Intraductal oncocytic papillary neoplasms of the pancreas and bile ducts: a description of five new cases and review based on a systematic survey of the literature.

PubMed

Liszka, Lukasz; Pajak, Jacek; Zielińska-Pajak, Ewa; Krzych, Lukasz; Gołka, Dariusz; Mrowiec, Sławomir; Lampe, Paweł

2010-05-01

Intraductal oncocytic papillary neoplasms (IOPN) are rare tumors of the pancreatic and biliary ductal system. It is not absolutely clear if the molecular and clinicopathologic characteristics of IOPN differ significantly from other related lesions, namely intraductal papillary mucinous neoplasms (IPMN). Therefore it is not clear if it is reasonable to consider IOPN as a separate diagnostic and clinical entity. In order to describe the clinicopathologic characteristics of IOPN and to compare them with the IPMN profile, we performed a systematic review of the literature and additionally studied five previously unreported IOPN cases. IOPN differ from IPMN by lack of K-ras gene mutations in all studied cases. Several differences in the clinical and biological profile between IOPN and IPMN exist, but they are of quantitative rather than of qualitative nature. Additionally, pancreaticobiliary or gastric-foveolar IPMN components may coexist with IOPN component within a single lesion, which suggests at least a partial relation of the pathogenetic pathways of IPMN and IOPN. Importantly, the pathogenesis of accumulation of mitochondria and oxyphilic appearance of IOPN remains unknown. At present, there are no reliable criteria other than histopathological picture and K-ras gene status to differentiate IOPN from IPMN. In particular, no clear differences in optimal treatment options and prognosis between these tumors are known. Further studies are needed to clarify the biology of IOPN and to establish their position in clinicopathologic classifications of pancreatic tumors.

Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers.

PubMed

Shimizu, Yasuhiro; Yamaue, Hiroki; Maguchi, Hiroyuki; Yamao, Kenji; Hirono, Seiko; Osanai, Manabu; Hijioka, Susumu; Hosoda, Waki; Nakamura, Yasushi; Shinohara, Toshiya; Yanagisawa, Akio

2013-07-01

The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

Plasma protein profiling of patients with intraductal papillary mucinous neoplasm of the pancreas as potential precursor lesions of pancreatic cancer.

PubMed

Ilies, Maria; Sappa, Praveen Kumar; Iuga, Cristina Adela; Loghin, Felicia; Gesell Salazar, Manuela; Weiss, Frank Ulrich; Beyer, Georg; Lerch, Markus M; Völker, Uwe; Mayerle, Julia; Hammer, Elke

2018-02-01

Efforts for the early diagnosis of the pancreatic ductal adenocarcinoma (PDAC) have recently been driven to one of the precursor lesions, namely intraductal papillary mucinous neoplasm of the pancreas (IPMN). Only a few studies have focused on IPMN molecular biology and its overall progression to cancer. Therefore, IPMN lacks comprehensive characterization which makes its clinical management controversial. In this study, we characterized plasma proteins in the presence of IPMNs in comparison to healthy controls, chronic pancreatitis, and PDAC by a proteomics approach using data-independent acquisition based mass spectrometry. We describe several protein sets that could aid IPMN diagnosis, but also differentiation of IPMN from healthy controls, as well as from benign and malignant diseases. Among all, high levels of carbonic anhydrases and hemoglobins were characteristic for the IPMN group. By employing ELISA based quantification we validated our results for human tissue inhibitor of metalloproteinase inhibitor 1 (TIMP-1). We consider IPMN management directed towards an early potential cancer development a crucial opportunity before PDAC initiation and thus its early detection and cure. Copyright © 2017 Elsevier B.V. All rights reserved.

Intraductal papillary mucinous neoplasms: does a family history of pancreatic cancer matter?

PubMed

Nehra, Deepika; Oyarvide, Vicente Morales; Mino-Kenudson, Mari; Thayer, Sarah P; Ferrone, Cristina R; Wargo, Jennifer A; Muzikansky, Alona; Finkelstein, Dianne; Warshaw, Andrew L; Castillo, Carlos Fernández-del

2012-01-01

The purpose of this study is to compare surgically resected intraductal papillary mucinous neoplasms (IPMNs) in patients with and without a family history of pancreatic cancer to gain insight into differences that may suggest the need for differential management. A retrospective review of patients who underwent resection of an IPMN at the Massachusetts General Hospital (1990-2011) was conducted. Three hundred and twenty-four patients of whom 45 (13.9%) had a family history of pancreatic cancer were identified. Patients with (PFH) and without (NFH) a family history of pancreatic cancer were compared. There were no differences in demographic characteristics between groups. Extra-pancreatic malignancies diagnosed prior to the IPMN were more common in those with a PFH (35.6% vs 20.1%, p = 0.03). There were no differences in IPMN characteristics between groups including no difference in the presence of invasive disease (p = 0.55). Concurrent pancreatic ductal adenocarcinomas were more common in those with a PFH (11.1% vs 2.9%, p = 0.02). The survival in the PFH group was marginally lower than the NFH group, a difference found to be attributable to the higher prevalence of extra-pancreatic malignancies. Characteristics of surgically resected IPMNs are not different between patients with and without a family history of pancreatic cancer. Most importantly, the incidence of invasive disease is not different, suggesting that these lesions may not be more aggressive when they occur in the presence of a family history of pancreatic cancer. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Intraoperative ultrasound of the pancreas.

PubMed

Shin, Lewis K; Brant-Zawadzki, Graham; Kamaya, Aya; Jeffrey, R Brooke

2009-03-01

Intraoperative ultrasound provides spatial resolution of the pancreas superior to computed tomography, magnetic resonance imaging, and transabdominal sonography. This pictorial essay will review common benign and malignant pancreatic processes including the following: pancreatic ductal adenocarcinoma, pancreatitis, endocrine tumors, mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, serous cystadenoma, and solid pseudopapillary tumor. The use of intraoperative ultrasound in specific surgical situations will be discussed, which include the following: (1) identification of insulinoma(s) which are not detectable preoperatively, (2) identification of the pancreatic duct to determine dissection planes for chronic pancreatitis surgery (eg, Puestow procedure) and for tumor resection, and (3) staging purposes for malignant disease.

Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

PubMed

Sai, Jin Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio; Maehara, Tadayuki

2009-03-01

The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. Single-center retrospective study. Academic medical center. The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. Single-center and small number of patients. Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

PubMed

Lawson, Robert D; Hunt, Gordon C; Giap, Andrew Q; Krinsky, Mary L; Slezak, Jeff; Tang, Raymond S; Gonzalez, Ingrid; Kwong, Wilson T; Fehmi, Syed A; Savides, Thomas J

2015-01-01

The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria"). Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG). After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk.

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

PubMed

Grützmann, Robert; Niedergethmann, Marco; Pilarsky, Christian; Klöppel, Günter; Saeger, Hans D

2010-01-01

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.

Measurement of indicator genes using global complementary DNA (cDNA) amplification, by polyadenylic acid reverse transcriptase polymerase chain reaction (poly A RT-PCR): A feasibility study using paired samples from tissue and ductal juice in patients undergoing pancreatoduodenectomy.

PubMed

Sanyal, Sudip; Siriwardena, Ajith K; Byers, Richard

2018-06-01

The aim of this study is to compare gene expression profiles in RNA isolated from pancreatic ductal juice with the RNA expression profiles of the same genes from matched intra-operative tissue samples from pancreatic tumours. Intra-operative sampling of pancreatic juice and collection of matched tissue samples was undertaken in patients undergoing pancreatoduodenectomy for clinically suspected pancreatic cancer and a precursor lesion, main-duct intraductal papillary mucinous neoplasm. RNA was isolated and Poly A PCR was used to globally amplify the RNA. Real-time polymerase chain reaction (RT-PCR) was used to measure expression levels of 17 genes selected from microarray studies. Spearman's rank correlation test was used to examine the relationship of gene expression between pancreatic juice and tissue. The study was approved by Regional Ethics Committee. Mesothelin (MSLN) showed significant correlation (p < 0.008) in expression levels between paired pancreatic juice and tissue samples in pancreas cancer. In intraductal papillary mucinous neoplasms (IPMN), Matrix Metalloproteinase 7 (MMP7), showed significant correlation (p < 0.01) in the expression levels between paired pancreatic juice and tissue samples. This study confirms that RNA analysis of paired pancreatic juice and tissue samples and establishment of cDNA using poly A PCR is technically feasible. Application of the technique to non-invasively obtained pancreatic juice during endoscopic assessment of tumours and the use of gene arrays of cancer indicator genes are the next steps in development of this technique. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Phosphorylated Akt/PKB controls cell growth and apoptosis in intraductal papillary-mucinous tumor and invasive ductal adenocarcinoma of the pancreas.

PubMed

Semba, Shuho; Moriya, Toshiyuki; Kimura, Wataru; Yamakawa, Mitsunori

2003-04-01

Akt/PKB promotes cell proliferation and rescues cells from apoptosis. To evaluate the role of Akt/PKB, a key molecule in phosphatidylinositol 3-OH kinase (PI3K) signaling, during the development of pancreatic duct neoplasias such as intraductal papillary-mucinous tumor (IPMT) and invasive ductal adenocarcinoma (IDAC) of the pancreas. In PK-45H pancreatic cancer cells, the growth-inhibitory and apoptosis-inducing effects of LY294002, a PI3K inhibitor, were detected in a concentration-dependent manner, followed by the reduction of phosphorylated Akt levels. Immunohistochemical analyses revealed that frequent overexpression of phosphorylated Akt (Ser473) was detected in 10 (63%) of 16 IPMTs and 14 (70%) of 20 IDACs. It is interesting that the incidence of Akt phosphorylation closely correlated with Ki-67 immunoreactivity and had an inverse association with the number of cases of apoptotic bodies in both IPMT and IDAC. Although there was no good correlation with other clinicopathologic parameters, the two patients with recurrent IPMT had high levels of phosphorylated Akt. Our findings suggest that activation of Akt plays an important role during the progression of these pancreatic duct neoplasias at the early stage. Furthermore, inhibition of the PI3K-Akt/PKB pathway may have therapeutic potential in the treatment of pancreatic duct tumors.

Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms.

PubMed

Xu, Bin; Ding, Wei-Xing; Jin, Da-Yong; Wang, Dan-Song; Lou, Wen-Hui

2013-03-07

To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer

PubMed Central

Lawson, Robert D.; Hunt, Gordon C.; Giap, Andrew Q.; Krinsky, Mary L.; Slezak, Jeff; Tang, Raymond S.; Gonzalez, Ingrid; Kwong, Wilson T.; Fehmi, Syed A.; Savides, Thomas J.

2015-01-01

Background The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the “high-risk stigmata” or “worrisome features” criteria proposed in the 2012 international consensus guidelines (“Fukuoka criteria”). Methods Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria (“Highest-Risk Group”, HRG) and those without these criteria (“Lowest-Risk Group”, LRG). Results After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). Conclusions This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with “high-risk stigmata” or “worrisome features” criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk. PMID:26423829

Molecular diagnostics in the neoplasms of the pancreas, liver, gall bladder, and extrahepatic biliary tract.

PubMed

Weindel, Michael; Zulfiqar, Muhammad; Bhalla, Amarpreet; Shidham, Vinod B

2013-12-01

Pancreatic neoplasms, including ductal adenocarcinoma, intraductal papillary mucinous neoplasm, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and ampullary carcinoma, are associated with different genetic abnormalities. Liver neoplasms, including hepatic adenomas, hepatocellular carcinomas, and cholangiocarcinomas, are associated with identifiable risk factors and genetic changes. Gall bladder adenomas and adenocarcinomas arise from distinct molecular pathways. The molecular abnormalities seen in these tumors are not used routinely in the molecular diagnostic laboratory. Copyright © 2013 Elsevier Inc. All rights reserved.

Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms

PubMed Central

Yu, Jun; Sadakari, Yoshihiko; Shindo, Koji; Suenaga, Masaya; Brant, Aaron; Almario, Jose Alejandro Navarro; Borges, Michael; Barkley, Thomas; Fesharakizadeh, Shahriar; Ford, Madeline; Hruban, Ralph H; Shin, Eun Ji; Lennon, Anne Marie; Canto, Marcia Irene; Goggins, Michael

2017-01-01

Objective Secretin-stimulated pancreatic juice contains DNA shed from cells lining the pancreatic ducts. Genetic analysis of this fluid may form a test to detect pancreatic ductal neoplasia. Design We employed digital next-generation sequencing (‘digital NGS’) to detect low-abundance mutations in secretin-stimulated juice samples collected from the duodenum of subjects enrolled in Cancer of the Pancreas Screening studies at Johns Hopkins Hospital. For each juice sample, digital NGS necessitated 96 NGS reactions sequencing nine genes. The study population included 115 subjects (53 discovery, 62 validation) (1) with pancreatic ductal adenocarcinoma (PDAC), (2) intraductal papillary mucinous neoplasm (IPMN), (3) controls with non-suspicious pancreata. Results Cases with PDAC and IPMN were more likely to have mutant DNA detected in pancreatic juice than controls (both p<0.0001); mutant DNA concentrations were higher in patients with PDAC than IPMN (p=0.003) or controls (p<0.001). TP53 and/or SMAD4 mutations were commonly detected in juice samples from patients with PDAC and were not detected in controls (p<0.0001); mutant TP53/SMAD4 concentrations could distinguish PDAC from IPMN cases with 32.4% sensitivity, 100% specificity (area under the curve, AUC 0.73, p=0.0002) and controls (AUC 0.82, p<0.0001). Two of four patients who developed pancreatic cancer despite close surveillance had SMAD4/TP53 mutations from their cancer detected in juice samples collected over 1 year prior to their pancreatic cancer diagnosis when no suspicious pancreatic lesions were detected by imaging. Conclusions The detection in pancreatic juice of mutations important for the progression of low-grade dysplasia to high-grade dysplasia and invasive pancreatic cancer may improve the management of patients undergoing pancreatic screening and surveillance. PMID:27432539

Fine-needle aspiration cytology of intraductal papillary-mucinous tumors: a retrospective analysis.

PubMed

Layfield, Lester J; Cramer, Harvey

2005-01-01

Intraductal papillary-mucinous tumor (IPMT) of the pancreas has become the accepted terminology for a group of mucin-producing epithelial proliferations lying within ectatic segments of the main pancreatic duct or its large branches. These neoplasms generally are associated with an indolent course, characteristic endoscopic ultrasonographic (EUS) findings, and a variable histo- and cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens obtained by endoscopic ultrasound-guided or percutaneous fine-needle aspiration (FNA) are characterized by a background containing abundant mucin in which are entrapped single or loosely cohesive clusters of neoplastic cells characteristically showing a goblet-cell morphology. The degree of nuclear atypia, cell crowding, and cell shape varies between smears within a single case and between cases. Cytomorphological examination, when coupled with EUS features, is accurate for the diagnosis of these lesions but often it underdiagnoses the grade of the neoplasm. (c) 2005 Wiley-Liss, Inc.

Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms.

PubMed

Roch, Alexandra M; Parikh, Janak A; Al-Haddad, Mohammad A; DeWitt, John M; Ceppa, Eugene P; House, Michael G; Nakeeb, Attila; Schmidt, C Max

2014-10-01

Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a "worrisome feature." We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and "cyst clinic" visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy (P = .51) or invasiveness (P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy (P < .0001 and P = .0009, respectively). Serum pancreatic enzyme levels above normal range (high) were associated with a greater rate of invasiveness (P = .02). In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes and the presence of invasive IPMN. These data suggest serum pancreatic enzymes may be useful markers in stratification of pancreatic cancer risk in patients with IPMN. Copyright © 2014 Elsevier Inc. All rights reserved.

Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

PubMed

Fukushima, N; Sakamoto, M; Mukai, K; Kanai, Y; Shimada, K; Kosuge, T; Hirohashi, S

2001-08-01

Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

Risk Factors for Progression or Malignancy in Main-Duct and Mixed-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas.

PubMed

Jang, Dong Kee; Ryu, Ji Kon; Chung, Kwang Hyun; Lee, Ban Seok; Park, Joo Kyung; Lee, Sang Hyub; Kim, Yong-Tae

2016-08-01

The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy. Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion. Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy. A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.

Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions.

PubMed

Terris, Benoît; Dubois, Sylvie; Buisine, Marie-Pierre; Sauvanet, Alain; Ruszniewski, Philippe; Aubert, Jean-Pierre; Porchet, Nicole; Couvelard, Anne; Degott, Claude; Fléjou, Jean-Francois

2002-08-01

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas. Copyright 2002 John Wiley & Sons, Ltd.

Evaluation of the International Consensus Guidelines for the Surgical Resection of Intraductal Papillary Mucinous Neoplasms.

PubMed

Tsukagoshi, Mariko; Araki, Kenichiro; Saito, Fumiyoshi; Kubo, Norio; Watanabe, Akira; Igarashi, Takamichi; Ishii, Norihiro; Yamanaka, Takahiro; Shirabe, Ken; Kuwano, Hiroyuki

2018-04-01

International consensus guidelines for intraductal papillary mucinous neoplasms (IPMNs) were revised in 2012. We aimed to evaluate the clinical utility of each predictor in the 2006 and 2012 guidelines and validate the diagnostic value and surgical indications. Forty-two patients with surgically resected IPMNs were included. Each predictor was applied to evaluate its diagnostic value. The 2012 guidelines had greater accuracy for invasive carcinoma than the 2006 guidelines (64.3 vs. 31.0%). Moreover, the accuracy for high-grade dysplasia was also increased (48.6 vs. 77.1%). When the main pancreatic duct (MPD) size ≥8 mm was substituted for MPD size ≥10 mm in the 2012 guidelines, the accuracy for high-grade dysplasia was 80.0%. The 2012 guidelines exhibited increased diagnostic accuracy for invasive IPMN. It is important to consider surgical resection prior to invasive carcinoma, and high-risk stigmata might be a useful diagnostic criterion. Furthermore, MPD size ≥8 mm may be predictive of high-grade dysplasia.

Intraductal papillary mucinous neoplasm penetrating to the stomach, duodenum, and jejunum demonstrated on MR cholangiopancreatography with an oral negative contrast agent.

PubMed

Tajima, Naoshi; Utano, Kenichi; Kijima, Shigeyoshi; Kawai, Akira; Fujita, Akifumi; Sakuma, Kazuya; Sugimoto, Hideharu; Fujii, Hirofumi

2013-07-01

A 65-year-old man was referred to our hospital due to epigastric pain. Abdominal enhanced computed tomography (CT) demonstrated marked dilatation of the main pancreatic duct (MPD) and communication to the gastric and duodenal lumen was suspected. Esophagogastroduodenoscopy (EGD) showed a villous tumor with white mucous discharge in the posterior wall of the gastric corpus and duodenal bulb. Pathological specimens showed mucin-producing epithelium with nuclear atypia that had developed in a papillary form. Based on these findings, we diagnosed intraductal papillary mucinous neoplasm (IPMN) arising in the MPD with penetration into the gastric and duodenal lumen. Magnetic resonance cholangiopancreatography (MRCP) with an oral negative contrast agent (manganese chloride tetrahydrate) showed a fistulous tract not only to the stomach and duodenum, but also to the jejunum. MRCP demonstrated mucous streaming with remarkably high intensity. In this case, an oral negative contrast agent was useful to distinguish mucous discharge from gastric fluid, facilitating the diagnosis of penetration to the jejunum. This finding was unobtainable by CT or EGD. When IPMN penetrating to other organs is suspected, MRCP with an oral negative contrast agent may provide important information. Copyright © 2012 Wiley Periodicals, Inc.

Does a family history of pancreatic ductal adenocarcinoma and cyst size influence the follow-up strategy for intraductal papillary mucinous neoplasms of the pancreas?

PubMed

Mandai, Koichiro; Uno, Koji; Yasuda, Kenjiro

2014-08-01

This study aimed to evaluate the relationship between pancreatic ductal adenocarcinoma (PDAC) family history and PDAC development in patients followed up for intraductal papillary mucinous neoplasms (IPMNs) and to assess the cyst size relevance in determining follow-up strategies. We analyzed 300 patients with branch duct and mixed-type IPMN who were followed up at our facility. Among the patients aged 70 years or older, the frequency of PDAC did not differ significantly between those with 1 first-degree relative with PDAC and those without a family history. Although patients with IPMNs of greater than or equal to 30 mm were followed up for a significantly shorter duration than those patients with IPMNs of less than 30 mm, the frequency of IPMN progression and malignant IPMN was significantly greater in the former. The frequency of IPMN progression and pancreatic cancer did not differ significantly according to IPMN size (<10, 10-20, and 20-30 mm) in cases without mural nodules. Patients with 1 first-degree relative with PDAC can be followed up using the same criteria for patients without a family history. Special attention should be paid to IPMN progression and malignant transformation in patients with IPMNs of greater than or equal to 30 mm, but cyst size need not be considered when determining follow-up strategies for patients with IPMNs of less than 30 mm without mural nodules.

Pancreatic cystic neoplasms: Review of current knowledge, diagnostic challenges, and management options

PubMed Central

Jana, Tanima; Shroff, Jennifer; Bhutani, Manoop S.

2015-01-01

Pancreatic cystic lesions are being detected with increasing frequency, largely due to advances in cross-sectional imaging. The most common neoplasms include serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms, and cystic pancreatic endocrine neoplasms. Computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are currently used as imaging modalities. EUS-guided fine needle aspiration has proved to be a useful diagnostic tool, and enables an assessment of tumor markers, cytology, chemistries, and DNA analysis. Here, we review the current literature on pancreatic cystic neoplasms, including classification, diagnosis, treatment, and recommendations for surveillance. Data for this manuscript was acquired via searching the literature from inception to December 2014 on PubMed and Ovid MEDLINE. PMID:25821410

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

PubMed

Moris, Demetrios; Damaskos, Christos; Spartalis, Eleftherios; Papalampros, Alexandros; Vernadakis, Spyridon; Dimitroulis, Dimitrios; Griniatsos, John; Felekouras, Evangelos; Nikiteas, Nikolaos

2017-05-01

Intraductal papillary mucinous neoplasms (IPMNs) are presumed to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma. Resection of lesions before the development of pancreatic cancer may prevent the development of an incurable process as, once IPMNs progress to invasive cancer, the prognosis may be as poor as resected conventional pancreatic ductal adenocarcinoma. Resection of IPMNs, particularly in the setting of high-grade dysplasia, is presumed to provide a survival benefit. IPMNs also present many challenges as the identification of high-grade dysplasia and early invasive carcinoma and the timing and frequency of malignant progression are not yet established. The limited predictive accuracy presents a challenge as pancreatic resection is associated with a risk of substantial morbidity and mortality; 20-30% and 2-4%, respectively. Diagnostic armamentarium contains pancreas-protocol computed tomography (CT) scan, gadolinium-enhanced magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). The most promising method is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as this technique allows analysis of cyst fluid using biomarkers. Until now, in clinical practice, we utilize two biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9); however, DNA analysis of pancreatic cystic fluid and genomic analysis could offer new tools to the diagnosis and administration of IPMNs. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach. More prospective studies are needed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Parenchyma-sparing pancreatectomy for presumed noninvasive intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Sauvanet, Alain; Gaujoux, Sébastien; Blanc, Benjamin; Couvelard, Anne; Dokmak, Safi; Vullierme, Marie-Pierre; Ruszniewski, Philippe; Belghiti, Jacques; Lévy, Philippe

2014-08-01

To assess the feasibility and outcomes of parenchyma-sparing pancreatectomy (PSP), including enucleation (EN), resection of uncinate process (RUP), and central pancreatectomy (CP), as an alternative to standard pancreatectomy for presumed noninvasive intraductal papillary and mucinous neoplasms (IPMNs). Pancreaticoduodenectomy and distal pancreatectomy are associated with significant perioperative morbidity, a substantial risk of pancreatic insufficiency, and may overtreat noninvasive IPMNs. From 1999 to 2011, PSP was attempted in 91 patients with presumed noninvasive IPMNs, after complete preoperative work-up including computed tomography, magnetic resonance imaging, and endoscopic ultrasonography. Intraoperative frozen section examination was routinely performed to assess surgical margins and rule out invasive malignancy. Follow-up included clinical, biochemical, and radiological assessments. Overall PSP was achieved with a feasibility rate of 89% (n = 81), including 44 ENs, 5 RUPs, and 32 CPs. Postoperative mortality rate was 1.3% (n = 1), and overall morbidity was noteworthy (61%; n = 47). Definitive pathological examination confirmed IPMN diagnosis in 95% of patients (n = 77), all except 2 (3%), without invasive component. After a median follow-up of 50 months, both pancreatic endocrine/exocrine functions were preserved in 92% of patients. Ten-year progression-free survival was 76%, and reoperation for recurrence was required in 4% of patients (n = 3). In selected patients, PSP for presumed noninvasive IPMN in experienced hands is highly feasible and avoids inappropriate standard resections for IPMN-mimicking lesions. Early morbidity is greater than that after standard resections but counterbalanced by preservation of pancreatic endocrine/exocrine functions and a low rate of reoperation for tumor recurrence.

Intraductal biliopancreatic imaging: European Society of Gastrointestinal Endoscopy (ESGE) technology review.

PubMed

Tringali, Andrea; Lemmers, Arnaud; Meves, Volker; Terheggen, Grischa; Pohl, Jürgen; Manfredi, Guido; Häfner, Michael; Costamagna, Guido; Devière, Jacques; Neuhaus, Horst; Caillol, Fabrice; Giovannini, Marc; Hassan, Cesare; Dumonceau, Jean-Marc

2015-08-01

This technology review expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) on the available techniques for intraductal biliopancreatic imaging. The three cholangioscopy techniques are described: the "dual-operator" and " single-operator" mother-baby approaches using dedicated instruments, and the "direct" technique using currently available ultrathin gastroscopes. The mother-baby method is standardized and reproducible, while direct cholangioscopy is technically demanding and its safety requires further evaluation. As well as direct visualization of the bile ducts, cholangioscopy has the further advantage of allowing targeted biopsy. Image quality is still suboptimal for single-operator cholangioscopy, while the other techniques have achieved adequately detailed imaging. The costs of mother-baby cholangioscopy are high and its application in clinical practice should be restricted to selected cases (i.e. indeterminate biliary strictures/intraluminal lesions, difficult biliary stones) and to the setting of tertiary care centers. Peroral pancreatoscopy may find an indication in situations where other imaging modalities (mainly EUS) are inconclusive (i.e. delineation of main duct intraductal papillary mucinous neoplasia extension, sampling of indeterminate main pancreatic duct strictures). Intraductal ultrasonography (IDUS) has a poorer performance than EUS in the staging of pancreatic malignancies and can increase the risk of pancreatitis. A promising indication for IDUS could be the evaluation of indeterminate biliary strictures and ampullary tumors. Probe-based confocal laser endomicroscopy (pCLE) of the bile ducts is a difficult and expensive technique. Appropriate training needs to be established, since interpretation of images is challenging. pCLE can be an important diagnostic tool in the setting of indeterminate biliary strictures. © Georg Thieme Verlag KG Stuttgart · New York.

Cystic neoplasms of the exocrine pancreas.

PubMed

Campbell, F; Azadeh, B

2008-04-01

The increasing use of radiological imaging has led to greater detection of small and asymptomatic cystic lesions of the pancreas. Most are resectable, but not all are neoplastic. This review provides an update on the histopathology, immunohistochemistry, molecular biology, pathogenesis and management of cystic neoplasms of the exocrine pancreas. These include the serous, the mucinous cystic, the intraductal papillary mucinous and the solid pseudopapillary neoplasms. Recently reported variants are described and very rare cystic variants of other pancreatic epithelial and mesenchymal neoplasms are briefly mentioned.

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

PubMed

Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

2003-02-01

Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

Endoscopic papillectomy: indications, techniques, and results.

PubMed

De Palma, Giovanni D

2014-02-14

Endoscopic papillectomy (EP) is currently accepted as a viable alternative therapy to surgery in sporadic ampullary adenoma and has been reported to have high success and low recurrence rates. At present, the indications for EP are not yet fully established. The accepted criteria for EP include size (up to 5 cm), no evidence of intraductal growth, and no evidence of malignancy on endoscopic findings (ulceration, friability, and spontaneous bleeding). Endoscopic ultrasound (EUS) is the imaging modality of choice for local T staging in ampullary neoplasms. Data reported in the literature have revealed that linear EUS is superior to helical computed tomography in the preoperative assessment of tumor size, detection of regional nodal metastases and detection of major vascular invasion. Endoscopic ampullectomy is performed using a standard duodenoscope in a similar manner to snare polypectomy of a mucosal lesion. There is no standardization of the equipment or technique and broad EP methods are described. Endoscopic ampullectomy is considered a ''high-risk'' procedure due to complications. Complications of endoscopic papillectomy can be classified as early (pancreatitis, bleeding, perforation, and cholangitis) and late (papillary stenosis) complications. The appropriate use of stenting after ampullectomy may prevent post-procedural pancreatitis and papillary stenosis. Tumor recurrence of benign lesions occurs in up to 20% of patients and depends on tumor size, final histology, presence of intraductal tumor, coexisting familial adenomatous polyposis (FAP), and the expertise of the endoscopist. Recurrent lesions are usually benign and most can be retreated endoscopically.

Prevalence of incidental pancreatic cyst on upper endoscopic ultrasound

PubMed Central

Martínez, Belén; Martínez, Juan F.; Aparicio, José R.

2018-01-01

Background: This study aimed to determine the prevalence of incidental pancreatic cysts in patients undergoing upper endoscopic ultrasound without a known pancreatic abnormality. Methods: This prospective study was conducted in two hospitals in Spain and enrolled consecutive patients referred for upper endoscopic ultrasound for a condition unrelated to the pancreas. Patients with a previous pancreatic anomaly, history of acute or chronic pancreatitis, evidence of acute pancreatitis, previous upper gastrointestinal surgery, or chronic abdominal pain suggestive of pancreatic origin were excluded. Univariate logistic regression was performed to evaluate individual covariates and the incidental pancreatic cyst risk. Results: A total of 298 patients were included, of whom 64 had pancreatic cysts (21.5%; 16.9-26.6%). The mean size of the cysts was 6.3±3.7 (range 3-25) mm. Six cysts (2%) were >10 mm and 16 (5.4%) were compatible with branch duct intraductal papillary mucinous neoplasm. The pancreatic cyst prevalence was similar in the two hospitals and increased significantly with age. Conclusion: The prevalence of incidental pancreatic cysts during endoscopic ultrasound was very high in our study population. PMID:29333072

Loss of Activin Receptor Type 1B Accelerates Development of Intraductal Papillary Mucinous Neoplasms in Mice With Activated KRAS.

PubMed

Qiu, Wanglong; Tang, Sophia M; Lee, Sohyae; Turk, Andrew T; Sireci, Anthony N; Qiu, Anne; Rose, Christian; Xie, Chuangao; Kitajewski, Jan; Wen, Hui-Ju; Crawford, Howard C; Sims, Peter A; Hruban, Ralph H; Remotti, Helen E; Su, Gloria H

2016-01-01

Activin, a member of the transforming growth factor-β (TGFB) family, might be involved in pancreatic tumorigenesis, similar to other members of the TGFB family. Human pancreatic ductal adenocarcinomas contain somatic mutations in the activin A receptor type IB (ACVR1B) gene, indicating that ACVR1B could be a suppressor of pancreatic tumorigenesis. We disrupted Acvr1b specifically in pancreata of mice (Acvr1b(flox/flox);Pdx1-Cre mice) and crossed them with LSL-KRAS(G12D) mice, which express an activated form of KRAS and develop spontaneous pancreatic tumors. The resulting Acvr1b(flox/flox);LSL-KRAS(G12D);Pdx1-Cre mice were monitored; pancreatic tissues were collected and analyzed by histology and immunohistochemical analyses. We also analyzed p16(flox/flox);LSL-Kras(G12D);Pdx1-Cre mice and Cre-negative littermates (controls). Genomic DNA, total RNA, and protein were isolated from mouse tissues and primary pancreatic tumor cell lines and analyzed by reverse-transcription polymerase chain reaction, sequencing, and immunoblot analyses. Human intraductal papillary mucinous neoplasm (IPMN) specimens were analyzed by immunohistochemistry. Loss of ACVR1B from pancreata of mice increased the proliferation of pancreatic epithelial cells, led to formation of acinar to ductal metaplasia, and induced focal inflammatory changes compared with control mice. Disruption of Acvr1b in LSL-KRAS(G12D);Pdx1-Cre mice accelerated the growth of pancreatic IPMNs compared with LSL-KRAS(G12D);Pdx1-Cre mice, but did not alter growth of pancreatic intraepithelial neoplasias. We associated perinuclear localization of the activated NOTCH4 intracellular domain to the apical cytoplasm of neoplastic cells with the expansion of IPMN lesions in Acvr1b(flox/flox);LSL-KRAS(G12D);Pdx1-Cre mice. Loss of the gene that encodes p16 (Cdkn2a) was required for progression of IPMNs to pancreatic ductal adenocarcinomas in Acvr1b(flox/flox);LSL-Kras(G12D);Pdx1-Cre mice. We also observed progressive loss of p16 in human IPMNs of increasing grades. Loss of ACVR1B accelerates growth of mutant KRAS-induced pancreatic IPMNs in mice; this process appears to involve NOTCH4 and loss of p16. ACVR1B suppresses early stages of pancreatic tumorigenesis; the activin signaling pathway therefore might be a therapeutic target for pancreatic cancer. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct: a case report.

PubMed

Budzynska, Agnieszka; Hartleb, Marek; Nowakowska-Dulawa, Ewa; Krol, Robert; Remiszewski, Piotr; Mazurkiewicz, Michal

2014-04-14

Cystic hepatic neoplasms are rare tumors, and are classified into two separate entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor. Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B. This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Biomarker Development for Intraductal Papillary Mucinous Neoplasms Using Multiple Reaction Monitoring Mass Spectrometry.

PubMed

Kim, Yikwon; Kang, MeeJoo; Han, Dohyun; Kim, Hyunsoo; Lee, KyoungBun; Kim, Sun-Whe; Kim, Yongkang; Park, Taesung; Jang, Jin-Young; Kim, Youngsoo

2016-01-04

Intraductal papillary mucinous neoplasm (IPMN) is a common precursor of pancreatic cancer (PC). Much clinical attention has been directed toward IPMNs due to the increase in the prevalence of PC. The diagnosis of IPMN depends primarily on a radiological examination, but the diagnostic accuracy of this tool is not satisfactory, necessitating the development of accurate diagnostic biomarkers for IPMN to prevent PC. Recently, high-throughput targeted proteomic quantification methods have accelerated the discovery of biomarkers, rendering them powerful platforms for the evolution of IPMN diagnostic biomarkers. In this study, a robust multiple reaction monitoring (MRM) pipeline was applied to discovery and verify IPMN biomarker candidates in a large cohort of plasma samples. Through highly reproducible MRM assays and a stringent statistical analysis, 11 proteins were selected as IPMN marker candidates with high confidence in 184 plasma samples, comprising a training (n = 84) and test set (n = 100). To improve the discriminatory power, we constructed a six-protein panel by combining marker candidates. The multimarker panel had high discriminatory power in distinguishing between IPMN and controls, including other benign diseases. Consequently, the diagnostic accuracy of IPMN can be improved dramatically with this novel plasma-based panel in combination with a radiological examination.

Differential Diagnosis of Benign and Malignant Intraductal Papillary Mucinous Tumors of the Pancreas: MR Cholangiopancreatography and MR Angiography

PubMed Central

Choi, Byung Se; Kim, Ah Young; Kim, Kyoung Won; Park, Sung Won; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon-Gyu; Kim, Song Cheol

2003-01-01

Objective To compare the usefulness of magnetic resonance cholangiopancreatography (MRCP) and MR angiography (MRA) in differentiating malignant from benign intraductal papillary mucinous tumors of the pancreas (IPMTs), and to determine the findings which suggest malignancy. Materials and Methods During a 6-year period, 46 patients with IPMT underwent MRCP. Morphologically, tumor type was classified as main duct, branch duct, or combined. The diameter of the main pancreatic duct (MPD), the extent of the dilated MPD, and the location and size of the cystic lesion, septum, and communicating channel were assessed. For all types of IPMTs, enhanced mural nodules and portal vein narrowing were evaluated at MRA. Results Combined-type IPMTs were more frequently malignant (78%) than benign (42%) (p < 0.05). Compared with benign lesions, malignant lesions were larger, and the caliber of the communicating channel was also larger (p < 0.05). Their dilated MPD was more extensive and of greater diameter (p < 0.05), and the presence of mural nodules was more frequent (p < 0.001). Conclusion Combined MRCP and MRA might be useful for the differential diagnosis of malignant and benign IPMTs of the pancreas. PMID:14530644

Intraductal papillary neoplasm of the bile duct: a case report.

PubMed

Peeters, Karen; Delvaux, Peter; Huysentruyt, Frederik

2017-08-01

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. The Western experience, however, remains limited. In this article, we report a 56-year-old man, referred to our hospital because of deranged liver function tests. Further imaging modalities showed a cystic lesion of 9 cm diameter, arising from the left hepatic duct. Inlying was a heterogeneous, lobulated mass. The patient underwent a left hemihepatectomy and adjuvant chemotherapy. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Early identification and resection of lesions, even in asymptomatic or minimally symptomatic patients, are however important prognostic factors.

Cystic lesions of the pancreas

PubMed Central

Karoumpalis, Ioannis; Christodoulou, Dimitrios K.

2016-01-01

Different types of benign or malignant cystic lesions can be observed in the pancreas. Pancreatic cystic lesions are classified under pathology terms into simple retention cysts, pseudocysts and cystic neoplasms. Mucinous cystic neoplasm is a frequent type of cystic neoplasm and has a malignant potential. Serous cystadenoma follows in frequency and is usually benign. Intraductal papillary mucinous neoplasms are the most commonly resected cystic pancreatic neoplasms characterized by dilated segments of the main pancreatic duct and/or side branches, the wall of which is covered by mucus secreting cells. These neoplasms can occupy the pancreatic head or any part of the organ. Solid pseudopapillary tumor is rare, has a low tendency for malignancy, and is usually located in the pancreatic body or tail. Endoscopic ultrasound with the use of fine-needle aspiration and cytology permits discrimination of those lesions. In this review, the main characteristics of those lesions are presented, as well as recommendations regarding their follow up and management according to recent guidelines. PMID:27065727

Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas.

PubMed

Furukawa, Toru

2007-01-01

Intraductal papillary-mucinous neoplasms of the pancreas show characteristic clinicopathological and molecular pathobiological features which are distinct from those of conventional ductal adenocarcinomas. Alterations of KRAS, AKT/PKB, CDKN2A, TP53, SMAD4, STK11/LKB1, and DUSP6, and other molecular alterations, including global expression studies as well as their clinical implications, are discussed.

[Duodenum-preserving total pancreatic head resection and pancreatic head resection with segmental duodenostomy].

PubMed

Takada, Tadahiro; Yasuda, Hideki; Nagashima, Ikuo; Amano, Hodaka; Yoshiada, Masahiro; Toyota, Naoyuki

2003-06-01

A duodenum-preserving pancreatic head resection (DPPHR) was first reported by Beger et al. in 1980. However, its application has been limited to chronic pancreatitis because of it is a subtotal pancreatic head resection. In 1990, we reported duodenum-preserving total pancreatic head resection (DPTPHR) in 26 cases. This opened the way for total pancreatic head resection, expanding the application of this approach to tumorigenic morbidities such as intraductal papillary mucinous tumor (IMPT), other benign tumors, and small pancreatic cancers. On the other hand, Nakao et al. reported pancreatic head resection with segmental duodenectomy (PHRSD) as an alternative pylorus-preserving pancreatoduodenectomy technique in 24 cases. Hirata et al. also reported this technique as a new pylorus-preserving pancreatoduodenostomy with increased vessel preservation. When performing DPTPHR, the surgeon should ensure adequate duodenal blood supply. Avoidance of duodenal ischemia is very important in this operation, and thus it is necessary to maintain blood flow in the posterior pancreatoduodenal artery and to preserve the mesoduodenal vessels. Postoperative pancreatic functional tests reveal that DPTPHR is superior to PPPD, including PHSRD, because the entire duodenum and duodenal integrity is very important for postoperative pancreatic function.

Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases.

PubMed

Adsay, Volkan; Jang, Kee-Taek; Roa, Juan Carlos; Dursun, Nevra; Ohike, Nobuyuki; Bagci, Pelin; Basturk, Olca; Bandyopadhyay, Sudeshna; Cheng, Jeanette D; Sarmiento, Juan M; Escalona, Oscar Tapia; Goodman, Michael; Kong, So Yeon; Terry, Paul

2012-09-01

The literature on the clinicopathologic characteristics of tumoral intraepithelial neoplasms (neoplastic polyps) of the gallbladder (GB) is fairly limited, due in part to the variability in definition and terminology. Most reported adenomas (pyloric gland type and others) were microscopic and thus regarded as clinically inconsequential, whereas papillary in situ carcinomas have been largely considered a type of invasive adenocarcinoma under the heading of "papillary adenocarcinomas." In this study, 123 GB cases that have a well-defined exophytic preinvasive neoplasm measuring ≥1 cm were analyzed. The patients were predominantly female (F/M=2:1) with a mean age of 61 y and a median tumor size of 2.2 cm. Half of the patients presented with pain, and in the other half the neoplasm was detected incidentally. Other neoplasms, most being gastrointestinal tract malignancies, were present in 22% of cases. Gallstones were identified in only 20% of cases. Radiologically, almost half were diagnosed as "cancer," roughly half with polypoid tumor, and in 10% the lesion was missed. Pathologic findings: (1) The predominant configuration was papillary in 43%, tubulopapillary in 31%, tubular in 26%. (2) Each case was assigned a final lineage type on the basis of the predominant pattern (>75% of the lesion) on morphology, and supported with specific immunohistochemical cell lineage markers. The predominant cell lineage could be identified as biliary in 50% (66% of which were MUC1), gastric foveolar in 16% (all were MUC5AC), gastric pyloric in 20% (92% MUC6), intestinal in 8% (100% CK20; 75% CDX2; 50%, MUC2), and oncocytic in 6% (17% HepPar and 17% MUC6); however, 90% of cases had some amount of secondary or unclassifiable pattern and hybrid immunophenotypes. (3) Of the cases that would have qualified as "pyloric gland adenoma," 21/24 (88%) had at least focal high-grade dysplasia and 18% had associated invasive carcinoma. Conversely, 8 of 47 "papillary adenocarcinoma"-type cases displayed some foci of low-grade dysplasia, and 15/47 (32%) had no identifiable invasion. (4) Overall, 55% of the cases had an associated invasive carcinoma (pancreatobiliary type, 58; others, 10). Factors associated significantly with invasion were the extent of high-grade dysplasia, cell type (biliary or foveolar), and papilla formation. Among systematically analyzed invasive carcinomas, tumoral intraepithelial neoplasia was detected in 6.4% (39/606). (5) The 3-year actuarial survival was 90% for cases without invasion and 60% for those associated with invasion. In contrast, those associated with invasion had a far better clinical outcome compared with pancreatobiliary-type GB carcinomas (3-yr survival, 27%), and this survival advantage persisted even with stage-matched comparison. Death occurred in long-term follow-up even in a few noninvasive cases (4/55; median 73.5 mo) emphasizing the importance of long-term follow-up. In conclusion, tumoral preinvasive neoplasms (≥1 cm) in the GB are analogous to their pancreatic and biliary counterparts (biliary intraductal papillary neoplasms, pancreatic intraductal papillary mucinous neoplasms, and intraductal tubulopapillary neoplasms). They show variable cellular lineages, a spectrum of dysplasia, and a mixture of papillary or tubular growth patterns, often with significant overlap, warranting their classification under 1 unified parallel category, intracholecystic papillary-tubular neoplasm. Intracholecystic papillary-tubular neoplasms are relatively indolent neoplasia with significantly better prognosis compared with pancreatobiliary-type GB carcinomas. In contrast, even seemingly innocuous examples such as those referred to as "pyloric gland adenomas" can progress to carcinoma and be associated with invasion and fatal outcome.

CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts.

PubMed

Kim, Hyoung Jung; Yu, Eun Sil; Byun, Jae Ho; Hong, Seung-Mo; Kim, Kyoung Won; Lee, Jong Seok; Kim, So Yeon

2014-01-01

The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p < 0.05 for each finding). When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucin-producing cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.

Prevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions

PubMed Central

Farrell, James J.

2015-01-01

Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed. PMID:26343068

Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence.

PubMed

Biankin, Andrew V; Kench, James G; Biankin, Sandra A; Lee, C-Soon; Morey, Adrienne L; Dijkman, Floriaan P; Coleman, Maxwell J; Sutherland, Robert L; Henshall, Susan M

2004-09-01

The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.

Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis.

PubMed

Crippa, Stefano; Bassi, Claudio; Salvia, Roberto; Malleo, Giuseppe; Marchegiani, Giovanni; Rebours, Vinciane; Levy, Philippe; Partelli, Stefano; Suleiman, Shadeah L; Banks, Peter A; Ahmed, Nazir; Chari, Suresh T; Fernández-Del Castillo, Carlos; Falconi, Massimo

2017-03-01

To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians' recommendation, patient personal choice or comorbidities precluding surgery. In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific survival (DSS) were obtained. Of 281 patients identified, 159 (57%) had BD-IPMNs and 122 (43%) had MD-IPMNs; 50 (18%) had high-risk stigmata and 231 (82%) had worrisome features. Median follow-up was 51 months. The 5-year OS and DSS for the entire cohort were 81% and 89.9%. An invasive pancreatic malignancy developed in 34 patients (12%); 31 had invasive IPMNs (11%) and 3 had IPMN-distinct pancreatic ductal adenocarcinoma (1%). Independent predictors of poor DSS in the entire cohort were age >70 years, atypical/malignant cyst fluid cytology, jaundice and MD >15 mm. Compared with MD-IPMNs, BD-IPMNs had significantly better 5-year OS (86% vs 74.1%, p=0.002) and DSS (97% vs 81.2%, p<0.0001). Patients with worrisome features had better 5-year DSS compared with those with high-risk stigmata (96.2% vs 60.2%, p<0.0001). In elderly patients with IPMNs that have worrisome features, the 5-year DSS is 96%, suggesting that conservative management is appropriate. By contrast, presence of high-risk stigmata is associated with a 40% risk of IPMN-related death, reinforcing that surgical resection should be offered to fit patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Targeted DNA Sequencing Reveals Patterns of Local Progression in the Pancreatic Remnant Following Resection of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

PubMed Central

Pea, Antonio; Yu, Jun; Rezaee, Neda; Luchini, Claudio; He, Jin; Molin, Marco Dal; Griffin, James F.; Fedor, Helen; Fesharakizadeh, Shahriar; Salvia, Roberto; Weiss, Matthew J.; Bassi, Claudio; Cameron, John L.; Zheng, Lei; Scarpa, Aldo; Hruban, Ralph H.; Lennon, Anne Marie; Goggins, Michael

2016-01-01

Objective The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS). Background Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm. Methods Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression. Results We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas. Conclusions Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas. PMID:27433916

Invasive intraductal papillary mucinous neoplasm vs. sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes

PubMed Central

Wasif, Nabil; Bentrem, David J.; Farrell, James J.; Ko, Clifford Y.; Hines, Oscar J.; Reber, Howard A.; Tomlinson, James S.

2010-01-01

Introduction Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. We compare survival and identify prognostic factors following resection for invasive IPMN vs. stage-matched PAC. Methods The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was utilized to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Results Patients with resected invasive IPMN experienced improved overall survival when compared to resected PAC (median survival 21mos vs. 14mos, p<0.001). Stratification by nodal status demonstrated no difference in survival among node positive patients, however, median survival of resected, node negative, invasive IPMN was significantly improved compared to node negative PAC (34mos vs. 18mos, p <0.001). On multivariate analysis PAC histology was an adverse predictor of overall survival (HR 1.31, 95% CI 1.15-1.50) compared to invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR 1.98, 95% CI 1.50- 2.60), high tumor grade (HR 1.74, 95% CI 1.31- 2.31), tumor size >2cm (HR 1.50, 95% CI 1.04- 2.19), and age >66 years (HR 1.33, 95% CI 1.03- 1.73) were adverse predictors of survival. Conclusions Although node negative invasive IPMN shows improved survival following resection compared to node negative PAC, the natural history of node positive invasive IPMN mimics that of node positive PAC. We also identify adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis following resection of invasive IPMN. PMID:20564064

Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes.

PubMed

Wasif, Nabil; Bentrem, David J; Farrell, James J; Ko, Clifford Y; Hines, Oscar J; Reber, Howard A; Tomlinson, James S

2010-07-15

Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC. The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival. Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN. Copyright (c) 2010 American Cancer Society.

Clinicopathological and prognostic significance of MUC13 and AGR2 expression in intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Mito, Kumiko; Saito, Michihiro; Morita, Kohei; Maetani, Iruru; Sata, Naohiro; Mieno, Makiko; Fukushima, Noriyoshi

2018-06-01

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Papillary lesions of the breast: To excise or observe?

PubMed

Khan, Sidrah; Diaz, Adrian; Archer, Kellie J; Lehman, Rebecca R; Mullins, Tiffany; Cardenosa, Gilda; Bear, Harry D

2018-05-01

Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long-term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long-term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention. © 2017 Wiley Periodicals, Inc.

Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

PubMed

Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

2018-03-16

Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast.

PubMed

Lininger, R A; Park, W S; Man, Y G; Pham, T; MacGrogan, G; Zhuang, Z; Tavassoli, F A

1998-10-01

Papillary carcinoma of the breast is a variant of predominantly intraductal carcinoma characterized by a papillary growth pattern with fibrovascular support. Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci (including loci reported to show frequent genetic alterations in breast cancer) to determine the frequency of genetic mutations in these tumors and their precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas, 12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid epithelial hyperplasia) were retrieved from the files of the Armed Forces Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected in each case and screened for LOH at INT-2 and p53 as well as several loci on chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on chromosome 16p13 was present in 10 of 16 (63%) informative cases of either papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10 (60%) informative cases of intraductal papilloma with florid epithelial hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53 in any of the papillary carcinomas or papillomas with florid IDH. In conclusion, a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in both papillary carcinomas of the breast as well as in papillomas with florid IDH, including a case with LOH present simultaneously in both components. These findings suggest that chromosome 16p contains a tumor suppressor gene that frequently is mutated early in papillary neoplasia.

Rare Nonneoplastic Cysts of Pancreas

PubMed Central

Cho, Jae Hee

2015-01-01

Pancreatic cysts represent a small proportion of pancreatic diseases, but their incidence has been recently increasing. Most pancreatic cysts are identified incidentally, causing a dilemma for both clinicians and patients. In contrast to ductal adenocarcinoma, neoplastic pancreatic cysts may be cured by resection. In general, pancreatic cysts are classified as neoplastic or non-neoplastic cysts. The predominant types of neoplastic cysts include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms, and solid pseudopapillary neoplasms. With the exception of serous type, neoplastic cysts, have malignant potential, and in most cases requires resection. Non-neoplastic cysts include pseudocyst, retention cyst, benign epithelial cysts, lymphoepithelial cysts, squamous lined cysts (dermoid cyst and epidermal cyst in intrapancreatic accessory spleen), mucinous nonneoplastic cysts, and lymphangiomas. The incidence of nonneoplastic, noninflammatory cysts is about 6.3% of all pancreatic cysts. Despite the use of high-resolution imaging technologies and cytologic tissue acquisition with endosonography, distinguishing nonneoplastic from neoplastic cysts remains difficult with most differentiations made postoperatively. Nonetheless, the definitive distinction between non-neoplastic and neoplastic cysts is crucial as unnecessary surgery could be avoided with proper diagnosis. Therefore, consideration of these rare disease entities should be entertained before deciding on surgery. PMID:25674524

Distinction of Invasive Carcinoma Derived From Intraductal Papillary Mucinous Neoplasms From Concomitant Ductal Adenocarcinoma of the Pancreas Using Molecular Biomarkers.

PubMed

Tamura, Koji; Ohtsuka, Takao; Date, Kenjiro; Fujimoto, Takaaki; Matsunaga, Taketo; Kimura, Hideyo; Watanabe, Yusuke; Miyazaki, Tetsuyuki; Ohuchida, Kenoki; Takahata, Shunichi; Ishigami, Kousei; Oda, Yoshinao; Mizumoto, Kazuhiro; Nakamura, Masafumi; Tanaka, Masao

2016-07-01

To clarify the usefulness of molecular biomarkers for distinguishing invasive carcinoma derived from intraductal papillary mucinous neoplasms (IPMNs [Inv-IPMN]) from concomitant pancreatic ductal adenocarcinoma (PDAC). Data from 19 patients with resected concomitant PDAC were retrospectively reviewed. KRAS/GNAS mutations and immunohistochemical (IHC) expression of p53 and p16/CDKN2A were assessed in both IPMN and distinct PDAC. As controls, KRAS/GNAS mutations and IHC labeling were assessed between invasive and noninvasive components in 1 lesion of 22 independent patients. KRAS/GNAS mutation status of invasive and noninvasive components in Inv-IPMN was consistent in 18 (86%) of 21 patients. Conversely, mutational patterns in IPMN and distinct PDAC in the same pancreas differed from each other in 17 (89%) of 19. There were 10 (53%) and 8 (42%) of 19 patients who showed the same p53 and p16/CDKN2A staining between concomitant PDAC and distinct IPMN. In the Inv-IPMN cohort, 19 (86%) of 22 patients showed the same IHC expression pattern between the noninvasive and invasive components. It may be possible to distinguish Inv-IPMN from concomitant PDAC by assessing these molecular biomarkers. More precise distinction of Inv-IPMN and concomitant PDAC will lead to adequate recognition of the natural history of IPMNs and hence optimal management.

Cystic precursors to invasive pancreatic cancer

PubMed Central

Matthaei, Hanno; Schulick, Richard D.; Hruban, Ralph H.; Maitra, Anirban

2011-01-01

Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not. PMID:21383670

Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

PubMed Central

Pelosi, Elvira; Castelli, Germana

2017-01-01

Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments. PMID:29156578

Pancreatic cancer: Advances in treatment

PubMed Central

Mohammed, Somala; Van Buren II, George; Fisher, William E

2014-01-01

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing. While patients with pancreatic cancer have traditionally faced a dismal prognosis, over the past several years various advances in diagnosis and treatment have begun to positively impact this disease. Identification of effective combinations of existing chemotherapeutic agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has improved survival for selected patients although concerns regarding their toxicity profiles remain. A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions, such as pancreatic intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic neoplasms. Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management. Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors, and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality. Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes. Lastly, a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents. PMID:25071330

Pancreatic cancer: advances in treatment.

PubMed

Mohammed, Somala; Van Buren, George; Fisher, William E

2014-07-28

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing. While patients with pancreatic cancer have traditionally faced a dismal prognosis, over the past several years various advances in diagnosis and treatment have begun to positively impact this disease. Identification of effective combinations of existing chemotherapeutic agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has improved survival for selected patients although concerns regarding their toxicity profiles remain. A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions, such as pancreatic intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic neoplasms. Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management. Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors, and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality. Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes. Lastly, a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents.

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.

PubMed

Moriya, Toshiyuki; Kimura, Wataru; Semba, Shuho; Sakurai, Fumiaki; Hirai, Ichiro; Ma, Jinfeng; Fuse, Akira; Maeda, Kunihiko; Yamakawa, Mitsunori

2005-01-01

Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015). In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.

Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas.

PubMed

Yamaguchi, Hiroshi; Kuboki, Yuko; Hatori, Takashi; Yamamoto, Masakazu; Shiratori, Keiko; Kawamura, Shunji; Kobayashi, Makio; Shimizu, Michio; Ban, Shinichi; Koyama, Isamu; Higashi, Morihiro; Shin, Nobuhiro; Ishida, Kazuyuki; Morikawa, Takanori; Motoi, Fuyuhiko; Unno, Michiaki; Kanno, Atsushi; Satoh, Kennichi; Shimosegawa, Tooru; Orikasa, Hideki; Watanabe, Tomoo; Nishimura, Kazuhiko; Harada, Youji; Furukawa, Toru

2011-12-01

Intraductal tubulopapillary neoplasm (ITPN) is a recently recognized rare variant of intraductal neoplasms of the pancreas. Molecular aberrations underlying the neoplasm remain unknown. We investigated somatic mutations in PIK3CA, PTEN, AKT1, KRAS, and BRAF. We also investigated aberrant expressions of phosphorylated AKT, phosphatase and tensin homolog (PTEN), tumor protein 53 (TP53), SMAD4, and CTNNB1 in 11 cases of ITPNs and compared these data with those of 50 cases of intraductal papillary mucinous neoplasm (IPMN), another distinct variant of pancreatic intraductal neoplasms. Mutations in PIK3CA were found in 3 of 11 ITPNs but not in IPMNs (P = 0.005; Fisher exact test). In contrast, mutations in KRAS were found in none of the ITPNs but were found in 26 of the 50 IPMNs (P = 0.001; Fisher exact test). PIK3CA mutations were associated with strong expression of phosphorylated AKT (P < 0.001; the Mann-Whitney U test). Moreover, the expression of phosphorylated AKT was apparent in most ITPNs but only in a few IPMNs (P < 0.001; the Mann-Whitney U test). Aberrant expressions of TP53, SMAD4, and CTNNB1 were not statistically different between these neoplasms. Mutations in PIK3CA and the expression of phosphorylated AKT were not associated with age, sex, tissue invasion, and patients' prognosis in ITPNs. These results indicate that activation of the phosphatidylinositol 3-kinase pathway may play a crucial role in ITPNs but not in IPMNs. In contrast, the mutation in KRAS seems to play a major role in IPMNs but not in ITPNs. The activated phosphatidylinositol 3-kinase pathway may be a potential target for molecular diagnosis and therapy of ITPNs.

Progression of Unresected Intraductal Papillary Mucinous Neoplasms of the Pancreas to Cancer: A Systematic Review and Meta-analysis.

PubMed

Choi, Sang Hyun; Park, Seong Ho; Kim, Kyung Won; Lee, Ja Youn; Lee, Sang Soo

2017-10-01

It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression to cancer. We sought to determine the cumulative incidence of development of pancreatic cancer in persons with unresected IPMNs (particularly low-risk IPMNs). We performed a systematic search of the MEDLINE and Embase databases through November 30, 2016 for studies reporting the cumulative incidence of pancreatic cancer in patients with unresected IPMNs or studies that provided data in sufficient detail for us to calculate cumulative incidence values. We categorized patient series as studies on low-risk IPMNs (lesions without main pancreatic duct involvement or mural nodules) or non-low-risk IPMNs. We calculated meta-analytic cumulative incidence values for pancreatic cancer at 1, 3, 5, and 10 years of follow-up by using the inverse variance method and random-effects model. Among 1514 articles screened, we identified 10 studies of low-risk IPMNs (n = 2411) and 9 studies of non-low-risk IPMNs (n = 825). In studies of low-risk IPMNs, the meta-analytic cumulative incidence values for pancreatic cancer were 0.02% at 1 year (95% confidence interval [CI], 0.0%-0.23%; I 2 = 0.0%), 1.40% at 3 years (95% CI, 0.58%-2.48%; I 2  = 58.5%), 3.12% at 5 years (95% CI, 1.12%-5.90%; I 2  = 88.0%), and 7.77% at 10 years (95% CI, 4.09%-12.39%; I 2  = 79.8%). These values were much higher in studies of non-low-risk IPMNs; cumulative incidence values for pancreatic cancer were 1.95% at 1 year (95% CI, 0.0%-5.99%; I 2  = 84.2%), 5.69% at 3 years (95% CI, 1.10%-12.77%; I 2  = 89.9%), 9.77% at 5 years (95% CI, 3.04%-19.27%; I 2  = 92.0%), and 24.68% at 10 years (95% CI, 14.87%-35.90%; I 2  = 74.3%). The pooled cumulative incidence steadily increased linearly as the follow-up duration increased. In a systematic review and meta-analysis, we found that low-risk IPMNs have almost 8% chance of progressing to pancreatic cancer within 10 years, and higher-risk IPMNs have almost 25% chance of progressing to cancer in 10 years; incidence values increase linearly with time. Continued long-term surveillance is therefore vital for patients with low-risk IPMNs. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Expression of MUC4 mucin is observed mainly in the intestinal type of intraductal papillary mucinous neoplasm of the pancreas.

PubMed

Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K; Goto, Masamichi; Yonezawa, Suguru

2013-10-01

This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). We performed immunohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of 2 anti-MUC4 monoclonal antibodies, 8G7 and 1G8, in cancer cell lines. Monoclonal antibody 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 messenger RNA. However, IHC signals detected by both monoclonal antibodies were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential.

Update on pancreatic cyst fluid analysis

PubMed Central

Rockacy, Matthew; Khalid, Asif

2013-01-01

Pancreatic cystic lesions (PCL) may be incidentally detected in up to 13.5% of patients. These represent a wide variety of lesions including mucinous cysts [intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN)] that have malignant potential. The difficulty in identifying the various PCL and their unpredictable potential for malignant degeneration makes their management cumbersome. The current diagnostic evaluation of PCL often includes EUS-guided fine needle aspiration (EUS-FNA) for cyst fluid analysis. Cyst fluid can be analyzed for tumor markers, cytology, mucins, DNA analysis and amylase. Pancreatic cyst CEA level is considered the most accurate tumor marker for diagnosing mucinous cysts. Approximately 0.2 to 1.0 mL of cyst fluid is required to run the test and a cut-off of 192 ng/ mL can be expected to capture ~75% of mucinous cysts. The presence of a KRAS mutation is very specific for a mucinous cyst but lacks sensitivity. Cytology is especially helpful in diagnosing malignancy typically in the presence of a solid component in the cyst. Newer markers to improve diagnostic accuracy are on the horizon, but clinical studies are awaited. PMID:24714589

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

PubMed Central

Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo

2015-01-01

AIM: To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. RESULTS: Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases. PMID:26167082

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms.

PubMed

Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo

2015-07-07

To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases.

Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

PubMed

Ma, Changqing; Gocke, Christopher D; Hruban, Ralph H; Belchis, Deborah A

2016-02-01

Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic value of selected markers and apoptotic pathways for pancreatic cancer

PubMed Central

Słotwińska, Sylwia Małgorzata

2017-01-01

Pancreatic cancer occupies the fourth place as a cause of death from cancer, and the mortality rate is similar to the number of newly detected cases. Due to the late diagnosis, only 5-6% of patients with pancreatic cancer survive for five years. Given that early diagnosis is critical for improving patients’ survival rates, there is an urgent need for the discovery and validation of new biomarkers with sufficient sensitivity and specificity to help diagnose pancreatic cancer early. Detection of serum tumor markers (CA19-9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer. The combination of miR-16, miR-196a and CA19-9 plasma level was more effective, especially in early tumor screening. Furthermore, recent studies reported that mainly miR-21, miR-155 and miR-196 were dysregulated in IPMN (intraductal papillary mucinous neoplasms) and PanIN (pancreatic intraepithelial neoplasia) lesions, suggesting their usefulness as early biomarkers of these diseases. The reduced rate of apoptosis plays a crucial role in carcinogenesis, and it is one of the most important characteristics acquired by pancreatic cancer cells, which protects them from attack by the immune system and reduces the effectiveness of pharmacological treatment. This review summarizes the data concerning the clinical utility of selected biomarkers in pancreatic cancer patients. The review mainly focuses on the genetic aspects of signaling pathway disorders associated with apoptosis in the pathogenesis and diagnosis of pancreatic cancer. PMID:28450803

Gli2 protein expression level is a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms.

PubMed

Sugiyama, Y; Sasajima, J; Mizukami, Y; Koizumi, K; Kawamoto, T; Ono, Y; Karasaki, H; Tanabe, H; Fujiya, M; Kohgo, Y

2016-06-01

The hedgehog pathway is known to promote proliferation of pancreatic ductal adenocarcinoma (PDA) and has been shown to restrain tumor progression. To understand how hedgehog causes these effects, we sought to carefully examine protein expression of hedgehog signaling components during different tumor stages. Genetically engineered mice, Pdx1-Cre;LSL-KrasG12D and Pdx1-Cre;LSL-KrasG12D;p53lox/+, were utilized to model distinct phases of tumorigenesis, pancreatic intraepithelial neoplasm (PanIN) and PDA. Human pancreatic specimens of intraductal papillary mucinous neoplasm (IPMN) and PDA were also employed. PanIN and IPMN lesions highly express Sonic Hedgehog, at a level that is slightly higher than that observed in PDA. GLI2 protein is also expressed in both PanIN/IPMN and PDA. Although there was no difference in the nuclear staining, the cytoplasmic GLI2 level in PDA was modest in comparison to that in PanIN/IPMN. Hedgehog interacting protein was strongly expressed in the precursors, whereas the level in PDA was significantly attenuated. There were no differences in expression of Patched1 at early and late stages. Finally, a strong correlation between Sonic Hedgehog and GLI2 staining was found in both human and murine pancreatic tumors. The results indicate that the GLI2 protein level could serve as a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms.

Expression of MUC4 mucin is observed mainly in the intestinal-type of intraductal papillary mucinous neoplasm of the pancreas

PubMed Central

Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K.; Goto, Masamichi; Yonezawa, Suguru

2013-01-01

Objectives This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). Methods We performed immonohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, in cancer cell lines. Results MAb 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 mRNA. However, IHC signals detected by both MAbs were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. Conclusions A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential. PMID:23921963

PIK3CA Mutations in Mucinous Cystic Neoplasms of the Pancreas

PubMed Central

Garcia-Carracedo, Dario; Chen, Zong-Ming; Qiu, Wanglong; Huang, Alicia S.; Tang, Sophia M.; Hruban, Ralph H.; Su, Gloria H.

2014-01-01

Objectives Mucinous cystic neoplasms (MCNs) are rare, potentially curable, mucin-producing neoplasms of the pancreas. We have previously reported PIK3CA (phosphoinositide-3-kinase catalytic subunit, p110α) mutations in intraductal papillary mucinous neoplasms, another mucin-producing neoplasm of the pancreas. In this study, we analyzed the presence of PIK3CA and AKT1/PKB (V-akt murine thymoma viral oncogene homolog 1) hot-spot mutations in MCN specimens. Methods Using the genomic DNA sequencing of tumor tissues isolated by laser capture microdissection, we evaluated 15 well-characterized MCNs for the E542K, E545K(exon 9), and H1047R (exon 20) hot-spotmutations in the PIK3CA gene and the E17K mutation in the AKT1 gene. Results A hot-spotmutation (E545K) of the PIK3CA gene was detected in 1 of the 15 MCNs and further confirmed by a mutant-enriched method. Interestingly, this mutation was found to be present only in the high-grade but not in low-grade dysplastic epithelium obtained from this neoplasm and coexisted with a KRASG12D mutation. No mutations were identified in the AKT1 gene. Conclusions Our data, when combined with previous reports on intraductal papillary mucinous neoplasms, indicate that oncogenic activation of the PI3K pathway involving PIK3CA gene mutations can contribute to the progression of mucin-producing neoplasms but not pancreatic intraepithelial neoplasia. PIK3CA status could be useful for understanding their progression to malignancy. PMID:24518503

Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma

PubMed Central

Ryu, Ji Kon; Matthaei, Hanno; dal Molin, Marco; Hong, Seung-Mo; Canto, Marcia I.; Schulick, Richard D.; Wolfgang, Christopher; Goggins, Michael G.; Hruban, Ralph H.; Cope, Leslie; Maitra, Anirban

2011-01-01

Background Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer. Methods Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The ‘mucinous’ cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the ‘nonmucinous’ cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas. Results Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%. Conclusion This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas. PMID:21757972

Management of intraductal papillary mucinous neoplasms.

PubMed

Crippa, Stefano; Fernández-del Castillo, Carlos

2008-04-01

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are being diagnosed with increasing frequency, probably due to the widespread use of cross-sectional imaging. The natural history of these tumors is still largely unknown. Several studies have shown topographical as well as biological differences between main duct and branch duct IPMNs. In the past few years, diagnostic work-up and, in particular, management of these tumors have evolved significantly. Data support the need for resection of main duct IPMNs and the possibility of nonoperative management in selected cases of branch duct tumors. In this systematic review, we analyze the most recent publications related to IPMNs, with particular emphasis on problems related to managing this challenging disease.

European evidence-based guidelines on pancreatic cystic neoplasms

PubMed Central

Del Chiaro, Marco

2018-01-01

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN. PMID:29574408

Diagnostic Pitfalls in Papillary Lesions of the Breast: Experience from a Single Tertiary Care Center

PubMed Central

Basavaiah, Sridevi Hanaganahalli; Sreeram, Saraswathy; Suresh, Pooja Kundapur; Kini, Hema; Adiga, Deepa; Sahu, Kausalya Kumari; Pai, Radha R

2016-01-01

Introduction Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. Aims This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. Materials and Methods A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient’s clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. Results During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. Conclusion Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis. PMID:27656446

Intraductal papillary neoplasm originating from an anomalous bile duct.

PubMed

Maki, Harufumi; Aoki, Taku; Ishizawa, Takeaki; Tanaka, Mariko; Sakatani, Takashi; Beck, Yoshifumi; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Kokudo, Norihiro

2017-04-01

An 82-year-old woman who had been suffering from repeated obstructive jaundice for 7 years was referred to our hospital. Although endoscopic aspiration of the mucin in the common bile duct had been temporally effective, origin of the mucin production had not been detectable. The patient thus had been forced to be on long-term follow-up without curative resection. Endoscopic retrograde cholangioscopy on admission revealed massive mucin in the common bile duct. In addition, an anomalous bile duct located proximal to the gallbladder was identified. Since the lumen of the anomalous duct was irregular and the rest of biliary tree was completely free of suspicious lesions, the anomalous duct was judged to be the primary site. Surgical resection of the segment 4 and 5 of the liver combined with the extrahepatic biliary tract was performed. Pathological diagnosis was compatible to intraductal papillary neoplasm with high-grade intraepithelial dysplasia of the anomalous bile duct. The patient has been free from the disease for 6.5 years after resection. This is the first case of intraductal papillary neoplasm derived from an anomalous bile duct, which was resected after long-term conservative treatment. The present case suggested the slow growing character of natural history of the neoplasm.

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

PubMed Central

Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

2012-01-01

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

Application of "papillary-like main pancreatic duct invaginated" pancreaticojejunostomy for normal soft pancreas cases.

PubMed

Zhang, Bo; Xu, Jin; Liu, Chen; Long, Jiang; Liu, Liang; Xu, Yongfeng; Wu, Chuntao; Luo, Guopei; Ni, Quanxing; Li, Min; Yu, Xianjun

2013-01-01

Pancreaticojejunostomy is the key procedure of pancreaticoduodenectomy. Our study introduced a new pancreaticojejunal (PJ) anastomosis named "papillary-like main pancreatic duct invaginated" pancreaticojejunostomy. Nighty-two patients underwent pancreaticojejunostomy with either conventional duct-to-mucosa pancreaticojejunostomy or the new "papillary-like main pancreatic duct invaginated" techniques were analyzed retrospectively from January 2010 to September 2012. The incidence of pancreatic fistula was 15.7% (8/51) for the "papillary-like main pancreatic duct invaginated" group and 19.5% (8/41) for the duct-to-mucosa fashion respectively. It is noteworthy that the rate of grade B/C postoperative pancreatic fistula (POPF) in the "papillary-like main pancreatic duct invaginated" group was significantly lower than that of the duct-to-mucosa group (P = 0.039). There were no differences in the incidence of postoperative morbidity and mortality such as postoperative hemorrhage, delayed gastric emptying or remnant pancreatitis. The "papillary-like main pancreatic duct invaginated" pancreaticojejunostomy could provide a feasible option to pancreatic surgeons for patients with normal soft pancreas.

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is a marker that predicts presence of invasion in papillary biliary tumors.

PubMed

Sasaki, Motoko; Sato, Yasunori

2017-04-01

Biliary tumors showing intraductal papillary growth (Pap-BTs) include intraductal papillary neoplasm of the bile duct (IPNB) and papillary cholangiocarcinoma (CC). A differential diagnosis between IPNB and papillary CC currently remains challenging. The aim of the present study is to identify histological features and immunohistochemical markers of malignant potential such as tumor invasion in Pap-BTs. Subjects comprised 37 patients with Pap-BT (intrahepatic and perihilar [proximal], 27: 17 noninvasive and 10 invasive; distal, 10: all invasive). We examined histological features and the expression of p53, enhancer of zeste homolog 2, insulin-like growth factor II mRNA-binding protein 3 (IMP3), and DNA methyltransferase-1 in the intraductal area in Pap-BTs. Noninvasive Pap-BT was characterized by the presence of a low-grade dysplastic area, edematous stroma, and the absence of necrosis. The expression of p53, enhancer of zeste homolog 2, IMP3, and DNA methyltransferase-1 was significantly weaker in noninvasive Pap-BTs than in invasive Pap-BTs (P<.01). Diffuse cytoplasmic IMP3 expression was absent in noninvasive Pap-BTs. IMP3 showed the greatest specificity to predict a presence of invasion. A heatmap demonstrated that proximal noninvasive Pap-BTs and distal Pap-BTs may be completely different. In bile duct biopsies, the expression of IMP3 was the most precise predictor of invasion in Pap-BTs. In conclusion, Pap-BTs may be separated into 3 subgroups: (1) proximal noninvasive Pap-BT, corresponding to IPNB; (2) distal invasive Pap-BT, corresponding to papillary CC; and (3) the remaining Pap-BT including IPNB with associated adenocarcinomas, based on histological and immunohistochemical features. IMP3 may be a useful marker for predicting invasion in Pap-BT. Copyright © 2017 Elsevier Inc. All rights reserved.

Utility of whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs).

PubMed

Hoffman, David H; Ream, Justin M; Hajdu, Christina H; Rosenkrantz, Andrew B

2017-04-01

To evaluate whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs), including in comparison with conventional MRI features. Eighteen branch-duct IPMNs underwent MRI with DWI prior to resection (n = 16) or FNA (n = 2). A blinded radiologist placed 3D volumes-of-interest on the entire IPMN on the ADC map, from which whole-lesion histogram metrics were generated. The reader also assessed IPMN size, mural nodularity, and adjacent main-duct dilation. Benign (low-to-intermediate grade dysplasia; n = 10) and malignant (high-grade dysplasia or invasive adenocarcinoma; n = 8) IPMNs were compared. Whole-lesion ADC histogram metrics demonstrating significant differences between benign and malignant IPMNs were: entropy (5.1 ± 0.2 vs. 5.4 ± 0.2; p = 0.01, AUC = 86%); mean of the bottom 10th percentile (2.2 ± 0.4 vs. 1.6 ± 0.7; p = 0.03; AUC = 81%); and mean of the 10-25th percentile (2.8 ± 0.4 vs. 2.3 ± 0.6; p = 0.04; AUC = 79%). The overall mean ADC, skewness, and kurtosis were not significantly different between groups (p ≥ 0.06; AUC = 50-78%). For entropy (highest performing histogram metric), an optimal threshold of >5.3 achieved a sensitivity of 100%, a specificity of 70%, and an accuracy of 83% for predicting malignancy. No significant difference (p = 0.18-0.64) was observed between benign and malignant IPMNs for cyst size ≥3 cm, adjacent main-duct dilatation, or mural nodule. At multivariable analysis of entropy in combination with all other ADC histogram and conventional MRI features, entropy was the only significant independent predictor of malignancy (p = 0.004). Although requiring larger studies, ADC entropy obtained from 3D whole-lesion histogram analysis may serve as a biomarker for identifying the malignant potential of IPMNs, independent of conventional MRI features.

Application of “Papillary-Like Main Pancreatic Duct Invaginated” Pancreaticojejunostomy for Normal Soft Pancreas Cases

PubMed Central

Zhang, Bo; Xu, Jin; Liu, Chen; Long, Jiang; Liu, Liang; Xu, Yongfeng; Wu, Chuntao; Luo, Guopei; Ni, Quanxing; Li, Min; Yu, Xianjun

2013-01-01

Pancreaticojejunostomy is the key procedure of pancreaticoduodenectomy. Our study introduced a new pancreaticojejunal (PJ) anastomosis named “papillary-like main pancreatic duct invaginated” pancreaticojejunostomy. Nighty-two patients underwent pancreaticojejunostomy with either conventional duct-to-mucosa pancreaticojejunostomy or the new “papillary-like main pancreatic duct invaginated” techniques were analyzed retrospectively from January 2010 to September 2012. The incidence of pancreatic fistula was 15.7% (8/51) for the “papillary-like main pancreatic duct invaginated” group and 19.5% (8/41) for the duct-to-mucosa fashion respectively. It is noteworthy that the rate of grade B/C postoperative pancreatic fistula (POPF) in the “papillary-like main pancreatic duct invaginated” group was significantly lower than that of the duct-to-mucosa group (P = 0.039). There were no differences in the incidence of postoperative morbidity and mortality such as postoperative hemorrhage, delayed gastric emptying or remnant pancreatitis. The “papillary-like main pancreatic duct invaginated” pancreaticojejunostomy could provide a feasible option to pancreatic surgeons for patients with normal soft pancreas. PMID:23797701

APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors.

PubMed

Ginesta, Mireia M; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

2016-09-01

Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71-80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms.

Differentiating neoplastic from benign lesions of the pancreas: translational techniques.

PubMed

Khalid, Asif

2009-11-01

There has been substantial recent progress in our ability to image and sample the pancreas leading to the improved recognition of benign and premalignant conditions of the pancreas such as autoimmune pancreatitis (AIP) and mucinous lesions (mucinous cystic neoplasms [MCN] and intraductal papillary mucinous neoplasms [IPMN]), respectively. Clinically relevant and difficult situations that continue to be faced in this context include differentiating MCN and IPMN from nonmucinous pancreatic cysts, the early detection of malignant degeneration in MCN and IPMN, and accurate differentiation between pancreatic cancer and inflammatory masses, especially AIP. These challenges arise primarily due to the less than perfect sensitivity for malignancy utilizing cytological samples obtained via EUS and ERCP. Aspirates from pancreatic cysts are often paucicellular further limiting the accuracy of cytology. One approach to improve the diagnostic yield from these very small samples is through the use of molecular techniques. Because the development of pancreatic cancer and malignant degeneration in MCN and IPMN is associated with well studied genetic insults including oncogene activation (eg, k-ras), tumor suppressor gene losses (eg, p53, p16, and DPC4), and genome maintenance gene mutations (eg, BRCA2 and telomerase), detecting these molecular abnormalities may aid in improving our diagnostic accuracy. A number of studies have shown the utility of testing clinical samples from pancreatic lesions and bile duct strictures for these molecular markers of malignancy to differentiate between cancer and inflammation. The information from these studies will be discussed with emphasis on how to use this information in clinical practice.

Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.

PubMed

Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y; Warshaw, Andrew L; Thayer, Sarah P; Iafrate, A John

2009-03-01

To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.

The expression of MUC4 and MUC5AC is related to the biologic malignancy of intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Kanno, Atsushi; Satoh, Kennichi; Kimura, Kenji; Hirota, Morihisa; Umino, Jun; Masamune, Atsushi; Satoh, Akihiko; Asakura, Tohru; Egawa, Shinichi; Sunamura, Makoto; Endoh, Mareyuki; Shimosegawa, Tooru

2006-11-01

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show heterogeneous proliferations with latent malignancy. Mucins (MUC) are high-molecular-weight glycoproteins, with an aberrant expression profile in various malignancies. Recently, MUC4 and MUC5AC expressions have been demonstrated to correlate with the unfavorable and the favorable prognosis of pancreatic duct cell carcinoma, respectively. However, little is known about these mucin expressions in IPMNs. To clarify the role of MUC4 and MUC5AC expressions in IPMNs, the expression profiles of MUC4 and MUC5AC were investigated in 50 lesions from 17 specimens with 16 IPMNs by immunohistochemistry, using each of their specific antibodies. The expression of MUC4 was found in the lesions ranging from adenoma to cancer lesions of IPMNs, whereas it was undetectable in normal and hyperplastic lesions. Frequent expression of MUC4 is found in the higher grade of IPMNs (borderline and cancer lesions; 16/18 lesions, 94%). The differences were independently significant (P < 0.001) when the cutoff point was set between adenoma and borderline IPMNs. Similarly, frequent expression of MUC5AC was detected in the lesions from adenoma to cancer of IPMNs (32/34, 94%), whereas no intense expression was detected in normal or hyperplastic lesions. The significant difference was found when the cutoff point was set between hyperplasia and adenoma of IPMNs (P < 0.001). These results indicated that the expressions of MUC4 and MUC5AC are potential markers to distinguish adenoma or above malignant lesions of IPMNs from lesser malignant ones, respectively.

Significance of aggressive surgery for an invasive carcinoma derived from an intraductal papillary mucinous neoplasm diagnosed preoperatively as borderline resectable.

PubMed

Aimoto, Takayuki; Mizutani, Satoshi; Kawano, Youichi; Suzuki, Hideyuki; Uchida, Eiji

2013-01-01

We investigated the clinicopathological features of borderline resectable invasive carcinomas (BRICs) derived from intraductal papillary mucinous neoplasms (IPMNs) and examined the significance of the aggressive "surgery first" approach compared with the treatment of conventional borderline resectable pancreatic ductal adenocarcinomas (BRPDAs). We retrospectively studied 7 patients with BRICs derived from IPMNs and 14 patients with conventional BRPDAs. Several factors were reviewed: initial symptoms, preoperative imaging, serum level of CA19-9, perioperative factors, pathological findings, adjuvant chemotherapy, and outcome. All BRICs derived from IPMN were huge tumors (more than 3 cm in diameter) suspected to involve <180° of the circumference of the vessel. Five patients (71%) underwent a modified Whipple procedure, and 2 (29%) underwent distal pancreatectomy. Only 3 patients (43%) required vascular resection. Curative resection was achieved in all 7 patients, who are alive with no evidence of recurrence. There were no severe postoperative complications. With regards to the pathological IPMN subtype, 2 tumors (29%) were gastric and 5 (71%) were intestinal. Only 2 patients (29%) had lymph node metastasis. The final stage was II in 4 (57%) cases and IVa in 3 cases (43%). The 3-year survival rate was 100%. Tumors of BRICs derived from IPMNs were larger than those of conventional BRPDAs (p<0.05). The BRICs derived from IPMN less frequently metastasized to lymph nodes (p<0.05) and were of an earlier stage (p<0.05) than were conventional BRPDAs. The 3-year survival rate was significantly higher for BRICs derived from IPMNs (100%) than for conventional BRPDAs (19%, p<0.001). The BRICs derived from an intestinal or gastric IPMN are less aggressive than conventional BRPDAs and have a more favorable prognosis. In addition, aggressive "surgery first" approach may contribute to this better prognosis.

Liver transplant patients have a similar risk of progression as sporadic patients with branch duct intraductal papillary mucinous neoplasms

PubMed Central

Lennon, Anne Marie; Victor, David; Zaheer, Atif; Ostovaneh, Mohammad Reza; Jeh, Jessica; Law, Joanna K.; Rezaee, Neda; Molin, Marco Dal; Ahn, Young Joon; Wu, Wenchuan; Khashab, Mouen A.; Girotra, Mohit; Ahuja, Nita; Makary, Martin A.; Weiss, Matthew J.; Hirose, Kenzo; Goggins, Michael; Hruban, Ralph H.; Cameron, Andrew; Wolfgang, Christopher L.; Singh, Vikesh K.; Gurakar, Ahmet

2015-01-01

Background Intraductal papillary mucinous neoplasms (IPMNs) have malignant potential, and can progress from low- to high-grade dysplasia to invasive adenocarcinoma. The management of patients with IPMNs is dependent on their risk of malignant progression, with surgical resection recommended for patients with branch duct-IPMN (BD-IPMN) who develop high-risk features. There is increasing evidence that liver transplant patients are at increased risk of extra-hepatic malignancy. However there are few data regarding the risk of progression of BD-IPMNs in liver transplant recipients. The aim of this study was to determine if liver transplant recipients with BD-IPMNs are at higher risk of developing high-risk features than patients with BD-IPMNs who did not receive a transplant. Methods Consecutive patients who underwent a liver transplant with BD-IPMNs were included. Patients with BD-IPMNs with no history of immunosuppression were used as controls. Progression of the BD-IPMNs was defined as development of a high-risk feature (jaundice, dilated main pancreatic duct, mural nodule, cytology suspicious or diagnostic for malignancy, cyst diameter ≥3cm). Results Twenty three liver transplant patients with BD-IPMN were compared with 274 control patients. The median length of follow-up was 53.7 and 24 months in liver transplant and control groups respectively. Four (17.4%) liver transplant patients and 45 (16.4%) controls developed high-risk features (p=0.99). In multivariate analysis, progression of BD-IPMNs was associated with age at diagnosis but not with liver transplantation. Conclusion There was no statistically significant difference in the risk of developing high-risk features between the liver transplant and control groups. PMID:25155689

Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

PubMed

Beger, Hans G; Schwarz, Michael; Poch, Bertram

2012-11-01

Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

[Value of MR imaging in the diagnosis of intraductal papillary neoplasm of the bile duct].

PubMed

Song, Fengxiang; Zhou, Jun; Shi, Yuxin; Zeng, Mengsu; Zhou, Kangrong; Ding, Yuqin; Cao, Yingli; Zhou, Jianjun

2015-01-01

To analyze the value of MR imaging in diagnosis of intraductal papillary neoplasm of the bile duct (IPN-B). Fourteen patients with intraductal papillary neoplasms of the bile duct confirmed by surgical pathology were included in this study. The patients underwent MR routine plain scanning and enhancement scanning (including T1WI, T2WI with fat suppression, FALSH T1WI, and three-phase enhancement scanning), diffusion weighted imaging(DWI) and magnetic resonance cholangiopancreatography (MRCP) before operation. The imaging data were reviewed and analyzed retrospectively in comparison with the surgical and pathological results. In these patients, 7 cases had tumors located in the left lobe, 2 cases had tumors in both the left and right lobes, 2 cases in the hepatic hilum, 2 cases in the common bile duct, and 1 case in both the right lobe and the common bile duct. Solitary or multiple intraductal masses could be found in 12 cases, with 11 cases appeared as papillary masses and one case as flat mass. In the other two cases the tumor was not visible (one case had too many stones, and in another case the tumor was too small). The tumors in the 12 cases showed hypointensity on T1WI and hyperintensity on T2WI. On the dynamic contrast-enhanced MRI, 11 cases showed mild and one showed moderate enhancement in arterial phase, and all the cases showed mildly and gradually delayed enhancement. On DWI, the lesion areas showed high signal intensity in all the cases, and the ADC value of the tumor area (1.697×10(-3)mm(2)/s) was significantly lower than that of the normal bile (3.973×10(-3)mm(2)/s) (t = -10.94, P < 0.05). Twelve cases demonstrated filling defects on primary MRCP coronary thin section images. On 3D-reconstruction MRCP images, 7 cases exhibited diffuse bile duct dilatation with the tumor areas more prominent, 3 cases exhibited aneurysmal bile dilatation, while the rest 4 cases exhibited segmental or lobar bile duct dilatation ( including 2 with invisible tumors ). In the 3 cases with aneurysmal bile dilatation, the multiple directions of MRCP images helped to find the communication between the aneurysmal dilatation and the bile duct. All the cases showed significant proximal bile duct dilatation (the extent of dilatation >100%), and 9 cases also showed distal bile duct dilatation. Bile duct stones were noted in 6 cases, 4 at the tumor area, and the other 2 away from the tumor area. No adjacent tissue invasion and no distal tissue or lymph node metastasis were observed. Intraductal papillary neoplasms of the bile ducts have characteristic imaging appearances on MRI, and MRI is an important method helpful to making correct diagnosis.

Laparoscopic pancreaticoduodenectomy via a reverse-''V'' approach with four ports: initial experience and perioperative outcomes.

PubMed

Liu, Zhao; Yu, Mu-Chuan; Zhao, Rui; Liu, Yan-Feng; Zeng, Jian-Ping; Wang, Xian-Qiang; Tan, Jing-Wang

2015-02-07

To evaluate the feasibility, safety, and efficacy of laparoscopic pancreaticoduodenectomy (LPD) using a reverse-"V" approach with four ports. This is a retrospective study of selected patients who underwent LPD at our center between April 2011 and April 2012. The following data were collected and reviewed: patient characteristics, tumor histology, surgical outcome, resection margins, morbidity, and mortality. All patients were thoroughly evaluated preoperatively by complete hematologic investigations, triple-phase helical computed tomography, upper gastrointestinal endoscopy, and biopsy of ampullary lesions (when present). Magnetic resonance cholangiopancreatography was performed for doubtful cases of lower common bile duct lesions. There was no perioperative mortality. LPD was performed with tumor-free margins in all patients, including patients with pancreatic ductal adenocarcinoma (n = 6), ampullary carcinoma (n = 6), intra-ductal papillary mucinous neoplasm (n = 2), pancreatic cystadenocarcinoma (n = 2), pancreatic head adenocarcinoma (n = 3), and bile duct cancer (n = 2). The mean patient age was 65 years (range, 42-75 years). The median blood loss was 240 mL, and the mean operative time was 368 min. LPD using a reverse-"V" approach can be performed safely and yields good results in elective patients. Our preliminary experience showed that LDP can be performed via a reverse-"V" approach. This approach can be used to treat localized malignant lesions irrespective of histopathology.

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases.

PubMed

Alsadoun, Nadjla; MacGrogan, Gaëtan; Truntzer, Caroline; Lacroix-Triki, Magali; Bedgedjian, Isabelle; Koeb, Marie-Hélène; El Alam, Elsy; Medioni, Dan; Parent, Michel; Wuithier, Pascal; Robert, Isabelle; Boidot, Romain; Arnould, Laurent

2018-05-21

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors.

aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

PubMed

Kato, Shingo; Akimoto, Kazunori; Nagashima, Yoji; Ishiguro, Hitoshi; Kubota, Kensuke; Kobayashi, Noritoshi; Hosono, Kunihiro; Watanabe, Seitaro; Sekino, Yusuke; Sato, Takamitsu; Sasaki, Kazunori; Nakaigawa, Noboru; Kubota, Yoshinobu; Inayama, Yoshiaki; Endo, Itaru; Ohno, Shigeo; Maeda, Shin; Nakajima, Atsushi

2013-01-01

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report.

PubMed

Kumar, Mayank; Pottipati, Bhaswanth; Arakeri, Surekha U; Javalgi, Anita P

2017-06-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.

Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report

PubMed Central

Pottipati, Bhaswanth; Arakeri, Surekha U.; Javalgi, Anita P.

2017-01-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast. PMID:28764176

Pathological criteria and practical issues in papillary lesions of the breast - a review.

PubMed

Ni, Yun-Bi; Tse, Gary M

2016-01-01

Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized. © 2015 John Wiley & Sons Ltd.

Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

PubMed

José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

2013-01-01

Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer

PubMed Central

Kang, Rui; Xie, Yangchun; Zhang, Qiuhong; Hou, Wen; Jiang, Qingping; Zhu, Shan; Liu, Jinbao; Zeng, Dexing; Wang, Haichao; Bartlett, David L; Billiar, Timothy R; Zeh, Herbert J; Lotze, Michael T; Tang, Daolin

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) driven by oncogenic K-Ras remains among the most lethal human cancers despite recent advances in modern medicine. The pathogenesis of PDAC is partly attributable to intrinsic chromosome instability and extrinsic inflammation activation. However, the molecular link between these two events in pancreatic tumorigenesis has not yet been fully established. Here, we show that intracellular high mobility group box 1 (HMGB1) remarkably suppresses oncogenic K-Ras-driven pancreatic tumorigenesis by inhibiting chromosome instability-mediated pro-inflammatory nucleosome release. Conditional genetic ablation of either single or both alleles of HMGB1 in the pancreas renders mice extremely sensitive to oncogenic K-Ras-driven initiation of precursor lesions at birth, including pancreatic intraepithelial neoplasms, intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms. Loss of HMGB1 in the pancreas is associated with oxidative DNA damage and chromosomal instability characterized by chromosome rearrangements and telomere abnormalities. These lead to inflammatory nucleosome release and propagate K-Ras-driven pancreatic tumorigenesis. Extracellular nucleosomes promote interleukin 6 (IL-6) secretion by infiltrating macrophages/neutrophils and enhance oncogenic K-Ras signaling activation in pancreatic lesions. Neutralizing antibodies to IL-6 or histone H3 or knockout of the receptor for advanced glycation end products all limit K-Ras signaling activation, prevent cancer development and metastasis/invasion, and prolong animal survival in Pdx1-Cre;K-RasG12D/+;Hmgb1−/− mice. Pharmacological inhibition of HMGB1 loss by glycyrrhizin limits oncogenic K-Ras-driven tumorigenesis in mice under inflammatory conditions. Diminished nuclear and total cellular expression of HMGB1 in PDAC patients correlates with poor overall survival, supporting intracellular HMGB1 as a novel tumor suppressor with prognostic and therapeutic relevance in PDAC. PMID:28374746

Evaluation of diagnostic cytology via endoscopic naso-pancreatic drainage for pancreatic tumor

PubMed Central

Iwata, Tomoyuki; Kitamura, Katsuya; Yamamiya, Akira; Ishii, Yu; Sato, Yoshiki; Nomoto, Tomohiro; Ikegami, Akitoshi; Yoshida, Hitoshi

2014-01-01

AIM: To evaluate the usefulness of cytology of the pancreatic juice obtained via the endoscopic naso-pancreatic drainage tube (ENPD-C). METHODS: ENPD was performed in cases where a diagnosis could not be made other than by using endoscopic retrograde cholangiopancreatography and in cases of pancreatic neoplasms or cystic tumors, including intraductal papillary mucinous neoplasm (IPMN) suspected to have malignant potential. 35 patients (21 males and 14 females) underwent ENPD between January 2007 and June 2013. The pancreatic duct was imaged and the procedure continued in one of ENPD-C or ENPD-C plus brush cytology (ENPD-BC). We checked the cytology result and the final diagnosis. RESULTS: The mean patient age was 69 years (range, 48-86 years). ENPD-C was performed in 24 cases and ENPD-C plus brush cytology (ENPD-BC) in 11 cases. The ENPD tube was inserted for an average of 3.5 d. The final diagnosis was confirmed on the basis of the resected specimen in 18 cases and of follow-up findings at least 6 mo after ENPD in the 18 inoperable cases. Malignancy was diagnosed in 21 cases and 14 patients were diagnosed as having a benign condition. The ratios of class V/IV:III:II/I findings were 7:7:7 in malignant cases and 0:3:11 in benign cases. The sensitivity and specificity for all patients were 33.3% and 100%, respectively. The cytology-positive rate was 37.5% (6/16) for pancreatic cancer. For IPMN cases, the sensitivity and specificity were 33% and 100%, respectively. CONCLUSION: Sensitivity may be further increased by adding brush cytology. Although we can diagnosis cancer in cases of a positive result, the accuracy of ENPD-C remains unsatisfactory. PMID:25132920

KRAS and GNAS Mutations in Pancreatic Juice Collected From the Duodenum of Patients at High Risk for Neoplasia Undergoing Endoscopic Ultrasound

PubMed Central

Eshleman, James R.; Norris, Alexis L.; Sadakari, Yoshihiko; Debeljak, Marija; Borges, Michael; Harrington, Colleen; Lin, Elaine; Brant, Aaron; Barkley, Thomas; Almario, J. Alejandro; Topazian, Mark; Farrell, James; Syngal, Sapna; Lee, Jeffrey H.; Yu, Jun; Hruban, Ralph H.; Kanda, Mitsuro; Canto, Marcia Irene; Goggins, Michael

2014-01-01

BACKGROUND & AIMS Pancreatic imaging can identify neoplastic cysts but not microscopic neoplasms. Mutation analysis of pancreatic fluid following secretin stimulation might identify microscopic neoplasias in the pancreatic duct system. We determined the prevalence of mutations in KRAS and GNAS genes in pancreatic juice from subjects undergoing endoscopic ultrasound for suspected pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms, or pancreatic adenocarcinoma. METHODS Secretin-stimulated juice samples were collected from the duodenum of 272 subjects enrolled in Cancer of the Pancreas Screening studies; 194 subjects were screened because of a family history of, or genetic predisposition to, pancreatic cancer and 78 were evaluated for pancreatic cancer (n=30) or other disorders (controls: pancreatic cysts, pancreatitis, or normal pancreata, n=48). Mutations were detected by digital high-resolution melt-curve analysis and pyrosequencing. The number of replicates containing a mutation determined the mutation score. RESULTS KRAS mutations were detected in pancreatic juice from larger percentages of subjects with pancreatic cancer (73%) or undergoing cancer screening (50%) than controls (19%) (P=.0005). A greater proportion of patients with pancreatic cancer had at least 1 KRAS mutation detected 3 or more times (47%) than screened subjects (21%) or controls (6%, P=.002). Among screened subjects, mutations in KRAS (but not GNAS) were found in similar percentages of patients with or without pancreatic cysts. However, a greater proportion of patients over 50 ys old had KRAS mutations (54.6%) than younger patients (36.3%) (P=.032); the older subjects also more mutations in KRAS (P=.02). CONCLUSIONS Mutations in KRAS are detected in pancreatic juice from the duodenum of 73% of patients with pancreatic cancer, and 50% of asymptomatic individuals with a high risk for pancreatic cancer. However, KRAS mutations are detected in pancreatic juice from 19% of controls. Mutations detected in individuals without pancreatic abnormalities, based on imaging analyses, likely arise from small PanIN lesions. ClinicalTrials.gov no: NCT00438906 and NCT00714701 PMID:25481712

GLUT-1 Expression in Pancreatic Neoplasia

PubMed Central

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N. Volkan

2011-01-01

Objectives GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Methods Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. Results There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). Conclusions GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression. PMID:21206329

GLUT-1 expression in pancreatic neoplasia: implications in pathogenesis, diagnosis, and prognosis.

PubMed

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N Volkan

2011-03-01

GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression.

A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

PubMed Central

Springer, Simeon; Wang, Yuxuan; Molin, Marco Dal; Masica, David L.; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P.; Wolfgang, Christopher L.; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J.; Klimstra, David S.; Schattner, Mark A.; Schmidt, C. Max; Yip-Schneider, Michele; Cummings, Oscar W.; Brand, Randall E.; Zeh, Herbert J.; Singhi, Aatur D.; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H.; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J.; Cameron, John; Pittman, Meredith; Eshleman, James R.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Karchin, Rachel; Hruban, Ralph H.; Vogelstein, Bert; Lennon, Anne Marie

2016-01-01

Background & Aims The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid-pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53 and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers were compared with that of clinical markers, and a combination of molecular and clinical markers. Results We identified molecular markers and clinical features that classified cyst type with 90%–100% sensitivity and 92%–98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery, and could therefore reduce the number of unnecessary operations by 91%. Conclusions We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. PMID:26253305

MicroRNAs for Detection of Pancreatic Neoplasia

PubMed Central

Vila-Navarro, Elena; Vila-Casadesús, Maria; Moreira, Leticia; Duran-Sanchon, Saray; Sinha, Rupal; Ginés, Àngels; Fernández-Esparrach, Glòria; Miquel, Rosa; Cuatrecasas, Miriam; Castells, Antoni; Lozano, Juan José; Gironella, Meritxell

2017-01-01

Objective: The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia. Objective: Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates. Methods: Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1—52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2—95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C). Results: In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively. Conclusions: miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer. PMID:27232245

Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective.

PubMed

Rooney, Sarah L; Shi, Jiaqi

2016-10-01

-Intraductal tubulopapillary neoplasm (ITPN) is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management. -To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options. -Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials. -Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options.

Assessment of a Revised Management Strategy for Patients With Intraductal Papillary Mucinous Neoplasms Involving the Main Pancreatic Duct.

PubMed

Sugimoto, Motokazu; Elliott, Irmina A; Nguyen, Andrew H; Kim, Stephen; Muthusamy, V Raman; Watson, Rabindra; Hines, O Joe; Dawson, David W; Reber, Howard A; Donahue, Timothy R

2017-01-18

According to the 2012 International Consensus Guidelines, the diagnostic criterion of intraductal papillary mucinous neoplasms (IPMNs) involving the main duct (MD IPMNs) or the main and branch ducts (mixed IPMNs) of the pancreatic system is a main pancreatic duct (MPD) diameter of 5.0 mm or greater on computed tomography (CT) or magnetic resonance imaging (MRI). However, surgical resection is recommended for patients with an MPD diameter of 10.0 mm or greater, which is characterized as a high-risk stigma. An MPD diameter of 5.0 to 9.0 mm is not an indication for immediate resection. To determine an appropriate cutoff (ie, one with high sensitivity and negative predictive value) of the MPD diameter on CT or MRI as a prognostic factor for malignant disease and to propose a new management algorithm for patients with MD or mixed IPMNs. This retrospective cohort study included 103 patients who underwent surgical resection for a preoperative diagnosis of MD or mixed IPMN and in whom IPMN was confirmed by surgical pathologic findings at a single institution from July 1, 1996, to December 31, 2015. Malignant disease was defined as high-grade dysplasia or invasive adenocarcinoma on results of surgical pathologic evaluation. An appropriate MPD diameter on preoperative CT or MRI to predict malignant disease was determined using a receiver operating characteristic curve analysis. The prognostic value of the new management algorithm that incorporated the new MPD diameter cutoff was evaluated. Among the 103 patients undergoing resection for an MD or mixed IPMN (59 men [57.3%]; 44 women [42.7%]; median [range] age, 71 [48-86] years), 64 (62.1%) had malignant disease. Diagnostic accuracy for malignant neoplasms was highest at an MPD diameter cutoff of 7.2 mm (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.81). An MPD diameter of 7.2 mm or greater was also an independent prognostic factor for malignant neoplasms (odds ratio, 12.76; 95% CI, 2.43-66.88; P = .003) on logistic regression analysis after controlling for preoperative variables. The new management algorithm, which included an MPD diameter of 7.2 mm or greater as one of the high-risk stigmata, had a higher sensitivity (100%), negative predictive value (100%), and accuracy (66%) for malignant disease than the 2012 version of the International Consensus Guidelines (95%, 57%, and 63%, respectively). In this single-center, retrospective analysis, an MPD diameter of 7.2 mm was identified as an optimal cutoff for a prognostic factor for malignant disease in MD or mixed IPMN. These data support lowering the accepted criteria for MPD diameter when selecting patients for resection vs surveillance so as not to overlook cancer in IPMN.

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.

PubMed

Singhi, Aatur D; Zeh, Herbert J; Brand, Randall E; Nikiforova, Marina N; Chennat, Jennifer S; Fasanella, Kenneth E; Khalid, Asif; Papachristou, Georgios I; Slivka, Adam; Hogg, Melissa; Lee, Kenneth K; Tsung, Allan; Zureikat, Amer H; McGrath, Kevin

2016-06-01

The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Update on endoscopic management of main pancreatic duct stones in chronic calcific pancreatitis.

PubMed

Choi, Eun Kwang; Lehman, Glen A

2012-03-01

Pancreatic duct stones are a common complication during the natural course of chronic pancreatitis and often contribute to additional pain and pancreatitis. Abdominal pain, one of the major symptoms of chronic pancreatitis, is believed to be caused in part by obstruction of the pancreatic duct system (by stones or strictures) resulting in increasing intraductal pressure and parenchymal ischemia. Pancreatic stones can be managed by surgery, endoscopy, or extracorporeal shock wave lithotripsy. In this review, updated management of pancreatic duct stones is discussed.

Robotic total pancreatectomy with or without autologous islet cell transplantation: replication of an open technique through a minimal access approach.

PubMed

Zureikat, Amer H; Nguyen, Trang; Boone, Brian A; Wijkstrom, Martin; Hogg, Melissa E; Humar, Abhinav; Zeh, Herbert

2015-01-01

Total pancreatectomy (TP) is a morbid but sometimes necessary operation. Robotic TP is not often reported but may harbor some advantages compared to the open approach. This manuscript details a single institution's outcomes and technique of robotic TP. An accompanying video demonstrates a robotic TP with auto islet cell transplantation (IAT) in which (1) the arterial blood supply and venous drainage are kept intact until the last step of the TP to minimize warm ischemia time and (2) extirpation of the entire pancreas is performed without dividing the pancreatic neck to maximize islet recovery. This study is a retrospective review of a prospective database of perioperative outcomes of all consecutive robotic TPs at a single institution. This included a single robotic TP with IAT performed on a twenty-year-old patient with chronic pancreatitis. Between 2010 and January 2014, ten robotic TPs were performed (7 males, mean age 58 years), one of which included an IAT. Median body mass index was 28. Indications were intraductal papillary mucinous neoplasms (6), pancreatic adenocarcinoma (1), and chronic pancreatitis (3). The median operative time was 560 min with a median estimated blood loss of 650 ml. One case was converted to laparotomy. Ninety days mortality and Clavien III-IV complication rate were 0 and 20 %, respectively. The average length of stay was 10 ± 3 days, with only 1 readmission within 90 days. The single TP and IAT were completed successfully without conversion, and were achieved without division of the pancreatic neck thereby maintaining vascular inflow to an entire specimen up until extraction. This represents the largest series of robotic TP, demonstrating its safety and feasibility. Additionally, TP and IAT using the technique described above can be recapitulated using the robotic approach.

A combination of molecular markers and clinical features improve the classification of pancreatic cysts.

PubMed

Springer, Simeon; Wang, Yuxuan; Dal Molin, Marco; Masica, David L; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P; Wolfgang, Christopher L; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J; Klimstra, David S; Schattner, Mark A; Schmidt, C Max; Yip-Schneider, Michele; Cummings, Oscar W; Brand, Randall E; Zeh, Herbert J; Singhi, Aatur D; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J; Cameron, John; Pittman, Meredith; Eshleman, James R; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Karchin, Rachel; Hruban, Ralph H; Vogelstein, Bert; Lennon, Anne Marie

2015-11-01

The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Quantification of CT images for the classification of high- and low-risk pancreatic cysts

NASA Astrophysics Data System (ADS)

Gazit, Lior; Chakraborty, Jayasree; Attiyeh, Marc; Langdon-Embry, Liana; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

2017-03-01

Pancreatic cancer is the most lethal cancer with an overall 5-year survival rate of 7%1 due to the late stage at diagnosis and the ineffectiveness of current therapeutic strategies. Given the poor prognosis, early detection at a pre-cancerous stage is the best tool for preventing this disease. Intraductal papillary mucinous neoplasms (IPMN), cystic tumors of the pancreas, represent the only radiographically identifiable precursor lesion of pancreatic cancer and are known to evolve stepwise from low-to-high-grade dysplasia before progressing into an invasive carcinoma. Observation is usually recommended for low-risk (low- and intermediate-grade dysplasia) patients, while high-risk (high-grade dysplasia and invasive carcinoma) patients undergo resection; hence, patient selection is critically important in the management of pancreatic cysts.2 Radiologists use standard criteria such as main pancreatic duct size, cyst size, or presence of a solid enhancing component in the cyst to optimally select patients for surgery.3 However, these findings are subject to a radiologist's interpretation and have been shown to be inconsistent with regards to the presence of a mural nodule or solid component.4 We propose objective classification of risk groups based on quantitative imaging features extracted from CT scans. We apply new features that represent the solid component (i.e. areas of high intensity) within the cyst and extract standard texture features. An adaptive boost classifier5 achieves the best performance with area under receiver operating characteristic curve (AUC) of 0.73 and accuracy of 77.3% for texture features. The random forest classifier achieves the best performance with AUC of 0.71 and accuracy of 70.8% with the solid component features.

Biomarker validation for intraductal papillary mucinous neoplasms of the pancreas | Division of Cancer Prevention

Cancer.gov

A critical component to successful cancer screening is the identification of a lesion for which intervention will result in prolonged survival or cure.The five-year survival of patients with resected stage IA pancreas cancer (the earliest identifiable lesion and |

The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and controls: a pilot study.

PubMed

Olson, Sara H; Satagopan, Jaya; Xu, Youming; Ling, Lilan; Leong, Siok; Orlow, Irene; Saldia, Amethyst; Li, Peter; Nunes, Pamela; Madonia, Vincent; Allen, Peter J; O'Reilly, Eileen; Pamer, Eric; Kurtz, Robert C

2017-09-01

Poor oral health appears to be a risk factor for pancreatic cancer, possibly implicating the oral microbiota. In this pilot study, we evaluated the characteristics of the oral microbiota in patients with pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasms (IPMN), and healthy controls. Forty newly diagnosed PDAC patients, 39 IPMN patients, and 58 controls, excluding current smokers and users of antibiotics, provided saliva samples. Common oral bacterial species were comprehensively surveyed by sequencing of the 16S rRNA microbial genes. We obtained measures of diversity and the mean relative proportions of individual taxa. We explored the degree to which these measures differed according to respondent characteristics based on individual interviews. PDAC cases did not differ in diversity measures from either controls or IPMN cases. PDAC cases had higher mean relative proportions of Firmicutes and related taxa, while controls had higher mean relative proportions of Proteobacteria and related taxa. Results were generally similar when comparing PDAC to IPMN cases. Among IPMNs and controls combined, younger individuals had higher levels of several taxa within the Proteobacteria. The only other variable consistently related to mean relative proportions was mouthwash use, with taxa within Firmicutes more common among users. While there were no differences in diversity of the oral microbiota among these groups, there were differences in the mean relative proportions of some taxa. Characteristics of the oral microbiota are not associated with most measures of oral health.

A case of gastrointestinal bleeding due to right hepatic artery pseudoaneurysm following total remnant pancreatectomy: A case report.

PubMed

Fujio, Atsushi; Usuda, Masahiro; Ozawa, Yohei; Kamiya, Kurodo; Nakamura, Takanobu; Teshima, Jin; Murakami, Kazushige; Suzuki, On; Miyata, Go; Mochizuki, Izumi

2017-01-01

Pseudoaneurysm is a serious complication after pancreatic surgery, which mainly depends on the presence of a preceding pancreatic fistula. Postpancreatectomy hemorrhage following total pancreatectomy is a rare complication due to the absence of a pancreatic fistula. Here we report an unusual case of massive gastrointestinal bleeding due to right hepatic artery (RHA) pseudoaneurysm following total remnant pancreatectomy. A 75-year-old man was diagnosed with intraductal papillary mucinous carcinoma recurrence following distal pancreatectomy and underwent total remnant pancreatectomy. After discharge, he was readmitted to our hospital with melena because of the diagnosis of gastrointestinal bleeding. Gastrointestinal endoscopy was performed to detect the origin of bleeding, but an obvious bleeding point could not be detected. Abdominal computed tomography demonstrated an expansive growth, which indicated RHA pseudoaneurysm. Emergency angiography revealed gastrointestinal bleeding into the jejunum from the ruptured RHA pseudoaneurysm. Transcatheter arterial embolization was performed; subsequently, bleeding was successfully stopped for a short duration. Because of improvements in his general condition, the patient was discharged. To date, very few cases have described postpancreatectomy hemorrhage following total remnant pancreatectomy. We suspect that the aneurysm ruptured into the jejunum, possibly because of the scarring and inflammation associated with his two complex surgeries. Pseudoaneurysm should be considered when the fragility of blood vessels is suspected, despite no history of anastomotic leak and intra-abdominal abscess. Our case also highlighted that detecting gastrointestinal bleeding is necessary to recognize sentinel bleeding if the origin of bleeding is undetectable.

Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer

PubMed Central

Bardeesy, Nabeel; Cheng, Kuang-hung; Berger, Justin H.; Chu, Gerald C.; Pahler, Jessica; Olson, Peter; Hezel, Aram F.; Horner, James; Lauwers, Gregory Y.; Hanahan, Douglas; DePinho, Ronald A.

2006-01-01

SMAD4 is inactivated in the majority of pancreatic ductal adenocarcinomas (PDAC) with concurrent mutational inactivation of the INK4A/ARF tumor suppressor locus and activation of the KRAS oncogene. Here, using genetically engineered mice, we determined the impact of SMAD4 deficiency on the development of the pancreas and on the initiation and/or progression of PDAC—alone or in combination with PDAC-relevant mutations. Selective SMAD4 deletion in the pancreatic epithelium had no discernable impact on pancreatic development or physiology. However, when combined with the activated KRASG12D allele, SMAD4 deficiency enabled rapid progression of KRASG12D-initiated neoplasms. While KRASG12D alone elicited premalignant pancreatic intraepithelial neoplasia (PanIN) that progressed slowly to carcinoma, the combination of KRASG12D and SMAD4 deficiency resulted in the rapid development of tumors resembling intraductal papillary mucinous neoplasia (IPMN), a precursor to PDAC in humans. SMAD4 deficiency also accelerated PDAC development of KRASG12D INK4A/ARF heterozygous mice and altered the tumor phenotype; while tumors with intact SMAD4 frequently exhibited epithelial-to-mesenchymal transition (EMT), PDAC null for SMAD4 retained a differentiated histopathology with increased expression of epithelial markers. SMAD4 status in PDAC cell lines was associated with differential responses to transforming growth factor-β (TGF-β) in vitro with a subset of SMAD4 wild-type lines showing prominent TGF-β-induced proliferation and migration. These results provide genetic confirmation that SMAD4 is a PDAC tumor suppressor, functioning to block the progression of KRASG12D-initiated neoplasms, whereas in a subset of advanced tumors, intact SMAD4 facilitates EMT and TGF-β-dependent growth. PMID:17114584

Juvenile Papillomatosis (Swiss-Cheese Disease) of Breast in an Adult Male With Sequential Diagnoses of Ipsilateral Intraductal, Invasive, and Widely Metastatic Carcinoma: A Case Report and Review of the Disease in Males.

PubMed

Viswanathan, Kartik; McMillen, Brian; Cheng, Esther; D'Alfonso, Timothy; Patel, Ami; Hoda, Syed A

2017-09-01

Juvenile papillomatosis of the breast (JPB, also known as Swiss cheese disease) is a rare ailment that typically afflicts young females, and presents as a mass-forming lesion. The lesional mass usually comprises multiple cysts and duct stasis, amid a variety of proliferative and nonproliferative epithelial changes. The proliferative changes include papillary hyperplasia, florid hyperplasia, and papillary apocrine hyperplasia. Concurrent carcinoma (either in situ or invasive) is present in approximately 10% of cases at presentation, and subsequent carcinoma (either in situ or invasive) is diagnosed in about 10% of patients. About 20% of patients have a strong family history of breast carcinoma. A total of 10 cases of JPB have been previously reported in males, both children and adults, only one of which, in a 33-year-old, was associated with invasive carcinoma. Here, another case of JPB in a 45-year-old male-one with subsequent sequential diagnoses of ipsilateral intraductal carcinoma, invasive carcinoma, and widely metastatic carcinoma over the course of 15 years-is reported.

Biliary intraductal papillary neoplasm with metachronous multiple tumors - true multicentric tumors or intrabiliary dissemination: A case report and review of the literature.

PubMed

Yokode, Masataka; Yamashita, Yukimasa; Zen, Yoh

2017-03-01

Intraductal papillary neoplasms of the bile duct (IPNBs) are recognized as a distinct type of biliary tumor. We herein discuss the possible mechanisms underlying the development of multiple tumors in patients with IPNBs through a case presentation and literature review. A 64-year-old woman initially underwent extended right hepatectomy for IPNB in the right hepatic duct. Although the surgical margin of the common bile duct was tumor-free, recurrence was detected in the intrapancreatic bile duct 26 months later. Both tumors had similar histopathological characteristics (intestinal-type IPNB with high-grade dysplasia, but no invasive cancer). A literature review identified 9 additional cases of multiple IPNBs. Unlike conventional IPNBs, which typically affect the intrahepatic or hilar bile duct, 80% of recurrent multiple tumors developed in the extrahepatic bile duct. Although multicentric tumors have been suggested in such cases, the intrabiliary dissemination of tumor cells appears to be more likely, as the majority of recurrent tumors develop in more distal parts of the bile duct compared with the primary tumor.

Current recommendations for surveillance and surgery of intraductal papillary mucinous neoplasms may overlook some patients with cancer.

PubMed

Nguyen, Andrew H; Toste, Paul A; Farrell, James J; Clerkin, Barbara M; Williams, Jennifer; Muthusamy, V Raman; Watson, Rabindra R; Tomlinson, James S; Hines, O Joe; Reber, Howard A; Donahue, Timothy R

2015-02-01

The 2012 Sendai Criteria recommend that patients with 3 cm or larger branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any additional "worrisome features" or "high-risk stigmata" may undergo close observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD-IPMN <2 cm. These changes have generated concern among physicians treating patients with pancreatic diseases. The purposes of this study were to (i) apply the new Sendai guidelines to our institution's surgically resected BD-IPMN and (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring high-grade dysplasia or invasive cancer. We retrospectively reviewed 150 patients at a university medical center with preoperatively diagnosed and pathologically confirmed IPMNs. Sixty-six patients had BD-IPMN. Pathologic grade was dichotomized into low-grade (low or intermediate grade dysplasia) or high-grade/invasive (high-grade dysplasia or invasive cancers). Fisher's exact test, chi-square test, student's t test, linear regression, and receiver operating characteristic (ROC) analyses were performed. The median BD-IPMN size on imaging was 2.4 cm (interquartile range 1.5-3.0). Fifty-one (77 %) low-grade and 15 (23 %) high-grade/invasive BD-IPMN were identified. ROC analysis demonstrated that cyst size on preoperative imaging is a reasonable predictor of grade with an area under the curve of 0.691. Two-thirds of high-grade/invasive BD-IPMN were <3 cm (n = 10). Compared to a cutoff of 3, 2 cm was associated with higher sensitivity (73.3 vs. 33.3 %) and negative predictive value (83.3 vs. 80 %, NPV) for high-grade/invasive BD-IPMN. Mural nodules on endoscopic ultrasound (EUS) or atypical cells on endoscopic ultrasound-fine needle aspiration (EUS-FNA) were identified in all cysts <2 and only 50 % of those <3 cm. Forty percent of cysts >3 cm were removed based on size alone. Our results suggest that "larger" size on noninvasive imaging can indicate high-grade/invasive cysts, and EUS-FNA may help identify "smaller" cysts with high-grade/invasive pathology.

Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma.

PubMed

Graham, Rondell P; Barr Fritcher, Emily G; Pestova, Ekaterina; Schulz, John; Sitailo, Leonid A; Vasmatzis, George; Murphy, Stephen J; McWilliams, Robert R; Hart, Steven N; Halling, Kevin C; Roberts, Lewis R; Gores, Gregory J; Couch, Fergus J; Zhang, Lizhi; Borad, Mitesh J; Kipp, Benjamin R

2014-08-01

Patients with cholangiocarcinoma often present with locally advanced or metastatic disease. There is a need for effective therapeutic strategies for advanced stage cholangiocarcinoma. Recently, FGFR2 translocations have been identified as a potential target for tyrosine kinase inhibitor therapies. This study evaluated 152 cholangiocarcinomas and 4 intraductal papillary biliary neoplasms of the bile duct for presence of FGFR2 translocations by fluorescence in situ hybridization and characterized the clinicopathologic features of cases with FGFR2 translocations. Thirteen (10 women, 3 men; 8%) of 156 biliary tumors harbored FGFR2 translocations, including 12 intrahepatic cholangiocarcinomas (12/96; 13%) and 1 intraductal papillary neoplasm of the bile duct. Histologically, cholangiocarcinomas with FGFR2 translocations displayed prominent intraductal growth (62%) or anastomosing tubular glands with desmoplasia (38%). Immunohistochemically, the tumors with FGFR2 translocations frequently showed weak and patchy expression of CK19 (77%). Markers of the stem cell phenotype in cholangiocarcinoma, HepPar1 and CK20, were negative in all cases. The median cancer-specific survival for patients whose tumors harbored FGFR2 translocations was 123 months compared to 37 months for cases without FGFR2 translocations (P = .039). This study also assessed 100 cholangiocarcinomas for ERBB2 amplification and ROS1 translocations. Of the cases tested, 3% and 1% were positive for ERBB2 amplification and ROS1 translocation, respectively. These results confirm that FGFR2, ERRB2, and ROS1 alterations are potential therapeutic targets for intrahepatic cholangiocarcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

PubMed

Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

2013-07-01

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

PubMed

Murata, Yasuhiro; Mizuno, Shugo; Kato, Hiroyuki; Kishiwada, Masashi; Ohsawa, Ichiro; Hamada, Takashi; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Nishimura, Keisuke; Fukutome, Kazuo; Isaji, Shuji

2011-08-01

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

Minimally invasive central pancreatectomy and pancreatogastrostomy: current surgical technique and outcomes.

PubMed

Ronnekleiv-Kelly, Sean M; Javed, Ammar A; Weiss, Matthew J

2016-01-01

Recent improvements in imaging techniques and more frequent use of cross-sectional imaging have led to an increase in the identification of benign and low-grade lesions of the pancreas. Patients with resectable cancers are commonly treated by either a Whipple procedure or distal pancreatectomy (DP) based on the location of the tumor. Central pancreatectomy (CP) is a less commonly performed operation that has recently been utilized for resection of these now more frequently diagnosed low-grade and benign lesions located in the mid pancreas. Lesions that may have a relatively more indolent nature include branch-type intraductal papillary mucinous neoplasm (IPMNs), mucinous cystic neoplasms, neuroendocrine tumors, and solid pseudopapillary tumors. The goal of a CP is complete extirpation of the lesion, while preserving pancreatic parenchyma to reduce the risks of developing diabetes and exocrine insufficiency (EI). Although open CP has been shown to be safe and efficacious, the outcomes of a minimally invasive approach are still relatively underreported and therefore unknown. In this paper, we describe our surgical approach to performing a CP with an accompanying video demonstration of the key portions of the operation.

Specific Radiological Imaging Findings in Patients With Hereditary Pancreatitis During a Long Follow-up of Disease.

PubMed

van Esch, Aura A J; Drenth, Joost P H; Hermans, John J

2017-03-01

Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP. We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging). We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency. In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.

Feasibility of Newly Developed Endoscopic Ultrasound with Zone Sonography Technology for Diagnosis of Pancreatic Diseases

PubMed Central

Itoh, Akihiro; Kawashima, Hiroki; Ohno, Eizaburo; Itoh, Yuya; Nakamura, Yosuke; Hiramatsu, Takeshi; Sugimoto, Hiroyuki; Sumi, Hajime; Hayashi, Daijiro; Ohmiya, Naoki; Miyahara, Ryoji; Nakamura, Masanao; Funasaka, Kohei; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi

2013-01-01

Background/Aims To confirm the feasibility of using newly developed endoscopic ultrasound (EUS) with Zone sonography™ technology (ZST; Fujifilm Corp.). Methods Seventy-five patients with pancreatic disorders were enrolled: 45 with intraductal papillary mucinous neoplasm; 15 with ductal carcinoma; five with neuroendocrine tumors; three with serous cystic neoplasms; and seven with simple cysts. The endoscopes used were EG-530UR2 and EG-530UT2 (Fujifilm Corp.). Two items were evaluated: visualization depth among four frequencies and image quality after automatic adjustment of sound speed (AASS), assessed using a 5-scale Likert scale by two endosonographers blinded to disease status. Because sound speed could be manually controlled, besides AASS, image quality at sound speeds of 1,440 and 1,600 m/sec were also assessed. Results In all cases, sufficient images were obtained in the range of 3 cm from the EUS probe. Judgments of image quality before AASS were 3.49±0.50, 3.65±0.48, respectively. After AASS, A and B scored 4.36±0.48 and 4.40±0.49 (p<0.0001). There were significant differences in the data before and after AASS and plus 60 m/sec, but no significant difference between the datasets were seen after AASS and at sound speeds manually set for minus 100 m/sec. Conclusions EUS with ZST was shown to be feasible in this preliminary experiment. Further evaluation of this novel technology is necessary and awaited. PMID:23898392

Feasibility of newly developed endoscopic ultrasound with zone sonography technology for diagnosis of pancreatic diseases.

PubMed

Hirooka, Yoshiki; Itoh, Akihiro; Kawashima, Hiroki; Ohno, Eizaburo; Itoh, Yuya; Nakamura, Yosuke; Hiramatsu, Takeshi; Sugimoto, Hiroyuki; Sumi, Hajime; Hayashi, Daijiro; Ohmiya, Naoki; Miyahara, Ryoji; Nakamura, Masanao; Funasaka, Kohei; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi

2013-07-01

To confirm the feasibility of using newly developed endoscopic ultrasound (EUS) with Zone sonography™ technology (ZST; Fujifilm Corp.). Seventy-five patients with pancreatic disorders were enrolled: 45 with intraductal papillary mucinous neoplasm; 15 with ductal carcinoma; five with neuroendocrine tumors; three with serous cystic neoplasms; and seven with simple cysts. The endoscopes used were EG-530UR2 and EG-530UT2 (Fujifilm Corp.). Two items were evaluated: visualization depth among four frequencies and image quality after automatic adjustment of sound speed (AASS), assessed using a 5-scale Likert scale by two endosonographers blinded to disease status. Because sound speed could be manually controlled, besides AASS, image quality at sound speeds of 1,440 and 1,600 m/sec were also assessed. In all cases, sufficient images were obtained in the range of 3 cm from the EUS probe. Judgments of image quality before AASS were 3.49±0.50, 3.65±0.48, respectively. After AASS, A and B scored 4.36±0.48 and 4.40±0.49 (p<0.0001). There were significant differences in the data before and after AASS and plus 60 m/sec, but no significant difference between the datasets were seen after AASS and at sound speeds manually set for minus 100 m/sec. EUS with ZST was shown to be feasible in this preliminary experiment. Further evaluation of this novel technology is necessary and awaited.

Higher Growth Rate of Branch Duct Intraductal Papillary Mucinous Neoplasms Associates With Worrisome Features.

PubMed

Kolb, Jennifer M; Argiriadi, Pamela; Lee, Karen; Liu, Xiaoyu; Bagiella, Emilia; Lucas, Aimee L; Kim, Michelle Kang; Kumta, Nikhil A; Nagula, Satish; Sarpel, Umut; DiMaio, Christopher J

2018-03-11

For patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs, cysts), it is a challenge to identify those at high risk for malignant lesions. We sought to identify factors associated with development of pancreatic cancer, focusing on neoplasm growth rate. We performed a retrospective study of 189 patients with BD-IPMNs who underwent at least 2 contrast-enhanced cross-sectional imaging studies, 1 year or more apart, at a tertiary referral center from January 2003 through 2013. Patients with cysts that had Fukuoka worrisome or high-risk features were excluded. Two radiologists reviewed all images. Cyst size was recorded at the initial and final imaging studies and growth rate was calculated. We collected patient demographic data, cyst characteristics, and clinical outcomes; univariate logistic regression models were used to determine the odds of developing worrisome features. The primary outcomes were to determine growth rate of low-risk BD-IPMNs and to assess whether cyst growth rate correlates high-risk features of IPMNs. Based on image analyses, cysts were initially a median 11 mm (range, 3-31 mm) and their final size was 12.5 mm (range, 3-42 mm). After a median follow-up time of 56 months (range, 12-163 months), the median cyst growth rate was 0.29 mm/year. Twelve patients developed worrisome features, no patients developed high-risk features, 4 patients had surgical resection, and no cancers developed. The rate of BD-IPMN growth was greater in patients who developed worrisome features than those who did not (2.84 mm/year vs 0.23 mm/year; P < .001). The odds of developing worrisome features increased for each unit (mm) increase in cyst size (odds ratio, 1.149; 95% CI, 1.035-1.276, P = .009). In a retrospective analysis of images from patients with BD-IPMN, we found low-risk BD-IPMNs to grow at an extremely low rate (less than 0.3 mm/year). BD-IPMNs in only about 6% of patients developed worrisome features, and none developed high-risk features or invasive cancers. BD-IPMNs that developed worrisome features were associated with a significantly higher rate of growth than lesions with low-risk features. Low risk BD-IPMNs that grow more than 2.5 mm/year might require surveillance. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature.

PubMed

Nilsson, Linda N; Keane, Margaret G; Shamali, Awad; Millastre Bocos, Judith; Marijinissen van Zanten, Monica; Antila, Anne; Verdejo Gil, Cristina; Del Chiaro, Marco; Laukkarinen, Johanna

The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management. A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015. MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%. Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Outcomes after resection of occupational cholangiocarcinoma.

PubMed

Kubo, Shoji; Takemura, Shigekazu; Tanaka, Shogo; Shinkawa, Hiroji; Kinoshita, Masahiko; Hamano, Genya; Ito, Tokuji; Koda, Masaki; Aota, Takanori; Yamamoto, Takatsugu; Terajima, Hiroaki; Tachiyama, Gorou; Yamada, Terumasa; Nakamori, Shoji; Arimoto, Akira; Fujikawa, Masahiro; Tomimaru, Yoshito; Sugawara, Yasuhiko; Nakagawa, Kei; Unno, Michiaki; Mizuguchi, Toru; Takenaka, Kenji; Kimura, Koichi; Shirabe, Ken; Saiura, Akio; Uesaka, Katsuhiko; Taniguchi, Hiroki; Fukuda, Akira; Chong, Ja-Mun; Kuwae, Yuko; Ohsawa, Masahiko; Sato, Yasunori; Nakanuma, Yasuni

2016-09-01

Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Tulla, Kiara A; Maker, Ajay V

2018-03-01

Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

Neutrophil-to-lymphocyte ratio and mural nodule height as predictive factors for malignant intraductal papillary mucinous neoplasms.

PubMed

Watanabe, Yusuke; Niina, Yusuke; Nishihara, Kazuyoshi; Okayama, Takafumi; Tamiya, Sadafumi; Nakano, Toru

2018-01-15

Accurate preoperative prediction for malignant IPMN is still challenging. The aim of this study was to investigate the validity of neutrophil-to-lymphocyte ratio (NLR) and mural nodule height (MNH) for predicting malignant intraductal papillary mucinous neoplasm (IPMN). The medical records of 60 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. NLR tended to be higher in malignant IPMN (median: 2.23) than in benign IPMN (median: 2.04; p = .14). MNH was significantly greater in malignant IPMN (median: 16 mm) than in benign IPMN (median: 8 mm; p < .01). The optimal cutoff values for the NLR and MNH were 3.60 and 11 mm, respectively. The sensitivity and specificity of NLR ≥3.60 for predicting malignant IPMN were 40% and 93%, and those of MNH ≥11 mm were 73% and 77%, respectively. Univariate analysis revealed that NLR ≥3.60 (p < .01) and MNH ≥11 mm (p < .01) were significant predictive factors. On multivariate analysis, enhanced solid component was identified as an independent factor, but NLR ≥3.60 and MNH ≥11 mm were not. NLR and MNH are suboptimal tests in predicting malignant IPMN; however, they can be useful to assist in clinical decision-making.

Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics

PubMed Central

Yoneyama, Toshihiro; Ohtsuki, Sumio; Honda, Kazufumi; Kobayashi, Makoto; Iwasaki, Motoki; Uchida, Yasuo; Okusaka, Takuji; Nakamori, Shoji; Shimahara, Masashi; Ueno, Takaaki; Tsuchida, Akihiko; Sata, Naohiro; Ioka, Tatsuya; Yasunami, Yohichi; Kosuge, Tomoo; Kaneda, Takashi; Kato, Takao; Yagihara, Kazuhiro; Fujita, Shigeyuki; Huang, Wilber; Yamada, Tesshi; Tachikawa, Masanori; Terasaki, Tetsuya

2016-01-01

Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor-binding protein (IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19–9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of IDACP patients. PMID:27579675

Validation of the 2012 Fukuoka Consensus Guideline for Intraductal Papillary Mucinous Neoplasm of the Pancreas From a Single Institution Experience.

PubMed

Yu, Songfeng; Takasu, Naoki; Watanabe, Toshihiro; Fukumoto, Tsuyoshi; Okazaki, Shinji; Tezuka, Koji; Sugawara, Shuichiro; Hirai, Ichiro; Kimura, Wataru

2017-08-01

The 2012 Fukuoka consensus guideline has stratified the risks of malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas into "high-risk stigmata" (HRS) and "worrisome feature" (WF). This study aimed to evaluate its clinical validity based on a single institution experience. Eighty-nine patients who underwent surgical resection with pathological diagnosis of IPMN were retrospectively studied. High-risk stigmata was significantly correlated with the prevalence of malignant IPMN as compared with WF. The positive predictive values of HRS and WF were 66.7% and 35.7% for branch duct IPMN and 80% and 38.1% for main duct IPMN, respectively. Univariate analysis indicated that all the factors in HRS and WF had statistical significance. Whereas multivariate analysis revealed only enhanced solid component (odds ratio [OR], 50.01; P = 0.008), presence of mural nodule (OR, 73.83; P < 0.001) and lymphadenopathy (OR, 20.85; P = 0.03) were independent predictors. Scoring HRS and WF by different numbers of positive factors resulted in improved predictive value. The area under the curve of HRS score was significantly lower than that of WF or HRS + WF score (0.680 vs 0.900 or 0.902, respectively; P < 0.001). As supplementary to the 2012 Fukuoka guideline, we suggest that calculating scores of WF and HRS may have superior diagnostic accuracy in predicting malignant IPMN.

Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas.

PubMed

Kuboki, Yuko; Shimizu, Kyoko; Hatori, Takashi; Yamamoto, Masakazu; Shibata, Noriyuki; Shiratori, Keiko; Furukawa, Toru

2015-03-01

We aimed to identify molecular biomarkers for assessing the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN). We retrospectively investigated molecular aberrations and their associations with clinicopathological features in 172 IPMNs. GNAS and KRAS mutations were detected in 48% and 56% of IPMNs, respectively. No mutations of EGFR, PIK3CA GNAO1, GNAQ, or GNAI2 were observed. Significant associations were observed between IPMN morphological types and GNAS mutations, KRAS mutations, the expression of phosphorylated MAPK (pMAPK), AKT, and phosphorylated AKT (pAKT), nuclear accumulation of β-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear β-catenin, and SMAD4 loss; and prognosis and SMAD4 loss and TP53 overexpression. Multivariate analysis to compare prognostic impacts of multiple molecular features revealed that TP53 overexpression was an independent prognostic factor (P = 0.030; hazard ratio, 5.533). These results indicate that mutations in GNAS and KRAS, the expression of EGFR and pMAPK, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression may be relevant for assessing the clinical course of IPMN, including its progression into different morphological types, invasion, and prognosis.

Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT

PubMed Central

Dong, Aisheng; Wang, Yang; Lu, Jianping; Zuo, Changjing

2016-01-01

Abstract Interpretation of 18F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. PMID:26975010

Pathological aspects of so called "hilar cholangiocarcinoma"

PubMed Central

Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

2013-01-01

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, “hilar and perihilar CC” are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed. PMID:23919110

Pathological aspects of so called "hilar cholangiocarcinoma".

PubMed

Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

2013-07-15

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, "hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

PubMed Central

Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

2015-01-01

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

PubMed Central

Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E.; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L.; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E.; Krenn, Veit; Mayerle, Julia; Lerch, Markus M.; Schett, Georg; Wirtz, Stefan; Neurath, Markus F.; Herrmann, Martin; Becker, Christoph

2016-01-01

Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts. PMID:26964500

Comparison of clinicopathological characteristics between patients with occupational and non-occupational intrahepatic cholangiocarcinoma.

PubMed

Hamano, Genya; Kubo, Shoji; Takemura, Shigekazu; Tanaka, Shogo; Shinkawa, Hiroji; Kinoshita, Masahiko; Ito, Tokuji; Yamamoto, Takatsugu; Wakasa, Kenichi; Shibata, Toshihiko

2016-07-01

An outbreak of cholangiocarcinoma has been reported among workers of an offset color proof-printing department at a printing company in Japan. In this study, we compared the clinicopathological findings of this type of intrahepatic cholangiocarcinoma (occupational ICC) and non-occupational ICC. The clinical records of 51 patients with perihilar-type ICC who underwent liver resection, including five patients with occupational ICC were retrospectively reviewed. The clinicopathological features were compared. In the occupational group, the patients were significantly younger (P < 0.01), while serum γ-glutamyl transpeptidase activity and the proportions of patients with regional dilatation of the bile ducts without tumor-induced obstruction were significantly higher (P = 0.041 and P < 0.01, respectively); the indocyanine green retention rate at 15 min was significantly lower (P = 0.020). On pathological examinations, precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct, were observed at various sites of the bile ducts in all occupational ICC patients; such lesions were observed in only six patients in the control group (P < 0.01). The clinicopathological findings including age, liver function test results, diagnostic imaging findings, and pathological findings differed between the occupational and control groups. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Direct peroral cholangioscopy using an ultraslim upper endoscope for biliary lesions.

PubMed

Omuta, Shigefumi; Maetani, Iruru; Ukita, Takeo; Nambu, Tomoko; Gon, Katsushige; Shigoka, Hiroaki; Saigusa, Yoshinori; Saito, Michihiro

2014-02-01

The development of direct peroral cholangioscopy (DPOC) using an ultraslim endoscope simplifies biliary cannulation. The conventional techniques are cumbersome to perform and require advanced skills. The recent introduction of the guidewires and balloons has improved the therapeutic outcomes. Here we describe an effective and easier method for performing DPOC using an ultraslim upper endoscope. Indications for DPOC were the presence of stones on follow-up of patients who had previously undergone complete sphincteroplasty, including endoscopic sphincterotomy or endoscopic papillary large balloon dilatation. Fifteen patients underwent DPOC. An ultraslim endoscope was inserted perorally and was advanced into the major papilla. The ampulla of Vater was visualized by retroflexing the endoscope in the distal second portion of the duodenum, and then DPOC was performed using a wire-guided cannulation technique with an anchored intraductal balloon catheter. One patient failed in the treatment due to looping of the endoscope in the fornix of the stomach. Fourteen (93.3%) were successfully treated with our modified DPOC technique. Only one patient (6.7%) experienced an adverse event (pancreatitis) who responded well to conservative management. Residual stones of the common bile duct were completely removed in 3 patients. The modified method of DPOC is simple, safe and easy to access the bile duct.

Inverted ductal papilloma of the oral cavity secondary to lower lip trauma. A case report and literature review

PubMed Central

Sala-Pérez, Sergi; España-Tost, Antoni; Vidal-Bel, August

2013-01-01

Inverted ductal papilloma of the oral cavity is an infrequent benign neoplasm of papillary appearance that originates in the secretory duct of a salivary gland. The etiology is unknown, though some authors have related it to human papillomavirus (HPV) infection. We present the case of a 40-year-old woman with a tumor of the lower lip mucosa. Histopathological study of the lesion diagnosed inverted ductal papilloma of the oral cavity. Human papillomavirus DNA detection and typing based on tumor lesion DNA amplification and posterior hybridization, revealed no presence of viral DNA. The antecedents of trauma reported by the patient could have played an important role in the development of this tumor. Key words:Inverted ductal papilloma, intraductal papilloma, oral papilloma, papillary epidermoid adenoma. PMID:24455058

Mucinous Cystic Neoplasm of the Liver or Intraductal Papillary Mucinous Neoplasm of the Bile Duct? A Case Report and a Review of Literature.

PubMed

Kunovsky, Lumir; Kala, Zdenek; Svaton, Roman; Moravcik, Petr; Mazanec, Jan; Husty, Jakub; Prochazka, Vladimir

2018-01-01

Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.

Systematic review of the clinical utility and validity of the Sendai and Fukuoka Consensus Guidelines for the management of intraductal papillary mucinous neoplasms of the Pancreas.

PubMed

Srinivasan, Nandhini; Teo, Jin-Yao; Chin, Yung-Ka; Hennedige, Tiffany; Tan, Damien M; Low, Albert S; Thng, Choon Hua; Goh, Brian K P

2018-02-24

This systematic review was performed to assess the clinical utility of the Sendai Consensus Guidelines (SCG) and Fukuoka Consensus Guidelines (FCG) for intraductal papillary mucinous neoplasm (IPMN). A computerized search of PubMed was performed to identify all the studies which evaluated the SCG and FCG in surgically resected, histologically confirmed IPMNs. Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign. The FCG had a higher PPV compared to the SCG. However, the NPV of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines. Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm.

PubMed

Shimura, Tatsuo; Kofunato, Yasuhide; Okada, Ryo; Yashima, Rei; Okada, Koji; Araki, Kenichiro; Hosouchi, Yasuo; Kuwano, Hiroyuki; Takenoshita, Seiichi

2016-08-01

Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non-invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB-1 labeling index as an indicator of invasive IPMN. The MIB-1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non-invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut-off level for the MIB-1 labeling index should be set to 15.5% to distinguish invasive from non-invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB-1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171-83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039-36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB-1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.

Imaging Follow-up of Low-Risk Incidental Pancreas and Kidney Findings: Effects of Patient Age and Comorbidity on Projected Life Expectancy.

PubMed

Raphel, Tiana J; Weaver, Davis T; Berland, Lincoln L; Herts, Brian R; Megibow, Alec J; Knudsen, Amy B; Pandharipande, Pari V

2018-05-01

Purpose To determine the effects of patient age and comorbidity level on life expectancy (LE) benefits associated with imaging follow-up of Bosniak IIF renal cysts and pancreatic side-branch (SB) intraductal papillary mucinous neoplasms (IPMNs). Materials and Methods A decision-analytic Markov model to evaluate LE benefits was developed. Hypothetical cohorts with varied age (60-80 years) and comorbidities (none, mild, moderate, or severe) were evaluated. For each finding, LE projections from two strategies were compared: imaging follow-up and no imaging follow-up. Under follow-up, it was assumed that cancers associated with the incidental finding were successfully treated before they spread. For patients without follow-up, mortality risks from Bosniak IIF cysts (renal cell carcinoma) and SBIPMNs (pancreatic ductal adenocarcinoma) were incorporated. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. Results In the youngest, healthiest cohorts (age, 60 years; no comorbidities), projected LE benefits from follow-up were as follows: Bosniak IIF cyst, 6.5 months (women) and 5.8 months (men); SBIPMN, 6.4 months (women) and 5.3 months (men). Follow-up of Bosniak IIF cysts in 60-year-old women with severe comorbidities yielded a LE benefit of 3.9 months; in 80-year-old women with no comorbidities, the benefit was 2.8 months, and with severe comorbidities the benefit was 1.5 months. Similar trends were observed in men and for SBIPMN. Results were sensitive to the performance of follow-up for cancer detection; malignancy risks; and stage at presentation of malignant, unfollowed Bosniak IIF cysts. Conclusion With progression of age and comorbidity level, follow-up of low-risk incidental findings yields increasingly limited benefits for patients. © RSNA, 2018 Online supplemental material is available for this article.

Biliary and pancreatic duct pressures measured by ERCP manometry in patients with suspected papillary stenosis.

PubMed

Bar-Meir, S; Geenen, J E; Hogan, W J; Dodds, W J; Stewart, E T; Arndorfer, R C

1979-03-01

Papillary stenosis is an imprecisely defined clinical syndrome which eludes definitive diagnosis. In this study we evaluated 26 patients with suspected papillary stenosis by manometric examination of the sphincter of Oddi done during ERCP examination. Basal pressure in the sphincter of Oddi was elevated in 14 of the patients. Of these 14 patients, 10 underwent sphincterotomy and all experienced improvement in clinical symptoms after their surgery. We suggest that ERCP manometry is a useful procedure for identifying patients with papillary stenosis who may benefit from sphincterotomy.

Latest advances in chronic pancreatitis.

PubMed

Enrique Domínguez-Muñoz, J

2016-09-01

This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the definition of the disease, the etiological diagnosis of idiopathic disease, the correlation between fibrosis degree and pancreatic secretion in the early stages of chronic pancreatitis, the treatment of the disease and of pain, the clinical relevance of pancreatic exocrine insufficiency, and the diagnosis of autoimmune pancreatitis. A new mechanistic definition of chronic pancreatitis has been proposed. Genetic testing is mainly of help in patients with relapsing idiopathic pancreatitis. A significant correlation has been shown between the degree of pancreatic fibrosis as evaluated by elastography and pancreatic secretion of bicarbonate. New data supports the efficacy of antioxidants and simvastatin for the therapy of chronic pancreatitis. The pancreatoscopy-guided intraductal lithotripsy is an effective alternative to extracorporeal shock wave lithotripsy in patients with chronic calcifying pancreatitis. The presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significant risk of cardiovascular events. Fine needle biopsy and contrast enhanced harmonic endoscopic ultrasonography are of help for the diagnosis of autoimmune pancreatitis and its differential diagnosis with pancreatic cancer. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis.

PubMed

Zhu, Yaohui; Mehta, Kshama; Li, Cuiping; Xu, Guang-Yin; Liu, Liansheng; Colak, Tugba; Shenoy, Mohan; Pasricha, Pankaj Jay

2012-01-01

We have previously shown that pancreatic sensory neurons in rats with chronic pancreatitis (CP) display increased excitability associated with a decrease in transient inactivating potassium currents (I(A)), thus accounting in part for the hyperalgesia associated with this condition. Because of its well known role in somatic hyperalgesia, we hypothesized a role for the nerve growth factor (NGF) in driving these changes. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. After 3 wk, anti-NGF antibody or control serum was injected intra-peritoneally daily for 1 wk. This protocol was repeated in another set of experiments in control rats (receiving intraductal PBS instead of TNBS). Pancreatic nociceptors labeled with the dye Dil were identified, and patch-clamp recordings were made from acutely dissociated DRG neurons. Sensory neurons from anti-NGF-treated rats displayed a lower resting membrane potential, increased rheobase, decreased burst discharges in response to stimulatory current, and decreased input resistance compared with those treated with control serum. Under voltage-clamp condition, neuronal I(A) density was increased in anti-NGF-treated rats compared with rats treated with control serum. However, anti-NGF treatment had no effect on electrophysiological parameters in neurons from control rats. The expression of Kv-associated channel or ancillary genes Kv1.4, 4.1, 4.2, 4.3, and DPP6, DPP10, and KCHIPs 1-4 in pancreas-specific nociceptors was examined by laser-capture microdissection and real-time PCR quantification of mRNA levels. No significant differences were seen among those. These findings emphasize a key role for NGF in maintaining neuronal excitability in CP specifically via downregulation of I(A) by as yet unknown mechanisms.

Proposed Nomogram Predicting the Individual Risk of Malignancy in the Patients With Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas.

PubMed

Jang, Jin-Young; Park, Taesung; Lee, Selyeong; Kim, Yongkang; Lee, Seung Yeoun; Kim, Sun-Whe; Kim, Song-Cheol; Song, Ki-Byung; Yamamoto, Masakazu; Hatori, Takashi; Hirono, Seiko; Satoi, Sohei; Fujii, Tsutomu; Hirano, Satoshi; Hashimoto, Yasushi; Shimizu, Yashuhiro; Choi, Dong Wook; Choi, Seong Ho; Heo, Jin Seok; Motoi, Fuyuhiko; Matsumoto, Ippei; Lee, Woo Jung; Kang, Chang Moo; Han, Ho-Seong; Yoon, Yoo-Seok; Sho, Masayuki; Nagano, Hiroaki; Honda, Goro; Kim, Sang Geol; Yu, Hee Chul; Chung, Jun Chul; Nagakawa, Yuichi; Seo, Hyung Il; Yamaue, Hiroki

2017-12-01

This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Percutaneous intraductal radiofrequency ablation for treatment of biliary stent occlusion: A preliminary result.

PubMed

Xia, Ning; Gong, Ju; Lu, Jian; Chen, Zhi-Jin; Zhang, Li-Yun; Wang, Zhong-Min

2017-03-14

To assess the feasibility and effectiveness of a novel application of percutaneous intraductal radiofrequency (RF) for the treatment of biliary stent obstruction. We specifically report a retrospective study presenting the results of percutaneous intraductal RF in patients with biliary stent occlusion. A total of 43 cases involving biliary stent obstruction were treated by placing an EndoHPB catheter and percutaneous intraductal RF was performed to clean stents. The stent patency was evaluated by cholangiography and follow-up by contrast enhanced computed tomography or ultrasound after the removal of the drainage catheter. Following the procedures, of the 43 patients, 40 survived and 3 died with a median survival of 80.5 (range: 30-243) d. One patient was lost to follow-up. One patient had the stent patent at the time of last follow-up. Two patients with stent blockage at 35 d and 44 d after procedure underwent percutaneous transhepatic drain insertion only. The levels of bilirubin before and after the procedure were 128 ± 65 μmol/L and 63 ± 29 μmol/L, respectively. There were no related complications (haemorrhage, bile duct perforation, bile leak or pancreatitis) and all patients' stent patency was confirmed by cholangiography after the procedure, with a median patency time of 107 (range: 12-180) d. This preliminary clinical study demonstrated that percutaneous intraductal RF is safe and effective for the treatment of biliary stent obstruction, increasing the duration of stent patency, although randomized controlled trials are needed to confirm the effectiveness of this approach.

Percutaneous intraductal radiofrequency ablation for treatment of biliary stent occlusion: A preliminary result

PubMed Central

Xia, Ning; Gong, Ju; Lu, Jian; Chen, Zhi-Jin; Zhang, Li-Yun; Wang, Zhong-Min

2017-01-01

AIM To assess the feasibility and effectiveness of a novel application of percutaneous intraductal radiofrequency (RF) for the treatment of biliary stent obstruction. METHODS We specifically report a retrospective study presenting the results of percutaneous intraductal RF in patients with biliary stent occlusion. A total of 43 cases involving biliary stent obstruction were treated by placing an EndoHPB catheter and percutaneous intraductal RF was performed to clean stents. The stent patency was evaluated by cholangiography and follow-up by contrast enhanced computed tomography or ultrasound after the removal of the drainage catheter. RESULTS Following the procedures, of the 43 patients, 40 survived and 3 died with a median survival of 80.5 (range: 30-243) d. One patient was lost to follow-up. One patient had the stent patent at the time of last follow-up. Two patients with stent blockage at 35 d and 44 d after procedure underwent percutaneous transhepatic drain insertion only. The levels of bilirubin before and after the procedure were 128 ± 65 μmol/L and 63 ± 29 μmol/L, respectively. There were no related complications (haemorrhage, bile duct perforation, bile leak or pancreatitis) and all patients’ stent patency was confirmed by cholangiography after the procedure, with a median patency time of 107 (range: 12-180) d. CONCLUSION This preliminary clinical study demonstrated that percutaneous intraductal RF is safe and effective for the treatment of biliary stent obstruction, increasing the duration of stent patency, although randomized controlled trials are needed to confirm the effectiveness of this approach. PMID:28348491

Pancreatic cystic tumors.

PubMed

Salvia, R; Festa, L; Butturini, G; Tonsi, A; Sartori, N; Biasutti, C; Capelli, P; Pederzoli, P

2004-04-01

Cystic tumors of the pancreas are less frequent than other tumors in neoplastic pancreatic pathology, but in recent years the literature has reported an increasing number. After the first report by Becourt in 1830, cystic tumors were classified into 2 different types by Compagno and Oertel in 1978: benign tumors with glycogen-rich cells and mucinous cystic neoplasms with overt and latent malignancy. The WHO classification of exocrine tumors of the pancreas, published in 1996, is based on the histopathological features of the epithelial wall, which are the main factor in differential diagnosis with cystic lesions of the pancreas. Thanks to the knowledge acquired up to now, a surgical procedure is not always required because the therapeutic choice is conditioned by the correct classification of this heterogeneous group of tumors. Clinical signs are not really useful in the clinical work up, most patients have no symptoms and when clinical signs are present, they may help us to pinpoint the organ of origin but never to identify the type of pathology. In the last few years, the great improvement in imaging has enabled us not only to discriminate cystic from solid lesions, but also to identify the features of the lesions and label them preoperatively. More invasive diagnostic procedures such as fine needle aspiration and intracystic fluid tumor marker level are not really useful because they are not sensitive and the cystic wall can show different degrees of dysplasia and de-epithelialization. These are the reasons for sending the entire specimen to pathology. Good cooperation between surgeons, pathologists, radiologists and gastroenterologists is mandatory to increase the chances of making a proper diagnosis. Therefore, we must analyze all the information we have, such as age, sex, clinical history, location of the tumor and radiological features, in order to avoid the mistake of treating a cystic neoplasm as a benign lesion or as a pseudocyst, as described in the literature. Except for inoperable cases due to the critical condition of the patient or non-resectable lesions, surgical treatment differs with the diagnosis. Cystic tumors of the pancreas, therefore, are a heterogeneous group of tumors, with a real problem regarding differential diagnosis between neoplastic and inflammatory lesions. Even with a proper work up, some perplexity may remain about the nature of the lesion and in these cases the surgical procedure has a therapeutic value as well as playing a diagnostic role. The role of surgery is central in the treatment of these tumors because it could be curative when complete resection is possible. In this way, the lack of good therapeutic results with chemotherapy and radiotherapy force the surgeon to go ahead with the procedure. Intraductal papillary mucinous neoplasms represent a new and, from the epidemiological point of view, important chapter in the world of cystic tumors. The margin of resection is important and the surgeon has to be aware that in order to have a curative resection, total pancreatectomy is sometimes required. In the last few years the therapeutic approach has changed thanks to new knowledge of the biological behavior of these tumors. In fact, from a surgical approach in all cases, we are now discussing the possibility of a follow-up not only for asymptomatic serous cystadenomas but also for the little branch side intraductal papillary mucinous neoplasms (IPMNs) in critical patients. A follow-up could be planned even for solid pseudopapillary tumors but it seems risky to leave untreated big tumors in young patients without a certain diagnosis and with so few studies reported in the literature.

High-grade dysplasia and adenocarcinoma are frequent in side-branch intraductal papillary mucinous neoplasm measuring less than 3 cm on endoscopic ultrasound.

PubMed

Wong, Joyce; Weber, Jill; Centeno, Barbara A; Vignesh, Shivakumar; Harris, Cynthia L; Klapman, Jason B; Hodul, Pamela

2013-01-01

Surgical resection for intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the last decade. While IPMN with main duct communication are generally recommended for resection, indications for resection of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single institutional experience with SDIPMN and indications for resection. Patients who underwent resection for IPMN were identified from a prospectively maintained IRB-approved database. Patients with main pancreatic duct communication were excluded. Outcome, clinical and pathologic characteristics were correlated with endoscopic ultrasound (EUS) findings. From 2000 to 2010, 105 patients who underwent preoperative EUS evaluation and resection for SDIPMN were identified. The mean age was within the sixth decade of life, and there was a slight female predominance (55 vs. 45 %). The most common presenting symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %) and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at presentation; seven (70 %) had suspicious features on EUS. Of the total cohort, few patients had intracystic septations (N = 27, 26 %) or presence of mural nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA) demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12 (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed 24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11 %) with cyst size 1-2 cm, and 21of 44 (48 %) with cyst size 2-3 cm. Fifteen of 35 (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients with cyst size <3 cm, 16 (23 %) had high-grade dysplasia on final pathology: 3 of 7 (43 %) with cyst size <1 cm, 3 of 19 (16 %) with cyst size 1-2 cm, and 10 of 44 (23 %) with cyst size 2-3 cm. Seven of 35 (20 %) patients with cyst size >3 cm had high-grade dysplasia on final pathology. Although overall survival (OS) at 48 months stratified by EUS cyst size did not significantly differ between groups, patients with PDAC on final pathology had significantly worse OS compared to noninvasive pathology. A total of eight patients (8 %) developed recurrent disease, all of whom had PDAC on final pathology. EUS is a helpful modality for the diagnostic evaluation of SDIPMN. Considering the high incidence of malignancy as well as high-grade dysplasia in SDIPMN greater than 2 cm, EUS features should be used in conjunction with other clinical criteria to guide management decisions. Patients with SDIPMN greater than 2 cm that do not undergo surgical resection may benefit from more intensive surveillance.

New developments in diagnosis and non-surgical treatment of chronic pancreatitis.

PubMed

Inui, Kazuo; Yoshino, Junji; Miyoshi, Hironao; Yamamoto, Satoshi; Kobayashi, Takashi

2013-12-01

Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Performance of a fully disposable, digital, single-operator cholangiopancreatoscope.

PubMed

Shah, Raj J; Raijman, Isaac; Brauer, Brian; Gumustop, Bora; Pleskow, Douglas K

2017-07-01

Background and study aim  Our aim was to evaluate the first use in humans of a new, single-use, digital, single-operator intraductal cholangiopancreatoscopy system (IDCP). Patients and methods  Data were collected retrospectively from four US institutions between February 2015 and April 2015. The visual impression of neoplasia or benign findings with IDCP was determined by the performing endoscopist. High grade dysplasia, intraductal papillary mucinous neoplasm, neuroendocrine tumor, and malignancy were categorized as neoplasia. Benign disease was defined as the absence of neoplasia during ≥ 6 months of follow-up. Results  Patients (n = 108) with indeterminate strictures, dilatation, or difficult stones underwent IDCP. Of 74 patients with indeterminate stricture or dilatation, 29 (39 %) had neoplasia, of which 25 were confirmed by miniature biopsy forceps, 2 by surgical pathology, and 2 by the presence of metastatic disease on follow-up imaging. In patients with benign disease, 15 had concentric stenosis or normal/erythematous changes, 5 had low papillary mucosal projections, 6 had coarse granular mucosa, and 4 had nodular mucosa. Findings in patients with neoplastic disease included dilated, tortuous vessels ("tumor vessels"; n = 13), irregular margins with partial occlusion of the lumen (infiltrative stricture, n = 12), villous or nodular mass (n = 9), and finger-like villiform projections (n = 5). Operating characteristics for indeterminate stricture or dilatation were: 97 % sensitivity, 93 % specificity, 90 % positive predictive value, 98 % negative predictive value. Targeted biopsy yielded 86 % sensitivity and 100 % specificity. Stone clearance was noted in all cases. Adverse events occurred in 3 %. Conclusion  The new IDCP system provides enhanced image resolution, and may improve the ability to target difficult stones and diagnose indeterminate strictures. © Georg Thieme Verlag KG Stuttgart · New York.

The differences in imaging features of malignant and benign branch duct type of Intraductal Papillary Mucinous Tumor.

PubMed

Zhang, Hui-mao; Yao, Fang; Liu, Gui-feng; Wang, Xiao-bin; Xiu, Dian-hui; Gen, Iinuma

2011-12-01

To investigate the difference in the radiological features of malignant and benign branch duct type of IPMT (Intraductal Papillary Mucinous Tumor) of the pancreas. Thirty-six patients who were referred for operation with branch duct type of IPMT of the pancreas were included in this study. All cases underwent both CT and MRI with contrast enhancement. The size of the cystic lesions, the presence and size of mural nodules, and the amount of dilatation of the MPD were assessed by two independent radiologists, and the results were compared with pathological findings. Histological examination revealed adenoma in 8 cases, AH (atypical hyperplasia) in 8 cases, CIS (carcinoma in situ) in 8 cases and invasive carcinoma in 12 cases. Patients of the malignant group were older than those in the benign group (mean age: 67 yrs vs 60 yrs, respectively), but no statistically significant (p=0.05). Males (16/4 vs 10/6) more often complained weight loss and jaundice. The malignant tumor was more frequently located in the head-body and body. Compared with the benign group, the mean sizes of the cyst, mural nodules, MPD of the malignant group were 44 mm, 13 mm, 7.5 mm and benign group were 31 mm, 5 mm, 3.5 mm respectively. All these difference are statistically significant (p<0.05). In 4 cases of the 20 in the malignant group, soft tissue suggesting spread of disease into the adjacent viscera and peritoneum was detected. Cyst size over 30 mm and mural nodule over 8 mm, irregular thick septa, dilatation of the MPD, and accompany with soft tissue mass may be helpful factors in determining malignancy. Copyright © 2011. Published by Elsevier Ireland Ltd.

Utility of the sendai consensus guidelines for branch-duct intraductal papillary mucinous neoplasms: a systematic review.

PubMed

Goh, Brian K P; Tan, Damien M Y; Ho, Mac M F; Lim, Tony K H; Chung, Alexander Y F; Ooi, London L P J

2014-07-01

The Sendai Consensus Guidelines (SCG) was formulated in 2006 to guide the management of intraductal papillary mucinous neoplasms (IPMN). The main area of controversy is the criteria for selection of branch duct (BD)-IPMN for resection. Although these guidelines have gained widespread acceptance, there is limited data to date supporting its use. This systematic review is performed to evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN. Studies evaluating the clinical utility of the SCG in surgically resected neoplasms were identified. The SCG were retrospectively applied to all resected neoplasms in these studies. BD-IPMNs which met the criteria for resection were termed SCG+ve and those for surveillance were termed SCG-ve. Twelve studies were included, of which, 9 were suitable for pooled analysis. There were 690 surgically resected BD-IPMNs, of which, 24% were malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG-ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52% and the NPV of SCG-ve neoplasms ranged from 90 to 100%. Overall, there were 150/501 (29.9%) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90%) of benign BD-IPMNs in the SCG-ve group. Of the 18 reported malignant (11 invasive) BD-IPMNs in the SCG-ve group, 17 (including all 11 invasive) were from a single study. When the results from this single study were excluded, 170/171 (99%) of SCG-ve BD-IPMNs were benign. The results of this review confirm the limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant BD-IPMN was low and some malignant lesions may be missed based on these guidelines.

Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis.

PubMed

Xiong, Guang-Su; Wu, Shu-Ming; Wang, Zhen-Hua; Mo, Jian-Zhong; Xiao, Shu-Dong

2007-03-01

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of acute pancreatitis and related systemic complications. The authors hypothesized that it may also play an important role in the development of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of the study was to evaluate the effectiveness of thalidomide, an immunomodulator that exerts an inhibitory action on TNF-alpha by enhancing mRNA degradation, in reducing post-ERCP pancreatitis in a rat model. A total of 200 mg/kg thalidomide was given intragastric once a day (total 8 days) before the experimental models of post-ERCP pancreatitis were established. After 24 h, histology and edema of pancreas, serum amylase, and TNF-alpha mRNA in the pancreatic tissue were evaluated. Intraductal contrast infusion caused increases in serum amylase, edema, histological grade, and TNF-alpha mRNA of pancreas. The prophylactic use of thalidomide significantly reduced serum amylase, pancreatic edema and the histologic grade of pancreatitis accompanied by a decrease in mRNA expression of TNF-alpha in the pancreatic tissue. Prophylactic intragastric administration of thalidomide provides a protective effect in post-ERCP pancreatitis. The mechanism of the protective effects of thalidomide seems to be the reduction of expression of TNF-alpha mRNA in pancreatic tissue.

Percutaneous intraductal radiofrequency ablation in the management of unresectable Bismuth types III and IV hilar cholangiocarcinoma.

PubMed

Wang, Yu; Cui, Wei; Fan, Wenzhe; Zhang, Yingqiang; Yao, Wang; Huang, Kunbo; Li, Jiaping

2016-08-16

To assess the feasibility and safety of percutaneous intraductal radiofrequency ablation (RFA) for unresectable Bismuth types III and IV hilar cholangiocarcinoma. Percutaneous intraductal RFA combined with metal stent placement was successful in all patients without any technical problems; the technical success rate was 100%. Chemotherapy was administered to two patients. After treatment, serum direct bilirubin levels were notably decreased. Six patients died during the follow-up period. Median stent patency from the time of the first RFA and survival from the time of diagnosis were 100 days (95% confidence interval (CI), 85-115 days) and 5.3 months (95% CI, 2.5-8.1 months), respectively. No acute pancreatitis, bile duct bleeding and perforation, bile leakage, or other severe complications occurred. Four cases of procedure-related cholangitis, three cases of postoperative abdominal pain, and five cases of asymptomatic transient increase in serum amylase were observed. One patient who presented with stent blockage 252 days' post-procedure underwent repeat ablation. Between September 2013 and May 2015, nine patients with unresectable Bismuth types III and IV hilar cholangiocarcinoma who were treated with percutaneous intraductal RFA combined with metal stent placement after the percutaneous transhepatic cholangial drainage were included in the retrospective analysis. Procedure-related complications, stent patency, and survival after treatment were investigated. Percutaneous intraductal RFA combined with metal stent placement is a technically safe and feasible therapeutic option for the palliative treatment of unresectable Bismuth types III and IV hilar cholangiocarcinoma. Its long-term efficacy and safety is promising, but needs further study via randomized and prospective trials that include a greater number of patients.

Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes.

PubMed

Liu, Bo-Nan; Zhang, Tai-Ping; Zhao, Yu-Pei; Liao, Quan; Dai, Meng-Hua; Zhan, Han-Xiang

2010-08-01

Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

Impact of total pancreatectomy: short- and long-term assessment.

PubMed

Barbier, Louise; Jamal, Wisam; Dokmak, Safi; Aussilhou, Béatrice; Corcos, Olivier; Ruszniewski, Philippe; Belghiti, Jacques; Sauvanet, Alain

2013-11-01

The aim was to assess the outcome of a total pancreatectomy (TP). From 1993 to 2010, 56 patients underwent an elective TP for intraductal papillary mucinous neoplasia (n = 42), endocrine tumours (n = 6), adenocarcinoma (n = 5), metastases (n = 2) and chronic pancreatitis (n = 1). Morbidity and survival were analysed. Long-term survivors were assessed prospectively using quality-of-life (QoL) questionnaires. Five patients developed gastric venous congestion intra-operatively. Post-operative morbidity and mortality rates were 45% and 3.6%, respectively. An anastomotic ulcer occurred in seven patients, but none after proton pump inhibitor therapy. There were five inappropriate TPs according to definitive pathological examination. Overall 3- and 5-year survival rates were 62% and 55% respectively; five deaths were related to TP (two postoperative deaths, one hypoglycaemia, one ketoacidosis and one anastomotic ulcer). Prospective evaluation of 25 patients found that 14 had been readmitted for diabetes and that all had hypoglycaemia within the past month. The glycated haemoglobin (HbA1c) was 7.8% (6.3-10.3). Fifteen patients experienced weight loss. The QLQ-C30 questionnaire showed a decrease in QoL predominantly because of fatigue and diarrhoea, and the QLQ-PAN26 showed an impact on bowel habit, flatulence and eating-related items. Morbidity and mortality rates of TP are acceptable, although diabetes- and TP-related mortality still occurs. Endocrine and exocrine insufficiency impacts on the long-term quality of life. © 2013 International Hepato-Pancreato-Biliary Association.

Clinicopathological features and prognosis of mucin-producing bile duct tumor and mucinous cystic tumor of the liver: a multi-institutional study by the Japan Biliary Association.

PubMed

Kubota, Keiichi; Nakanuma, Yasuni; Kondo, Fukuo; Hachiya, Hiroyuki; Miyazaki, Masaru; Nagino, Masato; Yamamoto, Masakazu; Isayama, Hiroyuki; Tabata, Masami; Kinoshita, Hisafumi; Kamisawa, Terumi; Inui, Kazuo

2014-03-01

The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB). We performed a multi-institutional, retrospective study of patients with MCN or M-IPNB pathologically defined by the presence or absence of an ovarian-like stroma. The M-IPNB and MCN were diagnosed in 119 and nine patients, respectively. MCN was observed in female patients, while M-IPNB produced symptoms of cholangitis. M-IPNBs were classed as low or intermediate grade in 53 cases, high grade in 23 and invasive carcinoma in 43. Fifty-one of the M-IPNBs were the pancreatobiliary type (PT), 33 were the intestinal type (IT), 23 were the oncocytic type (OT), and 12 were the gastric type (GT). The 1-, 5- and 10-year survival rates for the 105 patients with M-IPNB were 96%, 84% and 81%, respectively, while the 5-year survival rate for patients with MCN was 100%. OT and GT M-IPNB had better 10-year survival rates than PT and IT M-IPNB. Although MCN has different features from M-IPNB, both diseases have a good prognosis after resection. The cellular type of M-IPNB appears to predict outcome. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Unique presentation of giant metastatic microcystic serous adenocarcinoma of the pancreas.

PubMed

Philips, Cyriac Abby; Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, Kn Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures.

Unique Presentation of Giant Metastatic Microcystic Serous Adenocarcinoma of the Pancreas

PubMed Central

Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, KN Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures. PMID:24782930

PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer.

PubMed

Ghaneh, Paula; Hanson, Robert; Titman, Andrew; Lancaster, Gill; Plumpton, Catrin; Lloyd-Williams, Huw; Yeo, Seow Tien; Edwards, Rhiannon Tudor; Johnson, Colin; Abu Hilal, Mohammed; Higginson, Antony P; Armstrong, Tom; Smith, Andrew; Scarsbrook, Andrew; McKay, Colin; Carter, Ross; Sutcliffe, Robert P; Bramhall, Simon; Kocher, Hemant M; Cunningham, David; Pereira, Stephen P; Davidson, Brian; Chang, David; Khan, Saboor; Zealley, Ian; Sarker, Debashis; Al Sarireh, Bilal; Charnley, Richard; Lobo, Dileep; Nicolson, Marianne; Halloran, Christopher; Raraty, Michael; Sutton, Robert; Vinjamuri, Sobhan; Evans, Jonathan; Campbell, Fiona; Deeks, Jon; Sanghera, Bal; Wong, Wai-Lup; Neoptolemos, John P

2018-02-01

Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. Patients with suspected pancreatic malignancy. All patients to undergo PET/CT following standard diagnostic work-up. The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUV max. ) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity ( p  = 0.01) and specificity ( p  = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios ( p  < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients ( p  = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. Current Controlled Trials ISRCTN73852054 and UKCRN 8166. The National Institute for Health Research Health Technology Assessment programme.

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity

PubMed Central

Affirul, C.A.; Qisti, F.N.; Zamri, Z.; Azlanuddin, A.; Hairol, A.O.; Razman, J.

2014-01-01

INTRODUCTION Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. PRESENTATION OF CASE This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. DISCUSSION We discuss the presentations, diagnosis and pathology findings of this rare pathology. CONCLUSION The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. PMID:25462046

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity.

PubMed

Affirul, C A; Qisti, F N; Zamri, Z; Azlanuddin, A; Hairol, A O; Razman, J

2014-01-01

Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. We discuss the presentations, diagnosis and pathology findings of this rare pathology. The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Management of intraductal papilloma without atypia of the breast diagnosed on core biopsy: Size and sampling matter.

PubMed

Symbol, Brittany; Ricci, Andrew

2018-04-23

Due to the potential for atypia (atypical ductal or lobular hyperplasia) or carcinoma (in situ or invasive) on excision, aggressive reflex surgical excision protocols following core biopsy diagnosis of papillary lesions of the breast (ie, intraductal papilloma) are commonplace. Concepts in risk stratification, including radiologic-pathologic correlation, are emerging in an effort to curb unnecessary surgeries. To this end, we examined all excised intraductal papillomas diagnosed at our institution from 2010-2015 (N = 336) and found an overall atypia rate of 20%. To investigate further, we stratified all excised papillomas according to total lesion size (range = 1-40 mm) and found that the atypia rate for lesions ≤1.2 cm (16% with atypia) was statistically significantly lower (P = .008) than the atypia rate for lesions >1.2 cm (36% with atypia). To explore to effects of radiologic-pathologic correlation on the ability of the core biopsy to accurately predict nonatypical lesions we assessed thirteen consecutive paired nonatypical core biopsy/follow-up surgical excision specimens for the percent of the total lesion (on imaging) sampled by the core biopsy (measured histologically). None of the thirteen paired specimens showed upgrade on excision (0/13); the percent of total lesion sampled by biopsy in this cohort averaged 59%. We propose that in the absence of discordant clinical/radiological findings, small lesions (≤1.2 cm) with radiologic-pathologic concordance (>50% sampling of total lesion by core biopsy) may safely forego surgery for close clinical and radiographic follow-up. © 2018 Wiley Periodicals, Inc.

[Surgical treatment of chronic pancreatitis complicated by biliary hypertension].

PubMed

Pylypchuk, V I

2015-01-01

The results of 29 patients treatment, suffering chronic pancreatitis, complicated by biliary hypertension, in whom operative interventions in Department of Surgery of Regional Ivano-Frankivsk clinical hospital in 2009 - 2014 yrs, were analyzed. The drainage, resectional and combined interventions were performed. Direct intervention on pancreatic gland was not applied in 5 (17.2%) patients. Operation to Frey was performed in 7 (24.1%) patients, in 4--it was added by choledochojejunoanastomosis formation, longitudinal pancreatojejunostomy--in 13 (44.8%). In 4 (14.8%) patients while functional disorders of adjacent organs present a pancreaticoduodenal resection to Whipple was done. For biliary hypertension diagnosis (including the occult one) the method of intraoperative pressure measurement in common biliary duct (CBD) was proposed. The operation was added by biliodigestive anastomosis formation, using choledochoenterostomy to Roux method if while operations to Frey or Beger after intervention on pancreatic head with the intrapancreatic CBD freeing the intraductal pressure witnessed the biliary hypertension presence. In all the patients good and satisfactory results of operative treatment were noted.

A Review of Double Common Bile Duct and Its Sequelae.

PubMed

Kolli, Sindhura; Etienne, Denzil; Reddy, Madhavi; Shahzad, Ghulamullah

2018-02-01

A double or accessory common bile duct (ACBD) is a rare congenital anomaly. We report the case of a 60-year-old American Asian male, who was found to have a double or duplicated common bile duct after being admitted for evaluation of a pancreatic mass. A duplicated bile duct has the same mucosa histologically as a single bile duct. However, the opening of a duplicated bile duct lacks a sphincter allowing retrograde flow of gut contents which results in a higher probability of intraductal calculus formation. On rare occasions, it can predispose to liver abscesses, pancreatitis, pancreatic cancer, gallbladder cancer, gastric cancer, and ampullary cancer depending on the location of the opening of the ACBD. We present an integrative review of the limited cases of ACBD with correlation to the current case and discussion regarding the aspects of diagnosis and management.

Temperature Profiles of Different Cooling Methods in Porcine Pancreas Procurement

PubMed Central

Weegman, Brad P.; Suszynski, Thomas M.; Scott, William E.; Ferrer, Joana; Avgoustiniatos, Efstathios S.; Anazawa, Takayuki; O’Brien, Timothy D.; Rizzari, Michael D.; Karatzas, Theodore; Jie, Tun; Sutherland, David ER.; Hering, Bernhard J.; Papas, Klearchos K.

2014-01-01

Background Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. Methods This study examines the effect of 4 different cooling Methods on core porcine pancreas temperature (n=24) and histopathology (n=16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all 3 cooling Methods. Results Surface cooling alone (Method A) gradually decreased core pancreas temperature to < 10 °C after 30 minutes. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15–20 °C within the first 2 minutes of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (p=0.36). Histological scores were different between the cooling Methods (p=0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (p=0.02) and Methods A and D (p=0.02), but not between Methods C and D (p=0.95), which may highlight the importance of early cooling using an intraductal infusion. Conclusions In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and histopathology scores. These data may also have implications on human pancreas procurement since use of an intraductal infusion is not common practice. PMID:25040217

Management of Pancreatic Calculi: An Update.

PubMed

Tandan, Manu; Talukdar, Rupjyoti; Reddy, Duvvur Nageshwar

2016-11-15

Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the end result, irrespective of the etiology of CP. PC contains an inner nidus surrounded by successive layers of calcium carbonate. These calculi obstruct the pancreatic ducts and produce ductal hypertension, which leads to pain, the cardinal feature of CP. Both endoscopic therapy and surgery aim to clear these calculi and decrease ductal hypertension. In small PC, endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction is the treatment of choice. Large calculi require fragmentation by extracorporeal shock wave lithotripsy (ESWL) prior to their extraction or spontaneous expulsion. In properly selected cases, ESWL followed by ERCP is the standard of care for the management of large PC. Long-term outcomes following ESWL have demonstrated good pain relief in approximately 60% of patients. However, ESWL has limitations. Per oral pancreatoscopy and intraductal lithotripsy represent techniques in evolution, and in current practice their use is limited to centers with considerable expertise. Surgery should be offered to all patients with extensive PC, associated multiple ductal strictures or following failed endotherapy.

Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

ClinicalTrials.gov

2013-01-24

Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

Use of activated protein C has no avail in the early phase of acute pancreatitis.

PubMed

Akay, Sinan; Ozutemiz, Omer; Yenisey, Cigdem; Simsek, Nilufer Genc; Yuce, Gul; Batur, Yucel

2008-01-01

Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

Concurrent fibroadenoma and intraductal papilloma - A recurring complex lesion in a premenarcheal girl.

PubMed

Alessandrini, Lara; Gobbi, Dalia; Zanon, Giovanni Franco; Dall'Igna, Patrizia; Cecchetto, Giovanni; Alaggio, Rita

2013-02-15

Breast diseases are rare in childhood and adolescence, most lesions being fibroadenomas and papillomas. We report the case of an 11-year old girl with a complex breast lesion with hybrid features of fibroadenoma and intraductal papilloma with an early recurrence. Microscopically, the lesion was composed of dilated ducts showing intraluminal papillary projections with small to broad fibrovascular stalks. The typical leaf-like appearance of fibroadenoma was determined by the presence at the periphery of ducts compressed and distorted by the prominent stromal component. Despite its florid epithelial hyperplasia and mild cytological atypia (more evident in the relapse), immunohistochemical staining for p63 and smooth muscle actin highlighted a continuum outer myoepithelial layer, confirming the non-invasive appearance of the lesion. Two pathogenetic links have been hypothesized: one is based on the morphological continuum between these two entities, which may represent different evolutive stages in the same lesion; the other is based on epithelial/mesenchymal interactions. The possible malignant transformation of such complex lesion is also discussed, along with its differential diagnoses. The relevance of this case lies in its rarity, as well as in the therapeutic strategies related to its biological potential and to the necessity of a conservative treatment, due to the young age of the patient. Copyright © 2012. Published by Elsevier GmbH.

Percutaneous intraductal radiofrequency ablation for clearance of occluded metal stent in malignant biliary obstruction: feasibility and early results.

PubMed

Pai, Madhava; Valek, Vlastimil; Tomas, Andrasina; Doros, Attila; Quaretti, Pietro; Golfieri, Rita; Mosconi, Cristina; Habib, Nagy

2014-02-01

The major complication occurring with biliary stents is stent occlusion, frequently seen because of tumour in-growth, epithelial hyperplasia, and sludge deposits, resulting in recurrent jaundice and cholangitis. We report a prospective study with the results of first in man percutaneous intraductal radiofrequency (RF) ablation to clear the blocked metal stents in patients with malignant biliary obstruction using a novel bipolar RF catheter. Nine patients with malignant biliary obstruction and blocked metal stents were included. These patients underwent intraductal biliary RF ablation through the blocked metal stent following external biliary decompression with an internal-external biliary drainage. All nine patients had their stent patency restored successfully without the use of secondary stents. Following this intervention, there was no 30-day mortality, haemorrhage, bile duct perforation, bile leak, or pancreatitis. Of the nine patients, six are alive and three patients are dead with a median follow-up of 122 (range 50-488) days and a median stent patency of 102.5 (range 50-321) days. Six patients had their stent patent at the time of last follow-up or death. Three patients with stent blockage at 321, 290, and 65 days postprocedure underwent percutaneous transhepatic drain insertion and repeat ablation. In this selective group of patients, it appears that this new approach is safe and feasible. Efficacy remains to be proven in future, randomized, prospective studies.

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.

PubMed

Kawakubo, Kazumichi; Ohnishi, Shunsuke; Fujita, Hirotoshi; Kuwatani, Masaki; Onishi, Reizo; Masamune, Atsushi; Takeda, Hiroshi; Sakamoto, Naoya

2016-01-01

Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously. The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas. Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.

Tumoral Versus Flat Intraepithelial Neoplasia of Pancreatobiliary Tract, Gallbladder, and Ampulla of Vater.

PubMed

Jang, Kee-Taek; Ahn, Sangjeong

2016-05-01

-The identification of a precursor lesion is important to understanding the histopathologic and genetic alterations in carcinogenesis. There are a plethora of terminologies that describe precursor lesions of the pancreatobiliary tract, ampulla of Vater, and gallbladder. The current terminologies for precursor lesions may make it difficult to understand the tumor biology. Here, we propose the concept of tumoral and flat intraepithelial neoplasia to improve our understanding of precursor lesions of many epithelial organs, including the pancreatobiliary tract, ampulla of Vater, and gallbladder. -To understand the dichotomous pattern of tumoral and flat intraepithelial neoplasia in carcinogenesis of pancreatobiliary tract, ampulla of Vater, and gallbladder. -Review of relevant literatures indexed in PubMed. -Tumoral intraepithelial neoplasia presents as an intraluminal or intraductal, mass-forming, polypoid lesion or a macroscopic, visible, cystic lesion without intracystic papillae. Microscopically, tumoral intraepithelial neoplasia shows various proportions of papillary and tubular architecture, often with a mixed pattern, such as papillary, tubular, and papillary-tubular. The malignant potential depends on the degree of dysplasia and the cell phenotype of the epithelium. Flat intraepithelial neoplasia presents as a flat or superficial, spreading, mucosal lesion that is frequently accompanied by an invasive carcinoma. Tumoral and flat intraepithelial neoplasias are not homogeneous entities and may exhibit histopathologic spectrum changes and different genetic profiles. Although intraepithelial neoplasia showed a dichotomous pattern in the tumoral versus flat types, they can coexist. Tumoral and flat intraepithelial neoplasia can be interpreted as part of a spectrum of changes in the carcinogenesis pathway of each organ.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells.

PubMed

Sessa, F; Bonato, M; Frigerio, B; Capella, C; Solcia, E; Prat, M; Bara, J; Samloff, I M

1990-06-01

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.

Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material.

PubMed Central

Nagai, H; Kuroda, A; Morioka, Y

1986-01-01

Eight autopsy cases of pancreatic cancer (duct cell adenocarcinoma) with T1 and T2 primary tumors were studied histologically to examine the exact extent of lymphatic and local spread. Six of them had microscopic metastasis in grossly negative lymph nodes near the primary tumor. In addition, four of them had a few metastatic nodes in the para-aortic region. In cases with lymphatic metastases, the extent of cancer infiltration within lymphatic vessels, nerves, and/or connective tissues was almost the same as that of lymph node metastasis. Major vascular involvement was found in four cases. There was no case in which multicentricity or marked intraductal spread of cancer cells was observed in the pancreas. It has been suggested that most of T1 and T2 pancreatic cancers have a fairly widespread microscopic extension, although extremely small T1 cancers have a very limited extension. Images FIG. 2. FIGS. 4a-c. FIGS. 5a-c. PMID:3015059

Successful endoscopic removal of a rare, large impacted pancreatic duct stone using grasping forceps: A case report with video.

PubMed

Liu, Qin; Wang, Yiping; Zeng, Hongze; Hu, Bing

2018-04-01

As a main complication of chronic pancreatitis (CP), pancreatic duct stones (PDSs) are often associated with ductal obstruction resulting in increasing intraductal and parenchymal pressure and long-lasting pain. There are many methods for removing PDSs. However, for large stones, it is technically difficult to remove them entirely by endoscopic retrograde cholangiopancreatography (ERCP). A 57-year-old man presented with a chief complaint of severe epigastric pain radiating to his back 3 or 4 times annually for 2 years. The abdominal computed tomography scan revealed dilation of the proximal pancreatic duct with an irregular high-density calcification shadow located at the head of the pancreas. A pancreatic stent was placed initially by ERCP to relieve epigastric pain and alleviate symptom. Repeated ERCP was subsequently performed 2 months later to extract the impacted large pancreatic stone. By using grasping forceps, the huge coralloid stone (272 × 0 mm) was successfully extracted in an en bloc manner. Then, a 7-French × 5 cm plastic pancreatic stent was placed for 2 weeks. The patient was free of any pancreatic pain during the 2-year follow-up. Generally, for large or impacted pancreatic stones, endoscopic removal is technically difficult to achieve. Pancreatic stenting can be an effective method of alleviating abdominal pain and facilitating subsequent endoscopic lithoextraction. Extraction of large stones with grasping forceps can be an alternative approach instead of extracorporeal shock wave lithotripsy or surgery when stones are impacted at the papilla's orifice and partially protruding into the duodenal lumen.

Temperature profiles of different cooling methods in porcine pancreas procurement.

PubMed

Weegman, Bradley P; Suszynski, Thomas M; Scott, William E; Ferrer Fábrega, Joana; Avgoustiniatos, Efstathios S; Anazawa, Takayuki; O'Brien, Timothy D; Rizzari, Michael D; Karatzas, Theodore; Jie, Tun; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

2014-01-01

Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. This study examines the effect of four different cooling Methods on core porcine pancreas temperature (n = 24) and histopathology (n = 16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all three cooling Methods. Surface cooling alone (Method A) gradually decreased core pancreas temperature to <10 °C after 30 min. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15-20 °C within the first 2 min of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (P = 0.36). Histological scores were different between the cooling Methods (P = 0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (P = 0.02) and Methods A and D (P = 0.02), but not between Methods C and D (P = 0.95), which may highlight the importance of early cooling using an intraductal infusion. In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and histopathology scores. These data may also have implications on human pancreas procurement as use of an intraductal infusion is not common practice. © 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.

Pathogenesis and prevention of early pancreatic infection in experimental acute necrotizing pancreatitis.

PubMed Central

Foitzik, T; Fernández-del Castillo, C; Ferraro, M J; Mithöfer, K; Rattner, D W; Warshaw, A L

1995-01-01

OBJECTIVE: The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis. BACKGROUND: Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon. METHODS: Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney. RESULTS: The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics. CONCLUSIONS: Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis. PMID:7639584

Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis.

PubMed

Michael, E S; Kuliopulos, A; Covic, L; Steer, M L; Perides, G

2013-03-01

Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2(-/-) mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca(2+) concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury induced by endoscopic retrograde cholangiopancreatography (ERCP). This reduction in pancreatitis severity is observed when the pepducin is given before or 2 h after bile acid infusion but not when it is given 5 h after bile acid infusion. Conversely, P2pal-18S increases the severity of secretagogue-induced pancreatitis. In vitro studies indicate that P2pal-18S protects acinar cells against bile acid-induced injury/death, but it does not alter bile acid-induced intracellular zymogen activation. These studies are the first to report the effects of an effective PAR2 pharmacological inhibitor on pancreatic acinar cells and on the severity of experimental pancreatitis. They raise the possibility that a pepducin such as P2pal-18S might prove useful in the clinical management of patients at risk for developing severe biliary pancreatitis such as occurs following ERCP.

Current surgical treatment for chronic pancreatitis.

PubMed

Aimoto, Takayuki; Uchida, Eiji; Nakamura, Yoshiharu; Yamahatsu, Kazuya; Matsushita, Akira; Katsuno, Akira; Cho, Kazumitsu; Kawamoto, Masao

2011-01-01

Chronic pancreatitis (CP) is a painful, yet benign inflammatory process of the pancreas. Surgical management should be individualized because the pain is multifactorial and its mechanisms vary from patient to patient. Two main pathogenetic theories for the mechanisms of pain in CP have been proposed: the neurogenic theory and the theory of increased intraductal/intraparenchymal pressures. The latter theory is strongly supported by the good results of drainage procedures in the surgical management of CP. Other possible contributing factors include pancreatic ischemia; a centrally sensitized pain state; and the development of complications, such as pseudocysts and stenosis of the duodenum or common bile duct. Common indications for surgery include intractable pain, suspicion of neoplasm, and complications that cannot be resolved with radiological or endoscopic treatments. Operative procedures have been historically classified into 4 categories: decompression procedures for diseased and obstructed pancreatic ducts; resection procedures for the proximal, distal, or total pancreas; denervation procedures of the pancreas; and hybrid procedures. Pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy, once the standard operations for patients with CP, have been replaced by hybrid procedures, such as duodenum-preserving pancreatic head resection, the Frey procedure, and their variants. These procedures are safe and effective in providing long-term pain relief and in treating CP-related complications. Hybrid procedures should be the operations of choice for patients with CP.

Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

PubMed

Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

2014-02-01

To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

PubMed Central

Sinha, Jessica; Cao, Zheng; Dai, Jianliang; Tang, Huiyuan; Partyka, Katie; Hostetter, Galen; Simeone, Diane M.; Feng, Ziding; Allen, Peter J.; Brand, Randall E.; Haab, Brian B.

2016-01-01

Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc) in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN), whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN). The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts. PMID:27992432

Management of Pancreatic Calculi: An Update

PubMed Central

Tandan, Manu; Talukdar, Rupjyoti; Reddy, Duvvur Nageshwar

2016-01-01

Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the end result, irrespective of the etiology of CP. PC contains an inner nidus surrounded by successive layers of calcium carbonate. These calculi obstruct the pancreatic ducts and produce ductal hypertension, which leads to pain, the cardinal feature of CP. Both endoscopic therapy and surgery aim to clear these calculi and decrease ductal hypertension. In small PC, endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction is the treatment of choice. Large calculi require fragmentation by extracorporeal shock wave lithotripsy (ESWL) prior to their extraction or spontaneous expulsion. In properly selected cases, ESWL followed by ERCP is the standard of care for the management of large PC. Long-term outcomes following ESWL have demonstrated good pain relief in approximately 60% of patients. However, ESWL has limitations. Per oral pancreatoscopy and intraductal lithotripsy represent techniques in evolution, and in current practice their use is limited to centers with considerable expertise. Surgery should be offered to all patients with extensive PC, associated multiple ductal strictures or following failed endotherapy. PMID:27784844

Use of activated protein C has no avail in the early phase of acute pancreatitis

PubMed Central

Ozutemiz, Omer; Yenisey, Cigdem; Genc Simsek, Nilufer; Yuce, Gul; Batur, Yucel

2008-01-01

Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435±432 U/L vs. 27,426±118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970±323 pg/mL vs. 330±368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions. PMID:19088933

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

ClinicalTrials.gov

2017-07-10

Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

Trypsin Reduces Pancreatic Ductal Bicarbonate Secretion by Inhibiting CFTR Cl- channel and Luminal Anion Exchangers

PubMed Central

Pallagi, Petra; Venglovecz, Viktória; Rakonczay, Zoltán; Borka, Katalin; Korompay, Anna; Ózsvári, Béla; Judák, Linda; Sahin-Tóth, Miklós; Geisz, Andrea; Schnúr, Andrea; Maléth, József; Takács, Tamás; Gray, Mike A.; Argent, Barry E.; Mayerle, Julia; Lerch, Markus M.; Wittmann, Tibor; Hegyi, Péter

2012-01-01

Background & Aims The effects of trypsin on pancreatic ductal epithelial cells (PDEC) vary among species and depend on localization of proteinase-activated receptor-2 (PAR-2). Bicarbonate secretion is similar in human and guinea pig PDEC; we compared its localization in these cell types and isolated guinea pig ducts to study the effects of trypsin and a PAR-2 agonist on this process. Methods PAR-2 localization was analyzed by immunohistochemistry in guinea pig and human pancreatic tissue samples (from 15 patients with chronic pancreatitis and 15 without pancreatic disease). Functions of guinea pig PDEC were studied by microperfusion of isolated ducts, measurements of intracellular pH (pHi) and Ca2+ concentration [Ca2+]i, and patch clamp analysis. The effect of pH on trypsinogen autoactivation was assessed using recombinant human cationic trypsinogen. Results PAR-2 localized to the apical membrane of human and guinea pig PDEC. Trypsin increased [Ca2+]i and pHi, and inhibited secretion of bicarbonate by the luminal anion exchanger and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Autoactivation of human cationic trypsinogen accelerated when the pH was reduced from 8.5 to 6.0. PAR-2 expression was strongly down-regulated, at transcriptional and protein levels, in the ducts of patients with chronic pancreatitis, consistent with increased activity of intraductal trypsin. Importantly, in PAR-2 knockout mice, the effects of trypsin were PAR-2 dependent. Conclusions Trypsin reduces pancreatic ductal bicarbonate secretion via PAR-2–dependent inhibition of the apical anion exchanger and the CFTR Cl- channel. This could contribute to the development of chronic pancreatitis, decreasing luminal pH and promoting premature activation of trypsinogen in the pancreatic ducts. PMID:21893120

Role of somatostatin and its analogues in the treatment of acute and chronic pancreatitis.

PubMed Central

Büchler, M W; Binder, M; Friess, H

1994-01-01

Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This approach is somewhat controversial, however, as it is not clear whether pancreatic secretion continues to occur during the course of acute pancreatitis. Animal studies show an appreciable reduction of secretion in the inflamed pancreas, but studies in humans are not conclusive. The use of somatostatin or its analogue, octreotide, has been investigated in several clinical studies. A meta analysis of six individual studies in which somatostatin was given for acute pancreatitis showed that somatostatin significantly reduces mortality. A trial in patients with moderate to severe acute pancreatitis showed a lower rate (although not statistically significant) of complications in patients treated with 3 x 200 and 3 x 500 micrograms/day octreotide, compared with controls and patients receiving a lower dose of octreotide. A further study showed a significant reduction in patient controlled analgesics in patients treated with octreotide compared with controls. Pain is the important clinical symptom of chronic pancreatitis, possibly resulting from an increased intraductal pressure during secretion. The effect on pain of the inhibition of pancreatic secretion by octreotide has been investigated in two studies. One showed no significant reduction in pain after treatment with octreotide for three days. In the other, in which octreotide was used for three weeks, significantly less pain and analgesic use was recorded during octreotide treatment than during placebo. The most common complication of chronic pancreatitis is the formation of pseudocysts. There is some evidence that octreotide may be useful in their treatment. PMID:7911442

An Interesting Case of Oral Inverted Ductal Papilloma.

PubMed

Berridge, Natasha; Kumar, Mahesh

2016-12-01

Ductal papillomas are rare benign papillary tumours of the minor salivary glands. Previously they have been classified into three subtypes: inverted ductal papilloma (IDP), sialadenoma papilliferum and intraductal papilloma. The oral inverted ductal papilloma is the least common of these lesions, with 48 cases reported to date in a search of the English-language literature. We describe an interesting case of oral IDP and highlight the pertinent clinical and histopathological features. Importantly, unlike the histologically similar inverted papilloma (IP) of the nose and paranasal sinuses, oral IDP is a completely benign lesion and is not associated with malignant change. Clinical relevance: This case report aims to raise awareness of the lesion, oral inverted ductal papilloma (IDP). We outline the clinical features and unique histopathology of oral IDP so that clinicians may correctly diagnose such a lesion and implement appropriate treatment.

Results of a phase I-II study on intraductal confocal microscopy (IDCM) in patients with common bile duct (CBD) stenosis.

PubMed

Giovannini, M; Bories, E; Monges, G; Pesenti, C; Caillol, F; Delpero, J R

2011-07-01

Confocal endomicroscopy is an emergent technique and allows real optical biopsies in the gastrointestinal (GI) tract. The aim of this study was to evaluate a new intraductal confocal miniprobe in patients with a normal common bile duct (CBD) or with a suspicion of a malignant stenosis (cholangiocarcinoma). Thirty-seven patients (23 males) underwent endoscopic retrograde cholangiopancreatography (ERCP) for bile duct stone removal (7 cases) or bile duct stenosis (30 cases). Intraductal confocal microscopy (IDCM) was performed during the ERCP using a probe-based confocal laser endomicroscopy (pCLE) technique. IDCM was done with the CholangioFlex probe with Cellvizio (Mauna Kea Technologies, Paris, France). The depth of penetration of theCholangioFlex probe was 40-70 μm and magnification was 400×. Images were reviewed by an experienced pathologist in GI disease and compared to ERCP findings, CBD biopsies performed during ERCP or EUS, and in 15 patients to the resected specimen (Wipple resection). No complications related to the CholangioFlex insertion occurred after the ERCP. Good images were obtained in 33 patients. Final histology diagnosis was a normal CBD in 7 cases, 23 malignant stenoses (4 ampullary carcinomas, 13 cholangiocarcinomas, and 6 pancreatic cancer), and 7 inflammatory stenoses (4 chronic pancreatitis, 1 stenosis of hepaticojejunal anastomosis, 1 postcholecystectomy CBD stenosis, and 1 primary sclerosing cholangitis). IDCM of a normal CBD showed a thin black band (<20 μm), normal vessels (thin and regular), and no visible glands. IDCM of malignant strictures revealed irregular vessels with lack of contrast in the CBD wall, large black band (>20 μm), and an aggregate of irregular black cells (black clumps). These aspects were seen in all malignant stenoses and none were seen in benign or normal CBD. The presence of irregular vessels, large black bands, and black clumps seen with confocal laser microscopy enabled prediction of neoplasia with an accuracy rate of 86%, sensitivity of 83%, and specificity of 75%. The respective numbers for standard histopathology were 53, 65, and 53%. This phase I-II study on IDCM showed that IDCM is feasible. This new technique will open a new door for optical biopsy of the CBD.

Ensuring excision of intraductal lesions: marker placement at time of ductography.

PubMed

Woodward, Suzanne; Daly, Caroline P; Patterson, Stephanie K; Joe, Annette I; Helvie, Mark A

2010-11-01

To propose grid coordinate marker placement for patients with suspicious ductogram findings occult on routine workup. To compare the success of marker placement and wire localization (WL) with ductogram-guided WL. A retrospective search of radiology records identified all patients referred for ductography between January 2001 and May 2008. Results for 16 patients referred for ductogram-guided WL and 5 patients with grid coordinate marker placement at the time of ductography and subsequent WL were reviewed. Surgical pathology results and clinical follow-up were reviewed for concordance. Nine of 16 patients (56.3%) underwent successful ductogram-guided WL. Eight of nine patients had papillomas, one of which also had atypical ductal hyperplasia (ADH). One of nine patients had ectatic ducts with inspisated debris. Seven patients who failed ductogram-guided WL eventually underwent open surgical biopsy. Four of seven patients had papillomas, one of which also had lobular carcinoma in situ. Remaining patients had ADH (1/7) and fibrocystic changes with chronic inflammation (3/7). All five (100%) patients with grid coordinate marker placement underwent successful WL and marker excision. Pathology results included three papillomas, papillary intraductal hyperplasia, and fibrocystic change. Grid coordinate marker placement at the time of abnormal ductogram provided an accurate method of localizing ductal abnormalities that are occult on routine workup, thus facilitating future WL. Marker placement obviated the need for repeat ductogram on the day of surgery and ensured surgical removal of the ductogram abnormality. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

PubMed

Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

2018-06-06

Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

Adrenergic signaling mediates mechanical hyperalgesia through activation of P2X3 receptors in primary sensory neurons of rats with chronic pancreatitis.

PubMed

Wang, Shusheng; Zhu, Hong-Yan; Jin, Yi; Zhou, Youlang; Hu, Shufen; Liu, Tong; Jiang, Xinghong; Xu, Guang-Yin

2015-04-15

The mechanism of pain in chronic pancreatitis (CP) is poorly understood. The aim of this study was designed to investigate roles of norepinephrine (NE) and P2X receptor (P2XR) signaling pathway in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Mechanical hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. P2XR-mediated responses of pancreatic dorsal root ganglion (DRG) neurons were measured utilizing calcium imaging and whole cell patch-clamp-recording techniques. Western blot analysis and immunofluorescence were performed to examine protein expression. TNBS injection produced a significant upregulation of P2X3R expression and an increase in ATP-evoked responses of pancreatic DRG neurons. The sensitization of P2X3Rs was reversed by administration of β-adrenergic receptor antagonist propranolol. Incubation of DRG neurons with NE significantly enhanced ATP-induced intracellular calcium signals, which were abolished by propranolol, and partially blocked by protein kinase A inhibitor H-89. Interestingly, TNBS injection led to a significant elevation of NE concentration in DRGs and the pancreas, an upregulation of β2-adrenergic receptor expression in DRGs, and amplification of the NE-induced potentiation of ATP responses. Importantly, pancreatic hyperalgesia was markedly attenuated by administration of purinergic receptor antagonist suramin or A317491 or β2-adrenergic receptor antagonist butoxamine. Sensitization of P2X3Rs, which was likely mediated by adrenergic signaling in primary sensory neurons, contributes to pancreatic pain, thus identifying a potential target for treating pancreatic pain caused by inflammation. Copyright © 2015 the American Physiological Society.

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis.

PubMed

Zhu, Hong-Yan; Liu, Xuelian; Miao, Xiuhua; Li, Di; Wang, Shusheng; Xu, Guang-Yin

2017-01-01

Background Pain in patients with chronic pancreatitis is critical hallmark that accompanied inflammation, fibrosis, and destruction of glandular pancreas. Many researchers have demonstrated that stromal cell-derived factor 1 (also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) involved in mediating neuropathic and bone cancer pain. However, their roles in chronic pancreatic pain remain largely unclear. Methods Chronic pancreatitis was induced by intraductal injection of trinitrobenzene sulfonic acid to the pancreas. Von Frey filament tests were conducted to evaluate pancreas hypersensitivity of rat. Expression of CXCL12, CXCR4, NaV1.8, and pERK in rat dorsal root ganglion was detected by Western blot analyses. Dorsal root ganglion neuronal excitability was assessed by electrophysiological recordings. Results We showed that both CXCL12 and CXCR4 were dramatically up-regulated in the dorsal root ganglion in trinitrobenzene sulfonic acid-induced chronic pancreatitis pain model. Intrathecal application with AMD3100, a potent and selective CXCR4 inhibitor, reversed the hyperexcitability of dorsal root ganglion neurons innervating the pancreas of rats following trinitrobenzene sulfonic acid injection. Furthermore, trinitrobenzene sulfonic acid-induced extracellular signal-regulated kinase activation and Nav1.8 up-regulation in dorsal root ganglias were reversed by intrathecal application with AMD3100 as well as by blockade of extracellular signal-regulated kinase activation by intrathecal U0126. More importantly, the trinitrobenzene sulfonic acid-induced persistent pain was significantly suppressed by CXCR4 and extracellular signal-regulated kinase inhibitors. Conclusions The present results suggest that the activation of CXCL12-CXCR4 signaling might contribute to pancreatic pain and that extracellular signal-regulated kinase-dependent Nav1.8 up-regulation might lead to hyperexcitability of the primary nociceptor neurons in rats with chronic pancreatitis.

Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

ClinicalTrials.gov

2018-06-13

Breast Cancer; Cholangiocarcinoma; Colorectal Cancer; Head and Neck Neoplasms; Lymphoma, Large-Cell, Anaplastic; Melanoma; Neuroendocrine Tumors; Non-Small Cell Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Primary Brain Tumors; Renal Cell Carcinoma; Sarcomas; Salivary Gland Cancers; Adult Solid Tumor

Pancreatic Transduction by Helper-Dependent Adenoviral Vectors via Intraductal Delivery

PubMed Central

Morró, Meritxell; Teichenne, Joan; Jimenez, Veronica; Kratzer, Ramona; Marletta, Serena; Maggioni, Luca; Mallol, Cristina; Ruberte, Jesus; Kochanek, Stefan; Bosch, Fatima

2014-01-01

Abstract Pancreatic gene transfer could be useful to treat several diseases, such as diabetes mellitus, cystic fibrosis, chronic pancreatitis, or pancreatic cancer. Helper-dependent adenoviral vectors (HDAds) are promising tools for gene therapy because of their large cloning capacity, high levels of transgene expression, and long-term persistence in immunocompetent animals. Nevertheless, the ability of HDAds to transduce the pancreas in vivo has not been investigated yet. Here, we have generated HDAds carrying pancreas-specific expression cassettes, that is, driven either by the elastase or insulin promoter, using a novel and convenient plasmid family and homologous recombination in bacteria. These HDAds were delivered to the pancreas of immunocompetent mice via intrapancreatic duct injection. HDAds, encoding a CMV-GFP reporter cassette, were able to transduce acinar and islet cells, but transgene expression was lost 15 days postinjection in correlation with severe lymphocytic infiltration. When HDAds encoding GFP under the control of the specific elastase promoter were used, expression was detected in acinar cells, but similarly, the expression almost disappeared 30 days postinjection and lymphocytic infiltration was also observed. In contrast, long-term transgene expression (>8 months) was achieved with HDAds carrying the insulin promoter and the secretable alkaline phosphatase as the reporter gene. Notably, transduction of the liver, the preferred target for adenovirus, was minimal by this route of delivery. These data indicate that HDAds could be used for pancreatic gene therapy but that selection of the expression cassette is of critical importance to achieve long-term expression of the transgene in this tissue. PMID:25046147

PANCREAS METASTASES FROM PAPILLARY THYROID CARCINOMA: A REVIEW OF THE LITERATURE.

PubMed

Davidson, Maja; Olsen, Randall J; Ewton, April A; Robbins, Richard J

2017-12-01

Although locoregional metastases occur in 5 to 10% of patients with papillary thyroid cancer (PTC), distant metastases are rare, especially to the pancreas. Here we review the literature regarding metastases to the pancreas from PTC and present an illustrative patient. The literature search was performed through using the PubMed database. The information regarding our illustrative case was obtained from the medical records of our institution. Since 1991, 11 cases of pancreas metastases of PTC have been reported. The average age at diagnosis was 55.3 years. There were 8 males and 3 females. Three had classic PTC histology, 2 had tall cell variant, and 2 had follicular variant. Four had T4 tumors, and 2 had T3 tumors. Seven had thyroid cancer spread to regional lymph nodes. One had distant metastasis. Pancreas metastases were diagnosed from 1 month to 13 years after primary PTC was detected; the average was 7 years. Our patient was an 84-year-old female diagnosed with PTC with a BRAFV600E mutation following total thyroidectomy. A whole-body scan after radioactive iodine (RAI) remnant ablation was negative for metastases. A pancreatic tumor was identified 2 years later on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. A biopsy of the tumor was histologically similar to PTC and positive for thyroglobulin, thyroid transcription factor-1, and the BRAFV600E mutation. The biological reasons why PTCs metastasize to the pancreas remain to be elucidated. Older patients with non-RAI avid, FDG-PET-positive metastases, and symptoms of pancreatitis are at increased risk of this rare entity. FDG = fluorodeoxyglucose FNA = fine-need aspiration PTC = papillary thyroid cancer RAI = radioactive iodine Tg = thyroglobulin TgAb = antithyroglobulin antibodies TNM = tumor-node-metastasis.

Comparison of endoscopic papillary balloon dilation and sphincterotomy in young patients with CBD stones and gallstones.

PubMed

Seo, Yu Ri; Moon, Jong Ho; Choi, Hyun Jong; Kim, Dong Choon; Ha, Ji Su; Lee, Tae Hoon; Cha, Sang-Woo; Cho, Young Deok; Park, Sang-Heum; Kim, Sun-Joo

2014-05-01

Endoscopic biliary sphincterotomy (EBS) results in permanent loss of sphincter function and its long-term complications are unknown. Endoscopic papillary balloon dilation (EPBD) is an alternative procedure that preserves sphincter function, although it is associated with a higher risk of pancreatitis than is EBS. The aim of this study was to evaluate the safety and outcomes of EPBD with limited indications for removal of common bile duct (CBD) stones combined with gallstones in patients younger than 40 years. Young (age < 40 years) patients who had CBD stones combined with gallstones on imaging studies were enrolled in this study. A total of 132 patients were randomly divided into the EPBD group (n = 62) or the EBS group (n = 70) for extraction of CBD stones. The ballooning size of EPBD ranged from 6 to 10 mm. Complete bile duct clearance was achieved in 98.4 % (61/62) of the EPBD group and 100 % (70/70) of the EBS group. Mechanical lithotripsy was required in 8.1 % (5/62) of the EPBD group and 8.6 % (6/70) of the EBS group. The early complication rates were 8.1 % (5/62) (five pancreatitis) in the EPBD group and 11.4 % (8/70) (five [7.1 %] pancreatitis, two bleeding and one perforation) in the EBS group. The recurrence rates of CBD stones were 1.6 % (1/62) in the EPBD group and 5.7 % (4/70) in the EBS group. EPBD with limited indications was safe and effective as EBS for removal of CBD stones combined with gallstones in young patients who had a longer life expectancy.

Intraductal fibroadenoma under the nipple in an 11-year-old female.

PubMed

Hayano, Fumiko; Yamada, Sohsuke; Nakano, Shigeo; Watanabe, Teruo; Sasaguri, Yasuyuki; Koga, Sunao

2014-02-10

Recently, Chung et al. have reported the detailed clinicopathological features of an extremely rare case sharing similar histopathological characteristics with fibroadenomas, phyllodes tumours, intraductal papillomas or ductal adenomas, given the name of intraductal fibroadenomatosis, as an unusual variant of intracanalicular fibroadenoma. Herein we demonstrated a very unusual case of intraductal fibroadenoma of the breast with admixture of components of intracanalicular type fibroadenoma or benign phyllodes tumour and a smaller amount of intraductal papilloma, occupying the one duct and some adjacent ductules, presenting as a well-demarcated nodule.

Intraductal fibroadenoma under the nipple in an 11-year-old female

PubMed Central

2014-01-01

Recently, Chung et al. have reported the detailed clinicopathological features of an extremely rare case sharing similar histopathological characteristics with fibroadenomas, phyllodes tumours, intraductal papillomas or ductal adenomas, given the name of intraductal fibroadenomatosis, as an unusual variant of intracanalicular fibroadenoma. Herein we demonstrated a very unusual case of intraductal fibroadenoma of the breast with admixture of components of intracanalicular type fibroadenoma or benign phyllodes tumour and a smaller amount of intraductal papilloma, occupying the one duct and some adjacent ductules, presenting as a well-demarcated nodule. PMID:24512699

Intraductal papilloma

MedlinePlus

... page: //medlineplus.gov/ency/article/001238.htm Intraductal papilloma To use the sharing features on this page, please enable JavaScript. Intraductal papilloma is a small, noncancerous (benign) tumor that grows ...

Role of stents and laser therapy in biliary strictures

NASA Astrophysics Data System (ADS)

Chennupati, Raja S.; Trowers, Eugene A.

2001-05-01

The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), hilar biliary cancer (19% including metastatic disease), nonhilar biliary cancer (14%) and papillary cancer (10%). Endoscopic stenting has widely replaced palliative surgery for malignant biliary obstruction because of its lower risk and cost. Self-expandable metal stents are the preferred mode of palliation for hilar malignancies. Plastic stents have a major role in benign biliary strictures. Major complications and disadvantages associated with metallic stents include high cost, cholangitis. malposition, migration, unextractability, and breakage of the stents, pancreatitis and stent dysfunction. Dysfunction due to tumor ingrowth can be relieved by thermal methods (argon plasma coagulator therapy). We present a concise review of the efficacy of metallic stents for palliation of malignant strictures.

Short-type single balloon enteroscope for endoscopic retrograde cholangiopancreatography with altered gastrointestinal anatomy

PubMed Central

Yamauchi, Hiroshi; Kida, Mitsuhiro; Okuwaki, Kosuke; Miyazawa, Shiro; Iwai, Tomohisa; Takezawa, Miyoko; Kikuchi, Hidehiko; Watanabe, Maya; Imaizumi, Hiroshi; Koizumi, Wasaburo

2013-01-01

AIM: To evaluate the effectiveness of a short-type single-balloon-enteroscope (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) in patients with a reconstructed intestine. METHODS: Short-type SBE was developed to perform ERCP in postoperative patients with a reconstructed intestine. Short-type SBE is a direct-viewing endoscope with the following specifications: working length, 1520 mm; total length, 1840 mm; channel diameter, 3.2 mm. In addition, short-type SBE has a water-jet channel. The study group comprised 22 patients who underwent 31 sessions of short-type SBE-assisted ERCP from June 2011 through May 2012. Reconstruction was performed by Billroth-II (B-II) gastrectomy in 6 patients (8 sessions), Roux-en-Y (R-Y) gastrectomy in 14 patients (21 sessions), and R-Y hepaticojejunostomy in 2 patients (2 sessions). We retrospectively studied the rate of reaching the blind end (papilla of Vater or choledochojejunal anastomosis), mean time required to reach the blind end, diagnostic success rate (defined as the rate of successfully imaging the bile and pancreatic ducts), therapeutic success rate (defined as the rate of successfully completing endoscopic treatment), mean procedure time, and complications. RESULTS: Among the 31 sessions of ERCP, the rate of reaching the blind end was 88% in B-II gastrectomy, 91% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The mean time required to reach the papilla was 18.3 min in B-II gastrectomy, 21.1 min in R-Y gastrectomy, and 32.5 min in R-Y hepaticojejunostomy. The diagnostic success rates in all patients and those with an intact papilla were respectively 86% and 86% in B-II gastrectomy, 90% and 87% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The therapeutic success rates in all patients and those with an intact papilla were respectively 100% and 100% in B-II gastrectomy, 94% and 92% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. Because the channel diameter was 3.2 mm, stone extraction could be performed with a wire-guided basket in 12 sessions, and wire-guided intraductal ultrasonography could be performed in 8 sessions. As for complications, hyperamylasemia (defined as a rise in serum amylase levels to more than 3 times the upper limit of normal) occurred in 1 patient (7 sessions) with a B-II gastrectomy and 4 patients (19 sessions) with an R-Y gastrectomy. After ERCP in patients with an R-Y gastrectomy, 2 patients (19 sessions) had pancreatitis, 1 patient (21 sessions) had gastrointestinal perforation, and 1 patient (19 sessions) had papillary bleeding. Pancreatitis and bleeding were both mild. Gastrointestinal perforation improved after conservative treatment. CONCLUSION: Short-type SBE is effective for ERCP in patients with a reconstructed intestine and allows most conventional ERCP devices to be used. PMID:23555161

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pai, Madhava, E-mail: madhava.pai@imperial.ac.uk; Valek, Vlastimil; Tomas, Andrasina

PurposeThe major complication occurring with biliary stents is stent occlusion, frequently seen because of tumour in-growth, epithelial hyperplasia, and sludge deposits, resulting in recurrent jaundice and cholangitis. We report a prospective study with the results of first in man percutaneous intraductal radiofrequency (RF) ablation to clear the blocked metal stents in patients with malignant biliary obstruction using a novel bipolar RF catheter.MethodsNine patients with malignant biliary obstruction and blocked metal stents were included. These patients underwent intraductal biliary RF ablation through the blocked metal stent following external biliary decompression with an internal–external biliary drainage.ResultsAll nine patients had their stent patencymore » restored successfully without the use of secondary stents. Following this intervention, there was no 30-day mortality, haemorrhage, bile duct perforation, bile leak, or pancreatitis. Of the nine patients, six are alive and three patients are dead with a median follow-up of 122 (range 50–488) days and a median stent patency of 102.5 (range 50–321) days. Six patients had their stent patent at the time of last follow-up or death. Three patients with stent blockage at 321, 290, and 65 days postprocedure underwent percutaneous transhepatic drain insertion and repeat ablation.ConclusionsIn this selective group of patients, it appears that this new approach is safe and feasible. Efficacy remains to be proven in future, randomized, prospective studies.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mizandari, Malkhaz; Pai, Madhava, E-mail: madhava.pai@imperial.ac.uk; Xi Feng

Purpose. Previous clinical studies have shown the safety and efficacy of this novel radiofrequency ablation catheter when used for endoscopic palliative procedures. We report a retrospective study with the results of first in man percutaneous intraductal radiofrequency ablation in patients with malignant biliary obstruction. Methods. Thirty-nine patients with inoperable malignant biliary obstruction were included. These patients underwent intraductal biliary radiofrequency ablation of their malignant biliary strictures following external biliary decompression with an internal-external biliary drainage. Following ablation, they had a metal stent inserted. Results. Following this intervention, there were no 30-day mortality, hemorrhage, bile duct perforation, bile leak, or pancreatitis.more » Of the 39 patients, 28 are alive and 10 patients are dead with a median survival of 89.5 (range 14-260) days and median stent patency of 84.5 (range 14-260) days. One patient was lost to follow-up. All but one patient had their stent patent at the time of last follow-up or death. One patient with stent blockage at 42 days postprocedure underwent percutaneous transhepatic drain insertion and restenting. Among the patients who are alive (n = 28) the median stent patency was 92 (range 14-260) days, whereas the patients who died (n = 10) had a median stent patency of 62.5 (range 38-210) days. Conclusions. In this group of patients, it appears that this new approach is feasible and safe. Efficacy remains to be proven in future, randomized, prospective studies.« less

Early institution of pre-cutting for difficult biliary cannulation: a prospective study comparing conventional vs. a modified technique.

PubMed

Kaffes, Arthur J; Sriram, Parupudi V J; Rao, Guduru V; Santosh, Darisetti; Reddy, D Nageshwar

2005-11-01

Pre-cutting techniques have been used to gain biliary access at the expense of an increased complication rate. This may be because of the multiple attempts to achieve cannulation by using standard methods before pre-cutting and causing excess edema and papillary trauma. There are limited data on the early use of pre-cutting techniques. We performed a prospective study of the early introduction of needle-knife techniques in patients with difficult biliary cannulation. Standard biliary cannulation was attempted with a sphincterotome and a guidewire. If this failed within 10 minutes or if there were more than 5 pancreatic cannulations, the needle-knife technique was used. Either a standard method of pre-cutting (below-upward) from the papillary orifice or the modified technique of pre-cutting (above-downward), stopping short of the papillary orifice, was adopted, as per the discretion of the endoscopist. If pre-cutting failed, the cannulation was reattempted 24 to 48 hours later. A total of 346 therapeutic biliary ERCP procedures were performed between April and August 2003. Of these, 70 patients (20%) (mean age, 54 years; 38 men) underwent needle-knife pre-cut sphincterotomy (16 with the standard technique). In 58 patients (83%), the procedure was successful with the initial pre-cutting, making the total success at initial ERCP 334/346 (96.5%). Nine patients in whom pre-cut failed, returned for a second-attempt ERCP, with 7 completed successfully. The total success rate of pre-cutting was 65/70 (93%). The overall success rate of biliary cannulation, after two ERCP attempts, was 341/346 (98.5%). Six patients had mild bleeding, and one had mild pancreatitis. There was no difference in these complications between the two types of pre-cut techniques. The early use of needle knife for difficult biliary cannulation is safe and effective, irrespective of the technique used.

Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion.

PubMed

Lakey, J R; Warnock, G L; Shapiro, A M; Korbutt, G S; Ao, Z; Kneteman, N M; Rajotte, R V

1999-01-01

Effective intraductal delivery of the enzyme collagenase into the pancreas is crucial to the subsequent ability to isolate viable islets. Most clinical islet transplant centers load the enzyme into the pancreas by retrograde injection using a syringe following cannulation of the pancreatic duct. An alternative approach is to perfuse the pancreas via the pancreatic duct with collagenase solution using a recirculating perfusion device system. This provides control over perfusion pressures and collagenase temperature. This study reports on our evaluation of the delivery of Liberase-HI into the pancreas of 14 consecutive adult multiorgan cadaveric donors. Alternate glands were procured and processed using an identical protocol with the exception of collagenase delivery. The first group of pancreases was loaded using the perfusion technique where cold (4 degrees C) Liberase-HI was perfused at 80 mmHg for 5 min after which the pressure was increased to 180 mmHg. The collagenase solution was then slowly warmed to 35 degrees C, transferred to the dissociation chamber and mechanically dissociated, and then purified using discontinuous gradients of Ficoll. Pancreases in the second group were loaded with collagenase (28-32 degrees C) using the syringe technique before mechanical dissociation and purification. There were no significant differences in pancreas cold ischemia, donor age, body mass index, maximum blood glucose, or serum amylase of the donors between the two groups. Mean collagenase digestion time in the digestion chamber was not different between the two groups; however, the amount of undigested tissue remaining after dissociation was significantly higher in the syringe-loaded group (15.3 +/- 2.6 g vs. 4.6 +/- 2.1 g, mean +/- SEM, p < 0.05). Postdigestion recovery of islets was 471 +/- 83 x 10(3) IE in the perfusion group compared with 391 +/- 57 x 10(3) IE for the syringe-loaded group. Postpurification recovery was higher in the perfused group (379 +/- 45 vs. 251 +/- 28 x 10(3) IE, p < 0.05, two-tailed paired t-test). No difference in in vitro islet viability was observed between the two groups following glucose perifusion with the calculated stimulation index of 4.6 +/- 0.6 for the perfusion group and 4.2 +/- 0.7 for the syringe-loaded group. Controlled perfusion via the pancreatic duct allows the effective delivery of the enzyme achieving maximal distension to all regions of the pancreas leading to an increased recovery of the islets with no detrimental effect on subsequent in vitro islet function.

Post-ERCP acute pancreatitis and its risk factors.

PubMed

Iorgulescu, A; Sandu, I; Turcu, F; Iordache, N

2013-03-15

Endoscopic retrograde cholangiopancreatography (ERCP) is a complex endoscopic technique that evolved from a diagnostic to a mainly therapeutic procedure. This was due to the identification of post-procedural complications that can follow both simple ERCP and that associated with the instrumentation of the biliary and pancreatic ductals. The identification of post ERCP complications in a proportion of 5 to 10% of cases, with a mortality rate of 0.33%, imposed their analysis and study of risk factors involved in their occurrence. The significance of post ERCP complications reveals the necessity of their avoidance by adopting additional measures if risk factors are identified. We have retrospectively analyzed 900 cases that underwent ERCP in the Surgery Department of "Sf. Ioan" Clinical Hospital in a period of 17 years. The complications of the procedure were studied. Among them, a special attention was given to post-ERCP acute pancreatitis (pERCP-AP), the most common complication that occurred in the study group. We also tried to find out and highlight the risk factors for this complication. ERCP is a relatively safe invasive procedure, yet it has complications (8% of cases), some of them potentially fatal (mortality 0.43%). The most common complications after ERCP are acute pancreatitis (3.7%), papillary bleeding (1.04%), retroperitoneal duodenal perforation (0.69%) and biliary septic complications like acute cholecystitis and cholangitis (1.21%). Acute pancreatitis is by far the most common complication. Risk factors for its occurrence are difficult sphincterotomy with precut use, failure of CBD desobstruction, pancreatic sphincterotomy, repeated injection of contrast in the pancreatic ductal system, dysfunction of the sphincter of Oddi and the absence of changes of chronic pancreatitis. When risk factors are identified, the patients' selection must be very strict and diagnostic ERCP should be avoided in favor of non-invasive diagnostic methods (MRI-cholangiography, echo-endoscopy).

Cholangiocarcinoma in a middle-aged patient working at a printing plant.

PubMed

Tanaka, Shogo; Fukumoto, Nobusuke; Ohno, Kohichi; Tanaka, Sayaka; Ohsawa, Masahiko; Yamamoto, Takatsugu; Nakanuma, Yasuni; Kuboo, Shoji

2014-06-01

A 39-year-old male with elevated serum transferases consulted our hospital in September 2010. Since 1999, he had worked at a printing company using organic solvents. Cholangiography revealed stenosis of the left hepatic duct with peripheral dilation, stricture of the right hepatic duct, and irregularity of the extrahepatic bile duct. As a preoperative diagnosis of sclerosing cholangitis and cholangiocarcinoma was made, extended left hepatectomy with resection of the extrahepatic bile duct and anastomosis of the anterior and posterior branches of the bile duct and the jejunum (Roux-en Y reconstruction) were performed. A histological examination showed papillary carcinoma of the medial hepatic bile duct with intraductal growth, and biliary intraepithelial neoplasia-2/3 lesions from the medial hepatic bile duct to the right hepatic and the common bile ducts. Chronic cholangitis was shown around the tumors. Postoperatively, the patient was treated with adjuvant chemo-radiation, and he is doing well 30 months after the operation, without recurrence. Unknown causes, including exposure to organic solvents, might have induced chronic bile duct injury and contributed to the development of cholangiocarcinoma.

Innovative Microcapsules for Pancreatic β-Cells Harvested from Mature Double-Transgenic Mice: Cell Imaging, Viability, Induced Glucose-Stimulated Insulin Measurements and Proinflammatory Cytokines Analysis.

PubMed

Mooranian, Armin; Tackechi, Ryu; Jamieson, Emma; Morahan, Grant; Al-Salami, Hani

2017-06-01

Recently we demonstrated that microencapsulation of a murine pancreatic β-cell line using an alginate-ursodeoxycholic acid (UDCA) matrix produced microcapsules with good stability and cell viability. In this study, we investigated if translation of this formulation to microencapsulation of primary β-cells harvested from mature double-transgenic healthy mice would also generate stable microcapsules with good cell viability. Islets of Langerhans were isolated from Ngn3-GFP/RIP-DsRED mice by intraductal collagenase P digestion and density gradient centrifugation, dissociated into single cells and the β-cell population purified by Fluorescence Activated Cell Sorting. β-cells were microencapsulated using either alginate-poly-l-ornithine (F1; control) or alginate-poly-l-ornithine-UDCA (F2; test) formulations. Microcapsules were microscopically examined and microencapsulated cells were analyzed for viability, insulin and cytokine release, 2 days post-microencapsulation. Microcapsules showed good uniformity and morphological characteristics and even cell distribution within microcapsules with or without UDCA. Two days post microencapsulation cell viability, mitochondrial ATP and insulin production were shown to be optimized in the presence of UDCA whilst production of the proinflammatory cytokine IL-1β was reduced. Contradictory to our previous studies, UDCA did not reduce production of any other pro-inflammatory biomarkers. These results suggest that UDCA incorporation improves microcapsules' physical and morphological characteristics and improves the viability and function of encapsulated mature primary pancreatic β-cells.

Metabolic system alterations in pancreatic cancer patient serum: potential for early detection

PubMed Central

2013-01-01

Background The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects. Methods A non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasims (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population. Results FI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long-chain fatty acid), was further validated using an independently-collected US Caucasian population (blinded analysis, n=60, p=9.9E-14, AUC=0.97 ±0.02). PC-594 levels across 1000 reference subjects showed an inverse correlation with age, resulting in a drop in the AUC from 0.99 ±0.01 to 0.90 ±0.02 for subjects aged 30 to 80, respectively. A PC-594 test positivity rate of 5.0% in low-risk reference subjects resulted in a PC sensitivity of 87% and a significant improvement in net clinical benefit based on decision curve analysis. Conclusions The serum metabolome of PC patients is significantly altered. The utility of serum metabolite biomarkers, particularly PC-594, for identifying subjects with elevated risk of PC should be further investigated. PMID:24024929

216 cases of pancreaticoduodenectomy: risk factors for postoperative complications.

PubMed

Fathy, O; Wahab, M Abdel M; Elghwalby, N; Sultan, A; EL-Ebidy, G; Hak, N GadEl; Abu Zeid, M; Abd-Allah, T; El-Shobary, M; Fouad, A; Kandeel, Th; Abo Elenien, A; Abd El-Raouf, A; Hamdy, E; Sultan, A M; Hamdy, E; Ezzat, Farouk

2008-01-01

Surgical resection remains the best treatment for patients with periampullary tumors. Many series have been reported with low or zero mortality, however, high incidence of complications is the rule. This study aims to present the results of pancreaticoduodenectomy and factors predisposing to postoperative complications, especially pancreatic leak, at our center. Between January 2000 and December 2006, 216 periampullary tumors were treated by Whipple pancreaticoduodenectomy. Pancreaticogastrostomy was done in 183 patients and pancreaticojejunostomy in 33 patients. Hospital mortality and surgical complications were recorded with special emphasis on pancreatic leak. All specimens were histologically examined for the presence and origin of malignant tissue. The mean age was 58 years and male to female ratio was 2:1. The commonest symptom was jaundice (97.7%) followed by abdominal pain (74%). Operative mortality in 7 patients (3.2%). 71 (33%) patients developed 1 or more complications, pancreatic leak occurred in 23 (10.6%) patients, abdominal collection in 23 patients (10.6%) and delayed gastric emptying in 19 (8.8%) patients. Factors that influenced the development of postoperative complications included type of pancreaticoenteric anastomosis, pancreatic texture and intraoperative blood transfusion of 4 or more blood units. Pancreatic leak was commoner with PJ (p=0.001), soft pancreatic texture (p=0.008), intraoperative blood transfusion of 4 or more units (p<0.0001). Periampullary adenocarcinoma was found in 204 (94.4%) patients, chronic pancreatitis in 9 (4.2%) patients, 2 patients with solid and papillary neoplasm, and 1 patient with NHL (Non-Hodgkin's Lymphoma). Surgery is the only hope for patients with periampullary tumors. Postoperative complications after pancreaticoduodenectomy depend largely on surgical technique and can be reduced reasonably with the adoption of pancreaticogastrostomy, which is safer and easier to learn than pancreaticojejunostomy.

Efficacy of plastic stent placement inside bile ducts for the treatment of unresectable malignant hilar obstruction (with videos).

PubMed

Kaneko, Takashi; Sugimori, Kazuya; Shimizu, Yuro; Miwa, Haruo; Kameta, Eri; Koh, Ryonho; Numata, Kazushi; Tanaka, Katsuaki; Maeda, Shin

2014-05-01

Recent reports have addressed the utility of plastic stent (PS) placement inside bile ducts for treating biliary obstructions. Here, we evaluated the utility and safety of PS placement inside bile ducts for treating unresectable malignant hilar biliary obstruction. We conducted a retrospective study of 27 patients with unresectable malignant hilar biliary obstruction who underwent intraductal modified PS placement. We modified the PS, by cutting off the distal end to facilitate insertion through the papilla of Vater, and attached a nylon thread to the distal end for removal. We evaluated complications, the time to recurrent biliary obstruction (TRBO), and removability. Bilateral stenting was performed in nine of the 27 patients. Mild acute pancreatitis occurred in one patient (4%). Recurrent biliary obstruction (RBO) occurred in 16 patients (59%), with a median TRBO of 190 days (95% confidence interval: 174-205 days). Reintervention was necessary in 13 of the 16 patients (81%) with RBO, and we were able to remove the initial stents in all the patients who required reintervention. A relatively long stent patency period (>6 months) and removability make placement of a modified PS inside bile ducts a viable treatment for unresectable malignant hilar biliary obstruction. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Factors predictive of adverse events following endoscopic papillary large balloon dilation: results from a multicenter series.

PubMed

Park, Soo Jung; Kim, Jin Hong; Hwang, Jae Chul; Kim, Ho Gak; Lee, Don Haeng; Jeong, Seok; Cha, Sang-Woo; Cho, Young Deok; Kim, Hong Ja; Kim, Jong Hyeok; Moon, Jong Ho; Park, Sang-Heum; Itoi, Takao; Isayama, Hiroyuki; Kogure, Hirofumi; Lee, Se Joon; Jung, Kyo Tae; Lee, Hye Sun; Baron, Todd H; Lee, Dong Ki

2013-04-01

Lack of established guidelines for endoscopic papillary large balloon dilation (EPLBD) may be a reason for aversion of its use in removal of large common bile duct (CBD) stones. We sought to identify factors predictive of adverse events (AEs) following EPLBD. This multicenter retrospective study investigated 946 consecutive patients who underwent attempted removal of CBD stones ≥10 mm in size using EPLBD (balloon size 12-20 mm) with or without endoscopic sphincterotomy (EST) at 12 academic medical centers in Korea and Japan. Ninety-five (10.0 %) patients exhibited AEs including bleeding in 56, pancreatitis in 24, perforation in nine, and cholangitis in six; 90 (94.7 %) of these were classified as mild or moderate in severity. There were four deaths, three as a result of perforation and one due to delayed massive bleeding. Causative factors identified in fatal cases were full-EST and continued balloon inflation despite a persistent waist seen fluoroscopically. Multivariate analyses showed that cirrhosis (OR 8.03, p = 0.003), length of EST (full-EST: OR 6.22, p < 0.001) and stone size (≥16 mm: OR 4.00, p < 0.001) were associated with increased bleeding, and distal CBD stricture (OR 17.08, p < 0.001) was an independent predictor for perforation. On the other hand, balloon size was associated with deceased pancreatitis (≥14 mm: OR 0.27, p = 0.015). EPLBD appears to be a safe and effective therapeutic approach for retrieval of large stones in patients without distal CBD strictures and when performed without full-EST.

Role of Magnetic Resonance Imaging Targeted Biopsy in Detection of Prostate Cancer Harboring Adverse Pathological Features of Intraductal Carcinoma and Invasive Cribriform Carcinoma.

PubMed

Prendeville, Susan; Gertner, Mark; Maganti, Manjula; Pintilie, Melania; Perlis, Nathan; Toi, Ants; Evans, Andrew J; Finelli, Antonio; van der Kwast, Theodorus H; Ghai, Sangeet

2018-07-01

The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate. We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI-RADS™ (Prostate Imaging-Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern. A total of 154 patients were included in study. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and systematic sextant biopsy of magnetic resonance imaging negative regions were negative for prostate carcinoma in 51 patients, leaving 103 available for the correlation of multiparametric magnetic resonance imaging and the intraductal/cribriform pattern. Prostate carcinoma was identified by multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy in 93 cases and by systematic sextant biopsy of magnetic resonance imaging negative regions in 76 (p = 0.008). Intraductal/cribriform positive tumor was detected in 23 cases, including at the multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy site in 22 and at the systematic sextant biopsy of magnetic resonance imaging negative region site in 3 (p <0.001). The intraductal/cribriform pattern was significantly associated with a PI-RADS score of 5 and a decreasing apparent diffusion coefficient value (p = 0.008 and 0.005, respectively). In 19 of the 23 cases with the intraductal/cribriform pattern prior 12-core standard systematic biopsy was negative in 8 and showed Grade Group 1 disease in 11. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy was associated with significantly increased detection of intraductal/cribriform positive prostate carcinoma compared to systematic sextant biopsy of multiparametric magnetic resonance imaging negative regions. This supports the role of magnetic resonance imaging to enhance the detection of clinically aggressive intraductal/cribriform positive prostate carcinoma. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma.

PubMed

Nguyen Canh, Hiep; Harada, Kenichi

2016-12-01

Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.

Progress in the study of pancreatic cancer and its pathology.

PubMed

Yanagisawa, A

1998-01-01

Recent advances in diagnostic techniques allow detection of relatively small ductal cancers and mucinous cystic neoplasms of the human pancreas. The histopathological characteristics of a series of such small pancreatic carcinomas encountered in our hospital were: 1) all were invasive ductal carcinomas accompanied by fibrosis, 2) four of seven carcinomas were thought to originate in the branch ducts, 3) no precancerous lesions were found, and 4) lymph node metastasis was detected in only one patient. Mucinous cystic neoplasms were of two types: megacystic and ductectatic. The megacystic type is the classical mucinous cystic neoplasm. The ductectatic type is characterized by the presence of multilocular cysts (reminiscent of bronchiectasia of the lung), and papillary proliferation of the lining epithelium-differing from typical ductal carcinomas as well as from megacystic lesions in terms of morphological features, intrapancreatic location, patient age, and sex. The ductectatic type occurs exclusively in the head and body of the pancreas, and is found predominantly in aging males.

Feasibility of placing a modified fully covered self-expandable metal stent above the papilla to minimize stent-induced bile duct injury in patients with refractory benign biliary strictures (with videos).

PubMed

Moon, Jong Ho; Choi, Hyun Jong; Koo, Hyun Cheol; Han, Seung Hyo; Lee, Tae Hoon; Cho, Young Deok; Park, Sang-Heum; Kim, Sun-Joo

2012-05-01

Endoscopic placement of fully covered self-expandable metal stents (FCSEMS) has been attempted to manage benign biliary strictures, but currently available FCSEMSs may be associated with unintended complications, including de novo strictures, in patients with normal life expectancy. To evaluate the feasibility of an intraductally placed modified FCSEMS to minimize stent-induced bile duct injury in patients with benign biliary strictures. Prospective observational clinical feasibility study. Tertiary-care academic center. This study involved 21 patients with symptomatic benign biliary strictures in whom conventional endoscopic management failed. Strictured segments were 15 mm above the ampulla of Vater. The modified FCSEMS has convex margins, a lasso, and an anti-migrating waist on the central portion. Stents were placed entirely above the papilla and removed after 3 to 5 months. Success, complications, removability, midterm outcome. FCSEMSs were successfully placed inside the bile duct in all patients. No episodes of pancreatitis, cholangitis, or sepsis were noted during the stenting period. Stent migration occurred in 4 patients (19.0%), but 3 were asymptomatic during follow-up. All stents were removed successfully with rat-tooth forceps without complications. Post-stenting cholangiograms showed improvement of strictures in 20 of 21 patients, without de novo focal stricture. The clinical success rate was 95.2%, with one recurrent stricture. The small number and lack of comparison with other types of FCSEMSs. Temporary intraductal placement of a newly modified FCSEMS effectively improved strictures and prevented potential stent-induced complications in patients with benign biliary strictures. Controlled large-scale trials are needed to confirm the long-term efficacy. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Biliary intraductal metastasis from advanced gastric cancer: radiologic and histologic characteristics, and clinical outcomes of percutaneous metallic stent placement.

PubMed

Lee, JooYeon; Gwon, Dong Il; Ko, Gi-Young; Kim, Jong Woo; Sung, Kyu-Bo

2016-06-01

To investigate the radiologic and histological characteristics of biliary intraductal metastasis of advanced gastric cancer and the clinical outcomes of percutaneous, metallic stent placement. We retrospectively assessed 24 patients with obstructive jaundice related to biliary intraductal metastasis of gastric cancers who underwent PTBD and subsequent metallic stent placement between 2003 and 2012. Intraductal metastases appeared as uniform, concentric, linear (n = 17) or band-like (n = 7), enhanced wall thickening on CT, and 20 patients (83.3 %) had cystic ductal lesions. On pathology specimens, malignant cells scattered in the submucosal layer caused a desmoplastic reaction. The technical and clinical success rate of stent placement was achieved in all 24 patients. The median survival time was 203 days. Stent occlusion was observed in four patients with 49-278 days following stent placement. The median stent patency time was 156 days. The radiologic and histological characteristics of biliary intraductal metastasis of advanced gastric cancer consist of uniform, linear or band-like, enhanced biliary wall thickening and malignant cells scattered in the submucosal layer, together with the desmoplastic reaction without any disruption of the epithelial layer. Uncovered metallic stent placement was also a safe and effective method of palliative treatment in these patients. • The CT findings of intraductal metastasis were linear/band-like, enhanced biliary wall thickening. • The histological finding was malignant cells scattered in the submucosal layer. • It showed a desmoplastic reaction without any disruption of the epithelial layer. • Uncovered metallic stent placement was a safe and effective palliative treatment.

Intraductal fibroadenomatosis: an unusual variant of fibroadenoma.

PubMed

Chung, Alice; Scharre, Karen; Wilson, Matthew

2008-01-01

We present a case of a benign breast lesion that contains histopathologic characteristics of fibroadenoma, phyllodes tumor, intraductal adenoma and papilloma. This may represent an unusual variant of fibroadenoma that has not been described in the literature and its likelihood of recurrence is unknown.

Percutaneous Intraductal Radiofrequency Ablation for Extrahepatic Distal Cholangiocarcinoma: A Method for Prolonging Stent Patency and Achieving Better Functional Status and Quality of Life

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Tian-tian, E-mail: matthewwu1979@hotmail.com; Li, Wei-min, E-mail: weimin-li-surgery@126.com; Li, Hu-cheng, E-mail: hucheng-li-surgery@126.com

PurposeThe clinical efficacy of intraductal radiofrequency ablation (RFA) with Habib™ EndoHPB catheter, a newly developed intervention for malignant extrahepatic biliary obstruction, remains uncertain. The aim of this study was to investigate the clinical efficacy of intraductal RFA.MethodsData from 71 patients with extrahepatic distal cholangiocarcinoma were retrospectively analyzed. The study patients were divided into RFA and control groups. The RFA group had undergone percutaneous transhepatic intraductal RFA with a Habib™ EndoHPB catheter, followed by placement of covered or uncovered biliary self-expandable metallic stents (SEMs) whereas the control group had undergone percutaneous transhepatic covered or uncovered SEMs placement. Procedure-related complications, stent patency,more » patient survival, and postoperative serum bilirubin concentrations were compared between the two groups. The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire was administered to evaluate functional status, improvement in clinical manifestations, and quality of life.ResultsThe RFA group had a longer median stent patency than the control group (p = 0.001 for uncovered SEMs placement). Higher functional well-being, hepatobiliary-specific cancer subscale, Trial Outcome Index, and total FACT-Hep scores were observed during post-procedure follow-up in the RFA group. However, median survival did not differ significantly between the two groups (p > 0.05).ConclusionsProlongation of stent patency and better functional status and quality of life, which are all important clinical endpoints, were observed in patients treated with intraductal RFA. Prospective randomized controlled clinical trials are necessary to further investigate the clinical efficacy and long-term benefits of intraductal RFA.« less

Intraductal papilloma in an axillary lymph node of a patient with human immunodeficiency virus: a case report and review of the literature.

PubMed

Cottom, Hannah; Rengabashyam, Bhavani; Turton, Philip E; Shaaban, Abeer M

2014-05-23

Inclusions of ectopic breast tissue in axillary lymph nodes are reported very infrequently and typically are only identified microscopically as an incidental finding. Furthermore the development of a benign proliferative lesion in the form of an intraductal papilloma from intranodal ectopic breast tissue is an extremely rare phenomenon with only three previous cases reported. This report describes an unusual and rare case of an intraductal papilloma arising in an axillary lymph node of a patient known to have the human immunodeficiency virus. A 40-year-old Black African woman underwent excision of an enlarged palpable axillary lymph node. In the preceding 7 years she had received at least six separate surgical excisions to her ipsilateral breast for papillomatosis. The last surgical intervention was performed 1 year prior to presentation with an enlarged axillary lymph node. Histological examination of her axillary lymph node revealed a papillomatous proliferative epithelial lesion within an apparent encompassing duct, resembling a mammary intraductal papilloma. In the surrounding lymphoid tissue small groups of duct-like structures were additionally noted. Immunostaining with a panel of myoepithelial markers in conjunction with oestrogen receptor produced a mixed heterogeneous staining pattern in both the papillomatous lesion and the peripheral duct-like structures. This confirmed the diagnosis of a benign intraductal papilloma within an axillary lymph node, considered to have arisen from ectopic breast tissue. This case demonstrates that intranodal ectopic breast tissue has the potential to undergo benign proliferative change albeit extremely rarely. Therefore this possibility must be considered to ensure the correct diagnosis is made. In addition, to the best of our knowledge, this is the first case report which has described recurrent intraductal papillomas and the subsequent development of an intraductal papilloma within an ipsilateral axillary lymph node, in a patient who is human immunodeficiency virus positive. There is minimal literature investigating the specific types of breast pathologies experienced by patients infected with human immunodeficiency virus and it remains unexplored as to whether human immunodeficiency virus may lead to proliferative papillomatous epithelial changes. This report considers the role of the human papillomavirus and recommends that further investigatory studies are required.

Diagnosis of Nipple Discharge: Value of Magnetic Resonance Imaging and Ultrasonography in Comparison with Ductoscopy.

PubMed

Yılmaz, Ravza; Bender, Ömer; Çelik Yabul, Fatma; Dursun, Menduh; Tunacı, Mehtap; Acunas, Gülden

2017-04-05

Pathologic nipple discharge, which is a common reason for referral to the breast imaging service, refers to spontaneous or bloody nipple discharge that arises from a single duct. The most common cause of nipple discharge is benign breast lesions, such as solitary intraductal papilloma and papillomatosis. Nevertheless, in rare cases, a malignant cause of nipple discharge can be found. To study the diagnostic value of ultrasonography, magnetic resonance imaging, and ductoscopy in patients with pathologic nipple discharge, compare their efficacy, and investigate the importance of magnetic resonance imaging in the diagnosis of intraductal pathologies. Diagnostic accuracy study. Fifty patients with pathologic nipple discharge were evaluated by ultrasonography and magnetic resonance imaging. Of these, 44 ductoscopic investigations were made. The patients were classified according to magnetic resonance imaging, ultrasonography, and ductoscopy findings. A total of 25 patients, whose findings were reported as intraductal masses, underwent surgery oincluding endoscopic excision for two endoscopic excision. Findings were compared with the pathology results that were accepted as the gold standard in the description of the aetiology of nipple discharge. In addition, magnetic resonance imaging, ultrasonography and ductoscopy findings were analysed comparatively in patients who had no surgery. Intraductal masses were reported in 26 patients, 20 of whom operated and established accurate diagnosis of 18 patients on magnetic resonance imaging. According to the ultrasonography, intraductal masses were identified in 22 patients, 17 of whom underwent surgery. Ultrasonography established accurate diagnoses in 15 patients. Intraductal mass was identified in 22 patients and ductoscopy established accurate diagnoses based on histopathologic results in 16 patients. The sensitivities of methods were 75% in ultrasonography, 90% in magnetic resonance imaging, and 94.6% in ductoscopy. The specificities were 66.7% in ultrasonography, 66.7% in magnetic resonance imaging, and 40% in ductoscopy. Intraductal papillomas were mostly observed as oval nodules with well-circumscribed smooth margins within dilated ducts and persistant in the dynamic analysis. Lesions that protruded into the lumen of the ducts, either solitary or multiple, were characteristic ductoscopy findings of our patients who were diagnosed as having papilloma/papillomatosis. Magnetic resonance imaging and ductoscopy had no statistical superiority over each other, however they were superior to ultrasonography in the diagnosis of pathologic nipple discharge. Magnetic resonance imaging may be highly sensitive for diagnosing nipple discharge with new techniques and sequences and a non-invasive method that more advantageous for showing ductal tree visualization and is able to detect completely obstructed intraductal lesions.

Intraductal Radiofrequency Ablation Followed by Locoregional Tumor Treatments for Treating Occluded Biliary Stents in Non-Resectable Malignant Biliary Obstruction: A Single-Institution Experience

PubMed Central

Duan, Xu-Hua; Wang, Yan-Li; Han, Xin-Wei; Ren, Jian-Zhuang; Li, Teng-Fei; Zhang, Jian-Hao; Zhang, Kai; Chen, Peng-Fei

2015-01-01

Objectives To determine the safety and feasibility of intraductal radiofrequency ablation (RFA) followed by locoregional tumor treatments in patients with non-resectable malignant biliary obstruction and stent re-occlusion. Methods Fourteen patients with malignant biliary obstruction and blocked metal stents were studied retrospectively. All had intraductal RFA followed by locoregional tumor treatments and were monitored clinically and radiologically. The practicality, safety, postoperative complications, jaundice remission, stent patency and survival time were analyzed. Results Combination treatment was successful for all patients. There were no severe complications during RFA or local treatments. All patients had stent patency restored, with a decline in serum bilirubin. Three patients had recurrent jaundice by 195, 237 and 357 days; two patients underwent repeat intraductal RFA; and one required an internal-external biliary drain. The average stent patency time was 234 days (range 187-544 days). With a median follow-up of 384 days (range 187-544 days), six patients were alive, while eight had died. There was no mortality at 30 days. The 3, 6, 12 and 18 month survival rates were 100%, 100%, 64.3% and 42.9%, respectively. Conclusion Intraductal RFA followed by locoregional tumor treatments for occluded metal stents is safe and practically feasible and potential increase stent patency and survival times. PMID:26244367

Exploring Early Detection Methods: Using the Intraductal Approach to Predict Breast Cancer

DTIC Science & Technology

2005-06-01

Evidence of intraductal and atypical hyperplasia in from mutations. Prehn (1994) wrote that mutations may have epithelial cells may allow for prediction and...Cler, L., Shivapurkar, N., Milchgrub, S., Peters, G.N., Leitch, Prehn , R.T. (1994). Cancers beget mutations versus mutations beget cancers. A.M., et

Histological changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in high-risk prostate cancer patients

PubMed Central

O’Brien, Catherine; True, Lawrence D.; Higano, Celestia S.; Rademacher, Brooks L. S.; Garzotto, Mark; Beer, Tomasz M.

2011-01-01

Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high risk prostate cancer. Little is known about the clinical significance of post-chemotherapy tumor histopathology. We assessed the prognostic and predictive value of histological features (intraductal carcinoma, vacuolated cell morphology, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with pre-prostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) at 2 and 5 years was 65% and 49%, respectively. In univariate analyses (using Kaplan-Meier method and log-rank tests) intraductal (p=0.001) and cribriform (p=0.014) histologies were associated with shorter RFS. In multivariate analyses, using Cox’s proportional hazards regression, baseline PSA (p=0.004), lymph node metastases (p<0.001), and cribriform histology (p=0.007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (p=0.007) predicted lymph node metastases. Intraductal and cribriform histologies apparently predict post-chemotherapy outcome. PMID:20231619

[Surgical treatment of gynecomastia].

PubMed

Târcoveanu, E; Lupaşcu, C; Vasilescu, A; Moldovanu, R; Ichim, Mihaela; Georgescu, St; Niculescu, D; Dănilă, N; Dimofte, G; Anton, Raluca; Crumpei, Felicia; Florea, Niculina; Ungureanu, Cristina

2008-01-01

Gynecomastia describes a benign increase of the mammary gland in men. When medical treatment fails, the surgical procedure is the treatment of choice. There are two main surgical procedures: subdermal mastectomy and liposuction. To evaluate the results after surgical treatment (mastectomy) performed in a general surgery unit. We performed a retrospective study; all the patients operated for gynecomastia were reviewed. The clinical, imaging, biological, intraoperative and histological data were included into a MS Access database and statistical analyzed. From 1990-2007, 114 patients were admitted in the First Surgical Clinic Iaşi for gynecomastia. Only 12.6% from the patients were with bilateral gynecomastia. The mean age was 40.54 +/- 1.83 years old (range 12-84). Mean body mass was 26.72 +/- 0.46 kg/m2 (range 18.5-41), and about 20% from the patients had a BMI of over 30 kg/m2. We also noted that 46.5% were smokers. Simon classification was used for preoperative staging: 2.6% from the cases (N = 3) were included in stage I, 16.7% (N = 19) in stage IIa, 50% (N = 57) in stage IIb and 30.7% in stage III. The patients included in stages IIa and I are younger then the patients included in stage III (p = 0.024). Mastodynia was noted in 46 cases (40.4%). Ultrasound exam was performed in all the cases, and the larger diameter of the nodule measured was 3.75 +/- 0.18 cm (range 0.5-9.7). Only three cases were preoperatively treated with tamoxifen. Most of the cases were operated using general anesthesia (53.5%). Mastectomy was performed by peri-areolar (70.2%), elliptical (28.9%) or radial (0.9%) incisions. The subdermal mastectomy using peri-areolar approach was performed especially for the cases included in stages I, IIa and IIb--p < 10(-3). The epi-pectoral vacuum drainage has been used in 79.8%. The postoperative morbidity rate was 15.8%--4 cases of hematoma, 13 cases of seroma and 1 case complicated with skin necrosis. No specific risk factors for postoperative complications were found by univariate and multivariate statistical analysis. The pathological exam revealed pseudo-gynecomastia in 6 cases; the other cases presented dilated ducts. We also noted intraductal papillary hyperplasia in 87 cases and chronic inflammation in 35 cases. The histological exam also revealed intraductal papilloma--9 cases, fibro-adenoma--1 case, papillary ductal carcinoma--1 case and mucinous carcinoma--1 case. From all these data, the etiological diagnosis in presented series was: pseudo-gynecomastia--5.3% (N = 6), idiopathic--64.9% (N = 73), endocrine--7.9% (N = 9), drug induce--5.3% (N = 6), metabolic--7.9% (N = 9), tumoral--8.8% (N = 10). The postoperative hospital stay was 4.04 +/- 0.26 days (range 1-12). A literature review has also been performed. The management of gynecomastia has to be performed by a multidisciplinary team. Gynecomastia it is possible to be associated with a breast cancer, even in younger people. The surgical treatment, especially the type of incision, will be chosen from point of view of Simon stages. Liposuction can be associated in selected cases.

Sequencing of intraductal biopsies is feasible and potentially impacts clinical management of patients with indeterminate biliary stricture and cholangiocarcinoma.

PubMed

Bankov, Katrin; Döring, Claudia; Schneider, Markus; Hartmann, Sylvia; Winkelmann, Ria; Albert, Joerg G; Bechstein, Wolf Otto; Zeuzem, Stefan; Hansmann, Martin Leo; Peveling-Oberhag, Jan; Walter, Dirk

2018-04-30

Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies. Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied. Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0-4) as well as 2.3 per biopsy (0-6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen. Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation. The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.

A nomogram based on mammary ductoscopic indicators for evaluating the risk of breast cancer in intraductal neoplasms with nipple discharge.

PubMed

Lian, Zhen-Qiang; Wang, Qi; Zhang, An-Qin; Zhang, Jiang-Yu; Han, Xiao-Rong; Yu, Hai-Yun; Xie, Si-Mei

2015-04-01

Mammary ductoscopy (MD) is commonly used to detect intraductal lesions associated with nipple discharge. This study investigated the relationships between ductoscopic image-based indicators and breast cancer risk, and developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge. A total of 879 consecutive inpatients (916 breasts) with nipple discharge who underwent selective duct excision for intraductal neoplasms detected by MD from June 2008 to April 2014 were analyzed retrospectively. A nomogram was developed using a multivariate logistic regression model based on data from a training set (687 cases) and validated in an independent validation set (229 cases). A Youden-derived cut-off value was assigned to the nomogram for the diagnosis of breast cancer. Color of discharge, location, appearance, and surface of neoplasm, and morphology of ductal wall were independent predictors for breast cancer in multivariate logistic regression analysis. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.36. Area under the curve values of 0.812 (95 % confidence interval (CI) 0.763-0.860) and 0.738 (95 % CI 0.635-0.841) was obtained in the training and validation sets, respectively. The accuracies of the nomogram for breast cancer diagnosis were 71.2 % in the training set and 75.5 % in the validation set. We developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge based on MD image findings. This model may aid individual risk assessment and guide treatment in clinical practice.

Endoscopic treatment of bile duct complications after orthotopic liver transplantation.

PubMed

Polese, L; Cillo, U; Brolese, A; Boccagni, P; Neri, D; Bassi, D; Erroi, F; Zanus, G; D'Amico, D F; Norberto, L

2007-01-01

To assess the indications and results of endoscopic retrograde cholangio-pancreatography (ERCP) in patients who have undergone ortotopic liver transplantation (OLT). We reviewed data from 42 consecutive patients who underwent ERCP for biliary complications after OLT over an 8-year period, in particular recording indications and success of the treatment after a mean of 17 months follow-up. Cholangiograms performed in 33/42 patients (79%) displayed anastomotic strictures in 17 patients (52%), bile duct stones in 8 (24%), both bile duct stones and an anastomotic stricture in 2 (6%), papillary stenosis in 1 (3%), and anastomotic biliary leakage in 1 (3%). In contrast, the contrastogram was normal in four patients (12%). Stone extraction was completed in 9/10 patients (90%) with a mean of 1.2 sessions, while stricture dilation was achieved in 12/19 patients (63%) after a mean of 1.7 sessions, by stent positioning (n = 7), balloon dilation (n = 4), or Soehendra dilator (n = 1). Both biliary leakage and papillary stenosis were cured by ERCP. Only one procedure-related complication -- severe pancreatitis (2.4%) -- was observed and no mortality. ERCP is a safe and effective mode of management of bile duct complications after OLT. It should be attempted before a surgical approach. Better results are obtained for treatment of biliary stones than of anastomotic strictures.

Single-operator EUS-guided cholangiopancreatography for difficult pancreaticobiliary access (with video).

PubMed

Brauer, Brian C; Chen, Yang K; Fukami, Norio; Shah, Raj J

2009-09-01

When conventional ERCP methods fail because of periampullary or ductal obstruction, EUS-guided cholangiopancreatography (EUS-CP) may aid in pancreaticobiliary access. To report our experience when using single-operator EUS-CP. An academic tertiary-referral center. Consecutive patients undergoing EUS-CP were prospectively identified. These patients had undergone failed attempt(s) at therapeutic ERCP. A data sheet was used to record indications, reasons for failed ERCP, EUS-CP visualization of the duct of interest, transpapillary or transenteric intervention, clinical follow-up, and complications. Technical success was decompression of the duct of interest. Clinical success was resolution of jaundice or a > or = 50% reduction in pain or narcotics, as applicable. Between February 2003 and June 2007, EUS-CP was attempted in 20 patients (11 men, 9 women; mean [SD] age 58 +/- 14.9 years). Indications included jaundice (n = 8), biliary stones (n = 3), chronic pancreatitis (n = 6), acute pancreatitis (n = 2), and papillary stenosis (n = 1). Reasons for failed ERCP included periampullary mass (n = 8), intradiverticular papillae (n = 4), and pancreatic duct (PD) stricture (n = 7) or stone (n = 1). Technical success was achieved in 18 of 20 patients (90%). Biliary decompression was obtained in 11 of 12 patients (92%) (7 transpapillary and 4 transenteric-transcholedochal). Pancreatic decompression was obtained in 7 of 8 patients (88%) (3 transpapillary, 4 transgastric). On follow-up, clinical improvement was noted in 15 of 20 patients (70%). For treatment of pain associated with chronic pancreatitis, pain scores decreased by a mean of 1.75 (P = .18). Complications (in 2 of 20 [10%]) included perforation (n = 1) and respiratory failure (n = 1). A single-center nonrandomized observational study with a small patient population. At our academic referral center, single-operator EUS-CP provided decompression of obstructed ducts and may be performed after a failed attempt at conventional ERCP during the same endoscopic session.

Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis: Cross-sectional imaging evaluation

PubMed Central

Lee, Nam Kyung; Kim, Suk; Kim, Hyun Sung; Jeon, Tae Yong; Kim, Gwang Ha; Kim, Dong Uk; Park, Do Youn; Kim, Tae Un; Kang, Dae Hwan

2011-01-01

Various mucin-producing neoplasms originate in different abdominal and pelvic organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging appearance. Mucinous carcinoma, in which at least 50% of the tumor is composed of large pools of extracellular mucin and columns of malignant cells, is associated with a worse prognosis. Signet ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the periphery. Its prognosis is also generally poor. In contrast, intraductal papillary mucinous neoplasm of the bile duct and pancreas, which is characterized by proliferation of ductal epithelium and variable mucin production, has a better prognosis than other malignancies in the pancreaticobiliary tree. Imaging modalities play a critical role in differentiating mucinous from non-mucinous neoplasms. Due to high water content, mucin has a similar appearance to water on ultrasound (US), computed tomography (CT), and magnetic resonance imaging, except when thick and proteinaceous, and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and hypointense on T2-weighted images, compared to water. Therefore, knowledge of characteristic mucin imaging features is helpful to diagnose various mucin-producing neoplastic conditions and to facilitate appropriate treatment. PMID:22147976

Pepducin Based Intervention of Breast Cancer Invasion

DTIC Science & Technology

2006-08-01

low amounts in normal and premalignant atypical intraductal hyperplasia . PAR1 expression levels increased by up to 10-fold in 106 invasive ductal and 17...found in infiltrating ductal carcinomas and very low amounts in normal and premalignant atypical intraductal hyperplasia . PAR1 expression levels...chronic inflammatory conditions (Nelken et al., 1992).Summary Beyond its roles in vascular biology and tissue re- modeling, PAR1 was identified as an

Intraductal glycogen-rich clear cell carcinoma of the breast: a rare presentation and review of the literature.

PubMed

Salemis, Nikolaos S

2012-08-01

Glycogen-rich clear cell carcinoma of the breast is a rare histological subtype of breast cancer, accounting for 0.9-2.8% of all breast cancer cases. Fewer than 100 cases have been reported in the literature. Most of these tumors are invasive carcinomas. The intraductal glycogen-rich clear cell carcinoma is a very rare occurrence. Herein is described a case of a pure intraductal glycogen-rich clear cell carcinoma of the breast in a 42-year-old premenopausal woman. A literature review has also been carried out. Mammography was inconclusive due to the presence of dense breast tissue, but magnetic resonance imaging (MRI) showed several nodular lesions measuring 7 × 6 cm in diameter and involving the upper aspect of the right breast suggestive of multifocal malignancy. A modified radical mastectomy was performed. The patient started hormonal therapy with tamoxifen and is currently well 16 months after surgery. A pure intraductal glycogen-rich clear cell carcinoma of the breast is a very rare occurrence. The case presented here exhibited uncommon MRI features, whereas the tumor size is one of the largest reported in the literature. Mammography may be inconclusive in the presence of dense breast tissue, but MRI is of great importance in the preoperative evaluation of the patient.

Therapeutic effect of intraductal irrigation of the salivary gland: A technical report.

PubMed

Lee, Chena; Kim, Jo-Eun; Huh, Kyoung-Hoe; Yi, Won-Jin; Heo, Min-Suk; Lee, Sam-Sun; Choi, Soon-Chul

2017-06-01

Obstructive and inflammatory disease often occurs in the major salivary glands, and no predictive treatment has yet been developed for this condition. The aim of this report was to introduce an intraductal irrigation procedure and to illustrate its application to practical patient cases. Two patients complaining of pain and swelling in the parotid gland during meals who underwent sialography were diagnosed as having sialodochitis with sialadenitis. Intraductal irrigation was then performed on the parotid gland on the side of the complaint. The irrigation procedure was conducted in the same manner as the sialography procedure, except that saline was used as the filling solution. Symptom severity was evaluated with a numerical rating scale (NRS) at the initial visit and a month after the irrigation. The initial NRS value of patient 1 was 10. The value decreased to 6 and then to 0 after 2 irrigation procedures. The NRS value of patient 2 regarding the symptoms involving the left parotid gland decreased from 4-5 to 1 after 4 irrigation procedures performed at 1-month intervals. Intraductal irrigation of the salivary gland may be a simple, safe, and effective treatment option for patients with obstructive and inflammatory disease of the salivary gland that is capable of resolving their symptoms.

Therapeutic effect of intraductal irrigation of the salivary gland: A technical report

PubMed Central

Lee, Chena; Kim, Jo-Eun; Huh, Kyoung-Hoe; Yi, Won-Jin; Lee, Sam-Sun; Choi, Soon-Chul

2017-01-01

Purpose Obstructive and inflammatory disease often occurs in the major salivary glands, and no predictive treatment has yet been developed for this condition. The aim of this report was to introduce an intraductal irrigation procedure and to illustrate its application to practical patient cases. Materials and Methods Two patients complaining of pain and swelling in the parotid gland during meals who underwent sialography were diagnosed as having sialodochitis with sialadenitis. Intraductal irrigation was then performed on the parotid gland on the side of the complaint. The irrigation procedure was conducted in the same manner as the sialography procedure, except that saline was used as the filling solution. Symptom severity was evaluated with a numerical rating scale (NRS) at the initial visit and a month after the irrigation. Results The initial NRS value of patient 1 was 10. The value decreased to 6 and then to 0 after 2 irrigation procedures. The NRS value of patient 2 regarding the symptoms involving the left parotid gland decreased from 4-5 to 1 after 4 irrigation procedures performed at 1-month intervals. Conclusion Intraductal irrigation of the salivary gland may be a simple, safe, and effective treatment option for patients with obstructive and inflammatory disease of the salivary gland that is capable of resolving their symptoms. PMID:28680849

Nasobiliary drainage after endoscopic papillary balloon dilatation may prevent postoperative pancreatitis

PubMed Central

Xu, Xiao-Dan; Dai, Jian-Jun; Qian, Jian-Qing; Wang, Wei-Jun

2015-01-01

AIM: To evaluate the necessity of endoscopic nasobiliary drainage (ENBD) catheter placement after clearance of common bile duct (CBD) stones. METHODS: Patients enrolled in this study were randomly divided into two groups, according to whether or not they received ENBD after the removal of CBD stones. Group 1 (ENBD group) was then subdivided into three groups: G1a patients received an endoscopic papillary balloon dilatation (EPBD), G1b patients received an endoscopic sphincterotomy (EST), and G1c patients received neither. Group 2 (non-ENBD group) patients were also subdivided into three groups (G2a, G2b, and G2c), similar to Group 1. The maximum CBD diameter, the time for C-reactive protein (CRP) to normalize, levels of serum amylase, total serum bilirubin (TB) and alanine aminotransferase (ALT), and postoperative hospitalization duration (PHD) were measured. RESULTS: A total of 218 patients (139 males, 79 females), with an average age of 60.1 ± 10.8 years, were enrolled in this study. One hundred and thirteen patients who received ENBD were included in Group 1, and 105 patients who did not receive ENBD were included in Group 2. The baseline clinical characteristics were similar in both groups. There were no significant differences in post-endoscopic retrograde cholangiopancreatography (ERCP)-related complications when Groups 1 and 2 were compared. Seventy-seven patients underwent EPBD, and 41 received an ENBD tube (G1a) and 36 did not (G2a). Seventy-three patients underwent EST, and 34 patients received an ENBD tube (G1b) and 39 did not (G2b). The remaining 68 patients underwent neither EPBD nor EST; of these patients, 38 received an ENBD tube (G1c) and 30 did not (G2c). For each of the three pairs of subgroups (G1a vs G2a, G1b vs G2b, G1c vs G2c), there were no significant differences detected in the PHD or the time to normalization of CRP, TB and ALT. In the EPBD group, the incidence of post-ERCP pancreatitis, hyperamylasemia and overall patient complications was significantly higher for G2a (post-ERCP pancreatitis: 6/36 vs 0/41, P = 0.0217; hyperamylasemia: 11/36 vs 4/41, P = 0.0215; overall patient complications: 18/36 vs 7/41, P = 0.0029). CONCLUSION: After successful CBD stone clearance, ENBD is only beneficial when an EPBD procedure has been performed. PMID:25741153

Intraductal Glycogen-Rich Clear Cell Carcinoma of the Breast: A Rare Presentation and Review of the Literature

PubMed Central

Salemis, Nikolaos S.

2012-01-01

Background Glycogen-rich clear cell carcinoma of the breast is a rare histological subtype of breast cancer, accounting for 0.9–2.8% of all breast cancer cases. Fewer than 100 cases have been reported in the literature. Most of these tumors are invasive carcinomas. The intraductal glycogen-rich clear cell carcinoma is a very rare occurrence. Case Report Herein is described a case of a pure intraductal glycogen-rich clear cell carcinoma of the breast in a 42-year-old premenopausal woman. A literature review has also been carried out. Mammography was inconclusive due to the presence of dense breast tissue, but magnetic resonance imaging (MRI) showed several nodular lesions measuring 7 × 6 cm in diameter and involving the upper aspect of the right breast suggestive of multifocal malignancy. A modified radical mastectomy was performed. The patient started hormonal therapy with tamoxifen and is currently well 16 months after surgery. Conclusion A pure intraductal glycogen-rich clear cell carcinoma of the breast is a very rare occurrence. The case presented here exhibited uncommon MRI features, whereas the tumor size is one of the largest reported in the literature. Mammography may be inconclusive in the presence of dense breast tissue, but MRI is of great importance in the preoperative evaluation of the patient. PMID:23904836

Diagnostic and therapeutic direct peroral cholangioscopy using an intraductal anchoring balloon

PubMed Central

Parsi, Mansour A; Stevens, Tyler; Vargo, John J

2012-01-01

AIM: To report our experience using a recently introduced anchoring balloon for diagnostic and therapeutic direct peroral cholangioscopy (DPOC). METHODS: Consecutive patients referred for diagnostic or therapeutic peroral cholangioscopy were evaluated in a prospective cohort study. The patients underwent DPOC using an intraductal anchoring balloon, which was recently introduced to allow consistent access to the biliary tree with an ultraslim upper endoscope. The device was later voluntarily withdrawn from the market by the manufacturer. RESULTS: Fourteen patients underwent DPOC using the anchoring balloon. Biliary access with an ultraslim upper endoscope was accomplished in all 14 patients. In 12 (86%) patients, ductal access required sphincteroplasty with a 10-mm dilating balloon. Intraductal placement of the ultraslim upper endoscope allowed satisfactory visualization of the biliary mucosa to the level of the confluence of the right and left hepatic ducts in 13 of 14 patients (93%). Therapeutic interventions by DPOC were successfully completed in all five attempted cases (intraductal biopsy in one and DPOC guided laser lithotripsy in four). Adverse events occurred in a patient on immunosuppressive therapy who developed an intrahepatic biloma at the site of the anchoring balloon. This required hospitalization and antibiotics. Repeat endoscopic retrograde cholangiopancreatography 8 wk after the index procedure showed resolution of the biloma. CONCLUSION: Use of this anchoring balloon allowed consistent access to the biliary tree for performance of diagnostic and therapeutic DPOC distal to the biliary bifurcation. PMID:22912549

Diagnostic and therapeutic direct peroral cholangioscopy using an intraductal anchoring balloon.

PubMed

Parsi, Mansour A; Stevens, Tyler; Vargo, John J

2012-08-14

To report our experience using a recently introduced anchoring balloon for diagnostic and therapeutic direct peroral cholangioscopy (DPOC). Consecutive patients referred for diagnostic or therapeutic peroral cholangioscopy were evaluated in a prospective cohort study. The patients underwent DPOC using an intraductal anchoring balloon, which was recently introduced to allow consistent access to the biliary tree with an ultraslim upper endoscope. The device was later voluntarily withdrawn from the market by the manufacturer. Fourteen patients underwent DPOC using the anchoring balloon. Biliary access with an ultraslim upper endoscope was accomplished in all 14 patients. In 12 (86%) patients, ductal access required sphincteroplasty with a 10-mm dilating balloon. Intraductal placement of the ultraslim upper endoscope allowed satisfactory visualization of the biliary mucosa to the level of the confluence of the right and left hepatic ducts in 13 of 14 patients (93%). Therapeutic interventions by DPOC were successfully completed in all five attempted cases (intraductal biopsy in one and DPOC guided laser lithotripsy in four). Adverse events occurred in a patient on immunosuppressive therapy who developed an intrahepatic biloma at the site of the anchoring balloon. This required hospitalization and antibiotics. Repeat endoscopic retrograde cholangiopancreatography 8 wk after the index procedure showed resolution of the biloma. Use of this anchoring balloon allowed consistent access to the biliary tree for performance of diagnostic and therapeutic DPOC distal to the biliary bifurcation.

Prognostic significance of atypical papillary urothelial hyperplasia.

PubMed

Swierczynski, Sharon L; Epstein, Jonathan I

2002-05-01

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms. Copyright 2002, Elsevier Science (USA). All rights reserved.

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

ClinicalTrials.gov

2016-12-02

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.

PubMed

Sato, Yasunori; Kinoshita, Masahiko; Takemura, Shigekazu; Tanaka, Shogo; Hamano, Genya; Nakamori, Shoji; Fujikawa, Masahiro; Sugawara, Yasuhiko; Yamamoto, Takatsugu; Arimoto, Akira; Yamamura, Minako; Sasaki, Motoko; Harada, Kenichi; Nakanuma, Yasuni; Kubo, Shoji

2017-03-01

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

The breast lesion excision system (BLES) A preliminary experience.

PubMed

Citgez, Bulent; Atay, Murat; Yetkin, Gu Rkan; Kartal, Abdulcabbar; Mihmanli, Mehmet; Uludag, Mehmet

2016-01-01

BLES (Intact Breast lesion Excision System) is a new defined system which can remove the lesion completely. We aimed to evaluate and compare the results of BLES used for breast lesions requiring histological verification with other percutaneous biopsy methods in the literature. Patients with breast lesions smaller than 20mm and for whom biopsy was indicated were involved in the study. 18(1 male, 17 female, mean age: 41. 83, age range: 26-72) patients were included the study. BLES is applied with a single insertion. Radiofrequency is used to excise the breast tissue after the insertion. Around the lesion, tissue capture basket is moved back and forth. Once captured, the basket and the probe is removed from the incision area. All of the lesions were excised en-bloc. The only complication occured was subdermal hematoma in one case (5.5%) which resolved spontenously. Pathological analysis of the specimens revealed 9 fibroadenoma, 3 fibroadenomatosis hyperplasia, 3 complicated and calcified cysts, 1 ductal epithelial hyperplasia, 1 carcinoma in situ with intraductal papillary carcinoma focus and 1 ductal carcinoma in situ with 2 mm invasive carcinoma focus. The last two cases underwent resectıon and sentınal lymph node procedure. BLES is a is non-invasive method which has no need for additional initiatives in benign cases, provide sufficient samples for pathological diagnosis and remove the lesion in one piece. BLES method can be applied in selected cases. Breast Lesion Excision System, Breast, Biopsy, Radiofrequency, Lesion.

Endoscopic diagnosis of extrahepatic bile duct carcinoma: Advances and current limitations

PubMed Central

Tamada, Kiichi; Ushio, Jun; Sugano, Kentaro

2011-01-01

The accurate diagnosis of extrahepatic bile duct carcinoma is difficult, even now. When ultrasonography (US) shows dilatation of the bile duct, magnetic resonance cholangiopancreatography followed by endoscopic US (EUS) is the next step. When US or EUS shows localized bile duct wall thickening, endoscopic retrograde cholangiopancreatography should be conducted with intraductal US (IDUS) and forceps biopsy. Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity. In patients with papillary type bile duct carcinoma, three biopsies are sufficient. In patients with nodular or infiltrating-type bile duct carcinoma, multiple biopsies are warranted, and IDUS can compensate for the limitations of biopsies. In preoperative staging, the combination of dynamic multi-detector low computed tomography (MDCT) and IDUS is useful for evaluating vascular invasion and cancer depth infiltration. However, assessment of lymph nodes metastases is difficult. In resectable cases, assessment of longitudinal cancer spread is important. The combination of IDUS and MDCT is useful for revealing submucosal cancer extension, which is common in hilar cholangiocarcinoma. To estimate the mucosal extension, which is common in extrahepatic bile duct carcinoma, the combination of IDUS and cholangioscopy is required. The utility of current peroral cholangioscopy is limited by the maneuverability of the “baby scope”. A new baby scope (10 Fr), called “SpyGlass” has potential, if the image quality can be improved. Since extrahepatic bile duct carcinoma is common in the Far East, many researchers in Japan and Korea contributed these studies, especially, in the evaluation of longitudinal cancer extension. PMID:21611097

Broad fibrovascular cores may not be an exclusively benign feature in papillary lesions of the breast: a cautionary note.

PubMed

Yamaguchi, Rin; Tanaka, Maki; Tse, Gary M; Yamaguchi, Miki; Terasaki, Hiroshi; Nomura, Yoriko; Takenaka, Miki; Naito, Yoshiki; Akiba, Jun; Yano, Hirohisa

2014-03-01

A prominent fibrovascular stromal core is one of the widely accepted histological features of breast papillomas, but some papillary carcinomas also show such broad fibrovascular cores, leading to confusion in diagnosis, particularly in needle biopsy specimens. We investigated the histological characteristics of papillary lesions, focusing on broad fibrovascular cores and their relationship with the architectural patterns. Among 185 cases of needle biopsies of papillomas and papillary carcinomas, the number of cases with broad fibrovascular cores in each group was compared. The broad fibrovascular core density in the subsequently resected specimens was evaluated and compared between papillary predominant pattern (papillary structures >80% of tumours) and mixed pattern (papillary, solid, cribriform and others) within the lesions. Significantly more papillary carcinomas than papillomas and B3 atypical papillary lesions had broad fibrovascular cores (p=0.0091 and p=0.0164, respectively). The papillary predominant pattern was more prominent in carcinomas than in papillomas in the needle biopsies (p=0.048) and showed the same tendency in the resections (p=0.058). The broad fibrovascular core density was significantly lower in the 18 papillomas than in the 37 papillary carcinomas (p=0.0079) and was not significantly different between the papillary predominant and mixed patterns in carcinomas and papillomas. Broad fibrovascular cores in mammary papillary lesions are not specific for papillomas, as they are also present focally in papillary carcinomas. As the frequency of papillary carcinoma with broad fibrovascular cores is relatively high, caution in diagnosis has to be exercised, especially in needle biopsy specimens.

p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma.

PubMed

Erickson, L A; Yousef, O M; Jin, L; Lohse, C M; Pankratz, V S; Lloyd, R V

2000-09-01

In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.

Recent Advances in the Classification of Low-grade Papillary-like Thyroid Neoplasms and Aggressive Papillary Thyroid Carcinomas: Evolution of Diagnostic Criteria.

PubMed

Guo, Zhenying; Ge, Minghua; Chu, Ying-Hsia; Asioli, Sofia; Lloyd, Ricardo V

2018-07-01

Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms.

Benign papilloma of the male breast following chronic phenothiazine therapy.

PubMed

Sara, A S; Gottfried, M R

1987-05-01

Benign intraductal papilloma is a rare lesion in the male breast. The authors report the occurrence of an intraductal papilloma in a male with more than a ten-year history of phenothiazine therapy (Mellaril and Prolixin). Phenothiazines have been demonstrated to cause elevated serum prolactin levels. The literature regarding the relationship between prolactin and mammary tumors in rodents and in humans remains controversial. The occurrence of this rare male breast tumor in the setting of chronic phenothiazine therapy raises further questions as to the role of prolactin in the development of mammary tumors.

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1.

PubMed

Casey, Mary B; Lohse, Christine M; Lloyd, Ricardo V

2003-01-01

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.

Differential effect of extracellular matrix derived from papillary and reticular fibroblasts on epidermal development in vitro.

PubMed

Janson, David; Rietveld, Marion; Mahé, Christian; Saintigny, Gaëlle; El Ghalbzouri, Abdoelwaheb

2017-06-01

Papillary and reticular fibroblasts have different effects on keratinocyte proliferation and differentiation. The aim of this study was to investigate whether these effects are caused by differential secretion of soluble factors or by differential generation of extracellular matrix from papillary and reticular fibroblasts. To study the effect of soluble factors, keratinocyte monolayer cultures were grown in papillary or reticular fibroblast-conditioned medium. To study the effect of extracellular matrix, keratinocytes were grown on papillary or reticular-derived matrix. Conditioned medium from papillary or reticular fibroblasts did not differentially affect keratinocyte viability or epidermal development. However, keratinocyte viability was increased when grown on matrix derived from papillary, compared with reticular, fibroblasts. In addition, the longevity of the epidermis was increased when cultured on papillary fibroblast-derived matrix skin equivalents compared with reticular-derived matrix skin equivalents. The findings indicate that the matrix secreted by papillary and reticular fibroblasts is the main causal factor to account for the differences in keratinocyte growth and viability observed in our study. Differences in response to soluble factors between both populations were less significant. Matrix components specific to the papillary dermis may account for the preferential growth of keratinocytes on papillary dermis.

Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience.

PubMed

Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo

2016-06-28

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into "simple" or "complex" growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia).

Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience

PubMed Central

Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo

2016-01-01

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into “simple” or “complex” growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia). PMID:27322430

Clear cell papillary renal cell carcinoma as part of histologically discordant multifocal renal cell carcinoma: A case report and review of literature.

PubMed

Shao, Tiffany; Yousef, Peter; Shipilova, Irina; Saleeb, Rola; Lee, Jason Y; Krizova, Adriana

2016-03-01

Multifocal renal cell carcinoma of different histological subtypes within a single kidney is rare. We report a recently classified clear cell (tubulo) papillary renal cell carcinoma as part of an unusual case of multifocal renal cell carcinoma of discordant histological subtypes. A 57 year-old-man was found to have multiple renal tumors and cysts on imaging and underwent a laparoscopic left radical nephrectomy. Pathological review showed multifocal renal cell carcinoma (clear cell (tubulo) papillary, clear cell and papillary renal cell carcinomas and papillary adenomas). Morphology of clear cell papillary renal cell carcinoma was supported by immunohistochemical profile (CK7+, HMWK+, CAIX+, AMACR-, CD10-, TFE3-). This is the first report of clear cell papillary renal cell carcinoma as part of multifocal renal cell carcinoma of different histological subtypes. Related lineage of clear cell renal cell carcinoma and papillary renal cell carcinoma is supported by the highest prevalence of their combination within multifocal renal cell carcinoma of different histological subtypes along with their molecular interconnection. Clear cell papillary renal cell carcinoma may be uniquely placed between clear cell and papillary renal cell carcinomas since it shows morphological features intermediate between clear cell and papillary renal cell carcinoma along with overlapping but unique immunohistochemical profile. Clear cell papillary renal cell carcinoma may be molecularly related to clear cell and papillary renal cell carcinomas since the tumors overexpress markers of HIF pathway activation with normal/elevated VHL mRNA expression and some tumors show losses of chromosome 3. Due to the overlapping morphology, it is possible that cases of clear cell papillary renal cell carcinoma may have been misclassified as papillary or clear cell renal cell carcinoma in the literature, incorrectly increasing their reported prevalence. Identification of multifocal RCCs may be related to the extent of pathological sampling. Copyright © 2016 Elsevier GmbH. All rights reserved.

Percutaneous transhepatic cholangiography and intraductal radiofrequency ablation combined with biliary stent placement for malignant biliary obstruction.

PubMed

Li, Teng-Fei; Huang, Guo-Hao; Li, Zhen; Hao, Chang-Fu; Ren, Jian-Zhuang; Duan, Xu-Hua; Zhang, Kai; Chen, Chen; Han, Xin-Wei; Jiao, De-Chao; Zhang, Meng-Fan; Wang, Yan-Li

2015-05-01

To determine the safety and feasibility of percutaneous transhepatic cholangiography (PTC) and intraductal radiofrequency (RF) ablation combined with biliary stent placement for malignant biliary obstruction. Data from patients with unresectable malignant biliary obstruction who underwent PTC, intraductal RF ablation, and biliary stent placement (n = 12) or PTC and biliary stent placement only (control group; n = 14) were reviewed. Postoperative complications, jaundice remission, and stent patency were assessed. All procedures were successful. No severe complications (eg, biliary bleeding, perforation) occurred. Two experimental group patients developed cholangitis, which resolved with conservative treatment. The 1-week jaundice remission and 3-month stent patency rates were similar in both groups, but the 6-month stent patency rate was higher in the experimental group (P < .05). In the experimental group, one death occurred as a result of gastrointestinal hemorrhage (unrelated to stent placement) by 3 months, and there were two cases of recurrent jaundice by 6 months. The latter two patients underwent repeat PTC, ablation, and stent placement. In the control group, one death occurred as a result of hepatic failure caused by progressive jaundice at 3 months, and another death resulted from disseminated intravascular coagulation caused by jaundice recurrence at 138 days after stent placement. In addition, seven patients developed jaundice recurrence (50-151 d after stent placement). PTC and repeat stent placement were performed in these patients. Percutaneous transhepatic cholangiography and intraductal RF ablation combined with biliary stent placement for malignant biliary obstruction is safe and feasible and effectively prolongs stent patency time. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid.

PubMed

Nath, Meryl C; Erickson, Lori A

2018-05-01

Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.

Hereditary Papillary Renal Cell Carcinoma

MedlinePlus

... of papillary cancer called type 1 papillary renal cell cancer. Individuals with HPRC have an increased risk of ... that the risk for type 1 papillary renal cell cancer can be passed from generation to generation in ...

Morphological variations of papillary muscles in the mitral valve complex in human cadaveric hearts.

PubMed

Gunnal, Sandhya Arvind; Wabale, Rajendra Namdeo; Farooqui, Mujeebuddin Samsamuddin

2013-01-01

Papillary muscle rupture and dysfunction can lead to complications of prolapsed mitral valve and mitral regurgitation. Multiple operative procedures of the papillary muscles, such as resection, repositioning and realignment, are carried out to restore normal physiological function. Therefore, it is important to know both the variations and the normal anatomy of papillary muscles. This study was carried out on 116 human cadaveric hearts. The left ventricles were opened along the left border in order to view the papillary muscles. The number, shape, position and pattern of the papillary muscles were observed. In this series, the papillary muscles were mostly found in groups instead of in twos, as is described in standard textbooks. Four different shapes of papillary muscles were identified - conical, broad-apexed, pyramidal and fan-shaped. We also discovered various patterns of papillary muscles. No two mitral valve complexes have the same architectural arrangement. Each case seems to be unique. Therefore, it is important for scientists worldwide to study the variations in the mitral valve complex in order to ascertain the reason behind each specific architectural arrangement. This will enable cardiothoracic surgeons to tailor the surgical procedures according to the individual papillary muscle pattern.

Lenvatinib and Pembrolizumab in DTC

ClinicalTrials.gov

2018-05-21

Columnar Cell Variant Thyroid Gland Papillary Carcinoma; Follicular Variant Thyroid Gland Papillary Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Preventive effects of fermented brown rice and rice bran against N-nitrosobis (2-oxopropyl) amine-induced pancreatic tumorigenesis in male hamsters.

PubMed

Kuno, Toshiya; Takahashi, Satoru; Tomita, Hiroyuki; Hisamatsu, Kenji; Hara, Akira; Hirata, Akihiro; Kobayashi, Hiroshi; Mori, Hideki

2015-12-01

Fermented brown rice by Aspergillus oryzae (FBRA) is known to have the potential to prevent chemical carcinogenesis of the colon, liver, esophagus, urinary bladder, stomach and lungs in rodents. The present study examined the possible chemopreventive effects of FBRA on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumorigenesis in hamsters. Five-week-old male Syrian golden hamsters were divided into seven groups. Groups 1-5 were subcutaneously injected with BOP (10 mg/kg body weight) four times during week 6 to induce pancreatic tumors, while groups 6 and 7 were injected with saline. Groups 2 and 3 were fed diets containing 5 and 10% FBRA, respectively, during the initiation phase. By contrast, groups 4 and 5 were fed diets containing 5 and 10% FBRA, respectively, during the post-initiation phase. Group 6 received a diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as the untreated control. At the termination of the study (week 22), oral intake of 10% FBRA (group 5) during the post-initiation phase was identified to have significantly reduced the multiplicity (number of lesions/animal) of ductal adenocarcinoma [pancreatic intraepithelial neoplasia 3 (PanIN3); carcinoma in situ and invasive carcinoma] in comparison with group 1 control hamsters (0.24±0.44 vs. 0.71±0.72; P<0.05). Treatment with 10% FBRA in the post-initiation phase inhibited the progression of normal/precancerous lesions (PanIN1, mild hyperplastic lesions; and PanIN2, papillary hyperplasia) to ductal adenocarcinomas. Furthermore, dietary exposure to 10% FBRA during the initiation (group 3) and post-initiation phases (group 5) significantly reduced the multiplicity of PanIN2 (group 3, 0.55±0.69; group 5, 0.45±0.69; versus group 1, 1.26±1.24; P<0.05 and P<0.01, respectively). A significant reduction of Ki-67 positivity of PanIN2 in group 5 was also confirmed (group 5, 0.05±0.03; group 1, 0.22±0.12; P<0.01). Using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, augmentation of apoptosis by FBRA exposure in the non-lesional ductal epithelium and proliferative lesions was not evident. These findings indicate that FBRA exhibits inhibitory effects on BOP-induced pancreatic tumorigenesis in hamsters due to the reduced proliferation rate of tumor cells. Thus, FBRA may be a promising chemopreventive agent in human pancreatic cancer.

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.

PubMed

Miyai, Kosuke; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.

Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

ClinicalTrials.gov

2014-08-20

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

ClinicalTrials.gov

2018-05-23

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma AJCC v7; Stage I Thyroid Gland Papillary Carcinoma AJCC v7; Stage II Thyroid Gland Follicular Carcinoma AJCC v7; Stage II Thyroid Gland Papillary Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan.

PubMed

Sato, Yasunori; Kubo, Shoji; Takemura, Shigekazu; Sugawara, Yasuhiko; Tanaka, Shogo; Fujikawa, Masahiro; Arimoto, Akira; Harada, Kenichi; Sasaki, Motoko; Nakanuma, Yasuni

2014-01-01

Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of γ-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development.

Changes in laboratory test results and diagnostic imaging presentation before the detection of occupational cholangiocarcinoma.

PubMed

Kubo, Shoji; Takemura, Shigekazu; Sakata, Chikaharu; Urata, Yorihisa; Nishioka, Takayoshi; Nozawa, Akinori; Kinoshita, Masahiko; Hamano, Genya; Nakanuma, Yasuni; Endo, Ginji

2014-01-01

A cholangiocarcinoma outbreak among workers of an offset color proof-printing department in a printing company was recently reported. It is important to understand the clinical course leading to occupational cholangiocarcinoma development for investigation of the carcinogenesis process and for surveillance and early detection. We evaluated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma. We investigated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma in 2 patients because the data were available. Results The clinical courses observed in the 2 participating patients showed persistent elevation of serum γ-glutamyl transpeptidase levels with or without elevated serum levels of alanine aminotransferase and/or aspartate aminotransferase before cholangiocarcinoma detection. Dilatation of the bile ducts without tumor-induced stenosis was observed several years before cholangiocarcinoma detection and progressed gradually in both patients. The serum concentration of carbohydrate 19-9 also increased prior to cholangiocarcinoma detection in both patients. Eventually, observation of stenosis of the bile duct and a space-occupying lesion strongly suggested cholangiocarcinoma. Pathological examination of the resected specimens showed chronic bile duct injury and neoplastic lesions, such as "biliary intraepithelial neoplasia" and "intraductal papillary neoplasm of the bile duct" in various sites of the bile ducts, particularly in the dilated bile ducts. The changes in laboratory test results and diagnostic imaging might be related to the development of cholangiocarcinoma. It is important to monitor diagnostic imaging presentation and laboratory test results in workers with extended exposure to organic solvents.

Warthin tumor-like papillary thyroid carcinoma with a minor dedifferentiated component: report of a case with clinicopathologic considerations.

PubMed

Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano

2010-01-01

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course.

Warthin Tumor-Like Papillary Thyroid Carcinoma with a Minor Dedifferentiated Component: Report of a Case with Clinicopathologic Considerations

PubMed Central

Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano

2010-01-01

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course. PMID:20593036

The many faces and mimics of papillary thyroid carcinoma.

PubMed

Albores-Saavedra, Jorge; Wu, Jianhua

2006-01-01

This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto's thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.

Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture.

PubMed

Janson, David; Saintigny, Gaëlle; Mahé, Christian; El Ghalbzouri, Abdoelwaheb

2013-01-01

The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high-passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high-passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti-skin-ageing strategies. © 2013 John Wiley & Sons A/S.

Sequential algorithm analysis to facilitate selective biliary access for difficult biliary cannulation in ERCP: a prospective clinical study.

PubMed

Lee, Tae Hoon; Hwang, Soon Oh; Choi, Hyun Jong; Jung, Yunho; Cha, Sang Woo; Chung, Il-Kwun; Moon, Jong Ho; Cho, Young Deok; Park, Sang-Heum; Kim, Sun-Joo

2014-02-17

Numerous clinical trials to improve the success rate of biliary access in difficult biliary cannulation (DBC) during ERCP have been reported. However, standard guidelines or sequential protocol analysis according to different methods are limited in place. We planned to investigate a sequential protocol to facilitate selective biliary access for DBC during ERCP. This prospective clinical study enrolled 711 patients with naïve papillae at a tertiary referral center. If wire-guided cannulation was deemed to have failed due to the DBC criteria, then according to the cannulation algorithm early precut fistulotomy (EPF; cannulation time > 5 min, papillary contacts > 5 times, or hook-nose-shaped papilla), double-guidewire cannulation (DGC; unintentional pancreatic duct cannulation ≥ 3 times), and precut after placement of a pancreatic stent (PPS; if DGC was difficult or failed) were performed sequentially. The main outcome measurements were the technical success, procedure outcomes, and complications. Initially, a total of 140 (19.7%) patients with DBC underwent EPF (n = 71) and DGC (n = 69). Then, in DGC group 36 patients switched to PPS due to difficulty criteria. The successful biliary cannulation rate was 97.1% (136/140; 94.4% [67/71] with EPF, 47.8% [33/69] with DGC, and 100% [36/36] with PPS; P < 0.001). The mean successful cannulation time (standard deviation) was 559.4 (412.8) seconds in EPF, 314.8 (65.2) seconds in DGC, and 706.0 (469.4) seconds in PPS (P < 0.05). The DGC group had a relatively low successful cannulation rate (47.8%) but had a shorter cannulation time compared to the other groups due to early switching to the PPS method in difficult or failed DGC. Post-ERCP pancreatitis developed in 14 (10%) patients (9 mild, 1 moderate), which did not differ significantly among the groups (P = 0.870) or compared with the conventional group (P = 0.125). Based on the sequential protocol analysis, EPF, DGC, and PPS may be safe and feasible for DBC. The use of EPF in selected DBC criteria, DGC in unintentional pancreatic duct cannulations, and PPS in failed or difficult DGC may facilitate successful biliary cannulation.

[The Management of Common Bile Duct Stones].

PubMed

Park, Chang Hwan

2018-05-25

Common bile duct (CBD) stone is a relatively frequent disorder with a prevalence of 10-20% in patients with gallstones. This is also associated with serious complications, including obstructive jaundice, acute suppurative cholangitis, and acute pancreatitis. Early diagnosis and prompt treatment is the most important for managing CBD stones. According to a recent meta-analysis, endoscopic ultrasonography and magnetic resonance cholangiopancreatography have high sensitivity, specificity, and accuracy for the diagnosis of CBD stones. Endoscopic ultrasonography, in particular, has been reported to have higher sensitivity between them. A suggested management algorithm for patients with symptomatic gallstones is based on whether they are at low, intermediate, or high probability of CBD stones. Single-stage laparoscopic CBD exploration and cholecystectomy is superior to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy with respect to technical success and shorter hospital stay in high risk patients with gallstones and CBD stones, where expertise, operative time, and instruments are available. ERCP plus laparoscopic cholecystectomy is usually performed to treat patients with CBD stones and gallstones in many institutions. Patients at intermediate probability of CBD stones after initial evaluation benefit from additional biliary imaging. Patients with a low probability of CBD stones should undergo cholecystectomy without further evaluation. Endoscopic sphincterotomy and endoscopic papillary balloon dilation in ERCP are the primary methods for dilating the papilla of Vater for endoscopic removal of CBD stones. Endoscopic papillary large balloon dilation is now increasingly performed due to the usefulness in the management of giant or difficult CBD stones. Scheduled repeated ERCP may be considered in patients with high risk of recurrent CBD stones.

Surgical relocation of the papillary muscles in functional ischemic mitral regurgitation: what are the forces of the relocation stitches acting on the myocardium?

PubMed

Jensen, Henrik; Jensen, Morten O; Vind-Kezunovic, Stefan; Vestergaard, Rikke; Ringgaard, Steffen; Smerup, Morten H; Hønge, Jesper L; Hasenkam, J Michael; Nielsen, Sten L

2013-07-01

In patients with chronic functional ischemic mitral regurgitation (FIMR), papillary muscle relocation has the potential to induce reverse left ventricular remodeling. However, in order to optimize function and durability, the forces imposed on the left ventricular myocardium by papillary muscle relocation should be assessed. Eight pigs with FIMR were subjected to down-sized ring annuloplasty in combination with relocation of the anterior (5 mm) and posterior (15 mm) papillary muscles towards the respective trigone. Papillary muscle relocation was obtained by a 2-0 expanded polytetrafluoroethylene stitch fixed to the trigone, exteriorized through the myocardium overlying the papillary muscle, and fixed to an epicardial disc. Tension in these stitches was measured at a systolic blood pressure > 80 mmHg using a custom-made sliding caliper with a strain gauge mounted in line. This allowed assessment of the cyclic change from minimal diastolic to maximum systolic papillary muscle relocation stitch tension. Maximum cyclic change in the posterior papillary muscle (PPM) stitch tension was 1.1 N at 15 mm relocation. In comparison, the anterior papillary muscle (APM) tension was increased to a maximum of 1.4 N with only 5 mm relocation. Surprisingly, during each step of isolated PPM relocation, the APM stitch tension increased concomitantly, but in contrast APM relocation did not influence the magnitude of PPM stitch tension. There was no statistically significant difference between cyclic changes in APM and PPM stitch tension at any step of relocation. Papillary muscle relocation using stitches attached between epicardial discs and respective trigones induced a cyclic change in papillary muscle relocation stitch tension of 1.1-1.4 N. These values were in the range of normal tension in the mitral valve apparatus, and equivalent to only 19-24% of the total papillary muscle forces. Therefore, this technique does not appear to induce a non-physiologically high cyclic load on the mitral valve complex.

Assessment of the rotation motion at the papillary muscle short-axis plane with normal subjects by two-dimensional speckle tracking imaging: a basic clinical study.

PubMed

Ni, Xian-Da; Huang, Jun; Hu, Yuan-Ping; Xu, Rui; Yang, Wei-Yu; Zhou, Li-Ming

2013-01-01

The aim of this study was to observe the rotation patterns at the papillary muscle plane in the Left Ventricle(LV) with normal subjects using two-dimensional speckle tracking imaging(2D-STI). We acquired standard of the basal, the papillary muscle and the apical short-axis images of the LV in 64 subjects to estimate the LV rotation motion by 2D-STI. The rotational degrees at the papillary muscle short-axis plane were measured at 15 different time points in the analysis of two heart cycles. There were counterclockwise rotation, clockwise rotation, and counterclockwise to clockwise rotation at the papillary muscle plane in the LV with normal subjects, respectively. The ROC analysis of the rotational degrees was performed at the papillary muscle short-axis plane at the peak LV torsion for predicting whether the turnaround point of twist to untwist motion pattern was located at the papillary muscle level. Sensitivity and specificity were 97% and 67%, respectively, with a cut-off value of 0.34°, and an area under the ROC curve of 0.8. At the peak LV torsion, there was no correlation between the rotational degrees at the papillary muscle short-axis plane and the LVEF in the normal subjects(r = 0.000, p = 0.998). In the study, we conclude that there were three rotation patterns at the papillary muscle short-axis levels, and the transition from basal clockwise rotation to apical counterclockwise rotation is located at the papillary muscle level.

Renal papillary calcification and the development of calcium oxalate monohydrate papillary renal calculi: a case series study.

PubMed

Grases, Fèlix; Costa-Bauzá, Antonia; Prieto, Rafel M; Conte, Antonio; Servera, Antonio

2013-03-11

The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi. From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis. The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency. Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi.

AAV-mediated pancreatic overexpression of Igf1 counteracts progression to autoimmune diabetes in mice.

PubMed

Mallol, Cristina; Casana, Estefania; Jimenez, Veronica; Casellas, Alba; Haurigot, Virginia; Jambrina, Claudia; Sacristan, Victor; Morró, Meritxell; Agudo, Judith; Vilà, Laia; Bosch, Fatima

2017-07-01

Type 1 diabetes is characterized by autoimmune destruction of β-cells leading to severe insulin deficiency. Although many improvements have been made in recent years, exogenous insulin therapy is still imperfect; new therapeutic approaches, focusing on preserving/expanding β-cell mass and/or blocking the autoimmune process that destroys islets, should be developed. The main objective of this work was to test in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, the effects of local expression of Insulin-like growth factor 1 (IGF1), a potent mitogenic and pro-survival factor for β-cells with immunomodulatory properties. Transgenic NOD mice overexpressing IGF1 specifically in β-cells (NOD-IGF1) were generated and phenotyped. In addition, miRT-containing, IGF1-encoding adeno-associated viruses (AAV) of serotype 8 (AAV8-IGF1-dmiRT) were produced and administered to 4- or 11-week-old non-transgenic NOD females through intraductal delivery. Several histological, immunological, and metabolic parameters were measured to monitor disease over a period of 28-30 weeks. In transgenic mice, local IGF1 expression led to long-term suppression of diabetes onset and robust protection of β-cell mass from the autoimmune insult. AAV-mediated pancreatic-specific overexpression of IGF1 in adult animals also dramatically reduced diabetes incidence, both when vectors were delivered before pathology onset or once insulitis was established. Transgenic NOD-IGF1 and AAV8-IGF1-dmiRT-treated NOD animals had much less islet infiltration than controls, preserved β-cell mass, and normal insulinemia. Transgenic and AAV-treated islets showed less expression of antigen-presenting molecules, inflammatory cytokines, and chemokines important for tissue-specific homing of effector T cells, suggesting IGF1 modulated islet autoimmunity in NOD mice. Local expression of Igf1 by AAV-mediated gene transfer counteracts progression to diabetes in NOD mice. This study suggests a therapeutic strategy for autoimmune diabetes in humans.

The relationship between dermal papillary structure and skin surface properties, color, and elasticity.

PubMed

Mizukoshi, K; Nakamura, T; Oba, A

2016-08-01

The skin contains an undulating structure called the dermal papillary structure between the border of the epidermis and dermis. The physiological importance of the dermal papillary structures has been discussed, however, the dermal papillary structures have never been evaluated for their contribution to skin appearance. In this study, we investigated the correlation between the dermal papillary structure and skin color and elasticity. In addition, the relationship was validated with skin model experiments. The dermal papillary structures in the skin of the female cheek were quantitatively measured by in vivo confocal laser scanning microscopy images. In addition, the skin color and elasticity were measured at the same site. A skin model with dermal papilla-like structures was created by referring to the optical and shape properties of the skin using agar gel and a scattering sheet. Correlations were found between the dermal papillary structures and skin color irregularity and skin elasticity. These relationships were verified by the experiments employing a skin model. The results of this study indicated that the dermal papillary structure is also an important factor for skin appearance such as color and elasticity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Papillary endothelial hyperplasia in angiokeratoma.

PubMed

Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

2003-01-01

Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

Assessment of the Rotation Motion at the Papillary Muscle Short-Axis Plane with Normal Subjects by Two-Dimensional Speckle Tracking Imaging: A Basic Clinical Study

PubMed Central

Ni, Xian-Da; Huang, Jun; Hu, Yuan-Ping; Xu, Rui; Yang, Wei-Yu; Zhou, Li-Ming

2013-01-01

Background The aim of this study was to observe the rotation patterns at the papillary muscle plane in the Left Ventricle(LV) with normal subjects using two-dimensional speckle tracking imaging(2D-STI). Methods We acquired standard of the basal, the papillary muscle and the apical short-axis images of the LV in 64 subjects to estimate the LV rotation motion by 2D-STI. The rotational degrees at the papillary muscle short-axis plane were measured at 15 different time points in the analysis of two heart cycles. Results There were counterclockwise rotation, clockwise rotation, and counterclockwise to clockwise rotation at the papillary muscle plane in the LV with normal subjects, respectively. The ROC analysis of the rotational degrees was performed at the papillary muscle short-axis plane at the peak LV torsion for predicting whether the turnaround point of twist to untwist motion pattern was located at the papillary muscle level. Sensitivity and specificity were 97% and 67%, respectively, with a cut-off value of 0.34°, and an area under the ROC curve of 0.8. At the peak LV torsion, there was no correlation between the rotational degrees at the papillary muscle short-axis plane and the LVEF in the normal subjects(r = 0.000, p = 0.998). Conclusions In the study, we conclude that there were three rotation patterns at the papillary muscle short-axis levels, and the transition from basal clockwise rotation to apical counterclockwise rotation is located at the papillary muscle level. PMID:24376634

Thyroid cancer - papillary carcinoma

MedlinePlus

... this page: //medlineplus.gov/ency/article/000331.htm Thyroid cancer - papillary carcinoma To use the sharing features on ... the lower neck. Causes About 80% of all thyroid cancers diagnosed in the United States are the papillary ...

Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern.

PubMed

Têtu, B; Vaillancourt, L; Camilleri, J P; Bruneval, P; Bernier, L; Tourigny, R

1993-11-01

We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.

Renal papillary calcification and the development of calcium oxalate monohydrate papillary renal calculi: a case series study

PubMed Central

2013-01-01

Background The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi. Methods From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis. Results The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency. Conclusions Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi. PMID:23497010

Percutaneous Intraductal Radiofrequency Ablation Combined with Biliary Stent Placement for Nonresectable Malignant Biliary Obstruction Improves Stent Patency but not Survival.

PubMed

Wang, Jianfeng; Zhao, Lizhen; Zhou, Chuanguo; Gao, Kun; Huang, Qiang; Wei, Baojie; Gao, Jun

2016-04-01

Although radiofrequency (RF) ablation has been accepted as a curative treatment modality for solid organ tumors, intraductal RF ablation for malignant biliary obstruction has not been widely described. The aim of this study was to evaluate the feasibility, safety, and efficacy (in terms of stent patency and survival) of intraductal RF ablation combined with biliary stent placement for nonresectable malignant biliary obstruction. A search of the nonresectable malignant extrahepatic biliary obstruction database (179 patients) identified 18 consecutive patients who were treated with biliary intraluminal RF ablation during percutaneous transhepatic cholangiodrainage and inner stent placement (RF ablation group) and 18 patients who underwent inner stent placement without biliary intraluminal RF ablation (control group). The patients were matched for tumor type, location of obstruction, tumor stage, and Child-Pugh class status. Primary endpoints included safety, stent patency time, and survival rates. The secondary endpoint was effectiveness of the technique. The RF ablation and control groups were closely matched in terms of age, diagnosis, presence of metastases, presence of locally advanced tumor, American Society of Anesthesiologists (ASA) grade, and chemotherapy regimen (all P > 0.05). The technical success rate for both groups was 100%. The median time of stent patency in the RF ablation and control groups were 5.8 (2.8-11.5) months and 4.5 (2.4-8.0) months, respectively (Kaplan-Meier analysis: P = 0.03). The median survival times in the RF ablation and control groups were 6.1 (4.8-15.2) months and 5.8 (4.2-16.5) months, with no significant difference according to Kaplan-Meier analysis (P = 0.45). In univariate and multivariate analyses, poorer overall survival was associated with advanced age and presence of metastases (P < 0.05). Intraductal RF ablation combined with biliary stent placement for nonresectable malignant biliary obstruction is safe and feasible and effectively increases stent patency time. However, it does not improve patient survival.

Intraductal Transanastomotic Stenting in Duct-to-Duct Biliary Reconstruction after Living-Donor Liver Transplantation: A Randomized Trial.

PubMed

Santosh Kumar, K Y; Mathew, Johns Shaji; Balakrishnan, Dinesh; Bharathan, Viju Kumar; Thankamony Amma, Binoj Sivasankara Pillai; Gopalakrishnan, Unnikrishnan; Narayana Menon, Ramachandran; Dhar, Puneet; Vayoth, Sudheer Othiyil; Sudhindran, Surendran

2017-12-01

Biliary complications continue to be the "Achilles heel" of living-donor liver transplantation (LDLT). The use of biliary stents in LDLT to reduce biliary complications is a controversial issue. We performed a randomized trial to study the impact of intraductal biliary stents on postoperative biliary complications after LDLT. Of the 94 LDLTs that were performed during a period of 16 months, ABO-incompatible transplants, left lobe grafts, 3 or more bile ducts on the graft, and those requiring bilioenteric drainage were excluded. Eligible patients were randomized to either a study arm (intraductal stent, n = 31) or a control arm (no stent, n = 33) by block randomization. Stratification was done, based on the number of ducts on the graft requiring anastomosis, into single (n = 20) or 2 ducts (n = 44). Ureteric stents of 3F to 5F placed across the biliary anastomosis and exiting into the duodenum for later endoscopic removal at 3 months were used. The primary end point was postoperative bile leak. Bile leak occurred in 15 of 64 (23.4%), the incidence was higher in the stented group compared with the control group (35.5% vs 12.1%; p = 0.03). Multiplicity of bile ducts and stenting were identified as risk factors for bile leak on multivariate analysis (p = 0.031 and p = 0.032). During a median follow-up of 2 years, biliary stricture developed in 9 patients (14.1%). Postoperative bile leak is a significant risk factor for the development of biliary stricture (p = 0.003). Intraductal transanastomotic biliary stenting and multiplicity of graft ducts were identified as independent risk factors for the development of postoperative biliary complications. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-05-15

Metastatic Thyroid Gland Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

Shear-Wave Elastography for the Differential Diagnosis of Breast Papillary Lesions

PubMed Central

Chung, Jin; Lee, Won Kyung; Cha, Eun-Suk; Lee, Jee Eun; Kim, Jeoung Hyun; Ryu, Young Hoon

2016-01-01

Objective To evaluate the diagnostic performance of shear-wave elastography (SWE) for the differential diagnosis of breast papillary lesions. Methods This study was an institutional review board-approved retrospective study, with a waiver of informed consent. A total of 79 breast papillary lesions in 71 consecutive women underwent ultrasound and SWE prior to biopsy. Ultrasound features and quantitative SWE parameters were recorded for each lesion. All lesions were surgically excised or excised using an ultrasound-guided vacuum-assisted method. The diagnostic performances of the quantitative SWE parameters were compared using the area under the receiver operating characteristic curve (AUC). Results Of the 79 lesions, six (7.6%) were malignant and 12 (15.2%) were atypical. Orientation, margin, and the final BI-RADS ultrasound assessments were significantly different for the papillary lesions (p < 0.05). All qualitative SWE parameters were significantly different (p < 0.05). The AUC values for SWE parameters of benign and atypical or malignant papillary lesions ranged from 0.707 to 0.757 (sensitivity, 44.4–94.4%; specificity, 42.6–88.5%). The maximum elasticity and the mean elasticity showed the highest AUC (0.757) to differentiate papillary lesions. Conclusion SWE provides additional information for the differential diagnosis of breast papillary lesions. Quantitative SWE features were helpful to differentiate breast papillary lesions. PMID:27893857

The CAROLE (CArdiac Related Oncologic Late Effects) Study

ClinicalTrials.gov

2018-03-29

Coronary Artery Disease; Cardiac Disease; Cardiac Toxicity; Radiation; Radiation Therapy; Atherosclerotic Heart Disease; Cardiotoxicity; Breast Cancer; Lung Cancer; Lymphoma; Cancer; Carcinoma, Intraductal, Noninfiltrating

PATHOLOGIC EVALUATION AND REPORTING OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS (IPMNs) OF THE PANCREAS AND OTHER TUMORAL INTRAEPITHELIAL NEOPLASMS OF PANCREATOBILIARY TRACT: RECOMMENDATIONS OF VERONA CONSENSUS MEETING

PubMed Central

Adsay, Volkan; Mino-Kenudson, Mari; Furukawa, Toru; Basturk, Olca; Zamboni, Giuseppe; Marchegiani, Giovanni; Bassi, Claudio; Salvia, Roberto; Malleo, Giuseppe; Paiella, Salvatore; Wolfgang, Christopher L.; Matthaei, Hanno; Offerhaus, G. Johan; Adham, Mustapha; Bruno, Marco J.; Reid, Michelle; Krasinskas, Alyssa; Klöppel, Günter; Ohike, Nobuyuki; Tajiri, Takuma; Jang, Kee-Taek; Roa, Juan Carlos; Allen, Peter; Castillo, Carlos Fernández-del; Jang, Jin-Young; Klimstra, David S.; Hruban, Ralph H.

2015-01-01

Background There are no established guidelines for pathologic diagnosis/reporting of IPMNs. Design An international multidisciplinary group brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. Results 1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. 2) Invasive component is to be documented in a full synoptic report including its size, type, grade, stage. 3) The term “minimally invasive” should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤0.5, >0.5–≤1, >1 cm), is to be documented. 4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. 5) A category of “indeterminate/(suspicious) for invasion” is acceptable for rare cases. 6) The term “malignant” IPMN should be avoided. 7) The highest grade of dysplasia in the non-invasive component is to be documented separately. 8) Lesion size is to be correlated with imaging findings in cysts with rupture. 9) The main duct diameter, and if possible, its involvement is to be documented; however, it is not required to provide main vs branch duct classification in the resected tumor. 10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. 11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. 12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, intra-biliary/cholecystic). Conclusion These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms. PMID:25775066

Management of benign papilloma without atypia diagnosed at ultrasound-guided core needle biopsy: Scoring system for predicting malignancy.

PubMed

Ahn, Soo Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Min Kyoon; Noh, Dong-Young; Jung, Bong-Wha; Kim, Sung-Won; Ko, Eunyoung

2018-01-01

The management of benign intraductal papilloma diagnosed on core needle biopsy (CNB) remains unclear. This study was designed to evaluate factors predicting malignancy in patients diagnosed with benign papilloma without atypia at ultrasound-guided CNB and to develop a scoring system predicting malignancy based on clinical, radiological and pathological factors on further excisional biopsy. The study enrolled patients diagnosed with benign papillomas (including benign and atypical papillary lesions) at CNB. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict malignancy. A total of 520 CNBs were diagnosed with benign or atypical papilloma. Of these, 452 were benign papilloma without atypia. Of the 250 lesions subsequently excised surgically from 234 women, 17 (6.8%) were diagnosed with malignancy. Multivariate analysis revealed that bloody nipple discharge, size on imaging ≥15 mm, BI-RADS≥4b, peripheral location and palpability were independent predictors of malignancy. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The area under the ROC curve was 0.947 (95% CI: 0.913-0.981, p < 0.001) and a negative predictive value was 100%. In a validation set of 62 patients, an area under the ROC curve was 0.926 (95% CI: 0.857-0.995, p < 0.001). A scoring system predicting malignancy in patients diagnosed by CNB with benign papilloma without atypia was developed. This system was able to identify a subset of patients with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Agreement among Magnetic Resonance Imaging/Magnetic Resonance Cholangiopancreatography (MRI-MRCP) and Endoscopic Ultrasound (EUS) in the evaluation of morphological features of Branch Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN).

PubMed

Uribarri-Gonzalez, Laura; Keane, Margaret G; Pereira, Stephen P; Iglesias-García, Julio; Dominguez-Muñoz, J Enrique; Lariño-Noia, Jose

2018-03-01

To evaluate the agreement between the imaging modalities MRI-MRCP and EUS in cystic lesions of the pancreas which were thought to be a BD-IPMN. Multicenter retrospective study included all patients between 2010 and 2015 with a suspected BD-IPMN who underwent an EUS and MRI-MRCP within 6 months or less of each other. Location, number, size, worrisome features and high-risk stigmata were evaluated. Interobserver agreement was evaluated by Kappa score. 173 patients were included (97 UHSC, 76 UCLH-RFH), mean age 65 (range 25-87 years), 66 males. When comparing both modalities there was good agreement for the location of the cyst. The median lesion size was larger by MRI-MRCP than EUS although it was not significant. With regards to worrisome features, there was moderate agreement for main PD of 5-9 mm and abrupt change (k = 0.45 and 0.52). Fair agreement was seen for the cyst wall thickening (k = 0.25). No agreement was seen between the presence of non-enhanced mural nodules or lymphadenopathy (k < 0). With regards to high-risk stigmata, poor agreement was obtained for the detection of an enhanced solid component (k = 0.12). No agreement was observed for main PD > 10 mm (k < 0). In this multicentre study of patients with a BD-IPMN under active surveillance, most disagreement between these modalities was seen in the proximal pancreas. There was generally only minimal concordance between the imaging findings of EUS and MRI-MRCP for the detection of high-risk stigmata and worrisome features. Copyright © 2018 IAP and EPC. All rights reserved.

Solid pseudopapillary neoplasm of the pancreas: report of a rare case and review of the literature.

PubMed

Yener, Arzu Neşe; Manukyan, Manuk; Mıdı, Ahmet; Cubuk, Rahmi

2014-01-01

Solid pseudopapillary neoplasm, a rare primary neoplasm of the pancreas that typically affects young women, is a relatively indolent entity with favorable prognosis. We here report a 20-year-old young girl with solid pseudopapillary neoplasm who presented with mild dull abdominal discomfort without any significant laboratory findings. On MRI, a heterogenous mass was found at the distal pancreas. The patient underwent en-block distal pancreatectomy with splenectomy with the presumptive diagnosis of cystic neoplasm of the pancreas. The tumor was well-circumscribed, encapsulated, 5.5 cm in the greatest dimension and showed typical papillary and pseudopapillary structures. Capsular invasion was seen on focal areas. The patient was not given any adjuvant therapy and shows no sign of disease after six months follow-up. It is important to differentiate this tumor from other pancreatic neoplasms because this neoplasm is amenable to cure after complete surgical resection even in cases with capsular invasion, unlike malignant tumors of the pancreas.

Management of late biliary complications in patients with gallbladder stones in situ after endoscopic papillary balloon dilation.

PubMed

Tsujino, Takeshi; Kawabe, Takao; Isayama, Hiroyuki; Yashima, Yoko; Yagioka, Hiroshi; Kogure, Hirofumi; Sasaki, Takashi; Arizumi, Toshihiko; Togawa, Osamu; Ito, Yukiko; Matsubara, Saburo; Nakai, Yousuke; Sasashira, Naoki; Hirano, Kenji; Tada, Minoru; Omata, Masao

2009-04-01

Patients with untreated gallbladder stones in situ are at high risk for late biliary complications after endoscopic papillary balloon dilation (EPBD) and bile duct stone extraction. Few data exist on the short-term and long-term results in these patients after the recurrence of bile duct stones and acute cholecystitis. The aim of this study was to evaluate the outcome of late biliary complications in patients with gallbladder stones in situ after EPBD. Fifty-six patients who developed late biliary complications, including bile duct stone recurrence (n=43) and acute cholecystitis (n=13), were managed at our institutions. We investigated the short-term and long-term outcomes after the management of late biliary complications. Complete removal of recurrent bile duct stones was achieved in 38 of 43 patients (88%) by repeated EPBD alone. Pancreatitis after repeated EPBD occurred in two patients (5%). After successful bile duct stone extraction by EPBD, none of the 16 patients who underwent cholecystectomy developed late biliary complications (mean follow-up period of 5.2 years), wheras re-recurrent bile duct stones occurred in three of the 21 patients (14%) with gallbladder stones left in situ (mean follow-up period of 4.4 years)(P=0.1148). Re-recurrent bile duct stones were successfully treated endoscopically. One of the eight patients who did not undergo cholecystectomy for acute cholecystitis had a recurrence of cholecystitis, which was managed conservatively. The long-term outcomes of late biliary complications are favorable when patients with concomitant gallbladder stones undergo cholecystectomy. Re-recurrent bile duct stones are considerable when gallbladder stones are left in situ, but should be treated endoscopically.

Management of late biliary complications in patients with gallbladder stones in situ after endoscopic papillary balloon dilation.

PubMed

Tsujino, Takeshi; Kawabe, Takao; Isayama, Hiroyuki; Yashima, Yoko; Yagioka, Hiroshi; Kogure, Hirofumi; Sasaki, Takashi; Arizumi, Toshihiko; Togawa, Osamu; Ito, Yukiko; Matsubara, Saburo; Nakai, Yousuke; Sasashira, Naoki; Hirano, Kenji; Tada, Minoru; Omata, Masao

2009-04-01

Patients with untreated gallbladder stones in situ are at high risk for late biliary complications after endoscopic papillary balloon dilation (EPBD) and bile duct stone extraction. Few data exist on the short-term and long-term results in these patients after the recurrence of bile duct stones and acute cholecystitis. The aim of this study was to evaluate the outcome of late biliary complications in patients with gallbladder stones in situ after EPBD. Fifty-six patients who developed late biliary complications, including bile duct stone recurrence (n=43) and acute cholecystitis (n=13), were managed at our institutions. We investigated the short-term and long-term outcomes after the management of late biliary complications. Complete removal of recurrent bile duct stones was achieved in 38 of 43 patients (88%) by repeated EPBD alone. Pancreatitis after repeated EPBD occurred in two patients (5%). After successful bile duct stone extraction by EPBD, none of the 16 patients who underwent cholecystectomy developed late biliary complications (mean follow-up period of 5.2 years), whereas re-recurrent bile duct stones occurred in three of the 21 patients (14%) with gallbladder stones left in situ (mean follow-up period of 4.4 years)(P=0.1148). Re-recurrent bile duct stones were successfully treated endoscopically. One of the eight patients who did not undergo cholecystectomy for acute cholecystitis had a recurrence of cholecystitis, which was managed conservatively. The long-term outcomes of late biliary complications are favorable when patients with concomitant gallbladder stones undergo cholecystectomy. Re-recurrent bile duct stones are considerable when gallbladder stones are left in situ, but should be treated endoscopically.

Is endoscopic papillary large balloon dilation safe for treating large CBD stones?

PubMed

Shim, Chan Sup; Kim, Ji Wan; Lee, Tae Yoon; Cheon, Young Koog

2016-01-01

In recent years, endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been shown to be an effective technique for the removal of large or difficult common bile duct (CBD) stones, as an alternative to EST. Reviewing the literature published since 2003, it is understood that EPLBD has fewer associated overall complications than EST. Bleeding occurred less frequently with EPLBD than with EST. There was no significant difference in postendoscopic retrograde cholangiopancreatography pancreatitis or perforation. Recent accumulated results of EPLBD with or even without EST suggest that it is a safe and effective procedure for the removal of large or difficult bile duct stones without any additional risk of severe adverse events, when performed under appropriate guidelines. Since use of a larger balloon can tear the sphincter as well as the bile duct, possibly resulting in bleeding and perforation, a balloon size that is equal to or smaller in diameter than the diameter of the native distal bile duct is recommended. The maximum transverse diameter of the stone and the balloon-stone diameter ratio have a tendency to affect the success or failure of complete removal of stones by large balloon dilation to prevent adverse effects such as perforation and bleeding. One should take into account the size of the native bile duct, the size and burden of stones, the presence of stricture of distal bile duct, and the presence of the papilla in or adjacent to a diverticulum. Even though the results of EPLBD indicate that it is a relatively safe procedure in patients with common duct stones with a dilated CBD, the recommended guidelines should be followed strictly for the prevention of major adverse events such as bleeding and perforation.

Cytomorphologic features of papillary lesions of the male breast: a study of 11 cases.

PubMed

Reid-Nicholson, Michelle D; Tong, Guoxia; Cangiarella, Joan F; Moreira, Andre L

2006-08-25

Breast masses occur in men far less commonly than women and are infrequently subjected to fine-needle aspiration (FNA) biopsy. Papillary lesions of the male breast are rare and are comprised of a spectrum of lesions ranging from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. The following study describes the cytomorphology of papillary breast lesions in 11 men. The patients ranged in age from 23 to 78 years old and each presented with an unilateral subareolar or periareolar breast mass that varied in size from 0.5 to 3 cm. Two patients presented with bloody nipple discharge. Archival material (8-year period) from FNA biopsies of papillary lesions of the male breast was reviewed. The reviewed cases were correlated with appropriate clinicopathologic follow-up. The smears had variable cellularity but all showed papillary clusters of mammary epithelial cells with and without fibrovascular cores. Single epithelial cells with a high nuclear-to-cytoplasmic ratio and eccentric nuclei were seen in all smears; however, these were more numerous in cases of adenocarcinoma. Hemosiderin-laden macrophages were present in all cases. Nipple discharge was seen only in the 2 benign lesions. All adenocarcinomas occurred in older men. The only cytologic criteria that differentiated benign from malignant papillary lesions were marked cellularity and the presence of abundant 3-dimensional clusters. To the best of the authors' knowledge, the current series is the largest in the English literature to date that examines the cytomorphologic features of papillary breast lesions in men. Copyright 2006 American Cancer Society.

A Case of Post Myocardial Infarction Papillary Muscle Rupture.

PubMed

Anuwatworn, Amornpol; Milnes, Christopher; Kumar, Vishesh; Raizada, Amol; Nykamp, Verlyn; Stys, Adam

2016-06-01

Papillary muscle rupture is a rare, life-threatening post myocardial infarction mechanical complication. Without surgical intervention, prognosis is very poor. Clinicians need to recognize this complication early, as prompt therapy is crucial. We present a case of inferior ST elevation myocardial infarction complicated by posteromedial papillary muscle rupture resulting in severe acute mitral regurgitation (flail anterior mitral leaflet), acute pulmonary edema and cardiogenic shock. In our patient, a new mitral regurgitation murmur suggested this mechanical complication. Complete disruption of papillary muscle was visualized by transesophageal echocardiography. This case illustrates the importance of good physical examination for early diagnosis of papillary muscle rupture, so that life-saving treatment can be administered without delay.

An unusual location of a papillary fibroelastoma.

PubMed

Bajaj, Sharad; Nandigam, Harish; Gupta, Nishant; Alkhouri, Yazan; Galldin, Lars M; Parikh, Nalini S; Patel, Nilesh; Shamoon, Fayez

2014-03-01

Papillary fibroelastomas are benign, avascular tumors and 90 % of them are attached to the cardiac valves. We present an unusual case, where papillary fibroelastoma was found attached to the interventricular septum, flopping in and out of the left ventricular outflow tract.

Warthin-like papillary carcinoma of the thyroid: a case series and review of the literature.

PubMed

Erşen, Ayça; Durak, Merih Güray; Canda, Tülay; Sevınç, Ali Ibrahim; Saydam, Serdar; Koçdor, Mehmet Ali

2013-01-01

Warthin-like tumor of the thyroid is a recently described rare variant of thyroid papillary carcinoma. The distinguishing histological feature of this variant is papillary foldings lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. Its prognosis has been reported to be almost similar to conventional papillary carcinoma. In this case series, we report four cases with Warthin-like papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul University Faculty of Medicine Department of Pathology in 2008 and 2009. Three patients were female. The mean patient age was 39 years (range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). All of the cases had lymphocytic thyroiditis in the background. None of the tumors showed lymphovascular invasion. The patients are free of any recurrence and/or distant metastasis with a mean follow-up of 25 months. This rare variant of thyroid papillary carcinoma with distinct histopathological features should be indicated in pathology reports. Further studies and long-term follow-up of patients are needed to highlight the biological behavior of this variant.

Evaluation of the presence of Epstein-Barr virus (EBV) in Iranian patients with thyroid papillary carcinoma.

PubMed

Homayouni, Maryam; Mohammad Arabzadeh, Seyed Ali; Nili, Fatemeh; Razi, Farideh; Amoli, Mahsa Mohammad

2017-07-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma. In this study the presence of Epstein-Barr Nuclear Antigen 1 (EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N=41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene. In 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages. The significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important. Copyright © 2017 Elsevier GmbH. All rights reserved.

Risk of invasive breast cancer and ductal carcinoma in situ in women with atypical papillary lesions of the breast.

PubMed

Cuneo, Kyle C; Dash, Rajesh C; Wilke, Lee G; Horton, Janet K; Koontz, Bridget F

2012-09-01

Benign papillary lesions of the breast include papilloma and papillomatosis. A retrospective analysis of patients with a papillary breast lesion diagnosed between October 1992 and December 2009 was performed. Patients were excluded if they had a previous or concurrent diagnosis of invasive or in situ cancer or less than 6 months of follow-up. The Kaplan-Meier method was used to determine the risk of developing subsequent malignancy. The log rank test was used to compare groups of patients. Median follow-up for the 167 patients included in the study was 4.6 years. Fifty-one patients had a papillary lesion with atypia and 116 patients had a papillary lesion without atypia. Patients with a papillary lesion with atypia were more likely to develop invasive or in situ breast cancer with a 5 year risk of 13.0% versus 4.6% in patients with no atypia (p = 0.03). © 2012 Wiley Periodicals, Inc.

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

PubMed Central

Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Papillary bile duct dysplasia in primary sclerosing cholangitis.

PubMed

Ludwig, J; Wahlstrom, H E; Batts, K P; Wiesner, R H

1992-06-01

A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9-year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC.

Septic disruption of lactiferous ducts with heterogeneous carcinoma of the breast in a lactating woman.

PubMed

Naim, Mohammed; John, Vanesa T; Gaur, Kavita; Anees, Afzal

2010-08-06

This report documents the diagnostic histopathological features of heterogeneous breast carcinoma following sepsis and disruption of the lactiferous ducts in a lactating woman and discusses the pathogenesis. Sections from the nipple revealed disrupted collecting lactiferous ducts presenting with intraduct precarcinoma and carcinoma of the epidermoid type, and attached reparative sprouts lined by lactiferous cells. Breast lobules showed generalised benign adenotic change with various foci of carcinoma microscopically identifiable as intraduct primitive lactiferal ectodermal carcinoma, lactating carcinoma, primitive neuroendocrine carcinoma and myoepithelioid granulomatous carcinoma. The findings led to the conclusion that the lactiferous ducts are susceptible to sepsis and disruption, which may predispose a patient to breast carcinoma. The pattern of carcinoma suggested that lactiferous epithelial cells behaved colonially, with different metaplastic changes, precarcinoma and carcinoma.

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-04-18

BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; RAS Family Gene Mutation; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Unusual presentation of Warthin variant of Papillary thyroid carcinoma with lymph nodal metastases in a patient of Graves' disease.

PubMed

Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Arun, B R

2015-01-01

Warthin-like Papillary thyroid carcinoma (WPTC) is a rare variant of papillary carcinoma of thyroid, PTC which derives its name by closely resembling Warthin's tumor of salivary gland. Hallmark histological feature of this variant is papillary folding lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. It is thought to be one of those differentiated thyroid cancers with favorable prognosis. We report a case of Graves' disease with a cold nodule harboring WPTC with initial presentation of lymph nodal metastases. It is important to identify this peculiar variant of PTC as 5 to 10% of them undergo dedifferentiation and 30% have the lymph nodal metastases and extra thyroidal extension.

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K.

PubMed

Han, Fei; Zhang, Long; Zhang, Suxia; Zhou, Hong; Yi, Xianghua

2015-01-01

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAF(V600K) mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations.

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K

PubMed Central

Han, Fei; Zhang, Long; Zhang, Suxia; Zhou, Hong; Yi, Xianghua

2015-01-01

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAFV600K mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations. PMID:26191315

Papillary renal cell carcinoma embedded in an oncocytoma: Case report of a rare combined tumour of the kidney

PubMed Central

Sejben, István; Szabó, Zoltán; Lukács, Nándor; Loránd, Márta; Sükösd, Farkas; Cserni, Gábor

2013-01-01

An asymptomatic 1-cm large papillary renal cell carcinoma (RCC) embedded in a 3.5-cm large oncocytoma was diagnosed and removed by right nephrectomy in a 68-year-old male investigated for the abdominal symptoms associated with cholelithiasis. The papillary RCC displayed positive immunohistochemical stainings with cytokeratin 7, alpha-methylacyl-CoA racemase and vimentin and was negative for the E-cadherin and CD117 immunostains, whereas the oncocytoma part showed opposite staining patterns. No gains of chromosomes 7 and 17 or loss of chromosome Y was detected in the papillary carcinoma by fluorescent in situ hybridization with centromeric enumeration probes. This finding is in keeping with the morphologic diagnosis of type 2 papillary RCC reported to have lower rates of these characteristic chromosomal changes. The combination of papillary RCC and oncocytoma, two tumours of different postulated origin, is extremely rare. It may represent a simple coincidence, but 2 previous cases and our current one share a few features, including the intimate embedment of the papillary RCC in the oncocytoma, the small size of the RCC and the old age of the patients. This case raises the point that renal oncocytomas can contain a hidden malignant tumour. PMID:23914273

The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

2010-08-01

Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

PubMed Central

Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-01

Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

Endoscopic ultrasound-guided fine needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas: a report of 3 cases.

PubMed

Chatzipantelis, Paschalis; Salla, Charitini; Apostolou, George; Christodoulou, Lambrini; Kakiopoulos, George; Patralexis, Charalambos

2010-01-01

Solid pseudopapillary tumor of the pancreas (SPTP) is an exceedingly rare pancreatic tumor. We present the clinical, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytologic features and immunohistochemical findings performed on cell blocks of 3 SPTPs. Three females (17-32 years old) were admitted to our hospital due to unexplained episodic abdominal pain. EUS confirmed the presence of a mass in the body and tail of the pancreas (2 cases) and in the head (1 case), with distinct borders and occassional dilation of the peripheral part of the pancreatic duct. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform polyhedral cells, forming branching papillary clusters with delicate fibrovascular cores and nuclear overlapping (2 cases) and glandlike structures (1 case). Variable hyaline, myxoid stromal elements and naked capillaries were also seen. The cells had bland nuclear features, small nucleoli, nuclear grooves in some of them and focally cytoplasmic projections. Mitoses and necrosis were not observed. The immunohistochemistry on cell blocks revealed: vimentin+ (3 cases), CA19.9+ (2 cases), cytokeratin 7+ (focal, intensive, 1 case), synaptophysin+ (1 case), MUC1+ (focal, intensive, 1 case), EMA+ (diffuse weak, 1 case), a1-antitrypsin and a1-antichymotrypsin+ (focal intensive, 2 cases), progesterone+ (1 case), chromogranin-A- (3 cases) and NSE- (3 cases). Cytologic and immunohistochemical findings were strongly suggestive of SPTP. Surgical resection confirmed the diagnosis in all cases. EUS-FNA cytology features and immunohistochemistry provide the diagnosis of SPTP with accuracy.

Breast biopsy -- ultrasound

MedlinePlus

... hyperplasia Atypical lobular hyperplasia Flat epithelial atypia Intraductal papilloma Lobular carcinoma-in-situ Radial scar Abnormal results ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

ClinicalTrials.gov

2015-11-04

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Prevalence of maxillary midline papillae recession and association with interdental smile line: a cross-sectional study.

PubMed

Kotsakis, Georgios A; Maragou, Theodora; Ioannou, Andreas L; Romanos, Georgios E; Hinrichs, James E

2014-01-01

The objectives of this study were to record the prevalence and degree of absence of the maxillary midline interdental papilla and the proportion of patients displaying the maxillary midline papilla during maximum smile among a Caucasian population. Papillary recession was found in 46.4% of study participants (n = 211), while the prevalence of visible recession among maxillary midline papilla during maximum smile was 38.4%, which was statistically significantly less than that of patients diagnosed intraorally with loss of papillary height (P < .001). Correlations between age and level of lip line as well as age and visible papillary recession were identified for individuals over 65 years of age. The high prevalence of midline papillary recession in the maxilla found in this population suggests that loss of papillary height constitutes a substantial clinical challenge.

Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michigishi, T.; Mizukami, Y.; Mura, T.

1991-05-01

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.

Coexistence of papillary thyroid cancer and Hashimoto thyroiditis in children: report of 3 cases.

PubMed

Koibuchi, Harumi; Omoto, Kiyoka; Fukushima, Noriyoshi; Toyotsuji, Tomonori; Taniguchi, Nobuyuki; Kawano, Mikihiko

2014-07-01

This report documents 3 pediatric papillary thyroid carcinoma cases with associated Hashimoto thyroiditis. In all 3 cases, hypoechoic nodules accompanied by multiple echogenic spots were noted on sonography of the thyroid. Hashimoto thyroiditis was suspected on the basis of positive thyroid autoantibody test results and pathologic examinations of thyroidectomy specimens, which revealed chronic thyroiditis with lymphocytic infiltration as the background of papillary thyroid carcinoma development. The potential for papillary carcinoma development warrants close follow-up, and meticulous sonographic examinations must be performed in children with Hashimoto thyroiditis. © 2014 by the American Institute of Ultrasound in Medicine.

Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.

PubMed

Yu, Yang; Yu, Xiaohui; Fan, Chenling; Wang, Hong; Wang, Renee; Feng, Chen; Guan, Haixia

2018-06-25

Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT 2 -PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells. These results were later confirmed via real-time PCR, Western blots, and immunohistochemical staining. We found that the levels of glutaminase were significantly correlated with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. The proliferative, viable, migratory, and invasive abilities of papillary thyroid cancer cells were impaired by both the pharmacological inhibition and the genetic knockdown of glutaminase. Additionally, the inhibition of glutaminase deactivated the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and apoptosis. Collectively, these findings show that glutaminase-mediated glutamine dependence may be a potential therapeutic target for papillary thyroid cancer. PTC cells are glutamine-dependent, and GLS is aberrantly overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells. GLS blockade causes deactivation of mTORC1 and induction of autophagy and apoptosis. GLS may be a potential therapeutic target for PTC.

Not all occult papillary carcinomas are minimal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allo, M.D.; Christianson, W.; Koivunen, D.

1988-12-01

Occult papillary carcinomas are characterized as small papillary tumors of less than 1.5 cm in maximum diameter, with or without bulky metastatic deposits in cervical nodes. The primary lesion is usually not palpable, and although the clinical behavior usually follows a benign course, tumors with unfavorable histologic features (invasiveness, multifocality) or extrathyroidal disease or a combination of both may not do so. In this report six cases are presented to illustrate this entity. No patient had a history of irradiation to the head or neck. All had primary lesions smaller than 1.5 cm. None had a palpable nodule or abnormalmore » thyroid scan results, and the diagnosis of thyroid cancer was based on cervical lymph node or lung biopsy specimens, which revealed papillary thyroid cancer. All of the patients underwent total or near-total thyroidectomies and were found to have small, invasive papillary lesions with additional metastases to cervical nodes noted at the time of thyroidectomy. Adjunctive treatment consisted of a 5 mCi iodine-131 scan, ablative iodine-131 therapy, and suppression with L-thyroxine. Although distant metastasis to lung or other organs is uncommon and the mortality rate is low (as in larger papillary cancers), these invasive lesions--despite their small size--have a high propensity for recurrence and should be considered to behave more like encapsulated papillary tumors with extrathyroidal extension than like their small, unencapsulated intrathyroidal counterparts.« less

Analysis of papillary renal adenocarcinoma.

PubMed

Mydlo, J H; Bard, R H

1987-12-01

A retrospective review was conducted comparing the angiographic findings, tumor volumes, staging, and survival of patients with papillary renal adenocarcinoma as compared with the more common clear and granular cell renal adenocarcinoma. The data suggest that the papillary histopathologic organization confers an improved prognosis, which concurs with previous findings. We speculate on why this tumor behaves differently from clear cell carcinoma.

Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu

ClinicalTrials.gov

2013-02-27

Advanced Adult Primary Liver Cancer; Anaplastic Thyroid Cancer; Bone Metastases; Carcinoma of the Appendix; Distal Urethral Cancer; Fallopian Tube Cancer; Gastrinoma; Glucagonoma; Inflammatory Breast Cancer; Insulinoma; Liver Metastases; Localized Unresectable Adult Primary Liver Cancer; Lung Metastases; Male Breast Cancer; Malignant Pericardial Effusion; Malignant Pleural Effusion; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Parathyroid Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Newly Diagnosed Carcinoma of Unknown Primary; Occult Non-small Cell Lung Cancer; Pancreatic Polypeptide Tumor; Primary Peritoneal Cavity Cancer; Proximal Urethral Cancer; Pulmonary Carcinoid Tumor; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adrenocortical Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Carcinoma of Unknown Primary; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Parathyroid Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Thyroid Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Skin Metastases; Small Intestine Adenocarcinoma; Somatostatinoma; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Adrenocortical Carcinoma; Stage III Bladder Cancer; Stage III Cervical Cancer; Stage III Colon Cancer; Stage III Endometrial Carcinoma; Stage III Esophageal Cancer; Stage III Follicular Thyroid Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Ovarian Epithelial Cancer; Stage III Pancreatic Cancer; Stage III Papillary Thyroid Cancer; Stage III Prostate Cancer; Stage III Rectal Cancer; Stage III Renal Cell Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Anal Cancer; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Anal Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Adrenocortical Carcinoma; Stage IV Anal Cancer; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Endometrial Carcinoma; Stage IV Esophageal Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Gastric Cancer; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Pancreatic Cancer; Stage IV Papillary Thyroid Cancer; Stage IV Prostate Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Stage IVB Vulvar Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer; Urethral Cancer Associated With Invasive Bladder Cancer; WDHA Syndrome

Intraductal location of the sclerosing adenosis of the breast.

PubMed

Unal, Bulent; Gur, A Serhat; Bhargava, Rohit; Edington, Howard; Ahrendt, Gretchen; Soran, Atilla

2009-01-01

Sclerosing adenosis is a benign breast disease with non-specific images on ultrasound or mammogram. It can mimic infiltrating carcinoma when the above mentioned imaging techniques are used. Herein we present a patient with breast cancer who received neoadjuvant chemotherapy and subsequently underwent mastectomy. Ductoscopy was performed to the mastectomised breast specimen as per the ductoscopy research protocol. Ductoscopy revealed several nodular lesions in the duct with no additional demonstrable intraductal pathology. The lesions were reported as sclerosing adenosis by pathologist. As to our knowledge, this is the first case in literature that demonstrates the use of ductoscopy in diagnosing the sclerosing adenosis in the breast tissue. Ductoscopy and development of ductoscopy guided biopsy techniques may be used as an early diagnostic method for the ductal breast lesions (Fig. 2, Ref. 10). Full Text (Free, PDF) www.bmj.sk.

Breast intraductal papillomas without atypia in radiologic-pathologic concordant core-needle biopsies: Rate of upgrade to carcinoma at excision.

PubMed

Pareja, Fresia; Corben, Adriana D; Brennan, Sandra B; Murray, Melissa P; Bowser, Zenica L; Jakate, Kiran; Sebastiano, Christopher; Morrow, Monica; Morris, Elizabeth A; Brogi, Edi

2016-09-15

The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core-needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC). This study identified women with a CNB diagnosis of intraductal papilloma without atypia or carcinoma at a cancer center between 2003 and 2013. Radiologic-pathologic concordance was assessed for all cases, and discordant cases were excluded. The radiologic and clinicopathologic features of patients with a CNB diagnosis of IDP were correlated with an upgrade to carcinoma at EXC. The study population consists of 189 women with 196 IDPs; 166 women (171 IDPs) underwent EXC. The upgrade rate was 2.3% (4 of 171). The upgraded lesions were 2 invasive lobular carcinomas and 2 cases of ductal carcinoma in situ (DCIS). One case of DCIS involved the residual IDP, whereas the other 3 carcinomas were ≥ 8 mm away. Twenty-four women (25 IDPs) did not undergo EXC and had stable imaging on follow-up (median, 23.5 months). The upgrade rate at EXC for IDPs diagnosed at CNB with radiologic-pathologic concordance was 2.3%. These findings suggest that observation is appropriate for patients with radiologic-pathologic concordant CNB yielding IDP, regardless of its size. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2819-2827. © 2016 American Cancer Society. © 2016 American Cancer Society.

Outcome of breast lesions diagnosed as lesion of uncertain malignant potential (B3) or suspicious of malignancy (B4) on needle core biopsy, including detailed review of epithelial atypia.

PubMed

Rakha, Emad A; Ho, Bernard C; Naik, Veena; Sen, Soumadri; Hamilton, Lisa J; Hodi, Zsolt; Ellis, Ian O; Lee, Andrew H S

2011-03-01

To provide updated evidence of the outcome of breast lesions of uncertain malignant potential (B3) and suspicious of malignancy (B4) diagnosed on needle core biopsy (NCB) and analyse the outcome of the different types of intraductal epithelial atypia. One-hundred and forty-nine B3 and 26 B4 NCBs diagnosed over a 2-year period (2007-2008) were compared with those diagnosed over a previous 2-year period (1998-2000). The proportion of B3 diagnoses increased from 3.1% to 4.5%, and the positive predictive value (PPV) of malignancy of a B3 core decreased from 25% to 10%. Increased diagnosis of radial scar and reductions in the PPV of lobular neoplasia and of atypical intraductal proliferation may explain the reduction in the PPV of the B3 group as a whole. There were no significant changes in the proportion of B4 diagnosis (1.1% and 0.8%) or the PPV of B4 (83% and 88%). Review of cores with intraductal atypia showed a wide range of PPVs, from 100% for suspicious of ductal carcinoma in situ, to 40% for atypical ductal hyperplasia categorized as B3, and 14% for isolated flat epithelial atypia. The study has found a decrease in the PPV for a B3 diagnosis and suggests possible explanations. © 2011 Blackwell Publishing Limited.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

PubMed

Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-14

Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: radiological findings mimicking papillary subtype.

PubMed

Kato, Hiroki; Kanematsu, Masayuki; Yokoi, Shigeaki; Miwa, Kousei; Horie, Kengo; Deguchi, Takashi; Hirose, Yoshinobu

2011-01-01

The authors describe the computed tomography (CT) and magnetic resonance imaging (MRI) findings of an 18-year-old man with renal cell carcinoma (RCC) associated with the Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion (Xp11 translocation carcinoma). The lesion was hyperdense on unenhanced CT, hypovascular on contrast-enhanced studies, hypointense on T2-weighted MR images, and hemosiderin deposition was suspected on phase-shift gradient-echo MR images. Histopathological specimens revealed pathological findings resembling papillary RCC predominantly and exhibited immunoreactivity for TFE3. Because there is often considerable morphological overlap between this carcinoma and papillary RCC, the imaging findings of Xp11 translocation carcinoma may be similar to those of the papillary subtype. Therefore, Xp11 translocation carcinoma should be considered, particularly in young patients when radiologic images demonstrate a renal tumor mimicking the papillary subtype. Copyright © 2010 Wiley-Liss, Inc.

Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-08-18

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.

PubMed Central

Saito, T; Endo, T; Kawaguchi, A; Ikeda, M; Katoh, R; Kawaoi, A; Muramatsu, A; Onaya, T

1998-01-01

Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue. PMID:9525971

Warthin-Like Papillary Carcinoma of the Thyroid Gland: Case Report and Review of the Literature

PubMed Central

Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario

2012-01-01

We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable. PMID:23243533

Warthin-like papillary carcinoma of the thyroid gland: case report and review of the literature.

PubMed

Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario

2012-01-01

We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable.

A Case of Solitary Well-Differentiated Papillary Mesothelioma with Invasive Foci in the Pleura.

PubMed

Shimizu, Shigeki; Yoon, Hyung-Eun; Ito, Norimasa; Tsuji, Taisuke; Funakoshi, Yasunobu; Utsumi, Tomoki; Sakaguchi, Masahiro; Tsujimura, Toru; Kasai, Takahiko; Hiroshima, Kenzo; Matsumura, Akihide

2017-01-01

Well-differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor consisting of mesothelial cells with a papillary architecture, bland cytological features, and a tendency toward superficial spread without invasion. Rare cases with superficial invasion are termed WDPM with invasive foci. We report a case of solitary WDPM with invasive foci in the pleura. A 61-year-old woman presented with a lung adenocarcinoma. A small papillary lesion measuring 29 × 10 × 8 mm was incidentally found in the parietal pleura during a lobectomy for the lung adenocarcinoma. The fibrovascular core of the small papillary lesion was surrounded by a single layer of cuboidal cells with mild to moderate atypia and large nucleoli. Atypical mesothelial cells focally invaded the submesothelial layer. The cells of the papillary lesion were positive for cytokeratins and mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on fluorescence in situ hybridization. We could not detect atypical mesothelial cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci is prone to multifocality; however, our case represents a solitary case in the pleura. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

PubMed Central

2014-01-01

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

[Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

PubMed

Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

2017-02-01

Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

Sphincterotomy by triple lumen needle knife using guide wire in patients with Billroth II gastrectomy

PubMed Central

Park, Su Bum; Kim, Hyung Wook; Kang, Dae Hwan; Choi, Cheol Woong; Yoon, Ki Tae; Cho, Mong; Song, Byeong Jun

2013-01-01

AIM: To investigate the usefulness of a guide wire and triple lumen needle knife for removing stones in Billroth II (B-II) gastrectomy patients. METHODS: Endoscopic sphincterotomy in patients with B-II gastrectomy is challenging. We used a new guide wire technique involving sphincterotomy by triple lumen needle knife through a forward-viewing endoscopy. This technique was performed in nine patients between August 2010 and June 2012. Sphincterotomy as described above was performed. Adequate sphincterotomy, successful stone removal, and complications were investigated prospectively. RESULTS: Sphincterotomy by triple lumen needle knife using guide wire was successful in all nine patients. Sphincterotomy started towards the 4-5 o’clock direction and continued to the upper margin of the papillary roof. Complete stone removal in one session was achieved in all patients. There were no procedure related complications, such as bleeding, pancreatitis, or perforation. CONCLUSION: In patients with B-II gastrectomy, guide wire using sphincterotomy by triple lumen needle knife through a forward-viewing endoscopy seems to be an effective and safe procedure for the removal of common bile duct stones. PMID:24409069

The Origin and Significance of Mammary Intraductal Foam Cells

DTIC Science & Technology

2005-09-01

hematopoeitic origin developed in mammary tissue with both benign and malignant differentiation, depending on environmental cues. Progression of the cells...contribution of hematopoeitic precursors to the heterogeneity of cell types in benign and malignant mammary tissue.

BRAF V600E mutations in papillary craniopharyngioma

PubMed Central

Brastianos, Priscilla K.; Santagata, Sandro

2016-01-01

Papillary craniopharyngioma is an intracranial tumor that results in high levels of morbidity. We recently demonstrated that the vast majority of these tumors harbor the oncogenic BRAF V600E mutation. The pathologic diagnosis of papillary craniopharyngioma can now be confirmed using mutation specific immunohistochemistry and targeted genetic testing. Treatment with targeted agents is now also a possibility in select situations. We recently reported a patient with a multiply recurrent papillary craniopharyngioma in whom targeting both BRAF and MEK resulted in a dramatic therapeutic response with a marked anti-tumor immune response. This work shows that activation of the MAPK pathway is the likely principal oncogenic driver of these tumors. We will now investigate the efficacy of this approach in a multicenter phase II clinical trial. Post-treatment resection samples will be monitored for the emergence of resistance mechanisms. Further advances in the non-invasive diagnosis of papillary craniopharyngioma by radiologic criteria and by cell-free DNA testing could someday allow neo-adjuvant therapy for this disease in select patient populations. PMID:26563980

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

PubMed

Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua

2017-05-01

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

The follicular variant of papillary thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PubMed

Scharpf, Joseph; Kamani, Dipti; Sadow, Peter M; Randolph, Gregory W

2017-01-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new terminology proposed for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Recently, thyroid cancer incidence has increased dramatically, without affecting related mortality rate. This increase is widely attributed to the intensified surveillance leading to a substantial increase in the diagnosis of small classic papillary thyroid cancers and EFVPTCs. Recent studies emphasize the indolent behavior of the EFVPTC. Recently, there has been a reclassification of EFVPTC as NIFTP, a benign entity. The financial and emotional burden of 'cancer' diagnosis and treatment can be significant. This review recapitulates the literature supporting the reclassification of EFVPTC as NIFTP, a benign entity, and reviews standardized diagnostic criteria for EFVPTC. The information highlighted in this review will affect surgical decision making and may promote the offering of hemithyroidectomy over a total thyroidectomy to some patients with 'indeterminate' cytopathological category; postoperative radioiodine ablation will not be required for NIFTP patients.

Papillary Necrosis in Experimental Analgesic Nephropathy

PubMed Central

Saker, B. M.; Kincaid-Smith, Priscilla

1969-01-01

A proprietary aspirin, phenacetin, and caffeine preparation given to rats in a dose equivalent to that taken by patients with analgesic nephropathy produced papillary necrosis in 55%. There was a higher incidence in rats deprived of fluids overnight. Papillary necrosis was not noted in rats receiving twice as much phenacetin. These findings support the argument that phenacetin should not be singled out as the substance responsible for analgesic nephropathy in man. PMID:5762278

Anatomy of the septomarginal trabecula in goat hearts.

PubMed

Leão, Camila Ribeiro; Pacha, Diego Lago; Cyriaco, Thiago; da Silva, Cavalcante; Wafae, Nader; Pereira, Heloisa Maria Lemes; Ruiz, Cristiane Regina

2010-01-01

Our aim in this study was to examine the right septomarginal trabecula of goats regarding the frequency, origin course of the septal and free component, attachment to the papillaris magnus muscle and size . The material used consisted in 32 hearts from non-pedigree goats of both sexes, preserved in 10% formalin. The right septomarginal trabecula was present in all hearts. It could also present a prominence in the form of a cord in the septum before detaching and going towards the wall or the papillary muscle. We called this a septal component and found it in 69% of all hearts studied. In the remaining specimens, the exit of the septomarginal trabecula was abrupt, without presenting a septal component. It could be attached solely to the papillaris magnus muscle or to the papillary muscle and the ventricle wall, originated in the cranial third of the septum, and was attached to the middle third of the papillary muscle or its caudal third. Its free part, from the septum to the papillaris magnus muscle, ranged in length from 1.3 cm to 2.6 cm. The mean value was 1.7 cm, and the most frequent values were 1.9 and 1.5 cm. In conclusion, in goats, the septomarginal trabecula is a constant and invariable structure.

Characteristics of young adults of Belarus with post-Chernobyl papillary thyroid carcinoma: a long-term follow-up of patients with early exposure to radiation at the 30th anniversary of the accident.

PubMed

Fridman, Mikhail; Lam, Alfred King-Yin; Krasko, Olga

2016-12-01

Studies of thyroid cancer related to the Chernobyl accident have focused on children as they are the most vulnerable group with the highest risk of developing radiation-associated cancer. In contrast, our research aimed to look at the clinical and pathological features of patients with post-Chernobyl papillary thyroid carcinoma that were 2 years old or less at the time of the Chernobyl accident. The study subjects were patients (n = 359) aged 0 to 2 at the time of the Chernobyl accident and aged ≥19 years at presentation/surgery who were treated in Belarus for papillary thyroid carcinoma during the period 2003-2013. In conventional or oncocytic variant of papillary thyroid carcinoma, the prevalence of extra-thyroidal extension, nodal disease, infiltrative growth or lymphatic vessel invasion was above 50%. These features were less pronounced when compared to tall cell or diffuse sclerosing variants of papillary thyroid carcinoma. The highest frequency of central lymph node metastases was found in patients aged 1-2 years at exposure (P = 0·004). Subjects exposed in utero were characterized by absent/insignificant lymphocytic infiltration around the carcinoma (P = 0·025), predominance of conventional papillary architecture and an association with lymphocytic thyroiditis. A number of features were associated with this group of patients that were very young at the time of radiation exposure. In addition, the incidence and basic characteristics of adult papillary thyroid carcinoma varied depending on the types of exposure conditions. © 2016 John Wiley & Sons Ltd.

Clinicopathological Characteristics and KRAS Mutation Status of Endometrial Mucinous Metaplasia and Carcinoma.

PubMed

Sung, Ji-Youn; Jung, Yoon Yang; Kim, Hyun-Soo

2018-05-01

Mucinous metaplasia of the endometrium occurs as a spectrum of epithelial alterations ranging from the formation of simple, tubular glands to architecturally complex glandular proliferation with intraglandular papillary projection and cellular tufts. Endometrial mucinous metaplasia often presents a diagnostic challenge in endometrial curettage. We analyzed the clinicopathological characteristics and the mutation status for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) of 11 cases of endometrial mucinous metaplasia. Electronic medical record review and histopathological examination were performed. KRAS mutation status was analyzed using a pyrosequencing technique. Cases were classified histopathologically into simple (5/11) or papillary (6/11) mucinous metaplasias. All (6/6) papillary mucinous metaplasias were associated with atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN; 1/6) or carcinoma (5/6), whereas in a single patient with simple mucinous metaplasia, grade 1 endometrioid carcinoma was incidentally detected. The difference in frequency of association of the metaplasia with AH/EIN or carcinoma was significant (p=0.015). KRAS mutations were identified in five out of six cases of papillary mucinous metaplasias, comprising three cases with G12D and two with G12V mutations; the frequency of KRAS mutation was significantly higher (p=0.015) than in cases of simple mucinous metaplasia (0/5). Papillary mucinous metaplasia is frequently associated with endometrial neoplastic lesions. The high incidence of KRAS mutations in papillary mucinous metaplasia suggests that papillary mucinous metaplasia may be a precancerous lesion of a certain subset of mucinous carcinomas of the endometrium. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Morphological three-dimensional analysis of papillary muscles in borderline left ventricles.

PubMed

Velasco Forte, Mari N; Nassar, Mohamed; Byrne, Nick; Silva Vieira, Miguel; Pérez, Israel V; Ruijsink, Bram; Simpson, John; Hussain, Tarique

2017-09-01

Mitral valve anatomy has a significant impact on potential surgical options for patients with hypoplastic or borderline left ventricle. Papillary muscle morphology is a major component regarding this aspect. The purpose of this study was to use cardiac magnetic resonance to describe the differences in papillary muscle anatomy between normal, borderline, and hypoplastic left ventricles. We carried out a retrospective, observational cardiac magnetic resonance study of children (median age 5.36 years) with normal (n=30), borderline (n=22), or hypoplastic (n=13) left ventricles. Borderline and hypoplastic cases had undergone an initial hybrid procedure. Morphological features of the papillary muscles, location, and arrangement were analysed and compared across groups. All normal ventricles had two papillary muscles with narrow pedicles; however, 18% of borderline and 46% of hypoplastic cases had a single papillary muscle, usually the inferomedial type. In addition, in borderline or hypoplastic ventricles, the supporting pedicle occasionally displayed a wide insertion along the ventricular wall. The length ratio of the superolateral support was significantly different between groups (normal: 0.46±0.08; borderline: 0.39±0.07; hypoplastic: 0.36±0.1; p=0.009). No significant difference, however, was found when analysing the inferomedial type (0.42±0.09; 0.38±0.07; 0.39±0.22, p=0.39). The angle subtended between supports was also similar among groups (113°±17°; 111°±51° and 114°±57°; p=0.99). A total of eight children with borderline left ventricle underwent biventricular repair. There were no significant differentiating features for papillary muscle morphology in this subgroup. The superolateral support can be shorter or absent in borderline or hypoplastic left ventricle cases. The papillary muscle pedicles in these patients often show a broad insertion. These changes have important implications on surgical options and should be described routinely.

[Study on the relationship between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis].

PubMed

Wang, X Q; Wei, W; Wei, X; Xu, Y; Wang, H L; Xing, X J; Zhang, S

2018-03-23

Objective: To investigate the correlation between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis. Methods: We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC), pathologically confirmed after surgery in Tianjin Medical University Cancer Institute & Hospital. All patients were divided into central cervical lymph node metastasis group and non-metastasis group. No lateral cervical lymph node metastasis was found in preoperative ultrasonography and postoperative pathology. The characteristics of the ultrasound was observed and analyzed. Results: 297 out of 486 patients with papillary thyroid carcinomahad central metastasis, and the other 189 cases did not. Take pathology results as a standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of preoperative ultrasound diagnosis in PTC patients with central cervical lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively. Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm, located in the lower pole, ill-defined margin, hypoechogenicity, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma were significantly associated with central cervical lymph node metastasis (all P <0.05). Multivariate analysis showed that diameter>1 cm, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma became independent risk factors of central cervical neck lymph node metastasis (all P <0.05). Conclusions: Preoperative description of ultrasonographical features has important value to assess central cervical lymph node metastasis in patients with papillary thyroid carcinoma. More information could be provided for clinical treatment. When the papillary thyroid carcinoma presented as diameter>1 cm, micro-calcification, and capsule invasion more than 1/4 perimeter of, there will be a greater risk of central cervical lymph node metastasis, and we shall suggest prophylactic central lymph cervical node dissection.

Likelihood ratio-based differentiation of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in patients with sonographically evident diffuse hashimoto thyroiditis: preliminary study.

PubMed

Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi

2012-11-01

To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for discrimination of nodular Hashimoto thyroiditis from papillary thyroid carcinoma; therefore, it is a promising risk index for thyroid nodules and warrants further investigation.

The papillary muscles as shock absorbers of the mitral valve complex. An experimental study.

PubMed

Joudinaud, Thomas M; Kegel, Corrine L; Flecher, Erwan M; Weber, Patricia A; Lansac, Emmanuel; Hvass, Ulrich; Duran, Carlos M G

2007-07-01

Although it is known that the papillary muscles ensure the continuity between the left ventricle (LV) and the mitral apparatus, their precise mechanism needs further study. We hypothesize that the papillary muscles function as shock absorbers to maintain a constant distance between their tips and the mitral annulus during the entire cardiac cycle. Sonomicrometry crystals were implanted in five sheep in the mitral annulus at the trigones (T1 and T2), mid anterior annulus (AA) mid posterior annulus (PA), base of the posterior lateral scallops (P1 and P2), tips of papillary muscles (M1 and M2), and LV apex. LV and aortic pressures were simultaneously recorded and used to define the different phases of the cardiac cycle. No significant distance changes were found during the cardiac cycle between each papillary muscle tip and their corresponding mitral hemi-annulus: M1-T1, (3.5+/-2%); M1-P1 (5+/-2%); M1-PA (5+/-3%); M2-T2 (2.7+/-2%); M2-P2 (6.1+/-3%); and M2-AA (4.2+/-3%); (p>0.05, ANOVA). Significant changes were observed in distances between each papillary muscle tip and the contralateral hemi-mitral annulus: M1-T2 (1.7+/-3%); M1-P2 (23+/-6%); M1-AA (6+/-3%); M2-T1 (8+/-3%); M2-P1 (10.5+/-6%); and M2-PA (12.6+/-8%); (p<0.05 ANOVA). The distance changes between LV apex and each papillary muscle tip were significantly different: apex-M1 (12.9+/-1%) and apex-M2 (10.5+/-1%) and different from the averaged distance change between the LV apex and each annulus crystal (8.3+/-1%) with p<0.05. The papillary muscles seem to be independent mechanisms designed to work as shock absorbers to maintain the basic mitral valve geometry constant during the cardiac cycle.

MDCT findings of renal cell carcinoma associated with Xp11.2 translocation and TFE3 gene fusion and papillary renal cell carcinoma.

PubMed

Woo, Sungmin; Kim, Sang Youn; Lee, Myoung Seok; Moon, Kyung Chul; Kim, See Hyung; Cho, Jeong Yeon; Kim, Seung Hyup

2015-03-01

OBJECTIVE. The purpose of this study was to compare the MDCT features of renal cell carcinoma (RCC) associated with Xp11.2 translocation and TFE3 gene fusion (Xp11 RCC) and papillary RCC. MATERIALS AND METHODS. The study included 19 and 39 patients with histologically proven Xp11 RCC and papillary RCC, respectively, who underwent multiphase renal MDCT before nephrectomy. CT findings were compared between Xp11 RCC and papillary RCC using the Student t test and chi-square test. Subgroup analyses of small (< 4 cm) renal masses for these features were performed. RESULTS. Patients with Xp11 RCC were younger (p < 0.001), and it was more prevalent in women (p = 0.007). Tumor size was greater in Xp11 RCC (p = 0.004) and more common in cystic change (p < 0.001). Calcification and unenhanced high-attenuating areas were more frequent in Xp11 RCC (p = 0.001 and 0.026, respectively). Xp11 RCCs were more prevalent in lymph node and distant metastasis (p < 0.001 and p = 0.031, respectively). Xp11 RCC and papillary RCC showed no significant difference in epicenter, margin, and venous and collecting duct invasion (p = 0.403-1.000). Although Xp11 RCC and papillary RCC had lower attenuation than the renal cortex on corticomedullary and early excretory phases (p < 0.001), only Xp11 RCCs were hyperattenuating to the cortex on the unenhanced phase (p < 0.001). Xp11 RCCs had significantly higher attenuation compared with papillary RCCs on all phases (p ≤ 0.02). Regarding small masses, cystic change, calcification, and lymph node metastasis were still more frequent in Xp11 RCCs (p ≤ 0.016). CONCLUSION. Greater size, more cystic change, calcification, high-attenuating areas on unenhanced imaging, and lymph node and distant metastasis were helpful for differentiating Xp11 RCC from papillary RCC.

The Increasing Incidence of Thyroid Cancer: The Influence of Access to Care

PubMed Central

Sikora, Andrew G.; Tosteson, Tor D.

2013-01-01

Background The rapidly rising incidence of papillary thyroid cancer may be due to overdiagnosis of a reservoir of subclinical disease. To conclude that overdiagnosis is occurring, evidence for an association between access to health care and the incidence of cancer is necessary. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to examine U.S. papillary thyroid cancer incidence trends in Medicare-age and non–Medicare-age cohorts over three decades. We performed an ecologic analysis across 497 U.S. counties, examining the association of nine county-level socioeconomic markers of health care access and the incidence of papillary thyroid cancer. Results Papillary thyroid cancer incidence is rising most rapidly in Americans over age 65 years (annual percentage change, 8.8%), who have broad health insurance coverage through Medicare. Among those under 65, in whom health insurance coverage is not universal, the rate of increase has been slower (annual percentage change, 6.4%). Over three decades, the mortality rate from thyroid cancer has not changed. Across U.S. counties, incidence ranged widely, from 0 to 29.7 per 100,000. County papillary thyroid cancer incidence was significantly correlated with all nine sociodemographic markers of health care access: it was positively correlated with rates of college education, white-collar employment, and family income; and negatively correlated with the percentage of residents who were uninsured, in poverty, unemployed, of nonwhite ethnicity, non-English speaking, and lacking high school education. Conclusion Markers for higher levels of health care access, both sociodemographic and age-based, are associated with higher papillary thyroid cancer incidence rates. More papillary thyroid cancers are diagnosed among populations with wider access to healthcare. Despite the threefold increase in incidence over three decades, the mortality rate remains unchanged. Together with the large subclinical reservoir of occult papillary thyroid cancers, these data provide supportive evidence for the widespread overdiagnosis of this entity. PMID:23517343

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast].

PubMed

Oliveira, Agliberto Barbosa de; De Luca, Laurival Antônio; Carvalho, Grigna Teixeira; Arias, Victor Eduardo Arua; Carvalho, Lídia Raquel de; Assunção, Maria do Carmo

2004-01-01

Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ClinicalTrials.gov

2018-06-27

Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Rare Disorder; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm; Squamous Cell Carcinoma of the Penis; Teratoma With Malignant Transformation; Testicular Non-Seminomatous Germ Cell Tumor; Thyroid Gland Carcinoma; Tracheal Carcinoma; Transitional Cell Carcinoma; Undifferentiated Gastric Carcinoma; Ureter Adenocarcinoma; Ureter Squamous Cell Carcinoma; Urethral Adenocarcinoma; Urethral Squamous Cell Carcinoma; Vaginal Adenocarcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified; Vulvar Carcinoma

Reflux-Associated Cholecystopathy: Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma.

PubMed

Muraki, Takashi; Memis, Bahar; Reid, Michelle D; Uehara, Takeshi; Ito, Tetsuya; Hasebe, Osamu; Okaniwa, Shinji; Horigome, Naoto; Hisa, Takeshi; Mittal, Pardeep; Freedman, Alexa; Maithel, Shishir; Sarmiento, Juan M; Krasinskas, Alyssa; Koshiol, Jill; Adsay, Volkan

2017-09-01

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

Stages of Bladder Cancer

MedlinePlus

... section. Stage 0 (Noninvasive Papillary Carcinoma and Carcinoma in Situ) Treatment of stage 0 ( noninvasive papillary carcinoma and carcinoma in situ ) may include the following: Transurethral resection with fulguration . ...

Oncofetal Protein IMP3: A Novel Molecular Marker That Predicts Metastasis of Papillary and Chromophobe Renal Cell Carcinomas

PubMed Central

Jiang, Zhong; Lohse, Christine M.; Chu, Peigou G.; Wu, Chin-Lee; Woda, Bruce A.; Rock, Kenneth L.; Kwon, Eugene D.

2009-01-01

BACKGROUND Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated. METHODS The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses. RESULTS IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n = 33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40–23.96; P <.001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13–3.22; P =.016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively. In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00–30.14; P <.001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15–3.31; P =.013) compared with patients with IMP3-negative tumors. CONCLUSIONS IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis. PMID:18412154

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

PubMed

Agrawal, Nidhi; Abbott, Collette E; Liu, Cheng; Kang, Stella; Tipton, Laura; Patel, Kepal; Persky, Mark; King, Lizabeth; Deng, Fang-Ming; Bannan, Michael; Ogilvie, Jennifer B; Heller, Keith; Hodak, Steven P

2017-04-02

Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

Breast cancer in men

MedlinePlus

... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

Renal papillary tip extract stimulates BNP production and excretion from cardiomyocytes

PubMed Central

Hashizume, Ryotaro; Suzuki, Noboru; Ito, Rie; Yamanaka, Keiichi; Saito, Hiromitsu; Kiyonari, Hiroshi; Tawara, Isao; Kageyama, Yuki; Ogihara, Yoshito; Ali, Yusuf; Yamada, Norikazu; Katayama, Naoyuki; Ito, Masaaki

2018-01-01

Background Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear. Methods and results We developed a BNP reporter mouse and occasionally found that this promoter was activated specifically in the papillary tip of the kidneys, and its activation was not accompanied by BNP mRNA expression. No evidence was found to support the existence of BNP isoforms or other nucleotide expression apart from BNP and tdTomato. The pBNP-tdTomato-positive cells were interstitial cells and were not proliferative. Unexpectedly, both the expression and secretion of BNP increased in primary cultured neonatal cardiomyocytes after their treatment with an extract of the renal papillary tip. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure from 210 mmHg to 165 mmHg, the decrease being accompanied by an increase in serum BNP and urinary cGMP production in stroke-prone spontaneously hypertensive (SHR-SP) rats. Furthermore the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes. Conclusions These results suggested that the papillary tip express a substance that can stimulate BNP production and secretion from cardiomyocytes. PMID:29734386

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Can Cytology Face the Challenge of Diagnosis in the Light of the New Classification?

PubMed

Díaz Del Arco, Cristina; Fernández Aceñero, M Jesús

2018-06-01

To assess the cytological findings of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), conventional papillary thyroid carcinomas (C-PTC), and invasive follicular variants of papillary thyroid carcinomas (IFV-PTC) to determine if there are cytological differences between groups. We have reviewed all thyroid fine-needle aspiration cytology samples diagnosed between 2000 and 2017. We have included all NIFTP cases (n = 6) and randomly selected cases of C-PTC (n = 14) and IFV-PTC (n = 8). Comparing NIFTP and C-PTC cases, NIFTP cases showed significantly less papillary or pseudopapillary architecture, more bidimensional groups and microfollicles, and less tridimensionality, giant cells, and nuclear folds. We observed a trend towards significance for smear cellularity and amount of cytoplasm. Presence of nuclear folds was the only significant difference between NIFTP and IFV-PTC cases. The differences between groups in percent papillary or pseudopapillary architecture, cellularity, and tridimensionality showed a trend towards significance. Amount of colloid, dirty background, pleomorphism or atypia, nuclear pseudoinclusions, type of chromatin, and nucleolus were not significant. No cytopathological feature can differentiate between invasive and encapsulated IFV-PTC. In accordance with the recently accepted category, PTC smears with cells arranged in a predominantly follicular architecture should be reported as Bethesda IV category with descriptive terms to avoid false-positive cases. © 2018 S. Karger AG, Basel.

Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.

PubMed

Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo

2008-12-01

Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

PubMed

Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

2014-06-01

In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of human papilloma virus with atypical and malignant oral papillary lesions.

PubMed

McCord, Christina; Xu, Jing; Xu, Wei; Qiu, Xin; Muhanna, Nidal; Irish, Jonathan; Leong, Iona; McComb, Richard John; Perez-Ordonez, Bayardo; Bradley, Grace

2014-06-01

This study aimed to examine atypical and malignant papillary oral lesions for low- and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison. Low-risk HPV was found in 10 of 66 cases, including 9 APLs and 1 papilloma. All low-risk HPV-positive cases showed suprabasilar MIB-1 staining, and the agreement was statistically significant (P < .0001). Diffuse p16 staining combined with high-risk HPV was not seen in any of the cases. A subset of HPV(-) APLs progressed to carcinoma. Oral papillary lesions are a heterogeneous group. Low-risk HPV infection is associated with a subset of APLs with a benign clinical course. Potentially malignant APLs and MPLs are not associated with low- or high-risk HPV. Copyright © 2014 Elsevier Inc. All rights reserved.

Papillary Thyroid Microcarcinoma Arising Within a Mature Ovarian Teratoma: Case Report and Review of the Literature

PubMed Central

Pineyro, Maria M; Pereda, Jimena; Schou, Pamela; de los Santos, Karina; de la Peña, Soledad; Caserta, Benedicta; Pisabarro, Raul

2017-01-01

Mature cystic teratoma is the most common kind of ovarian germ cell tumor. Malignant transformation is uncommon, with thyroid cancer rarely found. Papillary thyroid microcarcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-year-old woman who presented with abdominal pain and an ovarian mass. After surgery, the patient was diagnosed with a follicular variant papillary thyroid microcarcinoma that arose within a mature cystic ovarian teratoma. Based on the small size of the primary lesion and patient preferences, no further treatment was performed. To our knowledge, this is the third reported case of papillary thyroid microcarcinoma arising within a mature ovarian teratoma without struma ovarii. There is no consensus on the surgical approach and postoperative management of this condition. Whether further therapy with total thyroidectomy and radioiodine ablation may be beneficial is unknown. In conclusion, papillary thyroid microcarcinoma can also arise within mature ovarian teratomas. Although a favorable prognosis is anticipated, there is limited information about its history or prognosis. PMID:28615984

Papillary Thyroid Microcarcinoma Arising Within a Mature Ovarian Teratoma: Case Report and Review of the Literature.

PubMed

Pineyro, Maria M; Pereda, Jimena; Schou, Pamela; de Los Santos, Karina; de la Peña, Soledad; Caserta, Benedicta; Pisabarro, Raul

2017-01-01

Mature cystic teratoma is the most common kind of ovarian germ cell tumor. Malignant transformation is uncommon, with thyroid cancer rarely found. Papillary thyroid microcarcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-year-old woman who presented with abdominal pain and an ovarian mass. After surgery, the patient was diagnosed with a follicular variant papillary thyroid microcarcinoma that arose within a mature cystic ovarian teratoma. Based on the small size of the primary lesion and patient preferences, no further treatment was performed. To our knowledge, this is the third reported case of papillary thyroid microcarcinoma arising within a mature ovarian teratoma without struma ovarii. There is no consensus on the surgical approach and postoperative management of this condition. Whether further therapy with total thyroidectomy and radioiodine ablation may be beneficial is unknown. In conclusion, papillary thyroid microcarcinoma can also arise within mature ovarian teratomas. Although a favorable prognosis is anticipated, there is limited information about its history or prognosis.

[Differential diagnosis of papillary carcinomas of the thyroid, using image analysis and three dimensional reconstruction from serial sections].

PubMed

Holschbach, A; Kriete, A; Schäffer, R

1990-01-01

Papillae with fibrovascular cores are characteristic of papillary carcinoma of the thyroid. Papillae may be found in diffuse hyperplasia, nodular hyperplasia, Hashimoto's disease and follicular adenoma. Tissues from ten benign hyperplasias and ten papillary carcinomas were reconstructed from serial sections with three dimensional reconstruction programs. Significant qualitative and quantitative differences were found between the hyperplasia and the carcinoma. The principal differences between papillae of papillary carcinoma and hyperplasia were more clearly seen in the three dimensional reconstruction, than by means of morphometric methods. Certain criteria, e.g. the volume of papillae, were useful only with regard to the third dimension. Nevertheless, three dimensional reconstruction of biological tissue is a time consuming procedure which is not yet suitable for routine examination.

Comparison of the diagnostic efficacy between ultrasound elastography and magnetic resonance imaging for breast masses

PubMed Central

Cheng, Rong; Li, Jing; Ji, Li; Liu, Huining; Zhu, Limin

2018-01-01

The present study compared the efficacy of ultrasound elastography (UE), magnetic resonance imaging (MRI) and the combination of the two methods (UE+MRI) in the differential diagnosis of benign and malignant breast tumors. In total, 86 patients with breast masses were recruited and evaluated by UE, MRI and UE+MRI. Strain ratios of UE were calculated for the breast mass and adjacent normal tissues. In addition, the receiver operating characteristic (ROC) curve was obtained, while the sensitivity and specificity were calculated to determine the optimal cut-off point for the differential diagnosis. The area under the ROC curve (AUC) was also calculated to evaluate the diagnostic performance of these methods. The results indicated that the diagnostic accuracy of UE+MRI was significantly higher compared with the UE or MRI methods in the differential diagnosis of invasive ductal, invasive lobular, intraductal papillary, medullary and mucinous carcinomas (all P<0.05). The optimal cut-off points of ROC curve of the Strain Ratio in the diagnosis of breast lesions were 2.81, 3.76 and 3.42 for UE, MRI and UE+MRI, respectively. Furthermore, the AUC values were 86.7, 79.2 and 91.4%, while the diagnostic accuracy rates were 82.5, 75.5 and 95.3%, for UE, MRI and UE+MRI, respectively. Accuracy rate differences between UE and MRI or between UE and UE+MRI were statistically significant (P<0.05), whereas no significant difference existed between MRI and UE+MRI (P>0.05). Finally, the diagnostic consistency of the UE+MRI method with the pathological diagnosis was higher compared with UE or MRI alone. In conclusion, the combination of UE and MRI is superior to the use of UE or MRI alone in the differential diagnosis of benign and malignant breast masses. PMID:29456656

A unique case of spontaneous regression of metastatic papillary renal cell carcinoma: a case report

PubMed Central

Lim, Rebecca; Tan, Puay Hoon; Cheng, Christopher; Agasthian, Thirugnanam; Tan, Hwei Ling; Teh, Bin Tean

2009-01-01

Spontaneous regression of cancer is a rare, but well documented, phenomenon. We present a unique case of an 82 year old Chinese male who experienced spontaneous regression of histologically-verified metastatic type II papillary renal cell carcinoma in the absence of intervening systemic therapy or surgery. This is the first reported case of spontaneous regression of papillary renal cell carcinoma. The mechanism of spontaneous regression remains unknown, and represents a challenge for existing oncology paradigms. PMID:19918481

Synchronous papillary thyroid carcinoma and primary hyperparathyroidism: diagnosis and management issues.

PubMed

Vysetti, Suneetha; Sridhar, Preethi; Theckedath, Boby; Gilden, Janice L; Morawiecki, Peter

2012-10-01

The occurrence of a papillary thyroid carcinoma in a patient with primary hyperparathyroidism is rare. Awareness of this condition will enable clinicians to evaluate for possible thyroid pathology in patients with primary hyperparathyroidism. Both of these endocrine conditions could then be managed with a single surgery involving concomitant resection of the thyroid and parathyroid glands. We report a case of a 53-year-old woman with a parathyroid adenoma and a unilateral papillary thyroid carcinoma, and detail the clinical features, diagnosis, and management.

Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma

PubMed Central

Miftari, Rame; Topçiu, Valdete; Nura, Adem; Haxhibeqiri, Valdete

2016-01-01

Purpose: Papillary carcinoma is the most frequent type of thyroid cancer and was considered the most benign of all thyroid carcinomas, with a low risk of distant metastases. However, there are some variants of papillary thyroid carcinoma that have affinity to spread in many organs, such as: lymph nodes, lungs and bones. Aim: The aim of this study was presentation of a case with papillary carcinoma of the thyroid gland, very persistent and resistant in treatment with I 131. Material and results: A man 56 years old were diagnosed with papillary carcinoma of thyroid gland. He underwent a surgical removal of the tumor and right lobe of thyroid gland. With histopathology examination, were confirmed follicular variant of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin was found elevated above upper measured limits (more than 500 ng/ml). Patient underwent surgical removal of 10 metastatic lymph nodes in the left side of the neck and has been treated with 145 mCi of radioiodine I 131. The examination after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and focally uptake of J 131 in the left lung. Patient was treated once again with 150 mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of radioiodine in the middle of the left collarbone. After a month, patient refers the enlargement of the lymph node in the right side of the neck. Currently patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We have identified first positive response in treatment. Enlarged lymph node in the neck was reduced and the patient began feeling better. Conclusion: This study suggests that some subtypes of papillary thyroid carcinoma appear to have more aggressive biological course. Subtypes of papillary thyroid carcinoma such as diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants, appears to have more aggressive biological course and need early detection and other kind of treatment. PMID:27703298

Parametric imaging of clear cell and papillary renal cell carcinoma using contrast-enhanced ultrasound (CEUS).

PubMed

Rübenthaler, J; Reimann, R; Hristova, P; Staehler, M; Reiser, M; Clevert, D A

2015-10-16

The aim of this study was to analyse clear cell and papillary renal cell carcinoma (RCC) examined with contrast-enhanced ultrasound (CEUS) and a second generation blood pool agent (SonoVue®, Bracco, Milan, Italy) before clinical intervention. A total of 41 patients with histologically proven subtypes of RCC were examined. 29 patients had a clear cell RCC and 12 patients showed a papillary RCC. Average size in the clear cell RCC group was 6.07 cm and 1.88 cm in the papillary RCC group. An experienced radiologist examined all patients with CEUS. The following parameters were analysed: maximum signal intensity (PEAK), time elapsed until PEAK is reached (MTT), local blood flow (RBF), area under the time intensity curve (AUC) and the signal intensity (SI) during the course of time. For both groups all comparisons were made based on healthy renal parenchyma. In the clear cell RCC significant differences (significance level p < 0.05) between cancerous tissue and the healthy renal parenchyma were noticed in all four parameters. The clear cell RCC showed a significant reduced blood volume. It reached the PEAK reading relatively rapidly and its signal intensity was always lower than that of the healthy renal parenchyma. In the arterial phase retarded absorption of the contrast agent was observed, followed by fast washing out of the contrast agent bubbles.In the papillary RCC group, significant findings as to PEAK and RBF as well as a slightly significant difference as to AUC were recorded. The papillary RCC had a lower blood supply and reached its PEAK reading later. Its signal intensity was also reduced. The signal intensity of papillary NCC was significantly lower compared with clear cell RCC; absorption and washing out of the contrast agent was delayed. CEUS seems to be an useful additional method to clinically differentiate between clear cell and papillary RCC. In daily clinical use, patients with contraindication for other imaging methods, especially the magnetic resonance imaging, might particularly benefit from this method.

Craniopharyngioma: a clinicopathological study of 141 cases.

PubMed

Tavangar, Seyed Mohammad; Larijani, Bagher; Mahta, Ali; Hosseini, Seyed Mehdi Abdolahzadeh; Mehrazine, Masoud; Bandarian, Fatemeh

2004-01-01

Craniopharyngioma is a tumor of the suprasellar region that histologically has two distinct variants with some differences in clinical behavior. The papillary type is almost always seen in adults and has a more indolent course compared with the adamantinomatous type, which is more common in childhood. In the present study, surgical specimens of craniopharyngiomas from 141 patients were reviewed. Their histomorphologic types were determined and the clinical features and prognosis of each group were assessed. The sizes of papillary type tumors were smaller and during the follow-up period there was no recurrence in the squamous papillary group. Aside from surgical resection (total vs subtotal), the recurrence rate for papillary type craniopharyngioma was lower than for adamantinomatous type. Histologic typing of craniopharyngioma especially in adults is useful for decision making with regard to treatment and follow-up.

Simple and complex hyperplastic papillary proliferations of the endometrium: a clinicopathologic study of nine cases of apparently localized papillary lesions with fibrovascular stromal cores and epithelial metaplasia.

PubMed

Lehman, M B; Hart, W R

2001-11-01

The clinicopathologic features of nine cases of papillary proliferation of the endometrium devoid of malignant nuclear features were studied. The patients ranged in age from 33 to 71 years (median 57 years). All were postmenopausal, except the youngest. The most common symptom was postmenopausal bleeding. Two patients were receiving hormonal replacement therapy and two were taking megestrol acetate. Two lesions were incidental findings in a hysterectomy specimen. Seven were diagnosed in endometrial biopsy or curettage specimens. In six cases (67%) the lesion involved an endometrial polyp. In all cases the papillae had fibrovascular stromal cores and variable degrees of branching. Two architectural patterns were found. A simple papillary pattern with involvement of only a few glands and little epithelial proliferation occurred in five cases, including three that were entirely intracystic. A complex papillary pattern with more extensive involvement of endometrial glands, a greater degree of branching of the papillae, and cellular tufting occurred in four cases. One or more metaplastic epithelial changes occurred in all cases, including endocervical-type mucinous metaplasia in nine cases (90%), eosinophilic cell change in eight (89%), ciliated cell change in seven (70%), focal squamous metaplasia in two cases (22%), and hobnail cell change in two (22%). Mitotic figures were found in three cases. In four lesions (44%), all with a complex papillary pattern, the proliferating cells had mild nuclear atypia. Three of these patients underwent hysterectomy within 5 months. Simple nonpapillary hyperplasia and two endometrial polyps were found in one patient, complex nonpapillary hyperplasia in one, and atrophic endometrium in the other. Two patients had additional endometrial samplings within 4 months that contained small residual simple papillary lesions. One of these had another biopsy at 16 months that showed only atrophy. One patient had no subsequent diagnostic or therapeutic procedures. One patient was a recent case. Of the three patients with intact uteri and appreciable follow-up, all were alive and well at 14, 96, and 102 months, respectively. We conclude that these papillary proliferations are a form of hyperplasia that is closely associated with endometrial epithelial metaplasia. Polypectomy and/or curettage may be effective in removing them because they often are localized lesions. Although all of our patients had an uneventful outcome, the number of cases is small. Our findings question the validity of diagnosing endometrial lesions as well-differentiated carcinoma solely because of a complex papillary architectural pattern.

GNAq mutations are not identified in papillary thyroid carcinomas and hyperfunctioning thyroid nodules.

PubMed

Cassol, Clarissa A; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

2010-12-01

Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.

[Papillary cystadenoma of the epididymis: a report of 2 cases and review of the literature].

PubMed

Zhang, Wei; Tu, Pin; Wang, Jian-jun; He, Yan; Yu, Bo; Wang, Hai; Shi, Qun-li

2015-02-01

To study the clinicopathological characteristics of papillary cystadenoma of the epididymis. Using routine pathology and immunohistochemistry, we observed the surgically obtained samples from 2 cases of papillary cystadenoma of the epididymis, analyzed their pathological features and clinical presentations, and reviewed the related literature. The 2 patients were both adult males. The tumors typically manifested as painless swelling in the epididymis, with occasionally dull pain and tenesmus in 1 of the cases. Pathologically, the lesions exhibited three morphological features, i. e., dilated ducts and small cysts surrounded by fibrous connective tissue, adenoid papillary hyperplasia into the cysts embraced by fibrovascular stroma, and acidophil substance present in the cysts. Immunohistochemistry showed that the tumors were strongly positive for CK8/18, CK7, and EMA, but negative for CK20, CEA, MC, Calretenin, P53, P63, SMA, VHL, and CD10, with the positive rate of Ki-67 <1%. Follow-up visits revealed good prognosis in both cases. Papillary cystadenoma of the epididymis is a rare benign tumor in the male urogenital system, which may be accompanied by the VHL syndrome. Surgery is the first choice for its treatment.

Thyroid Cancer—Health Professional Version

Cancer.gov

There are four types of thyroid cancer. These are papillary, follicular, medullary, and anaplastic thyroid cancer. Papillary is the most common type of thyroid cancer. Find evidence-based information on thyroid cancer treatment, screening, research, genetics, and statistics.

[Papillary cystadenoma of the epididymis. 2 case reports].

PubMed

Raimoldi, A; Berti, G L; Canclini, L; Giola, V; Leidi, G L; Maccaroni, A; Sironi, M; Veneroni, L; Bacchioni, A M; Assi, A

1997-12-01

Tumors of the epididymis are very rare. They are benign tumors in 75 per cent of the cases. Papillary cystadenoma represents 4-9 per cent of epididymal benign tumors. Often associated with the syndrome of von Hippel Lindau and infertility, histologically it can be confused with metastatic renal cell carcinoma. We report two cases of papillary cystadenoma located in the head of the right epididymis, with no concomitance with the syndrome of von Hippel Lindau, cured by the removal of the neoplastic nodule. There was no recidivation, in confirmation of the neoplastic benignity.

Papillary fibroelastoma diagnosed through multimodality cardiac imaging: a rare tumour in an uncommon location with review of literature.

PubMed

Anand, Senthil; Sydow, Nicole; Janardhanan, Rajesh

2017-08-08

We describe the case of a woman presenting with transient ischaemic attack, who was found to have a papillary fibroelastoma arising from the aortic wall, an extremely rare location. We describe the multimodality imaging techniques used in diagnosing this patient and review the most recent literature on evaluation and management of patients with cardiac papillary fibroelastomas. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Aggressive Digital Papillary Adenocarcinoma in a Young Female-a Rare Presentation.

PubMed

Gole, Gautam Nandkumar; Tati, Shekhar Y; Deshpande, Ashok Kumar; Gole, Sheetal G

2011-06-01

A 20 year old female presented with a recurrent soft tissue swelling over the medial aspect of proximal phalanx of left little finger. It had recurred one year after excision. There was no lymphadenopathy or bony involvement. Previous histopathology reports were not available. After excision histopathological diagnosis was aggressive digital papillary adenocarcinoma. Later Ray's amputation of little finger was planned. Aggressive digital papillary adenocarcinomas are rare sweat gland tumors which occur on hands, fingers, and toes. They have high local recurrence rate and may metastasize to lungs and lymph nodes.

Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report

PubMed Central

K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-01-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039

Papillary carcinoma in median aberrant thyroid (ectopic) - case report.

PubMed

Hebbar K, Ashwin; K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-06-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed.

Diffuse lipomatosis of the thyroid gland with papillary microcarcinoma: Report of a rare entity.

PubMed

Nandyala, Hariharanadha Sarma; Madapuram, Srinivasulu; Yadav, Megha; Katamala, Sudheer Kumar

2015-01-01

Presence of lobules of adipose tissue either focally or diffusely is very rare in the thyroid gland. Fat accumulation can be macroscopic or microscopic. Focal infiltrates of fat have been reported in conditions such as adenolipoma, intrathyroid lipoma, and encapsulated papillary carcinoma. Diffuse lipomatosis has been reported in conditions such as amyloid goitre, heterotopic fat nests, thyrolipoma and liposarcoma. The exact mechanism of fat accumulation is not known although there are many theories postulated. Investigations such as ultrasound, computed tomography scan, and magnetic resonance imaging can detect the presence of macroscopic fat in the thyroid gland. Accurate diagnosis of the type of fat accumulation is necessary because tumorous and nontumorous conditions fall into the differential diagnosis. Only nine cases of papillary carcinoma associated with lipomatosis of thyroid are reported so far. We report possibly the first case of diffuse lipomatosis of the thyroid gland with a focus of papillary microcarcinoma.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma.

PubMed

Kim, Jisup; Lim, Beom Jin; Hong, Soon Won; Pyo, Ju Yeon

2018-03-01

Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma

PubMed Central

Kim, Jisup; Lim, Beom Jin; Hong, Soon Won; Pyo, Ju Yeon

2018-01-01

Background Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Methods Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. Results WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. Conclusions The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA. PMID:29429327

Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia.

PubMed

Yan, Dong; Cheng, Lu-feng; Song, Hong-Yan; Turdi, Subat; Kerram, Parhat

2007-08-01

Overdoses of haloperidol are associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. The aim of this experiment was to study the effect of haloperidol on the action potentials in cardiac Purkinje fibers and papillary muscles under normal and simulated ischemia conditions in rabbits and guinea pigs. Using the standard intracellular microelectrode technique, we examined the effects of haloperidol on the action potential parameters [action potential amplitude (APA), phase 0 maximum upstroke velocity (V(max)), action potential amplitude at 90% of repolarization (APD(90)), and effective refractory period (ERP)] in rabbit cardiac Purkinje fibers and guinea pig cardiac papillary cells, in which both tissues were under simulated ischemic conditions. Under ischemic conditions, different concentrations of haloperidol depressed APA and prolonged APD(90) in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 micromol/L) significantly depressed APA and prolonged APD(90), and from 1 micromol/L, haloperidol showed significant depression on V(max); ERP was not significantly affected. In guinea pig cardiac papillary muscles, the thresholds of significant reduction in APA, V(max), EPR, and APD(90) were 10, 0.3, 1, and 1 mumol/L, respectively, for haloperidol. Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD(90) in a concentration-dependent manner and precipitated the decrease in V(max) induced by ischemia. The shortening of ERP and APD(90) in papillary muscle action potentials may be inhibited by haloperidol.

[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].

PubMed

Liu, Yan; Miao, Yuhua; Li, Xiaoming

2015-06-01

To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.

Papillary Fibroelastoma of the Aortic Valve: Analysis of 21 Cases, Including a Presentation with Cardiac Arrest

PubMed Central

Andrei, Adin-Cristian; Li, Zhi; McCarthy, Patrick M.; Malaisrie, S. Chris

2015-01-01

Cardiac papillary fibroelastoma is a rare, benign tumor, arising predominantly from cardiac valves. This tumor can cause a variety of symptoms due to thromboembolism. We describe our single-center surgical experience with papillary fibroelastoma of the aortic valve. From April 2004 through June 2013, 6,530 patients underwent cardiac surgery. Of those, 6,098 patients were included in the final analysis. Twenty-one patients (0.34%) underwent surgical resection of 30 papillary fibroelastomas of the aortic valve. Most patients (67%) were incidentally diagnosed to have cardiac papillary fibroelastoma. The usual symptom was cerebral infarction (in 5 of 7 symptomatic patients). A rare presentation of papillary fibroelastoma in one patient was cardiac arrest caused by left main coronary artery ostial obstruction. Tumor size was not related to patient age (Pearson correlation coefficient, 0.34; P=0.13). Neither the number of tumors (1.43 ± 0.72 vs 1.43 ± 0.62) nor tumor size (8.14 ± 2.42 vs 8.07 ± 3.31 mm) was significantly different between symptomatic and asymptomatic patients. All lesions were resected by means of the simple shave technique. There were no operative or 30-day deaths. Follow-up echocardiograms showed no tumor recurrence (mean follow-up duration, 17 ± 14 mo). We identified no significant relationship among tumor size, number of tumors, symptoms, or patient age. Because simple shave excision of the tumor can be safely achieved without evidence of tumor recurrence, we conclude that surgical resection can be reasonable in asymptomatic patients. PMID:25873822

Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

PubMed

Ip, Philip Pun-Ching

2018-02-14

Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.

Papillary neoplasia of the breast: immunohistochemically defined myoepithelial cells in the diagnosis of benign and malignant papillary breast neoplasms.

PubMed

Raju, U B; Lee, M W; Zarbo, R J; Crissman, J D

1989-11-01

The presence or absence of myoepithelial cells (ME) has been considered as an important feature in the differential diagnosis of benign and malignant papillary lesions of the breast. We evaluated the distribution of myoepithelial cells in formalin-fixed paraffin-embedded tissue sections of 25 papillomas and 18 papillary carcinomas by ABC immunoperoxidase technique with antibodies to muscle actin (HHF-35) and high molecular weight (HMW) keratin (clone 34BE12, cytokeratins 1, 5, 10, and 14; reacting preferentially with ME cells) and an antiserum to S-100 protein. Also included in the study were eight cases of micropapillary ductal carcinoma in situ (DCIS) having a few fibrovascular cores and five peripheral papillomas with accompanying ductal carcinoma in situ or atypical hyperplasia. The antibodies to muscle actin were sensitive and relatively specific for ME cells of the breast and uniformly labeled ME cells in all 25 papillomas. ME cells were absent or extremely sparse in papillary carcinomas. They were present focally in some of the fibrovascular cores of the micropapillary DCIS, and a mixed pattern was observed in peripheral papillomas with areas of carcinoma. HMW keratin was variably expressed in ME cells in most cases with positive internal controls and was present in several normal ductal and papilloma epithelial cells but not in epithelial cells of papillary carcinomas. HMW keratin, although less specific for ME cells, was a useful adjunct because of its reactivity with ME cells as well as hyperplastic epithelial cells in papillomas, which resulted in a combined positive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

ClinicalTrials.gov

2017-01-24

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients.

PubMed

Gambardella, Claudio; Tartaglia, Ernesto; Nunziata, Anna; Izzo, Graziella; Siciliano, Giuseppe; Cavallo, Fabio; Mauriello, Claudio; Napolitano, Salvatore; Thomas, Guglielmo; Testa, Domenico; Rossetti, Gianluca; Sanguinetti, Alessandro; Avenia, Nicola; Conzo, Giovanni

2016-09-19

Lymph nodal involvement is very common in differentiated thyroid cancer, and in addition, cervical lymph node micrometastases are observed in up to 80 % of papillary thyroid cancers. During the last decades, the role of routine central lymph node dissection (RCLD) in the treatment of papillary thyroid cancer (PTC) has been an object of research, and it is now still controversial. Nevertheless, many scientific societies and referral authors have definitely stated that even if in expert hands, RCLD is not associated to higher morbidity; it should be indicated only in selected cases. In order to better analyze the current role of prophylactic neck dissection in the surgical treatment of papillary thyroid cancers, an analysis of the most recent literature data was performed. Prophylactic or therapeutic lymph node dissection, selective, lateral or central lymph node dissection, modified radical neck dissection, and papillary thyroid cancer were used by the authors as keywords performing a PubMed database research. Literature reviews, PTCs large clinical series and the most recent guidelines of different referral endocrine societies, inhering neck dissection for papillary thyroid cancers, were also specifically evaluated. A higher PTC incidence was nowadays reported in differentiated thyroid cancer (DTC) clinical series. In addition, ultrasound guided fine-needle aspiration citology allowed a more precocious diagnosis in the early phases of disease. The role of prophylactic neck dissection in papillary thyroid cancer management remains controversial especially regarding indications, approach, and surgical extension. Even if morbidity rates seem to be similar to those reported after total thyroidectomy alone, RCLD impact on local recurrence and long-term survival is still a matter of research. Nevertheless, only a selective use in high-risk cases is supported by more and more scientific data. In the last years, higher papillary thyroid cancer incidence and more precocious diagnoses were worldwide reported. Among endocrine and neck surgeons, there is agreement about indications to prophylactic treatment of node-negative "high-risk" patients. A recent trend toward RCLD avoiding radioactive treatment is still debated, but nevertheless, prophylactic dissections in low-risk cases should be avoided. Prospective randomized trials are needed to evaluate the benefits of different approaches and allow to drawn definitive conclusions.

Biliary Ascariasis: MR Cholangiography Findings in Two Cases

PubMed Central

Hwang, Cheol Mok; Ha, Hyun Kwon; Kim, Pyo Nyun; Lee, Moon-Gyu

2001-01-01

We describe the imaging features of two cases of biliary ascariasis. Ultrasonography and CT showed no specific abnormal findings, but MR cholangiography clearly demonstrated an intraductal linear filling defect that led to the correct diagnosis. MR cholangiography is thus a useful technique for the diagnosis of biliary ascariasis. PMID:11752990

Genetic drivers of papillary renal cell carcinoma - TCGA

Cancer.gov

A comprehensive genomic analysis of 161 tumors from people with papillary renal cell carcinoma (PRCC) – the second most common form of kidney cancer –provided insights into the molecular basis of this cancer and may inform its classification and treatment.

Well-Differentiated Papillary Mesothelioma of the Tunica Vaginalis: A Case Study and Review of the Literature

PubMed Central

Acikalin, Arbil; Zeren, Handan; Gonlusen, Gulfılız; Zorludemir, Suzan; Izol, Volkan

2014-01-01

Well-differentiated papillary mesothelioma is an uncommon tumor of the testes that usually presents as a hydrocele. Here, we present the case of one patient who did not have a history of asbestos exposure. The tumor was localized in the tunica vaginalis and was composed of three pedunculated masses macroscopically. Microscopically, branching papillary structures with focal coagulative necrosis were present. In addition to immunohistochemistry, simian virus 40 DNA was also tested by polymerase chain reaction. This report presents one case of this rare entity, its clinical and macroscopic features, and follow-up results. PMID:25013421

Marine-Lenhart syndrome with papillary thyroid carcinoma.

PubMed

Atmaca, Hulusi; Çolak, Ramis; Yazici, Zihni Acar; Kefeli, Mehmet; Tosun, Fevziye Canbaz

2015-04-01

Graves' disease with accompanying functioning nodules is known as Marine-Lenhart syndrome. Autonomously functioning thyroid nodules (AFTNs) also within Graves' thyroid tissue are almost always bening in nature. A 45-year-old man developed hyperthyroidism due to the coexistence of Graves' disease and AFTN. Total thyroidectomy was performed. The hyperfunctioning nodule with centrally hypoactive foci detected by technetium-99m thyroid scanning was histologically diagnosed as papillary thyroid carcinoma that was 2.5 cm in diameter. We report the presence of papillary thyroid carcinoma within AFTN in patients with Marine-Lenhart syndrome, which has not been reported so far.

An unusual metastasis of a papillary thyroidian carcinoma with follicular pattern.

PubMed

Coconu, M; Berdan, G; Roşculescu, I; Herlea, V

1998-01-01

The case of a 67-year-old man is presented. He was admitted for the presence of a left parietal tumour with progressive growing, without any other objective or subjective symptomatology. CT-scan detects a left parietal osteolytic area. The histopathological aspect suggested an adenocarcinomatous metastasis with papillary pattern, moderately differentiated. With the purpose of diagnosing the original tumour, immunnohistochemical techniques were performed, which led to a diagnosis of a thyroidian carcinoma. At the histological examination of the surgical extirpated thyroid, it was proved to be a papillary carcinoma (Chan, 1990, Hay, 1990), the follicular pattern.

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid.

PubMed

Rossi, E D; Raffaelli, M; Mule', A; Miraglia, A; Lombardi, C P; Vecchio, F M; Fadda, G

2006-06-01

The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

Intravascular papillary endothelial hyperplasia of the foot.

PubMed

Cisco, R W; McCormac, R M

1994-01-01

Intravascular papillary endothelial hyperplasia is a rare benign reactive lesion usually found in thrombosed subcutaneous blood vessels. The lesion resembles malignant angiosarcoma clinically and histopathologically, and must be diagnosed correctly to avoid inappropriate treatment. The following is a case presentation involving the foot.

Solid papillary carcinoma of the breast: A special entity needs to be distinguished from conventional invasive carcinoma avoiding over-treatment.

PubMed

Guo, Shuangping; Wang, Yingmei; Rohr, Joseph; Fan, Chaoliang; Li, Qinglong; Li, Xia; Wang, Zhe

2016-04-01

Solid papillary carcinoma of the breast, a newly-defined entity, is poorly recognized, and its nature and management is still debated. Eleven cases of pure solid papillary breast carcinoma in our archive and 253 cases reported in previous literature were retrospectively analyzed for their clinicopathological features and outcomes. The eleven cases occurred in elderly females. Grossly, all tumors were well-circumscribed and typically composed of solid papillary nodules. The tumor cells were bland-looking with low-grade atypia and mitoses < 5/10HPF. Immunophenotypically, all eleven cases showed positivity for ER and PR, negativity for CK5/6 and HER2, and a low proliferative index of Ki67. Five cases showed scattered positivity for myoepithelial marker p63, and four cases were positive for CK5/6 and CD10 around the nodules, whereas the other cases were completely negative for all myoepithelial markers. Five cases expressed the neuroendocrine marker synaptophysin, and six cases expressed chromogranin. In nine cases, mastectomy and axillary lymph nodes excision were performed, and only one showed micrometastasis in an axillary lymph node. There was no local recurrence or distant metastasis or breast carcinoma related-death during the follow-up periods of 50 months. Out of 253 solid papillary breast carcinomas reported in literature, the percentage of axillary lymph node metastasis was 4/136 (3%), with rare local recurrences and distant metastasis; only three patients died of breast carcinoma. Solid papillary carcinoma of the breast is a rare entity with distinctive clinicopathological features and excellent prognosis and should be distinguished from conventional breast carcinoma to avoid over-treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thyroid cancer profile in Mures County (Romania): a 20 years study.

PubMed

Cătană, Ramona; Boilă, Adela; Borda, Angela

2012-01-01

The aim of the present study was to present data on frequency of thyroid cancer in Mures County (Romania) and border counties, a goiter endemic area, and to analyze its histopathological characteristics, over a 20 years period (1990-2009). Demographic, clinical and pathological data were obtained from database registries. Histological subtypes of thyroid cancer were classified according to the WHO criteria (sixth edition, 2004) in the following categories: papillary thyroid carcinoma with its histological subtypes, follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, undifferentiated thyroid carcinoma, medullary carcinoma, lymphoma, metastatic tumors. Our analyze included 524 cases of thyroid cancer of the 3460 surgical thyroid specimens resected between 1990-2009: 410 (78.2%) cases of papillary carcinoma, 19 (3.6%) cases of follicular carcinoma, 24 (4.6%) cases of poorly differentiated carcinoma, 33 (6.3%) cases of undifferentiated carcinoma, 22 (4.1%) medullary carcinomas, eight (1.6%) lymphomas, and eight (1.6%) metastatic tumors. Papillary thyroid carcinoma is the most common histological form (78%) and an increasing incidence of this form was observed. A statistical significant increase in the incidence of the follicular variant of papillary carcinoma was noticed between 2000-2009, compared to 1990-2000. An increased incidence of small tumors was also found (6.66%, 1990-1999 vs. 23.5%, 2000-2009). The undifferentiated thyroid cancer had a marked decreasing trend (20%, 1990-1999 vs. 3.45%, 2000-2009). Our study demonstrates an increasing trend in the incidence of thyroid cancer in the last 20 years. This increase is mainly due to the small papillary cancers, by contrast to the undifferentiated thyroid cancers that have a decreasing trend. A better understanding and description of the morphological criteria could explained the increasing incidence of the follicular variant of papillary carcinoma.

Influence of optic disc leakage on objective optic nerve head assessment in patients with uveitis.

PubMed

Heinz, Carsten; Kogelboom, Katy; Heiligenhaus, Arnd

2016-02-01

Secondary glaucoma is a common complication in patients with uveitis. Heidelberg Retina Tomography (HRT) and retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT) are widely used for examining optic nerve head changes. We evaluated these parameters in patients with uveitis and secondary glaucoma and with inflammatory papillary leakage on fluorescein angiography. Prospective single-center analysis of patients with uveitis, evaluating the impact of optic disc leakage on objective optic disc imaging parameters. Overall, 96 eyes of 59 patients were included. Papillary leakage was found in 42 eyes (43.8 %), and secondary glaucoma was found in 41 eyes (42.7 %). Glaucoma and papillary leakage were present in 12 (29 %) eyes with leakage and in 29 (54 %) eyes without leakage (p = 0.023). Neuroretinal rim area (p = 0.004), rim volume on HRT (p = 0.004), and RNFL thickness on OCT (p = 0.0008) were significantly increased in eyes with papillary leakage, while RNFL on HRT was unchanged (p = 0.255). When only eyes with normal IOP were examined, all objective parameters on OCT and HRT were significantly increased, whereas in eyes with secondary glaucoma, there was only a trend in the same direction, which did not reach significance. A comparison of eyes with secondary glaucoma and optic disc leakage to normal eyes with no glaucoma or leakage revealed no difference in any of the parameters. The objective parameters of optic nerve head imaging tools are significantly influenced by papillary leakage. In patients with secondary glaucoma and papillary leakage, these techniques are unable to detect and monitor glaucomatous damage.

Surface Papillary Epithelial Hyperplasia (Rough Mucosa) is a Helpful Clue for Identification of Polymorphous Low-Grade Adenocarcinoma.

PubMed

Chi, Angela C; Neville, Brad W

2015-06-01

The purpose of this study is to evaluate surface papillary epithelial hyperplasia, a microscopic finding that corresponds to the clinical finding of rough or stippled mucosa, as a predictor of polymorphous low-grade adenocarcinoma (PLGA). We conducted a retrospective review of minor salivary gland neoplasms submitted to our biopsy service from 1991 to 2013. Our review was limited to lesions involving the oral cavity/soft palate with the following diagnoses: PLGA, pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). A total of 202 minor salivary gland neoplasms were included in the study. Among cases in which surface epithelium was present for evaluation (n = 112), surface papillary epithelial hyperplasia was evident in 30 % of PLGA and 1 % of non-PLGA (i.e., MEC, ACC, PA). The greater frequency of surface papillary epithelial hyperplasia in the PLGA versus non-PLGA cases and in the benign versus malignant cases was significant (p = .0001 and p = .041, respectively). The sensitivity and specificity of papillary epithelial hyperplasia for PLGA were 30 % (95 % confidence interval (CI) 11.97-54.27 %) and 99 % (95 % CI 94-99.82 %), respectively. The clinical presentation of PLGA appeared relatively nonspecific, with all analyzed tumor types exhibiting a predilection for females, middle-aged to older adults, palatal location, pink/tan/normal color, and firm consistency. In conclusion, papillary epithelial hyperplasia was evident in only a minority of PLGA. However, when present within the context of a palatal salivary gland neoplasm, it appears to indicate a high probability of PLGA. Accordingly, rough mucosa may be a useful clinical pearl for identification of PLGA.

Localization of premature ventricular contractions from the papillary muscles using the standard 12-lead electrocardiogram: a feasibility study using a novel cardiac isochrone positioning system.

PubMed

van Dam, Peter M; Boyle, Noel G; Laks, Michael M; Tung, Roderick

2016-12-01

The precise localization of the site of origin of a premature ventricular contraction (PVC) prior to ablation can facilitate the planning and execution of the electrophysiological procedure. In clinical practice, the targeted ablation site is estimated from the standard 12-lead ECG. The accuracy of this qualitative estimation has limitations, particularly in the localization of PVCs originating from the papillary muscles. Clinical available electrocardiographic imaging (ECGi) techniques that incorporate patient-specific anatomy may improve the localization of these PVCs, but require body surface maps with greater specificity for the epicardium. The purpose of this report is to demonstrate that a novel cardiac isochrone positioning system (CIPS) program can accurately detect the specific location of the PVC on the papillary muscle using only a 12-lead ECG. Cardiac isochrone positioning system uses three components: (i) endocardial and epicardial cardiac anatomy and torso geometry derived from MRI, (ii) the patient-specific electrode positions derived from an MRI model registered 3D image, and (iii) the 12-lead ECG. CIPS localizes the PVC origin by matching the anatomical isochrone vector with the ECG vector. The predicted PVC origin was compared with the site of successful ablation or stimulation. Three patients who underwent electrophysiological mapping and ablation of PVCs originating from the papillary muscles were studied. CIPS localized the PVC origin for all three patients to the correct papillary muscle and specifically to the base, mid, or apical region. A simplified form of ECGi utilizing only 12 standard electrocardiographic leads may facilitate accurate localization of the origin of papillary muscle PVCs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Optimizing treatment for children and adolescents with papillary thyroid carcinoma in post-Chernobyl exposed region: The roles of lymph node dissections in the central and lateral neck compartments.

PubMed

Fridman, Mikhail; Krasko, Olga; Lam, Alfred King-Yin

2018-06-01

There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991-2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

The value of the repeated examination of BRAF V600E mutation status in diagnostics of papillary thyroid cancer.

PubMed

Beiša, Augustas; Beiša, Virgilijus; Stoškus, Mindaugas; Ostanevičiūtė, Elvyra; Griškevičius, Laimonas; Strupas, Kęstutis

2016-01-01

Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics.

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

Perigastric lymph node metastasis from papillary thyroid carcinoma in a patient with early gastric cancer: the first case report.

PubMed

Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok

2014-09-01

Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.

Encapsulated Papillary Carcinoma in A Man with Gynecomastia: Ultrasonography, Mammography and Magnetic Resonance Imaging Features with Pathologic Correlation.

PubMed

Yılmaz, Ravza; Cömert, Rana Günöz; Aliyev, Samil; Toktaş, Yücel; Önder, Semen; Emirikçi, Selman; Özmen, Vahit

2018-04-01

Male breast cancer is an uncommon disease that constitutes 1% of all breast cancers and encapsulated papillary carcinoma (EPC) is a rare subtype of malignant male diseases. Gynecomastia is the most common disease of the male breast. We report a 63-year-old male patient with EPC accompanied by gynecomastia that was diagnosed and treated at our breast center. Mammography showed an oval-shaped dense mass with circumscribed margins on the ground of nodular gynecomastia. On ultrasonographic exam, we saw a well-circumscribed complex mass with a solid component which was vascular on Doppler ultrasonography. Magnetic resonance imaging revealed a complex cystic mass containing solid components. Dynamic images showed enhancement of the cystic mass wall and mural components. Tumor stage was evaluated as T2N0. The lesion's histologic examination and immunohistochemical analysis by showing no myoepithelial layer revealed an encapsulated papillary carcinoma. To our knowledge, this is the first case report which describes MR imaging findings of male breast encapsulated papillary cancer.

Intraluminal measurement of papillary duct urine pH, in vivo: a pilot study in the swine kidney.

PubMed

Handa, Rajash K; Lingeman, James E; Bledsoe, Sharon B; Evan, Andrew P; Connors, Bret A; Johnson, Cynthia D

2016-06-01

We describe the in vivo use of an optic-chemo microsensor to measure intraluminal papillary duct urine pH in a large mammal. Fiber-optic pH microsensors have a tip diameter of 140-µm that allows insertion into papillary Bellini ducts to measure tubule urine proton concentration. Anesthetized adult pigs underwent percutaneous nephrolithotomy to access the lower pole of the urinary collecting system. A flexible nephroscope was advanced towards an upper pole papilla with the fiber-optic microsensor contained within the working channel. The microsensor was then carefully inserted into Bellini ducts to measure tubule urine pH in real time. We successfully recorded tubule urine pH values in five papillary ducts from three pigs (1 farm pig and 2 metabolic syndrome Ossabaw pigs). Our results demonstrate that optical microsensor technology can be used to measure intraluminal urine pH in real time in a living large mammal. This opens the possibility for application of this optical pH sensing technology in nephrolithiasis.

Dual malignancy in adolescence: A rare case report of metachronous papillary carcinoma of thyroid following dysgerminoma of ovary

PubMed Central

Chakrabarti, Suvadip; Desai, Sanjay M.; Mehta, Dharmendra Y.; Somanath, Shreyas

2016-01-01

Dual malignancy is rare in adolescents. Dual malignancy with the second malignancy of thyroid is rare. No association has been reported between dysgerminoma of ovary and carcinoma thyroid in medical literature. Despite a thorough PubMed search (key words — Papillary carcinoma of thyroid, metachronous, dysgerminoma ovary), we were unable to find a previous reported case of metachronous papillary carcinoma of thyroid (PTC) following dysgerminoma of the ovary. After surgery, the patient is being regularly followed up for recurrence/development of new primary. We report this unusual and rare case in a 17-year-old female patient. PMID:27904567

[Multifocal tubulopapillary tumors of the kidney. Morphologic features and prognosis. Three cases].

PubMed

Abdelmoula, N B; Boudawara, T; Bahloul, A; Hmida, M B; Hachicha, J; Rebai, T; Mhiri, N; Jlidi, R

1999-01-01

Tubulopapillary tumors of the kidney represent a particular group of renal tumors characterized by their less aggressive behavior. These tumors are distinguished from non papillary tumors by their morphologic, cytochemical and genotypic features. They correspond to a continuous spectrum of tumors ranging from papillary renal cell adenoma to papillary renal cell carcinoma. These TTPR show multifocal, bilateral development and chronic lesions of the kidney parenchyma in nearly all cases. The authors report three cases of multifocal TTPR, including one bilateral case. Based on analysis of these cases and a review of the literature, they discuss the histogenetic features and prognosis of TTPR.

Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy.

PubMed

Rostami, Elham; Witt Nyström, Petra; Libard, Sylwia; Wikström, Johan; Casar-Borota, Olivera; Gudjonsson, Olafur

2017-11-01

Craniopharyngiomas are histologically benign but locally aggressive tumors in the sellar region that may cause devastating neurological and endocrine deficits. They tend to recur following surgery with high morbidity; hence, postoperative radiotherapy is recommended following sub-total resection. BRAFV600E mutation is the principal oncogenic driver in the papillary variant of craniopharyngiomas. Recently, a dramatic tumor reduction has been reported in a patient with BRAFV600E mutated, multiply recurrent papillary craniopharyngioma using a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Here, we report on near-radical reduction of a growing residual BRAFV600E craniopharyngioma using the same neoadjuvant therapy.

Distinct Fibroblasts in the Papillary and Reticular Dermis: Implications for Wound Healing.

PubMed

Woodley, David T

2017-01-01

Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units or other appendages. Dermal fibroblasts come from 2 distinct lineages of cells that have distinct cell markers and, more importantly, distinct functional abilities. Human skin wound healing largely involves the dermal fibroblast lineage from the reticular dermis and not the papillary dermis. If scientists could find a way to stimulate the dermal fibroblast lineages from the papillary dermis in early wound healing, perhaps human skin wounds could heal without scarring and with skin appendages. Copyright © 2016 Elsevier Inc. All rights reserved.

Intraductal ultrasonographic anatomy of biliary varices in patients with portal hypertension.

PubMed

Takagi, Tadayuki; Irisawa, Atsushi; Shibukawa, Goro; Hikichi, Takuto; Obara, Katsutoshi; Ohira, Hiromasa

2015-01-01

The term, portal biliopathy, denotes various biliary abnormalities, such as stenosis and/or dilatation of the bile duct, in patients with portal hypertension. These vascular abnormalities sometimes bring on an obstructive jaundice, but they are not clear which vessels participated in obstructive jaundice. The aim of present study was clear the bile ductal changes in patients with portal hypertension in hopes of establishing a therapeutic strategy for obstructive jaundice caused by biliary varices. Three hundred and thirty-seven patients who underwent intraductal ultrasound (IDUS) during endoscopic retrograde cholangiography for biliary abnormalities were enrolled. Portal biliopathy was analyzed using IDUS. Biliary varices were identified in 11 (2.7%) patients. IDUS revealed biliary varices as multiple, hypoechoic features surrounding the bile duct wall. These varices could be categorized into one of two groups according to their location in the sectional image of bile duct: epicholedochal and paracholedochal. Epicholedochal varices were identified in all patients, but paracholedochal varices were observed only in patients with extrahepatic portal obstruction. IDUS was useful to characterize the anatomy of portal biliopathy in detail.

Discrepant serum and urine β-hCG results due to production of β-hCG by a cribriform-morular variant of thyroid papillary carcinoma.

PubMed

Alikhan, Mir; Koshy, Anoopa; Hyjek, Elizabeth; Stenson, Kerstin; Cohen, Ronald N; Yeo, Kiang-Teck J

2015-01-01

Although patients with medullary thyroid cancer are known to present with paraneoplastic hormone production, this is much less common with papillary thyroid cancer. We present a patient with the cribriform morular variant of papillary thyroid cancer in association with familial adenomatous polyposis who developed a positive pregnancy test in the absence of known pregnancy. The patient had developed vaginal bleeding, and her laboratory testing was characterized by elevated serum human chorionic gonadotropin (β-hCG) concentrations, but negative qualitative urine results. After a thorough gynecological evaluation to exclude unexpected normal, ectopic, or molar pregnancy, we pursued an evaluation for other sources of β-hCG production. We showed that the elevated serum β-hCG concentrations were not the result of heterophile antibody interferences, and ultimately we proved that her recurrent tumor produced the ectopic β-hCG. This is the first report of β-hCG production by papillary thyroid cancer. Thus, the possibility of ectopic production of β-hCG by papillary thyroid cancer needs to be included in the differential diagnosis of elevated hCG concentration in the absence of pregnancy. This study of an unusual paraneoplastic syndrome highlights the importance of investigating discrepancies in the clinical laboratory. Copyright © 2014 Elsevier B.V. All rights reserved.

Endoscopic papillary large balloon dilation for the removal of bile duct stones.

PubMed

Kim, Jin Hong; Yang, Min Jae; Hwang, Jae Chul; Yoo, Byung Moo

2013-12-14

Endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been widely used as the alternative to EST along with endoscopic mechanical lithotripsy (EML) for the removal of large or difficult bile duct stones. Furthermore, EPLBD without EST was recently introduced as its simplified alternative technique. Thus, we systematically searched PubMed, Medline, the Cochrane Library and EMBASE, and analyzed all gathered data of EPLBD with and without EST, respectively, by using a single standardized definition, reviewing relevant literatures, published between 2003 and June 2013, where it was performed with large-diameter balloons (12-20 mm). The outcomes, including the initial success rate, the rate of needs for EML, and the overall success rate, and adverse events were assessed in each and compared between both of two procedures: "EPLBD with EST" and "EPLBD without EST". A total of 2511 procedures from 30 published articles were included in EPLBD with EST, while a total of 413 procedures from 3 published articles were included in EPLBD without EST. In the results of outcomes, the overall success rate was 96.5% in EPLBD with EST and 97.2% in EPLBD without EST, showing no significant difference between both of them. The initial success rate (84.0% vs 76.2%, P < 0.001) and the success rate of EPLBD without EML (83.2% vs 76.7%, P = 0.001) was significantly higher, while the rate of use of EML was significantly lower (14.1% vs 21.6%, P < 0.001), in EPLBD with EST. The rate of overall adverse events, pancreatitis, bleeding, perforation, other adverse events, surgery for adverse events, and fatal adverse events were 8.3%, 2.4%, 3.6%, 0.6%, 1.7%, 0.2% and 0.2% in EPLBD with EST and 7.0%, 3.9%, 1.9%, 0.5%, 0.7%, 0% and 0% in EPLBD without EST, respectively, showing no significant difference between both of them. In conclusion, recent accumulated results of EPLBD with or even without EST suggest that it is a safe and effective procedure for the removal of large or difficult bile duct stones without any additional risk of severe adverse events, when performed under appropriate guidelines.

Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis

PubMed Central

Gulwani, Hanni; Jain, Aruna

2010-01-01

Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome. PMID:21151719

Success and complications of an intra-ductal fully covered self-expanding metal stent (ID-FCSEMS) to treat anastomotic biliary strictures (AS) after orthotopic liver transplantation (OLT).

PubMed

Aepli, Patrick; St John, Andrew; Gupta, Saurabh; Hourigan, Luke F; Vaughan, Rhys; Efthymiou, Marios; Kaffes, Arthur

2017-04-01

Anastomotic biliary strictures (AS) after orthotopic liver transplantation (OLT) belong to the most common biliary complications and cause the biggest morbidity burden after OLT. Metal stents for benign biliary strictures are gaining acceptance with many published series. Traditional metal stent designs seem to have poor durability in AS after OLT. Novel intra-ductal stents are showing promise in these strictures. As a result, we designed a special stent with an antimigration waist and a short stent length with a long removal string that rests in the duodenum for easy removal. This is a retrospective multi-centre Australian study of AS after OLT treated with a novel intra-ductal fully covered self-expanding metal stent. From August 2008 to October 2014, records from three liver transplant centres were reviewed. Totally 36 ID-FCSEMS were inserted in 31 cases to treat an AS after OLT. The mean age of the patients was 56 years, and 61 % were male. The mean time of AS presentation after OLT was 20.3 months. Eight out of our 31 patients were previously treated using multiple plastic stenting over time without any success. Treatment with the ID-FCSEMS was performed with an average treatment time of 3.8 months. Stricture resolution was achieved in 100 %. All attempted stents removals were successful without any difficulty. Complications were reported in 6.5 %. It was pleasing that only one case of stent migration (2.8 %) was seen. Follow-up showed seven cases of AS recurrence (24.1 %), and all were treated successfully with repeat ERCP and stenting (some metal, some plastic). This novel ID-FCSEMS has a high clinical success and low complication rate, and in particular, there was only one case of stent migration. As a result, this stent type is preferred to traditional metal stents for treating AS after OLT.

Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

PubMed Central

Mahoney, M. Ellen; Gordon, Eva J.; Rao, Jian Yu; Jin, Yusheng; Hylton, Nola; Love, Susan M.

2014-01-01

Many women with ductal carcinoma in situ (DCIS) are treated with extensive surgery, radiation, and hormone therapy due to the inability to monitor the disease and to determine which cases will progress to invasive cancer. We assessed the safety and feasibility of administering chemotherapy directly into DCIS-containing ducts in 13 women before definitive surgery. The treatment was safe, feasible, and well tolerated, supporting further development of this strategy for management of DCIS. Introduction Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. Patients and Methods Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. Results Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. Conclusions Intraductal therapy offers a nonsurgical strategy to treat DCIS at the site of disease, potentially minimizing the adverse effects of systemic treatment while preventing development of invasive cancer. PMID:23664819

Computational Pathology to Discriminate Benign from Malignant Intraductal Proliferations of the Breast

PubMed Central

Oh, Eun-Yeong; Lerwill, Melinda F.; Brachtel, Elena F.; Jones, Nicholas C.; Knoblauch, Nicholas W.; Montaser-Kouhsari, Laleh; Johnson, Nicole B.; Rao, Luigi K. F.; Faulkner-Jones, Beverly; Wilbur, David C.; Schnitt, Stuart J.; Beck, Andrew H.

2014-01-01

The categorization of intraductal proliferative lesions of the breast based on routine light microscopic examination of histopathologic sections is in many cases challenging, even for experienced pathologists. The development of computational tools to aid pathologists in the characterization of these lesions would have great diagnostic and clinical value. As a first step to address this issue, we evaluated the ability of computational image analysis to accurately classify DCIS and UDH and to stratify nuclear grade within DCIS. Using 116 breast biopsies diagnosed as DCIS or UDH from the Massachusetts General Hospital (MGH), we developed a computational method to extract 392 features corresponding to the mean and standard deviation in nuclear size and shape, intensity, and texture across 8 color channels. We used L1-regularized logistic regression to build classification models to discriminate DCIS from UDH. The top-performing model contained 22 active features and achieved an AUC of 0.95 in cross-validation on the MGH data-set. We applied this model to an external validation set of 51 breast biopsies diagnosed as DCIS or UDH from the Beth Israel Deaconess Medical Center, and the model achieved an AUC of 0.86. The top-performing model contained active features from all color-spaces and from the three classes of features (morphology, intensity, and texture), suggesting the value of each for prediction. We built models to stratify grade within DCIS and obtained strong performance for stratifying low nuclear grade vs. high nuclear grade DCIS (AUC = 0.98 in cross-validation) with only moderate performance for discriminating low nuclear grade vs. intermediate nuclear grade and intermediate nuclear grade vs. high nuclear grade DCIS (AUC = 0.83 and 0.69, respectively). These data show that computational pathology models can robustly discriminate benign from malignant intraductal proliferative lesions of the breast and may aid pathologists in the diagnosis and classification of these lesions. PMID:25490766

A Tale of Two Cancers: Traveling to Treat Pancreatic and Thyroid Cancer.

PubMed

White, Michael G; Applewhite, Megan K; Kaplan, Edwin L; Angelos, Peter; Huo, Dezheng; Grogan, Raymon H

2017-07-01

Patients diagnosed with a malignancy must decide whether to travel for care at an academic center or receive treatment at a nearby hospital. Here we examine differences in demographics, treatment, and outcomes of those traveling to academic centers for their care vs those not traveling, as well as compare travel for an aggressive vs indolent malignancy. All patients with papillary thyroid carcinoma (PTC) or pancreatic ductal adenocarcinoma (PDAC) undergoing surgical resection and in the National Cancer Database were examined. Travel for care was abstracted from "crowfly" distance between patients' ZIP codes and treatment facility, region, county size, urban/metro/rural status, and facility type. In total, 105,677 patients with PTC and 22,983 patients with PDAC were analyzed. There were no survival differences by travel in the PTC group. Survival was improved for patients with PDAC traveling from urban/rural settings (hazard ratio = 0.89; 95% CI 0.82 to 0.96; p = 0.002). Patients traveling with PDAC were more likely to have a complete resection and lymph node dissection. Those traveling were less likely to receive chemotherapy or radiotherapy (all p < 0.001). Those traveling with PTC were older, more likely to be male, have Medicare insurance, and had a higher stage of disease (all p < 0.001). Rates of radioactive iodine were lower, American Thyroid Association guidelines were more likely followed, and lymph node dissection was more common for those traveling for care of their PTC (all p < 0.001). There are improvements in both quality and survival for those traveling to academic centers for their cancer care. In the case of PTC, this difference in quality did not affect overall survival. In PDAC, however, differences in quality translated to a survival advantage. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Cytological features of warthin-like papillary thyroid carcinoma: A case report with review of previous cytology cases.

PubMed

Vallonthaiel, Archana George; Agarwal, Shipra; Jain, Deepali; Yadav, Rajni; Damle, Nishikant A

2017-09-01

Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC. © 2017 Wiley Periodicals, Inc.

Mixed papillary-sarcomatoid carcinoma of the penis: report of an aggressive subtype.

PubMed

Bovolim, Graziele; da Costa, Walter Henriques; Guimaraes, Gustavo Cardoso; Soares, Fernando Augusto; da Cunha, Isabela Werneck

2017-12-01

Several different histological subtypes of penile carcinoma had been described in the last decades, many with different biological behavior and prognosis. The association of two histological subtypes (mixed tumors) can be observed in one third of the cases. The most common association is of warty and basaloid tumors, two HPV-related carcinomas. Here, we described a mixed papillary-sarcomatoid carcinoma, never reported before. Although it is a clinical aspect of a low-grade verruciform tumor, its prognosis showed it to be very aggressive due to the sarcomatoid component hidden above the papillary component. The two components showed opposite cadherin/vimentin expression pointed to epithelial-mesenchymal transition between them.

[Solid cystic papillary tumor of the pancreas].

PubMed

Bahri, I; Njim, L; Khabir, A; Mahmoudi, H; Ghorbel, A; Zakhama, A; Jlidi, R

2001-11-01

Solid cystic papillary tumors of the pancreas are rare; they occur most commonly in young women. Despite their characteristic microscopic appearance, their immunophenotype is not specific. Their prognosis is excellent after complete surgical resection. The study aim was to report two cases in female patients who were 15 and 20 years old; the first tumor was discovered fortuitously and the second girl presented with abdominal pain and vomiting. Both tumors were encapsulated and located in the tail of the pancreas. The histological study showed the papillary architecture mixed with solid areas. Immunohistochemical staining was positive only for vimentin in one case and positive for cytokeratin, chromogranin, synaptophysin, neuron specific enolase, vimentin and protein S100 in the second case.

Association of a renal papillary carcinoma with a low grade tumour of the collecting ducts

PubMed Central

Daniel, L; Zattara-Cannoni, H; Lechevallier, E; Pellissier, J

2001-01-01

This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 <7> and 45, XY, -8, add(12)(q–ter)<10> for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished. Key Words: renal cell carcinoma • low grade tumour of the collecting ducts PMID:11477121

Subcentimeter noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PubMed

Rosario, Pedro Weslley

2018-05-23

Recently, it was proposed that the noninvasive encapsulated follicular variant of papillary thyroid carcinoma (noninvasive E-FVPTC) start to be called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). 1 As the original cohort of 109 patients with NIFTP studied by the consensus conference included only tumors which were equal or more than 1 cm in size, the consensus diagnostic criteria of NIFTP did not explicitly address subcentimeter lesions. 1,2 In fact, in a recent review published in this journal, Hung & Barletta recognize that there are a few published subcentimetre NIFTP in the literature. 3 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Papillary tumor of the pineal region: Case report and review of the literature.

PubMed

Cañizares Méndez, María de Los Ángeles; Amosa Delgado, Manuel; Álvarez Salgado, Juan Antonio; Villaseñor Ledezma, Jorge Javier; Capilla Cabezuelo, Elena; Díaz Crespo, Francisco

2018-04-22

Papillary tumor of the pineal region is a rare neuroepithelial tumor characterized by papillary architecture and epithelial cytology, immunopositivity for cytokeratin and ependymal differentiation. It is considered grade II-III by the World Health Organization and was first described by Jouvet in 2003. We present a 34-year-old male with headaches, blurred vision and normal examination. Radiological study showed a nodulocystic lesion in the pineal region compatible with pineocytoma. Surgery was performed using an infratentorial supracerebellar approach, finding a cystic tumor in the quadrigeminal cistern which was completely resected. Histopathology reported a papillary tumor of the pineal region. The patient made good progress without adjuvant therapy, and after 57 months of follow-up he remained asymptomatic and free of recurrence. A review of the literature was performed to collect all the cases published with gross total resection and no complementary treatment. In conclusion, there is still much to be learned about the pathogenesis, prognosis and management of this tumor. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Well-differentiated papillary mesothelioma with invasion to the chest wall.

PubMed

Torii, Ikuko; Hashimoto, Masaki; Terada, Takayuki; Kondo, Nobuyuki; Fushimi, Hiroaki; Shimazu, Kohki; Takeda, Shin-Ichi; Takuwa, Teruhisa; Okumura, Yoshitomo; Sato, Ayuko; Yamamoto, Tadashi; Fukuoka, Kazuya; Tanaka, Fumihiro; Nishigami, Takashi; Nakano, Takashi; Hasegawa, Seiki; Tsujimura, Tohru

2010-02-01

Well-differentiated papillary mesothelioma (WDPM) is an uncommon tumor with a papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and good prognosis with prolonged survival. WDPM occurs primarily in the peritoneum of women, but also rarely in the pleura. We here report a case of 48-year-old woman who developed WDPM in the pleura with no history of asbestos exposure. Tumors were multifocal and widespread with a velvety appearance on the surface of parietal and visceral pleurae resected by extrapleural pneumonectomy (EPP). Tumors showed papillary structures with fibrovascular cores and lined by epithelioid cells. Immunohistochemically, these epithelioid tumor cells were positive for epithelial membrane antigen (EMA), a marker of malignant mesothelioma, with more than 50% positive for p53. Tumor cells microinvaded into subpleural parenchyma of the lung and minimally spread to adipose tissues of the mediastinal lesion. In addition, tumor cells invaded into the chest wall with a trabecular or glandular architecture. Based on these findings, this case is pathologically considered as WDPM of the pleura with malignant potential. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma.

PubMed

Kaushal, Seema; Sharma, Mehar Chand; Mathur, Sandeep R; Rastogi, Shishir; Bal, Chander Shekhar; Chumber, Sunil

2011-01-01

A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131) ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

Bilateral pheochromocytoma associated with paraganglioma and papillary thyroid carcinoma: report of an unusual case.

PubMed

Yang, Jeong Hoon; Bae, Sung Jin; Park, Sanghui; Park, Hyun-Kyung; Jung, Hye Seung; Chung, Jae Hoon; Min, Yong-Ki; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

2007-04-01

A 42-year old woman presented with headache, palpitation and facial flushing. Ultrasonograms and computed tomograms revealed tumors in both of the adrenal glands, anterior aspect of the inferior vena cava, and the right lobe of the thyroid gland. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum calcitonin, CEA, intact PTH and calcium levels were within normal limits. Markedly elevated levels of urinary normetanephrine and vanillylmandelic acid, and the result of 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy indicated that both adrenal masses were pheochromocytoma. Bilateral adrenalectomy, paracaval mass removal and total thyroidectomy together with central lymph node dissection were performed. The final pathological diagnosis was bilateral adrenal pheochromocytoma, paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia. Analysis of the RET proto-oncogene mutation, von Hippel Lindau mutation, succinate dehydrogenase subunit B mutation, and succinate dehydrogenase subunit D mutation yielded negative results. The relationship of these lesions could not be determined. This is the first report of a combination of bilateral pheochromocytoma, abdominal paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia without hyperparathyroidism.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

A pediatric intramedullary spinal cord tumor with unusual solid-cystic and papillary features: a case report.

PubMed

Iwasaki, Takeshi; Kato, Masako; Horie, Yasushi; Kato, Shinsuke; Akatsuka, Keiichi; Watanabe, Takashi; Kuwamoto, Satoshi; Murakami, Ichiro; Hayashi, Kazuhiko

2011-12-01

Spinal cord tumors are rare in children. We report a novel case of pediatric intramedullary spinal cord tumor with unusual solid-cystic and papillary features. Clinically, the patient presented at the age of 3 years with motor deficit and urinary incontinence, and MRI demonstrated multilocular cystic lesions in the thoracic spine. Histologically the tumor consisted of solid, sheet-like components and branching papillary structures, and immunohistochemistry demonstrated positive reactivity for epithelial membrane antigen, cytokeratins (7, AE1/3, CAM5.2), E-cadherin and transthyretin, and negativity for GFAP, S-100 protein, synaptophysin and neurofilament. These histological and immunohistochemical findings appeared to be unique, and were not compatible with the features of classical ependymoma or choroid plexus papilloma. The clinical behavior, characterized by relatively rapid tumor regrowth after surgical resection and a relatively high MIB-1 labeling index, suggest that this tumor might have had moderate malignant potential. This pediatric case appears to be particularly informative with regard to the tumor biology or tumorigenesis of intramedullary spinal cord tumor with unusual solid-cystic and papillary features. © 2011 Japanese Society of Neuropathology.

[A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].

PubMed

Tajima, Yusuke; Kumamoto, Kensuke; Yamamoto, Azusa; Chika, Noriyasu; Watanabe, Yuichiro; Matsuzawa, Takeaki; Ishibashi, Keiichiro; Mochiki, Erito; Iwama, Takeo; Akagi, Kiwamu; Ishida, Hideyuki

2015-11-01

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.

Molecular Profiling of Intraductal Carcinoma of the Prostate

DTIC Science & Technology

2015-10-01

Publication of the Society for Applied Immunohistochemistry. 2011;19(2):173-83. 19. Gumuskaya B, Gurel B, Fedor H, Tan HL, Weier CA, Hicks JL, et al...Focus. 2015;in press. 26. Hawley S, Fazli L, McKenney JK, Simko J, Troyer D, Nicolas M, et al. A model for the design and construction of a resource

Inflammatory papillary hyperplasia: A systematic review

PubMed Central

Gual-Vaqués, Patricia; Jané-Salas, Enric; Egido-Moreno, Sonia; Ayuso-Montero, Raúl; Marí-Roig, Antoni

2017-01-01

Introduction Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa. It is usually found in denture-wearers but also has been reported in patients without a history of use of a maxillary prosthesis use. Objetives The aim of this study is to review the literature to assess the prevalence of denture stomatitis and inflammatory papillary hyperplasia and the etiological factors associated. Material and Methods A search was carried out in PubMed (January 2005 to October 2015) with the key words “inflammatory papillary hyperplasia”, “denture stomatitis”, “granular stomatitis” and “Newton’s type III” The inclusion criteria were studies including at least a sample of 50 apparently healthy patients, articles published from 2005 to 2015 written in English. The exclusion criteria were reviews and non-human studies. Results Out of the 190 studies obtained initially from the search 16 articles were selected to be included in our systematic review. The prevalence of denture stomatitis was 29.56% and 4.44% for IPH. We found 5 cases of denture stomatitis among non-denture-wearer individuals. All IPH cases were associated with the use of prosthesis. Smoking and continued use of ill-fitting dentures turned out to be the most frequent risk factors for developing IPH. Conclusions IPH is a rare oral lesion and its pathogenesis still remains unclear. Its presentation among non-denture-wearers is extremely unusual. Key words:Inflammatory papillary hyperplasia, denture stomatitis, prevalence, granular stomatitis, Newton’s type III stomatitis. PMID:27918740

Papillary Microcarcinoma of the Thyroid among Atomic Bomb Survivors: Tumor Characteristics and Radiation Risk

PubMed Central

Hayashi, Yuzo; Lagarde, Frederic; Tsuda, Nobuo; Funamoto, Sachiyo; Preston, Dale L.; Koyama, Kojiro; Mabuchi, Kiyohiko; Ron, Elaine; Kodama, Kazunori; Tokuoka, Shoji

2009-01-01

Background Radiation exposure is an established cause of clinical thyroid cancer, but little is known about radiation effects on papillary microcarcinoma (PMC) of the thyroid, a relatively common subclinical thyroid malignancy. Because the incidence of these small thyroid cancers has been increasing, it is important to better understand them and their relationship to radiation. Methods PMCs were identified in a subset of 7659 members of the Life Span Study of atomic-bomb survivors who had archived autopsy or surgical materials. We conducted a pathology review of these specimens and evaluated the histological features of the tumors and the association between PMCs and thyroid radiation dose. Results From 1958 to1995, 458 PMCs were detected among 313 study subjects. The majority of cancers exhibited pathologic features of papillary thyroid cancers. Overall, 81% of the PMCs were of the sclerosing variant and 91% were nonencapsulated, psammoma bodies occurred in 13% and calcification was observed in 23%. Over 95% had papillary or papillary-follicular architecture and most displayed nuclear overlap, clear nuclei, and nuclear grooves. Several of these features increased with increasing tumor size, but no association was found with radiation dose. A significant radiation-dose response was found for the prevalence of PMCs (estimated excess odds ratio/Gy=0.57; 95% CI: 0.01-1.55), with the excess risk observed primarily among females. Conclusion Low-to-moderate doses of ionizing radiation appears to increase the risk of thyroid PMCs, even when exposure occurs during adulthood. PMID:20120034

Genetic Architecture of the Variation in Male-Specific Ossified Processes on the Anal Fins of Japanese Medaka.

PubMed

Kawajiri, Maiko; Fujimoto, Shingo; Yoshida, Kohta; Yamahira, Kazunori; Kitano, Jun

2015-10-28

Traits involved in reproduction evolve rapidly and show great diversity among closely related species. However, the genetic mechanisms that underlie the diversification of courtship traits are mostly unknown. Japanese medaka fishes (Oryzias latipes) use anal fins to attract females and to grasp females during courtship; the males have longer anal fins with male-specific ossified papillary processes on the fin rays. However, anal fin morphology varies between populations: the southern populations tend to have longer anal fins and more processes than the northern populations. In the present study, we conducted quantitative trait locus (QTL) mapping to investigate the genetic architecture underlying the variation in the number of papillary processes of Japanese medaka fish and compared the QTL with previously identified QTL controlling anal fin length. First, we found that only a few QTL were shared between anal fin length and papillary process number. Second, we found that the numbers of papillary processes on different fin rays often were controlled by different QTL. Finally, we produced another independent cross and found that some QTL were repeatable between the two crosses, whereas others were specific to only one cross. These results suggest that variation in the number of papillary processes is polygenic and controlled by QTL that are distinct from those controlling anal fin length. Thus, different courtship traits in Japanese medaka share a small number of QTL and have the potential for independent evolution. Copyright © 2015 Kawajiri et al.

Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival.

PubMed

Zidan, Jamal; Karen, Drumea; Stein, Moshe; Rosenblatt, Edward; Basher, Walid; Kuten, Abraham

2003-03-01

The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Copyright 2003 American Cancer Society.

Bmp7 and Lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in medaka.

PubMed

Ogino, Yukiko; Hirakawa, Ikumi; Inohaya, Keiji; Sumiya, Eri; Miyagawa, Shinichi; Denslow, Nancy; Yamada, Gen; Tatarazako, Norihisa; Iguchi, Taisen

2014-02-01

Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.

Diagnostic value of TROP-2 expression in papillary thyroid carcinoma and comparison with HBME-1, galectin-3 and cytokeratin 19.

PubMed

Murtezaoglu, Afsin Rahman; Gucer, Hasan

In this study, we compared the diagnostic value of TROP-2 expression in distinguishing between benign and malignant thyroid lesions to those of HBME-1, CK19 and galectin-3. We selected 102 cases from our archive including 20 normal thyroid tissues, 23 follicular nodular diseases, 17 follicular adenomas, 20 follicular variant papillary carcinomas and 22 classical variant papillary carcinomas. Tissue microarrays constructed from these cases were immunohistochemically analyzed with HBME-1, CK19, galectin-3 and TROP-2. Respectively 73.8%, 83.3%, 69% and 50% of all papillary carcinomas were positive with HBME-1, CK19, galectin-3 and TROP-2. CK19 was positive respectively by 100%, 43.5% and 35.3% in cases of normal thyroid, follicular nodular diseases and follicular adenoma, while the other markers were negative. In distinguishing benign and malignant lesions, which constitutes this study, HBME-1, CK19, galectin-3 and TROP-2 were statistically significant (p < 0.001). In distinguishing cases of follicular variant papillary carcinoma from follicular nodular diseases and follicular adenoma, HBME-1 and galectin-3 were statistically significant (p < 0.001). Consequently, in this study, we found that all immunohistochemical markers were effective in distinguishing benign and malignant thyroid lesions. In determining malignancy, HBME-1 had the highest diagnostic accuracy, while CK19 was the most sensitive marker. The sensitivity increased when the markers were used together.

[The significance of lymph node status in papillary and follicular thyroid gland carcinoma for the nuclear medicine physician].

PubMed

Farahati, J; Mörtl, M; Reiners, C

2000-01-01

The impact of lymph node metastases on prognosis of differentiated thyroid cancer is discussed controversially. Therefore the data of 596 patients with papillary or follicular thyroid cancer are analysed retrospectively, which have been treated between 1980 and 1995 at the Clinic and Policlinic for Nuclear Medicine of the University of Würzburg. The influence of lymph node metastases on prognosis with respect to survival is analysed with the univariate Kaplan-Meier-method and with the multivariate discriminant analysis. In addition, the influence of the prognostic factor "lymph node involvement" on distant metastases is analysed by a stratified comparison and an univariate test. In papillary thyroid cancer, the 15 year-survival-rate for stage pN1 is significantly lower (p < 0.001) with 88.7% as compared to stage pN0 (99.4%). In patients with follicular thyroid cancer this difference is even more pronounced (64.7% versus 97.2%, p < 0.001). However, the multivariate discriminant analysis shows that the only prognostic factors are tumour stage and distant metastases, and--in papillary thyroid cancer--patient's age. So lymph node metastases are not an independent prognostic factor concerning survival. However, lymph node metastases have a prognostic unfavourable influence with respect to distant metastases especially in papillary thyroid cancer stage pT4 (distant metastases in patients with negative lymph nodes 0% and in patients with positive lymph nodes 35.3% [p < 0.001]).

Significance of expression of suppressor of cytokine signaling proteins: Suppressor of cytokine signaling-1, suppressor of cytokine signaling-2, and suppressor of cytokine signaling-3 in papillary thyroid cancer.

PubMed

Kobawala, Toral Pundrik; Trivedi, Trupti I; Gajjar, Kinjal Kevin; Patel, Girish H; Ghosh, Nandita R

2017-01-01

Uncontrolled cytokine signal transduction largely associated with oncogene activation, can have disastrous biological consequences. The suppressor of cytokine signaling (SOCS) proteins represent one of the mechanisms by which this rampant signaling can be dissipated. Thus, we aimed to study the expression of SOCS-1, SOCS-2, and SOCS-3 in patients having benign thyroid disease and papillary thyroid cancer. SOCS protein expression was studied in 45 patients with benign thyroid disease and in 83 papillary thyroid cancer patients by immunohistochemistry and their association with clinicopathological characteristics and overall survival in cancer patients were analyzed using SPSS software. Expressions of SOCS proteins were significantly higher in papillary thyroid cancer than in patients having benign disease. SOCS-1 expression was predominantly higher in males (P = 0.004), unilateral tumors (P = 0.030), and noninflammatory conditions (P = 0.028). SOCS-1 expression was also able to predict poor overall survival in subgroup of papillary thyroid cancer patients having larger tumor size (P = 0.013) and advanced stage disease (P = 0.033). Expression of SOCS-2 significantly correlated with tumor size (P = 0.017), extrathyroidal extension (P = 0.000), residual disease (P = 0.043), and treatment (P = 0.007), while preponderance of SOCS-3 expression was observed in males (P = 0.030) and in patients having extrathyroidal extension (P = 0.011) and absence of metastasis (P = 0.032). Expression of the studied SOCS proteins may be a consequence of activation of Janus kinase-signal transducers and activators of transcription and other pathways supporting growth and survival of cancer cells that are sustained by several cytokines. Thus, SOCS-1, SOCS-2, and SOCS-3 proteins may directly or indirectly, have important roles in development and pathogenesis of papillary thyroid cancer.

Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model.

PubMed

Solis, Jorge; Levine, Robert A; Johnson, Benjamin; Guerrero, J Luis; Handschumacher, Mark D; Sullivan, Suzanne; Lam, Kaitlyn; Berlin, Jason; Braithwaite, Gavin J C; Muratoglu, Orhun K; Vlahakes, Gus J; Hung, Judy

2010-10-01

Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm(2)to 7.6±1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, τ (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

Skin metastasis on the neck: an unusual presentation of recurrence of papillary thyroid carcinoma

PubMed Central

Soylu, Selen; Teksoz, Serkan; Ozcan, Murat; Bukey, Yusuf

2017-01-01

Skin metastasis of papillary thyroid carcinoma (PTC) is rare. Here, two cases of skin metastases of PTC are presented. Both of the patients were females, one is 83 and the other is 65 years old. The patients were admitted to the hospital with a movable skin lesion on anterior neck region. Free T3 and T4 levels were in normal levels and TSH levels were low in both patients. The 83-year-old patient underwent total thyroidectomy due to papillary thyroid cancer and received 131I ablation therapy and then thyroid suppression therapy. After the surgery, the patient lived without evidence of disease for 3 years and then skin metastasis occurred. The 65-year-old patient had a total thyroidectomy 5 years ago due to PTC then neck dissection due to metastasis 3 years later and then received 131I ablation therapy. Thyroid ultrasonography of both patients showed hypoechoic nodules with central vascularization. In the histological examination of both patients, cystic lesions filled with papillary structures were seen. Fine needle aspiration biopsy (FNAB) taken from both patients were papillary carcinoma with solid trabecular pattern. PTC tends to metastasize to regional lymph nodes but distant metastasis is rare. When distant metastasis develops, prognosis of the disease is poor. Therefore, skin metastasis of papillary thyroid cancer is a poor prognostic factor. If the patient does not have a thyroid malignancy history, diagnosis of PTC metastatic to the skin may be difficult since primary skin tumors such as apocrine tumors have similar histopathological features. However, in the presented cases since there was a PTC history, the diagnosis was easier with the help of histopathological examination. Skin metastasis of PTC should be kept in mind when differential diagnosis of atypical skin lesions are made especially in the patients with thyroid malignancy history. PMID:29142854

A case of carcinoma of the papilla of Vater in a young man after subtotal colectomy for familial adenomatous polyposis.

PubMed

Komori, Shuji; Kawai, Masahiko; Nitta, Toyoo; Murase, Yusuke; Matsumoto, Keita; Shinoda, Chika; Kuno, Masashi; Sasaguri, Yuki; Fukada, Masahiro; Asano, Yoshimi; Kiyama, Shigeru; Tanaka, Chihiro; Nagao, Yasuko; Nagao, Narutoshi; Kunieda, Katsuyuki

2016-02-24

Carcinoma and adenoma of the duodenum, including the papilla of Vater, are problematic diseases in patients with familial adenomatous polyposis (FAP). A 36-year-old man underwent a periodic medical examination for early colon cancer originating from FAP for which laparoscopic-assisted subtotal colectomy with a J-shaped ileal pouch-rectal anastomosis was performed 3 years earlier. A tumor was detected at the papilla of Vater along with elevation of total bilirubin and hepatobiliary enzymes. Although cytology did not determine the tumor to be an adenocarcinoma, we suspected adenocarcinoma due to its hypervascularity shown by contrast-enhanced computed tomography. Pylorus-preserving pancreaticoduodenectomy with modified Imanaga reconstruction and regional lymph node dissection (D2) was performed. The pathological study showed that the tumor was a papillary and moderately differentiated tubular adenocarcinoma. The patient is currently in good health without recurrence, weight loss, or severe diarrhea at 12 months after surgery. Awareness of biliary-pancreatic symptoms and periodic gastroduodenoscopy might contribute both to the early detection of duodenal or periampullary polyps and cancer and to the radical treatment of FAP. Modified Imanaga reconstruction has the potential to become one of the more effective procedures for providing good quality of life to FAP patients with duodenal or periampullary cancer.

Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas.

PubMed

Englert, H C; Gerlach, U; Goegelein, H; Hartung, J; Heitsch, H; Mania, D; Scheidler, S

2001-03-29

Sulfonylthioureas exhibiting cardioselective blockade of ATP-sensitive potassium channels (K(ATP) channels) were discovered by stepwise structural variations of the antidiabetic sulfonylurea glibenclamide. As screening assays, reversal of rilmakalim-induced shortening of the cardiac action potential in guinea pig papillary muscles was used to probe for activity on cardiac K(ATP) channels as the target, and membrane depolarization in CHO cells stably transfected with hSUR1/hKir6.2 was used to probe for unwanted side effects on pancreatic K(ATP) channels. Changing glibenclamide's para-arrangement of substituents in the central aromatic ring to a meta-pattern associated with size reduction of the substituent at the terminal nitrogen atom of the sulfonylurea moiety was found to achieve cardioselectivity. An additional change from a sulfonylurea moiety to a sulfonylthiourea moiety along with an appropriate substituent in the ortho-position of the central aromatic system was a successful strategy to further improve potency on the cardiac K(ATP) channel. Among this series of sulfonylthioureas HMR1883, 1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methylthiourea, and its sodium salt HMR1098 were selected for development and represent a completely new therapeutic approach toward the prevention of life-threatening arrhythmias and sudden cardiac death in patients with coronary heart disease.

Papillary squamous cell carcinoma, not otherwise specified (NOS) of the penis: clinicopathologic features, differential diagnosis, and outcome of 35 cases.

PubMed

Chaux, Alcides; Soares, Fernando; Rodríguez, Ingrid; Barreto, José; Lezcano, Cecilia; Torres, José; Velazquez, Elsa F; Cubilla, Antonio L

2010-02-01

There is a group of low-grade papillomatous squamous cell carcinomas (SCC) of the penis, collectively designated as "verruciform," that are difficult to classify. A proposal of classification grouped these tumors in warty (condylomatous), verrucous, and papillary carcinomas. Papillary SCC, not otherwise specified is the third distinctive type of penile low-grade verruciform neoplasms. We are presenting clinicopathologic features of 35 cases from 2 institutions. All specimens were penectomies or circumcisions. Mean age was 57 years. Sites of involvement were glans alone in 18 cases (51%), glans, coronal sulcus and foreskin in 13 cases (37%), glans and sulcus in 3 cases (9%), and foreskin in 1 case (3%). Papillary carcinomas were large (mean 5.6 cm) exophytic low-grade squamous neoplasms with hyperkeratosis and papillomatosis. Papillae were variable in length and shape. The tip was straight, undulated, spiky, or blunt. There was no koilocytosis. The interface between tumor and stroma was characteristically jagged and a moderate stromal reaction was evident in most cases. The majority of the tumors (94%) showed a low-grade histology with focally present poorly differentiated areas in 6% of the cases. The mean thickness of the tumor was 9.4 mm. The most commonly invaded anatomic levels were the corpus spongiosum and/or dartos (77% cases). Corpus cavernosum was invaded in 8 cases (23%). Vascular and perineural invasion were unusual. Frequent associated lesions were squamous hyperplasia, differentiated penile intraepithelial neoplasia, and lichen sclerosus (74%, 46%, and 34%, respectively). Nodal metastases were identified in 3 of 12 patients with bilateral groin dissections. Of the 20 patients followed, 18 were either with no evidence of disease (15 cases) or died from unrelated causes (3 cases). One patient was alive with evidence of systemic metastases and 1 died from disseminated penile cancer 32 months after original penectomy. In conclusion, papillary carcinomas were exophytic albeit, often deeply invasive low-grade neoplasms, with a low rate of nodal metastasis characterized by complex papillae, irregular fibrovascular cores, and jagged tumor base. Papillary SCC should be distinguished from other penile verruciform tumors, including verrucous and variants, warty and papillary basaloid carcinomas, and carcinoma cuniculatum. Helpful morphologic features for differential diagnosis are provided.

Interdental papillary house: a new concept and guide for clinicians.

PubMed

Gonzalez, Marly Kimie Sonohara; Almeida, Ana Lucia Pompeia Fraga; Greghi, Sebastiao Luiz Aguiar; Pegoraro, Luiz Fernando; Mondelli, Jose; Moreno, Tatiana

2011-01-01

Surgical and nonsurgical techniques have been proposed to regenerate interdental papillae. The results are influenced by the morphology of the interdental space, which is the housing for the papilla. The concept of the interdental papillary "house" has been established not only to allow diagnosis of the causes of papillary loss, but also to manage and predict reconstruction of the interdental gingival tissue. The adjacent teeth in contact, involving the proximal contact, contour and shape of the teeth, course of the cementoenamel junction, interdental distance, and underlying bone crest, determine the outline of the house. Since the components are combined, an understanding of each allows adequate treatment planning involving interdisciplinary procedures. This new concept serves as a guide and teaching aid for the practitioner.

Use of Combination Thermal Therapy and Radiation in Breast-Conserving Treatment of Extensive Intraductal Breast Cancer

DTIC Science & Technology

1997-07-01

Review Board of the DFCI is provided in Appendix A . The investigator will keep the following information on each patient: 1. Past medical ...treatments, you will receive radiation therapy to your breast. Your radiation oncologist will decide what radiation dose you receive . On the basis of... Activities 6/87 Controversies in radiation therapy in

Nipple Discharge: An Early Warning Sign of Breast Cancer

PubMed Central

Parthasarathy, Veda; Rathnam, Usharani

2012-01-01

Nipple discharge (ND) can be the earliest presenting symptom of breast cancer. We hereby present two cases of breast cancer with no palpable mass manifesting as isolated ND, which was whitish in color. In both cases, cytology of the discharge revealed highly pleomorphic cells indicating a high grade malignancy. Mammography showed diffuse, extensive microcalcifications. Simple mastectomy with axillary clearance was done. Histology in both cases revealed diffusely spreading intraductal carcinoma, with focus of microinvasion in one case. ND if scanty or not blood stained is often ignored by the patients and at times, the clinicians. This article highlights that ND can be an early warning sign of intraductal carcinomas that are non-invasive in early stage. Irrespective of the color or nature of the discharge, unilateral ND needs to be evaluated. Proper clinical assessment, cytological evaluation of the ND, and mammography ought to be performed in all such cases. Considering the low level of awareness in women regarding the warning signs of breast cancer, the current focus is to create “breast awareness.” Women should be sensitized to recognize any unusual changes in their breasts and report to their health care providers at the earliest. PMID:23189234

Sialoendoscopically assisted open sialolithectomy for removal of large submandibular hilar calculi.

PubMed

Su, Yu-xiong; Liao, Gui-qing; Zheng, Guang-sen; Liu, Hai-chao; Liang, Yu-jie; Ou, De-ming

2010-01-01

The management of large hilar calculi is a technically challenging issue during sialoendoscopic surgery. The aim of the present study was to evaluate the clinical efficacy of sialoendoscopically assisted open sialolithectomy for the removal of large submandibular hilar calculi to avoid sialoadenectomy. The present study was undertaken among patients with sialolithiasis scheduled for sialoendoscopic surgery from August 2005 to October 2008. When we failed to remove large submandibular hilar stones intraductally, we performed sialoendoscopically assisted open sialolithectomy. The clinical characteristics, pre- and intraoperative data, and outcomes were documented in a prospective fashion. Of 78 consecutive patients with submandibular sialolithiasis, 18 were treated with sialoendoscopically assisted open sialolithectomy immediately after failure of intraductal removal of calculi by sialoendoscopy. For 17 patients, large hilar sialoliths were successfully removed using this surgical technique. The surgery failed in 1 patient with multiple sialoliths, and the procedure was converted to open sialoadenectomy. Temporary numbness of the tongue for 1 week postoperatively was documented in 3 patients. The patients were followed up for a median period of 18 months without any symptoms or signs of recurrence. Our results suggest that sialoendoscopically assisted open sialolithectomy is an effective and safe surgical technique to remove large submandibular hilar calculi.

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors.

PubMed

Olkhov-Mitsel, Ekaterina; Siadat, Farshid; Kron, Ken; Liu, Liyang; Savio, Andrea J; Trachtenberg, John; Fleshner, Neil; van der Kwast, Theodorus; Bapat, Bharati

2017-07-01

The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann-Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T-box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer.

HIF-1α and VEGF expression correlates with thrombus remodeling in cases of intravascular papillary endothelial hyperplasia

PubMed Central

Kim, Sunzoo; Jun, Jae Hun; Kim, Jeongshik; Kim, Do Won; Jang, Yong Hyun; Lee, Weon Ju; Chung, Ho Yun; Lee, Seok-Jong

2013-01-01

Intravascular papillary endothelial hyperplasia (IPEH) is histopathologically characterized by endothelium-lined papillary structures encircling an acellular fibrin core. The process of IPEH pathogenesis is unclear. The purpose of our study was to identify histopathological and immunohistochemical characteristics of IPEH to better understand the pathogenesis of this disease. After reviewing microscopic and medical records from Kyungpook National University Hospital, we selected 16 cases of IPEH. Masson’s trichrome and immunohistochemical staining as well as hematoxylin-eosin staining for 16 cases of IPH were performed. Immunohistochemical studies included CD31, CD68, mast cell tryptase, hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF). Sections from all our cases showed three distinct histological regions including a papillary portion with hyalinized fibrous or fibroblastic cores, an area containing an unorganized thrombus, and organization area with an ingrowth of endothelial cells, myofibroblasts, and fibroblasts. In the organization area, HIF-1α-positive cells were identified in the loose connective tissue. Endothelial cells forming vascular channels were negative for HIF-1α while VEGF was highly expressed in both interstitial mononuclear and endothelial cells. In the papillary portion, the cellular cores were strongly positive for both HIF-1α and VEGF, but the acellular cores were negative. Our investigation confirmed that IPEH is a reactive lesion that incidentally arises during the organization process of older thrombi. It was also found that HIF-1α and VEGF expression was dependent on the thrombus remodeling stage in cases of IPEH. PMID:24294378

Up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis in human papillary thyroid cancer cells.

PubMed

Mo, Xiao-Mei; Li, Li; Zhu, Ping; Dai, Yu-Jie; Zhao, Ting-Ting; Liao, Ling-Yao; Chen, George G; Liu, Zhi-Min

2016-08-15

17β-estradiol (E2) has been suggested to play a role in the development and progression of papillary thyroid cancer. Heat shock protein 27 (Hsp27) is a member of the Hsp family that is responsible for cell survival under stressful conditions. Previous studies have shown that the 5'-promoter region of Hsp27 gene contains a specificity protein-1 (Spl) and estrogen response element half-site (ERE-half), which contributes to Hsp27 induction by E2 in breast cancer cells. However, it is unclear whether Hsp27 can be up-regulated by E2 and which estrogen receptor (ER) isoform and tethered transcription factor are involved in this regulation in papillary thyroid cancer cells. In the present study, we demonstrated that Hsp27 can be effectively up-regulated by E2 at mRNA and protein levels in human K1 and BCPAP papillary thyroid cancer cells which have more than two times higher level of ERα than that of ERβ. The up-regulation of Hsp27 by E2 is mediated by ERα/Sp1 and ERβ has repressive effect on this ERα/Sp1-mediated up-regulation of Hsp27. Moreover, we showed that the up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis through interaction with procaspase-3. Targeting this pathway may be a potential strategy for therapy of papillary thyroid cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Isolated Effect of Geometry on Mitral Valve Function for In-Silico Model Development

PubMed Central

Siefert, Andrew William; Rabbah, Jean-Pierre Michel; Saikrishnan, Neelakantan; Kunzelman, Karyn Susanne; Yoganathan, Ajit Prithivaraj

2013-01-01

Computational models for the heart’s mitral valve (MV) exhibit several uncertainties which may be reduced by further developing these models using ground-truth data sets. The present study generated a ground-truth data set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle displacement, and asymmetric papillary muscle displacement on leaflet coaptation, mitral regurgitation (MR), and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile hemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction, and anterior leaflet strain in the radial and circumferential directions were successfully quantified for increasing levels of geometric distortion. From these data, increasing levels of isolated papillary muscle displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase), and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric papillary muscle displacement. Asymmetric papillary muscle displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data may be used to parametrically evaluate and develop modeling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools. PMID:24059354

Papillary Thyroid Cancer: The Good and Bad of the "Good Cancer".

PubMed

Randle, Reese W; Bushman, Norah M; Orne, Jason; Balentine, Courtney J; Wendt, Elizabeth; Saucke, Megan; Pitt, Susan C; Macdonald, Cameron L; Connor, Nadine P; Sippel, Rebecca S

2017-07-01

Papillary thyroid cancer is often described as the "good cancer" because of its treatability and relatively favorable survival rates. This study sought to characterize the thoughts of papillary thyroid cancer patients as they relate to having the "good cancer." This qualitative study included 31 papillary thyroid cancer patients enrolled in an ongoing randomized trial. Semi-structured interviews were conducted with participants at the preoperative visit and two weeks, six weeks, six months, and one year after thyroidectomy. Grounded theory was used, inductively coding the first 113 interview transcripts with NVivo 11. The concept of thyroid cancer as "good cancer" emerged unprompted from 94% (n = 29) of participants, mostly concentrated around the time of diagnosis. Patients encountered this perception from healthcare providers, Internet research, friends, and preconceived ideas about other cancers. While patients generally appreciated optimism, this perspective also generated negative feelings. It eased the diagnosis of cancer but created confusion when individual experiences varied from expectations. Despite initially feeling reassured, participants described feeling the "good cancer" characterization invalidated their fears of having cancer. Thyroid cancer patients expressed that they did not want to hear that it's "only thyroid cancer" and that it's "no big deal," because "cancer is cancer," and it is significant. Patients with papillary thyroid cancer commonly confront the perception that their malignancy is "good," but the favorable prognosis and treatability of the disease do not comprehensively represent their cancer fight. The "good cancer" perception is at the root of many mixed and confusing emotions. Clinicians emphasize optimistic outcomes, hoping to comfort, but they might inadvertently invalidate the impact thyroid cancer has on patients' lives.

Primary Papillary Serous Carcinoma of the Fallopian Tube Presenting as a Vaginal Mass: A Case Report and Review of the Literature.

PubMed

Kadour-Peero, Einav; Sagi-Dain, Lena; Cohen, Gil; Korobochka, Roman; Agbarya, Abed; Bejar, Jacob; Sagi, Shlomi

2018-05-07

BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.

BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors.

PubMed

Roque, Ashley; Odia, Yazmin

2017-04-01

We present a patient with BRAF-V600E mutant papillary craniopharyngioma successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved refractory to radiation. Serial brain MRIs and PET revealed marked tumor reduction with gradual neurological improvement and permanent panhypopituitarism.

Aortic valve replacement for papillary fibroelastoma.

PubMed

Arikan, Ali Ahmet; Omay, Oğuz; Aydın, Fatih; Kanko, Muhip; Gür, Sibel; Derviş, Emir; Yılmaz, Cansu Eda; Müezzinoğlu, Bahar

2017-06-01

Surgery is indicated for symptomatic patients with papillary fibroelastomas (PFE) on the aortic valve. The valve is commonly spared during tumor excision. Rarely, aortic valve replacement (AVR) is needed. We present a case requiring AVR for an aortic valve PFE and review the literature to determine the risk factors for failure of aortic valve-sparing techniques in patients with PFE. © 2017 Wiley Periodicals, Inc.

Struma Ovarii with Papillary Thyroid Carcinoma

PubMed Central

Alvarez, Daniel M.; Lee, Victor; Bhatt, Shweta; Dogra, Vikram S.

2011-01-01

Struma ovarii is an uncommon condition, in which thyroid tissue is the predominant or exclusive element in an ovarian teratoma. Thyroid tissue may demonstrate the same spectrum of pathological features as in the normal thyroid including benign and malignant changes. We present a case of papillary thyroid carcinoma arising in a struma ovarii of the left ovary in a 21-year-old female. PMID:22315711

Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.

PubMed

Vukasović, Anamarija; Kuna, Sanja Kusacić; Ostović, Karmen Trutin; Prgomet, Drago; Banek, Tomislav

2012-11-01

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.

[Use of esophageal small balloon or papillary sphincter knife in the treatment of stent implantation 
for colorectal malignant obstruction].

PubMed

Xiao, Dinghua; Liu, Shaojun; Yan, Hanguang; Wang, Xiaoyan

2018-05-28

To explore the function of esophageal small balloon or papillary sphincter knife in the treatment of stent implantation for colorectal malignant obstruction, and to improve the success rate of colonic stent placement in such patients.
 Methods: A total of 49 patients with colorectal cancer complicated with almost complete obstruction or colorectal cancer were enrolled for this study. The esophageal small balloon or papillary sphincter knife was used in the guide wires. The guide wires gradually crossed the tumor gap and they were placed in the contralateral intestinal cavity with balloon progression. X-ray was then used to confirm whether the guide wire was inserted in the lesion intestinal cavity, and then the metal bare stent was inserted.
 Results: The guide wires was successfully inserted with conventional methods in these 49 cases, while they were also successfully placed the guide wire and the stent in the new way.
 Conclusion: For the patients with colorectal cancer complicated with complete obstruction or colorectal cancer located in obviously angled location, the use of esophageal small balloon or papillary sphincter knife can help the guide wire insert. They greatly improve the success rate of stent implantation.

Blockade of the inotropic effect of Bay K 8644 by cytochalasin-B and phloretin.

PubMed Central

Dresel, P. E.; Ogbaghebriel, A.

1988-01-01

1. The positive inotropic effect in rabbit atria and papillary muscles of Bay K 8644 is blocked by cytochalasin-B (Cyto-B) and phloretin, two compounds known to block the facilitated diffusion of glucose. These compounds do not change the concentration-response curve of calcium. 2. Cyto-B is more potent in atria than in papillary muscles, 10(-7) M having a maximal effect in atria whereas 2 x 10(-5) M was required for a maximal effect in papillary muscles. Phloretin was fully effective at 10(-4) M, the only concentration tested. 3. The inotropic effect of Bay K 8644 was virtually abolished in atria bathed in a glucose-free medium or one containing 5 mM pyruvate. The contractile response to Bay K 8644 of papillary muscles was not changed significantly in glucose-free or in pyruvate-containing medium. 4. Cyto-B (2 x 10(-5) M) caused a slight but significant increase in the KD for the binding of nitrendipine to a crude sarcolemnal preparation from rabbit ventricles. The Bmax was unchanged. 5. These results may best be explained by the hypothesis that there is a metabolic requirement for the inotropic effect of Bay K 8644. PMID:2456118

American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

PubMed

Haugen, Bryan R; Sawka, Anna M; Alexander, Erik K; Bible, Keith C; Caturegli, Patrizio; Doherty, Gerard M; Mandel, Susan J; Morris, John C; Nassar, Aziza; Pacini, Furio; Schlumberger, Martin; Schuff, Kathryn; Sherman, Steven I; Somerset, Hilary; Sosa, Julie Ann; Steward, David L; Wartofsky, Leonard; Williams, Michelle D

2017-04-01

American Thyroid Association (ATA) leadership asked the ATA Thyroid Nodules and Differentiated Thyroid Cancer Guidelines Task Force to review, comment on, and make recommendations related to the suggested new classification of encapsulated follicular variant papillary thyroid carcinoma (eFVPTC) without capsular or vascular invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The task force consists of members from the 2015 guidelines task force with the recusal of three members who were authors on the paper under review. Four pathologists and one endocrinologist were added for this specific review. The manuscript proposing the new classification and related literature were assessed. It is recommended that the histopathologic nomenclature for eFVPTC without invasion be reclassified as a NIFTP, given the excellent prognosis of this neoplastic variant. This is a weak recommendation based on moderate-quality evidence. It is also noted that prospective studies are needed to validate the observed patient outcomes (and test performance in predicting thyroid cancer outcomes), as well as implications on patients' psychosocial health and economics.

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

The Role of the Papillary Epithelium in Stone Growth

NASA Astrophysics Data System (ADS)

Bergsland, Kristin J.

2007-04-01

The papillary surface epithelium (PSE) covers the renal papilla in mammalian kidneys and serves as a diffusion barrier between the urine on the apical surface and the interstitium on the basolateral surface. The PSE also plays a physiological role in transport of solutes between the urine and interstitium both by active transport and paracellular pathways. Permeability of the PSE may be affected by alterations in specific transporters, components of intercellular tight junctions, cell surface glycosaminoglycans and urine composition. In idiopathic calcium oxalate (CaOx) stone formers, apatite deposits known as Randall's plaque form in the papillary interstitium and lodge beneath the PSE. The presence of plaque may perturb the normal function of the PSE, possibly by provoking the up-regulation of pro-inflammatory cytokines such as TNFα in the interstitium. Disruption of the epithelial barrier may lead to increased permeability and exposure of the plaque matrix to urine constituents, followed by loss of the PSE and growth of CaOx stone over the plaque. To investigate the role of the PSE in stone development, new experimental systems are needed, including animal models of plaque formation as well as cell culture systems for papillary epithelial cells.

Molecular changes in thyroid neoplasia.

PubMed

Jarzab, B; Włoch, J; Wiench, M

2001-01-01

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.

The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma.

PubMed

Taşli, Funda; Ozkök, Güliz; Argon, Asuman; Ersöz, Didem; Yağci, Ayşe; Uslu, Adam; Erkan, Nazif; Salman, Tarik; Vardar, Enver

2014-12-01

Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p < 0.004). Multifocality was found to be at a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4 (+) plasma cells with adverse prognostic parameters such as multifocality and extrathyroidal extension is attention-grabbing. To render these possibilities evaluable, studies to be carried out with larger case series are needed. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

ClinicalTrials.gov

2018-03-20

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

Papillary thyroid carcinoma formation in a thyroglossal cyst. A case report.

PubMed

Ali, Ma; Abussa, A; Hashmi, H

2007-09-01

Thyroglossal cyst rarely presents with carcinoma formation in the remnants of the thyroid gland. We report a 40 year old male with papillary thyroid carcinoma formation in a thyroglossal cyst. The patient underwent surgical intervention for the cyst. His pathology was positive for thyroid carcinoma and he underwent complete thyroidectomy with postoperative radioactive iodine treatment. His follow up revealed no evidence of recurrence.

Laser Tissue Welding - Distal Pancreatectomy Sealing Study

ClinicalTrials.gov

2018-04-20

Pancreatic Tumor, Benign; Pancreatic Neoplasms; Pancreatic Adenocarcinoma; Pancreatic Pseudocyst; Pancreatic Neuroendocrine Tumor; Pancreas; Insulinoma; Pancreatic Cyst; Pancreatic Teratoma; Pancreatic Polypeptide Tumor; Pancreatic Vipoma; Pancreatic Cystadenoma; Pancreas Injury; Pancreatic Gastrinoma; Pancreatic Glucagonoma

Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.

PubMed

Haffner, Michael C; Weier, Christopher; Xu, Meng Meng; Vaghasia, Ajay; Gürel, Bora; Gümüşkaya, Berrak; Esopi, David M; Fedor, Helen; Tan, Hsueh-Li; Kulac, Ibrahim; Hicks, Jessica; Isaacs, William B; Lotan, Tamara L; Nelson, William G; Yegnasubramanian, Srinivasan; De Marzo, Angelo M

2016-01-01

Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for intraductal carcinoma adjacent to invasive adenocarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The impact of contrast enhanced spectral mammogram (CESM) and three dimensional breast ultrasound (3DUS) on the characterization of the disease extend in cancer patients.

PubMed

Helal, Maha Hussien; Salem, Dorria Saleh; Salaleldin, Lamia Adel; Mansour, Sahar Mahmoud; Alkalaawy, Basma Mohamed; Mokhtar, Nadia Mahmoud

2018-04-11

The main importance of imaging breast cancer is to guide conservative surgeries. In this study we evaluated the role of CESM in correlation with 3D breast ultrasound in characterizing the extension of the intramammary cancer in view of the: (i) the size of the main tumour, (ii) the multiplicity of the breast cancer, and (iii) the peri-tumoral stromal involvement (i.e. free or intra-ductal extension of the cancer). The study is a prospective analysis that included 300 breast masses proved to be malignant. The masses were evaluated for their size, multiplicity and surrounding stromal involvement. Contrast-based mammography performed with low (22-33 kVp) and high (44-49 kVp) energy exposures that were taken after IV injection of contrast agent and followed by bilateral 3D breast ultrasound. Operative data were the gold standard reference. There was no significant difference between the sizes of the included cancers as measured by CESM and 3DUS and that measured at the pathological analysis. CESM showed higher accuracy (32.7%, n = 98) than 3DUS (24.7%, n = 74) in the size agreement within 5% range. CESM was the most accurate modality (94%, n = 282) in detecting tumor multiplicity, followed by traditional sonomammogram (88%, n = 264), then 3D breast US (84%, n = 252). Intra-ductal extension of the breast cancer was best evaluated by the 3DUS with an accuracy value of 98% (n = 294) compared to only 60% (n = 180) by CESM. CESM is a recommend investigation in breast cancer to increase the accuracy of size measurement and the detection of multiple tumors. The addition of 3DUS can enhance the detection of intra-ductal extension. Advances in knowledge: Choice of conservative breast surgery versus mastectomy is still a debate. We used an advanced, contrast-based, application of the mammogram: contrast enhanced spectral mammogram and a non-invasive three-dimensional breast ultrasound in the assessment of the local extension of the breast cancer regarding size, perifocal stromal infiltration and multiplicity to guide the selection of proper management in proved cases of breast cancer.

Large prospective investigation of meat intake, related mutagens, and risk of renal cell carcinoma.

PubMed

Daniel, Carrie R; Cross, Amanda J; Graubard, Barry I; Park, Yikyung; Ward, Mary H; Rothman, Nathaniel; Hollenbeck, Albert R; Chow, Wong-Ho; Sinha, Rashmi

2012-01-01

The evidence for meat intake and renal cell carcinoma (RCC) risk is inconsistent. Mutagens related to meat cooking and processing, and variation by RCC subtype may be important to consider. In a large US cohort, we prospectively investigated intake of meat and meat-related compounds in relation to risk of RCC, as well as clear cell and papillary RCC histologic subtypes. Study participants (492,186) completed a detailed dietary assessment linked to a database of heme iron, heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAHs), nitrate, and nitrite concentrations in cooked and processed meats. Over 9 (mean) y of follow-up, we identified 1814 cases of RCC (498 clear cell and 115 papillary adenocarcinomas). HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Red meat intake [62.7 g (quintile 5) compared with 9.8 g (quintile 1) per 1000 kcal (median)] was associated with a tendency toward an increased risk of RCC [HR: 1.19; 95% CI: 1.01, 1.40; P-trend = 0.06] and a 2-fold increased risk of papillary RCC [P-trend = 0.002]. Intakes of benzo(a)pyrene (BaP), a marker of PAHs, and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), an HCA, were associated with a significant 20-30% elevated risk of RCC and a 2-fold increased risk of papillary RCC. No associations were observed for the clear cell subtype. Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP. Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant. This study is registered at clinicaltrials.gov as NCT00340015.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

PubMed

Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario

2014-01-01

The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study

PubMed Central

Cash, Stephanie Whisnant; Ma, Huiyan; Horn-Ross, Pamela L.; Reynolds, Peggy; Canchola, Alison J.; Sullivan-Halley, Jane; Beresford, Shirley A.A.; Neuhouser, Marian L.; Vaughan, Thomas L.; Heagerty, Patrick J.; Bernstein, Leslie

2012-01-01

Purpose Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women. Methods 116,939 women in the California Teachers Study, aged 22 to 79 years with no history of thyroid cancer at cohort entry, were followed from 1995-1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort). Results Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR=0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI<25.0 kg/m2, trend p=0.03) than among overweight or obese women (trend p=0.35; homogeneity-of-trends p=0.03). A similar pattern of risk was observed for recent activity (BMI<25 kg/m2, trend p=0.11; BMI≥25 kg/m2, trend p=0.16; homogeneity-of-trends p=0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood). Conclusions Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women. PMID:23116823

Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

PubMed

Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

2016-10-01

Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.

[Cellular architecture of papillary and nonpapillary transitional cell carcinoma].

PubMed

Moriyama, M

1989-07-01

To characterize the cellular architecture of papillary and nonpapillary transitional cell carcinoma. 2 normal ureters, 6 papillary bladder cancers and 5 nonpapillary bladder cancers were subjected to light and electron microscopic study as well as three dimensional reconstruction by 0.5 microns thick serial sections. Normal urothelium consisted of three cell layers of the basal, intermediate and superficial cells, each of which was morphologically characterized in terms of cell shape and development of cell organelles. Over 90% of the epithelial cells were proved to be connected to the uniform basement membrane directly or with long, fine cytoplasmic processes, forming hemidesmosomes at the junctional portion. Papillary tumors had, as a rule, the same cellular architecture as that of normal epithelium in terms of the regularity of cellular polarity, arrangement and differentiation, and the connection to the basement membrane. But, in G2 tumors, the connection between the intermediate and superficial cells and the basement membrane failed to be confirmed in 7 to 44% of the cells, suggesting the heterogeneity of the tumors. In contrast, nonpapillary tumors showed a high irregularity of the cellular architecture in both lesions of stromal and intra-epithelial invasion. The development of the basement membrane was indefinite, often showing thinning or disruption where occasional cytoplasmic protrusion of the tumor cells into the lamina propria was found. Nearly all of the intermediate and superficial cells in the intraepithelial lesions proved not to communicate with the basement membrane. The present results indicate distinct differences of cellular architecture between the papillary and nonpapillary urothelial tumors, which may reflect not only the growth pattern but also the biological behaviour of the individual tumors.

Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.

PubMed

Demeure, Michael J; Aziz, Meraj; Rosenberg, Richard; Gurley, Steven D; Bussey, Kimberly J; Carpten, John D

2014-06-01

Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In radioiodine resistant aggressive papillary thyroid cancers, there remain few effective therapeutic options. A 62-year-old man who underwent multiple operations for papillary thyroid cancer and whose metastases progressed despite standard treatments provided tumor tissue. We analyzed tumor and whole blood DNA by whole genome sequencing, achieving 80× or greater coverage over 94 % of the exome and 90 % of the genome. We determined somatic mutations and structural alterations. We found a total of 57 somatic mutations in 55 genes of the cancer genome. There was notably a lack of mutations in NRAS and BRAF, and no RET/PTC rearrangement. There was a mutation in the TRAPP oncogene and a loss of heterozygosity of the p16, p18, and RB1 tumor suppressor genes. The oncogenic driver for this tumor is a translocation involving the genes for anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4). The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib. This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4-ALK translocation of a TRAPP oncogene mutation. These findings suggest that this tumor has a more distinct oncogenesis than BRAF mutant papillary thyroid cancer. Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.

Cytopathology of non-invasive follicular thyroid neoplasm with papillary-like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants.

PubMed

Mahajan, S; Agarwal, S; Kocheri, N; Jain, D; Mathur, S R; Iyer, V K

2018-06-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well-defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features. Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC-FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared. There were 23 NIFTP cases, 18 FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003). NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC-FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology. © 2018 John Wiley & Sons Ltd.

Results of Cryoenergy and Radiofrequency-Based Catheter Ablation for Treating Ventricular Arrhythmias Arising From the Papillary Muscles of the Left Ventricle, Guided by Intracardiac Echocardiography and Image Integration.

PubMed

Rivera, Santiago; Ricapito, Maria de la Paz; Tomas, Leandro; Parodi, Josefina; Bardera Molina, Guillermo; Banega, Rodrigo; Bueti, Pablo; Orosco, Agustin; Reinoso, Marcelo; Caro, Milagros; Belardi, Diego; Albina, Gaston; Giniger, Alberto; Scazzuso, Fernando

2016-04-01

Catheter radiofrequency ablation of ventricular arrhythmias (VAs) arising from the left ventricle's papillary muscles has been associated with inconsistent results. The use of cryoenergy versus radiofrequency has not been compared yet. This study compares outcomes and complications of catheter ablation of VA from the papillary muscles of the left ventricle with either cryoenergy or radiofrequency. Twenty-one patients (40±12 years old; 47% males; median ejection fraction 59±7.3%) with drug refractory premature ventricular contractions or ventricular tachycardia underwent catheter cryoablation or radiofrequency ablation. VAs were localized using 3-dimensional mapping, multidetector computed tomography, and intracardiac echocardiography, with arrhythmia foci being mapped at either the anterolateral papillary muscle or posteromedial papillary muscles of the left ventricle. Focal ablation was performed using an 8-mm cryoablation catheter or a 4-mm open-irrigated radiofrequency catheter, via transmitral approach. Acute success rate was 100% for cryoenergy (n=12) and 78% for radiofrequency (n=9; P=0.08). Catheter stability was achieved in all patients (100%) treated with cryoenergy, and only in 2 (25%) patients treated with radiofrequency (P=0.001). Incidence of multiple VA morphologies was observed in 7 patients treated with radiofrequency (77.7%), whereas none was observed in those treated with cryoenergy (P=0.001). VA recurrence at 6 months follow-up was 0% for cryoablation and 44% for radiofrequency (P=0.03). Cryoablation was associated with higher success rates and lower recurrence rates than radiofrequency catheter ablation, better catheter stability, and lesser incidence of polymorphic arrhythmias. © 2016 American Heart Association, Inc.

Comparing the treatment outcomes of endoscopic papillary dilation and endoscopic sphincterotomy for removal of bile duct stones.

PubMed

Ochi, Y; Mukawa, K; Kiyosawa, K; Akamatsu, T

1999-01-01

To compare the clinical usefulness of endoscopic papillary dilation (EPD) and endoscopic sphincterotomy (EST) for removal of bile duct stones, 110 patients with stones up to 15 mm in diameter and less than 10 in number were randomly treated with either EPD (55 patients) or EST (55 patients). The patients were followed up for a median period of 23 months and endoscopic manometry with the administration of morphine was carried out in 17 patients who were observed more than 12 months after the procedures to evaluate the post-procedure papillary function. Duct clearance was achieved in 51 EPD (92.7%) and 54 EST patients (98.1%, not significantly different). Forty EPD (78.4%) and 51 EST patients (94.4%) achieved duct clearance in the initial procedure (P=0.02). Early complications occurred in one EPD (2.0%) and in three EST patients (5.6%, P=0.62). Complications during the follow-up period occurred in two EPD and eight EST patients. Recurrence of bile duct stones was observed in two EPD and three EST patients (P=0.98). Acute cholecystitis was observed in one EPD and five EST patients (P=0.06) and among patients with gall-bladder stones in situ, the rate of acute cholecystitis after EPD was significantly lower than that after EST (P=0.03). Endoscopic manometry showed the existence of a choledochoduodenal pressure gradient only after EPD, while papillary contractile function was observed after both procedures. In conclusion, both EPD and EST are safe therapeutic modalities, although EPD is more clinically effective in decreasing the risk of acute cholecystitis in patients with gall-bladder stones in situ and in preserving post-procedure papillary function.

[Experimental mitral regurgitation in ischemia-induced papillary muscle dysfunction].

PubMed

Matsuzaki, M; Yonezawa, F; Toma, Y; Miura, T; Katayama, K; Fujii, T; Kohtoku, N; Otani, N; Ono, S; Tateno, S

1988-01-01

Mitral regurgitation (MR) reportedly develops by ischemia of the papillary muscles, which is called papillary muscle dysfunction. This report deals with the roles of papillary muscles and left ventricular walls on the pathogenesis of MR using graded injuries of these structures in 23 dogs. Implanted ultrasonic microcrystal and occluder with an electromagnetic flowmetry for the left circumflex coronary artery were the main experimental setting. Graded occlusion of the artery was done by the six-step approach regarding coronary blood flow (CBF) reduction (C1-C6). Left ventricular (LV) pressure, systolic thickening (%W: sonomicrometry) of the LV anterior (AW) and posterior walls (PW), and systolic longitudinal shortening (%S: sonomicrometry) of both the anterior and posterior papillary muscles (PPM) were measured. MR was assessed by left ventricular contrast two-dimensional echocardiography. In eight dogs, all the data were adequate for analysis. In category 3 (C3: 55-70% CBF of control), %S in PPM decreased, but %W did not change significantly, and only mild MR developed in three of the eight dogs. MR clearly developed in category 4 (C4: 40-54% CBF as compared with the control stage), where %S was replaced by holosystolic lengthening and %W reduced to 50% of the control state, and total occlusion (C6) accompanied by significant thinning of both the PW and AW. Thus, the asynergy of the LVPW was needed to induce the MR in seven of the eight dogs. It was concluded that the injury of the PPM alone is not sufficient to cause MR, and the associated ischemic changes of the LV free wall as well as LV dilatation are necessary to induce severe MR.

Encapsulated papillary oncocytic neoplasms of the thyroid: morphologic, immunohistochemical, and molecular analysis of 18 cases.

PubMed

Woodford, Randall Lyndon; Nikiforov, Yuri E; Hunt, Jennifer L; Bellizzi, Andrew M; Zhang, Xiaotang; Mills, Stacey E; Stelow, Edward B

2010-11-01

Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms.

Pheochromocytoma, papillary thyroid carcinoma.

PubMed

Nasser, Tariq; Qari, Faiza

2009-08-01

A 53-year-old woman presented with labile and difficult to control hypertension on 3 different anti-hypertensive medications. Abdominal computed tomography and ultrasonography of the thyroid gland showed a 1.8 cm thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum thyroid stimulating hormone and free thyroxine, calcitonin, carcinoembryonic antigen, intact parathyroid hormone, and calcium levels were within normal limits. A 24-hour urine metanephrine showed significant elevation in urine metanephrine of approximately 3 times the upper limit of normal, and the result of 131I-metaiodobenzyleguanjdjne (131I-MIBG) scintigraphy confirmed that the adrenal mass was pheochromocytoma. Right adrenalectomy and total thyroidectomy were performed. The final pathology was pheochromocytoma and papillary thyroid carcinoma. An analysis of c-ret porto-oncogene mutation yielded a negative result. This unusual association of 2 tumors represents a new entity.