Rare Cancer News & Clinical Trials

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p53 and p16(Ink4a)/p19(Arf) Loss Promotes Different Pancreatic Tumor Types from PyMT-Expressing Progenitor Cells.

Fetched: September 26th, 2016, 1:00am EDT

p53 and p16(Ink4a)/p19(Arf) Loss Promotes Different Pancreatic Tumor Types from PyMT-Expressing Progenitor Cells.

Neoplasia. 2016 Sep 21;18(10):610-617

Authors: Azzopardi S, Pang S, Klimstra DS, Du YN

Abstract
In human studies and mouse models, the contributions of p53 and p16(Ink4a)/p19(Arf) loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs. Concurrent loss of p53 and Ink4a/Arf resembles loss of p53 alone, suggesting that Ink4a/Arf loss has no additive effect to PACC progression. Our results show that specific tumor suppressor genotypes provocatively influence the tumor biological phenotypes in pancreatic progenitor cells. Additionally, in a mouse model of β-cell hyperplasia, we demonstrate that p53 and Ink4a/Arf play cooperative roles in constraining the progression of PanNETs.

PMID: 27664376 [PubMed - as supplied by publisher]

Permalink for 'A comparison study of pancreatic acinar cell carcinoma with ductal adenocarcinoma using computed tomography in Chinese patients.'

A comparison study of pancreatic acinar cell carcinoma with ductal adenocarcinoma using computed tomography in Chinese patients.

Fetched: September 25th, 2016, 1:00am EDT

A comparison study of pancreatic acinar cell carcinoma with ductal adenocarcinoma using computed tomography in Chinese patients.

Onco Targets Ther. 2016;9:5475-81

Authors: Wang Q, Wang X, Guo R, Li G

Abstract
Pancreatic acinar cell carcinoma (ACC) is a rare tumor that is difficult to diagnose preoperatively. The aim of this study was to evaluate and describe the computed tomography (CT) features of ACC and compare the results with pancreatic ductal adenocarcinoma (DAC) for improving preoperative diagnosis. The control group consisted of 34 patients with DAC collected from the pathology electronic database. The CT imaging from nine patients with pathologically confirmed ACC was retrospectively reviewed. Two radiologists independently assessed the tumor location, size, texture, and enhancement patterns. We found that 64.3% (9/14) of ACC tumors were homogeneous and 35.7% (5/14) had necrosis. The percentage of common bile duct and pancreatic ductal dilation was 14.3% (2/14) and 7.1% (1/14), respectively. The mean size of ACC was 50.1±24.2 mm. The mean attenuation of ACC was 35.4±3.9 Hounsfield unit (HU) before enhancement, 73.1±42.9 HU in arterial phase, and 71.8±15.6 HU in port venous phase. It is difficult to distinguish ACC from DAC preoperatively only based on CT findings. However, compared with DAC, we found that ACC tumors are likely to be larger and contain more heterogeneous intratumoral necrotic hypovascular regions, and less pancreatic ductal and common biliary dilation.

PMID: 27660464 [PubMed]

[Metastatic lymph node collision of a prostatic adenocarcinoma and an urothelial carcinoma and review of the literature].

Fetched: September 23rd, 2016, 1:00am EDT

[Metastatic lymph node collision of a prostatic adenocarcinoma and an urothelial carcinoma and review of the literature].

Ann Pathol. 2015 Dec;35(6):496-501

Authors: Junca A, Frouin E, Irani J, Fromont G, Levillain P

Abstract
INTRODUCTION: Tumor collision is the encounter of two tumors from two different topographical sites. Cases of metastatic lymph node collision are exceptional. We report the case of a metastatic lymph node collision of an urothelial carcinoma and a prostatic adenocarcinoma.
OBSERVATION: A 61-year-old man was hospitalized for a right nephroureterectomy with peri-ureteral lymph node dissection. He was followed since 2004 for prostatic adenocarcinoma and treated with radical prostatectomy then radiation therapy 4 years later due to a new increase of PSA. In the follow-up, an urothelial carcinoma of the lower right ureter was discovered in 2014. Histological analysis of a peri-ureteral lymph node showed a double metastasis of urothelial and prostatic origin. The prostatic adenocarcinoma was composed of acinar and ductal subtypes. Immunohistochemical study including CK7, CK20, PSA, GATA3, P63 antibodies confirmed the distinct phenotype of the 2 tumors.
DISCUSSION: Metastatic collision of urothelial carcinoma and prostatic adenocarcinoma has been reported in 4 cases only. Our review of literature shows that prostatic adenocarcinoma always precedes the urothelial carcinoma. Immunohistochemical study, when carried out for distinguishing both tumors, should include CK7, CK20 and PSA. GATA3, androgen receptor and P63 could be added in a second time.

PMID: 26597142 [PubMed - indexed for MEDLINE]

Cytomorphology of clear cell papillary renal cell carcinoma.

Fetched: September 18th, 2016, 1:00am EDT

Cytomorphology of clear cell papillary renal cell carcinoma.

Cancer Cytopathol. 2016 Sep 16;

Authors: Lin X

Abstract
BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) shares some morphologic and immunohistochemical markers with clear cell RCC and papillary RCC. To the author's knowledge, its cytomorphology on fine-needle aspiration (FNA) or touch preparations (TPs) of core needle biopsy specimens has not been well delineated in the English language literature.
METHODS: The FNA/TP cytomorphology of 7 retrieved cases was studied.
RESULTS: The tumor cells were arranged in small nests (100%), 3-dimensional clusters (71%), papillary/tubular/acinar arrays (43%), and as single cells (57%). The tumor cells were columnar (100%) and polygonal (57%) in shape, with eccentric, small, round-to-oval nuclei. The nuclei contained evenly distributed, fine granular chromatin and demonstrated a smooth nuclear membrane (100%) (Fuhrman grade 1 to 2). The tumor cells had a moderate amount of delicate or clear cytoplasm containing small vacuoles (100%) and ill-defined cytoplasmic borders (100%). Scattered macrophages (57%) and necrosis (29%) were identified in the background. Vessels were noted within the papillary cores, transversing or surrounding nests of tumors. Immunochemical studies demonstrated expression of cytokeratin 7 (CK7) (100%), carbonic anhydrase IX (CA 9) (100% in a cup-shaped membranous pattern), α-methylacyl-CoA racemase (AMACR) (50%), and CD10 (43%). The tumor cells were negative for CD117.
CONCLUSIONS: CCPRCC was found to demonstrate cytologic features that when taken together are helpful in diagnosing CCPRCC on FNA smears and TPs. If core needle biopsy specimens or cell blocks are available, an immunohistochemical panel including CK7, CA IX, CD10, and AMACR may help in excluding congeners. This subtype of RCC requires differentiation from clear cell RCC and papillary RCC due to its low-grade indolent behavior. Cancer Cytopathol 2016. © 2016 American Cancer Society.

PMID: 27636377 [PubMed - as supplied by publisher]

Permalink for 'Metastatic pancreatic acinar cell carcinoma in a younger male with marked AFP production: A potential pitfall on fine needle aspiration biopsy.'

Metastatic pancreatic acinar cell carcinoma in a younger male with marked AFP production: A potential pitfall on fine needle aspiration biopsy.

Fetched: September 18th, 2016, 1:00am EDT

Metastatic pancreatic acinar cell carcinoma in a younger male with marked AFP production: A potential pitfall on fine needle aspiration biopsy.

Diagn Cytopathol. 2016 Sep 15;

Authors: Valente K, Yacoub G, Cappellari JO, Parks G

Abstract
A 30-year-old male presented to his doctor with complaints of abdominal pain and was found to have retroperitoneal as well as multiple hepatic masses. A serum alpha-fetoprotein (AFP) level was significantly elevated (17,373 ng mL(-1) ), raising suspicions for a metastatic germ cell tumor. Fine needle aspiration biopsy of the pancreatic lesion revealed atypical epithelioid cells with round nuclei, large prominent nucleoli, and granular cytoplasm. The morphologic differential diagnosis included pancreatic neoplasm, metastatic germ cell tumor, other metastatic carcinoma, and melanoma. An extensive panel of immunohistochemical stains confirmed the diagnosis of acinar cell carcinoma. The diagnosis of acinar cell carcinoma could be confounded by the markedly increased AFP level, particularly in the setting of a retroperitoneal mass in a younger male. The increased AFP level in the setting of an acinar cell tumor is a potential pitfall to correct diagnosis by cytology. As the treatment for these two entities differs considerably, acute awareness of the phenomenon is important. We present a case of pancreatic ACC with an increased AFP level diagnosed on a cytology specimen. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

PMID: 27634114 [PubMed - as supplied by publisher]

Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study.

Fetched: September 17th, 2016, 1:00am EDT

Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study.

J Clin Diagn Res. 2016 Jul;10(7):ZC12-5

Authors: Mohan SP, Chitturi RT, Ragunathan YT, Lakshmi SJ, Nallusamy J, Joseph I

Abstract
INTRODUCTION: The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation.
AIM: The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC.
MATERIALS AND METHODS: A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands.
RESULTS: In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia.
CONCLUSION: According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours.

PMID: 27630945 [PubMed]

Permalink for 'Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.'

Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.

Fetched: September 17th, 2016, 1:00am EDT

Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.

J Cancer Res Clin Oncol. 2016 Sep 14;

Authors: Kruger S, Haas M, Burger PJ, Ormanns S, Modest DP, Westphalen CB, Kleespies A, Angele MK, Hartwig W, Bruns CJ, Kirchner T, Werner J, Heinemann V, Boeck S

Abstract
PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC.
METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively.
RESULTS: A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12 months) observed in 6 out of 7 patients (86 %). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58 %), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery.
CONCLUSIONS: 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

PMID: 27629876 [PubMed - as supplied by publisher]

Primary Pulmonary Salivary Gland-type Tumors: A Review and Update.

Fetched: September 14th, 2016, 1:00am EDT

Primary Pulmonary Salivary Gland-type Tumors: A Review and Update.

Adv Anat Pathol. 2016 Jan;23(1):13-23

Authors: Falk N, Weissferdt A, Kalhor N, Moran CA

Abstract
Pulmonary salivary gland-type tumors (SGT) comprise a very small proportion of primary lung neoplasms. The most common tumors among this group are mucoepidermoid carcinoma and adenoid cystic carcinoma. Contrary to the head and neck region, benign SGT such as pleomorphic adenomas are exceedingly rare in the pulmonary system. More recently, 2 additional SGT, namely hyalinizing clear cell carcinoma and salivary duct-like carcinoma were recognized as primary lung tumors expanding the spectrum of SGT that have been described to originate in the tracheobronchial system. Primary pulmonary SGT must be clinically excluded from metastatic salivary gland neoplasms as their morphology is indistinguishable from that of their salivary gland counterparts. Little is known about the clinical behavior and best treatment approach for these unusual tumors. In this review, we provide a comprehensive summary of primary pulmonary SGT with particular emphasis on morphologic characteristics and latest developments in terms of immunohistochemical and molecular techniques.

PMID: 26645458 [PubMed - indexed for MEDLINE]

Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Fetched: September 14th, 2016, 1:00am EDT

Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Sci Rep. 2015;5:16759

Authors: Morvaridi S, Dhall D, Greene MI, Pandol SJ, Wang Q

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis.

PMID: 26567630 [PubMed - indexed for MEDLINE]

Analysis of Axin2 expression and function in murine models for pancreatic cancer.

Fetched: August 26th, 2016, 1:00am EDT

Analysis of Axin2 expression and function in murine models for pancreatic cancer.

Cell Biosci. 2016;6(1):49

Authors: Zechner D, Kroemer T, Albert AC, Schönrogge M, Radecke T, Vollmar B

Abstract
BACKGROUND: The involvement of Wnt in carcinogenesis and progression of pancreatic cancer is currently intensely discussed. We evaluated activation of the Wnt signaling pathway by using a Wnt reporter mouse strain expressing β-galactosidase under the control of the Axin2 promotor during pancreatitis induced formation of precancerous lesions. We also evaluated activation of Wnt signaling during interaction of pancreatic cancer with the tumor stroma.
RESULTS: Activation of Wnt signaling was observed during acinar-to-ductal metaplasia after chronic as well as acute pancreatitis. Activation of Wnt signaling was also noticed during growth of pancreatic cancer in an orthotopic syngeneic pancreas cancer model. Activation of Wnt signaling was, however, not observed in carcinoma associated fibroblasts, but was detected in few cell clusters inside the tumor. Genetic ablation of Axin2 significantly reduced body weight without having a major impact on blood glucose concentration. However, ablation of Axin2 had no influence on the observed β-galactosidase positive cell clusters or on tumor weight.
CONCLUSION: These data demonstrate that the Wnt signaling pathway is activated during acinar-to-ductal metaplasia after injury to the pancreas. However these data do not support a major role of Wnt signaling or of Axin2 in carcinoma associated fibroblasts and tumor growth.

PMID: 27555909 [PubMed]

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype.

Fetched: August 24th, 2016, 1:00am EDT

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype.

Hum Pathol. 2016 May;51:16-24

Authors: Conlon N, Sadri N, Corben AD, Tan LK

Abstract
Acinic cell carcinoma of breast is a rare subtype of triple-negative breast carcinoma and demonstrates extensive morphologic overlap with acinic cell carcinoma of the salivary gland. In this study, we perform a detailed morphologic and immunohistochemical description of 2 cases of this rare entity and undertake a comprehensive review of all reported cases of breast acinic cell carcinoma in the English language literature to date. One-third of reported cases of breast acinic cell carcinoma have been associated with the presence of a ductal carcinoma not otherwise specified component, which is frequently poorly differentiated. Breast acinic cell carcinoma can demonstrate focal morphologic features similar to microglandular adenosis; these areas are frequently negative for collagen IV and laminin on immunohistochemistry. The true relationship between these 2 entities remains unclear, but we advocate that microglandular adenosis-like areas at the periphery of a breast acinic cell carcinoma should be considered part of the carcinomatous process and re-excised if this process extends to the initial surgical margins.

PMID: 27067778 [PubMed - indexed for MEDLINE]

A case of three synchronous primary lung cancers within the same lung lobe.

Fetched: August 17th, 2016, 1:00am EDT

A case of three synchronous primary lung cancers within the same lung lobe.

Kardiochir Torakochirurgia Pol. 2016 Jun;13(2):154-6

Authors: Wcisło S, Misiak P, Brocki M

Abstract
We present the case of a 74-year-old patient with three synchronous primary lung cancers within the same lung lobe. Computed tomography and positron emission tomography investigations revealed two suspicious nodular lesions in the upper lobe of the left lung. Fine-needle aspiration biopsy confirmed that one of the lesions was non-small cell lung cancer. The patient was qualified for surgical treatment, and left upper lobectomy plus lymphadenectomy was performed. Histopathological examination confirmed the presence of three primary cancers in the left lung: keratinizing squamous cell carcinoma, neuroendocrine carcinoma, and acinar adenocarcinoma, localized within the same lung lobe. The patient was classified as having stage T3N1M0 lung cancer (stage IIIA) according to the latest, 7(th) edition of the TNM classification.

PMID: 27516792 [PubMed]

Pulmonary cavitary lesion and haemoptysis: rare aetiology on biopsy.

Fetched: August 13th, 2016, 1:00am EDT

Pulmonary cavitary lesion and haemoptysis: rare aetiology on biopsy.

BMJ Case Rep. 2016;2016

Authors: Kim J, Thomashow B, Saqi A

Abstract
Pleomorphic carcinoma of the lung is a rare form of malignancy that can present similarly to other necrotising cavitary lung diseases. We present a case of a Caucasian woman who presented with recurrent haemoptysis and a right upper lobe cavitary lesion on CT scan. She underwent selective embolisation of the right bronchial artery by interventional radiology to control her haemoptysis. Positron emission tomography/CT scan was performed which showed significant fluorodeoxyglucose uptake in the right upper lobe cavitary lesion. There was a discussion among her providers about the aetiology of this lesion including infection and malignancy. Cultures from bronchoalveolar lavage and blood were negative for infection as the patient underwent right upper lobectomy which showed invasive sarcomatoid pleomorphic carcinoma with a minor component of acinar adenocarcinoma. She was diagnosed with stage IB (T2aN0M0) sarcomatoid pleomorphic carcinoma and underwent adjuvant chemotherapy after her lobectomy with recurrence and metastasis to her stomach and pancreas.

PMID: 27507695 [PubMed - in process]

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

Fetched: August 13th, 2016, 1:00am EDT

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3078-83

Authors: Saloman JL, Albers KM, Li D, Hartman DJ, Crawford HC, Muha EA, Rhim AD, Davis BM

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

PMID: 26929329 [PubMed - indexed for MEDLINE]

Diagnostic role of DOG1 and p63 immunohistochemistry in salivary gland carcinomas.

Fetched: August 13th, 2016, 1:00am EDT

Diagnostic role of DOG1 and p63 immunohistochemistry in salivary gland carcinomas.

Int J Clin Exp Pathol. 2015;8(8):9214-22

Authors: Abd Raboh NM, Hakim SA

Abstract
BACKGROUND: The differential diagnosis of salivary carcinomas is always difficult and challenging. Salivary neoplasms often shows more than one growth pattern and significant morphologic variability may exist within a single tumor and between different tumors. The aim of this study was to examine the role of DOG1 (discovered on gastrointestinal tumor-1) and p63 immunohistochemistry in the diagnosis and differential diagnosis of salivary carcinomas.
METHODS: we examined the expression of DOG1 and p63 immunohistochemistry in 33 mucoepidermoid carcinomas (MEC), 9 acinic cell carcinomas (ACC), 10 adenoid cystic carcinomas (AdCC) and 4 myoepithelial carcinomas.
RESULTS: All ACC showed strong to moderate positivity for DOG1 (P=0.001) and all were totally negative for p63. All MEC expressed strong to moderate positivity for p63 (P=0.001) while only (9.1%) were weak to moderately positive for DOG1. (80%) AdCC were moderately positive for DOG1 in ductal and myoepithelial components and (100%) showed moderate positivity for p63 in myoepithelial cells only (P=0.001). All myoepithelial carcinomas were DOG1 negative, 2 (50%) were weakly positive for p63 while the other 2 were moderately positive (P=0.5).
CONCLUSION: DOG1 is a sensitive marker in the diagnosis of acinic cell carcinoma, p63 is sensitive in the diagnosis of mucoepidermoid carcinoma, the combined use of both markers is helpful and statistically significant in the differential diagnosis of acinic cell carcinoma versus mucoepidermoid carcinoma, both markers can help in the diagnosis of adenoid cystic carcinoma but they have no role in the diagnosis of myoepithelial carcinoma.

PMID: 26464669 [PubMed - indexed for MEDLINE]

Pancreatic panniculitis associated with pancreatic carcinoma: A case report.

Fetched: August 10th, 2016, 1:00am EDT

Pancreatic panniculitis associated with pancreatic carcinoma: A case report.

Medicine (Baltimore). 2016 Aug;95(31):e4374

Authors: Zhang G, Cao Z, Yang G, Wu W, Zhang T, Zhao Y

Abstract
INTRODUCTION: Pancreatic panniculitis is a very rare complication of pancreatic cancer, most often accompanying rare acinar cell carcinoma. We herein report a case of pancreatic panniculitis that was associated with pancreatic mucinous adenocarcinoma.
PATIENT INFORMATION: A 57-year-old male was referred to our hospital for weight loss. A physical examination revealed subcutaneous nodules on his lower extremities. The blood test showed abnormal increases in amylase, lipase, and carbohydrate antigen 19-9 levels. A computed tomography scan detected a hypodense 2 × 1.5 cm solid mass with an unclear margin in the head of the pancreas. The biopsy of subcutaneous nodules on the lower extremities was conducted and revealed lobular panniculitis. Pancreatic cancer and pancreatic panniculitis were strongly suspected. After the administration of octreotide acetate and the Whipple procedure, the serous amylase and lipase levels returned to normal, and the pancreatic panniculitis had almost resolved by 4 weeks later.
CONCLUSION: Pancreatic panniculitis is a rare complication of pancreatic cancer. However, in the presence of a pancreatic mass, as in this case, clinicians should be aware that panniculitis may be the sentinel of pancreatic carcinoma.

PMID: 27495045 [PubMed - in process]

Permalink for 'KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis.'

KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis.

Fetched: July 29th, 2016, 1:00am EDT

KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis.

Cancer Cell. 2016 Mar 14;29(3):324-38

Authors: Wei D, Wang L, Yan Y, Jia Z, Gagea M, Li Z, Zuo X, Kong X, Huang S, Xie K

Abstract
Understanding the molecular mechanisms of tumor initiation has significant impact on early cancer detection and intervention. To define the role of KLF4 in pancreatic ductal adenocarcinoma (PDA) initiation, we used molecular biological analyses and mouse models of klf4 gain- and loss-of-function and mutant Kras. KLF4 is upregulated in and required for acinar-to-ductal metaplasia. Klf4 ablation drastically attenuates the formation of pancreatic intraepithelial neoplasia induced by mutant Kras(G12D), whereas upregulation of KLF4 does the opposite. Mutant KRAS and cellular injuries induce KLF4 expression, and ectopic expression of KLF4 in acinar cells reduces acinar lineage- and induces ductal lineage-related marker expression. These results demonstrate that KLF4 induces ductal identity in PanIN initiation and may be a potential target for prevention of PDA initiation.

PMID: 26977883 [PubMed - indexed for MEDLINE]

Are acinic cell carcinomas of the breast and salivary glands distinct diseases?

Fetched: July 22nd, 2016, 1:00am EDT

Are acinic cell carcinomas of the breast and salivary glands distinct diseases?

Histopathology. 2015 Oct;67(4):529-37

Authors: Piscuoglio S, Hodi Z, Katabi N, Guerini-Rocco E, Macedo GS, Ng CK, Edelweiss M, De Mattos-Arruda L, Wen HY, Rakha EA, Ellis IO, Rubin BP, Weigelt B, Reis-Filho JS

Abstract
AIMS: Acinic cell carcinomas (AcCC) of the breast have been reported to constitute the breast counterpart of salivary gland AcCCs, based on the similarities of their histological and immunohistochemical features. Breast AcCC is a vanishingly rare form of triple-negative breast cancer (TNBC). Recent studies have demonstrated that in TNBCs, the two driver genes most frequently mutated are TP53 (82%) and PIK3CA (10%). We sought to define whether breast AcCCs would harbour TP53 and PIK3CA somatic mutations, and if so, whether these would be present in salivary gland AcCCs.
METHODS AND RESULTS: Sanger sequencing of the entire coding region of TP53 and of PIK3CA hotspot mutation sites of 10 breast and 20 salivary gland microdissected AcCCs revealed eight TP53 (80%) and one PIK3CA (10%) somatic mutations in breast AcCCs. No somatic mutations affecting these genes were found in the 20 salivary gland AcCCs analysed.
CONCLUSIONS: Our findings demonstrate that breast AcCCs display TP53 and PIK3CA mutations at frequencies similar to those of common types of TNBCs, whereas these genes appear not to be altered in salivary gland AcCCs, suggesting that despite their similar histological appearances, AcCCs of the breast and salivary glands probably constitute unrelated diseases.

PMID: 25688711 [PubMed - indexed for MEDLINE]

Expression of Markers of Hepatocellular Differentiation in Pancreatic Acinar Cell Neoplasms: A Potential Diagnostic Pitfall.

Fetched: July 20th, 2016, 1:00am EDT

Expression of Markers of Hepatocellular Differentiation in Pancreatic Acinar Cell Neoplasms: A Potential Diagnostic Pitfall.

Am J Clin Pathol. 2016 Jul 17;

Authors: Askan G, Deshpande V, Klimstra DS, Adsay V, Sigel C, Shia J, Basturk O

Abstract
OBJECTIVES: Pancreatic acinar cell carcinoma (ACC) is a rare tumor that frequently metastasizes to the liver and may present a diagnostic challenge due to its morphologic similarity to hepatocellular carcinoma. We investigated α-fetoprotein (AFP), hepatocyte paraffin antigen 1 (HepPar 1), glypican 3, arginase 1, and albumin messenger RNA (mRNA) in situ hybridization (ISH) in pancreatic neoplasms with ACC differentiation to assess their diagnostic value.
METHODS: AFP, HepPar 1, glypican 3, and arginase 1 immunohistochemical staining was performed on 28 ACCs using a tissue microarray. Albumin mRNA ISH was performed on full-faced sections.
RESULTS: Fifteen tumors were positive for at least one marker. Glypican 3 was positive in seven of 28, AFP in five 28, and albumin mRNA ISH in five of 20. None expressed arginase 1.
CONCLUSIONS: Hepatocellular differentiation markers, including albumin mRNA ISH, may be positive in ACC, but arginase 1 appears to be uniformly negative. Thus, its use may improve the accuracy in distinguishing these neoplasms from hepatocellular carcinoma. If ACC diagnosis is considered, acinar differentiation can be reliably demonstrated by trypsin/chymotrypsin.

PMID: 27425386 [PubMed - as supplied by publisher]

Pancreatic Acinar Cell Carcinoma.

Fetched: July 14th, 2016, 1:00am EDT

Pancreatic Acinar Cell Carcinoma.

Case Rep Gastroenterol. 2016 Jan-Apr;10(1):174-80

Authors: Béchade D, Desjardin M, Salmon E, Désolneux G, Bécouarn Y, Evrard S, Fonck M

Abstract
Pancreatic acinar cell carcinoma (ACC) is a rare malignant neoplasm that accounts for 1-2% of all pancreatic neoplasms. Here we report two cases of ACC and describe their clinical features, the therapies used to treat them, and their prognosis. The first patient was a 65-year-old woman who had an abdominal CT scan for a urinary infection. Fortuitously, a rounded and well-delimited corporeal pancreatic tumor was discovered. An endoscopic ultrasound (EUS)-guided fine needle aspiration revealed an ACC. During the puncture, a hypoechoic cavity appeared inside the lesion, corresponding to a probable necrotic area. Treatment consisted of a distal splenopancreatectomy. The second patient was a 75-year-old man who complained of abdominal pain. An abdominal CT scan showed a cephalic pancreatic lesion and two hepatic metastases. An EUS-guided fine needle aspiration showed a pancreatic ACC. The patient received chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen), which enabled an objective response after 6 cycles.

PMID: 27403122 [PubMed]

[Nasal endoscope surgery of acinic cell carcinoma of salivary gland on nasal septum: a case report].

Fetched: July 14th, 2016, 1:00am EDT

[Nasal endoscope surgery of acinic cell carcinoma of salivary gland on nasal septum: a case report].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016 Feb;30(3):249-51

Authors: Tang Y, Sun X, Wang J

Abstract
A 67-year-old male patient was admitted because of "the right side nasal obstruction repeatedly for 4 years". He got nasal obstruction 4 years ago, especially for the right side nasal cavity, sometimes got blood in his nasal discharge, then the symptom relieved after accepting treatment in local hospital. During the 4 years, the symptom repeatedly occurrence. Three days before hospitalization, the CT examination indicated abnormal things in his nasal cavity and the bone of his nasal sinus had been destroyed. Some abnormal organism were sent to pathological examination, and the report indicated it is acinic cell carcinoma of salivary gland. During the nasal endoscope surgery, a red goiter was found in his nose with its surface crude and brittle. Then we cut the goiter by nasal endoscope, during the operation we find the bottom of the goiter is on the nasal septum. Two weeks after the operation, the patient received the radiation therapy. One year after the operation he doesn't get the abnormal symptom and the nasal MRI not found recidivation.

PMID: 27373103 [PubMed - indexed for MEDLINE]

The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.

Fetched: July 6th, 2016, 1:00am EDT

The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.

Oncotarget. 2016 Jun 21;

Authors: Martínez-Bosch N, Guerrero PE, Moreno M, José A, Iglesias M, Munné-Collado J, Anta H, Gibert J, Orozco CA, Vinaixa J, Fillat C, Viñals F, Navarro P

Abstract
Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc- derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment.

PMID: 27374084 [PubMed - as supplied by publisher]

Acinar cell carcinoma: a report of 19 cases with a brief review of the literature.

Fetched: July 1st, 2016, 1:00am EDT

Acinar cell carcinoma: a report of 19 cases with a brief review of the literature.

World J Surg Oncol. 2016;14(1):172

Authors: Wang Y, Wang S, Zhou X, Zhou H, Cui Y, Li Q, Zhang L

Abstract
BACKGROUND: Acinar cell carcinoma (ACC) is a relatively rare pancreatic neoplasm with poorly defined prognosis. This study aimed to investigate this rare pancreatic neoplasm through comparing patients with ACC to pancreatic ductal cell adenocarcinoma (DCA).
METHODS: Tianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 1995 to 2015, and 19 patients with pathologically confirmed ACC were enrolled while 19 conventional DCA patients assigned randomly as control. Retrospective review and follow-up were performed for each patient. Regression methods were used to identify differences between ACC and DCA.
RESULTS: In our study, most patients suffered from abdominal or back pain, and no lipase hypersecretion syndrome was observed. For ACC, resected cases had better survival than those without resection, and earlier staging was related to longer survival. Resection with postoperative adjuvant therapy had a better outcome than surgery alone. Twelve cases developed recurrence. Compared to DCA, ACC had earlier staging and better survival. The overall 1-, 2-, and 5-year survival rates for patients with ACC were 73.7, 26.3, and 5 %, respectively.
CONCLUSIONS: ACC carries a better prognosis than DCA and a similarly high recurrence rate, while surgical resection proved the best first-line approach for it. A well-planned neoadjuvant or adjuvant chemoradiotherapy indeed benefit the patients with ACC.

PMID: 27352960 [PubMed - in process]

Identification of BRAF Kinase Domain Duplications Across Multiple Tumor Types and Response to RAF Inhibitor Therapy.

Fetched: July 1st, 2016, 1:00am EDT

Identification of BRAF Kinase Domain Duplications Across Multiple Tumor Types and Response to RAF Inhibitor Therapy.

JAMA Oncol. 2016 Feb;2(2):272-4

Authors: Klempner SJ, Bordoni R, Gowen K, Kaplan H, Stephens PJ, Ou SH, Ali SM

PMID: 26562024 [PubMed - indexed for MEDLINE]

The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice.

Fetched: June 30th, 2016, 1:00am EDT

The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice.

Gut. 2016 Mar;65(3):476-86

Authors: Martinelli P, Madriles F, Cañamero M, Pau EC, Pozo ND, Guerra C, Real FX

Abstract
BACKGROUND AND AIMS: Gata6 is required to complete and maintain acinar differentiation in the mouse pancreas. Pancreas-specific Gata6 ablation during development causes extensive and persistent acinar-ductal metaplasia, which is considered an initial step of mutant KRas-driven carcinogenesis. Therefore, the Gata6-null pancreas might represent a tumour-prone environment. We investigated whether Gata6 plays a role during pancreatic tumorigenesis.
DESIGN: We analysed genetically engineered mouse models and human pancreatic ductal adenocarcinoma (PDAC) cell lines, using a combination of histopathological studies, genome-wide expression and chromatin immunoprecipitation experiments to understand the role of Gata6 in the initiation and progression of KRas(G12V)-driven tumours
RESULTS: We show that Gata6 maintains the acinar differentiation programme, both directly and indirectly, and it concomitantly suppresses ectopic programmes in the pancreas. Gata6 ablation renders acinar cells more sensitive to KRas(G12V), thereby accelerating tumour development. Gata6 expression is spontaneously lost in a mouse model of KRas(G12V)-driven PDAC, in association with altered cell differentiation. Using a combination of ChIP-Seq and RNA-Seq, we show that Gata6 exerts its tumour-suppressive effect through the promotion of cell differentiation, the suppression of inflammatory pathways, and the direct repression of cancer-related pathways. Among them is the epidermal growth factor receptor (EGFR) pathway, the activity of which is upregulated in the normal and preneoplastic Gata6-null pancreas. Accordingly, GATA6-silencing in human PDAC cells leads to an upregulation of EGFR.
CONCLUSIONS: We propose that, in the pancreas, Gata6 acts as a tumour suppressor by enforcing acinar cell differentiation, by directly and indirectly repressing ectopic differentiation programmes, and by regulating crucial cancer-related gene expression pathways.

PMID: 25596178 [PubMed - indexed for MEDLINE]

[Primary Squamous Cell Carcinoma of the Prostate in which Docetaxel Therapy was Effective : A Case Report].

Fetched: June 22nd, 2016, 4:00am EDT

[Primary Squamous Cell Carcinoma of the Prostate in which Docetaxel Therapy was Effective : A Case Report].

Hinyokika Kiyo. 2016 May;62(5):259-64

Authors: Moriyama H, Kajiwara M, Yonehara S

Abstract
The patient was a 73-year-old man who visited our hospital with asymptomatic gross hematuria. Cystoscopy revealed a bladder tumor in two places. Serum prostatic specific antigen was normal (2.535 ng/ml). Transurethral resection of bladder tumors was performed. In order to complete resection of bladder tumor, transurethral resection of right lobe of the prostate whitch had protruded into the bladder, was needed. Histology of the prostatic tissue revealed squamous cell carcinoma with no grandular and acinar structures. Serum SCC-antigen level was evaluated (6.2 ng/ml) after establishment of the diagnosis. Thoraco-abdominal computed tomography and 18-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) showed prostate cancer and multiple metastases in the lymph nodes, such as right external iliac, right common iliac, para-aortic and left supraclavicular region. The patient received external radiation therapy to the prostate and underwent systemic chemotherapy using docetaxel. After 2 courses of docetaxel therapy, multiple lymph nodes metastases were reduced and serum SCC-antigen level was normalized. Docetaxel therapy could not be continued because of a side effect of interstitial pneumonia.

PMID: 27320118 [PubMed - in process]

Acinar neoplasms of the pancreas-A summary of 25 years of research.

Fetched: June 22nd, 2016, 4:00am EDT

Acinar neoplasms of the pancreas-A summary of 25 years of research.

Semin Diagn Pathol. 2016 May 13;

Authors: Klimstra DS, Adsay V

Abstract
Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related. Cystic and extrapancreatic forms have been described. These neoplasms share molecular alterations that are distinct from the more common ductal and neuroendocrine neoplasms of the pancreas. Although there is a broad range of genetic findings, a number of potential therapeutic targets have emerged. This review explores the clinical and pathologic features of pancreatic acinar neoplasms along with their more common molecular phenotypes. The differential diagnosis with other pancreatic neoplasms is explored as well.

PMID: 27320062 [PubMed - as supplied by publisher]

KRAS Mutations in Canine and Feline Pancreatic Acinar Cell Carcinoma.

Fetched: June 14th, 2016, 4:00am EDT

KRAS Mutations in Canine and Feline Pancreatic Acinar Cell Carcinoma.

J Comp Pathol. 2016 Jun 8;

Authors: Crozier C, Wood GA, Foster RA, Stasi S, Liu JH, Bartlett JM, Coomber BL, Sabine VS

Abstract
Companion animals may serve as valuable models for studying human cancers. Although KRAS is the most commonly mutated gene in human ductal pancreatic cancers (57%), with mutations frequently occurring at codons 12, 13 and 61, human pancreatic acinar cell carcinomas (ACCs) lack activating KRAS mutations. In the present study, 32 pancreatic ACC samples obtained from 14 dogs and 18 cats, including seven metastases, were analyzed for six common activating KRAS mutations located in codons 12 (n = 5) and 13 (n = 1) using Sequenom MassARRAY. No KRAS mutations were found, suggesting that, similar to human pancreatic ACC, KRAS mutations do not play a critical role in feline or canine pancreatic ACC. Due to the similarity of the clinical disease in dogs and cats to that of man, this study confirms that companion animals offer potential as a suitable model for investigating this rare subtype of pancreatic carcinoma.

PMID: 27290644 [PubMed - as supplied by publisher]

Expression of DOG1 (Using SP31) in Poorly Differentiated Carcinoma of the Head and Neck.

Fetched: June 10th, 2016, 4:00am EDT

Expression of DOG1 (Using SP31) in Poorly Differentiated Carcinoma of the Head and Neck.

Anticancer Res. 2016 Jun;36(6):3117-22

Authors: Friedrich RE, Wunder T, Schumacher U, Bartel-Friedrich S, Zustin J

Abstract
BACKGROUND: The calcium-activated chloride channel protein discovered on gastrointestinal stromal tumour 1 (DOG1) is expressed in a variety of normal and neoplastic tissues. DOG1 is a specific marker for gastrointestinal stromal tumour. In the head and neck region, DOG1 is a sensitive discriminator for acinar cell carcinoma. Only a few publications have presented data concerning the expression of DOG1 in head and neck squamous cell carcinoma (HNSCC). The expression of DOG1 in HNSCC appears to be associated with a poor prognosis. The aim of this study was to analyze the expression pattern of DOG1 in poorly differentiated carcinoma of the upper aerodigestive tract.
MATERIALS AND METHODS: A total of 84 specimens from 31 patients with carcinomas of the upper aerodigestive tract were immunohistochemically investigated for DOG1 expression. Inclusion criterion was poorly to undifferentiated carcinoma of the head and neck, but samples of the same resection site that exhibited moderate or well-differentiated squamous cell carcinoma were also enrolled. Immunoreactivity in carcinomas was estimated using a visual score (0: negative; 1: basally positive, 2: parabasally positive, 3: completely positive, 4: basally and parabasally positive).
RESULTS: Fifteen out of 84 specimens were immunoreactive to antibody to DOG1 (17.8%). DOG1 immunoreactivity was restricted to eight patients (25.8%). However, DOG1 expression was considerably heterogeneous in tumours, with three (9.6%) cases showing a positive reaction in all samples. Basal and parabasal staining patterns (five specimens each) dominated.
DISCUSSION: This study demonstrated expression of DOG1 to be restricted to some poorly differentiated carcinomas of the upper aerodigestive tract. Although the proportion of DOG1-positive carcinomas was moderate compared to results of previous studies on head and neck cancer tissues, DOG1 expression possibly indicates a subset of HNSCC. Further studies are necessary to investigate the heterogeneity and clinical relevance of DOG1 expression in HNSCC.

PMID: 27272836 [PubMed - in process]

Pancreatic-type Acinar Cell Carcinoma of the Stomach Included in Multiple Primary Carcinomas.

Fetched: June 10th, 2016, 4:00am EDT

Pancreatic-type Acinar Cell Carcinoma of the Stomach Included in Multiple Primary Carcinomas.

Anticancer Res. 2016 Jun;36(6):2855-64

Authors: Yonenaga Y, Kurosawa M, Mise M, Yamagishi M, Higashide S

Abstract
BACKGROUND/AIM: Pancreatic-type acinar cell carcinoma (ACC) in the stomach is extraordinarily rare. We pathologically examined two cases with multiple primary carcinomas, including gastric tumors.
PATIENTS AND METHODS: Gastric cancer specimens were examined by immunostaining and electron microscopy.
RESULTS: Both cases had cancer cells with acinar patterns, resembling pancreatic ACC. The cancer cells in the first case were positive for exocrine markers, including chymotrypsin, lipase and alpha-1 antichymotrypsin (ACT), as well as neuroendocrine markers, including chromogranin A and synaptophysin. The cancer cells in the second case were positive for chymotrypsin and alpha-1 ACT, while being slightly positive for chromogranin A and synaptophysin. Ultrastructurally, cancer cells contained zymogen granules in both cases. The final diagnosis was pancreatic mixed acinar-neuroendocrine carcinoma and pure pancreatic ACC, respectively.
CONCLUSION: We confirmed two cases with gastric pancreatic-type ACC included in multiple primary carcinomas. This type of double cancer has not been reported previously.

PMID: 27272797 [PubMed - in process]

Surgical and molecular pathology of pancreatic neoplasms.

Fetched: June 10th, 2016, 4:00am EDT

Surgical and molecular pathology of pancreatic neoplasms.

Diagn Pathol. 2016;11(1):47

Authors: Hackeng WM, Hruban RH, Offerhaus GJ, Brosens LA

Abstract
BACKGROUND: Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance.
MAIN BODY: Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment.
CONCLUSION: This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma.

PMID: 27267993 [PubMed - in process]

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

Fetched: June 5th, 2016, 4:00am EDT

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

BMJ Case Rep. 2016;2016

Authors: Anderson MJ, Kwong CA, Atieh M, Pappas SG

Abstract
Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies.

PMID: 27257019 [PubMed - in process]

A Rare Pancreatic Tumor That Underwent a Change in Morphology and Histopathologic Features During Chemotherapy.

Fetched: June 5th, 2016, 4:00am EDT

A Rare Pancreatic Tumor That Underwent a Change in Morphology and Histopathologic Features During Chemotherapy.

Gastroenterology. 2016 Feb;150(2):e11-3

Authors: Seino S, Tsuchiya A, Natsui M

PMID: 26718170 [PubMed - indexed for MEDLINE]

Permalink for 'Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.'

Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

Fetched: May 26th, 2016, 4:00am EDT

Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

J Pathol. 2016 Feb;238(3):434-45

Authors: Grabliauskaite K, Saponara E, Reding T, Bombardo M, Seleznik GM, Malagola E, Zabel A, Faso C, Sonda S, Graf R

Abstract
Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer.

PMID: 26510396 [PubMed - indexed for MEDLINE]

Permalink for 'Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.'

Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.

Fetched: May 25th, 2016, 4:00am EDT

Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.

J Pathol. 2016 Jan;238(1):31-41

Authors: Haffner MC, Weier C, Xu MM, Vaghasia A, Gürel B, Gümüşkaya B, Esopi DM, Fedor H, Tan HL, Kulac I, Hicks J, Isaacs WB, Lotan TL, Nelson WG, Yegnasubramanian S, De Marzo AM

Abstract
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.

PMID: 26331372 [PubMed - indexed for MEDLINE]

Efficacy of contrast-enhanced harmonic endoscopic ultrasonography in the diagnosis of pancreatic ductal carcinoma.

Fetched: May 19th, 2016, 1:00am EDT

Efficacy of contrast-enhanced harmonic endoscopic ultrasonography in the diagnosis of pancreatic ductal carcinoma.

Saudi J Gastroenterol. 2016 May-Jun;22(3):198-202

Authors: Uekitani T, Kaino S, Harima H, Suenaga S, Sen-Yo M, Sakaida I

Abstract
BACKGROUND/AIMS: Distinguishing pancreatic ductal carcinoma (DC) from other pancreatic masses remains challenging. This study aims at evaluating the efficacy of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) in the diagnosis of DC.
PATIENTS AND METHODS: Forty-nine patients with solid pancreatic mass lesions underwent CEH-EUS. EUS (B-mode) was used to evaluate the inner echoes, distributions, and borders of the masses. The vascular patterns of the masses were evaluated with CEH-EUS at 30-50 s (early phase) and 70-90 s (late phase) after the administration of Sonazoid®.
RESULTS: The final diagnoses included DCs (37), mass-forming pancreatitis (6), endocrine neoplasms (3), a solid pseudopapillary neoplasm (1), a metastatic carcinoma (1), and an acinar cell carcinoma (1). The sensitivity, specificity, and accuracy of the diagnoses of DC in hypoechoic masses using EUS (B-mode) were 89.2%, 16.7%, and 71.4%, respectively. The sensitivity, specificity, and accuracy for the diagnosis of DC in hypovascular masses using CEH-EUS were 73.0%, 91.7%, and 77.6% in the early phase and 83.8%, 91.7%, and 85.7% in the late phase, respectively.
CONCLUSIONS: CEH-EUS for the diagnosis of DC is superior to EUS. CEH-EUS in the late phase was particularly efficacious in the diagnosis of DC.

PMID: 27184637 [PubMed - in process]

Permalink for 'Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands.'

Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands.

Fetched: May 16th, 2016, 1:00am EDT

Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands.

Head Neck Pathol. 2016 May 13;

Authors: Mariano FV, Gómez CA, de Souza do Nascimento J, Dos Santos HT, Egal ES, Montalli VA, Vargas PA, de Almeida OP, Altemani A

Abstract
Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial-myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical-luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical-luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical-luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.

PMID: 27177644 [PubMed - as supplied by publisher]

Permalink for 'Novel patient-derived xenograft mouse model for pancreatic acinar cell carcinoma demonstrates single agent activity of oxaliplatin.'

Novel patient-derived xenograft mouse model for pancreatic acinar cell carcinoma demonstrates single agent activity of oxaliplatin.

Fetched: May 14th, 2016, 1:00am EDT

Novel patient-derived xenograft mouse model for pancreatic acinar cell carcinoma demonstrates single agent activity of oxaliplatin.

J Transl Med. 2016;14(1):129

Authors: Hall JC, Marlow LA, Mathias AC, Dawson LK, Durham WF, Meshaw KA, Mullin RJ, Synnott AJ, Small DL, Krishna M, von Hoff D, Schüler J, Hart SN, Couch FJ, Colon-Otero G, Copland JA

Abstract
BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare malignancy, accounting for <1 % of all pancreatic neoplasms. Very few retrospective studies are available to help guide management. We previously reported the case of a patient with metastatic PACC who achieved prolonged survival following doxorubicin treatment. Personalized treatment was based on molecular and in vitro data collected from primary cells developed from their liver metastasis. We now report the characterization of a patient derived tumor xenograft (PDTX) mouse model that originated from this patient's PACC liver metastasis.
METHODS: Fragments of biopsy tissue (5 mm(3)) from PACC liver metastasis were implanted into athymic nude mice. Tumors were grown and passaged from the host mice into new mice to be tested for therapeutic response. Immuno-histochemical (IHC) biomarkers were used to confirm that the PDTX model represents human PACC. The antitumor activities of multiple drugs (5-FU, irinotecan, oxaliplatin, gemcitabine, bevacizumab, erlotinib, doxorubicin and imatinib) were tested. Tumor size was measured over 74 days or until they reached an endpoint volume of ~800 mm(3). Tests to measure serum lipase levels and histological analyses of tumor tissues were also conducted to assess PACC progression and re-differentiation.
RESULTS: The model presented here expresses the same IHC markers found in human PACC. In the chemotherapy study, oxaliplatin produced a prolonged durable growth response associated with increased apoptosis, decreased serum lipase levels and increased healthy acinar cells. Bevacizumab also produced a significant growth response, but the effect was not prolonged as demonstrated by oxaliplatin treatment. The other chemotherapies had moderate to little effect, particularly after treatment ceased. Mutations in DNA repair genes are common in PACC and increase tumor susceptibility to oxaliplatin. To explore this we performed IHC and found no nuclear expression of BRCA2 in our model, indicating a mutation affecting nuclear localization. Gene sequencing confirms BRCA2 has a homozygous gene deletion on Exon 10, which frequently causes a protein truncation.
CONCLUSIONS: In summary, we report the development and characterization of the first and only preclinical PACC PDTX model. Here we show sustained anti-tumor activity of single agent oxaliplatin, a compound that is more effective in tumors that harbor mutations in DNA repair genes. Our data shows that BRCA2 is mutated in our PACC model, which could contribute to the oxaliplatin sensitivity observed. Further studies on this rare PACC model can serve to elucidate other novel therapies, biomarkers, and molecular mechanisms of signaling and drug resistance.

PMID: 27165126 [PubMed - in process]

Immunohistochemical localization of LLC1 in human tissues and its limited expression in non-small cell lung cancer.

Fetched: May 14th, 2016, 1:00am EDT

Immunohistochemical localization of LLC1 in human tissues and its limited expression in non-small cell lung cancer.

Histol Histopathol. 2015 Sep;30(9):1111-20

Authors: Chandra V, Choi YB, Hwang HL, Lee JH, Park SY, Kim HK, Poojan S, Koh JS, Kim HS, Hong KM

Abstract
We have shown both LLC1 expression in the lung epithelium by in situ hybridization and its inactivation in lung cancer by epigenetic modification. However, LLC1 protein's cellular localization or its role in normal lung or cancer tissues has not yet been evaluated. In the present study, a monoclonal antibody against recombinant LLC1 was produced, and immunohistochemical staining was performed on arrays including various human tissues, normal lung and non-small cell lung cancer (NSCLC) tissues for LLC1 localization. The immunohistochemical results showed LLC1 expression in the cilia of normal-airway epithelial cells and in the cytoplasm of type II pneumocytes in bronchiectatic patients, but no expression in most of the NSCLC tissues, which is consistent with our previous report positing LLC1 as a tumor suppressor. However, LLC1 over-expression in NSCLC cell lines NCI-H1299 and NCI-H23 did not show any change in proliferation or migration, which does not indicate any LLC1 tumor-suppressor role. As for the other human tissues, LLC1 was localized in renal tubular cells, pancreatic acinar cells, and epithelial cells of the stomach, duodenum, and gallbladder. In summary, our findings suggest that LLC1 is not a tumor suppressor, and that it is localized in the cilia of the normal lung epithelium but is absent in most NSCLC cases, probably due to the loss of cilia during lung carcinogenesis.

PMID: 25786037 [PubMed - indexed for MEDLINE]

Clinicopathological features of prostate ductal carcinoma: matching analysis and comparison with prostate acinar carcinoma.

Fetched: May 12th, 2016, 1:00am EDT

Clinicopathological features of prostate ductal carcinoma: matching analysis and comparison with prostate acinar carcinoma.

J Korean Med Sci. 2015 Apr;30(4):385-9

Authors: Kim A, Kwon T, You D, Jeong IG, Go H, Cho YM, Hong JH, Ahn H, Kim CS

Abstract
We evaluated the clinicopathological features and prognosis of 29 cases of prostate ductal carcinoma was considered to be an aggressive subtype of prostate acinar carcinoma. We selected 29 cases who were diagnosed prostate ductal carcinoma and had a radical prostatectomy (RP). The acinar group (n = 116) was selected among 3,980 patients who underwent a prostatectomy. The acinar group was matched to the ductal group for prostate specific antigen (PSA), clinical stage, Gleason score, and age. The mean (range) of the follow-up periods for the ductal and acinar group was 23.8 ± 20.6 and 58 ± 10.5 months, respectively. The mean age of the prostate ductal and acinar carcinoma patients was 67.3 and 67.0 yr and the mean PSA level was 14.7 and 16.2 ng/mL, respectively. No statistical differences were evident between groups in terms of the final pathologic stage or positive resection margin rate other than the postoperative Gleason score. A greater proportion of the ductal group demonstrated a postoperative Gleason score ≥ 8 in comparison with the acinar group (P = 0.024). Additionally, we observed significant prognostic difference in our patient series in biochemical recurrence. The ductal group showed a poorer prognosis than the acinar group (P = 0.016). There were no differences significantly in terms of final pathology and rate of positive resection margin, but a greater proportion of the ductal group demonstrated a Gleason score ≥ 8 than the acinar group after matching for PSA, Gleason score in biopsy and clinical stage. The ductal group also showed a poorer prognosis.

PMID: 25829805 [PubMed - indexed for MEDLINE]

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

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

Fetched: May 4th, 2016, 1:00am EDT

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

Gastroenterology. 2016 Jan;150(1):218-228.e12

Authors: Qiu W, Tang SM, Lee S, Turk AT, Sireci AN, Qiu A, Rose C, Xie C, Kitajewski J, Wen HJ, Crawford HC, Sims PA, Hruban RH, Remotti HE, Su GH

Abstract
BACKGROUND & AIMS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

PMID: 26408346 [PubMed - indexed for MEDLINE]

Human papillomavirus and salivary gland neoplasia: a p16INK4 immunohistochemical and in situ hybridisation study.

Fetched: May 4th, 2016, 1:00am EDT

Human papillomavirus and salivary gland neoplasia: a p16INK4 immunohistochemical and in situ hybridisation study.

J Laryngol Otol. 2015 Oct;129(10):1000-3

Authors: Miah MS, Majumdar S, White S, Robinson M, Kernohan N

Abstract
OBJECTIVE: This study aimed to evaluate the association between human papillomavirus infection and salivary gland tumours in a Scottish cohort.
METHODS: Specimens from a range of salivary gland tumours operated on between 1997 and 2012 were studied. A tissue microarray constructed from tissue blocks was subjected to p16INK4 (cyclin-dependent kinase inhibitor 2A) immunohistochemistry and in situ hybridisation using probes specific for human papillomavirus, including types 16 and 18.
RESULTS: A total of 61 tumours (benign and malignant) were deemed suitable for the study. p16INK4 staining yielded three (4.9 per cent) positive samples: one small cell carcinoma, one squamous cell carcinoma and one poorly differentiated carcinoma. Human papillomavirus in situ hybridisation demonstrated a positive signal in the latter sample only (1.6 per cent).
CONCLUSION: This study demonstrated a very low human papillomavirus detection rate in salivary gland tumours. It can therefore be concluded that human papillomavirus infection is unlikely to play a role in salivary gland neoplasia. Rare human papillomavirus positive cases should be carefully evaluated to exclude the possibility of a metastatic lesion.

PMID: 26190415 [PubMed - indexed for MEDLINE]

Pancreatic panniculitis as a paraneoplastic phenomenon of a pancreatic acinar cell carcinoma.

Fetched: April 28th, 2016, 1:00am EDT

Pancreatic panniculitis as a paraneoplastic phenomenon of a pancreatic acinar cell carcinoma.

Acta Clin Belg. 2016 Apr 26;:1-3

Authors: Naeyaert C, de Clerck F, De Wilde V

Abstract
We present the case of a 59-year-old patient admitted with extreme painful erythematous subcutaneous nodules of the lower extremities in association with arthritis and peripheral eosinophilia. Upon skin biopsy, the diagnosis of pancreatic panniculitis was made. On further investigation, an underlying acinar cell type pancreas carcinoma was revealed. This clinical case does illustrate how a seemingly innocuous skin condition may herald an underlying malignant disease. The presence of pancreatic panniculitis should trigger clinicians to undertake further thorough diagnostic investigation of the pancreas.

PMID: 27112929 [PubMed - as supplied by publisher]

PTEN loss and ERG protein expression are infrequent in prostatic ductal adenocarcinomas and concurrent acinar carcinomas.

Fetched: April 28th, 2016, 1:00am EDT

PTEN loss and ERG protein expression are infrequent in prostatic ductal adenocarcinomas and concurrent acinar carcinomas.

Prostate. 2015 Oct;75(14):1610-9

Authors: Morais CL, Herawi M, Toubaji A, Albadine R, Hicks J, Netto GJ, De Marzo AM, Epstein JI, Lotan TL

Abstract
BACKGROUND: Prostatic ductal adenocarcinoma is an unusual and aggressive morphologic subtype of prostate cancer. PTEN gene deletion and ERG gene rearrangement are among the most common genomic changes in acinar prostate cancers. Though ductal adenocarcinoma most commonly occurs with synchronous usual-type acinar adenocarcinoma, little is known about the molecular phenotype of these mixed tumors.
METHODS: We used genetically validated immunohistochemistry (IHC) assays to assess PTEN and ERG status in a group of 37 surgically treated ductal adenocarcinomas and 18 synchronous acinar adenocarcinomas where we have previously reported ERG gene rearrangement status by fluorescence in situ hybridization (FISH). A group of 34 stage and grade-matched pure acinar adenocarcinoma cases was studied as a control.
RESULTS: ERG IHC was highly concordant with ERG FISH results, with 100% (36/36) concordance among ductal adenocarcinomas and 91% (31/34) concordance among 34 pure acinar carcinomas. Similar to previous FISH results, ERG expression by IHC was significantly less common among ductal adenocarcinomas (11% or 4/37) and their synchronous acinar tumors (6% or 1/18) compared to matched pure acinar adenocarcinoma cases (50% or 17/34; P = 0.0005 and 0.002, respectively). PTEN loss by IHC was also less common among ductal adenocarcinomas (18% or 6/34) and their synchronous acinar tumors (22% or 4/18) compared to matched pure acinar carcinomas (50% or 17/34; P = 0.01 and 0.08, respectively). As expected, PTEN loss was enriched among ERG positive compared to ERG-negative tumors in the pure acinar tumor control group (2.5-fold enrichment; P = 0.04) however this was not observed among the ductal adenocarcinomas (1.5 fold enrichment; P = NS). Of ductal adenocarcinomas with an evaluable synchronous acinar component, ERG status was concordant in 94% (17/18) and PTEN status was concordant in 94% (16/17).
CONCLUSIONS: Based on PTEN and ERG, ductal adenocarcinomas and their concurrent acinar carcinomas may be clonally related in some cases and show important molecular differences from pure acinar carcinoma.

PMID: 26178158 [PubMed - indexed for MEDLINE]

Factors influencing survival in acinic cell carcinoma: a retrospective survival analysis of 2061 patients.

Fetched: April 24th, 2016, 1:00am EDT

Factors influencing survival in acinic cell carcinoma: a retrospective survival analysis of 2061 patients.

Head Neck. 2015 Jun;37(6):870-7

Authors: Biron VL, Lentsch EJ, Gerry DR, Bewley AF

Abstract
BACKGROUND: Acinic cell carcinoma is an uncommon salivary neoplasm with clinical and histologic features known to influence prognosis. The purpose of this study was to further describe variables influencing survival in a large cohort of patients with acinic cell carcinoma.
METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we obtained demographic, clinicopathologic, and treatment data pertaining to patients diagnosed with acinic cell carcinoma. Kaplan-Meier and Cox regression analyses were performed to compare survival with various clinical and pathological parameters.
RESULTS: We identified 2061 patients with acinic cell carcinoma from 1973 to 2009. Sex, staging, grade, subsite, and treatment were significant predictors of disease-specific survival (DSS). Patients who received surgery alone had the highest 20-year DSS (92.4%), followed by those treated with surgery and radiation (71.9%) or radiation alone (62.3%).
CONCLUSION: Our results suggest that histologic grade is a stronger predictor of survival than TNM classification, survival after surgical resection alone is excellent, and adjuvant radiation may be of limited benefit

PMID: 24623677 [PubMed - indexed for MEDLINE]

Permalink for 'Alpha-methylacyl-CoA racemase is expressed in a majority of pancreatic neoplasms of neuroendocrine, acinar, and solid pseudopapillary differentiation.'

Alpha-methylacyl-CoA racemase is expressed in a majority of pancreatic neoplasms of neuroendocrine, acinar, and solid pseudopapillary differentiation.

Fetched: April 23rd, 2016, 1:00am EDT

Alpha-methylacyl-CoA racemase is expressed in a majority of pancreatic neoplasms of neuroendocrine, acinar, and solid pseudopapillary differentiation.

Pathology. 2015 Aug;47(5):466-8

Authors: Liszka Ł

PMID: 26126032 [PubMed - indexed for MEDLINE]

Ectopic adrenocortical adenoma in the renal hilum: a case report and literature review.

Fetched: April 22nd, 2016, 1:00am EDT

Ectopic adrenocortical adenoma in the renal hilum: a case report and literature review.

Diagn Pathol. 2016;11(1):40

Authors: Liu Y, Jiang YF, Wang YL, Cao HY, Wang L, Xu HT, Li QC, Qiu XS, Wang EH

Abstract
BACKGROUND: Ectopic (accessory) adrenocortical tissue, also known as adrenal rests, is a developmental abnormality of the adrenal gland. The most common ectopic site is in close proximity to the adrenal glands and along the path of descent or migration of the gonads because of the close spatial relationship between the adrenocortical primordium and gonadal blastema during embryogenesis. Ectopic rests may undergo marked hyperplasia, and occasionally induce ectopic adrenocortical adenomas or carcinomas.
CASE PRESENTATION: A 27-year-old Chinese female patient who presented with amenorrhea of 3 months duration underwent computed tomography urography after ultrasound revealed a solitary mass in the left renal hilum. Histologically, the prominent eosinophilic tumor cells formed an alveolar- or acinar-like configuration. The immunohistochemical profile (alpha-inhibin+, Melan-A+, synaptophysin+) indicated the adrenocortical origin of the tumor, diagnosed as ectopic adrenocortical adenoma. The patient was alive with no tumor recurrence or metastasis at the 3-month follow-up examination.
CONCLUSIONS: The unusual histological appearance of ectopic adrenocortical adenoma may result in its misdiagnosis as oncocytoma or clear cell renal cell carcinoma, especially if the specimen is limited. This case provides a reminder to pathologists to be aware of atypical cases of this benign tumor. Although uncommon, an ectopic adrenal lesion should be included in the differential diagnosis of tumors involving the renal hilum. A misdiagnosis of this benign condition as a malignant renal tumor may have severe consequences for the patient, including unnecessary radical nephrectomy. Preoperative biopsy and appropriate immunohistochemical staining will assist in determining the origin and nature of the tumor and in avoiding intraoperative uncertainty.

PMID: 27094262 [PubMed - in process]

Change isn't always better.

Fetched: April 22nd, 2016, 1:00am EDT

Change isn't always better.

Elife. 2015;4

Authors: Schofield H, Pasca di Magliano M

Abstract
Maintaining the identity of acinar cells in the pancreas could help to prevent the development of pancreatic cancer.

PMID: 26274776 [PubMed - indexed for MEDLINE]

The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma.

Fetched: April 21st, 2016, 1:00am EDT

The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma.

Elife. 2015;4

Authors: Krah NM, De La O JP, Swift GH, Hoang CQ, Willet SG, Chen Pan F, Cash GM, Bronner MP, Wright CV, MacDonald RJ, Murtaugh LC

Abstract
Understanding the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) may provide therapeutic strategies for this deadly disease. Recently, we and others made the surprising finding that PDAC and its preinvasive precursors, pancreatic intraepithelial neoplasia (PanIN), arise via reprogramming of mature acinar cells. We therefore hypothesized that the master regulator of acinar differentiation, PTF1A, could play a central role in suppressing PDAC initiation. In this study, we demonstrate that PTF1A expression is lost in both mouse and human PanINs, and that this downregulation is functionally imperative in mice for acinar reprogramming by oncogenic KRAS. Loss of Ptf1a alone is sufficient to induce acinar-to-ductal metaplasia, potentiate inflammation, and induce a KRAS-permissive, PDAC-like gene expression profile. As a result, Ptf1a-deficient acinar cells are dramatically sensitized to KRAS transformation, and reduced Ptf1a greatly accelerates development of invasive PDAC. Together, these data indicate that cell differentiation regulators constitute a new tumor suppressive mechanism in the pancreas.

PMID: 26151762 [PubMed - indexed for MEDLINE]

Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases.

Fetched: April 20th, 2016, 1:00am EDT

Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases.

J Pathol Transl Med. 2016 Apr 18;

Authors: Lee T, Lee B, Choi Y, Han J, Ahn MJ, Um SW

Abstract
Background: Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Materials and Methods: In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results: All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7-29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusion: EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

PMID: 27086595 [PubMed - as supplied by publisher]

Mixed acinar-neuroendocrine carcinoma of the pancreas: a case report and a review.

Fetched: April 17th, 2016, 1:00am EDT

Mixed acinar-neuroendocrine carcinoma of the pancreas: a case report and a review.

Histol Histopathol. 2016 Apr 15;:11767

Authors: Jakobsen M, Klöppel G, Detlefsen S

Abstract
62-year-old woman presented with abdominal discomfort. Imaging studies showed a tumor in the pancreatic tail. At contrast-enhanced CT and macroscopy, the tumor showed cystic, solid and hemorrhagic areas. Histologically, the tumor was well-circumscribed and entirely encapsulated. Some of the tumor cells in the cystic areas were reminiscent of acinar cells, and the majority was arranged in a solid growth pattern. Immunohistochemistry revealed >30% positivity for chymotrypsin, chromogranin A, synaptophysin, and CD56. The diagnosis of a mixed acinar-neuroendocrine carcinoma (MAEC) was made. Review of the English language literature revealed 44 previously published cases of resected MAECs. We found that, compared to classical acinar cell carcinoma, patients with MAECs have a slightly higher age, are less frequently males and that the tumors more often are located in the pancreatic head. The histogenesis of MAEC is still controversial. Due to the small number of cases it is at present not possible to define an evidence-based optimal treatment strategy for these patients.

PMID: 27081013 [PubMed - as supplied by publisher]

Assessing the histological type and grade of primary parotid carcinoma by fine-needle aspiration and frozen section.

Fetched: April 16th, 2016, 1:00am EDT

Assessing the histological type and grade of primary parotid carcinoma by fine-needle aspiration and frozen section.

Auris Nasus Larynx. 2015 Dec;42(6):463-8

Authors: Nishikawa S, Kawata R, Higashino M, Lee K, Terada T, Kurisu Y, Tsuji M

Abstract
OBJECTIVE: The aim of this study is to compare preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section (FS) for the correct identification of malignancy, histological grade, and histological type.
METHODS: FNAC was performed on all 105 patients and FS on 71 patients with parotid carcinoma.
RESULTS: The rate of correctly determining the histological grade by FNAC and FS was 32% and 73%, respectively. The correct diagnosis rate for both the histological type and grade by FNAC and FS was 20% and 48%, respectively.
CONCLUSIONS: The correct grading of both high and low/intermediate grade carcinoma is possible in 70-80% of patients by FS. If the histological grade is identified correctly, the extent of resection can usually be decided appropriately. Therefore, we should put emphasis on determining the histological grade.

PMID: 26065980 [PubMed - indexed for MEDLINE]

Permalink for 'Expression of SOX10 in Salivary Gland Oncocytic Neoplasms: A Review and a Comparative Analysis with Other Immunohistochemical Markers.'

Expression of SOX10 in Salivary Gland Oncocytic Neoplasms: A Review and a Comparative Analysis with Other Immunohistochemical Markers.

Fetched: April 13th, 2016, 1:00am EDT

Expression of SOX10 in Salivary Gland Oncocytic Neoplasms: A Review and a Comparative Analysis with Other Immunohistochemical Markers.

Acta Cytol. 2015;59(5):384-90

Authors: Schmitt AC, Cohen C, Siddiqui MT

Abstract
OBJECTIVES: We evaluated SOX10 (SRY-related HMG-box 10) in differentiating acinic cell carcinoma (AciCC) from other salivary gland neoplasms with oncocytic features on fine-needle aspiration cell blocks (FNA CB) and compared its performance to DOG1 (discovered on gastrointestinal stromal tumor 1).
MATERIAL AND METHODS: 35 FNA CB of oncocytic salivary gland neoplasms, i.e. 13 cases of AciCC, 16 of Warthin tumor (WT), 3 of mucoepidermoid carcinoma (MEC) and 3 of oncocytoma (ONC), and 75 salivary gland resections, i.e. 26 AciCC, 7 WT, 36 MEC, 3 ONC, 2 mammary analog secretory carcinomas (MASC) and 1 papillary cystadenoma were stained for SOX10 and DOG1.
RESULTS: None of the benign oncocytic neoplasms were immunoreactive for SOX10 on CB or resection, similar to DOG1. On CB, 61.5 and 77% of AciCC were positive for SOX10 and DOG1, respectively. All surgically resected AciCC cases were positive for SOX10 and DOG1; other malignant oncocytic lesions such as MEC and MASC demonstrated variable SOX10 and DOG1 staining.
CONCLUSION: The use of SOX10 may increase the diagnostic accuracy of oncocytic lesions on FNA. In this context, SOX10 is equivalent to DOG1 in ruling out benign lesions such as WT and ONC; however, negative results for SOX10 as well as DOG1 do not favor a benign diagnosis since MEC is often negative for both markers.

PMID: 26619208 [PubMed - indexed for MEDLINE]

Permalink for 'Reconstruction of Complex Total Parotidectomy Defect With a Chimeric Anterolateral Thigh Perforator Flap and Vascularized Motor Branch of Femoral Nerve Grafting.'

Reconstruction of Complex Total Parotidectomy Defect With a Chimeric Anterolateral Thigh Perforator Flap and Vascularized Motor Branch of Femoral Nerve Grafting.

Fetched: April 10th, 2016, 1:00am EDT

Reconstruction of Complex Total Parotidectomy Defect With a Chimeric Anterolateral Thigh Perforator Flap and Vascularized Motor Branch of Femoral Nerve Grafting.

J Oral Maxillofac Surg. 2015 Dec;73(12):2448.e1-7

Authors: Xu ZF, Duan WY, Tan XX, Sun CF

Abstract
Reconstruction of complex total parotidectomy defects after ablation is always a challenge for surgeons. The surgical technique in reconstructing total parotidectomy defects using an anterolateral thigh (ALT) flap has not been described in detail. This report describes the treatment of a difficult case with a complex total parotidectomy defect. An ALT flap composed of a vascularized motor branch of the femoral nerve and a narrow portion of the vastus lateralis muscle was harvested. An 8-cm-long vascularized nerve was transplanted into the gap, which can be considered a cable transplant graft, and a myocutaneous paddle was used to cover and fill in the soft tissue defect. There were no complications after surgery, and the patient was satisfied with the reconstructed facial contours. This case shows that using a chimeric ALT flap for reconstruction is possible in a complex total parotidectomy defect.

PMID: 26342951 [PubMed - indexed for MEDLINE]

Immunohistochemical expression of cytokeratins in human salivary gland acinic cell carcinomas.

Fetched: April 10th, 2016, 1:00am EDT

Immunohistochemical expression of cytokeratins in human salivary gland acinic cell carcinomas.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Aug;120(2):248-57

Authors: Li X, Shi Z, Wang Y, Liu Y, Liu T

Abstract
OBJECTIVE: To compare the expression of cytokeratins (CKs) in the solid, microcystic, follicular, and papillary-cystic subtypes of salivary gland acinic cell carcinoma (AcCC) in order to characterize the cell origin.
STUDY DESIGN: The expression of CK7, CK14, CK19, CK20, and alpha-smooth muscle actin (α-SMA) in 18 cases of AcCC was assessed with the use of immunohistochemical staining. Ten normal salivary glands were used as controls.
RESULTS: The expression of CKs in AcCCs varied according to their growth patterns. CK7 showed strong and diffuse positive staining in the microcystic, follicular, and papillary-cystic subtypes, whereas staining was weakly positive or negative in the solid subtype. CK14 expression was negative in almost all AcCCs. Expression of CK19 was observed in the microcystic, follicular, and papillary-cystic subtypes, but was minimally observed in the solid subtype. No cells positive for CK20 or α-SMA were found in any AcCCs.
CONCLUSIONS: We demonstrated that the microcystic, follicular and papillary-cystic subtypes of AcCC exhibit features of ductal luminal cells with expression of CK7 and CK19, suggesting their ductal origination. By contrast, the solid subtype might originate from different cells with no ductal CK expression.

PMID: 26166029 [PubMed - indexed for MEDLINE]

Permalink for 'New insights into plasticity of pancreatic cancer: cancer to acinar cell reprogramming by the basic helix-loop-helix transcription factor E47.'

New insights into plasticity of pancreatic cancer: cancer to acinar cell reprogramming by the basic helix-loop-helix transcription factor E47.

Fetched: April 10th, 2016, 1:00am EDT

New insights into plasticity of pancreatic cancer: cancer to acinar cell reprogramming by the basic helix-loop-helix transcription factor E47.

Pancreas. 2015 Jul;44(5):683-5

Authors: Bailey JM, Hendley AM, Maitra A

PMID: 26061556 [PubMed - indexed for MEDLINE]

Permalink for 'The basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential.'

The basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential.

Fetched: April 9th, 2016, 1:00am EDT

The basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential.

Pancreas. 2015 Jul;44(5):718-27

Authors: Kim S, Lahmy R, Riha C, Yang C, Jakubison BL, van Niekerk J, Staub C, Wu Y, Gates K, Dong DS, Konieczny SF, Itkin-Ansari P

Abstract
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) initiates from quiescent acinar cells that attain a Kras mutation, lose signaling from basic helix-loop-helix (bHLH) transcription factors, undergo acinar-ductal metaplasia, and rapidly acquire increased growth potential. We queried whether PDA cells can be reprogrammed to revert to their original quiescent acinar cell state by shifting key transcription programs.
METHODS: Human PDA cell lines were engineered to express an inducible form of the bHLH protein E47. Gene expression, growth, and functional studies were investigated using microarray, quantitative polymerase chain reaction, immunoblots, immunohistochemistry, small interfering RNA, chromatin immunoprecipitation analyses, and cell transplantation into mice.
RESULTS: In human PDA cells, E47 activity triggers stable G0/G1 arrest, which requires the cyclin-dependent kinase inhibitor p21 and the stress response protein TP53INP1. Concurrently, E47 induces high level expression of acinar digestive enzymes and feed forward activation of the acinar maturation network regulated by the bHLH factor MIST1. Moreover, induction of E47 in human PDA cells in vitro is sufficient to inhibit tumorigenesis.
CONCLUSIONS: Human PDA cells retain a high degree of plasticity, which can be exploited to induce a quiescent acinar cell state with reduced tumorigenic potential. Moreover, bHLH activity is a critical node coordinately regulating human PDA cell growth versus cell fate.

PMID: 25894862 [PubMed - indexed for MEDLINE]

The pathology of unusual subtypes of prostate cancer.

Fetched: April 6th, 2016, 1:00am EDT

The pathology of unusual subtypes of prostate cancer.

Chin J Cancer Res. 2016 Feb;28(1):130-43

Authors: Li J, Wang Z

Abstract
There are some current literatures describing the morphologic change of prostate carcinoma variants. Some subtypes do not respond to hormone deprivation therapy, for example adenosquamous and squamous cell carcinoma (SQCC), basaloid and adenoid cystic carcinoma (ACC), small cell carcinoma (SmCC), sarcomatoid carcinoma, urothelial carcinoma; some are defined in special Gleason grade, some develop different prognosis. So, it is very important to identify these rare subtypes to avoid misdiagnosis. In this review, we aim to describe the typical clinicopathological features of the rare variants of prostate cancer, including prostate acinar adenocarcinoma morphologic variants.

PMID: 27041935 [PubMed]

Prognostic Factors and Treatment Outcomes of Parotid Gland Cancer: A 10-Year Single-Center Experience.

Fetched: April 6th, 2016, 1:00am EDT

Prognostic Factors and Treatment Outcomes of Parotid Gland Cancer: A 10-Year Single-Center Experience.

Otolaryngol Head Neck Surg. 2015 Dec;153(6):981-9

Authors: Chang JW, Hong HJ, Ban MJ, Shin YS, Kim WS, Koh YW, Choi EC

Abstract
OBJECTIVE: To investigate the treatment outcomes of parotid gland cancer at a single center over a 10-year period and to evaluate the prognostic significance of maximum standardized uptake value.
STUDY DESIGN: Retrospective case series with chart review.
SETTING: Academic care center.
SUBJECTS AND METHODS: Ninety-eight patients with primary parotid gland cancer who were surgically treated at Yonsei University Head & Neck Cancer Clinic between January 1999 and December 2008 were analyzed. Patient data were collected retrospectively from medical charts. The investigators analyzed the association of clinicopathological factors and maximum standardized uptake value on (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scan with disease-specific survival.
RESULTS: Mean patient age was 49.7 years. Mean follow-up was 48.8 months. Thirty-three, 40, 30, and 23 patients had stage I, II, III, and IVA disease, respectively. Mucoepidermoid carcinoma was the most common histologic type (34.7%), followed by acinic cell carcinoma (27.6%). Eighteen patients (18.4%) experienced recurrences (mean recurrence gap, 20.6 months; range, 2-87 months). Five- and 10-year disease-specific survival rates were 93.6% and 81.8%, respectively. In the univariate analysis, pathologic T stage, pathologic lymph node status, resection margin, external parenchymal extension, and maximum standardized uptake value were significantly associated with disease-specific survival. Pathologic lymph node status and maximum standardized uptake value were independent prognostic factors in the multivariate analysis.
CONCLUSION: Our single-center experience with parotid gland cancer treatment is consistent with the literature. Cervical lymph node metastasis and high maximum standardized uptake value are associated with poor survival in parotid gland cancer.

PMID: 26203086 [PubMed - indexed for MEDLINE]

Relevant infrastructural alterations in invasive pancreatic ductal adenocarcinoma.

Fetched: April 6th, 2016, 1:00am EDT

Relevant infrastructural alterations in invasive pancreatic ductal adenocarcinoma.

Rom J Morphol Embryol. 2015;56(1):207-22

Authors: Constantin VD, Mirancea GV, Moroşanu AM, Mirancea N

Abstract
In this study, we focus our interest on some peculiar infrastructural abnormalities detected in a pancreatic cancer case. Our electron microscopic observations underline the high plasticity of the pancreatic parenchyma cells. Tumor pancreatic exocrine lesions are represented by putative ductal and acinar cells, which proliferate and grow in a haphazard pattern, detrimental to endocrine counterpart. The tumor cells do not exhibit neither a pure ductular or ductal nor a pure acinar phenotype, but tumor lesions represented by neoplastic ductal cells with invasive growth are by far prevalently. In our pancreatic cancer case, electron microscopic investigation clearly shows that a plethora of the epithelial cells from the tumor lesions contain large areas of autophagy leading to the pleomorphic inclusions represented by fibrillary÷filamentous inclusions frequently associated with hyaline-amorphous material, and secondary lysosomes. One of the mostly striking and important finding in this report for a case of pancreatic cancer is the high fragility (extensive dissolutions) of plasma membrane of tumor cells leading to pseudo-syncytia formation. Desmosomal junctions are severely altered, almost missing. Plasma membranes showed shedding membrane vesicles. Extravasated inflammatory cells contribute to the dramatic and extensive destructive areas of epithelial cells as well as tumor-stroma counterpart, including the basement membrane. All above severe infrastructural abnormalities, especially down regulation of cell-cell and cell-extracellular matrix adhesions might result in aberrant cell behavior and, consequently, much care should be taken for the postoperatory patient evolution.

PMID: 25826507 [PubMed - indexed for MEDLINE]

Surgical Techniques for Sinonasal Malignancies.

Fetched: March 31st, 2016, 1:00am EDT

Surgical Techniques for Sinonasal Malignancies.

Neurosurg Clin N Am. 2015 Jul;26(3):403-12

Authors: Farag A, Rosen M, Evans J

Abstract
Sinonasal malignancies are a rare subset of malignancies of the upper aerodigestive tract which had been traditionally approached via open techniques. This article primarily addresses a paradigm shift in endoscopic endonasal oncological resection utilizing principles of tumor disassembly and negative margins. The surgical steps to these endoscopic techniques are detailed, emphasizing principles of sound oncological resection.

PMID: 26141359 [PubMed - indexed for MEDLINE]

DAPK3 suppresses acini morphogenesis and is required for mouse development.

Fetched: March 31st, 2016, 1:00am EDT

DAPK3 suppresses acini morphogenesis and is required for mouse development.

Mol Cancer Res. 2015 Feb;13(2):358-67

Authors: Kocher BA, White LS, Piwnica-Worms D

Abstract
UNLABELLED: Death-associated protein kinase (DAPK3) is a serine/threonine kinase involved in various signaling pathways important to tissue homeostasis and mammalian biology. Considered to be a putative tumor suppressor, the molecular mechanism by which DAPK3 exerts its suppressive function is not fully understood and the field lacks an appropriate mouse model. To address these gaps, an in vitro three-dimensional tumorigenesis model was used and a constitutive DAPK3-knockout mouse was generated. In the 3D morphogenesis model, loss of DAPK3 through lentiviral-mediated knockdown enlarged acinar size by accelerated acini proliferation and apoptosis while maintaining acini polarity. Depletion of DAPK3 enhanced growth factor-dependent mTOR activation and, furthermore, enlarged DAPK3 acini structures were uniquely sensitive to low doses of rapamycin. Simultaneous knockdown of RAPTOR, a key mTORC1 component, reversed the augmented acinar size in DAPK3-depleted structures indicating an epistatic interaction. Using a validated gene trap strategy to generate a constitutive DAPK3-knockout mouse, it was demonstrated that DAPK3 is vital for early mouse development. The Dapk3 promoter exhibits spatiotemporal activity in developing mice and is actively expressed in normal breast epithelia of adult mice. Importantly, reduction of DAPK3 expression correlates with the development of ductal carcinoma in situ (DCIS) and more aggressive breast cancer as observed in the Oncomine database of clinical breast cancer specimens.
IMPLICATIONS: Novel cellular and mouse modeling studies of DAPK3 shed light on its tumor-suppressive mechanisms and provide direct evidence that DAPK3 has relevance in early development.

PMID: 25304685 [PubMed - indexed for MEDLINE]

Permalink for 'Expression of p53 protein, Jaagsiekte sheep retrovirus matrix protein, and surfactant protein in the lungs of sheep with pulmonary adenomatosis.'

Expression of p53 protein, Jaagsiekte sheep retrovirus matrix protein, and surfactant protein in the lungs of sheep with pulmonary adenomatosis.

Fetched: March 28th, 2016, 1:00am EDT

Expression of p53 protein, Jaagsiekte sheep retrovirus matrix protein, and surfactant protein in the lungs of sheep with pulmonary adenomatosis.

J Vet Diagn Invest. 2016 Mar 26;

Authors: İlhan F, Vural SA, Yıldırım S, Sözdutmaz İ, Alcigir ME

Abstract
Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring cancer in sheep that is caused by theJaagsiekte sheep retrovirus(JSRV). Because the pathological and epidemiological features of OPA are similar to those of bronchoalveolar carcinoma in humans, OPA is considered a useful animal model for pulmonary carcinogenesis. In this study, 3,512 lungs from various breeds of sheep were collected and macroscopically examined. OPA was identified in 30 sheep, and samples of these animals were further examined by histologic, immunohistochemical (p53 protein, surfactant protein A [SP-A], proliferating cell nuclear antigen [PCNA], JSRV matrix protein [MA]), and polymerase chain reaction (PCR) methods. Papillary or acinar adenocarcinomas were detected microscopically in the affected areas. Immunoreactivity for p53 PAb240 was detected in 13 sheep, whereas p53 DO-1 was not detected in any of the OPA animals. PCNA immunoreactivity was recorded in 27 animals. SP-A and JSRV MA protein was immunopositive in all 30. JSRV proviral DNA was detected by PCR analysis in all of the lung samples collected from OPA animals. In addition, the pulmonary SP-A levels were increased in tumor cells. The results of this study suggest that PCNA and p53 protein expression may be useful indicators in monitoring malignancy of pulmonary tumors.

PMID: 27016721 [PubMed - as supplied by publisher]

ACINAR CELL CARCINOMA OF PANCREAS IN A CHILD: A RADIOLOGICAL PERSPECTIVE.

Fetched: March 25th, 2016, 1:00am EDT

ACINAR CELL CARCINOMA OF PANCREAS IN A CHILD: A RADIOLOGICAL PERSPECTIVE.

J Ayub Med Coll Abbottabad. 2015 Oct-Dec;27(4):936-7

Authors: Husen Y, Saeed MA, Siddiqui S

Abstract
Acinar cell carcinoma is a rare tumour arising from pancreatic acinar cells. Typical radiological patterns associated with it may suggest the unusual diagnosis even before final confirmation by histopathology. We present a case of an 8 year old boy who presented to clinic with symptoms of abdominal pain without associated jaundice or vomiting. Imaging revealed an atypical mass arising from head of the pancreas. Histopathology confirmed the diagnosis of acinar cell carcinoma. An idea about atypical and rare pancreatic masses is necessary to help direct the diagnosis and guide the pathologist for suspecting atypical pathology.

PMID: 27004357 [PubMed - in process]

Permalink for 'Molecular mechanism of intraductal papillary mucinous neoplasm and intraductal papillary mucinous neoplasm-derived pancreatic ductal adenocarcinoma.'

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

Fetched: March 25th, 2016, 1:00am EDT

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

J Hepatobiliary Pancreat Sci. 2015 Jul;22(7):519-23

Authors: Fukuda A

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

PMID: 25900667 [PubMed - indexed for MEDLINE]

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours.

Fetched: March 23rd, 2016, 1:00am EDT

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours.

Eur Urol. 2016 Mar 17;

Authors: Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE

Abstract
It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report.
PATIENT SUMMARY: Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential.

PMID: 26996659 [PubMed - as supplied by publisher]

Lung adenocarcinoma with concurrent KRAS mutation and ALK rearrangement responding to crizotinib: case report.

Fetched: March 17th, 2016, 1:00am EDT

Lung adenocarcinoma with concurrent KRAS mutation and ALK rearrangement responding to crizotinib: case report.

Int J Biol Markers. 2015 Apr-Jun;30(2):e254-7

Authors: Campos-Gomez S, Lara-Guerra H, Routbort MJ, Lu X, Simon GR

Abstract
Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene was recently identified as a novel genetic alteration in a subset of non-small cell lung cancer (NSCLC). EML4-ALK translocations are rare events associated with specific clinicopathological features, such as never or light smoking history, young age and adenocarcinoma with signet ring or acinar histology. Reports suggest ALK gene arrangements are mutually exclusive with EGFR and KRAS mutations. To the best of to our knowledge, this is the first case report of a patient with concurrent KRAS mutation and ALK translocation. This patient had an excellent response to crizotinib, suggesting that the ALK translocation was the oncogenic driver.

PMID: 25588859 [PubMed - indexed for MEDLINE]

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Posted: July 13th, 2016, 10:00am EDT

Conditions: Acinar Cell Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bladder Adenocarcinoma; Bronchioloalveolar Carcinoma; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Endometrial Adenocarcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; 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 Skin Neoplasm; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary Origin; 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; 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; 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 Adenocarcinoma; Vulvar Squamous Cell Carcinoma
Interventions: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting - verified July 2016

Permalink for 'High Volume Washing of the Abdomen in Increasing Survival After Surgery in Patients With Pancreatic Cancer That Can Be Removed by Surgery'

High Volume Washing of the Abdomen in Increasing Survival After Surgery in Patients With Pancreatic Cancer That Can Be Removed by Surgery

Posted: April 29th, 2016, 1:00pm EDT

Conditions: Acinar Cell Carcinoma; Ampulla of Vater Adenocarcinoma; Cholangiocarcinoma; Duodenal Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary Mucinous Neoplasm, Pancreatobiliary-Type; Periampullary Adenocarcinoma
Interventions: Procedure: Pancreatectomy; Other: Lavage
Sponsor: Thomas Jefferson University
Recruiting - verified May 2016

Permalink for 'Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery'

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery

Posted: July 16th, 2014, 1:00pm EDT

Conditions: Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
Interventions: Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Other: Pharmacological Study; Other: Placebo; Drug: WEE1 Inhibitor AZD1775
Sponsor: National Cancer Institute (NCI)
Recruiting - verified August 2016

Permalink for 'Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Metastatic Pancreatic Cancer'

Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Metastatic Pancreatic Cancer

Posted: June 23rd, 2014, 10:00am EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Stage IV Pancreatic Cancer
Interventions: Drug: gemcitabine hydrochloride; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: selinexor; Other: pharmacological study; Other: laboratory biomarker analysis
Sponsors: Barbara Ann Karmanos Cancer Institute; National Cancer Institute (NCI)
Recruiting - verified February 2016

Permalink for 'Stereotactic Radiosurgery and Metformin Hydrochloride in Treating Patients With Borderline-Resectable or Locally-Advanced Pancreatic Cancer'

Stereotactic Radiosurgery and Metformin Hydrochloride in Treating Patients With Borderline-Resectable or Locally-Advanced Pancreatic Cancer

Posted: May 30th, 2014, 10:00am EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage I-III Pancreatic Cancer
Interventions: Drug: metformin hydrochloride; Radiation: stereotactic radiosurgery
Sponsors: Case Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting - verified September 2016

Combination Chemotherapy Before and After Surgery in Treating Patients With Localized Pancreatic Cancer

Posted: January 24th, 2014, 10:00am EST

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Stage I Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer
Interventions: Drug: oxaliplatin; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: fluorouracil; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis
Sponsors: Yale University; National Cancer Institute (NCI)
Recruiting - verified August 2016

Alisertib and Gemcitabine Hydrochloride in Treating Patients With Solid Tumors or Pancreatic Cancer

Posted: August 13th, 2013, 10:00am EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific
Interventions: Drug: alisertib; Drug: gemcitabine
Sponsors: University of California, Davis; National Cancer Institute (NCI); Millennium Pharmaceuticals, Inc.
Recruiting - verified August 2016

CPI-613 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

Posted: April 23rd, 2013, 10:00am EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
Intervention: Drug: 6,8-bis(benzylthio)octanoic acid
Sponsors: Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI)
Recruiting - verified July 2016

Permalink for 'ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery'

ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery

Posted: March 27th, 2013, 10:00am EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Duct Cell Adenocarcinoma of the Pancreas; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Gallbladder Cancer; Recurrent Pancreatic Cancer; Stage II Gallbladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Pancreatic Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer
Interventions: Drug: ADH-1; Drug: cisplatin; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis
Sponsors: University of Nebraska; National Cancer Institute (NCI); Adherex Technologies, Inc.
Recruiting - verified May 2013

Ultrasound-Guided Photodynamic Therapy With Photofrin & Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

Posted: January 15th, 2013, 10:00am EST

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Stage III Pancreatic Cancer
Interventions: Drug: porfimer sodium; Procedure: endoscopic ultrasonography; Procedure: photodynamic therapy; Drug: gemcitabine hydrochloride
Sponsors: John DeWitt; American Society for Gastrointestinal Endoscopy; Pinnacle Biologics Inc.
Recruiting - verified August 2016

Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer

Posted: August 14th, 2012, 1:00pm EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer
Interventions: Drug: metformin hydrochloride; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: laboratory biomarker analysis
Sponsors: Case Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting - verified June 2016

Permalink for 'Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies'

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

Posted: July 16th, 2012, 10:00am EDT

Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer
Interventions: Drug: oxaliplatin; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: fluorouracil; Other: laboratory biomarker analysis
Sponsors: University of Chicago; National Cancer Institute (NCI)
Recruiting - verified July 2016

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