms in surgeons performing conventional laparoscopic surgery, but not robotic surgery. To decrease pain, surgeons changed positions (78%), limited the number of cases per day (14%), spread cases throughout the week (6%), or limited the total number of cases (3%). Only 29% had received treatment at any time for pain symptoms. Treatment included physical therapy (59%), medical management (28%), surgery (13%), and time off (1%). Only 16% of those with pain symptoms had received formal ergonomic training. CONCLUSION Physical strain rates of 88% are far greater than previously reported. Such prevalent occupational strain presents a growing problem in the face of increasing demand for MIS.