Predictive validity of American College of Surgeons: National Surgical Quality Improvement Project risk calculator in patients with ovarian cancer undergoing interval debulking surgery.

INTRODUCTION: In gynecologic patients, few studies describe the accuracy of the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) pre-operative risk calculator for women undergoing surgery for ovarian cancer. OBJECTIVE: To determine whether the ACS-NSQIP risk calculator accurately predicts post-operative complications and length of stay in patients undergoing interval debulking surgery for advanced stage epithelial ovarian cancer. METHODS: For this multi-institutional retrospective cohort study, pre-operative risk factors, post-operative complication rates, and Current Procedural Terminology codes were abstracted from records of patients with ovarian cancer managed with open interval debulking surgery from January 2010 to July 2015. A power calculation was done to estimate the minimum number of complications needed to evaluate the accuracy of the ACS-NSQIP risk calculator. Predicted risk compared with observed risk was calculated using logistic regression. The predictive accuracy of the ACS-NSQIP risk calculator in estimating post-operative complications or length of stay was assessed using c-statistics and Briar scores. Complications with a c-statistic of >0.70 and Brier score of <0.01 were considered to have high discriminative ability. RESULTS: A total of 261 patients underwent interval debulking surgery, encompassing 21 unique Current Procedural Terminology codes. Readmission (n=25), surgical site infection (n=35), urinary tract infection (n=12), and serious post-operative complications (n=57) met the minimum event threshold (n>10). All predicted complication rates fell within the IQR of the observed incidence rates. However, the ACS-NSQIP calculator demonstrated neither discriminative ability nor accuracy for any post-operative complications based on c-statistics and Brier scores. The calculator accurately predicted length of stay within 1 day for only 32% of patients and could not accurately predict which patients were likely to have a prolonged length of stay (c-statistic=0.65). CONCLUSION: Among patients undergoing interval debulking surgery, the ACS-NSQIP did not accurately discriminate which patients were at increased risk of complications or extended length of stay. The risk calculator should be considered to have limited utility in informing pre-operative counseling or surgical planning.

Fragmentation of surgery and chemotherapy in the initial phase of ovarian cancer care and its association with overall survival.

BACKGROUND: Fragmentation occurs when a patient receives care at more than one hospital, and the long-term effects in ovarian cancer are unknown. We examined the association between fragmentation of primary debulking surgery (PDS) and adjuvant chemotherapy (AC) and overall survival (OS). METHODS: The National Cancer Database was used to identify women with stage II-IV epithelial ovarian cancer between 2004 and 2016 who underwent PDS followed by AC. Fragmentation was defined as receipt of AC at a different institution than where PDS was performed. After propensity score weighting, proportional hazard models were developed to estimate the association between fragmented care and OS. RESULTS: Of the 36,300 patients identified, 13,347 (36.8%) had fragmented care. Patient factors associated with fragmentation included older age, higher income, and longer travel distance for PDS; hospital factors included PDS performed at a community center or a facility with lower annual surgical volume (P < 0.05, all). Fragmentation was associated with a 15% risk of 30-day delay to AC (aRR 1.15, 95% CI 1.09-1.22). In a propensity scoring weighted analysis, mortality was reduced when AC was fragmented (HR 0.95, 95% CI 0.92-0.97). Sensitivity analyses indicated fragmentation was associated with improved survival in metropolitan residents. Stratified analyses indicated patients who traveled 50 miles or more with PDS and AC at the same institution had the worst OS. CONCLUSION: Fragmentation of PDS and AC has no adverse effects on long-term survival. Survival outcomes were worst for those who received care at the same institution 50 miles or more away.

The effect of frailty on postoperative readmissions, morbidity, and mortality in endometrial cancer surgery.

OBJECTIVES: To determine the impact of frailty on postoperative readmission, morbidity, and mortality among patients undergoing surgery for endometrial cancer. METHODS: Patients with endometrial cancer undergoing hysterectomy between 2010 and 2014 were identified using the Nationwide Readmissions Database. Frailty was classified using criteria outlined by the Johns Hopkins Adjusted Clinical Groups Frailty Diagnoses Indicators. Primary outcomes were divided by index surgical admission (intensive level of care, mortality, non-routine discharge), 30-days (readmission and mortality), and 90-days (readmission and mortality) after discharge. Multivariable log linear regression models were fit to analyze the effect of frailty on these outcomes, adjusting for patient, hospital, and clinical factors. RESULTS: From 2010 to 2014, there were 144,809 surgical endometrial cancer cases with a 1.8% frailty rate. Frailty was associated with an increased risk of intensive level of care (aRR = 3.61, 95% CI: 2.95, 4.42), non-routine discharge (aRR = 1.59, 95% CI: 1.51, 1.68), and inpatient mortality (aRR = 2.05, 95% CI: 1.68, 2.51) during index admission. Frail patients were more likely to be readmitted within 30 days (RR 1.33, 95% CI 1.22-1.47) and 90-days (RR 1.21, 95% CI 1.12, 1.32), and were at increased risk of mortality during their 30-day readmission (aRR = 1.75, 95% CI: 1.28-2.39). Frailty was not associated with 90-day mortality. Hospitalization costs for frail patients were significantly higher than for non-frail patients during index admission and readmissions within 30 and 90 days (p < 0.05 for all). CONCLUSIONS: Frailty affects postoperative outcomes in endometrial cancer patients and is associated with an increased rate of readmission and 30-day mortality among those who are readmitted. Gynecologic cancer providers should screen for frailty and consider outcomes in frail patients when counseling them for surgery.

Advanced ovarian cancer and cytoreductive surgery: Independent validation of a risk-calculator for perioperative adverse events.

OBJECTIVE: To independently validate a published risk-calculator for adverse perioperative outcomes in patients with epithelial ovarian cancer undergoing debulking surgery at a high-volume surgical center. METHODS: Using our institution's curated prospective ovarian cancer database, we identified patients with epithelial ovarian cancer who underwent a debulking procedure from 7/2015 to 5/2019, to be used as the validation cohort. Variables used in the published nomogram were collected. These included American Society of Anesthesiology classification, preoperative albumin, history of bleeding disorder, presence of ascites on preoperative imaging, designation of elective or emergent surgery, age of the patient, and a procedure score. Patients were included if they had information available for all the variables used in the nomogram, and 30-day follow-up within our institution. The primary outcome was Clavien-Dindo Class IV with specific conditions (postoperative sepsis, septic shock, cardiac arrest, myocardial infarction, pulmonary embolism, ventilation >48 h, or unplanned intubation) and 30-day mortality. The combination of these endpoints is called the combined complication rate. RESULTS: A total of 700 patients who underwent debulking surgery for epithelial ovarian cancer during the timeframe met inclusion criteria. The combined complication rate was 11.7%; 9.9% of patients were readmitted; 2.7% required reoperation. Sepsis was the most common primary endpoint complication (4.4%), followed by septic shock (1.4%). There was no 30-day mortality in our cohort. The nomogram performed well, with a c index of 0.715 (95% CI 0.66-0.768), which was comparable to the published nomogram. CONCLUSIONS: We independently validated a complication nomogram at a high-volume surgical center. This nomogram performs well at predicting a lower likelihood of serious postoperative complications. An enhanced nomogram would help identify patients at higher risk for serious complications.

Effect of frailty on postoperative readmissions and cost of care for ovarian cancer.

OBJECTIVES: Frailty, defined as loss of reserve and vulnerability to changes in health, affects many ovarian cancer patients who are planned to undergo surgery. The effect of frailty on postoperative readmissions in ovarian cancer patients remains poorly defined. We investigated the effect of frailty on unplanned readmission, morbidity, and mortality among patients undergoing surgery for ovarian cancer. STUDY DESIGN: Patients who underwent laparotomy for ovarian cancer between 2010 and 2014 were identified using the Nationwide Readmissions Database. Frailty was classified using the Johns Hopkins Adjusted Clinical Groups Frailty Diagnoses Indicators. Primary outcomes were divided into index admission (intensive level of care, mortality, non-routine discharge,) 30-days (readmission and mortality), and 90-days (readmission and mortality). Multivariable regression models were fit, adjusting for patient, hospital, and clinical factors. RESULTS: From 2010 to 2014, there were 76,441 inpatient laparotomies identified with a 6.1% frailty rate. Frailty was associated with an increased risk of intensive level of care (aRR = 1.76, 95% CI: 1.68, 1.85), non-routine discharge (aRR = 1.39, 95% CI: 1.33, 1.45), and inpatient mortality (aRR = 1.91, 95% CI: 1.63, 2.23) during the index admission. Frail patients were more likely to be readmitted within 90 days (aRR = 1.11, 95% CI: 1.04-1.18), sustain mortality during 90-day readmission (aRR = 1.31, 95% CI 1.01-1.69), and have longer and costlier index hospital stays. Hospital readmission costs did not differ significantly between frail and non-frail patients. CONCLUSIONS: Frailty affects postoperative outcomes in ovarian cancer patients and is associated with an increased rate of 90-day readmission and mortality among those who are readmitted. Gynecologic oncologists should screen for frailty and consider outcomes in frail ovarian cancer patients when counseling for surgery.

Fragmentation of postoperative care after surgical management of ovarian cancer at 30 days and 90 days.

BACKGROUND: Fragmentation of care, wherein a patient is discharged from an index hospital and undergoes an unexpected readmission to a nonindex hospital, is associated with increased risk of adverse outcomes. Fragmentation has not been well-characterized in ovarian cancer. OBJECTIVE: The objective of this study was to assess risk factors and outcomes that are associated with fragmentation of care among women who undergo surgical treatment of ovarian cancer. STUDY DESIGN: The Nationwide Readmission Database was used to identify all-cause 30-day and 90-day postoperative readmissions after surgical management of ovarian cancer from 2010-2014. Postoperative fragmentation was defined as readmission to a hospital other than the index hospital of the initial surgery. Multivariable regression analyses were used to identify predictors of fragmentation in both 30-day and 90-day readmissions. Similarly, multivariable models were developed to determine the association between fragmentation and death among women who were readmitted. RESULTS: A total of 10,445 patients (13.3%) were readmitted at 30 days, and 14,124 patients (18.0%) were readmitted at 90 days. Of these, there was a 20.8% and 25.7% rate of postoperative care fragmentation for 30-day and 90-day readmissions, respectively. Patient risk factors that were associated with fragmented postoperative care included Medicare insurance, lower income quartiles, and nonroutine discharge to facility. Hospital factors that were associated with decreased risk of fragmentation included operation at a metropolitan teaching hospital and performance of extended procedures. Cost and length of stay for the readmission were similar among those who had fragmented and nonfragmented readmissions at both 30 and 90 days. Although there was no association between death and fragmentation for patients who were readmitted within 30 days (odds ratio, 1.19; 95% confidence interval, 0.93-1.51), patients who had a fragmented readmission at 90 days were 22% more likely to die than those who were readmitted at 90 days to their index hospital (odds ratio, 1.22; 95% confidence interval, 1.00-1.49). CONCLUSION: Fragmentation of care is common in women with ovarian cancer who require postoperative readmission. Fragmented postoperative care is associated with an increased risk of death among women who are readmitted within 90 days of surgery.

Development and validation of a risk-calculator for adverse perioperative outcomes for women with ovarian cancer.

BACKGROUND: Primary cytoreduction followed by platinum-based chemotherapy is the primary treatment for advanced ovarian cancer. However, neoadjuvant chemotherapy followed by interval debulking is an alternative option, particularly in those who may be poor surgical candidates. OBJECTIVE: The objective of this study was to determine factors associated with short-term, significant perioperative morbidity and mortality for women undergoing surgery for ovarian cancer and to create a nomogram to predict the risk of adverse perioperative outcomes. STUDY DESIGN: We used the National Surgical Quality Improvement Program database to identify women with ovarian, fallopian tube, or primary peritoneal cancer who underwent surgery from 2011 to 2015. Demographic factors, clinical characteristics, comorbidity, functional status, and the extent of surgery were used to predict the risk of severe perioperative complications or death using multivariable models. Multiple imputation methods were employed for missing data. A nomogram was developed based on the final model. The discrimination ability of the model was assessed with a calibration plot and discrimination concordance index. RESULTS: We identified a total of 7029 patients. Overall, 5.8% of patients experienced a Clavien-Dindo IV complication, 9.8% of patients were readmitted, 3.0% of patients required a reoperation, and 0.9% of patients died within 30 days. Among the baseline variables assessed, increasing age, emergent surgery, ascites, bleeding disorder, low albumin, higher American Society of Anesthesiology classification score, and a higher extended procedure score were associated with serious perioperative morbidity or mortality. Of these factors, performance of ≥3 cytoreductive procedures (adjusted odds ratio 4.53, 95% confidence interval 3.01-6.82), American Society of Anesthesiology classification score ≥ class 4 (adjusted odds ratio 2.89, 95% confidence interval 1.17-7.14), bleeding disorder (adjusted odds ratio 2.73, 95% confidence interval 1.82-4.10), and age ≥80 years (adjusted odds ratio 2.46, 95% confidence interval 1.66-3.63) were most strongly associated with risk of an event. The final nomogram included the above variables and had an internal discrimination concordance index of 0.71, with accurate predictions in an internal validation set, indicating a 71% correct identification of patients across all possible pairs. CONCLUSION: Women undergoing surgery for ovarian cancer are at significant risk for the occurrence of adverse perioperative outcomes. Using readily identifiable characteristics, this nomogram can predict adverse outcomes.

Utility of radiation therapy for early-stage uterine papillary serous carcinoma.

OBJECTIVE: Early-stage uterine papillary serous carcinoma (UPSC) has a poor prognosis and high recurrence rate. While adjuvant chemotherapy is generally recommended, the role of radiation is uncertain. We examined the association between vaginal brachytherapy and whole pelvic radiation and survival in women treated with and without adjuvant chemotherapy. METHODS: The National Cancer Data Base was used to identify women with stage I-II UPSC treated between 1998 and 2012. Trends in use of chemotherapy, brachytherapy, and external beam radiation over time were examined. The association between these treatments and mortality were examined using multivariable Cox proportional hazards models. RESULTS: A total of 7325 patients were identified. Overall, 2779 (37.9%) received chemotherapy. The use of vaginal brachytherapy increased from 7.2% in 1998 to 29.1% in 2012 (P<0.0001), while use of external beam radiation decreased from 18.2% to 11.7% over the same period (P<0.0001). Use of chemotherapy was associated with a 22% reduction in mortality (HR=0.78; 95% CI, 0.69-0.88). While brachytherapy was associated with decreased mortality (HR=0.67; 95% CI, 0.57-0.78), use of external beam radiation was not associated with survival (HR=1.03; 95% CI, 0.92-1.17). Stratified by stage, use of chemotherapy was associated with decreased mortality for women with stage IB and II tumors, but not for stage IA neoplasms. Vaginal brachytherapy was associated with reduced mortality for stage IA and II neoplasms. CONCLUSION: For women with early-stage UPSC, chemotherapy is associated with improved survival. Vaginal brachytherapy was also associated with improved survival, however, there was little benefit to use of external beam radiation.

Utilization of sentinel lymph node biopsy for uterine cancer.

BACKGROUND: To limit the potential short and long-term morbidity of lymphadenectomy, sentinel lymph node biopsy has been proposed for endometrial cancer. The principle of sentinel lymph node biopsy relies on removal of a small number of lymph nodes that are the first drainage basins from a tumor and thus the most likely to harbor tumor cells. While the procedure may reduce morbidity, efficacy data are limited and little is known about how commonly the procedure is performed. OBJECTIVE: We examined the patterns and predictors of use of sentinel lymph node biopsy and outcomes of the procedure in women with endometrial cancer who underwent hysterectomy. STUDY DESIGN: We used the Perspective database to identify women with uterine cancer who underwent hysterectomy from 2011 through 2015. Billing and charge codes were used to classify women as having undergone lymphadenectomy, sentinel lymph node biopsy, or no nodal assessment. Multivariable models were used to examine clinical, demographic, and hospital characteristics with use of sentinel lymph node biopsy. Length of stay and cost were compared among the different methods of nodal assessment. RESULTS: Among 28,362 patients, 9327 (32.9%) did not undergo nodal assessment, 17,669 (62.3%) underwent lymphadenectomy, and 1366 (4.8%) underwent sentinel lymph node biopsy. Sentinel lymph node biopsy was performed in 1.3% (95% confidence interval, 1.0-1.6%) of abdominal hysterectomies, 3.4% (95% confidence interval, 2.7-4.1%) of laparoscopic hysterectomies, and 7.5% (95% confidence interval, 7.0-8.0%) of robotic-assisted hysterectomies. In a multivariable model, more recent year of surgery was associated with performance of sentinel lymph node biopsy. Compared to abdominal hysterectomy, those undergoing laparoscopic (adjusted risk ratio, 2.45; 95% confidence interval, 1.89-3.18) and robotic-assisted (adjusted risk ratio, 2.69; 95% confidence interval, 2.19-3.30) hysterectomy were more likely to undergo sentinel lymph node biopsy. Among women who underwent minimally invasive hysterectomy, length of stay and cost were lower for sentinel lymph node biopsy compared to lymphadenectomy. CONCLUSION: The use of sentinel lymph node biopsy for endometrial cancer increased from 2011 through 2015. The increased use was most notable in women who underwent a robotic-assisted hysterectomy.

Utilization and Outcomes of Sentinel Lymph Node Biopsy for Vulvar Cancer.

OBJECTIVE: To examine the use and predictors of sentinel node biopsy in women with vulvar cancer. METHODS: The Perspective database, an all-payer database that collects data from more than 500 hospitals, was used to perform a retrospective cohort study of women with vulvar cancer who underwent vulvectomy and lymph node assessment from 2006 to 2015. Multivariable models were used to determine factors associated with sentinel node biopsy. Length of stay and cost were compared between women who underwent sentinel node biopsy and lymphadenectomy. RESULTS: Among 2,273 women, sentinel node biopsy was utilized in 618 (27.2%) and 1,655 (72.8%) underwent inguinofemoral lymphadenectomy. Performance of sentinel node biopsy increased from 17.0% (95% confidence interval [CI] 12.0-22.0%) in 2006 to 39.1% (95% CI 27.1-51.0%) in 2015. In a multivariable model, women treated more recently were more likely to have undergone sentinel node biopsy, whereas women with more comorbidities and those treated at rural hospitals were less likely to have undergone the procedure. The median length of stay was shorter for those undergoing sentinel node biopsy (median 2 days, interquartile range 1-3) compared with women who underwent inguinofemoral lymphadenectomy (median 3 days, interquartile range 2-4). The cost of sentinel node biopsy was $7,599 (interquartile range $5,739-9,922) compared with $8,095 (interquartile range $5,917-11,281) for lymphadenectomy. CONCLUSION: The use of sentinel node biopsy for vulvar cancer has more than doubled since 2006. Sentinel lymph node biopsy is associated with a shorter hospital stay and decreased cost compared with inguinofemoral lymphadenectomy.

Dynamic Parathyroid Computed Tomography (4DCT) Facilitates Reoperative Parathyroidectomy and Enables Cure of Missed Hyperplasia.

BACKGROUND: Four-dimensional computed tomography (4DCT) is an emerging imaging modality in the evaluation of primary hyperparathyroidism (PHPT). We assessed the role of 4DCT in patients presenting for reoperative parathyroidectomy. METHODS: A prospective database of patients with persistent or recurrent PHPT undergoing reoperative parathyroidectomy during the years 2006-2014 was analyzed. Patients treated before versus after the advent of 4DCT were compared for operative eligibility, operative success, operative time, and concordance of imaging results with surgical findings. RESULTS: Ninety patients were included in the study (61 before 4DCT, 29 after 4DCT). The post-4DCT group had a higher rate of surgical concordance with imaging results (63 vs. 90 %, p < 0.01) and shorter operative time (114 vs. 76 min, p < 0.05). The operative success rate was not different (87 vs. 86 %). A similar pattern was observed in the subset of sestamibi-negative patients, with post-4DCT patients having a higher rate of surgical concordance (12 vs. 83 %, p < 0.0001) and shorter operative time (181 vs. 89 min, p < 0.05). Among patients ultimately found to have parathyroid hyperplasia, 4DCT correctly identified multiple enlarged glands in 80 % (4 of 5) and correctly lateralized one or more glands in 100 % (5 of 5) of cases, facilitating successful subtotal parathyroidectomy in the reoperative setting. CONCLUSIONS: 4DCT enables successful and efficient reoperative parathyroidectomy. These benefits extend to difficult cases, including sestamibi-negative patients and those with missed hyperplasia.

Risk-based ultrasound screening for thyroid cancer in obese patients is cost-effective.

BACKGROUND: A higher body mass index (BMI) is associated with more advanced stages of thyroid cancer. Screening obese patients for thyroid cancer has been proposed but has yet to be examined for cost-effectiveness. The objective of this study was to assess the cost-effectiveness of ultrasound (US) screening of obese patients for thyroid cancer. METHODS: A decision-tree model compared cost savings for the following: (i) base case scenario of an obese patient with thyroid nodule found by palpation, (ii) universal US screening of all obese patients, and (iii) risk-based US screening in obese patients. Risk-based screening consisted of patients who had at least one of four major identified risk factors for thyroid cancer (family history of thyroid cancer, radiation exposure, Hashimoto's thyroiditis, and/or elevated thyrotropin). Patients with nodules underwent established treatment and management guidelines. The model accounted for recurrence, complications, and long-term treatment/follow-up for five years. Outcome probabilities were identified from a literature review. Costs were estimated using a third-party payer perspective. Sensitivity analyses were performed to examine the impact of risk factor prevalence and US cost on the model. RESULTS: The resulted costs per patient were $210.73 in the base case scenario, $434.10 in the universal US screening arm, and $166.72 in the risk-based screening arm. Risk-based screening remained cost-effective until more than 14% of obese patients had risk factors and with a wide variation of US costs ($0-$1113). CONCLUSION: Risk-based US screening in selected obese patients with risk factors for thyroid cancer is cost-effective. Recommendations for screening this subgroup will result in cost savings and a likely decreased morbidity and mortality in this subpopulation with more aggressive disease.