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Current Oncology (Toronto, Ont.) Jul 2023Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next... (Review)
Review
Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.
Topics: Humans; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Chemotherapy, Adjuvant
PubMed: 37504342
DOI: 10.3390/curroncol30070482 -
Korean Journal of Radiology Jun 2024Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic... (Review)
Review
Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic lesions, determining when to recommend aggressive actions such as surgical resection or endoscopic ultrasound with sampling is difficult. In this article, we review the common types of cystic pancreatic lesions including serous cystadenoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm with imaging examples of each. We also discuss high-risk or worrisome imaging features that warrant a referral to a surgeon or endoscopist and provid several examples of these features. These imaging features adhere to the latest guidelines from the International Consensus Guidelines, American Gastroenterological Association (2015), American College of Gastroenterology (2018), American College of Radiology (2010, 2017), and European Guidelines (2013, 2018). Our focused article addresses the imaging dilemma of managing incidental cystic pancreatic lesions, weighing the options between imaging follow-up and aggressive interventions.
Topics: Humans; Pancreatic Cyst; Incidental Findings; Pancreatic Neoplasms; Diagnosis, Differential; Pancreas; Tomography, X-Ray Computed
PubMed: 38807337
DOI: 10.3348/kjr.2024.0085 -
Japanese Journal of Clinical Oncology Aug 2023Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a... (Review)
Review
Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments.
Topics: Humans; Retrospective Studies; Pancreatic Neoplasms; Carcinoma; Pancreas
PubMed: 37325968
DOI: 10.1093/jjco/hyad062 -
Biomedicine & Pharmacotherapy =... Dec 2023Pancreatic cancer, including pancreatic ductal adenocarcinomas (PDACs), is a malignant tumor with characteristics of tumor-stroma interactions. Patients often have a... (Review)
Review
Pancreatic cancer, including pancreatic ductal adenocarcinomas (PDACs), is a malignant tumor with characteristics of tumor-stroma interactions. Patients often have a poor prognosis and a poor long-term survival rate. In recent years, rapidly-developing single-cell sequencing techniques have been used to analyze cell populations at a single-cell resolution, so that it is now possible to have a more in-depth and clearer understanding of the genetic composition of pancreatic cancer. In this review, we provide an overview of the current single-cell sequencing techniques and their applications in the exploration of intratumoral heterogeneity, the tumor microenvironment, therapy resistance, and novel treatments. Our hope is to provide new insight into the potential of precision therapy, which will perhaps one day lead to significant advances in PDAC treatment.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tumor Microenvironment
PubMed: 37837881
DOI: 10.1016/j.biopha.2023.115664 -
International Journal of Surgery... Sep 2023Upfront resection (UR) followed by adjuvant chemotherapy remains the standard treatment for resectable pancreatic cancer. There is increasing evidence suggesting...
BACKGROUND
Upfront resection (UR) followed by adjuvant chemotherapy remains the standard treatment for resectable pancreatic cancer. There is increasing evidence suggesting favourable outcomes toward neoadjuvant chemotherapy (NAC) followed by surgery.
METHODS
All clinical staging with resectable pancreatic cancer patients treated at a tertiary medical centre from 2013 to 2020 were identified. The baseline characteristics, treatment course, surgery outcome and survival results of UR or NAC were compared.
RESULTS
Finally, in 159 resectable patients, 46 patients (29%) underwent NAC and 113 patients (71%) received UR. In NAC, 11 patients (24%) did not receive resection, 4 (36.4%) for comorbidity, 2 (18.2%) for patient refusal and 2 (18.2%) for disease progression. In UR, 13 patients (12%) were unresectable intraoperatively; 6 (46.2%) for locally advanced and 5 (38.5%) for distant metastasis. Overall, 97% of patients in NAC and 58% of patients in UR completed adjuvant chemotherapy. As of data cut-off, 24 patients (69%) in NAC and 42 patients (29%) in UR were still tumour free. The median recurrence-free survival in NAC, UR with adjuvant chemotherapy and without adjuvant chemotherapy were 31.3 months (95% CI, 14.4-not estimable), 10.6 months (95% CI, 9.0-14.3) and 8.5 months (95% CI, 5.8-11.8), P =0.036; and the median overall survival in each group were not reached (95% CI, 29.7-not estimable), 25.9 months (95% CI, 21.1-40.5) and 21.7 months (12.0-32.8), P =0.0053. Based on initial clinical staging, the median overall survival of NAC was not significantly different from UR with a tumour less than or equal to 2 cm, P =0.29. NAC patients had a higher R0 resection rate (83% versus 53%), lower recurrence rate (31% versus 71%) and harvested median number lymph node (23 versus 15).
CONCLUSION
This study demonstrates that NAC is superior to UR in resectable pancreatic cancer with better survival.
Topics: Humans; Neoadjuvant Therapy; Cross-Sectional Studies; Pancreatic Neoplasms; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37300888
DOI: 10.1097/JS9.0000000000000495 -
Biomedicine & Pharmacotherapy =... Sep 2023Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy. In recent years, targeting epigenetic pathways has emerged as a promising approach to overcome tumor immunosuppression and cancer progression. Moreover, the progress in nanotechnology has provided new opportunities for enhancing the efficacy of conventional and epigenetic drugs. Nano-based drug delivery systems (NDDSs) offer several advantages, including improved drug pharmacokinetics, enhanced tumor penetration, and reduced systemic toxicity. Smart NDDSs enable precise targeting of stromal components and augment the effectiveness of immunotherapy through multiple drug delivery options. This review offers an overview of the latest nano-based approaches developed to achieve superior therapeutic efficacy and overcome drug resistance. We specifically focus on the TME and epigenetic-targeted therapies in the context of PDAC, discussing the advantages and limitations of current strategies while highlighting promising new developments. By emphasizing the immense potential of NDDSs in improving therapeutic outcomes in PDAC, our review paves the way for future research in this rapidly evolving field.
Topics: Humans; Nanomedicine; Nanoparticle Drug Delivery System; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tumor Microenvironment
PubMed: 37481927
DOI: 10.1016/j.biopha.2023.115179 -
World Journal of Gastroenterology Mar 2024This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors (pan-NETs), emphasizing tailored approaches... (Review)
Review
This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors (pan-NETs), emphasizing tailored approaches for specific subtypes. Cytoreductive surgery and somatostatin analogs (SSAs) play pivotal roles in managing tumors, while palliative options such as molecular targeted therapy, peptide receptor radionuclide therapy, and chemotherapy are reserved for SSA-refractory patients. Gastrinomas, insulinomas, glucagonomas, carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies. Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research. This review underscores the evolving landscape of pan-NET treatment, offering renewed hope and improved outcomes for patients facing this complex disease.
Topics: Humans; Neuroendocrine Tumors; Immunotherapy; Carcinoid Tumor; Cytoreduction Surgical Procedures; Pancreatic Neoplasms
PubMed: 38617746
DOI: 10.3748/wjg.v30.i12.1670 -
International Journal of Molecular... Aug 2023There is an urgent unmet need for robust and reliable biomarkers for early diagnosis, prognosis, and prediction of response to specific treatments of many aggressive and... (Review)
Review
There is an urgent unmet need for robust and reliable biomarkers for early diagnosis, prognosis, and prediction of response to specific treatments of many aggressive and deadly cancers, such as pancreatic cancer, and liquid biopsy-based miRNA profiling has the potential for this. MiRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many cancers, functioning as either oncomes or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling of dysregulated miRNAs in pancreatic cancer has been shown to correlate with disease diagnosis, indicate optimal treatment options and predict response to a specific therapy. Specific miRNA signatures can track the stages of pancreatic cancer and hold potential as diagnostic, prognostic, and predictive markers, as well as therapeutics such as miRNA mimics and miRNA inhibitors (antagomirs). Furthermore, identified specific miRNAs and genes they regulate in pancreatic cancer along with downstream pathways can be used as potential therapeutic targets. However, a limited understanding and validation of the specific roles of miRNAs, lack of tissue specificity, methodological, technical, or analytical reproducibility, harmonization of miRNA isolation and quantification methods, the use of standard operating procedures, and the availability of automated and standardized assays to improve reproducibility between independent studies limit bench-to-bedside translation of the miRNA biomarkers for clinical applications. Here I review recent findings on miRNAs in pancreatic cancer pathogenesis and their potential as diagnostic, prognostic, and predictive markers.
Topics: Humans; Circulating MicroRNA; Reproducibility of Results; Pancreatic Neoplasms; MicroRNAs; Biomarkers
PubMed: 37686149
DOI: 10.3390/ijms241713340 -
Frontiers in Bioscience (Landmark... Mar 2024Pancreatic adenocarcinoma (PDAC) is disease with a 5-year survival of only 12%. Many patients with PDAC present with late-stage disease and even early-stage disease can... (Review)
Review
Pancreatic adenocarcinoma (PDAC) is disease with a 5-year survival of only 12%. Many patients with PDAC present with late-stage disease and even early-stage disease can often be characterized by an aggressive tumor biology. Standard therapy for metastatic PDAC consists mainly of chemotherapy regimens like FOLFIRINOX, FOLFOX, or gemcitabine and nab-paclitaxel. Research has focused on sequencing PDAC tumors to understand better the mutational landscape and transcriptomics of PDAC with the goal to develop targeted therapies. Targeted therapies may potentially minimize the toxic risks of chemotherapy and provide a long-term survival benefit. We herein review the underlying molecular pathogenesis of PDAC, as well as the classification schema created from current sequencing data, and recent updates related to targeted therapy for PDAC.
Topics: Humans; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Adenocarcinoma; Gemcitabine
PubMed: 38538278
DOI: 10.31083/j.fbl2903101 -
Pancreatology : Official Journal of the... Dec 2023Probing relevant proteomic biomarkers may facilitate effective pancreatic adenocarcinoma (PDAC) diagnosis, treatment and prevention. Here, we developed a protein-based...
BACKGROUND
Probing relevant proteomic biomarkers may facilitate effective pancreatic adenocarcinoma (PDAC) diagnosis, treatment and prevention. Here, we developed a protein-based prognostic model for PDAC by using relevant proteomic biomarkers data from The Cancer Genome Atlas (TCGA).
METHODS
We obtained PDAC's proteomic and clinical data from TCGA and used various analytical tools to identify differentially expressed proteins between normal and cancer tissues. We constructed our protein-based prognostic model and confirmed its accuracy using receiver operating characteristic curve and Kaplan-Meier survival analyses. We elucidated clinical factor-signature protein correlations by clinical correlation assessments and protein coexpression networks. We also used immunohistochemistry (protein expression assessment), Gene Set Enrichment Analysis (protein role identification) and CIBERSORT (infiltrating immune cell distribution assessment).
RESULTS
CIITA, BRAF_pS445, AR, YTHDF2, IGFBP2 and CDK1_pT14 were identified as PDAC-associated prognostic proteins. All risk scores calculated using our model provided 1-, 3-, 5-year survival probability at 70 % accuracy. The reliability of our model was validated by the GEO as well. In high- and low-risk groups, age, sex, T- and N- stage disparities were significant, and prognostic and coexpressed proteins correlated. PDAC tissues demonstrated significant CDK1_pT14 overexpression but significant BRAF_pS445, YTHDF2, and IGFBP2 underexpression. Downstream proteins of BRAF were validated by IHC. Low-risk tissues demonstrated more naïve B cells, eosinophils, activated NK cells and regulatory T cells, whereas high-risk tissues demonstrated more activated memory T cells, monocytes, neutrophils, dendritic cells and resting NK cells.
CONCLUSIONS
Our protein-based prognostic model for PDAC, along with six signature proteins, might aid in predicting PDAC prognosis and therapeutic targets.
Topics: Humans; Pancreatic Neoplasms; Prognosis; Adenocarcinoma; Proteomics; Proto-Oncogene Proteins B-raf; Reproducibility of Results; Carcinoma, Pancreatic Ductal; Biomarkers; Biomarkers, Tumor
PubMed: 37923686
DOI: 10.1016/j.pan.2023.10.021