Helicobacter pylori is undetectable in intraductal papillary mucinous neoplasm

BackgroundAbout half of the world population is infected with Helicobacter pylori (H. pylori), a bacterium associated with gastric cancer and considered to be a risk factor for pancreatic ductal adenocarcinoma. Whether the bacterium is associated with intraductal papillary mucinous neoplasm, believed to be a precursor of pancreatic ductal adenocarcinoma, is unknown. The aim of this study was to investigate the presence of H. pylori DNA in tissue sections of intraductal papillary mucinous neoplasm.MethodsThe presence of H. pylori DNA was tested in a retrospective controlled study of formalin-fixed, paraffin-embedded pancreatic tissues from 24 patients who underwent surgery for intraductal papillary mucinous neoplasm. Histologically normal tissues surrounding neoplasms were used as control. H. pylori DNA was evaluated after deparaffinization, DNA extraction, and purification, and results were evaluated statistically.ResultsSamples were collected from 13 males and 11 females with mean age 59 years (range 44–77), and consisted of 19 cases of main-duct and three cases of branched-duct intraductal papillary mucinous neoplasm. Two patients were diagnosed with pancreatic cancer and main-duct intraductal papillary mucinous neoplasm. H. pylori DNA was not detected either in intraductal papillary mucinous neoplasm tissue, or in surrounding normal tissue.ConclusionsAlthough H. pylori has been implicated in pancreatic ductal adenocarcinoma, it may not play a key role in the development of intraductal papillary mucinous neoplasm.     

Endoscopic ultrasonography findings of pancreatic parenchyma for predicting subtypes of intraductal papillary mucinous neoplasms

Background and aimsThe subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS).MethodsSixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma.ResultsThe subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P < 0.0001). Early CP findings ≥2 and atrophic parenchyma were significantly correlated with I-type (P < 0.0001). PB-type was significantly associated with pancreatic parenchyma without early CP findings or fatty degeneration in comparison to the other subtypes (P < 0.0001). Using the above characteristic EUS findings, the sensitivity, specificity, and accuracy were as follows: 63%, 92% and 74%, respectively, in G-type, 57%, 96% and 87% in I-type, and 90%, 94% and 94% in PB-type.ConclusionsThe evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN.     

Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma

Background/objectivesResections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome.MethodsConsecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test.Results513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%–45%; p < 0.001 and 44%–57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001).ConclusionIn this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.     

Molecular mechanism of intraductal papillary mucinous neoplasm and intraductal papillary mucinous neoplasm‐derived pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies. Dissecting the mechanisms underlying PDA development is important for developing early detection methods and effective prevention and therapies for the disease. PDA is considered to arise from distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, little is known about molecular mechanisms of development of IPMN and IPMN‐derived PDA. We have recently reported that loss of Brg1, a core subunit of SWI/SNF chromatin remodeling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA. Brg1 null IPMN‐PDA is less lethal compared to PanIN‐derived PDA (PanIN‐PDA) driven by mutant Kras and hemizygous p53 deletion, mirroring prognostic trends in PDA patients. Brg1 null IPMN‐PDA possesses a distinct molecular signature that supports less malignant potential compared to PanIN‐PDA. Furthermore, Brg1 deletion inhibits Kras‐dependent PanIN development from adult acinar cells, but promotes Kras‐driven preneoplastic transformation in adult duct cells. Therefore, Brg1 is a determinant of context‐dependent Kras‐driven pancreatic tumorigenesis and chromatin remodeling may underlie the development of distinct PDA subsets. Understanding molecular mechanism of IPMN and IPMN‐derived PDA could provide critical clues for novel diagnostic and therapeutic strategies of the disease.     

Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy

BackgroundThe decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas.ObjectivesWe aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs.MethodsThis single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis.ResultsAfter excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group.ConclusionsIn patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.     

Endoscopic ultrasound in the diagnosis of pancreatic intraductal papillary mucinous neoplasms

Pancreatic cystic lesions are increasingly recognised due to the widespread use of different imaging modalities.Intraductal papillary mucinous neoplasms(IPMNs)of the pancreas represent a common,but also heterogeneous group of cystic tumors with a significant malignant potential.These neoplasms must be differentiated from other cystic tumors and properly classified into their different types,main-duct IPMNs vs branchduct IPMNs.These types have a different malignant potential and therefore,different treatment strategies need to be implemented.Endoscopic ultrasound(EUS)offers the highest resolution of the pancreas and can aid in the differential diagnosis,classification and differentiation between benign and malignant tumors.The addition of EUS fine-needle aspiration can supply further information by obtaining fluid for cytology,measurement of tumor markers and perhaps DNA analysis.Novel techniques,such as the use of contrast and sophisticated equipment,like intraductal probes can provide information regarding malignant features and extent of these neoplasms.Thus,EUS is a valuable tool in the diagnosis and appropriate management of these tumors.     

Multifocal intraductal papillary mucinous neoplasm of the pancreas-A case report

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas （IPMNs）. IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively ＂new＂ but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head （75%） while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-year- old male diagnosed with IPMN （carcinoma in situ） in the pancreatic head and a branch duct type IPMN （duct atypia） in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.     

Synchronous pancreatic solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.     

Pancreatic intraductal papillary mucinous neoplasm in a patient with Lynch syndrome

Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing epithelial neoplasm that carries a risk of progression to invasive pancreatic ductal adenocarcinoma. Lynch syndrome is an autosomal dominant condition caused by germline mutations in mismatch repair genes such as MSH2 that lead to microsatellite instability and increased risk of tumor formation. Although families with Lynch syndrome have an increased risk of pancreatic cancer, a clear connection between Lynch syndrome and IPMN has not been drawn. We present a report of a 58 year-old Caucasian woman with multiple cancers and a germline mutation of MSH2 consistent with Lynch syndrome. A screening abdominal computed tomography scan revealed a dilated main pancreatic duct and cystic ductular structure in the uncinate process that were consistent with IPMN of the main pancreatic duct on excision. Immunohistochemistry and polymerase chain reaction of the patient’s pancreas specimen did not reveal microsatellite instability or mismatch repair gene loss of expression or function. Our findings may be explained by the fact that loss of mismatch repair function and microsatellite instability is a late event in neoplastic transformation. Given the relative rarity of main duct IPMN, its appearance in the setting of somatic MSH2 mutation suggests that IPMN may fit into the constellation of Lynch syndrome related malignancies.     

胰腺导管内乳头状黏液瘤

胰腺导管内乳头状黏液瘤（IPMN）是由胰腺导管内产生黏液的上皮细胞呈乳头状增殖形成的肿瘤。与经典的胰腺癌相比,IPMN具有低度恶性、生长缓慢、少有侵犯周围组织、淋巴结转移率和再发率低的特点。IPMN根据肿瘤累及的部位可分为主胰管型、分支胰管型和混合型,病理组织特征涵盖从单纯腺瘤到浸润癌等多个亚型,临床表现多样,多种影像学检查手段可显示弥漫性或节段性扩张的主胰管和囊状扩张的分支胰管,ERCP经扩大的乳头获取黏液和胰液,取胰腺导管内皮组织和壁结节供活检均有助于诊断。IPMN确诊后应积极手术,手术切除率高,术后5年生存率高于一般的胰腺癌。本文就其临床表现、分类、病理特征、影像学诊断和治疗等方面做一综述。     

Diagnosis of intraductal papillary mucinous neoplasm using endoscopic ultrasound guided microbiopsies:A case report

Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging,but current diagnostic modalities have limited diagnostic accuracy.Recently,a novel through-the-needle microbiopsy forceps has become available,offering the possibility of obtaining cyst-wall biopsies.We present a case of 41-year-old male with chronic pancreatitis and a 2-cm pancreatic cyst,initially considered a pseudocyst.Subsequently,endoscopic ultrasou-nd guided microbiopsies were successfully obtained,which surprisingly revealed an intraductal papillary mucinous neoplasm of mixed subtype with low grade dysplasia.In conclusion,obtaining biopsies from the wall of the pancreatic cystic lesions with this novel instrument is feasible and,as demonstrated in this case,can possibly alter the clinical outcome.Microbiopsies offered enough cellular material,allowing supplemental gene mutation analysis,which combined with other modalities could lead to a more individual approach when treating pancreatic cysts.However,prospective studies are warranted before routine clinical implementation.     

Predictive factors associated with malignancy of intraductal papillary mucinous pancreatic neoplasms

AIM:To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms(IPMNs) of the pancreas.METHODS:Between April 1995 and April 2010,129 patients underwent surgical resection for IPMNs at our institute and had confirmed pathologic diagnoses.The medical records were retrospectively reviewed and immunohistochemical staining for mucin(MUC) in pancreatic tissues was performed.RESULTS:Univariate analysis showed that the following five variables were closely asso...     

Experience of limited pancreatic head resection for management of branch duct intraductal papillary mucinous neoplasm in a single center

AIM： To share our surgical experience and the outcome of limited pancreatic head resection for the management of branch duct intraductal papillary mucinous neoplasm （IPMN）.
METHODS： Between May 2005 and February 2008, nine limited pancreatic head resections （LPHR） were performed for IPMN of the pancreatic head. We reviewed the nine patients, retrospectively.
RESULTS： Tumor was located in the uncinate process of the pancreas in all nine patients. Three patients had stents inserted in the main pancreatic duct due to inju- ry. The mean size of tumor was 28.4 mm. Postoperative complications were found in five patients： 3 pancreatic leakages, a pancreatitis, and a duodenal stricture. Pancreatic leakages were improved by external drainage. No perioperative mortality was observed and all patients are recorded alive during the mean follow-up period of 17.2 mo.
CONCLUSION： In selected patients after careful evaluation, LPHR can be used for the treatment of branch duct type IPMN. In order to avoid pancreatic ductal injury, pre- and intra-operative definite localization and careful operative techniques are required.     

Long-term follow-up of branch-duct intraductal papillary mucinous neoplasms with No change in first 5 Years of diagnosis

BackgroundDiscontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated.MethodsWe performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS).ResultsOf 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12–23) vs. 12 (9–17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4–6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively.ConclusionsIncidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients’ overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.     

Metachronous occurrence of main-duct intraductal papillary mucinous neoplasm (IPMN) and adenocarcinoma in a chronic pancreatitis patient: A case report

Rationale:Chronic pancreatitis (CP) is a risk factor for developing pancreatic ductal adenocarcinoma (PDAC). In addition, a patient with partial pancreatectomy for intraductal papillary mucinous neoplasm (IPMN) can also lead to PDAC. In contrast, IPMN is a distinct disease entity, independent of CP, and there have been few reports that CP is the cause of IPMN. To the best of our knowledge, this is the first clinical case report of the metachronous occurrence of main-duct IPMN and PDAC with a 9 and half-year interval in a patient with chronic alcoholic pancreatitis.Patient concerns:A 50-year-old man with a long medical history of recurrent alcoholic pancreatitis and hepatitis over a decade was diagnosed with another episode of acute pancreatitis based on laboratory findings and clinical symptoms. The patient underwent pylorus-preserving pancreaticoduodenectomy (PPPD) for a small nodular lesion in the main duct of the pancreatic head and was diagnosed with main-duct IPMN low-grade dysplasia and associated fibrosing CP. Nine and a half years later, a 59-year-old man lost 7 kg over 3 months and was diagnosed with new-onset diabetes mellitus.Diagnosis:The patient was diagnosed with metachronous, well-differentiated PDAC with concomitant CP.Interventions:The patient underwent radical antegrade modular pancreatosplenectomy (RAMPS) for a small nodular mass in the remnant pancreas.Outcomes:The patient was healthy for 44 months without evidence of tumor recurrence during clinical follow-up examinations including laboratory findings, tumor marker, and imaging studies.Lessons:Early diagnosis of metachronous pancreatic neoplasia in a patient with chronic pancreatitis could be made by correlating newly developed clinical symptoms and signs with careful radiological examinations.     

Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas

AIM: As intraductal papillary mucinous neoplasm (IPMN) has a favorable prognosis, associated malignancies have potential significance in these patients. We examined the incidence and characteristics of pre-existing, coexisting and subsequent malignancies in patients with IPMN. METHODS: Seventy-nine cases of IPMN were diagnosed by detection of mucous in the pancreatic duct during endoscopic retrograde pancreatography. Histological diagnosis was confirmed in 30 cases (adenoma (n=19) and adenocarcinoma (n =11). Other primary malignancies associated with IPMN, occurring in the prediagnostic or postdiagnostic period, were investigated. Postdiagnostic follow-up period was 3.3±0.5 years (range, 0.2-20 years). RESULTS: Other 40 malignancies occurred in 28 patients (35%). They were found before(n=15), at (n=19) and after (n=6) the diagnosis of IPMT. Major associated malignancies were gastric cancer (n=12), colonic cancer (n=7), esophageal cancer (n=4), pulmonary cancer (n=4), and independent pancreatic cancer (n=3). Pancreatic cancer was synchronous with IPMN in two patients and metachronous in one (3 years after diagnosis of IPMN). Thirty-one lesions were treated surgically or endoscopically. Fourteen patients died of associated cancers. Development of other malignancies was related to age (71.9±8.2 vs66.8±9.3, P<0.05), but not to gender or site of the tumor. CONCLUSION: IPMN is associated with a high incidence of other malignancies, particularly gastric and colonic cancers. Common genetic mechanisms between IPMN and other associated malignancies might be present. Clinicians should pay attention to the possibility of associated malignancies in preoperative screening and follow-up of patients with IPMN.     

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.