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Frontiers in Immunology 2024This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved...
This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
Topics: Humans; Pancreatic Neoplasms; Antigens, Neoplasm; Liquid Biopsy; Precision Medicine; Cancer Vaccines; Liver Neoplasms; Male; Peptides; Middle Aged; Vaccines, Subunit; Immunization; Female; Biomarkers, Tumor
PubMed: 38938562
DOI: 10.3389/fimmu.2024.1414737 -
Gut and Liver Jun 2024The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic...
BACKGROUND/AIMS
The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals.
METHODS
This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies.
RESULTS
The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC.
CONCLUSIONS
Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.
PubMed: 38938175
DOI: 10.5009/gnl240241 -
BMC Medical Informatics and Decision... Jun 2024Pancreatic cancer possesses a high prevalence and mortality rate among other cancers. Despite the low survival rate of this cancer type, the early prediction of this...
BACKGROUND AND AIM
Pancreatic cancer possesses a high prevalence and mortality rate among other cancers. Despite the low survival rate of this cancer type, the early prediction of this disease has a crucial role in decreasing the mortality rate and improving the prognosis. So, this study.
MATERIALS AND METHODS
In this retrospective study, we used 654 alive and dead PC cases to establish the prediction model for PC. The six chosen machine learning algorithms and prognostic factors were utilized to build the prediction models. The importance of the predictive factors was assessed using the relative importance of a high-performing algorithm.
RESULTS
The XG-Boost with AU-ROC of 0.933 (95% CI= [0.906-0.958]) and AU-ROC of 0.836 (95% CI= [0.789-0.865] in internal and external validation modes were considered as the best-performing model for predicting the mortality risk of PC. The factors, including tumor size, smoking, and chemotherapy, were considered the most influential for prediction.
CONCLUSION
The XG-Boost gained more performance efficiency in predicting the mortality risk of PC patients, so this model can promote the clinical solutions that doctors can achieve in healthcare environments to decrease the mortality risk of these patients.
Topics: Humans; Pancreatic Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Aged; Machine Learning; Risk Assessment; Prognosis; Models, Statistical; Adult; Algorithms
PubMed: 38937795
DOI: 10.1186/s12911-024-02590-4 -
Lipids in Health and Disease Jun 2024Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged...
BACKGROUND
Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear.
METHODS
Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results.
RESULTS
Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P < 0.001), while elevated levels of phosphatidylcholine (16:1_20:4) increased the risk of developing esophageal cancer (OR = 1.31, P = 0.02). Conversely, phosphatidylcholine (18:2_0:0) had a protective effect against colorectal cancer (OR = 0.86, P = 0.036). The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships.
CONCLUSION
Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer prevention and treatment strategies. These results reinforce the value of MR in unraveling complex lipid-cancer interactions, offering new avenues for research and clinical application.
Topics: Humans; Mendelian Randomization Analysis; Digestive System Neoplasms; Genome-Wide Association Study; Lipid Metabolism; Lipids; Risk Factors; Lipidomics; Genetic Predisposition to Disease; Sphingomyelins; Esophageal Neoplasms
PubMed: 38937739
DOI: 10.1186/s12944-024-02191-0 -
Scientific Reports Jun 2024Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER)...
Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation's success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People's Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50-500) vs 310 (100-850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.
Topics: Humans; Male; Female; Middle Aged; Propensity Score; Robotic Surgical Procedures; Retrospective Studies; Laparoscopy; Aged; Bile Duct Neoplasms; Klatskin Tumor; Treatment Outcome; Plastic Surgery Procedures; Postoperative Complications
PubMed: 38937559
DOI: 10.1038/s41598-024-65875-8 -
Cell Death & Disease Jun 2024Hepatocellular carcinoma is a primary liver cancer, characterised by diverse etiology, late diagnoses, and poor prognosis. Hepatocellular carcinoma is mostly resistant...
Hepatocellular carcinoma is a primary liver cancer, characterised by diverse etiology, late diagnoses, and poor prognosis. Hepatocellular carcinoma is mostly resistant to current treatment options, therefore, identification of more effective druggable therapeutic targets is needed. We found microRNA miR-20a-5p is upregulated during mouse liver tumor progression and in human hepatocellular carcinoma patients. In this study, we elucidated the therapeutic potential of targeting oncogenic miR-20a-5p, in vivo, in a xenograft model and in two transgenic hepatocellular carcinoma mouse models via adeno-associated virus-mediated miR-20a-Tough-Decoy treatment. In vivo knockdown of miR-20a-5p attenuates tumor burden and prolongs survival in the two independent hepatocellular carcinoma mouse models. We identified and validated cytochrome c as a novel target of miR-20a-5p. Cytochrome c plays a key role in initiation of the apoptotic cascade and in the electron transport chain. We show for the first time, that miR-20a modulation affects both these key functions of cytochrome c during HCC development. Our study thus demonstrates the promising 'two birds with one stone' approach of therapeutic in vivo targeting of an oncogenic miRNA, whereby more than one key deregulated cellular process is affected, and unequivocally leads to more effective attenuation of HCC progression and significantly longer overall survival.
Topics: MicroRNAs; Carcinoma, Hepatocellular; Animals; Liver Neoplasms; Humans; Apoptosis; Mice; Cytochromes c; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Mice, Nude
PubMed: 38937450
DOI: 10.1038/s41419-024-06841-0 -
Journal of Neuroendocrinology Jun 2024Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included Lu (n = 142) and Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.
PubMed: 38937270
DOI: 10.1111/jne.13425 -
Zhonghua Wai Ke Za Zhi [Chinese Journal... Jun 2024The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular...
The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the gene.
PubMed: 38937132
DOI: 10.3760/cma.j.cn112139-20240102-00002 -
In Vivo (Athens, Greece) 2024Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors,...
BACKGROUND/AIM
Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing.
CASE REPORT
Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions.
CONCLUSION
This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.
Topics: Humans; Cyclin-Dependent Kinase Inhibitor p16; Astrocytoma; Cyclin-Dependent Kinase Inhibitor p15; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Genetic Predisposition to Disease; Male; Female; Adult; Brain Neoplasms; Pedigree; Magnetic Resonance Imaging; Gene Deletion
PubMed: 38936911
DOI: 10.21873/invivo.13617 -
International Journal of Surgery... Jun 2024The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparing upfront surgery with neoadjuvant treatments in patients with resectable, borderline resectable or locally advanced pancreatic cancer: a systematic review and network meta-analysis of randomized clinical trials.
BACKGROUND
The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use.
PATIENTS AND METHODS
The authors reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, The Cochrane Library, Web of Science from 2009 to 2023 to estimate relative odds ratios for resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials.
RESULTS
A total of nine studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer (RPC) patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline RPC. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer.
CONCLUSIONS
The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline RPC. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.
Topics: Humans; Pancreatic Neoplasms; Neoadjuvant Therapy; Network Meta-Analysis; Randomized Controlled Trials as Topic; Pancreatectomy
PubMed: 38935819
DOI: 10.1097/JS9.0000000000001313