Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Identification of breath volatile organic compounds to distinguish pancreatic adenocarcinoma,pancreatic cystic neoplasm,and patients without pancreatic lesions

BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Surgical management of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.

Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients

BACKGROUND Pancreatic mucinous cystic neoplasms(MCNs)represent one of the precursor lesions of pancreatic ductal adenocarcinoma,and their detection has been facilitated by advances in preoperative imaging.Due primarily to the rarity of MCNs,however,there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation.A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes.AIM To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma(MCNAIC).METHODS All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed.Only cases with ovarian-type stroma verified by progesterone receptor staining were included.Preoperative features,histological findings and postoperative course were documented.Multivariate logistic regression was employed to investigate variables related to malignancy.Survival analysis was performed using the Kaplan-Meier curve,and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC.RESULTS Among the 48 patients,36 had benign MCNs,and 12 had malignant MCNs(1 high-grade atypical hyperplasia and 11 MCN-AIC).Age,tumour size,presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy.The follow-up period ranged from 12 mo to 120 mo,with a median overall survival of 58.2 mo.Only three patients with MCN-AIC died,and the 5-year survival rate was 70.1%.All 11 cases of MCN-AIC were stage I,and extracapsular invasion was identified as a prognostic factor for poorer outcomes.CONCLUSION The risk factors independently associated with malignant transformation of MCNs included age,tumour size,presence of solid components or mural nodules,and pancreatic duct dilatation.Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.

Pancreatic cystic neoplasms:a comprehensive approach to diagnosis and management

Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.

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.

Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.

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.

Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge

Diagnosing early-stage pancreatic cancer(PC)remains a clinical challenge.Hence,studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative.This article aims to un-derscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC,thereby improving its management and prognosis.

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.

Early detection of pancreatic cancer

The diagnosis of pancreatic cancer associates an appalling significance.Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly disease.Premalignant lesions such as Intraductal Papillary Mucinous Neoplasms or Mucinous Cystic Neoplasms of the pancreas are detectable on imaging exams and this permits their management prior their invasive development.Pancreatic intraepithelial neoplasms(PanIN)are the most frequent precursors of pancreatic adenocarcinoma(PDAC),and its particular type PanIN high-grade represents the malignant non-invasive form of PDAC.Unfortunately,PanINs are not detectable on radiologic exams.Nevertheless,they can associate indirect imaging signs which would rise the diagnostic suspicion.When this suspicion is established,the patient will be enrolled in a follow-up strategy that includes performing of blood test and serial imaging test such as computed tomography or magnetic resonance imaging,which will cost in the best-case scenario a burden of healthcare systems,and potential mortality in the worst-case scenario when the patient underwent resection surgery,worthless when there is no moderate or high grade dysplasia in the final histopathology.This issue will be avoid having at its disposal a diagnostic technique capable of detecting high-grade PanIN lesions,such is the cytology of pancreatic juice obtained by nasopancreatic intubation.Herein,we review the possibility of detection of early malignant lesions before they become invasive PADC.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria

BACKGROUND Traditional treatments for pancreatic cancer(PC)are inadequate.Photodynamic therapy(PDT)is non-invasive,and proven safe to kill cancer cells,including PC.However,the mitochondrial concentration of the photosensitizer,such as verteporfin,is key.AIM To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs,post-PDT.METHODS Workable survival rates of PC cells(AsPC-1,BxPC-3)were determined with chemotherapy[doxorubicin(DOX)and gemcitabine(GEM)]and non-chemotherapy[sirolimus(SRL)and cetuximab(CTX)]drugs in vitro,with or without verteporfin,as measured via MTT,flow cytometry,and laser confocal microscopy.Reduced cell proliferation was associated with GEM that was more enduring compared with DOX.Confocal laser microscopy allowed observation of GEM-and verteporfin-treated PC cells co-stained with 4’,6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin,respectively.RESULTS Cell survival significantly dropped upon exposure to either chemotherapy drug,but not to SRL or CTX.Both cell lines responded similarly to GEM.The intensity of fluorescence was associated with the concentration of verteporfin.Additional experiments using GEM showed that survival rates of the PC cells treated with 10μmol/L verteporfin(but not less)were significantly lower relative to nil verte-porfin.Living and dead stained cells treated with GEM were distinguishable.After GEM treatment,verteporfin was observed primarily in the mitochondria.CONCLUSION Verteporfin was observed in living cells.In GEM-treated human PC cells,verteporfin was particularly prevalent in the mitochondria.This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.

Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy

Background:Patients with pancreatic ductal adenocarcinoma(PDAC)who undergo surgical resection and receive effective chemotherapy have the best chance for longterm survival.Unfortunately,because of the heterogeneity of pancreatic cancer,it is difficult to find a personalized treatment strategy for patients.Organoids are ideal preclinical models for personalized medicine.Therefore,we explore the cultivation conditions and construction methods of PDAC organoid models to screen the individualized therapy strategy.Methods:Fresh PDAC tissues from surgical resection were collected and digested with digestive enzymes;then the tumor cells were embedded in Matrigel with a suitable medium to establish the PDAC organoid models.The genetic stability of the organoids was analyzed using whole exon sequencing;hematoxylin and eosin staining and immunohistochemistry of organoids were performed to analyze their consistency with the pathological morphology of the patient's tumor tissue;After 2 days of organoid culture,we selected four commonly used clinical chemotherapy drugs for single or combined treatment to analyze drug sensitivity.Results:Two cases of PDAC organoid models were successfully established,and the results of their pathological characteristics and exome sequencing were consistent with those of the patient's tumor tissue.Both PDAC organoids showed more sensitivity to gemcitabine and cisplatin,and the combined treatment was more effective than monotherapy.Conclusion:Both organoids better retained the pathological characteristics,genomic stability,and heterogeneity with the original tumor.Individual PDAC organoids exhibited different sensitivities to the same drugs.Thus,this study provided ideal experimental models for screening individualized therapy strategy for patients with PDAC.

Personalized pancreatic cancer therapy:from the perspective of mRNA vaccine

Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.

Recent advances in targeted therapy for pancreatic adenocarcinoma

Pancreatic adenocarcinoma(PDAC)is a fatal disease with a 5-year survival rate of 8%and a median survival of 6 mo.In PDAC,several mutations in the genes are involved,with Kirsten rat sarcoma oncogene(90%),cyclin-dependent kinase inhibitor 2A(90%),and tumor suppressor 53(75%–90%)being the most common.Mothers against decapentaplegic homolog 4 represents 50%.In addition,the selfpreserving cancer stem cells,dense tumor microenvironment(fibrous accounting for 90%of the tumor volume),and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC.Molecular targeted therapy is widely utilized and effective in several solid tumors.In PDAC,targeted therapy has been extensively evaluated;however,survival improvement of this aggressive disease using a targeted strategy has been minimal.There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC–erlotinib,but the absolute benefit of erlotinib in combination with gemcitabine is also minimal(2 wk).In this review,we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process,analyze possible reasons for the lack of positive results in clinical trials,and suggest ways to improve them.We also discuss emerging trends in targeted therapies for PDAC:combining targeted inhibitors of multiple pathways.The PubMed database and National Center for Biotechnology Information clinical trial website(www.clinicaltrials.gov)were queried to identify completed and published(PubMed)and ongoing(clinicaltrials.gov)clinical trials(from 2003-2022)using the keywords pancreatic cancer and targeted therapy.The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.

Percutaneous transhepatic intraportal biopsy using gastroscope biopsy forceps for diagnosis of a pancreatic neuroendocrine neoplasm:A case report

BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA),these approaches may be impeded by gastric varices,poor access windows,or anatomically contiguous critical structures.Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported.CASE SUMMARY A 72-year-old man was referred to our hospital for abdominal pain and melena.Abdominal contrast-enhanced magnetic resonance imaging revealed a wellenhanced tumor(size:2.4 cm×1.2 cm×1.2 cm)in the pancreatic tail with portal vein invasion.Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices.We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps.Histopathologic examination revealed a pancreatic neuroendocrine neoplasm(G2)with somatostatin receptors 2(+),allowing systemic treatment.CONCLUSION Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis.Although welldesigned clinic trials are required to obtain more definitive evidence,this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.

Rapid transformation of branched pancreatic duct-derived intraductal tubulopapillary neoplasm into an invasive carcinoma: A case report

BACKGROUND Intraductal tubulopapillary neoplasm(ITPN)is a rare disease accounting for approximately 3%of all intraductal pancreatic tumors,with intraductal papillary mucinous neoplasm(IPMN)being one of the most common differential diagnoses.Both ITPN and IPMN display slow growth.A branched pancreatic duct type is commonly observed in IPMN,whereas ITPN derived from the branched pancreatic duct has been reported in a limited number of cases;hence,its pathogenesis remains unclear.CASE SUMMARY Here,we present the case of a patient with ITPN localized in a branched pancreatic duct,with poorly controlled irritable bowel syndrome.A contrastenhanced computed tomography scan of the abdomen incidentally revealed a 5-mm oligemic nodule-like change in the body of the pancreas.Endoscopic ultrasound(EUS)indicated a 10-mm hypoechoic mass without any cystic structures that had grown within 2 mo.EUS-guided fine needle aspiration was performed for definitive diagnosis,and the findings suggested ductal papillary carcinoma.Distal pancreatectomy was performed,and the tumor was pathologically diagnosed as ITPN with an invasive cancerous component,pT3N1aM0,pStage IIB(International Cancer Control,8^(th) edition).The patient underwent treatment with postoperative adjuvant chemotherapy(S-1 monotherapy);however,relapse was observed 1 year and 10 mo after surgical resection,and subsequent treatment involving a combination of chemotherapy and radiotherapy was administered.Maintenance therapy has since facilitated a stable disease state.CONCLUSION Regardless of the microscopic size of the neoplasm,early diagnosis of ITPN with EUS-guided fine needle aspiration and surgical resection are crucial.