Carrie L. Langstraat

Morbidity, mortality and overall survival in elderly women undergoing primary surgical debulking for ovarian cancer: A delicate balance requiring individualization

OBJECTIVE To assess outcomes and identify underlying predictors of outcomes in a cohort of women over the age of 65 treated for primary ovarian cancer (OC). METHODS Consecutive patients ≥ 65 with stage IIIC or IV OC treated with primary surgery and adjuvant chemotherapy at Mayo Clinic between January 1, 1994 and December 31, 2004 were retrospectively assessed. We analyzed the impact of perioperative factors (age, albumin, CA125, American Society of Anesthesiologist (ASA) score, amount of ascites, presence of carcinomatosis, creatinine, need for urgent surgery, stage of disease, surgical complexity score and amount of residual disease) on surgical outcomes (morbidity, mortality, overall survival (OS) and ability to receive chemotherapy). RESULTS Two hundred eighty patients met inclusion criteria. Age was associated with higher ASA score, lower albumin, and higher creatinine; stage, diffuse peritoneal disease, and surgical complexity were not associated with age. Median OS decreased with increasing age and residual disease (RD), and the impact of RD was greater on older patients. All patients benefited similarly when RD=0 [median OS 5.9 years for age 65-69 vs. 5.0 years in those ≥ 80 (p=0.5516)], for RD<1cm, and OS was 3.4 vs. 2.1 years respectively for youngest vs. oldest patients (p=0.068). Perioperative morbidity was observed in 37.5% of patients ≥ 75. Independent predictors of poor perioperative outcome included preoperative albumin ≤ 3g/dL, urgent surgery, age, and stage (p<0.05). Independent predictors of overall survival included creatinine, albumin, surgical complexity score, amount of residual disease, stage and age. CONCLUSION Age is an independent predictor of OS in OC. A significant number of elderly women are able to undergo a complete cytoreduction and experience OS similar to that of younger patients. However, the benefits to incomplete cytoreduction are less clear in women ≥ 75. These observations highlight the need to use emerging predictors of outcomes in decision making and to focus care in centers able to render patients with no visible residual disease.

Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer

OBJECTIVE Preoperative thrombocytosis has been implicated as a negative prognostic marker for epithelial ovarian cancer (EOC). We assessed whether thrombocytosis is an independent risk factor for EOC recurrence and death. METHODS Perioperative patient characteristics and process-of-care variables (National Surgical Quality Improvement Program (NSQIP)-defined) were retrospectively abstracted from 587 women who underwent EOC staging between 1/2/03-12/29/08. Thrombocytosis was defined as platelet count > 450 × 10(9)/L. Disease-free survival (DFS) and overall survival (OS) were determined using Kaplan-Meier methods. Associations were evaluated with Cox proportional hazards regression and hazard ratios (HR). RESULTS The incidence of preoperative thrombocytosis was 22.3%. DFS was 70.8% and 36.0% at 1 and 3 years. OS was 83.3% and 54.3% at 1 and 3 years. Ascites, lower hemoglobin, advanced disease, and receipt of perioperative packed red blood cell transfusion were independently associated with thrombocytosis. Older age and the presence of coronary artery disease were associated with lower likelihood of thrombocytosis. Overall, thrombocytosis was an independent predictor of increased risk of recurrence. Among early stage (I/II) cases, there was a 5-fold increase in the risk of death and nearly 8-fold risk of disease recurrence independently associated with thrombocytosis. CONCLUSION Preoperative thrombocytosis portends worse DFS in EOC. In early stage disease, thrombocytosis is a potent predictor of worse DFS and OS and further assessment of the impact of circulating platelet-derived factors on EOC survival is warranted. Thrombocytosis is also associated with extensive initial disease burden, measurable residual disease, and postoperative sequelae. Preoperative platelet levels may have value in primary cytoreduction counseling.

Using Bundled Interventions to Reduce Surgical Site Infection After Major Gynecologic Cancer Surgery.

OBJECTIVE: To investigate whether implementing a bundle, defined as a set of evidence-based practices performed collectively, can reduce 30-day surgical site infections. METHODS: Baseline surgical site infection rates were determined retrospectively for cases of open uterine cancer, ovarian cancer without bowel resection, and ovarian cancer with bowel resection between January 1, 2010, and December 31, 2012, at an academic center. A perioperative bundle was prospectively implemented during the intervention period (August 1, 2013, to September 30, 2014). Prior established elements were: patient education, 4% chlorhexidine gluconate shower before surgery, antibiotic administration, 2% chlorhexidine gluconate and 70% isopropyl alcohol coverage of incisional area, and cefazolin redosing 3–4 hours after incision. New elements initiated were: sterile closing tray and staff glove change for fascia and skin closure, dressing removal at 24–48 hours, dismissal with 4% chlorhexidine gluconate, and follow-up nursing phone call. Surgical site infection rates were examined using control charts, compared between periods using &khgr;2 or Fisher exact test, and validated against the American College of Surgeons National Surgical Quality Improvement Program decile ranking. RESULTS: The overall 30-day surgical site infection rate was 38 of 635 (6.0%) among all cases in the preintervention period, with 11 superficial (1.7%), two deep (0.3%), and 25 organ or space infections (3.9%). In the intervention period, the overall rate was 2 of 190 (1.1%), with two organ or space infections (1.1%). Overall, the relative risk reduction in surgical site infection was 82.4% (P=.01). The surgical site infection relative risk reduction was 77.6% among ovarian cancer with bowel resection, 79.3% among ovarian cancer without bowel resection, and 100% among uterine cancer. The American College of Surgeons National Surgical Quality Improvement Program decile ranking improved from the 10th decile to first decile; risk-adjusted odds ratio for surgical site infection decreased from 1.6 (95% confidence interval 1.0–2.6) to 0.6 (0.3–1.1). CONCLUSION: Implementation of an evidence-based surgical site infection reduction bundle was associated with substantial reductions in surgical site infection in high-risk cancer procedures.

Nutritional status, CT body composition measures and survival in ovarian cancer

OBJECTIVE Body composition measures (BCMs) are an important predictor of nutritional status in patients with cancer. Poor nutritional status is common in ovarian cancer (OC) and is a well-known variable that influences cancer treatment and outcome. We aim to establish the role of BCMs measured by computed tomography (CT) in predicting outcomes in patients with OC. METHODS We retrospectively searched our institutional database for patients with stage IIIC/IV OC who underwent surgery as primary treatment at Mayo Clinic between 1996 and 2005 and had adequate presurgical CT images available. For each patient, 1 axial CT image at the level of the 3rd lumbar vertebra was evaluated. Adipose and lean tissues were discriminated using commercially available software. Cox models were fit to evaluate the relationship between patient factors and overall survival (OS). Associations were summarized using hazard ratios (HRs) and corresponding 95% CIs. RESULTS A total of 82 patients were identified, with a median age of 68.4 years. OS at 1 and 5 years was 84.1% and 24.1%, respectively. Older age (P=.01), stage IV disease (P<.001), and subcutaneous and muscular fat<77.21cm(2) (P<.001) were independently associated with poor OS. Longer hospital stay was independently predicted by albumin≤3g/dL (P=.03), suboptimal surgery (P=.02), and subcutaneous and muscular fat<77.21cm(2) (P<.001). Surgical complications were independently predicted only by albumin≤3g/dL (P<.01). CONCLUSIONS CT BCMs, as indicators of nutritional status, are independent predictors of longer hospital stay and poor OS in patients with OC.

Muscle composition measured by CT scan is a measurable predictor of overall survival in advanced ovarian cancer

OBJECTIVES To assess the impact of muscle composition and sarcopenia on overall survival in advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS Women with stage IIIC/IV EOC who underwent PDS with curative intent between 1/1/2006 and 12/31/2012 were included. Patient variables and vital status were abstracted. Body composition was evaluated in a semi-automated process using Slice-O-Matic software v4.3 (TomoVision). Skeletal muscle area and mean skeletal muscle attenuation were recorded. Associations with overall survival were evaluated using Cox proportional hazards models and recursive partitioning. RESULTS We identified 296 patients and 132 (44.6%) were classified as sarcopenic. The average mean skeletal muscle attenuation of the entire cohort was 33.4 Hounsfield units (HU). A multivariate model of overall risk of death included histology, residual disease, and mean skeletal attenuation. Among patients without residual disease, overall survival, but not progression free survival was significantly different between patients with low versus high mean skeletal attenuation (median survival, 2.8 vs. 3.3years). Among patients with residual disease, overall survival was significantly different between patients with low versus high mean skeletal attenuation ≥36.40 vs. <36.40 HU (median survival, 2.0 vs. 3.3years). CONCLUSIONS Sarcopenia and low mean skeletal muscle attenuation are common in women undergoing PDS for advanced EOC. These factors are associated with poorer outcomes, and can be used in preoperative risk stratification and patient counseling. Further research into body composition and whether this risk factor can be altered via nutrition or fitness in this population is 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.

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 surgeons 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.

Abdominal Incision Injection of Liposomal Bupivacaine and Opioid Use After Laparotomy for Gynecologic Malignancies.

OBJECTIVE: To investigate opioid use and pain scores associated with incisional injection of liposomal bupivacaine compared with bupivacaine hydrochloride after laparotomy for gynecologic malignancies. METHODS: A retrospective cohort study was conducted to compare abdominal incision infiltration with liposomal bupivacaine with bupivacaine hydrochloride after modification of a pre-existing enhanced recovery pathway. Patients undergoing staging laparotomy or complex cytoreductive surgery under the updated pathway were compared with patients treated under the original pathway (historic controls). Endpoints included cumulative opioid use (primary outcome) in oral morphine equivalents and cumulative pain score. RESULTS: In the complex cytoreductive cohort, median oral morphine equivalents were lower in the liposomal bupivacaine group through 24 hours (30 compared with 53.5 mg, P=.002), 48 hours (37.5 compared with 82.5 mg, P=.005), and the length of stay (62 compared with 100.5 mg, P=.006). Fewer liposomal bupivacaine patients required intravenous rescue opioids (28.9% compared with 55.6%, P<.001) or patient-controlled analgesia (4.1% compared with 33.3%, P<.001). Cumulative pain score was no different between groups through 48 hours (161 compared with 158, P=.69). Postoperative nausea and ileus were less frequent in patients receiving liposomal bupivacaine. Median hospital stay was 5 days in both groups. In the staging laparotomy cohort, cumulative opioids and cumulative pain score were no different between groups (through 48 hours: 162 compared with 161, P=.62; 38 compared with 38, P=.68, respectively). Intravenous rescue opioids (15.3% compared with 28.6%, P=.05) and patient-controlled analgesia (1.4% compared with 8.3%, P=.05) were used less frequently in the liposomal bupivacaine group. Median hospital stay was 4 days in both groups. Despite the higher cost of liposomal bupivacaine, total pharmacy costs did not differ between groups. CONCLUSION: Abdominal incision infiltration with liposomal bupivacaine was associated with less opioid and patient-controlled analgesia use with no change in pain scores compared with bupivacaine hydrochloride after complex cytoreductive surgery for gynecologic malignancies. Improvements were also seen in patients undergoing staging laparotomy.

Risk-prediction model of severe postoperative complications after primary debulking surgery for advanced ovarian cancer

OBJECTIVES To refine models to predict surgical morbidity and 90-day mortality after primary debulking surgery (PDS) for advanced epithelial ovarian cancer (EOC). METHODS Women with stage IIIC/IV EOC who underwent PDS with curative intent between 1/2/2003 and 12/30/2011 were included. Patient characteristics, intraoperative and postoperative outcomes, and vital status were abstracted. Complications were graded using the Accordion classification. Nomograms were generated based on multivariate modeling. RESULTS 138 (22.3%) of the 620 patients who underwent PDS experienced a grade≥3 complication. Age (OR 1.21 per 10 years increase in age), BMI (OR 1.35 for BMI<25 kg/m2 versus reference, OR 2.83 for BMI≥40 kg/m2 versus reference), ASA score≥3 (OR 1.49), stage (OR 1.69 stage IV) and surgical complexity (OR 2.32 high complexity versus intermediate) were predictive of an accordion grade≥3 complication Within 90 days of surgery, 55 (8.9%) patients died. A multivariable model included age (OR 1.76 per 10 year increase in age), ASA score≥3 (OR 3.28), preoperative albumin<3.5 (OR 4.31), and BMI (OR 2.04 for BMI<25 kg/m2 versus reference, OR 3.64 for BMI≥ 40 kg/m2 versus reference) was predictive of 90-day mortality. CONCLUSION Using an independent cohort we report the importance of age, ASA score, preoperative albumin, FIGO stage, and surgical complexity, and BMI, to refine a prediction model for complications after PDS for advanced EOC. This information is useful in preoperative counseling and can be utilized to aid in patient-centered decision making and risk stratification.

Efforts at maximal cytoreduction improve survival in ovarian cancer patients, even when complete gross resection is not feasible

OBJECTIVE We sought to determine survival associated with residual disease (RD) after primary debulking surgery (PDS) for advanced ovarian cancer (OC), and evaluate impact on complications and survival after practice changes to improve PDS. METHODS Outcome variables were collected for patients undergoing PDS for FIGO (2009) stage IIIC OC from 2003 to 2011. The cohort was divided into time periods (2003-2006 vs. 2007-2011), before and after cytoreduction standardization. RD categories were: RD0, RD 0.1-0.5cm, RD 0.6-1.0cm, and RD>1cm. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. RESULTS 447 patients (mean age, 65.3years) met inclusion criteria. RD for the entire cohort: RD0=44.5%; RD 0.1-0.5cm=30.9%; RD 0.6-1.0cm=11.4%; and RD>1cm=13.2%, with median OS of 58months, 35months, 29months, and 22months, respectively. OS was significantly better for RD0 vs. all other RD categories (p≤0.001), and for RD 0.1-1.0cm vs. RD>1cm (p=0.01). RD0 improved from 32.7% to 54.3% (p<0.001), and RD>1cm decreased from 20.3% to 7.3% (p<0.001) when comparing the 2003-2006 (n=202) vs. 2007-2011 (n=245) cohorts. Surgical complexity increased in the latter time period (24.3% vs. 41.2%). 30-day Accordion grade 3-4 morbidity remained consistent (18.8% vs. 20.8%, p=0.60), 30-day mortality decreased (4.5% to 1.2%, p=0.035), and median OS improved from 36 to 40months after cytoreduction standardization. CONCLUSION Patients with RD0 had longest OS, with survival advantage for RD1 when compared to RD>1cm. These data support PDS to lowest RD even when RD0 cannot be obtained. Practice improvement efforts can increase RD0 rates, improving OS without compromising morbidity.