Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas

Intraductal papillary mucinous neoplasms(IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree.Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning(FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive,in order to avoid an excessive pancreatic resection.Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease.FS accuracy averages 95%.Eroded epithelium on the main duct,severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results.FS results change the planned extent of resection in up to 30% of cases.The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatec-tomy if FS reveals:(1) at least IPMN adenoma on the main duct;or(2) at least borderline IPMN on branch ducts;or(3) invasive carcinoma.However,the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age,general condition and expected prognosis after resection.The main limitation of using FS is the existence of discontinuous("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.

Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm(IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucinproducing cells arising in the main duct(MD) and/or branch ducts(BD) of the pancreas.Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity.IPMN lacks ovarian-type stroma,unlike mucinous cystic neoplasm,and is defined as a grossly visible entity(≥ 5 mm),unlike pancreatic intraepithelial neoplasm.With the use of high-resolution imaging techniques,very small IPMNs are increasingly being identified.Most IPMNs are solitary and located in the pancreatic head,although 20%-40% are multifocal.Macroscopic classification in MD type,BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications.Based on cytoarchitectural atypia,IPMN is classified into low-grade,intermediategrade and high-grade dysplasia.Based on histological features and mucin(MUC) immunophenotype,IPMNs are classified into gastric,intestinal,pancreatobiliary and oncocytic types.These different phenotypes can be observed together,with the IPMN classified according to the predominant type.Two pathways have been suggested:gastric phenotype corresponds to less aggressive uncommitted cells(MUC1-,MUC2-,MUC5 AC +,MUC6 +) with the capacity to evolve to intestinal phenotype(intestinal pathway)(MUC1-,MUC2 +,MUC5 AC +,MUC6- or weak +) or pancreatobiliary /oncocytic phenotypes(pyloropancreatic pathway)(MUC1 +,MUC 2-,MUC5 AC +,MUC 6 +) becoming more aggressive.Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises(about 40% of IPMNs),except in some cases of minimal invasion.The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer.Once resected,they must be extensively sampled or,much better,submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

Reoperation for heterochronic intraductal papillary mucinous neoplasm of the pancreas after bile duct neoplasm resection:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)and intraductal papillary mucinous neoplasm(IPMN)of the pancreas have similar pathological manifestations.However,they often develop separately and it is rare for both to occur together.Patients presenting with heterochronic IPMN after IPNB are prone to be misdiagnosed with tumor recurrence.CASE SUMMARY A 67-year-old male patient was admitted 8.5 years after IPNB carcinoma and 4 years after the discovery of a pancreatic tumor.A left hepatic bile duct tumor with distal bile duct dilatation was found 8.5 years ago by the computed tomography;therefore,a left hepatectomy was performed.The postoperative pathological diagnosis was malignant IPNB with negative cutting edge and pathological stage T1N0M0.Magnetic resonance imaging 4 years ago showed cystic lesions in the pancreatic head with pancreatic duct dilatation,and carcinoembryonic antigen continued to increase.Positron emission tomography showed a maximum standard uptake value of 11.8 in the soft tissue mass in the pancreatic head,and a malignant tumor was considered.Radical pancreatoduodenectomy was performed.Postoperative pathological diagnosis was pancreatic head IPMN with negative cutting edge,pancreaticobiliary type,stage T3N0M0.He was discharged 15 d after the operation.Follow-up for 6 mo showed no tumor recurrence,and quality of life was good.CONCLUSION IPNB and IPMN are precancerous lesions with similar pathological characteristics and require active surgery and long-term follow-up.

Simultaneous intraductal papillary neoplasms of the bile duct and pancreas treated with chemoradiotherapy

Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient's age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.

Tumors with macroscopic bile duct thrombi in non-HCC patients:Dynamic multi-phase MSCT findings

Non-hepatocellular carcinoma （non-HCC） with macroscopic bile duct tumor thrombus （BDTI） formation is rare, few radiological studies have been reported. In this case report, we retrospectively analyzed the imaging findings of three cases of non-HCC with macroscopic BDTT on dynamic enhanced multislice computed tomography （MSCT） scan. One case of primary hepatic carcinosarcoma was presented as a solitary, large welldefined tumor with significant necrotic changes. One case of liver metastasis from colon cancer was presented as a Iobulated, large ill-defined tumor. One case of intraductal oncocytic papillary neoplasm involved the entire pancreas, presented as a cystic and solid mass with multilocular changes （the individual Ioculi were less than 5.0 mm in diameter）. The bile duct was dilated due to expansible growth of the BDFE in all three patients. The BDTT was contiguous with hepatic or pancreatictumor, and both of them showed the same enhancement patterns on dynamic contrast-enhanced computed tomography scan： early enhancement in the hepatic arterial phase and a quick wash out of contrast agent in the portal and equilibrium phases. Macroscopic BDTT- in non-HCC patient is rare, dynamic enhanced MSCT scan may be valuable in the diagnosis of non-HCC with BDTT.

Tubulopapillary adenoma of the gallbladder accompanied by bile duct tumor thrombus

Intraductal papillary mucinous neoplasm of the bile duct(IPNB)is recognized as a precancerous lesion;however,both its pathogenesis and progression remain unclear.We present here a case of IPNB arising from the gallbladder accompanied by bile duct tumor thrombus in a 79-year-old female.The resected specimen revealed a tubulopapillary adenoma with no malignant cells.This case suggests that even in the absence of malignant cells,these tumors can behave as malignant tumors requiring aggressive treatment.Even if no malignant cells are present,intraepithelial neoplasms occurring in the ampullopancreatobiliary tract can behave as malignant tumors.

Molecular alterations in pancreatic tumors

Genetic alterations in pancreatic tumors can usually be classified in:(1)Mutational activation of oncogenes;(2)Inactivation of tumor suppressor genes;and(3)Inactivation of genome maintenance genes controlling the repair of DNA damage.Endoscopic ultrasound-guided fine-needle aspiration has improved preoperative diagnosis,but the management of patients with a pancreatic lesion is still challenging.Molecular testing could help mainly in solving these“inconclusive”specimens.The introduction of multi-gene analysis approaches,such as next-generation sequencing,has provided a lot of useful information on the molecular characterization of pancreatic tumors.Different types of pancreatic tumors(e.g.,pancreatic ductal adenocarcinomas,intraductal papillary mucinous neoplasms,solid pseudopapillary tumors)are characterized by specific molecular alterations.The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.

Similarities and differences in guidelines for the management of pancreatic cysts

Accurate diagnosis of Pancreatic cysts(PC) is key in the management. The knowledge of indications for surgery, the role of endoscopic ultrasound-guided fine needle aspiration, cyst fluid analysis, imaging, and surveillance of PC are all important in the diagnosis and management of PC. Currently, there are many guidelines for the management of PC. The optimal use of these guidelines with a patient-centered approach helps diagnose early cancer and prevent the spread of cancer.

Role of pancreatoscopy in management of pancreatic disease:A systematic review

BACKGROUND Per-oral pancreatoscopy(POP) plays a role in the diagnosis and therapy of pancreatic diseases. With recent technological advances, there has been renewed interest in this modality.AIM To evaluate the efficacy and safety of POP in management of pancreatic stone disease and pancreatic ductal neoplasia.METHODS To determine the safety and efficacy of POP in the management of pancreatic diseases, a systematic search was conducted in MEDLINE, EMBASE and Ovid.Articles in languages other than English and case reports were excluded. All published case series were eligible. Data specific to POP were extracted from studies, which combined cholangiopancreatoscopy. Ten studies were included in the analysis of POP therapy for pancreatic stone disease, and 15 case series satisfied the criteria for inclusion for the role of POP in the management of pancreatic ductal neoplasia. The examined data were subcategorized according to adjunctive modalities, such as direct tissue sampling, cytology, the role of intraoperative POP, intraductal ultrasound(IDUS) and POP combined with image-enhancing technology.RESULTS The success rate for complete ductal stone clearance ranged from 37.5%-100%.Factors associated with failure included the presence of strictures, multiple stonesand the inability to visualize the target area. Although direct visualization can identify malignant and premalignant conditions, there is significant overlap with benign diseases. Visually-directed biopsies provide a high degree of accuracy,and represent a unique approach for tissue acquisition in patients with ductal abnormalities. Addition of pancreatic fluid cytology increases diagnostic yield for indeterminate lesions. Protrusions larger than 3 mm noted on IDUS are significantly more likely to be associated with malignancy. The rate of adverse events associated with POP ranged from 0%-35%.CONCLUSION Current evidence supports wider adoption of pancreatoscopy, as it is safe and effective. Improved patient selection and utilization of novel technologies may further enhance its role in managing pancreatic disease.

In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study

To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs).METHODSIn a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively.RESULTSA total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a “fern pattern” of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology.CONCLUSIONIn vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

Pancreatic cystic neoplasms:a comprehensive approach to diagnosis and management

Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.

内镜下胰胆管逆行造影术在胆胰管导管内乳头状黏液性瘤中的应用价值

目的探讨内镜下胰胆管逆行造影术(ERCP)对胆胰管导管内乳头状黏液瘤(IPMN)的诊治作用。方法回顾性分析经ERCP诊治的9例IPMN,分析临床表现、实验室检查、影像学表现等方面特点,经ERCP结合超声内镜作出初步诊断,采用超细内镜进入囊腔活检,以求术后病理确诊,后根据具体病情予相应内镜处理。结果 5例胆管导管内乳头状黏液瘤(IPMNs-B),4例胰管导管内乳头状黏液瘤(IPMNs-P),均无特异性的临床表现和实验室检查;超声、CT、MRI主要表现为胆胰管扩张,仅1例IPMNs-P胰头部见囊实性团块、壁结节及主胰管明显扩张(5.5 cm);ERCP均显示乳头开口扩张,胶冻样黏液流出,胰胆管不同程度扩张。9例行ERCP抽吸黏液后,1例IPMNs-B同时置入胆管及胰管支架,3例IPMNs-P置入胰管支架,1例放置胆道金属支架;术后1例出现轻症胰腺炎(11.1%,1/9),3例出现淀粉酶升高而无症状(33.3%,3/9),无出血或穿孔等并发症发生。结论ERCP是一种安全可靠的诊断方法选择,对IPMN的诊治具有重要作用。结合病理诊断,可为外科术前提供明确的诊断和可靠的证据。

胆胰管内超声内镜对胰腺疾病的诊断价值

目的评估胆胰管内超声内镜检查(IDUS)在胰腺疾病中的诊断价值。方法回顾分析2005年2月至2010年2月间行IDUS的63例胰腺疾病患者的影像学资料,IDUS均在经内镜逆行胰胆管造影(ERCP)时用经导丝的UMG20-29R腔内超声探头扫查胰腺。比较IDUS与CT、MRI、超声内镜(EUS)及腹部B超等5种方法在诊断胰腺疾病中的区别,以进一步评估IDUS在胰腺疾病的临床诊断中的应用价值。结果 IDUS对慢性胰腺炎(23例)、胰腺癌(10例)、导管内乳头状黏液瘤(IPMT,25例)、胰腺囊腺瘤(4例)的诊断准确率和Kappa检测值分别为93.7%(59/63),0.854;100.0%(63/63),1.00;90.5%(57/63),0.898以及96.8%(61/63),0.848。IDUS诊断准确率和Kappa检测值均优于其他4种方法 ,并且对1例胰腺囊腺癌也做出正确的术前诊断。结论 IDUS对胰腺疾病的诊断有较高的应用价值。

胰腺导管内乳头状黏液性肿瘤的临床病理学分析(附29例报告)

目的:回顾性分析胰腺导管内乳头状黏液性肿瘤(IPMT)的诊治经验及预后,以期提高对该病的治疗水平。方法:1993年5月至2006年8月,共29例IPMT病人在我院接受手术治疗,男17例,女12例。现回顾性分析其临床表现、病理学分类以及术后随访情况。结果:术后病理证实,本组共有11例是类腺瘤,2例交界性肿瘤,16例腺癌。其中,主胰管型11例,分支胰管型16例,混合型2例。2例病人由于病变累及全胰而施行全胰切除术,其余病人分别施行胰十二指肠切除术(16例)、胰体尾切除术(7例)及局部切除术(4例)。在腺癌病例中,有37.5%(6/16)发生淋巴结转移。结论:IPMT有独特的临床病理学特征。对主胰管直径≥10mm、肿瘤直径>40mm以及主胰管型病例,应高度怀疑恶性病变的可能性。如术前考虑IPMT有恶性可能,则应施行合并淋巴结清扫的根治性切除术。

MSCT动态增强扫描诊断胰腺导管内乳头状黏液性肿瘤的临床分析

目的:探讨多层螺旋CT(MSCT)动态增强扫描诊断胰腺导管内乳头状黏液性肿瘤的临床价值。方法:采用回顾性分析法,收集2015年1月-2020年1月于三门峡市中心医院接受治疗的30例胰腺导管内乳头状黏液性肿瘤患者临床资料,所有受检者均行MSCT动态增强扫描检查,以病理检查结果作为“金标准”,观察胰腺导管内乳头状黏液性肿瘤良、恶性特征,并评估MSCT动态增强扫描鉴别胰腺导管内乳头状黏液性肿瘤良、恶性的准确度、灵敏度、特异度、阳性预测值及阴性预测值。结果:恶性肿瘤患者主胰管扩张≥7mm、肿瘤最大径≥50mm、有胆管扩张、壁结节≥5mm占比均较对较良性肿瘤患者高,差异具有统计学意义(P<0.05);MSCT动态扫描检查的准确度为90.00%(27/30),灵敏度为89.47%(17/19),特异度为90.91%(10/11),恶性预测值为94.44%(17/18),良性预测值为83.33%(10/12),MSCT动态扫描检查与病理检查结果具有极好的一致性(Kappa=0.798)。结论:MSCT动态增强扫描在胰腺导管内乳头状黏液性肿瘤良、恶性诊断中具有较高的准确度、灵敏度与特异度,且与病理诊断具有极好的一致性,可为临床早期判断胰腺导管内乳头状黏液性肿瘤良、恶性提供可靠依据,值得临床推广应用。

58例胰腺导管内乳头状黏液性肿瘤临床分析

目的 探讨胰腺导管内乳头状黏液性肿瘤（intraductal papillary mucinous neoplasm,IPMN）的诊断和治疗.方法 回顾性分析2004年12月至2014年12月10年间收治58例IPMNs病人的临床资料、病理分型、治疗方式.男性36例,女性22例,男女比例为1.6∶1,年龄39～82岁,中位年龄67岁.58例IPMNs病人均行手术治疗.其中行胰十二指肠切除术31例（53.45％）,胰头部局部切除术9例（15.52％）,胰体尾切除术7例（12.07％）,胰体部局部切除术4例（6.90％）,胰尾切除术4例（6.90％）,胰尾联合脾切除1例（1.72％）,全胰腺切除2例（3.44％）.结果 58例IPMNs病人中主胰管型26例;分支胰管型9例;混合型23例;术后病理：腺瘤26例,交界瘤13例,非浸润癌10例,浸润性癌9例;全组的中位生存期为42.6个月;1、2和5年的生存率分别为94.5％、79.3％和65.5％.其中病理类型为浸润性癌的病人1、2、5年生存率分别为62.5％、47.5％、12.5％.结论 IPMN是一种比较罕见的肿瘤,手术治疗是目前比较好的治疗方式.

胰腺导管内乳头状黏液性肿瘤的病理学及预后分析

目的研究胰腺导管内乳头状黏液性肿瘤的病理学并进行预后分析。方法回顾性分析2009年2月至2011年1月于本院附属医院接受手术切除的胰腺导管内乳头状黏液性肿瘤患者93例，其中浸润性癌患者51例、非浸润性癌患者42例。对所有患者病历资料进行统计，并对两组患者病理特征及手术效果进行分析。结果浸润性组消瘦、CA199〉37U／ml以及皮肤巩膜黄染发生率均显著高于非浸润性组。浸润性组复发率为41．18％（21／51），显著高于非浸润性组的7．14％（3／42）；而5年生存率为56．86％（29／51），明显低于非浸润性组的97．62％（41／42），差异均有统计学意义（P〈0．05）。结论经手术治疗后非浸润性胰腺导管内乳头状黏液性肿瘤患者预后较好，尽早进行手术治疗可防止病变发展，改善预后。

胰腺导管内乳头状黏液性肿瘤32例诊疗分析

目的分析胰腺导管内乳头状黏液性肿瘤（IPMN）的临床表现及诊治方法。方法回顾性分析2000年1月—2015年6月于哈尔滨医科大学附属第二医院普外科就诊的32例IPMN患者的临床资料,总结其诊治方法。结果 32例患者男9例,女23例,年龄24~73岁。所有患者临床表现多无特征性。32例患者均接受手术治疗,手术效果良好。32例术后病理回报均为IPMN：非浸润性IPMN 29例,其中单纯胰腺导管内乳头状黏液性肿瘤19例,胰腺导管内乳头状黏液性肿瘤伴不典型增生9例,胰腺导管内乳头状黏液性肿瘤伴钙化1例;浸润性IPMN伴中分化腺癌3例。随访1~36个月患者预后良好,1例患者合并中分化腺癌,于术后12个月死亡。结论对于IPMN患者,MRCP有助于明确诊断。而针对不同类型IPMN的个体化治疗,可使患者获得良好的预后。

胰腺常见囊性肿瘤的临床特点、影像学表现和鉴别

胰腺囊性肿瘤(PCN)是以囊性改变为主胰腺肿瘤的统称。常见的PCN分为浆液性囊性肿瘤(SCN)、黏液性囊性肿瘤(MCN)、导管内乳头状黏液性肿瘤(IPMN)、实性假乳头性肿瘤(SPT)等。各型肿瘤生物学特性各异,良恶性均有涉及,因此提高PCN的术前影像学诊断对临床有一定的指导意义。本文就PCN的影像学表现、病理特点及鉴别诊断进行综述。