Nonsurgical management of early-stage endometrial cancer due to obesity: a survey of the practice patterns of current Society of Gynecologic Oncology members

Objective: Nonsurgical management for endometrial cancer in patients with class 3 obesity (BMI ≥ 40 kg/m2) is a challenging scenario given lack of consensus on patient selection and treatment options. Our objective was to evaluate trends in practice patterns and physician opinions in the Society of Gynecologic Oncology (SGO) on nonsurgical management of endometrial cancer and complex atypical hyperplasia due to obesity. Methods: An online survey was sent to all gynecologic oncologist members of the SGO with questions centered on decision-making for nonsurgical approaches for patients with class 3 obesity patients. Fisher's exact tests were used to assess the associations between offering nonsurgical management and geographic region, practice type, and time in practice. Results: 255 (19.8 %) members from 6 geographic regions responded, of which 183 (71.8 %) offered primary nonsurgical management of endometrial cancer to patients with class 3 obesity and 72 (28.2 %) do not. The choice to offer initial nonsurgical management did not vary based on geographic region, time in practice or practice type. When asked to select BMI cutoff, the majority (65.2 %) started to offer nonsurgical management was BMI 60–64 kg/m2. Progesterone intrauterine device was the preferred treatment (68.3 %, 125/183). Of those who offered nonsurgical management, 97.3 % (178/183) recommended resampling in 3–6 months. Conclusion: Primary nonsurgical management of endometrial cancer in patients with class 3 obesity is offered by most gynecologic oncologists in SGO. However, almost one-third of gynecologic oncologists indicated they do not offer nonsurgical management for endometrial cancer for obesity alone. Additional data are needed to determine the safety of both approaches in these complex patients

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Intraoperative hypothermia during cytoreductive surgery for ovarian cancer and perioperative morbidity

OBJECTIVE: To evaluate intraoperative hypothermia as a predictor for morbidity after open abdominal surgery for ovarian cancer. METHODS: This cohort study included 146 women with stage IIIC and IV ovarian cancer who underwent debulking surgery at our institution from January 1, 2001, through December 31, 2003. Hypothermia was defined as end operative temperature lower than 36\ub0 C. Early complications (occurring within 30 days of surgery) included: mortality, infectious morbidities, cardiovascular events, venous thromboembolic (VTE) events, anastomotic leak, readmission, and reoperation. Survival was also evaluated. Logistic regression models were used to adjust for known confounders. RESULTS: The mean age was 63.9\ub111.7 years; 46 (32%) patients had a body mass index higher than 30; mean operative time was 239\ub185 minutes. There were five deaths perioperatively, all in the hypothermic group. Hypothermia was associated with an increased risk of any early complications (34 [42.0%] compared with 11 [16.9%]) with an adjusted odds ratio (OR) of 3.40 (95% confidence interval [CI] 1.48-8.33). For individual complications, hypothermic patients were at higher risk for VTE events with an adjusted OR of 3.53 (95% CI 1.02-16.44); infectious morbidity with an adjusted OR of 2.99 (95% CI 0.97-11.35); and reoperation with an adjusted OR of 4.96 (95% CI 0.80 -95.7). The overall survival was shorter in hypothermic group with a median of 34 compared with 45 months (P=.045); this remained significant for an optimally resected subgroup with a median overall survival of 40 compared with 48 months (P=.049). CONCLUSION: Surgical hypothermia is an independent predictor of early perioperative complications and overall survival after cytoreductive surgery for ovarian cancer. This is a critically important finding, because maintaining normothermia is an inexpensive modifiable factor, which could result in reduced morbidity

Extra-peritoneal laparoscopic para-aortic lymphadenectomy : a prospective cohort study of 293 patients with endometrial cancer

Objective: To determine if extra-peritoneal laparoscopic para-aortic (PA) lymphadenectomy allows a reliable assessment of PA nodes in patients with endometrial cancer (EC). Methods: In October of 2005, a single surgeon began performing extra-peritoneal laparoscopic PA lymphadenectomy for patients with EC. A prospective cohort study was initiated from October 2005 through October 2007. Staging of Group A included extra-peritoneal laparoscopic PA lymphadenectomy, while Group B underwent staging via laparotomy. Results: In a 24\ua0month period, 293 patients underwent surgical treatment for EC, 203 of them underwent complete staging as determined by previously published criteria. Extra-peritoneal laparoscopic PA lymphadenectomy to the renal veins was successful in 35/38 patients (92%). Mean BMI was 33.0 for Group A and 32.3 for Group B (p = NS). Mean EBL and hospital stay were lower in Group A compared to Group B (163 vs 373\ua0cm3, p 35, (21.6 vs 13.1), while in Group B fewer nodes were removed in obese patients (17.8 vs 20.5). Conclusions: Extra-peritoneal laparoscopy is a reliable method to routinely reach the level of the renal veins, even in obese patients. This approach was feasible in over 90% of unselected patients and well-tolerated

Multiple large bowel resections: Potential risk factor for anastomotic leak

Objectives Identify risk factors of anastomotic leak (AL) after large bowel resection (LBR) for ovarian cancer (OC) and compare outcomes between AL and no AL. Methods All cases of AL after LBR for OC between 01/01/1994 and 05/20/2011 were identified and matched 1:2 with controls for age (\ub1 5 years), sub-stage (IIIA/IIIB; IIIC; IV), and date of surgery (\ub1 4 years). Patient-specific and intraoperative risk factors, use of protective stomas, and outcomes were abstracted. A stratified conditional logistic regression model was fit to determine the association between each factor and AL. Results 42 AL cases were evaluable and matched with 84 controls. Two-thirds of the AL had stage IIIC disease and > 90% of both cases and controls were cytoreduced to < 1 cm residual disease. No patient-specific risk factors were associated with AL (pre-operative albumin was not available for most patients). Rectosigmoid resection coupled with additional LBR was associated with AL (OR = 2.73, 95% CI 1.13-6.59, P = 0.025), and protective stomas were associated with decreased risk of AL (0% vs. 10.7%, P = 0.024). AL patients had longer length of stay (P < 0.001), were less likely to start chemotherapy (P = 0.020), and had longer time to chemotherapy (P = 0.007). Cases tended to have higher 90-day mortality (P = 0.061) and were more likely to have poorer overall survival (HR = 2.05, 95% CI 1.18-3.57, P = 0.011). Conclusions Multiple LBRs appear to be associated with increased risk of AL and protective stomas with decreased risk. Since AL after OC cytoreduction significantly delays chemotherapy and negatively impacts survival, surgeons should strongly consider temporary diversion in selected patients (poor nutritional status, multiple LBRs, previous pelvic radiation, very low anterior resection, steroid use)

Aggressive surgical effort and improved survival in advanced-stage ovarian cancer

OBJECTIVE: Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival. METHODS: A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival. RESULTS: The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001). CONCLUSION: Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis

Discovery of ovarian cancer biomarkers in serum using NanoLC electrospray ionization TOF and FT-ICR mass spectrometry

Abstract. Treatment of cancer patients is greatly facilitated by detection of the cancer prior to metastasis. One of the obstacles to early cancer detection is the lack of availability of biomarkers with sufficient specificity. With modern differential proteomic techniques, the potential exists to identify high specificity cancer biomarkers. We have delineated a set of protocols for the isolation and identification of serum biomarkers for ovarian cancer that exist in the low molecular weight serum fraction. After isolation of the low molecular weight fraction by ultrafiltration, the potential biomarkers are separated by reversed phase nano liquid chromatography. Detection via TOF or FT-ICR yields a data set for each sample. We compared stage III/IV ovarian cancer serum with postmenopausal age-matched controls. Using bioinformatics tools developed at Mayo, we normalized each sample for intensity and chromatographic alignment. Normalized data sets are subsequently compared and potential biomarkers identified. Several candidate biomarkers were found. One of these contains the sequence of fibrinopeptide-A known to be elevated in many types of cancer including ovarian cancer. The protocols utilized will be examined and would be applicable to a wide variety of cancers or disease states

Influence of intraoperative capsule rupture on outcomes in stage i epithelial ovarian cancer

Objective: To evaluate the effect of tumor capsule rupture on disease prognosis in stage I epithelial ovarian cancer. Methods: All patients with International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified. Relevant tumor characteristics, procedures performed, adjuvant therapies, and follow-up were recorded and analyzed. Inclusion criteria included comprehensive staging. Cox proportional hazards, Kaplan-Meier estimation, log rank test, and \u3c7 test were used for statistical analyses. Results: There were 161 cases that met inclusion criteria. Seventy-four (46%) patients had intact capsules without positive cytology or surface involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22 (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12 of 161 (7%) patients died of their disease. In univariable analysis, both intraoperative capsule rupture and positive cytologic washings portended worse disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-8.9; P=.004 and HR 5.2, 95% CI 2.1-12.3; P<.001, respectively) and disease-specific survival (HR 4.1, 95% CI 1.3-15.4; P=.018 and HR 5.9, 95% CI 1.8-19.3; P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI 1.8-10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5-16.0; P<.001) remained independent predictors of worse disease-free survival. Disease-free survival and disease-specific survival were shortest for stage IC cases with positive cytology, surface involvement, or both, that also had intraoperative rupture. Conclusion: In stage I epithelial ovarian cancer, intraoperative capsule rupture portends a higher risk of disease recurrence and death from disease. Careful intraoperative removal of ovarian masses is important, and recognizing the higher-risk nature of such cases is imperative

Feasibility and Safety of Extensive Upper Abdominal Surgery in Elderly Patients with Advanced Epithelial Ovarian Cancer

We performed a retrospective study to evaluate the feasibility and safety of extensive upper abdominal surgery (EUAS) in elderly (≥65 yr) patients with advanced ovarian cancer. Records of patients with advanced epithelial ovarian cancer who received surgery at our institution between January 2001 and June 2005 were reviewed. A total of 137 patients including 32 (20.9%) elderly patients were identified. Co-morbidities were present in 37.5% of the elderly patients. Optimal cytoreduction was feasible in 87.5% of the elderly while 95.2% of young patients were optimally debulked (P=0.237). Among 77 patients who received one or more EUAS procedures, 16 (20.8%) were elderly. Within the cohort, the complication profile was not significantly different between the young and the elderly, except for pleural effusion and pneumothorax (P=0.028). Elderly patients who received 2 or more EUAS procedures, when compared to those 1 or less EUAS procedure, had significantly longer operation times (P=0.009), greater blood loss (P=0.002) and more intraoperative transfusions (P=0.030). EUAS procedures are feasible in elderly patients with good general condition. However, cautious peri-operative care should be given to this group because of their vulnerability to pulmonary complications and multiple EUAS procedures