The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3.

Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2's role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p-SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.

Ribosome profiling: a powerful tool in oncological research.

Neoplastic cells need to adapt their gene expression pattern to survive in an ever-changing or unfavorable tumor microenvironment. Protein synthesis (or mRNA translation), an essential part of gene expression, is dysregulated in cancer. The emergence of distinct translatomic technologies has revolutionized oncological studies to elucidate translational regulatory mechanisms. Ribosome profiling can provide adequate information on diverse aspects of translation by aiding in quantitatively analyzing the intensity of translating ribosome-protected fragments. Here, we review the primary currently used translatomics techniques and highlight their advantages and disadvantages as tools for translatomics studies. Subsequently, we clarified the areas in which ribosome profiling could be applied to better understand translational control. Finally, we summarized the latest advances in cancer studies using ribosome profiling to highlight the extensive application of this powerful and promising translatomic tool.

Epidemiology of pancreatic cancer: New version, new vision.

Pancreatic cancer (PC) is a devastating malignancy with an extremely high mortality rate and poses significant challenges to healthcare systems worldwide. The prevalence of PC risk factors spiked over the years, leading to a global increase in PC incidence rates. The contribution of different risk factors, however, varied from region to region due to genetic predisposition, environmental, social, and political factors underlying disease prevalence in addition to public health strategies. This comprehensive review aims to provide a thorough analysis of the epidemiology of PC, discussing its incidence, risk factors, screening strategies and socioeconomic burden. We compiled a wide range of seminal studies as well as epidemiological investigations to serve this review as a comprehensive guide for researchers, healthcare professionals, and policymakers keen for a more profound understanding of PC epidemiology. This review highlights the essentiality of persistent research efforts, interdisciplinary collaboration, and public health initiatives to address the expanding burden of this malignancy.

Novel strategies optimize immunotherapy by improving the cytotoxic function of T cells for pancreatic cancer treatment.

Pancreatic cancer (PC) is considered highly malignant due to its unsatisfying prognosis and limited response to therapies. Immunotherapy has therefore been developed to harness the antigen-specific properties and cytotoxicity of the immune system, aiming to induce a robust anti-tumor immune response that specifically demolishes PC cells while minimizing lethality in healthy tissue. The activation and augmentation of cytotoxic T cells play a critical role in the initiation and final success of immunotherapy. PC, however, is often immunotherapy resistant due to its intrinsic immunosuppressive tumor microenvironment that consequently hampers effective T cell priming. Emerging therapeutic approaches are orientated to modulate the tumor microenvironment in PC to enhance immune system involvement and heighten T cell efficacy. These novel strategies have shown promising therapeutic effects in the treatment of PC either as standalone approaches or combinatorial with other therapeutic schemes. The objective of this article is to explore innovative approaches to optimize immunotherapy for PC patients through T cell cytotoxic function augmentation.

From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.

PURPOSE: This study aims to review the multifaceted roles of a membrane protein named Fibroblast Activation Protein (FAP) expressed in tumor tissue, including its molecular functionalities, regulatory mechanisms governing its expression, prognostic significance, and its crucial role in cancer diagnosis and treatment. METHODS: Articles that have uncovered the regulatory role of FAP in tumor, as well as its potential utility within clinical realms, spanning diagnosis to therapeutic intervention has been screened for a comprehensive review. RESULTS: Our review reveals that FAP plays a pivotal role in solid tumor progression by undertaking a multitude of enzymatic and nonenzymatic roles within the tumor stroma. The exclusive presence of FAP within tumor tissues highlights its potential as a diagnostic marker and therapeutic target. The review also emphasizes the prognostic significance of FAP in predicting tumor progression and patient outcomes. Furthermore, the emerging strategies involving FAPI inhibitor (FAPI) in cancer research and clinical trials for PET/CT diagnosis are discussed. And targeted therapy utilizing FAP including FAPI, chimeric antigen receptor (CAR) T cell therapy, tumor vaccine, antibody-drug conjugates, bispecific T-cell engagers, FAP cleavable prodrugs, and drug delivery system are also introduced. CONCLUSION: FAP's intricate interactions with tumor cells and the tumor microenvironment make it a promising target for diagnosis and treatment. Promising strategies such as FAPI offer potential avenues for accurate tumor diagnosis, while multiple therapeutic strategies highlight the prospects of FAP targeting treatments which needs further clinical evaluation.

Organoid: Bridging the gap between basic research and clinical practice.

Nowadays, the diagnosis and treatment system of malignant tumors has increasingly tended to be more precise and personalized while the existing tumor models are still unable to fully meet the needs of clinical practice. Notably, the emerging organoid platform has been proven to have huge potential in the field of basic-translational medicine, which is expected to promote a paradigm shift in personalized medicine. Here, given the unique advantages of organoid platform, we mainly explore the prominent role of organoid models in basic research and clinical practice from perspectives of tumor biology, tumorigenic microbes-host interaction, clinical decision-making, and regenerative strategy. In addition, we also put forward some practical suggestions on how to construct a new generation of organoid platform, which is destined to vigorously promote the reform of basic-translational medicine.

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Objective: Pancreatic cancer (PC) is highly malignant, but the underlying mechanisms of cancer progression remain unclear. PRKRA is involved in cellular stress response, but its role in PC was unknown. Methods: The expression of PRKRA between normal and tumor tissues were compared, and the prognostic value of PRKRA was evaluated. SiRNA and plasmids were applied to investigate the effects of PRKRA on PC cells. Organoids and cell lines with knockout and overexpression of PRKRA were established by CRISPR/Cas9 and lentivirus. The effects of PRKRA on PC were evaluated in vivo by cell-derived xenografts. The downstream genes of PRKRA were screened by transcriptome sequencing. The regulation of the target gene was validated by RT-qPCR, western blot, ChIP and dual luciferase reporter assay. Besides, the correlation between PRKRA and gemcitabine sensitivity was investigated by PC organoids. Results: PRKRA was significantly overexpressed in PC tissues and independently associated with poor prognosis. PRKRA promoted the proliferation, migration, and chemoresistance of PC cells. The proliferation of PC organoids was decreased by PRKRA knockout. The growth and chemoresistance of xenografts were increased by PRKRA overexpression. Mechanistically, PRKRA upregulated the transcription of MMP1 via NF-κB pathway. ChIP and dual luciferase reporter assay showed that NF-κB subunit P65 could bind to the promoter of MMP1. The sensitivity of PC organoids to gemcitabine was negatively correlated with the expression of PRKRA and MMP1. Conclusions: Our study indicated that the PRKRA/NF-κB/MMP1 axis promoted the progression of PC and may serve as a potential therapeutic target and prognosis marker.

Comparing the clinical value of baseline [68 Ga]Ga-FAPI-04 PET/CT and [18F]F-FDG PET/CT in pancreatic ductal adenocarcinoma: additional prognostic value of the distal pancreatitis.

PURPOSE: Anatomical and molecular staging strategies are needed for the personalized treatment of localized pancreatic ductal adenocarcinoma (PDAC). This study evaluated the performance of [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT on the disease staging and prognostic value of patients with localized PDAC on contrast-enhanced (CE)-CT images. METHODS: Patients with suspected localized PDAC on CE-CT were recruited for static [68 Ga]Ga-FAPI-04 and 18[F]F-FDG and PET/CT, and select patients underwent simultaneous 60-min dynamic 68 Ga-FAPI-04 PET/CT. The diagnostic and staging performances of the static PET/CT results were evaluated by delineating regions of interest in the primary tumor, whole pancreas, and distal pancreas in both types of scans and then evaluating correlations between the PET/CT findings and clinicopathological characteristics. Furthermore, Kaplan-Meier and hazard ratio (log-rank) methods were used to evaluate the prognostic value of the combined dynamic [68 Ga]Ga-FAPI-04 and static [18F]F-FDG PET/CT method. RESULTS: We included 49 patients with histologically confirmed PDAC adenocarcinomas; 32 underwent 60-min dynamic [68 Ga]Ga-FAPI-04 PET/CT imaging simultaneously. The static [68 Ga]Ga-FAPI-04 method had significantly higher accuracy and uptake values than the static [18F]F-FDG method for primary PDAC lesions, metastatic lymph nodes, and distal metastases. Furthermore, 18.4% and 10.2% of the patients' stages changed after using the [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT methodologies, respectively, compared to the CE-CT-designated stage. The Ki values obtained from dynamic [68 Ga]Ga-FAPI-04 PET/CT did not differ between PDAC and distal obstructive pancreatitis lesions. Pathologically enlarged tumor size, poor differentiation, and perineural invasion were associated with increased [68 Ga]Ga-FAPI-04 uptake but not with [18F]F-FDG uptake. The preoperative prognostic performance of [68 Ga]Ga-FAPI-04 was better than that of [18F]F-FDG. Interestingly, combined [68 Ga]Ga-FAPI-04 and [18F]F-FDG uptake results in the whole pancreas could further stratify patients based on their postoperative prognosis. CONCLUSION: 6[68 Ga]Ga-FAPI-04 PET/CT was more sensitive and accurate than [18F]F-FDG PET/CT for tumor, node, and metastasis staging of PDAC identified on CE-CT. Additionally, [68 Ga]Ga-FAPI-04 uptake was significantly associated with pathologically aggressive tumor features. Combined [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT findings improved the prognostic value, potentially providing a non-invasive guide for clinical management. Finally, increased fibroblast activity in PDAC-induced obstructive pancreatitis may be associated with poor patient survival rates.

Genomic analysis and filtration of novel prognostic biomarkers based on metabolic and immune subtypes in pancreatic cancer.

PURPOSE: Patients with pancreatic cancer (PC) can be classified into various molecular subtypes and benefit from some precise therapy. Nevertheless, the interaction between metabolic and immune subtypes in the tumor microenvironment (TME) remains unknown. We hope to identify molecular subtypes related to metabolism and immunity in pancreatic cancer METHODS: Unsupervised consensus clustering and ssGSEA analysis were utilized to construct molecular subtypes related to metabolism and immunity. Diverse metabolic and immune subtypes were characterized by distinct prognoses and TME. Afterward, we filtrated the overlapped genes based on the differentially expressed genes (DEGs) between the metabolic and immune subtypes by lasso regression and Cox regression, and used them to build risk score signature which led to PC patients was categorized into high- and low-risk groups. Nomogram were built to predict the survival rates of each PC patient. RT-PCR, in vitro cell proliferation assay, PC organoid, immunohistochemistry staining were used to identify key oncogenes related to PC RESULTS: High-risk patients have a better response for various chemotherapeutic drugs in the Genomics of Drug Sensitivity in Cancer (GDSC) database. We built a nomogram with the risk group, age, and the number of positive lymph nodes to predict the survival rates of each PC patient with average 1-year, 2-year, and 3-year areas under the curve (AUCs) equal to 0.792, 0.752, and 0.751. FAM83A, KLF5, LIPH, MYEOV were up-regulated in the PC cell line and PC tissues. Knockdown of FAM83A, KLF5, LIPH, MYEOV could reduce the proliferation in the PC cell line and PC organoids CONCLUSION: The risk score signature based on the metabolism and immune molecular subtypes can accurately predict the prognosis and guide treatments of PC, meanwhile, the metabolism-immune biomarkers may provide novel target therapy for PC.

Comprehensive study of clinical features, prognostic factors, and survival in patients with pancreatic solid pseudopapillary neoplasms based on the 2019 WHO classification.

BACKGROUND: Pancreatic solid pseudopapillary neoplasms (pSPNs) are a rare tumor type with a limited understanding of their clinical characteristics and survival outcomes. We aimed to investigate potential prognostic factors among the existing clinical features in patients diagnosed with pSPN. METHODS: For this study, we utilized data from the Surveillance Epidemiology and End Results (SEER) database, specifically selecting patients with a histology type of pSPN from the years 2000 to 2019. Subsequently, we conducted both univariate and multivariate Cox regression analyses in a systematic manner to identify potential prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in the selected group of patients. To assess the disparity in OS and CSS among different clinical features and treatments, Kaplan-Meier curves were generated. Furthermore, utilizing the results obtained from the multivariate analysis, we developed a nomogram predictive model to effectively forecast the prognosis of patients diagnosed with pSPN. Calibration plots were presented to demonstrate the predictive accuracy and reliability of the nomogram predictive model. RESULTS: The study comprised a total of 433 participants, with 85.7% of the patients diagnosed with pSPN being female and the remaining 14.3% being male. The Kaplan-Meier curves indicated that patients with pSPN who underwent primary tumor resection (PTR) and those who were younger than 70 years old had significantly improved OS and CSS compared to those who did not undergo PTR or were aged 70 years or older, respectively (P < 0.001). Male patients diagnosed with pSPN exhibited poor OS compared to female pSPN patients (P = 0.015). The multivariate Cox regression analysis indicated that age (OS: HR = 1.055, 95% CI = 1.027-1.084, P < 0.001. CSS: HR = 1.054, 95% CI = 1.019-1.091, P = 0.002) and PTR (OS: HR = 6.074, 95% CI = 1.922-19.194, P = 0.002. CSS: HR = 4.912, 95% CI = 1.188-20.312, P = 0.028) were independent prognostic factors for both OS and CSS. Moreover, tumor size (≥ 5 vs < 5 cm CSS: HR = 4.788, 95% CI = 1.012-22.661, P = 0.048) was an independent prognostic factor for CSS. The independent prognostic factors identified through the multivariate Cox regression analysis were utilized to construct a nomogram model for predicting both OS and CSS in patients with pSPN. The accuracy of the nomogram model was visually testified by the calibration plot with acceptable predictive performance. CONCLUSION: Although the majority of patients diagnosed with pSPN are females, it was observed that male patients tend to have poorer OS compared to their female counterparts. The independent prognostic factors identified in the study were age and PTR, which were associated with both OS and CSS. Tumor size was an independent prognostic factor for CSS. Patients who underwent PTR exhibited improved OS and CSS outcomes. The developed nomogram and corresponding reference table provided promising prognostic predictions for pSPN outcoms, serving as a valuable resource for clinicians and patients alike.

Prognostic value of preoperative [68 Ga]Ga-FAPI-04 PET/CT in patients with resectable pancreatic ductal adenocarcinoma in correlation with immunohistological characteristics.

PURPOSE: Our aim was to assess the prognostic value of [68 Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed treatment-naïve PDAC patients who underwent preoperative [68 Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUVmax), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF). Spearman's correlation analysis was performed to evaluate the association between [68 Ga]Ga-FAPI-04 PET/CT imaging and ex vivo immunohistological FAP expression and pathological characteristics of surgical specimens (differentiation, size, vascularity, perineural invasion, and lymph node metastases). Kaplan-Meier and hazard ratio (HR, log-rank) methods were used to evaluate the prognostic value of [68 Ga]Ga-FAPI-04 PET/CT and clinicopathological factors. RESULTS: Thirty-seven surgical PDAC patients were included. The ex vivo expression of FAP was significantly associated with the tumor SUVmax and TLF. FAP expression was more abundant in poorly differentiated PDAC than in well- to moderately differentiated neoplasms. Tumor SUVmax or TLF and pancreatic TSUVmax or TPF were significantly correlated with tumor size, differentiation, and perineural invasion, respectively. SUVmax had a significant independent prognostic value for recurrence-free survival (HR = 2.46, P < 0.05), while [68 Ga]Ga-FAPI-04 TPF predicted overall survival (HR = 12.82, P < 0.05). CONCLUSION: The in vivo [68 Ga]Ga-FAPI-04 uptake in localized PDAC showed a significant correlation with ex vivo FAP expression and aggressive pathological characteristics. [68 Ga]Ga-FAPI-04 PET/CT also presented a potential for postoperative prognostication of PDAC. Elevated fibroblast activity induced by obstructive pancreatitis might be associated with the patient's survival.

mTOR inhibitor, gemcitabine and PD-L1 antibody blockade combination therapy suppresses pancreatic cancer progression via metabolic reprogramming and immune microenvironment remodeling in Trp53flox/+LSL-KrasG12D/+Pdx-1-Cre murine models.

OBJECTIVE: Resistance to immunotherapy and chemotherapy hinders the prognosis of pancreatic cancer(PC). We hypothesized that the combination of mTOR inhibitor sirolimus and gemcitabine would change the metabolic landscape of PC and enhance the anti-PD-L1 therapy. METHODS: In KPC mice, the following regimens were administered and tumor growth inhibition rates(TGI%) were calculated: sirolimus(S), PD-L1 antibody(P), gemcitabine(G), sirolimus + PD-L1 antibody(SP), sirolimus + gemcitabine(SG), PD-L1 + gemcitabine(PG) and sirolimus + PD-L1 antibody + gemcitabine(SPG). The metabolic changes of tumors were identified by LC-MS and subpopulations of immune cells were measured by flow cytometry. Sirolimus treated macrophages were co-cultured with PC cells in vitro, and the metabolic changes of macrophages and tumor cells as well as tumor cells' viability were detected. RESULTS: The monotherapy of S, P and G didn't inhibit tumor growth significantly. The combination of SP, PG and SG didn't improve the TGI% significantly compared with monotherapy. However, the TGI% of SPG combination was higher than other groups. The proportion of CD68+ macrophages increased in the peripheral blood and CD8+ T cells decreased in the tumor tissues after SPG treatment. LC-MS identified 42 differential metabolites caused by sirolimus in SPG group, among which 10 metabolites had potential effects on macrophages. Sirolimus treated M1 and M2 macrophages inhibited the proliferation of tumor cells and decreased tumor cells' glycolysis. The glycolysis of M2 macrophages was increased by sirolimus. CONCLUSIONS: mTOR inhibitor can change the immune microenvironment of PC via metabolic reprogramming, thus promoting the efficacy of PD-L1 blockade when combined with gemcitabine.

Cancer-specific survival and metastasis in pancreatic mucinous cystadenocarcinoma: A SEER-based cohort study.

Aims: This study aimed to investigate the prognostic value of clinical features for cancer-specific survival (CSS) and metastasis in patients with pancreatic mucinous cystadenocarcinoma (MCAC). We further constructed and validated an effective nomogram to predict CSS. Methods: We screened patients diagnosed with pancreatic MCAC from Surveillance Epidemiology and End Results (SEER) database. Kaplan-Meier curves were used to determine the CSS time. Univariate and multivariate Cox and logistic regression analyses were conducted to identify the prognostic factors for CSS and metastasis. The nomogram was constructed to predict the prognosis of pancreatic MCAC based on the results from the multivariate analysis. We used the concordance index (C-index), the area under the curve (AUC), and the calibration plots to determine the predictive accuracy and discriminability of the nomogram. Results: Multivariate Cox analysis revealed that age, primary site, grade, and radiotherapy were independent prognostic factors associated with CSS. Multivariate logistic regression analysis revealed that surgery and grade were independent risk factors associated with metastasis. The independent risk factors were included to construct a prognosis prediction model for predicting CSS in patients with pancreatic MCAC. The concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration plots of the training cohort and the validation cohort showed that the nomogram had an acceptable predictive performance. Conclusion: We established a nomogram that could determine the 3- and 5-year CSS, which could evaluate individual clinical outcomes and provide individualized clinical decisions.

Meta-analysis of robotic versus open pancreaticoduodenectomy in all patients and pancreatic cancer patients.

Purposes: To compare perioperative outcomes of robotic pancreaticoduodenectomy (RPD) to open pancreaticoduodenectomy (OPD) using evidence from cohort studies. Methods: Outcomes of interest include operative time, blood loss, R0 resection rate, lymph nodes harvested, overall complication rate, pancreatic fistula rate, delayed gastric emptying rate and 90-day mortality. Results: 6 prospective studies and 15 retrospective studies were included. Five of these studies were limited to patients with pancreatic cancer. Operative time was significantly longer in RPD (WMD: 64.60 min; 95% CI: 26.89 to 102.21; p = 0.001). Estimated blood loss was lower in RPD (WMD: -185.44 ml; 95% CI: -239.66 to -131.21; p < 0.001). Overall complication rates (OR: 0.66; 95% CI: 0.44 to 0.97; p < 0.001) and pancreatic fistula rate (OR: 0.67; 95% CI: 0.55 to 0.82; p < 0.001) were both lower in RPD. Length of hospital stay was longer in OPD (WMD: -1.90; 95% CI: -2.47 to -1.33). 90-day mortality was lower in RPD [odds ratio (OR): 0.77; 95% CI: 0.45 to 0.95; p = 0.025]. Conclusion: At current level of evidence, RPD is a safer alternative than OPD with regard to post-operative outcomes and blood loss. However, in terms of oncological outcomes RPD show no advantage over OPD, and the cost of RPD was higher. In general, RPD is now considered a reliable technology, but high-quality randomized controlled trial (RCT) studies are still needed to support this conclusion.

HIF-1α-regulated stanniocalcin-1 mediates gemcitabine resistance in pancreatic ductal adenocarcinoma via PI3K/AKT signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) has a poor response to the first-line chemotherapy drug gemcitabine. We previously identified stanniocalcin-1 as a gemcitabine-resistant-related gene, but its specific role and function in pancreatic cancer remain unclear. RT-qPCR and Western blot were used to evaluate differential protein and mRNA expressions. The biological functions of genes were determined using proliferation and drug-resistance experiments. Subcutaneous tumorigenesis experiment was performed on nude mice. Prognostic analysis was performed using public databases and our clinical data. We found HIF-1α-regulated STC1 expression mediated chemoresistance in pancreatic cancer. Deeper, we explored the action mechanism of STC1 and identified PI3K/AKT as the downstream signaling pathway of STC1. Furthermore, we analyzed clinical data and found that STC1 expression was related to the prognosis of gemcitabine-treated patients after surgery. In general, we proved the HIF-1α/STC1/PI3K-AKT axis participated in PDAC progression and chemoresistance, and STC1 may serve as a potential prognostic factor and therapeutic target for PDAC treatment.

A randomised, multicentre trial of somatostatin to prevent clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy.

BACKGROUND: Prophylactic somatostatin to reduce the incidence of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy remains controversial. We assessed the preventive efficacy of somatostatin on clinically relevant postoperative pancreatic fistula in intermediate-risk patients who underwent pancreaticoduodenectomy at pancreatic centres in China. METHODS: In this multicentre, prospective, randomised controlled trial, we used the updated postoperative pancreatic fistula classification criteria and cases were confirmed by an independent data monitoring committee to improve comparability between centres. The primary endpoint was the rate of clinically relevant postoperative pancreatic fistula within 30 days after pancreaticoduodenectomy. RESULTS: Eligible patients (randomised, n = 205; final analysis, n = 199) were randomised to receive postoperative intravenous somatostatin (250 µg/h over 120 h; n = 99) or conventional therapy (n = 100). The primary endpoint was significantly lower in the somatostatin vs control group (n = 13 vs n = 25; 13% vs 25%, P = 0.032). There were no significant differences for biochemical leak (P = 0.289), biliary fistula (P = 0.986), abdominal infection (P = 0.829), chylous fistula (P = 0.748), late postoperative haemorrhage (P = 0.237), mean length of hospital stay (P = 0.512), medical costs (P = 0.917), reoperation rate (P > 0.99), or 30 days' readmission rate (P = 0.361). The somatostatin group had a higher rate of delayed gastric emptying vs control (n = 33 vs n = 21; 33% vs 21%, P = 0.050). CONCLUSIONS: Prophylactic somatostatin treatment reduced clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy. TRIAL REGISTRATION: NCT03349424.

Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review.

Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Currently, screening is often applied in high-risk individuals to achieve the early diagnosis of pancreatic cancer. Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high-risk population and achieve early diagnosis and timely treatment of pancreatic cancer. Notably, accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) which is the golden standard for pancreatic cancer diagnosis. In addition, there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis of pancreatic cancer to be applied in the clinic. As the only serum biomarker approved by the United States Food and Drug Administration, carbohydrate antigen 19-9 (CA19-9) is not recommended to be used in the early screening of pancreatic cancer because of its limited specificity. Recently, increasing numbers of studies focused on the discovering of novel serum biomarkers and exploring their combination with CA19-9 in the detection of pancreatic cancer. Besides, the application of liquid biopsy involving circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes in blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis are drawing more and more attention. Furthermore, many innovative technologies such as artificial intelligence, computer-aided diagnosis system, metabolomics technology, ion mobility spectrometry (IMS) associated technologies, and novel nanomaterials have been tested for the early diagnosis of pancreatic cancer and have shown promising prospects. Hence, this review aims to summarize the recent progress in the development of early screening and diagnostic methods, including imaging, pathological examination, serological examination, liquid biopsy, as well as other potential diagnostic strategies for pancreatic cancer.

Comprehensive Analysis of Autophagy-Associated lncRNAs Reveal Potential Prognostic Prediction in Pancreatic Cancer.

Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. Both long noncoding RNAs (lncRNAs) and autophagy play vital roles in the development and progress of PC. Here, we constructed a prognostic risk score system based on the expression profile of autophagy-associated lncRNAs for prognostic prediction in PC patients. Firstly, we extracted the expression profile of lncRNA and clinical information from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The autophagy-associated genes were from The Human Autophagy Database. Through Cox regression and survival analysis, we screened out seven autophagy-associated lncRNAs and built the risk score system in which the patients with PC were distinguished into high- and low-risk groups in both training and validation datasets. PCA plot displayed distinct discrimination, and risk score system displayed independently predictive value for PC patient survival time by multivariate Cox regression. Then, we built a lncRNA and mRNA co-expression network via Cytoscape and Sankey diagram. Finally, we analyzed the function of lncRNAs in high- and low-risk groups by gene set enrichment analysis (GSEA). The results showed that autophagy and metabolism might make significant effects on PC patients of low-risk groups. Taken together, our study provides a new insight to understand the role of autophagy-associated lncRNAs and finds novel therapeutic and prognostic targets in PC.

Novel therapies targeting hypoxia mechanism to treat pancreatic cancer.

Pancreatic cancer (PC) is one of the deadliest malignancies. The high mortality rate of PC largely results from delayed diagnosis and early metastasis. Therefore, identifying novel treatment targets for patients with PC is urgently required to improve survival rates. A major barrier to successful treatment of PC is the presence of a hypoxic tumor microenvironment, which is associated with poor prognosis, treatment resistance, increased invasion and metastasis. Recent studies have identified a number of novel molecules and pathways in PC cells that promote cancer cells progression under hypoxic conditions, which may provide new therapy strategies to inhibit the development and metastasis of PC. This review summarizes the latest research of hypoxia in PC and provides an overview of how the current therapies have the capacity to overcome hypoxia and improve PC patient treatment. These findings will eventually provide guidance for future PC management and clinical trials and hopefully improve the survival of patients with PC.