{"title":"Integrative Bioinformatics Analysis: Unraveling Variant Signatures and Single-Nucleotide Polymorphism Markers Associated with 5-FU-Based Chemotherapy Resistance in Colorectal Cancer Patients.","authors":"Masomeh Askari, Ebrahim Mirzaei, Leila Navapour, Mina Karimpour, Leili Rejali, Somayeh Sarirchi, Ehsan Nazemalhosseini-Mojarad, Stefania Nobili, Claudia Cava, Amir Sadeghi, Nayeralsadat Fatemi","doi":"10.1007/s12029-024-01102-x","DOIUrl":"10.1007/s12029-024-01102-x","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance in colorectal cancer (CRC) is modulated by multiple molecular factors, which can be ascertained through genetic investigation. Single nucleotide polymorphisms (SNPs) within key genes have the potential to impair the efficacy of chemotherapeutic agents such as 5-fluorouracil (5-FU). Therefore, the identification of SNPs linked to drug resistance can significantly contribute to the advancement of tailored therapeutic approaches and the enhancement of treatment outcomes in patients with CRC.</p><p><strong>Material and method: </strong>To identify dysregulated genes in 5-FU-based chemotherapy responder or non-responder CRC patients, a meta-analysis was performed. Next, the protein-protein interaction (PPI) network of the identified genes was analyzed using the STRING database. The most significant module was chosen for further analysis. In addition, a literature review was conducted to identify drug resistance-related genes. Enrichment analysis was conducted to validate the main module genes and the genes identified from the literature review. The associations between SNPs and drug resistance were investigated, and the consequences of missense variants were assessed using in silico tools.</p><p><strong>Result: </strong>The meta-analysis identified 796 dysregulated genes. Then, to conduct PPI analysis and enrichment analysis, we were able to discover 23 genes that are intricately involved in the cell cycle pathway. Consequently, these 23 genes were chosen for SNP analysis. By using the dbSNP database and ANNOVAR, we successfully detected and labeled SNPs in these specific genes. Additionally, after careful exclusion of SNPs with allele frequencies below 0.01, we evaluated 6 SNPs from the HDAC1, MCM2, CDK1, BUB1B, CDC14B, and CCNE1 genes using 8 bioinformatics tools. Therefore, these SNPs were identified as potentially harmful by multiple computational tools. Specifically, rs199958833 in CDK1 (Val124Gly) was predicted to be damaging by all tools used. Our analysis strongly indicates that this specific SNP could negatively affect the stability and functionality of the CDK1 protein.</p><p><strong>Conclusion: </strong>Based on our current understanding, the evaluation of CDK1 polymorphisms in the context of drug resistance in CRC has yet to be undertaken. In this investigation, we showed that rs199958833 variant in the CDK1 gene may favor resistance to 5-FU-based chemotherapy. However, these findings need validation in an independent cohort of patients.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1607-1619"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saira Rafaqat, Huma Khurshid, Ramsha Hafeez, Mehnaz Arif, Ayesha Zafar, Mahrukh Gilani, Habiba Ashraf, Sana Rafaqat
{"title":"Role of Interleukins in Pancreatic Cancer: A Literature Review.","authors":"Saira Rafaqat, Huma Khurshid, Ramsha Hafeez, Mehnaz Arif, Ayesha Zafar, Mahrukh Gilani, Habiba Ashraf, Sana Rafaqat","doi":"10.1007/s12029-024-01111-w","DOIUrl":"10.1007/s12029-024-01111-w","url":null,"abstract":"<p><strong>Purpose: </strong>This review article summarizes the pathophysiological aspects of interleukins (ILs) including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in pancreatic cancer (PC).</p><p><strong>Methods: </strong>Science Direct, PubMed, and Google Scholar were used for the literature review. The search was conducted until August 12, 2024, and particular keywords such as \"Pancreatic Cancer,\" \"Interleukins,\" \"Pathophysiological Aspects,\" \"Immunosuppression,\" \"Invasiveness,\" and \"Metastasis\" were used. Focusing on interleukins related to pancreatic cancer, 61 original studies were included: 32 studies for human patients, 16 studies for animal models, and 13 studies for both animal models and human patients. All types of PC were considered. The timeframe of 1991 to 2024 was chosen for clinical studies.</p><p><strong>Results: </strong>In epithelial pancreatic tumors, IL-1 is a major inflammation factor. Serum concentrations of soluble interleukin-2-receptor were considerably greater in patients with PC and chronic pancreatitis than in healthy individuals. In comparison to controls, pancreatic cancer patients had considerably greater levels of macrophage colony-stimulating factor and significantly lower levels of stem cell factor and IL-3. The tissues and cells of pancreatic cancer have higher concentrations of IL-4 receptors. IL-5 has a role in the accumulation of pancreatic fibrosis. For individuals with pancreatic ductal adenocarcinoma (PDAC), a high serum level of IL-6 may be a separate risk factor for the development of widespread liver metastases. PDAC patients' peripheral blood mononuclear cells exhibit a substantial upregulation of IL-7 receptor. The role of IL-8 in the growth and spread of PC in humans. The miR-200a/β-catenin axis may be the mechanism by which IL-9 stimulates the proliferation and metastasis of PC cells. Blocking IL-10 in the local microenvironment appears to result in a significant reversal of tumor-induced immunosuppression.</p><p><strong>Conclusion: </strong>The article concludes that interleukins 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 played significant roles in the pathogenesis of PC.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1498-1510"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Qahar Khan Yasinzai, Kue Tylor Lee, Imran Khan, Bisma Tareen, Amir Humza Sohail, Asif Iqbal, Israr Khan, Abdul Waheed, Bhavishya U Ramamoorthy, Asad Ullah, Andrew M Blakely
{"title":"Colorectal Leiomyosarcoma: Demographics Patterns, Treatment Characteristics, and Survival Analysis in the U.S. Population.","authors":"Abdul Qahar Khan Yasinzai, Kue Tylor Lee, Imran Khan, Bisma Tareen, Amir Humza Sohail, Asif Iqbal, Israr Khan, Abdul Waheed, Bhavishya U Ramamoorthy, Asad Ullah, Andrew M Blakely","doi":"10.1007/s12029-024-01110-x","DOIUrl":"10.1007/s12029-024-01110-x","url":null,"abstract":"<p><strong>Background: </strong>Colorectal leiomyosarcoma (CR-LMS) is a rare neoplasm arising from smooth muscle cells. It accounts for less than 0.1% of all colorectal malignancies. In this population-based study, we aim to understand the demographics, treatment characteristics, and pathologic factors associated with survival in CR-LMS.</p><p><strong>Methods: </strong>Data from the SEER Program (2000-2018) were analyzed using SEER*Stat and SPSS. Statistical methods included descriptive analysis, Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazards regression to assess the impact of various factors on disease-specific and overall survival.</p><p><strong>Results: </strong>A total of 191 cases of CR-LMS were identified. Most patients were 60-69 years of age (median: 64 years) and Caucasian (78%). There was nearly the same distribution in sex (M:F ratio; 1:1.2). The overall 5-year observed survival was 50.3% (95% C.I., 46.3-54.2). The 5-year disease-specific survival (DSS) was 66.1% (95% C.I., 62.0-70.1). The 5-year overall survival after resection was 60.8% (95% C.I., 56.3-65.3). Multivariable analysis identified grades III and IV (p = 0.028) as negative predictors of overall survival. Regional spread and distant stage are negative predictors of overall survival (p < 0.01).</p><p><strong>Conclusion: </strong>Our data reveals that colorectal leiomyosarcoma (CR-LMS) often presents in patients around 64 years old with advanced stages and poor differentiation. Key adverse prognostic factors include older age, high tumor grade, large tumor size, and distant metastases, with surgical resection showing the best survival outcomes. To improve outcomes, further research and consolidation of data are essential for developing targeted therapies and comprehensive guidelines.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1588-1597"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exceptional Response to Pembrolizumab in HER2-Positive Gallbladder Carcinoma with High Tumor Mutational Burden.","authors":"Akinori Sasaki, Satoru Nakajima, Yasuaki Motomura","doi":"10.1007/s12029-024-01112-9","DOIUrl":"10.1007/s12029-024-01112-9","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with advanced cholangiocarcinoma, including gallbladder cancer, typically have a poor prognosis owing to limited effective chemotherapy options. The field of genotype-directed therapy in patients with cholangiocarcinoma is advancing. However, limited clinical data are currently available to evaluate the efficacy of molecularly targeted therapy.</p><p><strong>Methods: </strong>Herein, we report the case of a 67-year-old man diagnosed with human epidermal growth factor receptor-2 (HER2)-positive and tumor mutation burden-high (TMB-H) cholangiocarcinoma. The HER2-positive and TMB-H characteristics were identified using comprehensive genomic profiling after showing resistance to gemcitabine and S-1 therapy. In the absence of clinical trials for HER2-positive cancer at that time, the patient was treated with pembrolizumab, which is used for TMB-H solid tumors in clinical practice.</p><p><strong>Results: </strong>After receiving pembrolizumab, the patient experienced significant shrinkage in the primary tumor and liver metastases. Thus far, the patient has been receiving pembrolizumab for approximately 10 months.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first report showing the efficacy of pembrolizumab in a patient with cholangiocarcinoma harboring both HER2-positive and TMB-H.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1628-1633"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yusuf Nawras, Nooraldin Merza, Katie Beier, Aya Dakroub, Hasan Al-Obaidi, Ahmed Dheyaa Al-Obaidi, Hajera Amatul-Raheem, Eshak Bahbah, Tony Varughese, Jerome Hosny, Mona Hassan, Abdallah Kobeissy
{"title":"Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database.","authors":"Yusuf Nawras, Nooraldin Merza, Katie Beier, Aya Dakroub, Hasan Al-Obaidi, Ahmed Dheyaa Al-Obaidi, Hajera Amatul-Raheem, Eshak Bahbah, Tony Varughese, Jerome Hosny, Mona Hassan, Abdallah Kobeissy","doi":"10.1007/s12029-024-01096-6","DOIUrl":"10.1007/s12029-024-01096-6","url":null,"abstract":"<p><strong>Background: </strong>The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research.</p><p><strong>Methods: </strong>Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50 years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software.</p><p><strong>Results: </strong>Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49 years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men.</p><p><strong>Conclusion: </strong>The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1511-1519"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trinh Nguyen, Jaijo Vennatt, Lincoln Downs, Venkateswar Surabhi, Nir Stanietzky
{"title":"Advanced Imaging of Hepatocellular Carcinoma: A Review of Current and Novel Techniques.","authors":"Trinh Nguyen, Jaijo Vennatt, Lincoln Downs, Venkateswar Surabhi, Nir Stanietzky","doi":"10.1007/s12029-024-01094-8","DOIUrl":"10.1007/s12029-024-01094-8","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common primary carcinoma arising from the liver. Although HCC can arise de novo, the vast majority of cases develop in the setting of chronic liver disease. Hepatocarcinogenesis follows a well-studied process during which chronic inflammation and cellular damage precipitate cellular and genetic aberrations, with subsequent propagation of precancerous and cancerous lesions. Surveillance of individuals at high risk of HCC, early diagnosis, and individualized treatment are keys to reducing the mortality associated with this disease. Radiological imaging plays a critical role in the diagnosis and management of these patients. HCC is a unique cancer in that it can be diagnosed with confidence by imaging that meets all radiologic criteria, obviating the risks associated with tissue sampling. This article discusses conventional and emerging imaging techniques for the evaluation of HCC.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1469-1484"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming-Zhi Xie, Yong-Qiang Li, Rong Liang, Shi-Ying Huang, Shan-Yu Qin, Bang-Li Hu
{"title":"Synergistic Effects of Fruquintinib Combined with Immune Checkpoint Inhibitors on Metastatic Colorectal Cancer.","authors":"Ming-Zhi Xie, Yong-Qiang Li, Rong Liang, Shi-Ying Huang, Shan-Yu Qin, Bang-Li Hu","doi":"10.1007/s12029-024-01108-5","DOIUrl":"10.1007/s12029-024-01108-5","url":null,"abstract":"<p><strong>Background: </strong>Fruquintinib has received approval for the management of patients with chemotherapy-resistant metastatic colorectal cancer (mCRC). However, combination of fruquintinib with immune checkpoint inhibitors (ICIs) is yet to be extensively studied. This study aims to assess the clinical efficacy, safety, and prognostic indicators of treatment regimen combining fruquintinib with ICIs in mCRC patients.</p><p><strong>Methods: </strong>We analyzed data from mCRC patients who were administered fruquintinib either as a monotherapy or in conjunction with ICIs following conventional chemotherapy. Parameters such as the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and incidence of adverse events were meticulously evaluated. Furthermore, the relationship between blood markers and patient prognosis was examined.</p><p><strong>Results: </strong>A total of 72 mCRC patients were included in this study, with a median observation period of 48 months, 19 were treated with fruquintinib alone, while 53 received a combination therapy involving fruquintinib and ICIs. The combined therapy group exhibited superior ORR and DCR compared to the fruquintinib monotherapy group. Additionally, significant improvements in OS and PFS were observed in the combined treatment group. The occurrence of adverse events was generally manageable and well-tolerated across both groups, with no significant difference in incidence rates. Notably, albumin levels were identified as a prognostic marker for PFS and OS in the univariate Cox regression analysis.</p><p><strong>Conclusions: </strong>The combination of fruquintinib with ICIs demonstrated enhanced clinical efficacy and improved survival outcomes compared to fruquintinib monotherapy in mCRC patients. The safety of the combination regimen was deemed manageable and acceptable.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1620-1627"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endoscopic Resection of Stage T1 Colorectal Adenocarcinoma Followed by Surgical Intervention: a Single-center Retrospective Study.","authors":"Dongdong Zhang, Lin Chen, Jixiang Wu","doi":"10.1007/s12029-024-01109-4","DOIUrl":"10.1007/s12029-024-01109-4","url":null,"abstract":"<p><strong>Background: </strong>Domestic and international guidelines recommend endoscopic resection for stage T1 colorectal adenocarcinoma with indications. However, completion surgery remains imperative for patients exhibiting high-risk factors subsequent to endoscopic procedures.</p><p><strong>Objective: </strong>To investigate the evidence, pathological features, and surgical outcomes of completion surgery in patients with T1 colorectal adenocarcinoma following endoscopic resection.</p><p><strong>Methods: </strong>We retrospectively collect data on the clinical features and treatment outcomes of patients with stage T1 colorectal adenocarcinoma who underwent endoscopic resection followed by surgical resection and those who initially completed surgical intervention at Peking University International Hospital between January 2019 and October 2022, with the aim of assessing the necessity and feasibility of surgical intervention.</p><p><strong>Results: </strong>Seventeen patients (Group A) with high-risk factors following endoscopic procedure, especially with deep submucosal invasion and vascular or lymphatic invasion, experienced further surgical resection. The median interval between endoscopic resection and completion surgery was 23.71 days ± 15.89. Sixteen patients (Group B) underwent radical resection without any prior interventions. The surgical approach involves integration of laparoscopy and colonoscopy for precise localization and quantitative diagnosis, followed by radical surgery. The two groups demonstrated significant differences statistically with reference to tumor diameter (1.65 cm ± 0.77 vs 3.36 cm ± 1.39, P = 0.000) and the attainment of standard lymph node count (cases of detected lymph nodes larger than or equal to 12, 5 vs 12, P = 0.015). Postoperative complications and hospital stay manifested no significant disparity statistically in two groups. Patients who underwent completion surgery had no inferior outcomes compared with those who underwent direct surgery in terms of 5-year disease-free survival (Log rank test: P = 0.083, Breslow test: P = 0.089). The two groups also exhibited no significant differences statistically in the context of overall survival (Log rank test: P = 0.652, Breslow test: P = 0.758).</p><p><strong>Conclusion: </strong>Completion surgery is a safe and feasible treatment option for T1 colorectal adenocarcinoma patients with high-risk factors, particularly those with deep submucosal invasion and vascular or lymphatic invasion following endoscopic treatment. Furthermore, subsequent treatment should be chosen based on a comprehensive analysis of the patient's history of abdominal surgery, willingness, and pathological features.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1598-1606"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paola Mattiolo, Mario De Bellis, Andrea Mafficini, Matteo Fassan, Michele Bevere, Calogero Ciulla, Samantha Bersani, Rita T Lawlor, Michele Milella, Aldo Scarpa, Claudio Luchini, Andrea Ruzzenente
{"title":"Long-Term Survivor of Intrahepatic Cholangiocarcinoma for over 18 Years: Case Study with Longitudinal Histo-molecular and Tumor Immune Microenvironment Characterization and Systematic Review of the Literature.","authors":"Paola Mattiolo, Mario De Bellis, Andrea Mafficini, Matteo Fassan, Michele Bevere, Calogero Ciulla, Samantha Bersani, Rita T Lawlor, Michele Milella, Aldo Scarpa, Claudio Luchini, Andrea Ruzzenente","doi":"10.1007/s12029-024-01113-8","DOIUrl":"10.1007/s12029-024-01113-8","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease. In this study, we report the case of a patient affected by intrahepatic cholangiocarcinoma with multiple relapses and still alive for over 18 years. We also provide a systematic review regarding long-survivor (> 60 months) of intrahepatic cholangiocarcinoma.</p><p><strong>Case presentation: </strong>A 41-year-old woman with no pathological history was diagnosed with localized intrahepatic cholangiocarcinoma and surgically treated with left hepatectomy. After the first intervention, the patients underwent three further surgical resections because of locoregional recurrences. Histologically, there were some significant similarities among all neoplasms, including the tubule-glandular architecture, but also morphological heterogeneity. The tumor immune microenvironment remained stable across the different lesions. The molecular analysis with next-generation sequencing demonstrated that all neoplasms shared the same genomic profile, including NBN and NOTCH3 mutations and chromosomes 1 and 3 alterations.</p><p><strong>Conclusions: </strong>This case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1634-1646"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Patterns and Predictors of Recurrence After Curative Resection of Colorectal Liver Metastasis (CRLM).","authors":"Satya Niharika Vadisetti, Mufaddal Kazi, Shraddha Patkar, Rohit Mundhada, Ashwin Desouza, Avanish Saklani, Mahesh Goel","doi":"10.1007/s12029-024-01105-8","DOIUrl":"10.1007/s12029-024-01105-8","url":null,"abstract":"<p><strong>Background: </strong>Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection.</p><p><strong>Methods: </strong>A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1 cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables.</p><p><strong>Results: </strong>The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38 months (30-54) and 13 months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5 cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5 cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences.</p><p><strong>Conclusion: </strong>The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1559-1568"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}