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.

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.

Liver-Directed Therapy in Neuroendocrine Neoplasms Metastatic to Both Liver and Bone.

Bone metastases from gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) have been associated with poor prognosis, but it is unclear whether patients with concurrent bone metastases who receive liver-directed therapy (LDT) would derive survival benefit. The California Cancer Registry dataset, merged with data from the California Office of Statewide Health Planning and Development, was used to perform a retrospective study of GEPNENs metastatic to both liver and bone between 2000 and 2012. A total of 203 patients were identified. Of these, 14.8% underwent LDT after bone metastasis diagnosis, 22.1% received LDT prior to that diagnosis, and 63.1% never received LDT. The median overall survival from the time of bone metastasis diagnosis was significantly longer in those that received LDT after diagnosis when compared with those that never received LDT (p = 0.005) and was not significantly different from the median overall survival of those that had received LDT prior to diagnosis (p = 0.256). LDT may still be associated with improved survival even after a diagnosis of bone metastasis.

Medicare Advantage: A Disadvantage for Complex Cancer Surgery Patients.

PURPOSE: Nearly half of all Medicare beneficiaries are enrolled in privatized Medicare insurance plans (Medicare Advantage [MA]). Little comparative information is available about access, outcomes, and cost of inpatient cancer surgery between MA and Traditional Medicare (TM) beneficiaries. We set out to assess and compare access, postoperative outcomes, and estimated cost of inpatient cancer surgery among MA and TM beneficiaries. METHODS: Retrospective cohort analysis of MA or TM beneficiaries undergoing elective inpatient cancer surgery (for cancers located in lung, esophagus, stomach, pancreas, liver, colon, or rectum) was performed using the Office of Statewide Health Planning Inpatient Database linked to California Cancer Registry from 2000 to 2020. For each cancer site, risk-standardized access to high-volume hospitals, postoperative 30-day mortality, complications, failure to rescue, and surgery-specific estimated costs were compared between MA and TM beneficiaries. RESULTS: This analysis of 76,655 Medicare beneficiaries (median age 74 years, 51% female, 39% MA) included 31,913 colectomies, 10,358 proctectomies, 4,604 hepatectomies, 2,895 pancreatectomies, 3,639 gastrectomies, 1,555 esophagectomies, and 21,691 lung resections. Except for colon surgery, MA beneficiaries were less likely to receive care at a high-volume hospital. Mortality was significantly higher among MA beneficiaries (v TM) for gastrectomy (adjusted risk difference [ARD], 1.5%; 95% CI, 0.01 to 2.9; P = .036), pancreatectomy (ARD, 2.0%; CI, 0.80 to 3.3; P = .002), and hepatectomy (ARD, 1.4%; 95% CI, 0.1 to 2.9; P = .04). By contrast, compared with TM, MA beneficiaries incurred lower estimated hospital costs. CONCLUSION: Enrollment in MA plan is associated with lower estimated hospital costs. However, compared with TM, MA beneficiaries had lower access to high-volume hospitals and increased 30-day mortality for stomach, pancreas, or liver surgery.

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.

Does surgery provide a survival advantage in non-disseminated poorly differentiated gastroenteropancreatic neuroendocrine neoplasms?

BACKGROUND: Attributable to the high likelihood of developing distant metastatic disease, resection of poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is generally contraindicated. Some patients with no distant metastatic disease will nonetheless undergo surgical resection and their outcomes are not known. We aimed to determine whether surgery confers survival advantage over systemic therapy alone for patients with non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms. METHODS: We performed a retrospective cohort study (2000-2012) of adults in the California Cancer Registry who had poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (World Health Organization Grade 3) and no clinical evidence of distant metastasis (M0). Patients who underwent surgery were compared with those managed non-operatively. The adjusted Cox proportional hazards model was used to assess the risk of death. RESULTS: Among 2,245 patients (45% female, 21% pancreatic, 79% gastrointestinal), 1,549 (69%) were treated with surgery, and 696 (31%) received either systemic therapy or palliative measures alone. Median survival was 31 months after surgery versus 9 months after non-operative therapy (log-rank test, P < .001). Rates of 5-year overall survival were 39% after surgery versus 10% in the non-operative group. Adjusting for age, sex, comorbidities, receipt of chemotherapy, and tumor size and location, patients treated with surgery had a 58% lower likelihood of death compared with non-operative therapy (hazard ratio: 0.42, 95% confidence interval: 0.36-0.50, P < .001). Restricting our results to those patients who were found to have no distant metastasis intraoperatively (ie, pathologically M0), 5-year survival after surgery reached 44%. CONCLUSION: While poorly differentiated gastroenteropancreatic neuroendocrine neoplasms carries a poor prognosis, for patients with no evidence of metastatic disease, resection appears to confer significant improvement in long-term survival. Although caution and an individualized approach in treating poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is advised, future guidelines might reflect this survival advantage.

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.

Multivisceral Resection for Locally Advanced Gastric Cancer.

BACKGROUND: Locally advanced gastric cancer (LAGC) presents a therapeutic dilemma, particularly as it often involves adjacent organs through desmoplasia or true pathologic invasion. To obtain a margin-negative resection, these tumors require en bloc gastrectomy with multivisceral resection (G+MVR), and contention remains regarding its safety and oncologic benefit. METHODS: We used the National Cancer Database to retrospectively evaluate the short- and long-term outcomes of patients with LAGC treated in the USA between 2004 and 2016. Associations with margin status and perioperative outcomes were calculated using logistic regression. Survival was estimated using Cox proportional hazards regression and the Kaplan-Meier method. RESULTS: Overall, 785 pathologic stage T4b (pT4b) patients diagnosed with LAGC underwent gastrectomy (n = 438) or G+MVR (n = 347). There was no association between G+MVR and short- or long-term mortality. Positive resection margins (HR 1.68, 95% CI 1.40-2.03), the presence of nodal disease (HRs 1.46-1.50), treatment at a high-volume center (HR 0.76, 95% CI 0.68-0.85), and the receipt of adjuvant chemotherapy (HR 0.64, 95% CI 0.51-0.80) were independently associated with overall survival. Diffuse-type histology was associated with higher rates of an R1 resection (OR 3.60, 95% CI 2.20-5.87). Perioperative and long-term survival metrics were comparable between patients with pT4a and pT4b LAGC who underwent a margin-negative G+MVR. Undergoing a margin-negative G+MVR imparted a 6-month survival benefit over non-curative gastrectomy alone (p < 0.001). CONCLUSIONS: Our study demonstrates the safety and long-term feasibility of G+MVR for disease clearance in well-selected patients with LAGC, and we advocate for their referral to high-volume centers for optimal care.

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.

Systematic failure to operate on colorectal cancer liver metastases in California.

BACKGROUND: Despite evidence that liver resection improves survival in patients with colorectal cancer liver metastases (CRCLM) and may be potentially curative, there are no population-level data examining utilization and predictors of liver resection in the United States. METHODS: This is a population-based cross-sectional study. We abstracted data on patients with synchronous CRCLM using California Cancer Registry from 2000 to 2012 and linked the records to the Office of Statewide Health Planning Inpatient Database. Quantum Geographic Information System (QGIS) was used to map liver resection rates to California counties. Patient- and hospital-level predictors were determined using mixed-effects logistic regression. RESULTS: Of the 24 828 patients diagnosed with stage-IV colorectal cancer, 16 382 (70%) had synchronous CRCLM. Overall liver resection rate for synchronous CRCLM was 10% (county resection rates ranging from 0% to 33%) with no improvement over time. There was no correlation between county incidence of synchronous CRCLM and rate of resection (R2  = .0005). On multivariable analysis, sociodemographic and treatment-initiating-facility characteristics were independently associated with receipt of liver resection after controlling for patient disease- and comorbidity-related factors. For instance, odds of liver resection decreased in patients with black race (OR 0.75 vs white) and Medicaid insurance (OR 0.62 vs private/PPO); but increased with initial treatment at NCI hospital (OR 1.69 vs Non-NCI hospital), or a high volume (10 + cases/year) (OR 1.40 vs low volume) liver surgery hospital. CONCLUSION: In this population-based study, only 10% of patients with liver metastases underwent liver resection. Furthermore, the study identifies wide variations and significant population-level disparities in the utilization of liver resection for CRCLM in California.

Natural History of Renal Neuroendocrine Neoplasms: A NET by Any Other Name?

Renal neuroendocrine neoplasms are rare, with descriptions of cases limited to individual reports and small series. The natural history of this group of neuroendocrine neoplasms is poorly understood. In this study, we queried the Surveillance, Epidemiology and End Results (SEER) database over a four-decade period where we identified 166 cases of primary renal neuroendocrine neoplasms. We observed a 5-year overall survival of 50%. On multivariate analysis, survival was influenced by stage, histology, and if surgery was performed. We observed that patients managed by operative management had a greater frequency of localized or regional stage disease as well as a greater frequency of neuroendocrine tumor, grade 1 histology; whereas those managed non-operatively tended to have distant disease and histologies of neuroendocrine carcinoma, NOS and small cell neuroendocrine carcinoma. This is the largest description of patients with renal neuroendocrine neoplasms. Increased survival was observed in patients with earlier stage and favorable histologies.

Causes of Death and Hospitalization in Long-term Lung Cancer Survivors: A Population-based Appraisal.

INTRODUCTION: Lung cancer survivorship is emerging as an important topic owing to improved survival, but information about health issues among survivors of lung cancer is still lacking. This study used a population dataset to assess causes of death (COD) and hospitalization among long-term (5-year) survivors of lung cancer. MATERIALS AND METHODS: Using linked data from the California Cancer Registry and Office of Statewide Health Planning and Development, all patients with lung cancer diagnosed from 2000 to 2012 were identified. COD and principal admission diagnoses were categorized for all survivors beginning 5 years after diagnosis. Annual proportional distribution of diagnoses and COD were calculated over time. RESULTS: Among 102,768 patients with lung cancer, 12,048 (11.7%) survived at least 5 years after diagnosis. Lung cancer was the most common reason for admission in the first 5 years after diagnosis. In the sixth year after diagnosis, 3662 (41.8%) of 8755 long-term survivors had at least 1 hospitalization, which declined to 804 (10.4%) of 7718 in year 10. Among long-term survivors, pulmonary disease (18.3%) became the most common reason for admission, followed by cardiovascular and gastrointestinal disease. However, 48.7% of 4728 deaths occurring among long-term survivors were still owing to lung cancer. The next most common COD were cardiovascular disease, pulmonary disease, and secondary neoplasm. CONCLUSIONS: Hospitalizations among long-term survivors of lung cancer are common and occur most often owing to cardiovascular, pulmonary, and gastrointestinal diseases. Lung cancer remains the dominant COD even after 5-year survival. Active control of chronic cardiopulmonary disease and cancer surveillance should be priorities when providing patient-centered, comprehensive survivorship care.

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.

Neuroendocrine Tumors of Meckel's Diverticula: Rare but Fare Well.

Neuroendocrine tumors (NETs) are the most common malignancy arising in Meckel's diverticula (MDs). To date, there are no large series characterizing these tumors. The National Cancer Database was queried for patients with MD NETs (n = 162) from 2004 to 2014. Patient and tumor characteristics as well as outcomes were analyzed. MD NETs were more common in men (72.8%) at a median age of 62 years; 95.1 per cent of patients were white. All patients underwent surgery. Clinical M0 disease was present in 97.4 per cent of patients, and 88.2 per cent of tumors were well differentiated. Lymphovascular invasion was present in 13.2 per cent. Most (60.4%) tumors were less than 10 mm. Lymphadenectomy was performed in 32.9 per cent of patients, with 52.1 per cent of these found to have metastatic lymph node disease. Although most MD NETs are well differentiated, smaller than 10 mm, and do not have lymphovascular invasion, lymph node metastases are commonly found, suggesting that mesenteric lymphadenectomy with adequate resection of the small bowel may be necessary for adequate staging and disease clearance.

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.

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.

Hospital factors strongly influence robotic use in general surgery.

BACKGROUND: We hypothesized that general surgeons are more likely to use a robotic surgical platform at hospitals where more urologic and gynecologic robotic operations are performed, suggesting that hospital-related factors are important for choice of usage of minimally invasive platforms. METHODS: We queried the National Inpatient Sample from 2010 to 2014 for patients who underwent stomach, gallbladder, pancreas, spleen, colon and rectum, or hernia (general surgery), prostate or kidney (urologic surgery), and ovarian or uterine surgery (gynecologic surgery). Hospitals were grouped into quartiles according to percent volume of robotic urologic or gynecologic operations. Multivariable logistic regression modeling determined independent variables associated with robotics. RESULTS: Survey-weighted results represented 482,227 open, 240,360 laparoscopic, and 42,177 robotic general surgical operations at 3,933 hospitals. Robotics use increased with each year studied and was more likely to be performed on younger men with private insurance. The odds of a general surgery patient receiving a robotic operation increased with urologic and gynecologic use at the hospital. Patients at top quartile hospitals for robotic urologic surgery had 1.34 times greater odds of receiving robotic general surgery operations (confidence interval 1.15-1.57, P < .001) and 1.53 times greater odds (confidence interval 1.32-1.79, P < .001) at top quartile robotic gynecologic hospitals. These findings were independent of study year, surgical site, insurance type, and hospital type and persisted when only comparing laparoscopic to robotic procedures. CONCLUSION: Use of robotics in general surgery is independently associated with use in urologic and gynecologic surgery at a hospital, suggesting that institutional factors are important drivers of use when considering laparoscopy versus robotics in general surgery.

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.