伴有破骨细胞样巨细胞的胰腺未分化癌1例临床病理特征

伴有破骨细胞样巨细胞的胰腺未分化癌(Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, UCPOGC)又名为胰腺含破骨细胞样巨细胞型多形性癌或伴有破骨样巨细胞的胰腺间变性癌,在胰腺恶性肿瘤中占比1%~2%^([1])。因缺乏典型临床影像学特征,就诊时多已处于进展期,且缺乏有效治疗药物,故总体预后不良。

1例伴破骨细胞样巨细胞的胰腺未分化癌的影像学分析及文献复习

伴破骨细胞样巨细胞的胰腺未分化癌(undifferentiated carcinoma with osteoclast-like giant cells of the pancreas,UCOGCP)影像特征复杂多变,通过对本例患者的影像学特征及病理对照分析发现,UCOGCP多表现为混杂的囊实性肿块,其内出血、钙化较常见。因此肿瘤内常可见CT稍高密度或T_(1)WI高、T_(2)WI低的出血信号,肿瘤实性成分和分隔均可见强化,这些影像特征对UCOGCP的初步诊断具有一定的辅助作用。

伴有破骨细胞样巨细胞的胰腺未分化癌诊治分析:附一例报道及文献复习

目的：探讨伴有破骨细胞样巨细胞的胰腺未分化癌（ UCWOGCs）的临床病理特征及其诊断与治疗。方法报道第二军医大学附属长海医院2011年12月收治的1例UCWOGCs患者的临床资料，并检索1990-2013年国内文献报道11篇12例患者，对所有13例UCWOGCs患者的临床表现、病理特征及随访资料进行分析。结果本院收治的1例患者3个月前无明显诱因出现上腹部胀痛不适，伴恶心、食欲不振，无黄疸、发热、腹泻等症状，查体剑突下可触及一包块，大小约16 cm ×15 cm；CT示：腹腔内占位，肝内多发占位。行胰体尾＋全胃＋脾切除术，病理诊断：胰体尾UCWOGCs。13例患者中，男6例，女7例。临床表现上腹部不适或疼痛12例，体检发现上腹部肿块1例。行B超及CT检查，11例提示胰体尾部肿块影。肿瘤直径4-23 cm。13例均行手术治疗。结论 UCWOGCs是一种罕见的恶性肿瘤，临床表现多为非特异性症状，腹部可触及包块，其组织学起源尚有争议，诊断需与胰腺恶性纤维组织细胞瘤、骨巨细胞瘤等鉴别。手术为其主要治疗手段。

伴有破骨细胞样巨细胞的胰腺未分化癌1例报告

伴有破骨细胞样巨细胞的胰腺未分化癌（undifferentiated carcinoma with osteoclast like giant cells of pancreas,UCWOGCs）是一种罕见的恶性肿瘤,属于胰腺非内分泌肿瘤,仅占胰腺恶性肿瘤的0. 2%。本文报道最近我院收治的1例胰腺未分化癌,现结合文献资料总结分析其临床和病理学特点。

伴有破骨细胞样巨细胞的胰腺未分化癌MRI表现与病理分析

目的探索总结伴有破骨细胞样巨细胞的胰腺未分化癌的MRI表现与病理,提高正确诊断率。方法回顾性分析本院3例经病理证实的伴有破骨细胞样巨细胞的胰腺未分化癌的MRI表现、病理特征及临床资料,并结合相关文献加以分析讨论。3例患者均接受MR多序列扫描及增强检查。结果3例均呈囊实性,DWI高信号,增强扫描延迟强化,2例体积大的肿瘤在T2WI可见中断的包膜,ADC可见点条状低信号。病理切片可见多形性肿瘤细胞、破骨细胞样巨细胞及含铁血黄素沉积。结论伴有破骨细胞样巨细胞的胰腺未分化癌较罕见,MR平扫、DWI及增强具有一定特征性,将有助于肿瘤的诊断。

含破骨细胞样巨细胞的胰腺未分化癌1例

患者,女性,69岁,因腹胀不适一月余来我院就诊,既往健康,无肿瘤家族史,无发热、黄疸,无糖尿病、高血压。全腹部CT平扫+增强示:胰腺尾部占位性病灶,大小约54mm×46mm×42mm,中度不均匀强化,伴延迟强化,局部见小片状囊变、坏死,无钙化,胰管无扩张,病灶部分边缘与邻近脾脏、胃大弯侧胃壁分界不清,提示邻近脏器受侵,周围未见明显肿大淋巴结,远处脏器未见转移灶。实验室检查肿瘤相关标志物:AFP 0.4ug/L,CEA 0.6ug/L,CA199 10ku/L,CA125 30kU/L。

多步骤诱导逐步筛选法建立高效的胚胎干细胞定向分化为胰岛祖细胞的分化方案

目的探讨胚胎干细胞(ESCs)体外定向分化为胰岛祖细胞的分化潜能,应用多步骤诱导逐步筛选法建立高效的胚胎干细胞定向分化为胰岛祖细胞的分化方案,提高胚胎干细胞向胰岛祖细胞分化的效率。方法体外传代培养ESCs,采用逐步筛选分化方案,在不同的分化阶段,给予不同的生长因子诱导分化后,RT-PCR法检测胰腺特异性基因的表达,筛选最佳的诱导因子组合,并用免疫细胞化学方法鉴定相关特异蛋白的表达,从而建立体外高效的定向分化方案。结果从未分化ESCs定向分化为定形内胚层细胞,以活化素A诱导组的Sox17和Foxa2基因表达最显著;从定形内胚层细胞分化到后前肠细胞,以维甲酸+FGF10诱导组的Hnf4a和Hnf6基因表达最显著;从后前肠细胞定向分化到胰腺内胚层细胞,以维甲酸+环杷明+DAPT+Exendin 4诱导组的Pdx1、Ptf1a、Hblx9等胰腺特异性基因表达最显著;从胰腺内胚层细胞定向分化到胰岛祖细胞,以维甲酸+DAPT+Exendin 4诱导组的Ngn3、Nkx6.1、Pax4、Pax6等基因表达最显著。免疫细胞化学方法检测可见胰腺特异性的相关蛋白表达,多数Ngn3+细胞同时表达胰腺特异性基因Nkx6.1和Pdx1。结论应用多步骤诱导逐步筛选法可以建立高效的ESCs定向分化为胰岛祖细胞的分化方案,提高ESCs向胰腺内胚层分化的分化效率,为1型糖尿病的β细胞再生治疗提供试验依据和可行性方案。

伴破骨细胞样巨细胞的未分化胰腺癌5例分析并文献复习

目的探讨伴破骨细胞样巨细胞的未分化胰腺癌(PUC-OGC)病人的临床与病理学特征及诊治要点。方法回顾性分析哈尔滨医科大学附属第一医院2014年10月到2017年12月期间收治的5例PUC-OGC病人的临床资料与随访结果。结果 5例病人中,以上腹部疼痛不适为主诉者4例,寒战、发热者1例。5例病人中4例术前癌胚抗原(CEA)、CA19-9均正常,仅1例CA19-9轻度升高。其中4例行胰体尾脾切除术,1例行胆总管空肠吻合、胃空肠吻合术。病理学特点:肿瘤位于胰腺体尾部者4例,位于头颈部者1例,肿瘤的中位直径为4.0(3.2~10.0)cm;切面呈囊实性者3例,且同时伴出血或坏死,呈实性者1例,所有病例送检淋巴结均未见癌转移。镜下可见大量梭形的单核肿瘤细胞和散在分布的多核的体积较大的非肿瘤性破骨细胞样巨细胞(OGC)。5例PUCOGC中1例伴有黏液性囊腺癌。1例病人接受吉西他滨联合替吉奥化疗。随访至2017年12月,4例无病存活,1例已死亡,术后生存时间为8(1~28)个月。结论 PUC-OGC临床表现缺乏特异性,确诊主要依据病理学检查,完整手术切除和术后辅助治疗可能是治疗的最佳方案,预后尚无定论。

L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma

AIM： To determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. METHODS： We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody U3127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendo- crine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULTS： LI was detected in 5 （7.9%） of 63 pancreatic neuroendocrine tumors. Four （44.4%） of 9 poorlydifferentiated carcinomas expressed L1. In contrast, only 1 （1.9%） of 54 well-differentiated tumors or carcinomas was positive for LI. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas （P〈0.01）. CONCLUSION： L1 is specifically expressed in poorlydifferentiated pancreatic neuroendocrine carcinomas that are known to have the worst prognosis. L1 might be a marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.

Endoscopic ultrasound-guided fine needle aspiration in the differentiation of type 1 and type 2 autoimmune pancreatitis

AIM:To investigate the usefulness of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) in the differentiation of autoimmune pancreatitis(AIP).METHODS:We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA and met the Asian diagnostic criteria.On 47 EUS-FNA specimens,we evaluated the presence of adequate material and characteristic features of lymphoplasmacytic sclerosing pancreatitis(LPSP) and idiopathic duct-centric pancreatitis(IDCP) mentioned in the International Consensus Diagnostic Criteria and examined if these findings make a contribution to the differential diagnosis of type 1 and type 2 AIP.A disposable 22-gauge needle was used for EUS-FNA.RESULTS:Adequate specimens including pancreatic tissue for differentiating AIP from cancer were obtained from 43 of 47 patients who underwent EUSFNA.EUS-FNA was performed from the pancreatic head in 21 cases,which is known to be technically difficult when performed by core biopsy;there was no significant difference in the results compared with pancreatic body-tail.Nine of 47 patients met level 1 findings of LPSP and 5 patients met level 2 findings of LPSP.No one met level 1 findings of IDCP,but 3 patients met level 2 findings of IDCP.Of 10 seronegative cases,2 cases were diagnosed with "definitive type 1 AIP",and 3 cases were diagnosed with "probable type 2 AIP" when considering both the level 2 histological findings and response to steroids.CONCLUSION:EUS-FNA is useful in the differentiation of type 1 and type 2 AIP,particularly in seronegative cases.

Treatment of pancreatic pseu do cysts in line with D'Egidio's classification

AIM: To explore the implications of underlying diseases in treatment of pancreatic pseudocysts (PPC). METHODS: Clinical data of 73 cases of pancreatic pseudocyst treated in a 12-year period were reviewed comprehensively. Pancreatic pseudocysts were classified according to the etiological criteria proposed by D'Egidio. The correlation between the etiological classification, measure of treatment and clinical outcome of the patients was analyzed. RESULTS: According to the etiological criteria proposed by D'Egidio, 73 patients were divided into three groups. Group I was comprised of 37 patients with type I pseudocyst, percutaneous drainage was successful in the majority (9/11, 82%) while external or internal drainage was not satisfactory with a low success rate (8/16, 50%). Group II was comprised of 24 patients with type II pseudocyst, and internal drainage was curative for most of the cases (11/12, 92%), but the success rate of percutaneous or external drainage was unacceptably low (4/9, 44%). Group III consisted of 12 patients with type III pseudocyst. Internal drainage or pancreatic resection performed in 10 of these patients produced a curative rate of 80% (8/10) with the correction of the ductal pathology as a prerequisite. CONCLUSION: The classification of pancreatic pseudocyst based on its underlying diseases is meaningful for its management. Awareness of the underlying diseases of pancreatic pseudocyst and detection of the ductal pathology in type II and III pancreatic pseudocysts with endoscopic retrograde cholangiopancreatography may help make better decisions of treatment to reduce the rate of complications and recurrence.

Molecular determinants of the profibrogenic effects of endothelin-1 in pancreatic stellate cells

AIM： To gain molecular insights into the expression and functions of endothelin-1 （ET-1） in pancreatic stellate cells （PSC）.METHODS： PSCs were isolated from rat pancreas tissue, cultured, and stimulated with ET-1 or other extracellular mediators. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2＇-deoxyuridine into DNA and cell migration was studied in a transwell chamber assay. Gene expression at the level of mRNA was quantified by real-time Polymerase chain reaction. Expression and phosphorylation of proteins were monitored by immunoblotting, applying an infrared imaging technology. ET-1 levels in cell culture supernatants were determined by an enzyme immunometric assay. To study DNA binding of individual transcription factors, electrophoretic mobility shift assays were performed.RESULTS： Among several mediators tested, transforming growth factor-β1 and tumour necrosis factor-α displayed the strongest stimulatory effects on ET-1 secretion. The cytokines induced binding of Smad3 and NF-κB, respectively, to oligonucleotides derived from the ET-1 promoter, implicating both transcription factors in the induction of ET-1 gene expression. In accordance with previous studies, ET-1 was found to stimulate migration but not proliferation of PSC. Stimulation of ET-1 receptors led to the activation of two distinct rnitogen-activated protein kinases, p38 and extracellular signal-regulated kinases （ERK）1/2, as well as the transcription factor activator protein-1. At the mRNA level, enhanced expression of the PSC activation marker, α-smooth muscle actin and two proinflammatory cytokines, interleukin （IL）-1β and IL-6, was observed. CONCLUSION： This study provides novel lines of evidence for profibrogenic and proinflammatory actions of ET-1 in the pancreas, encouraging further studies with ET-1 inhibitors in chronic pancreatitis.

AN EFFICIENT METHOD FOR ISOLATION AND PURIFICATION OF THE PANCREATIC ISLETS

On the base of the one step, operator independent method which was set up by Christophe A.E., the pancreas was infused with cold University of Wisconsin(UW) solution for the preservation, digested by the collagenase P, circuited with HBSS+5%fetal calf serum(FCS)+10mmol/L Hepes solution, and separated with the stainless steel mesh. The number of the collected islets were 400000～1800000 per pancreas, i.e. about 12150/g pancreas. After purification, the recovery was 350000～1700000 per pancreas, i.e. about 10250/g pancreas, the recovery rate was above 80%, and the purity of the final preparation was above 95%. The insulin secretion in the response to the high concentration glucose (22 mmol/L) stimulation was apparently different on the 1,3,5 day of the cultural islets, which the high level of insulin was three times the low level (5.5 mmol/L) on the 5th day, and the insulin level of the double stimulation under perfusion conditions is apparently higher than low glucose. The result demonstrated that the purified islets were functionally alive. Histological studies also show that the shape of islets are complete, and the β cell was specially stained by the dithizone (DTZ). The Trypan Blue staining had shown the living cell was above 90%. In conclusion, the new method was highly practical and yielded higher concentration of active pancreatic islets.

Chronic pancreatitis: Maldigestion, intestinal ecology and intestinal inflammation

Exocrine pancreatic insufficiency caused by chronic pancreatitis results from various factors which regulate digestion and absorption of nutrients. Pancreatic function has been extensively studied over the last 40 years, even if some aspects of secretion and gastrointestinal adaptation are not completely understood. The main clinical manifestations of exocrine pancreatic insufficiency are fat malabsorption, known as steatorrhea, which consists of fecal excretion of more than 6 g of fat per day, weight loss, abdominal discomfort and abdominal swelling sensation. Fat malabsorption also results in a deficit of fat-soluble vitamins (A, D, E and K) with consequent clinical manifestations. The relationships between pancreatic maldigestion, intestinal ecology and intestinal inflammation have not received particular attention, even ifin clinical practice these mechanisms may be responsible for the low efficacy of pancreatic extracts in abolishing steatorrhea in some patients. The best treatments for pancreatic maldigestion should be re-evaluated, taking into account not only the correction of pancreatic insufficiency using pancreatic extracts and the best duodenal pH to permit optimal efficacy of these extracts, but we also need to consider other therapeutic approaches including the decontamination ofintestinal lumen, supplementation of bile acids and, probably, the use of probiotics which may attenuate intestinal inflammation in chronic pancreatitis patients.

Endoscopic papillectomy of minor papillar adenoma associated with pancreas divisum

Tumors of the minor papilla of the duodenum are quite rare.We successfully and safely treated an 18-mm adenoma of the minor papilla associated with pancreas divisum using endoscopic papillectomy.A 64-year-old man was admitted to our hospital for treatment of an asymptomatic mass in the minor papilla detected by upper gastrointestinal endoscopy.Endscopic analysis showed an 18-mm,whitish,sessile mass,located in the duodenum proximal to a normal-appearing major papilla.Endoscopic retrograde pancreatography did not reveal the pancreatic duct.Magnetic resonance cholangiopancreatography showed a lack of the ventral pancreatic duct.We suspected this case was associated with pancreatic divisum;therefore,we performed endoscopic papillectomy of the minor papilla tumor.Subsequently,endoscopic pancreatic stent placement in the minor papilla was done to prevent drainage disturbance.The patient has been asymptomatic without recurrence of tumor or stenosis of the Santorini orifice upon endoscopic examination for the past 2 years.

胚胎干细胞体外定向分化为Ngn3＋胰岛祖细胞的基因表达谱分析

目的探讨胚胎干细胞体外定向分化为胰岛祖细胞的基因表达谱。方法采用逐步诱导分化方案体外传代培养胚胎干细胞，应用RT—PCR和免疫细胞化学方法鉴定各分化阶段相关特异基因的表达，应用Illumina MouseRef-8 v1．1小鼠基因表达谱芯片测定胚胎干细胞来源的不同阶段的分化细胞（第4、8、15、20、22和25天）与未分化胚胎干细胞的基因组表达谱。结果本研究得到了86个阶段特异性表达基因．6组具有相同表达趋势的基因簇，6组阶段差异表达基因组。从数量上看，差异表达基因最多的阶段是后前肠阶段（201个基因），接下来是定形内胚层细胞阶段（17个基因）。结论应用基因芯片对胰腺发育过程中具有相同表达趋势的基因和阶段差异表达基因的分析为早期胚胎发育和胰腺发育研究提供了试验依据。

Cell therapy in diabetes: current progress and future prospects

Diabetes mellitus, characterized by the impaired metabolism of insulin secretion in β cells, is becoming one of the most prevalent diseases around the world. Recently, cell replacement based on differentiation of various pluripotent stem cells, including embryonic stern cells, induced pluripo- tent stem cells and multipotent stem cells, such as bone mar- row mesenchymal stem cells, adipose-derived stem cells and gnotobiotic porcine skin-derived stem cells, is becoming a promising therapeutic strategy. Cells derived from pancreatic tissues or other tissues that are relevant to β cell differentiation have also been used as cell source. However, in spite of hopeful experimental results, cell therapy in diabetes still confronts certain obstacles, such as purity of cells, functional differentiation of stem cells and possible tumorigenesis, which, in turn, lead to the seeking of new-generation tools, such as xenogenetic materials. In this review, we will sum- marize the current knowledge and future prospects of cell therapy in diabetes mellitus.