Pancreatic Duct Patterns in Acute Pancreatitis: A MRI Study

Objectives

To study the MRI findings of the pancreatic duct in patients with acute pancreatitis.

Materials and Methods

A total of 239 patients with acute pancreatitis and 125 controls were analyzed in this study. The severity of acute pancreatitis was graded using the MR severity index (MRSI) and the Acute Physiology And Chronic Healthy Evaluation II(APACHE II) scoring systems. The number of main pancreatic duct (MPD) segments visualized, and both MPD diameter and pancreatic duct disruption were noted and compared with the severity of acute pancreatitis.

Results

The frequency of MPD segment visualization in the control group was higher than that in the acute pancreatitis group (p<0.05). The number of MPD segments visualized was negatively correlated with the MRSI score (p<0.05) and the APACHE II score (p<0.05). There was no difference in the MPD diameter between the acute pancreatitis and control groups or among the patients with different severities of acute pancreatitis (p>0.05). The prevalence of pancreatic duct disruption was 7.9% in the acute pancreatitis group. The prevalences of pancreatic duct disruption were 4.8% and 15.3% in the mild and severe acute pancreatitis groups based on the APACHE II score, respectively, and were 0%, 5.7% and 43.5% in the mild, moderate and severe acute pancreatitis groups according the MRSI score, respectively. The prevalence of pancreatic duct disruption was correlated with the severity of acute pancreatitis based on the APACHE II score (p<0.05) and MRSI score (p<0.05).

Conclusion

The pancreatic duct in acute pancreatitis patients was of normal diameter. The number of MPD segments visualized and visible pancreatic duct disruption on MRI may be supplementary indicators for determining the severity of acute pancreatitis.     

Clinical Study on the Prevention of Post-ERCP Pancreatitis by Pancreatic Duct Stenting

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most common and serious complications of ERCP, which has become a major concern for digestive endoscopists. In the present study, we examine whether pancreatic duct stenting can reduce the incidence of PEP. Forty patients who underwent an ERCP in our hospital were selected according to their risk factors for PEP. They were randomly divided into two groups: (1) 20 subjects received a pancreatic duct stenting after ERCP to prevent pancreatitis (stent group, S); and (2) the other 20 subjects did not receive pancreatic duct stenting after ERCP (non-stent group, NS). Urine and serum amylase, and serum lipase were determined after the operation; symptoms of abdominal pain were monitored; cost of hospitalization was evaluated for the comparison. The results show that (1) 18 cases developed PEP, and they were significantly less in S group than in NS group (4 vs. 14 cases; P < 0.01); (2) Serum amylase was significantly lower in S group than in NS group (197.8 ± 339.7 vs. 825.4 ± 1253.4 U/l, respectively; P < 0.05); (3) The intensity of abdominal pain was 3.4 ± 0.8 in S group, compared to 4.1 ± 1.2 in NS group; (4) Duration of pharmaceutical treatment was not significantly different between the two groups (4.2 ± 1.4 vs. 6.1 ± 2.3 days, in S and NS group, respectively); and (5) The total hospitalization cost was significantly less in S group (8928 ± 2635 RMB) than in NS group (11288 ± 4325 RMB; P < 0.05). It is concluded that pancreatic duct stenting can reduce the incidence of PEP, shorten the duration of hospitalization, and therefore, lessen patients’ financial burden. It is shown to be an effective way to prevent PEP.     

Perineural Mast Cells Are Specifically Enriched in Pancreatic Neuritis and Neuropathic Pain in Pancreatic Cancer and Chronic Pancreatitis

Background

Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown.

Methods

Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients.

Results

In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients.

Conclusion

Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.     

Dimethyl Fumarate Protects Pancreatic Islet Cells and Non-Endocrine Tissue in L-Arginine-Induced Chronic Pancreatitis

Background

Chronic pancreatitis (CP) is a progressive disorder resulting in the destruction and fibrosis of the pancreatic parenchyma which ultimately leads to impairment of the endocrine and exocrine functions. Dimethyl Fumarate (DMF) was recently approved by FDA for treatment of patients with multiple sclerosis. DMF''s unique anti-oxidant and anti-inflammatory properties make it an interesting drug to test on other inflammatory conditions. This study was undertaken to determine the effects of DMF on islet cells and non-endocrine tissue in a rodent model of L-Arginine-induced CP.

Methods

Male Wistar rats fed daily DMF (25 mg/kg) or vehicle by oral gavage were given 5 IP injections of L-Arginine (250 mg/100 g×2, 1 hr apart). Rats were assessed with weights and intra-peritoneal glucose tolerance tests (IPGTT, 2 g/kg). Islets were isolated and assessed for islet mass and viability with flow cytometry. Non-endocrine tissue was assessed for histology, myeloperoxidase (MPO), and lipid peroxidation level (MDA). In vitro assessments included determination of heme oxygenase (HO-1) protein expression by Western blot.

Results

Weight gain was significantly reduced in untreated CP group at 6 weeks. IPGTT revealed significant impairment in untreated CP group and its restoration with DMF therapy (P <0.05). Untreated CP rats had pancreatic atrophy, severe acinar architectural damage, edema, and fatty infiltration as well as elevated MDA and MPO levels, which were significantly improved by DMF treatment. After islet isolation, the volume of non-endocrine tissue was significantly smaller in untreated CP group. Although islet counts were similar in the two groups, islet viability was significantly reduced in untreated CP group and improved with DMF treatment. In vitro incubation of human pancreatic tissue with DMF significantly increased HO-1 expression.

Conclusion

Administration of DMF attenuated L-Arginine-induced CP and islet function in rats. DMF treatment could be a possible strategy to improve clinical outcome in patients with CP.     

Pancreatic Degenerative Atrophy and Chronic Pancreatitis in Dogs a Comparative Study of 60 Cases

During the years 1977–1980 60 cases of non-neoplastic chronic exocrine pancreatic disease in dogs were investigated clinically and pathologically. The disorders were clinically divided into pancreatic degenerative atrophy (PDA) and chronic pancreatitis. Fifty dogs had PDA and 45 of them were German shepherd dogs. The PDA cases formed both clinically and pathologically a homogeneous group except for 1 case. All the dogs had maldigestion and protease activity was absent from the faeces. General inanition and highly atrophic pancreas were the most typical macroscopic findings. Histologically the exocrine pancreas contained atypical acinar tissue and mononuclear cell infiltrations. Five of the dogs died spontaneously, 4 of them had intestinal torsion and 1 had paralytic ileus. There were 10 dogs with chronic pancreatitis. This group was rather heterogeneous both clinically and pathologically. The pancreas was slightly enlarged and the consistency was firm. The histologic picture was one of fibrous tissue proliferation and inflammatory cell infiltrations in the interstitium. The dogs nutritional state as well as faecal protease activity were normal.     

Comparative Characterization of Stroma Cells and Ductal Epithelium in Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive stroma being also present in chronic pancreatitis (CP). Using immunohistochemistry, the stroma of CP and PDAC was comprehensively analyzed and correlated with epithelial/carcinoma-related alterations and clinicopathological patient characteristics. While there were no significant differences between CP and PDAC regarding the distribution of CD3+ T cells and α-SMA+ fibroblasts, proportions of CD4+ and CD8+ T cells were significantly lower and numbers of CD25+(CD4+) and FoxP3+(CD4+) regulatory T cells were greater in PDAC compared with CP. Macrophages were more prevalent in CP, but localized more closely to carcinoma cells in PDAC, as were γδ-T cells. Duct-related FoxP3 and L1CAM expression increased from CP to PDAC, while vimentin expression was similarly abundant in both diseases. Moreover, stromal and epithelial compartments of well-differentiated tumors and CPs shared considerable similarities, while moderately and poorly differentiated tumors significantly differed from CP tissues. Analysis of 27 parameters within each pancreatic disease revealed a significant correlation of i) CD4+ and FoxP3+CD4+ T cells with FoxP3 expression in PDAC cells, ii) α-SMA+ fibroblasts with L1CAM expression and proliferation in PDAC cells, iii) CD3 and CD8 expression with γδ-TCR expression in both pancreatic diseases and iv) CD68+ and CD163+ macrophages with vimentin expression in PDAC cells. High expression of FoxP3, vimentin and L1CAM in PDAC cells as well as a tumor-related localization of macrophages each tended to correlate with higher tumor grade. Multivariate survival analysis revealed a younger age at time of surgery as a positive prognostic marker for PDAC patients with the most frequently operated disease stage T3N1M0. Overall this study identified several interrelationships between stroma and epithelial/carcinoma cells in PDACs but also in CP, which in light of previous experimental data strongly support the view that the inflammatory stroma contributes to malignancy-associated alterations already in precursor cells during CP.     

山羊精子发生不同阶段的显微与超微结构观察

应用光镜和透射电镜技术研究山羊精子发生不同阶段各级生精细胞显微、超微结构及山羊精子分化成熟过程。结果表明：山羊精子发生经历了精原细胞、初级精母细胞、次级精母细胞、精子细胞及变态精子阶段发育成成熟的精子。精原细胞期核呈椭圆形,染色质凝集成团分布于核质中,线粒体开始出现;精母细胞期有高尔基体分布;精子细胞经过核质浓缩、线粒体迁移等过程发育成成熟精子,成熟的山羊精子头部细长,核质高度浓缩,中段膨大,线粒体丰富。线粒体、中心粒对精子变态发生起重要作用,同时观察到头部与中段脱落的畸形精子。     

胰腺发育相关maf基因在胰腺导管和胰岛的表达

为探讨胰岛功能和发育相关maf基因在胰腺导管上皮中的表达情况,对新鲜小鼠胰腺组织切片进行显微切割,分离纯化胰腺组织中的导管和胰岛,以及外分泌腺组织细胞作为对照,利用荧光实时定量PCR的方法完成对目的基因的相对定量.结果显示,mafa mRNA,mafb mRNA水平在胰岛及导管中非常接近,无统计学差异.而c-maf在导管的表达高于胰岛(P<0.05),外分泌腺则无上述基因的表达.胰腺导管中mafa,mafb,cmaf均有表达,肯定了导管上皮细胞向内分泌细胞分化的潜能,而c-maf在导管中的表达高于胰岛,提示导管上皮c-maf的下调可能有助于导管上皮细胞向内分泌细胞的分化成熟.     

Rhein,a Natural Anthraquinone Derivative,Attenuates the Activation of Pancreatic Stellate Cells and Ameliorates Pancreatic Fibrosis in Mice with Experimental Chronic Pancreatitis

Pancreatic fibrosis, a prominent histopathological feature of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma, is essentially a dynamic process that leads to irreversible scarring of parenchymal tissues of the pancreas. Though the exact mechanisms of its initiation and development are poorly understood, recent studies suggested that the activation of pancreatic stellate cells (PSCs) plays a critical role in eliciting such active course of fibrogenesis. Anthraquinone compounds possess anti-inflammatory bioactivities whereas its natural derivative rhein has been shown to effectively reduce tissue edema and free-radical production in rat models of inflammatory conditions. Apart from its anti-inflammatory properties, rhein actually exerts strong anti-fibrotic effects in our current in-vivo and in-vitro experiments. In the mouse model of cerulein-induced CP, prolonged administration of rhein at 50 mg/kg/day significantly decreased immunoreactivities of the principal fibrotic activators alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β) on pancreatic sections implicating the activation of PSCs, which is the central tread to fibrogenesis, was attenuated. Consequently, the overwhelmed deposition of extracellular matrix proteins fibronectin 1 (FN1) and type I collagen (COL I-α1) in exocrine parenchyma was found accordingly reduced. In addition, the expression levels of sonic hedgehog (SHH), which plays important roles in molecular modulation of various fibrotic processes, and its immediate effector GLI1 in pancreatic tissues were positively correlated to the degree of cerulein-induced fibrosis. Such up-regulation of SHH signaling was restrained in rhein-treated CP mice. In cultured PSCs, we demonstrated that the expression levels of TGF-β-stimulated fibrogenic markers including α-SMA, FN1 and COL I-α1 as well as SHH were all notably suppressed by the application of rhein at 10 μM. The present study firstly reported that rhein attenuates PSC activation and suppresses SHH/GLI1 signaling in pancreatic fibrosis. With strong anti-fibrotic effects provided, rhein can be a potential remedy for fibrotic and/or PSC-related pathologies in the pancreas.     

3.0T磁共振多序列成像对鉴别胰头癌与胰头肿块型慢性胰腺炎的应用价值

目的：探讨磁共振多序列成像对鉴别胰头癌与胰头肿块型慢性胰腺炎的临床价值及意义。方法：对已确诊的16例胰头癌患者和5例胰头肿块型慢性胰腺炎患者的磁共振多序列成像MR进行回顾性分析。主要征象包括：①肿块信号及形态学特点;②胰管及胆管扩张情况;③动态增强的特征;④胰周及大血管受累情况;⑤邻近器官受累与淋巴结肿大情况。检查方法包括：平扫T1WI＋FST2WI＋FS,MRCP,3D—VIBE动态增强扫描。结果：1）肿块形态信号异常：胰头癌与胰头肿块型胰头慢性胰腺炎的信号有较多重叠,在TlwI上均表现为相对低信号,T2WI表现为不均匀稍高、相等或低信号。2）胰管与胆管的异常：胰头癌表现为胰管扩张至肿块处突然截断12例,胆总管突然截断10例,“双管征”10例。胰头肿块型慢性胰腺炎胰管扩张3例,2例为串珠样扩张,扩张的胰管可贯通病灶区,胆总管5例均扩张,远端呈短锥形狭窄3例,鼠尾样狭窄2例。3）3D—VIBE强化特征分析结果：随着时间的延长胰头癌强化程度和强化百分率较胰头肿块型慢性胰腺炎明显减低。4）胰周大血管受累情况：胰头癌肿块与血管分界不清者8例,部分包绕血管6例完全包绕血管6例;胰头肿块型慢性胰腺炎1例与血管分界不清,1例部分被包绕。5）邻近器官受累与淋巴结肿大情况：胰头癌有7例淋巴结肿大主要分布在胰周及腹主动脉旁,胰头肿块型慢性胰腺炎,未见明显肿大淋巴结,有四例肾周筋膜增厚,两例肾前筋膜增厚。结论：磁共振多序列成像的联合使用及征象分析,有助于鉴别胰头癌与胰头肿块型慢性胰腺炎。     

Imbalance of Wnt/Dkk Negative Feedback Promotes Persistent Activation of Pancreatic Stellate Cells in Chronic Pancreatitis

The role of persistent activation of pancreatic stellate cells (PSCs) in the fibrosis associated with chronic pancreatitis (CP) is increasingly being recognized. Recent studies have shown that Wnt signaling is involved in the development of fibrosis in multiple organs, however, the role of specific Wnts in pancreatic fibrosis remains unknown. We investigated the role of Wnt signaling during PSC activation in CP and the effect of β-catenin inhibition and Dickkopf-related protein 1 (Dkk1) restoration on the phenotype of PSCs. CP was induced in mice by repetitive caerulein injection and mouse PSCs were isolated and activated in vitro. The expression of Wnts, β-catenin, secreted frizzled-related proteins (sFRPs) and Dkks was analyzed by quantitative RT-PCR and western blotting. The canonical Wnt signaling pathway was examined by immunofluorescence and western blot detection of nuclear β-catenin expression. The effect of recombinant mouse Dkk-1 (rmDkk-1) on cell proliferation and apoptosis was assessed by flow cytometry, immunofluorescence, immunocytochemistry and Cell Counting Kit-8 (CCK-8) analysis. The expression of β-catenin, collagen1α1, TGFβRII, PDGFRβ and α-SMA in PSCs treated with different concentrations of rmDkk-1 or siRNA against β-catenin was determined by quantitative RT-PCR and western blotting. Wnt2 was the only Wnt whose expression was significantly upregulated in response to PSC activation, and Wnt2 and β-catenin protein levels were significantly increased in the pancreas of CP mice, whereas Dkk-1 expression was evidently decreased. Nuclear β-catenin levels were markedly increased in activated PSCs, and rmDkk-1 suppressed the nuclear translocation of β-catenin and the proliferation and extracellular matrix production of PSCs through the downregulation of PDGFRβ and TGFβRII. Upregulation of Dkk-1 expression increased apoptosis in cultured PSCs. These results indicate that Wnt signaling may mediate the profibrotic effect of PSC activation, and Wnt2/Dkk-1 could be potential therapeutic targets for CP.     

北方山溪鲵精子发生不同阶段的显微与超微结构

用光镜和电镜观察了北方山溪鲵(Batrachuperus tibetanus)精子发生过程中各种类型生精细胞的显微与超微结构变化。结果显示,北方山溪鲵在4~8月时处于精子发生期,精子形成在7~8月。成熟精子的结构具有小鲵科精子的一些共同特征,如顶体前端呈三叶草状,尾部由轴纤维、波动膜、轴丝及轴丝旁纤维构成,轴纤维粗大呈圆柱形,尾部无线粒体等。比较分析认为,在两栖类的系统发育中,轴纤维、波动膜和轴丝旁纤维的消失为近裔性状。     

Light Sheet Fluorescence Microscopy: A Review

Light sheet fluorescence microscopy (LSFM) functions as a non-destructive microtome and microscope that uses a plane of light to optically section and view tissues with subcellular resolution. This method is well suited for imaging deep within transparent tissues or within whole organisms, and because tissues are exposed to only a thin plane of light, specimen photobleaching and phototoxicity are minimized compared to wide-field fluorescence, confocal, or multiphoton microscopy. LSFMs produce well-registered serial sections that are suitable for three-dimensional reconstruction of tissue structures. Because of a lack of a commercial LSFM microscope, numerous versions of light sheet microscopes have been constructed by different investigators. This review describes development of the technology, reviews existing devices, provides details of one LSFM device, and shows examples of images and three-dimensional reconstructions of tissues that were produced by LSFM.