Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

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.

Pathophysiology of severe gallstone pancreatitis:A new paradigm

Severe gallstone pancreatitis(GSP)refractory to maximum conservative therapy has wide clinical variations,and its pathophysiology remains controversial.This Editorial aimed to investigate the pathophysiology of severe disease based on Opie’s theories of obstruction,the common channel,and duodenal reflux and describe its types.Severe GSP might be a hybrid disease with pathology polarized between acute cholangitis with mild pancreatitis(biliary type)and necrotizing pancreatitis uncomplicated with biliary tract disease(pancreatic type),in which hepatobiliary and pancreatic lesion severity is inversely related to the presence or absence of impacted ampullary stones.Severe GSP is caused by stones that are persistently impacted at the ampulla with biliopancreatic obstruction(biliary type),and probably,stones that are either temporarily lodged at the duodenal orifice or passed into the duodenum,thereby permitting reflux of bile or possible duodenal contents into the pancreas(pancreas type).When the status of the stones and the presence or absence of impacted ampullary stones with biliopancreatic obstruction are determined,the clinical course and outcome can be predicted.Gallstones represent the main cause of acute pancreatitis globally,and clinicians are expected to encounter GSP more often.Awareness of the etiology and pathogenesis of severe disease is mandatory.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

A Deep Learning Framework forMass-Forming Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma Classification Based on Magnetic Resonance Imaging

Pancreatic diseases, including mass-forming chronic pancreatitis (MFCP) and pancreatic ductal adenocarcinoma(PDAC), present with similar imaging features, leading to diagnostic complexities. Deep Learning (DL) methodshave been shown to perform well on diagnostic tasks. Existing DL pancreatic lesion diagnosis studies basedon Magnetic Resonance Imaging (MRI) utilize the prior information to guide models to focus on the lesionregion. However, over-reliance on prior information may ignore the background information that is helpful fordiagnosis. This study verifies the diagnostic significance of the background information using a clinical dataset.Consequently, the Prior Difference Guidance Network (PDGNet) is proposed, merging decoupled lesion andbackground information via the Prior Normalization Fusion (PNF) strategy and the Feature Difference Guidance(FDG) module, to direct the model to concentrate on beneficial regions for diagnosis. Extensive experiments inthe clinical dataset demonstrate that the proposed method achieves promising diagnosis performance: PDGNetsbased on conventional networks record an ACC (Accuracy) and AUC (Area Under the Curve) of 87.50% and89.98%, marking improvements of 8.19% and 7.64% over the prior-free benchmark. Compared to lesion-focusedbenchmarks, the uplift is 6.14% and 6.02%. PDGNets based on advanced networks reach an ACC and AUC of89.77% and 92.80%. The study underscores the potential of harnessing background information in medical imagediagnosis, suggesting a more holistic view for future research.

Portal Venous Thrombosis and Splenic Hemangioma, Secondary to Acute Pancreatitis: Case Report

We present an unusual case of portal vein thrombosis with a splanchnic hemangioma secondary to acute biliary pancreatitis. We report a 45-year-old patient, who has systemic arterial hypertension in treatment, was admitted for abdominal pain in the epigastrium, with irradiation to the right hypochondrium, accompanied by nausea and vomiting of 10 occasions of bile content, physical examination with pain in the right hypochondrium, Murphy positive. We have laboratory studies with a lipase of 788, so a diagnosis of pancreatitis is made with an etiology to be determined. The laboratories suggestive of acute biliary pancreatitis (lipase 788.71);an imaging study was subsequently performed (ultrasonography) with the result of stone in the common bile duct. A laparoscopy was performed with relative improvement, so he was discharged and returned 20 days after surgery due to abdominal pain of the same intensity in the left hypochondrium. Ending his hospitalization with a splenectomy for splenic hemangioma with portal vein thrombosis.

Innovative pathways allow safe discharge of mild acute pancreatitis from the emergency room

Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Progress in the Study of Laboratory Indicators Related to Acute Pancreatitis

Acute pancreatitis (AP) is one of the more common gastrointestinal diseases in clinics and is characterized by rapid progression, many complications, and high mortality. When it develops into severe pancreatitis, its prognosis is poor. Therefore, early assessment of the degree of inflammatory response plays a crucial role in the treatment plan and prognosis of patients. More and more studies have shown that the levels of D-dimer (D-D), angiotensin-2 (Ang-2), phosphate, heparin-binding protein (HBP), retinol-binding protein-4 (RBP4), and osteoblastic protein (OPN) are closely related to the severity of acute pan-creatitis and can be used as effective indicators for early assessment of AP. In this paper, the research progress of the above indicators in assessing the severity of AP is summarized.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Chronic pancreatitis:Pain and computed tomography/magnetic resonance imaging findings

Chronic pancreatitis(CP)is a fibroinflammatory disease characterized by irreversible destruction of pancreatic tissue.With the development of the disease,it may lead to exocrine and/or endocrine insufficiency.CP is one of the common diseases that cause abdominal pain,which will not get permanent spontaneous relief as the disease evolves.The American College of Gastroenterology clinical guidelines recommend computed tomography or magnetic resonance imaging as the first-line examination for the diagnosis of CP.CP common imaging findings include pancreatic atrophy,irregular dilatation of the pancreatic duct,calcification of pancreatic parenchyma,pancreatic duct stones,etc.In clinical practice,whether any correlations between CP-induced abdominal pain patterns(no pain/constant/intermittent pain)and corresponding imaging findings present are not well known.Therefore,this review aims to comprehensively sort out and analyze the relevant information by collecting lots of literature on this field,so as to construct a cross-bridge between the clinical manifestations and imaging manifestations of CP patients.Also,it provides an imaging basis and foundation for the classification and diagnosis of abdominal pain types in clinical CP patients.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis

BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.

Anemarsaponin B mitigates acute pancreatitis damage in mice through apoptosis reduction and MAPK pathway modulation

Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.Anemarsaponin B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP treatment.Methods:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical genes.Additionally,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on AP.Results:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably lower.Treatment with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum findings.Hematoxylin and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to ASB.Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model.Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP model.Furthermore,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species.The combined metabolome and microbiome analysis suggested an association between certain microbes(e.g.,unclassified-Saprospiraceae and unclassified-Micavibrionales)and metabolites(e.g.,LysoPE(0:0/20:0),PC(DiMe(13,5)/PGJ2)),and Heptanoic acid,indicating potential pathways through which ASB may exert its therapeutic effects in AP.Conclusions:ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide(LPS),primarily through modulating the mitogenactivated protein kinase(MAPK)signaling pathway.This discovery offers fresh perspectives for AP drug development,underscoring the potential of targeting specific cellular pathways.Additionally,the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets,suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management.These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation.

Clinical efficacy and safety of erlotinib combined with chemotherapy in the treatment of advanced pancreatic cancer:A meta-analysis

BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.

Early selective enteral feeding in treatment of acute pancreatitis: A case report

BACKGROUND Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis.However,the method of adminis-tration of enteral nutrition remains debatable.We present the experience of treating a patient with moderate-severe acute pancreatitis,at high risk of progressing to a severe or fatal condition,using a novel method of selective feeding with duodenal isolation.CASE SUMMARY A 27-year-old female patient presented to the emergency unit of the hospital with a typical manifestation of acute pancreatitis.Despite a conventional treatment,the patient’s condition deteriorated by day 2 of hospitalization.Using an endoscopic approach,a novel catheter PandiCathffwas placed to the duodenum of the patient,isolating its segment between the duodenal bulb and the ligament of Treitz.In the isolated area created,a negative pressure was applied,followed by introduction of early selective enteral feeding.The patient’s condition subsequently improved in a rapid manner,and no complications often associated with moderate-to-severe acute pancreatitis developed.CONCLUSION Within 48 h of starting treatment with the novel method,it can prevent the development of multiple organ failure and,when combined with minimally invasive drainage methods,help prevent infection.

Extended survival with metastatic pancreatic cancer under fruquintinib treatment after failed chemotherapy:Two case reports

BACKGROUND Pancreatic cancer is a highly malignant disease.After decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more limited.Anti-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic cancer.Preclinical data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune microenvironment.CASE SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 months.Patient 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 months.Moreover,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was observed.The patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)infection.The patient died in February 2023.Patient 2 also took two prior lines of chemotherapy and then local radiotherapy combined with S-1.After confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third line.After the patient had COVID-19 in December 2022,fruquintinib was discontinued.The patient died in January 2023 due to disease progression.CONCLUSION Both cases achieved a PFS benefit from later-line single-agent fruquintinib therapy.With its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.