Shitanshu Uppal

Management for Elderly Women With Advanced-Stage, High-Grade Endometrial Cancer.

OBJECTIVE: To examine the treatment and survival of elderly women diagnosed with advanced-stage, high-grade endometrial cancer. METHODS: We performed a retrospective cohort study of women diagnosed between 2003 and 2011 with advanced-stage, high-grade endometrial cancers (grade 3 adenocarcinoma, carcinosarcoma, clear-cell carcinoma, and uterine serous carcinoma) using the National Cancer Database. Women were stratified by age: younger than 55, 55–64, 65–74, 75–84, and 85 years old or older. Multivariate logistic regression models and Cox proportional hazards survival methods for all-cause mortality were used for analyses. RESULTS: Twenty thousand four hundred sixty-eight patients were included, 14.9% younger than 55 years, 30.9% 55–64 years, 31.1% 65–74 years, 18.8% 75–84 years, and 4.3% 85 years old or older. Patients younger than 55 years had surgery more frequently compared with patients 75–84 years (97.2% compared with 95.8%; P<.001) and 85 years or older (97.2% compared with 94.8%; P<.001) and a higher rate of lymph node dissection (78.7% compared with 70.5%; P<.001 and 78.7% compared with 59.5%; P<.001, respectively). Women younger than 55 years old were more likely to receive chemotherapy compared with those 75–84 years (63.9% compared with 42.2%; P<.001) and 85 years old or older (63.9% compared with 22%; P<.001). After adjusting for prognostic factors, women ages 75–84 and 85 years or older were less likely to have received chemotherapy compared with women younger than 55 years (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.29–0.38 and OR 0.12, 95% CI 0.10–0.14). The same was true with surgery (OR 0.63, 95% CI 0.45–0.88 and OR 0.46, 95% CI 0.30–0.70) and radiotherapy (OR 0.61, 95% CI 0.53–0.70 and OR 0.45, 95% CI 0.37–0.56). The Cox regression model showed that in women with stage III disease, women 75–84 years had a twofold higher risk of death (hazard ratio [HR] 2.38, 95% CI 2.14–2.65) and those 85 years or older had a threefold higher risk (HR 3.16, 95% CI 2.76–3.61) compared with patients younger than 55 years. Patients with stage IV and age 75–84 years had a 24% increased risk of death (HR 1.24, 95% CI 1.11–1.40) and those 85 years or older had a 52% increased risk (HR 1.52, 95% CI 1.29–1.79). CONCLUSION: Elderly women with high-grade endometrial cancer are less likely to be treated with surgery, chemotherapy, or radiation. LEVEL OF EVIDENCE: II

Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the United States.

OBJECTIVE Neoadjuvant chemotherapy and interval debulking surgery for the treatment of advanced ovarian cancer has remained controversial, despite the publication of two randomized trials comparing this modality with primary cytoreductive surgery. This study describes temporal trends in the utilization of neoadjuvant chemotherapy and interval debulking surgery in clinical practice in the United States. METHODS We completed a time trend analysis of the National Cancer Data Base. We identified women with stage IIIC and IV epithelial ovarian cancer diagnosed between 2004 and 2013. We categorized subjects as having undergone one of four treatment modalities: primary cytoreductive surgery followed by adjuvant chemotherapy, neoadjuvant chemotherapy followed by interval debulking surgery, surgery only, and chemotherapy only. Temporal trends in the frequency of treatment modalities were evaluated using Joinpoint regression, and χ2 tests. RESULTS We identified 40,694 women meeting inclusion criteria, of whom 27,032 (66.4%) underwent primary cytoreductive surgery and adjuvant chemotherapy, 5429 (13.3%) received neoadjuvant chemotherapy and interval surgery, 5844 (15.4%) had surgery only, and 2389 (5.9%) received chemotherapy only. The proportion of women receiving neoadjuvant chemotherapy and surgery increased from 8.6% to 22.6% between 2004 and 2013 (p<0.001), and adoption of this treatment modality occurred primarily after 2007 (95%CI 2006-2009; p=0.001). During this period, the proportion of women who received primary cytoreductive surgery and chemotherapy declined from 68.1% to 60.8% (p<0.001), and the proportion who underwent surgery only declined from 17.8% to 9.9% (p<0.001). CONCLUSION Between 2004 and 2013 the frequency of neoadjuvant chemotherapy and interval surgery increased significantly in the United States.

Predictors of 30-day readmission and impact of same-day discharge in laparoscopic hysterectomy

OBJECTIVE The objective of the study was to identify the predischarge predictors of 30-day readmission and the impact of same-day discharge after laparoscopic hysterectomy. STUDY DESIGN Patients undergoing only laparoscopic hysterectomy with or without bilateral salpingo-oophorectomy participated in the study. RESULTS The 30-day readmission rate was 3.1% (277 of 8890). Factors predictive of higher rates of readmission were diabetes (4.4% vs 3.0%; P = .03), chronic obstructive pulmonary disease (8.5% vs 3.1%; P = .02), disseminated cancer (20% vs 3.1%; P < .001), chronic steroid use (7.1% vs 3.1%; P = .03), daily alcohol use of more than 2 drinks (12.5% vs 2.5%; P = .04), and bleeding disorder (10.8% vs 3%; P = .001). Operative factors included surgical time of 2 hours or greater (3.5% vs 2.7%; P = .014). After surgery, patients had a higher rate of readmission when they experienced any 1 or more complications prior to discharge, (6.9% vs 3.1%; P = .01) as well as any complication after discharge (3.6% vs 1.6%; P = .01). Infections (35.7%) and surgical complications (24.2%) were the most common reasons of readmissions. Of these patients, 20.9% were discharged the same day (n = 1855) and had a similar rate of readmission (2.6% vs 3.2%; P = n.s.). Laparoscopic hysterectomy readmission score (LHRS) can be calculated by assigning 1 point to diabetes, chronic obstructive pulmonary disease, disseminated cancer, chronic steroid use, bleeding disorder, length of surgery of 2 hours or longer, and 2 points to any postoperative complication prior to discharge. Readmission rates for the LHRS score were score 1 (2.4%), score 2 (3.3%), score 3 (5.8%), or score 4 (9.5%). CONCLUSION The overall readmission rate after laparoscopic hysterectomy is low. Patients discharged the same day have similar rates of readmission. Higher LHRS is indicative of higher rates of readmission and may identify a population not suitable for same-day discharge and in need of higher vigilance to prevent readmissions.

Prophylactic Antibiotic Choice and Risk of Surgical Site Infection After Hysterectomy.

OBJECTIVE: To evaluate associations between prophylactic preoperative antibiotic choice and surgical site infection rates after hysterectomy. METHODS: A retrospective cohort study was performed of patients in the Michigan Surgical Quality Collaborative undergoing hysterectomy from July 2012 to February 2015. The primary outcome was a composite outcome of any surgical site infection (superficial surgical site infections or combined deep organ space surgical site infections). Preoperative antibiotics were categorized based on the recommendations set forth by the American College of Obstetricians and Gynecologists and the Surgical Care Improvement Project. Patients receiving a recommended antibiotic regimen were categorized into those receiving &bgr;-lactam antibiotics and those receiving alternatives to &bgr;-lactam antibiotics. Patients receiving nonrecommended antibiotics were categorized into those receiving overtreatment (excluded from further analysis) and those receiving nonstandard antibiotics. Multivariable logistic regression models were developed to estimate the independent effect of antibiotic choice. Propensity score matching analysis was performed to validate the results. RESULTS: The study included 21,358 hysterectomies. The overall rate of any surgical site infection was 2.06% (n=441). Unadjusted rates of “any surgical site infection” were 1.8%, 3.1%, and 3.7% for &bgr;-lactam, &bgr;-lactam alternatives, and nonstandard groups, respectively. After adjusting for patient and operative factors within clusters of hospitals, compared with the &bgr;-lactam antibiotics (reference group), the risk of “any surgical site infection” was higher for the group receiving &bgr;-lactam alternatives (odds ratio [OR] 1.7, confidence interval [CI] 1.27–2.07) or the nonstandard antibiotics (OR 2.0, CI 1.31–3.1). CONCLUSION: Compared with women receiving &bgr;-lactam antibiotic regimens, there is a higher risk of surgical site infection after hysterectomy among those receiving a recommended &bgr;-lactam alternative or nonstandard regimen.

Association of Hospital Volume With Racial and Ethnic Disparities in Locally Advanced Cervical Cancer Treatment.

OBJECTIVE To evaluate racial-ethnic disparities in guideline-based care in locally advanced cervical cancer and their relationship to hospital case volume. METHODS Using the National Cancer Database, we performed a retrospective cohort study of women diagnosed between 2004 and 2012 with locally advanced squamous or adenocarcinoma of the cervix undergoing definitive primary radiation therapy. The primary outcome was the race-ethnicity-based rates of adherence to the National Comprehensive Cancer Network guideline-based care. The secondary outcome was the effect of guideline-based care on overall survival. Multivariable models and propensity matching were used to compare the hospital risk-adjusted rates of guideline-based adherence and overall survival based on hospital case volume. RESULTS The final cohort consisted of 16,195 patients. The rate of guideline-based care was 58.4% (95% confidence interval [CI] 57.4-59.4%) for non-Hispanic white, 53% (95% CI 51.4-54.9%) for non-Hispanic black, and 51.5% (95% CI 49.4-53.7%) for Hispanic women (P<.001). From 2004 to 2012, the rate of guideline-based care increased from 49.5% (95% CI 47.1-51.9%) to 59.1% (95% CI 56.9-61.2%) (Ptrend<.001). Based on a propensity score-matched analysis, patients receiving guideline-based care had a lower risk of mortality (adjusted hazard ratio 0.65, 95% CI 0.62-0.68). Compared with low-volume hospitals, the increase in adherence to guideline-based care in high-volume hospitals was 48-63% for non-Hispanic white, 47-53% for non-Hispanic black, and 41-54% for Hispanic women. CONCLUSION Racial and ethnic disparities in the delivery of guideline-based care are the highest in high-volume hospitals. Guideline-based care in locally advanced cervical cancer is associated with improved survival.

Changing trends in lymphadenectomy for endometrioid adenocarcinoma of the endometrium

OBJECTIVE: To describe trends in the use of lymphadenectomy for endometrioid adenocarcinoma of the endometrium between 1998 and 2012. METHODS: A time-trend analysis was conducted using a population-based cancer registry covering 28% of the population of the United States. To quantify differences over the study period time, the frequency of lymphadenectomy and nodal metastasis among women who underwent surgical treatment of endometrioid endometrial adenocarcinoma was compared among consecutive 3- to 4-year periods. Biannual frequency of lymphadenectomy was modeled with Joinpoint regression to identify when potential changes in trends occurred and calculate annual percentage change. RESULTS: A total of 74,365 women who underwent surgery between 1998 and 2012 were analyzed. Frequency of lymphadenectomy increased by 4.2% annually (95% confidence interval [CI] 3.7–4.6) from 1998 to 2007, after which the frequency declined by 1.6% per year (95% CI 0.9–2.2). Between 1998–2000 and 2007–2009, the frequency of lymphadenectomy rose from 48.7% to 65.5% (risk difference 16.8%, 95% CI 15.4–18.1), the proportion of women found to have nodal metastasis increased by 1.1% (95% CI 0.4–1.7), and the frequency of negative lymphadenectomy increased by 15.7% (95% CI 14.3–17.1). The decline in frequency of lymphadenectomy after 2007 was associated a 3.1% (95% CI 2.1–4.1) decline in the rate of negative lymphadenectomy, but no change in the proportion of women found to have nodal metastasis (P=.17). CONCLUSION: The frequency of lymphadenectomy in the surgical treatment of endometrioid endometrial cancer increased by 4.2% annually from 1998 to 2007 and decreased by 1.6% annually from 2007 to 2012. LEVEL OF EVIDENCE: II

Trends in hospice discharge, documented inpatient palliative care services and inpatient mortality in ovarian carcinoma

OBJECTIVE To investigate the trends in discharge to hospice, documented inpatient palliative care services, and inpatient mortality in metastatic ovarian cancer (mOvCa) patients. METHODS Patients≥18years with mOvCa and a non-elective admission between January 1, 2006 and December 31, 2011 were identified from the National Inpatient Sample (NIS). The primary outcome of interest was the temporal trend in the annual proportion of hospitalizations for mOvCa where discharge destination was hospice. Secondary outcomes included temporal trend of inpatient mortality and documented palliative care services. Multivariable logistic regression models were used to ascertain independent factors predictive of hospice discharge and documented palliative services across the clusters of hospitals. RESULTS A total of 106,203 non-elective hospitalizations were identified. The rate of hospice discharge increased from 9.2% in 2004 to 11.1% in 2011 (ptrend<0.001). Similarly, the rate of documented palliative care services increased from 2.7% in 2004 to 10.4% in 2011 (ptrend<0.001). The inpatient mortality decreased from 9.6% in 2004 to 7.4% in 2011 (ptrend<0.001). In a subset of hospitalizations with extreme risk of dying, 22% were discharged to hospice and 11% received documented palliative care services. One fifth of the patients who died in the hospital received documented palliative care services. CONCLUSIONS The use of hospice as a discharge destination and documented palliative care services is relatively low but appears to be increasing over time for mOvCa patients. Monitoring this data is vital to plan educational programs regarding palliative care approaches in this at-risk population.

Surgical site infection following hysterectomy: adjusted rankings in a regional collaborative

BACKROUND Surgical site infection after abdominal hysterectomy (defined as open and laparoscopic) will be a metric used to rank and penalize hospitals in the Hospital Acquired Condition Reduction program. Hospitals whose Hospital Acquired Condition Reduction score places them in the bottom quartile will lose 1% of reimbursement from the Centers of Medicaid and Medicare Services. OBJECTIVES The objectives of this analysis were to develop a risk adjustment model for surgical site infection after hysterectomy, to calculate adjusted surgical site infection rates, to rank hospitals by the predicted to expected (P/E) ratio, and to compare the number of outlier hospitals with the number in the bottom quartile. STUDY DESIGN This was a retrospective analysis of hysterectomies from the Michigan Surgical Quality Collaborative performed between July 1, 2012, and July 1, 2014. Superficial, deep, and organ space surgical site infections were categorized according to Centers for Disease Control and Prevention criteria. Deep and organ space surgical site infections were considered 1 group for this analysis because these spaces are contiguous after hysterectomy. Hospital rankings focused on deep/organ space events because the Hospital Acquired Condition Reduction program will rank and penalize based on them, not superficial surgical site infection. Hierarchical multivariable logistic regression, which takes into account hospital effects, was used to identify risk factors for all surgical site infections and deep/organ space surgical site infections. Predicted to expected ratios for deep surgical site infection were calculated for each hospital and used to determine hospital rankings. Outliers were defined as those hospitals who predicted to expected confidence intervals crossed the reference line of 1. The number of outlier hospitals was compared with the number in the bottom quartile. RESULTS The overall surgical site infection rate following hysterectomy was 2.1% (351 of 16,548). Deep/organ space surgical site infection accounted for 1.0% (n = 167 of 16,548). Deep surgical site infection was associated independently with younger age, longer surgical times, gynecological cancer, and open hysterectomy. There was a marginal association with blood transfusion. After risk adjustment of rates and ranking by the predicted to expected ratio, there was a change in quartile rank for 42.8% of hospitals (21 of 49). Two hospitals were identified as outliers. However, if the bottom quartile was identified, as called for by the Hospital Acquired Condition Reduction program, 10 additional hospitals would be targeted for a penalty. Hospitals with < 300 beds were most likely to see their quartile rank worsen, whereas those > 500 beds were most likely to see their quartile rank improve (P = .01). CONCLUSION After adjusting for patient-related factors and site variation, more than 40% of hospitals will change quartile rank with respect to deep surgical site infection. Identifying a quartile of hospitals that are statistically different from others was not feasible in our collaborative because only 2 of 12 hospitals were outliers. These findings suggest that under the Hospital Acquired Condition Reduction program, many hospitals will be unjustly penalized.

Readmissions after major gynecologic oncology surgery

OBJECTIVES To examine the underlying indications, timing, and risk factors associated with unplanned hospital readmissions after major surgery for a gynecologic malignancy. METHODS This is a retrospective database cohort study utilizing the National Surgical Quality Improvement Program database (NSQIP). The association between risk factors with respect to 30-day unplanned readmission was modeled using logistic regression. Timing of readmission and the primary reason of readmission was abstracted from the database. RESULTS Overall, the unplanned readmission rate was 6.5% (832/12,804). On multivariate analysis, operative time≥3h (OR 1.39, p<0.001), open abdominal surgery (OR 2.2, p<0.001), any complication prior to discharge (OR 1.6, p<0.001), two or more additional surgical procedures (OR 1.34, p=0.003), or cervical cancer as the site of primary disease (OR 1.30, p=0.05) were noted to be independent predictors of readmission. To provide a convenient calculation of overall probability of readmission, we developed a nomogram of factors significantly predicting readmission. Overall, infections were a cause of 45% of the readmissions. Surgical Site Infections were the most common reason, accounting for 29.2% of all readmissions. A majority of the readmissions (approximately 75%) were within two weeks of discharge from the hospital. CONCLUSIONS Efforts to reduce readmission rates should focus on identifying patients at a high risk of readmission and reducing surgical site infections. Additionally, prospective evaluation of interventions targeted at reducing readmissions should focus on the first two weeks after discharge from the hospital.

Incidence and Timing of Thromboembolic Events in Patients With Ovarian Cancer Undergoing Neoadjuvant Chemotherapy

OBJECTIVE To identify the incidence and timing of venous thromboembolism as well as any associated risk factors in patients with ovarian, fallopian tube, or primary peritoneal cancer undergoing neoadjuvant chemotherapy. METHODS We conducted a retrospective cohort study of patients diagnosed with ovarian, fallopian tube, and primary peritoneal cancer and receiving neoadjuvant chemotherapy from January 2009 to May 2014 at a single academic institution. The timing and number of venous thromboembolic events for the entire cohort were categorized as follows: presenting symptom, during neoadjuvant chemotherapy treatment, after debulking surgery, and during adjuvant chemotherapy. RESULTS Of the 125 total patients with ovarian cancer undergoing neoadjuvant chemotherapy, 13 of 125 patients (10.4%, 95% confidence interval [CI] 6.1-17.2%) had a venous thromboembolism as a presenting symptom and were excluded from further analysis. Of the 112 total patients at risk, 30 (26.8%, 95% CI 19.3-35.9%) experienced a venous thromboembolism. Based on the phase of care, 13 (11.6%, 95% CI 6.8-19.1%) experienced a venous thromboembolism during neoadjuvant chemotherapy, six (5.4%, 95% CI 2.4-11.5%) developed a postoperative venous thromboembolism, and 11 (9.9%, 95% CI 5.5-17%) developed a venous thromboembolism during adjuvant chemotherapy. Two of the four patients with clear cell histology developed a venous thromboembolism in this cohort. CONCLUSION Overall new diagnosis of venous thromboembolism was associated with one fourth of the patients undergoing neoadjuvant chemotherapy for ovarian cancer with nearly half of these diagnosed during chemotherapy cycles before interval debulking surgery. Efforts to reduce venous thromboembolism so far have largely focused on the postoperative period. Additional attention to venous thromboembolic prophylaxis during chemotherapy (neoadjuvant and adjuvant) in this patient population is warranted in an effort to decrease the rates of venous thromboembolism.