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12 pages, 598 KB

Open AccessArticle

Beyond the Skin: Atopic Dermatitis and Increased Gastric Cancer Risk in Korea

by Ho Suk Kang, Kyeong Min Han, Joo-Hee Kim, Ji Hee Kim, Hyo Geun Choi, Dae Myoung Yoo, Ha Young Park, Nan Young Kim and Mi Jung Kwon

Cancers 2025, 17(19), 3214; https://doi.org/10.3390/cancers17193214 - 2 Oct 2025

Viewed by 481

Abstract

Background/Objectives: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, but its relationship with gastric cancer (GC) remains unclear. This study aimed to investigate the association between AD and GC using a nationwide Korean database. Methods: Using the Korean National Health Insurance [...] Read more.

Background/Objectives: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, but its relationship with gastric cancer (GC) remains unclear. This study aimed to investigate the association between AD and GC using a nationwide Korean database. Methods: Using the Korean National Health Insurance Service-National Sample Cohort, we conducted a nested case–control study including 10,174 GC patients and 40,696 matched controls (1:4 by age, sex, income, and region). Overlap propensity score weighting was used to control for confounders. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via logistic regression. Results: AD was significantly associated with an increased risk of GC (adjusted OR = 1.08; 95% CI: 1.01–1.15). Subgroup analyses revealed stronger associations among individuals aged ≥ 65 years (OR = 1.12), men (OR = 1.10), rural residents (OR = 1.14), and those without comorbidities (CCI = 0, OR = 1.15). Higher risks were also observed in participants with non-allergic rhinitis (OR = 1.43) or no asthma (OR = 1.12). Conclusions: AD may be associated with an increased risk of GC in the Korean population. These findings may highlight the importance of considering dermatological conditions in the context of systemic cancer risk. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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16 pages, 1931 KB

Open AccessArticle

Nationwide Trends and Projections of Early Onset Gastrointestinal Cancers in China

by Tianyu Li, Chen Lin and Weibin Wang

Cancers 2025, 17(18), 2954; https://doi.org/10.3390/cancers17182954 - 9 Sep 2025

Viewed by 821

Abstract

Early-onset (15–49 years) gastrointestinal cancers are an emerging public health concern in China, yet national trend analyses remain limited. Drawing on data from the Global Burden of Disease 2021 study, we evaluated nationwide trends in the incidence and mortality of early-onset gastrointestinal cancers [...] Read more.

Early-onset (15–49 years) gastrointestinal cancers are an emerging public health concern in China, yet national trend analyses remain limited. Drawing on data from the Global Burden of Disease 2021 study, we evaluated nationwide trends in the incidence and mortality of early-onset gastrointestinal cancers (esophagus, stomach, liver, colon and rectum, gallbladder and biliary tract, and pancreas) in China from 1990 to 2021 and projected future patterns through 2040 using Bayesian age–period–cohort models. Between 1990 and 2021, age-standardized rates for esophageal, stomach, and liver cancers declined markedly while those for colorectal and biliary tract cancers increased, and pancreatic cancer rates rose modestly. Mortality for upper-GI cancers fell substantially, whereas colorectal cancer deaths rose modestly, with the age-standardized mortality rate declining despite rising incidence. Projections suggest continued declines in upper-GI cancers, further increases in colorectal and biliary tract cancers, and a peak in the age-standardized incidence rate of pancreatic cancer around 2030. These divergent trends highlight an urgent need for targeted prevention and early-detection strategies focused on colorectal, biliary, and pancreatic cancers among patients aged 15–49 years in China. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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19 pages, 3100 KB

Open AccessArticle

Diminished Estrogen Induced Mitochondrial Protection and Immunosuppressive Microenvironment in Gastric Cancer with Depression

by Yixin Liu, Sheng Tian, Yujia Tan, Picheng Yan, Pan Liu, Huiying Zhu, Sachiyo Nomura, Tianhe Huang and Yongchang Wei

Cancers 2025, 17(17), 2789; https://doi.org/10.3390/cancers17172789 - 26 Aug 2025

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Abstract

Background: It is established that depression significantly contributes to tumor development, yet its molecular link to gastric cancer progression remains unclear. Methods: In this study, we examined depression-related gene expression profiles in relation to clinical prognosis and identified estradiol and the NOTCH3 gene [...] Read more.

Background: It is established that depression significantly contributes to tumor development, yet its molecular link to gastric cancer progression remains unclear. Methods: In this study, we examined depression-related gene expression profiles in relation to clinical prognosis and identified estradiol and the NOTCH3 gene as critical factors involved in gastric cancer progression in the context of depression. Using a chronic unpredictable stress-induced tumor-bearing mouse model, we validated the impact of depression on tumor development. Additionally, the underlying molecular mechanisms were explored through a range of biological techniques, including Western blotting, immunofluorescence, flow cytometry and immunohistochemistry. Results: Depression significantly accelerated gastric cancer growth in our mouse model, characterized by decreased estradiol levels and increased NOTCH3 expression. Importantly, exogenous estradiol supplementation effectively counteracted depression-induced tumor growth. Consistently, in vitro studies showed that estradiol treatment suppressed NOTCH3 expression in HGC-27 and YTN3 cell lines. Furthermore, NOTCH3 was shown to modulate intracellular reactive oxygen species levels by regulating SOD2 activity, thereby influencing cell proliferation. Conclusions: This work identified the estrogen/NOTCH3 signaling as a key link between depression and gastric cancer development, offering promising therapeutic strategies to improve outcomes for patients suffering from psychological disorders. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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14 pages, 1043 KB

Open AccessArticle

Endoscopic Management of Post-Esophagectomy Delayed Gastric Conduit Emptying (DGCE): Results from a Cohort Study in a Tertiary Referral Center with Comparison between Procedures

by Giuseppe Dell’Anna, Francesco Vito Mandarino, Jacopo Fanizza, Ernesto Fasulo, Alberto Barchi, Rukaia Barà, Edoardo Vespa, Edi Viale, Francesco Azzolini, Lorella Fanti, Silvia Battaglia, Francesco Puccetti, Andrea Cossu, Ugo Elmore, Lorenzo Fuccio, Vito Annese, Alberto Malesci, Riccardo Rosati and Silvio Danese

Cancers 2024, 16(20), 3457; https://doi.org/10.3390/cancers16203457 - 12 Oct 2024

Cited by 2 | Viewed by 1744

Abstract

Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods [...] Read more.

Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods: We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results: A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55–70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p = 0.02), and a Kaplan–Meier analysis with a log–rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8–1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1–3; p = 0.0001). Conclusions: Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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14 pages, 940 KB

Open AccessArticle

Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis

by Mark Ayoub, Rafi Aibani, Tiana Dodd, Muhammed Ceesay, Muhammad Bhinder, Carol Faris, Nisar Amin and Ebubekir Daglilar

Cancers 2024, 16(18), 3224; https://doi.org/10.3390/cancers16183224 - 22 Sep 2024

Cited by 7 | Viewed by 4008

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs [...] Read more.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. Methods: We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m², and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients’ baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. Results: A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. Conclusion: The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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15 pages, 1387 KB

Open AccessArticle

The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study

by Mark Ayoub, Carol Faris, Tajana Juranovic, Harleen Chela and Ebubekir Daglilar

Cancers 2024, 16(9), 1625; https://doi.org/10.3390/cancers16091625 - 23 Apr 2024

Cited by 20 | Viewed by 6210

Abstract

Background: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. Methods: We analyzed TriNetX’s deidentified research database using the U.S. Collaborative [...] Read more.

Background: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. Methods: We analyzed TriNetX’s deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. Results: Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. Conclusion: The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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Review

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13 pages, 274 KB

Open AccessReview

Early Rectal Cancer: Advances in Diagnosis and Management Strategies

by Huda Mohammed, Hadeel Mohamed, Nusyba Mohamed, Rajat Sharma and Jayesh Sagar

Cancers 2025, 17(4), 588; https://doi.org/10.3390/cancers17040588 - 9 Feb 2025

Cited by 3 | Viewed by 3247

Abstract

Colorectal cancer (CRC) is the second most prevalent cause of cancer-related death and the third most common cancer globally. Early-stage rectal cancer is defined by lesions confined to the bowel wall, without extension beyond the submucosa in T1 or the muscularis propria in [...] Read more.

Colorectal cancer (CRC) is the second most prevalent cause of cancer-related death and the third most common cancer globally. Early-stage rectal cancer is defined by lesions confined to the bowel wall, without extension beyond the submucosa in T1 or the muscularis propria in T2, with no indication of lymph node involvement or distant metastasis. The gold standard for managing rectal cancer is total mesorectal excision (TME); however, it is linked to considerable morbidities and impaired quality of life. There is a growing interest in local resection and non-operative treatment of early RC for organ preservation. Local resection options include three types of transanal endoscopic surgery (TES): transanal endoscopic microsurgery (TEM), transanal endoscopic operations (TEO), and transanal minimally invasive surgery (TAMIS), while endoscopic resection includes endoscopic mucosal resection (EMR), underwater endoscopic mucosal resection (UEMR), and endoscopic submucosal dissection (ESD). Although the oncological outcome of local resection of early rectal cancer is debated in the current literature, some studies have shown comparable outcomes with radical surgery in selected patients. The use of adjuvant and neoadjuvant chemoradiotherapy in early rectal cancer management is also controversial in the literature, but a number of studies have reported promising outcomes. This review focuses on the available literature regarding diagnosis, staging, and management strategies of early rectal cancer and provides possible recommendations. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

26 pages, 1570 KB

Open AccessReview

Progress in Biological Research and Treatment of Pseudomyxoma Peritonei

by Xi Li, Guodong Liu and Wei Wu

Cancers 2024, 16(7), 1406; https://doi.org/10.3390/cancers16071406 - 3 Apr 2024

Cited by 6 | Viewed by 8763

Abstract

Pseudomyxoma peritonei (PMP) is a rare disease characterized by extensive peritoneal implantation and mass secretion of mucus after primary mucinous tumors of the appendix or other organ ruptures. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the preferred treatment, with [...] Read more.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by extensive peritoneal implantation and mass secretion of mucus after primary mucinous tumors of the appendix or other organ ruptures. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the preferred treatment, with excellent efficacy and safety, and is associated with breakthrough progress in long-term disease control and prolonged survival. However, the high recurrence rate of PMP is the key challenge in its treatment, which limits the clinical application of multiple rounds of CRS-HIPEC and does not benefit from conventional systemic chemotherapy. Therefore, the development of alternative therapies for patients with refractory or relapsing PMP is critical. The literature related to PMP research progress and treatment was searched in the Web of Science, PubMed, and Google Scholar databases, and a literature review was conducted. The overview of the biological research, treatment status, potential therapeutic strategies, current research limitations, and future directions associated with PMP are presented, focuses on CRS-HIPEC therapy and alternative or combination therapy strategies, and emphasizes the clinical transformation prospects of potential therapeutic strategies such as mucolytic agents and targeted therapy. It provides a theoretical reference for the treatment of PMP and the main directions for future research. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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