Audrey S. Kulaylat

Utilization and trends in palliative therapy for stage IV pancreatic adenocarcinoma patients: a U.S. population-based study

BACKGROUND Pancreatic adenocarcinoma is an aggressive malignancy, with most patients diagnosed with advanced or metastatic disease. Palliative therapies comprise an important, but underutilized, aspect of care. This aim of this study was to characterize the trends, factors, and outcomes associated with utilization of palliative therapies. METHODS Patients with stage IV pancreatic adenocarcinoma from the 2003-2011 U.S. National Cancer Database were identified and stratified by receipt of palliative therapy. Linear regression, multivariable logistic regression, and survival analyses using multivariate proportional hazards models were performed. RESULTS Sixty-eight thousand and seventy-five patients with stage IV disease were identified, of which only 11,449 (16.8%) underwent designated palliative therapy. The majority received systemic chemotherapy (37.2%), followed by surgery (19.0%), pain management alone (15.3%), radiation (8.1%), referral alone (11.7%), or a combination thereof (8.7%). Utilization of palliative therapies increased from 12.9% in 2003 to 19.2% in 2011 (P<0.001). Patients were less likely to undergo palliation when older than 60 (OR 0.89, P<0.001), or of black or Hispanic race (OR 0.83, P<0.001; OR 0.80, P<0.001, respectively, vs. Caucasians). Presence of comorbidities increased the use of palliative therapy (OR 1.16 per comorbidity, P<0.001). Survival was improved in those receiving palliative systemic chemotherapy (HR 0.55, P<0.001) and palliative surgery (HR 0.94, P<0.001), although this may be due to selection bias. CONCLUSIONS Despite the continued dismal prognosis of pancreatic cancer, palliation of symptoms remains underutilized in this country, particularly in non-Caucasian, older patients. Increased awareness of palliative options may help increase its utilization.

Association of Preoperative Anti–Tumor Necrosis Factor Therapy With Adverse Postoperative Outcomes in Patients Undergoing Abdominal Surgery for Ulcerative Colitis

Importance Despite the increasing use of anti–tumor necrosis factor (TNF) therapy in ulcerative colitis, its effects on postoperative outcomes remain unclear, with many patients requiring surgical intervention despite optimal medical management. Objective To assess the association of preoperative use of anti-TNF agents with adverse postoperative outcomes. Design, Setting, and Participants This analysis used insurance claims data from a large national database to identify patients 18 years or older with ulcerative colitis. These insured patients had inpatient and/or outpatient claims between January 1, 2005, and December 31, 2013, with Current Procedural Terminology codes for a subtotal colectomy or total abdominal colectomy, a total proctocolectomy with end ileostomy, or a combined total proctocolectomy and ileal pouch-anal anastomosis. Only data regarding the first or index surgical admission within the time frame were abstracted. Use of anti-TNF agents, corticosteroids, and immunomodulators within 90 days of surgery was identified using Healthcare Common Procedure Coding System codes. Inclusion in the study required the patient to have an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for ulcerative colitis. Exclusion occurred if the patient had a secondary ICD-9-CM diagnosis code for Crohn disease or if the patient was not continuously enrolled in an insurance plan for at least 180 days before and after the index surgery. Data were collected and analyzed from February 1, 2015, to June 2, 2016. Main Outcomes and Measures Outcomes included 90-day complications, emergency department visits, and readmissions. Multivariable logistic regression was used to model covariates, including anti-TNF agent use, on the occurrence of outcomes. Results Of the 2476 patients identified, 1379 (55.7%) were men, and the mean (SD) age was 42.1 (12.9) years. Among these, 950 (38.4%) underwent subtotal colectomy or total abdominal colectomy, 354 (14.3%) underwent total proctocolectomy with end ileostomy, and 1172 (47.3%) received ileal pouch-anal anastomoses. In univariate analyses, increased postoperative complications were observed among patients in the ileal pouch cohort who received anti-TNF agents preoperatively vs those who did not (137 [45.2%] vs 327 [37.6%]; P = .02) but not among those in the colectomy or proctocolectomy cohorts. An increase in complications was also observed on multivariable analyses among patients in the ileal pouch cohort (odds ratio, 1.38; 95% CI, 1.05-1.82). Conclusions and Relevance Unlike preoperative anti-TNF agent use among patients who underwent colectomy or total proctocolectomy and experienced no significant increase in postoperative complications, anti-TNF agent use within 90 days of surgery among patients who underwent ileal pouch-anal anastomosis was associated with higher 90-day postoperative complication rates.

Adjuvant Chemotherapy Improves Overall Survival of Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Regardless of Pathologic Nodal Status

BackgroundAfter neoadjuvant chemoradiotherapy for rectal cancer, the interpretation of surgical pathology poses difficulties in deciding the need for adjuvant chemotherapy (AC). The aim of this study was to determine whether there is a survival benefit to providing AC in patients with node-negative disease on surgical pathology.MethodsPatients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation and definitive surgical resection from 2006 to 2012 were identified in the National Cancer Data Base. Patients were stratified by both receipt of AC and nodal status on surgical pathology. Propensity score matching was used to form two cohorts (AC vs. no AC) with otherwise balanced characteristics. Overall survival was compared by Kaplan–Meier analysis, and multivariable survival analysis was performed by a Weibull model.ResultsAfter propensity score matching, 4172 patients who received adjuvant therapy (2645 node negative and 1527 node positive) and 4172 patients who did not receive adjuvant therapy (3063 node negative and 1109 node positive) were identified. Among patients with either node-negative or node-positive disease, the use of AC was associated with a significant improvement in overall survival. These results were also observed after using a multivariable survival model to control for clinical stage as well as patient- and facility-related characteristics.ConclusionsIn both patients with node-negative and node-positive disease on surgical pathology, the use of AC is associated with a survival benefit. In the absence of contraindications, AC should continue to be routinely recommended to patients after neoadjuvant chemoradiotherapy for locally advanced rectal cancers.

A Surgical Clostridium-Associated Risk of Death Score Predicts Mortality After Colectomy for Clostridium difficile

BACKGROUND: A Clostridium difficile-associated risk of death score was recently developed and validated by using a national cohort of both nonsurgical and surgical patients admitted with C difficile infection. However, risk scores specifically derived from surgical cohorts and designed for patients with C difficile infection are currently unavailable. OBJECTIVE: The aim of this study was to develop a risk of death score for patients with C difficile infection who are being considered for total abdominal colectomy because of the failure of medical therapy. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted with the use of a national database. PATIENTS: All patients undergoing total colectomy for C difficile infection were identified in the National Surgical Quality Improvement Program database from 2005 to 2014. MAIN OUTCOME MEASURES: Variables similar to the original scoring system were used in multivariable analyses to determine the risk of 30-day mortality for patients, and a model was constructed to estimate the predicted probability of mortality after surgery. RESULTS: Of 532 patients who underwent surgery, 32.7% experienced 30-day postoperative mortality. Patient covariates associated with significantly increased mortality included age greater than 80 years (OR 5.5, p = 0.003), need for preoperative mechanical ventilation (OR 3.1, p < 0.001), chronic steroid use (OR 2.9, p < 0.001), underlying cardiopulmonary disease (OR 2.0, p = 0.001), and acute renal failure (OR=1.7, p = 0.03). These and other comorbidities, including hepatic disease, a cancer diagnosis, and both insulin- and noninsulin-dependent diabetes mellitus, were used to construct a model to estimate the predicted probability of mortality, which ranged from 8.0% to 96.1% based on individual comorbidity profiles. These estimates differed substantially when compared with those obtained using the National Surgical Quality Improvement Program risk calculator, which estimated the risk of mortality among surgical patients as being consistently lower. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Our surgical scoring system allows preoperative risk stratification for patients being evaluated for colectomy for C difficile infection, potentially helping to avoid futile surgery. See Video Abstract at http://links.lww.com/DCR/A434.

Squamous Cancers of the Rectum Demonstrate Poorer Survival and Increased Need for Salvage Surgery Compared With Squamous Cancers of the Anus

BACKGROUND: Squamous cell cancers of the anus are rare GI malignancies for which neoadjuvant chemoradiation is the first-line treatment for nonmetastatic disease. Squamous cancers of the rectum are far less common, and it is unclear to what degree chemoradiotherapy improves their outcomes. OBJECTIVE: The purpose of this study was to compare stage-specific survival for anal and rectal squamous cancers stratified by treatment approach. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at Commission on Cancer designated hospitals. PATIENTS: Patients (2006–2012) identified in the National Cancer Database with pretreatment clinical stage I to III cancers who underwent chemoradiotherapy, with and without subsequent salvage surgical resection (low anterior resection or abdominoperineal resection), ≥12 weeks after chemoradiotherapy were included in the study. MAIN OUTCOME MEASURES: Overall survival and the need for salvage surgery were measured. RESULTS: Anal cancers (n = 11,224) typically presented with stage II (45.7%) or III (36.3%) disease, whereas rectal cancer stages (n = 1049) were more evenly distributed (p < 0.001). More patients with rectal cancer underwent low anterior or abdominoperineal resections 12 weeks or later after chemoradiotherapy versus those undergoing abdominoperineal resection for anal cancer (3.8% versus 1.2%; p < 0.001). Stage I and II rectal cancer was associated with poorer survival compared with anal cancer (stage I, p = 0.017; stage II, p < 0.001); survival was similar for stage III disease. Salvage surgery for anal cancer was associated with worse survival for stage I to III cancers; salvage surgery did not significantly affect survival for rectal cancer. LIMITATIONS: This was a retrospective study without cancer-specific survival measures. CONCLUSIONS: Squamous rectal cancers are associated with significantly worse survival than squamous cancers of the anus for clinical stage I and II disease. Despite both cancers exhibiting squamous histology, rectal cancers may be less radiosensitive than anal cancers, as suggested by the greater incidence of salvage surgery that does not appear to significantly improve overall survival. See Video Abstract at http://links.lww.com/DCR/A422.

Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium difficile Infection

Importance Recent evidence from an animal model suggests that peripheral loss of eosinophils in Clostridium difficile infection (CDI) is associated with severe disease. The ability to identify high-risk patients with CDI as early as the time of admission could improve outcomes by guiding management decisions. Objective To construct a model using clinical indices readily available at the time of hospital admission, including peripheral eosinophil counts, to predict inpatient mortality in patients with CDI. Design, Setting, and Participants In a cohort study, a total of 2065 patients admitted for CDI through the emergency department of 2 tertiary referral centers from January 1, 2005, to December 31, 2015, formed a training and a validation cohort. The sample was stratified by admission eosinophil count (0.0 cells/&mgr;L or >0.0 cells/&mgr;L), and multivariable logistic regression was used to construct a predictive model for inpatient mortality as well as other disease-related outcomes. Main Outcomes and Measures Inpatient mortality was the primary outcome. Secondary outcomes included the need for a monitored care setting, need for vasopressors, and rates of inpatient colectomy. Results Of the 2065 patients in the study, 1092 (52.9%) were women and patients had a mean (SD) age of 63.4 (18.4) years. Those with an undetectable eosinophil count at admission had increased in-hospital mortality in both the training (odds ratio [OR], 2.01; 95% CI, 1.08-3.73; P = .03) and validation (OR, 2.26; 95% CI, 1.33-3.83; P = .002) cohorts in both univariable and multivariable analysis. Undetectable eosinophil counts were also associated with indicators of severe sepsis, such as admission to monitored care settings (OR, 1.40; 95% CI, 1.06-1.86), the need for vasopressors (OR, 2.08; 95% CI, 1.32-3.28), and emergency total colectomy (OR, 2.56; 95% CI, 1.12-5.87). Other significant predictors of mortality at admission included increasing comorbidity burden (for each 1-unit increase: OR, 1.13; 95% CI, 1.05-1.22) and lower systolic blood pressures (for each 1-mm Hg increase: OR, 0.99; 95% CI, 0.98-1.00). In a subgroup analysis of patients presenting without initial tachycardia or hypotension, only patients with undetectable admission eosinophil counts, but not those with an elevated white blood cell count, had significantly increased odds of inpatient mortality (OR, 5.76; 95% CI, 1.99-16.64). Conclusions and Relevance This study describes a simple, widely available, inexpensive model predicting CDI severity and mortality to identify at-risk patients at the time of admission.

Prognostic Significance of Tumor Deposits in Stage III Colon Cancer

AbstractBackgroundThe American Joint Committee on Cancer includes extranodal tumor deposits in the tumor–node–metastasis classification of colon cancer. However, it is unclear how tumor deposits compare with lymph node metastases in prognostic significance. This study evaluated the survival impact of tumor deposits relative to lymph node metastases in stage III colon cancer.Methods The US National Cancer Database (2010–2012) was reviewed for resectable stage III adenocarcinoma of the colon, and stratified by presence of tumor deposits and lymph node metastases. Univariate and multivariate survival analyses were performed.ResultsOf 6424, 10.1% had both tumor deposits and lymph node metastases [5-year survival (5YS) 40.2%], 2.5% had tumor deposits alone (5YS 68.1%), and 87.4% had lymph node metastases alone (5YS 55.4%). Patients with lymph node metastases alone tended to have a greater number of lymph nodes retrieved (20.9 versus 18.8, p = 0.0126) and were more likely to receive adjuvant therapy (66.9 vs 58.0%, p = 0.003) than those with only tumor deposits. Patients with both had significantly worse survival at all T stages (p < 0.05, all). There was no significant difference in survival between tumor deposits alone and lymph node metastases alone at any T stage (p > 0.8, all). After controlling for patient, disease, and treatment characteristics, patients with tumor deposits alone [hazard ratio (HR) 0.56, p = 0.001] or only lymph node metastases (HR 0.64, p < 0.001) were associated with improved survival relative to patients with both.ConclusionsConcomitant presence of tumor deposits and lymph node invasion carries poor prognostic significance. Tumor deposits alone appear to have prognostic implications similar to lymph node invasion alone.

Cost-utility analysis of smoking cessation to prevent operative complications following elective abdominal colon surgery

BACKGROUND Smoking is a known risk factor for postoperative complications after colectomy. Using the perspective of the provider, this study evaluated the cost-effectiveness of the pharmacologic interventions for smoking cessation. METHODS A decision tree model was constructed to represent a providers decision to provide either bupropion, nicotine replacement therapy, varenicline, or no cessation therapy to all patients presenting for elective colectomy. Incremental cost per quality-adjusted life year (QALY) was the primary outcome. RESULTS The base case analysis suggests that bupropion is cost-effective with an incremental cost-effectiveness ratio of approximately

Palliative therapy for stage IV rectal adenocarcinoma: how frequently is it used?

75,000 per QALY. Sensitivity analyses established ranges for which each medication might be cost-effective and dominant compared to offering no cessation therapy. CONCLUSIONS From a provider perspective, offering bupropion for smoking cessation to patients scheduled for elective colon resection is cost-effective. Furthermore, these results provide benchmarks to inform providers about whether targeted, short-term smoking cessation therapies represent good value in colectomies.