Intraductal papillary mucinous neoplasms of the pancreas: a surgical perspective

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a relatively "new", but increasingly recognized entity. The emergence of this entity is due primarily to the widespread use of modern imaging methods, but also to a heightened awareness of physicians regarding this cystic neoplasm of the pancreas. No signs or symptoms are pathognomonic of IPMNs, but frequently, patients have a pancreatitis-like abdominal pain. Fully one-third of patients with IPMN are asymptomatic at the time of diagnosis. Cross-sectional imaging (ultrasonography, computed tomography, magnetic resonance cholangiopancreatography), endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography are the diagnostic and staging methods of choice in the evaluation of patients with IPMNs. IPMNs show a wide spectrum of histologic changes, ranging from adenoma to invasive neoplasm, even within the same neoplasm, suggesting a "field defect" predisposing major segments or even the entire ductal epithelium to the development of IPMN. Fine-needle aspiration/cytology and/or analysis of the cystic fluid may be useful diagnostic tools; however, these examinations are associated with high false-negative rates. Complete surgical resection is the therapeutic method of choice. The extent and type of pancreatectomy remain somewhat controversial but should be based on morphologic changes of the pancreas. Even the role of adjuvant therapy remains unclear; however, being "duct-derived" neoplasms of potential malignant character, some form of adjuvant chemo- or ratio-therapy seems indicated in the presence of invasive disease, despite a "curative" resection. In the absence of invasive disease, prognosis after R0 resection is highly favorable with recurrences of 5-10%. However, invasive IPMNs behave quite similar to ductal adenocarcinoma of the pancreas when analyzed stage-by-stage, with a slightly better prognosis; however, even after an R0 resection, recurrence is common.     

Primary pancreatic cystic neoplasms revisited. Part I: serous cystic neoplasms

Primary pancreatic cystic neoplasms have been recognized increasingly during the two recent decades and include mainly serous cystic neoplasms, mucinous cystic neoplasms, and intraductal papillary mucinous neoplasms. Serous cystic neoplasms represent about 30% of all cystic neoplasms of the pancreas and are characterized by their microcystic appearance (on imaging, macroscopically, and microscopically) and their benign biologic behavior. Modern diagnostic methodology allows the preoperative diagnosis with an acceptable accuracy. Currently, indications for resection of serous cystic neoplasms of the pancreas include the presence of symptoms, size > 4 cm (because these ‘large’ neoplasms have a more rapid growth rate and probably will soon become symptomatic), and any uncertainty about the diagnosis of a serous versus a mucinous cystic neoplasm. Resection should also be considered for lesions in the body/tail of the pancreas. Conservative treatment is a reasonable option in selected patients (for example in the presence of small, asymptomatic lesions in the pancreatic head, especially in the frail or elderly patient).     

Primary pancreatic cystic neoplasms revisited: part II. Mucinous cystic neoplasms

Mucinous cystic neoplasms (MCNs) of the pancreas represent one of the most common primary pancreatic cystic neoplasms, accounting for approximately half of these cases. MCNs are observed almost exclusively in women, and most commonly are located in the body/tail of the pancreas. In contrast to SCNs, MCNs have malignant potential. Proliferative changes (hyperplasia with or without atypia, borderline changes, non-invasive or carcinomas in-situ, and invasive carcinomas) can often be observed within the same neoplasm. Several risk factors for the presence of underlying malignancy within an MCN have recently been recognized. Cross-sectional imaging is of key importance for the diagnostic evaluation of patients with a cystic pancreatic lesion. Cyst fluid examination (cytology, biochemical/genetic analysis) is possible by using fine needle aspiration of the MCN, usually under endoscopic guidance, and may provide useful information for the differential diagnosis. Since MCNs have malignant potential, surgical resection is the treatment of choice.     

Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies: A systematic review with meta-analysis

BackgroundIt is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies.AimsWe performed a pooled estimate of the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia, with a particular focus on the comparison to the general population.MethodsComputerized bibliographic search of main databases was performed through February 2021. The primary endpoint was the pooled incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms. Additional outcome was the comparison between intraductal papillary mucinous neoplasia patients and the general population, expressed in terms of standardized incidence ratio along with 95% confidence intervals.ResultsEighteen studies with 8709 patients were included. The pooled rate of metachronous extrapancreatic malignancies was 10 (6–13)/1000 persons-year. No difference was observed according to intraductal papillary mucinous neoplasia histology and sex, whereas a significantly superior incidence of extrapancreatic malignancies was observed in patients with main-duct (36.7%, 25.4%–48%) as compared to branch-duct intraductal papillary mucinous neoplasia (26.2%, 17.6%–34.8%; p = 0.03). Pooled standardized incidence ratio comparing expected rates in the general population was 1.01 (0.79–1.29); no difference was observed concerning rates of metachronous gastric cancer (standardized incidence ratio 1.60, 0.72–3.54) and colorectal cancer (1.29, 0.92–1.18), whereas biliary cancer was observed more frequently in intraductal papillary mucinous neoplasia patients (2.29, 1.07–4.93).ConclusionPatients with intraductal papillary mucinous neoplasia harbor an overall rate of extrapancreatic malignancies as high as 27.3%. The rate of metachronous extrapancreatic malignancies is not superior to the general population.     

Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) rank among the most common cystic tumors of the pancreas. For a long time they were misdiagnosed as mucinous cystadenocarcinoma, ductal adenocarcinoma in situ, or chronic pancreatitis. Only in recent years have IPMNs been fully recognized as clinical and pathological entities, although their origin and molecular pathogenesis remain poorly understood. IPMNs are precursors of invasive carcinomas. When resected in a preinvasive state patient prognosis is excellent, and even when they are already invasive, patient prognosis is more favorable than with ductal adenocarcinomas. Subdivision into macroscopic and microscopic subtypes facilitates further patient risk stratification and directly impacts treatment. There are main duct and branch duct IPMNs, with the main duct type including the intestinal, pancreatobiliary, and oncocytic types and the branch duct type solely harboring the gastric type. Whereas main duct IPMNs have a high risk for malignant progression, demanding their resection, branch duct IPMNs have a much lower risk for harboring malignancy. Patients with small branch duct/gastric-type IPMNs (<2 cm) without symptoms or mural nodules can be managed by periodic surveillance.     

Primary pancreatic cystic neoplasms of the pancreas revisited. Part IV: rare cystic neoplasms

Primary pancreatic cystic neoplasms are being recognized with increasing frequency due to modern imaging techniques. In addition to the more common cystic neoplasms-serous cystadenoma, primary mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm-there are many other less common neoplasms that appear as cystic lesions. These cystic neoplasms include solid pseudopapillary neoplasm of the pancreas (the most common rare cystic neoplasm), cystic neuroendocrine neoplasm, cystic degeneration of otherwise solid neoplasms, and then the exceedingly rare cystic acinar cell neoplasm, intraductal tubular neoplasm, angiomatous neoplasm, lymphoepithelial cysts (not true neoplasms), and few others of mesenchymal origin. While quite rare, the pancreatic surgeon should at the least consider these unusual neoplasms in the differential diagnosis of potentially benign or malignant cystic lesions of the pancreas. Moreover, each of these unusual neoplasms has their own natural history/tumor biology and may require a different level of operative aggressiveness to obtain the optimal outcome.     

Intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are neoplasms of the pancreatic duct epithelium characterized by intraductal papillary growth and thick mucin secretion. Quantities of mucin fill the main and/or branches of pancreatic ducts and cause ductal dilatation. This review encompasses IPMNs, including symptoms, diagnosis, management, and prognosis. METHODS: A Pubmed database search was performed. All abstracts were reviewed and all articles in which cases of IPMNs could be identified were further scrutinized. Further references were extracted by cross-referencing. RESULTS: Only one-third of all patients are symptomatic. According to the site of involvement, IPMNs are classified into three types: main duct type, branch duct type, and combined type. Most branch type IPMNs are benign, while the other two types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch type IPMN and marked dilatation of the main duct indicate the existence of adenoma at least. Synchronous or metachronous malignancies may be developed in various organs. Endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, while magnetic resonance pancreatography best visualizes the entire outline of IPMNs. CONCLUSIONS: Prognosis is excellent after complete resection of benign and non-invasive malignant IPMNs. The extent of pancreatic resection and the intraoperative management of resection margins remain controversial. Total pancreatectomy should be reserved for patients with resectable but extensive IPMNs involving the whole pancreas; its benefits, however, must be balanced against operative and postoperative risks. Regular monitoring for disease recurrence is important after surgery.     

Conditional survival analysis for patients with intraductal papillary mucinous neoplasms (IPMNs) undergoing curative resection

Background

Conditional survival (CS) analysis represents a novel method that may provide more clinically relevant perspectives to cancer management compared to conventional survival analysis. The purpose of this study was to evaluate conditional survival for patients with intraductal papillary mucinous neoplasms (IPMNs) undergoing curative resection.

胰腺黏液性囊性肿瘤的诊治进展

胰腺囊性肿瘤是一种比较少见的胰腺肿瘤,主要包括黏液性囊性肿瘤、浆液性囊性肿瘤、导管内乳头状黏液瘤。其中,胰腺黏液性囊性肿瘤是常见的原发性胰腺囊性肿瘤之一,由于它是一种具有潜在恶性的肿瘤,故术前诊断具有重要意义。近年来,随着现代影像技术如 CT、MRI 及 EUS 等的提高和完善,术前胰腺黏液性囊性肿瘤的诊断率比以往已有大大提高,但在治疗方面仍然没有统一的指南或规范。本文着重对胰腺黏液性囊性肿瘤的诊断、治疗进展做一综述。     

Intraductal papillary mucinous neoplasm of the pancreas rapidly xenografts in chicken eggs and predicts aggressiveness

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology, and marker expression. Of the IPMN tissues transplanted into eggs, 63% formed tumor xenografts within 4 days, while none of the 12 IPMN tissues transplanted into immunodeficient mice engrafted. In the eggs, the grafting efficiency of high‐grade (n = 14) and intermediate‐grade (n = 17) dysplasia was 77% and was significantly higher than the 39% grafting efficiency of low‐grade dysplasia (n = 18). According to mucinous expression, 46 IPMN tissues were classified into gastric (n = 6), intestinal (n = 3), oncocytic (n = 23), and pancreatobiliary (n = 14) subtypes. The grafting efficiency was highest for the pancreatobiliary subtype (86%), followed by the oncocytic (70%), gastric (33%) and intestinal (33%) subtypes. The morphology and expression patterns of mucins, progression markers and pancreatic ductal markers were comparable between the primary IPMN tissues and their xenograft copies. The individual tumor environment was largely maintained during subtransplantation, as evaluated upon passage 6. This new IPMN model may facilitate experimental studies and treatment decisions for the optimal personalized management of IPMN.     

Pancreatic intraductal papillary mucinous neoplasms: Current diagnosis and management

Intraductal papillary mucinous neoplasms (IPMNs) represent approximately 1% of all pancreatic neoplasms and 25% of cystic neoplasms. They are divided into three types: main duct-IPMN (MD-IPPMN), branch duct-IPMN (BD-IPMN), and mixed type-IPMN. In this review, diagnostics, including clinical presentation and radiological investigations, were described. Magnetic resonance imaging is the most useful for most IPMNs. Management depends on the type and radiological features of IPMNs. Surgery is recommended for MD-IPMN. For BD-IPMN, management involves surgery or surveillance depending on the tumor size, cyst growth rate, solid components, main duct dilatation, high-grade dysplasia in cytology, the presence of symptoms (jaundice, new-onset diabetes, pancreatitis), and CA 19.9 serum level. The patient’s age and comorbidities should also be taken into consideration. Currently, there are different guidelines regarding the diagnosis and management of IPMNs. In this review, the following guidelines were presented: Sendai International Association of Pancreatology guidelines (2006), American Gastroenterological Association guidelines, revised international consensus Fukuoka guidelines (2012), revised international consensus Fukuoka guidelines (2017), and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas (2018). The Verona Evidence-Based Meeting 2020 was also presented and discussed.     

Radiology of pancreatic neoplasms: An update

Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis.     

Intraductal papillary mucinous tumour of the pancreas: Imaging features

Intraductal papillary mucinous tumour of the pancreas is an uncommon distinctive pancreatic tumour characterized by dilatation of the main pancreatic duct or branch ducts as a result of excessive production and disturbance in the draining of mucin. The imaging characteristics of a case in an 82‐year‐old woman are compared.     

The faith of non-surveilled pancreatic cysts: a bicentric retrospective study

BackgroundIncidental discovery of pancreatic cystic neoplasms (PCLs) is a common and steadily increasing occurrence. The aim of this study was to investigate a cohort of patients presenting with incidentally detected PCLs which were not included in a surveillance protocol, and to compare their risk of malignant evolution with that of systematically surveilled lesions.Materials and methodsA population of PCLs which did not receive surveillance over a period >10 years (population A) was selected at the Medical University of Vienna. A group of “low risk” branch duct intraductal papillary mucinous neoplasm ≤15 mm in size upon diagnosis undergoing a regular follow-up of at least 5 years at the University of Verona was selected as control (population B). The incidence of pancreatic cancer (PC), cumulative risk of PC and disease-specific survival were compared.ResultsOverall, 376 patients with non-surveilled PCLs were included in study group A and compared to 299 patients in group B. This comparison resulted in similar incidence rates of PC (1.6% vs 1.7%, p = 0.938), a strong similarity in terms of disease-specific mortality rates (1.3% vs 0.3%, p = 0.171) and the 5- and 10-year cumulative risk of PC (? 1% and 2%, p = 0.589) and DSS (? 100% and 98%, p = 0.050).ConclusionThe “price to pay” for a negligence-based policy in the population of non-surveilled PCLs was reasonable, and the incidence of PC was comparable to that reported for a population of low-risk cysts enrolled to a standardized surveillance protocol.     

胰腺囊性肿瘤诊疗及进展

胰腺囊性肿瘤(PCNs)是少见肿瘤,发病原因尚不明确,不良生活习惯（吸烟、饮酒、重咖啡、高脂高蛋白饮食等）、慢性胰腺炎、环境污染因素及遗传因素等是潜在致病因素。PCNs分为浆液性囊性肿瘤（SCN）、黏液性囊性肿瘤（MCN）、胰腺导管内乳头状黏液肿瘤(IPMN)和实性假乳头状瘤（SPN）四种类型。发病症状常不典型,早期诊断难。PCNs具有典型影像特点,单个影像检查技术对PCNs的准确性和局限性不同,CT检查在胰腺病变中仍是最基本、最主要的检查方式。MRI对于小的囊性病灶比CT更有优势。超声内镜（EUS）充分结合了内镜和超声检查的优势,与CT、MRI检查相辅相成,同时还可进行细针穿刺取病理及囊液分析。尽管PCNs大部分为良性,但只要达到切除标准,均应推荐患者进行手术治疗,严格遵循PCNs诊治流程,制订个体化PCNs治疗策略,使患者利益最大化。     

Adjuvant chemotherapy seems beneficial for invasive intraductal papillary mucinous neoplasms

Aims

The incidence of intraductal papillary mucinous neoplasm (IPMN) is rising and these neoplasms now represent up to 25% of resected pancreatic neoplasms. The optimal postoperative management of resected invasive IPMN is still debated in the absence of large prospective clinical trials and of validated prognostic factors in this setting. The objective of our study was to identify potential prognostic factors and to investigate the role of adjuvant therapies for patients radically resected for invasive IPMN.

Methods

We retrospectively reviewed clinical and pathological data regarding a large series of patients with invasive IPMN who underwent surgical resection in the last six years at University Hospital of Pisa.

Results

Sixty-four patients were considered for the analysis, thirty-three of whom received adjuvant chemotherapy with gemcitabine. In our series node involvement and high tumoral grade emerged as the major pathologic prognostic factors. Patients treated with adjuvant chemotherapy with gemcitabine experienced a longer disease-free survival than those who received surgery alone.

Conclusions

Gemcitabine-based chemotherapy seems beneficial as adjuvant treatment for patients with resected invasive IPMN.     

肝胆管黏液性囊性肿瘤临床病理分析

 目的　探讨肝胆管黏液性囊性肿瘤的临床病理特点。方法　选取1993年5月至2007年5月间经手术病理证实的肝胆管黏液性囊性肿瘤9例,对其临床表现、影像学及病理特征进行回顾性分析。结果　肝胆管黏液性囊腺瘤6例,呈多房性,囊壁光整,厚薄一致,分隔均匀;囊腺癌3例,单囊性2例,多囊性1例,壁结节2例,乳头状突起及囊壁局部不均匀增厚1例,钙化2例,CT增强扫描动脉期囊壁及壁结节开始强化,门脉期及延迟期强化明显,呈"慢进慢出"特点,腹膜后淋巴结肿大1例。结论　肝胆管黏液性囊性肿瘤临床表现缺乏特异性,CT表现具有一定特征,单囊、囊壁不均匀增厚、壁上结节或乳头状突起及斑块状钙化者考虑为囊腺癌,但确诊需依靠病理。