Concomitant venous thromboembolism at the time of primary EOC diagnosis: Perioperative outcomes and survival analyses.

OBJECTIVE: To compare outcomes among women with epithelial ovarian cancer (EOC) undergoing primary surgery who present without venous thromboembolism (VTE) versus with VTE and placement of inferior vena cava (IVC) filter. METHODS: Women who underwent primary surgery for EOC between 1/2/2003 and 12/30/2011 were identified. Patient characteristics were retrospectively abstracted, including diagnosis of VTE within 30days prior to surgery and placement of IVC filter. Associations with overall survival (OS) were evaluated using Cox proportional hazards models. RESULTS: A total of 843 patients met inclusion criteria; 817 patients (Group 1) did not have VTE at the time of EOC diagnosis and 26 patients (Group 2) had a VTE and IVC placement within 30days prior to surgery. Group 2 had worse performance status, lower albumin, and more likely to have clear cell histology. Groups 1 and 2 were similar in terms of perioperative outcomes. Mortality within 90days of surgery was 6.4% in Group 1 versus 11.5% in Group 2 (p=0.24). Although median OS for group 1 was much higher than group 2, 56.6m versus 25.7m, in this cohort this difference did not reach statistical significance (adjusted HR 1.39, 95% CI 0.85-2.29, p=0.19). CONCLUSIONS: Patients with VTE diagnosed at the time of EOC diagnosis have poor outcomes. This may reflect more aggressive tumor biology, worse overall health of the patient following VTE, or may reflect worse survival secondary to the VTE. Patients must be carefully selected for surgery in the setting of VTE.

Surgical site infection after primary surgery for epithelial ovarian cancer: predictors and impact on survival.

OBJECTIVE: Surgical site infection (SSI) following epithelial ovarian cancer (EOC) primary surgery (PS) occurs in 10-15% of women. Perioperative factors associated with SSI and impact of SSI on survival were determined. METHODS: EOC cases that underwent PS from 1/2/2003 to 12/30/2011 were retrospectively reviewed. SSIs were defined according to ACS NSQIP. Logistic regression models were fit to identify factors associated with SSI. Cox proportional hazards models were utilized to evaluate the association of patient and perioperative characteristics with overall survival (OS) and disease-free survival (DFS). RESULTS: Among 888 cases, 96 (10.8%) developed SSI: 32 superficial, 2 deep, and 62 organ/space. Factors independently associated with superficial SSI were increasing BMI (odds ratio 1.41 [95% confidence interval, 1.12, 1.76] per 5kg/m(2)), increasing operative time (1.24 [1.02, 1.50] per hour), and advanced stage (III/IV) (10.22 [1.37, 76.20]). Factors independently associated with organ/space SSI were history of gastroesophageal reflux disease (2.13 [1.23, 3.71]), surgical complexity (intermediate 3.11 [1.02, 9.49]; high 8.07 [2.60, 25.09]; referent: low), and residual disease (RD) (measureable ≤1cm 1.77 [0.96, 3.27]; suboptimal >1cm (3.36 [1.48, 7.61]; referent: microscopic). Occurrence of superficial (hazard ratio 1.69 [1.12, 2.57]) or organ/space (1.46 [1.07, 2.00]) SSI was independently associated with worse OS. SSI occurrence was not independently associated with DFS. CONCLUSIONS: SSI after PS is associated with decreased OS. Most risk factors for SSI are not modifiable. Alternative measures to lower rates of SSIs are needed as this may improve OS. Preoperative identification of SSI risk factors may assist in risk-assessment and operative planning.

Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: a histologic dichotomy.

BACKGROUND: Treatment failures in stage IIIC endometrial carcinoma (EC) are predominantly due to occult extrapelvic metastases (EPM). The impact of chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs G3EC. METHODS: All surgical-stage IIIC EC cases from January 1, 1999, through December 31, 2008, from Mayo Clinic were included. Patient-, disease-, and treatment-specific risk factors were assessed for association with overall survival, cause-specific survival, and extrapelvic disease-free survival (DFS) using Cox proportional hazards regression. RESULTS: 109 cases met criteria, with 92 (84%) having systematic lymphadenectomy (>10 pelvic and >5 paraaortic lymph nodes resected). In patients with documented recurrence sites, occult EPM accounted for 88%. Among G1/2EC cases (n=48), the sole independent predictor of extrapelvic DFS was grade 2 histology (hazard ratio [HR], 0.28; 95% CI, 0.08-0.91; P=.03) while receipt of adjuvant chemotherapy approached significance (HR 0.13; 95% CI, 0.02, 1.01; P=.0511). The 5-year extrapelvic DFS with and without adjuvant chemotherapy was 93% and 54%, respectively (log-rank, P=.02). Among G3EC (n=61), the sole independent predictor of extrapelvic DFS was lymphovascular space involvement (HR, 2.63; 95% CI, 1.16-5.97; P=.02). Adjuvant chemotherapy did not affect occult EPM in G3EC; the 5-year extrapelvic DFS for G3EC with and without adjuvant chemotherapy was 43% and 42%, respectively (log-rank, P=.91). CONCLUSIONS: Chemotherapy improves extrapelvic DFS for stage IIIC G1/2EC but not stage IIIC G3EC. Future efforts should focus on prospectively assessing the impact of chemotherapy on DFS in G3EC and developing innovative phase I and II trials of novel systemic therapies for advanced G3EC.

The impact of perioperative packed red blood cell transfusion on survival in epithelial ovarian cancer.

OBJECTIVE: Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC. METHODS: Perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively. RESULTS: The rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥ IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT. CONCLUSIONS: Perioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.

Incidence and predictors of venous thromboembolism after debulking surgery for epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to determine the incidence and the risk factors of venous thromboembolism (VTE) within 30 days after primary surgery for epithelial ovarian cancer (EOC). METHODS: In a historical cohort study, we estimated the postoperative 30-day cumulative incidence of VTE among consecutive Mayo Clinic patients undergoing primary cytoreduction for EOC between January 2, 2003, and December 29, 2008. We tested perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program, >130 variables) as potential predictors of postoperative VTE using the Cox proportional hazards modeling. RESULTS: Among 569 cases of primary EOC cytoreduction and/or staging and no recent VTE, 35 developed symptomatic VTE within 30 days after surgery (cumulative incidence = 6.5%; 95% confidence interval, 4.4%-8.6%). Within the cohort, 95 (16.7%) received graduated compression stockings (GCSs), 367 (64.5%) had sequential compression devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs + postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%, respectively (P = 0.07, χ(2) test). The remaining 38 (6.7%) received various other chemical and mechanical prophylaxis regimens. In the multivariate analysis, current or past tobacco smoking, longer hospital stay, and a remote history of VTE significantly increased the risk for postoperative VTE. CONCLUSIONS: Venous thromboembolism is a substantial postoperative complication among women with EOC, and the high cumulative rate of VTE within 30 days after primary surgery suggests that a more aggressive strategy is needed for VTE prevention. In addition, because longer hospital stay is independently associated with a higher risk for VTE, methods to decrease length of stay and minimize factors that contribute to prolonged hospitalization are warranted.

Risk-scoring model for prediction of non-home discharge in epithelial ovarian cancer patients.

BACKGROUND: Identification of preoperative factors predictive of non-home discharge after surgery for epithelial ovarian cancer (EOC) may aid counseling and optimize discharge planning. We aimed to determine the association between preoperative risk factors and non-home discharge. STUDY DESIGN: Patients who underwent primary surgery for EOC at Mayo Clinic between January 2, 2003 and December 29, 2008 were included. Demographic, preoperative, and intraoperative factors were retrospectively abstracted. Logistic regression models were fit to identify preoperative factors associated with non-home discharge. Multivariable models were developed using stepwise and backward variable selection. A risk-scoring system was developed for use in preoperative counseling. RESULTS: Within our cohort of 587 EOC patients, 12.8% were not discharged home (61 went to a skilled nursing facility, 1 to a rehabilitation facility, 1 to hospice, and there were 12 in-hospital deaths). Median length of stay was 7 days (interquartile range [IQR] 5, 10 days) for patients dismissed home compared with 11 days (IQR 7, 17 days) for those with non-home dismissals (p < 0.001). In multivariable analyses, patients with advanced age (odds ratio [OR] 3.75 95% CI [2.57, 5.48], p < 0.001), worse Eastern Cooperative Oncology Group (ECOG) performance status (OR 0.92 [95% CI 0.43, 1.97] for ECOG performance status 1 vs 0 and OR 5.40 (95% CI 2.42, 12.03) for score of 2+ vs 0; p < 0.001), greater American Society of Anesthesiologists (ASA) score (OR 2.03 [95% CI 1.02, 4.04] for score ≥3 vs < 3, p = 0.04), and higher CA-125 (OR 1.28 [95% CI 1.12, 1.46], p < 0.001) were less likely to be discharged home. The unbiased estimate of the c-index was excellent at 0.88, and the model had excellent calibration. CONCLUSIONS: Identification of preoperative factors associated with non-home discharge can assist patient counseling and postoperative disposition planning.

Predictors and costs of surgical site infections in patients with endometrial cancer.

OBJECTIVE: Technological advances in surgical management of endometrial cancer (EC) may allow for novel risk modification in surgical site infection (SSI). METHODS: Perioperative variables were abstracted from EC cases surgically staged between January 1, 1999, and December 31, 2008. Primary outcome was SSI, as defined by American College of Surgeons National Surgical Quality Improvement Program. Counseling and global models were built to assess perioperative predictors of superficial incisional SSI and organ/space SSI. Thirty-day cost of SSI was calculated. RESULTS: Among 1369 EC patients, 136 (9.9%) had SSI. In the counseling model, significant predictors of superficial incisional SSI were obesity, American Society of Anesthesiologists (ASA) score >2, preoperative anemia (hematocrit <36%), and laparotomy. In the global model, significant predictors of superficial incisional SSI were obesity, ASA score >2, smoking, laparotomy, and intraoperative transfusion. Counseling model predictors of organ/space SSI were older age, smoking, preoperative glucose >110 mg/dL, and prior methicillin-resistant Staphylococcus aureus (MRSA) infection. Global predictors of organ/space SSI were older age, smoking, vascular disease, prior MRSA infection, greater estimated blood loss, and lymphadenectomy or bowel resection. SSI resulted in a $5447 median increase in 30-day cost. CONCLUSIONS: Our findings are useful to individualize preoperative risk counseling. Hyperglycemia and smoking are modifiable, and minimally invasive surgical approaches should be the preferred surgical route because they decrease SSI events. Judicious use of lymphadenectomy may decrease SSI. Thirty-day postoperative costs are considerably increased when SSI occurs.

Impact of tubal ligation on routes of dissemination and overall survival in uterine serous carcinoma.

OBJECTIVE: Abdominal peritoneal implants are characteristic of uterine serous carcinoma (USC). The presumed mechanism of dissemination is retrograde transit via the fallopian tube. We assessed the impact of tubal ligation (TL) on the metastatic profile and survival of USC patients. METHODS: Patient risk factors, process-of-care variables, and disease-specific parameters were annotated. Categorical variables were compared using the χ(2) test. Overall survival (OS) was estimated via the Kaplan-Meier method. RESULTS: Among 211 USC patients, fallopian tube status was documented in 142 patients; 35 had a history of TL and 107 did not. When comparing patients with and without TL, positive peritoneal cytology was present, respectively, in 18.8% vs 45.0% (P=.01) and stage IV disease in 14.3% vs 34.6% (P=.02). Using Cox models, age was the sole significant determinant of OS in stage I/II USC. By contrast, age, lymphovascular space involvement, positive cytology, and TL independently and adversely affected survival in stage III/IV USC. Adjusting for these factors in a multivariable model, the association between TL and OS among patients with advanced disease yielded a hazard ratio of 8.61 (95% CI, 3.08-24.03; P<.001). The prevalence of lymphatic metastasis and nodal tumor burden was significantly greater in patients who underwent ligation. CONCLUSION: Patients with TL had significantly lower rates of positive cytology and stage IV disease than patients without TL. The lymphatic system appeared to be the dominant mode of spread after TL and was associated with a paradoxic worsening of OS, perhaps reflecting a delay in diagnosis.

Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma.

OBJECTIVE: Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC. METHODS: We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed. Univariate analyses were used to identify POI risk factors; variables with P ≤.20 were included in multivariate analysis. RESULTS: Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P=.002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6 days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs 3 days) gastrointestinal tract (P<.001 for each). CONCLUSIONS: The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed.