Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 13.414
Filter
1.
Saudi Med J ; 45(6): 639-642, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38830651

ABSTRACT

OBJECTIVES: To describe the current real-world treatment landscape, sequence of therapies, and outcomes in patients with prostate cancer (PC). METHODS: A retrospective cohort study for PC patients diagnosed at King Abdullah Medical City Cancer Center in Makkah, Saudi Arabia, between January 2011 and December 2021. Data extracted from electronic medical records. RESULTS: A total of 282 patients with PC, with a mean age of 70 years and body mass index of 27. Among them, 274 (99%) had no family history of cancer, while 164 (58%) had hypertension and 125 (44%) had diabetes mellitus. Adenocarcinoma was the most common histology, found in 275 (97%) patients, with 99 (35%) having a Gleason score of 9. Notably, 184 (65%) patients presented with metastatic disease, and 147 (52%) with bone metastasis. While 198 (70%) patients underwent surgery, 184 (65%) did not receive radiotherapy. The most common first-line metastatic therapy was abiraterone in 23 (8%) patients, followed by enzalutamide in 7 (2.5%). During the study period, 167 (59%) patients survived, with an average treatment duration of 2.5 years. CONCLUSION: This study provides insights into real-world treatment patterns and clinical outcomes in patients with PC. The findings of this study highlight the importance of adhering to treatment standards and making informed clinical decisions.


Subject(s)
Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Saudi Arabia/epidemiology , Retrospective Studies , Aged , Middle Aged , Treatment Outcome , Phenylthiohydantoin/therapeutic use , Phenylthiohydantoin/analogs & derivatives , Nitriles/therapeutic use , Neoplasm Grading , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Androstenes/therapeutic use , Prostatectomy , Cohort Studies , Aged, 80 and over , Benzamides
2.
BMJ ; 385: e074962, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830686

ABSTRACT

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Adenocarcinoma/therapy , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Squamous Cell Carcinoma/pathology , Esophagoscopy/methods , Barrett Esophagus/therapy , Barrett Esophagus/diagnosis , Barrett Esophagus/pathology
3.
Cancer Rep (Hoboken) ; 7(6): e2101, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831124

ABSTRACT

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.


Subject(s)
Adenocarcinoma , Gastrectomy , Hepatectomy , Liver Neoplasms , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Stomach Neoplasms/surgery , Retrospective Studies , Aged , Middle Aged , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma/surgery , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Prognosis , Survival Rate , Aged, 80 and over , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Female
4.
BMC Cancer ; 24(1): 668, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824512

ABSTRACT

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.


Subject(s)
Gastrointestinal Neoplasms , Humans , Spain/epidemiology , Middle Aged , Male , Female , Aged , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Adult , Age of Onset , Life Style , Adenocarcinoma/epidemiology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Tumor Microenvironment , Quality of Life , Incidence , Biomarkers, Tumor , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology
5.
J Gastrointest Surg ; 28(5): 605-610, 2024 May.
Article in English | MEDLINE | ID: mdl-38704197

ABSTRACT

BACKGROUND: Differential responses to neoadjuvant therapy (NAT) exist in pancreatic ductal adenocarcinoma (PDAC); however, contributing factors are poorly understood. Tobacco smoke is a common risk factor for PDAC, with nicotine-induced chemoresistance observed in other cancers. This study aimed to explore the potential association between tobacco use and NAT efficacy in PDAC. METHODS: A single-center, retrospective analysis was conducted that included all consecutive patients with PDAC who underwent surgical resection after NAT with a documented smoking history (N = 208). NAT response was measured as percentage fibrosis in the surgical specimen. Multivariable models controlled for covariates and survival were modeled using the Kaplan-Meier method. RESULTS: Postoperatively, major responses to NAT (>95% fibrosis) were less frequently observed in smokers than in nonsmokers (13.7% vs 30.4%, respectively; P = .021). Pathologic complete responses were similarly less frequent in smokers than in nonsmokers (2.1% vs 9.9%, respectively; P = .023). On multivariate analysis controlling for covariates, smoking history remained independently associated with lower odds of major fibrosis (odds ratio [OR], 0.25; 95% CI, 0.10-0.59; P = .002) and pathologic complete response (OR, 0.21; 95% CI, 0.03-0.84; P = .05). The median overall survival was significantly longer in nonsmokers than in smokers (39.1 vs 26.6 months, respectively; P = .05). CONCLUSION: Tobacco use was associated with diminished pathologic responses to NAT. Future research to understand the biology underlying this observation is warranted and may inform differential NAT approaches or counseling among these populations.


Subject(s)
Carcinoma, Pancreatic Ductal , Neoadjuvant Therapy , Pancreatic Neoplasms , Smoking , Humans , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Male , Female , Retrospective Studies , Middle Aged , Aged , Smoking/adverse effects , Smoking/epidemiology , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Treatment Outcome , Fibrosis , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Risk Factors , Kaplan-Meier Estimate
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(5): 471-477, 2024 May 25.
Article in Chinese | MEDLINE | ID: mdl-38778687

ABSTRACT

Objective: To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer. Methods: This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results: In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group (P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group (P>0.05). Conclusions: Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.


Subject(s)
Hyperthermic Intraperitoneal Chemotherapy , Paclitaxel , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/therapy , Paclitaxel/administration & dosage , Male , Female , Middle Aged , Retrospective Studies , Hyperthermic Intraperitoneal Chemotherapy/methods , Aged , Combined Modality Therapy , Adenocarcinoma/therapy , Adenocarcinoma/surgery , Adult
8.
Neoplasma ; 71(2): 201-208, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38766850

ABSTRACT

The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Adenocarcinoma/drug therapy , Retrospective Studies , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/drug therapy , Croatia/epidemiology , Male , Female , Aged , Middle Aged , Aged, 80 and over , Adult , Esophagogastric Junction/pathology
9.
BJS Open ; 8(3)2024 May 08.
Article in English | MEDLINE | ID: mdl-38814750

ABSTRACT

BACKGROUND: In contrast to the well-established multimodal therapy for localized oesophageal cancer, the metastatic stage is commonly treated only with systemic therapy as current international guidelines recommend. However, evidence suggesting that multimodal therapy including surgery could benefit selected patients with metastasized oesophageal cancer is increasing. The aim of this study was to investigate the survival of patients diagnosed with metastatic oesophageal cancer after different treatment regimens. METHODS: This was a retrospective single-centre study of patients with adenocarcinoma or squamous cell carcinoma of the oesophagus with synchronous or metachronous metastases who underwent Ivor Lewis oesophagectomy between 2010 and 2021. Each patient received an individual treatment for their metastatic burden based on an interdisciplinary tumour board conference. Survival differences between different treatments were assessed using the Kaplan-Meier method, as well as univariable and multivariable Cox regression models. RESULTS: Out of 1791 patients undergoing Ivor Lewis oesophagectomy, 235 patients diagnosed with metastases were included. Of all of the included patients, 42 (17.9%) only underwent surgical resection of their metastatic disease, 37 (15.7%) underwent multimodal therapy including surgery, 78 (33.2%) received chemotherapy alone, 49 (20.9%) received other therapies, and 29 (12.3%) received best supportive care. Patients who underwent resection or multimodal therapy including surgery of their metastatic burden showed superior overall survival compared with chemotherapy alone (median overall survival of 19.0, 18.0, and 11.0 months respectively) (P < 0.001). This was confirmed in subcohorts of patients with metachronous solid-organ metastases and with a single metastasis. In multivariable analyses, resection with or without multimodal therapy was an independent factor for favourable survival. CONCLUSION: Surgical resection could be a feasible treatment option for metastasized oesophageal cancer, improving survival in selected patients. Further prospective randomized studies are needed to confirm these findings and define reliable selection criteria.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Esophagectomy , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Retrospective Studies , Male , Female , Middle Aged , Aged , Combined Modality Therapy , Adenocarcinoma/therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adenocarcinoma/pathology , Kaplan-Meier Estimate , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/pathology , Proportional Hazards Models
10.
Front Immunol ; 15: 1416914, 2024.
Article in English | MEDLINE | ID: mdl-38817605

ABSTRACT

Background: Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking angiogenesis has shown success in treating different types of solid tumors, its relevance in prostate adenocarcinoma (PRAD) has not been thoroughly investigated. Method: This study utilized the WGCNA method to identify angiogenesis-related genes and assessed their diagnostic and prognostic value in patients with PRAD through cluster analysis. A diagnostic model was constructed using multiple machine learning techniques, while a prognostic model was developed employing the LASSO algorithm, underscoring the relevance of angiogenesis-related genes in PRAD. Further analysis identified MAP7D3 as the most significant prognostic gene among angiogenesis-related genes using multivariate Cox regression analysis and various machine learning algorithms. The study also investigated the correlation between MAP7D3 and immune infiltration as well as drug sensitivity in PRAD. Molecular docking analysis was conducted to assess the binding affinity of MAP7D3 to angiogenic drugs. Immunohistochemistry analysis of 60 PRAD tissue samples confirmed the expression and prognostic value of MAP7D3. Result: Overall, the study identified 10 key angiogenesis-related genes through WGCNA and demonstrated their potential prognostic and immune-related implications in PRAD patients. MAP7D3 is found to be closely associated with the prognosis of PRAD and its response to immunotherapy. Through molecular docking studies, it was revealed that MAP7D3 exhibits a high binding affinity to angiogenic drugs. Furthermore, experimental data confirmed the upregulation of MAP7D3 in PRAD, correlating with a poorer prognosis. Conclusion: Our study confirmed the important role of angiogenesis-related genes in PRAD and identified a new angiogenesis-related target MAP7D3.


Subject(s)
Adenocarcinoma , Immunotherapy , Machine Learning , Neovascularization, Pathologic , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Prostatic Neoplasms/therapy , Prognosis , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/immunology , Immunotherapy/methods , Adenocarcinoma/genetics , Adenocarcinoma/immunology , Adenocarcinoma/therapy , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Microtubule-Associated Proteins/genetics , Molecular Docking Simulation , Gene Expression Profiling , Angiogenesis
11.
Pathol Res Pract ; 258: 155328, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744002

ABSTRACT

Gastric cancer continues to have a high death rate despite advancements in their diagnosis and treatment. Novel treatment techniques are thus desperately needed. This is where double-stranded RNA molecules known as small interfering RNA (siRNA), which may selectively target the mRNA of disease-causing genes, may find use in medicine. For siRNAs to function properly in the human body, they must be shielded from deterioration. Furthermore, in order to maintain organ function, they must only target the tumor and spare normal tissue. siRNAs have been designed using clever delivery mechanisms including polymers and lipids to achieve these objectives. Although siRNA protection is not hard to acquire, it is still challenging to target cancer cells with them. Here, we first discuss the basic characteristics of gastric cancer before describing the properties of siRNA and typical delivery methods created specifically for gastric tumors. Lastly, we provide a succinct overview of research using siRNAs to treat gastric tumors.


Subject(s)
Adenocarcinoma , RNA, Small Interfering , Stomach Neoplasms , Humans , Stomach Neoplasms/therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , RNA, Small Interfering/therapeutic use , Adenocarcinoma/therapy , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Genetic Therapy/methods , Animals
12.
Aging (Albany NY) ; 16(9): 7596-7621, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38742936

ABSTRACT

Colon adenocarcinoma (COAD), a frequently encountered and highly lethal malignancy of the digestive system, has been the focus of intensive research regarding its prognosis. The intricate immune microenvironment plays a pivotal role in the pathological progression of COAD; nevertheless, the underlying molecular mechanisms remain incompletely understood. This study aims to explore the immune gene expression patterns in COAD, construct a robust prognostic model, and delve into the molecular mechanisms and potential therapeutic targets for COAD liver metastasis, thereby providing critical support for individualized treatment strategies and prognostic evaluation. Initially, we curated a comprehensive dataset by screening 2600 immune-related genes (IRGs) from the ImmPort and InnateDB databases, successfully obtaining a rich data resource. Subsequently, the COAD patient cohort was classified using the non-negative matrix factorization (NMF) algorithm, enabling accurate categorization. Continuing on, utilizing the weighted gene co-expression network analysis (WGCNA) method, we analyzed the top 5000 genes with the smallest p-values among the differentially expressed genes (DEGs) between immune subtypes. Through this rigorous screening process, we identified the gene modules with the strongest correlation to the COAD subpopulation, and the intersection of genes in these modules with DEGs (COAD vs COAD vs Normal colon tissue) is referred to as Differentially Expressed Immune Genes Associated with COAD (DEIGRC). Employing diverse bioinformatics methodologies, we successfully developed a prognostic model (DPM) consisting of six genes derived from the DEIGRC, which was further validated across multiple independent datasets. Not only does this predictive model accurately forecast the prognosis of COAD patients, but it also provides valuable insights for formulating personalized treatment regimens. Within the constructed DPM, we observed a downregulation of CALB2 expression levels in COAD tissues, whereas NOXA1, KDF1, LARS2, GSR, and TIMP1 exhibited upregulated expression levels. These genes likely play indispensable roles in the initiation and progression of COAD and thus represent potential therapeutic targets for patient management. Furthermore, our investigation into the molecular mechanisms and therapeutic targets for COAD liver metastasis revealed associations with relevant processes such as fat digestion and absorption, cancer gene protein polysaccharides, and nitrogen metabolism. Consequently, genes including CAV1, ANXA1, CPS1, EDNRA, and GC emerge as promising candidates as therapeutic targets for COAD liver metastasis, thereby providing crucial insights for future clinical practices and drug development. In summary, this study uncovers the immune gene expression patterns in COAD, establishes a robust prognostic model, and elucidates the molecular mechanisms and potential therapeutic targets for COAD liver metastasis, thereby possessing significant theoretical and clinical implications. These findings are anticipated to offer substantial support for both the treatment and prognosis management of COAD patients.


Subject(s)
Adenocarcinoma , Algorithms , Colonic Neoplasms , Gene Expression Regulation, Neoplastic , Immunotherapy , Humans , Colonic Neoplasms/genetics , Colonic Neoplasms/immunology , Colonic Neoplasms/therapy , Colonic Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma/immunology , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Prognosis , Gene Expression Profiling , Gene Regulatory Networks , Biomarkers, Tumor/genetics , Transcriptome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Databases, Genetic , Computational Biology
13.
Br J Surg ; 111(5)2024 May 03.
Article in English | MEDLINE | ID: mdl-38722804

ABSTRACT

BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.


Subject(s)
Adenocarcinoma , Adenomatous Polyposis Coli , DNA Glycosylases , Stomach Neoplasms , Humans , Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/therapy , Adenomatous Polyposis Coli/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Stomach Neoplasms/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/therapy , Adenocarcinoma/diagnosis , DNA Glycosylases/genetics , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/therapy , Neoplastic Syndromes, Hereditary/diagnosis , Europe , Adenomatous Polyps/genetics , Adenomatous Polyps/therapy , Polyps
14.
Zhonghua Fu Chan Ke Za Zhi ; 59(4): 307-319, 2024 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-38644277

ABSTRACT

Objective: To establish and validate a predicting nomogram for cervical adenocarcinoma based on surveillance, epidemiology and end results (SEER) database and Chinese single-center data, and to explore the optimal treatment for cervical adenocarcinoma. Methods: This study selected 2 478 cervical adenocarcinoma patients from the SEER database as the training cohort, and 195 cervical adenocarcinoma patients from Cancer Hospital of Dalian University of Technology, Liaouing Cancer Hospital and Institute as an external validation cohort. Clinicopathological information and follow-up data of the two cohorts were collected. The radiotherapy group was defined as receiving comprehensive treatment based on concurrent chemoradiotherapy after initial diagnosis, while the surgery group was defined as receiving comprehensive treatment based on radical surgery. Log-rank test and cox regression were used to evaluate factors affecting the prognosis of cervical adenocarcinoma patients. A nomogram was drawn to predict the 3-year and 5-year overall survival rates of cervical adenocarcinoma patients, and then internal validation of the training cohort from SEER database and external validation of the hospital cohort were conducted. Results: (1) In the SEER database training cohort, there were 385 patients (15.54%, 385/2 478) in the radiotherapy group and 2 093 patients (84.46%, 2 093/2 478) in the surgery group. Overall survival time of the radiotherapy group was (55.8±51.3) months, while that of the surgery roup was (94.4±61.7) months, the difference between the two groups was statistically significant (χ2=256.44, P<0.001). Log-rank test showed that age, marital status, maximum of tumor diameters, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and treatments were all significant factors affecting the overall survival time of cervical adenocarcinoma patients (all P<0.001). Multivariate Cox regression analysis showed that elder (>50 years old), single status, huge tumors (>4 cm), high pathological grades (G2, G3), and advanced FIGO stages (≥Ⅱa2 stage) were independent risk factors for the overall survival time of cervical adenocarcinoma patients (all P<0.05); compared with radiotherapy, surgery was a protective factor for the prognosis of cervical adenocarcinoma patients (HR=0.619, 95%CI: 0.494-0.777; P<0.001). Further analysis of locally advanced stage and Ⅲc stage of patients showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm (HR=0.414, 95%CI: 0.182-0.942; P=0.036) in locally advanced stage and Ⅲc T1 to T2 stage (HR=0.473, 95%CI: 0.307-0.728; P=0.001). (2) The external validation cohort consisted of 39 patients (20.00%, 39/195) in the radiotherapy group and 156 patients (80.00%, 156/195) in the surgery group. The overall survival time of patients in the radiotherapy group was (51.7±34.3) months, while that of the surgery group was (63.1±26.6) months (χ2=28.41, P<0.001). Further analysis was conducted on locally advanced stage and Ⅲc stage patients, and multivariate Cox regression analysis was performed after propensity score matching, which showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm in locally advanced stage (HR=0.141, 95%CI: 0.023-0.843; P=0.032) and Ⅲc T1 to T2 stage (HR=0.184, 95%CI: 0.036-0.947; P=0.043). (3) Establishment and internal and external validation of nomogram: based on the six factors screened out by the multivariate Cox regression model, the nomogram was developed to predict the prognosis of cervical adenocarcinoma patients. The consistency index of the internal and external validation were 0.801 and 0.766, respectively, and the calibration curves matched well with the ideal fitting line. Conclusions: The key to the treatment of cervical adenocarcinoma is to prioritize radical surgery for patients with conditions for radical tumor resection. Compared with concurrent chemoradiotherapy, patients with locally advanced stages (Ⅰb3, Ⅱa2), and Ⅲc (T1, T2) stages cervical adenocarcinoma could benefit from comprehensive treatment based on radical surgery. The nomogram of this study has been validated internally and externally, and show good survival prediction efficacy for cervical adenocarcinoma patients.


Subject(s)
Adenocarcinoma , Nomograms , SEER Program , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/mortality , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Retrospective Studies , Prognosis , Survival Rate , Neoplasm Staging , China/epidemiology , Chemoradiotherapy , Proportional Hazards Models , Middle Aged , Databases, Factual , East Asian People
15.
World J Gastroenterol ; 30(11): 1621-1635, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38617451

ABSTRACT

BACKGROUND: Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary. AIM: To investigate the benefits and complications of neoadjuvant modalities. METHODS: To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach. RESULTS: Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality (P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure (P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases. CONCLUSION: Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Humans , Neoadjuvant Therapy/adverse effects , Quality of Life , Adenocarcinoma/therapy , Chemoradiotherapy/adverse effects , Esophageal Neoplasms/therapy
16.
Br J Surg ; 111(4)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38659247

ABSTRACT

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.


Subject(s)
Neoplasm Recurrence, Local , Pancreatectomy , Pancreatic Neoplasms , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/therapy , Adenocarcinoma, Mucinous/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/administration & dosage , Capecitabine/therapeutic use , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/surgery , Chemotherapy, Adjuvant , Gemcitabine , Neoplasm Recurrence, Local/epidemiology , Pancreatic Intraductal Neoplasms/pathology , Pancreatic Intraductal Neoplasms/therapy , Pancreatic Intraductal Neoplasms/mortality , Pancreatic Intraductal Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/surgery , Propensity Score , Retrospective Studies
17.
Medicine (Baltimore) ; 103(15): e37795, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608051

ABSTRACT

Small bowel adenocarcinoma (SBA) is a rare tumor entity with a relatively poor prognosis. Diagnosis and management of SBA are still challenging despite recent advancement of diagnostic methods and publication of guidelines. This study aimed to analyze and visualize the trending of SBA research in the past 22 years in the 21st century through bibliometric analysis. Our study collected 1270 publication records of SBA from 2000 Jan 1st to 2022 December 31 from Web of Science and used VOSviewer and CiteSpace to analyze countries, institutions, journals, authors, references and keywords to present the latest trends in SBA research. The USA was the most productive country in terms of the total number of publications (n = 418). The Mayo Clinic (n = 22) and University of Texas MD Cancer Center (n = 22) were the institutions with top publications. The "World Journal Of Gastroenterology" (n = 30) had the largest publications. Overman Michael J (n = 17) was the most active and prolific author. The "small bowel adenocarcinoma" was the most frequent keyword. Our bibliometric analysis provides a comprehensive overview of the trends and gaps in the research of SBA. Despite the challenges faced, researchers from USA, Japan and China have made significant contributions to the field of SBA research, and further research is necessary to develop evidence-based guidelines, and advance the understanding and management of SBA.


Subject(s)
Adenocarcinoma , Duodenal Neoplasms , Humans , Adenocarcinoma/therapy , Bibliometrics , Ambulatory Care Facilities , China
18.
Medicine (Baltimore) ; 103(15): e37728, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608069

ABSTRACT

Stomach adenocarcinoma (STAD) is one of the subtype of gastric cancer with high invasiveness, extreme heterogeneity, high morbidity, and high mortality. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity and carcinogenesis. An integrative machine learning procedure including 10 methods was performed to develop a prognostic degradome-based prognostic signature (DPS) in TCGA, GSE15459, GSE26253, and GSE62254 datasets. Investigations of the DPS concerning immune infiltration, immunotherapy benefits, and drug priority were orchestrated. The DPS developed by Enet [alpha = 0.3] method was regarded as the optimal prognostic model. The DPS had a stable and powerful performance in predicting the clinical outcome of STAD and served as an independent risk factor in training and testing cohorts. The C-index of DPS was higher than that of age, sex, and clinical stage. STAD patients with low DPS scores had a higher abundance of B cells, CD8+ T cells, higher cytolytic scores, and T cell co-stimulation scores. Moreover, low DPS score indicated a lower tumor immune dysfunction and exclusion score, lower T cell dysfunction and exclusion score, higher PD1&CTLA4 immunophenoscore, and higher tumor mutation burden score in STAD, demonstrating a better immunotherapy response. STAD patients with a high DPS score had a lower IC50 value of common chemotherapy and targeted therapy regimens (Cisplatin, Docetaxel, Gefitinib, etc). Our study developed an optimal DPS for STAD. The DPS could predict the prognosis, risk stratification and guide treatment for STAD patients.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Humans , Stomach Neoplasms/therapy , Prognosis , Immunotherapy , Adenocarcinoma/therapy
19.
Prostate ; 84(9): 823-831, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38606933

ABSTRACT

BACKGROUND: There are limited preclinical orthotopic prostate cancer models due to the technical complexity of surgical engraftment and tracking the tumor growth in the mouse prostate gland. Orthotopic xenografts recapitulate the tumor microenvironment, tumor stromal interactions, and clinical behavior to a greater extent than xenografts grown at subcutaneous or intramuscular sites. METHODS: This study describes a novel micro-surgical technique for orthotopically implanting intact tumors pieces from cell line derived (transgenic adenocarcinoma mouse prostate [TRAMP]-C2) or patient derived (neuroendocrine prostate cancer [NEPC]) tumors in the mouse prostate gland and monitoring tumor growth using magnetic resonance (MR) imaging. RESULTS: The TRAMP-C2 tumors grew rapidly to a predetermined endpoint size of 10 mm within 3 weeks, whereas the NEPC tumors grew at a slower rate over 7 weeks. The tumors were readily detected by MR and confidently identified when they were approximately 2-3 mm in size. The tumors were less well-defined on CT. The TRAMP-C2 tumors were characterized by amorphous sheets of poorly differentiated cells similar to a high-grade prostatic adenocarcinoma and frequent macroscopic peritoneal and lymph node metastases. In contrast, the NEPC's displayed a neuroendocrine morphology with polygonal cells arranged in nests and solid sheets and high count. There was a local invasion of the bladder and other adjacent tissues but no identifiable metastases. The TRAMP-C2 tumors were more hypoxic than the NEPC tumors. CONCLUSIONS: This novel preclinical orthotopic prostate cancer mouse model is suitable for either syngeneic or patient derived tumors and will be effective in developing and advancing the current selection of treatments for patients with prostate cancer.


Subject(s)
Adenocarcinoma , Disease Models, Animal , Prostatic Neoplasms , Animals , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/diagnostic imaging , Mice , Humans , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Cell Line, Tumor , Mice, Transgenic , Neoplasm Transplantation/methods , Magnetic Resonance Imaging , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...