Cancers

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16 pages, 1142 KiB

Open AccessArticle

Rising Incidence of Non-Cardia Gastric Cancer among Young Women in the United States, 2000–2018: A Time-Trend Analysis Using the USCS Database

by Janice Oh, Yazan Abboud, Miguel Burch, Jun Gong, Kevin Waters, Jenan Ghaith, Yi Jiang, Kenneth Park, Quin Liu, Rabindra Watson, Simon K. Lo and Srinivas Gaddam

Cancers 2023, 15(8), 2283; https://doi.org/10.3390/cancers15082283 - 13 Apr 2023

Cited by 3 | Viewed by 2038

Abstract

Introduction: Although the global incidence of non-cardia gastric cancer (NCGC) is decreasing, there are limited data on sex-specific incidence in the United States. This study aimed to investigate time trends of NCGC from the SEER database to externally validate findings in a SEER-independent [...] Read more.

Introduction: Although the global incidence of non-cardia gastric cancer (NCGC) is decreasing, there are limited data on sex-specific incidence in the United States. This study aimed to investigate time trends of NCGC from the SEER database to externally validate findings in a SEER-independent national database, and to further assess trends among subpopulations. Methods: Age-adjusted incidence rates of NCGC were obtained from the SEER database from 2000 to 2018. We used joinpoint models to calculate average annual percentage change (AAPC) to determine sex-specific trends among older (≥55 years) and younger adults (15–54 years). Using the same methodology, findings were then externally validated using SEER-independent data from the National Program of Cancer Registries (NPCR). Stratified analyses by race, histopathology, and staging at diagnosis were also conducted in younger adults. Results: Overall, there were 169,828 diagnoses of NCGC from both independent databases during the period 2000–2018. In SEER, among those <55 years, incidence increased at a higher rate in women (AAPC = 3.22%, p < 0.01) than men (AAPC = 1.51%, p = 0.03), with non-parallel trends (p = 0.02), while a decreasing trend was seen in both men (AAPC = −2.16%, p < 0.01) and women (AAPC = −1.37%, p < 0.01) of the ≥55 years group. Validation analysis of the SEER-independent NPCR database from 2001 to 2018 showed similar findings. Further stratified analyses showed that incidence is disproportionately increasing in young non-Hispanic White women [AAPC = 2.28%, p < 0.01] while remaining stable in their counterpart men [AAPC = 0.58%, p = 0.24] with non-parallel trends (p = 0.04). This pattern was not observed in other race groups. Conclusion: NCGC incidence has been increasing at a greater rate in younger women compared to counterpart men. This disproportionate increase was mainly seen in young non-Hispanic White women. Future studies should investigate the etiologies of these trends. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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14 pages, 5330 KiB

Open AccessArticle

Increased SEC23A Expression Correlates with Poor Prognosis and Immune Infiltration in Stomach Adenocarcinoma

by Su Zhaoran, Christina Susanne Linnebacher and Michael Linnebacher

Cancers 2023, 15(7), 2065; https://doi.org/10.3390/cancers15072065 - 30 Mar 2023

Cited by 1 | Viewed by 1593

Abstract

Background: Previous studies have described that the SEC23A gene is involved in the occurrence and development of various tumor entities. However, little is known about its expression and relevance in stomach adenocarcinoma (STAD). The aim of this study was to bioinformatically analyze the [...] Read more.

Background: Previous studies have described that the SEC23A gene is involved in the occurrence and development of various tumor entities. However, little is known about its expression and relevance in stomach adenocarcinoma (STAD). The aim of this study was to bioinformatically analyze the role of SEC23A in STAD, followed by patient tissue sample analyses. Materials and methods: SEC23A expression levels in STAD and normal gastric tissues were analyzed in the Cancer Genome Atlas and Gene Expression Omnibus databases; results were verified in fresh clinical STAD specimens on both gene and protein expression levels. SEC23A expression correlated with survival parameters by Kaplan–Meier and multivariate Cox regression analyses. The top genes co-expressed with SEC23A were identified by gene set enrichment analysis (GSEA) using the clusterProfiler package in R. Furthermore, the R package (immunedeconv), integrating the CIBERSORT algorithm, was used to estimate immune cell infiltration levels in STAD. Results: SEC23A gene and sec23a protein expression were both significantly upregulated in STAD, and this correlated with the pT stage. Moreover, high SEC23A expression was associated with poor disease-free and overall survival of STAD patients. Cox analyses revealed that besides age and pathologic stage, SEC23A expression is an independent risk factor for STAD. GSEA indicated that SEC23A was positively associated with ECM-related pathways. In the CIBERSORT analysis, the level of SEC23A negatively correlated with various infiltrating immune cell subsets, including follicular helper T cells, Tregs, activated NK cells and myeloid dendritic cells. Finally, the expression levels of immune checkpoint-related genes, including HAVCR2 and PDCD1LG2, were significantly increased in the high SEC23A expression group. Conclusions: We observed the significantly upregulated expression of SEC23A in STAD, an association with disease progression, patients’ prognosis and infiltrating immune cell subsets. Thus, we propose SEC23A as an independent prognostic factor with a putative role in immune response regulation in STAD. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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18 pages, 1964 KiB

Open AccessArticle

Inhibition of Vascular Endothelial Growth Factor Protects against the Development of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome in Wild-Type but Not in CD39-Null Mice

by Sebastian Knitter, Gregor Duwe, Anika Sophie Beierle, Sina Pesthy, Paul Viktor Ritschl, Karl Herbert Hillebrandt, Alexander Arnold, Thomas Malinka, Dominik Paul Modest, Marcus Bahra, Johann Pratschke, Igor Maximilian Sauer, Moritz Schmelzle and Andreas Andreou

Cancers 2022, 14(23), 5992; https://doi.org/10.3390/cancers14235992 - 5 Dec 2022

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Abstract

(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition [...] Read more.

(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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13 pages, 563 KiB

Open AccessArticle

Identification of Risk Factors for Sexual Dysfunction after Multimodal Therapy of Locally Advanced Rectal Cancer and Their Impact on Quality of Life: A Single-Center Trial

by Peter Tschann, Markus Weigl, Thomas Brock, Jürgen Frick, Oliver Sturm, Jaroslav Presl, Tarkan Jäger, Michael Weitzendorfer, Philipp Schredl, Patrick Clemens, Helmut Eiter, Philipp Szeverinski, Christian Attenberger, Veronika Tschann, Walter Brunner, Alexander De Vries, Klaus Emmanuel and Ingmar Königsrainer

Cancers 2022, 14(23), 5796; https://doi.org/10.3390/cancers14235796 - 24 Nov 2022

Cited by 3 | Viewed by 1577

Abstract

Purpose: Sexual function is crucial for the quality of life and can be highly affected by preoperative therapy and surgery. The aim of this study was to identify potential risk factors for poor sexual function and quality of life. Methods: Female patients were [...] Read more.

Purpose: Sexual function is crucial for the quality of life and can be highly affected by preoperative therapy and surgery. The aim of this study was to identify potential risk factors for poor sexual function and quality of life. Methods: Female patients were asked to complete the Female Sexual Function Index (FSFI-6). Male patients were demanded to answer the International Index of Erectile Function (IIEF-5). Results: In total, 79 patients filled in the questionary, yielding a response rate of 41.57%. The proportion of women was represented by 32.91%, and the median age was 76.0 years (66.0–81.0). Sexual dysfunction appeared in 88.46% of female patients. Severe erectile dysfunction occurred in 52.83% of male patients. Univariate analysis showed female patients (OR: 0.17, 95%CI: 0.05–0.64, p = 0.01), older age (OR: 0.34, 95%CI 0.11–1.01, p = 0.05), tumor localization under 6cm from the anal verge (OR: 4.43, 95%CI: 1.44–13.67, p = 0.01) and extension of operation (APR and ISR) (OR: 0.13, 95%CI: 0.03–0.59, p = 0.01) as significant risk factors for poor outcome. Female patients (OR: 0.12, 95%CI: 0.03–0.62, p = 0.01) and tumors below 6 cm from the anal verge (OR: 4.64, 95%CI: 1.18–18.29, p = 0.03) were shown to be independent risk factors for sexual dysfunction after multimodal therapy in the multivariate analysis. Quality of life was only affected in the case of extensive surgery (p = 0.02). Conclusion: Higher Age, female sex, distal tumors and extensive surgery (APR, ISR) are revealed risk factors for SD in this study. Quality of life was only affected in the case of APR or ISR. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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14 pages, 1766 KiB

Open AccessArticle

Expansion of Liver Transplantation Criteria for Hepatocellular Carcinoma from Milan to UCSF in Australia and New Zealand and Justification for Metroticket 2.0

by Savio G. Barreto, Simone I. Strasser, Geoffrey W. McCaughan, Michael A. Fink, Robert Jones, John McCall, Stephen Munn, Graeme A. Macdonald, Peter Hodgkinson, Gary P. Jeffrey, Bryon Jaques, Michael Crawford, Mark E. Brooke-Smith and John W. Chen

Cancers 2022, 14(11), 2777; https://doi.org/10.3390/cancers14112777 - 3 Jun 2022

Cited by 5 | Viewed by 2029

Abstract

Background: Expansion in liver transplantation (LT) criteria for HCC from Milan to UCSF has not adversely impacted overall survival, prompting further expansion towards Metroticket 2.0 (MT2). In this study, we compared patient survival post-transplant before and after 2007 and long-term outcomes for LT [...] Read more.

Background: Expansion in liver transplantation (LT) criteria for HCC from Milan to UCSF has not adversely impacted overall survival, prompting further expansion towards Metroticket 2.0 (MT2). In this study, we compared patient survival post-transplant before and after 2007 and long-term outcomes for LT within Milan versus UCSF criteria (to determine the true benefit of the expansion of criteria) and retrospectively validated the MT2 criteria. Methods: Retrospective analysis of ANZLITR (including all patients transplanted for HCC since July 1997). The entire cohort was divided based on criteria used at the time of listing, namely, Milan era (1997–2006) and the UCSF era (2007–July 2015). Results: The overall 5- and 10-year cumulative survival rates for the entire cohort of 691 patients were 78% and 69%, respectively. Patients transplanted in UCSF era had significantly higher 5- and 10-year survival rates than in the Milan era (80% vs. 73% and 72% vs. 65%, respectively; p = 0.016). In the UCSF era, the 5-year survival rate for patients transplanted within Milan criteria was significantly better than those transplanted outside Milan but within UCSF criteria (83% vs. 73%; p < 0.024). Patients transplanted within the MT2 criteria had a significantly better 5- and 10-year survival rate as compared to those outside the criteria (81% vs. 64% and 73% vs. 50%, respectively; p = 0.001). Conclusion: Overall survival following LT for HCC has significantly improved over time despite expanding criteria from Milan to UCSF. Patients fulfilling the MT2 criteria have a survival comparable to the UCSF cohort. Thus, expansion of criteria to MT2 is justifiable. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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Review

Jump to: Research

24 pages, 939 KiB

Open AccessReview

Mutational Signatures in Gastric Cancer and Their Clinical Implications

by Pia Pužar Dominkuš and Petra Hudler

Cancers 2023, 15(15), 3788; https://doi.org/10.3390/cancers15153788 - 26 Jul 2023

Cited by 3 | Viewed by 1534

Abstract

Gastric cancer is characterised by high inter- and intratumour heterogeneity. The majority of patients are older than 65 years and the global burden of this disease is increasing due to the aging of the population. The disease is usually diagnosed at advanced stages, [...] Read more.

Gastric cancer is characterised by high inter- and intratumour heterogeneity. The majority of patients are older than 65 years and the global burden of this disease is increasing due to the aging of the population. The disease is usually diagnosed at advanced stages, which is a consequence of nonspecific symptoms. Few improvements have been made at the level of noninvasive molecular diagnosis of sporadic gastric cancer, and therefore the mortality rate remains high. A new field of mutational signatures has emerged in the past decade with advances in the genome sequencing technology. These distinct mutational patterns in the genome, caused by exogenous and endogenous mutational processes, can be associated with tumour aetiology and disease progression, and could provide novel perception on the treatment possibilities. This review assesses the mutational signatures found in gastric cancer and summarises their potential for use in clinical setting as diagnostic or prognostic biomarkers. Associated treatment options and biomarkers already implemented in clinical use are discussed, together with those that are still being explored or are in clinical studies. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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19 pages, 1300 KiB

Open AccessReview

Overcoming the Fibrotic Fortress in Pancreatic Ductal Adenocarcinoma: Challenges and Opportunities

by Kay K. Myo Min, Charlie B. Ffrench, Claire F. Jessup, Mia Shepherdson, Savio George Barreto and Claudine S. Bonder

Cancers 2023, 15(8), 2354; https://doi.org/10.3390/cancers15082354 - 18 Apr 2023

Cited by 3 | Viewed by 1914

Abstract

An overabundance of desmoplasia in the tumour microenvironment (TME) is one of the defining features that influences pancreatic ductal adenocarcinoma (PDAC) development, progression, metastasis, and treatment resistance. Desmoplasia is characterised by the recruitment and activation of fibroblasts, heightened extracellular matrix deposition (ECM) and [...] Read more.

An overabundance of desmoplasia in the tumour microenvironment (TME) is one of the defining features that influences pancreatic ductal adenocarcinoma (PDAC) development, progression, metastasis, and treatment resistance. Desmoplasia is characterised by the recruitment and activation of fibroblasts, heightened extracellular matrix deposition (ECM) and reduced blood supply, as well as increased inflammation through an influx of inflammatory cells and cytokines, creating an intrinsically immunosuppressive TME with low immunogenic potential. Herein, we review the development of PDAC, the drivers that initiate and/or sustain the progression of the disease and the complex and interwoven nature of the cellular and acellular components that come together to make PDAC one of the most aggressive and difficult to treat cancers. We review the challenges in delivering drugs into the fortress of PDAC tumours in concentrations that are therapeutic due to the presence of a highly fibrotic and immunosuppressive TME. Taken together, we present further support for continued/renewed efforts focusing on aspects of the extremely dense and complex TME of PDAC to improve the efficacy of therapy for better patient outcomes. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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Graphical abstract

12 pages, 1034 KiB

Open AccessReview

A Review of Translational Research for Targeted Therapy for Metastatic Colorectal Cancer

by Samantha M. Ruff and Timothy M. Pawlik

Cancers 2023, 15(5), 1395; https://doi.org/10.3390/cancers15051395 - 22 Feb 2023

Cited by 4 | Viewed by 3436

Abstract

Colorectal cancer is the third most common cause of cancer-related death in the United States, with 20% of patients presenting with metastatic disease at the time of diagnosis. Metastatic colon cancer is often treated with a combination of surgery, systemic therapy (chemotherapy, biologic [...] Read more.

Colorectal cancer is the third most common cause of cancer-related death in the United States, with 20% of patients presenting with metastatic disease at the time of diagnosis. Metastatic colon cancer is often treated with a combination of surgery, systemic therapy (chemotherapy, biologic therapy, immunotherapy), and/or regional therapy (hepatic artery infusion pumps). Utilizing the molecular and pathologic features of the primary tumor to tailor treatment for patients may improve overall survival. Rather than a “one size fits all” approach, a more nuanced treatment plan guided by the unique features of a patient’s tumor and the tumor’s microenvironment can more effectively treat the disease. Basic science work to elucidate new drug targets, understand mechanisms of evasion, and develop drugs and drug combinations is critical to inform clinical trials and identify novel, effective therapies for metastatic colorectal cancer. Through the lens of key targets for metastatic colorectal cancer, this review discusses how work in the basic science lab translates into clinical trials. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Gastrointestinal Cancers)

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