Janelle M. Fauci

The utilization of palliative care in gynecologic oncology patients near the end of life

BACKGROUND Palliative and supportive care services provide excellent care to patients near the end of life. It is estimated that enrollment in such services can reduce end-of-life costs; however, there is limited data available regarding the impact of palliative services in end-of-life care in gynecologic oncology patients. We examined the use of palliative services in gynecologic oncology patients during the last six months of life. METHODS After IRB approval, a retrospective chart review of patients with a diagnosis of a gynecologic malignancy who died between June 2007 and June 2010 was performed. Abstracted data included demographics, admission and procedural history, use of anti-cancer therapy, and palliative care utilization during the last six months of life. RESULTS 268 patients were identified. Most patients were white (76.9%) and had ovarian cancer (56.7%). During the last six months of life, 155 (57.8%) patients underwent anti-cancer therapy with chemotherapy, 19 (7.1%) patients were treated with radiation therapy, and 17 patients (6.3%) underwent treatment with both. 218 patients (81.3%) had at least one admission during this time (range 0-14). The most common reason for admission was gastrointestinal complaints (37.1%), followed by admissions for procedures (18.3%). The median time between the last admission and death was 32 days. 157 patients (58.6%) underwent at least one procedure during the last six months of life (range 0-11). The most common procedure performed was paracentesis (22.6%). 198 (73.9%) patients died at home or in a palliative care unit. 189 (70.5%) patients were referred to hospice or palliative care. 3.2% underwent a procedure or treatment with chemotherapy or radiation after hospice enrollment. The median time between hospice enrollment and death was 22 days. 55% of patients were enrolled in hospice less than 30 days before death. Of the 79 patients not referred to hospice, only 16.5% had documentation of refusing hospice services. CONCLUSIONS During the last six months of life, the majority of gynecologic oncology patients receive anticancer therapy and many have repeated hospital admissions. While the majority of patients are referred for palliative care, it appears that most patients spend less than 30 days on hospice. Earlier referral could decrease the number of hospital admissions and procedures while providing invaluable support during this end of life transition.

A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer

A number of members of the B7 superfamily of ligands have been implicated in tumor immunogenicity and cancer development. Two of these recently characterized ligands, B7-H4 and B7-H3, have been linked to ovarian tumors. B7-H4 is consistently overexpressed in ovarian tumor specimens, and its tissue and serum levels have been found to be a potential biomarker for ovarian cancer, either alone or in combination with CA125. More recently, B7-H3 has been found to be overexpressed in a large series of ovarian cancer tumor specimens and similar to other types of carcinomas, B7-H3 overexpression has been correlated with poor survival. On the basis of the results obtained by knocking down B7-H3 protein using siRNA, researchers have suggested that blocking the action of B7-H3 could reduce tumor growth, metastatic potential, and improve survival. Because siRNA knock-down is not an ideal clinical therapeutic vehicle, additional studies using antibody-mediated suppression of the B7-H3 protein are necessary to fully evaluate the clinical potential of this molecule as a therapeutic target.

Assessment of risk factors for 30-day hospital readmission after surgical cytoreduction in epithelial ovarian carcinoma.

Objective: To evaluate factors that place epithelial ovarian cancer (EOC) patients at increased risk for hospital readmission. Methods: A retrospective review of patients diagnosed with EOC undergoing surgical cytoreduction at the University of Alabama at Birmingham from 2001 to 2008 was performed. Patients who required readmission were identified. Demographic data, comorbidities, surgical data including bowel resections, and hospital length of stay were evaluated. Results: A total of 207 patients were identified. The mean age at diagnosis was 64 years (range, 32-89 years), 58% had optimal debulking (n = 120), and the mean number of comorbidities was 1.3 (range, 0-6). Readmission within 30 days of discharge occurred in 33 (16%) of 207 patients. The readmission group had a statistically higher number of comorbidities (1.75 vs 1.01, P = 0.025). The most common reasons for readmission were small bowel obstruction/ileus, wound complications, and thromboembolic events. Conclusions: The most common reason for readmission after cytoreductive surgery for EOC is small bowel obstruction/ileus. Studies assessing postoperative disease management programs including nursing telephone follow-up, administration of outpatient intravenous fluids, and continuation of antithrombotic agents may offer opportunities to reduce readmissions.

Diabetes mellitus and ovarian cancer: More complex than just increasing risk ☆

OBJECTIVE Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC. METHODS A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan-Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients. RESULTS 62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p=0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7kg/m(2), p<0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3months, p=0.024) and OS (26.1 vs. 42.2months, p=0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS. CONCLUSIONS EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.

Monoclonal antibody-based immunotherapy of ovarian cancer: Targeting ovarian cancer cells with the B7-H3-specific mAb 376.96

OBJECTIVE The high rate of relapse in patients with advanced ovarian cancer likely reflects the chemoresistance of cancer initiating cells (CICs). We evaluated the anti-tumor activity of monoclonal antibody (mAb) 376.96, which recognizes a B7-H3 epitope expressed on ovarian carcinoma cells (OCCs), in combination with the tyrosine kinase inhibitor Sunitinib and chemotherapy on chemosensitive and chemoresistant cells and CICs. METHODS Eight ovarian cancer cell lines including platinum- and taxane-resistant cell lines were analyzed by flow cytometry to establish expression of the mAb 376.96-defined-B7-H3-epitope on differentiated ovarian cancer cells and CICs. Samples from 10 ovarian cancer patients were analyzed via immunohistochemistry for mAb 376.96-defined-B7-H3-epitope expression. In vitro studies assessed mAb 376.96 alone and in combination with Sunitinib on the growth of chemosensitive and chemoresistant cell lines and on the content of CICs. RESULTS The mAb-376.96-defined-B7-H3 epitope is expressed on both differentiated cells and CICs in chemosensitive and chemoresistant ovarian cancer cell lines and 10 patient derived ovarian cancer tumors. In vitro treatment of chemoresistant cell lines with mAb 376.96 resulted in decreased cell viability. mAb 376.96 enhanced the cytotoxicity of Sunitinib and reduced the content of CICs. CONCLUSION The mAb-376.96-defined-B7-H3-epitope was found to be expressed on both differentiated ovarian cancer cells and CICs in chemosensitive and chemoresistant ovarian cancer cell lines. mAb 376.96 inhibited the in vitro growth of chemosensitive and chemoresistant OCCs and reduced the content of CICs when used with Sunitinib. Further studies examining B7-H3 as a potential target of mAb-based immunotherapy for this type of malignancy are warranted.

Double prophylaxis for deep venous thrombosis in patients with gynecologic oncology who are undergoing laparotomy: does preoperative anticoagulation matter?

Objective: Double prophylaxis for deep venous thrombosis (DVT) with thromboprophylaxis plus sequential compression devices (SCDs) is recommended for high-risk surgical patients with gynecologic oncology. Despite the use of preoperative thromboprophylaxis in clinical trials, the schedule of perioperative low molecular-weight heparin varies widely. We sought to determine the effectiveness and adverse effects of a preoperative dose of anticoagulation in patients with gynecologic oncology. Methods: A multi-institutional chart review from January 2006 to July 2008 was performed. Patients with gynecologic oncology who received double prophylaxis for laparotomy were eligible. The patients were grouped according to whether they received preoperative anticoagulation (YES PREOP vs NO PREOP). All patients received postoperative low molecular-weight heparin for thromboprophylaxis and SCDs until discharge. Demographic, surgicopathologic, and complication data were collected. Results: A total of 239 patients were identified: YES PREOP (n = 101) and NO PREOP (n = 138). Groups were similar with respect to demographics, diagnosis, and length of hospital stay. There were 2 DVTs in the YES PREOP group compared with 11 in the NO PREOP group (P = 0.04; relative risk, 0.77). There were also fewer DVT-attributable deaths in the YES PREOP group (0 vs 2; P < 0.001). Postoperative hematocrit (30.2% vs 31.4%; P = 0.42) and number of transfusions (26 vs 14; P = 0.31) were similar. Conclusion: The use of preoperative anticoagulation seems to significantly decrease the risk of DVT in this patient population, and complication rates are not increased. Patients receiving double prophylaxis should receive a preoperative dose of anticoagulation for maximum benefit.

Incidence of port site hernias and/or dehiscence in robotic-assisted procedures in gynecologic oncology patients.

OBJECTIVES The incidence of port site hernia and/or dehiscence using bladeless trocars is 0-1.2%. Robotic surgery uses additional port sites and increases manipulation of instruments, raising the concern for more complications. We sought to characterize the incidence of port site complications following robotic surgery when fascia was not routinely closed. METHODS Robotically-assisted (RA) procedures performed for suspected gynecologic malignancy between 1/2006 and 12/2011 were retrospectively reviewed. Bladeless 12 mm and 8mm robotic trocars were used. Fascial closure was not routinely performed except after specimen removal through the port site. The decision to close the fascia remained at the discretion of the surgeon. RESULTS Data from 842 procedures were included. Mean patient age was 55.6 years. Mean Body Mass Index was 33.6 kg/m(2). RA-total laparoscopic hysterectomy (TLH)± unilateral or bilateral salpingo-oophorectomy (BSO)± lymphadenectomy (LND) accounted for 91.6% of procedures. Final pathology confirmed malignancy in 58.6% of cases, primarily endometrial cancer. In 35 cases, the specimen was removed through the port site; fascia was closed in 54.3% of them and no port site hernias or dehiscences occurred. Only one patient underwent a RA-TLH/BSO/LND for endometrial adenocarcinoma and had a port site dehiscence of the 8mm trocar site. No port site hernias occurred. CONCLUSION Port site hernias and dehiscences are rare in RA gynecologic oncology procedures. When bladeless dilating trocars are used, routine closure of even up to a 12 mm port site is unnecessary, even in cases requiring removal of the specimen through the trocar sites.

Outcomes of patients with gynecologic malignancies undergoing video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion

OBJECTIVES We evaluated the indications and outcomes of patients with known gynecologic malignancies that underwent video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion. METHODS After IRB approval was obtained, a retrospective study of patients with gynecologic malignancies who underwent planned VATS/pleurodesis between 1/2000 and 7/2010 was performed. Abstracted data included demographics, diagnosis, disease status, treatment history, indication for VATS, complications, and outcomes. RESULTS Forty-two patients with a gynecologic malignancy underwent VATS/pleurodesis. Median age was 63 years. Twenty-nine patients (69%) had ovarian cancer. Fifty-seven percent had recurrent disease at the time of VATS and 57% were undergoing chemotherapy at the time of VATS. Eight patients (19%) underwent perioperative VATS to improve pulmonary status. Seven patients (17%) underwent a palliative VATS. The median length of stay was 7 days (range 1-53). Sixty-two percent had gross disease noted at the time of VATS. A mean of 1650 cc of fluid was drained at time of surgery (range 300-4500), and the majority (88%) of patients had a talc pleurodesis performed. Seven patients (17%) were readmitted within 30 days; 6 were for complications unrelated to their VATS. One patient was readmitted with hospital-acquired pneumonia and died during readmission. Median time to death after VATS was 104 days (range 4-1062). Patients who underwent a perioperative VATS had the longest survival (845 days). CONCLUSION Patients with gynecologic malignancies may require a VATS/pleurodesis for symptomatic pleural effusions. This procedure appears to be safe and effective in this patient population.

The effect of the APPRISE mandate on use of erythropoiesis-stimulating agents and transfusion rates in patients with ovarian cancer receiving chemotherapy.

Objective Erythropoiesis-stimulating agents (ESAs) support chemotherapy-induced anemia in patients with epithelial ovarian cancer (EOC). In response to research demonstrating that ESAs increase tumor growth and shorten survival, the Food and Drug Administration mandated the new APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) guidelines for consenting patients before ESAs administration. We sought to quantify the change in ESA and red blood cell (RBC) transfusion use after the APPRISE mandate was instituted. Methods/Materials After institutional review board approval, a retrospective chart review compared patients with EOC undergoing chemotherapy before and after the APPRISE mandate. Abstracted data included patient demographics, chemotherapy treatment status and regimen, and number of patients requiring ESAs or RBCs. A cost savings analysis was also performed. Results Eighty-four patients who underwent 367 cycles of chemotherapy after the APPRISE guidelines were compared with a matched set of 88 patients receiving 613 cycles of chemotherapy before the APPRISE guidelines. There were no statistically significant differences between the groups. Most patients had advanced stage disease and received primary taxane-/platinum-based chemotherapy. Of 88 patients, 45 (51%) in the pre-APPRISE group received a total of 196 ESA injections compared with 0 patients in the post-APPRISE group. Red blood cell transfusion in the post-APPRISE group was similar to that in the pre-APPRISE group (8.3% vs 14.8%, P = 0.28). Omission of ESAs in the post-APPRISE group resulted in a roughly

Referral patterns and incidence of cervical intraepithelial neoplasia in adolescent and pregnant patients: The impact of the 2006 guidelines

700,000 savings in billable charges. Conclusions In our institution, the APPRISE guidelines have resulted in complete cessation of the use of ESAs in patients with primary or recurrent EOC, resulting in considerable cost savings. Importantly, RBC transfusion rates did not significantly increase after the guidelines were imposed.