Vaginal cuff dehiscence (VCD) in the setting of acute infection is an uncommon but serious complication of total hysterectomy without clear guidelines for management. There is a need for further documentation of best practices around treatment, particularly when it comes to surgical drain utilization and placement. We present a case of a 68-year-old with primary peritoneal carcinoma who underwent a robot-assisted total laparoscopic hysterectomy as part of an interval debulking surgery and had a VCD. The cuff was repaired vaginally in the operating room with placement of a Malecot catheter for pelvic abscess drainage. The literature is sparse in regard to clear guidelines for management of VCD. Surgical and expectant management approaches are dependent on patient stability, surgical experience, local practice norms, and evidence of intra-abdominal injury. Interventional radiology has become a primary source of drain placement in management of VCD and vaginal cuff abscess. Malecot drains are a low cost, and effective intervention for such management and an important resource for the gynecologic surgeon.
5519 Background: Obesity and diabetes have been linked to poorer survival and increased recurrence rates in endometrial cancer. The anti-diabetic medication, metformin, has been shown to have anti-tumorigenic effects in vitro and in vivo, via AMPK activation and inhibition of the mTOR pathway. We conducted a pre-operative window clinical trial of metformin in obese endometrial cancer patients to evaluate short-term in vivo molecular changes. Methods: Women with endometrioid endometrial cancer who were obese (BMI>30) were recruited from a gynecologic oncology clinic. Once enrolled, patients had a repeat pre-treatment endometrial biopsy and then began metformin at a dose of 850 mg PO once daily for 1-4 weeks prior to hysterectomy/surgical staging. A tissue microarray, using triplicate cores from each specimen, was constructed from paired formalin-fixed, paraffin-embedded endometrial biopsy (pre-treatment) and hysterectomy (post-treatment) specimens. The expression of Ki-67, a marker of cell proliferation, was measured by immunohistochemistry. Individual slides were digitized using the Aperio ScanScope (Aperio Technologies, Vista, CA), and digital images were analyzed using Aperio ImageScope software. The Signed Rank Test was used for statistical analysis. Results: Sixteen patients have completed the protocol. The mean duration of treatment was 14.5 days. Percent Ki-67 staining decreased significantly with metformin treatment (mean of 19.5% decrease, p = 0.026). Two patients experienced grade 1 toxicities, including mild abdominal pain and loose stools. Ten of the 16 patients responded to metformin based on decreased proliferation from their pre- to post-treatment specimens. There were no differences in median age, BMI, HgbA1c, or number of doses taken between responders and non-responders to treatment. Pre-treatment Ki-67 levels were statistically higher in the women that responded to metformin treatment (52% versus 27.5%, p = 0.0067). Conclusions: Metformin significantly reduced proliferation in a pre-operative window study in obese endometrial cancer patients, providing further support for therapeutic clinical trials of metformin in this obesity-driven disease.
e16510 Background: Minimally invasive surgery (MIS) has gained increasing acceptance as an alternative to standard laparotomy in gynecologic cancer, but surgical approach with respect to non-epithelial ovarian cancers has not been extensively studied. We compared perioperative and long-term outcomes of women with ovarian granulosa cell tumors (GCTs) who underwent laparoscopy versus laparotomy. Methods: Inclusion criteria were surgical treatment and stage I-IV GCTs. Abstracted data included: surgical modality (laparoscopic vs open), demographics, operative details, and disease course. Survival was analyzed using the Kaplan-Meier method and Cox model. The chi square test of association, Wilcoxon rank-sum test and t-test were used for the group comparisons. Results: 166 women with ovarian GCTs were identified of which 160 were evaluable; 32 and 128 underwent laparoscopy and laparotomy, respectively. The overall survival (OS) and disease-free survival (DFS) were not significantly different between those treated with laparoscopy and laparotomy (OS 92% vs 77%, p=.42; DFS 55 vs 47%, p=.79). Advanced age at diagnosis was associated with decreased OS (HR 1.04 95% CI [1.01-1.07], p=.013). MIS was associated with lower EBL (106 vs 430cc, p<.001), earlier discharge (1.5 vs 4.2 days, p<.001), smaller tumor size (7.9 vs 15.7cm, p<.001), and fewer complications (3.4 vs 19.2%, p=.039). There was no difference in age (p=.20), race (p=.37), BMI (p=.89), pre-operative Inhibin B (263 vs 786 pg/mL, p=.13), stage (p=.15), and intra-operative cyst rupture (p=.36). Conclusions: Our findings suggest that MIS is reasonable for women with GCT with similar survival outcomes compared to laparotomy. Laparoscopy was associated with lower EBL, earlier discharge, and fewer complications.
Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.
Appendiceal adenocarcinoma is a rare malignancy for which there is no characteristic clinical presentation. We describe five women who presented with signs and symptoms characteristic of advanced ovarian cancer but whose final diagnosis was stage IV appendiceal cancer. Between 1998 and 1999, five women treated for presumed ovarian cancer were identified as having primary appendiceal cancer. Medical records and pathology were retrospectively reviewed. The median age was 47 years (range 36–61 years). All had elevated preoperative CA125 levels with a median value of 171 μ/ml (range 46–383). Four women underwent right hemicolectomy with two requiring radical surgical tumor debulking to render them optimally debulked. Four had postoperative chemotherapy, the most common agent used was 5-flourouracil. Median survival was 6.75 months (range 19 days-11 months). Primary adenocarcinoma of the appendix is rare; therefore, the clinical utility of radical tumor debulking and chemotherapy is not well described. Given the poor survival in our series, all efforts should be considered palliative. Although this disease process is uncommon, it should be entertained by gynecologic oncologists in the differential diagnosis of an intra-abdominal mass and ascites. The ability to make the correct diagnosis and differentiate between an ovarian and appendiceal primary is critical as the treatment modalities vary.
2582 Background: There is significant inter- and intra-patient variability in the PK and PD (efficacy and toxicity) of PLD in pts with EOC and other malignancies. This has been attributed to age and gender, but more specifically, may be related to the mononuclear phagocyte system (MPS). Clearance (CL) of PLD has been proposed to occur primarily via uptake by monocytes, dendritic cells, and macrophages mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PD in pts with EOC. Methods: Prior to (day -7 to -1) administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IV × 1. Dynamic planar and SPECT/CT images of the liver and spleen were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 1.5 h. Serial blood samples were collected up to 28 days after PLD. Plasma samples were processed to measure encapsulated (encap) and released doxorubicin via HPLC with fluorescence. Results: Six pts have undergone TSC imaging and blood PK, and PLD plasma PK studies. Mean ± SD encap doxorubicin CL and TSC CL were 25.4 ± 4.1 mL/h and 18.9 ± 5.4 mL/h, respectively. There was a positive linear relationship between TSC CL and encap doxorubicin CL (R2 = 0.58). Mean ± SD of encap doxorubicin area under the concentration versus time curve (AUC) and TSC splenic outflow were 2.4 ± 0.5 mg/mL·h and 0.5 ± 0.1 s-1, respectively. There was a positive linear relationship between TSC splenic outflow and encap doxorubicin AUC (R2 = 0.85). There was no relationship between TSC AUC in the liver and spleen and PLD PK. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and may be used to individualize PLD therapy in pts with EOC and other malignancies. Evaluation of the relationship between TSC and PLD PD is undergoing further investigation.
