Overview and comparison of guidelines for management of pancreatic cystic neoplasms

Pancreatic cysts are identified at an increasing frequency.Although mucinous cystic neoplasms represent a pre-malignant condition,the majority of these lesions do not progress to cancer.Over the last 10 years several societies have established guidelines for the diagnosis,initial evaluation and surveillance of these lesions.Here we provide an overview of five commonly used guidelines:2015 American Gastroenterological Association,2017 International Association of Pancreatology,American College of Gastroenterology 2018,European Study Group and American College of Radiology.We describe the similarities and differences between the methods used to formulate these guidelines,the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.     

胰管支架置入在预测为重症急性胆源性胰腺炎中的疗效分析

目的　探讨胰管支架置入在预测为重症急性胆源性胰腺炎中的疗效。方法　回顾性收集2017年1月1日至2021年6月30日就诊于西湖大学医学院附属杭州市第一人民医院消化内科预测为重症急性胆源性胰腺炎,并接受内镜逆行胰胆管造影术（endoscopic retrograde cholangiopancreatography, ERCP）治疗的病例。其中,将ERCP术中置入胰管支架的31例病例纳入观察组,于同期病例中选择31例ERCP术中未放置胰管支架的病例纳入对照组。比较两组患者术后1周和2周时炎症指标、肝功能指标和血清淀粉酶水平差异,同时比较两组患者临床改善情况（血清淀粉酶恢复正常时间、腹痛缓解时间、胰周积液好转时间）,住院时间和费用以及预后情况（远期并发症发生率、需内镜下引流或内镜下清创率）。结果　观察组和对照组患者的年龄、性别构成比、术前急性胰腺炎严重程度评分、肝功能指标、炎症性指标、首次进行ERCP时间差异均无统计学意义（P>0.05）。两组患者接受ERCP术后1周和2周时炎症指标、肝功能指标和血清淀粉酶水平差异均无统计学意义（P>0.05）。观察组和对照组患者血清淀粉酶恢复正常时间分别为3.5（1,5） d和5.0（3,6） d （Z=-2.20,P=0.028）,腹痛缓解时间分别为4.0（2.5,7.0） d和5.0（4.0,8.8） d （Z=-3.15,P=0.002）,胰周积液好转时间分别为（25.3±1.5） d和（27.8±2.2） d （t=-0.84,P=0.407）,住院时间分别为28（19, 49） d和40（27, 70） d （Z=-2.03,P=0.043）,住院总费分别为8.1（5.9,10.9）万元和9.8（6.9,17.3）万元 （Z=2.02,P=0.043）。观察组和对照组远期并发症发生率分别为22.6%（7/31）和54.8%（17/31） （χ2=6.80,P=0.009）,需内镜引流或清创率分别为16.1%（5/31）和38.7%（12/31） （χ2=3.97,P=0.046）。结论　对于预测为重症急性胆源性胰腺炎患者,内镜下解除胆道梗阻的同时放置胰管支架引流胰液降低胰管内压力,不仅可以加快缓解患者的临床症状,还可以有效改善患者的预后。     

Cystic neoplasms of the pancreas： A diagnostic challenge

Cystic neoplasms of the pancreas are increasingly recognized due to the expanding use and improved sensitivity of cross-sectional abdominal imaging. Major advances in the last decade have led to an improved understanding of the various types of cystic lesions and their biologic behavior. Despite significant improvements in imaging technology and the advent of endoscopic-ultrasound （EUS）-guided fine- needle aspiration, the diagnosis and management of pancreatic cystic lesions remains a significant clinical challenge. The first diagnostic step is to differentiate between pancreatic pseudocyst and cystic neoplasm. If a pseudocyst has been effectively excluded, the cornerstone issue is then to determine the malignant potential of the pancreatic cystic neoplasm. In the majority of cases, the correct diagnosis and successful management is based not on a single test but on incorporating data from various sources including patient history, radiologic studies, endoscopic evaluation, and cyst fluid analysis. This review will focus on describing the various types of cystic neoplasms of the pancreas, their malignant potential, and will provide the clinician with a comprehensive diagnostic approach.     

急性胰腺炎后患者血清再生相关细胞因子与胰腺功能的相关性研究

目的 探讨血清肝细胞生长因子(HGF)、表皮生长因子(EGF)、碱性成纤维生长因子(bFGF)、再生蛋白(Reg)-1、Reg-4的水平变化对急性胰腺炎(AP)恢复期胰腺内、外分泌功能的影响及机制.方法 根据2007年中国AP诊治指南草案对25例轻症AP恢复期和34例重症AP恢复期患者进行随访研究.同时选取20名健康志愿者作对照.应用酶联免疫吸附法检测血清HGF、EGF、bFGF、Reg-1、Reg-4表达水平,同时检测空腹血糖、胰岛素、C肽及粪弹力蛋白酶(FE)1水平,评估胰腺内、外分泌功能.统计分析胰腺功能与发病时临床指标的相关性以及这些再生相关因子与胰腺功能的相关性.结果 患者组FE1水平[(205.9±18.3)μg/g]较正常对照组[(333.9±19.7)μg/g]显著下降(P<0.01),空腹血糖、胰岛素及C肽水平则显著升高(P<0.01).轻、重症胰腺炎组恢复期胰腺内、外分泌功能差异无统计学意义(P值均>0.05).轻症与重症胰腺炎组HGF、EGF、bFGF、Reg-1、Reg-4表达水平差异无统计学意义(P值均>0.05).AP恢复期重度和轻、中度外分泌功能受损者血清HGF表达水平[分别为(983.76±372.65)和(946.80±254.47)pg/ml]高于外分泌功能正常者[(263.44±110.35)pg/ml,P值均<0.05].AP恢复期糖尿病患者EGF表达水平[(704.41±190.37)pg/ml]高于血糖正常者[(360.03±48.39)pg/ml,P<0.05].血清HGF水平与FE1水平负相关(r=-0.331,P<0.01).AP恢复期是否发生糖耐量异常或糖尿病与急性发病时的CT分级相关(P<0.05).结论 患者在AP恢复期存在明显胰腺内、外分泌功能不全.血清EGF、HGF表达水平可能分别与AP恢复期内、外分泌功能修复有关.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging （MRI）/magnetic resonance cholangio pancreatography （MRCP） and computer tomography （CT） scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms （IPMN）. While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm, was falsely diagnosed as a pseudocyst, based upon the lesion's sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis, the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature, including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include, total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199 and CEA levels for a suspicious cystic pancreatic mass.     

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.     

Unique circulating immune signatures for recurrent acute pancreatitis,chronic pancreatitis and pancreatic cancer: A pilot study of these conditions with and without diabetes

ObjectiveThis exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC).MethodsA retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis.ResultsA total of 179 patients’ samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAP patients, of which 20 controls, 20 CP, and 58 PDAC patients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64–0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64–0.90) and 0.76 (95% CI 0.67–0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93–1.00)ConclusionThis study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.     

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.     

Pancreatic volume does not correlate with histologic fibrosis in adult patients with recurrent acute and chronic pancreatitis

ObjectivesReduced pancreatic volume, often referred to as atrophy, is a commonly reported imaging feature of chronic pancreatitis (CP). This study evaluated whether there is an association between pancreatic volume and fibrosis, the criterion standard of CP, in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for recurrent acute pancreatitis (RAP) and CP.MethodsAll adult patients who underwent TPIAT between 2010 and 2019 were categorized into 3 groups: RAP, definite CP and indeterminate CP. Pancreatic volume was calculated by summing up the areas from each thin section of the pancreas on 3D CT imaging. Excisional biopsies of the pancreatic head as well as body/tail region were obtained at the time of TPIAT. Two different fibrosis scores were used for histologic assessment.ResultsA total of 16, 29 and 15 patients underwent TPIAT for RAP, definite CP and indeterminate CP, respectively. The mean pancreatic volumes for patients with RAP, definite CP and indeterminate CP were 65.7 ± 28.5 cc, 54.9 ± 22.9 cc and 61.8 ± 23.6 cc, respectively (p = 0.3). The mean fibrosis scores were significantly higher in patients with definite CP compared to RAP (p < 0.001) and indeterminate CP (p < 0.001). Pancreatic volume was not associated with either fibrosis score after adjusting for age, gender, duration of disease, BMI and diabetes in the multivariable analysis.ConclusionsWhile the fibrosis scores were higher in definite CP compared to both RAP and indeterminate CP, there was no correlation between pancreatic volume and fibrosis. This suggests that atrophy alone cannot be used to diagnose CP.     

Endoscopic ultrasound-guided injective ablative treatment of pancreatic cystic neoplasms

With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms(PCNs) has increased. PCNs comprise a broad differential spectrum with some PCNs having low or no malignant potential and others having high malignant potential. The morbidity and mortality rates related to major pancreatic surgical resection are high. Long-term surveillance may not only increase the financial burden and psychological stress for patients but also result in a missed malignancy. Minimally invasive endoscopic ultrasound(EUS)-guided ethanol ablation was first reported in 2005. Several other agents, such as paclitaxel, lauromacrogol, and gemcitabine, were reported to be effective and safe for the treatment of PCNs. These ablative agents are injected through a needle inserted into the cyst via transgastric or transduodenal puncture. This treatment method has been substantially developed in the last 15 years and is regarded as a promising treatment to replace surgical resection for PCNs. While several reviews of EUS-guided ablation have been published, no systematic review has evaluated this method from patient preparation to follow-up in detail. In the present review, we systematically describe EUS-guided injective ablation with regard to the indications, contraindications, preoperative treatment, endoscopic procedure, postoperative care and follow-up, evaluation method, treatment efficiency, safety profile, tips and tricks, and current controversies and perspectives.     

胰腺囊性肿瘤的外科治疗

胰腺囊性肿瘤较为少见,常缺乏典型临床表现。归纳了临床常见的胰腺囊性肿瘤的临床病理特点及外科处理,包括浆液性囊性肿瘤、黏液性囊性肿瘤、导管内乳头状黏液肿瘤、实性假乳头状肿瘤等。胰腺囊性肿瘤各自特殊的临床病理特征决定了不同的预后。指出应重视胰腺囊性肿瘤的正确诊断,选择恰当的外科治疗策略。     

急性胰周积液和胰腺坏死对急性胰腺炎预后的影响

目的 探讨急性胰周积液和胰腺坏死对急性胰腺炎(AP)预后的影响.方法 回顾分析2003年1月至2007年12月收治的323例AP患者早期CT影像学表现,探讨急性胰周积液、胰腺坏死程度与全身炎症反应综合征(SIRS)、胰腺感染及病死率的关系.结果 发病5 d内出现SIRS并持续2 d或以上者97例(30%),12例(3.7%)在病程中、后期出现胰腺感染;病死14例(4.3%).有急性胰周积液者142例(44.0%).单个部位发生急性胰周积液者76例,其中31例发生SIRS,病死2例;多个部位急性胰周积液者66例,发生SIRS 62例,病死11例.急性胰周积液部位数量与早期SIRS发生及病死率显著相关(P＜0.01).277例(85.8%)无胰腺坏死,均未继发胰腺感染,病死4例;46例(14.2%)有不同程度胰腺坏死.胰腺坏死面积≤30%32例,胰腺感染发生率12.5%,病死率15.6%;＞30%～≤50%7例,感染发生率42.9%,病死率28.6%;＞50%7例,感染发生率为71.4%,病死率42.9%,胰腺坏死的程度与胰腺感染的发生及病死率显著相关(P＜0.05).结论 急性胰周积液和胰腺坏死对AP预后的影响不同.急性胰周积液与病程早期SIRS的发生及病死率相关;胰腺坏死与胰腺继发感染的发生及病死率有关,坏死面积越大,越容易发生胰腺感染,病死率越高.     

Characteristics and long-term survival of resected pancreatic cystic neoplasms in Finland. The first nationwide retrospective cohort analysis

Background

Pancreatic cystic neoplasms (PCN) are being found increasingly in imaging studies. Even though the characteristics of PCN lesions have been studied extensively in single and multicentre settings, nationwide data is lacking. The aim of this study was to determine the nationwide epidemiologic characteristics and long-term survival of all resected PCNs.

Ansa pancreatica as a predisposing factor for recurrent acute pancreatitis

AIM To determine the non-biased prevalence and clinical significance of ansa pancreatica in patients with acute pancreatitis using magnetic resonance imaging(MRI).METHODS Our institutional review board approved this crosssectional study, which consisted of a community-based cohort of 587 consecutive participants in a whole-body health-check program, and 73 subjects with episode of acute pancreatitis(55 patients with a single episode of acute pancreatitis, and 18 patients with recurrent acute pancreatitis). All of the subjects underwent abdominal MRI including magnetic resonance cholangiopancreatography, medical examinations, and blood tests. Two board-certified, diagnostic, abdominal radiologists evaluated the images, and ansa pancreatica was diagnosed based on its characteristic anatomy on MRI.RESULTS Compared with the community group [5/587(0.85%)], patients with recurrent acute pancreatitis had a significantly higher frequency of ansa pancreatica [2/18(11.1%)](P = 0.016; OR = 14.3; 95%CI: 1.27-96.1), but not compared with patients with single-episode acute pancreatitis [1/55(1.8%)](P = 0.42; OR = 2.1; 95%CI: 0.44-19.7). Multiple logistic regression analysis using age, alcohol intake, presence of ansa pancreatica, and presence of autoimmune disease as independent covariates, revealed a significant relationship between the presence of ansa pancreatica and recurrent acute pancreatitis. The presence of autoimmune disease was also significantly associated with the onset of recurrent acute pancreatitis. On the other hand, neither age nor alcohol intake were significantly related to the onset of recurrent acute pancreatitis.CONCLUSION The present study is the first to provide robust evidence that the presence of ansa pancreatica is significantly associated with recurrent acute pancreatitis.     

国际专家组关于超声内镜引导下胰腺囊性肿瘤消融的立场声明

背景和目的最近,一些有关胰腺囊性肿瘤(pancreatic cystic neoplasms,PCNs)治疗的指南建议已经发表,但是超声内镜(endoscopic ultrasound,EUS)引导下PCNs消融的作用在这些指南中尚未明确。本文的目的是通过提出一系列临床问题并根据可获得的最佳科学证据提供答案来探讨围绕EUS引导下PCNs消融的问题。 方法我们从亚洲EUS学组和一个国际专家组中招募了一个EUS引导下PCNs消融专家小组。创建了一个临床问题列表,并将每个问题分配给一个成员以产生一个陈述。然后在2016年10月至2017年10月的三次互联网会议上讨论了这些陈述。之后相互协商对这些陈述进行修改,直到取得协商一致意见。之后,将完整的陈述总结集体发送给所有小组成员,以对陈述的强度进行投票,对陈述进行分类,对证据进行分级。 结果制定了关于EUS引导下PCNs的23个陈述。这些陈述涉及操作步骤、操作技术、操作前和操作后管理,并发症的管理以及手术中所需能力和培训。 结论在所有内镜学会中,本共识是关于EUS引导下PCNs消融的首篇共识。有兴趣进行这项技术的临床医生应参考这些共识,未来的研究应设法解决本共识中提出的重要问题。     

Molecular analysis of pancreatic cystic neoplasm in routine clinical practice

BACKGROUNDCystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques. Of these, mucinous cysts are especially relevant due to their risk of malignancy. However, morphological findings are often suboptimal for their differentiation. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts.AIMTo determine the impact of molecular analysis on the detection of mucinous cysts and malignancy.METHODSAn 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted. These cysts included those > 15 mm with unclear diagnosis, and a change in follow-up or with concerning features in which results might change clinical management. EUS-FNA with cytological, biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts. The cysts were classified as mucinous and non-mucinous by the combination of morphological, cytological and biochemical analyses when surgery was not performed. Malignancy was defined as cytology positive for malignancy, high-grade dysplasia or invasive carcinoma on surgical specimen, clinical or morphological progression, metastasis or death related to neoplastic complications during the 6-mo follow-up period. Next-generation sequencing results were compared for cyst type and malignancy.RESULTSOf the 36 lesions included, 28 (82.4%) were classified as mucinous and 6 (17.6%) as non-mucinous. Furthermore, 5 (13.9%) lesions were classified as malignant. The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25 (69.4%) pancreatic cysts. The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions. Analysis of KRAS and/or GNAS showed 83.33% [95% confidence interval (CI): 63.34-100] sensitivity, 60% (95%CI: 7.06-100) specificity, 88.24% (95%CI: 69.98-100) positive predictive value and 50% (95%CI: 1.66-98.34) negative predictive value (P = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in KRAS and GNAS were found in 2/5 (40%) of the lesions classified as non-mucinous, thus recategorizing those lesions as mucinous neoplasms, which would have led to a modification of the follow-up plan in 8% of the cysts in which molecular analysis was successfully performed. All 4 (100%) malignant cysts in which molecular analysis could be performed had mutations in KRAS and/or GNAS, although they were not related to malignancy (P > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance (P > 0.05). CONCLUSIONMolecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesions.     

加贝酯预防急性胰腺炎的作用机制研究

目的通过观察加贝酯对胰腺细胞凋亡及Bax、Bcl-2蛋白表达的影响,探讨加贝酯预防大鼠胰管注射法诱导的急性胰腺炎(AP)的相关机制。方法16只SD大鼠随机分为假手术组(4只)、AP组和加贝酯治疗组(各6只)。以50mmHg(1mmHg=0.133kPa)的恒压向胰胆管内注入30%泛影葡胺诱导SD大鼠AP模型,制模前15～20min加贝酯(4mg.h-1.kg-1体重)静脉持续滴注60min进行预防。组织病理检查观察胰腺炎症程度,应用TUNEL染色、免疫组化检测胰腺细胞凋亡和Bcl-2、Bax蛋白表达。结果加贝酯治疗组的胰腺组织病理改变较AP组减轻(P<0.05)。治疗组凋亡指数(AI)、Bax和Bcl-2表达值分别为8.00±1.80,10.12±1.52和1.83±0.39,前两者较AP组显著增高,而Bcl-2蛋白无显著差别。治疗组AI、Bax表达与胰腺的炎症程度呈负相关。结论加贝酯静脉滴注对大鼠胰管注射法诱导的AP有一定的预防作用。其机制可能与促进细胞凋亡和Bax蛋白表达上调有关。     

Chronic immunosuppression does not potentiate the malignant progression of mucinous pancreatic cystic lesions

BackgroundPremalignant mucinous pancreatic cystic lesions (mPCLs) are increasingly identified.AimsIn this study, we aim to assess the effect of selected immunosuppressive therapies on the progression of mPCLs, including side-branch intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.MethodsWe performed a retrospective cohort study of patients with mPCLs diagnosed over a 24-year period who received chronic immunosuppression. Controls were matched on age at cyst diagnosis (±11 yrs) and cyst size (±8 mm). Measured outcomes included increase in cyst size, development of “worrisome features” as defined by consensus guidelines, progression to malignancy, and rate of surgical resection.Results39 patients (mean age 60 yrs) with mPCLs were on immunosuppression. Leading indications for immunosuppression were solid organ transplant (n = 14), inflammatory bowel disease (n = 6), and rheumatoid arthritis (n = 5). 33% were on biologics, 77% on antimetabolites and 79% on multiple medications. Mean cyst size increased from 12.6 mm to 17.8 mm over a median of 16.5 months. 6 patients elected for surgical resection, and none ultimately developed malignancy. 26 cases with follow-up were matched to control subjects, with no significant differences among cases and controls in initial cyst size (12.8 mm vs 11.9 mm, P = 0.69), mean size increase (6.9 mm vs 5 mm, P = 0.47), follow-up interval (24.3 months vs 21.5 months, P = 0.44). No significant differences in the rate of worrisome features, malignancy, or surgical resection.ConclusionsPatients with mPCLs exposed to immunosuppressive medications did not have higher rates of malignancy or development worrisome features in the short term. This suggests that patients with mPCLs can be initiated or maintained on these agents without changes to surveillance practices.