Association between intra-pancreatic fat deposition and diseases of the exocrine pancreas: A narrative review

Intrapancreatic fat deposition(IPFD)has garnered increasing attention in recent years.The prevalence of IPFD is relatively high and associated with factors such as obesity,age,and sex.However,the pathophysiological mechanisms underlying IPFD remain unclear,with several potential contributing factors,including oxida-tive stress,alterations in the gut microbiota,and hormonal imbalances.IPFD was found to be highly correlated with the occurrence and prognosis of exocrine pan-creatic diseases.Although imaging techniques remain the primary diagnostic approach for IPFD,an expanding array of biomarkers and clinical scoring systems have been identified for screening purposes.Currently,effective treatments for IPFD are not available;however,existing medications,such as glucagon-like peptide-1 receptor agonists,and new therapeutic approaches explored in animal models have shown considerable potential for managing this disease.This paper reviews the pathogenesis of IPFD,its association with exocrine pancreatic disea-ses,and recent advancements in its diagnosis and treatment,emphasizing the significant clinical relevance of IPFD.

Role of pancreatic juice cytology in diagnosis of high-grade pancreatic intraepithelial neoplasia

High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.

Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Unraveling the landscape of pediatric pancreatic tumors:Insights from Japan

Pediatric pancreatic tumors,though rare,pose significant diagnostic and manage-ment challenges.The recent,22-year nationwide survey on pediatric pancreatic tumors in Japan by Makita et al offers valuable insights into this uncommon enti-ty,revealing striking geographical variations and questioning current treatment paradigms.This editorial commentary analyzes the study's key findings,inclu-ding the predominance of solid pseudopapillary neoplasms and their younger age of onset,which contrast sharply with Western data.It explores the implications for clinical practice and research,emphasizing the need for population-specific approaches to diagnosis and treatment.The revealed limited institutional expe-rience and surgical management patterns prompt a reevaluation of optimal care delivery for these complex cases,suggesting benefits of centralizing healthcare services.Furthermore,the commentary advocates for international collaborative studies to elucidate the genetic,environmental,and lifestyle factors influencing the development and progression of pediatric pancreatic tumors across diverse populations.It also outlines future directions,calling for advancements in precision medicine and innovative care delivery models to improve global patient outcomes.Unraveling Makita et al's findings within the broader landscape of pediatric oncology can stimulate further research and clinical advancements in managing pancreatic and other rare tumors in children.

Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.

Retrospective analysis of pathological types and imaging features in pancreatic cancer: A comprehensive study

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late diagnosis.Understanding the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment planning.AIM To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging features.METHODS We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2010 and December 2020 at our institution.Pathological types were determined by histopathological examination of the surgical spe-cimens or biopsy samples.The imaging features were assessed using computed tomography,magnetic resonance imaging,and endoscopic ultrasound.Statistical analyses were performed to identify significant associations between pathological types and specific imaging characteristics.RESULTS There were 320(64%)cases of pancreatic ductal adenocarcinoma,75(15%)of intraductal papillary mucinous neoplasms,50(10%)of neuroendocrine tumors,and 55(11%)of other rare types.Distinct imaging features were identified in each pathological type.Pancreatic ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography,whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural nodules.Neuroendocrine tumors often appear as hypervascular lesions in contrast-enhanced imaging.Statistical analysis revealed significant correlations between specific imaging features and pathological types(P<0.001).CONCLUSION This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging features.These findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.

Pancreatic stent improves the success rate of needle-knife papillotomy in patients with difficult biliary cannulation

BACKGROUND Needle-knife precut papillotomy(NKP)is typically performed freehand.However,it remains unclear whether pancreatic stent(PS)placement can improve the outcomes of NKP.AIM To explore whether PS placement improves the success rate of NKP in patients with difficult biliary cannulation.METHODS This single-center retrospective study included 190 patients who underwent NKP between January 2017 and December 2021 after failed conventional biliary cannulation.In cases with incidental pancreatic duct cannulation during conventional biliary cannulation,the decision for pre-NKP PS placement was made at the endoscopist's discretion.The primary outcome was the difference in the NKP success rate between patients with and without PS placement;the secondary outcome was the adverse event rate.RESULTS Among the 190 participants,82 received pre-NKP PS(PS-NKP group)whereas 108 did not[freehand or freehand NKP(FH-NKP)group].Post-NKP selective biliary cannulation was successful in 167(87.9%)patients,and the PS-NKP had a significantly higher success rate than the FH-NKP group(93.9%vs 83.3%,P=0.027).The overall adverse event rates were 7.3%and 11.1%in the PS-NKP and FH-NKP groups,respectively(P=0.493).A periampullary diverticulum(PAD)and significant intraoperative bleeding during NKP were independently associated with NKP failure;however,a pre-NKP PS was the only predictor of NKP success.Among the 44 participants with PADs,the PS-NKP group had a non-significantly higher NKP success rate than the FH-NKP group(87.5%and 65%,respectively;P=0.076).CONCLUSION PS significantly improved the success rate of NKP in patients with difficult biliary cannulation.

Molecular mechanism of pancreatic ductal adenocarcinoma:The heterogeneity of cancer-associated fibroblasts and key signaling pathways

Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.

Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer

Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.

Improving postoperative outcomes in patients with pancreatic cancer:Inflammatory and nutritional biomarkers

This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term outcomes.These biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk index.The PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.

Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.

Pancreatic cancer:Future challenges and new perspectives for an early diagnosis

This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

Phytochemical and anti-neuropathic investigations of Crocus sativus via alleviating inflammation, oxidative stress and pancreatic beta-cells regeneration

Objective:The aim of this study is to investigate the phytochemical and the long-term anti-neuropathic potentials of Crocus sativus cultivated in the University botanical garden,and explore its most bioactive compounds and their underlying mechanisms of action.Methods:Phytochemical analysis and bio-guided isolation-procedures including RP-HPLC and1 H and13 C NMR utilizing biological models of diabetes,inflammation,and diabetic-neuropathy were used.Cultivated saffron(S-RCED)and Spanish-saffron stigma(S-SP)alone or in combination with Camellia sinus(CS)were investigated.Results:The RP-HPLC analyses showed the presence of picrocrocin,crocin I,crocin II,crocin I’,crocin II’,and safranal(SAF)in both S-SP and S-RCED extracts with higher-concentrations.It had been shown that SAF was the most bioactive-compound in Crocus sativus.Both S-SP and S-RCED possessed significant(P<0.05)anti-diabetic activities in acute(6 h),subchronic(8 d)and chronic(8 weeks)models.S-RCED had been proven with more hypoglycemic potentials when compared to S-SP and SAF.S-SP,S-RCED,and SAF produced significant anti-inflammatory and anti-nociceptive activities against carrageenan-induced inflammatory,hyperalgesic and tactile diabetic-neuropathy models,respectively.S-SP,S-RCED,and SAF elevated serum catalase,reduced glutathione,and insulin serum levels,ameliorated lipid peroxidation and Hb A1 c levels,and histopathologically regenerated the pancreatic beta-cells.Combinations with CS showed more significant efficacy than the single component.Conclusion:The oxidative stress reduction,insulin secretagogue,and pancreatic beta-cells regeneration potentials might be responsible for the mechanism underlying the anti-diabetic,anti-inflammatory and anti-diabetic neuropathy activities.Thus,the cultivated Crocus sativus might be clinically useful for protecting against many serious-disorders.

Alterations of the Ca2＋ signaling pathway in pancreatic beta-cells isolated from db/db mice

Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2＋-dependent manner. In diabetic animal models, different aspects of the calcium signaling path- way in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca2＊ （[Ca2＊]~） via Ca2＋ influx, Ca2＊ mobilization from endoplasmic reticulum （ER） calcium stores, and the removal of Ca2＋ via multiple mechanisms in beta-cells from both diabetic db/db mice and non- diabetic C57BL/6J mice. We refined our previous quan- titative model to describe the slow [Ca2＋]i recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca2＋-ATPase （SERCA） pump, SERCA2 and SERCA3, were severely down-reg- ulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduc- tion in the Ca2＋ concentration in the ER, a compensatory up-regulation of the plasma membrane Na＋/Ca2＋ exchanger （NCX） and a reduction in depolarizationevoked Ca2＋ influx. As a result, the patterns of glucosestimulated calcium oscillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic beta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.

High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

Endoscopic intramural cystogastrostomy for treatment of peripancreatic fluid collection: A viewpoint from a surgeon

Percutaneous or endoscopic drainage is the initial choice for the treatment of peripancreatic fluid collection in symptomatic patients.Endoscopic transgastric fenestration(ETGF)was first reported for the management of pancreatic pseu-docysts of 20 patients in 2008.From a surgeon’s viewpoint,ETGF is a similar procedure to cystogastrostomy in that they both produce a wide outlet orifice for the drainage of fluid and necrotic debris.ETGF can be performed at least 4 wk after the initial onset of acute pancreatitis and it has a high priority over the surgical approach.However,the surgical approach usually has a better success rate because surgical cystogastrostomy has a wider outlet(>6 cm vs 2 cm)than ETGF.However,percutaneous or endoscopic drainage,ETGF,and surgical approach offer various treatment options for peripancreatic fluid collection patients based on their conditions.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Early prediction and prevention of infected pancreatic necrosis

Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal complication.Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes.In the past two decades,several markers and predictive tools have been proposed and evaluated for this purpose.Conventional biomarkers like C-reactive protein,procalcitonin,lymphocyte count,interleukin-6,and interleukin-8,and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN.On the other hand,scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested,and the results showed that they may provide better accuracy.For early prevention of IPN,several new therapies were tested,including early enteral nutrition,anti-biotics,probiotics,immune enhancement,etc.,but the results varied.Taken together,several evidence-supported predictive markers and scoring systems are readily available for predicting IPN.However,effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition.In this editorial,we summarize evidence concerning early prediction and prevention of IPN,providing insights into future practice and study design.A more homo-geneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN,thereby achieving individualized treatment.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.