Dario R. Roque

Long-term follow-up of vulvar cancer patients evaluated with sentinel lymph node biopsy alone

OBJECTIVE The objective of this study was to examine SLN evaluation alone in women with squamous cell carcinoma (SCC) of the vulva and evaluate the inguinal recurrence and complication rates. METHODS An IRB approved prospective study enrolled patients with SCC of the vulva. Peritumoral injection of Tc-99 sulfur colloid and blue dye was used to identify SLNs intraoperatively. Patients with negative SLN for metastasis were followed clinically without further treatment. Patients with metastasis to a SLN underwent full groin node dissection followed by standard treatment protocols. RESULTS A total of 73 women were enrolled onto protocol with 69 patients undergoing SLN dissection. Mean age was 66.9years (range: 29-91) with 47 stage I, 12 stage II, 9 stage III, 2 stage IV and 3 unstaged patients. SLN dissections were successful in 63 patients. Of the 111 groins evaluated with a SLN dissection 93% had a SLN identified with an average of 2 SLN per groin. There were 92 groins with negative SLN and 11 groins with positive SLN. 57 patients had negative SLN and underwent conservative management with the median follow-up of 58.3months. Three patients experienced groin recurrences (2 unilateral, 1 bilateral) for a recurrence rate of 5.2% (3/57). The complication rate for the inguinal incisions was 17.5% (1 cellulitis, 1 abscess, 2 lymphoceles, 5 lymphedema and leg pain). CONCLUSIONS Isolated SLN dissection alone has a low inguinal recurrence rate with decreased complications and should be considered as an option for women with SCC of the vulva.

Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling

OBJECTIVES Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer. METHODS ECC-1 and Ishikawa cells were treated with low glucose (1mM), normal glucose (5mM) and high glucose (25mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated. RESULTS Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways. CONCLUSIONS Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer.

The surgical management of cervical cancer: an overview and literature review.

Importance Surgery has evolved into the standard therapy for nonbulky carcinoma of the cervix. The mainstay of surgical management is radical hysterectomy; however, less radical procedures have a small but important role in the management of cervical tumors. Objective Our objective was to discuss the literature behind the different procedures utilized in the management of cervical cancer, emphasizing the radical hysterectomy. In addition, we aimed to discuss ongoing trials looking at the utility of less radical surgeries as well as emerging technologies in the management of this disease. Evidence Acquisition We performed a PubMed literature search for articles in the English language that pertained to the topic of surgical techniques and their outcomes in the treatment of cervical cancer. Results The minimally invasive approaches to radical hysterectomy appear to reduce morbidity without affecting oncological outcomes, although further data are needed looking at long-term outcomes with the robotic platform. Trials are currently ongoing looking at the role of less radical surgery for patients with low-risk disease and the feasibility of sentinel lymph node mapping. Conclusions and Relevance Radical hysterectomy with pelvic lymphadenectomy has evolved into the standard therapy for nonbulky disease, and there is a clear advantage in the use of minimally invasive techniques to perform these procedures. However, pending ongoing trials, less radical surgery in patients with low-risk invasive disease as well as sentinel lymph node mapping may emerge as standards of care in selected patients with cervical carcinoma. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to describe the role of cold knife cone and simple hysterectomy in the management of carcinoma of the cervix, identify the primary treatment options for patients with cervical cancer and their associated complications/adverse effects, compare the differences in surgical outcomes and complication rates between the different kinds of radical hysterectomies, and identify which patients qualify for fertility-sparing surgery.

Obesity and perioperative pulmonary complications in robotic gynecologic surgery

OBJECTIVE Robotic gynecological surgery is feasible in obese patients, but there remain concerns about the safety of this approach because the positioning required for pelvic surgery can exacerbate obesity-related changes in respiratory physiology. The objective of our study was to evaluate pulmonary and all-cause complication rates in obese women undergoing robotic gynecological surgery and to assess variables that may be associated with complications. STUDY DESIGN A retrospective chart review was performed on obese patients (body mass index of ≥30 kg/m(2)) who underwent robotic gynecological surgery at 2 academic institutions between 2006 and 2012. The primary outcome was pulmonary complications and the secondary outcome was all-cause complications. Univariate and multivariate logistic regression analyses were used to determine the associations between patient baseline variables, operative variables, ventilator parameters, and complications. RESULTS Of 1032 patients, 146 patients (14%) had any complication, whereas only 33 patients (3%) had a pulmonary complication. Median body mass index was 37 kg/m(2). Only age was significantly associated with a higher risk of pulmonary complications (P = .01). Older age, higher estimated blood loss, and longer case length were associated with a higher rate of all-cause complications (P = .0001, P < .0001, and P = .004, respectively). No other covariates were strongly associated with complications. CONCLUSION The vast majority of obese patients can successfully tolerate robotic gynecological surgery and have overall low complications rates and even lower rates of pulmonary complications. The degree of obesity was not predictive of successful robotic surgery and subsequent complications.

Gemcitabine and Docetaxel Compared with Observation, Radiation, or Other Chemotherapy Regimens as Adjuvant Treatment for Stage I-to-IV Uterine Leiomyosarcoma

Objectives We aimed to compare progression-free survival (PFS) and overall survival (OS) among patients with stage I-to-IV uterine leiomyosarcoma (uLMS) who received adjuvant gemcitabine-docetaxel, were observed, received radiation only, or were treated with a chemotherapy regimen other than gemcitabine-docetaxel. Methods/Materials This is a retrospective cohort study of 128 women with uLMS. Data included age, body mass index, race, stage, mitotic count, residual disease, adjuvant treatment, PFS, and OS. Variables were compared by Fisher exact or Wilcoxon rank-sum tests. Time to progression or death was plotted using Kaplan-Meier curves. Cox proportional hazards regression was used to estimate hazard ratios for progression or death by patient and tumor characteristics. Results Fifty-six (44%) women received adjuvant chemotherapy, 41 (32%) received adjuvant radiation, and 31 (24%) were observed. Of those receiving chemotherapy, 30 received gemcitabine-docetaxel, and 26 received other chemotherapy. Disease stage for the chemotherapy groups was evenly distributed. In the radiation group, 80% of patients had early-stage disease. Age, body mass index, and residual disease were similar between the groups. Mitotic count was uniformly 10 or greater only in the gemcitabine-docetaxel group. Age, stage, and residual disease were associated with worst PFS and OS. After adjusting for these variables, there was no difference in PFS or OS between gemcitabine-docetaxel and the other treatment groups. Conclusions There was no difference in PFS or OS in women with uLMS treated with adjuvant gemcitabine-docetaxel versus those who were observed or received radiation only or a chemotherapy regimen other than gemcitabine-docetaxel. There is a need to identify novel therapies to treat this aggressive disease.

Knockdown of hTERT and Treatment with BIBR1532 Inhibit Cell Proliferation and Invasion in Endometrial Cancer Cells.

Telomerase activity and expression of the catalytic protein hTERT are associated with cell proliferation and advanced stage in endometrial cancer. Our objective was to evaluate the effect of inhibition of hTERT by siRNA and BIBR1532 on cell growth, apoptosis and invasion in endometrial cancer cells. Knockdown of hTERT or treatment of the cells with BIBR1532 decreased telomerase activity, inhibited cell proliferation, induced apoptosis, and reduced cell invasion in Ishikawa and ECC-1 cells. Either hTERT siRNA or BIBR1532 in combination with paclitaxel promoted a synergistic inhibitory effect on cell growth through induction of Annexin V expression and a remarkable reduction in cell invasion through reduction of protein expression of MMP9, MMP2, and MMP3. Increased telomerase activity and hTERT protein expression by transfections enhanced the protein expression of MMPs and increased the cell invasion ability. BIBR1532 significantly antagonized cell invasion induced by increased hTERT expression. These findings suggest that telomerase and hTERT facilitate cell invasion via MMP family in human endometrial cancer cells.

Use of topical hemostatic agents in gynecologic surgery.

&NA; Sutures, hemoclips, and electrocautery are the primary mechanisms used to achieve hemostasis during gynecologic surgery, but in situations in which these are inadequate or not feasible, an array of hemostatic agents are available to help achieve hemostasis. These agents include physical agents such as cellulose, collagen, or gelatin products as well as biologic agents such as thrombin and fibrin products. Limited data are available on many of these agents, although their use is increasing, sometimes at high costs. In gynecologic surgery, hemostatic agents are likely most effective when used in areas of oozing or slow bleeding and as an adjunct to conventional surgical methods of hemostasis. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to identify various topical hemostatic agents and distinguish them from each other on the basis of mechanism of action, evaluate the potential complications associated with the use of topical hemostatic agents, and choose the optimal situations in which to use topical hemostatic agents in gynecologic surgery.

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial

OBJECTIVE AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. METHODS A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. RESULTS The ICER associated with B+CT is

Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer

410,455 per QALY gained and

Abstract 3084: The effects of NT-1044, a novel AMPK activator, on endometrial cancer cell proliferation, apoptosis, cell stress, and tumor growth

217,080 per PF-LYS. At a willingness to pay (WTP) threshold of