scholarly journals Relevance of gene mutations and methylation to the growth of pancreatic intraductal papillary mucinous neoplasms based on pyrosequencing

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Go Asano ◽  
Katsuyuki Miyabe ◽  
Hiroyuki Kato ◽  
Michihiro Yoshida ◽  
Takeshi Sawada ◽  
...  

AbstractWe aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions (p = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation (r =  − 0.3739, p = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion (p = 0.0128), perineural invasion (p = 0.0377), and lymph node metastasis (p = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation (p = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types (p = 0.0319). Methylation of RASSF1A, CDKN2A, and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.

2019 ◽  
Vol 07 (09) ◽  
pp. E1130-E1134
Author(s):  
Jean-Michel Gonzalez ◽  
Diane Lorenzo ◽  
Jean-Philippe Ratone ◽  
Adrian Culetto ◽  
Frédérique Maire ◽  
...  

Abstract Introduction Branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) require follow-up to detect worrisome features (WF). Data are missing about endoscopic pancreatic sphincterotomy (PS) for symptomatic IPMN. Patients and methods This was a retrospective multicenter study in four expert centers. Patients treated with endoscopic PS for symptomatic (painful) BD-IPMN without WF were included. Age, sex, follow-up time, characteristics of IPMNs and endoscopic retrograde cholangiopancreatographies (ERCPs), and indications for surgery were recorded. Results In total, 21 patients were included (median age 68 years, range 45 – 87 years). The median number of cysts was 2 (range 1 – 10), located in the head (59 %), body/tail (17 %), or multifocal (24 %). ERCP including PS was completed in all of the cases, with biliary sphincterotomy in 33 %. Clinical efficacy after one session was 81 % (17/21). Among the failures, one had a second successful PS and three were operated. The final efficacy was 86 % (18/21). Seven patients were operated after a mean of 19 months: four for WF, three for pain. The histopathology showed four low grade dysplasia, one high grade dysplasia, and two no dysplasia. No adenocarcinoma occurred during a follow-up of 99 months (range 14 – 276 months). Conclusions Endoscopic PS for symptomatic IPMN without WF is effective in more than 80 % of cases, without increasing the risk for adenocarcinoma.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Stefano Palmucci ◽  
Claudia Trombatore ◽  
Pietro Valerio Foti ◽  
Letizia Antonella Mauro ◽  
Pietro Milone ◽  
...  

Intraductal papillary mucinous neoplasms (IPMNs) represent a group of cystic pancreatic neoplasms with large range of clinical behaviours, ranging from low-grade dysplasia or borderline lesions to invasive carcinomas. They can be grouped into lesions originating from the main pancreatic duct, main duct IPMNs (MD-IPMNs), and lesions which arise from secondary branches of parenchyma, denominated branch-duct IPMNs (BD-IPMNs). Management of these cystic lesions is essentially based on clinical and radiological features. The latter have been very well described in the last fifteen years, with many studies published in literature showing the main radiological features of IPMNs. Currently, the goal of imaging modalities is to identify “high-risk stigmata” or “worrisome feature” in the evaluation of pancreatic cysts. Marked dilatation of the main duct (>1 cm), large size (3–5 cm), and intramural nodules have been associated with increased risk of degeneration. BD-IPMNs could be observed as microcystic or macrocystic in appearance, with or without communication with main duct. Their imaging features are frequently overlapped with cystic neoplasms. The risk of progression for secondary IPMNs is lower, and subsequently an imaging based follow-up is very often proposed for these lesions.


2015 ◽  
Vol 143 (5-6) ◽  
pp. 332-336 ◽  
Author(s):  
Dejan Stevanovic ◽  
Dragos Stojanovic ◽  
Nebojsa Mitrovic ◽  
Damir Jasarovic ◽  
Sanja Milenkovic ◽  
...  

Introduction. Intraductal papillary mucinous neoplasms (IPMN) are among the most common cystic neoplasms of the pancreas, but they represent only 1-3% of all exocrine pancreas tumors. With the development of diagnostic possibilities the number of patients with IPMN is constantly increasing and represents approximately 20% of all surgically treated pancreatic tumors. The development of laparoscopic surgery has led to advances in the treatment of cystic tumors of the pancreas with the emergence of new surgical dilemma in the choice of surgical techniques in patients with IPMN. Case Outline. A 23-year-old patient was admitted to the hospital with non-specific symptoms of upper abdomen. Performed diagnostics indicated the existence of a tumor formation at the periphery of the pancreas, in the region of the proximal corpus, 8?5 cm in diameter. The cystic formation, wall thickness 3 mm, was filled with dense contents and injected into the tissue of the pancreas, but did not lead to an extension of the pancreatic duct. After adequate preoperative preparation the patient was operated on, when a laparoscopic enucleation of cystic tumor with coagulation and cutting off communication between the peripheral pancreatic duct and pancreatic tumors was performed by using ultrasound scissors. Histopathological analysis of the specimen indicated an IPMN of the branch duct type (BD-IPMN) with a low grade dysplasia. The line of resection was without cellular atypia. Immunohistochemical analysis showed positivity on tumor mucins (MUC-5 and MUC-2), which is typical for gastric type of BD-IPMN. Six months postoperatively the patient showed no signs of recurrence of the disease. Conclusion. Surgical treatment is the dominant choice for the treatment for IPMN. Although minimally invasive, laparoscopic enucleation of BD-IPMN is able to achieve an adequate level of radicality without the accompanying complications and with short postoperative recovery period.


2019 ◽  
Vol 14 ◽  
pp. 117727191985150 ◽  
Author(s):  
Riki Ohno ◽  
Ryuichi Kawamoto ◽  
Mami Kanamoto ◽  
Jota Watanabe ◽  
Masahiko Fujii ◽  
...  

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 ( P = .001), prognostic nutritional index (PNI) < 45 ( P = .016), CA 19-9 > 37 U/mL ( P = .039), and cystic diameter ⩾ 30 mm ( P = .010), and mural nodule ( P = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1


Surgery Today ◽  
2019 ◽  
Vol 50 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Seiko Hirono ◽  
Hiroki Yamaue

AbstractThe current treatment strategy for intraductal papillary mucinous neoplasms (IPMNs), based on the international consensus guideline, has been accepted widely. However, reported outcomes after surgical resection for IPMN show that once the tumor progresses to invasive intraductal papillary mucinous carcinoma (IPMC), recurrence is not uncommon. The surgical treatment for IPMN is invasive and sometimes followed by complications. Therefore, the best timing for resection might be at the point when high-grade dysplasia (HGD) is evident. According to previous reports, main duct type IPMN has a high malignant potential and its surgical resection is universally accepted, whereas, the incidence of HGD/invasive IPMC in branch duct and mixed type IPMNs is thought to be lower. In addition to mural nodules and a dilated main pancreatic duct, cytology and measurement of the carcinoembryonic antigen level in the pancreatic juice might be useful to differentiate HGD/invasive IPMC from low-grade dysplasia. The nomogram proposed recently to predict the risk of HGD/invasive IPMC in IPMN patients might help surgeons decide on the best treatment strategy, depending on the patient’s age and general condition. Second resection for high-risk lesions in the remnant pancreas might improve the survival of IPMN patients.


Pancreatology ◽  
2008 ◽  
Vol 8 (3) ◽  
pp. 277-284 ◽  
Author(s):  
Martha Bishop Pitman ◽  
Paul J. Michaels ◽  
Vikram Deshpande ◽  
William R. Brugge ◽  
Brenna C. Bounds

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 199 ◽  
Author(s):  
Giacomo Santandrea ◽  
Simonetta Piana ◽  
Riccardo Valli ◽  
Magda Zanelli ◽  
Elisa Gasparini ◽  
...  

The term “ovarian carcinoma” encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.


Digestion ◽  
2021 ◽  
pp. 1-8
Author(s):  
Shigeki Fukusada ◽  
Takaya Shimura ◽  
Hiroyasu Iwasaki ◽  
Yusuke Okuda ◽  
Takahito Katano ◽  
...  

<b><i>Introduction:</i></b> The natural history and prognosis of superficial nonampullary duodenal epithelial tumors (SNADETs) remain uncertain. We elucidated the relationship between immunophenotype and clinicopathological features. <b><i>Materials and Methods:</i></b> A total of 98 SNADETs were divided into 3 groups according to immunohistochemical findings: gastric phenotype (G type), gastrointestinal phenotype (GI type), and intestinal phenotype (I type). Cellular dysplasia was divided into low-grade dysplasia and high-grade dysplasia/adenocarcinoma (≥HGD). White opaque substance (WOS) deposition was categorized into diffuse WOS, partial WOS, and no WOS, based on endoscopic findings. <b><i>Results:</i></b> Of the 98 SNADETs, 4 lesions (4.1%) were G type, 32 lesions (32.7%) were GI type, and 62 lesions (63.2%) were I type. All G-type SNADETs were located in the oral side of the papilla including the bulb, and the rate of bulbar lesions was significantly higher in the G type than in the GI and I types (<i>p</i> = 0.004). The most frequent type of WOS was no WOS (4/4, 100%) for G type, partial WOS (19/32, 59.4%) for GI type, and diffuse WOS (34/62, 54.8%) for I type (<i>p</i> &#x3c; 0.001), and loss of intestinal character was significantly correlated with WOS deficiency. GI/I-type SNADETs with partial or no WOS and G-type SNADETs were associated with ≥HGD. Additionally, the frequency of ≥HGD lesion was significantly higher in the CD10-negative group than in the CD10-positive group (57.1 vs. 19.8%, <i>p</i> = 0.043). <b><i>Conclusion:</i></b> Pathological intestinal character was correlated with the presence of WOS, and CD10 loss was associated with malignant potential of SNADETs.


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