Which factors determine exocrine pancreatic dysfunction in diabetes mellitus?

The exocrine structure is significantly affected by diabetes because of endocrine structure-function disorder within the pancreas. Exocrine pancreatic dysfunction (EPD) is the general name of the malabsorption process resulting from inadequate production, release, decreased activation, and/or insufficient degradation of enzymes required for digestion from pancreatic acinar cells. It is important to diagnose patients early and correctly, since there may be both macro- and micro-nutrient deficiency in EPD. In this paper, EPD, the diabetes- EPD relationship, and the predictive, effective factors affecting the emergence of EPD are briefly explained and summarized with contemporary literature and our experienced based on clinical, lab, and radiological findings.

Less common etiologies of exocrine pancreatic insufficiency

Exocrine pancreatic insufficiency(EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases(diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin(CCK); celiac or inflammatory bowel disease(IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery(asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy(PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI(66%-92%). EPI occurs in patients with type 1(26%-57%) or type 2 diabetes(20%-36%) and is typically mild to moderate; by definition, all patients with type 3 c(pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease(4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD(14%-74%) and up to 100% of gastrointestinal surgery patients(47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

Pathological evaluation of pancreatic exocrine glands in experimental fluorosis

Objective:To monitor the pathological alterations in pancreas of rat during experimental fluorosis. Methods:Sixty Sprague Dawley albino rats of both sexes were divided into 12 experimental groups and one control group.The rats of control group were administered subcutaneously double distilled water 1 mL/kg bw daily.The experimental groups were injected with 30,45,and 75 mg NaF/kg bw/day.The experimental period was divided into 4 phases at interval of 15,22,30,and 36 days.Animals were sacrificed from each group at the end of 16,23,31,and 37 days.Results: The following changes were observed in this study:(1) Pathological examination of pancreas after 15 days of fluoride treatment revealed:hypertrophy of acini,leucocytes infilteration and pycnouc nuclei due to necrosis of acini in group 1;uremic alterations,invulsion and infoldings of reticular layer of islets of Langerhans in group 2;and a decrease in number of acini and interlobular connective tissues resulted in an increase in intercellular spaces in pancreas of rats in group 3.(2)Hyalinization and hypertrophy in the lobules of acini and hyperplasia and hypertrophy in intercalated duct with mucinous secretion in pancreas of rat of group 4;squamous metaplasia of pancreatic duct,adenoma of pancreas,hemorrhagic necrosis in group 5;and hyperplasia of acini and reduction in number of pancreatic islets in group 6.(3) Disorganization and atrophy of pancreatic lobules and presence of vacuoles in a group of six were visible in pancreas of rats in group 7;acute pancreatic and lamellated inflammatory cells in test rats of group 8;and islet adenoma and decrease in number of islets cells,and exudation in acini were noticed in experimental rats of group 9.(4) In the last phase of experimentation,atrophic alterations in pancreatic acini,invulsions,and necrosis was prominent in group 10,deep inflammation and proliferation of connective tissue of pancreas in experimental group 11,and periodical fibrosis, hyperplasia of acini,degenerative changes in pancreas of rats in group 12.Conclusion:The histopathological examination of pancreas of fluoridated rats exhibited structural alterations in the exocrine glands.The acini revealed hypertrophy,pyknotic nucleus,necrosis and uremic alterations.Acini became lobulated and reveal increased pigmentation.

Two rare cancers of the exocrine pancreas: to treat or not to treat like ductal adenocarcinoma?

Pancreatic cancer is an aggressive malignancy with increasing incidence.Pancreatic ductal adenocarcinoma(PDAC)accounts for>90%of pancreatic cancer diagnoses,while other exocrine tumors are much rarer.In this review,we have focused on two rare cancers of the exocrine pancreas:adenosquamous carcinoma of the pancreas(ASCP)and pancreatic acinar cell carcinoma(PACC).The latest findings regarding their cellular and molecular pathology,clinical characteristics,prognosis,and clinical management are discussed.New genetic and transcriptomic data suggest that ASCP is related to or overlaps with the basal transcriptomic subtype of PDAC.These tumors are highly aggressive and driven by activated KRAS and MYC expression.Clinical outcomes remain poor and effective treatments are limited.PACC has no morphologic or genetic resemblance to PDAC and more favorable outcomes.Early stage PACC patients have improved survival with surgical resection and patients with advanced disease benefit most from platinum-or fluoropyrimidine-containing chemotherapy.Frequency of actionable genetic mutations is high in this disease and case reports suggest good outcomes when matched therapy is given.Dedicated clinical studies examining ASCP and PACC are limited and difficult to accrue.Further research is needed to define optimal clinical management for these rare diseases.

Hypothesis that alpha-amylase evokes regulatory mechanisms originating in the pancreas,gut and circulation,which govern glucose/insulin homeostasis

The anti-incretin theory involving the abolishment of diabetes type(DT)II by some of methods used in bariatric surgery,first appeared during the early years of the XXI century and considers the existence of anti-incretin substances.However,to date no exogenous or endogenous anti-incretins have been found.Our concept of the acini-islet-acinar axis assumes that insulin intra-pancreatically stimulates alpha-amylase synthesis(“halo phenomenon”)and in turn,alphaamylase reciprocally inhibits insulin production,thus making alpha-amylase a candidate for being an anti-incretin.Additionally,gut as well as plasma alphaamylase,of pancreatic and other origins,inhibits the appearance of dietary glucose in the blood,lowering the glucose peak after iv or oral glucose loading.This effect of alpha-amylase can be interpreted as an insulin down regulatory mechanism,possibly limiting the depletion of pancreatic beta cells and preventing their failure.Clinical observations agree with the above statements,where patients with high blood alpha-amylase concentrations are seldom obese and seldom develop DT2.Obese-DT2,as well as DT1 patients,usually develop exocrine pancreatic insufficiency(EPI)and vice versa.Ultimately,DT2 patients develop DT1,when the pancreatic beta cells are exhausted and insulin production ceases.Studies on biliopancreatic diversion(BPD)and on BPD with duodenal switch,a type of bariatric surgery,as well as studies on EPI pigs,allow us to observe and investigate the above-mentioned phenomena of intra-pancreatic interactions.

小柴胡汤加减方对慢性胰腺炎大鼠胰腺外分泌功能的影响

[目的]观察小柴胡汤加减方对慢性胰腺炎大鼠胰腺外分泌的影响。[方法]体质量180～200 g健康雄性Wistar大鼠30只,随机分为3组：对照组、模型组及中药组。模型组及中药组大鼠尾静脉注射二氯二丁基酯（DBTC）溶液（7 mg/kg）,对照组仅尾静脉注射相同体积的溶剂。自造模第2天起中药组给予小柴胡汤加减方灌胃（10 mL/kg）,每日1次。常规饲28 d,3组大鼠行苯洛肽（BT-PABA）实验,收集6 h总尿量,计算6 h大鼠尿PABA排出率；同时留取粪便,用酶联免疫吸附试验（ELISA）法检测大鼠粪弹力蛋白酶1（FE-1）含量。之后,麻醉大鼠,下腔静脉取血,用于血清淀粉酶、脂肪酶检测；取胰腺组织,用于组织病理学观察。[结果]组织病理学可见模型组腺泡萎缩,纤维组织增生明显,中药组病理损伤程度减轻。与对照组比较,模型组大鼠尿PABA排出率下降（P〈0.05）,模型组粪FE-1含量降低（P〈0.05）。与模型组比较,中药组尿PABA排出率升高（P〈0.05）,粪FE-1含量明显增加（P〈0.05）。中药组血清淀粉酶及脂肪酶活性均较模型组降低（P〈0.05）。[结论]小柴胡加减方能够改善大鼠慢性胰腺炎胰腺外分泌功能。

日粮因素对反刍动物胰腺外分泌功能的调控

反刍动物消化系统在结构上与单胃动物不同,对营养物质的消化存在差异。营养物质在瘤胃内被微生物降解利用,产生的挥发性脂肪酸被瘤胃壁吸收供能;菌体蛋白与未降解的饲料流入小肠,由胰腺分泌的消化酶消化成小分子物质,如葡萄糖、氨基酸等被小肠上皮直接吸收利用。理论上小肠内淀粉类营养物质化学性消化利用效率远高于瘤胃,但淀粉小肠内的消化受到胰腺淀粉酶分泌不足的限制,因此调控营养物质在小肠内的化学性消化对于高产奶牛更加迫切。本课题组从胰腺外分泌功能的调控入手,研究反刍动物小肠营养物质的化学性消化的调控,尤其是日粮碳水化合物结构及功能性氨基酸的调控作用。基于此,本文综述反刍动物胰腺的生理结构、对碳水化合物的消化、外分泌的影响因素及其调控机理,旨在为提高反刍动物营养物质的消化利用效率、减少饲料资源的浪费提供理论依据。

胰腺内分泌与外分泌之间的相互作用

内分泌和外分泌胰腺向来被认为相互独立存在,但其解剖和功能关系紧密,任何疾病影响其中之一,必然会影响另一部分。胰腺疾病包括急性胰腺炎(acute pancreatitis,AP)、慢性胰腺炎(chronic pancreatitis,CP)、胰腺囊性纤维化和胰腺癌等可能导致糖尿病(diabetes mellitus,DM),而DM的进展极大地影响了外分泌胰腺疾病患者的预后及生活质量,可能会导致危及生命的并发症。在胰腺外分泌疾病患者中,DM是一个独立的死亡危险因素。文中将以胰腺内、外分泌主要疾病为线索,对近年来国内外关于胰腺内、外分泌之间相互作用的研究进展进行综述。

急性胰腺炎与新发糖尿病的关系

胰腺是内、外分泌功能整合的器官,其胰岛B细胞产生的胰岛素是体内惟一降低血糖的激素,对保持体内血糖的稳态起重要作用,因此,胰腺疾病可能导致糖尿病的发生。急性胰腺炎是最常见的胰腺疾病,但其与糖尿病的发生关系一直未得到重视。目前更多的研究表明急性胰腺炎与新发糖尿病相关,监测急性胰腺炎后患者血糖具有重要意义。

胰腺外分泌功能检查的临床应用现状与评价

胰腺外分泌功能检查是评估胰腺功能的主要方法,其分为直接胰功能试验和间接胰功能试验。目前许多胰腺外分泌功能检测的试验由于侵入性,操作复杂或稳定性差等因素,临床应用诊断价值有限。为此,对目前已应用于临床的胰腺外分泌功能试验方法进行分析评估,

5-氟脲嘧啶对胰腺外分泌的影响

目的 探讨 5 氟脲嘧啶 ( 5 FU)对人胰腺外分泌功能的影响。方法 通过 8例胰十二肠切除术后患者胰管内置管获得的纯胰液观察 5 FU对人胰腺外分泌功能的作用。术后第 10天开始 ,静脉缓慢滴注 5 FU 5 0 0mg/d ,连续 3天。检测 5 FU使用前和使用后 1d、2d及 3d胰液中淀粉酶、pH、HCO3 -、Na+ 、K+ 、Cl-、Ca2 + 及Mg2 + 水平 ,并记录胰液量变化。结果 使用 5 FU前、后胰液量及胰液中淀粉酶、pH、HCO3 -、Na+ 、K+ 、Cl-、Ca2 + 及Mg2 + 水平均无显著变化。结论 短期内使用 5 FU对胰腺外分泌功能未见明显影响 ,5 FU是否通过抑制胰酶的合成治疗急性胰腺炎有待进一步探讨。

胰腺肿瘤的病理诊断和鉴别诊断

胰腺肿瘤发病率近年呈上升趋势,本文仅就胰腺外分泌的上皮性肿瘤的主要类型加以介绍。其中包括胰腺导管腺癌及其主要的变型和腺泡细胞癌、胰母细胞瘤等。文中还包括了浆液性囊性肿瘤、黏液性囊性肿瘤、导管内乳头状黏液肿瘤(IPMN)和导管内乳头状嗜酸性肿瘤以及实性-假乳头状肿瘤,对上述个性肿瘤的免疫组化特点和分子特征也进行了阐述。

高强度聚焦超声消融胰腺癌后对胰腺内分泌和外分泌功能的影响

目的探讨高强度聚焦超声(HIFU)消融进展期胰腺癌胰后对胰腺内外分泌功能的影响。方法通过回顾性分析2009年2月至2015年12月33例经HIFU消融后胰腺癌患者的血糖、血清淀粉酶的水平,了解胰腺癌患者经HIFU消融后对胰腺内外分泌功能的影响。结果 HIFU消融前的平均血糖及血淀粉酶水平分别为6.30 mmol/L和72.5 U/L。消融后3天平均血糖及血淀粉酶水平分别为6.71 mmol/L和69.4 U/L。消融7天后平均血糖及血淀粉酶水平为6.24 mmol/L和74.51 U/L。各数据组间无显著统计学差异。术后无急性胰腺炎的发生。结论高强度聚焦超声消融进展期胰腺癌后对胰腺内外分泌功能无显著影响,HIFU消融胰腺癌是安全可行的。

胰泌素增强MRI对胰腺外分泌功能诊断的系统评价和Meta分析

目的系统评价胰泌素增强MRI胰胆管成像(S-MRCP)诊断胰腺外分泌功能的准确性。资料与方法采用计算机检索Cochrane图书馆、Medline、EMbase、中国生物医学文献数据库(CBM)、Pub Med、EBSCO、Ovid、Springer、中国知网(CNKI)、万方和维普数据库1997年1月—2013年12月国内外公开发表的关于S-MRCP评估胰腺外分泌功能的相关文献。由2名高年资影像科医师按照纳入及排除标准独立选择文献并根据QUADAS评价条目标准进行质量评价。采用Meta-Disc软件进行Meta分析,绘制森林图及汇总受试者工作特征曲线。结果共检索到99篇文献,6篇符合纳入标准,纳入的6篇文献具有同质性(I^2<50%,P>0.05),使用固定效应模型计算出的汇总敏感度、特异度分别为0.79(95%CI 0.68~0.88)和0.91(95%CI0.86~0.94)。汇总受试者工作特征曲线下面积为0.9188。结论 S-MRCP对胰腺外分泌功能具有较高的诊断效能。

促胰液素、八肽胆囊收缩素、胰岛素对大鼠离体胰腺外分泌的作用

本实验采用血管灌流大鼠离体胰腺制备技术，探讨促胰液素、八肽胆囊收缩素（ＣＣＫ－８）和胰岛素对离体胰腺外分泌的作用。结果表明：（１）促胰液素、ＣＣＫ－８和胰岛素都可使离体胰腺分泌的胰液量、ＨＣＯ３－和蛋白排出量明显增加。（２）促胰液素和ＣＣＫ－８对离体胰腺有相加作用，其胰液的分泌量、ＨＣＯ３－及蛋白的排出量与两者单独作用相比有显著性增加。上述结果提示：促胰液素、ＣＣＫ－８和胰岛素都是刺激胰腺外分泌的重要激素，并且促胰液素和ＣＣＫ－８对离体胰腺外分泌有明显的相互加强作用。

静脉注射小剂量obestatin对大鼠胰腺外分泌的影响

背景:目前对obestatin的生理学功能存在较多争议,有研究发现大剂量外源性obestatin(30、100、300 nmol/kg)可增加大鼠胰液蛋白分泌。目的:研究静脉注射小剂量obestatin对大鼠胰腺外分泌的影响。方法:雄性Sprague-Dawley大鼠随机分为A、B、C三组,麻醉后建立胰腺外分泌模型。每15 min经胆胰管插管收集一次胆胰混合液(P-BJ),测定P-BJ体积和蛋白含量。将第一次收集的P-BJ作为基础胰腺分泌,A、B组经尾静脉持续注射obestatin(1 nmol.kg-1.h-1和5 nmol.kg-1.h-1),30 min后再经股静脉持续注射胆囊收缩素-8(CCK-8,400 pmol.kg-1.h-1),C组仅注射CCK-8作为对照。结果:大鼠基础胰腺分泌量为(136±44)μl/15 min,基础胰液蛋白分泌量为(11.9±2.2)mg/15 min。A、B组静脉注射obestatin后,P-BJ体积和胰液蛋白分泌量与基础值相比无明显差异。静脉注射CCK-8 15 min后,三组P-BJ体积和胰液蛋白分泌量均开始升高,于注射后30 min或45 min达高峰,与基础值相比差异有统计学意义(P<0.05)。A、B组各时点P-BJ体积和胰液蛋白分泌量与同时点C组相比,差异均无统计学意义。结论:静脉注射小剂量obestatin对大鼠胰腺外分泌无明显影响,且不能改变由CCK-8刺激引起的胰腺外分泌增加。

韦格纳肉芽肿并发高血糖症一例报告并文献复习

目的：提高对韦格纳肉芽肿（WG）并发高血糖症的认识。方法结合一例 WG 并发高血糖症患者的临床资料进行文献复习，对 WG 和高血糖症的内在联系进行分析。结果患者入院后在 CT 引导下行肺活检，病理检查结果提示：肉芽肿性炎，高度考虑为 WG。查胞浆型抗中性粒细胞胞浆抗体（cANCA）：阳性，核周型 ANCA（pANCA）：阴性，抗髓过氧化物酶抗体＜2．0，抗蛋白酶3抗体144．80。入院后监测血糖发现，餐前餐后血糖水平均明显高于正常，经激素＋环磷酰胺＋复方新诺明控制 WG 病情后血糖恢复正常。结论 WG 并发高血糖症原因可能为 WG 累及胰腺导致胰岛β细胞损伤、胰岛素内源性分泌减少。

禽胰液分泌的调节

综述近年来对家禽胰液分泌的研究进展。胰液含有多种消化酶 ,在家禽对饲料的消化中起重要作用 ,是研究动物消化代谢的主题之一。

加贝酯对犬胰腺移植后Oddi括约肌及外分泌功能的影响

目的研究加贝酯对膀胱引流式犬胰腺移植后移植物Oddi括约肌(SO)和外分泌功能的影响。方法正常犬和膀胱引流式胰腺移植后犬应用加贝酯前后进行SO测压,检测移植后犬应用加贝酯前后尿中胰蛋白原激活肽(TAP)和淀粉酶水平。结果正常犬SO有规律收缩,基础压为(19．4±3．2)mmHg,收缩频率为(9．9±1．6)次／min,收缩幅度为(45．1±6．5)mmHg,动力指数为355．4±31．3。应用加贝酯后SO收缩频率和动力指数分别下降为(4．8±0．9)次／min和206．5±21．4,与用药前相比,差异均有统计学意义(P<0．01)。基础压和收缩幅度无明显变化(P>0．05)。胰腺移植后,犬移植物SO基础压和收缩频率分别升高为(27．2±5．6)mmHg和(13．8±2．5)次／min,收缩幅度缩小为(8．6±2．5) mmHg,动力指数无明显变化。移植犬应用加贝酯后,SO基础压、收缩频率、收缩幅度和动力指数分别降低为(18．6±2．9)mmHg、(8．6±2．5)次／min、(5．4±0．9)mmHg和136．9±3．5,与用药前相比,差异均有统计学意义(P<0．01)。用加贝酯后尿淀粉酶和TAP水平分别为(6 000±290)IU／L和(16．7±3．8) nom／L,与用药前相比,有显著性差异(P<0．01)。结论加贝酯可抑制犬SO运动,尤其胰腺移植后,抑制作用更加显著。加贝酯还可以降低膀胱引流式犬胰腺移植后尿中的胰蛋白酶原激活肽和尿淀粉酶水平,从而有助于防治移植物胰腺炎。

移植胰腺病理学诊断标准及其进展

胰腺移植和胰肾联合移植是治疗1型糖尿病和部分2型糖尿病及其并发症导致的肾衰竭的最佳治疗方法。胰腺移植的类型主要包括同期胰肾联合移植(SPK)、肾移植后胰腺移植(PAK)和单纯胰腺移植(PTA)。在所有的胰腺移植类型中,对移植胰腺的活组织检查(活检)仍然是明确诊断其排斥反应并与其他并发症进行鉴别的最佳方法。本文对移植胰腺活检的方法及其相关的研究进展、移植胰腺活检排斥反应诊断标准及其进展、移植胰腺主要的并发症及其病理学表现进行阐述,旨在为指导临床对上述并发症予以准确诊断,良好地保障移植胰腺和受者的长期存活提供参考。