The increasing prevalence and aggressive, potentially fatal, nature of early-onset colorectal cancer (EOCRC) makes it critical to identify risk factors that can facilitate earlier screening and detection. With electronic medical record data, we compared adults ages 20 to 49 years diagnosed with EOCRC (2017-2023) to control patients without EOCRC who were 1:2 exact-matched based on age and sex. We extracted data on patients' sociodemographics, comorbidities, hereditary syndromes, family history, symptoms, specialty visits, and medications within 12 to 24 months prior to or on their diagnostic visit. Using a model-building approach, we analyzed data with univariate then multivariate logistic regressions to predict the odds of EOCRC diagnosis. We constructed three models using high-risk background characteristics as predictors (baseline and high-risk) and exclusion criteria (sporadic), respectively. Our final analysis included 684 EOCRC cases and 1,368 controls. The mean age was 42 years, with 53% male, 72% White, and 72% non-Hispanic/Latino. Across all models, several predictors were significantly associated with higher EOCRC odds, including alcohol use history, higher number of comorbidities, abdominal pain, rectal bleeding, constipation, iron deficiency anemia, and prescriptions for metformin, non-steroidal anti-inflammatory drugs (NSAID), and multivitamins. Significant predictors of lower EOCRC odds were employment and Medicare/Medicaid insurance. By concurrently including symptoms, medical history, and sociodemographic characteristics, we constructed and validated well-fitting models with good discrimination that replicated and extended prior case-control research. To facilitate earlier screening and detection, these EOCRC risk factors can be used to identify patients who would benefit from screening earlier than 45 years of age.Prevention Relevance: There is a need for risk stratification models that simultaneously consider symptoms, medical history, and sociodemographic characteristics. This study identified a set of risk factors that can be used to recommend early screening to symptomatic and asymptomatic patients below the age of 45, even among those without high-risk familial background.

BACKGROUND:Early-onset colorectal cancer disease burden is rising, but it remains unclear whether this trend is driven by increased colonoscopy use or reflects a true epidemiologic shift, particularly across racial/ethnic groups. We analyzed predictors of early onset colorectal cancer, temporal trends in colonoscopy utilization (2017-2023), the correlation between utilization and the proportion of early onset colorectal cancer diagnoses over time, and differential predicted risk by health care engagement and ethnicity. METHODS:In a retrospective matched nested case-control study within a multi-institutional health care system population, 2,776 patients (1,388 patients with early-onset colorectal cancer and 1,388 negative controls) were analyzed. Nine hundred eighty-three patients were identified to have sporadic early onset colorectal cancer. Conditional multivariable logistic regression identified independent risk factors. Colonoscopy utilization and early onset colorectal cancer composition were normalized (2017 = 1.0) to generate indexed trends by race and ethnicity. Pearson correlations between utilization and proportion of annual early onset colorectal cancer diagnoses were calculated. Predicted probabilities of sporadic early onset colorectal cancer by number of medical visits were estimated, stratified by Hispanic versus non-Hispanic groups. RESULTS:Between 2017 and 2023, colonoscopy utilization increased substantially across all age groups, with the greatest absolute volume among adults aged 41-50 years. Over the same period, early onset colorectal cancer diagnoses rose disproportionately, including a 93% increase among patients aged 41-50 years. Marked racial and ethnic disparities were observed: compared with 2017, early onset colorectal cancer diagnoses increased by 300% among Black patients, 192% among Hispanic patients, and 144% among Asian patients. In multivariable analysis, iron-deficiency anemia (odds ratio, 3.56; 95% confidence interval, 2.10-6.03), former alcohol use (odds ratio, 2.04; 95% confidence interval, 1.44-2.90), American Indian/Alaska Native race (odds ratio, 4.03; 95% confidence interval, 1.12-14.5), Black race (odds ratio, 1.94; 95% confidence interval, 1.07-3.53), and Hispanic ethnicity (odds ratio, 1.72; 95% confidence interval, 1.13-2.61) were independently associated with increased odds of early onset colorectal cancer. Trends in overall survival differed by ethnicity, with early-onset colorectal cancer Hispanic/Latino patients experiencing inferior outcomes. Greater health care utilization was strongly associated with lower odds of sporadic early onset colorectal cancer diagnosis, with each additional medical visit associated with a 25% reduction in sporadic early onset colorectal cancer odds (odds ratio, 0.75; 95% confidence interval, 0.72-0.78); however, this inverse association was attenuated among Hispanic patients, who demonstrated persistently higher predicted probabilities across increasing levels of health care engagement. CONCLUSION:Colonoscopy utilization increased substantially among adults younger than the traditional colorectal cancer screening age between 2017 and 2023; however, these increases did not translate into proportional reductions in disparities in early onset colorectal cancer diagnosis or outcomes. Ethnic minority populations experienced disproportionate and persistently worse survival. These findings suggest that improvements in screening utilization alone are insufficient to mitigate early onset colorectal cancer disparities and underscore the need for targeted, equity-focused strategies beyond screening access.

Introduction At-home stool tests are an increasingly popular practice for colorectal cancer screening, especially when access to healthcare facilities is challenging. However, there is limited information about whether stool tests provide sufficient coverage when patients must undergo repeat testing. This study evaluates repeat preventative stool tests over 2 year periods in a healthcare system with 51 hospitals and over 1000 clinics across seven western US states, before and after the onset of the COVID-19 pandemic. Methods We conduct a real-world, observational, retrospective and longitudinal study based on electronic medical records. We measure the rate of repeat screening and mean delay in repeat screening among patients who receive an initial stool test. We estimate the changes in the likelihood of colorectal cancer screening using a Cox proportional hazard model. Results Our sample included 4 03 085 patients. The share of patients with an initial negative stool test who received a repeat screening ranged from 38% to 49% across different years. Among patients who received a repeat screening, there is a delay of 3 months on average. The volume of stool tests increased during the pandemic: the HR of screening after the onset of the pandemic to that before the pandemic was 1.18 (95% CI (1.15, 1.20), p<0.001). Conclusions Our findings show that less than 50% of patients received a repeat stool test, creating gaps in their screening coverage. The increase in stool tests during the pandemic is partly due to a substitution away from colonoscopies, underscoring the increasing importance of stool tests in CRC screening. Programmes that aim to increase CRC screening uptake should focus on repeated testing after an initial screening.

BACKGROUND AND OBJECTIVES:Treatment guidelines on cytoreductive surgery (CRS) for metastatic colorectal cancer (mCRC) continue to have variability. This study investigated survival outcomes and utilization trends of CRS on mCRC. METHODS:Patients from the National Cancer Database with mCRC who received systemic chemotherapy 2004-2015 were categorized by colectomy, colectomy and metastasectomy (CRS), and no surgery (NS). Kaplan-Meier analyses with inverse probability of treatment weighting (IPTW) were performed. RESULTS:Of 88 593 patients in the study cohort, 39 028 had a colectomy, 21 462 CRS, and 28 103 NS. CRS utilization increased from 33.1% (2004) to 38.3% (2015). CRS (aHR = 0.36) and colectomy (aHR = 0.47) were associated with significantly improved OS compared to NS. Median OS with IPTW remained longer in CRS versus colectomy versus NS (34.4 months vs. 26.7 vs. 13.2) (p < 0.001). Patients who received hyperthermic intraperitoneal chemotherapy (HIPEC) had improved OS compared to non-HIPEC patients (aHR = 0.55, p < 0.001). CONCLUSIONS:National utilization of CRS for mCRC is steadily increasing and associated with improved OS, supporting the use of more aggressive surgical approaches in select patients.

Background: Medicare expenditures have steadily increased over the decades, and yet Medicare Physician Fee Schedule payments for individual services have declined. We examine trends in Medicare Physician Fee Schedule payments for office visits, inpatient visits, and surgical procedures. Methods: The Medicare Physician Fee Schedule Look-Up Tool was queried for payment data for office visits, inpatient visits, and surgical procedures between 2013 and 2023. All data were adjusted for inflation using the Consumer Price Index. Trends in payments were calculated for 5 common procedures in each surgical specialty. Trends in aggregate national health expenditures were compared to Medicare Physician Fee Schedule payments for physician services from 2013 to 2021. Results: The Consumer Price Index increased by 29.3% from 2013 to 2023. Inflation-adjusted per-visit Medicare Physician Fee Schedule payments decreased by 12.2% for outpatient office visits, 19.1% for inpatient visits, and 22.8% for surgical procedures from 2013 to 2023. This varied by surgical specialty: vascular (-25.8%), endocrine (-22.0%), general surgery (-27.0%), thoracic (-19.2%), surgical oncology (-22.1%), breast (-22.4%), urology (-2.2%), neurosurgery (-22.8%), obstetrics/gynecology (-19.9%), and orthopedics (-24.7%). Adjusted for inflation, national health expenditures increased by 33.9% for physician services from 2013 to 2021. In comparison, Medicare Physician Fee Schedule payments over the same time period 2013 to 2021 increased by 1.3% for outpatient office visits but decreased by 10.6% for inpatient visits and 9.8% for surgical procedures. Conclusion: Controlling rising national health expenditures is important and necessary, but 10 years of declining Medicare Physician Fee Schedule payments on a per-procedure basis in surgery would suggest that this strategy alone may not achieve those goals and could ultimately threaten access to quality surgical care. Surgeons must advocate for permanent payment reforms. (c) 2023 Elsevier Inc. All rights reserved.

AbstractBackgroundOverall patients with melanoma liver metastasis (MLiM) have a dismal prognosis and poor responses to the standard of care treatment. Understanding the role of the tumour microenvironment (TME) is critical for discovering better strategies to overcome intrinsic therapy resistance in MLiM. The aim was to understand the crosstalk signalling pathways between hepatocytes and metastatic melanoma cells in the TME of MLiM.MethodsHepatocytes and melanoma tumour cells of MLiM were assessed using transcriptomic NanoString GeoMx digital spatial profiling (NGDSP) assay. Functional assays were performed using normal hepatocytes and MLiM‐derived cell lines. Validation was performed using multiplex immunofluorescence.ResultsIn NGDSP analysis adjacent normal hepatocytes (ANH) had higher CXCR4 and COL1A1/2 levels than distant normal hepatocytes (DNH), while melanoma cells had higher TNF‐α levels. In vitro, MLiM cell lines released TNF‐α which upregulated CXCR4 and CXCL12 levels in ANH. CXCL12 activated CXCR4, which triggered AKT and NFκB signalling pathways. Consequently, AKT signalling induced the upregulation of collagen type I. MLiM were significantly encircled by a shield of collagen, whereas other liver metastases showed reduced levels of collagen. Of all the liver metastasis analyzed, the presence of collagen in melanoma liver metastasis was associated with a reduction in tumour‐infiltrating lymphocytes.ConclusionsMLiM modified ANH to increase collagen production and created a physical barrier. The collagen barrier was associated with a reduction of immune cell infiltration which could potentially deter MLiM immune surveillance and treatment responses.Highlights Spatial analyses of melanoma liver metastasis show that adjacent normal hepatocytes have increased collagen‐type I levels. Melanoma liver metastases tumour cells secrete enhanced levels of TNF‐α to stimulate CXCR4/CXCL12 upregulation in adjacent normal hepatocytes. Activation of CXCR4 promotes AKT and NF‐κB signalling pathways to promote collagen‐type I secretion in adjacent normal hepatocytes. Elevated collagen levels were associated with reduced tumour‐infiltrating lymphocytes

BACKGROUND:Bundled Payment (BP) models are becoming more common in surgery. We share our early experiences with Bundled Payments for Care Improvement for major bowel surgery.METHODS:Patients undergoing major bowel surgery between January and October 2021 were identified using Medicare Severity-Diagnosis Related Group (MS-DRG) codes. Major drivers of cost in a BP model are reported and compared to the Fee-For-Service (FFS) payment model.RESULTS:A total of 202 cases (173 FFS vs 29 BP) were analyzed. The mean BP cost per Clinical Episode was $28,340. Eleven patients (38%) in the BP model had costs greater than the Target Price. The drivers of cost in the BP model were 59% acute care facility, 17% physician services, 9% post-acute care facilities, 8% other, and 7% readmissions. Clinical Episode of care costs varied considerably by MS-DRG case complexity. Robotic surgery increased costs by 35% (mean increase $3724, P < .01). The 90-day readmission rate was 17% for a mean cost of $11,332 per readmission. Three patients (10%) were discharged to a skilled nursing facility at an average cost of $11,009, while fifteen patients (52%) received home health services at a mean cost of $2947. Acute care facility costs were similar in the BP vs FFS groups (mean difference $1333, P = .22).CONCLUSIONS:Patients undergoing major bowel surgery are a heterogeneous population. Physicians are ideally positioned to deliver high-value, patient-centered care and are crucial to the success of a BP model. The post-acute care setting is a key component of improving efficiency and quality of care.

Pancreatic tumors are being discovered more frequently secondary to the widespread use of cross-sectional imaging for diagnostic purposes. Malignant tumors of the pancreas most commonly arise from intrinsic pancreatic cells rather than as metastases from other primary sites. Most of these primary pancreatic malignancies arise from the ductal system and are classified as adenocarcinomas. Because this is the most prevalent subtype of pancreatic malignancies, the recommended management of this disease has been well standardized. Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare primary pancreatic malignancy that constitutes approximately 1% of pancreatic malignancies. The rarity of this disease precludes study with large randomized controlled trials to guide best practice standards. The accepted strategies for diagnosis, treatment, and surveillance are based off a limited amount of published data or extrapolated form pancreatic adenocarcinoma. Surgical resection has been associated with survival advantage. One study demonstrated a median overall survival (OS) of 26 months in all patients diagnosed with UC-OGC compared to a 48-month median OS in the patients who underwent surgical resection. Another topic in management is the use of positron emission tomography (PET) scan in the management of UC-OGC. As expected, there is very limited data on the subject. One case report describes using PET scan in the diagnosis of a 1.0 × .8 cm tumor with a standardized uptake value (SUV) max of 5.0 found in the body of the pancreas. The imaging was performed to assist in delineation between a benign vs malignant lesion that was determined to be equivocal when found on an abdominal computed tomography (CT) scan performed for nonspecific abdominal pain. Another case report describes a patient with metastatic non-small cell lung cancer who was found to have a 4.2 cm mass in the tail of the pancreas on surveillance CT imaging. A PET scan was performed which showed the lesion had an SUV max of 14.7. The patient subsequently underwent distal pancreatectomy with final pathology demonstrating UC-OGC. We describe the diagnosis and management of a patient with UC-OGC which was discovered on a PET scan performed for staging of a newly diagnosed marginal B-cell lymphoma. An 80-year-old female was diagnosed with low-grade marginal zone B-cell lymphoma with minimal bone marrow involvement after workup prompted by hypercalcemia. She was subsequently diagnosed with thrombocytopenia believed to be paraneoplastic idiopathic thrombocytopenic purpura (ITP) which required treatment with steroids and intravenous immunoglobulin. She underwent a staging whole body PET scan and was found to have focal severe fluorodeoxyglucose (FDG) uptake in the pancreatic head with an SUV max of 9.2 (Figure 1). She had no evidence of biliary obstruction at that time. She underwent endoscopic ultrasound (EUS) which demonstrated a 19 × 19 mm oval mass in the pancreatic head with well-defined borders and lack of invasion into surrounding structures. A biopsy performed at the time of EUS resulted as undifferentiated carcinoma of the pancreas. The patient was then treated with rituximab for refractory ITP with clinical improvement. The patient then underwent a Whipple procedure. Pathology demonstrated a 2.3 cm UC-OGC with 0/16 lymph nodes harboring metastatic carcinoma. All surgical margins were negative for dysplasia or malignancy. The patient tolerated the procedure well and was discharged to a rehabilitation facility. She subsequently returned to her previous living condition. The patient has no evidence of recurrent disease 4 months after her operation.

The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment (TME) in EOCC are not fully understood. The aim of this study is to unravel unique spatial transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs). Here, we divide the sporadic colon cancer tissue samples with transcriptomic data into patients diagnosed with EOCC (<50 yrs) and late-onset colon cancer (LOCC, ≥50 yrs) and then, analyze the data using CIBERSORTx deconvolution software. EOCC tumors are more enriched in CAFs with fibroblast associated protein positive expression (FAP(+)) than LOCC tumors. EOCC patients with higher FAP mRNA levels in CAFs have shorter OS (Log-rank test, p < 0.029). Spatial transcriptomic analysis of 112 areas of interest, using NanoString GeoMx digital spatial profiling, demonstrate that FAP(+) CAFs at the EOCC tumor invasive margin show a significant upregulation of WNT signaling and higher mRNA/protein levels of fibroblast growth factor 20 (FGF20). Tumor epithelial cells at tumor invasive margin of EOCC tumors neighboring FAP(+) CAFs show significantly higher mRNA/protein levels of fibroblast growth factor receptor (FGFR2) and PI3K/Akt signaling activation. NichNET analysis show a potential interaction between FGF20 and FGFFR2. The role of FGF20 in activating FGFR2/pFGFR2 and AKT/pAKT was validated in-vitro. In conclusion, we identify a unique FAP(+) CAF population that showed WNT signaling upregulation and increased FGF20 levels; while neighbor tumor cells show the upregulation/activation of FGFR2-PI3K/Akt signaling at the tumor invasive margin of EOCC tumors.

Incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment (TME) of EOCC as well as their clinical implications are not understood. The aim was to unravel unique spatial transcriptomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs) of EOCC compared to late-onset colon cancer (LOCC). Initially, 26 sporadic colon cancer (CC) tissue samples from 26 patients were assessed. CC patients received surgery at SJHC and did not have previous therapies, MSI-H, hereditary CC family history, or inflammatory bowel disease. Patients were grouped into EOCC (<50 yrs) and LOCC (≥50 yrs) and analyzed using NanoString GeoMx DSP (NGDSP) and HTG EdgeSeq PIP platforms. Validation cohorts of EOCC and LOCC with transcriptomic data and clinical annotations were assessed from CC TCGA database and GEO datasets. Bioinformatic analysis included CIBERSORTx and NicheNET. CAFs having fibroblast associated protein positive expression (FAP(+) were significantly enriched in EOCC compared to LOCC tumors. EOCC patients with higher FAP mRNA levels in CAFs had shorter Overall Survival (OS, p < 0.029) and Disease-Free Survival (DFS, p < 0.038). Spatial transcriptomic analysis using NGDSP demonstrated that FAP(+) CAFs at the EOCC tumor invasive margin (TIM) had significant upregulation of WNT signaling and higher levels of fibroblast growth factor 20 (FGF20). Tumor epithelial cells at TIM of EOCC tumors, neighboring FAP(+) CAFs, showed significantly higher levels of fibroblast growth factor receptor 2 (FGFR2, p < 0.05) and PI3K/Akt signaling activation (p < 0.05). In-vitro assays showed FGF20 activates FGFR2-PI3K/Akt signaling in EOCC tumor cells. High levels FAP(+) CAF in EOCC tumors represent a prognostic factor for DFS and OS. Comparing TIM, EOCC tumors had enhanced FAP(+) CAF cells with significant WNT signaling upregulation and increased FGF20 levels compared to LOCC. Conversely, tumor cells, neighboring FAP(+) CAFs, showed significant activation of FGFR2-PI3K/Akt signaling at the EOCC TIM.

Introduction: Frozen section (FS) is often performed to confirm negative margins during pancreaticoduodenectomies (PD). This incurs significant cost, despite lack of evidence of survival benefit. We sought to determine the frequency of positive FS during PD, associated costs per positive margin identified, and association with locoregional recurrence (LRR) and overall survival (OS). Methods: A database of 526 PDs performed from 2014 to 2017 at a multi-institution integrated health-care system was queried. Charts and imaging were reviewed for systemic treatment, FS and PM results, pathologic stage, LRR and OS. Direct facility and professional costs for FS were determined from billing data. Cox proportional hazards for LRR and OS were performed. Results: 9.2% of all initial FS were positive. Average cost per FS was $148, with a cost of $1,538 per positive FS identified. Positive FS was not associated with LRR (HR 1.32, 95% CI: 0.50-3.52, p = 0.58) or median OS (25.9 vs 36.2 months, p = 0.38). Conclusion: Routine FS during PD is a low-yield test with significant associated costs. Positive FS was not associated with locoregional recurrence or overall survival. Routine FS does not provide substantial benefit for valuebased care when performing PD.

Background/Objectives: Systemic chemotherapy is recommended for all stages of pancreatic ductal adenocarcinoma (PDAC), with a recent shift towards neoadjuvant chemotherapy (NAC) for resectable PDAC. The objective of this study was to compare outcomes of NAC versus AC for early stage resectable PDAC in the NCDB. Methods: Patients aged 18 or older with stage I or II PDAC in the National Cancer Database (NCDB) from 2010 to 2017 were identified. Logistic regression evaluated oncologic outcomes. Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability of treatment weighting (IPTW) using propensity score matching was used to compare overall survival (OS). Results: NAC led to a 13% risk reduction of a positive resection margin (OR:0.87; 95%CI 0.78-0.97), and a 59% decreased risk of positive lymph nodes (OR:0.41; 95%CI 0.38-0.45). The median OS for all patients treated with NAC was 2.56 years versus 1.95 years for surgery +/- AC (p< 0.001). NAC had an OS benefit for all patients (HR:0.80; 95%CI 0.78-0.83), as well as for Stage I (HR:0.89; 95%CI 0.84-0.94) and Stage II patients (HR:0.71; 95%CI 0.68-0.75). Conclusions: NAC appears to be associated with a survival benefit for patients with resectable PDAC. NAC also decreased the risk of a positive resection margin and positive lymph nodes at the time of surgery.

Background: Undifferentiated carcinoma of the pancreas (UPC) is a rare malignancy. There are no standardized guidelines for treatment. Current management has been extrapolated from smaller reviews. Methods: 858 patients with UPC were identified in the 2004-2017 NCDB. Kaplan-Meier method followed by Cox proportional-hazards regression examined independent prognostic factors associated with overall survival (OS). Logistic regression analyses were performed to determine independent predictors of surgical intervention and the status of surgical resection by histologic subtype. Results: Patients with osteoclast-like giant cells (OCLGC) had a longer median OS compared to those without (aHR 0.52: 95% CI 0.41-0.67). Of the non-OCLGC subtypes, pleomorphic large cell demonstrated the shortest median OS (2.4 months). Surgical resection was associated with improved survival in all histologies except for pleomorphic cell carcinoma. R0 resection and negative lymph nodes were independently associated with an improved OS. Conclusion: This is the largest database review published to date on UCP. OCLGC histology is associated with an improved survival compared to those without OCLGC. Of the non-OCLGC subtypes, pleomorphic large cell is associated with the shortest overall survival. Surgical resection is associated with a significant survival advantage for all histologies except for pleomorphic cell carcinoma.

Brain metastasis (BM) frequently occurs in patients with cutaneous melanoma, lung, and breast cancer; although, BM rarely arises from cancers of the gastrointestinal tract (GIT). The reported incidence of GIT cancer BM is less than 4%. In the last few years, effective systemic therapy has prolonged the survival of GIT patients and consequently, the incidence of developing BM is rising. Therefore, the epidemiology and biology of BM arising from GIT cancer requires a more comprehensive understanding. In spite of the development of new therapeutic agents for patients with metastatic GIT cancers, survival for patients with BM still remains poor, with a median survival after diagnosis of less than 4 months. Limited evidence suggests that early detection of isolated intra-cranial lesions will enable surgical resection plus systemic and/or radiation therapy, which may lead to an increase in overall survival. Novel diagnostic methods such as blood-based biomarker biopsies may play a crucial role in the early detection of BM. Circulating tumor cells and circulating cell-free nucleic acids are known to serve as blood biomarkers for early detection and treatment response monitoring of multiple cancers. Blood biopsy may improve early diagnosis and treatment monitoring of GIT cancers BM, thus prolonging patients’ survivals.

BACKGROUND:Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the United States. We examined the determinant factors of the high survival in Japan compared with the United States. METHODS:We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a United States population-based cancer registry data from 2004-2010. We estimated 5-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined. RESULTS:Five-year relative survival in Japan was 81.0%, compared with 45.0% in the United States. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. CONCLUSION:Although the wide differences in GC survival between Japan and United States can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.