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.

MiR-135a biogenesis and regulation in malignancy:a new hope for cancer research and therapy

MicroRNAs(miRNAs)are evolutionarily conserved small non-coding RNAs that affect posttranscriptional regulation by binding to the 3′-untranslated region of target messenger RNAs.MiR-135a is a critical miRNA that regulates gene expression,and many studies have focused on its function in cancer research.MiR-135a is dysregulated in various cancers and regulates cancer cell proliferation and invasionvia several signaling pathways,such as the MAPK and JAK2/STAT3 pathways.MiR-135a has also been found to promote or inhibit the epithelial-mesenchymal transition and chemoresistance in different cancers.Several studies have discovered the value of miR-135a as a novel biomarker for cancer diagnosis and prognosis.These studies have suggested the potential of therapeutically manipulating miR-135a to improve the outcome of cancer patients.Although these findings have demonstrated the role of miR-135a in cancer progression and clinical applications,a number of questions remain to be answered,such as the dual functional roles of miR-135a in cancer.In this review,we summarize the available studies regarding miR-135a and cancer,including background on the biogenesis and expression of miR-135a in cancer and relevant signaling pathways involved in miR-135a-mediated tumor progression.We also focus on the clinical application of miR-135a as a biomarker in diagnosis and as a therapeutic agent or target in cancer treatment,which will provide a greater level of insight into the translational value of miR-135a.

Pancreatic head cancer: Open or minimally invasive pancreaticoduodenectomy?

Pancreatic head cancer still represents an insurmountable barrier for patients and pancreatic surgeons.Pancreaticoduodenectomy(PD)continues to be the operative standard of care and potentially curative procedure for pancreatic head cancer.Despite the rapid development of minimally invasive techniques,whether the efficacy of minimally invasive pancreaticoduodenectomy(MIPD)is noninferior or superior to open pancreaticoduodenectomy(OPD)remains unclear.In this review,we summarized the history of OPD and MIPD and the latest staging and classification information for pancreatic head cancer as well as the proposed recommendations for MIPD indications for patients with pancreatic head cancer.By reviewing the MIPD-vs.OPD-related literature,we found that MIPD shows noninferiority or superiority to OPD in terms of safety,feasibility,enhanced recovery after surgery(ERAS)and several short-term and long-term outcomes.In addition,we analyzed and summarized the different MIPD outcomes in the USA,Europe and China.Certain debates over MIPD have continued,however,selection bias,the large number of low-volume centers,the steep MIPD learning curve,high conversion rate and administration of neoadjuvant therapy may limit the application of MIPD for pancreatic head cancer.

Current epidemiology of pancreatic cancer: Challenges and opportunities

Pancreatic cancer(PC) is an increasingly common disease worldwide. Having a better understanding of worldwide and regional epidemiologic features and risk factors of PC is essential to identify new approaches for prevention,early diagnosis, surveillance, and treatment. In this article, we review the epidemiologic features and risk factors for PC and discuss opportunities and challenges of PC future treatment.

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.

Analysis of clinical characteristics and treatment of pancreatic cystic tumors

Objective： To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms.Methods： This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations, radiologieal and pathological images and surgical recordings, were collected. Results： Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years. Malignancy was more common in older patients who presented with marasmus and jaundice. Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers. Surgical treatment was required when a malignant tumor was suspected. The operation approach was selected based on the location, size and characteristics of the tumor. The position of the tumor relative to the pancreatic duct also played a significant role.

Effect of K_(2)CO_(3) doping on CO_(2) sorption performance of silicate lithium-based sorbent prepared from citric acid treated sediment

In this paper,a low-cost and environmental-friendly leaching agent citric acid(C_(6)H_(8)O_(7))was used to treat the sediment of Dianchi Lake(SDL)to synthesize lithium silicate(Li_(4)SiO_(4))based CO_(2)sorbent.The results were compared with that treated with strong acid.Moreover,the effects of preparation conditions,sorption conditions and desorption conditions on the CO_(2)sorption performance of prepared Li_(4)SiO_(4)were systematically studied.Under optimal conditions,the Li_(4)SiO_(4)sorbent was successfully synthesized and its CO_(2)sorption capacity reached 31.37%(mass),which is much higher than that synthesized from SDL treated with strong acid.It is speculated that the presence of some elements after C_(6)H_(8)O_(7)treatment may promote the sorption of synthetic Li_(4)SiO_(4)to CO_(2).In addition,after doping with K_(2)CO_(3),the CO_(2)uptake increases from the original 12.02%and 22.12%to 23.96%and 32.41%(mass)under the 20%and 50%CO_(2)partial pressure,respectively.More importantly,after doping K_(2)CO_(3),the synthesized Li_(4)SiO_(4)has a high cyclic stability under the low CO_(2)partial pressure.

Current status of minimally invasive surgery for pancreatic cancer

Pancreatic cancer(PC)is the most lethal cancer among digestive system cancers.Although the only way to radically cure PC is surgical resection,complex surgical procedures and severe post-operative complications lead to high mortality.In recent years,minimally invasive surgery has become more common for PC.Minimally invasive pancreatic resection(MIPR)with the laparoscopic or robotic method has shown its superiority compared with traditional surgery.However,increasing evidence indicates that the long-term or even short-term outcomes of MIPR for PC patients remain controversial.Moreover,the indications and learning curve of MIPR require further assessment.This review aims to discuss the progress in current MIPR,analyze the specific problems and obstacles in the development of MIPR,and try to standardize MIPR procedures and improve the outcomes of MIPR.

Surgical treatment of pancreatic head cancer: concept revolutions and arguments

As we have a deeper and more thorough understanding of the biological behavior of pancreatic head cancer, surgical treatment concepts of this lethal disease are changing all the time. Meanwhile, numerous arguments emerge. Thus, we will probe into the focuses and arguments in the surgical treatment of pancreatic head cancer in this article, including the scope of lymphadenectomy, total mesopancreas excision（TMp E）, vascular resection, minimally invasive pancreaticoduodenectomy（PD）, palliative resection, surgery for recurrent disease and surgery for primary pancreatic cancer and liver metastasis.

The crown jewelry of the surgeries for pancreatic cancer

We are very pleased to organize this issue of Chinese Journal of Cancer Research.Authors come from the most distinguished groups of pancreatic cancer surgeons and oncologists in China and in USA.The first two articles make overviews on the historic and contemporary progresses in surgical management of pancreatic cancer.

Minimally invasive pancreatic surgery:An upward spiral

Minimally invasive techniques have been widely applied in general surgery for decades,but the generalization in pancreatic resection underwent a hard process for the complexity of the procedure.The current studies suggested that the safety and feasibility of minimally invasive pancreatic surgery(MIPS)were approximately equivalent to that of open surgery,but the overall benefit and the oncological outcomes of MIPS remained to be verified.Inferior outcomes were observed in the initial learning curve phase and low-volume hospitals,thus establishing a program that can well assess the learning process and minimize the harm to patients was essential.To ensure safety,the patients should be strictly selected in the early phase of the learning curve,and a careful and judicious stepwise should be considered to broaden the indications.

Pancreatic ductal adenocarcinoma chemoresistance:From metabolism reprogramming to novel treatment

As pancreatic cancer(PC)is highly malignant,its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies.First-line chemotherapies for PC,according to current guidelines,include fluoropyrimidine-and gemcitabine-based regimens.Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC,especially those involving glycolysis and glutamine metabolism,are highly associated with chemoresistance.Additionally,lipid metabolism is a major factor in chemoresistance.However,emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance.This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

Pancreatic cystic neoplasms(PCNs)are recognized as precursor lesions of pancreatic cancer,with a marked increase in prevalence.Early detection of malignant PCNs is crucial for improving prognosis;however,current diagnostic methods are insufficient for accurately identifying malignant PCNs.Here,we utilized mass spectrometry(MS)-based glycosite-and glycoform-specific glycoproteomics,combined with proteomics,to explore potential cyst fluid diagnostic biomarkers for PCN.The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated,and its characteristics during the malignant transformation of PCN were analyzed.Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN,a group of cyst fluid glycoprotein biomarkers was identified.Through parallel reaction monitoring(PRM)-based targeted glycoproteomic analysis,we validated these chosen glycoprotein biomarkers in a second cohort,ultimately confirming N-glycosylated PHKB(Asn-935,H5N2F0S0;Asn-935,H4N4F0S0;Asn-935,H5N4F0S0),CEACAM5(Asn-197,H5N4F0S0)and ATP6V0A4(Asn-367,H6N4F0S0)as promising diagnostic biomarkers for distinguishing malignant PCNs.These glycoprotein biomarkers exhibited robust performance,with an area under the curve ranging from 0.771 to 0.948.In conclusion,we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN.These findings hold significant clinical implications,providing valuable insights for PCN decision-making,and potentially offering therapeutic targets for PCN treatment.

Network prediction of surgical complication clusters:a prospective multicenter cohort study

Complicated relationships exist in both occurrence and progression of surgical complications,which are difficult to account for using a separate quantitative method such as prediction or grading.Data of 51,030 surgical inpatients were collected from four academic/teaching hospitals in a prospective cohort study in China.The relationship between preoperative factors,22 common complications,and death was analyzed.With input from 54 senior clinicians and following a Bayesian network approach,a complication grading,cluster-visualization,and prediction(GCP)system was designed to model pathways between grades of complication and preoperative risk factor clusters.In the GCP system,there were 11 nodes representing six grades of complication and five preoperative risk factor clusters,and 32 arcs representing a direct association.Several critical targets were pinpointed on the pathway.Malnourished status was a fundamental cause widely associated(7/32 arcs)with other risk factor clusters and complications.American Society of Anesthesiologists(ASA)score≥3 was directly dependent on all other risk factor clusters and influenced all severe complications.Grade III complications(mainly pneumonia)were directly dependent on4/5 risk factor clusters and affected all other grades of complication.Irrespective of grade,complication occurrence was more likely to increase the risk of other grades of complication than risk factor clusters.

Fano resonance-enhanced Si/MoS_(2) photodetector

In this work,a Si∕MoS_(2) heterojunction photodetector enhanced by hot electron injection through Fano resonance is developed.By preparing Au oligomers using capillary-assisted particle assembly(CAPA)on the silicon substrate with a nanohole array and covering few-layer MoS_(2) with Au electrodes on top of the oligomer structures,the Fano resonance couples with a Si∕MoS_(2) heterojunction.With on-resonance excitation,Fano resonance generated many hot electrons on the surface of oligomers,and the hot electrons were injected into MoS_(2),providing an increased current in the photodetector under a bias voltage.The photodetectors exhibited a broadband photoresponse ranging from 450 to 1064 nm,and a large responsivity up to 52 A/W at a wavelength of 785 nm under a bias voltage of 3 V.The demonstrated Fano resonance-enhanced Si∕MoS_(2) heterojunction photodetector provides a strategy to improve the photoresponsivity of two-dimensional materials-based photodetectors for optoelectronic applications in the field of visible and near-infrared detection.

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

Pancreatic ductal adenocarcinoma(PDAC)has poor prognosis due to limited therapeutic options.This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets.We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness.HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4.Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC(log-rank P=0.036;HR=1.60,95%CI=1.03–2.47).We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.Furthermore,Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC(log-rank P=0.022;HR=0.31,95%CI=0.14–0.68)but not in patients with SMAD4-normal PDAC.Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway.These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

International expert consensus on laparoscopic pancreaticoduodenectomy

Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for LPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane Library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD.LPD is currently in its development and exploration stages,as defined by the international IDEAL framework for surgical innovation.More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.

Integrated analysis of gene expression and methylation profiles of novel pancreatic cancer cell lines with highly metastatic activity

Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, highly metastatic human pancreatic cancer cell lines suitable for studies of metastasis are currently lacking. Here we established two highly metastatic human pancreatic cancer cell lines, MIA PaCa-2 In8 and Panc-1 In8, by Matrigel induction assay. The cell lines were further characterized both in vitro and in vivo. MIA PaCa-2 In8 and Panc-1 In8 cells demonstrated increased migration and invasion compared with their respective parental cells. Following injection into nude mice, MIA PaCa-2 In8 and Panc-1 In8 cells resulted in more pulmonary metastases compared with the parental cells. Furthermore, analyses of m RNA, long non-coding RNA, micro RNA, and methylation profiling revealed that these factors were aberrantly regulated in the highly metastatic cells,indicating that they probably affected metastasis. We thus established and characterized two highly metastatic human pancreatic cell lines that could be used as valuable tools for future investigations into the pathogenesis, metastasis, and potential treatment of human pancreatic cancer.

The Chinese guidelines for neoadjuvant therapy of pancreatic cancer(2020)

Aiming to keep pace with the renewal of international guidelines and refine the domestic treatment system of pancreatic cancer,the Chinese Pancreatic Surgery Association,Chinese Medical Association and Pancreatic Disease Committee of China Research Hospital Association launched this Chinese guidelines for neoadjuvant therapy of pancreatic cancer(2020 edition).Based on the Grading of Recommendations Assessment,Development,and Evaluation system,the guidelines have conducted a discussion on the indication,regimen selection,therapeutic effect evaluation,pathological diagnosis,surgery strategy,etc.The guidelines have quantified the evidence level of the current clinical researches and provided recommendations for the clinical practice in neoadjuvant therapy of pancreatic cancer.The guidelines have highlighted the role of multiple disciplinary team and represented the conversion of treatment concepts in pancreatic cancer.Neoadjuvant therapy has prolonged the survival of part of pancreatic cancer patients.However,more high-quality clinical researches are in urgent need to improve the level of evidence,optimize the clinical practice,and improve the survival of patients.