Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database.

BACKGROUND: There is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer. METHODS: Using the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching. RESULTS: Overall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77-0.95; p = 0.004). CONCLUSION: Using a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers.

Association of negative pressure wound therapy and surgical site infections in patients undergoing cytoreductive surgery: An entropy balanced analysis.

BACKGROUND AND OBJECTIVES: Surgical site infections (SSIs) after cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) are a major cause of potentially avoidable morbidity. We explored the association of negative pressure wound therapy (NPWT) with SSI in patients undergoing CRS/HIPEC. METHODS: Retrospective analysis of consecutive patients undergoing CRS/HIPEC for non-gynecologic cancers. Exposure was the receipt of NPWT versus traditional skin closure. Primary outcome was SSI within 90 days of surgery. We performed multivariable logistic regression (before and after entropy balancing) to evaluate the association of exposure with outcomes. RESULTS: A total of 251 patients were included, of which 43 (17%) received NPWT and 26 (10.4%) developed SSIs. Baseline demographics and clinicopathologic characteristics were similar between the two groups with some exceptions: Patients who received NPWT had a higher Peritoneal Carcinomatosis Index (median 19 vs. 11, p = 0.002) and operative time (10 vs. 8.2 h, p = 0.003) but were less likely to undergo HIPEC (84% vs. 95%, p < 0.05). After entropy balancing, on multivariable logistic regression, NPWT was not associated with 90-day SSI (odds ratio = 0.90; 95% confidence interval = 0.21-3.80; p = 0.89). CONCLUSION: NPWT was not associated with a reduction in SSIs. These findings prompt a reevaluation of the routine use of NPWT in CRS/HIPEC.

Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy.

BACKGROUND AND OBJECTIVES: Total mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients. METHODS: A retrospective cohort study of stage 1-3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch-and-wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group. RESULTS: One hundred seventy-one patients (Male 59%) were included with a median surveillance of 43 months. Twenty-nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups. CONCLUSION: A significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging.

Age-adjusted incidence rates of synchronous liver metastases for stage IV colorectal cancer compared by sex, race, and age group.

BACKGROUND: Reports on age-adjusted incidence rates of synchronous colorectal liver metastases (CRLM) among patients with stage IV colorectal cancer (CRC) are uncommon. This study presents in detail differences in CRLM incidence rates by sex, race, and age group. METHODS: Incidence rates were obtained for adults diagnosed with Stage IV CRC in the years 2010-2015 using SEER. The ratio of CRLM incidence to stage IV CRC incidence was used to calculate the rate ratio. RESULTS: Average age-adjusted CRLM incidence rate was 7.09 per 100,000 (95% CI, 6.93-7.26). CRLM incidence was higher at 8.68 (95% CI, 8.35-9.03) for males compared with 5.77 (95% CI, 5.64-5.90) for females. Highest incidence rate of 11.50 (95% CI, 10.43-11.76) was observed among Blacks. By age group the highest CRLM incidence was 24.42 (95% CI, 23.13-25.71) among adults age >75. The average rate ratio of CRLM to CRC incidence rate was 0.72 (95% CI, 0.71-0.73). CONCLUSION: Age-adjusted incidence rates of synchronous CRLM are higher for men, Blacks, and older patients. The risk ratio indicates that 72% of stage IV CRC cases are at risk of synchronous CRLM, although CRLM risk appears to decline with age.

Association of Living in Urban Food Deserts with Mortality from Breast and Colorectal Cancer.

BACKGROUND: Food deserts are neighborhoods with low access to healthy foods and are associated with poor health metrics. We investigated association of food desert residence and cancer outcomes. METHODS: In this population-based study, data from the 2000-2012 California Cancer Registry was used to identify patients with stage II/III breast or colorectal cancer. Patient residence at time of diagnosis was linked by census tract to food desert using the USDA Food Access Research Atlas. Treatment and outcomes were compared by food desert residential status. RESULTS: Among 64,987 female breast cancer patients identified, 66.8% were < 65 years old, and 5.7% resided in food deserts. Five-year survival for food desert residents was 78% compared with 80% for non-desert residents (p < 0.0001). Among 48,666 colorectal cancer patients identified, 50.4% were female, 39% were > 65 years old, and 6.4% resided in food deserts. Five-year survival for food desert residents was 60% compared with 64% for non-desert residents (p < 0.001). Living in food deserts was significantly associated with diabetes, tobacco use, poor insurance coverage, and low socioeconomic status (p < 0.05) for both cancers. There was no significant difference in rates of surgery or chemotherapy by food desert residential status for either diagnosis. Multivariable analyses showed that food desert residence was associated with higher mortality. CONCLUSION: Survival, despite treatment for stage II/III breast and colorectal cancers was worse for those living in food deserts. This association remained significant without differences in use of surgery or chemotherapy, suggesting factors other than differential care access may link food desert residence and cancer outcomes.

Disparate and Alarming Impact of Gastrointestinal Cancers in Young Adult Patients.

BACKGROUND: The rise in the incidence of gastric cancer (GC) and colorectal cancer (CRC) in young adults (YA) remains unexplained. We aim to identify differences in these malignancies between YA and older patients. PATIENTS AND METHODS: We retrospectively analyzed the California Cancer Registry for all GC and CRC cases from 2000 to 2012. Pearson's Chi square analysis and stepwise regression model with backward elimination were used to analyze differences in demographic, clinical, and histopathologic features, and log-rank test to compare survival between young (≤ 40 years) and older adults (41-90 years) with GC or CRC, separately. RESULTS: We analyzed 19,368 cases of GC and 117,415 cases of CRC. YA accounted for 4.6% of GC (n = 883) and 2.8% of CRC (n = 3273) patients. Compared with older patients, YA were more likely to be Hispanic (P < 0.0001) and have poorly differentiated (P < 0.0001), higher histologic grade (P < 0.0001), and signet ring features (P < 0.0001). Synchronous peritoneal metastases were more common in YA patients (32.1% vs. 14.1% GC, 8.8% vs. 5.4% CRC, P < 0.0001). The 5-year overall survival (OS) of YA with CRC or GC was longer than that of older patients with the same stage of malignancy; except YA with stage I GC, who demonstrated poor OS and disease-specific survival (DSS) (65.1% and 67.9%, respectively) which were significantly worse than those of adults aged 41-49 years (70.7% and 76.2%, respectively) and 50-64 years (69.1% and 78.1%, respectively). CONCLUSIONS: YA with GC or CRC have distinctly worse clinical and histopathologic features compared with older patients and are disproportionately of Hispanic ethnicity. These results contribute to improving understanding of younger versus older GI cancer patients.

A Comparison of Liver-Directed Therapy and Systemic Therapy for the Treatment of Liver Metastases in Patients with Gastrointestinal Neuroendocrine Tumors: Analysis of the California Cancer Registry.

PURPOSE: To compare the outcomes of patients with gastrointestinal neuroendocrine tumor liver metastases treated with liver-directed therapy (LDT) to those treated with systemic therapy (ST) in a statewide cancer database. MATERIALS AND METHODS: A retrospective study was performed of patients with metastatic gastrointestinal tract neuroendocrine tumors treated with either LDT or ST alone between the years 2000-2012 in the California Cancer Registry. Overall survival and disease-specific survival were assessed using multivariable Cox proportional hazards analysis and propensity score matching. RESULTS: A total of 154 patients (ST, n = 87 and LDT, n = 67) were studied. The median overall survival and disease-specific survival for patients that received ST was 29 and 35 months versus 51 and >60 months for patients that received LDT. On multivariate analysis, LDT and the resection of the primary tumor were associated with improved survival (hazard ratio [HR] 0.52, P = .002; HR 0.43, P = .001). Non-white race, Medicaid/uninsured status, and the presence of lung metastases were associated with poor survival (HR 1.76, P = .014; HR 2.29, P = .009; and HR 1.79, P = .031). Propensity score matching demonstrated an improvement in disease-specific survival for LDT compared to ST (HR 0.53, P = .036). The improvement in overall survival on propensity score matching did not achieve statistical significance (HR 0.70, P = .199). CONCLUSIONS: LDT is associated with improved overall and disease-specific survival as compared to ST in patients with gastrointestinal neuroendocrine tumor liver metastases. Further investigation is needed to determine whether combination or sequential treatment can improve outcomes in this population.

Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. METHODS: The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. RESULTS: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. CONCLUSIONS: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.

The Association of Tumor Laterality and Survival After Cytoreduction for Colorectal Carcinomatosis.

BACKGROUND: Primary tumor location has emerged as an important surrogate for tumor biology in metastatic colorectal cancer treated with systemic chemotherapy. It is unclear if primary tumor location is associated with survival after cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) for colorectal carcinomatosis. METHODS: Study of a contemporary cohort merged data from the California Cancer Registry, 2004-2012, and the Office of Statewide Health Planning and Development inpatient database. For patients undergoing CRS/HIPEC, clinicopathologic variables, treatment characteristics, and survival were compared by right versus left colon primary site. Survival was analyzed by Cox proportional hazards. RESULTS: Of 272 patients identified, 128 (47.1%) had right-sided tumors. Left- and right-sided cohorts had similar patient, tumor, and treatment factors. Patients with left-sided primary tumors had significantly prolonged overall survival (mean 34 versus 15.5 mo, P = 0.0010). Factors independently associated with decreased overall survival included age >80 (HR 7.0, P < 0.0001), advanced T4 stage (HR 3.6, P = 0.0031), and positive lymph nodes (HR 2.2, P = 0.0004). Metachronous peritoneal involvement (HR 0.38, P < 0.0001) and left-sided primary tumors (HR 0.72, P = 0.041) were independently associated with improved overall survival. CONCLUSIONS: This study identifies location of primary tumor as an important determinant of long-term survival after CRS/HIPEC. Patients with left-sided tumors have a more favorable prognosis.

Trends and outcomes of robotic surgery for gastrointestinal (GI) cancers in the USA: maintaining perioperative and oncologic safety.

OBJECTIVE: Minimally invasive surgery (MIS) continues to gain traction as a feasible approach for the operative management of gastrointestinal (GI) malignancies. The aim of this study is to quantify national trends, perioperative and oncologic outcomes of MIS for the most common GI malignancies including the esophagus, stomach, pancreas, colon, and rectum. We hypothesize that with more widespread use of MIS techniques, perioperative outcomes and oncologic resection quality will remain preserved. METHODS: The National Cancer Database (2010-2014) was utilized to assess perioperative outcomes and pathologic quality of MIS (robotic and laparoscopic) compared to open, in patients who underwent resection for cancers of the esophagus, stomach, pancreas, colon, and rectum. Multilevel logistic regression models were constructed to identify independent factors associated with postoperative and long-term outcomes. RESULTS: Data from 11,023 esophageal, 30,664 gastric, 30,689 pancreas, 260,669 colon, and 52,239 rectal resections were analyzed. Although laparoscopy is the most prevalent MIS approach, the number of robotic resections increased nearly fourfold from 2010 to 2014 in all organ sites (increase by factor: esophagus: 3.8, stomach: 4.4, pancreas: 4.4, colon: 3.8 and rectum: 4). The number of laparoscopic resections increased at a slower rate (factor: 1.3-1.9), whereas the number of open resections decreased (factor: 0.67-0.77). Patients who underwent robotic-assisted resections were younger for stomach and colorectal resections and with lower Charlson Comorbidity Index across all sites. Patients who underwent robotic or laparoscopic resections had shorter hospitalizations, fewer readmissions (with the exception of rectal resections) and lower postoperative mortality at 90 days. Robotic-assisted resections had comparable negative margin resections and number of lymph nodes to laparoscopic and open resections across all sites. CONCLUSION: The utilization of robotic-assisted resections of GI cancers is rapidly increasing with more frequent use in younger and healthier patients. This study demonstrates that with the rising utilization of robotic-assisted resections, perioperative outcomes and oncologic safety have not been compromised.

Liver Resection Improves Survival in Colorectal Cancer Patients: Causal-effects From Population-level Instrumental Variable Analysis.

OBJECTIVE: The aim of this study was to estimate population-level causal effects of liver resection on survival of patients with colorectal cancer liver metastases (CRC-LM). BACKGROUND: A randomized trial to prove that liver resection improves survival in patients with CRC-LM is neither feasible nor ethical. Here, we test this assertion using instrumental variable (IV) analysis that allows for causal-inference by controlling for observed and unobserved confounding effects. METHODS: We abstracted data on patients with synchronous CRC-LM using the California Cancer Registry from 2000 to 2012 and linked the records to the Office of Statewide Health Planning and Development Inpatient Database. We used 2 instruments: resection rates in a patient's neighborhood (within 50-mile radius)-NALR rate; and Medical Service Study Area resection rates-MALR rate. IV analysis was performed using the 2SLS method. RESULTS: A total of 24,828 patients were diagnosed with stage-IV colorectal cancer of which 16,382 (70%) had synchronous CRC-LM. Liver resection was performed in 1635 (9.8%) patients. NALR rates ranged from 8% (lowest-quintile) to 11% (highest-quintile), whereas MALR rates ranged from 3% (lowest quintile) to 19% (highest quintile). There was a strong association between instruments and probability of liver resection (F-statistic at median cut-off: NALR 24.8; MALR 266.8; P < 0.001). IV analysis using both instruments revealed a 23.6 month gain in survival (robust SE 4.4, P < 0.001) with liver resection for patients whose treatment choices were influenced by the rates of resection in their geographic area (marginal patients), after accounting for measured and unmeasured confounders. CONCLUSION: Less than 10% of patients with CRC-LM had liver resection. Significant geographic variation in resection rates is attributable to community biases. Liver resection leads to extensive survival benefit, accounting for measured and unmeasured confounders.

Resection of the Primary Gastrointestinal Neuroendocrine Tumor Improves Survival With or Without Liver Treatment.

OBJECTIVE: The aim of this study was to determine outcomes of primary tumor resection in metastatic neuroendocrine tumors across all primary tumor sites. BACKGROUND: Primary tumor resection (PTR) may offer a survival benefit in metastatic gastrointestinal neuroendocrine tumors (GI-NETs); however, few studies have examined the effect of primary site and grade on resection and survival. METHODS: This is a retrospective study of patients with metastatic GI-NETs at presentation between 2005 and 2011 using the California Cancer Registry (CCR) dataset merged with California Office of Statewide Health Planning and Development (OSHPD) inpatient longitudinal database. Primary outcome was overall survival (OS). Univariate and multivariate (MV) analyses were performed using the Pearson Chi-squared tests and Cox proportional hazard, respectively. OS was estimated using the Kaplan-Meier method and log-rank test. RESULTS: A total of 854 patients with GI-NET metastases on presentation underwent 392 PTRs. Liver metastases occurred in 430 patients; 240 received liver treatment(s). PTR improved OS in patients with untreated metastases (median survival 10 vs 38 months, P < 0.001). On MV analysis adjusted for demographics, tumor stage, grade, chemotherapy use, Charlson comorbidity index, primary tumor location, or treatment of liver metastases, PTR with/without liver treatment improved OS in comparison to no treatment [hazard ratio (HR) 0.50, P < 0.001 and 0.39, P < 0.001, respectively]. PTR offered a survival benefit across all grades (low-grade, HR 0.38, P = 0.002 and high-grade, HR 0.62, P = 0.025) CONCLUSION:: PTR in GI-NET is associated with a better survival, with or without liver treatment, irrespective of grade. This study supports the resection of the primary tumor in patients with metastatic GI-NETs, independent of liver treatment.

Lymphovascular Invasion Is Associated with Lymph Node Involvement in Small Appendiceal Neuroendocrine Tumors.

BACKGROUND: Appendiceal neuroendocrine tumors (NETs) are incidentally found in up to 1% of appendectomy specimens. The association of lymphovascular invasion (LVI) with risk of regional lymph node involvement is unclear. METHODS: From the National Cancer Database, 2004-2015, this study identified patients who had tumors 2 cm or smaller with one or more lymph nodes (LNs) pathologically evaluated. The histology was defined as typical, goblet cell, or composite NETs. Patient demographics, tumor characteristics, and treatment variables were analyzed. RESULTS: The histologies for the 1767 identified patients were typical (n = 921, 52.1%), goblet cell (n = 556, 31.5%), and composite (n = 290, 16.4%). The tumor grades were low (70.4%), moderate (18.6%), and high (11%). The overall LN positivity was 17%. Of 1052 tumors evaluated, 215 (20.4%) had LVI. Overall survival decreased with node involvement (mean 84 vs. 124 months; p < 0.0001, log-rank). In the multivariate logistic regression analysis, LVI was independently associated with node involvement [odds ratio (OR) 5.0; p < 0.0001] after adjustment for patient age and tumor histologic subtype, size, and grade. In the subset analysis of typical NETs, tumor size of 1-2 cm (ref. < 1 cm; OR 5.5; p < 0.001) and presence of LVI (ref. absence of LVI; OR 4.8; p < 0.0001) were the only factors independently associated with LN involvement. CONCLUSIONS: Node involvement is associated with worse overall survival in appendiceal NETs. The presence of LVI was strongly associated with lymph node involvement. An appendectomy specimen showing LVI should prompt strong consideration of colectomy with regional lymphadenectomy even for small, typical appendiceal NETs.

Using a Lymph Node Count Metric to Identify Underperforming Hospitals After Rectal Cancer Surgery.

BACKGROUND: Investigating methods to assess the quality of cancer surgery and then benchmarking hospitals on these quality indicators can lead to improvements in cancer care in the United States. We sought to determine the utility of lymph node count as a quality metric. METHODS: We performed a retrospective analysis of the California Cancer Registry database (2004-2011) merged with Office of Statewide Health Planning and Development inpatient database. Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant therapy and resection were included. Hospital quality score was defined as the proportion of patients at a particular hospital that had adequate examination with at least nine lymph nodes. High-quality score hospitals were those that retrieved nine or more nodes among ≥25% of operations. A multivariate Cox proportional hazards (standard and shared frailty) model was used to determine differences in overall survival adjusting for age, hospital volume, race, sex, insurance, comorbidity, T-stage, response to neoadjuvant therapy, adjuvant chemotherapy, and teaching hospital status as covariates. RESULTS: A total of 2704 patients were treated at 228 hospitals (low-scoring hospital = 85 and high-scoring hospital = 143). Patient- and disease-specific characteristics were similar between the groups. Socioeconomic status and hospital characteristics were strongly associated with score status. High-scoring hospitals had higher sphincter preservation (P = 0.004), lower complications (P = 0.021), and a trend toward lower mortality (P = 0.079). Care at high-scoring hospitals independently predicted overall survival (hazard ratio: 0.74; 95% confidence interval: 0.61-0.90; P = 0.003). CONCLUSIONS: This study demonstrates that hospital quality score based on lymph node count can be used to identify underperforming hospitals.

Robotic surgery trends in general surgical oncology from the National Inpatient Sample.

BACKGROUND: Robotic surgery is offered at most major medical institutions. The extent of its use within general surgical oncology, however, is poorly understood. We hypothesized that robotic surgery adoption in surgical oncology is increasing annually, that is occurring in all surgical sites, and all regions of the US. STUDY DESIGN: We identified patients with site-specific malignancies treated with surgical resection from the National Inpatient Sample 2010-2014 databases. Operations were considered robotic if any ICD-9-CM robotic procedure code was used. RESULTS: We identified 147,259 patients representing the following sites: esophageal (3%), stomach (5%), small bowel (5%), pancreas (7%), liver (5%), and colorectal (75%). Most operations were open (71%), followed by laparoscopic (26%), and robotic (3%). In 2010, only 1.1% of operations were robotic; over the 5-year study period, there was a 5.0-fold increase in robotic surgery, compared to 1.1-fold increase in laparoscopy and 1.2-fold decrease in open surgery (< 0.001). These trends were observed for all surgical sites and in all regions of the US, they were strongest for esophageal and colorectal operations, and in the Northeast. Adjusting for age and comorbidities, odds of having a robotic operation increased annually (5.6 times more likely by 2014), with similar length of stay (6.9 ± 6.5 vs 7.0 ± 6.5, p = 0.52) and rate of complications (OR 0.91, 95% CI 0.83-1.01, p = 0.08) compared to laparoscopy. CONCLUSIONS: Robotic surgery as a platform for minimally invasive surgery is increasing over time for oncologic operations. The growing use of robotic surgery will affect surgical oncology practice in the future, warranting further study of its impact on cost, outcomes, and surgical training.

Prophylactic Pancreatectomies Carry Prohibitive Mortality at Low-Volume Centers: A California Cancer Registry Study.

BACKGROUND: Pancreatectomy for malignancy is associated with improved outcomes when performed at high-volume centers. The goal of this study was to assess pancreatectomy outcomes for premalignant cystic lesions as a function of hospital volume. METHODS: The Healthcare Cost and Utilization Project (HCUP) was queried for all pancreatectomies performed in California from 2003 to 2011. Cases were stratified, separating benign versus malignant disease. Hospitals were categorized as low-volume (≤25 pancreatectomies/year; LV) or high-volume (>25; HV) centers. Perioperative morbidity, mortality, and length of stay were compared in HV vs. LV centers. RESULTS: There were 7554 pancreatectomies performed in 201 hospitals during the study period, where 5652 (75%) procedures were performed for malignancy, 338 (4%) for chronic pancreatitis, and 1564 (21%) for benign/premalignant cysts. The majority of pancreatectomies for cystic disease were performed at LV centers (65%). There were no significant differences in length of stay (7 vs. 8 days; p = 0.6) or 90-day readmission rates (12.8% vs. 12.9%; p = 1.0) in HV versus LV centers. However, there were higher surgical (46.2% LV vs. 41.1% HV, p = 0.05) and medical (13.3% LV vs. 9.2% HV; p = 0.017) complications at LV centers. Most importantly, there was a fourfold higher in-hospital mortality at LV centers (2.36% vs. 0.55%; p = 0.007). CONCLUSION: Pancreatic resection for benign lesions at HV hospitals is associated with significantly lower morbidity and mortality, suggesting that when feasible, patients should seek care at high-volume centers for these semi-elective surgeries.

Age greater than 60 years portends a worse prognosis in patients with papillary thyroid cancer: should there be three age categories for staging?

BACKGROUND: Age is an important prognostic factor in papillary thyroid cancer (PTC), with better survival observed in patients < 45 years of age, regardless of stage. Although the impact of increasing age on PTC-related survival is well-known, previous studies have focused on survival relative to age 45 years only. As the number of patients entering their 7th decade of life increases, PTC-related survival in this demographic becomes increasingly important. Survival in patients ≥ 60 years specifically compared to other groups has not previously been examined. We sought to determine whether age ≥ 60 years is an adverse prognostic factor for disease-specific survival and recurrence in patients with PTC. METHODS: The California Cancer Registry database was linked to inpatient and ambulatory patient records from the Office of Statewide Health Planning and Development for the years 2000-2011. This linked database was queried for patients diagnosed with papillary thyroid cancer and treated with surgery. We then identified prognostic factors related to both 5-year and 10-year disease-specific survival and disease-free survival in patients ≤ 45, 45-59, and ≥ 60 years. Multivariable Cox proportional hazard models were created to test the effect of age ≥ 60 on disease-specific and disease-free survival, controlling for clinical, treatment, and demographic factors. RESULTS: The final cohort included 15,675 patients. Of the group, 46.3% were between 18 and 44 years of age, 33.6% were 45-59 years, and 20.1% were ≥ 60. Univariate analysis showed that compared to other groups, patients ≥ 60 were more likely to be male (p < 0.001), present with tumors > 5 cm (p < 0.001), more likely to have metastatic disease (p < 0.001), less likely to receive radioactive iodine (p < 0.001), and more likely to receive external beam radiation therapy (p < 0.001). In multivariable Cox proportional hazards models for 5 and 10-year disease-free survival, age ≥ 60 was associated with higher risk of disease at 5 and 10-years (HR 2.3 and 1.9 respectively, p < 0.001). Similar results were observed for 5 and 10-year disease-specific survival (HR 38.0 and 30.0 respectively, p < 0.001) after controlling for gender, race, co-morbidity, stage, surgical procedure, radioactive iodine, insurance, and hospital volume. CONCLUSIONS: Patients ≥ 60 years of age have worse DSS and DFS after a diagnosis of PTC, across all stages of disease. Given that patients over the age of 45 years have progressively worse survival as they age, these data support having three age groups, 18-44 years of age, 45-59 years, and ≥ 60 as an independent predictor of survival and recurrence to current staging guidelines.

Primary liver sarcomas in the modern era: Resection or transplantation?

BACKGROUND AND OBJECTIVES: Primary liver sarcomas (PLS) are rare. Published series are limited by small numbers of patients. METHODS: We reviewed the National Cancer Database (2004-2014) for patients who underwent surgical resection of PLS. RESULTS: Of 237 patients identified, the majority were female (60.8%), with median age of 52 years. Histologies were: epithelioid hemangioendothelioma (n = 67), angiosarcoma (n = 64), leiomyosarcoma (n = 33), embryonal rhabdomyosarcoma (n = 31), carcinosarcoma (n = 16), giant cell sarcoma (n = 14), spindle cell sarcoma (n = 12). Ninety-seven (40.9%) patients underwent lobectomies or extended lobectomies, 41 patients (17.3%) underwent transplantation. Surgical margins were negative in 82.9%. Tumors were well differentiated in 11.3%. Histology type correlated with outcome with the best prognosis for epithelioid hemangioendothelioma (OS: not reached, similar for resection and transplantation) and the worst for angiosarcoma (OS:16.6 mo with resection; 6 mo with transplantation; P = 0.04). Resections with microscopically negative margins were associated with improved survival (58.7 vs 11.3 mo for positive margins; P < 0.001). Chemotherapy and radiation therapy were used in a minority of patients (32.9% and 4.3% respectively) with no improvement in outcomes. CONCLUSIONS: Both hepatic resection and liver transplantation can be associated with long term survival for selected primary liver sarcomas such as epitheliod hemangioendotheliomas. Histology type and the ability to resect the tumor with negative margins correlate with outcomes and the decision to operate should be carefully weighed for subtypes with particularly dismal prognosis such as angiosarcomas.

The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study.

BACKGROUND: The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. OBJECTIVE: To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. DESIGN: Retrospective cohort study. SETTING: An integrated health care delivery system. PARTICIPANTS: All enrollees with biochemically confirmed PHPT from 1995 to 2010. MEASUREMENTS: Bone mineral density (BMD) changes and fracture rate. RESULTS: In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (-6.6% and -7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. LIMITATION: Retrospective study design and nonrandom treatment assignment. CONCLUSION: Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. PRIMARY FUNDING SOURCE: National Institute on Aging.

Predictors of Antiestrogen Recommendation in Women With Estrogen Receptor-Positive Ductal Carcinoma In Situ.

BACKGROUND: Antiestrogen (anti-e) use in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS) has been shown to reduce the incidence of noninvasive and invasive breast cancer. Few studies have evaluated factors associated with anti-e recommendation in ER+ DCIS. METHODS: The California Cancer Registry was queried for female patients diagnosed with ER+ DCIS and treated with lumpectomy or unilateral mastectomy from 2004 to 2011. Patient demographics, comorbidities, and clinical characteristics were analyzed for association with anti-e recommendation. RESULTS: Of 5,527 patients identified, 76.4% patients underwent lumpectomy and 23.6% underwent unilateral mastectomy. Of the total cohort, 31.6% patients were recommended anti-e therapy, 60.4% were not, and the remaining 8.0% were recommended anti-e, but administration was not documented. Performance of lumpectomy predicted anti-e use compared with mastectomy (odds ratio [OR], 2.08; 95% CI, 1.77-2.43). Asian/Pacific Islanders were more often recommended anti-e therapy when compared with whites (OR, 1.28; 95% CI, 1.10-1.49). Patients younger than 70 years were more often recommended anti-e (age, 18-49 years: OR, 1.38; CI, 1.12-1.71; and age, 50-69 years: OR, 1.43; CI, 1.20-1.71). CONCLUSIONS: Despite current guidelines to consider the use of anti-e therapy, recommendation of anti-e after surgical treatment of DCIS is low, having been recommended to 40% of patients, and used by fewer than one-third. Significant predictors include lumpectomy compared with unilateral mastectomy, Asian/Pacific Islander race, younger age, and number of comorbidities. Further work is merited to understand patterns of anti-e therapy recommendation by providers in patients with DCIS.