Incidence rates of appendiceal adenocarcinoma (AA) are increasing across all age groups in the United States. Birth cohort patterns of AA can provide new, etiologic clues into increasing rates but have not been examined.

To estimate incidence rates of AA across birth cohorts in the United States.

Retrospective cohort study.

The National Institutes of Health and National Cancer Institute SEER (Surveillance, Epidemiology, and End Results) Program of 8 population-based cancer registries.

A total of 4858 persons aged 20 years or older when diagnosed with a pathologically confirmed primary AA (nonmucinous, mucinous, goblet cell, or signet ring cell carcinoma) from 1975 to 2019.

Five-year age groups and time periods were used to create 21 overlapping birth cohorts (1891-1899 to 1991-1999). The ratio of age-specific incidence rates was estimated in each birth cohort relative to the 1945 birth cohort (birth years 1941 to 1949) and reported as incidence rate ratios (IRRs) with 95% CIs.

Incidence rates of AA more than tripled among the 1980 birth cohort (IRR, 3.41 [95% CI, 2.54 to 4.56]) and quadrupled among the 1985 birth cohort (IRR, 4.62 [CI, 3.12 to 6.82]) compared with the 1945 birth cohort. Age-specific incidence rates of AA increased across successive birth cohorts after 1945-although to varying degrees-for all tumor histologic types.

The rarity of AA precluded investigations specific to signet ring cell carcinomas of the appendix and across population groups (for example, sex and race).

There are strong yet distinct birth cohort effects for AAs across histologic subtypes that remain unexplained-particularly among persons born after 1945. Given these patterns, there is a timely need for etiologic research as well as increased AA awareness among providers and the public. Similar trends have been reported for other gastrointestinal cancers, suggestive of potential shared cause contributing to this increasing cancer burden across generations.

Appendix Cancer Pseudomyxoma Peritonei Research Foundation, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute.

HER2 overexpression is a marker for targeted therapy in adenocarcinoma of the gastroesophageal junction (GEJ) and stomach. The present study aimed to evaluate the frequency of HER2 overexpression with reference to clinicopathological characteristics in subjects from King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 10-year period. A retrospective cross-sectional study was conducted on all biopsy and resection specimens diagnosed with either gastric cancer (GC) or GEJ adenocarcinomas from patients between January 2014 and December 2023 that had a final pathology report. Demographic characteristics of 122 patients, including age and sex, were collected, along with pathological details such as tumor grade, histological subtype and HER2 status. χ2 test was used to analyze the association between collected clinicopathological characteristics and HER2 status of the tumor. Most patients were aged 40-60 years. Males constituted 66% of the patients, and the ethnic distribution between Saudi and non-Saudi was almost equal. The most common subtype of cancer was the intestinal type (49%), and the majority of cases were poorly differentiated (64%). HER2 status was assessed in only 61% of cases, with 13.5% showing gene amplification. There was no significant association found between HER2 status and clinicopathological features.

Gastric cancer (GC) is a prevalent malignancy with a high mortality rate and limited treatment options. Aging significantly contributes to tumor progression, and GC was confirmed as an aging-related heterogeneous disease. This study established an aging-associated index (AAI) using a machine learning-derived gene panel to stratify GC patients. High AAI scores associated with poor prognosis and indicated potential benefits from adjuvant chemotherapy, while showing resistance to immunotherapy. Single-cell transcriptome analysis revealed that AAI was enriched in monocyte cells within the tumor microenvironment. Two distinct molecular subtypes of GC were identified through unsupervised clustering, leading to the development of a subtype-specific regulatory network highlighting SOX7 and ELK3 as potential therapeutic targets. Drug sensitivity analyses indicated that patients with high ELK3 expression may respond to FDA-approved drugs (axitinib, dacarbazine, crizotinib, and vincristine). Finally, a user-friendly Shiny application was created to facilitate access to the prognostic model and molecular subtype classifier for GC.

This study aims to compare the short-term outcomes after minimally invasive gastrectomy between obese and non-obese population. Our analysis included data of 713 patients from ten departments of surgery. They were divided in non-obese group and obese group with 617 and 96 patients respectively. Significant differences were found in terms of mortality at 90 days (obese: 0 vs non-obese: 27, p = 0.037). Intraoperative data showed no significant differences in terms of conversion (obese: 4 vs non-obese: 43, p = 0.303). About postoperative complications, significant differences between the two groups were found only in terms of surgical infection (obese: 13 vs non-obese: 38, p = 0.009). About oncological outcomes, no differences were found about retrieved lymph nodes (obese: 30.71 ± 18.44 vs non-obese: 32.93 ± 17.62, p = 0.596) and about surgical radicality (R0) (obese:94 vs non-obese:594, p = 0.415). Obesity doesn't worsen postoperative outcomes and minimally invasive gastrectomy in obese patients is related to a lower postoperative mortality.

Examined lymph node (ELN) count is a critical factor affecting the number of metastatic lymph nodes (MLNs). The impact of the ELN number on survival and staging remains unclear.

This study included 4,291 stage N3 GC patients from the SEER database (training cohort) and 567 stage N3 GC patients from the FAHZZU database (validation cohort). The optimal ELN count and stage migration were investigated, and a modified TNM (mTNM) staging system including the ELN count was proposed. LASSO regression and random forest analyses were used to screen and evaluate the variables associated with survival, and an mTNM-based nomogram was constructed. The performance of the mTNM staging system and mTNM-based nomogram were compared with that of the 8th edition of the TNM staging system.

The optimal threshold of the ELN count was identified as 21. An insufficient number of ELNs (≤ 21) was associated with poorer survival outcomes and led to stage migration in all N3 patients. A new mTNM staging system was proposed, integrating the ELN count into the TNM staging system (8th edition). LASSO regression analysis revealed that age, tumor size, adjuvant chemotherapy, adjuvant radiotherapy, and the mTNM system were associated with overall survival (OS) outcomes, and random forest analysis revealed that the mTNM system was the most important variable for predicting survival. An mTNM-based nomogram was constructed to predict 1-, 3-, and 5-year OS rates. Compared with the TNM staging system (8th edition), the mTNM staging system and mTNM-based nomogram showed superior prognosis discriminative ability, better predictive accuracy, and greater net improvement in survival outcomes.

The optimal ELN count for N3 GC patients was 21. The mTNM staging system and mTNM-based nomogram showed superior discriminative ability, predictive accuracy, and greater net benefit for OS outcomes.

Upper gastrointestinal (UGI) cancers, comprising malignancies of the esophagus, stomach, duodenum, pancreas, liver, biliary tract, and gallbladder, are the second leading cause of cancer-related mortality in the United States and are associated with significant comorbidities. Recent studies show a disproportionate rise in pancreatic and stomach cancer among young adults. This study aims to use a nationwide, population-based cohort to (i) evaluate the trend of all UGI cancer as an aggregate and (ii) examine the role of demographics, histology, and tumor stage in UGI cancer incidence among young adults.

Individuals diagnosed with UGI cancer in the United States from 2001 to 2019 were identified and obtained from the Surveillance, Epidemiology, and End Results-National Program of Cancer Registries database. The primary outcomes were incidence rates of UGI cancer (calculated per 100,000, age-adjusted to the year 2000 US population), stratified by sex and age (< 55 years for young adults and ≥ 55 years for older adults). Trends, annual percentage change, and average annual percentage change were calculated using the parametric method. Sensitivity analysis was performed according to primary site and histology; further analysis examining race and cancer stage was performed in the young adult subgroup.

A total of 2,333,161 patients with UGI cancer were identified. Most cases were male, and 14.3% were < 55 years of age. Incidence of UGI cancer increased most in women younger than 55 years, driven primarily by pancreatic and stomach cancers, as well as neuroendocrine tumor and gastrointestinal stromal tumor histology. African American race and localized tumors and malignancy with distant spread are also contributing to the disparate increase among young women. UGI mortality rates have not changed significantly in young adults.

The overall incidence rate of upper gastrointestinal cancer is increasing significantly in young women compared with men. Increased endoscopic procedures and disparate exposure to risk factors are likely contributing to these trends.

Gastric cancer (GC) has a high prevalence in Asian countries, and there is an unmet need for non-invasive and efficient GC screening methods. This study evaluated the diagnostic efficacy of GASTROClear, a panel of blood serum miRNAs for the detection of GC, in a Japanese population.

We conducted a pilot cohort study, comprising 103 patients with GC and 122 healthy controls. Serum samples were prospectively collected from study participants at two Japanese hospitals using a predefined blood-processing protocol. The diagnostic performance of GASTROClear was analyzed using a receiver operating characteristic curve and cutoff. By applying a logistic regression algorithm, we evaluated the diagnostic efficacy of novel combinations of GC diagnostic biomarker panels, consisting of GASTROClear and alternative serum markers (anti-Helicobacter pylori [Hp] antibody and pepsinogen).

Most patients had Stage I (58%) GC and were asymptomatic (59%). The area under the curve (AUC) value for the detection of GC using GASTROClear was 0.80, with 70.9% sensitivity and 75.2% specificity. GASTROClear performed equally well within the subgroups based on age, sex, symptoms, Hp status, and tumor characteristics. We improved the diagnostic performance of GASTROClear by combining it with an anti-Hp antibody and pepsinogen. This yielded an AUC value of 0.88, with the highest specificity (86.9%) at a fixed sensitivity (70.9%).

GASTROClear demonstrated competent diagnostic efficacy for GC in the detection of GC in our Japanese cohort, even in the early stages of cancer and asymptomatic cases. Its combination with existing serum markers may contribute to efficient risk stratification to detect GC.

There has been a paradoxical rise in young-onset gastric cancer (YOGC), defined as gastric cancer (GC) diagnosed before age 50. Precursor lesions may contribute to pathogenesis, though their role in progression to different histologic subtypes is unclear. The impact of self-reported race is also poorly characterized and may be unreliable as a proxy for genetic differences. We aimed to compare differences in histology and genetic ancestry between YOGC and average-onset gastric cancer (AOGC).

This retrospective cohort included all patients with GC at Memorial Sloan Kettering (MSK) from January 2013 to March 2021. Data on demographics, tumor characteristics, and precursor lesions were collected. Genetic ancestry was inferred from MSK-Integrated Mutation Profiling of Actionable Cancer Targets panel.

Of 1685 individuals with GC, 290 had YOGC. Compared to AOGC, individuals with YOGC tended to be female, Hispanic, foreign-born, and feature diffuse-type histology. YOGC was less likely to have precursor lesions, including intestinal metaplasia (20% vs. 37%, p < 0.01) and dysplasia (4% vs. 14%, p < 0.01). Of 560 patients with ancestry data, 127 had YOGC. Admixed, East Asian, and South Asian ancestries were more likely to present with YOGC while Europeans presented with AOGC. Intestinal metaplasia was enriched among East Asians, maintained when stratifying by histology and GC onset.

We observed YOGC was more common in East and South Asians, and while YOGC may be less likely to develop in the setting of precursor lesions these high-risk states may also be enriched in East Asians. Future research is needed to understand drivers behind such differences and outcome disparities given these individuals may be less amenable to endoscopic interventions.

There are few studies on early-onset and late-onset nasopharyngeal cancer (EONPC and LONPC, defined as cancers in those aged < 50 and ≥ 50 years, respectively). This study aimed to determine the clinical and survival characteristics of patients with NPC in these two age groups.

This study involved patients diagnosed with NPC between 2000 and 2018, as per the Surveillance, Epidemiology, and End Results (SEER) database, and in our institution from 2014 to 2017. The clinicopathological characteristics, treatment modalities, and survival outcomes of patients with EONPC and LONPC were analyzed and compared.

A total of 2943 patients from the SEER database and 833 domestic patients from our center were enrolled in the study. The EONPC group showed a better prognosis than LONPC (p < 0.001), despite a worse staging of regional lymph node metastasis (p < 0.001). Similar results were validated at our center; further, patients with EONPC presented more EBV-DNA positive rates (58% vs. 36.8%, p < 0.001) than those with LONPC. Further, the EONPC group had a superior overall survival (OS) (p = 0.017) and cancer-specific survival (CSS) (p = 0.004) compared to that of the LONPC patients. Univariate and multivariate Cox regression analyses revealed EONPC to be independently associated with a higher five-year OS.

Though the EONPC group presented with more advanced clinical stages and lymph node metastasis, they showed better survival than the LONPC group. Age ≤ 50 years was an independent prognostic factor for survival outcomes in patients with NPC. Further studies on EONPC are warranted to achieve a better individualized therapeutic regimen.

Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024.

The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi's world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024.

Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77-4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5-63.2%) in 2010 to 34.4% (95%CI, 32.1-36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5-55.1%) in 2010 to 34.2% (95%CI, 32.0-36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024.

From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

Introduction Gastric cancer is a significant major global health concern, particularly prevalent in Asia. In recent years, a large number of new cases have been diagnosed worldwide, leading to a substantial number of deaths. The disease tends to present more aggressively in these cases, leading to debates about the prognosis and survival outcomes. Nonetheless, research has shown that survival rates improve significantly when the tumor is completely surgically resected. Materials and methods This retrospective study included patients between 16 and 45 years old, diagnosed with gastric cancer, with the support of the pathology department, who underwent surgery in the upper GI service, in the period from January 2006 to December 2012. Data collected encompassed variables such as gender, age, tumor size, type of surgery, overall survival, disease-free period, type and histological degree of the tumor, clinical stage of the cancer, and R0 resection (curative resection). All patients with a confirmed diagnosis of gastric cancer were included and treated with surgery and D1 limited dissection or extended D2 dissection. Patients who have received chemotherapy prior to surgical treatment and those who have been surgically treated outside the XXI Century National Medical Center were excluded. Results A total of 104 patients were included; the predominant histological type was diffuse adenocarcinoma accounting for 79.8% and 81.7% of the cases were histological grade 3. The most common clinical stage was IIIA in 41.3% of the cases. In 53.8% of the cases, we obtained an R0 resection. D2 lymphadenectomy was performed in 53.8% of the cases, with an overall survival rate of 82.69%. Significant prognostic factors for survival included T4 depth with an increase in risk for mortality (OR: 25.93; 95% CI: 6.41-53.54; p=0.001), lymph node status (OR: 14.76; 95% CI: 4.6-46.83; p<0.001), and size greater than 5 cm (OR: 1.8; 95% CI: 0.61-6.35; p<0.001). Conclusions Gastric cancer is more common in adults aged above 60 years old, but the incidence in young adults under 45 years old has been increasing. Although young gastric cancer patients present with more aggressive tumor behavior, these patients can have similar or even better overall survival compared to older patients, being 35% in some cases, especially in the resectable setting. Further research is still needed to fully characterize the unique biology and optimal management of gastric cancer in young adults.

Gastric cancer exerts a significant healthcare burden worldwide and is highly geographically heterogeneous. This study investigates the burden of gastric cancer in China from 1990 to 2019 and compares it with Japan, South Korea, and the United States. The results indicated a declining trend in ASIR and ASDR in four countries. However, the incidence and death rates in China remain disproportionately high. Significant gender disparities exist in the incidence and death rates, with males experiencing significantly higher rates than females. Incidence and death rates were found to increase with age in all studied countries. In China, a transient upward trend was observed in the period effect, whereas the cohort effect has been declining. In contrast, the remaining countries showed decreasing patterns in both period and cohort effects. The burden of disease remains high in China, therefore, broaden the scope of gastroscopy screening and concentrate on high-risk groups is vital.

Gastric cancer poses a significant global health challenge, with high incidence and mortality rates each year. Despite advancements in screening and treatment, late detection remains a critical issue. Efforts to address this include raising public awareness and implementing targeted screening programs for high-risk populations. The increasing incidence of gastric cancer among younger individuals underscores the need for lifestyle adjustments and targeted interventions to mitigate risks and improve outcomes. Understanding the various factors contributing to gastric cancer risk is essential for effective prevention strategies, including Helicobacter pylori eradication, lifestyle modifications, and regular screening for high-risk groups. A comprehensive approach addressing both individual behaviors and broader societal factors is crucial in the fight against gastric cancer. This review provides an in-depth examination of gastric cancer epidemiology, risk factors, preventive measures, and screening initiatives, with a particular focus on the rising incidence among younger demographics. Emphasizing the importance of early detection and intervention, the review highlights the need for proactive screening to improve patient outcomes and reduce mortality rates. By addressing these aspects comprehensively, this paper aims to enhance the understanding of gastric cancer dynamics, particularly its incidence among younger individuals, and to inform future strategies for prevention and control.

The goal of a gastric cancer operation is a microscopically negative resection margin and D2 lymphadenectomy. Minimally invasive techniques (laparoscopic and robotic) have been proven to be equivalent for oncologic care, yet with faster recovery. Endoscopic mucosal resection can be used for T1a N0 tumor resection. Better understanding of hereditary gastric cancer and molecular subtypes has led to specialized recommendations for MSI-high tumors and patients with pathogenic CDH1 mutations. In the future, surgical management will support minimally invasive approaches and personalized cancer care based on subtype.

The purpose of this report was to present the computed tomography (CT) and magnetic resonance imaging (MRI) features of Krukenberg tumors and to review the pertinent clinical data about the rising incidence of this malignancy among young women.

This series included 8 women who ranged in age from 24 to 44 years (mean, 36.3 years). They were diagnosed to have Krukenberg tumors during a 5-year period (2011-2016). All patients were evaluated by abdominal CT and pelvic or transvaginal sonography. Five of them also had MRI of the abdomen, and 3 had positron emission tomography scans.

The primary cancer was located in the stomach of 7 patients and in the colon in 1. The initial presentation was due to large pelvic mass and abdominal distention by ascites in 3 patients, gastrointestinal symptoms in 4, and small bowel obstruction by carcinoma of the ascending colon in 1 woman. Ovarian metastases were demonstrated on the initial imaging examination of 5 patients and developed as metachronous lesion during follow-up in 3 cases. Six women died 3 to 23 months (mean, 11 months) after the diagnosis. One has survived for 6 years after extensive surgery, and 1 was lost to follow-up.

Krukenberg tumors are being diagnosed with an increasing frequency because of well-documented rising incidence of gastric and colorectal carcinomas among young women. Therefore, those presenting with gastrointestinal cancer should have careful imaging of their ovaries for possible metastases, and conversely, the clinical or sonographic detection of bilateral ovarian masses would require evaluation by CT or MRI of the abdomen in search for a potential primary gastrointestinal cancer. This report highlights the CT and MRI features of this neoplastic process and reviews the current concepts about its development and management.

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care.

This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods.

The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC.

Routine EHR data can stratify the general population for GAC risk.

Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.

Analysis of Lexis diagrams (population-based cancer incidence and mortality rates indexed by age group and calendar period) requires specialized statistical methods. However, existing methods have limitations that can now be overcome using new approaches.

We assembled a "toolbox" of novel methods to identify trends and patterns by age group, calendar period, and birth cohort. We evaluated operating characteristics across 152 cancer incidence Lexis diagrams compiled from United States (US) Surveillance, Epidemiology and End Results Program data for 21 leading cancers in men and women in four race and ethnicity groups (the "cancer incidence panel").

Nonparametric singular values adaptive kernel filtration (SIFT) decreased the estimated root mean squared error by 90% across the cancer incidence panel. A novel method for semi-parametric age-period-cohort analysis (SAGE) provided optimally smoothed estimates of age-period-cohort (APC) estimable functions and stabilized estimates of lack-of-fit (LOF). SAGE identified statistically significant birth cohort effects across the entire cancer panel; LOF had little impact. As illustrated for colon cancer, newly developed methods for comparative age-period-cohort analysis can elucidate cancer heterogeneity that would otherwise be difficult or impossible to discern using standard methods.

Cancer surveillance researchers can now identify fine-scale temporal signals with unprecedented accuracy and elucidate cancer heterogeneity with unprecedented specificity. Birth cohort effects are ubiquitous modulators of cancer incidence in the US. The novel methods described here can advance cancer surveillance research.

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case-control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

Screening esophagogastroduodenoscopy plays an important role in the early detection of upper gastrointestinal cancer. To provide more opportunities for patients with pancreaticobiliary disease to undergo this screening, we have performed esophagogastroduodenoscopy prior to endoscopic ultrasonography. However, the usefulness of this protocol is not elucidated. This study aimed to investigate the utility of screening esophagogastroduodenoscopy in this protocol in the detection of upper gastrointestinal epithelial neoplasms.

The outcomes of screening esophagogastroduodenoscopy performed prior to endoscopic ultrasonography in patients with pancreaticobiliary disease at our hospital between April 2020 and September 2022 were investigated. A logistic regression model was used to identify factors affecting the detection of epithelial neoplasms. Additionally, we compared the detection rate of gastric epithelial neoplasms between screening esophagogastroduodenoscopy performed prior to endoscopic ultrasonography and that performed at our medical checkup center.

A total of 615 screening esophagogastroduodenoscopies prior to endoscopic ultrasonography were performed, and 12 (2.0%) epithelial neoplasms were detected, including esophageal lesions (n = 2) and gastric lesions (n = 10). Of these lesions, 75% (9/12) underwent curative endoscopic resection. A multivariate analysis showed that open-type gastric mucosal atrophy (odds ratio, 7.7; 95% confidence interval, 1.5-38.4; p = 0.01) and the use of magnification endoscopy (odds ratio, 7.3; 95% confidence interval, 1.9-27.9; p < 0.01) independently affected the detection of epithelial neoplasms. The detection rate of gastric epithelial neoplasms was significantly higher using this protocol than that in our medical checkup center (1.6% versus 0.2%, p < 0.01).

A protocol of screening esophagogastroduodenoscopy prior to endoscopic ultrasonography may be recommended because epithelial neoplasms could be detected at a non-negligible rate.

Incidence and mortality of colorectal cancer (CRC) are increasing worldwide, suggesting broad changes in the epidemiology of CRC. In this Review, we discuss the changes that are becoming evident, including trends in CRC incidence and mortality by age and birth cohort, and consider the contributions of early-life exposures and emerging risk factors to these changes. Importantly, incidence of CRC has increased among people born since the early 1950s in nearly all regions of the world. These so-called birth cohort effects imply the involvement of factors that influence the earliest stages of carcinogenesis and have effects across the life course. Accumulating evidence supports the idea that early-life exposures are important risk factors for CRC, including exposures during fetal development, childhood, adolescence and young adulthood. Environmental chemicals could also have a role because the introduction of many in the 1950s and 1960s coincides with increasing incidence of CRC among people born during those years. To reverse the expected increases in the global burden of CRC, participation in average-risk screening programmes needs to be increased by scaling up and implementing evidence-based screening strategies, and emerging risk factors responsible for these increases need to be identified.

Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma.

Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years.

Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients.

In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Nerves can support tumor development by secreting neurotransmitters that promote cancer cell proliferation and invasion. 5-Hydroxytryptamine (5-HT) is a critical neurotransmitter in the gastrointestinal nervous system, and 5-HT signaling has been shown to play a role in tumorigenesis. Here, we found that expression of the 5-HT receptor HTR2B was significantly elevated in human gastric adenocarcinoma tissues compared with nontumor tissues, and high HTR2B expression corresponded to shorter patient survival. Both 5-HT and a specific HTR2B agonist enhanced gastric adenocarcinoma cell viability under metabolic stress, reduced cellular and lipid reactive oxygen species, and suppressed ferroptosis; conversely, HTR2B loss or inhibition with a selective HTR2B antagonist yielded the inverse tumor suppressive effects. In a patient-derived xenograft tumor model, HTR2B-positive tumors displayed accelerated growth, which was inhibited by HTR2B antagonists. Single-cell analysis of human gastric adenocarcinoma tissues revealed enrichment of PI3K/Akt/mTOR and fatty acid metabolism-related gene clusters in cells expressing HTR2B compared with HTR2B-negative cells. Mechanistically, HTR2B cooperated with Fyn to directly regulate p85 activity and trigger the PI3K/Akt/mTOR signaling pathway, which led to increased expression of HIF1α and ABCD1 along with decreased levels of lipid peroxidation and ferroptosis. Together, these findings demonstrate that HTR2B activity modulates PI3K/Akt/mTOR signaling to stimulate gastric cancer cell survival and indicate that HTR2B expression could be a potential prognostic biomarker in patients with gastric cancer.

Nerve cancer cross-talk mediated by HTR2B inhibits lipid peroxidation and ferroptosis in gastric cancer cells and promotes viability under metabolic stress, resulting in increased tumor growth and decreased patient survival.

This study constructed and validated a prognostic model to evaluate long-term cancer-specific survival (CSS) in middle-aged patients with early gastric cancer (EGC).

We extracted clinicopathological data from relevant patients between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided the patients into a training group (N = 688) and a validation group (N = 292). In addition, 102 Chinese patients were enrolled for external validation. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict CSS. We used the concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) to evaluate the predictive performance of the model.

Univariate and multivariate COX regression analyses showed that tumor location, differentiation grade, N stage, chemotherapy, and number of regional nodes examined were independent risk factors for prognosis, and these factors were used to construct the nomogram. The C-index of the model in the training cohort, internal validation cohort, and external validation cohort was 0.749 (95% CI 0.699-0.798), 0.744 (95% CI 0.671-0.818), and 0.807 (95% CI 0.721-0.893), respectively. The calibration curve showed that the model had an excellent fit. The DCA curve showed that the model had good predictive performance and practical clinical value.

This study developed and validated a new nomogram to predict CSS in middle-aged patients with EGC. The prediction model has unique and practical value and can help doctors carry out individualized treatment and judge prognosis.

Long non-coding RNAs (lncRNAs) can be utilized as prognostic indicators of gastric cancer since they can affect several cancer-related processes. Coumarin is a natural product with some useful anti-cancer properties. Here, we measured the expression of selected lncRNAs (RuPAR, SNHG6, CASC11, and their targets, miR-340-5p, p21, E-cadherin, and CDK1) in AGS gastric cancer cells treated with coumarin. MTT test has been utilized for assessing the AGS cells' cell viability after exposure to coumarin. The expression of the lncRNAs (RuPAR, SNHG6, and CASC11) and miR-340-5p was evaluated via qRT-PCR. Western blot analysis has been utilized to determine changes in p21, E-cadherin, and CDK1 expression. Coumarin decreased AGS viability in a dose-dependent manner. The coumarin treated cells had lower levels of the mRNAs known to be targets of lncRNAs SNHG6 and CASC11 compared to control. Additionally, the coumarin group had increased levels of lncRNA RuPAR expression when compared with the control group. Some lncRNA targets, including p21, E-cadherin, and CDK1, showed lower expression in the coumarin group compared to the control by Western blotting. Coumarin could be a promising pharmacological candidate to be included in gastric cancer treatment regimens because it modulates lncRNAs and their targets.

Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S.

However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear.

We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons.

Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%), GIST (6.7%), NET (6.4%), and MALT lymphoma (5.6%). Noncardia GA ASIR was significantly higher than other histologies and demonstrated the greatest differences by race and ethnicity. APCs for GA and MALT, both Helicobacter pylori-associated cancers, declined significantly over time, which was driven primarily by trends among individuals ≥50 years-old. NET and GIST APCs significantly increased irrespective of age group, with the highest APCs observed among non-Hispanic white individuals. Cardia GC was rarer than noncardia GC and comprised primarily by GA (87.9%). Cardia GC incidence fell during the study period, which was primarily driven by decline in cardia GA.

GA was the most common histology. On the basis of our findings, the rise in noncardia GC among certain U.S. populations appears predominantly driven by NET and GIST, not GA. Further studies are needed to clarify underlying etiologies for these findings.

Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer-related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome-mediated degradation, which further mediates the activation of the AKT/GSK3β/epithelial-to-mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin-3-gallate-lysozyme (EGCG-LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG-LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG-LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post-transcriptional gene silencing. In addition, EGCG-LYS carrying si-circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG-LYS fibrils delivery system provides a new tool and approach for the treatment of GC.

Long non-coding RNAs (lncRNAs), which comprise most non-coding RNAs (ncRNAs), have recently become a focus of cancer research. How many functional ncRNAs exist is still a matter of debate. Although insufficient evidence supports that most lncRNAs function as transcriptional by-products, it is widely known that an increasing number of lncRNAs play essential roles in cells. Small nucleolar RNAs (snoRNAs), 60-300 nucleotides in length, have been better studied than long non-coding RNAs (lncRNAs) and are predominantly present in the nucleolus. Most snoRNAs are encoded in introns of protein- and non-protein-coding genes called small nucleolar RNA host genes (SNHGs). In this article, we explore the biology and characteristics of SNHGs and their role in developing human malignancies. In addition, we provide an update on the ability of these snoRNAs to serve as prognostic and diagnostic variables in various forms of cancer.

As a complex and difficult condition, gastric cancer (GC) continues to have a big impact on the world's health. The goal of this review article is to give a thorough summary of the most recent developments and research discoveries in the field of stomach cancer. The review discusses a wide range of topics, such as the epidemiology and risk factors for GC, molecular insights into its pathogenesis, the use of biomarkers in diagnosis and prognosis, current and novel therapeutic approaches, and the intriguing potential of immunotherapy. In addition, procedures for surgery, therapy strategies, and imaging modalities for diagnosis and staging are examined. The paper emphasizes how crucial it is to comprehend the tumor microenvironment and how it affects the course of the disease. Overall, this review provides a comprehensive assessment of the current body of knowledge, highlights research gaps, and suggests future lines of inquiry to enhance the treatment of GC.

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach.