Controlling Gastric Cancer in a World of Heterogeneous Risk.

Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.

Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: a SEER Database Analysis of Mucinous and non-Mucinous Histologies.

BACKGROUND: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. PATIENTS AND METHODS: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. RESULTS: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. CONCLUSIONS: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.

Potentially Avoidable Admissions and Prolonged Hospitalization in Patients with Suspected Colon Cancer.

BACKGROUND: Suspicion of cancer in the Emergency Department (ED) may lead to potentially avoidable and prolonged admissions. We aimed to examine the reasons for potentially avoidable and prolonged hospitalizations after admissions from the ED for new colon cancer diagnoses (ED-dx). METHODS: A retrospective, single-institution analysis was conducted of patients with ED-dx between 2017 and 2018. Defined criteria were used to identify potentially avoidable admissions. Patients without avoidable admissions were examined for ideal length of stay (iLOS), using separate defined criteria. Prolonged length of stay (pLOS) was defined as actual length of stay (aLOS) being greater than 1 day longer than iLOS. RESULTS: Of 97 patients with ED-dx, 12% had potentially avoidable admissions, most often (58%) for cancer workup. Very little difference in demographic, tumor characteristics, or symptoms were found, except patients with potentially avoidable admissions were more functional (Eastern Cooperative Oncology Group [ECOG] score 0-1: 83% vs. 46%; p = 0.049) and had longer symptom duration prior to ED presentation {24 days (interquartile range [IQR] 7-75) vs. 7 days (IQR 2-21)}. Among the 60 patients who had necessary admissions but did not require urgent intervention, 78% had pLOS, most often for non-urgent surgery (60%) and further oncologic workup. The median difference between iLOS and aLOS was 12 days (IQR 8-16) for pLOS. CONCLUSIONS: Potentially avoidable admissions following Ed-dx were uncommon but were mostly for oncologic workup. Once admitted, the majority of patients had pLOS, most often for definitive surgery and further oncologic workup. This suggests a lack of systems to safely transition to outpatient cancer management.

The order of surgery and chemotherapy matters: Multimodality therapy and stage-specific differences in survival in gastric cancer.

BACKGROUND AND OBJECTIVES: Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj). METHODS: Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS). RESULTS: We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90). CONCLUSIONS: In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Evaluation of Survival and Postoperative Radiation Among Patients with Advanced Medullary Thyroid Carcinoma: An Analysis of the National Cancer Database.

BACKGROUND: This study compared survival between patients who had medullary thyroid cancer (MTC) treated with surgery alone and patients who underwent surgery and radiation (SRT). METHODS: Patients from the National Cancer Database (NCDB) with a diagnosis of stage 3 or 4 MTC, lymph node disease, and no distant metastases between 2008 and 2016 were studied. Kaplan-Meier analyses and log-rank statistics were used to estimate and compare overall survival between patients treated with surgery alone and those treated with SRT. Mutlivariable Cox proportional hazards models and propensity-matching were used to adjust for confounding and selection bias. RESULTS: Among 1370 patients, 1112 (81%) received surgery alone, and 258 (19%) received SRT. The hazard ratio for mortality in the SRT group was 1.784 (95% confidence interval [CI] 1.313-2.43) after multivariable adjustment for confounding variables. Furthermore, SRT remained associated with a higher mortality rate (p < 0.008) after propensity-matching in an effort to adjust for selection bias. CONCLUSIONS: This analysis of NCDB patients showed that SRT is associated with a significantly higher mortality rate among patients treated for stage 3 or 4 IV MTC with positive lymph node disease. Although this observation can be attributed to unmeasured confounders or selection bias, the cause for the profound survival differences deserves prospective evaluation, especially as adjuvant therapies for this disease continue to evolve.

Association Between Socioeconomic and Insurance Status and Delayed Diagnosis of Gastrointestinal Cancers.

INTRODUCTION: Association between socioeconomic status (SES) and stage at diagnosis in gastrointestinal (GI) cancers is poorly described. Relationship between low SES and stage at diagnosis as well as the mediating role of insurance status (IS) was examined. METHODS: The Surveillance, Epidemiology, and End Results database was queried for esophageal, gastric, liver, biliary, pancreatic, colon, and rectal cancers diagnosed in 2012-2016. Relationship between census-tract SES index quintiles and late diagnosis (distant disease at diagnosis) was examined. Uni and multivariable logistic regressions were performed. Mediation analyses were conducted to determine the degree to which IS (private/Medicare versus Medicaid/uninsured) mediates the relationship between SES and late diagnosis of cancer. RESULTS: Analysis included 236,713 adult patients from 18 Surveillance, Epidemiology, and End Results areas. In univariable analysis, lowest SES quintile was significantly associated with late diagnosis for all cancers except gastric and biliary cancers. In multivariable analysis controlling for age, gender, marital status and race, this association remained significant for liver (odds ratio (OR) 1.41 [95% confidence interval (CI) 1.25-1.58]), pancreatic (OR 1.13 [95% CI 1.06-1.21]), and rectal (OR 1.31 [95% CI 1.20-1.42]) cancers. Further controlling for IS showed the largest effect size reduction for rectal cancer (OR 1.18 [95% CI 1.09-1.29]), with IS mediating 36.5% (P < 0.0001) of SES effect. CONCLUSIONS: Low SES is an independent risk factor for late diagnosis in liver, pancreas, and rectal cancers. Insurance is not a critical mediator of difference by SES for most GI cancers, with the exception of rectal cancer. Further research is needed to understand factors beyond IS that can account for SES differences in late diagnosis for GI cancers. Insurance related differences for rectal cancer deserves further attention.

Clinical Stage of Cancer Affects Perioperative Mortality for Gastrointestinal Cancer Surgeries.

BACKGROUND: The impact of the stage of cancer on perioperative mortality remains obscure. The purpose of this study was to investigate whether cancer stage influences 30-d mortality for gastric, pancreatic, and colorectal cancers. METHODS: Data were collected from the National Cancer Database for patients undergoing resections for cancers of the stomach, pancreas, colon, or rectum between 2004 and 2015. The main analysis was conducted among patients with cancer stages 1-3. A sensitivity analysis also included cancer stage 4. Descriptive statistics were used to compare the patients' baseline characteristics. Generalized linear mixed models were used to evaluate the relationship between stage and 30-d mortality, controlling for other disease-, patient- and hospital-level factors. Pseudo R2 statistics (%Δ pseudo R2) were used to quantify the relative explanatory capacity of the variables to the model for 30-d mortality. All analyses were performed using SAS 9.4. RESULTS: The cohort included 24,468, 28,078, 176,285, and 64,947 patients with stomach, pancreas, colon, and rectal cancers, respectively. After adjusting for other variables, 30-d mortality was different by stage for all cancer types examined. The factor most strongly associated with 30-d mortality was age (%Δ pseudo R2 range 14%-39%). The prognostic impact of cancer stage (Stages 1, 2, or 3) on 30-d mortality was comparable to that of the Charlson comorbidity index. CONCLUSIONS: Cancer stage contributes to explaining differences observed in short-term mortality for gastrointestinal cancers. Short-term mortality models would benefit by including more granular cancer stage, beyond disseminated status alone.

Diagnosis Setting and Colorectal Cancer Outcomes: The Impact of Cancer Diagnosis in the Emergency Department.

BACKGROUND: The rate of diagnosis of colorectal cancer (CRC) in the emergency department (ED), its characteristics, and its effect on outcomes have been poorly described. MATERIALS AND METHODS: Chart review was conducted to identify presenting clinical setting leading to diagnosis, symptoms, and history of colonoscopy for patients diagnosed with CRC at a single institution from 2012-2014. Patients diagnosed with CRC as a result of an ED visit (EDDx) were compared with those diagnosed after presentation to other settings (non-EDDx). RESULTS: Of 638 patients meeting inclusion criteria, 271 (42.4%) were EDDx patients. These patients were more likely to be older than 80 y (29.89% versus 19.35%), have Medicare (59.78% versus 42.78%) or Medicaid (23.62% versus 12.81%) insurance, have stage IV cancer (45.02% versus 18.26%), and were symptomatic at the time of presentation (94.83% versus 64.03%). EDDx patients were less likely to ever have had a colonoscopy (21.77% versus 41.69%). In a model adjusted for patient demographics, cancer stage, presence of symptoms, and history of prior colonoscopy, EDDx was associated with increased mortality (hazard ratio, 1.89; 95% confidence interval, 1.3-2.8). On stratifying survival by stage, it was found that for all stages, EDDx was associated with decreased survival. CONCLUSIONS: More than 40% of patients with CRC received their diagnosis through the ED. EDDx was associated with a nearly twofold mortality risk increase. EDDx should be considered a marker of poor outcomes for CRC and may be related to unaccounted patient-level or systems-level factors. Efforts should be made to identify modifiable risks of cancer diagnosis in the ED to improve cancer outcomes.

Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism.

BACKGROUND: Primary aldosteronism (PA) occurs in 10%-20% of patients with resistant hypertension. Guidelines recommend adrenal vein sampling (AVS) to identify patients for surgical management. We evaluate the use of AVS in managing PA to better understand the selection and outcomes of medical versus surgical treatment. METHODS: A retrospective review was performed, and patients were divided into those who did (AVS) and did not have AVS (non-AVS). Demographics, aldosterone and renin levels, blood pressure, comorbidities, and antihypertensive medications were recorded. Reasons to defer AVS and medical versus surgical decision-making were examined and groups were compared. RESULTS: We included 113 patients; 39.8% (45/113) had AVS, whereas 60.2% (68/113) did not. Groups were similar in age, body mass index, and initial systolic blood pressure (SBP). In patients who underwent AVS, 31 of 45 (68.9%) had unilateral secretion and were referred for surgery, whereas 13 of 45 (28.9%) had bilateral secretion. Of the 31 referred for surgery, 26 underwent laparoscopic adrenalectomy, all cured; four refused surgery; and one counseled toward medical management by their physician. In 68 non-AVS patients, 6 (8.8%) underwent adrenalectomy without sampling and 2 with no clinical improvement. The remaining deferrals were because of normal or bilateral adrenal nodules on imaging (8/68, 11.8%); medical management due to poor surgical candidacy (12/68, 17.6%); patient refusal of intervention (13/68, 19.1%); or reasons not stated (28/68, 41.1%). At the follow-up, patients who underwent AVS had lower median SBP (135.4 mmHg versus 144.7 mmHg, P = 0.0241) and shorter follow-up (17.7 mo versus 54.0 mo, P < 0.0001). Surgically managed patients had biochemical resolution of PA with normalization of potassium levels (3.6 to 4.7mEq/L, P < 0.00001). CONCLUSIONS: AVS correctly selects patients for surgical management avoiding unnecessary surgery. However, despite guidelines, AVS is not always pursued as part of PA treatment, potentially excluding surgical candidates.

Lack of Cancer Recurrence Data in Large Databases: A National Survey of Hospital Cancer Registries.

BACKGROUND: Cancer recurrence information is not routinely collected by the US cancer registries. Prior research suggests hospital characteristics, staff qualifications, and chart access may be contributing factors but this has not been explored nationally. This study aimed to understand issues underlying poor collection of recurrence information and to identify targets for improvement. METHODS: A survey was sent to Commission on Cancer hospitals to investigate reasons for variations in recurrence data collection, examine resources allocated, and assess coding variability. Descriptive and multivariate analyses were performed. RESULTS: Eight hundred and forty-five of 1417 surveys to Commission on Cancer hospitals were analyzed. Sixty-nine percent reported annually examining charts for recurrence ("investigating" hospitals). They more likely had experienced registrars (91% versus 84%, P < 0.05), integrated electronic medical records (75% versus 68%, P < 0.05) and chart access to in-network hospitals (80% versus 73%, P < 0.05). Thirty-seven percent reported ability to follow-up using medical records on <50% of patients. Reasons for noncollection included inability to accurately collect (37%), limited resources (44%), and low priority (18%). Odds of being an investigating hospital increased with the percentage of patients who could be followed up with medical records (90%-100% OR = 6.72). There were minimal differences among hospitals in registry caseload and resources. 79.5% reported that without prior recurrence documentation, they would code the patient as not having a recurrence, 8.8% would change all recurrence variables to "unknown," and 7.2% would leave them blank. CONCLUSIONS: Those tasked with collecting recurrence information report significant barriers concerning data access, data quality, adequate resources, and coding variability. A unified effort is needed to improve collection.

Can a gastric cancer risk survey identify high-risk patients for endoscopic screening? A pilot study.

BACKGROUND: A questionnaire that distinguishes how variability in gastric cancer prevalence is associated with ethnicity/birth country/immigration/cultural diet along with known risk factors may improve targeting populations for gastric cancer screening in the United States. METHODS: Existing literature was used to identify the item pool. Cluster analysis, focus groups, and cognitive interviewing were used to reduce collinear items and refine the questionnaire. Logistic regression analysis was used to determine which items distinguished gastric cancer cases from the primary care and community controls. RESULTS: The results of analysis of data from 40 cases and 100 controls (primary care = 47; community = 53) were used to reduce the 227 item pool to 12 items. After ranking these variables using model bootstrapping, a logistic regression model using the highest ranked eight variables was chosen as the final model. Older age, foreign nativity, daily consumption of cultural food at ages 15-18, less than high-school education, and greater acculturation were significantly associated with being a gastric cancer case compared with the controls. CONCLUSIONS: An eight-item survey that addresses gastric cancer risk factors, ethnicity, cultural habits, and immigration patterns has potential to identify high-risk persons from multicultural areas within the US, who might benefit from endoscopic screening for gastric cancer.

The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

PURPOSE: New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. METHODS: Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). RESULTS: Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p < 0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index = 0.81, 95% CI, 0.79-0.83; ypStage: c index = 0.80, 95% CI, 0.73-0.87). CONCLUSION: The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.

Poor Outcomes of Gastric Cancer Surgery After Admission Through the Emergency Department.

BACKGROUND: Outcomes after nonelective surgery for gastric cancer (GC) are poorly defined. Our objective was to compare outcomes of patients undergoing nonelective GC surgery after admission through the emergency department (EDSx) with patients receiving elective surgery or surgery after planned admission (non-EDSx) nationally. METHODS: The Nationwide Inpatient Sample (NIS) database was used to examine patients undergoing GC surgery between 2008 and 2012. Demographics and outcomes were compared between EDSx and non-EDSx. Multivariable logistic regression was used to examine predictors of discharge to home. RESULTS: Of 9279 patients, 1143 (12%) underwent EDSx. They were more likely to be female (42 vs. 35%), nonwhite (56 vs. 33%), aged ≥75 years (40 vs. 26%), in the lowest quartile for household income (31 vs. 25%), have one or more comorbidities (87 vs. 70%), treated at a nonteaching hospital (46 vs. 25%), and have a concomitant diagnosis of obstruction, perforation, or bleeding (30 vs. 6%). They had longer total length of stay (LOS; 16 vs. 9 days), longer median postoperative stays (10 vs. 9 days), higher in-hospital mortality (8 vs. 3%), and were less likely to be discharged home (63 vs. 82%). EDSx was more expensive ($125,300 vs. $83,604). EDSx was associated with a lower likelihood of discharge to home (odds ratio 0.52, 95% CI 0.43-0.62). CONCLUSIONS: Nationally, 12% of GC surgeries are performed after emergency department admission, which occurs more frequently in vulnerable populations and results in worse outcomes. Understanding factors leading to increased EDSx and developing strategies to decrease EDSx may improve GC surgery outcomes.

Validation of the 8th Edition of the AJCC TNM Staging System for Gastric Cancer using the National Cancer Database.

BACKGROUND: The 8th edition AJCC gastric cancer staging manual was refined using Japanese and Korean data from the International Gastric Cancer Association (IGCA). This study evaluated the eighth edition's validity for U.S. METHODS: National Cancer Database (NCDB) was used to obtain data on gastric cancer patients diagnosed from 2004 to 2008 who underwent surgery and to examine differences in stage grouping and survival between AJCC 7th and 8th editions. Discrimination of models derived from NCDB and IGCA data was compared. RESULTS: Of 12,041 patients, median age was 65, 57.6% were male, median lymph nodes retrieved was 2 (0-76), 30.9% underwent distal/partial gastrectomy, and 49.8% received no adjuvant treatment. The 8th edition differed in that T1-T3 disease was upstaged with N3b, T4aN3a was downstaged from IIIC to IIIB, and T4bN0 and T4aN2 were downstaged from IIIB to IIIA. These changes resulted in increased patients in IIIA (1436 in the 7th edition to 2310 in the 8th) and IIIB (1737-1896) and decreased in IIIC (2100-1067). This also resulted in lower median survival for IIIA (28.7-25.0 months), IIIB (19.6-17.4), IIIC (13.7-11.8). The concordance index for the 8th edition applied to NCDB data was 0.719 [95% confidence interval (CI) 0.703-0.734), which is comparable to that for the 8th edition developed from IGCA data (0.775, 95% CI 0.770-0.780) and the 7th edition applied to NCDB data (0.720, 95% CI 0.704-0.735). CONCLUSIONS: The 8th edition is valid for U.S. populations, showing clear separation of data with preservation of group order.

Doubling of 30-Day Mortality by 90 Days After Esophagectomy: A Critical Measure of Outcomes for Quality Improvement.

OBJECTIVES: Our objectives were to (1) compare 30- and 90-day mortality rates after esophagectomy, (2) compare drivers of 30- and 90-day mortality, and (3) examine whether 90-day mortality affects hospital rankings. BACKGROUND: Operative mortality has traditionally been assessed at 30 days. Ninety-day mortality has been suggested as a more appropriate indicator of quality, particularly after complex cancer surgery. METHODS: Esophagectomies for nonmetastatic esophageal cancer patients diagnosed between 2007 and 2011 were identified in the National Cancer Data Base. Mortality rates were examined by patient demographics, tumor characteristics, and hospital procedural volume. Risk-adjusted hierarchical logistic regression models examined hospital performance for mortality. RESULTS: A total of 15,796 esophagectomy patients at 977 hospitals were available for analysis. Ninety-day overall mortality was more than double the 30-day mortality (8.9% vs 4.2%; P < 0.0001). In multivariate analysis, while both 30- and 90-day mortality were associated with patient factors such as age, comorbidity, and hospital volume, only 90-day mortality was influenced by tumor- and management-related variables such as stage, tumor location, and receipt of neoadjuvant therapy. Hospital performance was examined as top 10%, middle 10% to 90%, and lowest 10% as ranked using risk-adjusted odds of mortality. There was moderate correlation between ranking based on 30- and 90-day mortality [weighted κ = 0.45 (95% confidence interval, 0.39-0.52)]. Compared with 30-day mortality rankings, nearly 20% of hospitals changed their ranking category when 90-day mortality rankings were used. CONCLUSIONS: Examination of 90-day mortality after esophagectomy reflects cancer patient management decisions and may provide actionable targets for quality improvement.