Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

Etiology, Pathology, Management and Prognosis of Chronic Pancreatitis in Chinese Population: A Retrospective Study

The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis（50.70%）, 19 cases of alcoholic chronic pancreatitis（13.38%）, 14 cases of autoimmune pancreatitis（9.86%） and 37 cases of undetermined etiology（26.06%）. Pathologically, the average inflammatory mass diameter was 3.8±3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head（n=97）, neck（n=16）, body（n=12）, tail（n=15） and whole pancreas（n=2） influenced the choice of surgical procedures. Ninety-four patients（66.20%） received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer（QLQ-C30） a decrease from 76±22 to 14±18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.

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.

Visceral adipose tissue predicts severity and prognosis of acute pancreatitis in obese patients

Acute pancreatitis is a common systemic inflammatory disease, manifested by a spectrum of severity, ranging from mild in the majority of patients to severe acute pancreatitis. Patients with severe acute pancreatitis suffer from severe local and systemic complications and organ failure, leading to a poor prognosis. The early recognition of the severe condition is important to improve prognosis. Obesity has risen in tandem with an increase in the severity of acute pancreatitis in recent years. Studies have revealed that adipose tissue, particularly visceral adipose tissue is associated with the prognosis of acute pancreatitis. This review discussed the role of visceral adipose tissue in obese patients with acute pancreatitis and explored the possible mechanism involved.

Pathological changes at early stage of multiple organ injury in a rat model of severe acute pancreatitis

BACKGROUND: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal syndrome characterized by sudden onset, rapid progression and high mortality rate. The damage in peripheral organs may be more severe than that in the pancreas, and can even lead to multiple organ dysfunction. It is critical to recognize early pathological changes in multiple organs. This study aimed to assess the early pathological features of damaged organs in a rat model of SAP. METHODS: Thirty clean grade healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into a model control group (n=15) and a sham-operated group (n=15). The SAP rat model was induced by sodium taurocholate. Samples of blood and from multiple organs were collected 3 hours after operation. We assessed the levels of IL-6, TNF-alpha, PLA2, NO, ET-1, MDA, amylases and endotoxin in blood and observed the early pathological changes in multiple damaged organs. RESULTS: Levels of IL-6, TNF-alpha, PLA2, NO, ET-1 and MDA in serum and of amylase and endotoxin in plasma of the model control group rats were significantly higher than those of the sham-operated group (P<0.01). Different degrees of pathological change were observed in multiple damaged organs. CONCLUSION: Multiple organ injury may occur at the early stage of SAP in rats.

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.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

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.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

Implementation of gastrointestinal function protection in severe acute pancreatitis

Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone to exhibit gastrointestinal dysfunction.Meanwhile,gastrointestinal dysfunction further aggravates the systemic inflammatory response and metabolic abnormalities,resulting in a more critical condition of SAP.Gastrointestinal dysfunction is considered to be the“trigger”of multiple organ dysfunction syndrome[1].Thus,it is important to maintain gastrointestinal homeostasis in the treatment of SAP.

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.

Clinical and pathological differences between serum immunoglobulin G4-positive and -negative type 1 autoimmune pancreatitis

AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea. METHODS: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student's t test, Fischer's exact test and Mann-Whitney's U test. A P value of < 0.05 was considered statistically significant. As repeated com- parison was made, P values of less than 5% (P < 0.05) were considered significant. RESULTS: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequent- ly associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02). CONCLUSION: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Pathological changes in multiple organs of rats with severe acute pancreatitis treated by baicalin and octreotide

BACKGROUND: Severe acute pancreatitis (SAP) features fatal pathogenetic conditions and high mortality rate. The study of SAP complicated with multiple organ injuries is of important significance. In this study, we explored the protective effect of baicalin on multiple organs of SAP rats and compared it with that of octreotide through light and electron microscopic observations of the pathological changes. METHODS: The improved Aho method was used to prepare SAP rat models. These rats were then randomly divided into a sham-operated group (n=45), a model control group (n=45), baicalin-treated group (n=45) and octreotide-treated group (n=45). Based on the difference in time points after operation, these groups were subdivided into 3, 6 and 12 hour subgroups (n=15). At the corresponding time point after operation, the mortality rate of rats was recorded, and then the rats were humanely killed to take samples of multiple organs that were subsequently examined for pathological changes under light and electron microscopy. RESULTS: At 12 hours after operation, the mortality rate of rats in the baicalin- and octreotide-treated groups was lower than that in the model control group (P < 0.05). Compared to the model control group, the pathological changes and pathological scores in the baicalin- and octreotide-treated groups were mitigated and relieved to varying degrees. The pathological changes under electron microscopy were also improved. CONCLUSIONS: Both baicalin and octreotide show good protective effects on multiple organs of SAP rats. Baicalin as a new drug has good prospects in the treatment of SAP.

Pathology of pancreatic ductal adenocarcinoma:Facts,challenges and future developments

Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic and clinical medicine,has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition,by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC,a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC.This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results.Finally,recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response.The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.

Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis

BACKGROUND The incidence of hypertriglyceridemia(HTG)-induced acute pancreatitis(AP)is steadily increasing in China,becoming the second leading cause of AP.Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies.HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components.However,the impact of metabolic syndrome components on HTGAP clinical outcomes remains unclear.AIM To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP.METHODS In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University,we collected data on patient demographics,clinical scores,complications,and clinical outcomes.Subsequently,we analyzed the influence of the presence and number of individual metabolic syndrome components,including obesity,hyperglycemia,hypertension,and low high-density lipoprotein cholesterol(HDL-C),on the aforementioned parameters in HTG-AP patients.RESULTS This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP,with low HDL-C being the most significant risk factor for clinical outcomes.The risk of complications increased with the number of metabolic syndrome components.Adjusted for age and sex,patients with highcomponent metabolic syndrome had significantly higher risks of renal failure[odds ratio(OR)=3.02,95%CI:1.12-8.11)],SAP(OR=5.05,95%CI:2.04-12.49),and intensive care unit admission(OR=6.41,95%CI:2.42-16.97)compared to those without metabolic syndrome.CONCLUSION The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTGAP,making it crucial to monitor these components for effective disease management.

Tissue microarrays in pathological examination of apoptotic acinar cells induced by dexamethasone in the pancreas of rats with severe acute pancreatitis

BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response. to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy, efficiency and highly representative.

Different timing for abdominal paracentesis catheter placement and drainage in severe acute pancreatitis complicated by intraabdominal fluid accumulation

BACKGROUND Non-surgical methods such as percutaneous drainage are crucial for the treatment of patients with severe acute pancreatitis(SAP).However,there is still an ongoing debate regarding the optimal timing for abdominal paracentesis catheter place-ment and drainage.AIM To explore the influence of different timing for abdominal paracentesis catheter placement and drainage in SAP complicated by intra-abdominal fluid accumu-lation.METHODS Using a retrospective approach,184 cases of SAP complicated by intra-abdominal fluid accumulation were enrolled and categorized into three groups based on the timing of catheter placement:group A(catheter placement within 2 d of symptom onset,n=89),group B(catheter placement between days 3 and 5 after symptom onset,n=55),and group C(catheter placement between days 6 and 7 after symptom onset,n=40).The differences in progression rate,mortality rate,and the number of cases with organ dysfunction were compared among the three groups.RESULTS The progression rate of group A was significantly lower than those in groups B and groups C(2.25%vs 21.82%and 32.50%,P<0.05).Further,the proportion of patients with at least one organ dysfunction in group A was significantly lower than those in groups B and groups C(41.57%vs 70.91%and 75.00%,P<0.05).The mortality rates in group A,group B,and group C were similar(P>0.05).At postoperative day 3,the levels of C-reactive protein(55.41±19.32 mg/L vs 82.25±20.41 mg/L and 88.65±19.14 mg/L,P<0.05),procalcitonin(1.36±0.51 ng/mL vs 3.20±0.97 ng/mL and 3.41±0.98 ng/mL,P<0.05),tumor necrosis factor-alpha(15.12±6.63 pg/L vs 22.26±9.96 pg/L and 23.39±9.12 pg/L,P<0.05),interleukin-6(332.14±90.16 ng/L vs 412.20±88.50 ng/L and 420.08±87.65ng/L,P<0.05),interleukin-8(415.54±68.43 ng/L vs 505.80±66.90 ng/L and 510.43±68.23ng/L,P<0.05)and serum amyloid A(270.06±78.49 mg/L vs 344.41±81.96 mg/L and 350.60±80.42 mg/L,P<0.05)were significantly lower in group A compared to those in groups B and group C.The length of hospital stay in group A was significantly lower than those in groups B and group C(24.50±4.16 d vs 35.54±6.62 d and 38.89±7.10 d,P<0.05).The hospitalization expenses in group A were also significantly lower than those in groups B and groups C[2.70(1.20,3.55)ten-thousand-yuan vs 5.50(2.98,7.12)ten-thousand-yuan and 6.00(3.10,8.05)ten-thousand-yuan,P<0.05).The incidence of complications in group A was markedly lower than that in group C(5.62%vs 25.00%,P<0.05),and similar to group B(P>0.05).CONCLUSION Percutaneous catheter drainage for the treatment of SAP complicated by intra-abdominal fluid accumulation is most effective when performed within 2 d of onset.

Adult pancreatoblastoma: Current concepts in pathology

Adult pancreatoblastoma is an exceptionally rare malignant tumour of the pancreas that mimics other solid cellular neoplasms of the pancreas,which may pose diagnostic difficulties.Because of its rarity,little is known about its clinical and pathologic features.This article reviews the clinical and pathologic features of pancreatoblastoma in adults including differential diagnosis,treatment,and follow-up.Although pancreatoblastoma commonly occurs in childhood,there have now been more than 70 adult pancreatoblastomas described in the literature.There is a slight male predominance.There are no symptoms unique to pancreatoblastomas and adult patients are frequently symptomatic.The most common presenting symptom is abdominal pain.Grossly,the tumours are often large and well-circumscribed.Microscopically,pancreatoblastomas are composed of neoplastic cells with predominantly acinar differentiation and characteristic squamoid nests.These tumours are positive for trypsin,chymotrypsin,lipase,and BCL10.Loss of heterozygosity on chromosome 11p is the most common molecular alteration in pancreatoblastomas.Adult pancreatoblastomas are aggressive tumours with frequent local invasion,recurrence,and distant metastasis.Treatment consists of surgical resection.Chemotherapy and radiotherapy may have a role in the treatment of recurrent,residual,unresectable,and metastatic disease.It is important to distinguish pancreatoblastomas from morphological mimics such as acinar cell carcinomas,solid pseudopapillary neoplasms,and pancreatic neuroendocrine neoplasms.

Detecting circulating tumor material and digital pathology imaging during pancreatic cancer progression

Pancreatic cancer(PC) is a leading cause of cancerrelated death worldwide. Clinical symptoms typically present late when treatment options are limited and survival expectancy is very short. Metastatic mutations are heterogeneous and can accumulate up to twenty years before PC diagnosis. Given such genetic diversity, detecting and managing the complex states of disease progression may be limited to imaging modalities and markers present in circulation. Recent developments in digital pathology imaging show potential for early PC detection, making a differential diagnosis, and predicting treatment sensitivity leading to long-term survival in advanced stage patients. Despite large research efforts, the only serum marker currently approved for clinical use is CA 19-9. Utility of CA 19-9 has been shown to improve when it is used in combination with PC-specific markers. Efforts are being made to develop early-screening assays that can detect tumor-derived material, present in circulation, before metastasis takes a significant course. Detection of markers that identify circulating tumor cells and tumor-derived extracellular vesicles(EVs) in biofluid samples offers a promising non-invasive method for this purpose. Circulating tumor cells exhibit varying expression of epithelial and mesenchymal markers depending on the state of tumor differentiation. This offers a possibility for monitoring disease progression using minimally invasive procedures. EVs also offer the benefit of detecting molecular cargo of tumor origin and add the potential to detect circulating vesicle markers from tumors that lack invasive properties. This review integrates recent genetic insights of PC progression with developments in digitalpathology and early detection of tumor-derived circulating material.